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Iodine Supplementation in Mildly Iodine-Deficient Pregnant Women Does Not Improve Maternal Thyroid Function or Child Development: A Secondary Analysis of a Randomized Controlled Trial.
Verhagen, NJE, Gowachirapant, S, Winichagoon, P, Andersson, M, Melse-Boonstra, A, Zimmermann, MB
Frontiers in endocrinology. 2020;:572984
Abstract
Background: Iodine deficiency during pregnancy may be associated with lower offspring IQ, but there are few data on the safety and efficacy of maternal iodine supplementation on child development. In a previously reported multi-center randomized trial conducted in Thailand and India, we assessed the effect of iodine supplementation in mildly iodine-deficient pregnant women on offspring development. In this secondary analysis of that trial, we report data only from the Thai pregnant women in the study, who were more iodine deficient at entry. Methods: Pregnant women in Bangkok, Thailand, were randomized to receive daily 200 μg oral iodine or placebo until delivery. We assessed thyroid size and thyroid function during pregnancy and cognitive and motor development at ages 1, 2, and 5.7 years. The trial was registered at www.clinicaltrials.gov/NCT00791466. Findings: Women (n = 514) entered the trial between November 2008 and March 2011 at a mean ± SD gestational age of 11 ± 2.8 weeks; their median (IQR) UIC was 112 (75, 170) μg/L. Mean compliance with supplementation was 88%. We assessed 397 mothers in the 3rd trimester, 231 infants at age 2 y, and 157 children at mean age 5.7 y. During pregnancy, there was a slightly greater decrease in free and total thyroxine concentrations in the iodine group (p < 0.05). At age 2 years, the iodine group had borderline lower scores for combined fine and gross motor function (p = 0.05), but there were no other significant differences in development. At 5.7 years, there were no significant group differences in child development. Conclusion: Daily iodine supplementation in mildly iodine deficient pregnant women was associated with small negative effects on maternal thyroxine concentrations, but did not affect child development. The safety and efficacy of iodine supplementation in mildly-iodine deficient pregnant women needs to be evaluated further in large randomized controlled trials.
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Vitamin B-12 Supplementation during Pregnancy and Early Lactation Does Not Affect Neurophysiologic Outcomes in Children Aged 6 Years.
Srinivasan, K, Thomas, S, Anand, S, Jayachandra, M, Thomas, T, Strand, TA, Kurpad, AV, Duggan, CP
The Journal of nutrition. 2020;(7):1951-1957
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Abstract
BACKGROUND Deficiency of vitamin B-12 is common in pregnant Indian women. Assessment of neurophysiological measures using event-related potentials (ERPs) may yield additional information on the effects of maternal B-12 supplementation on child brain function. OBJECTIVES The objective of the study was to evaluate the effects of vitamin B-12 supplementation (50 μg daily orally) during pregnancy on the childhood ERP measures of positive waveform ∼300 ms after stimulus (P300) and mismatch negativity. METHODS This study was a follow-up of children born to pregnant women who received oral vitamin B-12 supplements (n = 62) compared with children of pregnant women who received placebo (n = 70) from a randomized controlled trial. The mean ± SD child age was 72 ± 1 mo. We used the Enobio system to assess the ERP measures P300 and mismatch negativity. RESULTS There were no significant differences in the primary outcomes, amplitudes, and latencies of the P300 results and the mismatch negativity between children in the supplementation and placebo groups. We combined the intervention and placebo groups for secondary analyses. On multiple variable regression analysis after adjusting for treatment group, intrauterine growth restriction, and home environment, P300 amplitude in children was significantly higher in the lowest tertile of third-trimester maternal methylmalonic acid (MMA) concentrations (β = 3034.04; 95% CI: 923.24, 5144.83) compared with the highest MMA tertile (β = 1612.12; 95% CI: -258.86, 3483.10, P = 0.005). CONCLUSIONS While no significant effects of maternal vitamin B-12 supplementation on children's ERP measures were seen at 72 mo, elevated maternal MMA concentrations in the third trimester were negatively associated with P300 amplitude in children. It may be worthwhile to study the impact of maternal and infant vitamin B-12 supplementation on childhood brain structure and function in longer and larger trials. The parent trial was registered at clinicaltrials.gov as NCT00641862.
