Impact of Screening and Co-located Parent Coaching Within Pediatric Primary Care on Child Health Care Use: A Stepped Wedge Design.

Childhood adversity and toxic stress have been associated with poor mental and physical health. This study examined if Parent Connext, a program that integrates adversity screening and parent coaching by co-located specialists within pediatric primary care, had an impact on health care utilization. This stepped wedge cluster randomized controlled trial evaluated Parent Connext across six pediatric primary care practices. All practices (clusters) were in the control period during year 1. Three practices were randomized to begin the Parent Connext intervention in year 2, and three practices were randomized to begin in year 3. Medical records of all patients under age 8 treated at these practices during these 3 years were queried retrospectively for participant-level primary outcomes (sick visits, emergency department visits, hospitalizations) and secondary outcomes (well-child and immunization adherence, referrals). The study sample included 27,419 patients followed for an average 1.39 (SD = 0.66) years in the control period and 1.07 (SD = 0.60) years in the intervention period. During the intervention period, patients had significantly fewer sick visits (IRR = 0.91, p < 0.001) which aligned with our hypothesis, decreased odds of well-child visit adherence (OR = 0.88, p < 0.001) which was unexpected, and increased odds of receiving a referral (OR = 1.45, p < 0.001). The odds of an emergency department visit, hospitalization, and 2-year immunization adherence did not differ between periods. Parent Connext resulted in a significant reduction in child sick visits, highlighting the potential benefit of two-generation approaches to pediatric care for child health.

Association Between Maternal Adverse Childhood Experiences and Neonatal SCG5 DNA Methylation-Effect Modification by Prenatal Home Visiting.

Maternal childhood adversity and trauma may elicit biological changes that impact the next generation through epigenetic responses measured in DNA methylation (DNAm). These epigenetic associations could be modified by the early postnatal environment through protective factors, such as early childhood home visiting (HV) programs that aim to mitigate deleterious intergenerational effects of adversity. In a cohort of 53 mother-child pairs recruited in 2015-2016 for the Pregnancy and Infant Development Study (Cincinnati, Ohio), we examined the association between maternal adverse childhood experiences (ACEs) and neonatal DNAm in the secretogranin V gene (SCG5), which is important in neuroendocrine function. We examined prenatal HV as an effect modifier. Mothers completed a questionnaire on ACEs during pregnancy, and infant buccal samples were collected 1 month postpartum. Multivariable linear regression was used to examine the association between maternal ACEs and neonatal DNAm expressed as M-values averaged across 4 cytosine-phosphate-guanine dinucleotide sites. A higher number of maternal ACEs (>3) was associated with a 5.79-percentage-point lower offspring DNAm (95% confidence interval: -10.44, -1.14), and the association was modified by the number of home visits received during pregnancy. In a population of at-risk mother-child dyads, preliminary evidence suggests that maternal ACEs have a relationship with offspring SCG5 DNAm that differs by the amount of prenatal HV.

Enrollment and outcomes of home visiting for mothers with and without a history of out-of-home care.

Women previously in out-of-home care (i.e., foster care) experience poorer health and psychosocial outcomes compared to peers, including higher pregnancy rates and child protective services involvement. Home visiting programs could mitigate risks. Studies examining home visiting enrollment for women with a history of out-of-home care are needed. Women previously in out-of-home care based on child welfare administrative data between 2012 and 2017 (n = 1375) were compared to a demographically matched sample (n = 1375) never in out-of-home care. Vital records data identified live births in the two groups. For those who had given live birth (n = 372), linked administrative data were used to determine and compare rates of referral and enrollment into home visiting, and two indicators of engagement: number of days enrolled, and number of visits received. Women previously in out-of-home care were referred for home visiting more often than their peers. There were no differences in rates of enrollment. Women previously in out-of-home care remained enrolled for shorter durations and completed fewer home visits than peers. Findings suggest barriers to home visiting enrollment and retention in home visiting programs for women previously in out-of-home care. Studies with larger samples and more complete assessments of outcomes are warranted.

