Materials and Methods

The Consecutive Pregnancies Study was a retrospective cohort study conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Detailed information on 114,679 pregnancies from 51,086 women with at least 2 deliveries after 20 weeks of gestation at 20 Utah hospitals from 2002-2010 were extracted from the maternal and infant electronic medical records and supplemented with International Classification of Diseases, ninth revision , discharge codes. Pregnancies were linked across an individual woman with the use of a unique maternal identification code. Institutional review board gave approval for all participating institutions; the Office of Human Subjects Research (OHSR) at the National Institute of Health granted an exemption because all of the data that were transferred were deidentified.

Analyses were restricted to women who were nulliparous at study entry (n = 27,741) because of the established relationship between increasing parity and placenta previa risk. The cohort was further limited to women with consecutive singleton pregnancies, because multiple gestation is also an established risk factor for placenta previa (n = 27,062). We performed a complete-case analysis and excluded a total of 75 women with missing data on 1 of the following items: ethnicity (n = 56; 0.21%), marital status (n = 2; 0.01%), or smoking status (n = 18; 0.07%). The final sample consisted of the 26,987 women with consecutive singleton pregnancies.

First pregnancy delivery mode was categorized as vaginal or cesarean delivery. We further categorized cesarean delivery into either (1) cesarean delivery performed before labor onset (prelabor cesarean delivery) or (2) cesarean delivery performed after labor onset (intrapartum cesarean delivery). Prelabor cesarean delivery was designated if a trial of labor was absent and if none of the following were documented: induction of labor, augmentation of labor, episiotomy, intrapartum tocolytics, shoulder dystocia, vaginal lacerations, a cesarean delivery indication noting failure to progress or failed induction, or a date/time of full cervical dilation or onset of spontaneous labor. All other cesarean deliveries that did not meet the aforementioned conditions were classified as intrapartum. There were 102 women with cervix dilated ≥6 cm at the time of the first examination after admission to labor and delivery; we considered them to have been in active labor, so they were classified as intrapartum cesarean delivery.

Cases of placenta previa in the second pregnancy were identified through the diagnosis documented in the prenatal and labor and delivery medical records. No additional cases were detected by International Classification of Diseases , ninth revision , codes (641.00-641.03; 641.10-641.13). Women with a diagnosis of placenta previa who delivered vaginally (n = 26) were not considered to be cases for the purposes of this study because partial and complete placenta previa require cesarean delivery.

Maternal race/ethnicity and second pregnancy age at delivery, insurance type, marital status, smoking during pregnancy, and gravidity were obtained from the medical record. Because of the homogenous nature of this cohort (>87% white), race/ethnicity was classified as white vs nonwhite. Maternal medical history of asthma, anemia, pregestational diabetes mellitus, chronic hypertension, kidney disease, thyroid disease, and chorioamnionitis in the second pregnancy were obtained from the medical record and supplemented with International Classification of Diseases, ninth revision, codes. Once classified with a chronic condition, women were considered to have the condition at all subsequent pregnancies. Given the reported association between a history of placenta previa and the risk of subsequent placenta previa, we also included a diagnosis of placenta previa that occurred in the first pregnancy using the case definition described earlier. Last, gestational age was determined as recorded in the medical record according to the best obstetric estimate. Consistency checks were performed with the use of repeated pregnancy data on all relevant covariates and conditions.

Differences in participant characteristics at the second pregnancy according to previous delivery mode were determined with the χ ² test, Fisher exact test, or the Student t test. The risk of placenta previa was estimated according to previous delivery mode by multivariable logistic regression with likelihood ratio tests. Serial models were constructed to explore the potential different confounders. Potential covariates for the adjusted models were explored based on previous literature, use of a directed acyclic graph, and evaluation of individual regression models; a probability value of < .10 was considered significant.

The first model (model A) was a multivariable logistic regression model with first pregnancy delivery mode as the independent variable and second pregnancy previa as the dependent variable that was adjusted for demographic and known baseline risk factors that included maternal age, insurance status, smoking status, history of pregnancy loss, and history of placenta previa. The second logistic regression model (model B) included all of the covariates in model A and further was adjusted for maternal comorbidities (anemia, pregestational diabetes mellitus, and thyroid disease) selected according to the aforementioned criteria. For the model interpretation, interest was focused on the assessment of the risk of previa and not on the risk of known confounding factors.

To examine the potential impact of cesarean incision type at first pregnancy on second pregnancy placenta previa occurrence, we performed sensitivity analyses by removing all first pregnancies that had a transverse fetal position delivered by cesarean section (n = 80; 0.3%) or cesarean section at <36 weeks’ gestation (n = 369; 1.4%); both conditions are indicative of a higher probability of classic, instead of a low transverse, uterine incision. Furthermore, it was possible that cases of placenta previa at the second pregnancy that was delivered preterm may have resolved spontaneously had the pregnancy been allowed to progress. To address this potential competing risk, another set of sensitivity analyses were performed that excluded 1897 pregnancies (7.0%) that delivered at <37 weeks’ gestation. All analyses were conducted with SAS software (version 9.3; SAS Institute Inc., Cary, NC), and 2-tailed probability values of < .05 were considered statistically significant.

Results

Women were mostly white (87%) and married (89%) and had private insurance (73%). The average maternal age at the second pregnancy was 26.2 years (range, 14–46 years). Most deliveries at the first pregnancy were vaginal (82%; n = 22,142), followed by intrapartum cesarean delivery (14.6%; n = 3931), or prelabor cesarean delivery (3.4%; n = 914). Distributions of race/ethnicity, maternal age, history of pregnancy loss, and occurrence of multiple maternal comorbidities were significantly different between the previous delivery types ( Table 1 ). Compared with women who previously had a vaginal delivery or prelabor cesarean delivery, women who previously underwent an intrapartum cesarean delivery were significantly more likely to be nonwhite. Women who previously had any type of cesarean delivery were significantly older and more likely to have chronic hypertension compared with women who previously delivered vaginally. Compared with women who previously had a vaginal delivery or an intrapartum cesarean delivery, women who previously underwent a prelabor cesarean delivery had significantly higher prevalence of pregestational diabetes mellitus, kidney disease, and thyroid disease and were more likely to have a history of pregnancy loss.

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