Safety of the 2011-12, 2012-13, and 2013-14 seasonal influenza vaccines in pregnancy: Preterm delivery and specific malformations, a study from the case-control arm of VAMPSS.

Background: Pregnant women have higher risks of influenza complications, but vaccine coverage is incomplete. Because concern about fetal harm limits uptake, we investigated risks for preterm delivery (PTD) and specific birth defects following vaccination in the 2011-12 through 2013-14 influenza seasons.

Methods: We used data from the Slone Epidemiology Center's Birth Defects Study.

Safety of the 2010-11, 2011-12, 2012-13, and 2013-14 seasonal influenza vaccines in pregnancy: Birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants, a study from the cohort arm of VAMPSS.

Introduction: There is a need for pregnancy safety information overall and for each seasonal formulation of the influenza vaccine.

Methods: As part of the cohort arm of the Vaccines and Medications in Pregnancy Surveillance System, vaccine-exposed and unexposed women in the U.S.

Application of data screening to drug exposure in large risk factor studies of birth defects.

Background: Birth defects are the leading cause of infant death. While causes of most are unknown, those that might be due to medication use are among the most preventable. This study describes an approach to identifying those medications that most warrant attention by using a "screen" program that calculates odds ratios for pairs of exposures and specific birth defects.

Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports.

Objective: To follow up on previously reported associations between periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects Prevention Study.

Design: Bayesian analysis combining results from independent published analyses with data from a multicenter population based case-control study of birth defects.

Setting: 10 centers in the United States.

Seasonal influenza vaccination during pregnancy and the risks of preterm delivery and small for gestational age birth.

Background: Influenza vaccination is routinely recommended for pregnant women, yet information on perinatal outcomes is sparse.

Methods: We investigated the associations between trivalent (seasonal) influenza vaccination during pregnancy and the risks of preterm delivery (PTD, live birth <37 weeks gestation) and small for gestational age birth (SGA, <10th percentile in weight for sex-specific gestational age) during the influenza seasons 2006-07 through 2009-10. The study population included 1619 mothers of live-born, non-malformed singleton infants interviewed as part of the Slone Epidemiology Center's Birth Defects Study.

Use of selective serotonin-reuptake inhibitors during pregnancy and the risk of clubfoot.

Background: Selective serotonin-reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. Previous studies have suggested that SSRIs may increase the risk of birth defects, including clubfoot. Using data from a population-based case-control study, we evaluated whether SSRI use increased the risk of clubfoot.

First-trimester exposure to bupropion and risk of cardiac malformations.

Purpose: Bupropion is a drug uniquely used both to treat depression and as an aid to smoking cessation. We investigated previously reported associations between first-trimester exposure to bupropion and cardiac defects.

Methods: Using data gathered since 2003 by the Slone Epidemiology Center's Case-control Birth Defects Study, we classified subjects with cardiac defects into subgroups.

Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants.

Introduction: There is a need for additional information on the fetal risks and relative safety of the pandemic H1N1 monovalent or trivalent influenza (pH1N1)-containing vaccines in women exposed during pregnancy.

Methods: To assess risks and relative safety of the pH1N1-containing vaccines, we conducted a prospective cohort study of pH1N1-vaccine-exposed and unexposed comparison women residing in the U.S.

Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: exposure prevalence, preterm delivery, and specific birth defects.

Unlabelled: We estimated exposure prevalence and studied potential risks for preterm delivery (PTD) and specific birth defects associated with exposure to the unadjuvanted pH1N1-containing vaccines in the 2009-2010 and 2010-2011 influenza seasons. We used data from 4 regional centers in the United States collected as part of the Slone Epidemiology Center's Birth Defects Study. For PTD, propensity score-adjusted time-varying hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for exposure anytime in pregnancy and for each trimester.

Maternal butalbital use and selected defects in the national birth defects prevention study.

Background: Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension-type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity.

Safety of macrolides during pregnancy.

Objective: Prior studies have reported increased risks of congenital heart defects (CHD) and pyloric stenosis (PS) after prenatal exposure to macrolide antibiotics. We sought to assess the association between maternal use of erythromycin and nonerythromycin macrolides and the risks of CHD and PS.

Study Design: Among participants in the Slone Epidemiology Center Birth Defects Study from 1994 through 2008, we identified 4132 infants with CHD and 735 with PS as cases, and 6952 infants without any malformation as controls.

Nonsteroidal antiinflammatory drugs in late pregnancy and persistent pulmonary hypertension of the newborn.

Objective: Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome of late-preterm and full-term infants associated with failure of the normal fetal-to-neonatal circulatory transition. This study was designed to test the hypothesis that risk for PPHN is increased after antenatal exposure to nonsteroidal antiinflammatory drugs (NSAIDs), with particular emphasis on late gestational exposures.

