Antenatal thiopurine exposure in women with IBD is associated with intrahepatic cholestasis of pregnancy.

BACKGROUND: Pregnant women with inflammatory bowel disease (IBD) continue thiopurines to maintain remission. Other studies have reported intrahepatic cholestasis of pregnancy (ICP) in IBD pregnancies exposed to thiopurines. We aimed to investigate whether thiopurines are associated with an increased risk of ICP. RESEARCH DESIGN AND METHODS: Single-center retrospective cohort study comparing incidence of ICP in thiopurine-exposed versus non-exposed patients with IBD compared with age-matched pregnant controls. RESULTS: The IBD cohort consisted of 386 pregnancies in 243 patients with IBD, with 386 age-matched controls. In patients with IBD, ICP was significantly more common among thiopurine-exposed pregnancies (9.0% vs 1.8%; odds ratio [95% confidence interval] = 5.34 [1.78-16.02]; p = 0.021). IBD patients with thiopurine exposure were significantly more likely to experience ICP compared to non-IBD controls (9.0% vs 1.3%; p < 0.001). Patients with IBD not exposed to thiopurines had a comparable ICP incidence with controls (1.8% vs 1.3%; p = 0.75). Severe ICP occurred in 80% of thiopurine-exposed ICP cases versus 40% in non-exposed (p = 0.25), versus 20% in controls (p = 0.09). CONCLUSION: Thiopurine exposure was associated with a significantly increased risk of ICP among patients with IBD compared to non-exposed IBD patients and age-matched general population controls. The course of ICP was not significantly different in thiopurine-exposed cases.

Risk of Adverse Pregnancy Outcomes for Women with IBD in an Expert IBD Antenatal Clinic.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of adverse outcomes from pregnancy. It is unclear whether IBD indications account for the higher rate of Caesarean section (CS) in IBD patients. Methods: A retrospective cohort study of 179 IBD patients cared for in a dedicated combined IBD antenatal clinic and 31,528 non-IBD patients was performed. The outcomes were method of delivery, preterm birth, birthweight, admission to neonatal intensive care unit (NICU), and stillbirth. We analysed the associations between disease activity, medication with method of delivery, and neonatal outcomes. Results: Delivery by CS was more common in IBD patients (RR 1.45, CI 1.16−1.81, p = 0.0021); emergency CS delivery was equally likely (RR 1.26, CI 0.78−2.07, p = 0.3). Forty percent of elective CS were performed for IBD indications. Stillbirth was five-fold higher in IBD patients (RR 5.14, CI 1.92−13.75, p < 0.001). Preterm delivery, low birthweight, and admission to NICU were not more common in patients with IBD, and IBD medications did not increase these risks. Active disease during pregnancy was not associated with adverse outcomes. Conclusions: Delivery by CS was more frequent in the IBD cohort, and most elective CSs were obstetrically indicated. A dedicated IBD antenatal clinic providing closer monitoring and early detection of potential issues may help improve outcomes.

Perineal Outcomes After Delivery in 179 Mothers with Inflammatory Bowel Disease Compared to 31 258 Controls: A Single-Centre Cohort Study.

BACKGROUND: Women with inflammatory bowel disease [IBD] have an increased risk for caesarean section [CS], but perineal obstetric outcomes, which may have significant consequences for women with IBD, have not been previously studied. METHOD: Maternal outcomes in singleton pregnancies of IBD and non-IBD patients [2014-2018] in a single centre were studied. RESULTS: In 31 528 non-IBD and 179 IBD patients delivery by CS was more likely in IBD patients (p = 0.0021, relative risk [RR] 1.45, confidence interval [CI] 1.16-1.81). Elective CS in IBD patients occurred in 40% for IBD indications, all in accordance with current international guidelines. Perineal trauma, including tears involving the anal sphincter, were equally uncommon in IBD [2.23%] and non-IBD patients [3.40%; p = 0.35, RR 0.64, CI 0.24-1.68]. Of the four IBD patients with clinically significant tears, none had pelvic floor dysfunction or incontinence at follow-up in a specialist postnatal perineal trauma clinic. One IBD patient who had a clinically non-significant second-degree perineal tear reported incontinence a year after giving birth. Previous perianal disease was not associated with significant perineal trauma. CONCLUSION: The low rate of perineal trauma is reassuring for promotion of vaginal delivery in most IBD patients. In those who experienced tears involving the anal sphincter no continence issues occurred. Women with IBD having a greater incidence of delivery by CS was only partially explained by IBD indications.

