Perinatal Outcomes Associated With Metformin Use During Pregnancy in Women With Pregestational Type 2 Diabetes Mellitus.

Objective: We emulated a modified randomized trial (Metformin in Women With Type 2 Diabetes in Pregnancy [MiTy]) to compare the perinatal outcomes in women continuing versus discontinuing metformin during pregnancy among those with type 2 diabetes treated with metformin plus insulin before pregnancy.

Research Design And Methods: This study used two health care claims databases (U.S.

Metformin Use in the First Trimester of Pregnancy and Risk for Nonlive Birth and Congenital Malformations: Emulating a Target Trial Using Real-World Data.

Background: Metformin is a first-line pharmacotherapy for type 2 diabetes, but there is limited evidence about its safety in early pregnancy.

Objective: To evaluate the teratogenicity of metformin use in the first trimester of pregnancy.

Design: In an observational cohort of pregnant women with pregestational type 2 diabetes receiving metformin monotherapy before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: insulin monotherapy (discontinue metformin treatment and initiate insulin within 90 days of LMP) or insulin plus metformin (continue metformin and initiate insulin within 90 days of LMP).

Predictive models of miscarriage on the basis of data from a preconception cohort study.

Objective: To use self-reported preconception data to derive models that predict the risk of miscarriage.

Design: Prospective preconception cohort study.

Setting: Not applicable.

A prospective cohort study of preconception COVID-19 vaccination and miscarriage.

Study Question: To what extent is preconception maternal or paternal coronavirus disease 2019 (COVID-19) vaccination associated with miscarriage incidence?

Summary Answer: COVID-19 vaccination in either partner at any time before conception is not associated with an increased rate of miscarriage.

What Is Known Already: Several observational studies have evaluated the safety of COVID-19 vaccination during pregnancy and found no association with miscarriage, though no study prospectively evaluated the risk of early miscarriage (gestational weeks [GW] <8) in relation to COVID-19 vaccination. Moreover, no study has evaluated the role of preconception vaccination in both male and female partners.

Preconception contraceptive use and miscarriage: prospective cohort study.

Objectives: To evaluate the association between preconception contraceptive use and miscarriage.

Design: Prospective cohort study.

Setting: Residents of the United States of America or Canada, recruited from 2013 until the end of 2022.

Risk of Miscarriage in Relation to Seasonal Influenza Vaccination Before or During Pregnancy.

Objective: To evaluate the association between seasonal influenza vaccination and miscarriage using data from an ongoing, prospective cohort study.

Methods: We analyzed 2013-2022 data from PRESTO (Pregnancy Study Online), a prospective prepregnancy cohort study of female pregnancy planners and their male partners in the United States and Canada. Female participants completed a baseline questionnaire and then follow-up questionnaires every 8 weeks until pregnancy, during early and late pregnancy, and during the postpartum period.

COVID-19 vaccination and menstrual cycle characteristics: A prospective cohort study.

We prospectively examined the association between COVID-19 vaccination and menstrual cycle characteristics in an internet-based prospective cohort study. We included a sample of 1,137 participants who enrolled in Pregnancy Study Online (PRESTO), a preconception cohort study of couples trying to conceive, during January 2021-August 2022. Eligible participants were aged 21-45 years, United States or Canadian residents, and trying to conceive without fertility treatment.

Emulating a Target Trial of Interventions Initiated During Pregnancy with Healthcare Databases: The Example of COVID-19 Vaccination.

Background: Observational studies are often the only option to estimate effects of interventions during pregnancy. Causal inference from observational data can be conceptualized as an attempt to emulate a hypothetical pragmatic randomized trial: the target trial.

Objective: To provide a step-by-step description of how to use healthcare databases to estimate the effects of interventions initiated during pregnancy.

The association between time-to-pregnancy and postpartum depressive symptoms in a North American prospective cohort study.

Purpose: To prospectively examine the association between time-to-pregnancy (TTP) and postpartum depression (PPD) and determine whether perceived stress during early pregnancy mediated this association.

Methods: In Pregnancy Study Online, an internet-based preconception cohort study of pregnancy planners, participants completed questionnaires every 8 weeks for up to 12 months or conception, during pregnancy, and at postpartum. A total of 2643 women provided information on sociodemographic factors, reproductive history, and stress (i.

