Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations With 24-Month Growth and Neurodevelopment.
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ABSTRACT:
SUBMITTER: Moraka NO
PROVIDER: S-EPMC7539691 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations With 24-Month Growth and Neurodevelopment.
Moraka Natasha O NO Moyo Sikhulile S Smith Christiana C Ibrahim Maryanne M Mayondi Gloria G Leidner Jean J Powis Kathleen M KM Cassidy Adam R AR Kammerer Betsy B Ajibola Gbolahan G Williams Paige L PL Weinberg Adriana A Musonda Rosemary R Shapiro Roger R Gaseitsiwe Simani S Lockman Shahin S
Open forum infectious diseases 20200822 10
<h4>Background</h4>We sought to identify predictors of child cytomegalovirus (CMV) infection overall and by maternal HIV status and to assess associations of child CMV status with growth and neurodevelopmental outcomes at 24 months of age in Botswana.<h4>Methods</h4>Data and samples were used from the Botswana-based observational Tshipidi study (2010-2014), enrolling pregnant women living with and without HIV and following their infants through 2 years of age. Child plasma samples were tested at ...[more]
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Project description:OBJECTIVE:Conflicting data exist regarding the impact of in-utero exposure to maternal combination antiretrovirals. We compared neurodevelopmental outcomes between HIV-exposed-uninfected (HEU) children exposed in utero to three-drug combination antiretroviral therapy (ART) vs. zidovudine (ZDV) monotherapy. DESIGN:Prospective study of child neurodevelopment, nested within two cohorts of HIV-infected mothers and their children in Botswana (one observational, one interventional). METHODS:The Tshipidi and Mma Bana studies enrolled HIV-infected women during pregnancy and followed their HEU children for 24 months. Mothers took three-drug ART or ZDV during pregnancy. ART-exposed babies were mostly breastfed, and ZDV-exposed were formula-fed. Neurodevelopmental outcomes, measured at 24 months using Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) and Development Milestones Checklist (DMC), were compared in adjusted linear regression according to antiretroviral exposure. RESULTS:Of 598 HEU children with valid neurodevelopment assessments, 382 were ART-exposed and 210 were ZDV-exposed. Adjusted mean Bayley-III scores were similar among ART-exposed vs. ZDV-exposed, with adjusted mean differences (95% confidence interval): Bayley-III Cognitive: -0.3 (-1.4, 0.9); Gross Motor: 0.8 (-0.1, 1.7); Fine Motor: 0.5 (-0.2, 1.3); Expressive Language: 0.7 (-0.3, 1.7); Receptive Language: 0.1 (-0.7, 0.8); and DMC Locomotor: 0.0 (-0.5, 0.6); Fine Motor: 0.3 (-0.3, 0.8); Language: -0.1 (-0.5, 0.4); Personal-Social: 0.2 (-0.7, 1.1). Similarly, when restricted to formula-fed children in one cohort (Tshipidi), there were no differences in adjusted mean scores. CONCLUSION:Neurodevelopmental outcomes at 24 months of age were similar in ART-exposed vs. ZDV-exposed HEU children. Maternal ART with breastfeeding does not appear to have an adverse effect on neurodevelopment.
| S-EPMC5945299 | biostudies-literature
Project description:BACKGROUND:Lead and psychosocial stress disrupt similar but not completely overlapping mechanisms. Exposure during the prenatal period to each of these insults singularly has been found to alter normal neurodevelopment; however, longitudinal associations with stress modifying the effect of lead have not been sufficiently analyzed in epidemiologic studies. OBJECTIVE:To evaluate prenatal stress as an effect modifier of gestational lead neurotoxicity. METHODS:We used a structural equations modeling approach with a trivariate response to evaluate cognitive, language and motor scores of the Bayley Scales of Infant Development-III in 24month-old children (n=360). Maternal blood lead levels were measured at the 2nd and 3rd trimester and psychosocial stress during pregnancy was assessed using a negative life events (NLE) scale derived from the CRYSIS questionnaire. RESULTS:3rd trimester lead (mean 3.9±3.0 SD?g/dL) and stress (median=3 NLE) were negatively associated with Bayley III scores. Using the model's results we generated profiles for 0, 2, 4 and 6 NLE across lead levels (up to 10?g/dL) and observed a dose-response for the developmental scores when lead levels were below 2?g/dL. Each NLE curve had a different shape across increasing lead levels. Higher stress (NLE=6) resulted in lower cognitive scores for both sexes, in lower language scores in girls but not boys. In the absence of stress we saw a negative association with lead for all scores, however for language and motor scores, higher stress seemed to mask this association. CONCLUSIONS:Our work examined and confirmed prenatal stress exposure as a modifier of the well-known neurotoxic effects of prenatal lead. It adds to the existing evidence pointing at the importance of studying the co-exposure of chemical and non-chemical exposures, specifically of considering the emotional environment of children at early developmental stages of life.