Provision of care for pregnant women with IBD in the UK: the current landscape.

INTRODUCTION: Suboptimal control of inflammatory bowel disease (IBD) can result in increased rates of adverse pregnancy-related outcomes. We aimed to describe the current landscape of provision of antenatal care for women with IBD in the UK. METHODS: This cross-sectional survey collected data on service setup; principles of care pre-conception, during pregnancy and post partum; and on perceived roles and responsibilities of relevant clinicians. RESULTS: Data were provided for 97 IBD units. Prepregnancy counselling was offered mostly on request only (54%) and in an ad hoc manner. In 86% of units, IBD antenatal care was provided by the patient's usual gastroenterologist, rather than a gastroenterologist with expertise in pregnancy (14%). Combined clinics with obstetricians and gastroenterologists were offered in 14% of units (24% academic vs 7% district hospitals; p=0.043). Communication with obstetrics was 'as and when required' in 51% and 30% of IBD units reviewed pregnant women with IBD 'only when required'. The majority of respondents thought gastroenterologists should be involved in decisions regarding routine vaccinations (70%), breast feeding (80%), folic acid dosage (61%) and venous thromboembolism (VTE) prophylaxis (53%). Sixty-five per cent of respondents thought that gastroenterologists should be involved in decisions around mode of delivery and 30% recommended caesarean sections for previous but healed perianal disease. CONCLUSIONS: This nationwide survey found considerable variation in IBD antenatal services. We identified deficiencies in service setup, care provided by IBD units and clinician knowledge. A basic framework to inform service setup, and better education on the available clinical guidance, is required to ensure consistent high-quality multidisciplinary care.

Standards for the provision of antenatal care for patients with inflammatory bowel disease: guidance endorsed by the British Society of Gastroenterology and the British Maternal and Fetal Medicine Society.

BACKGROUND: Pregnant women with inflammatory bowel disease (IBD) are at increased risk of adverse pregnancy outcomes. Comprehensive guidelines on medical management have been published; yet, there is limited guidance on service set-up and minimum standards of care for pregnant women with IBD. AIM: To develop a position statement on service set-up and minimum standards of care in the UK. METHODS: A working group consisting of 16 gastroenterologists, obstetricians, obstetric physician, IBD specialist nurses and midwives was assembled. Initial draft statements were produced and a modified Delphi process with two rounds of voting applied. Statements were modified according to voters' feedback after each round. Statements with ≥80% agreement were accepted. RESULTS: All 15 statements met criteria for inclusion. To facilitate optimal care, regular and effective communication between IBD and obstetric teams is required. There should be nominated link clinicians for IBD in obstetric units and for pregnancy in IBD units. Preconception counselling should be available for all women with IBD. All pregnant women should be advised on the safety of IBD medication during pregnancy and breast feeding, the optimal mode of delivery, the management of biologics (where applicable) and safety of childhood vaccinations. Regular audit of pregnancy outcomes and documentation of advice given is recommended. CONCLUSION: Position statements have been developed that advise on the importance of joined-up multidisciplinary care, proactive decision-making with clear documentation and communication to the woman and other healthcare practitioners.

IBD in pregnancy: recent advances, practical management.

