Objective
The purpose of this study was to examine whether the recurrence risk of preterm premature rupture of membranes (PPROM) is modified by the interpregnancy interval (IPI).
Study Design
We used the Missouri 1989–1997 longitudinally linked data to examine the recurrence risk of PPROM in women with first 2 (n = 150,929) and first 3 (n = 30,011) successive pregnancies. Race-specific recurrence risks were examined. Adjusted odds ratios (ORs) were used to estimate risks.
Results
Risks of PPROM in the second pregnancy among women with and without previous PPROM were 5.7% and 2.3%, respectively, among white women (OR, 8.7; 95% confidence interval, 6.7–11.4) and 10.3% and 4.3%, respectively, among African American women (OR, 7.2; 95% confidence interval, 5.1–10.1). Short IPI was associated with increased risk for PPROM recurrence, with substantially higher risk for African American women than white women. However, long IPI was associated with increased recurrence among African American women.
Conclusion
Women with previous PPROM are at increased risk for recurrence, and a short IPI is associated with increased risk.
Preterm premature rupture of membranes (PPROM), defined as the prelabor rupture of the fetal membranes at preterm gestations, complicates 2–5% of all pregnancies. Premature rupture of membranes (PROM) is one of the leading, yet identifiable, causes of preterm birth and remains a significant cause of subclinical intrauterine infection and inflammation that leads to maternal, fetal, and neonatal morbidity and, less commonly, stillbirth and infant death. PPROM is implicated in up to one-fourth of all preterm births and continues to pose major public health challenges.
The cause of PPROM remains elusive, but is likely multifactorial; genetic, maternal, and fetal factors are likely important contributors. Although ascending bacterial infection from the female genital tract remains the most widely speculated risk factor, recent data suggest that inflammatory processes at sites that are remote from the female genital tract (eg, periodontal infections) may also lead to increased levels of proinflammatory cytokines and chemokines at the maternal-fetal interface. Studies have identified a number of risk factors for PPROM, which include advanced maternal age, primiparity, smoking, respiratory conditions, short cervical length, structural abnormality of the chorioamniotic membranes, and PPROM and preterm birth in a previous pregnancy. Risk factors for PPROM also vary by maternal race, with African American women at higher risk than white women. Moreover, racial differences in the regulation of promoter activity of proinflammatory cytokines and matrix metalloproteinase also exist, both of which may play important roles in the disruption of the integrity of chorioamniotic membranes.
Despite the increased tendency of PPROM to recur in subsequent pregnancies, the extent to which such recurrence patterns vary by the number of previous preterm births and whether interpregnancy intervals (IPIs) influence such recurrence patterns remains unknown. We hypothesized that women with short IPIs may be at higher risk for recurrence of PPROM and examined this hypothesis in a population-based study of women who had had their first 2 and their first 3 consecutive singleton pregnancies.
Materials and Methods
We performed a retrospective analysis using the population-based data from the Missouri Department of Health and Senior Services comprised of births in the state between 1989 and 1997. The data provide an opportunity to link siblings to their biologic mothers with the use of unique maternal identifiers. The algorithms that were used in the linkage process and the validation of the linked data have been described previously.
PPROM was defined as a rupture of membranes at preterm gestation (<37 weeks) before the onset of labor. Gestational age, which was reported in completed weeks, was derived largely from date of last normal menses. Clinically estimated gestational age was substituted for last normal menses-based gestational age when the menstrual estimate was inconsistent with birthweight or when the day of last normal menses was missing (<5%).
Between 1989 and 1997, a total of 711,015 live births and fetal deaths were recorded in Missouri. Because our objective was to examine outcomes in successive pregnancies, we excluded 515,399 women who had only 1 pregnancy during the study period and those who had ≥1 pregnancies before 1989. From the remainder of births, we excluded multiple births (n = 19,598) and births at <20 weeks gestation (n = 13,294). We further excluded pregnancies to women who were neither white nor African American because of relatively small numbers (n = 11,646). Finally, we excluded records with missing PROM status (n = 149). These exclusions left us with 150,929 women who delivered their first 2 consecutive singleton infants and 30,011 women who delivered their first 3 consecutive singleton births.
