Maternal Lipid-based Nutrient Supplements Research Articles

Impact of Maternal Nutritional Supplementation during Pregnancy and Lactation on the Infant Gut or Breastmilk Microbiota: A Systematic Review.

Recent evidence indicates that maternal dietary intake, including dietary supplements, during pregnancy and lactation may alter the infant gut or breastmilk microbiota, with implications for health outcomes in both the mother and infant. To review the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota a systematic literature search was conducted. A total of 967 studies published until February 2020 were found, 31 were eligible and 29 randomized control trials were included in the qualitative synthesis. There were 23 studies that investigated the effects of probiotic supplementation, with the remaining studies investigating vitamin D, prebiotics or lipid-based nutrient supplements (LNS). The effects of maternal nutritional supplementation on the infant gut microbiota or breastmilk microbiota were examined in 21 and 12 studies, respectively. Maternal probiotic supplementation during pregnancy and lactation generally resulted in the probiotic colonization of the infant gut microbiota, and although most studies also reported alterations in the infant gut bacterial loads, there was limited evidence of effects on bacterial diversity. The data available show that maternal probiotic supplementation during pregnancy or lactation results in probiotic colonization of the breastmilk microbiota. There were no observed effects between probiotic supplementation and breastmilk bacterial counts of healthy women, however, administration of Lactobacillus probiotic to nursing women affected by mastitis was associated with significant reductions in breastmilk Staphylococcal loads. Maternal LNS supplementation during pregnancy and lactation increased bacterial diversity in the infant gut, whilst vitamin D and prebiotic supplementation did not alter either infant gut bacterial diversity or counts. Heterogeneity in study design precludes any firm conclusions on the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota, warranting further research.

The impact of maternal supplementation during pregnancy and the first 6 months postpartum on the growth status of the next child born after the intervention period: Follow-up results from Bangladesh and Ghana.

Pregnancy and breastfeeding make demands on maternal nutrient stores. The extent of depletion and the degree to which nutrient stores are replenished between pregnancies has implications for a mother's nutritional status at conception of the subsequent child and therefore that child's birth outcomes and growth. Using follow‐up data collected several years after a randomized effectiveness trial conducted in rural Bangladesh and a randomized efficacy trial conducted in semiurban Ghana, we evaluated the impact of maternal supplementation with small‐quantity lipid‐based nutrient supplements (LNS) or multiple micronutrients (MMN) through pregnancy (the index pregnancy) and 6 months postpartum on the growth status of the next living younger sibling conceived and born after the index pregnancy. In both Bangladesh (n = 472 younger siblings) and Ghana (n = 327 younger siblings), there were no overall differences in the growth status or the prevalence of undernutrition among younger siblings whose mothers had received LNS (or MMN, Ghana only) during and after the index pregnancy compared with the younger siblings of mothers who had received iron plus folic acid (IFA) during the index pregnancy (Ghana) or during and for 3 months after the index pregnancy (Bangladesh). These findings do not indicate that preconception nutrition interventions do not improve child growth. Rather, they suggest that any benefits of maternal LNS or MMN supplementation during one pregnancy and for 6 months postpartum are unlikely to extend to the growth of her next child beyond any effects due to IFA alone.

Lipid-based nutrient supplements and all-cause mortality in children 6–24 months of age: a meta-analysis of randomized controlled trials

Undernutrition is associated with an elevated risk of mortality among children in low- and middle-income countries. Small-quantity lipid-based nutrient supplements (LNS) have been evaluated as a method to prevent undernutrition and improve infant development, but the effects on mortality are unknown. Our objective was to evaluate the effect of LNS on all-cause mortality among children 6-24 mo old. We conducted a systematic review and meta-analysis of randomized controlled trials of LNS designed to prevent undernutrition, with or without other interventions. Literature was searched in May 2019 and trials were included if they enrolled children between 6 and 24 mo old and the period of supplementation lasted ≥6 mo. We extracted data from participant flow diagrams and contacted study investigators to request data. We conducted a meta-analysis to produce summary RR estimates. We identified 18 trials conducted in 11 countries that enrolled 41,280 children and reported 586 deaths. The risk of mortality was lower in the LNS arms than in the non-LNS comparison arms (RR: 0.73; 95% CI: 0.59, 0.89; 13 trials). Estimates were similar when trials with maternal LNS intervention arms were added or when alternative formulations of LNS were excluded. The results appeared stronger in trials in which LNS were compared with passive control arms. Excluding these contrasts and only comparing multicomponent arms with LNS groups and comparison groups that contained all the same components without LNS attenuated the effect estimate (RR: 0.82; 95% CI: 0.61, 1.10). LNS provided for the prevention of undernutrition may reduce the risk of mortality, but more trials with appropriate comparison groups allowing isolation of the effect of LNS alone are needed.This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019128718.

