Early Childhood Outcomes Research Articles

Maternal prenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort Study

Maternal prenatal depression is a known risk factor for early-life psychopathology among offspring; however, potential risk transmission mechanisms need to be distinguished. We aimed to test the relative importance of passive genetic transmission, direct exposure, and indirect exposure in the association between maternal prenatal depressive symptoms and early-life internalising and externalising psychopathology in offspring. We used structural equation modelling of phenotypic data and genetically informative relationships from the families of participants in the Norwegian Mother and Child Birth Cohort Study (MoBa). The analytic subsample of MoBa used in the current study comprises 22 195 mothers and 35 299 children. We used mothers' self-reported depressive symptoms during pregnancy, as captured by the Symptom Checklist, and their reports of symptoms of psychopathology in their offspring during the first few years of life (measured at 18, 36, and 60 months using the Child Behavior Checklist). Maternal prenatal depressive symptoms were found to be associated with early-life psychopathology primarily via intergenerationally shared genetic factors, which explained 41% (95% CI 36-46) of variance in children's internalising problems and 37% (30-44) of variance in children's externalising problems. For internalising problems, phenotypic transmission also contributed significantly, accounting for 14% (95% CI 5-19) of the association, but this contribution was found to be explained by exposure to concurrent maternal depressive symptoms, rather than by direct exposure in utero. Associations between maternal prenatal depressive symptoms and offspring behavioural outcomes in early childhood are likely to be at least partially explained by shared genes. This genetic confounding should be considered when attempting to quantify risks posed by in-utero exposure to maternal depressive symptoms. UK Economic and Social Research Council, Norwegian Research Council, Norwegian Ministries of Health and Care Services, and Education & Research, Wellcome Trust, Royal Society, and National Institute for Health Research.

Shared genetic factors, fetal programming, and the transmission of depression

Interest in prenatal exposures shaping later life has increased considerably in the past two decades. Set forth by Barker in the 1980s, the fetal programing hypothesis posits that in-utero exposures affect the early development of organs and tissues in ways that persist into adulthood. 1 Barker DJ The Wellcome Foundation Lecture, 1994. The fetal origins of adult disease. Proc R Soc Lond B. 1995; 262: 37-43 Crossref PubMed Scopus (238) Google Scholar The study of fetal programming has extended to neurodevelopment, with a growing amount of scientific literature of human and animal studies suggesting that prenatal maternal depression places offspring at increased risk for mental disorders. 2 Kim DR Bale TL Epperson CN Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep. 2015; 17: 5 Crossref PubMed Scopus (125) Google Scholar , 3 O'Donnell KJ Glover V Barker ED O'Connor TG The persisting effect of maternal mood in pregnancy on childhood psychopathology. Dev Psychopathol. 2014; 26: 393-403 Crossref PubMed Scopus (260) Google Scholar Although the need to account for genetic and shared environmental confounding has been previously argued, 4 Babineau V Green CG Jolicoeur-Martineau A et al. Prenatal depression and 5-HTTLPR interact to predict dysregulation from 3 to 36 months—a differential susceptibility model. J Child Psychol Psychiatry. 2015; 56: 21-29 Crossref PubMed Scopus (41) Google Scholar the field has not consistently obliged. The study by Laurie Hannigan and colleagues 5 Hannigan LJ Eilertsen EM Gjerde LC et al. Maternal prenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort Study. Lancet Psychiatry. 2018; (published online Sept 20.)http://dx.doi.org/10.1016/S2215-0366(18)30225-6 Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar will most certainly change that. Maternal prenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort StudyAssociations between maternal prenatal depressive symptoms and offspring behavioural outcomes in early childhood are likely to be at least partially explained by shared genes. This genetic confounding should be considered when attempting to quantify risks posed by in-utero exposure to maternal depressive symptoms. Full-Text PDF

Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18-22 months.

