OBJECTIVE:Paracetamol is the drug of choice for treating pain and fever during pregnancy. Concerns exist regarding risk of neurodevelopmental disorders in prenatally exposed offspring, especially autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Since September 2,013, most paracetamol sales are prescription-based in Denmark, enabling investigation in a population-based setting. We investigated the association between prescription-based paracetamol use during pregnancy and the risk of clinically diagnosed ASD and ADHD detected in early childhood among exposed offspring. METHOD:We included all singleton children live-born between 01 October 2,014 and 31 December 2,021, and their linked mothers using Danish nationwide health registers. Exposure was defined as ≥1 prescriptions redeemed for paracetamol during pregnancy. Children were followed until 6 years of age or the end of the study period (31 December 2,022). Using a triangulation approach, we compared i) exposed children to unexposed children, ii) exposed children to children of mothers who redeemed prescriptions before - but not during - pregnancy, and iii) used a paternal negative-exposure group. RESULTS:Adjusted risk ratios (aRR) for ASD and ADHD at 6 years of age among exposed children compared to unexposed were 1.15 (95% CI 0.96-1.39) and 1.09 (95% CI 0.85-1.40), respectively. No increased risks were observed when comparing to children of mothers redeeming prescriptions before - but not during - pregnancy (aRR 1.01 (95% CI 0.76-1.32) and (aRR 1.01 (95% CI 0.67-1.53)), suggesting confounding by underlying maternal illness. In the paternal negative-exposure group, aRRs were similar (ASD: 1.06 (95% CI, 0.88-1.28)) and slightly higher (ADHD: 1.23 (95% CI, 0.96-1.58)) to the primary estimates, the latter suggesting unmeasured familial confounding. CONCLUSION:Our findings suggest that prenatal exposure to prescription-based paracetamol is unlikely to confer a clinically meaningful increased risk of ASD or ADHD diagnosed by 6 years of age. Due to limited follow-up time, our findings only apply to early-diagnosed neurodevelopmental disorders which are likely to be the more severe cases.

BACKGROUND:Prenatal alcohol exposure (PAE) is a risk factor for early-onset psychopathology. Low birthweight (LBW), one potential consequence of PAE, increases the vulnerability of children for externalizing disorders. This study investigates potential sex-specific indirect pathways linking PAE to behavioral symptoms in offspring, focusing on LBW as a mediating and moderating factor. METHODS:Participants were 9-10-year-old singleton children whose biological parents reported on pregnancy experiences in the Adolescent Brain Cognitive Development (ABCD) study. PAE was a binary variable, indicating any use during pregnancy. Externalizing behavioral problems were assessed with the Child Behavior Checklist and modeled continuously. LBW (<2500 g) was calculated based on parental reports. We applied a four-way decomposition analysis with stratification by sex. This causal framework allows to dissect the total effect into controlled direct effect (CDE), reference interaction (INTref), mediated interaction (INTmed), and pure indirect effect (PIE). RESULTS:The analytic sample (N = 7502) was evenly split by sex, and nearly 50% were non-Hispanic White children. A total of 2083 children were exposed to PAE. The adjusted total effect of PAE on externalizing behavioral problems was identified (β = 0.91; 95%CI: 0.38, 1.44), with slightly weaker effects observed in males (β = 0.88; 95%CI: 0.12, 1.64) than in females (β = 0.98; 95%CI: 0.25, 1.71). Decomposition analysis indicated potential interaction with a major difference in CDE in the presence of LBW and in its absence, specifically for males (β = 4.30, 95% CI: 1.97, 8.40 and β = 0.70, 95%CI:-0.17, 1.57, respectively). This indicates higher externalizing behavioral problems in males with a joint exposure to PAE and LBW, also confirmed with the INTref parameter (β = 0.18, 95%CI: 0.08, 0.4). We found no evidence for mediation (PIE) or mediated interaction (INTmed) via LBW. CONCLUSION:Early identification and intervention for children with PAE have been shown to mitigate the risk of more severe secondary impacts. Our findings highlight the potential importance of birthweight as a factor that may exacerbate behavioral problems among PAE-exposed offspring, particularly males.