Introducción: Las mujeres que previamente han estado bajo cuidado fuera de cada (v.g. hogares de cuidado adoptivo temporal) experimentan una más débil salud y resultados sicosociales en comparación con las compañeras, incluyendo tasas más altas de embarazos y participación en servicios de protección a la niñez. Los programas de visitas a casa pudieran mitigar los riesgos. Se necesitan estudios que examinen la entrada en programas de visitas a casa de mujeres con un historial de cuidado fuera de casa. Métodos: Se comparó la información administrativa entre 2012 y 2017 de mujeres (n = 1375) que previamente estuvieron en cuidados fuera de casa basados en la beneficencia infantil con un grupo muestra demográficamente emparejado (n = 1375) que nunca habían estado bajo cuidado fuera de casa. Los datos vitales registrados identificaron nacimientos vivos en los dos grupos. Para quienes habían tenido un parto y nacimiento vivo (n = 372), se usó la información administrativa conectada para determinar y comparar las tasas de referencia y entrada en programas de visitas a casa, y dos indicadores de participación: el número de días en que estuvieron matriculadas y el número de visitas recibidas. Resultados: A las mujeres previamente bajo cuidado fuera de casa se les refirió a los programas de visita a casa más a menudo que a sus compañeras. No se dieron diferencias en las tasas de matrícula. Las mujeres previamente bajo cuidado fuera de casa permanecieron matriculadas por duraciones más cortas y completaron menos visitas a casa que sus compañeras. Conclusiones: Los resultados identifican barreras a la matrícula y retención en programas de visitas a casa para mujeres previamente bajo cuidado fuera de casa. Se justifican los estudios con grupos muestras más grandes y evaluaciones más completas de los resultados.

Les femmes ayant été placées en famille ou foyer d'accueil font l'expérience d'une plus mauvaise santé et de résultats psychologiques moins bons que les autres femmes, y compris des taux de grossesse plus élevés et l'intervention de services de protection de l'enfance. Les programmes de visite à domicile peuvent mitiger les risques. Les études examinant l'inscription aux visites à domicile pour les femmes ayant un passé de placement en famille ou en foyer sont nécessaires. Méthodes: des femmes ayant vécu un placement en famille ou en foyer selon les données administratives de la protection de l'enfance entre 2012 et 2017 (n = 1375) ont été comparées à un échantillon assorti démographiquement (n = 1375) de femmes n'ayant jamais été placées en famille ou foyer d'accueil. Nous avons identifié des naissances vivantes chez les deux groupes. Pour celles ayant donné naissance (naissance vivante) (n = 372) les données administratives liées ont été utilisées afin de déterminer et de comparer les taux d'orientation et d'inscription aux visites à domicile, et deux indicateurs d'engagement: le nombre de jours inscrites et le nombre de visites reçues. Résultats: les femmes ayant été placées dans des familles ou des foyers d'accueil étaient dirigées vers les visites à domicile plus souvent que leurs pairs. Il n'y avait aucune différence dans les taux d'inscription. Les femmes ayant été en familles ou foyers d'accueil sont restées inscrites pendant des durées plus courtes et ont eu moins de visites à domiciles que leurs pairs. Conclusions: les résultats suggèrent qu'il existe des barrières à l'inscription aux visites à domicile et à la rétention dans les programmes de visites à domicile pour les femmes ayant été placées en famille ou en foyer. Des études avec des échantillons plus grands et des évaluations plus compètes sont justifiées.

Objectively Diagnosed Diffuse White Matter Abnormality at Term Is an Independent Predictor of Cognitive and Language Outcomes in Infants Born Very Preterm.

