docGravid i Norge 2016 100 000 graviditeter i Norge Perinatal dødlighet
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Gravid i Norge 2016 100 000 graviditeter i Norge Perinatal dødlighet
100 000 graviditeter i Norge Gravid i Norge 2016 Spontan abort Ekstrauterint svangerskap 15 000 1500 Fødsel spontan abort indusert abort Fødsel EX uterint60 ssk000 Babill Stray-Pedersen Indusert abort Prof I em. 15 000 Kvinneklinikken, Rikshospitalet Oslo Universitetssykehus og Universitet i Oslo Norge Antall fødte 2014: Gravid i Norge 60 026 Gutt 51.4% - Pike 48.6% Antall barn per kvinne: 1.84 52 fødeinstitusjoner 21 neonatal enheter 20 % født uten neonatal service Lav spebarns dødlighet < 7d: > 28 uker: >22 uker: 2.8 av 1000 4.3 av 1000 Best i verden Foreldrepermisjon (49 / 59 uker) Mamma må ta 10 uker ( 3+7) Pappa må ta 10 uker + 5 uker per barn > 1 Amme permisjon: 2 t (1t) per dag Komplikasjoner I svangerskapet: Alder: 30.6 år 1. gangs fødende: 26 - 31 år (28.7) 20 % Far: 35% 3% 6% > 35 år: < 20 år: 4 eller flere barn: 1 av 4, stiger med alder Ved fødsel: 1 av 3 , stiger med alder For tidlig fødsel: 1 av 15 “Fjernkulturelle”: 1 av 6 ( 12%) 0.5-1.5 kg 1% (ca 600 barn) ( Oslo 1 av 4) Eldre mor Mødre og spebarnsdødlighet I Norge Antall fødsler Mor død perinatal død per 1000 Fødsler 70 000 107 100 60 000 20 21 40 000 47 Mor død 17 Perinatal død 1950 1960 10 11 14 5 1940 50 8 5 1970 Fødsels register 1980 1990 Perinatal komite 4 64 2000 Retninglinjer Perinatal dødlighet i Norge Mor er eldre i Norge idag Perinatale dødlighet Downs syndrom Mors dødlighet 6 per 1000 4 per 10 000 40 år: 20 per 1000 100 per 10 000 20 45 år: 30 per 1000 400 per 10 000 100 RR 23 år: 2010 191 dødfødte 3 per 1000 Biologiske klokke tikker Dødfødte etter 22 uke er halvert siden 1999 Risk of Maternal Death during Lifetime 1 : 140 Mødre dødlighet i Norge Per 1000 kvinner 1/ 7600 10 blødning 1/ 2400 5 1/ 11 barselsfeber 1 1 1/12000 1/ 120 1/ 31 Keisersnitt 1/ 190 1/240 1/ 7400 Penicillin Blod overføring 0,1 Tidlig mobilisering 1750 1800 1850 1900 1950 2000 UN, 2008 År Mødre dødlighet i Norge Maternal Mortality 2005 Betydningen av mors alder Direct causes per 100 000 74.2 75 70 Per 100 000 fødsler Hungary 11.9 France 11.3 Finland 9.9 Denmark 9.8 Austria 9.4 Portugal 9.0 Netherlands 7.7 UK 6.9 Belgium 4.7 Norway 4.5 1971-80 19.0 20 15 10.3 10 5 4.1 4.5 5.0 0 <20 20-24 25-29 30-34 35-39 >40 Alders-spesifikk mødredødelighets-rate S.Vangen Hva har skjedd de siste 45 år ? Alvorlig syklighet hos mor ved fødsel Fertilitet (barn perkvinne) Oslo: 1-2 av 100 kvinner 1/3 kan velges ut på forhånd 2/3 kommer helt uventet = 6 per 1000 fødsler = 1 per 150 fødsler Den norske mor barn undersøkelsen MoBa • Inkludert 100 000 svangerskap 2008. 1967 2012 3.0 1.8 Alder på førstegangsfødende 21 29 år 4 eller flere barn 15 % 6% Svangerskaps permisjon 12 49 u For tidlig fødsel 6.5 % 6 % under 28 uker 0.7% 1.8 % Keisersnitt 2.2 17 % Spebarnsdødlighet 20 5 Bekkenløsning • 15 % mente de hadde bekkenleddsyndrom. • 2,5 % mente å ha alvorlig grad • 7,7 % av de gravide brukte krykker pga smertene. Risikoen for BL økte med antall tidligere fødsler: • 11 % av de førstegangsfødende – 18 % av de andregangsfødende • Mor, far , barn • 21 % av de tredjegangsfødende. • 100 subprosjekter • Risikoen for alvorlig BL var • 3 ganger økt for 3 gangsfødende – sammenlignet med førstegangsfødende, justert for andre faktorer. Preterm fødsel MFR: 900 000 barn født > 23 uker 1967-1983 USA USA Norge IVF Sammenheng mellom 12,5 % avtagende svangerskapslengde og økt forekomst av 5% 9 8 • cerebral parese, 7 6 % 5 • psykisk utviklingshemning 4 3 2 • flere andre funksjonshemninger, 1 0 1980 1990 2000 Year • andel med uførepensjon som voksne. 7,6 7,5 7,4 Belgia: 7,3 7,6 % 7,2 7,1 7 Moster et al, N Eng J Med 2008 6,9 6,8 1995 2000 2002 2004 Assistert befruktning 2.9 % : 2000 / år totalt 32 000 barn Flerfødsler i Norge 2% 6000 IVF fødsler 1,6% Twins 24% Triplets etc 3% Barn: IVF - naturlig befruktning (2500 barn) • 25 gram lavere fødselsvekt, • 2 dager tidligere • 31 % høyere risiko for dødfødsel Romundstad, Lancet 2008 Fødsels fakta i Norge Fødsel • Økende alder på mor Overtid 41 og > 42 uker • Diabetes • Overtid > 42uker 3% • Barnet s vekt Fødselsvekt 1967- 2014 • Dobbling av tvillinger • Økende keisersnitt – 3500g Totalt Hjemme: stabilt siste år 60 000 153p + 195 Transport 125 Keisersnitt: 10 000 Induksjon18 % Epidural 34 % Operativ vaginal fødsel 9 % Keisersnitt Vacuum 9 % 10 700 Tang 1,5% Episiotomi 16.5 % Manuell uth.placenta 1% Perineal rift 3- 4 2,5% Keisersnitt i Norge 1967-2009 Mors alder Keisersnitt i Norge 1967-2011 17,1% > 35 yrs Total < 20 yrs Norgeshelsa‐FHI Komplikasjons risikoen ved keisersnitt øker ved Indikasjon - årsak 2778 pas i Norge Fosterstress (tegn på oksygenmangel) Langsom framgang Tidligere keisersnitt Seteleie etter 34. svangerskapsuke Mors ønske Svangerskapsforgiftning Mislykket igangsetting av fødsel Andre indikasjoner 608 248 234 172 112 602 % 22 21 9 8 8 6 4 22 • ikke planlagt keisersnitt (38% • gestasjons alder < 30 uker • stort foster • generell anestesi • cervix dilatasjon 0 cm: versus 18%) 16% 9-10cm: 33% Am J Ob Gyn. 2004;190:428-34. Vaginal fødsel etter keisersnitt VABAC • Velykket opp til 85% Kolaas T et al, 2003 • Amming i Norge Ruptur : 0,5 - 1,5 % ( normal fødsel - induksjon) Svangerskapsomsorgen i Norge 1 uke 6mnd 1984 1995 2006 12mnd Perinatal komiteer Jordmor i hver komune EB medisin Kunnskapsbasert De nye retningslinjer Risiko for foster • Informasjon til kvinnen, velge selv Velge lege/jordmor: samme person • Røyk • Alt er tilbud. (syfilis, HIV, ultralyd) • Alkohol • Færre kontroller ( 7-8 ) – Ikke gyn us, kun på indikasjon – Spør om liv – ikke alltid lytte på fosterlyd – Ikke barsels 6 ukers kontroll • Infeksjoner Røyking Mor røyker Norway: < 20år: 1.svangerskapskontroll 7% røker tidlig I svangerskapet 4% siste kontroll 19 % 10 % Behandling i svangerskapet Diskusjon i dag Før svangerskapet – Prekonsepsjonell undersøkelse og veiledning • Medisinen skal være: Kvinner > 38 år, • • • • sikker for fosteret effektiv anvendes i kortest mulig tid dosering: identisk eller høyere enn normal dose Kvinner med fedme KMI > 35: 4% Kvinner med sykdom, bruker medikamenter Tidligere født sykt barn Risikofylt arbeid : reiser, tungt fysisk arbeid Folinsyre 76% - livsstil • Kvinnens egne varianter: • Myk fødsel hjemme , alternativ fødestue Se Legemiddelhåndboken FASS • Keisersnitt på eget ønske • Hindre for tidlig fødsel Vi skal gjennomgå forandringer i: Hva skjer’a? • • • • • Mors fysiologi under graviditet 18. Januar 2016 Kurs O- 30576: Obstetrikk Hvorfor skjer det? Anne Cathrine (Annetine) Staff Professor I Det medisinske fakultet Universitetet i Oslo Overlege, Kvinneklinikken Oslo universitetssykehus • • • Viktig for å forstå fysiologiske forandringer i svangerskapet: Placenta viktigste årsak til endringer: essensiell for normal og patologisk svangerskapsutvikling Intet klart skille mellom «normal» og «patologisk» fysiologi i svangerskapet? Samspill kvinnen og fosterceller: essensielt for placentering og placentafunksjon og svangerskapshelse Store metabolske forandringer i svangerskapet Maternell anabolsk metabolisme tidlig i graviditeten: lagrer næringsstoffer for senere behov (økt fettvev ila første halvdel av svangerskapet: 3.5 kg ca) • Svangerskapet preges av en arteriovenøs shunt Maternell katabolisme i 3. trimester: • Shunter næringsstoffer til raskt voksende foster • Støtter fosterets svære anabolske vekst – Uteroplacentær sirkulasjon • Svangerskapet er en hyperterm tilstand – Fosteret produserer varme, den må avgis via mor • Placenta styrer produksjon av svangerskapshormoner – De molekylære mekanismene for mange fysiologiske prosesser i svangerskapet er stort sett ukjente, men hormonelle faktorer er viktige – HCG, hPL, østrogen, progesteron, prolactin, cortisol, cytokiner, adipokiner… Lever: • Forbruker glyserol og (i mindre grad) aminosyrer for å danne glukose som brukes av fosteret • Forbruker fett: danner ketoner som kan brukes av hjerne, muskler og foster Fettvev: • Frigjør fettsyrer til forbruk for lever og muskler Fosteret: • Forbruker aminosyrer, fett og halvparten av innkommende glukose for anabol vekst • Siste halvparten av glukoseforbruket brukes til energibehov Liu and Arany. Maternal cardiac metabolism in pregnancy. Cardiovasc Res 2014 Vi skal gjennomgå forandringer i: • • • • • Hjerte- kar Blod Respirasjon Nyrer Gastrointestinaltraktus Hjerte- kar Blod Respirasjon Nyrer Gastrointestinaltraktus Svangerskapet reprogrammerer maternell metabolisme: Maternell insulinresistens: begrenser maternell glukoseforbruk → shunting av det meste av glukose til fosteret Stor uteroplacentær sirkulasjon -essensielt i svangerskapsfysiologien ½ liter per minutt… (Hytten F, Chamberlain G: Clinical Physiology in Obstetrics. Boston, Blackwell Scientific Publications, 1980) Normal placentering er essensielt i svangerskapsfysiologien for normal uteroplacentær flow, -inkluderer remodellering av uteroplacentære spiralkar (<uke 18) Blod til uterus: Ca 50 ml/min tidlig i svangerskapet Ca 500 ml/min blod til uterus ved termin • Hjertet løftes opp og roteres fremover: • EKG-endringer (inverterte t-takker og STendringer kan forekomme) • Arytmier hyppige (ekstrasystoler, sjeldnere supraventrikulære tachycardier) • Hjertets størrelse: • Volum øker ca 10% (pga økt venøs fylning?) • Remodellering: Venstre ventrikkelvegg øker i tykkelse (ca 30% ved termin) Manglende glatt muskulatur i normalt remodellerte spiralarterier: Arteriovenøs shunt og dermed nedsatt perifer motstand Decidua= endometrium i graviditeten «Der mor ser far» : uterine maternelle NK-celler (KIR-reseptorer) «ser» invasive fetale trofoblaster med paternelle gener (HLA-C) Forandringer i puls og blodtrykk Perifer motstand reduseres Sirkulasjonen i placenta virker som en arteriovenøs shunt og bidrar til redusert perifer motstand Blodtrykket (MAP) synker fra første trimester 80 70 60 50 40 30 20 10 0 pp pp Systolisk BT: • Uendret eller faller litt 52 24 38 pp Puls Blodtrykk Diastolisk BT: • faller 5-10 mmHG utover i 2. trimester • Termin: ikke-gravide verdier rs Fø Manglende glatt muskulatur i normalt remodellerte spiralarterier: Arteriovenøs shunt og dermed nedsatt perifer motstand va ng e 12 32 24 8 16 rs ka p 85 84 83 82 81 80 79 78 77 76 75 Clapp AF III, Capeleas E: Am J Cardiol 1997; 80: 1469-73 Redusert perifer motstand: → BT-reduksjon, BT-reduksjon motvirkes av: ↑minuttvolum Aktivering av renin-angiotensin-systemet Clapp AF III, Capeleas E: Am J Cardiol 1997; 80: 1469-73 Store hemodynamiske endringer i svangerskapet Hjertets slagvolum og minuttvolum øker Blodvolumet og hjertefrekvensen øker Cardiac output, heart rate, stroke volume, and blood volume: - all increase between 5 and 8 weeks of gestation, peak by mid-pregnancy, and is sustained until the end of pregnancy. -are reversed by 6 months postpartum Liu and Arany. Maternal cardiac metabolism in pregnancy. Cardiovasc Res 2014 Graviditet:↑ Risiko for varicer og hemorrhoider • Stor uterus oØkt trykk i bekkenvener og v. femoralis • Økt vene-distensibilitet Plasmavolum Vi skal gjennomgå forandringer i: • • • • • • Hjerte- kar Blod Respirasjon Nyrer Gastrointestinaltraktus • • • Normalt plasmavolum hos ikke-gravid: 2600 ml Øker med ca 50% (1200 –1500 ml) i løpet av svangerskapet Årsak: ukjent Større økning ved flere og større fostre Hytten & Chamberlain 1980 Erytrocytter • • •Plasmavolum øker mer enn erytrocyttvolum i graviditeten: Volum hos ikke-gravide: 1400 ml Økning avhengig av jerntilskudd – – – Hemoglobin synker – Hematokrit synker Med jerntilskudd: 400 ml Uten jerntilskudd: 240 ml •Uforandret: – MCHC (mean corpuscular hemoglobin concentration) – MCV (mean corpuscular volume) Nedre normalgrense for Hb i (normalt) svangerskap: 9-10g/dl Hytten & Chamberlain 1980 Rasmusses S et al. Eur J of Obst and Gyn Reprod Biol 20115. 5024 haemoglobin measurements from a random sample of 552 pregnant women in three Scandinavian locations, by week of pregnancy. Lines denote the 5th, 10th, 50th, 90th, and 95th percentiles. Andre endringer i blod • • Hyperlipidemi (enda mer ved preeklampsi) – HDL uforandret – Total kolesterol og LDL øker 50% – Triglycerider tredobles Maternell insulinresistens: – starter tidlig, reduseres med 80% sent i svangerskapet – begrenser maternell glukoseforbruk (spesielt i musklene) → shunting av det meste av glukose til fosteret – Øker lipolyse i fettvevet→ gir fettsyrer som alternativ energikilde for mor og glyserol som substrat til leveren for glukoneogenese – enda mer insulinresistens ved preeklampsi/GDM.. • Inflammatorisk tilstand (sammenlignet med ikke-graviditet, enda mer ved preeklampsi) – CRP normal eller litt økt – Leukocytter stiger jevnt (10.2x109/l i 3. trimester) • Plasmaprotein (totalprotein og albumin)-konsentrasjonen ↓ (pga plasmavolumøkning) • Trombocytter lett redusert mot termin (N: 150-290x109/l) – Ca. 10 % har lett trombocytopeni (100- 150 x 109/l) – Økt aktivering og økt nedbrytning (?) • Kortere levetid (i hvert fall ved preeklampsi) Hemostase • • • • Fibrinogen øker betydelig i svangerskapet – Fordel for å forebygge blødning ved placenta-separasjon Andre koagulasjonsfaktorer øker også: – Faktor VIII og vWfaktor Fibrinolytisk aktivitet nedsatt – Pga fibrinolysehemmende faktorer fra placenta? – Som hos ikke-gravid ca 1 time etter fødsel Økt koagulabilitet og økt trykk fra gravid uterus (økt trykk i bekkenvener og v. femoralis):↑risiko for venøs trombose http://jama.jamanetwork.com/article.aspx?articleid=2297171 Respirasjon Vi skal gjennomgå forandringer i: • • • • • Hjerte- kar Blod Respirasjon Nyrer Gastrointestinaltraktus Diafragma ca 4 cm høyere ved termin enn hos ikkegravide, men interkostalvinkelen blir videre Respirasjonsforandringer i svangerskapet • Tidevolumet øker ca. 40 % (på bekostning av det ekspiratoriske reservevolumet) • Skyldes økt utslag av diafragma (fra 4-5 til 5-7 cm utslag) 100% • Respirasjonsfrekvens uendret – Minuttvolumet øker (40%) Lungefunksjon i svangerskapet 1 maks inspirasjon og maks ekspirasjon 3 vanlige inspirasjoner og ekspirasjoner: en gravid puster normalt inn, men puster dypere ut PEF = peak expiratory flow (= maksimal ekspirasjonshastighet) FVC = forced vital capacity (= inspiratorisk reservevolum + tidevolum + ekspiratorisk reservevolum) FEV1 = forced expiratory volume in 1 second +40% FVC hos para > 0, dvs. forandringene vedvarer etter svangerskapet 100% -20% Residualvolumet reduseres med 20% i graviditet fordi uterus presser diafragma oppover Det funksjonelle lungevolumet er uendret ---- gravid G Grindheim,K Toska,M-E Estensen,LA Rosseland, BJOG 2011 ___ ikke gravid Ventilasjon O2-forbruket øker i svangerskapet O2-behovet øker 15 % pga Foster, placenta, voksende uterus, økt hjerteog respirasjonsarbeid Produksjonen av CO2 øker tilsvarende • • • • • • • Ventilasjonen mer økt enn nødvendig ift økt metabolisme o fjerning av karbondioksid o kronisk respiratorisk alkalose – renalt kompensert Arteriell pCO2 5,3 kPa o 4,0 kPa Bicarbonat nedsatt pH uforandret Skyldes antakelig: Respirasjonssenterets sensitivitet for CO2 n (pga progesteron?) • Hensikten med redusert maternell pCO2? – Øke differansen mellom maternell og fetal pCO2 og dermed diffusjonshastigheten for CO2 over placenta? Vi skal gjennomgå forandringer i: • • • • • Hjerte- kar Blod Respirasjon Nyrer Gastrointestinaltraktus Diameter av calyces og ureteres øker i svangerskapet Kan vedvare 3-4 mnd postpartum Årsak? Mekanisk trykk i graviditet/økt venepleksus rundt indre genitalia? Større diameter på høyre enn på venstre side • Vena ovarica-syndrom: høyresidige ureterstenliknende smerter pga utvidelse av ureter i graviditet Peake et al. Radiology 1983; 146:167-70 Nyrefysiologi • Ukjent årsak til endringene: – Blodgjennomstrømning n 30 – 50 % – Glomerulusfiltrasjon øker – Tilbakeresorbsjon øker • Glukosuri – skyldes økt glomerulusfiltrasjon (reabsorbsjonen øker ikke alltid tilsvarende) Væskebalanse • 6-8 liter vann retineres ila svangerskapet – Økt plasmavolum – Ekstracellulær væske • Mange gravide: økende ødemer ila dagen, skilles ut om natten/hvile • Moderate svangerskapsødemer er normalt – Men rask økning KAN sees ved alvorlig preeklampsi pga dysfunksjonelt endotel • Utskillelse av vannløselige vitaminer og aminosyrer øker – Økt behov for inntak i svangerskapet Vi skal gjennomgå forandringer i: • • • • • Hjerte- kar Blod Respirasjon Nyrer Gastrointestinaltraktus Gastrointestinaltraktus • Nedsatt tonus og motilitet i glatt muskulatur – Forlenget tømningstid av ventrikkel • Spesielt under fødsel – Obs brekninger/aspirasjon ventrikkelinnhold ved narkose – Obstipasjon pga nedsatt kolonmotilitet – Bidrar til svangerskapskvalmen i 1. trimester? Normal vektøkning i svangerskapet: store variasjoner • Svangerskapsprodukter: • Foster • Placenta • Fostervann • Fettdepot øker (ca 2 kg ved god næring-tilgang) • Væskeretensjon (blodvolum og annen ekstracellulær væske) • Uterus og mamma vokser http://www.nap.edu/read/12584/chapter/5 Pitkin, 1976. Nutritional support in obstetrics and gynecology. Clinical Obstetrics and Gynecology 19(3): 489-513. Oppsummert: • • Metabolisme: øker 15% Hjerte- kar: – – – CO øker 30-40% Hjertefrekvens og slagvolum øker Vaskulær motstand reduseres (økt uteroplacentær flow) • Blod: • Respirasjon – – – • Ventilasjonen øker 50% O2-forbruk øker 20% Nyrer – – • Volum øker 30% GFR øker 50% Tubulær reabsorpsjon øker 50% Gastrointestinaltraktus – Tregt Placenta: the key to pregnancy success (og nøkkel til svangerskapsendringer) Svangerskap Ernæring og ernærings tilskudd i svangerskapet Maternell Føtal Ernæring Ernæring Janette Khoury MD, PhD Spesialist i Kvinnesykdommer og Fødselshjelp Post Doc Universitetet i Oslo Privatpraktiserendespesialist Brynmedisinske Senter E-mail: jakhoury@hotmail.com Januar 2016 Umbilical artery Carrying the fetal blood to the placenta for exchange of gases and nutrients Optimal forhold Sunt og balansert kosthold for føtal utvikling og tilvekst Metabolske tilpassninger i svangerskapet Metabolske tilpassninger i svangerskapet Maternell hyperkolesterolemi Maternell hypertriglyceridemi Plasma LDL 3 Cholesterol (mmol/l) HDL mmol/L 6 7,5 7 6,5 6 5,5 5 4,5 4 3,5 3 2,5 2 1,5 1 0,5 Trigly wk 8 wk 20 wk 30 wk 38 VLDL nonpregnant 8 14 20 28 36 wk pregnancy Lactation Pregnancy weeks Modified after Fåhraeus, MD et al. Obstetrics & Gynecology 1985; 66: 468. Avgjørende faktorer som påvirker føtal ernæring og føtal tilvekst Endringer i