Maternal And Infant Antipsychotic Study (MAIA)

Developmental Effects of Antenatal Exposure to Antipsychotics

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.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy; Antipsychotics
• Intervention / Treatment: Drug: Antipsychotics; Drug: Non-antipsychotic medication; Other: No Medication

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Veerle Bergink, MD, PhD; Phone Number: 2126591326; Email: veerle.bergink@mssm.edu
• Study Contact Backup: Name: Floriana Milazzo, MPH; Phone Number: (212) 659-1326; Email: floriana.milazzo@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Luz Ospina; Phone Number: 212-659-1326; Email: luz.ospina@mssm.edu
      • Contact: Thalia Robakis; Phone Number: 2126598893; Email: thalia.robakis@mssm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women with severe mental illness as defined in Eligibility Criteria

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Drug: Antipsychotics; 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.	Drug: Non-antipsychotic medication; Psychotropic medications are typically prescribed to manage symptoms of anxiety, depression, psychological distress, and/or insomnia.; Other Names: Benzodiazepines; Antidepressants
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.	Other: No Medication; Non-psychotropic medications

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-International Neuropsychiatric Interview	In the DSM-5 Mini-International Neuropsychiatric Interview (M.I.N.I.) researchers will conduct modules for major depressive episode, (hypo)manic episode, and psychotic disorders. A clinical structured interview with very precise questions about psychological problems will require a 'yes' or 'no' answer. The M.I.N.I. is divided into modules identified by letters, each corresponding to a diagnostic category. At the beginning of each diagnostic module (except for psychotic disorders module), screening questions(s) corresponding to the main criteria of the disorder are presented in a gray box. At the end of each module, diagnostic box(es) permit the clinician to indicate whether diagnostic criteria are met.	through study completion, an average of 6 months postpartum
Finnegan Neonatal Abstinence Scoring System	Symptoms of poor neonatal adaptation, as assessed by Finnegan scale at 24 hours of life. Finnegan Neonatal Abstinence Scoring System (NAS) is an observer-rated scale documenting signs of neonatal adaptation. The individual NAS symptoms are weighted (numerically scoring 1-5) depending on the symptom, and the severity of the symptom expressed. The total score ranges from 0 to 43. Infants scoring an 8 or greater are recommended to receive pharmacologic therapy.	24 hours postnatal
Ratio of auditory evoked potentials as measured by EEG	Electrical activity of brain cells in response to a sound stimulus, measured noninvasively on the outside of the scalp by electroencephalography	6 months postnatal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal weight gain	Total pregnancy weight gain	through delivery, approximately 40 weeks post conception
Oral glucose tolerance test score	A glucose screening test is a routine test during pregnancy that checks a pregnant woman's blood glucose (sugar) level. Score on oral glucose tolerance test will be recorded.	at 24 weeks
Fetal body size	Fetal ultrasound-based and infant anthropometric measurements	at 20 weeks
Fetal weight		at 20 weeks
Fetal head circumference		at 20 weeks
Fetal biparietal diameter		at 20 weeks
Fetal cerebellar diameter		at 20 weeks
Neonatal birth weight adjusted for gestational age at delivery, as a percentile score		at 20 weeks
Fetal femur length		at 20 weeks
Neonatal body size		at delivery
Neonatal length		at delivery
Neonatal weight		at delivery
Neonatal head circumference		at delivery
Changes in Infant length percentile		at delivery and 6 months postnatal
Changes in weight percentile		at delivery and 6 months postnatal
Bayley-III Score	Neurodevelopmental assessment scores are age dependent and based motor and behavioral abilities, often reported for normal or abnormal for age. Bayley Scales of Infant and Toddler Development, third edition, (Bayley III) is an instrument designed to measure the developmental functioning of infants and toddlers between the ages of 1 month and 42 months (age adjustments for prematurity are accommodated with the tool). It provides age specific composite scores for cognitive (91 items, score min 55 max 145), language (98 items, score min 47 max 153), and motor (138 items, score min 46 max 154) skills. For all scales, higher scores indicate favorable outcomes and lower scores indicate possible delay/deficit.	at 6 months postnatal
Vineland Interview	Socioemotional, cognitive, and motor development as measured by Vineland interviews. . The Vineland measures five domains: Communication, Daily Living Skills, Socialisation, Motor Skills, and Maladaptive Behaviour. Each domain is summed, and the domain scores are converted to standardized scores. The normative score is 100, with standard deviation of 15. A higher score (above 100) means better adaptive behavior.	at 6 months postnatal

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Erasmus Medical Center
• Investigators: Principal Investigator: Thalia Robakis, MD, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: September 16, 2023
• First Posted (Actual): September 22, 2023

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: pregnancy; severe mental illness; antipsychotic; neurodevelopment; neonatal adaptation syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Benzazepines; Central Nervous System Agents; Antipsychotic Agents; Antidepressive Agents; Benzodiazepines
• Other Study ID Numbers: STUDY 23-00239; R01HD111117-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data will be stored and shared in accordance with HIPAA and GDPR law. Deidentified data will be shared between the two sites for the purpose of analysis of study outcomes.

For this purpose:

• dataset will be deidentified
• datasets will be limited
• data will be aggregated
• no directly traceable data will be shared
• data keys will never be shared between sites
• data will be encrypted

The process will be legally supported by Data transfer Agreements.

Deidentified US data will be stored at the NICHD Data and Specimen Hub (DASH). Deidentified Dutch data will be stored at the electronic archives at the Erasmus MC. Repositories will be accessible for researchers of the MAIA study with the proper access rights, only

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No