Thiopurines (Azathioprine, Mercaptopurin)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Alami, 2017	prospective cohort	Data were obtained by structured telephone interviews within 22 weeks after the Last Menstrual Period (i.e. before the level II ultrasound scan).	Structured telephone interviews and/or questionnaires mailed to the mother and/or her physician after expected date of delivery. Data were detailed information about the outcome of the pregnancy. CA were classified as major/minor by a clinical geneticist, who was blind to the drug exposure status.	No adjustment.
Andreoli, 2022	nested case control	Interviews conducted retrospectively, by means of a maternal self-reported questionnaire.	Children’s follow-up made with a maternal self-reported questionnaire. Children’s diagnoses of Autoimmune diseases (AD) and/or neurodevelopmental disorders (ND) reported by the mothers were checked through a 2nd round of interview, and only cases certified by a medical specialist were considered.	None. No statistical difference in terms of preterm birth, children sex, maternal diagnosis.
Angelberger, 2011	retrospective cohort	Azathioprine and all other therapies of mothers were documented at each visit at the department and registered in a local pregnancy-registry.	Mothers were asked about the mental and physical development, infections, hospitalisations and vaccinations of their offspring. In addition, health status were retrieved from the 'Mutter-Kind-Pass' and from diaries kept by the mothers on her children, medical records, and the mothers' memory.	None.
Ban (Controls unexposed, disease free), 2014	retrospective cohort (claims database)	Among mothers with IBD, all prescriptions for 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids (including both oral and rectal corticosteroids) were extracted from their primary care electronic health records.	All diagnoses of major congenital anomalies were identified in the children’s medical records using Read codes, classified into system-specific groups according to the European Surveillance of Congenital Malformations subgroups. These subgroups were defined using ICD-10.	No adjustment for this group of controls. Singletons only. Children with records of genetic anomalies attributed to known teratogens (such as Read codes for anomalies caused by maternal infections and fetal alcohol syndrome) were excluded.
Ban (Controls unexposed, sick), 2014	retrospective cohort (claims database)	Among mothers with IBD, all prescriptions for 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids (including both oral and rectal corticosteroids) were extracted from their primary care electronic health records.	All diagnoses of major congenital anomalies were identified in the children’s medical records using Read codes, classified into system-specific groups according to the European Surveillance of Congenital Malformations subgroups. These subgroups were defined using ICD-10.	Adjusted for maternal age at childbirth, calendar year of childbirth, maternal smoking status, and socioeconomic deprivation measured using the Townsend Index of Deprivation. Singletons only. Children with records of genetic anomalies attributed to known teratogens (such as Read codes for anomalies caused by maternal infections and fetal alcohol syndrome) were excluded.
Bröms, 2016	nested case control	Information on drug treatment was obtained from the Prescribed Drug Register, the Medical Birth Register and from medical charts.	Data related to prematurity was obtained from the Medical Birth Register (structured forms throughout pregnancy, delivery and the neonatal period).	Cases and controls were matched 1:1 by maternal age, parity and Inflammatory bowel diseases (IBD) diagnosis (Crohn’s disease (CD) or ulcerative colitis (UC)). OR for preterm adjusted for previous preterm births and any comorbidity (hypertension, diabetes, infections, rheumatoid diseases, ...). Singletons only. Smoking and Body mass index were similar for cases and controls
Bröms (Crohn’s disease, stable disease), 2014	population based cohort retrospective	Filled drug prescriptions as recorded in the Prescribed Drug Register by date of dispensing, drug name, and preparation according to the Anatomical Therapeutic Chemical classification.	The Medical Birth Register that includes information from standardized records that are completed by physicians and midwives throughout the antenatal and perinatal care program.	Adjustments were made for maternal age, parity, smoking, body mass index, and comorbidity (a diagnosis of diabetes, hypertension, chronic autoimmune disease, or asthma). Singletons only.