spiral arterier Maternal side Gjennomblødning i The placenta uteroplacental årer kan øke med 10% Uteroplacental gjennomblødning kontrol mekanismer i (placentær svikt) Overføring av næringsstoffer over placenta åreveggen som styrer utvidelse eller konstriksjon Preeclampsia Normal Fetal side av blodårene. Morens endokrine og metabolsk faktorer (f.eks maternal hypercholesterolemia) (f.eks maternal hyperinsulinemia) uavhengig av maternal Secretary fase Mors ernærings tilstand, metabolsk kapasitet, og daglig inntak Fosterets evne til å nyttig seg næringsstoffene (medfødte misdannelse, kromosomfeil) Tore Henriksen, Acta Pædiatrica Suppl 1999; Godfrey et al Am J Clin Nutr,2000; Barker DJP Theriogenology 2000, Føtal tilvekst versus fødselsvekt Growth Normal Flere føtal tilvekst mønstre men samme fødselsvekt Large restricted A Late growth restriction B Early growth restriction C Normal growth D Late growth restriction followed by catch up growth Harding, International Journal of Epidemiology 2001; 30 (1): 15-23. Trenger ikke å spise for to 300-400 kcal ekstra fra 2 trimester Kost veiledning Nøvendig at det startes før svangerkapet - En ekstra liten mellom måltid (300-400 kcal) • 1 tykk skive grovt brød med mager pålegg + grønnsak • 1 glass skummet melk • 1 eple Vekt økning i svangerskapet Kost råd i svangerskapet Amerikanske anbefalinger Institute of Medicine (IOM) 2009: Balansert sun kost BMI kg/m2 Før konsepsjon Anbefalt vektøkning (kg) pr uke 2dre og Totalt / 3dje trimester Lav < 18,5 12,5-18,0 / ≥ 0,5 Normal 18,5-24.9 11,5-16,0/ 0,4 Høy 25,0-29.9 7,0-11,5 / ≤ 0,3 Fedme > 30,0 5-9 / ≤ 0,2 National academies press (US); 2009 • Fisk 2 ganger i uken. Gjerne fet fisk. • Skummet melk, ekstra lett melk, lett melk eller lett yoghurt • Lett margarin på brød. Flytende margarin eller vegetabilsk olje til matlaging. • Magert kjøtt, kylling, egg, bønner, linser / erter. • Grøvt brød, poteter, ris, pasta. Gjerne fullkornalternativer. • Frukt og grønnsaker. • Kutt ned på inntaket av sukker. Kost råd i svangerskapet Kosttilskudd Balansert sun kost • Kosttilskudd kan ikke erstatte det mangfoldet av stoffer som et sunt og variert kosthold gir. Tar kvinnen kosttilkudd, kan hun få i seg for mye av enkelte næringsstoffer. Total fett 30 E% Mettet fet Protein Karboydrater 10 E% 15 E% 55 E% Fisk 2 ganger i uken, frukt og grønnsaker daglig (3 forskjellige grønnsaker og 2 forskjellige frukt) Spesielle behov i svangerskapet • Høyere energi fra midten av svangerskapet. •Vitamin og mineral tilskudd? • Kvinner med spesial behov (melk intolerance, vegetarianer, malabsorption, anorexi, fedme) Folate • Ønske den gravide likevel å ta kosttilskudd, er det viktig å følge doseringen som er angitt på kosttilskuddet og ikke ta flere ulike typer kosttilskudd som inneholder de samme vitaminene og mineralene. Generelle spesial behov • Folate • Long chain essential fatty acids (omega 3) • Vitamin D • Calcium • Jern Folate Meabolism a donor of methyl group Folate - 400µg/d (under planlegging og opptil 12 uker) - 200µg/d (resten av svangerskapet) ? Source: Cummings AM, Kavlock RJ. Crit Rev Toxicol 2004;34:461-85. Drop in prevalence of spina bifida and anencephaly after food fortification with folic acid Maternal Vitamin B12 status og risiko for NTD Befolkning 6,0 Spina bifida 5,0 Prevalence (per 10,000) Anencephaly Irland, high NTD prevalens uten folat tilsettinger. 4,0 Resultater: 3,0 Mødre i lavere B12 kvartiler sammenliknet med mødre i høyeste kvartiler, hadde 2 to 3 økt odds for å bære en foster med NTD 2,0 1,0 Pre-fortification Optional Fortification Mandatory Fortification 0,0 1995 1996 1997 198 1999 2000 2001 Molloy et al . Pediatrics 2008 Teratology 2002; 66:33-39. Updated 6/2004. Long chain essential fatty acids Kan omega-3 forebygge preterm fødsel (omega 3) Fiske olje inntak - Få RCT Daglig behovet av omega-3 (0,7-1,2g) dekkes av: Tran 5ml/d (barne skje) eller (2 kapsler) Vitamin D 7.5 – 10 µg/d f.eks. Bruk en av følgende: -2 kapsler møllers dobbel - 5ml Tran - 1 tablett a’10μg D-vitamin - 10ml/d ‘Sanasol’ - 3 RCT inkludert i en metaanalyse hvor 10 studier var eksludert da de ikke fylte kriteriene. - Disse 3 RCT påvist 20-30% reduksjon i forekomst av prematur fødsel. Dosen som ble brukt var 2,7g/d. (Salvig JD et al. AOGS; 2011) Kolesterol reduserende kosthold i regi av en balansert sun kosthold (fetfisk x2 i uken) kan være lovende i risiko reduksjon av prematur fødsel men trenger mer forskning (KHOURY et al. AOGS; 2005) (CARRDIP STUDEIN). Calcium • 500 – 1000 mg /d til de med lavt inntak e.g. milk intolerance, vegetarians if they do not drink soya milk • Anbefalt daglig inntak (900 mg) - 3 glass skummet milk - 2 skiver ost - 1 porsjon yoghurt naturell • Vegetabilske matvarer rik in Ca++ : Mandler , Tørket fiken, Sesam frø, Grønn kål, Spinat. Iron • Daglig behov i kost 12-18mg/d (opptak 3-8g/d). _Jern absorbsjon øker i andre og tredje trimester Viktig å holde unna Grunnet bacteria eller dioksiner og PCB • Fisk lever • Upastørisert melk og melkeprodukter • Rå fisk og kjøtt produkter • ’Innmat’ fra crabbe • Hval kjøtt og stor tuna og andre stor fisk. Iron Norske anbefalinger fra 2005 Rutinemessig jerntilskudd anbefales ikke. Tilskudd anbefales når: • WHO råd hos kvinner i fertil alder 60 mg /d som tilskudd fra sv. Uke 20 hvis - Serum ferritin < 20µg/l eller Hgb < 11g/100ml WHO/CDC Technical consultation at the population level 2005 - Tilskudd i form av Fe2+: Ferromax 65mg x1/Hemofer 27mg x2. Drikke Hgb < 11g/100ml ved første kontroll og i uke 28. S-Ferritin < 20 Pg/l, jerntilskudd fra sv uke 20. Anbefales målt før sv. uke 15. Etter sv. uke 15, S-Ferritin ikke god indikator. Anbefales da å måle S-Transferrinreseptor i tillegg. Viktig å holde unna Vann er den beste drikke Grunnet bacteria eller dioksiner og PCB • Kaffe 1-2 kopper pr dag • Te 3 – 4 kopper pr dag • Akohol avholdene • Minst mulig ’brus’ • Fisk lever • Upastørisert melk og melkeprodukter • Rå fisk og kjøtt produkter • ’Innmat’ fra crabbe • Hval kjøtt og stor tuna og andre stor fisk. Sammendrag Grupper som trenger kost veiledning • BMI < 19-20 or BMI > 30 • Kvinner som har gjennomgått fedme operasjon. • Røykere • Tenår svangerskap • Lav socioeconomisk status • Innvandrere • Diabetes, anorexi, GI problemer • Tidligere spinabifida (4 mg folate i første trimester) • Tidligere svangerskaps komplikasjoner Kostveiledning bør helst starte før svangerskapet. Følge generelle råd for sunt og balansert kosthold. Kvinner med BMI > 30 eller < 19 ved start av svangerskapet, og kvinner med lav vekt økning under svangerskapet bør få kostveiledning. Vitamin and mineral tilskudd ikke nødvendig med unntak av: - Folat 400µg under planlegging og ut første trimester. - D-vitamin for alle spesielt vinter halv året. - Folate 200µg resten av svangerskapet, og Calcium tilskudd for de med marginal og lav inntak. Jern tilskudd ved indikasjon. Kolesterol reduserende kosthold i regi av en balansert sunt kosthold kan være lovende i risiko reduksjon av fortidlig fødsel men trenger mer forskning. Brosjyren ernæring i svangerskapet THE CARRDIP STUDY www.helsedirektoratet.no Cardiovascular risk reduction diet in pregnancy CARRDIP studien THE CARRDIP STUDY Kost Intervensjons gruppen 1. 2. 3. Spise fisk x 2 i uken spesielt fet fisk, rent kjøtt og fjærkre, olivenolje, rapsolje, frukt, grønnsaker,nøtter, belgfrukter, lett melk og magre oster Janette Khoury, Tore Henriksen, Bjørn Chrisophersen, Serena Tonstad. Effect of a cholesterol lowering diet on maternal, cord, neonatal lipids and pregnancy outcome. A randomized clinical trial. American Journal of Obstetrics and Gynecology 2005;193:1292-30. Janette Khoury, Tore Henriksen, Ingebjørg Seljeflot, Lars Mørkrid, Kathrine Frey Frøslie, Serena Tonstad. Effect of an antiatherogenic diet during pregnancy on markers of maternal and fetal endothelial activation and inflammation: the CARRDIP study. British Journal of Obstetrics and Gynecology Br J Obstet Gynaecol 2007;114:279 – 288. Janette Khoury, Guttorm Haugen, Serena Tonstad , Kathrine Frey Frøslie, Tore Henriksen Effect of a cholesterol-lowering diet during pregnancy on maternal and fetal Doppler velocimetry: The CARRDIP study. American Journal of Obstetrics and Gynecology 2007 Jun;196(6):549.e 1-7. SH direktoratet link for brosjyren ernæring i svangerskapet https://helsedirektoratet.no/ publikasjoner/gravid Seminars in Fetal & Neonatal Medicine (2005) 10, 493e503 www.elsevierhealth.com/journals/siny Physiology of the fetal circulation Torvid Kiserud a,b,* a Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Bergen, Bergen, Norway b Fetal Medicine Unit, Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway KEYWORDS Circulation; Blood flow; Fetus; Placenta; Ductus venosus; Ductus arteriosus; Foramen ovale; Liver Summary Our understanding of fetal circulatory physiology is based on experimental animal data, and this continues to be an important source of new insight into developmental mechanisms. A growing number of human studies have investigated the human physiology, with results that are similar but not identical to those from animal studies. It is time to appreciate these differences and base more of our clinical approach on human physiology. Accordingly, the present review focuses on distributional patterns and adaptational mechanisms that were mainly discovered by human studies. These include cardiac output, pulmonary and placental circulation, fetal brain and liver, venous return to the heart, and the fetal shunts (ductus venosus, foramen ovale and ductus arteriosus). Placental compromise induces a set of adaptational and compensational mechanisms reflecting the plasticity of the developing circulation, with both short- and long-term implications. Some of these aspects have become part of the clinical physiology of today with consequences for surveillance and treatment. ª 2005 Elsevier Ltd. All rights reserved. Introduction Many of the mechanisms described in animal experiments also occur in the human fetus, but with differences. The reasons for variation are many, e.g. a sheep fetus has a different anatomy compared with a human fetus, with a longer intrathoracic inferior vena cava (IVC), a smaller * Department of Obstetrics and Gynaecology, Haukeland University Hospital, N-5021 Bergen, Norway. Tel.: C47 55974200; fax: C47 55974968. E-mail address: torvid.kiserud@kk.uib.no brain, the fetal liver is positioned differently, two umbilical veins, a higher temperature, a lower Haemoglobin (Hgb), a higher growth rate and a shorter pregnancy. Ultrasound in obstetrics has been used increasingly to provide physiological data from human fetuses, and this is reflected in the present review. Blood volume The blood volume in the human fetus is estimated to be 10e12% of the body weight, compared with 7e8% 1744-165X/$ - see front matter ª 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2005.08.007 494 in adults.1 The main reason for this difference is the large pool of blood contained within the placenta; a volume that reduces as gestation progresses. The calculated blood volume of 90e105 ml/kg in fetuses undergoing blood transfusion during the second half of pregnancy2 is probably an underestimate. Other studies have indicated a volume of 110e115 ml/kg, which is more in line with experimental sheep studies.3 The estimated volume of 80 ml/kg contained within the fetal body is marginally more than that in adults. Compared with adults, the fetus is capable of much faster regulation and restoration of the blood volume due to high diffusion rates between fetal compartments.1 Arterial and venous blood pressure The mean arterial pressure in human fetuses was measured to be 15 mmHg during cordocentesis at gestational weeks 19e21.4 Intra-uterine recording of the intraventricular pressure in the human fetus suggests that the systemic systolic pressure increases from 15e20 mmHg at 16 weeks to 30e 40 mmHg at 28 weeks.5 There was no obvious difference between the left and right ventricles. This increase was also seen for diastolic pressure, which was %5 mmHg at 16e18 weeks and 5e 15 mmHg at 19e26 weeks. Umbilical venous pressure, recorded during cordocentesis and corrected for amniotic pressure, increased from 4.5 mmHg at 18 weeks to 6 mmHg at term.6 Cardiac performance Structural details of the heart are organized during the embryonic period but are dependent on the physical environment, including blood flow, in order to develop normally. The myocardium grows by cell division until birth, and growth beyond birth is due to cell enlargement. The density of myofibrils increases particularly in early pregnancy and the contractility continues to improve during the second half of pregnancy.7 The two ventricles perform differently in pressure/volume curves and when tested with intact peripheral vasculature.8 The fetal heart has limited capacity to increase stroke volume by increasing diastolic filling pressure, the right ventricle even less than the left, as they are already operating at the top of their function curves. The FrankeStarling mechanism does operate in the fetal heart, which is T. Kiserud apparent during arrhythmias.9 Adrenergic drive also shifts the function curve to increase stroke volume. However, increased heart rate may be the single most prominent means of increasing cardiac output in the fetus. The two ventricles pump in parallel (Fig. 1) and the pressure difference between them is minimal compared with postnatal life.5 However, experimental studies show some variation in pressure and velocity waves between the two sides, ascribed to the difference in compliance of the great arteries and downstream impedance (upper body vs lower body and placenta).10 Some of the ‘stiffness’ of the fetal myocardium is attributed to the constraint of the pericardium, lungs and chest wall,11 all of which have low compliance before air is introduced. However, with the shunts in operation and a metabolism capable of extracting oxygen at low saturation levels, the fetal heart appears to be a very flexible, responsive and adaptive structure. Cardiac output and distribution The fetal systemic circulation is fed from the left and right ventricles in parallel. The left ventricle is predominantly dedicated to the coronary circulation and upper body, while the right ventricle is the main distributor to the lower part of the body, the placenta and the lungs. When using outerinner diameter measurements of the vessels, the combined cardiac output (CCO) is reported to be 210 ml/min at mid-gestation and 1900 ml/min at 38 weeks12 (Table 1). When using inner diameters, these numbers are lower.13 The right ventricular output is slightly larger than that of the left ventricle, and pulmonary flow in the human fetus is larger (mean 13e25%) than in the classical fetal lamb studies (%10%). Interestingly, a developmental transition in fetal haemodynamics seems to occur at 28e32 weeks when the pulmonary blood flow reaches a maximum with a simultaneous change in oxygen sensitivity in the pulmonary vasculature.12,14 Another study found that less blood was distributed to the fetal lungs (11%),13 which is more in line with previous experimental studies. The three shunts (ductus venosus, ductus arteriosus and foramen ovale) are essential distributional arrangements that make the fetal circulation a flexible and adaptive system for intra-uterine life. A classical concept describes the pathway of oxygenated blood as the via sinistra (Fig. 1) leaving the umbilical vein through the ductus venosus to reach the foramen ovale, left ventricle and aorta, thus feeding the coronary Physiology of the fetal circulation 495 Figure 1 Pathways of the fetal heart and representative oxygen saturation values (in brackets). The via sinistra (red) directs well-oxygenated blood from the umbilical vein (UV) through the ductus venosus (DV) (or left half of the liver) across the inferior vena cava (IVC), through the foramen ovale (FO), left atrium (LA) and ventricle (LV) and up the ascending aorta (AO) to reach the descending AO through the isthmus aortae. De-oxygenated blood from the superior vena cava (SVC) and IVC forms the via dextra (blue) through the right atrium (RA) and ventricle (RV), pulmonary trunk (PA) and ductus arteriosus (DA). CCA, common carotid arteries; FOV, foramen ovale valve; LHV, left hepatic vein; LP, left portal branch; MHV, medial hepatic vein; MP, portal main stem; PV, pulmonary vein, RHV, right hepatic vein; RP, right portal branch. Copied and modified with permission from ref.16 and cerebral circuits. Conversely, a via dextra directs de-oxygenated blood from the caval veins through the tricuspid valve, pulmonary trunk and ductus arteriosus to reach the descending aorta, largely bypassing the pulmonary circuit. Oxygen saturation gives a picture of distribution and blending of flows in the central fetal circulation (Fig. 1). The lowest saturation is found in the abdominal IVC, and the highest saturation is found in the umbilical vein.10 Interestingly, the difference between the left and right ventricles is only 10%, and this increases to 12% during hypoxaemia. The small difference between the left and right ventricles is due to the abundant volume of oxygenated blood presented to the foramen ovale. In addition to the ductus venosus blood flow, the umbilical blood passing through the liver has had a modest reduction in saturation and represents another sizeable volume of oxygenated blood flowing in much the same direction as the ductus 496 T. Kiserud Table 1 Combined cardiac output and distribution in human fetuses during the second half of pregnancy according to Rasanen et al.12 % of combined cardiac output at gestational age 20 weeks 30 weeks 38 weeks Combined cardiac output Left ventricle Right ventricle Foramen ovale Lungs Ductus arteriosus 210 (ml/ min) 47 53 34 13 40 960 (ml/ min) 43 57 18 25 32 1900 (ml/ min) 40 60 19 21 39 venosus towards the foramen ovale. In addition to some blending, the abundance of oxygenated blood will cause a spillover to the right side when reaching the foramen ovale with its crista dividens (limbus) (Fig. 2). Ductus venosus and liver circulation In the human fetus, the ductus venosus is a slender trumpet-like shunt connecting the intra-abdominal umbilical vein to the IVC at its inlet to the heart. The inlet of the ductus venosus, the isthmus, is the restrictive area with a mean diameter of 0.5 mm at mid-gestation and hardly exceeds 2 mm for the rest