Association between progesterone treatment and neonatal outcome in preterm births: a retrospective analysis

This retrospective study was conducted to determine if infants born prematurely despite prophylactic maternal progesterone treatment during pregnancy may still benefit from its adjunct properties and have decreased neonatal complications. 248 women treated with vaginal/intramuscular progesterone during pregnancy and 2519 controls who gave birth to a preterm newborn (24 + 0-36 + 6 gestational weeks) at a tertiary medical centre in 2012-2019. The primary outcome measure was neonatal infectious composite outcome. Secondary outcome measures were other maternal and neonatal complications. Compared to controls, the study group was characterised by lower gestational age at birth (35.0 ± 2.66 vs. 36.0 ± 2.23 weeks, p < .001), lower birth weight (2294 vs. 2485 g, p < .001), higher rates of neonatal infectious composite outcome (27.82 vs. 21.36%, p = 0.024), NICU admission, periventricular leukomalacia, and mechanical ventilation. The higher neonatal infectious composite outcome is likely associated with the lower gestational age at birth in this high-risk group and not the progesterone treatment per se.IMPACT STATEMENTWhat is already known on this subject? Several randomised controlled trials have shown that progesterone administration in pregnancy significantly reduced the rate and complications of preterm birth. A recent study reported that vaginal administration of progesterone during pregnancy was more effective than intramuscular administration in decreasing vaginal group B Streptococcus (GBS) colonisation. This finding raises the question of whether progesterone treatment may have additional benefits besides preventing preterm birth and may reduce neonatal complication rate in preterm infants.What do the results of this study add? This is the first study examining the impact of gestational progesterone exposure on outcomes of preterm infants. The primary objective was a composite measure of infectious neonatal outcomes. Newborns who had progesterone exposure on average had lower gestational age, lower birth weight and higher neonatal infectious composite outcome. The significant difference is explained by lower gestational age.What are the implications of these findings for clinical practice and/or further research? Progesterone is widely used to prevent preterm birth, and may have important additive effects even when prematurity is not avoided. Although the findings did not support our initial hypothesis, they warrant further examination with larger cohorts.