Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study.

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Prediction of internalizing and externalizing symptoms in late childhood from attention-deficit/hyperactivity disorder symptoms in early childhood.

Limited analyses based on national samples have assessed whether early attention-deficit/hyperactivity disorder (ADHD) symptoms predict later internalizing and externalizing symptoms in youth and the influence of sex and pubertal timing on subsequent psychiatric symptoms. This study analyzed data (n = 2818) from the Environmental influences on Child Health Outcomes Program national cohort. Analyses used data from early childhood (mean age = 5.3 years) utilizing parent-reported ADHD symptoms to predict rates of internalizing and externalizing symptoms from late childhood/adolescence (mean age = 11.9 years). Within a subsample age at peak height velocity (APHV) acted as a proxy to assess pubertal timing from early childhood (mean age = 5.4 years) to adolescence (mean age = 12.3 years). Early-childhood ADHD symptoms predicted later psychiatric symptoms, including anxiety, depression, aggressive behavior, conduct problems, oppositional defiant disorder, and rule-breaking behavior. Earlier APHV was associated with increased Conduct Disorder symptoms from late childhood to adolescence for females only. A stronger relation between ADHD symptoms and later aggression was observed in females with earlier APHV, whereas this same pattern with aggression, conduct problems and depression was observed in males with later APHV. Clinicians should consider that both young girls and boys with elevated ADHD symptoms, particularly with off-set pubertal timing, may be at risk for later psychiatric symptoms.

A Qualitative Analysis of Perspectives on Self-directed Violence in a Prospective Longitudinal Study of Young Women With and Without Childhood ADHD.

OBJECTIVE: Non-suicidal self-directed violence (NSSDV) is a significant and growing youth public health crisis. Girls with ADHD are at increased risk of engaging in NSSDV, yet qualitative studies with this population-to better understand manifestations, motivations, and developmental course-are lacking. METHOD: We conducted semi-structured, qualitative interviews with a sub-sample of 57 young women (32 with childhood ADHD, 25 neurotypical comparisons; mean age of 27 years, part of a larger prospective longitudinal study) regarding histories and manifestations of NSSDV. RESULTS: Inductive and deductive analysis revealed several key themes, including self-perceived reasons for engaging in NSSDV (affect regulation, attention seeking, self-punishment, asserting control), impulsivity, secretiveness, and in some cases motivations for desistance. CONCLUSION: Findings underscore the importance of early education and screening, especially among high-risk clinical populations. Increased resources and supports for professionals, parents, and peers are indicated, along with countering the persistent stigma associated with ADHD and NSSDV.

Intergenerational transmission of stress: Multi-domain stressors from maternal childhood and pregnancy predict children's mental health in a racially and socioeconomically diverse, multi-site cohort.

PURPOSE: Despite growing recognition that unfortunately common maternal stress exposures in childhood and pregnancy may have intergenerational impacts on children's psychiatric health, studies rarely take a life course approach. With child psychopathology on the rise, the identification of modifiable risk factors is needed to promote maternal and child well-being. In this study, we examined associations of maternal exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE) with child mental health problems in a large, sociodemographically diverse sample. METHODS: Participants were mother-child dyads in the ECHO-PATHWAYS consortium's harmonized data across three U.S. pregnancy cohorts. Women completed questionnaires regarding their own exposure to CTE and PSLE, and their 4-6-year-old child's mental health problems using the Child Behavior Checklist (CBCL). Regression analyses estimated associations between stressors and child total behavior problems, adjusting for confounders. RESULTS: Among 1948 dyads (child age M = 5.13 (SD = 1.02) years; 38% Black, 44% White; 8.5% Hispanic), maternal history of CTE and PSLE were independently associated with children's psychopathology: higher CTE and PSLE counts were related to higher total problems ([ßCTE = 0.11, 95% CI [.06, .16]; ßSLE = 0.21, 95% CI [.14, 0.27]) and greater odds of clinical levels of problems (ORCTE = 1.41; 95% CI [1.12, 1.78]; ORPSLE = 1.36; 95% CI [1.23, 1.51]). Tests of interaction showed PSLEs were more strongly associated with child problems for each additional CTE experienced. CONCLUSION: Findings confirm that maternal exposure to CTE and PSLE are independently associated with child mental health, and history of CTE exacerbates the risk associated with PSLE, highlighting intergenerational risk pathways for early psychopathology. Given the prevalence of these exposures, prevention and intervention programs that reduce childhood trauma and stress during pregnancy will likely positively impact women's and their children's health.