Casanova, 2013	retrospective cohort	Data were obtained from the review of medical records and an interview with the patient when additional information was necessary was conducted. Collected data including data on drugs received during 3 months before conception and during pregnancy (during each trimester of pregnancy).	Review of medical record /- interview with the patient. Gestational age at the time of delivery, type of delivery, spontaneous/elective abortions, preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations, intensive care unit admissions or death.	In the multivariate analysis, the dependent variable was the GPO and the independent variables were: the type of Inflammatory Bowel disease (IBD), IBD surgeries before pregnancy, maternal age at conception, consumption of toxic substances during pregnancy, IBD activity at the moment of conception, activity of disease during pregnancy, exposure to thiopurines, and exposure to anti-TNF-α drugs.
Cleary (Controls unexposed, NOS), 2009	population based cohort retrospective	Medication exposures in early pregnancy are collected prospectively at the first antenatal care visit on a standard form used throughout the country : use of medication, when, what dose. Medication names are semiautomatically converted to ATC.	Multiple source : Medical Birth Register , the Register of Birth Defects and the Hospital Discharge Register were analyzed. (Malformations : use of ICD-9 and 10).	Adjustments were made for year of birth, maternal age, parity, smoking, and body mass index. For outcomes low birth weight, preterm and small for gestational age: only singleton infants are counted.
Cleary (Controls unexposed, sick), 2009	population based cohort retrospective	Medication exposures in early pregnancy are collected prospectively at the first antenatal care visit on a standard form used throughout the country : use of medication, when, what dose. Medication names are semiautomatically converted to ATC.	Multiple source : Medical Birth Register, the Register of Birth Defects and the Hospital Discharge Register were analyzed. (Malformations : use of ICD-9 and 10).	Adjustments were made for year of birth, maternal age, parity, smoking, and body mass index for the outcome malformations only.
Coelho (Controls exposed to 5-ASA), 2011	retrospective cohort	Information (medications, smoking and alcohol consumption, obstetric history) was recorded on website forms by the gastroenterologists belonging to the CESAME panel. Data were collected retrospectively for the year 2005 and prospectively from 1 January 2006 until 1 January 2007.	Information was recorded on website forms by the gastroenterologists belonging to the CESAME panel. Data were collected retrospectively for the year 2005 and prospectively from 1 January 2006 until 1 January 2007.	No adjustment.
Coelho (Controls unexposed, sick), 2011	retrospective cohort	Information was recorded on website forms by the gastroenterologists belonging to the CESAME panel. Data were collected retrospectively for the year 2005 and prospectively from 1 January 2006 until 1 January 2007.	Information was recorded on website forms by the gastroenterologists belonging to the CESAME panel. Data were collected retrospectively for the year 2005 and prospectively from 1 January 2006 until 1 January 2007.	No adjustment.
Colvin, 2010	retrospective cohort (claims database)	The national Pharmaceutical Benefits Scheme, with around 80% of prescriptions dispensed in Australia.	Health administrative data from the Western Australia (WA) Hospital Morbidity Data System, the Midwives’ Notification System, the WA Registry of Births and Deaths and the Birth Defect Registry of WA, enabling pregnancies and pregnancy outcomes to be ascertained.	None.
Dejaco, 2005	prospective cohort	Not specified.	Not specified.	No adjustment. The 2 groups did not differ in maternal age, body mass index, nicotine abuse, duration of disease or concomitant therapy with prednisolone and/or 5-aminosalicylates.
Francella, 2003	retrospective cohort	Verification of 6-mercaptopurine (6-MP) exposure was achieved by review of each patient’s individual medical records.	Review of medical records by the authors.	None.
Goldstein, 2007	prospective cohort	Data were collected at the time of exposure, before the pregnancy outcome was known. Information collected included Azathioprine dose and use of other treatments, teratogenic or potentially teratogenic (under current debate in the medical literature).	All women were contacted after the expected date of delivery for a follow-up telephone interview, and information was collected regarding outcome of the pregnancy, perinatal complications, birth weight, physical findings, and major birth defects.	None.
He, 2022	nested case control	The therapeutic data before and after pregnancy in both TAK patients and controls were collected and analyzed (NOS).	The demographic, laboratory, imaging, and therapeutic data before and after pregnancy in both TAK patients and controls were collected and analyzed (NOS).	No match/adjustment for analysis of medicines during pregnancy. Patients with a history of uterine surgery and subjects with pregnancies through assisted reproductive technology or multiple pregnancies were excluded.
