UC may increase the risk of preterm birth, low birth weight, birth defects, or cesarean section; however, no evidence supporting the hypothesis that inflammatory bowel disease increases perinatal mortality is currently available [4]. Moreover, these risks are associated with disease status as patients with active UC have a more pronounced risk of adverse pregnancy outcomes than patients in remission. Supporting this conclusion, in our study, patients with adverse pregnancy outcomes had higher SCCAI in the second trimester than those who had no adverse pregnancy outcomes. This also demonstrated that SCCAI did can truly reflect UC disease stage even in pregnant women. Some studies have shown that during the pregnancy, approximately one-third of the patients with UC were stable, one-third of the patients exacerbated, while in one-third of the patients, the disease went into remission [9]. A neonatal registration cohort study including 47,710 births in Sweden found that the adjusted odds ratios of preterm and low-birth-weight infants in women with UC flare were 2.72 and 2.10, respectively, and the risk of miscarriage increased by four times compared with that in patients in remission [95% confidence interval (CI) 1.2–13.9; P = 0.02] [3].
Pregnancy may cause UC flare, and its effect on the course of the disease depends on the disease state at the time of conception. Patients who are pregnant during the active period have a significantly higher recurrence rate than those who conceive during the remission period. Moreover, 55% and 29% of patients with active UC experienced recurrence at the time of conception and during remission, respectively, and the risk ratio was 2.0 (95% CI 1.5–3.0; P < 0.001) [2].
In our study, the recurrence/exacerbation rate was not significantly different between patients with UC remission and those with active UC (Table 1), which could be attributed to the strict disease management in the active group. The SCCAI during pregnancy in the remission and active groups showed an upward trend compared with the pre-pregnancy SCCAI, suggesting that pregnancy is associated with a certain risk of UC relapse or aggravation, which is consistent with the results of previous studies. In addition, although the gestational SCCAI in the remission group increased compared with the pre-pregnancy SCCAI, it decreased in the third trimester; in the active group, a continuous increase, even in the late pregnancy period, was observed. Thus, pregnancy is desirable when the disease is in remission, and the Toronto Consensus suggested that a sustained remission for at least 3 months may be a favorable time for conception [10]. None of the two groups discontinued medications during pregnancy, and no significant difference in the frequency of pregnancy-related complication and adverse pregnancy outcomes was noted between the two groups, which suggests that the use of appropriate medications during pregnancy is essential in managing UC and is critical for obtaining a satisfactory pregnancy outcome.
Considering the medications before and during pregnancy, the European Crohn’s and Colitis Organization guidelines indicate that 5-ASA, glucocorticoid, immunosuppressive agents, and anti-TNF-α monoclonal antibodies are safe during pregnancy and the benefits of controlling the disease are greater than the potential risks [11]. The Toronto Consensus also recommends that patients who take these drugs before pregnancy should continue to take them during pregnancy to maintain a stable condition [10]. One patient started receiving adalimumab before pregnancy until 12 weeks of gestation; although her newborn had a low birth weight (2460 g), no evidence of infection was found, which was consistent with the aforementioned guidelines. Hence, obstetricians, gastroenterologists, and gastrointestinal surgeons should patiently and thoroughly educate patients on the safety of the drugs and the effect of the disease activity on pregnancy, which could in turn help promote stability of the disease before and during pregnancy and achieve good pregnancy outcomes.
Moreover, patients with UC have an increased risk of adverse pregnancy outcomes, such as preterm birth and low birth weight, compared to the general population [4]. In our study, low birth weight was the most common adverse pregnancy outcome, which could be related to maternal anemia. Anemia was the most common manifestation in pregnant women with UC [12]. Moreover, a previous study showed a certain correlation between anemia in patients with UC and low-birth-weight infants [13], which is consistent with our results. In addition, no significant difference in the frequency of pregnancy-related complications and adverse pregnancy outcomes was noted between the two groups (Table 3); one case of artificial abortion and one case of labor induction were noted, and these cases resulted in a subjectively increased frequency of adverse pregnancy outcomes. The patient in our study underwent induction of labor because conservative treatment including systemic glucocorticoid administration was not effective, and the patient experienced acute massive gastrointestinal hemorrhage. She and her family members were strongly urged to terminate the pregnancy after they were informed about the potential adverse effects of the therapeutic drugs, surgery, and endoscopy on the fetus. After induction of labor, laparoscopic pancolectomy and ileostomy were successfully performed to control the gastrointestinal hemorrhage. Remission was achieved postoperatively with intravenous glucocorticoids combined with oral mesalamine and maintained by a combination of oral mesalazine and hydrocortisone. After 2 years, this patient conceived again and delivered a full-term live male baby vaginally (3240 g without any neonatal complication) after continuous monitoring and strict follow-up by obstetricians, gastroenterologists, and gastrointestinal surgeons. Except for mild anemia and premature rupture of membrane, no other serious maternal complication was observed, suggesting that the maintenance of remission and optimal pregnancy management are vital for satisfactory pregnancy outcomes.
Our study showed no significant difference in the mode of delivery between the remission and active groups (Table 3). Nevertheless, the rate of cesarean section was high in the remission (40%) and active (66.7%) groups or in all patients with UC (44.4%), suggesting that UC may increase the risk of cesarean section, which is consistent with the finding in a previous study [4]. However, the selection of the mode of delivery remains controversial. UC is not an independent risk factor of cesarean section, and the patient’s obstetric conditions have greater effect in the decision-making. Nevertheless, in patients with ileal pouch-anal anastomosis, cesarean section is recommended to terminate gestation and, thus, avoid sphincter and intestinal damage [14]; however, whether vaginal delivery increases the risks of sphincter and intestinal damage remains to be further established [15, 16]. Nonetheless, the mode of delivery in patients with UC must be discussed with obstetricians and gastroenterologists, should be based primarily on obstetric considerations, and should consider the patient’s preference.
As mentioned previously, patients with adverse pregnancy outcomes had higher SCCAI in the second trimester than patients with no adverse pregnancy outcomes, suggesting that a higher SCCAI in the second trimester may be associated with adverse pregnancy outcome. A multivariate regression analysis found no statistically significant risk factors for adverse pregnancy outcomes, indicating that multidisciplinary collaboration in the management of pregnancy in patients with UC is vital to achieve satisfactory outcomes.
This retrospective study had some limitations. The patients were all regularly followed before and during pregnancy. Thus, selection bias was possible. Moreover, the small sample size may have increased the risk of type I errors. In addition, this study lacked data on the long-term outcomes of the offspring of the enrolled patients.