OBJECTIVE: To externally validate the independent value of objectively diagnosed diffuse white matter abnormality (DWMA; also known as diffuse excessive high signal intensity) volume to predict neurodevelopmental outcomes in very preterm infants (≤31 weeks of gestational age). STUDY DESIGN: A prospective, multicenter, regional population-based cohort study in 98 very preterm infants without severe brain injury on magnetic resonance imaging (MRI). DWMA volume was diagnosed objectively on structural MRI at term-equivalent age using our published algorithm. Multivariable linear regression was used to assess the value of DWMA volume to predict cognitive and language scores on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years corrected age. RESULTS: Of the infants who returned for follow-up (n = 74), the mean (SD) gestational age was 28.2 (2.4) weeks, and 42 (56.8%) were boys. In bivariable analyses, DWMA volume was a significant predictor of Bayley-III cognitive and language scores. In multivariable analyses, controlling for known predictors of Bayley-III scores (ie, socioeconomic status, gestational age, sex, and global brain abnormality score), DWMA volume remained a significant predictor of cognitive (P < .001) and language (P = .04) scores at 2 years. When dichotomized, objectively diagnosed severe DWMA was a significant predictor of cognitive and language impairments, whereas visual qualitative diagnosis of DWMA was a poor predictor. CONCLUSIONS: In this multicenter, prospective cohort study, we externally validated our previous findings that objectively diagnosed DWMA is an independent predictor of cognitive and language development in very preterm infants. We also demonstrated again that visually-diagnosed DWMA is not predictive of neurodevelopmental outcomes.

Adherence to Well-Child Care and Home Visiting Enrollment Associated with Increased Emergency Department Utilization.

INTRODUCTION: Pediatric primary care and home visiting programs seek to reduce health disparities and promote coordinated health care use. It is unclear whether these services impact high-cost, emergency department (ED) utilization. We evaluated the association of well-child care (WCC) and home visiting with ED visit frequency for children < 1 year with an established medical home. METHODS: Retrospective cohort study using linked administrative data for infants ≥ 34 weeks' gestation from 2010 to 2014, within a multisite, academic primary care system. Latent class analysis characterized longitudinal patterns of WCC. Multivariable negative binomial regression models tested the independent association between WCC patterns and home visiting enrollment with ED visits. RESULTS: Among 10,363 infants, three WCC latent classes were identified: "Adherent" (83.4% of the cohort), "Intermediate" (9.7%), and "Decreasing adherence" (7.0%). Sixty-one percent of the sample had ≥ 1 ED visit in the first 12 months of life, and 73% of all ED visits were triaged as non-urgent. There was a significant interaction effect between WCC pattern and insurance status. Among Medicaid-insured infants, "Intermediate" and "Decreasing adherence" WCC patterns were associated with a lower incident rate of ED visits compared with the "Adherent" pattern (incident rate ratios (IRR) 0.88, p = 0.03 and 0.79, p < 0.001 respectively); this effect was not observed among privately-insured infants. Home visiting enrollment was independently associated with a higher rate of ED visits (IRR 1.24, p < 0.001). DISCUSSION: Among infants with an established medical home, adherence to recommended WCC and home visiting enrollment was associated with greater ED use for non-urgent conditions.

Parental Adverse Childhood Experiences and Pediatric Healthcare Use by 2 Years of Age.

OBJECTIVE: To determine whether maternal and paternal exposure to adverse childhood experiences (ACEs) has an association with offspring healthcare use by 2 years of age. STUDY DESIGN: A retrospective cohort study was performed on 454 patients at a large suburban pediatric primary care practice whose mother (n = 374) or father (n = 156) or both (n = 123) completed an ACE survey between October 2012 and June 2014. The association between self-reported parental ACEs and healthcare use by 2 years of age, including number of missed well-child visits, sick visits, and delayed or missed immunizations, was modeled using multivariable negative binomial regression. All analyses adjusted for child sex, payer source, and preterm birth. RESULTS: Maternal, but not paternal, ACE exposure was significantly associated with missed well-child visits by 2 years of age. For each additional maternal ACE, there was a significant 12% increase in the incidence rate of missed well-child visits (relative risk, 1.12; 95% CI, 1.03-1.22; P = .010). Maternal and paternal ACE scores were not significantly associated with increased sick visits or delayed or missed immunizations. CONCLUSIONS: The ACE exposure of mothers is negatively associated with adherence to preventive healthcare visits among their children early in life. Future research is needed to elucidate the mechanisms of this association and to develop and implement family-based intervention strategies.

Primary Care and Home Visiting Utilization Patterns among At-Risk Infants.

