Progesterone and prolactin levels in pregnant women living with HIV who delivered preterm and low birthweight infants: A nested case-control study

Background Antiretroviral therapy (ART) is associated with high rates of adverse birth outcomes, including preterm birth and low birthweight. Studies suggest that progesterone and prolactin may play important intermediary roles. Methods We analyzed data from the Antenatal Component of the PROMISE trial, a multi-center study of pregnant women taking antiretroviral regimens (lopinavir/ritonavir-containing ART or zidovudine alone) to prevent mother-to-child HIV transmission. In a nested case-control study, we compared data from women who gave birth to preterm (<37 weeks gestation) and/or low birthweight (<2500 g) infants to matched individuals who did not. We measured serum progesterone and prolactin at 24–34 weeks gestation. We used conditional logistic regression to describe relationships between hormone levels, birth outcomes, and antiretroviral regimens. Results 299 women and their newborns were included (146 cases, 153 controls). When compared to women receiving zidovudine alone, those on ART had higher odds of progesterone levels under the 10^th percentile (adjusted odds ratio [AOR]:2.34, 95%CI:1.41–3.89) and 25^th percentile (AOR:2.07, 95%CI:1.46–2.94). However, higher levels of progesterone—rather than lower levels—were associated with our composite case outcome at the 10^th percentile (AOR:1.88, 95%CI:0.77–4.59) and 25^th percentile (AOR:1.96, 95%CI:1.06–3.61). Associations were not observed between prolactin, antiretroviral regimen, and birth outcomes. Conclusion We observed lower progesterone levels among women allocated to ART regimens; however, higher progesterone levels were associated with preterm birth and/or low birthweight. While features of the study design may have contributed to these findings, they nevertheless highlight the potentially complex mechanisms underpinning adverse birth outcomes and HIV.