Current projects

2025 - 2033

A Pregnancy and Birth Outcomes Study After Exposure to PENMENVY Vaccine in the US: A Cohort Study
PI: Loreen Straub
GSK ​

​The PENMENVY vaccine – a new pentavalent meningococcal vaccine – is recommended in children, adolescents, and young adults 10 through 25 years of age, which includes women of reproductive potential. The overarching aim of this study is to generate evidence on the safety of PENMENVY for pregnant women; specifically, to assess whether exposure to PENMENVY during specific gestational periods is associated with an increased risk of pre-specified pregnancy and birth outcomes.

2025 - 2032

Postmarketing Safety Study of Pregnancy and Neonatal Outcomes Following Gepotidacin Use for Urinary Tract Infections
PI: Yanmin Zhu
GSK 

​This project aims to fulfill a U.S. Food and Drug Administration postmarketing safety requirement by assessing the risk of the newly approved antibiotic, gepotidacin, among pregnant women. Leveraging data from both publicly and commercially insured populations, the study will evaluate the risks of major congenital malformations, stillbirth, spontaneous abortion, small-for-gestational-age birth, and preterm birth.

2025 - 2029

The comparative effectiveness and safety of pharmacotherapies for the treatment of opioid use disorder in pregnancy
PIs: Brian Bateman & Krista Huybrechts
NIDA: National Institute on Drug Abuse R01-DA049822-01

​Clinical guidelines recommend medication treatment of opioid use disorder during pregnancy to improve fetal and maternal outcomes, but there are critical gaps in our understanding of the comparative safety and effectiveness of alternative treatment options. Using nationwide cohorts of publicly and commercially insured pregnancies, we will examine newly emerging questions related to the impact of co-exposure to other psychoactive substances, the surge in fentanyl in the drug supply, the safety of naltrexone, and modifiable factors affecting treatment retention. The resulting evidence will help guide providers toward optimal treatment choices for individual patients and will identify factors that can be intervened upon directly to improve retention in treatment, a critical aspect of successful substance use disorder treatment.

2024-2025

Clinically recognized congenital cytomegalovirus infection and risk of long-term neurologic and non-neurologic complications: evidence from a nationwide cohort
PI: Yanmin Zhu
​NIAID: National Institute of Allergy and Infectious Diseases R03AI178363

Although congenital cytomegalovirus (cCMV) infection is the most common congenital infection in the US, important questions remain regarding its long-term sequelae. To address this critical knowledge gap, we propose to leverage existing data on over 29 million neonates in order to generate high-quality evidence on the risks of long-term neurologic and non-neurologic sequelae of clinically recognized cCMV and on the benefits of available treatments for these outcomes. The findings from this research will not only inform the value of universal screening, early antiviral treatments and vaccines, but will also raise awareness among patients and clinicians for this important but underrecognized congenital infection.

2023-2033

Cohort study to evaluate fetal and infant outcomes following maternal exposure to Bimekizumab for treatment of psoriasis during pregnancy
PI:  Krista Huybrechts
UCB

The goal of this study is to prospectively monitor the safety of bimekizumab during pregnancy over a 10-year time period to fulfill the post-marketing surveillance requirement from the European Medicines Agency.

2023-2028

The development of a systemic approach to harness real-world evidence for the evaluation of medication safety and effectiveness in children
PI: Timothy Savage
NICHD: National Institute of Child Health and Human Development 1K08HD110600

There is a paucity of data to inform safe and effective prescribing practices in children. Real-world evidence (RWE) studies using data from routine clinical practice have the potential to generate high-quality evidence that could guide prescribing when randomized controlled trials do not but are underdeveloped in pediatrics. This study aims to develop a rigorous framework for RWE studies such that they can reliably address key evidence gaps of medication safety and effectiveness in pediatrics through emulating ten published randomized clinical trials using large healthcare utilization databases.

2022-2027

Comparative safety of antibiotics for common bacterial infections during pregnancy
PI: Yanmin Zhu
​NICHD: National Institute of Child Health and Human Development R01HD107759

​Antibiotics are among the most commonly used medications in pregnancy, yet the potential of teratogenicity and fetal toxicity of antibiotics in humans remains an area largely devoid of evidence. To address this critical information gap, we propose to generate high-quality evidence on the comparative safety of antibiotic treatment options for common bacterial infections during pregnancy by leveraging existing data on over 4.5 million pregnancies. The findings from this research will directly inform the treatment decisions regarding antibiotics selection in pregnant women and women of reproductive age who may become pregnant.