| S-EPMC5221478 | biostudies-literature
Project description:BackgroundOrganophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001.ObjectivesWe conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months.MethodsUsing general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (ΣDMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype.ResultsThere was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics.ConclusionsData pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.CitationEngel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. 2016. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environ Health Perspect 124:822-830; http://dx.doi.org/10.1289/ehp.1409474.
| S-EPMC4892910 | biostudies-literature
Project description:BackgroundPhthalate metabolites in gestational-maternal urine represents short-term maternal exposure, but meconium, the newborn's first stool may better capture cumulative fetal exposure. We quantified phthalate metabolites in meconium from two cohorts of children at higher risk of adverse neurodevelopment and evaluated associations with their cognitive function at 12 months.MethodsMeconium phthalate metabolites were quantified in the Safe Passage Study (SPS), N = 720, a pregnancy cohort with high community-levels of prenatal alcohol use, and the Early Autism Risk Longitudinal Investigation (EARLI), N = 236, a high familial autism risk pregnancy cohort. EARLI also had second and third trimester (T2/T3) maternal urine for exposure assessment. Molar sum of di (2-ethylhexyl) (∑DEHP) metabolites and an anti-androgenic score (AAS) using mono-isobutyl, mono-n-butyl, monobenzyl (MBZP), and DEHP metabolites were computed. Cognitive function was assessed at 12 months using the Mullen Scales of Early Learning-Composite (ELC). Multivariable linear regression assessed associations between loge-transformed metabolites and ELC. Quadratic terms explored nonlinearity and interaction terms of metabolite by child's sex examined effect modification.ResultsIn SPS, MBzP (βLinear = -6.73; 95% CI: 12.04, -1.42; βquadratic = 1.95; 0.27, 3.62) and mono (2-ethyl-5-carboxypentyl), (βLinear = -3.81; -7.53, -0.27; βquadratic = 0.93; 0.09, 1.77) had U-shaped associations with ELC. In EARLI, T2 urine mono-carboxyisononyl was associated with linear decrease in ELC, indicating lower cognitive function. Interaction with sex was suggested (P < 0.2) for several urine metabolites, mostly indicating negative association between phthalates and ELC among girls but reversed among boys. Only mono-isononyl phthalate and ∑DEHP had consistent main effect associations across matrixes and cohorts, but similar interaction with sex was observed for meconium-measured ∑DEHP, AAS, MBzP, and mono (2-ethylhexyl) in both cohorts.ConclusionsFew phthalate metabolites were consistently associated with children's cognitive function, but a similar set of meconium metabolites from both cohorts displayed sex-specific associations. Gestational phthalate exposure may have sexually-dimorphic associations with early cognitive function in children at higher risk for adverse neurodevelopment.
| S-EPMC9890962 | biostudies-literature
Project description:OBJECTIVES:HAART for prevention of mother-to-child HIV transmission (MTCT) may impact long-term survival of women and children. DESIGN:Randomized clinical trial. METHODS:HIV-infected pregnant women with CD4+ cell count at least 200 cells/µl were randomly assigned to abacavir, zidovudine, lamivudine (arm A) or lopinavir–ritonavir, zidovudine–lamivudine (arm B) from week 26 to 34 gestation through planned weaning by 6 months postpartum. Women with baseline CD4+ cell count less than 200 cells/µl received nevirapine–zidovudine–lamivudine indefinitely (Obs arm), as did randomized women later qualifying for treatment. RESULTS:Among 560 randomized and 170 observational women enrolled, there were 14 deaths (1.9%) – one antenatally (Obs), three from delivery to 6 months postpartum (1 arm A, 2 Obs), and 10 from 6 to 24 months postpartum (5 arm A, 3 arm B, 2 Obs). Time to death or CD4+ cell count below 200 cells/µl was shorter in arm A vs. B (P = 0.03). Of the 709 live-born children, 97% breastfed for a median of 5.8 months. Of 37 (5.2%) deaths by 24 months, nine were before breastfeeding initiated (3 arm A, 2 arm B, 4 Obs); six while breastfeeding (1 arm A, 2 arm B, 3 Obs); and 22 after weaning (9 arm A, 11 arm B, 2 Obs). Only eight children (1.1%) were HIV-infected at 24 months (6 arm A, 1 arm B, 1 Obs), all before 6 months. CONCLUSION:Low MTCT was maintained through extended follow-up in all arms. Disease progression appeared slower after discontinuing protease inhibitor-based HAART, but a concerning number of maternal deaths occurred after stopping either regimen. Strategies to improve maternal and child survival in the postintervention period are required.