OBJECTIVE: To describe well child care (WCC) utilization in the first year of life among at-risk infants, and the relationship to home visiting enrollment. STUDY DESIGN: Retrospective cohort study using linked administrative data for infants ≥34 weeks' gestation from 2010 to 2014, within a regional, academic primary care system. Association between WCC visits and home visiting enrollment was evaluated using bivariate comparisons and multivariable Poisson regression. Latent class analysis further characterized longitudinal patterns of WCC attendance. Multivariable logistic regression tested the association between home visiting and pattern of timeliest adherence to recommended WCC. RESULTS: Of 11 936 infants, mean number of WCC visits was 4.1 in the first 12 months of life. Of 3910 infants eligible for home visiting, 28.5% were enrolled. Among enrolled infants, mean WCC visits was 4.7 vs 4.4 among eligible, nonenrolled infants, P value < .001. After multivariable adjustment, there was no significant association between enrollment and WCC visit count (adjusted incident rate ratio 1.03, 95% CI 0.99, 1.07). Using latent class analysis, 3 WCC classes were identified: infants in class 1 (77.7%) were most adherent to recommended WCC, class 2 (12.5% of cohort) had progressively declining WCC attendance over the first year of life, and class 3 (9.8%) maintained moderate attendance. In multivariable regression, home visiting was associated with class 1 membership, aOR 1.27, 95% CI 1.04, 1.57. CONCLUSIONS: A pattern of timely WCC attendance was more likely among infants in home visiting; however, most infants eligible for home visiting were not enrolled.

Participation in Home Visitation is Associated with Higher Utilization of Early Intervention.

Objectives To determine whether participation in a home visiting program increases and expedites utilization of early intervention services for suspected developmental delays. Methods Children participating in Every Child Succeeds (ECS), a large home visiting (HV) program serving greater Cincinnati, between 2006 and 2012, were propensity score matched to a sample of children identified from birth records who did not receive services from ECS. Data were linked to early intervention (EI) data acquired from the Ohio Department of Health. Descriptive statistics were employed to evaluate success of the matching. Chi square and log-rank tests evaluated whether the proportion of children accessing EI and the time to EI services differed for families participating in HV compared to eligible children not participating. Logistic regression and Cox proportional hazards regression modeled the associations. Results Among 3574 HV and 3574 comparison participants, there was no difference in the time to EI service utilization; however a higher percentage of HV participants accessed services. Overall, 6% of the HV group and 4.3% of the comparison group accessed services (p = 0.001). Modeling revealed an odd ratio = 1.43 [95% confidence interval (CI) 1.16-1.78, p value = 0.001] and hazard ratio = 1.42 [95% CI 1.15-1.75, p value = 0.001]. Differences in utilization were greatest directly after birth and between approximately 2 and 3 years. Conclusions for Practise Participation in home visiting was associated with greater utilization of EI services during two important developmental time points, demonstrating that home visiting may serve as an important resource for facilitating access to early intervention services.

Comparison of Neonatal Abstinence Syndrome Treatment with Sublingual Buprenorphine versus Conventional Opioids.

OBJECTIVE: The objective of this study was to compare duration of opioid treatment and length of stay outcomes for neonatal abstinence syndrome (NAS) using sublingual buprenorphine versus traditional weaning with methadone or morphine. STUDY DESIGN: This retrospective cohort analysis evaluated infants treated for NAS at a single community hospital from July 2013 through June 2017. A standardized weaning protocol was introduced in June 2015, allowing for treatment with sublingual buprenorphine regardless of type of intrauterine opioid exposure. General linear models were used to calculate adjusted mean duration of opioid treatment and length of hospitalization with 95% confidence intervals for infants treated with buprenorphine compared with traditional weaning with either methadone or morphine. RESULTS: A total of 360 infants were treated with either buprenorphine (n = 174) or a traditional opioid (n = 186). Infants treated with buprenorphine experienced a 3.0-day reduction in opioid treatment duration of 7.4 (6.3-8.5) versus 10.4 (9.3-11.5) days (p < 0.001) and a 2.8-day reduction in length of stay of 12.4 (11.3-13.6) versus 15.2 (14.1-16.4) days (p < 0.001). CONCLUSION: Our study provides an independent confirmation that among infants experiencing NAS following a wide array of intrauterine opioid exposures, buprenorphine weaning supports a shortened treatment duration compared with conventional weaning agents.