2022-2027

TreeScan to evaluate the safety of new drugs in pediatric populations 
PIs: Shirley Wang & Krista Huybrechts
NICHD: National Institute of Child Health and Human Development R01HD110092

Children are not small adults; yet clinicians treating pediatric patients rely heavily on information collected in randomized and non-randomized studies of adult populations. To address this evidence gap – which puts pediatric patients at increased risk – we propose to develop and test the performance of tree-based scan statistic (TreeScan) approaches for the systematic and simultaneous evaluation of multiple potential adverse outcomes in pediatric populations, and to implement these methods for prospective sequential surveillance of new pediatric medications. This project will provide a critically needed tool that could lead to early detection of unsuspected adverse effects of drugs in pediatric populations if they exist and provide reassurance if no such safety concerns are detected.​​

2022-2027

Safety of benzodiazepines and non-benzodiazepine sedative hypnotics in pregnancy
PIs: Krista Huybrechts & Brian Bateman
NICHD: National Institute of Child Health and Human Development R01HD107772

Anxiety disorders and insomnia are common during pregnancy and treatment with benzodiazepines and non- benzodiazepine sedative hypnotics is often indicated, yet rigorous and comprehensive safety data to inform the risk-benefit trade-off are sparse, evidence is conflicting, and numerous safety concerns have been raised. To address this critical information gap we propose to generate high-quality evidence on the safety of benzodiazepines and non-benzodiazepine sedative hypnotics during pregnancy considering a broad range of clinically relevant adverse pregnancy outcomes. Evidence generated will not only prevent unnecessary exposure for mother and fetus at time points during pregnancy when the medication may be harmful but will also provide guidance and reassurance as to when the medication can be used safely.​

2021-2026

Active surveillance of the safety of antipsychotic medications in pregnancy
PIs: Shirley Wang & Krista Huybrechts
NICHD: National Institute of Child Health and Human Development R01HD104646

Mental health conditions are common among pregnant and postpartum women, and there is an urgent need to develop timely evidence regarding the safety of antipsychotic medications when used during pregnancy. We propose developing and implementing TreeScan, a novel signal detection method, for simultaneous evaluation of a broad range of potential maternal, fetal and neonatal adverse outcomes as part of a near real-time active safety surveillance system for antipsychotic medication use in pregnancy. Such an approach will not only avoid unnecessary exposure for mother and fetus to potentially harmful medications but, equally important, will provide re-assurance when no large harmful effects are detected so that women are not unnecessarily deprived of important medications for the treatment of psychiatric disorders.​

Paternal exposures, sperm epigenetic marks, and autism spectrum disorder in offspring
PI: Ran Rotem
NIEHS: National Institute of Environmental Health Sciences  K99ES035433

Examining the synergic roles of paternal pharmacological and environmental exposures in adverse neurodevelopment through sperm modifications.

Completed projects

2020-2024

The comparative effectiveness and safety of pharmacotherapies for the treatment of opioid use disorder in pregnancy
PIs: Brian Bateman & Krista Huybrechts
NIDA: National Institute on Drug Abuse R01-DA049822-01

The prevalence of opioid use disorders (OUD) during pregnancy has increased markedly over the past 15 years. It is recommended that pregnant women with OUD be treated with opioid agonist therapy (OAT) – i.e., methadone or buprenorphine – to prevent opioid withdrawal symptoms and to reduce the risk of illicit substance use during pregnancy; however, little is known about the comparative safety and effectiveness of methadone and buprenorphine, as well as of buprenorphine monotherapy compared to buprenorphine combined with naloxone, with respect to many important pregnancy outcomes. The goal of the proposed study is to provide robust information on the effects of available pharmacotherapies to treat OUD during pregnancy.​

2019-2024

Comparative safety of non-insulin agents in pregnant women with pre-gestational diabetes
PI: Sonia Hernandez-Diaz
NICHD: National Institute of Child Health and Human Development R01HD097778

The best way to reduce the known maternal and fetal risks associated with pre-gestational diabetes is to maintain excellent glycemic control before and during pregnancy. The lack of data on the safety of oral antidiabetic medications in the prenatal period has been a barrier to their use in pregnant women even when they may be beneficial, particularly for patients that don't need or don't tolerate insulin injections. The objective of the project is therefore to evaluate the comparative risks and benefits of non-insulin therapies in a large cohort of pregnant women and their infants.​

​2018-2023

In utero exposure to psychotropic medications and the risk of neurodevelopmental disorders
PI: Krista Huybrechts
NIMH: National Institute of Mental Health 1R01MH116194-01

Animal models suggest potential cognitive teratogenicity following in utero exposure to psychotropic medications, but there is limited to no information on the risk of neurodevelopmental disorders (i.e., autism spectrum disorder, attention deficit/hyperactivity disorder, and developmental delays) in humans. Using two national cohorts of over 4 million publicly and privately insured pregnancies and state of the art epidemiologic methods, we will evaluate the risk of neurodevelopmental outcomes following in utero exposure to specific psychotropic medications (i.e., mood stabilizers and other anticonvulsant drugs, antidepressants, antipsychotics, psychostimulants).