Background:Studies of early childhood outcomes of mild hypoxic-ischemic encephalopathy (HIE) identified in the first 6 hours of life are lacking.Objective:To evaluate neurodevelopmental outcomes at 18–22 months of PRIME study.Study design:Multicenter, prospective study of mild HIE defined as ≥1 abnormality using the modified Sarnat within 6h of birth and not meeting cooling criteria. Primary outcome was disability with Mild: Bayley III cognitive 70–84 or ≥ 85 and either Gross Motor Function Classification System (GMFCS) 1 or 2, seizures, or hearing deficit; Moderate: cognitive 70–84 and either GMFCS 2, seizures, or hearing deficit; Severe: cognitive < 70, GMFCS 3–5.Results:Of the 63 infants enrolled, 51 (81%) were evaluated at 19 ± 2 months and 43 (68%) completed Bayley III. Of the 43 infants, 7 (16%) were diagnosed with disability including 1 cerebral palsy and 2 autism. Bayley scores <85 in either cognition, motor, or language were detected in 17 (40%): 14 (32%) language, 7 (16%) cognitive, and 6 (14%) motor domain. Infants with disability had more abnormalities on discharge examination and brain MRI, with longer hospital stay (p<0.001).Conclusions:In this contemporary untreated cohort of mild HIE, disability occurred in 16% of infants at 18–22 months.

No increased risk in offspring after paternal antidepressant use

A prospective cohort study conducted in Sweden has concluded that fathers' use of an antidepressant around the time of conception had no adverse effect on a number of birth or early childhood outcomes in their offspring. The researchers found that, overall, results were more favorable for children of fathers who used an antidepressant around the time of conception compared with fathers who initiated antidepressant treatment later in the mother's pregnancy.

Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes.

Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse.Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations.Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation.Results: Child depression was inversely associated with maternal MDA (Bonferroni-corrected p = 0.041). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors [OR (95% CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile], for maladaptive behaviors [0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile] and for an index of autism spectrum disorder behaviors [0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile]. Offspring of women with the highest MDA tertile were less likely to exhibit depressive [OR = 0.28 (0.12, 0.64)] and anxiety [0.42 (0.18, 0.97)] behaviors and increased odds of social relatedness [2.31 (1.04, 5.19)] behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE [females: Beta (95% CI) = 1.66 (0.52, 2.80) – Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)], as well as both MEG3 and IGF2 in males [0.97 (0.00, 1.94)] and -0.92 (-1.65, -0.19) respectively.Conclusion: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.

Prenatal maternal smoking, maternal offending, and offspring behavioural and cognitive outcomes in early childhood.

Maternal smoking during pregnancy and parental offending are both linked to adverse offspring outcomes. Few studies have examined how these exposures together influence diverse offspring outcomes in early childhood. To examine associations between quantity of prenatal maternal smoking and frequency of maternal offending and offspring behavioural and cognitive outcomes at age 5years. Over 66,000 Australian children (mean age 5.6years) were drawn from an intergenerational data linkage study. Unadjusted and adjusted logistic regressions were conducted for the two key exposures (maternal prenatal smoking and mother having at least two criminal convictions) and offspring behavioural and cognitive vulnerabilities. Population attributable fractions (PAFs) were also estimated for each outcome for the two exposures. Prenatal smoking and maternal offending were, separately and together, associated with most of the developmental vulnerabilities examined, even after adjusting for other familial and prenatal risk factors. PAFs for prenatal smoking ranged from 5.3% to 15.8%, and PAFs for maternal offending ranged from 3.4% to 11.8% across the offspring outcomes. Maternal smoking during pregnancy and maternal offending were uniquely associated with a range of offspring vulnerabilities, but mothers who smoked during pregnancy tended to experience multiple problems that should also be considered as indicators of child vulnerabilities. While early behavioural difficulties were evident in these children, it was striking that they were also likely to have cognitive vulnerabilities. Early intervention to support cognitive development in these children may minimise their risk of academic underachievement, long-term disadvantage, and even offending.

Parenting beliefs and practices in toddlerhood as precursors to self‐regulatory, psychosocial, and academic outcomes in early and middle childhood in ethnically diverse low‐income families

AbstractEthnoracially diverse families living in poverty are vulnerable to stress, discrimination, and adversities that can be ‘toxic’ to parenting and to a wide range of psychosocial and academic outcomes in youth. Thus, there is high need to identify malleable protective and promotive factors that may lead to improved developmental trajectories and outcomes for at‐risk youth and families. In this study of 2,233 low‐income families with ethnoracially diverse children (49.5% girls; 42.5% European Americans, 38.4% African Americans, and 19.1% U.S. Latino/as), we tested a model positing that child‐rearing beliefs at 24 months and parenting practices at 36 months are precursors to the development of children’s self‐regulation at pre‐kindergarten, with self‐regulation as a mediating mechanism between parenting in toddlerhood and psychosocial and academic functioning at fifth grade. Results confirm that child‐rearing beliefs are precursors to parenting practices, and both parenting practices and self‐regulation are mediating mechanisms by which child‐rearing beliefs are linked to youths’ psychosocial and academic outcomes. The results have implications for early parent education and parenting interventions, including public health approaches that have the potential for positive impacts on vulnerable children, youth, and families.

