Main results and comparison with literature

The present study reports on the outcomes of 50 live births from 46 patients observed at a single IBD tertiary referral center located in Southwest Germany. The main study focus—corresponding to its primary study objective—was a description of early postnatal child development of children born to mothers with IBD. Its key findings are that early postnatal child health and development were not significantly influenced by either IBD activity or IBD drug exposure during pregnancy.

Several previously published studies revealed that pregnant women with IBD were at increased risk of adverse birth outcomes, such as stillbirth, growth retardation and preterm birth, particularly if they suffered from repeated IBD flares throughout pregnancy.22, 23 A recently published meta-analysis of 53 studies which included 7917 IBD pregnancies and 3253 healthy control pregnancies found that gestational diabetes and pre-term pre-labor rupture of membranes occurred more frequently in IBD patients than in healthy controls. In addition, Cesarean delivery was a more common event in IBD patients compared to healthy controls (OR 1.79, 95% CI 1.16–2.77).24

Unfortunately, it was not possible to include a healthy control group in our study. Therefore, our data can only be compared to those from existing literature or birth registries.

In Germany, the rate of preterm births was 9.2% in 2012 and 8.6% in 2016, which corresponds roughly to the time interval when our data were collected.25 At 17%, the rate of preterm births was nearly twice as high as in our cohort of pregnant women with IBD compared to the general population. Also, with 52%, we observed a high rate of Cesarean deliveries in our cohort. In comparison, rates of Cesarean delivery are in general around 30% in German hospitals.26 In a recent Canadian retrospective cohort study, Cesarean delivery rates in women with CD were 52% and with UC 48%, which are in conformity to our own results.27 In that study, the strongest predictors for the performance of Cesarean sections were a history of perianal disease and prior Cesarean delivery. The fact that the rate of Cesarean deliveries was by ca. 22% higher in our study as compared to that in the general population suggests that the difference should be explainable by the condition of IBD during pregnancy.

Nearly 89% of the patients for whom this piece of information was available initiated breastfeeding of their babies. In a Canadian population-based study published in 2009 which included 156 live births by women with IBD, the rate of breastfeeding initiation was 83.3% versus 77.1% in the general population (p > 0.05).28 Given the fact that a recent meta-analysis considering 35 studies revealed that breastfeeding protected against the development of CD and UC, this is an encouraging result, and IBD patients should be recommended to breastfeed their babies.29

Subgroup analysis within the cohort of pregnant IBD patients was performed and revealed that outcomes including pregnancy complications, birth outcomes, and early child health and development were not significantly different depending on whether or which IBD medication(s) were used by the women during their pregnancies. This confirms the findings of previous studies. However, a tendency of lower birth weight and birth size was seen in patients with IBD-related therapy during pregnancy (birth weight: MD −406 g; birth size: MD −1.9 cm). Medications included in our study were mainly steroids, thiopurines, and TNFα inhibitors; the latter usually being paused around week 22 of pregnancy, if possible. Pregnancies with any maternal IBD activity tended to be shorter than pregnancies of mothers without any documented IBD activity (37.4 vs. 38.9 weeks, MD −1.53 weeks), and showed a lower birth weight (MD −309 g) and smaller birth size (MD −0.9 cm). Potentially due to the small patient group, our data did not reach significance in contrast to previous studies. On the other hand, there are also recent studies, like the study of de Lima-Karagiannis et al., which did not confirm the higher risk of adverse pregnancy and birth outcomes in pregnant IBD patients with active disease.30 This may be an effect of the growing knowledge and awareness of potential pitfalls in IBD pregnancies, which might be able to compensate for naturally adverse courses of pregnancy in IBD. The primary study objectives of this study were to explore whether children born to mothers with IBD showed any abnormalities or problems directly after birth or in their early development. No congenital abnormalities or deaths were noted in the offspring of our cohort of IBD patients. Mean Apgar scores 1, 5, and 10 min after the birth were 8.4, 9.6, and 9.8, respectively. The Apgar score is the most routinely employed measure of health status for newborns. In a recent population-based cohort study from Sweden, only 11% of term infants had an Apgar score of 10 at 1 min, while 89% and 97% had a score of 10 at 5 and 10 min, respectively.31 Even the children of our cohort who had Apgar scores <7 reached scores of at least 8 at 5 and 10 min.

Even though we had no control group for comparison, we may conclude from our data that postnatal and early childhood health and development were not conspicuous in our cohort. Also, being fully aware that subgroups available for analyses were weakly powered, no significant differences were found between children of mothers with active IBD and inactive IBD, or in relation to IBD medications during pregnancies.

Investigating the influence of pregnancy on the course of IBD was not the focus of the present study. An interesting observation, however, was that disease relapses occurred more often in pregnancies of women with UC than of those suffering from CD. Similar findings were reported by de Lima-Karagiannis et al. in their study including 298 pregnancies in 229 IBD patients.30

Strengths and limitations of this study

The main strength of this study is that the analyzed data were recruited from different data sources. Thus, it was possible in a large part of the patients to assemble a complete picture of IBD during pregnancy as well as of birth outcomes and child development in their early years of life. This would not have been feasible without the inclusion of the questionnaires and the copies of official gynecological and pediatric screening documents. The most distinctive feature of the study is that it included data from the observed pregnancies as well as data from the born children in their early development. This is of great relevance because potential mothers with IBD and their physicians may tend to consider the child's health and development a priority, to the possible detriment of the mother's well-being.

However, there are also important limitations to the study: first of all, this is a retrospective study with a relatively small patient number. Thus the statistical power is low, and the generalizability of the outcomes is limited. Furthermore in the statistics for the secondary study objectives, four patients had to be excluded from the evaluation of pregnancy complications and two patients from the evaluation of pregnancy duration, which reduced the small patient number even more. Also, the study carries a relatively high risk of selection bias. By only including patients of a tertiary referral center treating especially IBD patients with complex disease courses, the resulting pregnancy outcomes may be worse than those expected for the general IBD population. Another type of selection bias relevant for the interpretation of the study results was the nonresponse bias. For the questionnaires, the response rate of the included patients was 80%, but only 52% of patients submitted their copies of medical screening documents. We suggest that there may have been two reasons why patients did not send copies of the screening documents: first, it took more effort than just filling in the questionnaires, especially if the patients had no copy machine at hand; second, patients may have had the feeling that giving away copies of their screening documents for a study was too invasive of their privacy.

IBD activity and medications did not significantly influence birth, postnatal health, and development of the children in our study. However, the result should be interpreted with caution due to relatively small sample sizes.