Provision of Pre- and Postnatal Nutritional Supplements Generally Did Not Increase or Decrease Common Childhood Illnesses in Bangladesh: A Cluster-Randomized Effectiveness Trial

Nutritional interventions may affect child morbidity. The aim of this study was to examine whether providing lipid-based nutrient supplements (LNSs) to pregnant and lactating women or LNS or micronutrient powder (MNP) to their infants influences child morbidity. In a 4-arm cluster-randomized effectiveness trial, participants enrolled at ≤20 weeks of gestation (n=4011) received: 1) maternal LNSs until 6 mo postpartum and child LNSs from 6-24 mo of age (LNS-LNS); 2) iron and folic acid (IFA) until 3 mo postpartum and child LNSs at 6-24 mo (IFA-LNS); 3) IFA (as above) and child MNP at 6-24 mo (IFA-MNP); or 4) IFA and no child supplement (IFA-Control). At 6, 12, 18, and 24 mo of age, we collected information on acute lower and upper respiratory infection (ALRI/AURI), diarrhea, and fever in the previous 14 d, and on episodes of illness in the previous 6 mo. At 6 mo, prevalence of ALRI, fever, or diarrhea in the previous 14 d (17.6%, 18.9% and 6.8%, respectively) did not differ between infants of women who received LNS and infants of women who received IFA, but prevalence of AURI was lower in the LNS-LNS group than in all other groups combined (27.7% compared with 31.7%; OR: 0.83; 95% CI: 0.70, 0.99). At 12, 18, and 24 mo, the 4 arms did not differ in prevalence of fever (∼18.3%) or ALRI (≤15%) in the previous 14 d, but prevalence of AURI at 12 mo was lower in IFA-LNS than in IFA-Control infants (27.6% compared with 33.9%, OR: 0.74; 95% CI: 0.56, 0.99). The mean±SD number of diarrhea episodes in the previous 6 mo was significantly higher among IFA-LNS than among IFA-Control infants at 6-12 (0.46±0.04 compared with 0.33±0.03) and 12-18 (0.45±0.03 compared with 0.33±0.02) mo. No other pairwise group differences were significant. Providing LNSs to women or LNSs or MNP to children generally did not increase or decrease childhood illnesses. This trial was registered at clinicaltrials.gov as NCT01715038.

Maternal and Infant Lipid-Based Nutritional Supplementation Increases Height of Ghanaian Children at 4–6 Years Only if the Mother Was Not Overweight Before Conception

ABSTRACTBackgroundFew studies have evaluated the long-term effects of nutritional supplementation during the first 1000 d of life. We previously reported that maternal and child lipid-based nutrient supplements (LNS) increased child length by 18 mo.ObjectiveThe aim of this study was to examine the effects of LNS on later growth and body composition at 4–6 y of age.DesignThis was a follow-up of children in the International Lipid-based Nutrient Supplements (iLiNS)-DYAD trial in Ghana. Women (n = 1320) at ≤20 weeks of gestation were randomly assigned to: 1) iron and folic acid during pregnancy and 200 mg calcium/d for 6 mo postpartum, 2) multiple micronutrients (1–2 RDA of 18 vitamins and minerals) during both periods, or 3) maternal LNS during both periods plus child LNS from 6 to 18 mo. At 4–6 y, we compared height, height-for-age z score (HAZ), and % body fat (deuterium dilution method) between the LNS group and the 2 non-LNS groups combined.ResultsData were available for 961 children (76.5% of live births). There were no significant differences between LNS compared with non-LNS groups in height [106.7 compared with 106.3 cm (mean difference, MD, 0.36; P = 0.226)], HAZ [−0.49 compared with −0.57 (MD = 0.08; P = 0.226)], stunting (< -2 SD) [6.5 compared with 6.3% (OR = 1.00; P = 0.993)], or % body fat [15.5 compared with 15.3% (MD = 0.16; P = 0.630)]. However, there was an interaction with maternal prepregnancy BMI (kg/m2) (P-interaction = 0.046 before correction for multiple testing): among children of women with BMI < 25 , LNS children were taller than non-LNS children (+1.1 cm, P = 0.017), whereas there was no difference among children of women with BMI ≥ 25 (+0.1 cm; P = 0.874).ConclusionsThere was no overall effect of LNS on height at 4–6 y in this cohort, which had a low stunting rate, but height was greater in the LNS group among children of nonoverweight/obese women. There was no adverse impact of LNS on body composition. This trial was registered at clinicaltrials.gov as NCT00970866.