of a normal pregnancy.15,16 The umbilical venous pressure ranges from 2 to 9 mmHg6 (the portocaval pressure gradient), and causes the blood to accelerate from a mean of 10e22 cm/s in the umbilical vein to 60e85 cm/s as it enters the ductus venosus and flows towards the IVC and foramen ovale.17,18 The blood flow with the highest oxygenation, coming from the ductus venosus, also has the highest kinetic energy in the IVC and predominantly presses open the foramen ovale valve to enter the left atrium, i.e. the ‘preferential streaming’ described in animal studies.19 While 30% of the umbilical blood is shunted through the ductus venosus at mid-gestation, this fraction is reduced to 20% at 30 weeks and remains so for the rest of the pregnancy, but with wide variations (Fig. 3).16 These results are similar to those of another study,20 but are at variance with experimental animal studies, admittedly using a different technique, which showed that approximately 50% was shunted through the ductus venosus.19,21 The redistributional mechanisms of increased shunting during hypoxaemia described in animal experiments also seem to operate in the human fetus.22,23 Figure 2 The foramen ovale acts as a flow distributor of the inferior venous inlet. (a) Ultrasound scan shows the inferior vena cava (IVC) and left and right atria (LA, RA). The atrial septum (AS) with its crista dividens (postnatal: limbus) faces the inlet of the IVC to divide the ascending column of blood. The terminal portion of the IVC expands, more to the left side, to receive blood from the liver and ductus venosus (DV). The high velocity, its position to the left and steep direction (b) makes the DV blood preferentially press open the foramen ovale valve (FOV) to enter the LA. IVC blood directed more anteriorly arrives predominantly in the RA. Increased pressure in LA or a premature apposition of FOV to the AS would divert more blood to the right. Reproduced with permission from ref.36 The ductus venosus is under tonic adrenergic control, and distends under the influence of nitroxide and prostaglandins.24,25 The most extensive dilatation is seen during hypoxaemia, leading to Physiology of the fetal circulation Figure 3 The fraction of umbilical venous return shunted through the ductus venosus in low-risk pregnancies is 30% at mid-gestation but approximately 20% at 30e40 weeks, signifying the developmental importance of the fetal liver receiving 70e80% of the umbilical blood. Reproduced with permission from ref.16 a 60% increase of the diameter in fetal sheep.25 However, the changes in diameter are not restricted to the isthmus but also include the entire length of the vessel, which has a far greater impact on resistance.25,26 The shunt obliterates within 1e3 weeks of birth in term infants, although this takes longer in premature births and in cases with persistent pulmonary hypertension or cardiac malformation.27e29 In contrast to the ductus arteriosus where increased oxygen tension triggers the closure, no trigger has been found for the ductus venosus.24 Equally important to the active regulatory mechanism is the passive regulation based on fluid dynamics, i.e. viscosity and pressure.30 Blood velocity in the ductus venosus is high and has Newtonian properties with low viscosity (similar to water). In contrast, liver tissue represents a huge capillary cross-section with a low blood velocity. At low velocities, the blood is non-Newtonian with an accordingly high viscosity (and resistance) and a closing pressure of 1e4 mmHg. It follows that an increase in haematocrit leads to increased viscous resistance in the low-velocity venous liver flow and has little effect on the high-velocity flow in the ductus venosus. Thus, the change in haematocrit alone leads to a shift of umbilical venous flow from the liver to the ductus venosus. 497 Along the same lines, variation in the umbilical venous pressure affects the two pathways differently.30 A reduction in venous pressure reduces liver perfusion more than ductus venosus flow, as a further reduction in an already low velocity in the large cross-section of the portal vasculature implies a considerable increase in viscous resistance. The result is a higher degree of shunting. In addition to these fluid dynamic determinants, the neural and endocrine regulation of the hepatic vascular bed also play a role.31 The portal vasculature shows a more pronounced constricting response to adrenergic stimulation compared with the ductus venosus.32 It all combines to make a distribution system that is extremely sensitive to both active and passive regulation, which is in line with the substantial normal variation of shunting seen in human fetuses.16,33 The physiological role of the ductus venosus is not well understood. The shunting seems more prominent in early pregnancy than after 30 weeks of gestation. The low degree of shunting through the ductus venosus during the last 8e10 weeks of pregnancy implies that approximately 80% of the umbilical blood perfuses the liver, signifying a very high developmental priority of the umbilical liver perfusion compared with the ductus venosus.16 However, during hypoxic challenges, the priority seems to be different. Fetuses maintain a higher degree of ductus venosus shunting, probably as a redistributional adaptation to hypoxic pressure, ensuring oxygenation of the heart and brain.21 The cost for responding to such needs could be permanently altered liver development.34 It should be borne in mind that oxygen extraction in the liver is rather modest (10e15% reduction in oxygen saturation),35 which means that blood coming from the median and left hepatic vein are important contributors of oxygenated blood. Actually, the position and direction of the left hepatic venous blood under the Eustachian valve (IVC valve) favour this blood to be delivered at the foramen ovale.36 Although agenesis of the ductus venosus has been linked to abnormalities and fetal demise,37 agenesis is also found in fetuses that have exhibited normal growth.16 Experimental obliteration of the vessel seems to have little haemodynamic effect,38 but causes an increase in insulin-like growth factor 2 and increases the growth of fetal organs.39 Recent studies have indicated that the fetal umbilical flow to the liver towards the end of pregnancy is influenced by the maternal nutritional state and diet.40 Umbilical venous flow constitutes 75% of the venous supply to the liver, with the remaining 25% coming from the main portal 498 stem.41 In human fetuses, the arterial supply to the liver is not known but it seems to have a more prominent role during compromise.42 Doppler examination of the ductus venosus is increasingly used to identify hypoxaemia, acidosis, cardiac decompensation and placental compromise, and is a promising tool for timing the delivery of critically ill fetuses.43,44 Increased pulsatility, mainly caused by the augmented atrial contraction wave, signifies increased atrial contraction due to adrenergic drive, or increased venous filling pressure, or both. In early pregnancy, the augmented a-wave in the ductus venosus is associated with an increased risk of chromosomal aberration and has been suggested as a secondary screening test.45,46 Foramen ovale A defect in the atrial septum is commonly associated with left-right or right-left shunting in postnatal life. It is conceivable that this concept is carried over to describe the function of the foramen ovale in the fetus,47 but this is not a fair representation of the actual haemodynamics. Rather, the inferior venous inlet to the heart should be viewed as a column of blood that ascends between the two atria from below.36,48 This column hits the interatrial ridge, the crista dividens, and is divided into a left and right arm (Fig. 2). The left arm fills the ‘windsock’, formed between the foramen ovale valve and the atrial septum, to enter the left atrium. The right arm is directed towards the tricuspid valve and joins the flow from the superior vena cava and coronary sinus to form the via dextra. This is an equilibrium easily influenced by changes in pressure on the two sides. Increased T. Kiserud resistance and pressure of the left side is instantaneously reflected in increased diversion of blood to the right side. In contrast to the hypertrophy of the left ventricle seen in aortic stenosis in adults, fetal stenosis commonly leads to a shift of blood volume from left to right at the level of the foramen ovale, with corresponding development of left-sided hypoplasia and compensatory growth of the right ventricle. The developing ventricle responds to the demands of the afterload and is stimulated by the blood volume of the preload. However, for the left side of the heart, the foramen ovale is an important limiting factor, particularly in cases of a maldeveloped foramen or a premature closure.49 Under physiological conditions, it is not the ovalshaped hole of the septum that constitutes the restricting area for the flow to the left atrium, but the horizontal area between the foramen ovale valve and the atrial septum above the foramen ovale.50 Interestingly, the growth of this area is somehow blunted after 28e30 weeks of gestation compared with the cross-section of the IVC. This effect coincides with changes in fetal lung perfusion12 and ductus venosus shunting,16 and may signify a transition into a more mature circulatory physiology. Ductus arteriosus and pulmonary circulation The ductus arteriosus constitutes a wide muscular vessel connecting the pulmonary arterial trunk to the descending aorta (Fig. 4).51 During the second trimester, the velocity in the ductus arteriosus increases more than that in the pulmonary trunk, reflecting the development of the wind-kessel function of the pulmonary trunk.52 During the Figure 4 (a) The ductus arteriosus (arrow) is a sizeable connection between the pulmonary trunk (PA) and the aorta (AO) in fetal rats. (b) Indomethacin induces severe constriction. Reproduced with permission from ref.51 Physiology of the fetal circulation second half of pregnancy, 40% or less of the CCO is directed through the ductus arteriosus12,13 (Table 1). The lungs receive 13% of the CCO at mid-gestation and 20e25% after 30 weeks,12 which is more than that reported in fetal sheep experiments10 and a more recent human study.13 Normally, the shunt closes 2 days after birth,53 but a patent duct is a common clinical problem. An increase in oxygen tension is regarded as the main trigger for its closure.24 The vessel is under the general influence of circulating substances, particularly prostaglandin E2, which is crucial in maintaining patency.54 Sensitivity to prostaglandin antagonists is at its highest in the third trimester and is enhanced by glucocorticoids and fetal stress.55 Nitric oxide has a relaxing effect prior to the third trimester. The increased reactivity of the ductus arteriosus in the third trimester makes it vulnerable to prostaglandin synthase inhibitors, such as indomethacin, which may cause severe and longlasting constriction.55,56 The ductus arteriosus bypasses the pulmonary circuit, but the distribution between these two pathways depends heavily on the impedance of the pulmonary vasculature, which is under the control of prostaglandin I2 and modified by a series of substances.24 In an elegant study, Rasanen et al. showed how reactivity in the pulmonary vascular bed increased in the third trimester.14 While fetuses at gestational age 20e26 weeks showed no changes during maternal hyperoxygenation, fetuses at 31e36 weeks had lower impedance in the pulmonary arteries assessed by the pulsatility index, and increased pulmonary blood flow. Correspondingly, the blood flow in the ductus arteriosus was reduced. Brain circulation Differences in circulation physiology between animal experiments and human fetuses are likely to be greatest when concerning the brain, as the human brain is relatively larger than in other species. In a study of human previable fetuses weighing 12e272 g (probably corresponding to 10e 20 weeks of gestation), it was found that the brain received approximately 15% of the systemic venous return (equal to the CCO less the pulmonary circuit).33 The proportion directed to the brain increased with low arterial pH, increased pCO2 and reduced placental perfusion. A study of the primate Macaca mulatta at an advanced stage of gestation found that 16% of the CCO was distributed to the brain, and this fraction increased to 31% during hypoxic challenge.21 Both of these studies 499 reflect redistributional preferences to the brain during hypoxaemia and acidosis. Clinical obstetrics has taken advantage of such ‘brain-sparing’ mechanisms, and uses the increased diastolic blood velocity recorded in the middle cerebral artery as a marker of compensatory redistribution of blood to the brain.57 Fetoplacental circulation In the fetal sheep, 45% of the CCO is directed to the umbilical arteries and placenta.58 This percentage is less in exteriorized human fetuses, but it increases from 17% at 10 weeks to 33% at 20 weeks of gestation.33 These results overestimate the placental fraction as the CCO calculation was based on systemic venous return, not including the pulmonary venous return. Secondly, the measurements were not performed under strict physiological conditions. Doppler studies of low-risk pregnancies have found similar results; one-third of the fetal CCO is directed to the placenta at 20e32 weeks of gestation,59,60 but this decreases to approximately one-fifth beyond 32 weeks of gestation.60 The introduction of Doppler ultrasound made it possible to assess umbilical venous blood flow61 in the human fetus in utero. Recent longitudinal observations in low-risk pregnancies have found that the umbilical blood flow increases from a mean of 36 ml/min at 20 weeks to 265 ml/min at 40 weeks of gestation.62 Umbilical flow normalized for fetal weight is at its highest (117 ml/min/ kg) at 25 weeks and at its lowest at 41 weeks (63 ml/min/kg) of gestation. These results are in accordance with earlier studies applying thermodilution at birth.63 The fact that human umbilical flow is considerably lower than that in the fetal sheep is not disconcerting as fetal sheep have a higher growth rate, a higher temperature and a lower Hgb. Resistance to flow is mainly determined by the peripheral vascular bed of the placenta. This vasculature has no neural regulation and catecholamines have little effect on the vasculature. Endothelin and prostanoid have a constricting effect64 and nitric oxide has a vasodilatory effect,65 but the exact role of humoral regulation is not fully understood.66 Placental blood flow has been found to be fairly stable and chiefly determined by arterial blood pressure.10 The substantial increase in the vascular cross-section during late gestation accounts for a reduction in impedance and the corresponding fall in umbilical artery pulsatility seen in longitudinal studies.67 Placental vasculature is believed to account for 55% of the umbilical 500 resistance.68 The waveform recorded by Doppler measurement in the umbilical artery reflects this downstream impedance and is used extensively to identify placental compromise.69 Watershed areas and the compromised circulation The watershed area in the brain circulation has long been used to explain certain lesions of neonates, and a concept of a watershed at the isthmus of the aorta, the left portal vein and the foramen ovale with its crista dividens has been proposed recently. It has long been known that fetuses with critical aorta stenosis or hypoplastic left heart syndrome direct ductus arteriosus blood in a retrograde direction through the isthmus aortae to feed the aortic arch. Recent studies have highlighted the isthmus aortae as a watershed between the aortic arch and the ductus arteriosus in anatomically normal fetuses.70,71 Since this watershed also reflects the difference in impedance between the cerebral circuit and that of the placenta and lower fetal body, the blood velocity pattern across the isthmus with various degrees of reversed flow was suggested to be an indicator of placental compromise. Similarly, the direction of flow in the left portal vein (Fig. 1) is suggested to reflect compromised venous return demanding a compensatory increase of blood from the main portal stem to maintain portal and umbilical pressure, with the result being a cessation of umbilical venous flow to the left portal branch, and, at a more advanced stage of compromise, reversed flow that permits splanchnic blood to enter the ductus venosus.72 A third watershed, the foramen ovale (Fig. 2), differs from the two former watersheds. It distributes blood to the left and right atria by dividing the ascending venous blood into two arms at the crista dividens. The horizontal area between the foramen ovale valve and the atrial septum is thought to be the restricting area for flow to the left atrium.50 In cases with increased venous return (e.g. arteriovenous malformation), an increased volume of blood is diverted to the right side, leading to increased growth of the right ventricle. In cases of abnormally small foramen ovale, the left side of the heart develops less in size (one of the possible mechanisms leading to hypoplastic left heart syndrome). These concepts are in need of detailed studies to make them clinically relevant. T. Kiserud Circulatory regulation Circulatory responses to hypoxaemia and hypovolaemia have been particularly well studied in animals during the last trimester of pregnancy,73 but even during mid-gestation and earlier, there seem to be neural and endocrine responses in addition to the prominent direct effect on cardiac function caused by hypoxic insults.74,75 A hypoxic insult in late pregnancy activates a chemoreflex mediated by the carotid bodies (and, to a lesser extent, the aortic bodies), causing an immediate vagal effect with reduced heart rate and a sympathetic vasoconstriction.76 This is followed by endocrine responses (e.g. adrenaline and noradrenaline) maintaining vasoconstriction (a-adrenergic), increasing heart rate (b-adrenergic) and reducing blood volume with renin release and increased angiotensin II concentration. The responses involve angiotensinevasopressin mechanisms, and increased concentrations of adrenocorticotrophic hormone, cortisol, atrial natriuretic peptide, neuropeptide Y and adrenomedullin orchestrate a circulatory redistributional pattern that maintains placental circulation and gives priority to the adrenal glands, myocardium and brain73 (Fig. 5). In clinical medicine, this translates into a frequently visualized coronary circulation,77 a shift in lefteright ventricular distribution,78 a cerebral circulation with high diastolic flow,57 and an increased impedance in the pulmonary circulation79 during circulatory compromise. Sustained hypoxia forces an adaptational shift to less oxygen demand, reduced DNA synthesis Figure 5 Redistribution of fetal combined cardiac output during acute hypoxaemia caused by reduced uterine blood flow. Based on ref.58 Physiology of the fetal circulation and growth, with a gradual return towards normal concentrations of blood gases and endocrine status,80 although with a residual deviation that may have a longlasting effect on fetal and newborn life. There is an increasing awareness that even subtle differences in the development of autocrine, paracrine, endocrine and metabolic functions induced by nutritional or circulatory variations during pregnancy could have lasting effects with increased risks of cardiovascular and endocrine diseases in adult life.81 Practice points Which of the two ventricles takes a larger volume load? From where comes the blood in the left atrium? How much of the umbilical venous return is shunted through the ductus venosus in the human fetus? In what sense is the aortic isthmus a watershed? Research directions More information on human fetal circulation is expected to substitute animal experimental studies as the basis for clinical medicine. More detailed adaptational pattern is expected to give a better background for fetal surveillance. More detailed knowledge of human fetal responses and adaptation is expected to unveil the mechanisms involved in in utero conditioning of health risk in adult life. References 1. Brace RA. Regulation of blood volume in utero. In: Hanson MA, Spencer JAD, Rodeck CH, editors. The circulation, Fetus and neonate. Physiology and clinical application, vol. 1. Cambridge: Cambridge University Press; 1993. p. 75e99. 