Maternal Interpersonal Trauma and Child Social-Emotional Development: An Intergenerational Effect.

BACKGROUND: Evidence suggests that maternal interpersonal trauma can adversely affect offspring health, but little is known about potential transmission pathways. We investigated whether interpersonal trauma exposure had direct and indirect associations with offspring social-emotional development at 12-months of age in an at-risk, home visited population. METHODS: A retrospective cohort study was conducted of 1172 mother-child dyads who participated in a multi-site, early childhood home visiting program. Children were born January 2007 to June 2010 and data were collected at enrolment (prenatal/birth) through 12-months of age. Multivariable path analyses were used to examine the relationship between maternal interpersonal trauma, subsequent psychosocial mediators (maternal depressive symptoms, social support, and home environment), and the outcome of child social-emotional development measured with the Ages and Stages Questionnaire: Social-Emotional (ASQ:SE). Maternal interpersonal trauma was characterized as any previous exposure, the level of exposure, and type (e.g. abuse) of exposure. RESULTS: The prevalence of maternal interpersonal trauma exposure was 69.1%, and exposures ranged from 1 type (19.3%) to 7 types (2.3%). Interpersonal trauma was associated with a 3.6 point (95% confidence interval 1.8, 5.4) higher ASQ:SE score among offspring and indicated greater developmental risk. An estimated 23.4% of the total effect was mediated by increased maternal depressive symptoms and lower social support. Differential effects were observed by the level and type of interpersonal trauma exposure. CONCLUSION: Maternal interpersonal trauma exposures can negatively impact child social-emotional development, acting in part through maternal psychosocial factors. Future research is needed to further elucidate the mechanisms of intergenerational risk.

Evaluation of Early Childhood Home Visiting to Prevent Medically Attended Unintentional Injury.

STUDY OBJECTIVE: We evaluated the influence of home visiting on the risk for medically attended unintentional injury during home visiting (0 to 3 years) and subsequent to home visiting (3 to 5 years). METHODS: A retrospective, quasi-experimental study was conducted in a cohort of mother-child pairs in Hamilton County, OH. The birth cohort (2006 to 2012) was linked to administrative home visiting records and data from a population-based injury surveillance system containing records of emergency department (ED) visits and hospitalizations. Cox proportional-hazard regression was used to compare medically attended unintentional injury risk (0 to 2, 0 to 3, and 3 to 5 years) in a home-visited group versus a propensity score-matched comparison group. The study population was composed of 2,729 mother-child pairs who received home visiting and 2,729 matched mother-child pairs in a comparison group. RESULTS: From birth to 2 years, 17.2% of the study population had at least one medically attended unintentional injury. The risk for medically attended unintentional injury from aged 0 to 2 and 0 to 3 years was significantly higher in the home-visited group relative to the comparison group (hazard ratio 1.17, 95% confidence interval 1.01 to 1.35; hazard ratio 1.15, 95% confidence interval 1.00 to 1.31, respectively). Additional injuries in the home-visited group were superficial, and the increased risk for medically attended unintentional injury was observed for ED visits and not hospitalizations. CONCLUSION: Home-visited children were more likely to have a medically attended unintentional injury from birth to aged 3 years. This finding may be partially attributed to home visitor surveillance of injuries or greater health care-seeking behavior. Implications and alternative explanations are discussed.

Evaluation of a Community-Based Approach to Strengthen Retention in Early Childhood Home Visiting.

Home visiting (HV) is a strategy for delivering services designed to promote positive parenting and prevent exposure to toxic stress during a critical period of child development. Home visiting programs are voluntary and family engagement and retention in service can influence outcomes. Most participants receive less home visits and for a shorter time than prescribed by evidence-based models. The purpose of this study was to evaluate community-based enrichment of HV (CBE-HV), an approach that was developed and implemented to increase engagement and retention in HV. CBE-HV strategies included (1) community engagement, (2) ancillary supports for families in HV, and (3) enhancements to a HV program. A retrospective, quasi-experimental study was conducted to estimate the effect of CBE-HV on the retention of families in a HV program. Comparisons of study participants were made post-implementation of CBE-HV (n = 2191) and over time (n = 3786)-pre- versus post-CBE-HV implementation in the study communities. The CBE-HV effect was statistically significant and protective (hazards ratio [HR] 0.77, 95 % confidence interval [CI]: 0.67, 0.88), indicating that attrition from HV was 23 % less in the CBE-HV group relative to the post-implementation comparison group. In the temporal comparison of study communities, CBE-HV was also associated with a significantly lower risk of HV attrition (HR: 0.71, 95 % CI: 0.56, 0.89). The study demonstrated that CBE-HV is a promising approach to achieve stronger retention and engagement in HV. Further research is needed to identify the components of CBE-HV approaches that are most effective.

