Effects of Opioid Use Disorder in Pregnancy on Long-Term Maternal and Child Outcomes

妊娠期阿片类药物使用障碍对母婴长期结局的影响

• 批准号: 10430172
• 负责人: Senthilkumar Sadhasivam
• 金额: $ 45.91万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10430172
• 关键词: 2 year old; ABCB1 gene; Adverse effects; Affect; American; Behavior; Brain; Brain imaging; Buprenorphine; Child; Childhood; Clinical; Cognitive; Consensus; DRD2 gene; Data; Drug Kinetics; Economic Burden; Environmental Risk Factor; Epigenetic Process; Exposure to; Fetal Development; Fetus; Functional Magnetic Resonance Imaging; Future; Genes; Genetic; Genetic Risk; Genetic Variation; Genotype; Goals; High Prevalence; High Risk Woman; Hospitalization; Image; Imaging Device; Infant; Infant Care; Infant Development; Injury; Knowledge; Length of Stay; Life; Magnetic Resonance Imaging; Modeling; Morphine; Mothers; Neonatal; Neonatal Abstinence Syndrome; Neurodevelopmental Problem; Opioid; Opioid replacement therapy; Oral; Outcome; Overdose; Pattern; Pharmacogenetics; Placenta; Postpartum Depression; Predictive Factor; Predisposing Factor; Pregnancy; Pregnancy Outcome; Pregnant Women; Problem behavior; Psychological Factors; Psychosocial Factor; Public Health; Relapse; Research; Rest; Risk; Risk Factors; Severities; Treatment Factor; Treatment outcome; Variant; Work; adverse pregnancy outcome; base; buprenorphine treatment; cognitive function; combinatorial; cost efficient; design; effective therapy; fetal; fetal opioid exposure; genetic signature; genetic variant; high risk; illicit opioid; imaging approach; imaging biomarker; improved; in utero; infant outcome; innovation; insight; inter-individual variation; longitudinal design; maternal opioid use; maternal outcome; medication-assisted treatment; multidisciplinary; neonatal brain; neonatal outcome; neonatal period; neurodevelopment; novel; opioid exposure; opioid misuse; opioid use; opioid use disorder; opioid use in pregnancy; opioid withdrawal; personalized intervention; predictive modeling; prenatal; prescription opioid; prospective; psychologic; psychosocial; public health relevance; relapse risk; response; risk prediction; socioeconomics; socioenvironmental factor; tool; treatment response; treatment strategy

Project Summary: In the US, 14-21% of pregnant women are exposed to opioids during pregnancy. This re- flects a doubling of prescribed opioid use and opioid use disorder (OUD) in pregnancy in the past dec- ade. Opioid relapse during pregnancy and after delivery is high due to post-partum depression and other psy- chosocial factors. In parallel, neonatal abstinence syndrome (NAS) rates have increased more than 3 to 20 fold since 2000. Every 25 minutes, a baby is born dependent to opioids in the US. Children exposed to opioids pre- natally and in the neonatal period are at risk of opioid misuse later in life, and may develop cognitive, behavior- al and neurodevelopmental problems. All these preventable public health crises confer a significant societal and economic burden, with loss of productive life. Despite the high prevalence of exposure to opioids, little is known about the factors predisposing to poor maternal outcomes, and neurodevelopmental outcomes in chil- dren with maternal OUD. Further, the effect of in-utero opioid exposure on placental function, fetal maturation and neonatal brain activity are unknown. Tackling maternal opioid misuse and NAS requires a comprehensive understanding of multiple maternal-infant factors. There is a critical need for early and targeted identification of pregnant women with OUD at risk for relapse and poor long term maternal and childhood outcomes. Our long- term goals are to reduce future maternal OUD and relapse on opioid maintenance therapy, decrease severity of NAS, personalize NAS treatment, and improve neurodevelopment in children with in-utero opioid exposure. The objective of this proposal is to determine multi-factorial genetic, psychosocial predictors of opioid related maternal and infant outcomes using rigorous prospective longitudinal design, innovative combinatorial phar- macogenetic approach, fetal MRI and neonatal brain resting state functional MRI analysis. Our earlier work showed that maternal/neonatal genetic variations and opioid-pharmacogenetics were associated with NAS se- verity and adverse effects of opioids. Our preliminary data show that children treated for NAS had significantly worse cognitive function at two years of life. Based on our previous results, we hypothesize that a combination of maternal and infant genetic profile, maternal psychosocial factors, maternal opioid treatment response, fetal and neonatal neurodevelopment and NAS treatment will affect maternal and childhood outcomes with prenatal opioid exposure.The specific aims are to: 1) Identify high-risk genetic profiles and psychosocial factors in preg- nant women with opioid use disorder, and predisposing to poor maternal opioid maintenance treatment out- comes; 2) Determine maternal-infant genetic profiles and maternal opioid treatment factors predicting adverse fetal development, severity of NAS, and neonatal brain function; and 3) Develop predictive models for maternal opioid relapse, and poor long-term neuro-developmental outcomes in children with in-utero opioid exposure. Critical new knowledge from this research will enable safe, effective treatment of maternal-infant opioid expo- sure and neurodevelopmental outcomes by enabling proactive risk predictions and personalized interventions.

项目总结：在美国，14-21%的孕妇在怀孕期间接触过阿片类药物。这个重新

项目成果

Resting state functional MRI in infants with prenatal opioid exposure-a pilot study.

• DOI: 10.1007/s00234-020-02552-3
• 发表时间: 2021-04
• 期刊: Neuroradiology
• 影响因子: 2.8

Pilot study of fetal brain development and morphometry in prenatal opioid exposure and smoking on fetal MRI.

• DOI: 10.1016/j.neurad.2020.12.004
• 发表时间: 2022-01
• 期刊: Journal of neuroradiology = Journal de neuroradiologie
• 作者: Radhakrishnan R;Brown BP;Haas DM;Zang Y;Sparks C;Sadhasivam S
• 通讯作者: Sadhasivam S

Thalamocortical functional connectivity in infants with prenatal opioid exposure correlates with severity of neonatal opioid withdrawal syndrome.

产前阿片类药物暴露婴儿的丘脑皮质功能连接与新生儿阿片类药物戒断综合征的严重程度相关。

• DOI: 10.1007/s00234-022-02939-4
• 发表时间: 2022
• 期刊: Neuroradiology
• 影响因子: 2.8
• 作者: Radhakrishnan,Rupa;Vishnubhotla,RamanaV;Guckien,Zoe;Zhao,Yi;Sokol,GregoryM;Haas,DavidM;Sadhasivam,Senthilkumar
• 通讯作者: Sadhasivam,Senthilkumar

Global Brain Functional Network Connectivity in Infants With Prenatal Opioid Exposure.

• DOI: 10.3389/fped.2022.847037
• 发表时间: 2022
• 期刊: Frontiers in pediatrics
• 影响因子: 2.6
• 作者: Radhakrishnan R;Vishnubhotla RV;Zhao Y;Yan J;He B;Steinhardt N;Haas DM;Sokol GM;Sadhasivam S
• 通讯作者: Sadhasivam S