A path model examination: maternal anxiety and parenting mediate the association between maternal adverse childhood experiences and children's internalizing behaviors.

BACKGROUND: Children of mothers with adverse childhood experiences (ACEs) are at increased risk for developmental problems. However, the mechanisms through which a mother's experience of ACEs are transmitted to her offspring are understudied. The current study investigates potential modifiable mediators (maternal psychopathology and parenting) of the association between maternal ACEs and children's behavioral problems. METHODS: We utilized data from a pregnancy cohort study (N = 1030; CANDLE study) to investigate longitudinal associations between maternal ACEs, postpartum anxiety, observed parenting behavior, and child internalizing behaviors (meanage = 4.31 years, s.d. age = 0.38) in a racially diverse (67% Black; 33% White/Other) sample. We used structural equation modeling to test for direct associations between maternal ACEs and children's internalizing behaviors, as well as indirect associations via two simple mediations (maternal anxiety and parenting), and one serial mediation (sequence of maternal anxiety to parenting). RESULTS: Simple mediation results indicated that maternal anxiety and cognitive growth fostering behaviors independently mediated the association between maternal ACEs and child internalizing. We observed no evidence of a serial mediation from ACEs to internalizing via the effects of maternal anxiety on parenting. CONCLUSIONS: This study supports and refines extant literature by confirming the intergenerational association between maternal ACEs and child internalizing behaviors in a large, diverse sample, and identifies potential modifiable mediators: maternal anxiety and parenting behaviors related to fostering cognitive development. Findings may inform interventions targeting mothers who have experienced ACEs and suggest that providing support around specific parenting behaviors and addressing maternal anxiety may reduce internalizing behaviors in children.

Intergenerational Transmission of Effects of Women's Stressors During Pregnancy: Child Psychopathology and the Protective Role of Parenting.

Objective: Experiences of stress and adversity, such as intimate partner violence, confer risk for psychiatric problems across the life span. The effects of these risks are disproportionately borne by women and their offspring-particularly those from communities of color. The prenatal period is an especially vulnerable period of fetal development, during which time women's experiences of stress can have long-lasting implications for offspring mental health. Importantly, there is a lack of focus on women's capacity for resilience and potential postnatal protective factors that might mitigate these intergenerational risks and inform intervention efforts. The present study examined intergenerational associations between women's prenatal stressors and child executive functioning and externalizing problems, testing maternal parenting quality and child sex as moderators, using a large, prospective, sociodemographically diverse cohort. Methods: We used data from 1,034 mother-child dyads (64% Black, 30% White) from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) pregnancy cohort within the ECHO PATHWAYS consortium. Women's prenatal stressors included stressful life events (pSLE) and intimate partner violence (pIPV). Measures of child psychopathology at age 4-6 included executive functioning and externalizing problems. Parenting behaviors were assessed by trained observers, averaged across two sessions of mother-child interactions. Linear regression models were used to estimate associations between women's prenatal stressors and child psychopathology, adjusting for confounders and assessing moderation effects by maternal parenting quality and child sex. Results: Women's exposures to pSLE and pIPV were independently associated with child executive functioning problems and externalizing problems in fully-adjusted models. Maternal parenting quality moderated associations between pSLE and both outcomes, such that higher parenting quality was protective for the associations between women's pSLE and child executive functioning and externalizing problems. No moderation by child sex was found. Discussion: Findings from this large, sociodemographically diverse cohort suggest women's exposures to interpersonal violence and major stressful events-common for women during pregnancy-may prenatally program her child's executive functioning and externalizing problems. Women's capacity to provide high quality parenting can buffer this intergenerational risk. Implications for universal and targeted prevention and early intervention efforts to support women's and children's wellbeing are discussed.

