Amniotic Fluid: The Role in Fetal Health A/Prof Henry Murray John Hunter Hospital University of Newcastle Australia

Perceived wisdom Oligohydramnios Hydramnios Poor placental perfusion → fetal hypoxia → fetal vasoconstriction incl renal arteries → oligohydramnios Oligohydramnios is a warning of fetal compromise Hydramnios Excess urine or interrupted swallowing

Daily contribution to amniotic fluid - near term (per 24 hours) Fetal urine 800 – 1200ml Fetal lung 170ml Oral-nasal secretions 25ml Transmembranous flows 10ml Fetal swallowing 500-1000ml Intramembranous flow 200 – 400ml Fetal circulation - Am Fluid interflow Beall et al Placenta 2007 28(8-9):816-23.

Daily contribution to amniotic fluid - near term (per 24 hours) Fetal urine 800 – 1200ml Fetal lung 170ml Oral-nasal secretions 25ml Transmembranous flows 10ml Fetal swallowing 500-1000ml Intramembranous flow 200 – 400ml Fetal circulation - Am Fluid interflow But what is normal and abnormal volume??

Amniotic fluid volume (AFV) Accurate measure of AFV is by direct measure at operation or dye dilution – Dieckman et al 1933 Am J Obstet Gynecol, 25:623 Neslen et al 1954 Obstet Gynecol, 3, 598 Charles et al 1965 Am J Obstet Gynecol 93:1042 Brace et al 1989 Am J Obstet Gynecol 161:282 Weeks 18 22 28 34 40 42 AFV (mls) 482 630 785 984 836 544 n = 1067+

Oligohydramnios - third trimester By definition - volume < 2.5%ile 2.5%ile at 30 weeks (300 mls) Brace et al 1989 Am J Obstet Gynecol 161:282 By default definition in 3rd trimester Less than 300 mls Accurate prediction by ultrasound 10-15%

SONOGRAPHIC ESTIMATIONS OF AMNIOTIC FLUID VOLUME Technique Hydramnios Normal Borderline Oligo hydramnios Single Deepest pocket >8 2-8 cm 1-2 cm <1 cm Two-diameter pocket >50 cm2 15.1-50.0 cm2    -- < 5 cm2 Amniotic fluid index >24 cm 8.1-24.0 cm 5.1-8.0 cm ≤5 cm Larmon et al Obstet Gynecol Clin North Am. 1998 Oligohydramnios:- 0.5 – 5% third trimester Up to 12% postterm

Oligohydramnios Causes vary with trimester

Oligohydramnios by trimester - what does it mean?? First trimester Gestational sac diameter – CRL <5mm Cause unknown – poor prognosis Second trimester Fetal anomaly - 51% PPROM - 34% Placental abrupt - 7% IUGR - 5% Idiopathic - 3% - Shipp et al, Ultrasound Obstet Gynecol, 1996, 7, 108.

Oligohydramnios by Trimester Third trimester 53% - no obvious cause ? Associated with abnormal aquaporin molecules in placental membranes 28% PPROM/maternal disease/fetal anomaly 19% IUGR/placental insufficiency Radius trial Initially low risk women Zhang et al BJOG 2004 111 220

Case 1 Mrs S G1 P0 32 weeks Presents with gestational hypertension BP 130/95, no protein Blood testing:- normal Started on Labetalol 100mg TDS

Case 1 Mrs S G1 P0 32 weeks Presents with gestational hypertension BP 130/95, no protein Blood testing:- normal Started on Labetalol 100mg TDS USS normal growth, normal Dopplers AFI 4.8cms - Oligohydramnios High risk??

Oligohydramnios in 3rd trimester - Does it predict poor outcomes? No evidence that oligohydramnios in the absence of abnormal Doppler flow indices in the morphologically normal fetus is an indication of significant risk or is an indication for induction or delivery Magann et al Am J Obstet Gynaecol 1999 180 1330 Magann et al Am J Obstet Gynaecol 1999 180 1354 Unterscheider et al Am J Obstet Gynecol 2013 208 290

‘Isolated Oligohydramnios’ - a word of warning 1 prospective cohort AFI ≤ 8cm vs normal AFI at 32 weeks Increased risk IUGR developing OR 5.2, 95%CI 1.6 – 22.0 Roberts et al J Perinatal Med 1998 26 390 Need to monitor pregnancy Maternal disease Placental dysfunction

Case 1 Mrs S Remained on Labetalol BP stable Rescanned in 4 days AFI stable, Dopplers normal Repeat scanning 3days later AFI 6 – 8cms Rescanned after 1 week - normal Delivered at 38 weeks

Oligohydramnios Given that isolated oligohydramnios does worry us Is there anything that we can do other than watch?

