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The Use of Lower or Higher Than Recommended Doses of Folic Acid Supplements during Pregnancy Is Associated with Child Attentional Dysfunction at 4-5 Years of Age in the INMA Project.
Compañ Gabucio, LM, García de la Hera, M, Torres Collado, L, Fernández-Somoano, A, Tardón, A, Guxens, M, Vrijheid, M, Rebagliato, M, Murcia, M, Ibarluzea, J, et al
Nutrients. 2021;(2)
Abstract
We assessed the association between the use of lower- and higher-than-recommended doses of folic acid supplements (FAs) during pregnancy and attentional function in boys and girls at age of 4-5. We analyzed data from 1329 mother-child pairs from the mother-child cohort INfancia y Medio Ambiente Project (INMA) study. Information on FAs use during pregnancy was collected in personal interviews at weeks 12 and 30, and categorized in <400, 400-999 (recommended dose), and ≥1000 μg/day. Child attentional function was assessed by Conners' Kiddie Continuous Performance Test. Multivariable regression analyses were used to estimate incidence rate ratios (IRR) and beta coefficients with 95% confidence intervals (CI). Compared to recommended FAs doses, the periconceptional use of <400 and ≥1000 μg/day was associated with higher risk of omission errors-IRR = 1.14 (95% CI: 1.01; 1.29) and IRR = 1.16 (95% CI: 1.02; 1.33), respectively. The use of FAs < 400 μg/day and ≥1000 μg/day was significantly associated with deficits of attentional function only in boys. FAs use < 400 μg/day was associated with higher omission errors with IRR = 1.22 and increased hit reaction time (HRT) β = 34.36, and FAs use ≥ 1000 μg/day was associated with increased HRT β = 33.18 and HRT standard error β = 3.31. The periconceptional use of FAs below or above the recommended doses is associated with deficits of attentional function in children at age of 4-5, particularly in boys.
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Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.
DeBoer, MD, Platts-Mills, JA, Elwood, SE, Scharf, RJ, McDermid, JM, Wanjuhi, AW, Jatosh, S, Katengu, S, Parpia, TC, Rogawski McQuade, ET, et al
PLoS medicine. 2021;(9):e1003617
Abstract
BACKGROUND Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage. METHODS AND FINDINGS We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother-child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: -2.05 CI -2.13, -1.96, placebo: -2.05 CI -2.14, -1.97; mean difference: 0.01 CI -0.13, 0.11, p = 0.91; nicotinamide: -2.06 CI -2.13, -1.95, placebo: -2.04 CI -2.14, -1.98, mean difference 0.03 CI -0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother's height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings. CONCLUSIONS In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions. TRIAL REGISTRATION ClinicalTrials.gov NCT03268902.
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The Gut‒Breast Axis: Programming Health for Life.
Rodríguez, JM, Fernández, L, Verhasselt, V
Nutrients. 2021;(2)
Abstract
The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.
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Breast Milk Micronutrients and Infant Neurodevelopmental Outcomes: A Systematic Review.
Lockyer, F, McCann, S, Moore, SE
Nutrients. 2021;(11)
Abstract
Micronutrients are fundamental for healthy brain development and deficiencies during early development can have a severe and lasting impact on cognitive outcomes. Evidence indicates that undernourished lactating individuals may produce breast milk containing lower concentrations of certain vitamins and minerals. Exclusively breastfed infants born to mothers deficient in micronutrients may therefore be at risk of micronutrient deficiencies, with potential implications for neurodevelopment. This systematic review aims to consider current knowledge on the effects of breast milk micronutrients on the developmental outcomes of infants. The databases Medline, Global Health, PsychInfo, Open Grey, and the Web of Science were searched for papers published before February 2021. Studies were included if they measured micronutrients in breast milk and their association with the neurodevelopmental outcomes of exclusively breastfed infants. Also, randomised control trials investigating neurocognitive outcomes following maternal supplementation during lactation were sought. From 5477 initial results, three observational studies were eligible for inclusion. These investigated associations between breast milk levels of vitamin B6, carotenoids, or selenium and infant development. Results presented suggest that pyroxidal, β-carotene, and lycopene are associated with infant neurodevelopmental outcomes. Limited eligible literature and heterogeneity between included papers prevented quantitative synthesis. Insufficient evidence was identified, precluding any conclusions on the relationship between breast milk micronutrients and infant developmental outcomes. Further, the evidence available was limited by a high risk of bias. This highlights the need for further research in this area to understand the long-term influence of micronutrients in breast milk, the role of other breast milk micronutrients in infant neurodevelopmental outcomes, and the impact of possible lactational interventions.