Anti-Ascaris IgE as a Risk Factor for Asthma Symptoms among 5-Year-Old Children in Rural Bangladesh with Even Decreased Ascaris Infection Prevalence.

BACKGROUND: Epidemiological studies have indicated that anti-Ascaris IgE enhances asthma and allergies under specific conditions although the association between them is still controversial. The association of anti-Ascaris IgE with increased asthma symptoms among children from a general population with a mild to moderate Ascaris infection prevalence was investigated. METHODS: A total of 126 children aged 5 years with wheezing during the previous year and 110 children who did not have wheezing were selected randomly from the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Serum levels of total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anti-cockroach IgEs were tested, and their risks for wheezing were analyzed. The wheezing children were then classified by hierarchical cluster analysis to investigate the contribution of anti-Ascaris IgE to wheezing. RESULTS: The anti-Ascaris IgE levels in wheezing and never-wheezing children were 1.07 and 0.65 UA/mL, and it contributed to 11% of wheezing in children. Anti-Ascaris IgE was significantly associated with wheezing (odds ratio [OR] per loge increment: 1.37 [95% CI: 1.01-1.87], p = 0.046). The ORs, which were adjusted for sex, parental asthma, pneumonia history, helminth infections, Haemophilus influenzae type B combination vaccination, antibiotic use during infancy, and total and specific IgE levels, increased even when only children with more specific symptoms of asthma were included in the analysis. Namely, the ORs for wheezing with sleep disturbance, four or more attacks, and wheezing with speech difficulties during the previous 1 year were OR = 1.44/loge increment [95% CI: 1.01-2.07], OR = 1.90/loge increment [95% CI: 1.11-3.25], and OR = 1.78/loge increment [95% CI: 1.01-3.14], respectively. CONCLUSIONS: The anti-Ascaris IgE levels in wheezing and never-wheezing children in the current study significantly decreased concurrently with Ascaris infection prevalence compared with their corresponding values in 2001. The contribution of anti-Ascaris IgE to wheezing also dropped from 26% in 2001 to 11% in the current study. Despite significant decreases in the levels and the seroprevalence and its contribution to wheezing, anti-Ascaris IgE remained significantly associated with increased risk of wheezing. Anti-Ascaris IgE significantly increased the risk of wheezing in a general population with a mild to moderate Ascaris infection prevalence, suggesting robustness as a risk factor and a possible dose-response relationship.

Maternal childhood trauma and prenatal stressors are associated with child behavioral health.

Maternal adversity and prenatal stress confer risk for child behavioral health problems. Few studies have examined this intergenerational process across multiple dimensions of stress; fewer have explored potential protective factors. Using a large, diverse sample of mother-child dyads, we examined associations between maternal childhood trauma, prenatal stressors, and offspring socioemotional-behavioral development, while also examining potential resilience-promoting factors. The Conditions Affecting Neurocognitive Development and Learning and Early Childhood (CANDLE) study prospectively followed 1503 mother-child dyads (65% Black, 32% White) from pregnancy. Exposures included maternal childhood trauma, socioeconomic risk, intimate partner violence, and geocode-linked neighborhood violent crime during pregnancy. Child socioemotional-behavioral functioning was measured via the Brief Infant Toddler Social Emotional Assessment (mean age = 1.1 years). Maternal social support and parenting knowledge during pregnancy were tested as potential moderators. Multiple linear regressions (N = 1127) revealed that maternal childhood trauma, socioeconomic risk, and intimate partner violence were independently, positively associated with child socioemotional-behavioral problems at age one in fully adjusted models. Maternal parenting knowledge moderated associations between both maternal childhood trauma and prenatal socioeconomic risk on child problems: greater knowledge was protective against the effects of socioeconomic risk and was promotive in the context of low maternal history of childhood trauma. Findings indicate that multiple dimensions of maternal stress and adversity are independently associated with child socioemotional-behavioral problems. Further, modifiable environmental factors, including knowledge regarding child development, can mitigate these risks. Both findings support the importance of parental screening and early intervention to promote child socioemotional-behavioral health.

