High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10: A randomized clinical trial.

BACKGROUND: Vitamin D deficiency in pregnancy may increase the risk of autism and attention deficit hyperactivity disorder (ADHD). OBJECTIVE: The objective of this study was to estimate the effect of vitamin D3 supplementation in pregnancy on risk of autism and ADHD. DESIGN: This randomized clinical trial was part of the COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPYCH) project nested within the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising a population-based sample of 700 healthy mother-child pairs enrolled at week 24 of pregnancy. Maternal 25-hydroxy-vitamin D (25(OH)D) was measured at inclusion and 623 mothers were randomized 1:1 to either high-dose (2800 IU/d) or standard dose (400 IU/d) vitamin D3 until 1 wk postpartum (315 received high-dose, 308 standard dose). At age 10, diagnoses and symptom load of autism and ADHD, respectively, were established using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. RESULTS: The psychopathologic evaluation was completed by 591 children aged 10 y, and 16 children (2.7%) were diagnosed with autism and 65 (11.0%) with ADHD. Hereof, 496 children participated in the vitamin D3 trial (246 received high-dose, 250 standard dose). Of these, 12 children (2.4%) were diagnosed with autism and 58 (11.7%) with ADHD. Higher maternal preintervention 25(OH)D levels were associated with a decreased risk of autism [odd ratio (OR) per 10 nmol/L: 0.76 (0.59,0.97); P = 0.034], lower autistic symptom load [ß per 10 nmol/L: -0.03 (-0.05,0.00); P = 0.024), and decreased risk of ADHD diagnosis (OR per 10 nmol/L: 0.88 (0.78,0.99); P = 0.033]. High-dose vitamin D3 supplementation was not associated with risk of autism or ADHD. CONCLUSIONS: Higher maternal preintervention 25(OH)D was associated with a decreased risk of autism, lower autistic symptom load, and decreased risk of ADHD diagnosis, but high-dose vitamin D3 supplementation in pregnancy had no effect on risk of autism and ADHD. This trial was registered at clinicaltrials.gov as NCT00856947.

Polyphenol Intake in Pregnant Women on Gestational Diabetes Risk and Neurodevelopmental Disorders in Offspring: A Systematic Review.

The intake of foods containing polyphenols can have a protective role to avoid comorbidities during pregnancy and, at the same time, promote transgenerational health. This review aims to describe the effect of polyphenol intake through supplements or polyphenol-rich foods during pregnancy on the incidence and evolution of gestational diabetes mellitus (GDM), as well as the link with the neurodevelopment of the fetus. Using PRISMA procedures, a systematic review was conducted by searching in biomedical databases (PubMed, Cinahl and Scopus) from January to June 2022. Full articles were screened (n = 419) and critically appraised. Fourteen studies were selected and were divided into two different thematic blocks considering (i) the effect of polyphenols in GDM and (ii) the effect of GDM to mental disorders in the offspring. A positive relationship was observed between the intake of polyphenols and the prevention and control of cardiometabolic complications during pregnancy, such as GDM, which could be related to thwarted inflammatory and oxidative processes, as well as neuronal factors. GDM is related to a greater risk of suffering from diseases related to neurodevelopment, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorder. Further clinical research on the molecule protective mechanism of polyphenols on pregnant women is required to understand the transgenerational impact on fetal neurodevelopment.

How the placenta-brain lipid axis impacts the nutritional origin of child neurodevelopmental disorders: Focus on attention deficit hyperactivity disorder and autism spectrum disorder.

Dietary fish is a rich source of omega-3 (n-3) fatty acids, and as such, is believed to have played an important role in the evolution of the human brain and its advanced cognitive function. The long chain polyunsaturated fatty acids, particularly the n-3 docosahexanoic acid (DHA), are critical for proper neurological development and function. Both low plasma DHA and obesity in pregnancy are associated with neurodevelopmental disorders such as attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in childhood, and n-3 supplementation has been shown to improve symptoms, as reviewed herein. The mechanisms underlying the connection between maternal obesity, n-3 fatty acid levels and offspring's neurological outcomes are poorly understood, but we review the evidence for a mediating role of the placenta in this relationship. Despite promising data that n-3 fatty acid supplementation mitigates the effect of maternal obesity on placental lipid metabolism, few clinical trials or animal studies have considered the neurological outcomes of offspring of mothers with obesity supplemented with n-3 FA in pregnancy.

Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants.

Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth-particularly brain development-that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification-including targeted and adjusted fortification-show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants.

Smoflipid Is Better Than Lipofundin for Long-Term Neurodevelopmental Outcomes in Preterm Infants.

Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospital with corresponding individual medical records up to July 2020 were analyzed. Long-term neurodevelopmental outcomes were defined by the international classification of disease codes -9 or -10. The prevalence of diseases was compared between LIPO and SMOF groups at five and five years old and further analyzed by stratification of 1500 g birth weight. The LIPO and SMOF groups each included 1120 neonates. Epilepsy, cerebral palsy, developmental disorder and attention-deficit hyperactivity disorder (ADHD) were significantly decreased at age two years in the SMOF group, and epilepsy, language delay (LD), ADHD and autism spectrum disorder (ASD) were significantly decreased in the SMOF group at age five years. In children with birth weight < 1500 g, ADHD was decreased in the SMOF group at ages two and five years, and ASD was decreased in the SMOF group at age five years. In children with birth weight ≥ 1500 g, epilepsy, LD and ADHD were decreased in the SMOF group at age two years. LD was decreased in the SMOF group at age five years. We conclude that lipid emulsions with fish oil improve the neurodevelopmental outcomes of children born prematurely.

Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial.

OBJECTIVES: To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN: This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS: In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater. CONCLUSIONS: A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01378273.

The Effects of an Infant Formula Enriched with Milk Fat Globule Membrane, Long-Chain Polyunsaturated Fatty Acids and Synbiotics on Child Behavior up to 2.5 Years Old: The COGNIS Study.

Although early life nutrition influences brain development and mental health, the long-term effects of supplemented infant formula on children´s behavior remain unclear. We analyzed the effects of a bioactive nutrients-enriched-infant formula on children's behavior up to 2.5 years, compared to a standard infant formula or breastfeeding. Current analysis involved 70 children who were fed a standard infant formula (SF, n = 29) or a bioactive compounds enriched-infant formula (EF, n = 41), during their first 18 months of life, and 33 breastfed (BF) children (reference group) participating in the COGNIS study. Behavioral problems were evaluated using the Child Behavior Checklist at 18 months and 2.5 years. Different statistical analyses were performed using SPSS. EF children aged 2.5 years presented fewer pathological affective problems than SF children. Besides, SF children were classified more frequently as bordering on internalizing problems than BF children. Rates of externalizing problems were increased in SF infants compared to EF and BF infants. Higher maternal IQ was found to have beneficial effects on internalizing and total problem rate in their offspring at 18 months of life; finally, higher maternal educational level was related with fewer ADHD problems in children at 18 months, as well as internalizing, externalizing, total and anxiety problems in children aged 2.5 years. Our analysis suggests that enriched infant formula fed infants seem to show fewer behavioral problems up to 2.5 years compared to a standard infant formula-fed infants. In addition to type of early feeding, maternal IQ and educational level seem to play a key role on children behavioral development.

High-Dose Vitamin D Supplementation in Pregnancy and Neurodevelopment in Childhood: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

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 (ß = 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.

In Utero HIV Exposure and the Early Nutritional Environment Influence Infant Neurodevelopment: Findings from an Evidenced Review and Meta-Analysis.

The developing brain is especially vulnerable to infection and suboptimal nutrition during the pre- and early postnatal periods. Exposure to maternal human immunodeficiency virus (HIV) infection and antiretroviral therapies (ART) in utero and during breastfeeding can adversely influence infant (neuro) developmental trajectories. How early life nutrition may be optimised to improve neurodevelopmental outcomes for infants who are HIV-exposed has not been well characterised. We conducted an up-to-date evidence review and meta-analysis on the influence of HIV exposure in utero and during breastfeeding, and early life nutrition, on infant neurodevelopmental outcomes before age three. We report that exposure to maternal HIV infection may adversely influence expressive language development, in particular, and these effects may be detectable within the first three years of life. Further, while male infants may be especially vulnerable to HIV exposure, few studies overall reported sex-comparisons, and whether there are sex-dependent effects of HIV exposure on neurodevelopment remains a critical knowledge gap to fill. Lastly, early life nutrition interventions, including daily maternal multivitamin supplementation during the perinatal period, may improve neurodevelopmental outcomes for infants who are HIV-exposed. Our findings suggest that the early nutritional environment may be leveraged to improve early neurodevelopmental trajectories in infants who have been exposed to HIV in utero. A clear understanding of how this environment should be optimised is key for developing targeted nutrition interventions during critical developmental periods in order to mitigate adverse outcomes later in life and should be a priority of future research.