Infant antibiotic treatment is associated with increased risk of developing non-communicable diseases, potentially through disruption of the gut microbiome. However, the impact of indirect antibiotic exposure via human milk remains largely unexplored. Here, we investigate a cohort (n=80) of antibiotic-treated breastfeeding mother-infant dyads and untreated matching controls using integrative multi-omics analyses of fecal, milk, and skin samples (n=1,455). Maternal antibiotic treatment was associated with different infant fecal microbiome and metabolome profiles, including lower abundance of Bacteroides, Lactobacillus, and Bifidobacterium, and higher levels of antimicrobial resistance gene reads. Further, fecal metabolic alterations associated with indirect antibiotic exposure were exacerbated by formula milk supplementation. In a subset of infants (n=61), indirect exposure was associated with higher body mass index (BMI). These findings suggest that maternal antibiotic treatment during lactation may influence the early-life infant gut microbiome with potential long-term implications.

BACKGROUND AND AIMS:We aimed to assess the safety of advanced therapies, excluding tumor necrosis factor inhibitors (anti-TNFs), for the treatment of immune-mediated inflammatory diseases (IMIDs), on pregnancy and neonatal outcomes. METHODS AND ANALYSIS:We performed a systematic review and meta-analysis. Study selection and data extraction were conducted independently by two reviewers. Primary outcomes included live births, major congenital malformations (MCMs), miscarriages, and stillbirths. Risk of bias was assessed using ROBINS-I, and the certainty of evidence was evaluated using GRADE. Meta-analyses of prevalence and odds ratios (ORs) comparing advanced therapies with anti-TNFs were conducted using fixed and random effect models. RESULTS:Of 14 661 manuscripts screened, 49 studies met the inclusion criteria: eight cohorts, nine case series, and 32 case reports. Most cohort studies were at a critical risk of bias. The majority of the available data related to ustekinumab (1324 exposed offspring) and vedolizumab (585 exposed offspring) whereas data on other biologics and JAK inhibitors were very limited. Pregnancies exposed to biologics had a pooled prevalence of 82.43% for live births, 0.55% for MCMs, 8.16% for miscarriage, and 0.00% for stillbirths. No significant differences in adverse pregnancy or neonatal outcomes were observed compared with women exposed to anti-TNFs. Overall, the level of evidence was very low, due largely to reliance on small observational studies and case reports. CONCLUSION:Current evidence does not suggest an increased risk of adverse pregnancy or neonatal outcomes with advanced therapies for IMIDs. However, larger, high-quality studies are needed, and these findings should be interpreted as hypothesis-generating.

Background: Prenatal alcohol exposure (PAE) may impair infant neurodevelopment; whether maternal micronutrients modify these effects remains unclear. We examined the influence choline, folate, and iron, individually and jointly, in relation to motor and cognitive outcomes.Methods: In a prospective Western Ukraine cohort, 290 mother–infant dyads were enrolled; a third-trimester subset (N=103) provided repeated measures. Infant neurodevelopment at 6–12 months was assessed using Bayley Scales of Infant Development II Psychomotor Development Index (PDI) and Mental Development Index (MDI). Structural equation modeling estimated direct and indirect pathways between PAE, micronutrients, and outcomes, adjusting for gestational age at blood sampling. Stabilized inverse probability weights accounted for maternal age, socioeconomic status, gravidity, prenatal vitamin use, and tobacco.Results: Among all women in the cohort, 45.2% reported moderate to heavy PAE at enrollment versus 46.6% in the third-trimester subset. At enrollment, direct effects of PAE were non-significant for PDI (β=–0.080, p=0.194) and MDI (β=–0.106, p=0.079), with <1% nutrient-mediated effects. Adjusted effects remained non-significant (PDI β= –0.058, p=0.468; MDI β=–0.013, p=0.853). Third trimester adjusted direct effects were non-significant for PDI (β=0.194, p=0.176) and significant for MDI (β=0.233, p=0.013), with indirect effects for PDI (β=0.021, p= 0.807; MDI(β=0.024, p= 0.756). Among males, PAE was significantly associated with reduced MDI (β=-0.199, p=0.015) but not PDI; combined nutrient mediation was borderline for PDI (β=0.060, p=0.057) and significant for MDI (β=0.072, p=0.033). Females showed negligible effects.Conclusions: PAE demonstrated sex-specific neurodevelopmental effects. Male infants appeared more vulnerable to direct alcohol-related deficits but also showed measurable compensatory benefit from combined maternal nutrients.