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The Revised WIC Food Package and Child Development: A Quasi-Experimental Study.
Guan, A, Hamad, R, Batra, A, Bush, NR, Tylavsky, FA, LeWinn, KZ
Pediatrics. 2021;(2)
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Abstract
BACKGROUND AND OBJECTIVES The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), one of the largest US safety net programs, was revised in 2009 to be more congruent with dietary guidelines. We hypothesize that this revision led to improvements in child development. METHODS Data were drawn from a cohort of women and children enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study from 2006 to 2011 (Shelby County, TN; N = 1222). Using quasi-experimental difference-in-differences analysis, we compared measures of growth, cognitive, and socioemotional development between WIC recipients and nonrecipients before and after the policy revision. RESULTS The revised WIC food package led to increased length-for-age z scores at 12 months among infants whose mothers received the revised food package during pregnancy (β = .33, 95% confidence interval: 0.05 to 0.61) and improved Bayley Scales of Infant Development cognitive composite scores at 24 months (β = 4.34, 95% confidence interval: 1.11 to 7.57). We observed no effects on growth at age 24 months or age 4 to 6 years or cognitive development at age 4 to 6 years. CONCLUSIONS This study provides some of the first evidence that children of mothers who received the revised WIC food package during pregnancy had improved developmental outcomes in the first 2 years of life. These findings highlight the value of WIC in improving early developmental outcomes among vulnerable children. The need to implement and expand policies supporting the health of marginalized groups has never been more salient, particularly given the nation's rising economic and social disparities.
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Probiotic Supplementation for Promotion of Growth in Children: A Systematic Review and Meta-Analysis.
Catania, J, Pandit, NG, Ehrlich, JM, Zaman, M, Stone, E, Franceschi, C, Smith, A, Tanner-Smith, E, Zackular, JP, Bhutta, ZA, et al
Nutrients. 2021;(1)
Abstract
Probiotics are commonly prescribed to promote a healthy gut microbiome in children. Our objective was to investigate the effects of probiotic supplementation on growth outcomes in children 0-59 months of age. We conducted a systematic review and meta-analysis which included randomized controlled trials (RCTs) that administered probiotics to children aged 0-59 months, with growth outcomes as a result. We completed a random-effects meta-analysis and calculated a pooled standardized mean difference (SMD) or relative risk (RR) and reported with a 95% confidence interval (CI). We included 79 RCTs, 54 from high-income countries (HIC), and 25 from low- and middle-income countries (LMIC). LMIC data showed that probiotics may have a small effect on weight (SMD: 0.26, 95% CI: 0.11-0.42, grade-certainty = low) and height (SMD 0.16, 95% CI: 0.06-0.25, grade-certainty = moderate). HIC data did not show any clinically meaningful effect on weight (SMD: 0.01, 95% CI: -0.04-0.05, grade-certainty = moderate), or height (SMD: -0.01, 95% CI: -0.06-0.04, grade-certainty = moderate). There was no evidence that probiotics affected the risk of adverse events. We conclude that in otherwise healthy children aged 0-59 months, probiotics may have a small but heterogenous effect on weight and height in LMIC but not in children from HIC.
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The Effects of Vitamin D Supplementation During Infancy on Growth During the First 2 Years of Life.
