Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

BACKGROUND: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development. OBJECTIVES: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024). RESULTS: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11). CONCLUSIONS: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. CONCLUSIONS: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Small-quantity lipid-based nutrient supplements for the prevention of child malnutrition and promotion of healthy development: overview of individual participant data meta-analysis and programmatic implications.

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12-14% lower prevalence of stunting, wasting, and underweight; were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

Gestational weight gain and newborn anthropometric outcomes in rural Bangladesh.

Low gestational weight gain (GWG) is a known predictor of fetal growth restriction in higher income countries, but there is little information on this association in lower income countries. Our objective is to describe the association between GWG and birth outcomes among pregnant women in rural Bangladesh. Pregnant women were identified in a community-based programme and enrolled into the study at an average of 13 weeks' gestation (n = 4,011). Maternal weight and height were measured at enrolment, maternal weight was measured at 36 weeks' gestation, and newborns were measured after birth. Rate of GWG (g/weeks) was calculated, and women were categorized as having adequate or inadequate GWG (Institute of Medicine recommendations). Newborn anthropometric outcomes included weight-for-age z score (WAZ), length-for-age z score (LAZ), head-circumference-for-age z score (HCZ), body mass index (BMI)-for-age z score (BMIZ), low birthweight (LBW < 2,500 g), WAZ < -2, LAZ < -2, HCZ < -2, BMIZ < -2, and small for gestational age (SGA: <10th percentile). Multivariate models were adjusted for confounders. Only 26% of the 2,562 women in these analyses had adequate GWG. Compared with newborns of women with inadequate GWG, infants of women with adequate GWG had a lower risk of adverse anthropometric outcomes (relative risk [95% confidence interval]: LBW = 0.68 [0.59, 0.80], LAZ < -2 = 0.64 [0.51, 0.80], HCZ < -2 = 0.75 [0.60, 0.93], BMIZ < -2 = 0.70 [0.59, 0.83], and SGA = 0.80 [0.73, 0.86]), but there was no significant difference in mean (SE) duration of gestation, 39.7 (0.08) versus 39.7 (0.05) weeks. In this population, GWG rate is a strong predictor of newborn anthropometric outcomes, but not duration of gestation.

Food Aid for Nutrition: Narrative Review of Major Research Topics Presented at a Scientific Symposium Held October 21, 2017, at the 21st International Congress of Nutrition in Buenos Aires, Argentina.

BACKGROUND: Food aid is a valuable tool for meeting global nutrition goals, particularly for vulnerable populations of children and reproductive-aged women. On October 21, 2017, the Food Aid Quality Review Project hosted a scientific symposium at the 21st International Congress on Nutrition in Buenos Aires, Argentina, to take stock of what the global community has learned about selected topics in the research literature on food aid used to address malnutrition. OBJECTIVE: This article presents the discussion that took place during the symposium, which was guided by presentations by 6 experts from the field of nutrition, food aid, and humanitarian response. CONCLUSION: The recent upsurge in research on food aid has advanced the collective knowledge of what food aid products and programs work for addressing nutrition, but there is much more to learn. Presentations in this symposium called for further inquiry on (1) different and novel food aid formulations, (2) the cost-effectiveness of products and programs, and (3) market-based approaches to food assistance. Continuing to expand the evidence base on these topics is critical to improving global nutrition programs.

The Relation between Breast Milk Sodium to Potassium Ratio and Maternal Report of a Milk Supply Concern.

We report that, among exclusively breastfeeding mothers at day 7 postpartum, those with milk supply concerns were significantly more likely to exhibit biochemical evidence of less progress toward mature lactation (elevated ratio of breast milk sodium to potassium concentration). Furthermore, an elevated ratio of breast milk sodium to potassium concentration was predictive of early weaning.

Effects of varied energy density of complementary foods on breast-milk intakes and total energy consumption by healthy, breastfed Bangladeshi children

Information is needed to design studies of the effects of complementary feeding regimens on children's intakes of complementary foods (CFs) and breast milk...

