Safety of Antimicrobials During Pregnancy: A Systematic Review of Antimicrobials Considered for Treatment and Postexposure Prophylaxis of Plague.

BACKGROUND: The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy. METHODS: We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes. RESULTS: Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported. CONCLUSIONS: For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.

Using Supervised Learning Methods to Develop a List of Prescription Medications of Greatest Concern during Pregnancy.

INTRODUCTION: Women and healthcare providers lack adequate information on medication safety during pregnancy. While resources describing fetal risk are available, information is provided in multiple locations, often with subjective assessments of available data. We developed a list of medications of greatest concern during pregnancy to help healthcare providers counsel reproductive-aged and pregnant women. METHODS: Prescription drug labels submitted to the U.S. Food and Drug Administration with information in the Teratogen Information System (TERIS) and/or Drugs in Pregnancy and Lactation by Briggs & Freeman were included (N = 1,186 medications; 766 from three data sources, 420 from two). We used two supervised learning methods ('support vector machine' and 'sentiment analysis') to create prediction models based on narrative descriptions of fetal risk. Two models were created per data source. Our final list included medications categorized as 'high' risk in at least four of six models (if three data sources) or three of four models (if two data sources). RESULTS: We classified 80 prescription medications as being of greatest concern during pregnancy; over half were antineoplastic agents (n = 24), angiotensin converting enzyme inhibitors (n = 10), angiotensin II receptor antagonists (n = 8), and anticonvulsants (n = 7). DISCUSSION: This evidence-based list could be a useful tool for healthcare providers counseling reproductive-aged and pregnant women about medication use during pregnancy. However, providers and patients may find it helpful to weigh the risks and benefits of any pharmacologic treatment for both pregnant women and the fetus when managing medical conditions before and during pregnancy.

Prevalence and maternal characteristics associated with receipt of prenatal care provider counseling about medications safe to take during pregnancy.

Use of some medications during pregnancy can be harmful to the developing fetus, and discussion of the risks and benefits with prenatal care providers can provide guidance to pregnant women. We used Pregnancy Risk Assessment Monitoring System data collected for 2015 births aggregated from 34 US states (n = 40,480 women) to estimate the prevalence of self-reported receipt of prenatal care provider counseling about medications safe to take during pregnancy. We examined associations between counseling and maternal characteristics using adjusted prevalence ratios (aPR). The prevalence of counseling on medications safe to take during pregnancy was 89.2% (95% confidence interval [CI]: 88.7-89.7). Women who were nulliparous versus multiparous (aPR 1.03; 95% CI: 1.02-1.04), who used prescription medications before pregnancy versus those who did not, (aPR 1.03; 95% CI: 1.02-1.05), and who reported having asthma before pregnancy versus those who did not, (aPR 1.05; 95% CI: 1.01-1.08) were more likely to report receipt of counseling. There was no difference in counseling for women with pre-pregnancy diabetes, hypertension, and/or depression compared to those without. Women who entered prenatal care after the first trimester were less likely to report receipt of counseling (aPR 0.93; 95% CI: 0.91-0.96). Overall, self-reported receipt of counseling was high, with some differences by maternal characteristics. Although effect estimates were small, it is important to ensure that information is available to prenatal care providers about medication safety during pregnancy, and that messages are communicated to women who are or might become pregnant.

Attention-Deficit/Hyperactivity Disorder Medication Prescription Claims Among Privately Insured Women Aged 15-44 Years - United States, 2003-2015.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects individuals across the lifespan. ADHD medication use among pregnant women is increasing (1), but consensus about the safety of ADHD medication use during pregnancy is lacking. Given that nearly half of U.S. pregnancies are unintended (2), and early pregnancy is a critical period for fetal development, examining trends in ADHD medication prescriptions among reproductive-aged women is important to quantify the population at risk for potential exposure. CDC used the Truven Health MarketScan Commercial Database* for the period 2003-2015 to estimate the percentage of women aged 15-44 years with private employer-sponsored insurance who filled prescriptions for ADHD medications each year. The percentage of reproductive-aged women who filled at least one ADHD medication prescription increased 344% from 2003 (0.9% of women) to 2015 (4.0% of women). In 2015, the most frequently filled medications were mixed amphetamine salts, lisdexamfetamine, and methylphenidate. Prescribing ADHD medications to reproductive-aged women is increasingly common; additional research on ADHD medication safety during pregnancy is warranted to inform women and their health care providers about any potential risks associated with ADHD medication exposure before and during pregnancy.

Making Decisions About Medication Use During Pregnancy: Implications for Communication Strategies.