We examined the distribution of maternal and fetal characteristics by PPROM status in the second pregnancy. Multiple logistic regression analysis was used to adjust for potential confounding factors that included maternal age (<20, 20–29, 30–34, and ≥35 years), maternal race/ethnicity categorized as non-Hispanic white (white) and non-Hispanic black (African American), maternal education (<12, 12, and ≥13 years of completed schooling), marital status (married or unmarried), initiation of prenatal care (early or first trimester and none or late initiation), smoking (yes/no), and IPI , which was defined as the interval between the end of the first pregnancy and estimated conception of the second pregnancy (categorized as <12, 12–17, 18–23, 24–29, 30–35, and ≥36 months). Odds ratios (ORs) and 95% confidence interval (CI) were used to quantify recurrence risks. Because some factors may have likely changed between 2 subsequent pregnancies (such as prenatal care, marital status, and smoking during pregnancy), we constructed a 4-level factor for every confounder: (1) absence of factor in both pregnancies (referent); (2) presence of factor in the first, but not in the second, pregnancy; (3) presence of factor in the second, but not in the first, pregnancy; and (4) presence of factor in both pregnancies.
We examined whether the interval between pregnancies modified the recurrence risk of PPROM. IPI was analyzed on the basis of restricted cubic spline transformation, with 5 knots located at 11, 16, 23, 34, and 63 months for African American women and at 12, 19, 27, 37, and 64 months for white women. We additionally checked for interaction between PPROM in the first pregnancy and IPI on the risk of PPROM in the second pregnancy.
Statistical analyses were performed with SAS software (version 9.1; SAS Institute, Cary, NC). The study was approved by the institutional review board of Kaiser Permanente Southern California, Pasadena, CA.
Results
Risks of PPROM in first and second pregnancies were 2.9% and 2.9% among African American women and 1.4% and 1.1% among white women, respectively. Women with PPROM in the second pregnancy were more likely to be at the extreme ends of the reproductive age, to have <12 years of formal education, to have smoked during pregnancy, and to have a shorter IPI ( Table 1 ). They were also more likely to be unmarried and to receive late or no prenatal care ( P < .001.
| Maternal characteristic | White women, % | African American women, % | ||
|---|---|---|---|---|
| No PPROM (n = 125,609) | PPROM (n = 1234) | No PPROM (n = 23,464) | PPROM (n = 622) | |
| Maternal age, y | ||||
| <20 | 8.0 | 8.6 | 23.8 | 26.1 |
| 20–29 | 56.8 | 60.4 | 58.8 | 56.0 |
| 30–34 | 25.7 | 20.4 | 12.5 | 12.5 |
| ≥35 | 9.6 | 10.6 | 4.9 | 5.3 |
| Education, y | ||||
| <12 | 16.3 | 22.5 | 34.9 | 41.4 |
| 12 | 35.6 | 37.0 | 41.1 | 41.6 |
| ≥13 | 48.2 | 40.5 | 24.0 | 17.0 |
| Maternal smoking | ||||
| No | 77.7 | 63.7 | 81.9 | 69.9 |
| Yes | 22.2 | 36.1 | 18.0 | 29.3 |
| Gestational age, wk | ||||
| 20–28 | 5.6 | 10.6 | 8.7 | 18.5 |
| 29–32 | 8.5 | 14.2 | 12.8 | 21.4 |
| 33–34 | 10.8 | 17.9 | 14.0 | 18.3 |
| 35–36 | 75.1 | 57.3 | 64.6 | 41.8 |
| Interpregnancy interval, mo | ||||
| <12 | 6.2 | 11.6 | 9.9 | 16.6 |
| 12–17 | 16.8 | 18.3 | 24.6 | 29.6 |
| 18–23 | 20.6 | 21.2 | 21.1 | 20.1 |
| 24–29 | 17.8 | 15.6 | 14.5 | 8.2 |
| 30–35 | 14.0 | 11.8 | 10.9 | 11.2 |
| ≥36 | 24.7 | 21.5 | 19.0 | 14.5 |
| Cervical incompetence | 0.3 | 2.4 | 0.3 | 2.3 |
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