Howren, 2020	retrospective cohort (claims database)	PharmaNet captures complete information on all drug prescriptions dispensed including drug identification number, dispensation date, dispensation quantity, dosage, and duration.	Data from the Medical Services Plan database (MSP), the hospital admissions in the Discharge Abstract Database (DAD) and the BC Perinatal Database Registry (BCPDR) which contains data from obstetrical and neonatal medical records on ~99% of births in BC.	Multivariate model. Potential confounders considered: maternal and pregnancy characteristics (body mass index, age, prior adverse pregnancy outcome...), maternal comorbidities (anxiety, depression, diabetes), other medication use before pregnancy and during pregnancy, and healthcare utilisation (considered markers of disease severity and health status).
Jolving, 2021	population based cohort retrospective	Prescription of thiopurines were extracted from the Danish National Prescription Register using Anatomical Therapeutic Chemical (ATC) classification.	Data were extracted from the health registers: the Danish Medical Birth Register (DMBR), the Danish National Patient Register and the Civil Registration System. (For malformations : DQ00-DQ89 in the first year of life).	Adjustment for Charlson comorbidity index, maternal underlying disease, maternal and paternal age at childbirth, parity, maternal smoking, sex of the child, small for gestational age, preterm birth and calendar year of childbirth.
Kanis, 2017	prospective cohort	Before pregnancy, patients were counseled on inflammatory bowel disease (IBD) medication use, during pregnancy, data regarding medication adherence were collected.	Antibiotic treatment (infection), allergies, and eczema were obtained through telephonic questionnaire with mothers and/or from the general practitioner. Mode of delivery and congenital abnormalities were noted during the first visit after delivery. No information for spontaneous abortion.	Spontaneous abortions: adjusted for disease activity during conception, fertility treatment, and diagnosis. Other outcomes : adjusted for smoking. No difference between the 2 groups for: maternal age, body mass index, smoking, folic acide use.
Kanis, 2021	retrospective cohort	Medication use during pregnancy was retrieved during a telephonic interview with mothers and information was later verified in their medical chart.	Outcomes were retrieved during a telephonic interview with mothers and information was later verified in their medical chart. Long-term health outcomes of children were retrieved during the telephonic interview with mothers and also collected from the general practitioner.	Preterm : adjusted on systemic corticosteroid use, obstetrical complications, disease activity and endoscopy during pregnancy. Antibiotic treated infections/severe infections : adjusted on smoking during pregnancy, obstetric complications, breast feeding, anti-TNF. Maternal age and smoking considered and not impacting.
Komoto, 2016	retrospective cohort	From the medical records, therapy was collected. Each patient was given a questionnaire to answer.	Each patient completed a questionnaire, notably regarding pregnancy outcomes: live birth, spontaneous abortion, birth weight, and presence of congenital abnormalities. To identify the course and outcome of their pregnancies, patients referred to the notebooks, filled out by physicians or nurses.	None.
Koslowsky, 2019	prospective cohort	The patients’ characteristics were collected from clinical files and a completed questionnaire. The doses and duration of thiopurines were documented prospectively.	Clinical files and a completed questionnaire : gestational age at delivery, neonatal birth week, and Apgar scores. National Health Program for anemia. Interview with the mother for other outcomes.	No adjustment. Patients exposed to steroids or biologics were excluded from the study.
Langagergaard (Controls unexposed, NOS), 2007	population based cohort retrospective	Exposition to a medication before or during pregnancy was based on the Danish Prescription database (using the ATC classification system).	The birth outcome data were collected from the Fertility Database (FTDB), including preterm birth and low birth weight at term. Information about congenital anomalies (including chromosomal abnormalities) was obtained from the Danish Hospital Discharge Registry (using ICD-8 and 10).	Comparison group matched by month and year of birth and the county in which the mother resided. Stratification for maternal age (<30 years, ≥ 30 years). Only singleton births. Parity did not change the risk estimates.
