The Antenatal Corticosteroids Trial (ACT)’s explanations for neonatal mortality - a secondary analysis

Abstract

BackgroundThe Antenatal Corticosteroid Trial assessed the feasibility, effectiveness, and safety of a multifaceted intervention to increase the use of antenatal corticosteroids (ACS) in mothers at risk of preterm birth at all levels of care in low and middle-income countries. The intervention effectively increased the use of ACS but was associated with an overall increase in neonatal deaths. We aimed to explore plausible pathways through which this intervention increased neonatal mortality.MethodsWe conducted a series of secondary analyses to assess whether ACS or other components of the multifaceted intervention that might have affected the quality of care contributed to the increased mortality observed: 1) we compared the proportion of neonatal deaths receiving ACS between the intervention and control groups; 2) we compared the antenatal and delivery care process in all births between groups; 3) we compared the rates of possible severe bacterial infection between groups; and 4) we compared the frequency of factors related to ACS administration or maternal high risk conditions at administration between the babies who died and those who survived 28 days among all births in the intervention group identified as high risk for preterm birth and received ACS.ResultsThe ACS exposure among the infants who died up to 28 days was 29 % in the intervention group compared to 6 % in controls. No substantial differences were observed in antenatal and delivery care process between groups. The risk of pSBI plus neonatal death was significantly increased in intervention clusters compared to controls (2.4 % vs. 2.0 %, adjusted RR 1.17, 95 % CI 1.04–1.30, p = 0.008], primarily for infants with birth weight at or above the 25th percentile. Regarding factors related to ACS administration, term infants who died were more likely to have mothers who received ACS within 7 days of delivery compared to those who survived 28 days (26.5 % vs 17.9 %, p = 0.014), and their mothers were more likely to have been identified as high risk for hypertension and less likely for signs of preterm labor.ConclusionsThese results suggest that ACS more than other components of the intervention may have contributed to the overall increased neonatal mortality. ACS may have also been involved in the observed increased risk of neonatal infection and death. Further trials are urgently needed to clarify the effectiveness and safety of ACS on neonatal health in low resource settings.

Risk factors for possible serious bacterial infection in a rural cohort of young infants in central India

“…This may have been due to the administration of corticosteroids to women thought to be at risk for preterm birth who ultimately delivered late preterm or term infants. On secondary analysis of these data, there was no significant increase in risk of PSBI in the intervention clusters who received antenatal corticosteroids when compared to the control clusters [ 31 ]. When the composite outcome of PSBI and death was analyzed, risk was increased in the intervention clusters (RR 1.17, 95 % CI 1.04–1.30), which was driven by the difference among infants with a birth weight greater than or equal to the 25 th percentile.…”

Low-dose betamethasone-acetate for fetal lung maturation in preterm sheep

“…A multicenter randomized trial in low- and middle-income countries found that ANS not only did not decrease mortality rates for infants who were born with a birthweight <5th percentile but it also increased neonatal mortality rates for all infants who were exposed to ANS prenatally, which could not be attributed to other components of the treatment intervention. 19 , 20 …”

Sinnvolle Steroidprophylaxe bei drohender Frühgeburt – State of the art

“…Publizierte Daten zur Anwendung der pränatalen Steroidtherapie in hoch entwickelten Versorgungssystemen stimmen mit Studien, die in Länder mit eingeschränkten Ressourcen und mit niedrigem Einkommen erhoben wurden, nicht überein. In ärmeren Ländern konnte bei der Antenatal Corticosteroids Trial (ACT) eine erhöhte Neugeborenen-Mortalität und eine steigende neonatale und maternale Infektionsrate nachgewiesen werden [31,32]. Auch wenn eine klare Interpretation der adversen Daten nicht möglich erscheint, sollte laut dem Ergebnis der sekundären Analyse die pränatale Kortikosteroidapplikation in Regionen mit wenig Ressourcen in derer Effektivität und Sicherheit weiter untersucht werden [31,32].…”