PurposeBreastfeeding plays an important role in supporting infant nutrition and health, but lack of adequate safety data on medication use during lactation poses significant challenges. The objective of this study was to assess the comparability of using breast milk and blood samples collected under mimicked home conditions versus standard clinic-based methods.MethodsPaired blood and breast milk samples were obtained from lactating participants prescribed a study drug per standard of care. Correlation analysis was performed to determine the association between drug concentrations in paired samples collected under clinic and home conditions.ResultsSamples were collected from 27 mothers. A total of 7, 10, and 10 participants were exposed to nifedipine, escitalopram, and sertraline, respectively. Paired dried blood spot (DBS) and paired plasma to DBS samples exhibited good correlation between clinic and home conditions. Breast milk samples demonstrated good correlation for escitalopram and sertraline.ConclusionsValidation of samples collected under home conditions provides an alternative method to increase enrollment and human data in lactating populations. Blood showed good correlation across all study drugs and breast milk showed good correlation for stable drugs across clinic and home condition samples. This study supports home collection of blood and breast milk samples for convenient research and clinical use.

BACKGROUND AND AIMS:Maternal infections have been proposed to play a role in the development of congenital heart defects (CHD). This study aims to synthesize contemporary evidence on the association between first-trimester maternal infection and risk of offspring CHD. METHODS:This systematic review and meta-analysis (PROSPERO number: CRD42024523638) used Embase, PubMed, Web of Science, Scopus, and the Cochrane Library to identify studies investigating first-trimester maternal infection and offspring CHD, published up until 30 September 2024. Human studies with a minimum of 50 cases were eligible. Inverse variance weighted random-effects models were conducted to pool estimates and stratify associations by infection type and heart defect type. RESULTS:A total of 30 studies (24 case-control, 3 cohort, and 3 cross-sectional studies) with 1 732 295 pregnancies were identified. Studies assessed maternal infectious status through self-reported questionnaires (n = 20, 66.7%), laboratory testing (n = 7, 23.3%) or medical records (n = 3, 10.0%). Overall, any first-trimester maternal infection was associated with higher risk of CHD in offspring, with a pooled odds ratio (OR) and 95% confidence interval (CI) of 1.63 (1.41, 1.88). Among specific types of infection, rubella virus, coxsackievirus, respiratory infections, and influenza presented higher risks of offspring CHD, with ORs (95% CI) of 2.78 (2.08, 3.72), 1.57 (1.12, 2.19), 1.57 (1.25, 1.96), and 1.50 (1.20, 1.87), respectively. Studies that reported associations by individual subtype of CHD relied on a comparatively modest number of cases. Pooled ORs for exposure to any first-trimester infection were 1.59 (1.16, 2.20) for ventricular septal defects, 1.55 (1.21, 1.99) for atrioventricular septal defects, and not statistically significant for other subtypes. CONCLUSIONS:First-trimester maternal infections are associated with increased risk of offspring CHD and appear to extend beyond infections commonly tested for during routine pregnancy screening. Larger-scale studies are warranted to confirm these findings using laboratory antibody testing and explore underlying mechanisms.

