Prof. Siew Ng on Maternal Factors Affecting Pregnancy in IBD

Professor Siew Ng from the Chinese University of Hong Kong explains maternal factors that should be considered when managing pregnant patients with inflammatory bowel disease, based on the PIANO Global Consensus.

Prof. Siew C. Ng is associate dean (Research), Croucher Professor in Medical Sciences, and professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong.

TRANSCRIPT:

Hello, I'm Siew Ng from the Chinese University of Hong Kong. I'm excited to share with you the global consensus for the management of IBD in pregnancy. I and other colleagues led the group on maternal factors impacting pregnancy.

So many maternal and interacting factors are known to affect the risks and complications of pregnancy in IBD ranging from genetic factors to microbiome factors to abnormal presentation. So for this group, our first grade statement reached that we suggest counseling that children with first-degree relatives with inflammatory bowel disease as compared to those without have an increased risk of development of IBD. So the level of evidence is very low and the recommendation is conditional. So these data are based on large-scale population-based studies showing that children who have a parent or mother with inflammatory bowel disease have an increased risk of IBD. I think we know that genetic factors play an important role in the path of physiology of diabetes, hence family history is an important risk factor to be considered.

So for the consensus statement, the first one will report that children born to a parent with Crohn's disease may have a higher risk of developing IBD than children born to a parent with ulcerative colitis. So there are nationwide case control studies to show that the risk of IBD in offspring is higher with maternal Crohn's disease than with maternal ulcer colitis. And interestingly, the children generally develop the IBD with the same type that their parents actually have. And the strength of association of inflammatory bowel disease in the infants is higher with increasing numbers of first-degree relatives, with a younger age of diagnosis in their parents, and also if their mothers have Crohn's disease. So the placenta is very unique organ, very highly immunogenic, and the placenta actually expressed an equal complement of maternal and paternal genes without eliciting a maternal immune response that reject the organ.

So a very important question is whether maternal inflammation in pregnancy also affect the center function in women with IBD, We know abnormal presentation is linked to major obstetric complications and also maternal inflammation can affect the placenta function leading to a higher risk of miscarriage, preterm birth, and small for gestational age infants. Therefore, it is likely that IBD can negatively affect development and function of the placenta. So we need to control maternal inflammation better to prevent this.

Another important question is what are the factors that increase IBD risk in offspring? So the 3 key factors are maternal antibiotic use, maternal diet, and microbiome. So the impact of perinatal or prenatal antibiotic use has been well studied in preclinical and clinical studies. And it is known that maternal antibiotic use has an associated increased risk of AUC ratio of 1.75 of the risks of IBD in the offspring. And the risk is higher for early onset IBD for example, the risk of very early onset Crohn's disease with intrauterine antibiotic usage has a hazard ratio of over 2. And we also have seen data that the risk of IBD with maternal exposure with more than 3 causes of antibiotics in pregnancy is higher.

Now the western diet is also associated with increased risk of IBD in the offspring. There are 2 studies, there's a study from Hong Kong and mainland China showing that IBD mothers had a higher food additive intake that non-IBD mothers. And this higher food additive intake was associated with depletion of certain bacteria and an increase in pathogenic bacteria. Interestingly, fecal calprotectin was higher in the gut of infants born to mothers with a higher food additive intake in the groups. And they're now an ongoing interventional trial called MELODY, looking at the impact of an anti-inflammatory diet on the microbiome of pregnant IBD women and the newborn infants; hopefully this will shed light on prevention in early life.

So the last question is whether maternal microbiome impact pregnancy and a risk of IBD in the offspring? So the MECONIUM study from Mount Sinai have shown an abnormal gut microbiome that persists in mothers with IBD during pregnancy, and this also was associated with changes in the bacteria species in the infant's stool. Thess findings were replicated from a study from the Chinese University of Hong Kong showing reduced commensal bacterial sharing in mothers as well as their infants and C-section and maternal antibiotic use led to a reduced in vertical transmission of certain bacterial communities in infants. And there are preclinical studies to show maternal lactobacillus rotatory supplementation may actually protect experimental colitis in female offspring.

So overall maternal factors during pregnancy does affect infant outcomes in IBD and we hope that you find these helpful and will help to guide your clinical practice. Thank you.