Hauta-Alus, HH, Holmlund-Suila, EM, Kajantie, E, Rosendahl, J, Valkama, SM, Enlund-Cerullo, M, Andersson, S, Mäkitie, O
The Journal of clinical endocrinology and metabolism. 2021;(3):e1140-e1155
Abstract
CONTEXT The relationship between maternal and infant vitamin D and early childhood growth remains inadequately understood. OBJECTIVE This work aimed to investigate how maternal and child 25-hydroxyvitamin D (25[OH]D) and vitamin D supplementation affect growth during the first 2 years of life. METHODS A randomized, double-blinded, single-center intervention study was conducted from pregnancy until offspring age 2 years. Altogether 812 term-born children with complete data were recruited at a maternity hospital. Children received daily vitamin D3 supplementation of 10 μg (group 10) or 30 μg (group 30) from age 2 weeks to 2 years. Anthropometry and growth rate were measured at age 1 and 2 years. RESULTS Toddlers born to mothers with pregnancy 25(OH)D greater than 125 nmol/L were at 2 years lighter and thinner than the reference group with 25(OH)D of 50 to 74.9 nmol/L (P < .010). Mean 2-year 25(OH)D concentrations were 87 nmol/L in group 10 and 118 nmol/L in group 30 (P < .001). When group 30 was compared with group 10, difference in body size was not statistically significant (P > .053), but group 30 had slower growth in length and head circumference between 6 months and 1 year (P < .047), and more rapid growth in weight and length-adjusted weight between 1 and 2 years (P < .043). Toddlers in the highest quartile of 25(OH)D (> 121 nmol/L) were shorter (mean difference 0.2 SD score [SDS], P = .021), lighter (mean difference 0.4 SDS, P = .001), and thinner (in length-adjusted weight) (mean difference 0.4 SDS, P = .003) compared with the lowest quartile (< 81.2 nmol/L). CONCLUSION Vitamin D and early childhood growth may have an inverse U-shaped relationship.
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Neurodevelopmental Outcomes and Gut Bifidobacteria in Term Infants Fed an Infant Formula Containing High sn-2 Palmitate: A Cluster Randomized Clinical Trial.
Wu, W, Zhao, A, Liu, B, Ye, WH, Su, HW, Li, J, Zhang, YM
Nutrients. 2021;(2)
Abstract
A few studies suggested high stereo-specifically numbered (sn)-2 palmitate in a formula might favor the gut Bifidobacteria of infants. The initial colonization and subsequent development of gut microbiota in early life might be associated with development and later life functions of the central nervous system via the microbiota-gut-brain axis, such as children with autism. This study aims to assess the hypothesized effect of increasing the amount of palmitic acid esterified in the sn-2 position in infant formula on neurodevelopment in healthy full-term infants and to explore the association of this effect with the altered gut Bifidobacteria. One hundred and ninety-nine infants were enrolled in this cluster randomized clinical trial: 66 breast-fed (BF group) and 133 formula-fed infants who were clustered and randomly assigned to receive formula containing high sn-2 palmitate (sn-2 group, n = 66) or low sn-2 palmitate (control group, n = 67), where 46.3% and 10.3% of the palmitic acid (PA) was sn-2-palmitate, respectively. Infants' neurodevelopmental outcomes were measured by the Ages and Stages Questionnaire, third edition (ASQ-3). Stool samples were collected for the analysis of Bifidobacteria (Trial registration number: ChiCTR1800014479). At week 16, the risk of scoring close to the threshold for fine motor skills (reference: scoring above the typical development threshold) was significantly lower in the sn-2 group than the control group after adjustment for the maternal education level (p = 0.036) but did not differ significantly versus the BF group (p = 0.513). At week 16 and week 24, the sn-2 group (week 16: 15.7% and week 24: 15.6%) had a significantly higher relative abundance of fecal Bifidobacteria than the control group (week 16: 6.6%, p = 0.001 and week 24:11.2%, p = 0.028) and did not differ from the BF group (week 16: 14.4%, p = 0.674 and week 24: 14.9%, p = 0.749). At week 16, a higher relative abundance of Bifidobacteria was associated with the decreased odds of only one domain scoring close to the threshold in the formula-fed infants group (odds ratio (OR), 95% confidence interval (CI): 0.947 (0.901-0.996)). Elevating the sn-2 palmitate level in the formula improved infants' development of fine motor skills, and the beneficial effects of high sn-2 palmitate on infant neurodevelopment was associated with the increased gut Bifidobacteria level.