In-hospital formula use increases early breastfeeding cessation among first-time mothers intending to exclusively breastfeed.

OBJECTIVE: To evaluate in-hospital formula supplementation among first-time mothers who intended to exclusively breastfeed and determined if in-hospital formula supplementation shortens breastfeeding duration after adjusting for breastfeeding intention. STUDY DESIGN: We assessed strength of breastfeeding intentions prenatally in a diverse cohort of expectant primiparae and followed infant feeding practices through day 60. Among mothers planning to exclusively breastfeed their healthy term infants for ≥1 week, we determined predictors, reasons, and characteristics of in-hospital formula supplementation, and calculated the intention-adjusted relative risk (ARR) of not fully breastfeeding days 30-60 and breastfeeding cessation by day 60 with in-hospital formula supplementation (n = 393). RESULTS: Two hundred ten (53%) infants were exclusively breastfed during the maternity stay and 183 (47%) received in-hospital formula supplementation. The most prevalent reasons mothers cited for in-hospital formula supplementation were: perceived insufficient milk supply (18%), signs of inadequate intake (16%), and poor latch or breastfeeding (14%). Prevalence of not fully breastfeeding days 30-60 was 67.8% vs. 36.7%, ARR 1.8 (95% CI, 1.4-2.3), in-hospital formula supplementation vs exclusively breastfed groups, respectively, and breastfeeding cessation by day 60 was 32.8% vs. 10.5%, ARR 2.7 (95% CI, 1.7-4.5). Odds of both adverse outcomes increased with more in-hospital formula supplementation feeds (not fully breastfeeding days 30-60, P = .003 and breastfeeding cessation, P = .011). CONCLUSIONS: Among women intending to exclusively breastfeed, in-hospital formula supplementation was associated with a nearly 2-fold greater risk of not fully breastfeeding days 30-60 and a nearly 3-fold risk of breastfeeding cessation by day 60, even after adjusting for strength of breastfeeding intentions. Strategies should be sought to avoid unnecessary in-hospital formula supplementation and to support breastfeeding when in-hospital formula supplementation is unavoidable.

Determinants of exclusive breastfeeding in a cohort of primiparous periurban peruvian mothers.

The authors aimed to identify factors associated with exclusive breastfeeding (EBF) among 117 Peruvian mothers planning to breastfeed exclusively. Data were collected on days 0 and 3, and months 1, 3, and 6. Exclusive breastfeeding status was evaluated with a 24-hour recall of infant diet. Exclusive breastfeeding rates were 74%, 72%, and 35% at 1, 3, and 6 months, respectively. At 3 months, lower maternal education, greater breastfeeding frequency (day 3), greater breast pain (day 3), and depot medroxyprogesterone acetate use (3 months) were associated with EBF, after adjusting for EBF intentions. At 6 months, greater infant birth weight and mother-not employed were associated with EBF, after controlling for EBF intentions. More educated and working mothers, and infants with lower birth weight should be targeted in interventions to promote EBF in urban Peru. Research is also warranted to explore the factors linking depot medroxyprogesterone acetate use and breast pain with EBF duration.

Risk factors for early lactation problems among Peruvian primiparous mothers.

