Maternal And Infant Antipsychotic Study

NCT ID: NCT06049953

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-09-29
• Study Completion Date: 2027-12-01

Brief Summary

The goal of this observational study is to learn about maternal psychiatric course and infant development in pregnant individuals with severe mental illness, comparing those treated with antipsychotics to those treated with other medications or without medication. The main questions it aims to answer are:

1. Is risk of psychiatric relapse different among individuals who take antipsychotic medication, other medication, or no medication?

2. Are pregnancy and neonatal health outcomes different among individuals who take antipsychotic medication, other medication, or no medication?

3. Do infant behavior and neurodevelopment differ among babies who were exposed to antipsychotic medication, other medication, or no medication in utero? Participants will

• complete a psychiatric interview and questionnaires while pregnant;
• donate blood from the mother and from the umbilical cord at delivery
• have their babies participate in infant behavior evaluations and an EEG procedure.

Researchers will compare these outcomes among individuals who were treated either with antipsychotic medication, with psychotropic medications of other classes, and with no medication, to see if psychiatric benefits for the mother and health outcomes for mother and child differ among these three types of treatment.

Detailed Description

Antipsychotic (AP) medications are widely prescribed for a range of mental illnesses including bipolar disorder and nonaffective psychosis. These disorders usually onset in adolescence or early adulthood; thus, women of childbearing age are among those prescribed APs. The number of pregnancies exposed to APs has been increasing over time. Yet their efficacy has never been definitively demonstrated in this population.

APs cross the placenta and block dopamine (DA) D2 receptors, which are functional in the developing fetus, including influencing the proliferation and differentiation of neural progenitor cells. Increased DA signaling in early development results in increased numbers of inhibitory cortical interneurons and decreased numbers of pyramidal cells, while decreased DA signaling has the reverse effect. Thus, tonic DA blockade in utero could alter the excitatory/inhibitory balance in mature prefrontal cortex, which could affect fear processing, social functioning, and spatial or working memory in the long term. Additionally, gestational diabetes mellitus (GDM) is an established short-term risk of AP in pregnancy, which is associated with both increased body size and impaired cognitive and motor development in offspring.

At present very limited data exist on developmental outcomes associated with antenatal exposure to APs. Infant studies have found some evidence of initial difficulty adapting to life outside the womb as well as early neuromotor problems, but existing studies lack adequate comparison groups, and longitudinal data are lacking. Regarding long-term outcomes, the research group has found sex-specific increases in risk for psychiatric disorders for male, but not female, offspring, in both a register-based dataset and a clinical pilot study. This potential neurodevelopmental vulnerability requires further investigation in a rigorous longitudinal cohort study.

This study aims to investigate efficacy and adverse effects of AP exposure in pregnant women with severe mental illness (SMI). The research team hypothesizes that APs will be efficacious for psychiatric disorders, but will be associated with increased weight gain in mothers, poor neonatal adaptation in neonates, and sex-specific neurodevelopmental changes in infants. The overall goal is to precisely describe the risk/benefit ratio associated with AP treatment in pregnancy, in order to allow pregnant women with SMI to make informed decisions about their care.

Study Aims:

Aim 1: To investigate efficacy and adverse effects of AP treatment for pregnant women.

Aim 1a: Efficacy of AP treatment for pregnant women with SMI. Hypothesis: Women taking either APs or non-AP mood stabilizers will be less likely to relapse with mood or psychotic episodes than those not medicated.

Aim 1b: Adverse pregnancy outcomes with AP treatment for pregnant women. Hypothesis: Women taking APs will have greater weight gain in pregnancy than women taking non-APs or women taking no medication.

Researchers will recruit women in pregnancy with SMI (bipolar or primary psychotic disorder, N=200) in three groups: taking AP, taking other psychotropic medication, and taking no psychotropic medication, via two specialized perinatal psychiatric centers in NYC and the Netherlands. Women will be followed naturalistically and assessed for psychiatric relapse in pregnancy and the postpartum period, as well as complications of pregnancy, including weight gain and gestational diabetes, This will be the first study of AP efficacy in pregnancy.