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Effects of improved complementary feeding and improved water, sanitation and hygiene on early child development among HIV-exposed children: substudy of a cluster randomised trial in rural Zimbabwe.
Chandna, J, Ntozini, R, Evans, C, Kandawasvika, G, Chasekwa, B, Majo, F, Mutasa, K, Tavengwa, N, Mutasa, B, Mbuya, M, et al
BMJ global health. 2020;(1):e001718
Abstract
INTRODUCTION HIV-exposed uninfected children may be at risk of poor neurodevelopment. We aimed to test the impact of improved infant and young child feeding (IYCF) and improved water, sanitation and hygiene (WASH) on early child development (ECD) outcomes. METHODS Sanitation Hygiene Infant Nutrition Efficacy was a cluster randomised 2×2 factorial trial in rural Zimbabwe ClinicalTrials.gov NCT01824940). Pregnant women were eligible if they lived in study clusters allocated to standard-of-care (SOC; 52 clusters); IYCF (20 g small-quantity lipid-based nutrient supplement/day from 6 to 18 months, complementary feeding counselling; 53 clusters); WASH (pit latrine, 2 hand-washing stations, liquid soap, chlorine, play space, hygiene counselling; 53 clusters) or IYCF +WASH (53 clusters). Participants and fieldworkers were not blinded. ECD was assessed at 24 months using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social skills); MacArthur Bates Communication Development Inventory (assessing vocabulary and grammar); A-not-B test (assessing object permanence) and a self-control task. Intention-to-treat analyses were stratified by maternal HIV status. RESULTS Compared with SOC, children randomised to combined IYCF +WASH had higher total MDAT scores (mean difference +4.6; 95% CI 1.9 to 7.2) and MacArthur Bates vocabulary scores (+8.5 words; 95% CI 3.7 to 13.3), but there was no evidence of effects from IYCF or WASH alone. There was no evidence that that any intervention impacted object permanence or self-control. CONCLUSIONS Combining IYCF and WASH interventions significantly improved motor, language and cognitive development in HIV-exposed children. TRIAL REGISTRATION NUMBER NCT01824940.
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The mediation effect of anthropometry and physical fitness on the relationship between birthweight and basal metabolic rate in children.
Nobre, IG, Moura-Dos-Santos, MA, Nobre, GG, Santos, RMD, da Costa Ribeiro, I, Carvalho Jurema Santos, G, da Silva da Fonseca, EV, Santos de Oliveira, TLP, Ferreira E Silva, WT, Nazare, JA, et al
Journal of developmental origins of health and disease. 2020;(6):640-647
Abstract
BACKGROUND Birthweight (BW) has been associated with anthropometry, body composition and physical fitness during growth and development of children. However, less is known about the mediation effect of those variables on the relationship between BW and basal metabolic rate (BMR) in children. OBJECTIVE To analyse the mediation effect of anthropometry, body composition and physical fitness on the association between BW and BMR in children. METHODS In total, 499 children (254 boys, 245 girls) aged 7-10 years were included. Anthropometry (weight, height, head, waist and hip circumferences), body composition (skinfolds thickness, body fat percentage), physical fitness (handgrip strength, flexibility, muscular endurance, muscular explosive power, agility, running speed) and BMR were evaluated. The analyses were conducted by: single-mediator analysis (SMA) and multi-mediator analysis (MMA). RESULTS The SMA indicates height, head, waist and hip circumferences and handgrip strength as significant mediators of BW on BMR for boys and height, hip circumference and handgrip strength as significant mediators of BW on BMR for girls. In MMA for girls, there were significant indirect effects for height, hip circumference and handgrip strength, with 79.08% of percent mediation. For boys, the head and waist circumferences mediation had a significant indirect effect, with 83.37% of percent mediation. CONCLUSION The anthropometric variables associated with BW were body height, head, hip and waist circumferences for boys and body height and hip circumference for girls. The current study provides new evidence that height and handgrip strength during childhood mediated the relationship between BW and BMR.