Maternal Lipid‐based Nutrient Supplements (LNS) Did Not Reduce Depressive Symptoms During Pregnancy and Lactation in Rural Bangladesh

BackgroundMaternal depression is a major global burden affecting not only women but also their children. Maternal intake and serum levels of polyunsaturated fatty acids have been inconsistently associated with reduced perinatal depression.ObjectiveWe aimed to determine the effects of lipid‐based nutrient supplement (LNS), containing macro and micronutrients, including essential fatty acids (4.6 g of linoleic acid and 0.6 g of alpha‐linolenic acid), on maternal depressive symptoms at 36 weeks of gestation and 6 months postpartum.MethodsWe conducted a cluster‐randomized effectiveness trial in Bangladesh (the Rang‐Din Nutrition Study), where women received either iron &amp; folic acid (IFA) or LNS during pregnancy and the first three or six months postpartum, respectively. Maternal depressive symptoms were assessed by trained interviewers using a validated Bangla version of the Edinburgh Postnatal Depression Scale (EPDS‐B) at 36 weeks of gestation (n=2937) and 6 months postpartum (n=3510) at local antenatal clinics. Outcomes included the EPDS score (range: 0–30) and prevalence of depressive symptoms, defined as an EPDS score ≥10.ResultsOverall median (interquartile range) EPDS scores were 2 (0–4) and 1(0–3) at 36 weeks of gestation and 6 months postpartum, respectively. Prevalence of reported maternal depressive symptoms was low in this population (2.1% at 36 weeks of gestation and 2.7% at 6 months postpartum). Cluster‐adjusted intention‐to‐treat analyses indicated no significant differences by treatment group in EPDS scores (square root back transformed Means ± SEs; 36 weeks of gestation: 1.4 ± 0.1 vs 1.5 ± 0.1 in the LNS and IFA groups, respectively, p=0.22; 6 months postpartum: 1.2 ± 0.1 vs 1.3 ± 0.1 in the LNS and IFA groups, respectively, p=0.12) or prevalence of depressive symptoms (36 weeks of gestation: 2.5% in the LNS and 2.0% in the IFA group, p=0.42; 6 months postpartum: 2.8% in the LNS and 2.6% in the IFA group, p=0.68). Per‐protocol analysis including only those who consumed the supplements regularly indicated lower EPDS scores in the LNS compared to the IFA group at 36 weeks of gestation (1.2 ± 0.1 vs 1.5 ± 0.1, respectively, p=0.01). No other significant differences by treatment group were observed in per‐protocol results.ConclusionIn Bangladesh, maternal LNS did not show an effect on reported depressive symptoms in late pregnancy and at 6 months postpartum. Reports of depressive symptoms in this population were less common than in other populations in Bangladesh, which may have limited our ability to detect effects of LNS.Support or Funding InformationU.S. Agency for International Development (USAID)'s Food and Nutrition Technical Assistance (FANTA) III Project, managed by FHI 360.

Antiretroviral Treatment Is Associated With Iron Deficiency in HIV-Infected Malawian Women That Is Mitigated With Supplementation, but Is Not Associated With Infant Iron Deficiency During 24 Weeks of Exclusive Breastfeeding.

In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (through fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. The Breastfeeding, Antiretrovirals, and Nutrition study was a randomized controlled trial conducted in Lilongwe, Malawi, from 2004 to 2010. HIV-infected mothers (CD4 >200 cells/μL) and their infants were randomly assigned to 28-week interventions: maternal LNS/maternal ARV (n = 424), maternal LNS/infant ARV (n = 426), maternal LNS (n = 334), maternal ARV (n = 425), infant ARV (n = 426), or control (n = 334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n = 537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR), and ferritin were tested with linear and Poisson regression. In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR >8.3 mg/L) (risk ratio: 3.1, P < 0.01), but not in ARV-treated mothers receiving LNS (P = 0.17). LNS without ARVs was not associated with iron deficiency or anemia (P > 0.1). In subsample infants, interventions were not associated with impaired iron status (all P > 0.1). Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not seem to influence infant iron status; however, extended use needs to be evaluated.