Methods: Between 1998 and 2003, we interviewed 377 women whose infants had PPHN and 836 control mothers of infants matched to cases by hospital and birth date.

Correcting for exposure misclassification using survival analysis with a time-varying exposure.

Purpose: Survival analysis is increasingly being used in perinatal epidemiology to assess time-varying risk factors for various pregnancy outcomes. Here we show how quantitative correction for exposure misclassification can be applied to a Cox regression model with a time-varying dichotomous exposure.

Methods: We evaluated influenza vaccination during pregnancy in relation to preterm birth among 2267 non-malformed infants whose mothers were interviewed as part of the Slone Birth Defects Study during 2006 through 2011.

Influenza vaccine safety in pregnancy: can we identify exposures?

Purpose: To assess the feasibility of identifying influenza vaccine exposure in pregnancy.

Methods: Two study designs were used. (i) Women who contacted the Organization of Teratology Information Specialists (OTIS) network and were referred to their research center or contacted the center directly were invited to participate.

Maternal exposure to amoxicillin and the risk of oral clefts.

Background: Prior studies have suggested an increased risk of oral clefts after exposure to amoxicillin in early pregnancy, but findings have been inconsistent.

Methods: Among participants in the Slone Epidemiology Center Birth Defects Study from 1994 to 2008, we identified 877 infants with cleft lip with/without cleft palate and 471 with cleft palate alone. Controls included 6952 nonmalformed infants.

Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects.

Background: Nausea and vomiting of pregnancy (NVP) occurs in up to 80% of pregnant women, but its association with birth outcomes is not clear. Several medications are used for the treatment of NVP; however, data are limited on their possible associations with birth defects.

Methods: Using data from the National Birth Defects Prevention Study (NBDPS)-a multi-site, population-based, case-control study-we examined whether NVP or its treatment was associated with the most common noncardiac defects in the NBDPS (nonsyndromic cleft lip with or without cleft palate [CL/P], cleft palate alone [CP], neural tube defects, and hypospadias) compared with randomly selected nonmalformed live births.

Drug certainty-response in interview-based studies.

Purpose: Imperfect recall of exposure timing challenges the ascertainment of medications in interview-based studies.

Methods: We propose an algorithm to classify medication exposure, taking into account recall certainty. The availability of medication use details, including duration of use, start and stop dates, and maternal estimates of how certain they were about these dates, allowed classification of subjects as either likely or possibly exposed in the first trimester of pregnancy.

Case-control studies for identifying novel teratogens.

The case-control study design offers an operationally efficient approach to measuring an association between an exposure and an outcome, especially when the outcome is rare, as is true for specific birth defects. For example, instead of following 50,000 pregnant women to have sufficient statistical power to identify a doubling in risk of oral clefts associated with a common exposure (e.g.

Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008.

Objective: The objective of the study was to provide information on overall medication use throughout pregnancy, with particular focus on the first trimester and specific prescription medications.

Study Design: The study design included the Slone Epidemiology Center Birth Defects Study, 1976-2008, and the National Birth Defects Prevention Study, 1997-2003, which together interviewed more than 30,000 women about their antenatal medication use.

Results: Over the last 3 decades, first-trimester use of prescription medication increased by more than 60%, and the use of 4 or more medications more than tripled.

Safety of influenza immunizations and treatment during pregnancy: the Vaccines and Medications in Pregnancy Surveillance System.

The Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) has been designed to assess systematically the safety of vaccines and medications during pregnancy and is suited ideally to evaluate the gestational safety of seasonal and pandemic influenza vaccine and influenza antivirals. VAMPSS is coordinated by the American Academy of Allergy Asthma and Immunology and includes 2 complimentary data collection arms (prospective cohort and case-control surveillance) and a standing independent advisory committee. Both data collection arms obtain information directly from the mother, which facilitates accurate capture of exposures and potential confounders.

Asthma in pregnancy and its pharmacologic treatment.

Background: Asthma is among the most common serious medical problems in pregnancy, and its prevalence may be increasing. Management is problematic because asthma may harm the fetus, yet little is known about fetal risks of asthma medications.

Objective: To examine the prevalence, symptom control, and pharmacologic treatment of asthma in pregnancy.

Use of herbal treatments in pregnancy.

Objective: Interest in herbal treatments has increased without data on safety, efficacy, or rates of use in pregnancy. We examined antenatal herbal and natural product use among mothers of nonmalformed infants in 5 geographic centers.

Study Design: We used data on nonmalformed infants from the Slone Epidemiology Center's case-control surveillance program for birth defects to examine rates and predictors of herbal use.