Activin A, hypoxia and the prediction of obstetric outcomes

On the back of sheep experiments showing that uterine hypoxia induces a rapid and sustained elevation of fetal activin A levels, we undertook two prospective studies to explore whether this novel observation could be exploited clinically. The first was a prospective labour ward study investigating whether umbilical arterial activin A levels at delivery correlated with either neonatal hypoxic ischaemic encephalopathy or pH. Unfortunately, we were unable to demonstrate a link with either, but found that levels were significantly depressed among those who had an emergency Caesarean section, suggesting a possible role in active labour. Second, we investigated the link between activin A and intrauterine growth restriction (IUGR), a condition of fetoplacental hypoxia, by measuring levels in women presenting for antenatal ultrasound biometry with clinical suspicion of a small baby. We found that, compared to pregnancies with a baby that was small for gestational age (SGA) but otherwise healthy, levels were 2.4 and 8 times higher, respectively, in pregnancies complicated by IUGR, and those complicated by both IUGR and preeclampsia. However, a single blood sample of activin A was unable to distinguish between IUGR and SGA pregnancies with sufficient sensitivity to be clinically useful. Our studies were unable to demonstrate clinical utility for the experimental observation linking activin A and hypoxia.