Jennifer N. Lind

Medications in the First Trimester of Pregnancy: Most Common Exposures and Critical Gaps in Understanding Fetal Risk

To determine which medications are most commonly used by women in the first trimester of pregnancy and identify the critical gaps in information about fetal risk for those medications.

Maternal Prepregnancy Body Mass Index and Child Psychosocial Development at 6 Years of Age

BACKGROUND: Both obesity and developmental disabilities have increased in recent decades. Limited studies suggest associations between maternal prepregnancy obesity and child neurodevelopment. METHODS: The Infant Feeding Practices Study II, a US nationally distributed longitudinal study of maternal health and infant health and feeding practices, was conducted from 2005 to 2007. In 2012, mothers were recontacted for information on their children’s health and development. We examined associations between maternal prepregnancy BMI and child psychosocial development in 1311 mother–child pairs included in this follow-up study. Children’s development was assessed by maternal report of child psychosocial difficulties from the Strengths and Difficulties Questionnaire, past developmental diagnoses, and receipt of special needs services. RESULTS: Adjusting for sociodemographic factors, children of obese class II/III mothers (BMI >35.0) had increased odds of emotional symptoms (adjusted odds ratio [aOR] 2.24; 95% confidence interval [CI], 1.27–3.98), peer problems (aOR 2.07; 95% CI, 1.26–3.40), total psychosocial difficulties (aOR 2.17; 95% CI, 1.24–3.77), attention-deficit/hyperactivity disorder diagnosis (aOR 4.55; 95% CI, 1.80–11.46), autism or developmental delay diagnosis (aOR 3.13; 95% CI, 1.10–8.94), receipt of speech language therapy (aOR 1.93; 95% CI, 1.18–3.15), receipt of psychological services (aOR 2.27; 95% CI, 1.09–4.73), and receipt of any special needs service (aOR 1.99; 95% CI, 1.33–2.97) compared with children of normal weight mothers (BMI 18.5–24.9). Adjustment for potential causal pathway factors including pregnancy weight gain, gestational diabetes, breastfeeding duration, postpartum depression, and child’s birth weight did not substantially affect most estimates. CONCLUSIONS: Children whose mothers were severely obese before pregnancy had increased risk for adverse developmental outcomes.

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

Medication use during pregnancy is common and increasing. Women are also increasingly getting healthcare information from sources other than their physicians.

Maternal Medication and Herbal Use and Risk for Hypospadias: Data from the National Birth Defects Prevention Study, 1997--2007

To investigate associations between maternal use of common medications and herbals during early pregnancy and risk for hypospadias in male infants.

Breastfeeding and later psychosocial development of children at 6 years of age.

OBJECTIVE: To examine the association of breastfeeding duration with psychosocial development at 6 years of age. METHODS: We analyzed data from the 2005–2007 Infant Feeding Practices Study II and its 2012 Year 6 Follow-Up (N = 1442). Our breastfeeding duration variable combined overall and exclusive breastfeeding reported during infancy (never breastfed, breastfed <6 months, breastfed ≥6 months + exclusive breastfeeding <3 months, and breastfed ≥6 months + exclusive breastfeeding ≥3 months). Maternal responses to the Strengths and Difficulties Questionnaire were used to create our child psychosocial outcome domains (emotional symptoms, conduct problems, hyperactivity, peer problems, prosocial behavior, and total difficulties). Separate multivariable logistic regression models controlling for maternal sociodemographic characteristics, maternal mental health, and child characteristics were used to assess the likelihood of having difficulties on the 6 domains based on breastfeeding duration. RESULTS: Compared with children who were never breastfed, those who were breastfed for ≥6 months and exclusively breastfed for ≥3 months had decreased odds of difficulties with emotional symptoms (odds ratio [OR]: 0.52; 95% confidence interval [CI]: 0.27–0.99), conduct problems (OR: 0.24; 95% CI: 0.10–0.54), and total difficulties (OR: 0.39; 95% CI: 0.18–0.85) before adjustment. These associations were no longer significant after adjustment. CONCLUSIONS: Although in our unadjusted analyses we observed significant associations between breastfeeding duration and later psychosocial development, including decreased odds of emotional, conduct, and total difficulties at 6 years of age, these findings were no longer detectable after adjusting for the many potential confounding factors that play a role in psychosocial development.

Relationship between Use of Labor Pain Medications and Delayed Onset of Lactation

Background: Despite estimates that 83% of mothers in the United States receive labor pain medications, little research has been done on how use of these medications affect onset of lactation. Objective: To investigate whether use of labor pain medications is associated with delayed onset of lactation (DOL). Methods: We analyzed data from the 2005-2007 Infant Feeding Practices Study II, a longitudinal study of women from late pregnancy through the entire first year after birth (n = 2366). In multivariable logistic regression analyses, we assessed the relationship between mothers’ use of labor pain medication/method and DOL (milk coming in > 3 days after delivery). Results: Overall, 23.4% of women in our sample experienced DOL. Compared with women who delivered vaginally and received no labor pain medication, women who received labor pain medications had a higher odds of experiencing DOL: vaginal with spinal/epidural only (aOR 2.05; 95% CI, 1.43-2.95), vaginal with spinal/epidural plus another medication (aOR 1.79; 95% CI, 1.16-2.76), vaginal with other labor pain medications only ([not spinal/epidural]; aOR 1.84; 95% CI, 1.14-2.98), planned cesarean section with spinal/epidural only (aOR 2.13; 95% CI, 1.39-3.27), planned cesarean with spinal/epidural plus another medication (aOR 2.67; 95% CI, 1.35-5.29), emergency cesarean with spinal/epidural only (aOR 2.17; 95% CI, 1.34-3.51), and emergency cesarean with spinal/epidural plus another medication (aOR 3.03; 95% CI, 1.77-5.18). Conclusion: Mothers who received labor pain medications were more likely to report DOL, regardless of delivery method. This information could help inform clinical decisions regarding labor/delivery.

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 Healths 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.

Risk comparison for prenatal use of analgesics and selected birth defects, National Birth Defects Prevention Study 1997–2011

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.

Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review

The objective of this report was to systematically review the available literature on maternal opioid use during pregnancy and congenital malformations. 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.

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.