BACKGROUND:Nonnarcotic analgesics are the recommended first-line treatment for postpartum pain, and low-dose aspirin is recommended in approximately 85% of pregnant patients who have preeclampsia risk factors. Timely evaluation of nonnarcotic analgesics allergy labels (NNAALs) is essential for high-quality perinatal care. OBJECTIVE:To address a knowledge gap in the relationship between maternal NNAALs and maternal and fetal outcomes. METHODS:A retrospective analysis was conducted using the Study of Outcomes in Mothers and Infants, a population-based cohort of all births in California between 2016 and 2021. Maternal and fetal outcomes were examined by NNAAL status using Poisson log-linear regression to calculate adjusted relative risks (aRRs), 95% confidence intervals (CIs), and P values adjusted for maternal characteristics. RESULTS:Maternal NNAALs were significantly associated with increased rates of preeclampsia (aRR, 1.16; P < .0001) and eclampsia (aRR, 1.64; P = .0047), cesarean delivery (aRR, 1.2; P < .0001), preterm birth (aRR, 1.17; P < .0001), infants with neonatal intensive care unit admission (aRR, 1.09; P = .0076), neonatal opioid withdrawal syndrome (aRR, 1.49; P < .0001), infant long length of hospital stay (aRR, 1.16; P < .0001), and a decreased rate of infants large for gestational age (aRR, 0.92; P = .0092), but were not associated with infants small for gestational age, major structural birth defects, or 5-minute Apgar score less than 7. CONCLUSIONS:Maternal NNAALs were significantly associated with various maternal and fetal adverse outcomes. Our data suggest that proactive evaluations of patients with NNAALs may improve perinatal outcomes.

PV187 / #637 Poster Topic:AS21 - Pregnancy and Reproductive Health Belimumab is a human monoclonal antibody that inhibits B lymphocyte stimulator protein (BLyS). Among other countries, belimumab is approved in the United States (US) and Canada for systemic lupus erythematosus (SLE) and lupus nephritis in people 5 years of age and older. Data on belimumab exposure during pregnancy is limited. The OTIS Pregnancy Exposure Registry is a US based study designed to monitor pregnancy and infant outcomes among people in the US and Canada. Pregnancy registries are an important component of post-marketing surveillance to assess the safety of new medications. Presented is an overview of the study design and recruitment into this pregnancy study. The study will monitor pregnancies for the occurrence of major structural birth defects, spontaneous abortion, elective termination, stillbirth, preterm delivery, pattern of 3 or more minor structural defects, small-for-gestational age, postnatal growth and developmental performance at approximately 1 year of age, and serious infections in the first year of life in pregnancies exposed to belimumab, relative toa disease comparison (DC) group of pregnant participants with SLE. This research study is a North American, prospective cohort study comparing pregnancy outcomes in participants exposed to belimumab to a DC group without belimumab exposure. Women with SLE who have been exposed to belimumab during pregnancy, or within 3 months of the last menstrual period, and who have not had any abnormal prenatal screening or diagnostic test indicating a major structural defect as eligible for enrollment. Those who do not meet the eligibility criteria are eligible for a “case series” cohort. These data may be used to illuminate any findings in the cohort study. Recruitment began in November 2022 and will continue through 2027, with a goal of 200 participants in each cohort. The study captures data on exposures, outcomes and covariates through maternal interviews and maternal and pediatric medical records, a dysmorphology exam, and developmental screening of the child using the Ages and Stages online questionnaire. Disease severity is captured with information from medical records. Between November 10, 2022 and November 1, 2024, 30 participants were enrolled (17 belimumab-exposed, 9 DC, and 3 in the belimumab-exposed case series). With the help of rheumatologists and other providers specializing in the care of patients with SLE, this study will collect information that will help healthcare professionals and their patients make informed treatment decisions during pregnancy.