2017-2021

The impact of prescription opioid use on pregnancy outcomes
PI: Brian Bateman
NIH: National Institute on Drug Abuse R01-DA044293

The study objective was to evaluate the association between prescription opioid exposure during the etiologically relevant pregnancy window and a variety of important adverse pregnancy outcomes previously hypothesized to be associated with such exposure.  We also assessed for the outcomes in relation to specific opioids and assessed the impact of duration of exposure and dose.

2017-2019

​Developing the capability of using national Medicaid data for FDA post-marketing surveillance to assess medication safety during pregnancy
PI: Krista Huybrechts
Food and Drug Administration (FDA) RFTOP-1180790

The objective of this project was to develop and validate Medicaid-specific algorithms to estimate gestational age for live birth and non-live birth pregnancies. We also developed analytic tools to assess the impact on relative risk estimates of exposure misclassification, outcome misclassification, selection bias, and residual confounding.

2017-2019

Ondansetron and risk of congenital malformations
PI: Krista Huybrechts
NIH: National Institute of Child Health and Human Development 1R03HD0916990-01

The study objective was to evaluate the risk of congenital heart defects and cleft palate associated with ondansetron use during the first trimester of pregnancy in a national cohort of 1.6 million pregnancies covered by Medicaid.

2017-2019

Pregnancy registries nested in international pooled health care databases 
PI: Sonia Hernandez-Diaz
NIH: National Institute of Child Health and Human Development R21-HD092879

The study objective was to develop an international collaboration to study the safety of drugs in pregnancy. By pooling health care information from large population-based databases in the Nordic Countries and the United States, we were able to identify global nested exposed pregnancy cohorts to study in utero exposure to individual drugs in relation to rare outcomes such as specific birth defects.

2016-2018

​Observational studies to assess maternal and fetal outcomes following exposure to duloxetine
PI: Krista Huybrechts
Eli Lilly and Company

The study objective was to evaluate maternal and fetal/infant outcomes associated with exposure to duloxetine; part of fulfillment of a Food and Drug Administration requirement for post-marketing surveillance.

2013-2018

Comparative safety and effectiveness of antihypertensive medications in pregnancy 
PI: Brian Bateman
NIH: National Institute of Child Health and Human Development 5K08HD075831-05

About 4% of all pregnant women will take an antihypertensive medication during pregnancy. Much is unknown about the comparative safety and effectiveness of different antihypertensives in pregnancy. The study aimed to define the class of antihypertensive agent that is safest for the fetus and the one most likely to assure a good pregnancy outcome.

2016-2017

​Observational study to assess maternal and fetal outcomes following exposure to albiglutide during pregnancy
PI: Sonia Hernandez-Diaz
GlaxoSmithKline

The study objective was to determine whether exposure to albiglutide during pregnancy is associated with an increased risk of pre-specified adverse maternal and fetal outcomes.

2016-2017

Observational cohort study to assess maternal asthma during pregnancy and its association with fetal outcomes
PI: Sonia Hernandez-Diaz
GlaxoSmithKline

The study goal was to describe the frequency of the most common fetal and neonatal outcomes within women with severe and non-severe asthma, as well as in a reference group of women without asthma. 

2004-2017

Comparative safety of commonly prescribed psychotropic drugs in pregnant women 
PI: Sonia Hernandez-Diaz
​NIH: National Institute of Mental Health R01-MH100216

The study objective was to provide direct evidence on the safety of alternative strategies used to manage mood disorders, psychosis, and attention deficit hyperactivity disorders (ADHD) in a population of pregnant women, which includes vulnerable indigent young women. In particular, we compared the risk of adverse pregnancy and neonatal outcomes following the use of specific anticonvulsants/mood stabilizers, antipsychotics, and stimulants; and assessed the effect of continuing versus discontinuing these drugs during pregnancy.

2009-2014

Comparative effectiveness and safety of depression treatments during pregnancy 
PI: Sonia Hernandez-Diaz
AHRQ R01-HS018533

The primary objective was to generate evidence on the outcomes of treatments to manage depression in low-income pregnant women and their children.