Effects of child care subsidy on school readiness of young children with or at-risk for special needs

Children with special needs are now a population of special interest under federal child care policy. Findings on the effects of child care subsidy for the general population are mixed, but no studies have considered the effects for children with or at-risk for special needs. The purpose of this study was to ascertain the average effects of child care subsidies on school readiness of children with or at-risk for special needs. Using data for 1250 participants in the Early Childhood Longitudinal Study–Birth Cohort, we applied propensity score matching and regression analyses to estimate subsidy’s effects on kindergarten academic and behavioral competencies of children with or at-risk for special needs who came from low-income families. Results indicated that for the average recipient, subsidized child care had significant negative effects on early literacy (d = 0.21) and numeracy (d = 0.18), and no significant effects on communication, impulsivity, hyperactivity, and prosocial behavior. These findings add to a growing number of largescale analyses showing negative or null effects of subsidized care on early childhood outcomes and highlight the need for continued attention to the appropriateness and effectiveness of subsidized child care, particularly for children with or at-risk for special needs.

No Strings Attached: The Impact of an Unconditional Prenatal Income Supplement on First Nations Birth and Early Childhood Outcomes

IntroductionIn Manitoba, low-income pregnant women are eligible for the Healthy Baby Prenatal Benefit (HBPB), an unconditional income supplement provided during the second and third trimester of pregnancy. HBPB is associated with improved birth outcomes for Manitoba women; its association with birth outcomes for First Nations (Indigenous) women is unknown.&#x0D; Objectives and ApproachTo determine the association between HBPB and First Nations’ (FN) newborn and early childhood outcomes, we linked whole-population data from health, public health, family services and education. We included only FN women receiving income assistance during pregnancy (n=7074) to develop comparable treatment (received HBPB; n=5283) and comparison (no HBPB; n=1791) groups. Propensity score weighting adjusted for differences in maternal characteristics between groups. Multi-variable regressions compared groups on breastfeeding initiation, low birth weight, preterm birth, small- and large-for-gestational age, Apgar scores, complete immunizations at 1 and 2 years, and developmental vulnerability in kindergarten measured with the Early Development Instrument (EDI).&#x0D; ResultsReceipt of the HBPB was associated with reductions in low birth weight births (adjusted Relative Risk (aRR): 0.77; 95% CI: 0.63, 0.93) and preterm births (aRR: 0.78 (0.68, 0.90)), and increases in breastfeeding initiation (aRR: 1.05 (1.00, 1.09)) and large-for-gestational age births (aRR: 1.11 (1.01, 1.23)). HBPB receipt during pregnancy was also associated with increases in 1- and 2-year immunizations for FN children (aRR: 1.14 (1.09, 1.19), and aRR: 1.28 (1.19, 1.36), respectively). Reductions in the risk of being developmentally vulnerable in the language and cognitive domain of the EDI were also found for FN children whose mothers had received the HBPB during pregnancy (aRR: 0.85 (0.74, 0.97).&#x0D; Conclusion/ImplicationsA modest unconditional income supplement during pregnancy was associated with improved birth outcomes, increased immunization rates, and improved language and cognitive development at kindergarten for children born to low-income First Nations women. Long-term strategies to address structural inequities and the ongoing effects of colonization are also needed.

More evidence for the importance of early life nutritional status on child health outcomes

A concept that continues to gain ground is that the in utero environment—including maternal health, nutritional status, diet, environmental exposures to medications, toxins, and more—can have an important influence on long-term health outcomes. Supported by numerous epidemiologic, clinical, and biological observations, the Developmental Origins of Health and Disease is a field of discovery that promises to shed new light on disease prevention and health promotion. The report in this volume of The Journal by Abera et al adds another important data point that underscores the importance of fetal growth and nutritional status on longer term health, in this case early childhood mental health. Using data from a well-characterized Ethiopian birth cohort study, the investigators examined the relationship between nutritional status (primarily body composition and growth status) in early infancy on one hand, and child mental health (a parent-reported brief behavioral screening questionnaire) on the other. The main findings were that fetal accretion of fat-free mass (as determined by body composition at birth) was associated with better child behavior scores at 5 years of age, as compared with fetal accretion of fat mass. Interestingly, there was no significant relationship between body composition at age 5 and behavior reports, further emphasizing the critical timing of in utero influences. Similar data that linked fat-free mass with neurologic outcomes at 2 years of age have also been recently reported (J Pediatr 2018;196:301-4). We look forward to continued follow-up of this well characterized cohort to evaluate longer term outcomes, as well as to more evidence along the Developmental Origins pathway in other settings. Article page 225 ▶ Body Composition during Early Infancy and Mental Health Outcomes at 5 Years of Age: A Prospective Cohort Study of Ethiopian ChildrenThe Journal of PediatricsVol. 200PreviewTo examine the relationship between body composition—specifically fat mass (FM) and fat-free mass (FFM)—in early infancy, and mental health outcomes in early childhood. Full-Text PDF

