Neurobehavioral outcomes of infants exposed to buprenorphine-naloxone compared with naltrexone during pregnancy.

BACKGROUND: Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined. AIMS: To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants. STUDY DESIGN: Multi-centered prospective cohort study. SUBJECTS: Pregnant people on prescribed buprenorphine-naloxone or naltrexone were enrolled during pregnancy and the dyad followed until 12 months after delivery. OUTCOME MEASURES: Infants were evaluated at 4-6 weeks corrected gestational age (CGA) using the NICU Neonatal Neurobehavioral Scale (NNNS) and at the 12-month CGA visit using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: There were 7 dyads in the naltrexone group and 34 in the buprenorphine-naloxone group. On the NNNS, infants exposed to naltrexone had higher median scores for arousal and excitability, and lower median scores for attention and regulation at 4-6 weeks CGA compared to the buprenorphine-naloxone group. None of the infants in the naltrexone group were monitored for NOWS and had shorter length of hospital stay compared with the buprenorphine-naloxone group. Although no statistically significant differences were observed, more infants in the buprenorphine-naloxone group were identified as at risk for development delays in the communication, problem solving, and personal social domains of the ASQ-3 at 12 months CGA. Results should be interpreted with caution given this study's small sample size and lack of a prospective comparison cohort. CONCLUSIONS: In this small cohort, there are differences noted in infant neurobehavior by NNNS at 4-6 weeks of age when comparing the buprenorphine-naloxone and naltrexone groups. At 12 months, ASQ-3 scores were similar but with percentage differences in potential development delay risk observed between the two groups. Larger cohort studies are needed to determine the long-term child outcomes after naltrexone exposure in pregnancy.

Real World Data are Not Always Big Data: The Case for Primary Data Collection on Medication Use in Pregnancy in the Context of Birth Defects Research.

Many examples of the use of real-world data in the area of pharmacoepidemiology include "big data" such as insurance claims, medical records, or hospital discharge databases. However, "big" is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are one such outcome, where specificity of exposure timing is critical. Studies with primary data collection can be designed to query details on the timing of medication use, as well as type, dose, frequency, duration, and indication, that can better characterize the "real world". Because birth defects are rare, etiologic studies are typically case-control in design, like the National Birth Defects Prevention Study, Birth Defects Study to Evaluate Pregnancy exposureS, and Slone Birth Defects Study. Recall bias can be a concern, but the ability to collect detailed information on both prescription and over-the-counter medication use and on other exposures such as diet, family history, and sociodemographic factors is a distinct advantage over claims and medical record data sources. Case-control studies with primary data collection are essential to advancing the pharmacoepidemiology of birth defects.

The timing, duration, and severity of nausea and vomiting of pregnancy and adverse birth outcomes among controls without birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive. OBJECTIVE: To determine whether NVP and reported medications are associated with adverse birth outcomes. METHODS: We used data from the population-based, multisite National Birth Defects Prevention Study (1997-2011) to evaluate whether self-reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy. RESULTS: Among 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4-6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7-9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7-9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication. CONCLUSION: Mild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long-lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA.

Antifungal medication use during early pregnancy and the risk of congenital heart defects in the National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Fungal infections are common among pregnant people. Recent studies suggest positive associations between oral antifungals used to treat fungal infections and congenital heart defects (CHDs). METHODS: We estimated associations between first trimester antifungal use and 20 major, specific CHDs using data from the National Birth Defects Prevention Study (NBDPS), a multi-site, case-control study that included pregnancies with estimated delivery dates from October 1997 through December 2011. Infants with CHDs ("cases") were ascertained from 10 birth defect surveillance programs. Live born infants without major birth defects ("controls") were randomly selected from birth records or hospital discharge lists. First trimester antifungal use was self-reported via maternal interview. We estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs) using logistic regression with Firth's penalized likelihood. RESULTS: First trimester antifungal use was reported by 148/11,653 (1.3%) case and 123/11,427 (1.1%) control participants. We estimated AORs for 12 CHDs; six had AORs >1.5 (tetralogy of Fallot, double outlet right ventricle with transposition of the great arteries [DORV-TGA], atrioventricular septal defect, hypoplastic left heart syndrome, pulmonary atresia, muscular ventricular septal defect), and one (pulmonary valve stenosis) had an AOR <0.7. All CIs included the null, except for DORV-TGA. CONCLUSIONS: First trimester antifungal use was rare. We observed some positive associations for several specific CHDs in our analysis, although the CIs largely included the null. Results do not support a large increase in risk, but smaller increases in risk for certain CHD cannot be ruled out.

