BACKGROUND: Bronchopulmonary dysplasia (BPD), a major source of morbidity in 
premature neonates, has been associated with intrauterine infection and preterm 
birth. Both preterm premature rupture of membranes (PPROM) and spontaneous 
preterm labor (sPTL) are linked with intrauterine inflammation. Whether PPROM 
and sPTL, as two phenotypic categories of preterm birth, are associated with 
exposure to different degrees and durations of inflammation that might impact 
fetal lung development is unknown. PPROM may be associated with longer latency 
until delivery, which is beneficial for neonatal mortality, but may impart 
greater injury risk to the developing fetal lungs. It is unknown if PPROM is 
associated with a greater risk of adverse neonatal respiratory outcomes than 
sPTL.
OBJECTIVE: The objective of this study was to determine if PPROM imparts a 
differentially greater risk for neonatal BPD than sPTL. A secondary objective 
was to determine if PPROM was associated with a greater risk of adverse neonatal 
respiratory outcomes other than BPD and whether gestational latency following 
PPROM or sPTL diagnosis constitutes a risk factor for fetal lung injury.
STUDY DESIGN: We conducted a retrospective secondary analysis of a large cohort 
of women at risk for spontaneous preterm birth, who were originally enrolled in 
a randomized controlled trial of magnesium sulfate versus placebo examining 
neuroprotection. For our study, we included women with a singleton pregnancy 
complicated by PPROM or sPTL and delivery between 24 and 34 weeks gestational 
age. Cases with multiple gestation, congenital anomalies, maternal 
seropositivity for human immunodeficiency virus, or hypertensive diseases of 
pregnancy (including preeclampsia) were excluded. The primary outcome was BPD. 
Secondary outcomes were respiratory distress syndrome (RDS), transient tachypnea 
of the newborn (TTN), requirement for mechanical ventilation, pneumonia, 
neonatal sepsis, fetal or neonatal death, and a composite of adverse neonatal 
respiratory outcomes including (BPD, pneumonia, RDS, and TTN). Statistical 
analyses included chi-square, Student's t-test and logistic and multiple 
regression.
RESULTS: A total of 1729 women were included in this analysis including 1554 
with PPROM and 175 with sPTL. Women in the PPROM group were more likely to be 
older, not of Hispanic race, married, more educated, have smoked during 
pregnancy and have a greater body mass index. The BPD rate was not significantly 
different following PPROM versus sPTL. Neonates in the PPROM group experienced a 
lower rate of pneumonia (p = .001), neonatal sepsis (p = .009) and patent ductus 
arterious (PDA) requiring either medical or surgical therapy (p < .001) than 
neonates in the sPTL group. Chorioamnionitis was more common in the PPROM group 
(p = .008) than the sPTL group. After multivariable logistic regression with BPD 
or composite of adverse neonatal respiratory outcomes as the dependent outcomes, 
and controlling for gestational age at delivery, maternal smoking history, 
duration of mechanical ventilation and RDS, there was no significant difference 
between PPROM and sPTL.
CONCLUSIONS: BPD rates were not significantly different in neonates born to 
women following PPROM versus sPTL. However, PPROM was associated with lower 
rates of pneumonia, neonatal sepsis, and PDA requiring therapy in the univariate 
analysis, but not the multivariate analysis. Neonatal respiratory outcomes may 
have a similar phenotypic overlap regardless of whether preterm birth follows 
PPROM or sPTL.