Effectiveness and safety of intrauterine insemination vs. assisted reproductive technology: emulating a target trial using an observational database of administrative claims.

Objective: To compare the effectiveness and safety of 1 cycle of assisted reproductive technology (ART) vs. 3 cycles of intrauterine insemination (IUI).

Design: Target trial emulation using observational data.

A prospective study of preconception asthma and spontaneous abortion.

Purpose: To evaluate the relationships among history of asthma, asthma severity, and spontaneous abortion (SAB).

Methods: Pregnancy Study Online is a preconception cohort study of North American couples. During the preconception period, female participants reported their history of physician-diagnosed asthma, age at first diagnosis, and use of asthma medications in the previous 4 weeks.

Misconceptions About the Direction of Bias From Nondifferential Misclassification.

Measurement error is pervasive in epidemiologic research. Epidemiologists often assume that mismeasurement of study variables is nondifferential with respect to other analytical variables and then rely on the heuristic that "nondifferential misclassification will bias estimates towards the null." However, there are many exceptions to the heuristic for which bias towards the null cannot be assumed.

A Prospective Study of Male Depression, Psychotropic Medication Use, and Fecundability.

We examined the associations of male depression and psychotropic medication use with fecundability in a North American preconception cohort study (2013-2020). Men aged ≥21 years completed a baseline questionnaire with questions on history of diagnosed depression, the Major Depression Inventory (MDI), and psychotropic medication use. Pregnancy status was updated via bimonthly female follow-up questionnaires until pregnancy or 12 menstrual cycles, whichever occurred first.

Emulating a target trial of the comparative effectiveness of clomiphene citrate and letrozole for ovulation induction.

Study Question: What are the comparative pregnancy outcomes in women who receive up to six consecutive cycles of ovulation induction with letrozole versus clomiphene citrate?

Summary Answer: The risks of pregnancy, livebirth, multiple gestation, preterm birth, neonatal intensive care unit (NICU) admission and congenital malformations were higher for letrozole compared with clomiphene in participants with polycystic ovarian syndrome (PCOS), though no treatment differences were observed in those with unexplained infertility.

What Is Known Already: Randomized trials have reported higher pregnancy and livebirth rates for letrozole versus clomiphene among individuals with PCOS, but no differences among those with unexplained infertility. None of these trials were designed to study maternal or neonatal complications.

Predictive models of pregnancy based on data from a preconception cohort study.

Study Question: Can we derive adequate models to predict the probability of conception among couples actively trying to conceive?

Summary Answer: Leveraging data collected from female participants in a North American preconception cohort study, we developed models to predict pregnancy with performance of ∼70% in the area under the receiver operating characteristic curve (AUC).

What Is Known Already: Earlier work has focused primarily on identifying individual risk factors for infertility. Several predictive models have been developed in subfertile populations, with relatively low discrimination (AUC: 59-64%).

Phthalate and DINCH urinary concentrations across pregnancy and risk of preterm birth.

Preconception and prenatal exposure to phthalates has been associated with an increased risk of preterm birth. However, it is unclear whether there are periods of heightened susceptibility during pregnancy. This prospective cohort study included 386 women undergoing fertility treatment who gave birth to a singleton infant during 2005 through 2018.

A North American prospective study of depression, psychotropic medication use, and semen quality.

Objective: To evaluate the associations of a history of diagnosed depression, current depressive symptoms, and recent use of psychotropic medications with semen quality and to consider mediation of the association between depression and semen quality by medication use.

Design: Prospective cohort study.

Setting: United States.

Pregravid contraceptive use and fecundability: prospective cohort study.

Objective: To evaluate the association between pregravid use of a variety of contraceptive methods and subsequent fecundability.

Design: Prospective cohort study.

Setting: Denmark and North America, 2007-19.

Perinatal Outcomes Associated with Maternal Asthma and Its Severity and Control During Pregnancy.

Background: Estimates of the effects of maternal asthma on pregnancy outcomes are inconsistent across studies, possibly because of differences in exposure definition.

Objective: To evaluate the risk of adverse perinatal outcomes associated with maternal asthma diagnosis, severity, and control in a large, nationally representative cohort.

Methods: This study was conducted within the IBM Health MarketScan Commercial Claims and Encounters Database (2011-2015) and the Medicaid Analytic eXtract database (2000-2014).