What can we do??? Cochrane review Maternal hydration 4 studies, 122 women, 2L oral rehydration Increase in AFV in normal and low AFI after 2 hours AFI increase Oligohydramnios 2.01cm 95%CI 1.43 – 2.60 Normal 4.50cm 95%CI 2.92 – 6.08 Hofmeyr GJ, etal. Cochrane Database of Systematic Reviews 2002, Issue 1. Art. No.: CD000134. DOI: 10.1002/14651858.CD000134. NB - Increase not sustained

Oligohydramnios in the third trimester - Management Pregnancy with AFI ≤ 5.0 at 28-40 weeks Assess for PPROM Abn Doppler IUGR Anomaly Maternal disease Fetal compromise Y Consider admission/steroids/ delivery as appropriate Are anomalies found? N Consider maternal oral rehydration - Is AFI still ≤ 5.0 Surveillance of mother and fetus - rescan 3 days Deliver if IUGR etc Y N Y Is AFI 5-8? Rescan in 7 days N If AFI > 8, Monitor growth/liquor 2 weekly

Oligohydramnios postdates Morris et al BJOG. 2003 Nov;110(11):989-94. An AFI <5 cm was significantly associated with birth asphyxia meconium aspiration, caesarean section for fetal distress in labour, a cord arterial pH <7.0 at delivery and low Apgar scores Sensitivity of AFI was low at 28.6%, 12% and 11.5% for major adverse outcome, fetal distress in labour or admission to the neonatal unit

Oligohydramnios postdates AFI < 5cms Morbidity from isolated oligohydramnios increases after 41+ weeks Morris et al BJOG. 2003 Nov;110(11):989-94. Reasonable to induce for low AFI at 41-42 weeks Oligohydramnios at 42 weeks associated with significant pathology Vayssiere et al Eur J Obstet Gynecol Reprod Biol 2013 169 10

Increased liquor (Hydramnios) Defined as liquor above 97.5%ile Single pocket > 8cm or AFI > 24cm Mild 24 - 30cms Moderate 30 – 40 cms Severe > 40 cms Polyhydramnios is a clinical definition Fetal parts not felt

Increased liquor Fetal morbidity and mortality is related to the degree of hydramnios (AFI > 40cms = 60% neonatal mortality)

Case 2 Mrs T G1 P0 Rh neg Now 31 weeks – SHH 39cms Uncomfortable, polyhydramnios, your USS shows AFI 34cms She cannot eat, sleep, is dyspnoeic. Not contracting – yet Normal USS at 18 weeks

Causes of anomaly found after 18 week scan Fetal anomaly of Swallowing Micturition Pressure in fetal chest/right heart

Abnormal Fetal Swallowing Fetal anomaly Neck Teratoma, thyroid Gut atresias Neurological/muscular abnormalities Myotonic dystrophy Aneuploidy

Excess Fetal Micturition Metabolic Diabetes Cardiac congestion TTTS, TRAP Immune and nonimmune hydrops Anaemia (haemoglobinopathy, parvovirus, Rh ) CMV, Toxo etc Renal Nephrosis

Excess pressure in the fetal chest/Right heart Skeletal dysplasias Cardiac anomalies Cardiac arrhythmias SVT Chest lesions CCAM Pulmonary sequestration etc

Causes of anomaly found after 18 week scan Fetal anomaly Placental Haemochorioma Idiopathic

Idiopathic Intramembranous fluid production ? Anomalous fluid channels 60+% transient and resolve before delivery Commoner in multips Genetic Fetal macrosomia (?epigenetics)

Excess liquor – Management of Mrs S Assessment Full history for ? familial muscular disorder, ? Infection, ? antibodies from transfusion Tertiary USS as AFI > 30cms Anomaly, fetal anaemia, congenital infection etc Aneuploidy assessment esp if IUGR present

Excess liquor – Management of Mrs S Assessment Full history for ? familial muscular disorder, ? Infection, ? antibodies from transfusion Tertiary USS as AFI > 30cms Anomaly, fetal anaemia, congenital infection etc Aneuploidy assessment esp if IUGR present Bloods for Haemoglobinopathy, Group and antibodies, GTT, Infection (Toxoplasmosis, CMV, Parvovirus)

Excess liquor – Management Appropriate intervention to avoid early delivery Fetal transfusion for anaemia Karyotype/Counselling for fetal anomaly Serial Amniorereduction/ nonsteroidals to 33 weeks If true symptomatic polyhydramnios only Deliver as close to term as possible with appropriate paediatric presence

Hydramnios is high risk - (AFI > 30cms) Perinatal mortality rate 4x increased 49 per 1000 births vs 14 per 1000 (P < .001). Prematurity, Anomaly, Asphyxia – poor placental perfusion Anomaly rate 25x increased 8.4% versus 0.3%; P < .001 Caesarean rate 3x increased 47.0% versus 16.4%; P < .001 Biggio et al Obstet Gynecol 1999;94:773-7

Amniotic fluid Window onto fetal health Oligohydramnios and Hydramnios Nonspecific Need close investigation

Risks - other Risks to mother Risks to fetus Discomfort, preterm labour, maternal mirror syndrome (esp in fetal hydrops), preeclampsia, respiratory compromise, PPROM +/- abruption, Labour dystocia, PPH Risks to fetus Decreased placental perfusion, prematurity

Issues with measurement Fetal position/movements Better to use Single deepest pocket/2D pocket Pressure of transducer Error Intraobserver error 11% Interobserver error 15% Better to use Amniotic fluid index NB:- AFI will increase the diagnosis of oligohydramnios compared with SDP (RR 1.7, 95% CI 1.5-1.8) Magann et AM J Obstet Gynecol, 1999, 180, 1330)

Correlation with AFV No Ultrasound technique can accurately measure AFV Is USS assessment of amniotic fluid any use?

