Materials and Methods

This is a retrospective cohort study of all pregnancies that were recorded in the state of California from 2005-2008. The search identified linked datasets of mothers and infants from the California Vital Statistics Birth Certificate Data, California Patient Discharge Data, Vital Statistics Death Certificate, and Vital Statistics Fetal Death File. We identified our cohort of women with pancreatitis based on Internal Classification of Diseases, 9th revision , codes 577.0 (acute) and 577.1 (chronic) noted during the delivery admission only. We excluded multiple gestations and pregnancies that were complicated by fetal anomalies. The institutional review boards at Oregon Health & Science University and the State of California approved the study. Informed consent was not required because the linked data sets did not include potential patient identifying information.

Specific maternal characteristics and outcomes of interest were identified. In particular, maternal age, race/ethnicity (white, black, Hispanic, Asian, other), public insurance, education level (≥12th grade and <12th), diabetes mellitus, and chronic hypertension. Additionally, the development of gestational diabetes mellitus, gestational hypertension, preeclampsia, and preeclampsia with severe features were evaluated. Fetal/neonatal outcomes of interest included preterm delivery (<37 weeks’ gestation), severe preterm delivery (<32 weeks’ gestation), intrauterine fetal death, neonatal death, infant death, small for gestational age (birthweight <10th percentile at time of delivery), respiratory distress syndrome, grade 3 or 4 intraventricular hemorrhage, and jaundice.

Univariate analyses with the use of chi-squared tests were conducted with Stata software (version 11; Stata Corporation, College Station, TX) to examine the association of pancreatitis in pregnancy with maternal characteristics and maternal and fetal outcomes. Multivariable logistic regression was performed to control for potential confounders that included chronic hypertension, gestational diabetes mellitus, ethnicity, maternal age, public insurance, and education level. A probability value of < .01 and 95% confidence intervals (CIs) were used to determine whether the comparisons were statistically significant, given the robustness of the sample size.

Results

Our cohort included 2,039,870 nonanomalous singleton pregnancies. Of these pregnancies, 342 were complicated by pancreatitis, which yielded an incidence of pancreatitis in pregnancy of 0.017% in our study population. The 342 pregnancies that were complicated by pancreatitis were then compared with the remaining 2,039,528 control pregnancies. In the unadjusted analysis that evaluated maternal demographics, women with pregnancy-associated pancreatitis were more likely to be black, followed by Hispanic, then white and Asian ( Table 1 ). Additionally, education of <12th grade, having public insurance, chronic hypertension, and diabetes mellitus all were associated significantly with the development of pancreatitis.

Maternal outcomes that were associated with pancreatitis in pregnancy included the development of gestational diabetes mellitus (12.0% vs 6.3%; P < .001) but not gestational hypertension (5.6% vs 3.2%; P < .012) with the probability value of < .01 ( Table 2 ). Of note, pancreatitis in pregnancy was found to be associated with both preeclampsia (13.5% vs 2.9%; P < .001) and preeclampsia with severe features (6.4% vs 0.8%; P < .001).

The development of pancreatitis during pregnancy was not associated statistically with neonatal (0.6% vs 0.21%; P < .124) or infant death (0.29% vs 0.1%; P < .265; Table 3 ). However, pancreatitis was associated with preterm delivery at <32 weeks’ gestation (4.68% vs 1.21%; P < .001) and preterm delivery at <37 weeks’ gestation (30.70% vs 8.91%; P < .001), small for gestational age (22.78% vs 10.70%; P < .001), jaundice (29.24% vs 15.26%; P < .001), respiratory distress syndrome (4.39% vs 0.86%; P < .001), and intrauterine fetal death (1.75% vs 0.33%; P < .001).

After adjustment for maternal age, ethnicity, type of insurance, education level, chronic hypertension, and gestational diabetes mellitus, pancreatitis in pregnancy was associated with an increased risk of several adverse perinatal outcomes ( Table 4 ). The odds of the development of gestational hypertension were not different between groups; however, compared with women without pancreatitis, women with pancreatitis had significantly higher odds of the development of preeclampsia (odds ratio [OR] 4.21; 95% CI, 2.99–5.93) and preeclampsia with severe features (OR, 7.85; 95% CI, 5.03–12.24). Furthermore, women with pancreatitis had higher odds of preterm delivery at <32 weeks gestation (OR, 3.31; 95% CI, 1.93–5.68) and at <37 weeks’ gestation (OR, 4.10; 95% CI, 3.23–5.21).

Table 4

Adjusted odds ratios for outcomes of pregnancy-associated pancreatitis vs the control population ^a

Outcome	Odds ratio	95% confidence interval
Gestational hypertension	1.18	0.67–2.06
Preeclampsia	4.21	2.99–5.93
Severe preeclampsia	7.85	5.03–12.24
Preterm delivery <32 wks’ gestation	3.31	1.93–5.56
Preterm delivery <37 wks’ gestation	4.10	3.23–5.21
Intrauterine fetal death	4.35	1.80–10.55
Small for gestational age	2.26	1.64–3.11
Respiratory distress syndrome	4.27	2.44–7.46
Jaundice	2.22	1.74–2.84
Neonatal death	1.47	0.21–10.46
Infant death	2.8	0.39–19.97

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