Maternal Chlamydia trachomatis infections and preterm birth:the impact of early detection and eradication during pregnancy.

The risks for preterm birth are heterogeneous and there remains much to elucidate regarding etiology of this adverse perinatal outcome. Antenatal infection with Chlamydia trachomatis, a highly prevalent sexually-transmitted infection, may convey a higher risk of preterm birth. Early detection and eradication of this sexually-transmitted infection without recurrent/persistent infection during pregnancy may serve as an intervention that reduces the risk of preterm birth. The objective of this study was to characterize the association between early antenatal detection and eradication of maternal C. trachomatis infection and the likelihood of preterm birth among pregnant women in an urban county. A retrospective cohort study was conducted in Hamilton County, Ohio (2006-2011) to evaluate the risk of preterm birth among women with maternal C. trachomatis infections detected and eradicated at or before 20 weeks gestation--the intervention group. Infected women whose infections were detected after 20 weeks gestation or persistent during the pregnancy represented the reference group. The study population contained 3,354 pregnant women with documented C. trachomatis infections. The relative risk for moderate to late spontaneous preterm birth (32-36 weeks gestation) was 0.54 (95 % CI 0.37-0.80) for women in the intervention group who were 19 years of age and younger. Pregnant adolescents benefited the most from early detection and eradication of antenatal C. trachomatis infections through a reduction in the risk of PTB at 32-36 weeks gestation. This finding suggests the importance of early antenatal detection and effective treatment of C. trachomatis.

Evaluation of gestational age estimate method on the calculation of preterm birth rates.

The objectives of this study is to evaluate the impact of vital record gestational age estimation method on resulting preterm birth (PTB) rate calculations. This retrospective analysis reviewed three methods of gestational age estimation using all Ohio live birth records from 2006 to 2009. PTB rates were calculated using each gestational age representation and agreement between classifications of PTB was evaluated with respect to maternal age and race. For each of 608,530 births, gestational age estimates based on last menstrual period (LMP) were compared to clinically-based obstetric estimates. When gestational age estimates did not perfectly agree, differences in the consequential classification of PTB status were evaluated with respect to a third reconciliatory combined gestational age estimate. Mean birth weight at each week of gestation was calculated and compared for all three estimate methods. Substantial agreement was found in PTB classification among gestational age estimates (kappa: 0.748; 95% Confidence Interval: 0.745-0.750); agreement was weakest among black mothers and among mothers less than 20 years of age. LMP-based gestational age estimates did not perfectly agree with obstetric estimates in 238,262 records (39.2%). Disagreement in gestational age led to disagreement in PTB status in 32,033 records (5.3% of total cases) resulting in a 1.8 percentage point difference in PTB rate calculations (11.0% using obstetric and 12.8% using combined estimates). Researchers and policy makers need consistency in selecting which gestational age estimate method to use when calculating or comparing PTB rates.

Prenatal tobacco smoke exposure and risk for cognitive delays in infants born very premature.