Objective To explore women's perceptions of the risks and benefits associated with medication use during pregnancy and to better understand how women make decisions related to medication use in pregnancy. Methods We conducted online focus groups with 48 women who used medication during pregnancy or while planning a pregnancy, and 12 in-depth follow-up interviews with a subset of these women. Results We found that women were aware of general risks associated with medication use but were often unable to articulate specific negative outcomes. Women were concerned most about medications' impact on fetal development but were also concerned about how either continuing or discontinuing medication during pregnancy could affect their own health. Women indicated that if the risk of a given medication were unknown, they would not take that medication during pregnancy. Conclusion This formative research found that women face difficult decisions about medication use during pregnancy and need specific information to help them make decisions. Enhanced communication between patients and their providers regarding medication use would help address this need. We suggest that public health practitioners develop messages to (1) encourage, remind, and prompt women to proactively talk with their healthcare providers about the risks of taking, not taking, stopping, or altering the dosage of a medication while trying to become pregnant and/or while pregnant; and (2) encourage all women of childbearing age to ask their healthcare providers about medication use.

CDC Grand Rounds: Public Health Strategies to Prevent Neonatal Abstinence Syndrome.

Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome that most commonly occurs in infants after in utero exposure to opioids, although other substances have also been associated with the syndrome (1). NAS usually appears within 48-72 hours of birth with a constellation of clinical signs, including central nervous system irritability (e.g., tremors), gastrointestinal dysfunction (e.g., feeding difficulties), and temperature instability (1) (Box 1). Opioid exposure during pregnancy might result from clinician-approved use of prescription opioids for pain relief; misuse or abuse of prescription opioids; illicit use (e.g., heroin); or medication-assisted treatment (MAT) of opioid use disorder (2) (Box 2).

Improving Safe Use of Medications During Pregnancy: The Roles of Patients, Physicians, and Pharmacists.

Our study sought to explore the actual and potential roles of patients, physicians, and pharmacists, as well as their shared challenges and opportunities, in improving the safety of medication use during pregnancy. We conducted virtual focus groups with 48 women and in-depth interviews with nine physicians and five pharmacists. Qualitative analysis revealed that all three groups of participants reported "playing it safe," the need for an engaged patient making informed decisions, challenges surrounding communication about pregnancy status, and a lack of patient-centric resources. Patients, physicians, and pharmacists are highly motivated to protect developing babies from potential harms of medication use during pregnancy while maintaining the patient's health. Strategic messaging could maximize the effectiveness of these interactions by helping physicians discuss the benefits and risks of medication use during pregnancy, pharmacists screen for pregnancy and counsel on medication safety, and patients using medications to share pregnancy intentions with their providers pre-pregnancy.

Antidepressant Prescription Claims Among Reproductive-Aged Women With Private Employer-Sponsored Insurance - United States 2008-2013.

Antidepressant medication use during pregnancy has been increasing in the United States (1). Many women require antidepressants on an ongoing basis, and a clear consensus on the safest medication options for both the mother and her fetus does not exist (2). Given that half of all U.S. pregnancies are unplanned (3), antidepressant use will occur during the first weeks of pregnancy, a critical period for fetal development. To understand trends among women of reproductive age, CDC used Truven Health's MarketScan Commercial Claims and Encounters data* to estimate the number of antidepressant prescriptions filled by women aged 15-44 years with private employer-sponsored insurance. During 2008-2013, an average of 15.4% of women aged 15-44 years filled at least one prescription for an antidepressant in a single year. The most frequently filled antidepressants included sertraline, bupropion, and citalopram. Prescribing of antidepressants is common, and research on antidepressant safety during pregnancy needs to be accelerated to provide evidence-based information to health care providers and women about the potential risks for antidepressant exposure before and during pregnancy and between pregnancies.

Maternal autoimmune disease and birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Little is known about the association between maternal autoimmune disease or its treatment and the risk of birth defects. We examined these associations using data from the National Birth Defects Prevention Study, a multi-site, population-based, case-control study. METHODS: Analyses included 25,116 case and 9897 unaffected control infants with estimated delivery dates between 1997 and 2009. Information on autoimmune disease, medication use, and other pregnancy exposures was collected by means of telephone interview. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for birth defects with five or more exposed cases; crude ORs and exact 95% CIs were estimated for birth defects with three to four exposed cases. RESULTS: Autoimmune disease was reported by 373 mothers (279 case and 94 control mothers). The majority of birth defects evaluated were not associated with autoimmune disease; however, a statistically significant association between maternal autoimmune disease and encephalocele was observed (OR, 4.64; 95% CI, 1.95-11.04). Eighty-two mothers with autoimmune disease used an immune modifying/suppressing medication during pregnancy; this was associated with encephalocele (OR, 7.26; 95% CI, 1.37-24.61) and atrial septal defects (OR, 3.01; 95% CI, 1.16-7.80). CONCLUSION: Our findings suggest maternal autoimmune disease and treatment are not associated with the majority of birth defects, but may be associated with some defects, particularly encephalocele. Given the low prevalence of individual autoimmune diseases and the rare use of specific medications, we were unable to examine associations of specific autoimmune diseases and medications with birth defects. Other studies are needed to confirm these findings. Birth Defects Research (Part A) 106:950-962, 2016. © 2016 Wiley Periodicals, Inc.

Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011.

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.Birth Defects Research (Part A) 106:940-949, 2016.© 2016 Wiley Periodicals, Inc.

Assessment of YouTube videos as a source of information on medication use in pregnancy.

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.

Opioid prescription claims among women of reproductive age--United States, 2008-2012.

Prescription opioid use in the United States has become widespread, and studies of opioid exposure in pregnancy suggest increased risk for adverse pregnancy outcomes, including neonatal abstinence syndrome and birth defects (e.g., neural tube defects, gastroschisis, and congenital heart defects). The development of birth defects often results from exposures during the first few weeks of pregnancy, which is a critical period for organ formation. Given that many pregnancies are not recognized until well after the first few weeks and half of all U.S. pregnancies are unplanned, all women who might become pregnant are at risk. Therefore, it is important to assess opioid medication use among all women of reproductive age. CDC used Truven Health's MarketScan Commercial Claims and Encounters and Medicaid data to estimate the number of opioid prescriptions dispensed by outpatient pharmacies to women aged 15-44 years. During 2008-2012, opioid prescription claims were consistently higher among Medicaid-enrolled women when compared with privately insured women (39.4% compared with 27.7%, p<0.001). The most frequently prescribed opioids among women in both groups were hydrocodone, codeine, and oxycodone. Efforts are needed to promote interventions to reduce opioid prescriptions among this population when safer alternative treatments are available.

Prevalence of prescription medication use among non-pregnant women of childbearing age and pregnant women in the United States: NHANES, 1999-2006.

Many prescription medications have limited information regarding safety for use during pregnancy. In order to inform research on safer medication use during pregnancy, we examined prescription medication use among women in the United States. We analyzed data from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) to estimate the prevalence of prescription medication use in the past 30 days among pregnant women and non-pregnant women of childbearing age (15-44 years) and to ascertain the most commonly reported prescription medications by women in these groups. We assessed how the most commonly reported medications differed among groups defined by selected demographic characteristics, including age, race/ethnicity, and markers of socioeconomic status. Prescription medication use in the past 30 days was reported by 22 % of pregnant women and 47 % of non-pregnant women of childbearing age. The most commonly reported prescription medications by NHANES participants differed somewhat by pregnancy status; allergy and anti-infective medications were more common among pregnant women, while oral contraceptives were more common among non-pregnant women. Use of prescription medication for asthma and thyroid disorders was reported by both groups. Although prescription medication use in the previous 30 days was less common among pregnant women than non-pregnant women, its use was reported among almost 1 in 4 pregnant women. Many of the most common medications reported were for the treatment of chronic medical conditions. Given the potential impact of medications on the developing fetus, our data underscore the importance of understanding the safety of these medications during pregnancy.

Developing a systematic approach to safer medication use during pregnancy: summary of a Centers for Disease Control and Prevention--convened meeting.

To address information gaps that limit informed clinical decisions on medication use in pregnancy, the Centers for Disease Control and Prevention (CDC) solicited expert input on a draft prototype outlining a systematic approach to evaluating the quality and strength of existing evidence for associated risks. The draft prototype outlined a process for the systematic review of available evidence and deliberations by a panel of experts to inform clinical decision making for managing health conditions in pregnancy. At an expert meeting convened by the CDC in January 2013, participants divided into working groups discussed decision points within the prototype. This report summarizes their discussions of best practices for formulating an expert review process, developing evidence summaries and treatment guidance, and disseminating information. There is clear recognition of current knowledge gaps and a strong collaboration of federal partners, academic experts, and professional organizations willing to work together toward safer medication use during pregnancy.

Safe lists for medications in pregnancy: inadequate evidence base and inconsistent guidance from Web-based information, 2011.

PURPOSE: Medication use during pregnancy is common and increasing. Women are also increasingly getting healthcare information from sources other than their physicians. METHODS: This report summarizes an environmental scan that identified 25 active Internet sites that list medications reported to be safe for use in pregnancy and highlights the inadequate evidence base and inconsistent guidance provided by these sites. RESULTS: These lists included 245 different products, of which 103 unique components had been previously evaluated in terms of fetal risk by the Teratogen Information System (TERIS), a resource that assesses risk of birth defects after exposure under usual conditions by consensus of clinical teratology experts. For 43 (42%) of the 103 components that were listed as 'safe' on one or more of the Internet sites surveyed, the TERIS experts were unable to determine the fetal risk based on published scientific literature. For 40 (93%) of these 43, either no data were available to assess human fetal risk or the available data were limited. CONCLUSIONS: Women who see a medication on one of these 'safe' lists would be led to believe that there is no increased risk of birth defects resulting from exposure. Thus, women are being reassured that fetal exposure to these medications is safe even though a sufficient evidence base to determine the relative safety or risk does not exist.