Inflammatory bowel disease (IBD) poses complex issues in pregnancy, but with high-quality care excellent pregnancy outcomes are achievable. In this article, we review the current evidence and recommendations for pregnant women with IBD and aim to provide guidance for clinicians involved in their care. Many women with IBD have poor knowledge about pregnancy-related issues and a substantial minority remains voluntarily childless. Active IBD is associated with an increased risk of preterm birth, low for gestation weight and fetal loss. With the exception of methotrexate and tofacitinib the risk of a flare outweighs the risk of IBD medication and maintenance of remission from IBD should be the main of care. Most women with IBD will experience a normal pregnancy and can have a vaginal delivery. Active perianal Crohn's disease is an absolute and ileal pouch surgery a relative indication for a caesarean section. Breast feeding is beneficial to the infant and the risk from most IBD medications is negligible.

Solar cycle predicts folate-sensitive neonatal genotypes at discrete phases of the first trimester of pregnancy: a novel folate-related human embryo loss hypothesis.

Folate, a key periconceptional nutrient, is ultraviolet light (UV-R) sensitive. We therefore hypothesise that a relationship exists between sunspot activity, a proxy for total solar irradiance (particularly UV-R) reaching Earth, and the occurrence of folate-sensitive, epigenomic-related neonatal genotypes during the first trimester of pregnancy. Limited data is provided to support the hypothesis that the solar cycle predicts folate-related human embryo loss: 379 neonates born at latitude 54°N between 1998 and 2000 were examined for three folate-sensitive, epigenome-related polymorphisms, with solar activity for trimester one accessed via the Royal Greenwich Observatory-US Air force/National Oceanic and Atmospheric Administration Sunspot Database (34,110 total observation days). Logistic regression showed solar activity predicts C677T-methylenetetrahydrofolate reductase (C677T-MTHFR) and A66G-methionine synthase reductase (A66G-MSR) genotype at discrete phases of trimester one. Total and maximal sunspot activity predicts C677T-MTHFR genotype for days 31-60 of trimester one (p=0.0181 and 0.0366, respectively) and A66G-MSR genotype for days 61-90 of trimester one (p=0.0072 and 0.0105, respectively). Loss of UV-R sensitive folate associated with the sunspot cycle might therefore interact with variant folate genes to perturb DNA methylation and/or elaboration of the primary base sequence (thymidylate synthesis), as well as increase embryo-toxic homocysteine. We hypothesise that this may influence embryo viability leading to 677CC-MTHFR and 66GG-MSR embryo loss at times of increased solar activity. This provides an interesting and plausible link between well recognised 'folate gene originated developmental disorders' and 'solar activity/seasonality modulated developmental disorders'.

Photoperiod at conception predicts C677T-MTHFR genotype: A novel gene-environment interaction.

Data is presented, which suggest that the day length a woman experiences during the periconceptional period predicts the C677T-MTHFR genotype of her child. Logistic regression analysis involving 375 neonates born in the same geographical location within a three year period demonstrated that photoperiod (minutes) at conception predicts both genotype (P = 0.0139) and mutant allele carriage (P = 0.0161); the trend clearly showing that the 677T-MTHFR allele frequency increases as photoperiod increases. We propose a number of explanations, including a hypothesis in which a long photoperiod around conception decreases maternal systemic folate because of UVA induced dermal oxidative degradation of 5-methyl-H(4)folate, leading to a lower cellular 5,10-methylene-H(4)folate status. In this scenario, 5,10-methylene-H(4)folate would be more efficiently used for dTMP and DNA synthesis by 677T-MTHFR embryos than wildtype embryos giving the 677T-MTHFR embryos increased viability, and hence increasing mutant T-allele frequency. Alternate hypotheses include: increased seasonal availability of folate rich foods that genetically buffer any negative effect of 677T-MTHFR in embryos; seasonal oxidative stress lowering embryo-toxic homocysteine; an undefined hormonal effect of photoperiod on the neuroendocrine axis, which mediates genotype/embryo selection. The effect of photoperiod on genotype seems clear, but the speculative molecular mechanism underpinning the effect needs careful examination.