Langagergaard (Controls unexposed, sick), 2007	population based cohort retrospective	Exposition to a medication before or during pregnancy was based on the Danish Prescription database (using the ATC classification system).	The birth outcome data were collected from the Fertility Database (FTDB), including preterm birth and low birth weight at term. Information about congenital anomalies (including chromosomal abnormalities) was obtained from the Danish Hospital Discharge Registry (using ICD-8 and 10).	Comparison group matched by month and year of birth and the county in which the mother resided. Stratification for maternal age (<30 years, ≥ 30 years). Only singleton births. Parity did not change the risk estimates.
Lazzaroni, 2020	retrospective cohort	Data regarding therapy prescribed during pregnancy were retrospectively retrieved from medical charts from the two centers and collected in a common database.	Data regarding neonatal features were retrieved from medical charts. The long-term neuropsychiatric outcome of the children was assessed through a specifically designed telephone interview, only disorders which had been certified by a child neurologist or psychiatrist were considered.	Matched for : renal involvement (present/absent); Antiphospholipid antibodies (aPL) status at the beginning of pregnancy (positive/negative); age of the mother at the beginning of pregnancy (±5 years); age of the child at the time of the study (±2 years). Only Singletons.
Mahadevan, 2021	prospective cohort	Information was collected on medication use prior to conception, during pregnancy, and for 1 year postpartum through questionnaires at each trimester of pregnancy, at the end of the pregnancy, 4, 9, and 12 months post-delivery, and once a year up to the age of 18 years of age.	Infant outcomes were collected by questionnaires. Developmental milestones were specifically assessed through the nationally validated Ages and Stages Questionnaire (ASQ3), at 12, 24, 36 and 48 months of age.	Adjusted for relevant confounders such as disease activity, maternal age, prior spontaneous abortions, and preterm birth if applicable. Singleton only. No statistical difference of Body Mass Index and smoking.
Marder, 2013	retrospective cohort	Medication use at conception and during pregnancy were recorded by a structured interview of the mother with a study team member, as well as medical record review (full medical records were available for 70% of the pregnancies).	Data were collected from the mothers through a structured interview with a study team member, as well as medical record review (full medical records were available for 70% of the pregnancies).	Multivariable logistic regression adjusted for maternal education level, duration of pregnancy, small for gestational age, and antiphospholipid syndrome. Propensity score used : variables judged to have clinical relevance based on a priori knowledge were retained : lupus nephritis, SLE flare during pregnancy, and non-fluorinated corticosteroid use (dose in mg).
Meyer, 2025	population based cohort retrospective	The Système National des Données de Santé (SNDS) that contains comprehensive outpatient (drugs, procedures) and inpatient (expensive drugs dispensed information.	Major congenital malformations identification was based on hospital discharge diagnosis and specific medical or surgical procedures performed.	Births exposed to any drug identified as teratogenic were excluded. Adjusted by propensity score weighting for: year of pregnancy, age, diabetes, antihypertensive treatment, obesity, alcohol, smoking, resources, IBD type, IBD duration, arthritis, psoriasis, IBD-related hospitalization, corticosteroids use 6 months before pregnancy, assisted reproduction, folic acid, multiple pregnancy, child’ sex.
Meyer a (Controls exposed to Anti-TNF), 2021	retrospective cohort (claims database)	Drugs dispensed before or during pregnancy were recorded in the French national health data system (Système National des Données de Santé (SNDS)).	Outcome about pregnancies are extracted from the French national health data system (Système National des Données de Santé (SNDS)).	Adjusted for year, age, income, deprivation index, IBD type and duration, IBD-related hospitalization, corticosteroid and aminosalicylate use during pregnancy, gravidity, preconception folic acid, place of pregnancy, multiple pregnancy, caesarean, pregnancy term, birth weight for gestational age... Exclusion of children exposed to methotrexate, vedolizumab, or ustekinumab during pregnancy.
Meyer a (Controls unexposed, sick), 2021	retrospective cohort (claims database)	Drugs dispensed before or during pregnancy were recorded in the French national health data system (Système National des Données de Santé (SNDS)).	Outcome about pregnancies are extracted from the French national health data system (Système National des Données de Santé (SNDS)).	Adjusted for year, age, income, deprivation index, IBD type and duration, IBD-related hospitalization, corticosteroid and aminosalicylate use during pregnancy, gravidity, preconception folic acid, place of pregnancy, multiple pregnancy, caesarean, pregnancy term, birth weight for gestational age... Exclusion of children exposed to methotrexate, vedolizumab, or ustekinumab during pregnancy.