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Influence of a Functional Nutrients-Enriched Infant Formula on Language Development in Healthy Children at Four Years Old.
Nieto-Ruiz, A, Diéguez, E, Sepúlveda-Valbuena, N, Catena, E, Jiménez, J, Rodríguez-Palmero, M, Catena, A, Miranda, MT, García-Santos, JA, G Bermúdez, M, et al
Nutrients. 2020;(2)
Abstract
Nutrition during early life is essential for brain development and establishes the basis for cognitive and language skills development. It is well established that breastfeeding, compared to formula feeding, has been traditionally associated with increased neurodevelopmental scores up to early adulthood. We analyzed the long-term effects of a new infant formula enriched with bioactive compounds on healthy children's language development at four years old. In a randomized double-blind COGNIS study, 122 children attended the follow-up call at four years. From them, 89 children were fed a standard infant formula (SF, n = 46) or an experimental infant formula enriched with functional nutrients (EF, n = 43) during their first 18 months of life. As a reference group, 33 exclusively breastfed (BF) were included. Language development was assessed using the Oral Language Task of Navarra-Revised (PLON-R). ANCOVA, chi-square test, and logistic regression models were performed. EF children seemed to show higher scores in use of language and oral spontaneous expression than SF children, and both SF and EF groups did not differ from the BF group. Moreover, it seems that SF children were more frequently categorized into "need to improve and delayed" in the use of language than EF children, and might more frequently present "need to improve and delayed" in the PLON-R total score than BF children. Finally, the results suggest that SF children presented a higher risk of suffering language development than BF children. Secondary analysis also showed a slight trend between low socioeconomic status and poorer language skills. The functional compound-enriched infant formula seems to be associated with beneficial long-term effects in the development of child's language at four years old in a similar way to breastfed infants.
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Updates on Assessment and Monitoring of the Postnatal Growth of Preterm Infants.
Cordova, EG, Belfort, MB
NeoReviews. 2020;(2):e98-e108
Abstract
Assessing and monitoring the physical growth of preterm infants is fundamental to NICU care. The goals of nutritional care are to approximate the growth and body composition of the healthy fetus and to support optimal brain development while minimizing future cardiometabolic risk. Both poor and excessive growth predict adverse long-term health outcomes. Growth curves are clinical tools used to assess the preterm infant's growth status. Several growth curves for preterm infants were developed in the past decade. To use them effectively, clinicians need to understand how each growth curve was developed; the underlying reference population; intended use; and strengths and limitations. Intrauterine growth curves are references that use size at birth to represent healthy fetal growth. These curves serve 2 purposes-to assign size classifications at birth and to monitor postnatal growth. The INTERGROWTH-21 st preterm postnatal growth standards were developed to compare the postnatal growth of preterm infants to that of healthy preterm infants rather than the fetus. Individualized weight growth curves account for the water weight loss that frequently occurs after birth. In addition, body mass index (BMI) curves are now available. In this review, we discuss the main characteristics of growth curves used for preterm infants as well as the use of percentiles, z scores, and their change over time to evaluate size and growth status. We also review the differences in body composition between preterm infants at term-equivalent age and term-born infants and the potential role of monitoring proportionality of growth using BMI curves.
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Feeding modifications and additional primary caregiver support for infants exposed to Zika virus or diagnosed with congenital Zika syndrome: a rapid review of the evidence.