Effect of Maternal Docosahexaenoic Acid (DHA) Supplementation on Offspring Neurodevelopment at 12 Months in India: A Randomized Controlled Trial.

Intake of dietary docosahexaenoic acid (DHA 22:6n-3) is very low among Indian pregnant women. Maternal supplementation during pregnancy and lactation may benefit offspring neurodevelopment. We conducted a double-blind, randomized, placebo-controlled trial to test the effectiveness of supplementing pregnant Indian women (singleton gestation) from ≤20 weeks through 6 months postpartum with 400 mg/d algal DHA compared to placebo on neurodevelopment of their offspring at 12 months. Of 3379 women screened, 1131 were found eligible; 957 were randomized. The primary outcome was infant neurodevelopment at 12 months, assessed using the Development Assessment Scale for Indian Infants (DASII). Both groups were well balanced on sociodemographic variables at baseline. More than 72% of women took >90% of their assigned treatment. Twenty-five serious adverse events (SAEs), none related to the intervention, (DHA group = 16; placebo = 9) were noted. Of 902 live births, 878 were followed up to 12 months; the DASII was administered to 863 infants. At 12 months, the mean development quotient (DQ) scores in the DHA and placebo groups were not statistically significant (96.6 ± 12.2 vs. 97.1 ± 13.0, p = 0.60). Supplementing mothers through pregnancy and lactation with 400 mg/d DHA did not impact offspring neurodevelopment at 12 months of age in this setting.

Effect of Vitamin D Status during Pregnancy on Infant Neurodevelopment: The ECLIPSES Study.

Vitamin D status during pregnancy is involved in numerous physiological processes, including brain development. In this study, we assess the association between vitamin D status during pregnancy and infant neurodevelopment (cognitive, language, and motor skills). From an initial sample of 793 women (mean age 30.6) recruited before the 12th week of pregnancy, 422 mother-infant pairs were followed up to a postpartum visit. Vitamin D levels were assessed in the first and third trimesters of pregnancy, and socio-demographic, nutritional, and psychological variables were collected. At 40 days postpartum, the Bayley Scales of Infant Development-III were administered to the infants and several obstetrical data were recorded. Independently from several confounding factors, deficient vitamin D levels in the first trimester of pregnancy (<30 nmol/L) predicted a worse performance in cognitive and language skills. Language performance worsened with lower vitamin D levels (<20 nmol/L). In the third trimester, this highly deficient level was also associated with lower motor skills. Vitamin D deficiency was therefore associated with worse neurodevelopmental outcomes. More studies are needed to determine specific recommendations with regard to vitamin D supplementation during pregnancy in order to promote an optimal course for pregnancy and optimal infant neurodevelopment.

The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders.

Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for brain and eye development. Additionally, DHA plays a significant role in mental health throughout early childhood and even into adulthood. In the brain, DHA is important for cellular membrane fluidity, function and neurotransmitter release. Evidence indicates that a low intake of marine omega-3s increases the risk for numerous mental health issues, including Attention Deficit Hyperactivity Disorder (ADHD), autism, bipolar disorder, depression and suicidal ideation. Studies giving supplemental marine omega-3s have shown promise for improving numerous mental health conditions. This paper will review the evidence surrounding marine omega-3s and mental health conditions.

A Randomized Trial of Parenteral Nutrition Using a Mixed Lipid Emulsion Containing Fish Oil in Infants of Extremely Low Birth Weight: Neurodevelopmental Outcome at 12 and 24 Months Corrected Age, A Secondary Outcome Analysis.

OBJECTIVE: To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants. STUDY DESIGN: The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24 months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 12 and 24 months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12 months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P = .71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P = .48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P = .69). At 24 months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P = .17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P = .54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P = .53). CONCLUSIONS: Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.

Valproate and folate: Congenital and developmental risks.