Risk factors for delay in starting age-appropriate vaccinations among infants in urban slums of Bangladesh.

Age-appropriate vaccination is crucial for infants, protecting them from vaccine-preventable diseases. Delaying in starting initial immunization may result in incomplete or non-vaccination in early life. However, limited vaccine coverage data are available regarding the starting age of vaccination. In this study, we determined the factors associated with the delay in infant immunization. We carried out a cross-sectional study at three maternal-child health clinics in Dhaka city. Mothers visited these clinics for their infant immunization were surveyed with structured questionnaires. A multivariate logistic regression model was used to estimate the significant influencing factors on untimely vaccination. A total of 548 mother-infant pairs were surveyed. 46.5% of mothers did not receive Tetanus (TT) vaccines, and mothers who had a previous pregnancy were less likely to receive TT-vaccine (p < .01). 41.2% of infants did not receive BCG vaccines within 1-week of birth. Mothers working outside the home showed a negative impact on BCG vaccination (p < .05). Among the infants' born in-clinic facilities, 39% were BCG unvaccinated, and 69% had c-section delivery. The median age of infants for starting vaccination was 6.57 wks (95% CI: 6.43-7.14); however, 17.3% infants received vaccination at ≥8 wks of age. Mother's schooling-years and infant normal body-weight positively associated with vaccination at <8 wks, whereas sickness after birth increased the age to start vaccination program recommended at 6 wks. Our analysis suggests the need for specific interventions based on potential maternal determinants, such as educating mothers about the timing and the importance of infant immunization, and addressing programmatic barriers to timely vaccination among infants in Bangladesh.

Impact of Haemophilus influenzae type b combination vaccination on asthma symptoms and pneumonia in 5-year-old children in rural Bangladesh: a longitudinal study and comparison with a previous cross-sectional study.

BACKGROUND: Although the prevalence of bronchial asthma has been increasing worldwide since the 1970's, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease. METHODS: A case-control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 - percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%). RESULTS: Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3-4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group. CONCLUSIONS: Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1-4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.

High-Dose Neonatal Vitamin A Supplementation to Bangladeshi Infants Increases the Percentage of CCR9-Positive Treg Cells in Infants with Lower Birthweight in Early Infancy, and Decreases Plasma sCD14 Concentration and the Prevalence of Vitamin A Deficiency at Two Years of Age.

BACKGROUND: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system. OBJECTIVE: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated. METHODS: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight. RESULTS: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y. CONCLUSIONS: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.

Attention-Deficit/Hyperactivity Disorder Symptom Dimensions Differentially Predict Adolescent Peer Problems: Findings From Two Longitudinal Studies.

Introduction: Previous findings that inattention (IA) and hyperactive/impulsive (HI) symptoms predict later peer problems have been mixed. Utilizing two culturally diverse samples with shared methodologies, we assessed the predictive power of dimensionally measured childhood IA and HI symptoms regarding adolescent peer relationships. Methods: A US-based, clinical sample of 228 girls with and without childhood diagnosed attention-deficit/hyperactivity disorder (ADHD; M age = 9.5) was assessed and followed 5 years later. A Norwegian, population-based sample of 3,467 children (53% girls; M age = 8.3) was assessed and followed approximately 4 years later. Both investigations used parent and teacher reports of ADHD symptoms and peer relations. Multivariate regression analyses examined the independent contributions of IA and HI symptoms to later peer problems, adjusting for baseline childhood peer problems. We also examined childhood sex as a potential moderator within the Norwegian sample. Results: Higher levels of childhood HI symptoms, but not IA symptoms, independently predicted adolescent peer problems in the all-female clinical sample. Conversely, higher levels of IA symptoms, but not HI symptoms, independently predicted preadolescent peer problems in the mixed-sex population sample. Results did not differ between informants (parent vs. teacher). Associations between ADHD symptom dimensions and peer problems within the Norwegian sample were not moderated by child sex. Discussion: Differential associations between childhood hyperactive/impulsive and inattention symptoms and adolescent peer problems were found across two diverse samples using a shared methodology. Potential explanations for different findings in the clinical vs. population samples include symptom severity as well as age, sex, and cultural factors. We discuss implications for future research, including the importance of dimensional measures of ADHD-related symptoms and the need for shared methodologies across clinical and normative samples.