The aim of this study was to determine the incidence and risk factors for early lactation problems [suboptimal infant breastfeeding behaviour (SIBB), delayed onset of lactogenesis (OL) and excessive neonatal weight loss] among mother-infant pairs in Lima, Peru. All primiparous mothers who gave birth to a healthy, single, term infant at a government hospital in a peri-urban area of Lima during the 8-month recruitment period were invited to participate in the study. Data were collected at the hospital (day 0) and during a home visit (day 3). Infant breastfeeding behaviour was evaluated using the Infant Breastfeeding Assessment Tool; SIBB was defined as < or = 10 score. OL was determined by maternal report of breast fullness changes; delayed OL was defined as perceived after 72 h. Excessive neonatal weight loss was defined as > or = 10% of birthweight by day 3. One hundred seventy-one mother-infant pairs participated in the study. SIBB prevalence was 52% on day 0 and 21% on day 3; it was associated with male infant gender (day 0), < 8 breastfeeds during the first 24 h (days 0 and 3), and gestational age < 39 weeks (day 3). Delayed OL incidence was 17% and was associated with infant Apgar score < 8. Excessive neonatal weight loss occurred in 10% of neonates and was associated with maternal overweight and Caesarean-section delivery. Early lactation problems may be influenced by modifiable factors such as delivery mode and breastfeeding frequency. Infant status at birth and maternal characteristics could indicate when breastfeeding dyads need extra support.

Early umbilical cord clamping contributes to elevated blood lead levels among infants with higher lead exposure.

OBJECTIVE: To investigate whether infant iron status, modified by umbilical cord clamping time and infant feeding mode, affected infant blood lead concentration at 6 months of age. STUDY DESIGN: Participants were a subset of women and their infants randomized to receive early (10 seconds) or delayed (2 minutes) umbilical cord clamping and were monitored to 6 months postpartum in Mexico City. Iron and lead status was analyzed in maternal, placental, and 6-month infant blood samples. Baseline maternal lead exposure data and infant feeding data at 2, 4, and 6 months were collected. RESULTS: In the total sample, maternal blood lead concentration, infant ferritin, and breast-feeding practices predicted infant blood lead concentration. Among infants with higher placental blood lead concentration and breast-fed infants not receiving any iron-fortified formula or milk at 6 months, early clamping increased infant blood lead concentration, an effect mediated in part via decreased infant iron status. CONCLUSIONS: Early cord clamping, by decreasing infant iron status, contributes to higher blood lead concentrations at 6 months of age among infants at high risk.

Effect of timing of umbilical cord clamping on iron status in Mexican infants: a randomised controlled trial.

BACKGROUND: Delayed clamping of the umbilical cord increases the infant's iron endowment at birth and haemoglobin concentration at 2 months of age. We aimed to assess whether a 2-minute delay in the clamping of the umbilical cord of normal-weight, full-term infants improved iron and haematological status up to 6 months of age. METHODS: 476 mother-infant pairs were recruited at a large obstetrics hospital in Mexico City, Mexico, randomly assigned to delayed clamping (2 min after delivery of the infant's shoulders) or early clamping (around 10 s after delivery), and followed up until 6 months postpartum. Primary outcomes were infant haematological status and iron status at 6 months of age, and analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00298051. FINDINGS: 358 (75%) mother-infant pairs completed the trial. At 6 months of age, infants who had delayed clamping had significantly higher mean corpuscular volume (81.0 fL vs 79.5 fL 95% CI -2.5 to -0.6, p=0.001), ferritin (50.7 mug/L vs 34.4 mug/L 95% CI -30.7 to -1.9, p=0.0002), and total body iron. The effect of delayed clamping was significantly greater for infants born to mothers with low ferritin at delivery, breastfed infants not receiving iron-fortified milk or formula, and infants born with birthweight between 2500 g and 3000 g. A cord clamping delay of 2 minutes increased 6-month iron stores by about 27-47 mg. INTERPRETATION: Delay in cord clamping of 2 minutes could help prevent iron deficiency from developing before 6 months of age, when iron-fortified complementary foods could be introduced.

Iron supplements reduce erythrocyte copper-zinc superoxide dismutase activity in term, breastfed infants.