Cochlear implantation and early outcomes in children with incompletely partition type Ⅲ malformation

Objective:To analyze the early effect of the cochlear implantation (CI) in children with cochlear incompletely partition type Ⅲ malformation (IP-Ⅲ). Method:Ten children with IP-Ⅲ malformation who underwent CI were recruited in this study. The hearing characteristics, preoperative speech performance and surgery were analyzed retrospectively. The aided hearing threshold with CI, the categories of auditory performance (CAP) score, speech intelligibility rating (SIR) score and speech perception were designed to access the benefits of CI. Ten children with normal cochlea were also enrolled as the control group. Demographic information of children in the control group including hearing loss and speech level before implantation, age at implantation, hearing aids using history, duration with CI were matched with those in the IP-Ⅲ group. The hearing threshold, CAP score and SIR score in the IP-Ⅲ group were compared with the control group using the SPSS 20.0 software. Result:The computed tomography of temporal bones showed typical IP-Ⅲ malformation in all patients. The electrode arrays were properly and totally implanted in all children. Cerebrospinal fluid gusher occurred intra-operatively, and no other complications in all patients. The pure tone average (PTA) threshold at the 3rd, 6th, 9th and 12th month after implantation were (40.8±8.5) dB HL, (36.1±9.1) dB HL, (32.5±6.8) dB HL and (33.0±7.3) dB HL, respectively. The PTA thresholds in the IP-Ⅲ group were similar to those in the control group at all tested time points (P>0.05). At the 3rd, 6th, 9th and 12th month after implantation, the CAP scores in the IP-Ⅲ group were lower than those in the control group, but there was no significantly difference (P>0.05). Furthermore, the SIR scores were lower than those in the control group, and there were significantly difference at the 6 th, 9 th and 12 th month after implantation (P<0.05). Conclusion:CI was an effective treatment for children with IP-Ⅲ malformation. Surgery on IP-Ⅲ was challenging, however, seldom complication would occur with excellent surgical skills. Though the CI was benefit for IP-Ⅲ, the development of hearing and speech ability were slower than children with normal cochlea.

Pregnancy and child developmental outcomes after preimplantation genetic screening: a meta-analytic and systematic review.

In in vitro fertilization (IVF) treatment, preimplantation genetic diagnosis/screening (PGD/S) attempts to detect chromosomal abnormalities in embryos before implantation. Using the meta-analytic and qualitative review approaches, this study aims to evaluate the effect of PGD/S on clinical pregnancy, live births, and childhood outcomes. We conducted a literature search using 1) PubMed and other search engines, and 2) an ancestry search by tracking references cited in prior work. After screening the studies, we extracted information pertinent to the meta-analysis. We calculated the effect sizes for clinical pregnancy and live birth rates, and performed a moderation analysis by maternal age, type of genetic screening, and timing of the biopsy. For childhood outcomes, we conducted a systematic review of studies reporting the anthropometric, psychomotor, cognitive, behavioral, and family functioning of PGD/S children. We included 26 studies for clinical pregnancy and live births, and 18 studies for childhood outcomes. Results indicated that women who underwent comprehensive chromosome screening-based PGD/S had significantly higher clinical pregnancy rates (rr 1.207, 95% CI 1.017-1.431) and live birth rates (rr 1.362, 95% CI 1.057-1.755) than those whose IVF treatment did not include PGD/S. Early childhood outcomes of PGD/S children did not differ from those of non-PGD/S children. Comprehensive chromosome screening-based PGD/S can improve clinical pregnancy and live birth rates without adversely affecting functioning in childhood at least up to age 9. Results are discussed in the context of bioethical, financial, legal, and psychological issues surrounding PGD/S.