Prenatal tobacco smoke exposure (TSE) and prematurity are independent risk factors for abnormal neurodevelopment. The objectives were to compare differences in Bayley-III cognitive, language, and motor scores at 2 years corrected age (CA) in 395 infants born very preterm (≤ 32 weeks gestation) with and without prenatal TSE. We performed multivariable linear regression analyses to examine associations between prenatal TSE and neurodevelopmental outcomes and a mediation analysis to estimate direct effects of prenatal TSE on outcomes and indirect effects through preterm birth. In total, 50 (12.6%) infants had prenatal TSE. Infants with prenatal TSE had lower mean [95% CI] Cognitive score (82.8 [78.6, 87.1]) vs. nonexposed infants (91.7 [90.1, 93.4]). In children with and without prenatal TSE, there were significant differences in mean [95% CI] Language scores (81.7 [76.0, 87.4] vs. 92.4 [90.2, 94.6], respectively) and mean [95% CI] Motor scores (86.5 [82.2, 90.7] vs. 93.4 [91.8, 95.0], respectively); scores remained significant after controlling for confounders. Preterm birth indirectly mediated 9.0% of the total effect of prenatal TSE on Cognitive score (P = NS). However, 91% of the remaining total effect was significant and attributable to TSE's direct harmful effects on cognitive development (ß = - 5.17 [95% CI - 9.97, - 0.38]). The significant association is largely due to TSE's direct effect on cognitive development and not primarily due to TSE's indirect effect on preterm birth.

Association between maternal prenatal depressive symptoms and offspring epigenetic aging at 3-5 weeks.

Epigenetic clocks are emerging as tools for assessing acceleration and deceleration of biological age during childhood. Maternal depression during pregnancy may affect the biological aging of offspring and related development. In a low-income cohort of mother-child dyads, we investigated the relationship between prenatal maternal depressive symptoms and infant epigenetic age residuals, which represent the deviation (acceleration or deceleration) that exists between predicted biological age and chronological age. The epigenetic age residuals were derived from a pediatric-specific buccal epithelial clock. We hypothesized that maternal depressive symptoms, both sub-clinical and elevated (clinical level), would be associated with estimated biological age deceleration in offspring during early infancy. We analyzed data from 94 mother-child dyads using the Edinburgh Postnatal Depression Scale (EPDS) and DNA methylation derived from offspring buccal cells collected at 3-5 weeks of age. There was a significant non-linear association between the EPDS score and epigenetic age residual (ß = -0.017, 95% confidence interval: -0.03,-0.01, P = <0.01). The results indicated that infants of mothers with sub-clinical depressive symptoms had the lowest infant epigenetic age residuals while infants of mothers with no-to-low depressive symptoms had the highest and experienced biological age acceleration. Maternal depressive symptoms may influence the biological aging of offspring living in poverty.

Infant Obesity Prevention Programs for Underrepresented Mothers in a Home Visiting Program: A Qualitative and Community-Engaged Needs Assessment.

A qualitative, community-engaged assessment was conducted to identify needs and priorities for infant obesity prevention programs among mothers participating in home visiting programs. Thirty-two stakeholders (i.e., community partners, mothers, home visitors) affiliated with a home visiting program serving low-income families during the prenatal to age three period participated in group level assessment sessions or individual qualitative interviews. Results indicated families face many challenges to obesity prevention particularly in terms of healthy eating. An obesity prevention program can address these challenges by offering realistic feeding options and non-judgmental peer support, improving access to resources, and tailoring program content to individual family needs and preferences. Informational needs, family factors in healthy eating outcomes, and the importance of access and awareness of programs were also noted. To ensure the cultural- and contextual-relevance of infant obesity prevention programs for underserved populations, needs and preferences among community stakeholders and the focal population should be used as a roadmap for intervention development.

Prenatal tobacco smoke exposure and risk of brain abnormalities on magnetic resonance imaging at term in infants born very preterm.