Martinez, SS, Pardo-Hernandez, H, Palacios, C
Tropical medicine & international health : TM & IH. 2020;(11):1353-1361
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Abstract
OBJECTIVE Infants exposed to Zika virus (ZIKV) or diagnosed with congenital Zika syndrome (CZVS) may present dysphagia, regurgitation and other feeding difficulties. They may require special feeding practices to minimise the risk of mortality, morbidity and developmental problems. Improving knowledge, skills and behaviours of caregivers may preserve health, maximise development and promote quality of life among affected infants. We reviewed intervention studies of modified feeding practices and additional primary caregiver support to improve outcomes among infants 0 to 12 months of age exposed to ZIKV or diagnosed with CZVS. METHODS Rapid review and meta-analysis. We searched PubMed/MEDLINE and contacted experts. The search is current to 18 July 2020. We planned a meta-analysis using fixed-effect models; if unfeasible, we intended to summarise studies narratively. We planned to assess risk of bias of included studies and quality of evidence using Cochrane guidance. RESULTS We identified 42 records for title and abstract screening; 14 were eligible for full-text assessment. Among these, no intervention studies were found. Eight observational studies reported on the nutritional status, feeding practices and outcomes among infants affected by ZIKV or diagnosed with CZVS. They are presented and discussed to provide a basis for future research. CONCLUSIONS While no intervention studies were found, evidence from eight observational studies highlights the need for early nutrition interventions and caregiver support among infants affected by ZIKV or diagnosed with CZSV. More research is needed to assess whether modifications of feeding practices and provision of additional primary caregiver support will impact outcomes of interest.
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Early application of caffeine improves white matter development in very preterm infants.
Liu, S, Zhang, X, Liu, Y, Yuan, X, Yang, L, Zhang, R, Zhang, X, Wang, X, Xu, F, Zhu, C
Respiratory physiology & neurobiology. 2020;:103495
Abstract
The aim of this study was to evaluate the effect of early prophylactic caffeine treatment on white matter development in very preterm infants using cerebral magnetic resonance imaging. A total of 194 preterm infants (≤32 weeks gestational age) were randomly assigned to the caffeine (n = 96) or placebo (n = 93) treatment group and administered with either caffeine or placebo within 72 h after birth. Cerebral magnetic resonance imaging, including diffuse tensor imaging examination, was performed at 34-36 weeks of corrected gestational age, and the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured. In total, 160 infants were included in the final analysis, including 80 cases in the placebo group and 80 cases in the caffeine group. There were fewer instances of apnea of prematurity and shorter assisted ventilation times for infants in the caffeine group compared to the placebo group (p < 0.05). Infants in the caffeine group had significantly higher FA values in white matter, including the posterior limb of the internal capsule, the corpus callosum, the frontal, occipital, and parietal white matter, the cerebellum, and the cerebral peduncle, compared to infants in the placebo group. ADC values in the above white matter areas were significantly reduced in the caffeine group. However, there were no significant differences regarding the FA and ADC in the gray matter between the two groups. These results demonstrate that early administration of caffeine improves white matter micro-structural development in preterm infants, but with no significant effect on short-term complications related to prematurity.
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High-Dose Vitamin D Supplementation in Pregnancy and Neurodevelopment in Childhood: A Prespecified Secondary Analysis of a Randomized Clinical Trial.
