In the current study we used the NIS, which is the largest all payer US healthcare database, to analyze the effect of IBD on maternal and fetal outcomes. Overall, pregnant women with IBD experienced worse maternal and perinatal outcomes when compared to their counterparts without IBD. Even after adjusting for pre-existing maternal metabolic conditions and harmful lifestyle habits, IBD remained associated with greater odds of gestational diabetes, gestational hypertension associated complications including pre-eclampsia, eclampsia, HELLP syndrome and post-partum hemorrhage. Perinatal outcomes were also adversely affected in pregnant women with IBD when compared to non-IBD pregnant group. We observed higher odds of FGR, pre-term birth and fetal death, after adjusting for maternal metabolic conditions and lifestyle habits.
In subsequent sub-group analysis of pregnant women with UC and CD, we found that more women with CD conceived when compared to women with UC. Both groups showed higher adjusted odds of worse maternal and fetal outcomes, except that CD was not associated with higher risk of LGA infants. This was true even after adjusting for maternal metabolic diseases and lifestyle habits including smoking and alcohol abuse. Furthermore, even after adjusting for long term use of inhaled and systemic corticosteroids, IBD in general and CD and UC independently, were associated with poor maternal and perinatal outcomes. We also found that pregnant women with IBD have prolonged mean LOS and increased resource utilization.
Previous studies on IBD affecting pregnancy showed conflicting evidence. Lee et al., studied the effect of IBD on pregnancy in a Korean cohort and concluded that women with moderate to severe IBD are associated with worse maternal and fetal outcomes, but with mild disease there was no difference in outcomes between the IBD and control group.3 These results were further reinforced by Kammerlander et al., who studied the effect of disease severity on pregnancy outcomes and concluded that moderate to severe disease was associated with increased odds of low birth weight and preterm delivery.16
Baird et al., reported that women diagnosed with IBD had low pregnancy and fertility rates, but this low fertility rate was not secondary to disease effect rather it was a voluntary childness resulting from fear of worse pregnancy outcome.17 Selinger et al., studied the rate of fertility in IBD patients and found that 17% of women chose not to conceive and the most important factor behind this decision was poor knowledge of disease and disease burden.5 Contrary to this Mayberry et al., documented that women with IBD had low fertility, regardless of the bowel segment involved. 18 Based on these results it is evident that women with IBD are fearful of having children or suffering from subfertility. Hence, better counselling and guidance is needed in this potentially high-risk pregnancy population.
In our analysis we found that IBD in general as well as UC and CD independently were associated with increased odds of gestational diabetes and glucose intolerance as compared to non-IBD control group. Tandon et al., performed a meta-analysis to study the risk of pregnancy outcomes in IBD patients and documented that gestational diabetes was more common in the IBD group. They reported no increased odds of developing gestational diabetes in pregnant IBD patients on long term corticosteroids.19 Another study by Leung et al., showed that IBD is independently associated with increased risk of gestational diabetes regardless of corticosteroid use, which further strengthens our findings.20 We also found increased odds of gestational hypertension associated complications like pre-eclampsia, eclampsia and HELLP syndrome in IBD as well UC and CD patient sub-groups. This is in consensus to previous findings reported by Boyd et al., that showed increased incidence of pre-eclampsia in IBD patients, but Boyd et al., labelled oral corticosteroid use as major contributing factor for the development of these complications.21 Interestingly in our study we demonstrated that even after adjusting for long term corticosteroid use, these pregnancies still carry a high risk for developing these complications.
Our analysis showed worse perinatal outcomes in pregnant women with IBD when compared to non-IBD controls. We included preterm birth, FGR, LGA and fetal death as our outcomes of interest. Similar results were seen in many of the previous studies. 3, 8, 9, 22–24 In contrast, Bortoli et al., conducted a prospective study and found that IBD had similar perinatal outcomes when compared to non-IBD controls25 and a study from Nogard et al., seconds these results.7 It is still ambiguous if active disease results in worse fetal outcomes, and the effect of IBD therapy can have on fetal outcomes. The studies performed earlier have not reached a clear conclusion. Baiocco et al., reported that active disease is associated with worse perinatal outcomes and treatment medications are not the central reason for these poor outcomes.26 These results were reinforced by the study conducted by Oron et al., who found that active disease at conception is associated with adverse birth outcomes.27 Contrary to these findings, a study performed by de Lima et al., showed that disease relapse was not associated with adverse birth outcomes in IBD patients.28 Based on our analysis we suggest that IBD is associated with worse fetal outcomes irrespective of the disease activity status. Corticosteroids are usually prescribed in active disease, in our analysis even after adjusting for long term corticosteroid use, pregnancy outcome remained the same.
Our study has certain limitations, first it is a retrospective study performed using administrative and claims-based datasets, which are susceptible to misclassification, missing codes, and inaccurate coding. Secondly, our study did not have randomization and blinding which limits the interpretation of results. In addition, NIS does not provide information about all the medications and laboratory values which limits us in analyzing the effect of various medications on patients’ outcomes.
Despite these limitations our study has many strengths. To our knowledge this is the most up to date and recent study performed using the US inpatient database to determine the effect of IBD on maternal and fetal outcomes. Around 48 states share their data with NIS which increases the sample size and makes it nationally representative. Moreover, NIS eliminates the commonly encountered limitation of single-center studies by allowing the use of a nationally representative large sample size. The other striking feature of our study is that we adjusted our result for long term inhaled and oral corticosteroid use which is associated with worse maternal and fetal outcomes.