2. Nicolaides KH, Clewell WH, Rodeck CH. Measurement of fetoplacental blood volume in erythroblastosis fetalis. Am J Obstet Gynecol 1987;157:50e3. 3. Brace RA. Fetal blood volume response to intravenous saline solution and dextrane. Am J Obstet Gynecol 1983;143: 777e81. 501 4. Castle B, Mackenzie IZ. In vivo observations on intravascular blood pressure in the fetus during mid-pregnancy. In: Rolfe P, editor. Fetal physiological measurements. London, Boston, Durban, Singapore, Toronto, Wellington: Butterworths; 1986. p. 65e9. 5. Johnson P, Maxwell DJ, Tynan MJ, Allan LD. Intracardiac pressures in the human fetus. Heart 2000;84:59e63. 6. Ville Y, Sideris I, Hecher K, Snijders RJM, Nicolaides KH. Umbilical venous pressure in normal, growth-retarded, and anemic fetuses. Am J Obstet Gynecol 1994;170:487e94. 7. Thornburg KL, Morton MJ. Development of the cardiovascular system. In: Thorburn GD, Harding R, editors. Textbook of fetal physiology. Oxford: Oxford University Press; 1994. 8. Reller MD, Morton MJ, Reid DL, Thornburg KL. Fetal lamb ventricles respond differently to filling and arterial pressures and to in utero ventilation. Pediatr Res 1987;22: 519e32. 9. Lingman G, Dahlström JA, Eik-Nes SH, Marsál K, Ohlin P, Ohrlander S. Hemodynamic evaluation of fetal heart arrhythmias. Br J Obstet Gynecol 1984;91:647e52. 10. Rudolph AM. Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ Res 1985;57:811e21. 11. Grant DA, Fauchère JC, Eede KJ, Tyberg JV, Walker AM. Left ventricular stroke volume in the fetal sheep is limited by extracardiac constraint and arterial pressure. J Physiol 2001;535:231e9. 12. Rasanen J, Wood DC, Weiner S, Ludomirski A, Huhta JC. Role of the pulmonary circulation in the distribution of human fetal cardiac output during the second half of pregnancy. Circulation 1996;94:1068e73. 13. Mielke G, Benda N. Cardiac output and central distribution of blood flow in the human fetus. Circulation 2001;103: 1662e8. 14. Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC. Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy. Circulation 1998;97:257e62. 15. Kiserud T, Hellevik LR, Eik-Nes SH, Angelsen BAJ, Blaas H-G. Estimation of the pressure gradient across the fetal ductus venosus based on Doppler velocimetry. Ultrasound Med Biol 1994;20:225e32. 16. Kiserud T, Rasmussen S, Skulstad SM. Blood flow and degree of shunting through the ductus venosus in the human fetus. Am J Obstet Gynecol 2000;182:147e53. 17. Kiserud T, Eik-Nes SH, Blaas H-G, Hellevik LR. Ultrasonographic velocimetry of the fetal ductus venosus. Lancet 1991;338:1412e4. 18. Huisman TWA, Stewart PA, Wladimiroff JW. Ductus venosus blood flow velocity waveforms in the human fetus e a Doppler study. Ultrasound Med Biol 1992;18:33e7. 19. Edelstone DI, Rudolph AM. Preferential streaming of ductus venosus blood to the brain and heart in fetal lambs. Am J Physiol 1979;237:H724e9. 20. Bellotti M, Pennati G, De Gasperi C, Battaglia FC, Ferrazzi E. Role of ductus venosus in distribution of umbilical flow in human fetuses during second half of pregnancy. Am J Physiol 2000;279:H1256e63. 21. Behrman RE, Lees MH, Peterson EN, de Lannoy CW, Seeds AE. Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 1970; 108:956e69. 22. Tchirikov M, Rybakowski C, Hünecke B, Schröder HJ. Blood flow through the ductus venosus in singleton and multifetal pregnancies and in fetuses with intrauterine growth retardation. Am J Obstet Gynecol 1998;178:943e9. 23. Bellotti M, Pennati G, De Gasperi C, Bozzo M, Battaglia FC, Ferrazzi E. Simultaneous measurements of umbilical 502 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses. Am J Obstet Gynecol 2004;190:1347e58. Coceani F, Olley PM. The control of cardiovascular shunts in the fetal and perinatal period. Can J Pharmacol 1988;66: 1129e34. Kiserud T, Ozaki T, Nishina H, Rodeck C, Hanson MA. Effect of NO, phenylephrine and hypoxemia on the ductus venosus diameter in the fetal sheep. Am J Physiol 2000; 279:H1166e71. Momma K, Takeuchi H, Hagiwara H. Pharmacological constriction of the ductus arteriosus and ductus venosus in fetal rats. In: Nora J, Takao A, editors. Congenital heart disease. Causes and processes. Mount Kisco: Futura; 1984. p. 313e27. Loberant N, Barak M, Gaitini D, Herkovits M, Ben-Elisha M, Roguin N. Closure of the ductus venosus in neonates: findings on real-time gray-scale, color-flow Doppler, and duplex Doppler sonography. AJR Am J Roentgenol 1992;159: 1083e5. Fugelseth D, Lindemann R, Liestøl K, Kiserud T, Langslet A. Postnatal closure of ductus venosus in preterm infants % 32 weeks. An ultrasonographic study. Early Hum Dev 1998;53: 163e9. Fugelseth D, Kiserud T, Liestøl K, Langslet A, Lindemann R. Ductus venosus blood velocity in persistent pulmonary hypertension of the newborn. Arch Dis Child 1999;81:F35e9. Kiserud T, Stratford L, Hanson MA. Umbilical flow distribution to the liver and ductus venosus: an in vitro investigation of the fluid dynamic mechanisms in the fetal sheep. Am J Obstet Gynecol 1997;177:86e90. Paulick RP, Meyers RL, Rudolph CD, Rudolph AM. Umbilical and hepatic venous responses to circulating vasoconstrictive hormones in fetal lamb. Am J Physiol 1991;260: H1205e13. Tchirikov M, Kertschanska S, Schroder HJ. Differential effects of catecholamines on vascular rings from the ductus venosus and intrahepatic veins of fetal sheep. J Physiol 2003;548:519e26. Rudolph AM, Heymann MA, Teramo K, Barrett C, Räihä N. Studies on the circulation of the previable human fetus. Pediatr Res 1971;5:452e65. Nathanielsz PW, Hanson M. Spare the brain and spoil the liver. J Physiol 2003;548:333. Bristow J, Rudolph AM, Itskovitz J, Barnes R. Hepatic oxygen and glucose metabolism in the fetal lamb. J Clin Invest 1982;71:1047e61. Kiserud T, Eik-Nes SH, Blaas H-G, Hellevik LR. Foramen ovale: an ultrasonographic study of its relation to the inferior vena cava, ductus venosus and hepatic veins. Ultrasound Obstet Gynecol 1992;2:389e96. Volpe P, Marasini M, Caruso G, Lituania M, Marzullo A, Volpe G. Prenatal diagnosis of ductus venosus agenesis and its association with cytogenetic/congenital anomalies. Prenat Diagn 2002;22:995e1000. Rudolph CD, Meyers RL, Paulick RP, Rudolph AM. Effects of ductus venosus obstruction on liver and regional blood flows in the fetal lamb. Pediatr Res 1991;29:347e52. Tchirikov M, Kertschanska S, Schroder HJ. Obstruction of ductus venosus stimulates cell proliferation in organs of fetal sheep. Placenta 2001;22:24e31. Haugen G, Hanson M, Kiserud T, Crozier S, Inskip HM, Godfrey K. Fetal liver-sparing cardiovascular adaptations linked to mother’s slimness and diet. Circ Res 2005;96:12e4. Haugen G, Kiserud T, Godfrey K, Crozier S, Hanson M. Portal and umbilical venous blood supply to the liver in the human fetus near term. Ultrasound Obstet Gynecol 2004;24:599e605. T. Kiserud 42. Kilavuz Ö, Vetter K. Is the liver of the fetus the 4th preferential organ for arterial blood supply besides brain, heart, and adrenal glands. J Perinat Med 1999;27:103e6. 43. Hecher K, Bilardo CM, Stigter RH, Ville Y, Hackelöer BJ, Kok HJ. Monitoring of fetuses with intrauterine growth restriction: a longitudinal study. Ultrasound Obstet Gynecol 2001;18:564e70. 44. Baschat AA, Gembruch U, Harman CR. The sequence of changes in Doppler and biophysical parameters as severe fetal growth restriction worsen. Ultrasound Obstet Gynecol 2001;18:571e7. 45. Borrell A, Martinez JM, Seres A, Borobio V, Cararach V, Fortuny A. Ductus venosus assessment at the time of nuchal translucency measurement in the detection of fetal aneuploidy. Prenat Diagn 2003;23:921e6. 46. Matias A, Gomes C, Flack N, Montenegro N, Nikolaides KH. Screening for chromosomal defects at 11e14 weeks: the role of ductus venosus blood flow. Ultrasound Obstet Gynecol 1998;12:380e4. 47. Wilson AD, Rao PS, Aeschlimann S. Normal fetal foramen ovale flap and transatrial Doppler velocity pattern. J Am Soc Echocardiogr 1989;3:491e4. 48. Lind J, Wegelius C. Angiocardiographic studies on the human foetal circulation. Pediatrics 1949;4:391e400. 49. Lenz F, Machlitt A, Hartung J, Bollmann R, Chaoui R. Fetal pulmonary venous flow pattern is determined by left atrial pressure: report of two cases of left heart hypoplasia, one with patent and the other with closed interatrial communication. Ultrasound Obstet Gynecol 2002;19:392e5. 50. Kiserud T, Rasmussen S. Ultrasound assessment of the fetal foramen ovale. Ultrasound Obstet Gynecol 2001;17: 119e24. 51. Momma K, Takao A. Increased constriction of the ductus arteriosus with combined administration of indomethacin and betamethasone in fetal rats. Pediatr Res 1989;25:69e75. 52. Brezinka C, Huisman TWA, Stijnen T, Wladimiroff JW. Normal Doppler flow velocity waveforms in the fetal ductus arteriosus in the first half of pregnancy. Ultrasound Obstet Gynecol 1992;2:397e401. 53. Huhta J, Cohen M, Gutgesell HP. Patency of the ductus arteriosus in normal neonates: two-dimensional echocardiography versus Doppler assessment. J Am Coll Cardiol 1984;4: 561e4. 54. Clyman RI, Mauray F, Roman C, Rudolph AM. PGE2 is a more potent vasodilator of the fetal lamb ductus arteriosus than is either PGI2 or 6 keto PGF1alpha. Prostaglandins 1978;16: 259e64. 55. Moise KJ, Huhta JC, Sharif DS, Ou CN, Kirshon B, Wasserstrum N. Indomethacin in the treatment of premature labor. Effect on the fetal ductus arteriosus. N Engl J Med 1988;319:327e31. 56. Huhta JC, Moise KJ, Fisher DJ, Sharif DS, Wasserstrum N, Martin C. Detection and quantitation of constriction of fetal ductus arteriosus by Doppler echocardiography. Circulation 1987;75:406e27. 57. Wladimiroff JW, Wijngaard JA, Degani S, Noordam MJ, van Eyck J, Tonge HM. Cerebral and umbilical arterial blood flow waveforms in normal and growth-retarded pregnancies. Obstet Gynecol 1987;69:705e9. 58. Jensen A, Roman C, Rudolph AM. Effect of reduced uterine flow on fetal blood flow distribution and oxygen delivery. J Dev Physiol 1991;15:309e23. 59. Sutton MSJ, Plappert T, Doubilet P. Relationship between placental blood flow and combined ventricular output with gestational age in normal fetuses. Cardiovasc Res 1991;25:603e8. Physiology of the fetal circulation 60. Kiserud T, Rasmussen S, Sethi V. Fetal blood flow distribution to the placenta. Ultrasound Obstet Gynecol 2003; 22:37. 61. Gill RW. Pulsed Doppler with B-mode imaging for quantitative blood flow measurement. Ultrasound Med Biol 1979; 5:223e35. 62. Acharya G, Wilsgaard T, Berntsen GKR, Maltau JM, Kiserud T. Reference ranges for umbilical vein blood flow in the second half of pregnancy based on longitudinal data. Prenat Diagn 2005;25:99e111. 63. Stembera ZK, Hodr J, Janda J. Umbilical blood flow in healthy newborn infants during the first minutes after birth. Am J Obstet Gynecol 1965;91:568e74. 64. Poston L. The control of bloodflow to the placenta. Exp Physiol 1997;82:377e87. 65. Sand AE, Andersson E, Fried G. Effect of nitric oxide donors and inhibitors of nitric oxide signalling on endothelin- and serotonin-induced contractions in human placental arteries. Acta Physiol Scand 2002;174:217e23. 66. Poston L, McCarthy AL, Ritter JM. Control of vascular resistance in the maternal and feto-placental arterial beds. Pharmacol Ther 1995;65:215e39. 67. Acharya G, Wilsgaard T, Berntsen GKR, Maltau JM, Kiserud T. Reference ranges for serial measurements of umbilical artery Doppler indices in the second half of pregnancy. Am J Obstet Gynecol 2005;192:937e44. 68. Adamson SL. Arterial pressure, vascular input impedance, and resistance as determinants of pulsatile blood flow in the umbilical artery. Eur J Obstet Gynecol Reprod Biol 1999;84:119e25. 69. Alfirevic Z, Neilson JP. Doppler ultrasonography in high-risk pregnancies: systematic review with meta-analysis. Am J Obstet Gynecol 1995;172:1379e87. 70. Fouron JC, Zarelli M, Drblik P, Lessard M. Flow velocity profile of the fetal aortic isthmus through normal gestation. Am J Cardiol 1994;74:483e6. 71. Sonesson S-E, Fouron J-C. Doppler velocimetry of the aortic isthmus in human fetuses with abnormal velocity waveforms in the umbilical artery. Ultrasound Obstet Gynecol 1997;10:107e11. 503 72. Kiserud T, Kilavuz Ö, Hellevik LR. Venous pulsation in the left portal branch e the effect of pulse and flow direction. Ultrasound Obstet Gynecol 2003;21:359e64. 73. Iwamoto HS. Cardiovascular effects of acute fetal hypoxia and asphyxia. In: Hanson MA, Spencer JAD, Rodeck CH, editors. The circulation, Fetus and neonate physiology and clinical application, vol. 1. Cambridge: Cambridge University Press; 1993. 74. Iwamoto HS, Kaufman T, Keil LC, Rudolph AM. Responses to acute hypoxemia in fetal sheep at 0.6e0.7 gestation. Am J Physiol 1989;256:H613e20. 75. Kiserud T, Jauniaux E, West D, Ozturk O, Hanson MA. Circulatory responses to acute maternal hyperoxaemia and hypoxaemia assessed non-invasively by ultrasound in fetal sheep at 0.3e0.5 gestation. Br J Obstet Gynaecol 2001;108: 359e64. 76. Hanson MA. Do we now understand the control of the fetal circulation? Eur J Obstet Gynecol Reprod Biol 1997;75: 55e61. 77. Chaoui R. The fetal ‘heart-sparing effect’ detected by the assessment of coronary blood flow: a further ominous sign of fetal compromise. Ultrasound Obstet Gynecol 1996;7: 5e9. 78. al-Ghazali W, Chita SK, Chapman MG, Allan LD. Evidence of redistribution of cardiac output in asymetrical growth retardation. Br J Obstet Gyanecol 1989;96:697e704. 79. Rizzo G, Capponi A, Chaoui R, Taddei F, Arduini D, Romanini C. Blood flow velocity waveforms from peripheral pulmonary arteries in normally grown and growth-retarded fetuses. Ultrasound Obstet Gynecol 1996;8:87e92. 80. Bocking AD. Effect of chronic hypoxaemia on circulation control. In: Hanson MA, Spencer JAD, Rodeck CH, editors. The circulation, Fetus and neonate physiology and clinical application, vol. 1. Cambridge: Cambridge University Press; 1993. 81. Barker DJP, Sultan HY. Fetal programming of human disease. In: Hanson MA, Spencer JAD, Rodeck CH, editors. Growth, Fetus and neonate physiology and clinical application, vol. 3. Cambridge: Cambridge University Press; 1995. p. 255e74. Ultrasound Obstet Gynecol 2006; 28: 126–136 Published online 6 July 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.2832 Fetal cardiac output, distribution to the placenta and impact of placental compromise T. KISERUD*†, C. EBBING*†, J. KESSLER*† and S. RASMUSSEN*†‡ *Department of Clinical Medicine, Section of Obstetrics and Gynaecology, University of Bergen, †Department of Obstetrics and Gynecology, Haukeland University Hospital and ‡Locus of Registry Based Epidemiology, Norwegian Birth Registry, Bergen, Norway K E Y W O R D S: blood flow; cardiac output; circulation; echocardiography; fetus; growth restriction; placenta; ultrasound ABSTRACT Objectives Intrauterine growth restriction is a common clinical problem, but the underlying hemodynamic changes are not well known. Our aim was to determine the normal distribution of fetal cardiac output to the placenta during the second half of pregnancy, and to assess the changes imposed by growth restriction with various degrees of placental compromise. Methods A cross-sectional study of 212 low-risk pregnancies with a gestational age of 18–41 weeks constituted the reference population. A second group of 64 pregnancies with an estimated fetal weight ≤ 2.5th percentile constituted the study group. Ultrasound measurements of inner diameters and velocities at the fetal left and right ventricular outlets and intra-abdominal umbilical vein were used to determine combined left and right cardiac output (CCO) and the fraction distributed to the placenta. Placental compromise was graded according to umbilical artery waveform: pulsatility index normal, > 97.5th percentile, or absent/reversed end-diastolic velocity. Regression analysis and Z-score (SD-score) statistics were used to establish normal ranges and to compare groups. Results During gestational weeks 18–41 the normal CCO/kg was on average 400 mL/min/kg and the fraction directed to the placenta was on average 32%, while after 32 weeks it was 21%. In intrauterine growth restriction the CCO/kg was not significantly different, but the fraction to the placenta was lower (P < 0.001). This effect was more pronounced in severe placental compromise (P < 0.001). Conclusions Normally, one third of the fetal CCO is distributed to the placenta in most of the second half of pregnancy, and one fifth near term. In placental compromise this fraction is reduced while CCO/kg is maintained at normal levels, signifying an increased recirculation of umbilical blood in the fetal body. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION Intrauterine growth restriction (IUGR) is one of the major challenges in antenatal care and an important determinant for perinatal mortality and morbidity1 . Low birth weight has also been associated with increased risk of cardiovascular diseases and Type 2 diabetes in adult life2 . Although impaired maternal nutrition may influence birth weight and health in later life, the effect on birth weight is rather modest. This suggests that additional powerful mechanisms, of which placental compromise is probably the most common, are involved in the clinically important group of growth-restricted fetuses seen during the second and third trimesters. Experimental data suggest that restriction in placentation leads to impaired fetal growth3 , and a sustained reduction in oxygen delivery imposed by a restriction in the maternal or fetal circulation of the placenta leads to down-regulation of DNA synthesis and fetal growth4 . In the human fetus, IUGR and compromised placenta are commonly linked to an augmented pulsatility of the umbilical artery. The extreme finding of absent or reversed end-diastolic flow (ARED) in the umbilical arteries is associated with a perinatal mortality rate of 36%5 . These fetuses show signs of increased afterload6 and circulatory redistribution7 . Thus, the circulatory pattern of these fetuses is emerging, but some fundamental pieces of information on the underlying hemodynamics are still lacking. One of these is the proportion of fetal cardiac output distributed to the placenta. In 1971, Abraham Rudolph et al.8 showed Correspondence to: Prof. T. Kiserud, Department of Clinical Medicine, Section of Obstetrics and Gynaecology, Haukeland University Hospital, N-5021 Bergen, Norway (e-mail: torvid.kiserud@kk.uib.no) Accepted: 29 November 2005 Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER Placental fraction of CCO that, under experimental conditions, roughly one third of the combined left and right cardiac output (CCO) was directed towards the umbilical circulation at midgestation in human pregnancies, and a later Doppler study9 , under physiological conditions, points in the same direction, although a low number of observations towards the end of pregnancy made the statistics at this point less reliable. As for compromised pregnancies causing umbilical hemodynamic compromise and fetal growth impairment, the fraction of fetal CCO directed to the placenta is not known. The aim of this study was to determine the fetal cardiac output and its distribution to the placenta in normal pregnancies during the second half of pregnancy, and to assess the changes imposed by IUGR with various degrees of placental compromise. METHODS Reference population The reference population consisted of 212 women with low-risk pregnancies recruited, after written consent, to a cross-sectional study acknowledged by the Regional Committee for Ethics in Medical Research. Excluded were those with an obstetric history of previous hypertensive complications, IUGR, placental abruption and history of smoking, diabetes, hypertension or any general chronic disease. Gestational age was assessed at the routine ultrasound examination at 17–20 weeks of gestation. Fetuses with malformations and known chromosomal aberrations were not included. One participant withdrew after cardiac malformation and trisomy 21 was identified during the study examination, and another due to social reasons. The median gestational age at birth was 40 + 3 (range, 34 + 3 to 42 + 2) weeks. The median birth weight was 3665 (range, 1400–4900) g, and in terms of percentiles for the Norwegian population, it was 50th percentile (range, 1–99th percentiles). The umbilical venous flow in this group has been presented previously and forms the reference ranges for the present study10 . In this study, we established new reference ranges for the blood flow in the cardiac outlets, left–right ventricular output differences, CCO, CCO/kg and the placental fraction of CCO in order to compare these with the results of growth-restricted fetuses. IUGR group This group consisted of 66 women recruited into the study when fetal biometry (biparietal diameter and middle abdominal diameter) identified an estimated fetal weight ≤ 2.5th percentile. Gestational age was determined by crown–rump length before 12 weeks of gestation, biparietal diameter at the routine scan at 17–20 weeks, or certain information of a regular last menstrual period (LMP). In cases of a discrepancy of ≥ 10 days between the gestational age determined by the second-trimester scan and that calculated from a certain LMP, we relied Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. 127 on LMP because growth impairment was assumed to start early, affecting size at the 17–20-week scan. Twins, chromosomal aberrations, malformations and infections in the present pregnancy excluded participation. Those with a birth weight > 10th percentile were excluded, leaving 64 for statistical analysis. These 64 had been examined at a median gestational age of 34 + 1 weeks (range, 23 + 5 to 39 + 5) weeks, and delivered at a median gestational age of 35 + 6 (range, 25 + 0 to 40 + 6) weeks. The median lag between examination and delivery was 3 (interquartile range (IQR), 1–7; range, 0–85) days. The majority of neonates were delivered by Cesarean section (47/64). In total there were 29 girls and 35 boys, with a median birth weight of 1870 (range, 270–3040) g. Of these, 51 were < 2.5th percentile, seven were between 2.5th and 5th percentiles, and six were between 5th and 10th percentiles according to gender-specific birth-weight charts11 . Three deaths occurred at delivery or in the delivery room (birth weights of 270, 280 and 350 g). Of the remaining 61, seven had an Apgar score of < 7 at 1 min and two had a score of < 7 at 5 min, 31 were admitted to the neonatal intensive care unit, and 19 required respiratory support. Sonography The participants were examined during a 45-min session using a Vingmed CFM 800 (GE Vingmed, Horten, Norway) ultrasound machine equipped with a multifrequency mechanical sector transducer (center frequency, 5 MHz) with color Doppler and pulsed Doppler facilities (4 MHz). The spatial peak temporal intensity was set at 45 mW/cm2 for pulsed Doppler. The inner diameter (D) of the aorta and the pulmonary artery was measured at an insonation angle perpendicular to the vessel wall, between the open semilunar valves, in a zoomed image (Figure 1). The optimal frame for measurement was searched in the memory buffer. For the aorta, the procedure was repeated three times or more in 163/174 cases, and an average of 5.2 (median, 5; IQR, 4–6; range, 1–14) times. For the pulmonary artery the measurement was repeated three times or more in 168/177 cases, and an average of 5.5 (median, 5; IQR, 4–7; range, 1–13) times. The calculated mean diameters were used in the statistical analysis. In a separate axial insonation, the sample volume was placed at the ostia of the aorta and pulmonary artery and the maximum velocity during systole was recorded for 2–4 s during fetal quiescence. The angle of insonation was kept as low as possible; for the aorta it was 0◦ in 153 recordings and the median was 10 (IQR, 2–18)◦ in the 27 remaining recordings, while for the pulmonary artery it was 0◦ in 153 recordings and the median was 14 (IQR, 8–33)◦ in the remaining 24. The systolic time-velocity integral (TVI) and heart rate (HR) were calculated as an average of four to six cardiac cycles. Left and right ventricular output were calculated as π · (D/2)2 · TVI · HR. The CCO was calculated as the sum of the two, and the normalized CCO was calculated by dividing this by the fetal weight. The Ultrasound Obstet Gynecol 2006; 28: 126–136. Kiserud et al. 128 the 95% CI of the mean to half or less, depending on the diameter12 . The same approach was used for the umbilical venous flow assessment. Statistical analysis Figure 1 Doppler recording (a,c) and diameter measurement (b,d) at the level of the aortic ostium (a,b) and at the pulmonary arterial ostium (c,d) in a fetus at 30 weeks of gestation. difference between left and right ventricular output was calculated as a percentage of the CCO. For the intra-abdominal umbilical vein the D was determined as an average of four or more measurements made before the first portal branches with an angle of insonation perpendicular to the vessel wall10 . The weighted mean blood velocity (Vwmean ) was recorded during 2–4 s in a separate insonation along the axis of the vessel with an expanded sample volume. The angle of insonation was 0◦ in 56 recordings and the median was 16 (IQR, 10–24)◦ in the remaining 141. The fetoplacental blood flow was calculated as π · (D/2)2 · Vwmean , and its fraction of the CCO was calculated as a percentage. In all fetuses, the fetal weight at the time of examination was estimated on the basis of the weight percentile at birth10 . In addition, the umbilical artery blood velocity was recorded in the free loop, the pulsatility index (PIua ) was calculated from five to six waveforms, and ARED was noted. Increasing waveform alteration was taken as increasing hemodynamic compromise of the placenta and the participants were grouped accordingly into those with normal PIua , those with PIua > 97.5th percentile, and those with ARED. Measures were taken to restrict random error. One person did all measurements (T.K.) in both groups. The intraobserver variation, calculated as the coefficient of variation for the diameter measurement, was 8.4% (95% CI, 7.8–9.0) for the aorta and 7.7% (95% CI, 7.2–8.3) for the pulmonary artery. The corresponding intraclass correlations were 94% (95% CI, 92–95) and 97% (95% CI, 96–97), respectively. In order to further control error, the diameters were determined as a mean of three or more repeat measurements, which we have shown to reduce Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. To produce means, fractional polynomial regression models were fitted to the ln-transformed data and SDs were modeled by the method of scaled absolute residuals13 . The 10th percentile was calculated as mean − 1.282 SD and the 90th percentile as mean + 1.282 SD using back-transformed values. To achieve a normal distribution, the outcome measures of the growth-restricted fetuses were ln-transformed and SD scores (Z-scores) were calculated based on ln-transformed mean and SD values of the normally grown fetuses. Analysis of variance and 95% CIs were used to assess differences. P ≤ 0.05 was regarded as statistically significant. The intraobserver coefficient of variation for repeated diameter measurements of the aorta and pulmonary artery was studied in 141 and 145 participants of the reference group with four or more observations, respectively. The intraobserver variation was also analyzed as the intraclass correlation. The SPSS statistical package (SPSS, Chicago, IL, USA) was used except for the intraobserver coefficient of variation, which was carried out according to the ‘logarithmic method’ of Bland14 . RESULTS Of the 210 examined successfully in the reference group, we obtained measurements of the umbilical flow in 195 and measurements from the cardiac outlets in 181, with complete sets in 170. Fetal movements, unfavorable position, maternal obesity and time constraints were the reasons for incomplete data. Of the 64 growthrestricted fetuses included, we obtained umbilical flow measurements in 62 and measurements in the heart in 32, with complete sets for output calculation in 29. In addition to the reasons for missing data mentioned for the low-risk group, fetuses with IUGR were examined for a shorter time, and priority was given to the umbilical circulation. Figures 2 and 3 show the diameters of the aorta and pulmonary artery measured at the ostia between open valves at gestational ages of 18–41 weeks. The relationship is almost linear. In fetuses with IUGR these diameters tended to be less than they were in the reference group (Figures 2 and 3, Table 1). The pulmonary arterial diameter was significantly smaller in fetuses with IUGR and normal PIua compared with the reference group, while the severely affected fetuses with ARED flow before 32 weeks of gestation maintained a normal pulmonary arterial diameter (Table 1). Normal left and right ventricular output and the results for growth-restricted fetuses are shown in Figures 4 and 5. Those with IUGR had lower output on both the left and the right sides, but without significant differences between Ultrasound Obstet Gynecol 2006; 28: 126–136. Placental fraction of CCO 129 9 9 8 8 7 7 Aortic diameter (mm) (b) 10 Aortic diameter (mm) (a) 10 6 5 4 6 5 4 3 3 2 2 1 1 0 17 22 27 32 37 Gestational age (completed weeks) 0 17 42 22 27 32 37 Gestational age (completed weeks) 42 Figure 2 Diameter of the fetal aorta measured at the ostium between the open valvular leaflets in (a) 181 low-risk pregnancies and (b) 32 pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = 1.63336229 − 307.1038719 · GA−2 + 0.00000716359 · GA3 , and SD = 0.088581647 + 0.00122008 · GA, where GA is gestational age in weeks. Data were ln-transformed. 10 10 Pulmonary arterial diameter (mm) (b) 12 Pulmonary arterial diameter (mm) (a) 12 8 6 4 2 0 17 8 6 4 2 22 27 32 37 42 Gestational age (completed weeks) 0 17 22 27 32 37 42 Gestational age (completed weeks) Figure 3 Diameter of the fetal pulmonary artery measured at the ostium between valvular leaflets in (a) 179 low-risk pregnancies and (b) 32 pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = 1.687988793 − 259.8188528 · GA−2 + 0.00001134 · GA3 , and SD = 0.150728212 − 0.000965064 · GA, where GA is gestational age in weeks. Data were ln-transformed. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2006; 28: 126–136. Kiserud et al. 130 Table 1 Combined cardiac output (CCO) and its distribution in intrauterine growth restriction (IUGR) compared with normal fetuses using Z-score (SD-score) statistics Measurement/fetus Aortic diameter Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Aortic flow Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Pulmonary arterial diameter Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Pulmonary arterial flow Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED CCO Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED CCO/kg Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Left-right flow difference Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Umbilical flow Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Umbilical flow/kg Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Placenta/CCO flow fraction Normal IUGR, PIua normal IUGR, PIua > 97.5th p. IUGR, ARED Mean SE 95% CI n Overall P 0.00 −0.98 −1.06 −0.49 0.08 0.30 0.30 0.37 −0.16 −1.58 −1.66 −1.22 0.15 −0.38 −0.46 0.24 181 12 12 8 < 0.001 0.00 −0.91 −2.01 −1.03 0.08 0.29 0.31 0.39 −0.15 −1.49 −2.62 −1.79 0.15 −0.33 −1.41 −0.27 175 12 11 7 < 0.001 0.00 −1.49 −0.14 0.01 0.08 0.30 0.30 0.37 −0.15 −2.09 −0.73 −0.71 0.16 −0.90 0.45 0.74 179 12 12 8 < 0.001 0.00 −1.45 −0.70 −0.93 0.11 0.31 0.31 0.40 −0.22 −2.06 −1.30 −1.72 0.22 −0.84 −0.09 −0.13 173 12 12 7 < 0.001 0.00 −1.55 −1.75 −1.35 0.08 0.33 0.33 0.41 −0.17 −2.20 −2.40 −2.17 0.17 −0.90 −1.10 −0.53 170 11 11 7 < 0.001 0.00 0.11 −0.11 0.61 0.08 0.32 0.32 0.40 −0.16 −0.52 −0.74 −0.18 0.16 0.74 0.52 1.40 170 11 11 7 0.485 0.00 −0.32 1.07 0.23 0.08 0.31 0.31 0.39 −0.16 −0.93 0.46 −0.54 0.16 0.29 1.68 1.00 170 11 11 7 < 0.001 0.00 −1.74 −2.47 −3.88 0.08 0.24 0.24 0.30 −0.16 −2.20 −2.94 −4.46 0.16 −1.27 −1.99 −3.29 195 24 23 15 < 0.001 0.00 −0.94 −1.32 −2.00 0.09 0.25 0.26 0.32 −0.17 −1.44 −1.83 −2.63 0.17 −0.45 −0.82 −1.38 195 24 23 15 < 0.001 0.00 −0.70 −1.19 −2.68 0.08 0.31 0.31 0.39 −0.16 −1.32 −1.81 −3.45 0.16 −0.08 −0.57 −1.90 164 11 11 7 < 0.001 IUGR fetuses were grouped according to umbilical artery waveform, i.e. pulsatility index normal (PIua ), PIua > 97.5th percentile (p.), or absent/reversed end-diastolic flow (ARED). the three sub-groups classified according to the umbilical artery waveform (Table 1). Comparing left and right ventricular output (Figure 6), there was a shift towards higher volume load in the right ventricle, this effect being augmented during the last weeks of pregnancy. The combined values before 32 weeks of gestation showed a 13% greater load in the right than in the left ventricle, and the corresponding difference after Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. 32 weeks was 26%. In fetuses with IUGR there was a significant overall shift towards greater load in the right ventricle compared with the reference group (Figure 6 and Table 1). However, when divided into subgroups, fetuses with IUGR and normal PIua were not different from the reference population. On the other hand, those with IUGR and PIua > 97.5th percentile shifted the distribution significantly to the right compared with the reference Ultrasound Obstet Gynecol 2006; 28: 126–136. Placental fraction of CCO 131 900 900 800 800 700 700 Aortic flow (mL/min) (b) 1000 Aortic flow (mL/min) (a) 1000 600 500 400 600 500 400 300 300 200 200 100 100 0 17 22 27 32 37 0 17 42 Gestational age (completed weeks) 22 27 32 37 42 Gestational age (completed weeks) Figure 4 Left ventricular output (aortic flow) in (a) 175 low-risk pregnancies and (b) 30 pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = 6.252257178 − 974.1413866 · GA−2 + 0.00000808794 · GA3 , and SD = 0.257218688 + 0.001375273 · GA, where GA is gestational age in weeks. Data were ln-transformed. 