Increasing awareness of the congenital and developmental risks associated with the use of sodium valproate (VPA) has led to recent European guidelines designed to avoid the use of this drug in pregnancy if effective alternative treatments are available. In the general population, it is well established that periconceptual folic acid reduces the risk of neural tube defects (NTDs) and possibly other congenital abnormalities. We here review the evidence 1) that VPA interferes with one-carbon metabolism, including the transport of methylfolate into the brain and the placenta by targeting folate receptors; 2) that VPA effects on the folate metabolic system contribute to congenital and developmental problems associated with VPA exposure; and 3) that genetic factors, notably polymorphisms related to one-carbon metabolism, contribute to the vulnerability to these VPA-induced risks. Based on these facts, we propose that the standard periconceptual use of 400 µg of folic acid may not adequately protect against VPA or other antiepileptic drug (AED)-induced congenital or developmental risks. Pending definitive studies to determine appropriate dose, we recommend up to 5 mg of folic acid periconceptually in at-risk women with the caveat that the addition of supplementary vitamin B12 may also be prudent because vitamin B12 deficiency is common in pregnancy in some countries and is an additional risk factor for developmental abnormalities.

Strategies to Prevent Severe Retinopathy of Prematurity: A 2020 Update and Meta-analysis.

The incidence of retinopathy of prematurity (ROP) is showing an increasing trend in the United States. This may be because of increasing survival rates among extremely preterm infants (<25 weeks' gestation) and targeting higher oxygen saturation. Five randomized clinical trials of low versus high oxygen saturation target ranges found increased mortality in the low oxygen saturation target group and an increased incidence of ROP in the high oxygen saturation target group. The American Academy of Pediatrics recommends using an oxygen saturation target range of 90% to 95% in extremely low-birthweight infants. The change of practice to target this higher oxygen saturation range, from admission until discharge, may be contributing to the increasing incidence of ROP in extremely preterm infants. To decrease the incidence of ROP without increasing mortality, 2 new cohort trials suggest gradually increasing oxygen saturation targets as preterm infants mature. There is evidence that human milk, vitamin A, and omega-3 fatty acids can help, in addition to continuous oxygen saturation monitoring, to decrease the risk of ROP. We review this literature and provide a meta-analysis to evaluate the evidence.

Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women.

BACKGROUND: Mild-to-moderate iodine deficiency, particularly in pregnancy, is prevalent; this is of concern because observational studies have shown negative associations with child neurodevelopment. Although neither the benefits nor the safety of iodine supplementation in pregnancy in areas of mild-to-moderate deficiency are well researched, such supplementation is increasingly being recommended by health authorities in a number of countries. OBJECTIVES: By reviewing the most recent published data on the effects of iodine supplementation in mildly-to-moderately deficient pregnant women on maternal and infant thyroid function and child cognition, we aimed to determine whether the evidence was sufficient to support recommendations in these areas. METHODS: A systematic review of randomized controlled trials (RCTs), non-RCT interventions, and observational studies was conducted. To identify relevant articles, we searched the PubMed and Embase databases. We defined mild-to-moderate iodine deficiency as a baseline median urinary iodine concentration (UIC) of 50-149 µg/L. Eligible studies were included in meta-analyses. RESULTS: In total, 37 publications were included-10 RCTs, 4 non-RCT interventions, and 23 observational studies. Most studies showed no effect of iodine supplementation on maternal or infant thyroid-stimulating hormone and free thyroxine. Most RCTs found that supplementation reduced maternal thyroglobulin and in 3 RCTs, it prevented or diminished the increase in maternal thyroid volume during pregnancy. Three RCTs addressed child neurodevelopment; only 1 was adequately powered. Meta-analyses of 2 RCTs showed no effect on child cognitive [mean difference (MD): -0.18; 95% CI: -1.22, 0.87], language (MD: 1.28; 95% CI: -0.28, 2.83), or motor scores (MD: 0.28; 95% CI: -1.10, 1.66). CONCLUSIONS: There is insufficient good-quality evidence to support current recommendations for iodine supplementation in pregnancy in areas of mild-to-moderate deficiency. Well-designed RCTs, with child cognitive outcomes, are needed in pregnant women who are moderately deficient (median UIC < 100 µg/L). Maternal intrathyroidal iodine stores should be considered in future trials by including appropriate measures of preconceptional iodine intake.This review was registered at www.crd.york.ac.uk/prospero as CRD42018100277.

Do infants of breast-feeding mothers benefit from additional long-chain PUFA from fish oil? A 6-year follow-up.