High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy.

BACKGROUND: Vitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function. OBJECTIVE: Our objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median). METHODS: Three hundred and six infants were randomly assigned to 50,000 IU vitamin A (VA) or placebo (PL) within 48 h of birth. Primary outcomes were measured at multiple ages and included 1) thymic index (TI) at 1, 6, 10, and 15 wk; 2) T-cell receptor excision circles (TREC), an index of thymic output of naïve T cells; and 3) total/naïve T cells in peripheral blood at 6 wk, 15 wk, and 2 y. A mixed linear model for repeated measures was used to assess group differences at each age and identify interactions with sex and birth weight. RESULTS: VAS did not significantly (P = 0.21) affect TI overall (i.e., at all ages) but decreased TI by 7.8% (P = 0.029) at 6 wk: adjusted TI means for the PL and VA groups at 1, 6, 10, and 15 wk were 4.09 compared with 3.80 cm2, 7.78 compared with 7.18 cm2, 8.11 compared with 7.84 cm2, and 7.91 compared with 7.97 cm2, respectively. VAS did not significantly (P = 0.25) affect TREC overall but decreased TREC by 19% (P = 0.029) at 15 wk: adjusted TREC means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 13.6 compared with 16.1 copies/pg DNA, 19.4 compared with 15.7 copies/pg DNA, and 11.8 compared with 10.0 copies/pg DNA, respectively. VAS did not significantly affect overall total (P = 0.10) or naïve (P = 0.092) T cells: adjusted naïve T-cell means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 3259 compared with 3109 cells/µL, 3771 compared with 3487 cells/µL, and 1976 compared with 1898 cells/µL, respectively. CONCLUSION: In contrast to our hypothesis, VAS decreased thymic function early in infancy but health effects are presumably negligible owing to the transience and small magnitude of this effect. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.

Use of Model-Based Compartmental Analysis and a Super-Child Design to Study Whole-Body Retinol Kinetics and Vitamin A Total Body Stores in Children from 3 Lower-Income Countries.

BACKGROUND: Model-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans. OBJECTIVES: We applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines. METHODS: Children ingested [13C10]retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma [13C10]retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data. RESULTS: Model-predicted TBS was 198, 533, and 1062 µmol for the Bangladeshi (age, 9-17 mo), Filipino (12-18 mo), and Guatemalan children (35-65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ∼2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2-3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 µg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively). CONCLUSIONS: By collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).

Concurrent decreases in the prevalence of wheezing and Ascaris infection among 5-year-old children in rural Bangladesh and their regulatory T cell immunity after the implementation of a national deworming program.

