Among the most immature infants, mortality and morbidity are common even if they receive active neonatal intensive care, a new systematic review has attempted to find out how common. Backes CH, et al. Proactive Neonatal Treatment at 22 Weeks of Gestation: A Systematic Review and Meta-Analysis. Am J Obstet Gynecol. 2020. The authors of this study searched for publications detailing survival among infants who received active neonatal intervention. Sample sizes range from 2 to over 1,000, and definitions of what constituted active interventions varied between the component studies. The range of survival was between 0 and 100%, both of those extremes being from very small studies. As you can see from this figure, Ehret’s multicentre study contributed by far the most weight to the analysis, which overall shows somewhere between 1/3 and 1/4 babies survive with active treatment.
Ehret et al, the largest of the studies, with over 1000 22 weeks babies, showed that survival was 18% among the babies who received active neonatal care without the benefit of antenatal steroids, compared to 39% among those who received both antenatal steroids and active neonatal care. This systematic review confirms a higher survival at 22 weeks among babies who received antenatal steroids. It is possible, of course, that steroids are more likely to be given when other risk factors are absent and perhaps, therefore, are given to lower risk mothers; as observational data they cannot be relied on as absolute proof of efficacy. But it is also likely that when the Obstetric and Neonatal team have a positive attitude they are more likely to give steroids and intervene appropriately.
The difficulties that Carl Backes and his group had doing this study can be illustrated by the fact that the estimate of survival without moderate or severe developmental difficulties is 37%, which is higher than the estimate of overall survival, 29%! Clearly, this is because the studies evaluating development were taken from groups with higher survival. The quality of the data for the death and developmental delay outcome was very low.
A survival rate of somewhere between a third and a quarter is a baseline against which risk factors in addition to gestational age should be included (sex, estimated weight, chorioamnionitis), and, despite the group’s appropriate concerns about the quality of the data, it is a reasonable starting point from which to have conversations with prospective parents with threatened profoundly preterm delivery. If there is a possibility of active intensive care, then the systematic review confirms the value of antenatal steroid administration, which can be started immediately, and does not necessarily commit the team to active intensive care.
Travelling to centres with good outcomes among these babies, I am struck by the variety of clinical protocols and processes of NICU care, what the centres have in common is a positive attitude, that these babies can survive, even though mortality is high, and that a team approach with close collaboration with the obstetricians is key.
The attitude of Obstetricians around the world, and in the USA, varies from person to person and from perinatal centre to perinatal centre. But the attitude of the US obstetrics professional organisation, ACOG, as far as it can be gathered from their patient information page on their website /faqs/pregnancy/extremely-preterm-birth is very concerning, here is an extract:
What are the health outcomes for extremely preterm babies?
Medical advances have helped some preterm babies survive and overcome health challenges. However, the chances that a baby born extremely early will survive without disability are still small. With very rare exceptions, babies born before 23 weeks of pregnancy do not survive. Although survival rates increase for babies born between 23 weeks and 25 weeks of pregnancy, most survivors face serious, often lifelong disabilities. As gestational age increases, the outlook for preterm babies improves.
The copyright at the bottom of the page is dated August 2019. It needs an update! One in four is not a “very rare exception” and most survivors do not have serious disabilities, most have no, minor or moderate disabilities.
I think that active intervention at 22 weeks should not be universal, babies with additional risk factors may have a very low chance of survival, but this data confirms that survival rates that are a reasonable justification for active intervention are possible in more than one centre. Tertiary/quaternary perinatal centres should train and put in place procedures for active care of babies thought to be at 22 weeks, or be prepared to transfer mothers to centres that have a positive attitude and teams ready to actively intervene.