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CONTEXT Opioid use and abuse have increased dramatically in recent years, particularly among women. OBJECTIVES We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations. DATA SOURCES We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies. STUDY SELECTION We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process. DATA EXTRACTION Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies. RESULTS Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation. LIMITATIONS Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement. CONCLUSIONS Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age.

OBJECTIVE: To describe delivery-related severe maternal morbidity and mortality among indigenous women compared with non-Hispanic white (white) women, distinguishing rural and urban residents. METHODS: We used 2012–2015 maternal hospital discharge data from the National Inpatient Sample to conduct a pooled, cross-sectional analysis of indigenous and white patients who gave birth. We used weighted multivariable logistic regression and predictive population margins to measure health conditions and severe maternal morbidity and mortality (identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure codes) among indigenous and white patients, to test for differences across both groups, and to test for differences between rural and urban residents within each racial category. RESULTS: We identified an estimated 7,561,729 (unweighted n=1,417,500) childbirth hospitalizations that were included in the analyses. Of those, an estimated 101,493 (unweighted n=19,080) were among indigenous women, and an estimated 7,460,236 (unweighted n=1,398,420) were among white women. The incidence of severe maternal morbidity and mortality was greater among indigenous women compared with white women (2.0% vs 1.1%, respectively; relative risk [RR] 1.8, 95% CI 1.6–2.0). Within each group, incidence was higher among rural compared with urban residents (2.3% for rural indigenous women vs 1.8% for urban indigenous women [RR 1.3, 95% CI 1.0–1.6]; 1.3% for rural white women vs 1.2% for urban white women [RR 1.1, 95% CI 1.1–1.2]). CONCLUSION: Severe maternal morbidity and mortality is elevated among indigenous women compared with white women. Incidence is highest among rural indigenous residents. Efforts to improve maternal health should focus on populations at greatest risk, including rural indigenous populations.

The promise and peril of antibody testing for COVID-19. JAMA.

Purpose To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects. Methods We used data from the National Birth Defects Prevention Study (1997–2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects. Results Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2–1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8–2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0–2.9). Conclusions Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment.

Background When making decisions about medication use in pregnancy, women consult many information sources, including the Internet. The aim of this study was to assess the content of publicly-accessible YouTube videos that discuss medication use in pregnancy. Methods Using 2,023 distinct combinations of search terms related to medications and pregnancy, we extracted metadata from YouTube videos using a YouTube video Application Programming Interface. Relevant videos were defined as those with a medication search term and a pregnancy-related search term in either the video title or description. We viewed relevant videos and abstracted content from each video into a database. We documented whether videos implied each medication to be ‘safe’ or ‘unsafe’ in pregnancy and compared that assessment with the medication’s Teratogen Information System (TERIS) rating. Results After viewing 651 videos, 314 videos with information about medication use in pregnancy were available for the final analyses. The majority of videos were from law firms (67%), television segments (10%), or physicians (8%). Selective serotonin reuptake inhibitors (SSRIs) were the most common medication class named (225 videos, 72%), and 88% percent of videos about SSRIs indicated they were ‘unsafe’ for use in pregnancy. However, the TERIS ratings for medication products in this class range from ‘unlikely’ to ‘minimal’ teratogenic risk. Conclusion For the majority of medications, current YouTube video content does not adequately reflect what is known about the safety of their use in pregnancy and should be interpreted cautiously. However, YouTube could serve as a valuable platform for communicating evidence-based medication safety information.

Background Previous studies noted associations between birth defects and some antibiotics (e.g., nitrofurantoin, sulfonamides) but not others (e.g., penicillins). It is unclear if previous findings were due to antibiotic use, infections, or chance. To control for potential confounding by indication, we examined associations between antibiotic use and birth defects, among women reporting urinary tract infections (UTIs). Methods The National Birth Defects Prevention Study is a multi-site, population-based case-control study. Case infants/fetuses have any of over 30 major birth defects and controls are live-born infants without major birth defects. We analyzed pregnancies from 1997 to 2011 to estimate the association between maternally reported periconceptional (month before conception through the third month of pregnancy) use of nitrofurantoin, trimethoprim-sulfamethoxazole, or cephalosporins and specific birth defects, among women with periconceptional UTIs. Women with periconceptional UTIs who reported penicillin use served as the comparator. Results Periconceptional UTIs were reported by 7.8% (2029/26,068) of case and 6.7% (686/10,198) of control mothers. Most (68.2% of case, 66.6% of control mothers) also reported antibiotic use. Among 608 case and 231 control mothers reporting at least one periconceptional UTI and certain antibiotic use, compared with penicillin, nitrofurantoin use was associated with oral clefts in the offspring (adjusted odds ratio, 1.97 [95% confidence interval, 1.10–3.53]), trimethoprim-sulfamethoxazole use with esophageal atresia (5.31 [1.39–20.24]) and diaphragmatic hernia (5.09 [1.20–21.69]), and cephalosporin use with anorectal atresia/stenosis (5.01 [1.34–18.76]). Conclusion Periconceptional exposure to some antibiotics might increase the risk for certain birth defects. However, because individual birth defects are rare, absolute risks should drive treatment decisions.

IMPORTANCETimely access to clinically appropriate obstetric services is critical to the provision of high-quality perinatal care. OBJECTIVE To examine the geographic distribution, proximity, and urban adjacency of US obstetric hospitals by annual birth volume. DESIGN, SETTING, AND PARTICIPANTS This retrospective population-based cohort study identified US hospitals with obstetric services using the American Hospital Association (AHA) Annual Survey of Hospitals and Centers for Medicare & Medicaid provider of services data from 2010 to 2018. Obstetric hospitals with 10 or more births per year were included in the study. Data analysis was performed from November 6, 2020, to April 5, 2021.