Intra-amniotic Categories of Preterm Prelabor Rupture of Membranes: Gestational Age-Specific Distribution, Amniotic...

Preterm prelabor rupture of membranes (PROM) comprises four intra-amniotic categories defined by the presence or absence of intra-amniotic inflammation and microbial invasion of the amniotic cavity. Their gestational age distribution, amniotic fluid microbial profiles, and associated perinatal and neonatal outcomes have not been comprehensively characterized.

The primary aim was to determine the gestational age-dependent prevalence, amniotic fluid microbial profiles, and short-term perinatal and neonatal outcomes of the intra-amniotic categories. The secondary aim was to evaluate the feasibility of identifying these categories in pregnancies complicated by preterm PROM.

This single-institution cohort study included women with singleton pregnancies complicated by preterm PROM between 23^0/7 and 36^6/7 weeks of gestation who underwent transabdominal amniocentesis at admission. Intra-amniotic inflammation was assessed by measuring amniotic fluid interleukin-6 concentrations using a point-of-care test or an automated electrochemiluminescence immunoassay and was defined as an elevated interleukin-6 concentration at or above the platform-specific threshold. Microbial invasion of the amniotic cavity was assessed by microbiologic analysis of amniotic fluid using culture and molecular methods and was defined as the detection of microorganisms and/or their nucleic acids in amniotic fluid. Based on the presence or absence of these conditions, women were classified into four intra-amniotic categories.

Among 961 pregnancies, 158 (17%) had intra-amniotic infection, 70 (7%) had sterile intra-amniotic inflammation, 106 (11%) had microbial invasion of the amniotic cavity without inflammation, and 627 (65%) had amniotic fluid negative for inflammation and microorganisms; their distribution varied with gestational age. Overall, 64 microbial species were identified in amniotic fluid, with Ureaplasma spp. accounting for nearly two-thirds of all microbial detections. The unadjusted frequencies of early-onset neonatal sepsis were 12% (19/154), 4% (3/68), 5% (5/106), and 2% (14/624) in the intra-amniotic infection, sterile intra-amniotic inflammation, microbial invasion without inflammation, and negative amniotic fluid for inflammation and microorganisms categories, respectively (P < 0.0001). In a focused analysis comparing intra-amniotic infection with the remaining three categories combined, intra-amniotic infection was associated, after adjustment, with higher odds of early-onset neonatal sepsis (adjusted odds ratio, 3.4; 95% confidence interval, 1.7-7.0; P < 0.001) and serious composite adverse perinatal outcome (adjusted odds ratio, 2.0; 95% confidence interval, 1.1-3.4; P = 0.02). Among pregnancies with microbial invasion of the amniotic cavity, bacteria other than Ureaplasma spp. in amniotic fluid were associated with worse perinatal and neonatal outcomes than Ureaplasma spp. alone or in combination with other bacteria. Transabdominal amniocentesis yielded amniotic fluid in 93% (961/1,037) of eligible pregnancies and 98% (961/979) of attempted procedures.

Preterm PROM is a heterogeneous syndrome comprising four intra-amniotic categories that differ in gestational age distribution, amniotic fluid microbial composition, and short-term perinatal and neonatal outcomes. Intra-amniotic infection and the presence of bacteria other than Ureaplasma spp. in amniotic fluid were associated with the highest risk of adverse perinatal and neonatal outcomes.