AIM: To investigate whether iron supplements compromise copper status in infants. METHODS: 214 healthy, term, breastfed Swedish and Honduran infants were randomized to (1) iron supplements (1 mg/kg/d) from 4-9 mo of age, (2) iron supplements from 6-9 mo, or (3) placebo. Blood samples were obtained at 4, 6, and 9 mo and analyzed for plasma copper (p-Cu) and, at 9 mo, for copper/zinc-dependent superoxide dismutase (CuZn-SOD) activity. RESULTS: P-Cu increased with infant age. At 9 mo, Honduran infants had significantly higher p-Cu (1.40+/-0.29 vs 1.09+/-0.22 mg/l, p<0.001) and CuZn-SOD activity (1.09+/-0.29 vs 0.93+/-0.21 U/mg Hb, p<0.001) than Swedish infants. Infants receiving iron supplements from 4-9 mo had significantly lower CuZn-SOD at 9 mo of age (0.95+/-0.27 vs 1.08+/-0.24 U/mg Hb, p=0.023) than those receiving placebo. CONCLUSION: There is a physiologic increase in p-Cu during the first 9 mo of life. Differences in copper status between Swedish and Honduran infants may be due to genetic or nutritional differences. Iron supplementation decreases CuZn-SOD activity, probably due to a negative effect on copper status. Possible clinical implications remain to be elucidated.

Infant weight-for-length is positively associated with subsequent linear growth across four different populations.

Several studies have documented that length gain often lags behind weight gain during infancy and early childhood, suggesting that linear growth is partly regulated by initial body mass or fatness. To investigate this hypothesis, we analysed data from four longitudinal studies on growth of infants in the first 12 months: (1) U.S. breast-fed and formula-fed infants (n = 89); (2) breast-fed infants in Ghana (n = 190); (3) normal birthweight, breast-fed infants in Honduras (n = 108); and (4) term, low-birthweight breast-fed infants in Honduras (n = 119). The dependent variable was length gain during each 3-month interval (1- 4, 2-5, 3-6, 4-7, 5-8, 6-9, 7-10, 8-11 and 9-12 months). Three main independent variables were examined: initial weight-for-length z-score (W/L), weight change during the prior 3 months, and initial skinfold thickness. Controlling for maternal height, infant sex, and initial length-for-age z-score, length gain was positively correlated with initial W/L and prior weight change during all age intervals and with initial skinfold thickness at 3 and 4 months (r = 0.15-0.36; P < 0.01). There was no evidence of a threshold effect. These associations were evident in all four populations, in both boys and girls, and in breast-fed and formula-fed infants. The consistency of this relationship across studies supports the hypothesis that linear growth is partly regulated by initial body mass or fatness in infants.

Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low-birthweight, breast-fed infants in Honduras.

There is little information on the risk of micronutrient deficiencies during the period of exclusive breast-feeding. We evaluated this among term, low-birthweight (LBW; 1500-2500 g) infants in Honduras. Mother-infant pairs were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, infants were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or be given iron-fortified complementary foods (rice, chicken, fruits, and vegetables) from 4 to 6 mo while continuing to breast-feed (SF, n = 60). Blood samples were collected at 2, 4, and 6 mo and analyzed for hemoglobin (Hb), hematocrit, plasma ferritin, % transferrin saturation, vitamin A, vitamin B-12, folate, zinc, and erythrocyte folate. Infants with Hb < 100 g/L at 2 or 4 mo were given medicinal iron supplements for 2 mo; the proportion administered iron drops did not differ significantly between groups. There was no significant effect of complementary foods on indices of vitamin A, B-12, folate, or zinc status. Among infants not given medicinal iron at 4-6 mo, iron status was higher in the SF group than the EBF group. In those given medicinal iron at 4-6 mo, iron status was higher in the EBF group, suggesting that complementary foods interfered with iron utilization. About half of the infants were anemic by 2 mo, before the age when complementary foods would be recommended. This supports the recommendation that LBW infants should receive iron supplementation in early infancy. Given that infants given iron supplements did not benefit from complementary foods at 4-6 mo, we conclude that exclusive breast-feeding for 6 mo (with iron supplementation) can be recommended for term, LBW infants.