Public health priorities for gastroschisis: Summary of a meeting sponsored by the Centers for Disease Control and Prevention and the March of Dimes.

BACKGROUND: Gastroschisis has increased worldwide over several decades; however, there are significant gaps in understanding risk factors for development of the defect, particularly those that might be modifiable. Despite advances in survival, little is known about longer-term outcomes for affected individuals. METHODS: On April 27- and 28, 2023, the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention (CDC) and March of Dimes sponsored a meeting entitled "Public Health Priorities for Gastroschisis". The meeting goals were to review current knowledge on gastroschisis, discuss research gaps, and identify future priorities for public health surveillance, research, and action related to gastroschisis. Meeting participants encompassed a broad range of expertise and experience, including public health, clinical care of individuals with gastroschisis, affected individuals and families, and representatives from professional organizations and federal agencies. RESULTS: Several goals were identified for future public health surveillance and research, including focused theory-driven research on risk factors and increased study of longer-term effects of gastroschisis through improved surveillance. Certain public health actions were identified, that which could improve the care of affected individuals, including increased education of providers and enhanced resources for patients and families. CONCLUSIONS: These efforts may lead to an improved understanding of pathogenesis, risk factors, and outcomes and to improved care throughout the lifespan.

Maternal exposure to zolpidem and risk of specific birth defects.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

Investigating the association between vitamin D dietary intake during pregnancy and incidence of clubfoot in neonates.

AIMS: Talipes equinovarus (clubfoot) is a congenital lower foot deformity that results from a neuromuscular deficiency, but the precise etiology remains elusive. Vitamin D is important for fetal neuromuscular development. In this study, we investigated the association between dietary vitamin D intake during pregnancy and incidence of clubfoot in neonates, since such a question has thus far been overlooked. METHODS: We conducted a secondary analysis of data collected in the United States, between 2007 and 2011 for a case-control study of children born with clubfoot. Participating mothers were interviewed by telephone about dietary and other health and life-style indicators. Exposure to vitamin D was recorded as the average daily intake of dietary vitamin D over a period of 6 months before pregnancy began. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: The dataset included 2667 study participants, of which 663 were cases. Logistic regression showed no significant association between dietary vitamin D or log10 (Vitamin D) intake during pregnancy and incidence of clubfoot in neonates (OR = 1.00, CI = 1.00-1.00, OR = 1.51, CI = 0.83-2.82, respectively). No interaction in the regression model was found between vitamin D and other predictor variables. Results were not confounded by supplement intake of vitamin D during pregnancy. CONCLUSIONS: Results show no evidence of an association between dietary vitamin D intake and incidence of clubfoot in neonates. The lack of association is not confounded by consumption of vitamin D supplements during pregnancy.

Hair Cortisol Concentrations in Opioid-Exposed versus Nonexposed Mother-Infant Dyads.

OBJECTIVE: To pilot measurement of hair cortisol concentration (HCC) in pregnant women with opioid use disorder and their infants over time and study the potential utility of hair cortisol as a biomarker of chronic stress in this population. STUDY DESIGN: In this pilot prospective cohort study of mother-infant dyads with and without prenatal opioid exposure, we obtained mother-infant HCCs at delivery and again within 1 to 3 months' postpartum. HCCs were compared between the opioid and control groups and between the two time points. RESULTS: There were no significant differences between opioid and control group maternal or infant HCCs at either time point. However, within the opioid-exposed group, there was a significant increase in infant HCCs across the two time points. CONCLUSION: This pilot study describes our experience with the measurement of HCCs in opioid-exposed mother-infant dyads. KEY POINTS: · Maternal stress impacts fetal and child health.. · Many stressors in pregnant women with opioid use disorder.. · Hair cortisol may be a useful stress biomarker..

Antifungal medication use during pregnancy and the risk of selected major birth defects in the National Birth Defects Prevention Study, 1997-2011.