Meyer b (Controls exposed to Anti-TNF), 2021	retrospective cohort (claims database)	Drugs dispensed before or during pregnancy were recorded in the French national health data system (Système National des Données de Santé (SNDS)).	Outcome about pregnancies are extracted from the French national health data system (Système National des Données de Santé (SNDS)).	Adjusted for age, income, complementary universal health insurance status, year, gravidity, place of end of pregnancy, assisted reproduction, IBD type, IBD duration, aminosalicylates exposure, hospitalisations before pregnancy, diabetes (only for SGA/LGA)... Exclusion of pregnancies exposed to methotrexate, vedolizumab or ustekinumab. Sensitivity analysis on Singleton only.
Meyer b (Controls unexposed, sick), 2021	retrospective cohort (claims database)	Drugs dispensed before or during pregnancy were recorded in the French national health data system (Système National des Données de Santé (SNDS)).	Outcome about pregnancies are extracted from the French national health data system (Système National des Données de Santé (SNDS)).	Adjusted for age, income, complementary universal health insurance status, year, gravidity, place of end of pregnancy, assisted reproduction, IBD type, IBD duration, aminosalicylates exposure, hospitalisations before pregnancy, diabetes (only for SGA/LGA)... Exclusion of pregnancies exposed to methotrexate, vedolizumab or ustekinumab. Sensitivity analysis on Singleton only.
Nguyen, 2019	prospective cohort	Data in the MSBase registry, including prospective pregnancy data, is entered in real time or near real time, as part of routine clinical visits. Information collected included: disease-modifying therapies exposure before and during pregnancy.	Data in the MSBase registry, including prospective pregnancy data, is entered in real time or near real time, as part of routine clinical visits. Information collected included pregnancy outcomes.	None.
Nguyen_IBD (Controls exposed to TNFi), 2025	population based cohort retrospective	Data on drug exposure were obtained from the Prescribed Drug Register, which contains information on all dispensations of prescribed drugs in pharmacies in Sweden	Intrahepatic cholestasis of pregnancy (ICP) was obtained from the Medical Birth Register (≥1 maternal ICD-10 code O26.6) or from the National Patient Register (NPR) (≥1 outpatient or inpatient visit from Last menstrual period to delivery date).	Singletons only. Propensity score matching controlled for maternal age, education, income, country of birth, smoking, body mass index, year, parity, disease duration, history of miscarriage, history of Intrahepatic cholestasis of pregnancy (ICP), hypertension, type 2 diabetes, diseases of the liver, gallstones, biliary tract, IBD subtypes, glucocorticoids, and advanced therapies.
Nguyen_IBD (Controls unexposed, sick), 2025	population based cohort retrospective	Data on drug exposure were obtained from the Prescribed Drug Register, which contains information on all dispensations of prescribed drugs in pharmacies in Sweden	Intrahepatic cholestasis of pregnancy (ICP) was obtained from the Medical Birth Register (≥1 maternal ICD-10 code O26.6) or from the National Patient Register (NPR) (≥1 outpatient or inpatient visit from Last menstrual period to delivery date).	Singletons only. Propensity score matching controlled for maternal age, education, income, country of birth, smoking, body mass index, year, parity, disease duration, history of miscarriage, history of Intrahepatic cholestasis of pregnancy (ICP), hypertension, type 2 diabetes, diseases of the liver, gallstones, biliary tract, IBD subtypes, glucocorticoids, and advanced therapies.
Nguyen_SLE (Controls exposed to TNFi), 2025	population based cohort retrospective	Data on drug exposure were obtained from the Prescribed Drug Register, which contains information on all dispensations of prescribed drugs in pharmacies in Sweden	Intrahepatic cholestasis of pregnancy (ICP) was obtained from the Medical Birth Register (≥1 maternal ICD-10 code O26.6) or from the National Patient Register (NPR) (≥1 outpatient or inpatient visit from Last menstrual period to delivery date).	Singletons only. Propensity score matching controlled for maternal age, education, income, country of birth, smoking, body mass index, year, parity, disease duration, history of miscarriage, history of Intrahepatic cholestasis of pregnancy (ICP), hypertension, type 2 diabetes, diseases of the liver, gallstones, biliary tract, IBD subtypes, glucocorticoids, and advanced therapies.