| S-EPMC3987116 | biostudies-literature
Project description:We sought to determine if HIV-exposed uninfected (HEU) children had worse neurodevelopmental outcomes at 24 months compared with HIV-unexposed uninfected (HUU) children in Botswana. HIV-infected and uninfected mothers enrolled in a prospective observational study ("Tshipidi") in Botswana from May 2010 to July 2012. Child neurodevelopment was assessed at 24 months with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III: cognitive, gross motor, fine motor, expressive language, and receptive language domains) and the Development Milestones Checklist (DMC), a caregiver-completed questionnaire (locomotor, fine motor, language and personal-social domains). We used linear regression models to estimate the association of in-utero HIV exposure with neurodevelopment, adjusting for socioeconomic and maternal health characteristics. We evaluated 670 children (313 HEU, 357 HUU) with ≥1 valid Bayley-III domain assessed and 723 children (337 HEU, 386 HUU) with a DMC. Among the 337 HEU children with either assessment, 122 (36%) were exposed in utero to maternal 3-drug antiretroviral treatment and 214 (64%) to zidovudine. Almost all HUU children (99.5%) breastfed, compared with only 9% of HEU children. No domain score was significantly lower among HEU children in adjusted analyses. Bayley-III cognitive and DMC personal-social domain scores were significantly higher in HEU children than in HUU children, but differences were small. HEU children performed equally well on neurodevelopmental assessments at 24 months of age compared with HUU children. Given the global expansion of the HEU population, results suggesting no adverse impact of in-utero HIV and antiretroviral exposure on early neurodevelopment are reassuring.
| S-EPMC5613819 | biostudies-literature
Project description:The developing fetus is especially vulnerable to environmental toxicants, including tobacco constituents. The aim of this study was to assess the impact of environmental tobacco smoke (ETS) exposure during pregnancy on child neurodevelopment within the first two years of life. The study population consisted of 461 non-smoking pregnant women (saliva cotinine level <10 ng/mL). Maternal passive smoking was assessed based on the cotinine level in saliva analyzed by the use of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS) and by questionnaire data. The cotinine cut-off value for passive smoking was established at 1.5 ng/mL (sensitivity 63%, specificity 71%). Psychomotor development was assessed in children at the age of one- and two-years using the Bayley Scales of Infant and Toddler Development. Approximately 30% of the women were exposed to ETS during pregnancy. The multivariate linear regression model indicated that ETS exposure in the 1st and the 2nd trimesters of pregnancy were associated with decreasing child language functions at the age of one (? = -3.0, p = 0.03, and ? = -4.1, p = 0.008, respectively), and two years (? = -3.8, p = 0.05, and ? = -6.3, p = 0.005, respectively). A negative association was found for cotinine level ?1.5 ng/mL in the 2nd trimester of pregnancy and child cognition at the age of 2 (? = -4.6, p = 0.05), as well as cotinine levels ?1.5 ng/mL in all trimesters of pregnancy and child motor abilities at two years of age (? = -3.9, p = 0.06, ? = -5.3, p = 0.02, and ? = -4.2, p = 0.05, for the 1st, the 2nd, and the 3rd trimester of pregnancy, respectively; for the 1st trimester the effect was of borderline statistical significance). This study confirmed that ETS exposure during pregnancy can have a negative impact on child psychomotor development within the first two years of life and underscore the importance of public health interventions aiming at reducing this exposure.