Isolated Oligohydramnios – is intervention justified? What do the experts do? Survey of MFM/perinatologists 92% respondents would induce before 39 weeks Only 33% believed there would be a better outcome due to the induction Schwartz et al J Mat Fetal Med 2009 22 357

Outcomes - High risk pregnancies - AFI ≤ 5 Outcomes - High risk pregnancies - AFI ≤ 5.0cms vs normal (antenatal to 41 weeks) Metaanalysis Chauhan et al 1999 Am J Obstet Gynecol 18 reports, 10,551 women Raised LUSCS for FHR anomaly RR 2.2 (1.5 – 3.4) Apgar < 7 @ 5min RR 5.2 (2.4 - 11.3) pH < 7.0 ns Historical comparative study Casey et al Am J Obstet Gynecol 2000 182 909 6423 women – 2.3% low AFI Raised induction - 42 vs 18% (p<0.001) Stillbirth - 1.4 vs 0.3% (p<0.03) Abnormal FHR - 48 vs 39% (p<0.03) NICU - 7 vs 2% (p<0.001) Neonatal death - 5.0 vs 0.3% (p<0.001)

Isolated oligohydramnios It is clear that isolated oligohydramnios worries us Can we do anything about it other than induce?

Cochrane review Conclusions ‘...may be beneficial in the management of oligohydramnios and the prevention of oligohydramnios during labour or prior to ECV. Controlled trials are needed to assess the clinical benefits....’ Given the lack of evidence that the low AFI is pathological, oral hydration is probably treating the obstetrician not the pregnancy!

Oligohydramnios postdates Morris et al BJOG. 2003 Nov;110(11):989-94. An AFI <5 cm, but not a single deepest pool <2 cm, was significantly associated with birth asphyxia meconium aspiration, caesarean section for fetal distress in labour, a cord arterial pH <7 at delivery and low Apgar scores Sensitivity of AFI was low at 28.6%, 12% and 11.5% for major adverse outcome, fetal distress in labour or admission to the neonatal unit

Oligohydramnios postdates Morris et al BJOG. 2003 Nov;110(11):989-94. Routine use of AFI is likely to lead to increased obstetric intervention without improvement in perinatal outcomes

Issues with measurement Fetal position/movements Fok et al Ultrasound Obstet Gynecol, 2006, 28, 162 Pressure of transducer Flack et al Am J Obstet Gynecol, 1994, 171, 218 Error Intraobserver error 11% Interobserver error 15% Brunner et al, Am J Obstet Gynecol, 1993, 168, 1309

Amniotic fluid volume vs ultrasound assessment 24 weeks – term Detection of oligohydramnios Sensitivity Specificity SDP (< 2cm) 0.18 0.68 AFI (≤ 5cm) 0.08 0.71 AFI over diagnosis of oligohydramnios 89% Dildy et al, 1992, Am J Obstet Gynecol 167 986 Magann et al 1994 Obstet Gynecol 83, 959 Chauhan et al 1997 Am J Obstet Gynecol 177 291 Magann et al 2004 Am J Obstet Gynecol 190 164

Isolated Oligohydramnios – is intervention justified? What do the experts do? Survey of MFM/perinatologists 92% respondents would induce before 39 weeks Only 33% believed there would be a better outcome due to the induction Schwartz et al J Mat Fetal Med 2009 22 357

Cochrane review Hofmeyer 2002 Conclusions ‘...may be beneficial in the management of oligohydramnios and the prevention of oligohydramnios during labour or prior to ECV. Controlled trials are needed to assess the clinical benefits....’ Given the lack of evidence that the low AFI is pathological, oral hydration is probably treating the obstetrician not the pregnancy!

Isolated oligohydramnios It is clear that isolated oligohydramnios worries us Can we do anything about it other than induce?

Hydramnios is high risk (AFI > 30 mm) Congenital malformations 44.5% 10.3% of the infants were stillborn, 41% had more than one malformation, 14.5% had a chromosomal abnormality. 290 cases of polyhydramnios in 225,669 consecutive pregnancies Stoll et al Community Genet 1999;2:36-42)

Isolated oligohydramnios - No fetal, maternal or Doppler pathology Perinatal outcomes Meta-analysis Rossi et al Eur J Obstet Gynecol Reprod Biol 2013 162 4 articles 679 low AFI vs 3264 normal AFI Tendency to increased intervention in low AFI OR 2.30 (95%CI 1.00 – 5.29) No differences in Meconium, Apgar scores, umbilical cord pH, SGA, NICU or Perinatal Death Small numbers and did induction save morbidity??

Induction in otherwise low risk women 54 women at 40 weeks randomised to induction vs expectant management for AFI ≤ 5cm No difference in UA pH, Apgar scores, NICU admission Ek et al, Fetal Diag Ther 2005 20 182 All studies have tiny numbers