Objective SLE is associated with increased risks of maternal cardiovascular events (CVEs) as well as adverse pregnancy outcomes. The influence of maternal CVEs on pregnancy complications in lupus is not clearly known. Our primary aim was to assess the risks of adverse pregnancy outcomes in individuals with SLE, specifically examining the influence of CVEs.Methods Using a California population-based birth cohort from 2005 to 2020, pregnant individuals with SLE were identified via International Classification of Diseases codes on maternal discharge records and further subdivided based on whether they had lupus nephritis (LN) or antiphospholipid syndrome (APS). We analysed adjusted relative risks (aRRs) of adverse pregnancy outcomes in SLE subgroups, comparing those with and without CVEs, to the reference group of pregnant individuals without autoimmune rheumatic diseases or APS and CVEs. CVEs were broadly defined to encompass thromboembolic and cardiovascular conditions associated with SLE.Results CVEs complicated 17 130/7004 334 (0.2%) of pregnancies in individuals without autoimmune rheumatic diseases or APS, and 176/8422 (2.1%) with SLE, including 52/903 (5.8%) with LN and 40/513 (7.8%) with APS. Compared with the reference group, the aRRs for maternal complications were higher in SLE subgroups: non-cardiac severe maternal morbidity (3.2-fold to 31.5-fold), intensive care admission (2.0-fold to 12.2-fold), 1 year re-admission (2.4-fold to 6.0-fold) and death (7.0-fold to 7.9-fold). Similarly, adverse infant outcomes were higher: preterm birth (2.3-fold to 6.8-fold), small-for-gestational-age infant (1.8-fold to 3.4-fold), neonatal intensive care admission (2.1-fold to 7.9-fold) and infant death (1.6-fold to 3.7-fold), with highest risk estimates for SLE with LN or APS, particularly when complicated by CVEs.Conclusions LN and APS in SLE contributed to incremental risks for adverse outcomes, with the combination of LN or APS with CVEs yielding the highest point estimates. This underscores the importance of disease severity but also the impact of CVEs, helping to individualise the risks of pregnancy complications for various SLE subpopulations.

Rationale: Asthma is the most common chronic disease affecting pregnant women, yet data on the safety of some asthma medications are limited. Inhaled corticosteroids (ICS) have been shown to be acceptable for the treatment of asthma in pregnancy, but there are limited data on the safety of long-acting beta agonists (LABA) or combination therapy with ICS-LABA. In the general non-pregnant population with uncontrolled asthma, the addition of a LABA to ICS therapy has been shown to be more effective than increasing the dose of ICS. We sought to determine the risk for birth defects and spontaneous abortion in pregnant LABA users. Methods: Pregnant participants residing in the US or Canada were recruited prior to 20 weeks’ gestation between 2009 and 2014 by MotherToBaby Pregnancy Studies at UC San Diego. Referrals to the study came from healthcare providers and women who were self-referred. The exposed group was comprised of pregnant asthmatic patients treated with LABA. Two comparison groups were recruited including pregnant asthmatic women who had used only SABAs and a non-diseased comparison group of pregnant women who did not have asthma. Data on exposures, major congenital malformations and spontaneous abortion were collected by maternal interviews and medical records abstraction. The relative risk (RR) and 95% Confidence Intervals (CI) for major malformations was calculated using exact methods, and the hazard ratio (HR) and 95% CI for spontaneous abortion was calculated using Cox proportional hazards. Results: 439 subjects with outcomes were enrolled with 100 exposed to LABAs, 103 exposed to SABAs only, and 236 unexposed comparison women. Twenty participants (4.6%) were lost to follow-up. Characteristics are shown in the Table. Infants of women exposed to LABA during pregnancy were not significantly more likely to have major birth defects compared to SABA alone (RR 1.20, 95% CI [0.42, 3.39]) or infants of non-asthmatic women (RR 1.27, 95% CI 0.45, 3.12). There was no increased risk of spontaneous abortion in those exposed to LABA versus SABA (HR 0.33, 95% CI [0.08, 1.27]) or LABA versus unexposed non-asthmatic women (HR 0.62, 95% CI 0.17, 2.31). Conclusion: There was no evidence of a significant increased risk of major birth defects or spontaneous abortion in pregnant women exposed to LABAs. Because ICS have also been shown to be safe in pregnancy, these data provide support for the use of ICS-LABA therapy in pregnant patients in accordance with the latest guidelines for asthma management in the general population.

Standardised procedures for performing and reporting safety monitoring studies investigating medications use in pregnancy may help improve data quality and the speed of data generation. The objective of this study was to provide recommendations on the statistical analysis and reporting of single-arm pregnancy medication safety studies using primary source datasets. A Delphi consensus-setting protocol was used to acquire agreement on recommendations from experts with extensive knowledge and experience in conducting studies investigating medication safety in pregnancy. A series of recommendations, along with their scientific justifications and examples of how to calculate and describe exposure and outcome incidences, were critiqued and improved through a series of online Delphi review rounds. Agreement to inclusion scoring was assessed using a five-point Likert scale. Recommendations with a median Likert-scale score of at least 4, where ≥ 80

OBJECTIVES:To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including additional drugs and adverse outcomes as well as paternal drug safety. METHODS:According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item. RESULTS:The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. CONCLUSIONS:The updated recommendations provide consensus guidance and will help to improve the quality of care of patients during the phases of reproduction, pregnancy, and lactation.