1800 (b) 1800 1600 1600 1400 1400 Pulmonary arterial flow (mL/min) Pulmonary arterial flow (mL/min) (a) 1200 1000 800 600 1200 1000 800 600 400 400 200 200 0 17 22 27 32 37 Gestational age (completed weeks) 42 0 17 22 27 32 37 Gestational age (completed weeks) 42 Figure 5 Right ventricular output (pulmonary arterial flow) in (a) 173 low-risk pregnancies and (b) 31 pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = 5.825881953 − 722.6681806 · GA−2 + 0.0000236 · GA3 . and SD = 0.27653547 − 0.000171845 · GA, where GA is gestational age in weeks. Data were ln-transformed. group (95% CI of the Z-scores, 0.46 to 1.68 vs. −0.16 to 0.16), but also compared with those with IUGR and normal PIua (95% CI, −0.93 to 0.29) (Table 1). Fetuses Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. with IUGR and ARED in the umbilical artery showed the same tendency but did not reach significance, their numbers being small (Table 1). Ultrasound Obstet Gynecol 2006; 28: 126–136. Kiserud et al. 132 (b) 100 80 80 60 60 Left−right difference (%) Left−right difference (%) (a) 100 40 20 0 20 0 − 20 − 40 17 40 − 20 22 27 32 37 Gestational age (completed weeks) − 40 17 42 22 27 32 37 Gestational age (completed weeks) 42 Figure 6 Difference between left and right ventricular output, calculated as the percentage of the combined left and right output, showing a dominance of the right ventricle, in (a) 170 low-risk pregnancies and (b) 29 fetuses with intrauterine growth restriction. These fetuses were subdivided to show those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = 5.199715945 − 0.028088562 · GA + 0.000013103 · GA3 , and SD = 0.133574716 + 0.000029348 · GA, where GA is gestational age in weeks. Left–right flow difference + 100 was ln-transformed. 1800 1800 1600 1600 1400 1400 1200 1200 CCO (mL/min) (b) 2000 CCO (mL/min) (a) 2000 1000 800 1000 800 600 600 400 400 200 200 0 17 22 27 32 37 Gestational age (completed weeks) 42 0 17 22 27 32 37 Gestational age (completed weeks) 42 Figure 7 Fetal combined left and right cardiac output (CCO) in (a) 170 low-risk pregnancies, and (b) 29 pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = 5.544717402 − 201.4738872 · GA−2 + 18.309430055 · GA−1 , and SD = 0.414476269 − 0.005064894 · GA, where GA is gestational age in weeks. Data were ln-transformed. The mean fetal CCO was 80 mL/min at 18 weeks and 1370 mL/min at 40 weeks (Figure 7). In fetuses with IUGR the CCO was less (Figure 7 and Table 1). Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. The CCO/kg was on average 400 mL/min/kg during the entire second half of the normal pregnancy and this was no different from that in the group with IUGR, Ultrasound Obstet Gynecol 2006; 28: 126–136. Placental fraction of CCO 133 (b) 1200 1000 1000 800 800 CCO/kg (mL/min/kg) CCO/kg (mL/min/kg) (a) 1200 600 400 200 0 17 600 400 200 22 27 32 37 Gestational age (completed weeks) 0 17 42 22 27 32 37 Gestational age (completed weeks) 42 Figure 8 Fetal normalized combined cardiac output (CCO/kg) in mL/min/kg for (a) 170 low-risk pregnancies and (b) 29 pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were not different from the normal group (P = 0.485). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = −3.137255228 + 1.794387574 · GA0.5 − 0.000015527 · GA3 , and SD = 0.205635425 + 0.000295948 · GA, where GA is gestational age in weeks. Data were ln-transformed. (b) 250 (a) 450 Umbilical venous flow/kg (mL/min/kg) Umbilical venous flow (mL/min) 400 350 300 250 200 150 100 200 150 100 50 50 0 17 22 27 32 37 42 Gestational age (completed weeks) 0 17 22 27 32 37 42 Gestational age (completed weeks) Figure 9 (a) Umbilical venous flow in 62 growth-restricted fetuses was lower than that in the reference group (P < 0.001). (b) The effect was also present when flow was normalized for fetal weight (UV flow/kg) (P < 0.001). Growth-restricted fetuses were divided into groups, showing various degrees of placental compromise: those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line for the UV flow was y = −10.08885345 + 4.68474999 · ln(GA) − 0.001042436 · GA2 , and SD = 0.337017961 − 0.000922071 · GA, and that for the regression line for the UV flow/kg was y = 4.90993362 − 27.62004561 · GA−2 − 0.000011856 · GA3 , and SD = 0.575534616 − 0.007815357 · GA, where GA is gestational age in weeks. All data were ln-transformed. or any sub-group of placental compromise (Figure 8 and Table 1). Umbilical blood flow was less in growth-restricted compared with normal fetuses (P < 0.001) (Figure 9), and Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. there was a significant effect of increasing hemodynamic compromise of the placenta (Table 1). This effect was less pronounced when umbilical flow was normalized for fetal weight, but was still significant (Figure 9 and Table 1). Ultrasound Obstet Gynecol 2006; 28: 126–136. Kiserud et al. 134 70 70 60 60 Placenta/CCO flow fraction (%) (b) 80 Placenta/CCO flow fraction (%) (a) 80 50 40 30 20 40 30 20 10 10 0 17 50 22 27 32 37 42 Gestational age (completed weeks) 0 17 22 27 32 37 42 Gestational age (completed weeks) Figure 10 The fraction of fetal combined cardiac output (CCO) directed to the placenta calculated as a percentage of CCO (a) in 164 low-risk pregnancies. (b) The 29 fetuses with intrauterine growth restriction directed a lower proportion of CCO to the placenta (P < 0.001), particularly in extreme degrees of compromise. Growth-restricted fetuses were divided into groups, showing various degrees of placental compromise: those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was y = 3.35420863 + 0.000060601 · GA3 − 0.000018693 · GA3 · ln(GA), and SD = 0.377370102 − 0.000755215 · GA, where GA is gestational age in weeks. Data were ln-transformed. The fraction of CCO directed to the placenta in normally grown fetuses was on average 32% before 32 weeks, and 21% beyond 32 weeks (Figure 10). In general, growth-restricted fetuses distributed less of the CCO to the placenta (P < 0.001) (Figure 10 and Table 1). While growth-restricted fetuses with normal PIua distributed a similar fraction of the CCO to the placenta compared with their normal peers, this was not the case for those that had hemodynamic compromise. Those with PIua > 97.5th percentile and particularly those with ARED flow in the umbilical artery had a reduced fraction of CCO distributed to the placenta (Table 1), implying an increased recirculation of umbilical blood in the fetal body. DISCUSSION In this study we showed that fetuses normally direct one third of their cardiac output to the placenta during the second half of pregnancy and one fifth during the last couple of months. Interestingly, this implies an increase in recirculation of umbilical blood in the fetal body towards the end of pregnancy. Furthermore, this effect is augmented in placental compromise. Growth-restricted fetuses direct a reduced volume of blood towards the placenta, both in absolute and in relative terms, while maintaining a relatively normal cardiac output. The effect seems to increase with the degree of placental compromise and signifies a more extensive recirculation of umbilical blood within the fetal body. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. The distribution of volume load within the fetal heart also seems to be affected. Although experimental data15,16 and some studies in humans17 suggest that the normal dominance of the right ventricle is cancelled during challenge, our study supports that in fetuses with increased pulsatility of the umbilical artery the right ventricle actually takes an increased proportion of the load18,19 . This is in keeping with other mechanisms seen in such fetuses: reduced size of and shunting through the foramen ovale7,20 , increased resistance in the pulmonary circuit21 , with correspondingly less venous return to the left heart, and retrograde blood flow at the aortic isthmus7,22 to further supply the aortic arch and carotid arteries with right ventricular blood via the ductus arteriosus. A shift to the left of the watershed area between portal and umbilical venous supply to the liver23,24 and an augmented blood velocity in the hepatic artery25 will change the fetal circulation in the same direction. These are mechanisms of redistribution but also of increased recirculation of umbilical blood in the fetal body, which correspond to more extensive oxygen extraction. On average, the oxygen concentration in the umbilical vein measured in the IUGR fetus during cordocentesis is lower than that in their normal peers26 . The fraction of fetal CCO directed to the placenta found in this study is in line with the two previous studies that examined this issue in humans, but with an important difference: the placental fraction was less (one fifth) near term. The study of Rudolph et al.8 using the microsphere technique found an average 33% Ultrasound Obstet Gynecol 2006; 28: 126–136. Placental fraction of CCO distribution of the CCO to the placenta at mid-gestation, but did not include higher gestational ages. Due to the method of calculating CCO (pulmonary venous return was not included) and the conditions not being strictly physiological (the fetuses were exteriorized), the results have awaited verification. Our study, applying a different technique, presents very similar results indeed; 32% of the CCO was directed to the placenta during gestational weeks 18–32. In the second study, Sutton et al.9 used Doppler ultrasound in physiological pregnancies to show that the placental fraction of the CCO is one third for the second half of pregnancy. Fewer numbers included and calculation of umbilical venous flow using maximum velocity (which tends to overestimate flow if not corrected for the parabolic velocity profile) may explain some of the differences from our study in late pregnancy. The normal fetal CCO found in our study had a similar pattern during the second half of pregnancy to that described in previous studies27 – 30 . Compared with those using leading edges (inner–outer diameter) for the vessel cross-section measurement, our results of CCO are lower (1300 vs. 1900 mL/min at 38 weeks)29 ; our results are more in agreement with those using inner diameters in their calculation, as they are for CCO/kg (400 vs. 425 mL/min/kg)30 . The 6% difference may be ascribed to technique (this study measured between valves at the ostium), or to chance. Knowing the variability of such measurements in the fetus31,32 , particularly diameter measurements, we restricted error by repeating measurements12,33 and by using a single operator. Coefficients of variation of 8.4 and 7.7%, and intraclass correlations of 94 and 97% for the diameter of the aorta and pulmonary artery, respectively, ensured that the study gave a fair representation of normal and abnormal flows. We acknowledge that having cardiac outflow measurements in less than half of the IUGR group might represent a limitation of the study, with a possible selection bias. A successful examination is least likely in small fetuses with oligohydramnios in overweight mothers; in our setting we believed that time constraints for such mothers and fetuses (which, due to clinical reasons, tended to be examined for a shorter period than did the low-risk group) were the main reason for the low success rate. The fact that umbilical venous flow was obtained successfully in 62/64 cases underscores the point that due to time limitation, the lower priority of cardiac measurements gave fewer results. In short, one third to one fifth of the fetal CCO circulates the normal placenta; in comparison, the compromised placenta shrinks this fraction, both in absolute and in relative terms, thus driving the circulation towards increased recirculation of umbilical blood within the fetal body. We believe this reflects an increased vulnerability in much the same way as does the low oxygen concentration found in growth-restricted fetuses. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. 135 ACKNOWLEDGMENT The study was supported by the Norwegian Research Council. REFERENCES 1. Kramer MS, Olivier M, McLean FH, Willis DM, Usher RH. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 1990; 86: 707–713. 2. Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993; 36: 62–67. 3. Robinson JS, Kingston EJ, Jones CT, Thorburn GD. Studies on experimental growth retardation in sheep. The effect of removal of endometrial caruncles on fetal size and metabolism. J Dev Physiol 1979; 1: 379–398. 4. Bocking AD. Effect of chronic hypoxaemia on circulation control. Fetus and Neonate Physiology and Clinical Application, Vol. 1, The Circulation, Hanson MA, Spencer JAD, Rodeck CH (eds). Cambridge University Press: Cambridge, 1993; 215–224. 5. Alfirevic Z, Neilson JP. Doppler ultrasonography in high-risk pregnancies: Systematic review with meta-analysis. Am J Obstet Gynecol 1995; 172: 1379–1387. 6. Hecher K, Campbell S, Doyle P, Harrington K, Nicolaides K. Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Circulation 1995; 91: 129–138. 7. Mäkikallio K, Jouppila P, Räsänen J. Retrograde aortic isthmus net blood flow and human fetal cardiac function in placental insufficiency. Ultrasound Obstet Gynecol 2003; 22: 351–357. 8. Rudolph AM, Heymann MA, Teramo K, Barrett C, Räihä N. Studies on the circulation of the previable human fetus. Pediatr Res 1971; 5: 452–465. 9. Sutton MSJ, Plappert T, Doubilet P. Relationship between placental blood flow and combined ventricular output with gestational age in normal fetuses. Cardiovasc Res 1991; 25: 603–608. 10. Kiserud T, Rasmussen S, Skulstad SM. Blood flow and degree of shunting through the ductus venosus in the human fetus. Am J Obstet Gynecol 2000; 182: 147–153. 11. Skjaerven R, Gjessing HK, Bakketeig LS. Birthweight by gestational age in Norway. Acta Obstet Gynecol Scand 2000; 79: 440–449. 12. Kiserud T, Saito T, Ozaki T, Rasmussen S, Hanson M. Validation of diameter measurements by ultrasound. Intra-observer and inter-observer variation assessed in vitro and in the fetal sheep. Ultrasound Obstet Gynecol 1999; 13: 52–57. 13. Royston P, Wright EM. How to construct ‘‘normal ranges’’ for fetal variables. Ultrasound Obstet Gynecol 1998; 11: 30–38. 14. Bland JM. How should I calculate a within-subject coefficient of variation? http://www-users.york.ac.uk/∼mb55/meas/cv.htm [Accessed 22 September 2005]. 15. Thornburg KL, Morton MJ. Filling and arterial pressures as determinants of RV stroke volume in the sheep fetus. Am J Physiol 1983; 244: H656–H663. 16. Rudolph AM. Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ Res 1985; 57: 811–821. 17. al-Ghazali W, Chita SK, Chapman MG, Allan LD. Evidence of redistribution of cardiac output in asymmetrical growth retardation. Br J Obstet Gynaecol 1989; 96: 697–704. 18. Reed KL, Anderson CF, Shenker L. Changes of intra-cardiac Doppler blood flow velocities in fetuses with absent umbilical artery diastolic flow. Am J Obstet Gynecol 1987; 157: 774–779. 19. Weiner Z, Farmakides G, Schulman H, Penny B. Central and peripheral hemodynamic changes in fetuses with absent end-diastolic velocity in umbilical artery: Correlation with Ultrasound Obstet Gynecol 2006; 28: 126–136. 136 20. 21. 22. 23. 24. 25. 26. computerized fetal heart rate pattern. Am J Obstet Gynecol 1994; 170: 509–515. Kiserud T, Chedid G, Rasmussen S. Foramen ovale changes in growth-restricted fetuses. Ultrasound Obstet Gynecol 2004; 24: 141–146. Rizzo G, Capponi A, Chaoui R, Taddei F, Arduini D, Romanini C. Blood flow velocity waveforms from peripheral pulmonary arteries in normally grown and growth-retarded fetuses. Ultrasound Obstet Gynecol 1996; 8: 87–92. Sonesson S-E, Fouron J-C. Doppler velocimetry of the aortic isthmus in human fetuses with abnormal velocity waveforms in the umbilical artery. Ultrasound Obstet Gynecol 1997; 10: 107–111. Kiserud T, Kilavuz Ö, Hellevik LR. Venous pulsation in the left portal branch – the effect of pulse and flow direction. Ultrasound Obstet Gynecol 2003; 21: 359–364. Kilavuz Ö, Vetter K, Kiserud T, Vetter P. The left portal vein is the watershed of the fetal venous system. J Perinat Med 2003; 31: 184–187. Kilavuz Ö, Vetter K. Is the liver of the fetus the 4th preferential organ for arterial blood supply besides brain, heart, and adrenal glands. J Perinat Med 1999; 27: 103–106. Soothill PW, Nicolaides KH, Campbell S. Prenatal asphyxia, hyperlactaemia and erythroblastosis in growth retarded fetuses. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. Kiserud et al. BMJ (Clin Res Ed) 1987; 294: 1051–1053. 27. Kenny JF, Plappert T, Saltzman DH, St John Sutton MG. Changes in intracardiac blood flow velocities and right and left ventricular stroke volumes with gestational age in the normal fetus. Circulation 1986; 74: 1208–1216. 28. De Smedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac output estimated by Doppler echocardiography during midand late gestation. Am J Cardiol 1987; 60: 338–342. 29. Rasanen J, Wood DC, Weiner S, Ludomirski A, Huhta JC. Role of the pulmonary circulation in the distribution of human fetal cardiac output during the second half of pregnancy. Circulation 1996; 94: 1068–1073. 30. Mielke G, Benda N. Cardiac output and central distribution of blood flow in the human fetus. Circulation 2001; 103: 1662–1668. 31. Beeby AR, Dunlop W, Heads A, Hunter S. Reproducibility of ultrasonic measurement of fetal cardiac haemodynamics. Br J Obstet Gynaecol 1991; 98: 807–814. 32. Simpson JM, Cook A. Repeatability of echocardiographic measurements in the human fetus. Ultrasound Obstet Gynecol 2002; 20: 332–339. 33. Kiserud T, Rasmussen S. How repeat measurements affect mean diameter of the umbilical vein and the ductus venosus. Ultrasound Obstet Gynecol 1998; 11: 419–425. Ultrasound Obstet Gynecol 2006; 28: 126–136. Diabetes i svangerskapet Hva er diabetes? En tilstand der blodsukkeret i fastende og/eller ikke-fastende tilstand er over et definert nivå Grunnkurs i Obstetrikk 2016 Tore Henriksen Fødeseksjonen, Rikshospitalet Oslo Universitetssykehus Hvorfor blir blodsukkeret for høyt? Blodglukosens kilde nr 1: Tarm Etter måltid Kort om omsetningen (metabolismen) av glukose Blodglucose Tarm Kilde nr 2: Lever De kvantitativt viktigste forbrukere av glukose I fastende tilstand Lever Glykogen! Insulin? Glukoneogenese (ved faste) Blodglucose Blodglucose Hjerne Tarm Fettvev Tarm Muskel Muskulatur og fettvev sammen med lever er sentrale i regulering av blodsukkeret Opptaket av glukose i muskel og fettvev er avhengig av at Insulin-systemet virker Glykogen! Glykolyse Glukoneogenese Insulin Insulin Glukose Glukose Blodglucose Blodglucose Insulin Insulin Hjerne Fettvev Muskel Tarm Fettvev Tarm Muskel Insulin-systemet kan svikte på to måter Insulin-systemet kan svikte på to måter Insulin 1. Svikt i pancreas’øyceller Glykolyse Glukoneogenese Glykolyse Glukoneogenese Insulin Glukose Glukose Blodglucose Fettvev Blodglucose Muskel Tarm Fettvev Tarm Muskel Type 1 diabetes: for lite insulin Insulin-systemet kan svikte på to måter 1. Svikt i pancreas’øyceller Glykolyse Glukoneogenese Glykolyse Glukoneogenese Insulin Insulin Glukose Glukose Blodglucose Blodglucose 2. Insulinet virker ikke på cellenivå (insulinresistens) Fettvev Tarm Muskel Fettvev Tarm Muskel Type 2 diabetes: Ofte høyt insulin, men insulin resistens, gjerne kombinert med en relativ svikt i øycellene Øycelleinsuffisiens Glykolyse Glukoneogenese Klassifikasjon av diabetes/glukoseintoleranse i svangerskapet Pregestasjonell diabetes, (“kjent diabetes”) Insulin Glukose Blodglucose 2. Insulinet virker ikke på cellenivå (insulinresistens) Fettvev Tarm Diabetes/glukoseintoleranse) oppdaget første gang i svangerskapet • • • • Type 1 diabetes. (IDDM) Type 2 diabetes (økende!) Nyoppdaget Type 1 og tType 2 diabetes Svangerskaps-(gestasjonell) diabetes Muskel Diabetes/glukoseintoleranse: Definisjoner (WHO/kriterier, 1999, men NYE ER PÅ VEI!) PREGESTASJONELL DIABETES Forekomst/epidemiologi. 