Developmental Effects of Antenatal Exposure to Antipsychotics
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 2
- 主要终点
- Finnegan Neonatal Abstinence Scoring System
研究概览
简要总结
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:
- Is risk of psychiatric relapse different among individuals who take antipsychotic medication, other medication, or no medication?
- Are pregnancy and neonatal health outcomes different among individuals who take antipsychotic medication, other medication, or no medication?
- 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.
详细描述
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:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Active substance use disorder in pregnancy
- •Insufficiently high-functioning to provide full informed consent and/or participate in study procedures
研究组 & 干预措施
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.
干预措施: No Medication (Other)
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.
干预措施: Antipsychotics (Drug)
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.
干预措施: Non-antipsychotic medication (Drug)
结局指标
主要结局
Finnegan Neonatal Abstinence Scoring System
时间窗: 24 hours postnatal
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.
Ratio of auditory evoked potentials as measured by EEG
时间窗: 6 months postnatal
Electrical activity of brain cells in response to a sound stimulus, measured noninvasively on the outside of the scalp by electroencephalography
Mini-International Neuropsychiatric Interview
时间窗: through study completion, an average of 6 months postpartum
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.
次要结局
- Fetal femur length(at 20 weeks)
- Oral glucose tolerance test score(at 24 weeks)
- Fetal body size(at 20 weeks)
- Fetal head circumference(at 20 weeks)
- Neonatal body size(at delivery)
- Neonatal head circumference(at delivery)
- Changes in weight percentile(at delivery and 6 months postnatal)
- Vineland Interview(at 6 months postnatal)
- 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 weight(at 20 weeks)
- Neonatal weight(at delivery)
- Maternal weight gain(through delivery, approximately 40 weeks post conception)
- Neonatal length(at delivery)
- Changes in Infant length percentile(at delivery and 6 months postnatal)
- Bayley-III Score(at 6 months postnatal)
研究者
Thalia Robakis
Associate Professor
Icahn School of Medicine at Mount Sinai