Fish-oil supplements are marketed as enhancing intelligence and cognitive performance. However, empirical data concerning the utility of these products in healthy term infants are mixed, particularly with respect to lasting effects into childhood. We evaluated whether fish-oil supplementation during infancy leads to better neurocognitive/behavioural development at 6 years. We conducted a double-blind randomised controlled trial of supplementation with n-3 long-chain PUFA in 420 healthy term infants. Infants received either fish oil (containing at least 250 mg DHA and at least 60 mg EPA) or placebo (olive oil) daily from birth to 6 months of age. Neurodevelopmental follow-up was conducted at a mean age of 6 years (sd 7 months), whereby 335 children were assessed for language, executive functioning, global intelligence quotient and behaviour. No significant differences were observed between the groups for the main neurocognitive outcomes. However in parent-report questionnaire, fish-oil supplementation was associated with negative externalising (P = 0·035, d = 0·24) and oppositional/defiant behaviour (P = 0·006, d = 0·31), particularly in boys (P = 0·01, d = 0·45; P = 0·004, d = 0·40). Our results provide evidence that fish-oil supplementation to predominantly breast-fed infants confers no significant cognitive or behavioural benefit to children at 6 years.

How complementary feeding in infants affects allergies, chronic disease, and neurodevelopment.

Recommendations for the timing and type of complementary foods to introduce to infants have recently changed. These changes are due to increased understanding of how these foods affect the development of food allergies, risk for obesity and other chronic diseases, and infant neurodevelopment. This article brings the current recommendations and recent research together and organizes them for clinicians in pediatrics to enable them to understand and convey this information to parents of infants.

Effect of prebiotic and probiotic supplementation on neurodevelopment in preterm very low birth weight infants: findings from a meta-analysis.

BACKGROUND: Preterm very low birth weight (VLBW) infants are at risk of gut dysbiosis and neurodevelopmental deficits. Prebiotics and probiotics may modulate gut microbiota and influence brain functions. This review synthesizes literature on effect of prebiotic and/or probiotic supplementation in preterm VLBW on their neurodevelopmental outcomes. METHODS: Search was done using PubMed and CENTRAL. Randomized controlled trials (RCTs) in preterm infants (<37 weeks gestation) and/or infants with birth weight <1500 g that evaluated the effect of prebiotic and/or probiotic supplementation on neurodevelopmental outcomes were included. Weighted mean difference in cognitive and motor scores; pooled relative risks for cognitive and motor impairment, cerebral palsy, hearing, and visual impairment were estimated. Quality of evidence was assessed using the GRADE criteria. RESULTS: Out of 275 articles identified, seven were included for review. All, except one, were done in preterms <33 weeks of gestation. Age of assessment of outcomes was ≥18-22 months of corrected age in five studies. Interventions did not decrease or increase the risk of cognitive and motor impairment, cerebral palsy, visual, and hearing impairment. Quality of evidence was "low" to "very low." CONCLUSIONS: Limited evidence from RCTs does not demonstrate a difference in neurodevelopmental outcomes between prebiotic/probiotic treated and untreated control groups.

Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model.

Maternal infection during pregnancy is considered a key risk factor for developing schizophrenia in offspring. There is evidence that maternal exposure to infectious agents is associated with fetal zinc deficiency. Due to the essential role of zinc in brain function and development, in the present study, we activated maternal immune system using lipopolysaccharide (LPS) as a model of schizophrenia to examine whether zinc supplementation throughout pregnancy can reverse LPS-induced deleterious effects. To test the hypothesis, pregnant rats were treated with intraperitoneal injection of either saline or LPS (0.5 mg/kg) at gestational day 15 and 16, and zinc supplementation (30 mg/kg) was administered throughout pregnancy by gavage. At postnatal day 60, Y-maze was used to evaluate working memory of offspring. Moreover, the expression levels of catechol O-methyltransferase (COMT) and glutamate decarboxylase 67 (GAD67) were measured in the frontal cortex of the brain samples. Only male offspring prenatally exposed to LPS showed a significant impairment in working memory. In addition, prenatal LPS exposure causes a moderate decrease in GAD67 expression level in the male pups, while COMT expression was found unchanged. Interestingly, zinc supplementation restored the alterations in working memory as well as GAD67 mRNA level in the male rats. No alteration was detected for neither working memory nor COMT/GAD67 genes expression in female offspring. This study demonstrates that zinc supplementation during pregnancy can attenuate LPS-induced impairments in male pups. These results support the idea to consume zinc supplementation during pregnancy to limit neurodevelopmental deficits induced by infections in offspring.