250 -300 kvinner med Type 1 diabetes og ca 150-200 med Type 2 gjennomfører et svangerskap per år i Norge. Gravide med pregestasjonell diabetes (Type 1 eller Type 2) 1. Godt regulert diabetes før de blir gravide!!, eventuell prekonsepsjonell veiledning. Komorbiditet? Kost, vekt og mosjon! HbA1c <7 før svangerskapet Folat fra det tidspunkt en kvinne ønsker å bli gravid Hvis antihypertensiva: Bruk (skift til) labetolol (event nifedipin eller metyldopa) Oppgave for primær og spesialisthelsetjenesten Spesialisthelsetjenesten: Vurdering (prekonsepsjonelt) av dem som bruker metformin (event insulinanaloger) Plasma glukose nivå mmol/l Manifest Diabetes Mellitus: Fastende 7.0 eller 2 t etter 75g glukose oralt Svangerskapsdiabetes (GDM): Fastende og 2 t etter 75 g glukose oralt 11.1 5.3, men <7.0 9.0, men <11.1 Metformin ved type 2 diabetes? • Synes ikke teratogent • Men: noe usikkerhet m h p metabolsk langtidseffekt på barnet Brukes i praksis når det er klar indikasjon der fordeler og usikkerhet er vektet. Pregestasjonell diabetes Oppfølging i svangerskapet: Spesialistoppgave Komplikasjoner: Gravide med pregestasjonell diabetes (type 1 eller type 2) (eller nyoppdaget insulinkrevende gestasjonell diabetes): 1. Misdannelser (både type 1 og type 2!) (HbA1c >8: tidlig/utvidet ultralyd) 2. Preeklampsi 3. Føtale vekstavvik (intrauterin veksthemning/makrosomi) 4. Økt perinatal mortalitet Oppfølging av pregestasjonell (type 1 og 2) diabetes i svangerskapet Henvises til fødepoliklinikk så raskt som mulig etter at graviditeten er bekreftet. På Fødepoliklinikken: 1. Generell gjennomgang (som ved pregestasjonell veiledning) + tidligere svangerskap Oppfølging av pregestasjonell (type 1 og 2) diabetes i svangerskapet, forts. 7. Blodglukosemåling før og etter hovedmåltidene og ved sengetid. Behandlingsmål: Blodglukose 3,5 – 5,5 mmol/l før måltid og under 7,0 mmol/l målt 1½-2 timer etter måltid. HbA1c < 6.0 % i 2. og 3. trimester. 2. HbA1c ≥ 8 % (nå eller rett før graviditeten): tilbys ekstra «utvidet ultralyd» i uke 15-16, i tillegg til den ordinære ultralydscreeningen noen uker senere 8. Hvis skifte fra metformin til insulin tidlig i svangerskapet: Obs hyperglykemi! 3. Urin dyrkning ved 1. kontroll? 9. Ved kostregulert Type 2: Blodsukkermåling fastende og ca 1.5 timer post-prandialt hver annen dag. Medisinsk behandling foreslås hvis pasienten i løpet av en uke har til sammen flere enn 2 målinger av enten fastende blodsukker > 5.5mmol/l eller > 7mmol/l postprandialt. 4. HbA1c måles hver 4. uke. 5. BT og stix; protein/ kreatinin ratio i urin med 4-6 ukers intervall. 6. Diabetes > 5 år: obs øyelege 11. Kostråd og mosjonståd. Se www.helsedirektoratet.no for generelle kostråd, for diabetes og for gravide. skapsuke 6 X 7 Obetetriske momenter i oppfølgingen av pregetasjonell Kontrollhyppighet, Insulinkrevende diabetes 8 X X X 9 10 X 11 • Reperterte tilvekstmålinger (ca hver 4. uke) fra ca uke 24. • Tegn til avtakende tilvekst (vektmessig) eller tegn til begynnende assymetri er alltid alvorlig selv om barnet er er ”normalt stort”. Snikende placentasvikt kan sees hos store barn! • Fostervannsmengde i nedre normalområde eller tegn til avtakende fostervannsmengde, selv om det er innenfor refranseverdiene. skal alltid vektlegges. • Doppler: Sentralisering? (arteria cerebri media) • CTG vektlegges: Obs: Basalfrekvens (endring?), kortidsvariabilitet (Oxford 8002), reaktivitet (akselerasjoner). • Bevegelser?! • Preeklampsi-utvikling ved pregestasjonell diabetes alltid alvorlig (placentasvikt slev om barnet er normal eller stort). 12 X 14 X 16 X 18 X 20 X 22 X 24 X 26 X 28 X 30 X X Evt. UL fosterm Scr. v/jordmor X X X X X X X X X X X X 31 32 Inidkasjon 33 34 inidikasjon 35 36 37 38 X 39 40 X X X X X X X X Vurdering X X X X Vurdering X Truende preterm fødsel ved insulinkrevende diabetes. Absolutt risiko ca 15 %. Rihemmende behandling ved diabetes i svangerskapet Atosiban (Tractocile) Blodsukkeret skal følges, da atosiban kan gi blodsukkerstigning. Induksjon av fødsel ved pregestasjonell diabetes: Induksjon vurderes fortløpende fra ca 38 fulle uker. Anbefales ikke å gå over termin. Keisersnitt: Vanlige obstetriske indikasjoner. Ved alvorlige vaskulære, nyre eller øyekomplikasjoner etter individuell vurdering. Keisersnitt vurderes ved mistanke om vekt over 4500g*. Celeston i to doser med (12-)24 timers intervall. Økt behov for insulin Økningen gjelder både hurtig og langsomtvirkende insulin. Forslag til dosering av insulin økes fra dag 2: Dag 1 (Dagen etter første dose Celeston). Ingen endring av insulindose Dag 2 30 % økning av den opprinnelige insulindosen Dag 3 40 % økning av den opprinnelige insulindosen Dag 4 20 % økning av den opprinnelige insulindosen Dag 5 10 % økning av den opprinnelige insulindosen Dag 6 Vanlig insulindose Ved blodsukker over 8 mmol/l gis ekstra hurtigvirkende insulin (4-6 enheter). Aktiv fødsel, Insulinkrevende diabetes Ved tidligere skulderdystoci keisersnitt vurderes mistanke om vekt over 4000g* *OBS! Vektestimering usikker business! Flere målinger over flere uker for å øke sannsynligheten for riktigere estimat. Se på AC-målet! Aktiv fødsel, insulinkrevende diabetes Tiltak ved ulike blodsukkernivåer: Blodsukkermåling ca hver time, eventuetl oftere, individuell vurdering. Mål blodglukose: 4-7 mmol/l. Insulin: Pasientens egen erfaring med insulin! LAVT blodsukker: Pasienten er bevisstløs eller kraftig føling: Glucose 200 mg/ml 40 ml i.v. i støt. Dosen gjentas hvis pasienten ikke kommer til bevissthet i løpet av 10. Blodsukker er under 4,0 mmol/l: Gi glucose 50 mg/ml i.v. infusjon etter kroppsvekt: 60 kg: 180 ml/t 80 kg: 250 ml/t 100 kg: 300 ml/t HØYT blodsukker: Blodsukker 8,0-10,0 mmol/l: 2- 4 E hurtigvirkende insulin s.c. Gjentas etter 2 timer hvis fortatt er for høyt: Blodsukker over 10,0 mmol/l : 4-8 E hurtigvirkende insulin s.c. Eventuelt gjentas etter 2 timer. Klassifikasjon av diabetes/glukoseintoleranse i svangerskapet Svangerskapsdiabetes (GDM) Nye retningslinjer: Definisjoner Hvordan finne de som har GDM («screening») Oppfølging Fødsel Pregestasjonell diabetes, (“kjent diabetes”) • • Diabetes/glukoseintoleranse oppdaget første gang i svangerskapet A. Nyoppdaget Diabetes: Type 1 (sjelden) eller Type 2 Type 1 diabetes. (IDDM) Type 2 diabetes (økende!) B. Svangerskapsdiabetes (GDM) Klassifikasjon av diabetes/glukoseintoleranse i svangerskapet Pregestasjonell diabetes, (“kjent diabetes”) • • Diabetes/glukoseintoleranse oppdaget første gang i svangerskapet A. Nyoppdaget Diabetes: Type 1 (sjelden) eller Type 2 Type 1 diabetes. (IDDM) Type 2 diabetes (økende!) B. Svangerskapsdiabetes Svangerskapsdiabetes (GDM) er en tilstand med glukoseintoleranse som diagnostiseres i svangerskapet, men der glukoseintoleransen ikke er av en slik grad at kriteriene for diabetes («ekte diabetes», «manifest diabetes») oppfylles. Diagnosen (definisjonen av) svangerskapsdiabetes baseres resultatet av en glukosebelastning (75 g etter minst 8 timers faste): Fastende glukose: ≥ 5.3, men ≤ 6.9 mmol/l og/eller 2‐timers verdi ≥ 9.0, men ≤ 11.0 mmol/l Hvis fastende glukose er ≥ 7.0 og eller 2‐timers verdien ≥11.1 mmol/l, har pasienten diabetes! Fem sentrale tanker ligger bak de nye retningslinjene for GDM 1. Grunnlaget for den nye definisjonen av GDM er ny. 2.GDM skal sees i en helhet, d v s sammen med overvekt/fedme og livsstil «To sider av samme mynt»!) 2.En vil finne de med tidlig innsettende svangerskapsdiabetes, fordi disse har størst risiko for GDM‐relaterte svangerskapskomplikasjoner (preeklampsi, makrosomi) og trenger oftere insulin Grunnlaget for definisjonen av GDM Risikoen for uheldige svangerskapsutfall, f eks store barn (LGA), er lineært relatert til plasmaglukosen HAPO-studien til mors plasmaglukose N Engl J Med 2008 Det er ingen ”breake point(s)”, sammenhengen mellom blodsukkerverdiene og uheldige utfall er kontinuerlig, altså ikke‐kategorisk! 3.En har beveget seg bort fra screening av risikogrupper og heller basere seg på å teste alle, med unntak av de med svært lav risiko (se senere) 4.Testingen baserer seg på a) måling av HBA1c (1. trimester) og b) senere glukosebelastning ved 26‐30 uker (se senere) Grunnlaget for definisjonen av GDM Risikoen for uheldige svangerskapsutfall, f eks store barn (LGA), er lineært relatert til plasmaglukosen HAPO-studien til mors plasmaglukose N Engl J Med 2008 Grunnlaget for definisjonen av GDM Risikoen for uheldige svangerskapsutfall, f eks store barn (LGA), er lineært relatert til plasmaglukosen HAPO-studien til mors plasmaglukose N Engl J Med 2008 Nå har vi valgt de (fastende og 2 timers) glukoseverdiene som medfører en dobling (Odds ratio=2) av uheldige svangerskapsutfall (makrosomi eller preeklampsI) Odds ratio=2 Hvorfor akkurat denne verdien? Nåværende WHO fastende glukose verdi Fastende ≥ 5.3 og 2–timers ≥ 9.0 Ved første kontroll (1. trimester): GDM skal sees i en helhet: Før svangerskapet (pregestasjonell veiledning): A.Rådgivning for å redusere risikoen for GDM (kost, fysisk, vektreduksjon) B.Vurdere HBA1c, eventuelt glukosebelastning, hos kvinner med høy risiko for diabetes (betydelig familiær belastning, fedme/ metabolsk syndrom, tidligere GDM, barn fødselsvekt over 4500g) Ta HBA1c av alle, unntatt de med «svært lav risiko». «Svært lav risiko»: Europeisk bakgrunn, generelt frisk, <25 år, BMI<25, ikke diabetes i familien, tidligere ukompliserte svangerskap Tiltak basert på HBA1c funn i 1. trimester: HBA1c <5.9%: ingen videre tiltak før glukosebelastning ved 26‐30 uker (men hvis overvektig likevel, livsstilsråd!) HBA1c ≥ 6.5 %: Diabetes! HBA1c ≥ 5.9%, men ≤ 6.4%: Obs! Sjekk risikofaktorer igjen. Råd! HBA1c ≥ 5.9%: Til spesialisthelsetjenesten. Obs: hvis HBA1c ≥ 6.5% har hun diabetes. Det må komme tydelig frem når pasienten henvises. Videre oppfølging i primærhelsetjenesten av de som har normal HBA1c (< 5.9 %): Vanlig oppfølging. MEN: ved 26‐30 uker tas Glukosebelastning på alle, unntatt de med «svært lav risiko» «Svært lav risiko»: Europeisk bakgrunn, generelt frisk, <25 år, BMI<25, ikke diabetes i familien, tidligere ukompliserte svangerskap Videre tiltak basert på glukosebelastningen: Hvis fastende verdi < 5.3 mmol/l: kontrollen fortsetter i primærhelsetjenesten. Ved eventuelt senere glukosuri: ingen tiltak. I spesialisthelsetjenesten (de med HbA1c ≥ 5.9%, men <6.5% eller patologisk glukosebelastning ved 26‐30 uker (fastende ≥ 5.3, men ≤ 6.9 mmol/l og/eller 2‐timers verdi ≥ 9.0, men ≤ 11.0 mmol/l): Oppplæring i egenmåling av blodglukose og kost og livsstilsråd Målet ved kost‐ og andre livsstilstiltak: a)Før måltid (preprandialt) < 5.3 og b)Etter måltid (postprandialt) <6.7 mmol/l Hvis målene oppnås med livsstilstiltak, kan pasienten fortsette i primærhelsetjenesten Hvis fastende glukose: ≥ 5.3 og/eller 2‐timers verdi ≥ 9.0,mmol/l: Henvis spesialisthelsetjenesten. Obs: Hvis fastende glukose er ≥ 7.0 og eller 2‐timers verdien ≥11.1 mmol/l, har pasienten diabetes! Det må komme tydelig frem når pasienten henvises. Hvis 3‐4 blodglukoseverdier er over disse verdiene i løpet av ca 2 uker er medikamentell behandling aktuelt (insulin eller metformin). Spesialistoppgave. Obstetrisk oppfølging ved svangerskapsdiabetes (GDM) Vektøkning i svangerskapet ved GDM: Følger generelle retningslinjer Institute of Medicine (IOM) retningslinjer: BMI BMI BMI BMI a (<20): (20-25.9): 26-29: >30: 12.5-18 kg 11.5-16 kg 7-11 kg 5-9 kg Men: Ved BMI 30‐35 reduseres risikoen for noen uheldige svangerskapsutfall (preeklampsi, makrosomi) ved vektøkning 0‐6 kg, kanskje litt økning av SGA Ved BMI over 35 forslås vektøkning på 0‐5 kg. I praksi vil noen gå noe ned i vekt. Det er akseptablet fortutsatt adekvat sammensatt kost og tilvekstkontroll slik som anbefalt OBS: mangelen vektøkning kan bety placentasvikt, derfor ultralydskontroll slik som anbefalt Alltid ultralyd ved første konsultasjon i spesialisthelsetjenesten, uansett gestasjonsalder Ved tidlig innsettende GDM gjøres alltid ultralyd ved 23‐25 uker For pasienter som fortsetter i spesialist helsetjenesten gjøres (etter 23‐25 uker) ultralyd generelt med 4‐6 ukers intervaller. Hvis pasienten går tilbake til primærhelsetjenesten henvises pasienten til ultralyd ved 31‐33 uker og ved 36‐37 uker for vekstkontroll. Det gjøres også CTG ved 36 uker. Videre oppfølging individualiseres (se nedenfor) Oppfølging etter ca 36 uker. Induksjon. Viktige momenter ved vurder av GDM, spesielt etter 36 uker De som er godt regulert på kost og livsstilstiltak: A. Hvis AC eller MAD er stigende til over 90p eller fallende til under 10p ved 36 uker gjøres ny ultralyd og CTG etter individuelle vurdering (komorbiditet? tidligere obstetrisk sykehistorie?BT/urin ? Fostervann? Doppler? (as)symmetri?). Induksjon etter individuell vurdering B. Ved fravær av relevant komorbiditet, godt regulert blodglukose, normal tilvekst (ikke akselererende) og normale biofysiske funn ellers, inklusive CTG, går de tilbake til primæhelsetjenesten. Kontrolleres de i løpet av første uke etter termin. Ved normale funn følges vanlige overtidsregler Medikamentelt behandlet GDM CTG gjøres ukentlig fra og med ca uke 36, før det på indikasjon Generelt gjøres ny ultralyd ved uke 38. Induksjon vurderes etter ca 38 uker. Generelt bør denne gruppen være indusert innen termindato Rask fostervekst henimot termin (akselererende AC eller MAD over 90 percentilen ) medfører økt risiko for fosterdød sannsynligvis p g a en relativ placentasvikt. Denne risikoen øker ved stigende blodtrykk/preeklampsi. PI i art umb kan være normal, men ved økende hypoksi vil endringen PI i art cerebri media falle og etter hvert PI i Ductus venosus øke. CTG påvirkes ved økende hypoksi og er en sentral undersøkelse ved mistanke om relativ placentasvikt. Fostervannsmengde i nedre normalområde hos et makrosomt barn kan bety «relativ oligohydramnion». Fosterbevegelser (anamnestisk og ved undersøkelsen) må også tillegges betydelig vekt. Fedme Tre hovedbudskap: Tore Henriksen Fødeseksjonen, Rikshospitalet OUS I: Fedme (adipositas) gir økt risiko for komplikasjoner i svangerskapet, fødsel og barseltid. II: Det transgenerasjonelle perspektivet: Effekten av det intrauterine miljø på neste generasjon(er) III. Den mest effektive måten å unngå fedme-relaterte komplikasjoner for mor og barn er å sikre en sunn livsstil og unngå fedme før svangerskapet inntrer Hvordan skaffer man seg kunnskap om det hjelper med tiltak for overvekt/fedme? 1. Fysiologisk kunnskap. For eksempel: Høyt blodsukker hos mor gir høyt blodsukker og høyt insulin hos barnet, som medfører høyt neonatalt kroppsfett 2. Klinisk erfaring. For eksempel: Reduser sukkerinntak i siste trimester stopper ofte en akslererende vekst av fostrets abdominalmål 3. Studier av befolkningsgrupper (populasjoner) Det går en grunnleggende forskjell mellom A. Observasjonsstudier og B. Intervensjonsstudier (clinical trials) A. Observasjonsstudier B. Intervensjonsstudier Observasjonsstudier f eks forekomsten av Svangerskapsdiabetes (GDM) Normalvektige Normalvektige Oddsen her kan være 2 av 100 for GDM Svangerskapsdiabetes, forekomst (prevalens). BMI over 30 Oddens her kan være 6 av 100 for GDM Observasjonsstudier Observasjonsstudier beskriver statistiskeSvangerskapssammenhenger mellom variable (f eks mellom fedme og diabetes), diabetes, forekomst. men sier ikke nødvendig noe om årsakssammenheng. BMI>30 RISIKOEN for å få GDM kan da angis som ODD RATIO (OR), som er: OR: 6 2 94 98 =3.1 Årsak? Overvekten (BMI)? Fordelingen av kroppsfett? Liten fysisk aktivitet? Miljøgifter? Ulik genetisk aktivitet (epigenetikk?) Gener? Intervensjonsstudier (randomisert studier, clinical trials) Observasjonsstudier viser tydelig at Studiepopulasjon: Kontrollgruppe Gravide Overvekt/fedme, vektøkning i svangerskapet og blodglukose (diabetes) Endepunkt (utfall, outcome): Loddtrekning F eks.: Svangerskapsdiabetes Intervensjonsgruppe a) Overvekt/fedme, b) høy vektøkning i svangerskapet c) Høyt blodsukker/diabetes hver for seg, og ikke minst sammen, Gruppene blir like (alderkjønn,vekt, udannelse etc ) øker risikoen for svangerskapskomplikasjoner og for sykdom hos mor og barn lengre sikt. Intervensjon: Kost og Fysisk aktivitet Risk of LGA (>90p) according to Maternal obesity, Gestational diabetes (GDM) and high Gestational Weight Gain (GWG) Overweight/obesity and pregnancy. Short and long term outcomes Bowers K et al Diabetologia 2013 10 Short term Consequences (mother/child) Risk of LGA Odds ratio Overweight/obesity Metabolic syndrome High blood glucose/ Diabetes High weight gain • Miscarriage • Preterm birth • Preeclampsia • Gestational diabetes • Thromboembolism • Congential malformations • Intrauterine fetal death • Delivery complications (Prolonged labour, Fetal distress, Vacuum/forceps, Cesarean section) • Neonate injuries • Maternal injuries/infections • Need for neonatal intensive care • Less breast feeding Long term consequences 0 GDM GWG Obesity GDM +GWG Obesity +GWH GDM +obesity BMI og risiko for fosterdød GDM +obesity+ GWG • Maternal Overweight Diabetes Anal dysf. • Child Diabetes Overweight Cancer Cardiovascular disease Overweight/obesity and pregnancy outcomes Observational studies: Cesarean section: Dose‐response Barau G et al BJOG 2006: Emergency Cesarean delivery: Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 Maternal pre-pregnancy BMI and fat mass index in the child at age of nine years Gale CR et al 2007 J Clin Endocrinol Meatbol at 9 years at 9 years * BMI >30kg/m2 versus BMI 20‐25 Overvekt/fedme hos gravide 1. Det er ingen tvil om at: Tilstanden fedme er en betydelig risikofaktor for svangerskapskomplikasjoner og helse senere (funnet ved observasjonelle studier) Men: 2. Hjelper det å intervenere i svangerskapet? Interventional studies Total gestational weight gain following dietary and/or physical activity intervention (in a general population) Interventional studies Total gestational weight gain following dietary intervention only (in a general population) The 2012 metaanalysis 2: Thangaratinam S et al BMJ May 2012 The 2012 metaanalysis 2: Thangaratinam S et al BMJ May 2012* Ved intervensjon med kost og fysisk aktivitet kan vektøkningen i svangersapet reduseres * Studyca population: med 1-2kg Any BMI 18.5 kg/m2 Diett synes å ha størst effekt (i svangerskapet) Interventional studies Pregnancy complications gain following dietary intervention during pregnancy (in a general population) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Interventional studies SGA and LGA following dietary intervention during pregnancy (in a general population) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Preeclampsia: Gestational Diabetes: Liten effekt på forekomsten av store barn (LGA). Ingen flere små barn (SGA) Preterm Delivery: Interventional studies Mean birth weight following dietary intervention during pregnancy Interventional studies Neonatal outcomes gain following dietary intervention during pregnancy (in a general population) (in a general population) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Shoulder dystocia 50 g reduksjon i fødselsvekt Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial. Posten L et al Lancet Diabetes Endocrinol. 