Neonatal Morbidities, Neurodevelopmental Impairments, and Positive Health among Children Surviving Birth before 32 Weeks of Gestation.

Objectives: To evaluate positive health outcomes among children born at < 32 weeks of gestation and to determine whether children with three common neonatal morbidities and 2 neurodevelopmental impairments would have similar positive health outcomes to children and adolescents without these exposures and impairments.

Study Design: In this secondary analysis of prospectively acquired data derived from 3 multicenter cohorts of children born very preterm (the Extremely Low Gestational Age Newborn cohort [birth years 2001 to 2004], the Neurobehavior And Outcomes in Very Preterm Infants cohort [birth years 2014 to 2016], and the Developmental Impact of Neurobehavior And Outcomes in Very Preterm Infants Exposures cohort [birth years 2010 to 2020]), we examined associations between the 3 common neonatal morbidities (bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage, diagnosed before hospital discharge), 2 neurodevelopmental impairments (developmental delays and cerebral palsy, diagnosed at preschool age follow-up), and perceptions of physical, mental, and social well-being (in either early childhood or adolescence), using the Patient-Reported Outcomes Measurement Information System scales for positive health.

Results: After adjusting for confounders, bronchopulmonary dysplasia, intraventricular hemorrhage, and cerebral palsy were associated with lower positive health scores, reported by parent-proxy during early childhood.

Prediction of site-specific pharmacologic therapy among newborns with neonatal opioid withdrawal syndrome.

Objective: To predict pharmacotherapy for NOWS based on factors available shortly after birth.

Study Design: A multi-center, retrospective study of 1377 opioid exposed newborns between 2016 and 2017 dichotomized based on pharmacologic treatment (N = 665 treated, N = 712 not treated) was conducted. A multilevel mixed-effect logistic regression model that considered cluster effect from sites determined significant maternal and newborn factors associated with pharmacotherapy, which were combined in a nomogram to predict probability of treatment for infants at each participating site.

A protocol for enhancing the diagnostic accuracy and predictive validity of neonatal opioid withdrawal syndrome: The utility of non-invasive clinical markers.

Every 15 minutes in the US, an infant exposed to opioids is born. Approximately 50% of these newborns will develop Neonatal Opioid Withdrawal Syndrome (NOWS) within 5 days of birth. It is not known which infants will develop NOWS, therefore, the current hospital standard-of-care dictates a 96-hour observational hold.

Neurobehavioral outcomes of preterm infants: toward a holistic approach.

Children born very preterm (VPT; <32 weeks gestation) are at high risk for adverse developmental outcomes, yet not all children fare poorly. Some children born VPT have few or no neurodevelopmental concerns, while others have significant impairment in one or more domains. Historically, research has taken a variable-centered approach, reporting rates of impairment in single domains or single assessments as if they are independent of one another.

Comparative Safety of In Utero Exposure to Buprenorphine Combined With Naloxone vs Buprenorphine Alone.

Importance: Buprenorphine combined with naloxone is commonly used to treat opioid use disorders outside of pregnancy. In pregnancy, buprenorphine alone is generally recommended because of limited perinatal safety data on the combination product.

Objective: To compare perinatal outcomes following prenatal exposure to buprenorphine with naloxone vs buprenorphine alone.

Maternal psychophysiology profiles: associations with prenatal opioid use, maternal emotion dysregulation, and newborn neurobehavior.

Background: Opioid use among pregnant women has more than quadrupled over the past 20 years; however, comorbid risk factors such as emotion dysregulation confound the developmental consequences of prenatal opioid use. Maternal respiratory sinus arrhythmia (RSA) may help to disentangle the comorbid risk factors of prenatal emotion dysregulation and substance use and isolate their consequences on newborn neurobehavior.

Methods: We examined maternal RSA in response to a mild, infant-related stress task in pregnant people (N = 192; 30 on medications for opioid use disorder) recruited from hospitals and a specialty prenatal clinic for substance use disorder.

Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants.

Importance: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized.

Objective: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants.

Evidence for neurobehavioral risk phenotypes at birth.

Observations of newborn behavior provide clinicians and researchers with a first description of the neurobehavioral organization of the newborn that is largely independent of the postnatal environment. The Neonatal Network Neurobehavioral Scale (NNNS) was developed in 2004 to evaluate how prenatal exposure to substances such as cocaine is related to neurobehavioral outcomes. There are now 156 empirical articles published using the NNNS, which we review and summarize.

Neonatal neurobehavior associated with developmental changes from age 2 to 3 in very preterm infants.

Objective: Understand how high-risk infants' development changes over time. Examine whether NICU Network Neurobehavioral Scale (NNNS) profiles are associated with decrements in developmental outcomes between ages 2 and 3 years in infants born very preterm.

Study Design: The Neonatal Outcomes for Very preterm Infants (NOVI) cohort is a multisite prospective study of 704 preterm infants born <30 weeks' gestation across nine university and VON affiliated NICUs.

Association of Growth During Infancy with Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental Influences on Child Health Outcomes Cohort.

Objective: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm.

Study Design: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age.

Associations between neighborhood characteristics and child well-being before and during the COVID-19 pandemic: A repeated cross-sectional study in the Environmental influences on Child Health Outcomes (ECHO) program.

The corona virus disease (COVID-19) pandemic disrupted daily life worldwide, and its impact on child well-being remains a major concern. Neighborhood characteristics affect child well-being, but how these associations were affected by the pandemic is not well understood. We analyzed data from 1039 children enrolled in the Environmental influences on Child Health Outcomes Program whose well-being was assessed using the Patient-Reported Outcomes Measurement Information System Global Health questionnaire and linked these data to American Community Survey (ACS) data to evaluate the impacts of neighborhood characteristics on child well-being before and during the pandemic.

Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure.

Background: Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.

Methods: We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020.

Toward a more holistic approach to the study of exposures and child outcomes.

The current work was designed to demonstrate the application of the exposome framework in examining associations between exposures and children's long-term neurodevelopmental and behavioral outcomes. Longitudinal data were collected from birth through age 6 from 402 preterm infants. Three statistical methods were utilized to demonstrate the exposome framework: exposome-wide association study, cumulative exposure and machine learning models, with and without epigenetic data.

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm.

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age.

Approaches to protocol standardization and data harmonization in the ECHO-wide cohort study.

The United States (U.S.) National Institutes of Health-funded Environmental influences on Child Health Outcomes (ECHO)-wide Cohort was established to conduct high impact, transdisciplinary science to improve child health and development.

Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability.

Prescription Stimulant Use During Pregnancy and Risk of Neurodevelopmental Disorders in Children.

Importance: Use of medications for attention-deficit/hyperactivity disorder (ADHD) during pregnancy is increasing in the US. Whether exposure to these medications in utero impacts the risk of neurodevelopmental disorders in children is uncertain.

Objective: To evaluate the association of childhood neurodevelopmental disorders with in utero exposure to stimulant medications for ADHD.

Opioid, methamphetamine, and polysubstance use: perinatal outcomes for the mother and infant.

The escalation in opioid pain relief (OPR) medications, heroin and fentanyl, has led to an increased use during pregnancy and a public health crisis. Methamphetamine use in women of childbearing age has now eclipsed the use of cocaine and other stimulants globally. Recent reports have shown increases in methamphetamine are selective to opioid use, particularly in rural regions in the US.