Aim 2: To describe neonatal adaptation and physical growth in neonates of the mothers either exposed or unexposed to APs during pregnancy. Aim 2a: Neonatal adaptation in neonates either exposed or unexposed to APs during pregnancy. Hypothesis: Neonates of mothers who took APs during pregnancy will evince poorer neonatal adaptation than neonates of mothers who took either non-AP psychotropics or no medication. Aim 2b: Physical growth in neonates either exposed or unexposed to APs during pregnancy. Hypothesis: Neonates of mothers who took APs during pregnancy will have larger body sizes than neonates of mothers who took either non-AP psychotropics or no medication. The research team will examine obstetric and neonatal outcomes of infants of women with SMI, including neonatal adaptation syndrome (NAS), with control for maternal diagnosis and level of functioning. This will be the first controlled study of NAS after antenatal AP exposure.

Aim 3: To describe neurobehavioral development through 6 months in children from Aim 2. Aim 3a: Auditory sensory gating in children exposed to AP antenatally. Hypothesis: All infants prenatally exposed to APs will have reduced inhibitory activity as measured by the P50 component in the EEG. Aim 3b (Exploratory): Neurobehavioral development through 6 months in children exposed to AP antenatally. Hypothesis: Researchers predict increased symptoms of anxiety and internalizing behaviors for males only. Reduced auditory sensory gating will mediate, and sex will moderate, socioemotional outcomes associated with AP exposure. Comprehensive interviews, behavioral observations, and electroencephalography (EEG) obtained in a home visit at 6 months will assess socioemotional, cognitive, and motor development. The research team will investigate whether infant sex moderates any observed effects of AP exposure. This will be the first study of neural activity after antenatal AP exposure.

Conditions

Antipsychotics; Pregnancy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Antipsychotic medication

Pregnant women with severe mental illness (diagnosis of bipolar disorder, primary psychotic disorder, or any history of psychiatric hospitalization) who are treated with any of the following medications during pregnancy: Quetiapine, olanzapine, risperidone, aripiprazole, ziprasidone, lurasidone, haloperidol, or any other medication in the first- or second-generation antipsychotic class. All orally administered, with dosages titrated to clinical effect by the participant's primary psychiatrist.

Antipsychotics

Intervention Type: DRUG

Antipsychotic medications are widely prescribed for severe mental illness such as affective and non-affective psychosis, mood stabilization, and augmentation of unipolar depression.

Non-antipsychotic medication

Pregnant women with severe mental illness (diagnosis of bipolar disorder, primary psychotic disorder, or any history of psychiatric hospitalization) who are treated with any psychotropic medications during pregnancy other than those listed.

Non-antipsychotic medication

Intervention Type: DRUG

Psychotropic medications are typically prescribed to manage symptoms of anxiety, depression, psychological distress, and/or insomnia.

No medication

Pregnant women with severe mental illness (diagnosis of bipolar disorder, primary psychotic disorder, or any history of psychiatric hospitalization) who are not treated with any psychotropic medications during pregnancy.

No Medication

Intervention Type: OTHER

Non-psychotropic medications

Interventions

Antipsychotics

Antipsychotic medications are widely prescribed for severe mental illness such as affective and non-affective psychosis, mood stabilization, and augmentation of unipolar depression.

Intervention Type: DRUG

Non-antipsychotic medication

Psychotropic medications are typically prescribed to manage symptoms of anxiety, depression, psychological distress, and/or insomnia.

Intervention Type: DRUG

No Medication

Non-psychotropic medications

Intervention Type: OTHER

Other Intervention Names

Antidepressants; Benzodiazepines

Eligibility Criteria

Inclusion Criteria

• Pregnant
• Severe mental illness, including:

• Psychotic disorder (affective and nonaffective)
• Bipolar disorder
• History of psychiatric hospitalization, regardless of diagnosis
• Able to complete study interviews and measures in English, Dutch, or Spanish

Exclusion Criteria

• Active substance use disorder in pregnancy
• Insufficiently high-functioning to provide full informed consent and/or participate in study procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Thalia Robakis

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thalia Robakis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Floriana Milazzo, MPH

Role: CONTACT

floriana.milazzo@mssm.edu

(212) 659-1326

Veerle Bergink, MD, PhD

Role: CONTACT

veerle.bergink@mssm.edu

2126591326

Facility Contacts

Thalia Robakis

Role: primary

thalia.robakis@mssm.edu

2126598893

Luz Ospina

Role: backup

luz.ospina@mssm.edu

212-659-1326

Other Identifiers

R01HD111117-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY 23-00239

Identifier Type: -

Identifier Source: org_study_id