Latency antibiotics linked to prolonged pregnancy duration and improved survival after previable PPROM

Administration of antibiotics after previable preterm prelabor rupture of membranes (PPROM) was associated with a significant prolongation of latency, along with higher rates of neonatal survival to discharge and lower rates of intrauterine fetal demise (IUFD), according to a single-center retrospective cohort study published in Pregnancy. The findings address a gestational age range in which clinical guidance on antibiotic use has remained limited due to a scarcity of data.

PPROM, defined as rupture of fetal membranes before the onset of labor prior to 37 0/7 weeks' gestation, complicates 2% to 3% of pregnancies. Previable PPROM, occurring before the gestational age of viability, is far rarer, affecting less than 1% of all pregnancies. While most US institutions consider 24 0/7 weeks the threshold of postnatal viability, some centers with appropriate resources may offer a trial of resuscitation as early as 22 0/7 weeks based on patient preference following counseling. Even in advanced care settings, previable PPROM carries significant fetal and neonatal morbidity and mortality, including fetal or neonatal demise, necrotizing enterocolitis, intraventricular hemorrhage, respiratory distress syndrome, and pulmonary hypoplasia, alongside substantial maternal risks such as intraamniotic infection, placental abruption, hemorrhage, and in some cases maternal sepsis or death.

Investigating antenatal antibiotics, latency after previable PPROM

While broad-spectrum antibiotics, often referred to as latency antibiotics, have become standard of care in expectant management of preterm PROM at 24 0/7 weeks and beyond due to their association with prolonged latency and reduced neonatal morbidity, guidance from the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists offers no clear recommendation before 24 0/7 weeks. These organizations note that antibiotics can be considered after 20 0/7 weeks but provide no recommendation prior to that point, and no published randomized trials have specifically addressed antibiotic therapy in the previable PPROM population. Existing observational data have been conflicting, with some studies reporting an association between antibiotic exposure and neonatal survival and others finding none, while 2 more recent studies described longer latency following antibiotic exposure.

Researchers conducted a single-center retrospective cohort study including pregnancies diagnosed with previable PPROM between 14 0/7 and 21 6/7 weeks' gestation and delivered between 2012 and 2024. The exposure of interest was administration of antibiotics at any time after membrane rupture intended to prolong latency. Chi-squared tests were used for categorical variables and the Wilcoxon rank-sum test for numerical variables, with statistical significance defined as P < 0.05. Multivariable linear regression was performed for the primary outcome, with gestational age at rupture of membranes included as a covariate.

Antibiotics & associated prolonged latency

After controlling for estimated gestational age at rupture of membranes, receipt of antibiotics following previable PPROM was associated with a 14.7-day increase in latency (SE = 6.86, P = 0.034). Antibiotic administration was also associated with a later gestational age at delivery (25.07 vs. 20.31 weeks' gestation) and a substantially higher rate of delivery at or beyond 22 0/7 weeks (80.95% vs. 15.62%). Additionally, antibiotic use was associated with lower rates of IUFD (20.63% vs. 65.62%, P < 0.001) and higher rates of neonatal survival to discharge (49.21% vs. 6.25%, P < 0.031).

These associations held across both singleton and multiple gestation pregnancies, with the study authors concluding that the findings support consideration of latency antibiotics in expectant management of previable PPROM while underscoring the need for larger prospective studies to confirm these results.

Reference:

Hammerquist AL, Saucedo AM, Bowler SL, et al. Antibiotic administration after previable preterm prelabor rupture of membranes is associated with prolonged latency. Pregnancy. doi:10.1002/pmf2.70342