PARTICIPANTS: A total of 1210 Japanese lactating women who satisfied the inclusion criteria, were invited across the country at various participating sites, between 2014 and 2019. Finally a total of 1122 women were enrolled in this study.
FINDINGS TO DATE: Among 1122 eligible participants, mean age at delivery was 31.2 (SD 4.4) years and mean prepregnancy BMI was 20.8 (SD 2.7). Among these women, 35% were previously nulliparous and 77.7% had college, university or higher education. The mean gestational period was 39.0 (SD 1.3) weeks. Caesarean section was reported among 11.9%; mean infant birth weight was 3082 (SD 360) g. Of the infants, 53.7% were male. Overall, our participants appeared to be healthier than the general population in Japan. Analyses of the 1079 eligible human milk samples obtained at the first and second months postpartum showed the following composition: carbohydrate, 8.13 (SD 0.32) g/100 mL; fat, 3.77 (SD 1.29) g/100 mL; and crude protein, 1.20 (SD 0.23) g/100 mL. We also analysed osteopontin, fatty acid, vitamin D and phospholipid levels in limited subcohorts of the samples.
FUTURE PLANS: Follow-up surveys will be conducted to obtain milk samples every 2 months for 12 months and to investigate mother and child health until the children reach 5 years of age. These will be completed in 2024. We plan to longitudinally analyse the composition of macronutrients and various bioactive factors in human milk and investigate the lifestyle and environmental factors that influence breastfeeding practices, maternal and child health, and child development.
TRIAL REGISTRATION NUMBER: UMIN000015494; pre-results.
METHODS: Male rat offspring from female Sprague-Dawley rats fed with a high-fat diet (HFD) alone, HFD + GBR, or HFD + GABA extract throughout pregnancy and lactation were weaned 4 weeks after delivery and followed up for 8 weeks. A biochemical analysis and an assessment of the hepatic expression of insulin signaling genes were performed.
RESULTS: The results showed that intrauterine exposure to HFD caused metabolic perturbations in rat offspring which gravitated towards insulin resistance even though the rat offspring did not consume an HFD. GBR and GABA attenuated the HFD-induced changes by underlying regulation of the insulin signaling genes.
CONCLUSIONS: The results suggest that intake of GBR and GABA during pregnancy and lactation can influence the programming of genes in rat offspring, thereby enhancing insulin sensitivity.
METHODS: We randomly selected 500 Nepali mother-infant pairs and measured maternal intake and infant and maternal vitamin B12 status using plasma cobalamin, total plasma homocysteine, and methylmalonic acid concentrations. We revisited available children when they were 5 years old and measured growth. The associations between intake and maternal and infant markers of vitamin B12 and growth were estimated in multiple linear regression models adjusting for relevant confounders (n = 331).
RESULTS: Maternal vitamin B12 intake and status and vitamin B12 status in infancy predicted linear growth at 5 years of age, but not during infancy. Each microgram increase in the vitamin B12 intake of the mother during infancy was associated with an increase in height of 0.4 (0.2, 0.6) height-for-age z-scores and 1.7 (0.7, 2.7) cm around the child's fifth birthday.
CONCLUSION: Vitamin B12 status and intake in early life is an important determinant for linear growth at school age. Our findings should be verified in randomized, placebo controlled trials before translated into public health recommendations.
OBJECTIVES: To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants.
SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers.
DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS: We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia.
AUTHORS' CONCLUSIONS: For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.