Associations between Linear Growth and Language Development in Ghana, Malawi, and Burkina Faso

Stunted growth and brain development are linked, though the strength of the association varies between contexts and few studies have examined moderating factors.Our objectives were 1) to examine the strength of the association between linear growth and language development in the iLiNS Project in Ghana (n=909), Burkina Faso (n=1116), and two cohorts in Malawi (n=1124 and 569) and 2) to examine the relative strength of the association during different periods of development. Participants were randomized to receive various formulations of lipid‐based nutrient supplements (LNS) during pregnancy and infancy or infancy alone, or to control groups. We examined the association between 18‐mo language scores and a) 18‐mo length‐for‐age z‐score (LAZ), b) LAZ at age 6 or 9 mo and c) the change in LAZ between infancy (6 or 9 mo) and 18 mo.The coefficients for the associations of language with concurrent LAZ were significant and similar across cohorts (B=0.10‐0.21), and the coefficients were similar for the periods before and after 6 or 9 mo (B=0.09‐0.30), except when maternal LNS was provided. Maternal LNS eliminated the association between language and 6‐mo LAZ (B=0.00‐0.03), but the association with change in LAZ from 6‐18 mo remained significant whether or not infant LNS was provided (B=0.09‐0.30).Linear growth faltering both before and after 6‐9 mo is linked with poorer language development, but the link for the early interval is attenuated by maternal LNS.Funded by the Bill &amp; Melinda Gates Foundation

Lipid-Based Nutrient Supplements Are Feasible As a Breastmilk Replacement for HIV-Exposed Infants from 24 to 48 Weeks of Age

AbstractThe Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study randomized HIV-infected mothers and their infants to receive either maternal lipid-based nutrient supplements (LNS) during lactation or no LNS and then to 1 of 3 antiretroviral drug (ARV) arms (maternal, infant, or no drugs). Assigned interventions were provided from 0 to 28 wk and all infants (n = 1619) were given LNS during (24–28 wk) and following (28–48 wk) weaning. This paper assesses the feasibility of infant LNS as a breastmilk replacement and uses longitudinal random effects models to examine associations of interventions, morbidity, and season with weight-for-age (WAZ), length-for-age (LAZ), and BMI-for-age (BMIZ) Z-scores from 24 to 48 wk. Infant LNS adherence was high (94.1% ate it daily). From 24 to 48 wk, mean WAZ (−0.42 to −0.76 SD; P < 0.001) and LAZ (−0.93 to −1.56 SD; P < 0.001) steadily declined, whereas BMIZ remained >0 throughout. A higher LAZ was associated with assignment to the maternal LNS arm (β=0.19; P < 0.05). Lower WAZ and BMIZ were associated with seasonal food insecurity (β=−0.08 and −0.09, respectively; both P < 0.001), fever (β=−0.07 and −0.13; both P < 0.001), diarrhea (β=−0.19 and −0.23; both P < 0.001), and assignment to the infant ARV arm (β=−0.17 and −0.17; both P < 0.05). The magnitude of the season and morbidity effects was small and BAN infants had higher weights and lengths than their counterparts in the general population. High LNS adherence and the modest impact of morbidity on growth indicate that LNS is a feasible breastmilk replacement for HIV-exposed infants weaned early, but controlled trials are needed to quantify the effects of LNS on growth in this population.

Maternal and infant iron status in HIV‐infected Malawian women and their exclusively breastfed infants

Identifying infants at risk of early depletion of iron stores is essential to prevent postnatal iron deficiency. Maternal iron status may be a determinant of infant iron status, especially in the context of HIV where iron deficiency is common. We evaluated how iron status of HIV infected Malawian women related to iron status of their exclusively breastfed infants in the Breastfeeding, Antiretroviral and Nutrition Study. Participants were randomized to receive maternal lipid‐based nutrient supplements (LNS), providing 15 mg iron/d, or no LNS, and maternal, infant or no antiretroviral drugs. Infant iron status (Hb, log ferritin, log transferrin receptors TfR) at 2 (n=355) or 6 wk (n=165), and 24 wk (n=532) were regressed on corresponding maternal indicators, each corrected for inflammation (elevated C‐reactive protein and/or α‐1‐acid glycoprotein). Maternal Hb was marginally associated with infant Hb (6 wk β: 0.14, p=0.07; 24 wk β: 0.08, p=0.06). Maternal ferritin was related to infant ferritin only at 2 wk (β: 0.16, p&lt;.01). Maternal TfR was associated with infant TfR at all periods (2 wk β: 0.14, 6 wk β: 0.30, 24 wk β: 0.21; all p&lt;0.001). Maternal LNS predicted marginally lower maternal ferritin at 6 and 24 wk (p&lt;0.1), but not maternal TfR, Hb or infant status. Given the observed maternal influence, optimizing maternal status at delivery and during lactation is important for reducing risk of iron depletion in infants.Grant Funding Source : CDC(U48‐DP000059‐01); Bill &amp; Melinda Gates Foundation(OPP53107); CPC(NICHD 5 R24 HD050924)