ImportanceThe association between maternal medications and the macronutrient composition of human milk has not been studied.ObjectiveTo compare macronutrient levels in milk samples from mothers treated with long-term medications with samples from untreated healthy and disease-matched control mothers (DMCs).Design, Setting, and ParticipantsA cross-sectional study using samples collected between October 2014 and January 2024 from breastfeeding mothers in the US and Canada invited to participate to the Mommy’s Milk Human Milk Research Biorepository at the University of California, San Diego. Of 3974 samples from unique individuals in the biorepository, 310 were from mothers treated with 1 of 4 categories of medications, 151 from DMCs with the same underlying disorders, and 73 from healthy untreated mothers, frequency matched on infant age and sex. Of these, 150 were excluded because they had more than 1 medication exposure or were outliers. Data were analyzed from March to June 2024.ExposuresContinuous treatment with selective serotonin reuptake inhibitors (SSRIs), monoclonal antibodies (MABs), systemic steroids, and other anti-inflammatory drugs (ADs) in the 14 days before milk sample collection.Main Outcomes and MeasuresLevels of protein, fat, carbohydrate, and total energy were measured with SpectraStar 2400 near infrared analyzer and compared across groups with analysis of covariance adjusted for infant and maternal age, parity, maternal body mass index, infant sex, exclusive breastfeeding, feeding frequency, collection time, maternal cannabis use, and occupation.ResultsA total of 384 samples were collected; 194 infants (50.5%) were female; the mean (SD) age of the maternal cohort was 33.5 (4.4) years, and infant age at collection was 6.6 (5.4) months. Mean (SD) protein levels were 15% to 21% lower in samples from exposed mothers (0.92 [0.56] g/100 mL for 63 SSRIs, 0.85 [0.51] g/100 mL for 63 MABs, 0.88 [0.37] g/100 mL for 33 steroids, and 0.85 [0.54] g/100 mL for 20 other ADs) compared with 64 samples from healthy mothers (1.08 [0.50] g/100 mL). Adjusted differences were significant for SSRIs and steroids (F1, 91 = 4.32; P = .04 and F1,59 = 5.00, P = 0.03, respectively). Mean (SD) fat and energy were 10% to 22% lower in samples from mothers with other ADs (3.40 [1.21] g/100 mL for fat and 69.56 [15.35] kcal/100 mL for energy) than from healthy (3.85 [1.66] g/100 mL for fat and 77.16 [22.08] kcal/100 mL for energy) and DMC (4.38 [1.90] g/100 mL for fat and 80.60 [24.70] kcal/100 mL for energy) mothers. Adjusted differences were only significant for fat compared with DMC (F1,88 = 6.22; P = .01).Conclusions and RelevanceIn this cross-sectional study, some maternal medications were associated with lower levels of protein and fat in milk, which could impose health risks for breastfed infants. Other factors that could influence macronutrient levels need to be clarified before the clinical implications of these findings can be confirmed.

Preventing fetal exposure to teratogenic medications is an important target for risk mitigation efforts. Decisions about risk mitigation efforts specific to teratogenic medications are complex. The Teratogenic Risk Impact and Mitigation (TRIM) tool was developed as an innovative decision support tool to facilitate prioritization of teratogenic medications for risk mitigation strategies. We employed a modified Delphi study design involving experts across teratology, obstetrics/gynecology, and medication safety. Panelists proposed decision criteria in three focus groups, followed by e-Delphi rounds to reach a consensus on criteria regarding three dimensions: (1) completeness; (2) relevance; and (3) distinctiveness. Aggregated feedback from each round was used to inform revision of the criteria in subsequent rounds. A total of 33 candidate criteria proposed by 32 focus group participants were organized into ten distinct criteria for the Delphi process. Consensus (defined as > 85