PURPOSE: Recent studies suggest increased birth defect risk associated with maternal use of specific oral antifungals. We estimated associations between first-trimester antifungal use and selected non-cardiac birth defects using National Birth Defects Prevention Study (NBDPS) data. METHODS: Participants with a pregnancy affected by a study-eligible birth defect ("cases") were ascertained from 10 birth defect surveillance programs; participants who delivered livebirths without a major birth defect ("controls") were randomly selected from birth records or hospital discharge lists. First-trimester antifungal use was self-reported via maternal interview. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for birth defects with ≥5 exposed cases using logistic regression. We estimated crude ORs and exact 95% CIs for birth defects with 3-4 exposed cases. Additionally, we conducted a probabilistic bias analysis of exposure misclassification. RESULTS: Our analysis included 19 624 cases and 11 427 controls; 257 (1.3%) cases and 123 (1.1%) controls reported first-trimester antifungal use. Of those who reported antifungals, 62.6% of cases and 64.2% of controls reported topical antifungals; 10.1% of cases and 4.9% of controls reported oral antifungals. We observed the strongest associations for encephalocele and Dandy-Walker malformation and modestly elevated estimates for several other defects. Bias-adjusted estimates were similar to the main analysis. CONCLUSION: First-trimester antifungal use was positively associated with several birth defects in our analysis, although CIs were imprecise. Further study is warranted to investigate associations between antifungal use and birth defects, including potential bias due to confounding by indication.

Natural Language Processing to Classify Caregiver Strategies Supporting Participation Among Children and Youth with Craniofacial Microsomia and Other Childhood-Onset Disabilities.

Customizing participation-focused pediatric rehabilitation interventions is an important but also complex and potentially resource intensive process, which may benefit from automated and simplified steps. This research aimed at applying natural language processing to develop and identify a best performing predictive model that classifies caregiver strategies into participation-related constructs, while filtering out non-strategies. We created a dataset including 1,576 caregiver strategies obtained from 236 families of children and youth (11-17 years) with craniofacial microsomia or other childhood-onset disabilities. These strategies were annotated to four participation-related constructs and a non-strategy class. We experimented with manually created features (i.e., speech and dependency tags, predefined likely sets of words, dense lexicon features (i.e., Unified Medical Language System (UMLS) concepts)) and three classical methods (i.e., logistic regression, naïve Bayes, support vector machines (SVM)). We tested a series of binary and multinomial classification tasks applying 10-fold cross-validation on the training set (80%) to test the best performing model on the held-out test set (20%). SVM using term frequency-inverse document frequency (TF-IDF) was the best performing model for all four classification tasks, with accuracy ranging from 78.10 to 94.92% and a macro-averaged F1-score ranging from 0.58 to 0.83. Manually created features only increased model performance when filtering out non-strategies. Results suggest pipelined classification tasks (i.e., filtering out non-strategies; classification into intrinsic and extrinsic strategies; classification into participation-related constructs) for implementation into participation-focused pediatric rehabilitation interventions like Participation and Environment Measure Plus (PEM+) among caregivers who complete the Participation and Environment Measure for Children and Youth (PEM-CY). Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-023-00149-y.

Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population-based case-control study of women meeting the folic acid recommendations.

BACKGROUND: Neural tube defects (NTDs) still occur among some women who consume 400 µg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. OBJECTIVES: To investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. METHODS: Data were from the National Birth Defects Prevention Study (United States population-based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 µg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. RESULTS: NTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. CONCLUSIONS: Our findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.

Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian-model-based analysis demonstrated that iHLHS was not due to single, large-effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with variation in CAPN2 (p = 1.8 × 10-5), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis and that in vivo loss of calpain function causes hypoplastic ventricle phenotypes and suggest that human CAPN2707C>T and CAPN21112C>T variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis.

Is gastroschisis associated with county-level socio-environmental quality during pregnancy?

BACKGROUND: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. METHODS: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). RESULTS: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. CONCLUSIONS: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis.

Kinetics of SARS-CoV-2 Serum Antibodies Through the Alpha, Delta, and Omicron Surges Among Vaccinated Health Care Workers at a Boston Hospital.

Background: Longitudinal serology studies can assist in analyzing the kinetics of antibodies to SARS-CoV-2, helping to inform public health decision making. Our study aims to characterize circulating antibody trends over 18 months in vaccinated participants with and without evidence of COVID-19 infection. Methods: A cohort of health care workers employed at Boston Medical Center was followed to collect serum samples and survey data over 6 time points from July 2020 through December 2021 (N = 527). History of SARS-CoV-2 infection, vaccination, and booster status were confirmed, where possible, through electronic medical records. Serum was assessed for the qualitative and semiquantitative detection of IgG antibody levels (anti-nucleoprotein [anti-N] and anti-spike [anti-S], respectively). Piecewise regression models were utilized to characterize antibody kinetics over time. Results: Anti-S IgG titers remained above the positivity threshold following infection and/or vaccination throughout the 18-month follow-up. Among participants with no evidence of COVID-19 infection, titers declined significantly faster in the initial 90 days after full vaccination (ß = -0.056) from December 2020 to March 2021 as compared with the decline observed following booster dose uptake (ß = -0.023, P < 0.001). Additionally, COVID-19 infection prior to vaccination significantly attenuated the decline of anti-S IgG when compared with no infection following vaccine uptake (P < 0.001). Lastly, fewer participants contracted Omicron when boosted (12.7%) compared to fully vaccinated (17.6%). Regardless of vaccination status, participants who were Omicron positive had lower anti-S IgG titers than those who did not test positive, but this difference was not significant. Conclusions: These findings provide novel 18-month kinetics of anti-S IgG antibodies and highlight the durability of hybrid immunity, underlining the strong humoral response stimulated by combined infection and vaccination.

Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors?

BACKGROUND: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations. METHODS: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction. RESULTS: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3). CONCLUSION: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors.

Patterns of Prescription Medication Use during the First Trimester of Pregnancy in the United States, 1997-2018.

The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and distributions of use within demographic subgroups. We conducted a descriptive secondary analysis using data from 9,755 women whose infants served as controls in two large United States case-control studies from 1997-2011 and 2014-2018. After excluding vitamin, herbal, mineral, vaccine, i.v. fluid, and topical products and over-the-counter medications, the proportion of women that reported taking at least one prescription medication in the first trimester increased over the study years, from 37% to 50% of women. The corresponding proportions increased with increasing maternal age and years of education, were highest for non-Hispanic White women (47%) and lowest for Hispanic women (24%). The most common indication for first trimester use of a medication was infection (12-15%). Increases were observed across the years for medications used for indications related to nausea/vomiting, depression/anxiety, infertility, thyroid disease, diabetes, and epilepsy. The largest relative increase in use among women was observed for medications to treat nausea/vomiting, which increased from 3.8% in the earliest years of the study (1997-2001) to 14.8% in 2014-2018, driven in large part by ondansetron use. Prescription medication use in the first trimester of pregnancy is common and increasing. Many medical conditions require treatments among pregnant women, often involving pharmacotherapy, which necessitates consideration of the risk and safety profiles for both mother and fetus.

A comparison of postpartum opioid consumption and opioid discharge prescriptions among opioid-naïve patients and those with opioid use disorder.

BACKGROUND: Management of patients with opioid use disorder during the acute postpartum period remains clinically challenging as obstetricians aim to mitigate postdelivery pain while optimizing recovery support. OBJECTIVE: This study aimed to evaluate postpartum opioid consumption and opioids prescribed at discharge among patients with opioid use disorder treated with methadone, buprenorphine, and no medication for opioid use disorder, as compared with opioid-naïve counterparts. STUDY DESIGN: We conducted a retrospective cohort study of pregnant patients who underwent delivery at >20 weeks' gestation at a tertiary academic hospital between May 2014 and April 2020. The primary outcome of this analysis was the mean daily quantity of oral opioids consumed after delivery while inpatient, in milligrams of morphine equivalents. Secondary outcomes included the following: (1) quantity of oral opioids prescribed at discharge, and (2) prescription for oral opioids in the 6 weeks after hospital discharge. Multiple linear regression was used to compare differences in the primary outcome. RESULTS: A total of 16,140 pregnancies were included. Patients with opioid use disorder (n=553) consumed 14 milligrams of morphine equivalents per day greater quantities of opioids postpartum than opioid-naïve women (n=15,587), (95% confidence interval, 11-17). Patients with opioid use disorder undergoing cesarean delivery consumed 30 milligrams of morphine equivalents per day greater quantities of opioids than opioid-naïve counterparts (95% confidence interval, 26-35). Among patients who underwent vaginal delivery, there was no difference in opioid consumption among patients with and without opioid use disorder. Compared with patients prescribed methadone, patients prescribed buprenorphine, and those prescribed no medication for opioid use disorder consumed similar opioid quantities postpartum following both vaginal and cesarean delivery. Among patients undergoing cesarean delivery, opioid-naïve patients were more likely to receive a discharge prescription for opioids than patients with opioid use disorder (77% vs 68%; P=.002), despite lower pain scores and less inhospital opioid consumption. CONCLUSION: Patients with opioid use disorder, regardless of treatment with methadone, buprenorphine, or no medication for opioid use disorder consumed significantly greater quantities of opioids after cesarean delivery but received fewer opioid prescriptions at discharge.