2015 Er effekten av intervensjon større ved fedme (BMI > 30)? BMI ≥ 30, Intervensjon (kost, fysisk, gnerelle helseråd) mellom uke 15-18 fulle uker Mean BMI of 36·3, (SD 4·8). 772parametre randomly assigned to standard care Ingen effekt på metabolske (glukose, insulinantenatal og lipider) and 783 were allocated the behavioural intervention Men ca 0.5 kg mindre vektøkning i svangerskapet etter intervensjon Gestational diabetes: No difference: 26% after standard care, versus 25% after the intervention, p=0·68). Large for gestational age: No difference: 8% after standard care versus 9% after intervention, p=0·40. Major obstetric haemorrhage: No difference (1% vs 3%). Small-for-gestational-age (SGA, ≤5th customised birthweight centile: No difference: 6% vs 5% The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial Jodie M Dodd et al BMJ and BMC Med, 2014 Jodie M Dodd et al BMJ and BMC Med, 2014 Study group: Overweight/obese (BMI≥ 25 kg/m2. Secondary outcomes: Primary outcomes: Large for gestational age (LGA): No difference Birth weight > 4500g: Lifestyle: 2.15% versus Standard Care 3.69%. P = 0.04. Birth weight above 4000 g : Lifestyle advice 15% versus standard care 19% (p=0.04) Adjusted risk ratio (aRR) = 0.59; 95% CI 0.36 to 0.98; number needed to treat (NNT) = 66; 95% CI 34 to 950. aRR 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04 Respiratory distress syndrome: Lifestyle Advice 1.22% versus Standard Care 2.57%. P = 0.02. aRR = 0.47; 95% CI 0.24 to 0.90; NNT = 75; 95% CI 40 to 532. Oppsummering av hvilke utfall som kan påvirkes av intervensjon i svangerskapet (kost og fysisk aktivitet) Svært kort oppsummering I en generell fødepopulasjon. 1. Vektøkning ca 1.5‐2 kg. Effekten av kost tiltak synes størst. Kost og annen livsstilsintervensjon i svangerskapet Følgende må avente en ny metanalyse 2.Preeklampsi ? (Tangaratinam: Ca 30 % reduksjon I forkomsten?) 3.Gestasjonell diabetes? (Tangaratinam: Med diett : 60 % reduksjon) 4.Preterm fødsel? (Tangaratinam: Bare diett: 30 % reduksjon) 5.Fødselsvekt? (Tangaratinam: Sannsynligvis liten effekt ) 6.Store barn ? (Tangaratinam:> 4000g eller LGA, Dodd>4000g)? 7.Skulderdystoci? (Tangaratinam: 60 % reduksjon) 7.Respiratory stress? (Dodd: færre ved intervensjon) 8.Andre utfall: Sectio?: Sannsynligvis ingen effekt. Induksjon av fødsel: Sannsynligvis ingen effekt. Dette leder til to spørsmål 1. Hvorfor synes effekten av å intervenere i svangerskapet begrenset? (dog ikke fraværende) 2. Hva er konsekvensen? Dete er sikekrt vist at: 1.Gir en moderat reduksjon i vektøkningen (1-2 kg) 2. Andre? Ny metananlyse kommer som kan endre denne listen Fedme er mer enn BMI (kg/m2)! Placenta Systemic inflammatory response Cytokines Endothelial Insulin resistance/ activation diabetes Preeclampsia Glucose Insulin FFA receptor Tore Henriksen 2012 Placental inflammatory reaction Increased fatty acid transport? Glucose transport? BMI relaterte METABOLSKE endringer Dene matabolske og inflammatoriske Tilstanden fedme er et resultat av (åre) lang endring I kroppen Metabolske og inflammatoriske endringer • Overvekt og fedme medfører generelt i befolkningen en betydelig helserisiko. Svangerskap er en motiverende periode for informasjon om og oppfølging av overvekt og fedme. Fedme • Det er ingen holdepunkter for at råd om sunn kost og fysisk aktivitet hos gravide gir uheldige svangerskapsutfall (aktive slankeprogrammer anbefales ikke for gravide). Normalvektig 15 år Samlet vurdering av nytten av å intervenere hos gravide med overvekt/fedme for svangerskapsutfall 27 år Svangerskap • Ovenfor er dokumentasjonsnivået angitt for de viktige kliniske utfall, som det finnes data for. Dokumentasjonen er i stor grad basert på nye meta-analyser av randomiserte studier, som viser gunstige effekter, særlig av kostråd, på noen utfall, men ikke alle. • Den samlede vurderingen er at intervensjon med kost og tilpasset fysisk aktivitet bør gis alle gravide og spesielt til dem med overvekt og fedme. Prekonsepsjonell veiledning. Anbefales, hvis praktisk mulig, for alle med BMI over 30: Ved første svangerskapskontroll kartlegges: Grundig anamnese, medisinsk og om livsstil. Klinisk erfaring og fysiologisk kunnskap taler for at: Redusert BMI, Godt fysisk aktivitetsnivå • En eller flere medfølgende sykdommer (co-morbiditet)* ? • Familieanamnese • Obstetrisk anamnese: tidligere preeklampsi, svangerskapsdiabetes, tilveksthemning/placentasvikt, forløsning, post partum blødning) Råd: Som under svangerskapet, vanligvis med unntak av de spesielle tilskuddene. Mål: Etterfølgelse av rådene om kost og mosjon, vektreduksjon (5-10% eller mer), bedret fysisk kondisjon. (se også Helsedirektoratets hefte ”Gravid”. eller www.helsedirektoratet.no • Blodprøver i tillegg til vanlige blodprøver: Glukosebelastning? Tyreoideastatus vurderes Andre relevante blodprøver ved co-morbiditet God kontroll på medfølgende sykdommer (co-morbiditet) på konsepsjonstidspunktet spiller en viktig rolle for å redusere risikoen for komplikasjoner. Co-morbiditet: • Diabetes/glukoseintoleranse (se Diabeteskapitlene) • Hypertensjon • Trombotiske sykdommer • Autoimmune sykdommer (SLE, vaskulitter, nefropati) • Maternell hjertesykdom, • Meternell lungesykdom • Fedmeopererte (bariatrisk kirurgi) • Komplisert psykososiale anamnese • Andre tilstander som kan gi økt risiko form svangerskaps og fødselskomplikasjoner i kombinasjonen med fedme . Kvinner med overvekt og fedme uten relevant komorbiditet: Følges i primærhelsetjenesten hvis BMI er under 35. Ved BMI over 30 legges en plan for en tettere oppfølging med kost og andre livsstilsråd enn for gravide generelt. Ved BMI over 35-40* (fedme klasse II og III) henvises kvinnen til spesialist ved ca 24 ukers svangerskap, med oppfølging spesialist ved ca 32 og ca 36 uker. Oppfølgingen ved ca 32 uker bør være ved aktuelle fødepoliklinikk for planlegging av fødselen. *Grensen må vurderes ut fra lokale forhold (samhandling med primærhelsetjenesten, kapasitetsvurderinger og kompetanse). Vektøkning i svangerskapet ved GDM: Følger generelle retningslinjer Institute of Medicine (IOM) retningslinjer: Kvinner med relevant co-morbiditet BMI BMI BMI BMI Aktuelle co-morbiditet vil avgjøre grad av oppfølging ved spesialist/fødepoliklinikk. Ofte vil oppfølging i primærhelsetjenesten i samarbeid med spesialist være det optimale. (<20): (20-25.9): 26-29: >30: 12.5-18 kg 11.5-16 kg 7-11 kg 5-9 kg Men: Ved BMI 30-35 reduseres risikoen for noen uheldige svangerskapsutfall (preeklampsi, makrosomi) ved vektøkning 0-6 kg, kanskje litt økning av SGA Kost og andre livsstilsråd vil generelt være som for adipøse uten co-morbiditet, men tilpasset aktuelle pasient. Også denne gruppen må sikres minst en konsultasjon (ca 32 uker) ved aktuelle fødepoliklinikk for planlegging av fødselen. Ved BMI over 35 forslås vektøkning på 0-5 kg. I praksi vil noen gå noe ned i vekt. Det er akseptablet fortutsatt adekvat sammensatt kost og tilvekstkontroll slik som anbefalt OBS: mangelen vektøkning kan bety placentasvikt, derfor ultralydskontroll slik som anbefalt Fødselen ved fedme (BMI<30). Fødselen ved fedme • Ved start av fødselen eller ved muligheten for akutt forløsning før fødselsstart (f eks ikke-normalt CTG) legges to intravenøse tilganger. Planlegging av fødselen er vesentlig for adipøse gravide. Konsultasjon ved fødepoliklinikken ved ca 32 uker anbefales ved BMI >35, der også anestesilege bør orienteres. Induksjon: Ved BMI under 35 følges de generelle indikasjonene for induksjon (spesifikke medisinske indikasjoner og overtid). Ved BMI over 35 med ukomplisert svangerskap tas pasienten inn til vurdering for induksjon i løpet av den første uken etter termindato. Tidspunktet for induksjon vurderes da individuelt. Ved innleggelse i fødeavdelingen (alle fedmekategoriene) bør anestesilege og vakthavende gynekolog orienteres. • Tidlig epiduralkateter vurderes, for eventuelt senere aktivering. • Ved avvik i fødselsforløpet informeres gynekolog og anestesilege. • Fosterovervåkning. Kontinuerlig CTG, eventuelt STAN, med tidlig amniotomi og skalpelektrode. Ved bruk av ekstern CTG-registrering kan U2-proben være best. Kontroll mot mors puls anbefales. • Ved forløsning er det økt risiko for skulderdystoci både ved spontan og instrumentell forløsning og beredskap for skulderdystoci anbefales. • Operativ vaginal forløsning foreslås utført på operasjonsstue med mulighet for godt forberedt omgjøring til sectio. Helse og sykdom i et utvidet perspektiv Sectio • Regional anestesi der det er mulig • Eventuell hengende buk kan trekkes opp med taping av abdomen, hvis det er tid. • Hudsnitt: fortrinnsvis tverrsnitt • Antibiotikaprofylakse: Anbefales både ved akutte og elektive keisersnitt. • Post partum: Økt risiko for post partum blødninger. Risiko for infeksjon Økt risiko for trombose. Rask mobilisering og støttestrømper anbefales. Lavmolekylært heparin Alle med BMI over 40 foreslås gitt tromboseprofylakse uansett forløsningsmåte. Preconception al Nutrition Metabolic state Infections Alcohol/drugs Stress Pollution Tore Henriksen 2011 Cardiovasc. Diabetes Mental health Next Etc Generation(s) Sunn livsstil kan aldri være usunt! Takk ! 21.01.13 Retningslinjer for svangerskapsomsorgen Svangerskapsomsorgen i Norge Faglige retningslinjer er i prinsippet anbefalinger og råd, og skal bygge på god, oppdatert faglig kunnskap. Retningslinjene er ment som et hjelpemiddel og er ikke direkte rettslig bindende for mottakerne Fokus i svangerskapsomsorgen er flyttet fra kontroll til informasjon, råd og veiledning slik at den gravide i større grad kan ta ansvar for egen helse. Svangerskapsomsorgen skal planlegges for denne helt spesielle kvinnen og hennes familie, i lys av seleksjon og risikovurderinger. • • ”Formålet med svangerskapskontrollen er å sikre at svangerskap og fødsel forløper på en naturlig måte, slik at morens somatiske og psykiske helse, og hennes sosiale velvære, blir best mulig, sikre fosterets helse, slik at det kan fødes levedyktig og uten sykdom eller skade som kunne vært forhindret, oppdage og behandle sykdom og andre helsetruende forhold hos moren, slik at svangerskapet medfører minst mulig risiko for henne og barnet”. 180116 S Sand Oslogynekologene 1 • • 180116 S Sand Oslogynekologene Svangerskapskontrollen ‐ 1 • • • • • • Gravide kvinner er ikke syke, og de skal ikke sykeliggjøres Gravide kan ha sykdom som kompliserer graviditeten Gravide kan bli syke Den medisinske tryggheten må være GOD NOK Perinatalkomiteens arbeid: en andel av perinatale dødsfall kunne vært unngått Kvinnen selv er barnets beste og viktigste advokat I noen få tilfeller er det nødvendig å beskytte barnet overfor mors livsførsel Kartlegg den gravides behov Sørg for kunnskapsbasert omsorg. I byer og tettsteder er det et stort tilbud av alternative behandlere i svangerskapsomsorgen 180116 S Sand Oslogynekologene 3 Svangerskapskontrollen ‐ 2 1.Ressursfokus, mao hva er viktig å bruke tid på overfor denne pasienten 2.Skriftlig informasjonsmateriale? Av hva 3.Utfyllingen av helsekortet, hva er viktig og hvorfor 4.Organisering av kontrollene, hvordan vil du gjøre det, hvorfor, sykehist. 5.Utnytting av medarbeidere; BT/vekt/urin/evt CTG. Frigitt tid ‐ til hva? 6.Åpne for valg hos kvinnen (informasjon); a. Fødested? b. Spesielle behov, tidlig/sent/hele svangerskapet? c. Prenatal diagnostikk? Uke 10‐14 (CVB, Duotest, AC) Alle henvises til gen.veil. d. Behov for annen ”ekstern” ekspertise ( hematolog, kardiolog, etc) e. ”Ønskebrev”??? 180116 S Sand Oslogynekologene Risikovurdering ut fra somatiske, psykiske og sosiale forhold Tillit (ulike samlivsformer, ulike valg) skapes, det bestemmes ikke Ukjente (for deg) problemstillinger? Søk råd! Alle kan ikke alt!! 1. Seksuelle overgrep? 2. Omskjæring? 3. Rusmisbruk? 4. Psykiske og fysiske funksjonsproblemer? 5. Kronisk sykdom? 6. Inaktivitet 7. Overvekt 2016 • • • • • • • • Hvor skal hva henvises? Skaff deg et repertoar av samarbeidspartnere • 180116 S Sand Oslogynekologene 5 s sand oslogynekologene 4 Helsekort for gravide Svangerskapskontrollen ‐ 3 • • • 2 Dagens arbeidsredskap Ofte manuelt utfylt; uoversiktlig Inneholder nok informasjon? Håndskrevet Merknadsfelt: Bør brukes! Medikamenter: Et lite felt Liten plass for tiltak som skjer kontinuerlig i svangerskapet ift effekt og utvikling Liten plass til vurdering av arb. situasjon, plan for barseltiden og lignende Best egnet for de som trenger det minst? 180116 S Sand Oslogynekologene 6 21.01.13 Svangerskapskontrollen ‐ 4 Utføres mellom 11 og 12 kontroller i svangerskapet i Norge •Jordmor •Fastlege •Praktiserende spesialist •Sykehus poliklinikker •Kombinasjon av en eller flere Svangerskapskontrollen – 5 • • Ulike modeller for ”riktig” antall svangerskapskontroller WHO : 4 rutinekontroller og en rutineultralyd hos lavrisikogravide vs 5‐7 kontroller • Svangerskapshypertoni ved fødsel • Preeklampsi ved fødsel Lav fødselsvekt (<2500g) Alvorlig anemi etter fødsel Behandlingstrengende UVI Bruker u.s.: De ulike aktørene utfyller hverandre med ulik kompetanse Bruker ønske: Velge selv, helst gå i kombinasjon mellom lege og jordmor 180116 S Sand Oslogynekologene 7 Svangerskapskontrollen ‐ 6 • Hvem utfører svangerskapskontrollene(lavrisiko) • 16% kun til fastlegen • 3% kun til jordmor • Resten i kombinasjon fastlege/jm, fastlege/jm/spesialist, jm/spesialist, fastlege/spesialist • Kvinner med spesielle risikofaktorer henvises til høyere kompetansenivå i helsetjenesten 180116 S Sand Oslogynekologene 8 Svangerskapsomsorg hos spesialist utenfor sykehus ‐3 Dersom det foregående oppfylt: • Stort potensiale for å flytte noe av svangerskapsomsorgen ut av sykehusenes fødepoliklinikker • I dag er det mye dobbeltkontroller • Vil frigjøre tid og resurser i sykehusavdelingene Forutsetning: • Seleksjon • Tilgjengelige retningslinjer fra ”moder”‐ sykehuset • Samarbeidsmøter , ‐avtaler • Avklart for hva og på hvilket tidspunkt pasienter henvises • Lett tilgjengelighet inn til sykehusavdelingen Samhandling i praksis 180116 S Sand Oslogynekologene 9 Samhandling utenfor sykehus • • 180116 S Sand Oslogynekologene 10 Den nye SF kurven(rosa) sammenlignet med den gamle(grønne) I mange fagdisipliner jobber kan man jobbe i sykehus og/eller avtalepraksis/privatpraksis når ferdig spesialist Dagens spesialistutdanning er i stor grad forankret i problemstilling relatert til behandling i sykehus Praktiserende spesialisters landsforening = PSL Har arbeidet sammen med helsemyndighetene for at ½ år av spesialistutdanningen kan gjøres under veiledning i en avtalepraksis 2014 startet dette i urologi og hud Enklere å ha samhandling mellom fastlegene og spesialisthelsetjenesten utenfor sykehus. Sikret kontinuitet for pasienten bedre. 180116 S Sand Oslogynekologene 11 s sand oslogynekologene 180116 S Sand Oslogynekologene 12 21.01.13 Utsatte grupper i svangerskapsomsorgen • • • Kontrollene uke 24 ‐41 Psykososiale problemer • Ernæring • Alkoholmisbruk • Stoff/medikamentmisbruk • Vold og traumatisk stress • Psykiatri • Ingen nære rollemodeller Innvandrergrupper (spes fra 3. verden) • Lavt kunnskapsnivå, analfabetisme • Dårlig egenomsorg • FGM • Dårlig nettverk • Følger dårligere opp svangerskapskontrollene , misforståelser, fordommer begge veier • Språkproblemer Kost/ernæring • Anorexi/bullemi • Overvekt 180116 S Sand Oslogynekologene 13 180116 S Sand Oslogynekologene Tiltak som ikke anbefales som en del av rutineundersøkelsene i svangerskapet: Diverse instanser • • • • • • • • • • • Nakmi , post@nakmi.no ”Kommunikasjon via tolk” , Temahefte fra www.udi.no. ”Psykisk helse hos flyktninger”, Temahefte fra www.udi.no Arbeidstilsynets publikasjoner: e‐post: kundeservice@gyldendal.no Nasjonalt Folkehelseinstitutt : e‐post: publikasjon@fhi.no Statens forvaltningstjeneste : e‐post: publikasjonsbestilling@ft.dep.no www.publikasjoner.dep.no Trykksakekspedisjonen Sosial‐ og helsedirektoratet : e‐post: trykksak@shdir.no Støttesenter mot incest: 23 31 46 50: www.sentermotincest.no Mental Helses Hjelpetelefon: 810 30 030 (døgnåpent): www.mentalhelse.no Organisasjonen Voksne for Barn: 23 10 06 10: www.vfb.no Angstringen: 22 22 35 30: www.angstringen.no 180116 S Sand Oslogynekologene 15 Jm el fastl. Spesialist 22 24 28 TVUL TAUL CTG X X X X X X X X X X X X X X X 26 X 30 31 X 32 X 33 34 X 35 X 36 X 37 X 38 X 39 180116 S Sand Oslogynekologene • • • • • • • • • • • Hb‐måling hver gang Brystundersøkelse Gynekologisk undersøkelse Rutinemessig bruk av jerntilskudd Rutinemessig ferritin‐prøver av kvinner uten anemi Screening for klamydia, CMV, Hep C, GBS, toksoplasmose Screening for prematur fødsel m/ cx vurdering: ved UL eller GU Telling av fosterbevegelser Rutinemessig CTG i svangerskap for kvinner med normalt svangerskap Rutinemessig UL etter 24 uker Rutinemessig dopplermåling av navlesnorsarterier for lavrisikogravide 180116 S Sand Oslogynekologene Lavrisiko tvillingsvangerskap Uke X 17 s sand oslogynekologene 14 16
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