BACKGROUND: Prenatal tobacco smoke exposure and preterm birth are associated with abnormal brain and neurodevelopmental outcomes in infants. Studies that can disentangle indirect mediating effects from direct effects of prenatal tobacco smoke exposure on sensitive early brain magnetic resonance imaging biomarkers in very preterm infants are needed. OBJECTIVE: This study aimed to determine whether prenatal tobacco smoke exposure in preterm infants posed any direct effects on magnetic resonance imaging-determined global brain abnormality score and secondary measures of brain abnormalities after removing any indirect mediating effects of preterm birth on neurostructural outcomes. STUDY DESIGN: We examined brain magnetic resonance imaging findings collected at 39 to 44 weeks postmenstrual age from a prospective cohort of 395 infants born very preterm (gestational age of ≤32 weeks). The primary outcome was global brain abnormality score, and the secondary outcomes were global efficiency of structural connectome, diffuse white matter abnormality volume, total brain tissue volume, total gray and white matter volumes, and cerebellar volume. Maternal reports of smoking during pregnancy were obtained. We performed multivariable linear regression analyses to examine the association between prenatal tobacco smoke exposure and our magnetic resonance imaging outcomes, controlling for prospectively collected confounders. Moreover, we performed a mediation analysis to estimate the direct effects of prenatal tobacco smoke exposure on brain abnormalities and any indirect effects through preterm birth. RESULTS: Overall, 12.6% of infants had prenatal tobacco smoke exposure. Infants with prenatal tobacco smoke exposure had a higher median global brain abnormality score than nonexposed infants (7 [interquartile range, 0-41] vs 5 [interquartile range, 0-34]; P≤.001); the findings remained significant (P<.001) after controlling for antenatal confounders. Global efficiency (P<.001), diffuse white matter volume (P=.037), and total brain tissue volume (P=.047) were significantly different between TSE groups in multivariable analyses. On mediation analysis, preterm birth mediated between 0% and 29% of the indirect effect of prenatal tobacco smoke exposure on several measures of brain abnormality outcomes. Thus, prenatal tobacco smoke exposure had a direct adverse effect between 71% and 100% on brain injury or abnormal development. CONCLUSION: Our study has identified multiple adverse effects of prenatal tobacco smoke exposure on sensitive and objective measures of neonatal brain injury and abnormal development; most cases seemed to be a direct effect of prenatal tobacco smoke exposure on fetal brain development. The results underscored the significant adverse neurostructural effects of prenatal tobacco smoke exposure to tobacco smoke pollutants.

Correlation of NICU anthropometry in extremely preterm infants with brain development and language scores at early school age.

Growth in preterm infants in the neonatal intensive care unit (NICU) is associated with increased global and regional brain volumes at term, and increased postnatal linear growth is associated with higher language scores at age 2. It is unknown whether these relationships persist to school age or if an association between growth and cortical metrics exists. Using regression analyses, we investigated relationships between the growth of 42 children born extremely preterm (< 28 weeks gestation) from their NICU hospitalization, standardized neurodevelopmental/language assessments at 2 and 4-6 years, and multiple neuroimaging biomarkers obtained from T1-weighted images at 4-6 years. We found length at birth and 36 weeks post-menstrual age had positive associations with language scores at 2 years in multivariable linear regression. No growth metric correlated with 4-6 year assessments. Weight and head circumference at 36 weeks post-menstrual age positively correlated with total brain volume and negatively with global cortical thickness at 4-6 years of age. Head circumference relationships remained significant after adjusting for age, sex, and socioeconomic status. Right temporal cortical thickness was related to receptive language at 4-6 years in the multivariable model. Results suggest growth in the NICU may have lasting effects on brain development in extremely preterm children.

Neonatal AVPR1a Methylation and In-Utero Exposure to Maternal Smoking.

(1) Introduction: Epigenetic changes have been proposed as a biologic link between in-utero exposure to maternal smoking and health outcomes. Therefore, we examined if in-utero exposure to maternal smoking was associated with infant DNA methylation (DNAm) of cytosine-phosphate-guanine dinucleotides (CpG sites) in the arginine vasopressin receptor 1A AVPR1a gene. The AVPR1a gene encodes a receptor that interacts with the arginine vasopressin hormone and may influence physiological stress regulation, blood pressure, and child development. (2) Methods: Fifty-two infants were included in this cohort study. Multivariable linear models were used to examine the effect of in-utero exposure to maternal smoking on the mean DNAm of CpG sites located at AVPR1a. (3) Results: After adjusting the model for substance use, infants with in-utero exposure to maternal smoking had a reduction in DNAm at AVPR1a CpG sites by -0.02 (95% CI -0.03, -0.01) at one month of age. In conclusion, in-utero exposure to tobacco smoke can lead to differential patterns of DNAm of AVPR1a among infants. Conclusions: Future studies are needed to identify how gene expression in response to early environmental exposures contributes to health outcomes.