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Association of Infant Physical Development and Rapid Growth With Pubertal Onset Among Girls in Rural China.
Wei, J, Liu, S, Cheng, Y, Yang, W, Zhu, Z, Zeng, L
JAMA network open. 2021;(5):e216831
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Abstract
IMPORTANCE Whether physical development and rapid growth during the first 2 years of life are associated with puberty onset in girls remains unclear. OBJECTIVE To examine the associations of infant physical development and rapid growth with the timing of puberty onset in girls. DESIGN, SETTING, AND PARTICIPANTS This prospective birth cohort study included girls whose mothers had participated in a randomized, double-blind cluster trial of micronutrient supplementation with a daily capsule of folic acid, iron and folic acid, or multiple micronutrients during pregnancy. A total of 547 singleton girls in rural western China who were born after 2004 were followed up at 3, 6, 12, and 24 months of age and were eligible for long-term follow-up. Of these, 294 adolescent girls (aged 10-12 years), representing 53.7% of the total sample, were included in the follow-up interview that was conducted from June 1 through December 31, 2016. Data analyses were conducted from November 1, 2019, to May 30, 2020. EXPOSURES Infant weight and length were assessed at birth and 3, 6, 12, and 24 months of age. Rapid growth, defined as a weight-for-age or length-for-age z score increase of greater than 0.67, was calculated during 5 periods: birth to 3 months, birth to 6 months, 6 to 12 months, 12 to 24 months, and birth to 24 months of age. MAIN OUTCOMES AND MEASURES Puberty stage was assessed using the standardized Tanner staging system. Onset of puberty was defined as attaining Tanner stage 2 of breast development or pubic hair growth, and the corresponding age at follow-up was recorded. RESULTS Of 294 girls included in the analysis (mean [SD] age, 11.25 [0.57] years), the median age of puberty onset was 11 (interquartile range, 10-11) years. A significant association with puberty onset was found for infancy weight-for-age z score at 12 months of age (adjusted hazard ratio [HR], 1.20; 95% CI, 1.01-1.44) and rapid weight gain from birth to 24 months of age (adjusted HR, 1.40; 95% CI, 1.01-1.93) and birth to 3 months of age (adjusted HR, 1.39; 95% CI, 1.02-1.91). However, length-related indicators during early life were not associated with adolescent puberty onset. CONCLUSIONS AND RELEVANCE This study found that a higher weight-for-age z score and rapid weight gain during infancy, particularly from birth to 3 months of age, were associated with an increased likelihood of puberty onset in girls. These findings suggest that weight-related indicators may serve as proxies of puberty onset among adolescent girls.
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Infant growth during the first year of life following a pregnancy lifestyle intervention in routine care-Findings from the cluster-randomised GeliS trial.
Hoffmann, J, Günther, J, Stecher, L, Spies, M, Geyer, K, Raab, R, Meyer, D, Rauh, K, Hauner, H
Pediatric obesity. 2021;(2):e12705
Abstract
BACKGROUND Lifestyle interventions in pregnancy may influence postpartum development and obesity risk in offspring. The impact of lifestyle interventions as health system-based approaches is unclear. OBJECTIVE To evaluate the effect of an antenatal lifestyle intervention conducted as public health approach on infant development and feeding practices. METHODS We followed offspring born to women participating in the cluster-randomised GeliS trial who received usual care (CG) or repeated lifestyle counselling (IG). We collected data on offspring development and complementary feeding until the 12th month postpartum. RESULTS Of the 1998 mother-child pairs, 1783 completed the follow-up. Mean infant weight at 12 months was comparable between groups (IG: 9497.9 ± 1137.0 g; CG: 9433.4 ± 1055.2 g; P = .177). There was no significant evidence of differences in sex- and age-adjusted z-scores or in the odds of offspring being overweight. More infants in the IG received whole-grain products compared to the CG (95.6% vs. 90.8%; P = .003). Despite small differences in the timing of introducing solid foods, there were no further significant differences in the pattern of complementary feeding. CONCLUSIONS The antenatal lifestyle intervention embedded in routine care did not substantially influence infant anthropometrics and is thus unlikely to impact future development.