Nguyen_SLE (Controls unexposed, sick), 2025	population based cohort retrospective	Data on drug exposure were obtained from the Prescribed Drug Register, which contains information on all dispensations of prescribed drugs in pharmacies in Sweden	Intrahepatic cholestasis of pregnancy (ICP) was obtained from the Medical Birth Register (≥1 maternal ICD-10 code O26.6) or from the National Patient Register (NPR) (≥1 outpatient or inpatient visit from Last menstrual period to delivery date).	Singletons only. Matching (or adjustment) for maternal age, education, income, country of birth, smoking, body mass index, year, parity, disease duration, history of miscarriage, history of ICP, hypertension, type 2 diabetes, diseases of the liver, gallstones, biliary tract, antiphospholipid syndrome and renal diseases, glucocorticoids, hydroxychloroquine, warfarin and heparin.
Norgard, 2020	population based cohort retrospective	Data on mothers’ use of thiopurines were retrieved from the Nationwide Prescription Registry and based on one or more filled prescriptions for azathioprin (using ATC system).	All outcomes were based on data from theMedical Birth Registry and the Danish National Patient Registry including data are obtained from birth forms and records of all discharges from Danish hospitals (using ICD-8 and 10).	Covariates were selected a priori. Adjusted for comorbidity of the mother, women's age at time of birth of the child, calendar year of child birth, maternal smoking in pregnancy, parity, gender of the child, child small for gestational age, child preterm birth. Singletons only.
Norgard (Controls unexposed, NOS), 2003	population based cohort retrospective	The population‐based Pharmaco‐Epidemiological Prescription Database of North Jutland was used to identify all pregnancies in which women had taken up prescriptions for azathioprine or mercaptopurine (using ATC system).	The Danish Medical Birth Registry and The County Hospital Discharge Registry were used with the International Classification of Diseases (ICD-8 and 10). In exposed women, cases of children with malformations were validated by review of the hospital records.	Adjusted for mother's age, parity and smoking in a logistic regression model. Low birth weight also for gestational age (continuous variable). Singletons only.
Norgard (Controls unexposed, sick), 2003	population based cohort retrospective	The population‐based Pharmaco‐Epidemiological Prescription Database of North Jutland was used to identify all pregnancies in which women had taken up prescriptions for azathioprine or mercaptopurine (using ATC system).	The Danish Medical Birth Registry and The County Hospital Discharge Registry were used with the International Classification of Diseases (ICD-8 and 10). In exposed women, cases of children with malformations were validated by review of the hospital records.	Adjusted for mother's age, parity and smoking in a logistic regression model. Low birth weight also for gestational age (continuous variable). Singletons only.
Reynolds, 2022	retrospective cohort	Retrospective data were collected using a previously piloted questionnaire, completed by women and by collection of maternal data via interview and reviewing the medical records. Pregnancy data collected included drug exposure at conception, during pregnancy, and during breastfeeding.	Retrospective data were collected using a previously piloted questionnaire. First part: completed by women and reviewing the medical records. A second part of the questionnaire was completed by the mother to collect data on outcomes in each child up to the age of 17 (malfo, infections...).	For low birth weight and infections : in the imputed model, data for hypertension and renal disease were imputed using chained equations. No adjustment for other outcomes.
Schramm, 2006	retrospective cohort	Review of medical records.	Review of medical records.	None.
Selinger (Controls unexposed, disease free), 2023	retrospective cohort	Complete medication exposure was prospectively recorded at inflammatory bowel disease (IBD) antenatal clinic visits and therefore captured all IBD medication exposure. For controls, data was obtained from the electronic pregnancy medical records.	Data was obtained from the electronic pregnancy medical records. Bile acid measurements were only undertaken when there was clinical suspicion of Intrahepatic cholestasis of pregnancy (ICP) when patients attended for antenatal care.	Controls matched by age (1:1) and from the same geographic area.