INTRODUCTION: Epidemiological research on the prevalence of asthma and helminthic infections in various countries has led to the hypothesis that helminthic infections protect against asthma by suppressing the host's immune response. This study was conducted to elucidate whether decreased Ascaris infection following a national deworming program was associated with increased recurrent wheezing among rural Bangladeshi children and to test their anti-inflammatory immunity. METHODS: This nested case-control study was conducted from December 2015 to October 2016 in the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Of the 1800 5-year old children randomly selected for the study, informed consent was obtained from the guardians of 1658 children. Data were collected using a semistructured questionnaire adopted from the International Study of Asthma and Allergies in Childhood and blood samples for the analysis of regulatory T (Treg) cell immune responses and the balance between Th1 and Th2 immunity in Ascaris infections. RESULTS: A total of 145 children were found to have wheezing, yielding a prevalence rate of 8.7%, which was significantly lower than the rate found in 2001 (16.2%, P < .001); Ascaris infection also decreased from 2001 to 2016. The 127 wheezing children who agreed to participate further were compared to 114 randomly selected never-wheezing children. Wheezing had a significant positive association with antibiotic use, history of pneumonia, parents' history of asthma, and Ascaris infection; children with Ascaris infection were twice as likely to have wheezing (adjusted odds ratio = 2.31, P = .053). Flow cytometry found no significant differences in the rates of Th1, Th2, and CD4 + CD25 + CD127low cells by the wheezing group. CONCLUSIONS: Ascaris infection had a positive rather than a negative association with wheezing and the rates of wheezing and Ascaris infections both decreased from 2001 to 2016. These findings undermines the hypothesis that such infections provide protection against asthma.

Neonatal Vitamin A Supplementation and Vitamin A Status Are Associated with Gut Microbiome Composition in Bangladeshi Infants in Early Infancy and at 2 Years of Age.

BACKGROUND: Infancy is a crucial period for establishing the intestinal microbiome. This process may be influenced by vitamin A (VA) status because VA affects intestinal immunity and epithelial integrity, factors that can, in turn, modulate microbiome development. OBJECTIVES: The aim of this study was to determine if neonatal VA supplementation (VAS) affected the abundance of Bifidobacterium, a beneficial commensal, or of Proteobacteria, a phylum containing enteric pathogens, in early (6-15 wk) or late (2 y) infancy. Secondary objectives were to determine if VAS affected the abundance of other bacterial taxa, and to determine if VA status assessed by measuring plasma retinol was associated with bacterial abundance. METHODS: Three hundred and six Bangladeshi infants were randomized by sex and birthweight status (above/below median) to receive 1 VA dose (50,000 IU) or placebo within 48 h of birth. Relative abundance at the genus level and above was assessed by 16S rRNA gene sequencing. A terminal restriction fragment-length polymorphism assay was used to identify Bifidobacterium species and subspecies at 6 wk. RESULTS: Linear regression showed that Bifidobacterium abundance in early infancy was lower in boys (median, 1st/3rd quartiles; 0.67, 0.52/0.78) than girls (0.73, 0.60/0.80; P = 0.003) but that boys receiving VAS (0.69, 0.55/0.78) had higher abundance than boys receiving placebo (0.65, 0.44/0.77; P = 0.039). However this difference was not seen in girls (VAS 0.71, 0.54/0.80; placebo 0.75, 0.63/0.81; P = 0.25). VAS did not affect Proteobacteria abundance. Sex-specific associations were also seen for VA status, including positive associations of plasma retinol with Actinobacteria (the phylum containing Bifidobacterium) and Akkermansia, another commensal with possible health benefits, for girls in late infancy. CONCLUSIONS: Better VA status in infancy may influence health both in infancy and later in life by promoting the establishment of a healthy microbiota. This postulated effect of VA may differ between boys and girls. This trial was registered at clinicaltrials.gov as NCT02027610.

Bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age.

