The results of the present meta‐analysis suggest that women with IBD are more likely to experience adverse pregnancy outcomes, in particular premature birth, LBW and a caesarean section. Patients with IBD were nearly twice as likely to have a premature delivery (<37 weeks gestation) as the normal population, a result which remained significant after the sensitivity analysis. No significant difference was seen in premature birth between patients with Crohn's disease and those with ulcerative colitis. The effect of premature delivery on an infant's physical, mental and social health may be substantial,12,13,16,17
and women with IBD must be aware of the increased risk of prematurity in their babies.
The OR of a woman with IBD having an infant with LBW (<2500 g) was 2.1 (p<0.001). This remained consistent in the sensitivity analysis of studies reporting on
100 patients with IBD; the outcome was not reported in the higher quality studies or studies published after 2000. Women with Crohn's disease were nearly three times more likely to have an infant with LBW (p
0.003), but not those with ulcerative colitis.
A higher rate of caesarean sections was seen in women with IBD than in the normal population. This was corroborated in all of the sensitivity analysis subgroups. A higher rate of caesarean sections was seen in patients with Crohn's disease versus controls, but not in those with ulcerative colitis. No significant difference was observed between ulcerative colitis and Crohn's disease; however, the number of patients was small. A large study to specifically compare the mode of delivery between the two groups is required in the future. The rationale behind the increased number of caesarean sections in patients with IBD is not dealt with in the studies analysed. No data exist on whether the caesarean sections were elective or emergencies or whether the outcomes of the infants differed after vaginal delivery and caesarean section. Controversy exists over the most appropriate method of delivery for patients with IBD, with some studies reporting that the risk of incontinence and anal sphincter tears is less in caesarean section than in vaginal delivery.31,32,33,34
This is disputed in other studies, which say that anal sphincter tears that occur in vaginal deliveries do not affect continence35
and that vaginal delivery reduces surgical procedures and adhesion formation in a group of high‐risk patients.
Previous studies have suggested an association between patients with IBD—in particular, patients with Crohn's disease—and SGA29
; however, this was not shown in this meta‐analysis. The results of the present study showed no increase in the incidence of SGA (small for gestational age) in the population with IBD in comparison to the normal population, or in patients with Crohn's disease versus ulcerative colitis. This was confirmed in the sensitivity subgroup analysis for studies published in or after 2000 and for studies reporting on
100 patients with IBD.
No significant difference was found in the incidence of still births in women with IBD and the normal population. The results of the sensitivity analysis also found no significant differences. There have been previous reports of an association of IBD with an increased risk of still births, although often in active disease.36
No significant difference was found in the risk of congenital abnormalities in women with IBD and the normal population; however, a significant difference was found in the subgroup analysis for later studies and those with larger patient groups. The analysis of all of the studies did find a significant difference in the risk of congenital abnormalities in patients with ulcerative colitis versus controls, but not in patients with Crohn's disease. The studies that reported on congenital abnormalities did not distinguish between the major and minor malformations; one study included chromosomal disorders,25
which may result in overestimation of the risk. One large case–control study37
compared the Hungarian congenital abnormality registry with data from the national birth registry office. The authors reported no overall increase in the risk of congenital abnormalities for patients with ulcerative colitis compared with controls; however, they did report an increased risk of selected congenital abnormalities. Further prospective studies are required, with clarification of the type of malformations.
It is important to mention the limitations of this meta‐analysis. It would be difficult and potentially unethical to perform a randomised controlled trial for the pregnancy outcomes; we must therefore base our clinical decisions on observational studies that are vulnerable to bias and confounding variables. The low frequency of the adverse outcomes makes statistical precision difficult. The studies included in the meta‐analysis did not report on disease activity in relation to adverse outcomes. Previous studies have suggested that if a woman conceives while her disease is active, she is more likely to have a premature infant or one with LBW than a woman who has quiescent disease activity.23,38
The incidence of still births and spontaneous abortions is also related to disease activity.39
A prospective study reporting on adverse outcomes and the association with disease activity is still required. In view of the probable increased risk of adverse pregnancy outcomes with active disease, the management of pregnancy in patients with IBD needs to focus on maintaining disease remission before and during pregnancy.
A total of 19 articles have been published to date on the effect of 5‐aminosalicylic acid (5‐ASA), corticosteroids, azathioprine and anti‐tumour necrosis factor α drugs (anti‐TNFα) for inflammatory bowel disease on pregnancy outcomes (table 4). These included two prospective studies and 17 retrospective studies on 1626 women. The results of a pooled analysis suggested no significant increase in the incidence of still births, ectopic pregnancies, spontaneous abortions or LBW for five ASA group of drugs, corticosteroids, azathioprine or anti‐TNFα. An increase was seen in the number of congenital abnormalities for 5‐ASA, anti‐TNFα and azathioprine; however, this may relate to the increased risk for women with IBD and not drug effects. A substantial increase was observed in the number of therapeutic terminations for fetuses exposed to anti‐TNFα during pregnancy, with one study reporting a 19% rate of therapeutic terminations.40
Whether the reason for the termination was drug exposure or another factor is not known. This has substantial implications if the number of adverse events in pregnancy is not increased after exposure to the drug.
Table 4Effect of drugs for inflammatory bowel disease on outcomes of pregnancy
Heterogeneity was seen in some results, which we tried to account for by sensitivity analysis. One limitation of the sensitivity analysis is that many of the larger studies have been published recently, and thus were in both subsets. Most of the studies did not report on disease activity of the patients with IBD or the drugs that the women were taking. Patients with a higher disease activity are reported to have an increased incidence of adverse pregnancy outcomes.23
However, this meta‐analysis also has its strengths, with large numbers of patients being analysed at once, which would have been difficult to gather in one primary randomised controlled trial.
In conclusion, women with inflammatory bowel disease have an increased risk, twice that of the normal population, of having a small or premature baby. Women who have IBD are more likely to have a caesarean section, especially those with Crohn's disease. The surgeon and obstetrician need to discuss between themselves the management of delivery in women with IBD. A definitive study is required to settle the issue of best management and from this a new set of guidelines, to help both patients and their clinicians determine best practice.