Individualized Family Service Plan Quality and Alignment of Child-Focused Outcomes to Federal Outcomes and State Early Learning Guidelines

We used two judgment-based scales to evaluate quality features of 623 individualized family service plans (IFSP) contributed by 73 service coordinators in one state. We also explored the alignment between the skills specified in child-focused IFSP outcomes, the three Individuals With Disabilities Education Act (IDEA) early childhood outcome categories, and the knowledge and skill statements included in state early learning guidelines. Findings showed IFSP content generally was family-centered and of good quality. Outcomes were more frequently aligned with the IDEA outcome categories addressing the use of appropriate behaviors to meet needs and the acquisition and use of knowledge and skills. Outcomes were aligned more frequently with early learning guidelines in the areas of physical development, speech/language development, and approaches to learning. We discuss how instruments and procedures could be used to evaluate IFSP quality and determine connections to expected knowledge and skills for all children identified by state and federal programs.

Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes

Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.

How consistent are associations between maternal and paternal education and child growth and development outcomes across 39 low-income and middle-income countries?

BackgroundMaternal and paternal education are associated with improved early child outcomes. However, less is known about how these relative associations compare for preschool children’s growth versus development outcomes; and across...

Multiple Postnatal Infections in Newborns Born Preterm Predict Delayed Maturation of Motor Pathways at Term-Equivalent Age with Poorer Motor Outcomes at 3 Years

To evaluate whether the number of postnatal infections is associated with abnormal white matter maturation and poorer motor neurodevelopmental outcomes at 36 months of corrected age. A prospective longitudinal cohort study was undertaken of 219 newborns born preterm at 24-32 weeks of gestational age recruited between 2006 and 2013 with magnetic resonance imaging of the brain both early in life and at term-equivalent age. Postnatal infection was defined as any clinical infection or positive culture ≥72 hours after birth. White matter maturation was assessed by magnetic resonance spectroscopic imaging, magnetic resonance diffusion tensor imaging, and tract-based spatial statistics. Neurodevelopmental outcomes were assessed in 175 (82% of survivors) infants with Bayley Scales of Infant and Toddler Development-III composite scores and Peabody Developmental Motor Scales at 35 months of corrected age (IQR 34-37 months). Infection groups were compared via the Fisher exact test, Kruskal-Wallis test, and generalized estimating equations. Of 219 neonates born preterm (median gestational age 27.9 weeks), 109 (50%) had no postnatal infection, 83 (38%) had 1 or 2 infections, and 27 (12%) had ≥3 infections. Infants with postnatal infections had more cerebellar hemorrhage. Infants with ≥3 infections had lower N-acetylaspartate/choline in the white matter and basal ganglia regions, lower fractional anisotropy in the posterior limb of the internal capsule, and poorer maturation of the corpus callosum, optic radiations, and posterior limb of the internal capsule on tract-based spatial statistics analysis as well as poorer Bayley Scales of Infant and Toddler Development-III (P = .02) and Peabody Developmental Motor Scales, Second Edition, motor scores (P < .01). In newborns born preterm, ≥3 postnatal infections predict impaired development of the motor pathways and poorer motor outcomes in early childhood.

Characteristics and early outcomes of children and adolescents treated with darunavir/ritonavir-, raltegravir- or etravirine-containing antiretroviral therapy in the Western Cape Province of South Africa

Background. There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. Objective. To describe the characteristics and early outcomes of treatment-experienced children (<20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens. Methods. This was a retrospective review of treatment-experienced children receiving a DRV/r-, RAL- or ETR-containing regimen as recommended by a paediatric expert review committee, based on HIV drug resistance testing. Results. Thirty-five children of median age 8.8 years (interquartile range (IQR) 5.5 - 11) who had received ART for a median of 6.9 years (IQR 5 - 9.9) and started a DRV/r-, RAL- or ETR-containing regimen were included. Before starting such a regimen, the median CD4+ lymphocyte count and HIV-1 RNA level were 405.5 cells/μL (IQR 251.5 - 541) and 28 314 copies/mL (IQR 5 595.5 – 120 186.5) (log 4.5 (IQR 3.7 - 5)), respectively, in 24 subjects with available results. After a median of 2 years (IQR 1.3 - 4) on treatment, 29/30 (96.7%) and 23/30 (76.7%) subjects with available results had HIV-1 RNA levels of <400 and <50 copies/mL, respectively. Conclusions. This study found DRV/r-, RAL- and ETR-containing regimens to be effective in a group of treatment-experienced children and adolescents with multidrug-resistant HIV. Although the treatment regimens in this study were individualised based on HIV genotyping results, further research evaluating the safety and efficacy of standardised third-line treatment regimens in children of all ages is needed.

