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Published on: June 29, 2013
Free Fetal Haemoglobin in Severe Early-Onset Fetal Growth Restriction: A Prospective Multi-Centre Study
Adam Brook1,2, Georgia Baynes1,2, Jonathan Scargill3
1Maternal and Fetal Health Research Centre, University of Manchester, Manchester, UK.
Insights
Elevated free foetal haemoglobin (fHbF) and inadequate heme defences are linked to fetal distress in early-onset fetal growth restriction (FGR). These factors correlate with poor umbilical artery Doppler findings, suggesting increased placental vascular resistance and inflammation.
Area of Science:
- Perinatal Medicine
- Foetal Physiology
- Maternal-Foetal Interface
Background:
- Severe early-onset foetal growth restriction (FGR) presents significant challenges in perinatal care.
- Understanding the biochemical and circulatory markers associated with FGR is crucial for improving foetal outcomes.
- Foetal haemoglobin (HbF) and heme metabolism play roles in foetal development and stress responses.
Purpose of the Study:
- To investigate foetal circulating free foetal haemoglobin (fHbF) levels and heme defence mechanisms in severe early-onset FGR.
- To correlate these biochemical markers with foetal circulatory biometry and foetal sex.
- To compare findings in FGR pregnancies with those of normal term births and late-onset FGR.
Main Methods:
- Prospective study of 20 pregnancies with severe early-onset FGR (EFW <3rd centile, <600g at 20-26 weeks).
- Measurement of cord blood fHbF and key heme-scavenger proteins (e.g., hemopexin).
- Comparison with 26 normal term births and 12 births with late-onset FGR; assessment of foetal vascular obstetric biometry.
Main Results:
- fHbF levels were significantly elevated in early-onset FGR compared to normal pregnancy (p<0.0001).
- Hemopexin was downregulated in both early- and late-onset FGR compared to normal pregnancy (p<0.001 and p<0.0001, respectively).
- Elevated fHbF was observed in male foetuses with early-onset FGR. Heme-scavenger levels correlated with indicators of placental vascular resistance and gestational age at delivery.
Conclusions:
- Overproduction of fHbF and insufficient heme defence likely contribute to foetal distress in early-onset FGR.
- These biochemical imbalances are associated with poor umbilical arterial Doppler findings, indicative of increased placental vascular resistance and inflammation.
- Findings highlight potential targets for therapeutic interventions in managing severe FGR.
Objective:
To assess fetal circulating free fetal haemoglobin (fHbF) levels and heme defences, correlated to fetal circulatory biometry and fetal sex in severe early-onset fetal growth restriction (FGR).
Design, Setting And Population:
A prospective study severe early-onset fetal growth restriction pregnancies with close clinical management (estimated fetal weight (EFW) < 3rd centile and < 600 g at 20-26 + 6 weeks; N = 20).
Method & Main Outcome Measures:
Temporal fetal vascular obstetric biometry was recorded. Cord blood fHbF and key heme-scavenger defences were measured and compared with normal term births (N = 26) and births with late-onset FGR (N = 12).
Results:
fHbF was elevated in early-onset FGR compared with normal pregnancy: 0.437(0.337/0.753) mg/mL; and 0.098 (0.045/0.264) mg/mL, respectively (p < 0.0001); whilst hemopexin was downregulated in early- (p < 0.001) and late-onset FGR (p < 0.0001), compared to normal pregnancy: 36(14/81) μg/mL, 25(19/40) μg/mL, and 155(132/219) μg/mL, respectively; median (interquartile ranges). Early-onset FGR male fetuses had higher HbF compared with the normal males: 0.710(0.433/0.857) mg/mL; (p < 0.001); 0.099(0.043/0.246) mg/mL, respectively; median (interquartile ranges). In early-onset FGR, ratios of mid-cerebral artery and umbilical artery pulsatility indices correlated positively with heme-scavenger levels (hemopexin and a heme-handling composite measure: p < 0.05, r = 0.672; and p < 0.01, r = 0.620; respectively), indicating lower levels are associated with cerebral vascular redistribution. These heme handling measures also positively correlated with gestational age at delivery (r = 0.713 and r = 0.642, respectively, p < 0.01, both) and birthweight (r = 0.742, p < 0.001; and r = 0.523, p < 0.05; respectively).
Conclusion:
Overproduction of fHbF and an inadequate heme defence may contribute to fetal distress and poor umbilical arterial Dopplers in early onset FGR due to elevated placental vascular resistance and vascular inflammation.