Maternal medication and herbal use and risk for hypospadias: data from the National Birth Defects Prevention Study, 1997-2007.

PURPOSE: To investigate associations between maternal use of common medications and herbals during early pregnancy and risk for hypospadias in male infants. METHODS: We used data from the National Birth Defects Prevention Study, a multi-site, population-based, case-control study. We analyzed data from 1537 infants with second-degree or third-degree isolated hypospadias and 4314 live-born male control infants without major birth defects, with estimated dates of delivery from 1997 to 2007. Exposure was reported use of prescription or over-the-counter medications or herbal products, from 1 month before to 4 months after conception. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, previous live births, maternal subfertility, study site, and year. RESULTS: We assessed 64 medication and 24 herbal components. Maternal uses of most components were not associated with an increased risk of hypospadias. A new associations was observed for venlafaxine (aOR 2.4; 95%CI 1.0, 6.0) [Correction made here after initial online publication.]. The previously reported association for clomiphene citrate was confirmed (aOR 1.9; 95%CI 1.2, 3.0). Numbers were relatively small for exposure to other specific patterns of fertility agents, but elevated aORs were observed for the most common of them. CONCLUSIONS: Overall, findings were reassuring that hypospadias is not associated with most medication components examined in this analysis. New associations will need to be confirmed in other studies. Increased risks for hypospadias associated with various fertility agents raise the possibility of confounding by underlying subfertility.

Polysubstance Use in Pregnancy: Surveillance, Interventions, and Next Steps.

Substance use during pregnancy increases risk for a wide range of adverse maternal and neonatal health outcomes. Polysubstance use is common among people who use substances during pregnancy; however, the risks of combined substance exposures during pregnancy are poorly understood. In this report, we provide an overview of the activities of the Centers for Disease Control and Prevention (CDC) and partners and identified gaps related to (1) surveillance, (2) routine screening, and (3) prevention of polysubstance use during pregnancy. Efforts by CDC and other partners to reduce polysubstance use during pregnancy can improve the health of pregnant people and their infants and children.

Influencing clinical practice regarding the use of antiepileptic medications during pregnancy: modeling the potential impact on the prevalences of spina bifida and cleft palate in the United States.

Selected antiepileptic drugs (AEDs) increase the risk of birth defects. To assess the impact of influencing AED prescribing practices on spina bifida and cleft palate we searched the literature for estimates of the association between valproic acid or carbamazepine use during pregnancy and these defects and summarized the associations using meta-analyses. We estimated distributions of the prevalence of valproic acid and carbamazepine use among women of childbearing age based on analyses of four data sets. We estimated the attributable fractions and the number of children born with each defect that could be prevented annually in the United States if valproic acid and carbamazepine were not used during pregnancy. The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0-21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3-9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3-7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1-4.5) in the United States. Approximately 40 infants (95% UI: 10-100) with spina bifida and 35 infants (95% UI: 10-70) with cleft palate could be born without these defects each year if valproic acid were not used during pregnancy; 5 infants (95% UI: 0-15) with spina bifida and 5 infants (95% UI: 0-15) with cleft palate could be born without these defects each year if carbamazepine were not used during pregnancy. This modeling approach could be extended to other medications to estimate the impact of translating pharmacoepidemiologic data to evidence-based prenatal care practice.

Maternal treatment with opioid analgesics and risk for birth defects.

OBJECTIVE: We examined whether maternal opioid treatment between 1 month before pregnancy and the first trimester was associated with birth defects. STUDY DESIGN: The National Birth Defects Prevention Study (1997 through 2005) is an ongoing population-based case-control study. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIS) for birth defects categories with at least 200 case infants or at least 4 exposed case infants. RESULTS: Therapeutic opioid use was reported by 2.6% of 17,449 case mothers and 2.0% of 6701 control mothers. Treatment was statistically significantly associated with conoventricular septal defects (OR, 2.7; 95% CI, 1.1-6.3), atrioventricular septal defects (OR, 2.0; 95% CI, 1.2-3.6), hypoplastic left heart syndrome (OR, 2.4; 95% CI, 1.4-4.1), spina bifida (OR, 2.0; 95% CI, 1.3-3.2), or gastroschisis (OR, 1.8; 95% CI, 1.1-2.9) in infants. CONCLUSION: Consistent with some previous investigations, our study shows an association between early pregnancy maternal opioid analgesic treatment and certain birth defects. This information should be considered by women and their physicians who are making treatment decisions during pregnancy.

Prescription opioid use during pregnancy and risk for preterm birth or term low birthweight.

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.