BACKGROUND: The intestinal microbiome in early infancy affects immunologic development and thus may affect vaccine memory, though few prospective studies have examined such associations. We examined the association of Bifidobacterium levels in early infancy with memory responses to early vaccination measured at 2 years of age. METHODS: In this prospective observational study, we examined the association of Bifidobacterium abundance in the stool of healthy infants at 6 to 15 weeks of age, near the time of vaccination, with T-cell and antibody responses measured at 6 weeks, 15 weeks, and 2 years of age. Infants were vaccinated with Bacillus Calmette-Guérin (BCG) (at birth), oral polio virus (at birth and at 6, 10, and 14 weeks), tetanus toxoid (TT) (at 6, 10, and 14 weeks), and hepatitis B virus (at 6, 10, and 14 weeks). Fecal Bifidobacterium was measured at 6, 11, and 15 weeks. Bifidobacterium species and subspecies were measured at 6 weeks. RESULTS: Mean Bifidobacterium abundance in early infancy was positively associated with the CD4 T-cell responses to BCG, TT, and hepatitis B virus at 15 weeks, with CD4 responses to BCG and TT at 2 years, and with plasma TT-specific immunoglobulin G and stool polio-specific immunoglobulin A at 2 years. Similar associations were seen for the predominant subspecies, Bifidobacterium longum subspecies infantis. CONCLUSIONS: Bifidobacterium abundance in early infancy may increase protective efficacy of vaccines by enhancing immunologic memory. This hypothesis could be tested in clinical trials of interventions to optimize Bifidobacterium abundance in appropriate populations.

Infant cortisol stress-response is associated with thymic function and vaccine response.

Stress can impair T cell-mediated immunity. To determine if infants with high stress responses had deficits in T-cell mediated immunity, we examined the association of pain-induced cortisol responsiveness with thymic function and vaccine responses in infants. This study was performed among 306 (male = 153 and female = 153) participants of a randomized, controlled trial examining the effect of neonatal vitamin A supplementation on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured before and 20 min after a needle stick (vaccination) at 6 weeks of age. The thymic index (TI) was determined by ultrasonography at 1, 6, 10 and 15 weeks. T-cell receptor excision circle and blood T-cell concentrations were measured at 6 and 15 weeks. Responses to Bacillus Calmette-Guérin (BCG), tetanus toxoid, hepatitis B virus and oral poliovirus vaccination were assayed at 6 and 15 weeks. Cortisol responsiveness was negatively associated with TI at all ages (p < .01) in boys only, was negatively associated with naïve helper T-cell concentrations in both sexes at both 6 (p = .0035) and 15 weeks (p = .0083), and was negatively associated with the delayed-type hypersensitivity (DTH) skin test response to BCG vaccination at 15 weeks (p = .034) in both sexes. Infants with a higher cortisol response to pain have differences in the T-cell compartment and a lower DTH response to vaccination. Sex differences in the immune system were seen as early as 6 weeks of age in these healthy infants.

Little evidence for late-onset ADHD in a longitudinal sample of women.

OBJECTIVE: Individuals with late-onset symptoms of attention-deficit/hyperactivity disorder (ADHD) are presenting to providers at increasing rates. Recent birth-cohort studies reveal evidence for late-onset ADHD, but conclusions are challenged by measurement methods as well as presence of participant impairment and psychiatric comorbidities. We examined the occurrence of late-onset ADHD in a small but thoroughly investigated group of diverse (47% white) women followed from childhood to adulthood. METHOD: From a larger, 16-year longitudinal study, a subsample of young women without childhood ADHD (N = 87) was assessed at four time points between childhood and adulthood via a multimethod, multiinformant approach. We used a stepped diagnostic procedure to identify those who initially met symptom criteria for ADHD after childhood and then evaluated them for remaining DSM ADHD diagnostic criteria, including impairment, cross-situational symptoms, and comorbid diagnoses. RESULTS: Of 87 participants, 17 met ADHD symptom criteria after childhood. Fifteen showed no evidence of childhood onset, 10 showed clear evidence of impairment, and nine had cross-situational symptoms. Of these nine, all but one showed clinically significant co-occurring or preexisting psychiatric diagnoses and/or substance use that might account for ADHD symptoms. CONCLUSIONS: Although 19.5% of women from our subsample without childhood ADHD met symptom criteria for ADHD during adolescence/adulthood, only one showed the needed combination of impairment and cross-situational symptoms without significant co-occurring mental health problems. It is possible that uncomplicated cases of adult ADHD do arise, yet we find little supporting evidence herein. (PsycINFO Database Record (c) 2018 APA, all rights reserved).