Sass, L, Vinding, RK, Stokholm, J, Bjarnadóttir, E, Noergaard, S, Thorsen, J, Sunde, RB, McGrath, J, Bønnelykke, K, Chawes, B, et al
JAMA network open. 2020;(12):e2026018
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IMPORTANCE Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. OBJECTIVE To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental assessments for offspring of these women were performed at ages 0 to 6 years. Children born prematurely (gestational week <37), with low birth weight (<2500 g), or with a neurological disease affecting neurodevelopment were excluded. Data were analyzed from August 2019 to February 2020. INTERVENTIONS High-dose (ie, 2800 IU/d) vs standard dose (ie, 400 IU/d) vitamin D3 supplementation from pregnancy week 24 until 1 week after birth. MAIN OUTCOMES AND MEASURES The primary outcome of interest was cognitive development assessed at 2.5 years using the Bayley Scales of Infant and Toddler Development. Other neurodevelopmental outcomes included age of motor milestone achievement (Denver Developmental Index and World Health Organization milestone registration), language development (MacArthur-Bates Communicative Development Inventories), general neurodevelopment at age 3 years (Ages and Stages Questionnaire), and emotional and behavioral problems at age 6 years (Strengths and Difficulties Questionnaire). RESULTS Among 623 women randomized, 315 were randomized to high-dose vitamin D3 and 308 were randomized to standard dose placebo. A total of 551 children were evaluated from birth to age 6 years, (282 [51.2%] boys; 528 [95.8%] White), with 277 children in the high-dose vitamin D3 group and 274 children in the standard dose group. There was no effect of the high-dose compared with standard dose of vitamin D3 supplementation during pregnancy on offspring achievement of motor milestones (β = 0.08 [95% CI, -0.26 to 0.43]; P = .64), cognitive development (score difference: 0.34 [95% CI, -1.32 to 1.99]; P = .70), general neurodevelopment (median [IQR] communication score: 50 [50-55] vs 50 [50-55]; P = .62), or emotional and behavioral problems (odds ratio, 0.76 [95% CI, 0.53 to 1.09]; P = .14). There was no effect on language development expressed by the word production at 1 year (median [IQR], 2 [0-6] words vs 3 [1-6] words; P = .16), although a decreased word production was apparent at 2 years in children in the high-dose vitamin D3 group (median [IQR], 232 [113-346] words vs 253 [149-382.5] words; P = .02). CONCLUSIONS AND RELEVANCE In this prespecified secondary analysis of an RCT, maternal high-dose vitamin D3 supplementation during the third trimester of pregnancy did not improve neurodevelopmental outcomes in the offspring during the first 6 years of life. These findings contribute essential information clarifying the effects of prenatal exposure to vitamin D on neurodevelopment in childhood. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00856947.
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Biomarkers of environmental manganese exposure and associations with childhood neurodevelopment: a systematic review and meta-analysis.
Liu, W, Xin, Y, Li, Q, Shang, Y, Ping, Z, Min, J, Cahill, CM, Rogers, JT, Wang, F
Environmental health : a global access science source. 2020;(1):104
Abstract
BACKGROUND Although prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive. There has yet been no consistent biomarker of environmental Mn exposure. Here, we summarized studies that investigated associations between manganese in biomarkers and childhood neurodevelopment and suggest a reliable biomarker. METHODS We searched PubMed and Web of Science for potentially relevant articles published until December 31th 2019 in English. We also conducted a meta-analysis to quantify the effects of manganese exposure on Intelligence Quotient (IQ) and the correlations of manganese in different indicators. RESULTS Of 1754 citations identified, 55 studies with 13,388 subjects were included. Evidence from cohort studies found that higher manganese exposure had a negative effect on neurodevelopment, mostly influencing cognitive and motor skills in children under 6 years of age, as indicated by various metrics. Results from cross-sectional studies revealed that elevated Mn in hair (H-Mn) and drinking water (W-Mn), but not blood (B-Mn) or teeth (T-Mn), were associated with poorer cognitive and behavioral performance in children aged 6-18 years old. Of these cross-sectional studies, most papers reported that the mean of H-Mn was more than 0.55 μg/g. The meta-analysis concerning H-Mn suggested that a 10-fold increase in hair manganese was associated with a decrease of 2.51 points (95% confidence interval (CI), - 4.58, - 0.45) in Full Scale IQ, while the meta-analysis of B-Mn and W-Mn generated no such significant effects. The pooled correlation analysis revealed that H-Mn showed a more consistent correlation with W-Mn than B-Mn. Results regarding sex differences of manganese associations were inconsistent, although the preliminary meta-analysis found that higher W-Mn was associated with better Performance IQ only in boys, at a relatively low water manganese concentrations (most below 50 μg/L). CONCLUSIONS Higher manganese exposure is adversely associated with childhood neurodevelopment. Hair is the most reliable indicator of manganese exposure for children at 6-18 years of age. Analysis of the publications demonstrated sex differences in neurodevelopment upon manganese exposure, although a clear pattern has not yet been elucidated for this facet of our study.