| S-EPMC5551234 | biostudies-literature
Project description:BackgroundSome maternal infections are associated with impaired infant cognitive and motor performance. Periodontitis results in frequent bacteremia and elevated serum inflammatory mediators.ObjectiveThe purpose of this study was to determine if periodontitis treatment in pregnant women affects infant cognitive, motor, or language development.MethodsChildren born to women who had participated in a previous trial were assessed between 24 and 28 months of age by using the Bayley Scales of Infant and Toddler Development (Third Edition) and the Preschool Language Scale (Fourth Edition). Information about the pregnancy, neonatal period, and home environment was obtained through chart abstractions, laboratory test results, and questionnaires. We compared infants born to women treated for periodontitis before 21 weeks' gestation (treatment group) or after delivery (controls). In unadjusted and adjusted analyses, associations between change in maternal periodontal condition during pregnancy and neurodevelopment scores were tested by using Student's t tests and linear regression.ResultsA total of 411 of 791 eligible mother/caregiver-child pairs participated. Thirty-seven participating children (9.0%) were born at <37 weeks' gestation. Infants in the treatment and control groups did not differ significantly for adjusted mean cognitive (90.7 vs 91.4), motor (96.8 vs 97.2), or language (92.2 vs 92.1) scores (all P > .5). Results were similar in adjusted analyses. Children of women who experienced greater improvements in periodontal health had significantly higher motor and cognitive scores (P = .01 and .02, respectively), although the effect was small (∼1-point increase for each SD increase in the periodontal measure).ConclusionNonsurgical periodontitis treatment in pregnant women was not associated with cognitive, motor, or language development in these study children.
| S-EPMC3081189 | biostudies-literature
Project description:BackgroundThere is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children's early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children's ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests.MethodsWe genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from cord blood and maternal blood of the Seychelles Child Development Study Nutrition Cohort 2. We determined prenatal MeHg exposure by measuring total mercury (Hg) in cord blood by atomic fluorescence spectrometry. We assessed neurodevelopment in children at approximately 20 months using the Bayley Scales of Infant Development (BSID-II). We used linear regression models to analyze covariate-adjusted associations of child genotype with cord MeHg and BSID-II outcomes (Mental Developmental and Psychomotor Developmental Indexes). We also evaluated interactions between genotypes, cord MeHg, and neurodevelopmental outcomes. All models were run with and without adjustment for maternal genotype.ResultsOf the six evaluated polymorphisms, only ABCC1 rs11075290 was associated with cord blood MeHg; children homozygous for the T-allele had on average 29.99 µg/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06 µg/L MeHg in cord blood (p < 0.001). No polymorphisms in the children were associated with either subscale of the BSID. However, the association between cord MeHg and the Mental Developmental Index (MDI) of the BSID differed significantly across the three genotypes of ABCB1 rs10276499 (2df F-test, p = 0.045). With increasing cord MeHg, the MDI decreased (slope=-0.091, p = 0.014) among children homozygous for the rare C-allele.ConclusionsThese findings support the possibility that child ABC genetics might influence prenatal MeHg exposure.
| S-EPMC9723801 | biostudies-literature
Project description:BackgroundMercury is a neurotoxin, and limited prenatal exposure to it can affect long-term child neurodevelopment. However, results of epidemiologic studies of such exposure have been inconsistent. We examined the association of prenatal mercury exposure from maternal fish consumption with child neurodevelopment in northern Italy.MethodsA population-based cohort of 606 children and their mothers was studied from pregnancy to age 18 months. Mercury levels were measured in maternal hair and blood during pregnancy and in umbilical cord blood and breast milk. Levels of polyunsaturated fatty acids (PUFAs) were measured in maternal serum. Maternal and child intakes of fish were assessed by using a food frequency questionnaire. The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was used to evaluate child neurodevelopment. Multivariate linear regression was used to examine the association of mercury exposure with BSID-III scores, after controlling for maternal fish intake, PUFAs during pregnancy, and several other confounders.ResultsMean weekly fish intake during pregnancy was less than 2 servings. Mercury concentrations in biological samples were low (mean, 1061 ng/g in hair) and moderately correlated with fish intake, particularly of carnivorous species. Maternal ?-3 PUFA concentrations were poorly correlated with fish intake. Maternal intelligence quotient (IQ) and child intake of fish were significantly associated with neurodevelopment scores. In multivariate models, the level of Hg exposure was not associated with neurodevelopmental performance at 18 months.ConclusionsIn this Italian population, neurodevelopment at 18 months was associated with child intake of fresh fish and maternal IQ rather than with mercury exposure. The expected beneficial effect of maternal fish intake (from maternal ?-3 PUFAs) was not found.
| S-EPMC3775530 | biostudies-literature