OBJECTIVE: Examine the relationship between prescription opioid analgesic use during pregnancy and preterm birth or term low birthweight. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from the National Birth Defects Prevention Study, a US multisite, population-based study, for births from 1997 to 2011. We defined exposure as self-reported prescription opioid use between one month before conception and the end of pregnancy, and we dichotomized opioid use duration by ≤7 days and >7 days. MAIN OUTCOME MEASURES: We examined the association between opioid use and preterm birth (defined as gestational age <37 weeks) and term low birthweight (defined as <2500 g at gestational age ≥37 weeks). RESULTS: Among 10,491 singleton mother/infant pairs, 470 (4.5 percent) reported opioid use. Among women reporting opioid use, 236 (50 percent) used opioids for > 7 days; codeine (170, 36 percent) and hydrocodone (163, 35 percent) were the most commonly reported opioids. Opioid use was associated with slightly increased risk for preterm birth [adjusted odds ratio, 1.4; 95 percent confidence interval, 1.0, 1.9], particularly with hydrocodone [1.6; 1.0, 2.6], meperidine [2.5; 1.2, 5.2], or morphine [3.0; 1.5, 6.1] use for any duration; however, opioid use was not significantly associated with term low birthweight. CONCLUSIONS: Preterm birth occurred more frequently among infants of women reporting prescription opioid use during pregnancy. However, we could not determine if these risks relate to the drug or to indications for use. Patients who use opioids during pregnancy should be counseled by their practitioners about this and other potential risks associated with opioid use in pregnancy.

BACKGROUND: Tuberculosis preventive treatment (TPT) reduces the development of tuberculosis (TB) disease and mortality in people living with human immunodeficiency virus (HIV) infection. Despite this known effectiveness, global uptake of TPT has been slow. We aimed to assess current status of TPT implementation in countries supported by the US President's Emergency Plan for AIDS Relief (PEPFAR).METHODS: We surveyed TB-HIV program staff at US Centers for Disease Control and Prevention (CDC) country offices in 42 PEPFAR-supported countries about current TPT policies, practices, and barriers to implementation. Surveys completed from July to December 2017 were analyzed.RESULTS: Of 42 eligible PEPFAR-supported countries, staff from 35 (83%) CDC country offices completed the survey. TPT was included in national guidelines in 33 (94%) countries, but only 21 (60%) reported nationwide programmatic TPT implementation. HIV programs led TPT implementation in 20/32 (63%) countries, but TB programs led drug procurement in 18/32 (56%) countries. Stock outs were frequent, as 21/28 (75%) countries reported at least one isoniazid stock out in the previous year.CONCLUSION: Despite widespread inclusion of TPT in guidelines, programmatic TPT implementation lags. Successful scale-up of TPT requires uninterrupted drug supply chains facilitated by improved leadership and coordination between HIV and TB programs.

BACKGROUND: Counseling for appropriate medication use and folic acid consumption are elements of preconception care critical for improving pregnancy outcomes. Hispanic women receive less preconception care than women of other race/ethnic groups. The objective of this analysis is to describe differences in these two elements of preconception care among Hispanic subsegments. MATERIALS AND METHODS: Porter Novelli's 2013 Estilos survey was sent to 2,609 U.S. Hispanic adults of the Offerwise QueOpinas Panel. Surveys were completed by 1,000 individuals (calculated response rate 42%), and results were weighted to the 2012 U.S. Census Hispanic proportions for sex, age, income, household size, education, region, country of origin, and acculturation. Responses were analyzed with weighted descriptive statistics, linear regression, and Rao-Scott chi-square tests. RESULTS: Of the 499 female respondents, 248 had a child under the age of 18 years and were asked about healthcare provider discussions concerning medication use before or during their last pregnancy. Timing of discussions varied by maternal age, marital status, income, youngest child's country of birth, and acculturation. Discussions before pregnancy were reported by 47% of the female respondents; high acculturated women more often reported never having such discussions. Among female respondents, 320 were of reproductive age, and 27% of those reported daily multivitamin use. Multivitamin use varied by pregnancy intention and youngest child's country of birth, but did not vary significantly by acculturation. CONCLUSIONS: Differences in discussions concerning medication use in pregnancy and multivitamin use exist among Hispanic subsegments based on pregnancy intention, marital status, income, youngest child's country of birth, and level of acculturation.

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.

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.

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.,

We thank Dr. Sasieta and Dr. Escalante for their interest in our article (1). We certainly agree with their conclusion that we might have misclassified the apparent etiology of some of the tuberculosis (TB) recurrences in our cohort. In addition to other listed limitations that might have led to misclassification, a possibility that they correctly raise is that some of the 15% of participants whom we classified as having novel reinfection might, in fact, have had undetected mixed infections (i.e., coinfection) during the initial TB episode. | | The frequency of mixed TB infections in the United States is difficult to ascertain, given that the National Tuberculosis Genotyping Service typically offers genotyping for only one isolate from every culture-positive TB case (2, 3). However, just as state public health laboratories have the option to submit multiple isolates to help investigate a possible false-positive Mycobacterium tuberculosis culture, they also have the option to submit multiple isolates if they suspect mixed infections (4). None of the initial or subsequent isolates in this analysis were flagged as either suspected false positives or mixed infections. The isolates from the 20 pairs of TB episodes that we classified as reinfections had substantially different M. tuberculosis genotype patterns (further details in Table 2 in Ref. 1), well beyond the single mycobacterial interspersed repetitive unit–variable number tandem repeat locus or IS6110-based restriction fragment-length polymorphism band difference occasionally seen with in situ clonal evolution.

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 2023 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% of videos about SSRIs indicated that 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 platform for communicating evidence-based medication safety information.

RATIONALE: The etiology of recurrent tuberculosis is typically presumed to be reactivation of residual Mycobacterium tuberculosis infection, but reinfection may account for a greater proportion of recurrent tuberculosis than previously recognized. OBJECTIVE: To use M. tuberculosis genotyping to characterize the etiology of recurrent tuberculosis ≥12 months after treatment completion. METHODS: The study population for this national population-based cohort was drawn from the estimated 3,039 persons reported to the National Tuberculosis Surveillance System with 2 episodes of tuberculosis in the United States during 1993-2011; 194 had genotyping results from both the initial and subsequent episode. We analyzed the proportion of recurrent tuberculosis attributable to and the risk factors associated with reinfection. MEASUREMENTS AND MAIN RESULTS: Among 136 recurrences meeting inclusion criteria, genotypes between episodes were the same for 116 (85%) recurrences during 1996-2011; the 20 (15%) with differing genotypes were categorized as reinfection. Using exact logistic regression, factors associated with reinfection included Mexican birth with both TB episodes diagnosed in the United States within 12 years of immigration (adjusted odds ratio, 10.7; 95% confidence interval, 1.7-86.3) and exclusive use of directly observed therapy for treatment of the first episode (adjusted odds ratio, 4.5; 95% confidence interval, 1.0-29.2). CONCLUSIONS: Reinfection was the cause for 15% of late recurrent tuberculosis cases in this US cohort. The proportion caused by reinfection increased to 60% in certain subpopulations, such as recent immigrants from Mexico, suggesting that despite successful treatment for TB during their first episode, they remain in a social environment where they are reexposed to M. tuberculosis. Public health interventions to prevent novel reinfection might require a broader focus on these communities.