Characteristics and early outcomes of children and adolescents treated with darunavir/ritonavir-, raltegravir- or etravirine-containing antiretroviral therapy in the Western Cape Province of South Africa.

There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. To describe the characteristics and early outcomes of treatment-experienced children (&lt;20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens. This was a retrospective review of treatment-experienced children receiving a DRV/r-, RAL- or ETR-containing regimen as recommended by a paediatric expert review committee, based on HIV drug resistance testing. Thirty-five children of median age 8.8 years (interquartile range (IQR) 5.5 - 11) who had received ART for a median of 6.9 years (IQR 5 - 9.9) and started a DRV/r-, RAL- or ETR-containing regimen were included. Before starting such a regimen, the median CD4+ lymphocyte count and HIV-1 RNA level were 405.5 cells/μL (IQR 251.5 - 541) and 28 314 copies/mL (IQR 5 595.5 - 120 186.5) (log 4.5 (IQR 3.7 - 5)), respectively, in 24 subjects with available results. After a median of 2 years (IQR 1.3 - 4) on treatment, 29/30 (96.7%) and 23/30 (76.7%) subjects with available results had HIV-1 RNA levels of &lt;400 and &lt;50 copies/mL, respectively. This study found DRV/r-, RAL- and ETR-containing regimens to be effective in a group of treatment-experienced children and adolescents with multidrug-resistant HIV. Although the treatment regimens in this study were individualised based on HIV genotyping results, further research evaluating the safety and efficacy of standardised third-line treatment regimens in children of all ages is needed.

Dose-Response Effects of Early Vitamin D Supplementation on Neurodevelopmental and Respiratory Outcomes of Extremely Preterm Infants at 2 Years of Age: A Randomized Trial

Background: Many extremely preterm infants have low vitamin D concentrations at birth, but early childhood outcomes after vitamin D supplementation have not been reported. Objective: To determine a dose-response relationship between increasing doses of enteral vitamin D in the first 28 days after birth and cognitive scores at 2 years of age. Methods: In this phase II double-blind dose-response randomized trial, infants with gestational ages between 23 and 27 weeks were randomly assigned to receive placebo or a vitamin D dose of 200 or 800 IU/day from day 1 of enteral feeding to postnatal day 28. The primary outcome of this follow-up study was Bayley III cognitive score at 22-26 months of age. Results: Seventy of 80 survivors had a follow-up evaluation at 2 years of age (88%). There were no significant differences in cognitive scores between supplementation groups (p = 0.47). Cognitive scores did not differ between the higher vitamin D dose group and the placebo group (median difference favoring the 800 IU group: +5 points; 95% CI: −5 to 15; p = 0.23). The linear trend between increasing doses of vitamin D and reduction of neurodevelopmental impairment (placebo group: 54%; 200 IU group: 43%; 800 IU group: 30%; p = 0.08) or language impairment (placebo group: 64%; 200 IU group: 57%; 800 IU group: 45%; p = 0.15) was not statistically significant. Respiratory outcomes at 2 years of age (need for supplemental oxygen or asthma medications) did not differ between groups. Conclusion: In extremely preterm infants, early vitamin D supplementation did not significantly improve cognitive scores. Though underpowered for clinically meaningful differences in early childhood outcomes, this trial may help determine dosing for further investigation of vitamin D supplementation.

How Does the Neighborhood "Come through the Door?" Concentrated Disadvantage, Residential Instability, and the Home Environment for Preschoolers.

Living in a disadvantaged neighborhood is associated with heightened risk for poor school readiness and health outcomes in early childhood, and the home environment is thought to be a primary mechanism by which neighborhood context impacts preschoolers. This study examined the effects of neighborhood concentrated disadvantage and neighborhood residential instability on the home physical environment and home learning environment for preschoolers in economically disadvantaged families (N=187). Using structural equationmodeling, mothers' perceived neighborhood disorder and depressive symptoms were examined as mechanisms by which neighborhood context "comes through the door." Mothers' neighborhood social embeddedness was also explored as a protective factor. Results showed that concentrated disadvantage was negatively associated with the quality of the home physical environment, and residential instability was negatively associated with the quality of the home learning environment. Concentrated disadvantage had an indirect effect on the home learning environment through mothers' perceived neighborhood disorder and depressive symptoms.The effects of concentrated disadvantage on thehome environment were buffered by mothers' neighborhood social embeddedness. Study findings advanceunderstanding of socioeconomic- and place-based disparities in developmental outcomes and identify potential targets for interventions aimed at lessening effects of neighborhood disadvantage on families with young children.