Selinger (Controls unexposed, sick), 2023	retrospective cohort	Complete medication exposure was prospectively recorded at inflammatory bowel disease (IBD) antenatal clinic visits and therefore captured all IBD medication exposure.	Data was obtained from the electronic pregnancy medical records. Bile acid measurements were only undertaken when there was clinical suspicion of Intrahepatic cholestasis of pregnancy (ICP) when patients attended for antenatal care.	None.
Shim, 2011	retrospective cohort	Medical records of eligible women were reviewed: medications used before and during pregnancy were recorded. Women reported taking medications during their first antenatal visit.	Medical records of eligible women were reviewed: single live births, low birth weight (LBW) at term (<2500 g), preterm births (<37 weeks gestation), congenital anomalies, and neonatal adverse outcomes (i.e outcomes necessitating admission to neonatal intensive care unit).	Age-matched controls (and women with inflammatory bowel disease (IBD)). Singletons only.
Tennenbaum, 1999	retrospective cohort	A postal questionnaire completed by the mother, including details on drugs related to IBD, 6 months before pregnancy and during pregnancy with details on the period of exposure during pregnancy.	A postal questionnaire completed by the mother, including details on neonatal outcomes: birth date, delivery, birth weight, birth length, head circumference and status health of child at the date of questionnaire. In case of interruption of pregnancy, circumstances should be detailed.	None.
Vestergaard, 2024	retrospective cohort	All data were obtained through review of medical records, and all data from both mothers and children were recorded prospectively in medical records from routine clinical care. Medication requiring a prescription was registered.	All data were obtained through review of medical records, and all data from both mothers and children were recorded prospectively in medical records from routine clinical care.	Singleton births. Infections: adjusted for preterm birth (<37 weeks), steroid administration in the 3rd trimester, disease activity during pregnancy and disease phenotype. Concomitant steroid usage anytime during pregnancy and SGA are left out of the multivariate analysis due to collinearity with other covariates.
Viktil (Controls exposed to other treatments), 2012	population based cohort propective	Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).	The Medical Birth Registry of Norway (MBRN), a population based register that contains information about all births, including late abortion, from 12 weeks of gestation onwards.	None for this group of exposure. Singletons only.
Viktil (Controls unexposed, NOS), 2012	population based cohort propective	Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).	The Medical Birth Registry of Norway (MBRN), a population based register that contains information about all births, including late abortion, from 12 weeks of gestation onwards.	None for this group of exposure. Singletons only.
Yeaman (Controls mainly exposed to biologics), 2023	prospective cohort	The physicians in this clinic use a standardized clinical care pathway to ensure consistent patient education about the safety of medications. Medications are recorded at each visit; and pregnancy complications and pregnancy outcomes are captured using standardized questionnaires.	Complete blood cell count (CBC) of the infants was done at the time of the newborn heel prick (universal screening program for all infants after birth). A neonatal specialist who did not have access to the in utero medication exposure then separately reviewed each case of cytopenia.	No significant differences in household income, undergraduate degree, maternal age and ethnicity. Pregnant individuals were not eligible to participate in this study if there was a history of anemia in the mother within 3 months of conception, acute perinatal blood loss, known congenital or chromosomal fetal anomaly, or hemolysis of the newborn due to alloimmune antibodies.
Yeaman (Controls unexposed, disease free), 2023	prospective cohort	The physicians in this clinic use a standardized clinical care pathway to ensure consistent patient education about the safety of medications. Medications are recorded at each visit; and pregnancy complications and pregnancy outcomes are captured using standardized questionnaires.	Complete blood cell count (CBC) of the infants was done at the time of the newborn heel prick (universal screening program for all infants after birth). A neonatal specialist who did not have access to the in utero medication exposure then separately reviewed each case of cytopenia.	No significant differences in household income, undergraduate degree, maternal age and ethnicity. Pregnant individuals were not eligible to participate in this study if there was a history of anemia in the mother within 3 months of conception, acute perinatal blood loss, known congenital or chromosomal fetal anomaly, or hemolysis of the newborn due to alloimmune antibodies.

master protocol