Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: 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 wasting and stunting. There is little information regarding effects on severe wasting or stunting. OBJECTIVES: We aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3). 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. 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 led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation. CONCLUSIONS: Including SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Association between prenatal provision of lipid-based nutrient supplements and caesarean delivery: Findings from a randomised controlled trial in Malawi.

In populations with a high prevalence of childhood and adolescent undernutrition, supplementation during pregnancy aiming at improving maternal nutritional status and preventing fetal growth restriction might theoretically lead to cephalopelvic disproportion and delivery complications. We investigated whether the prenatal provision of small-quantity lipid-based nutrient supplements (SQ-LNS) was associated with an increased risk of caesarean section (CS) or other delivery complications. Pregnant Malawian women were randomised to receive daily i) iron-folic acid (IFA) capsule (control), ii) multiple micronutrient (MMN) capsule of 18 micronutrients (second control), or iii) SQ-LNS with similar micronutrients as MMN, plus four minerals and macronutrients contributing 118 kcal. We analysed the associations of SQ-LNS, CS, and other delivery complications using log-binomial regressions. Among 1391 women enrolled, 1255 had delivery information available. The incidence of CS and delivery complications was 6.3% and 8.2%, respectively. The incidence of CS was 4.0%, 6.0%, and 8.9% (p = 0.017) in the IFA, MMN, and LNS groups, respectively. Compared to the IFA group, the relative risk (95% confidence interval) of CS was 2.2 (1.3-3.8) (p = 0.006) in the LNS group and 1.5 (0.8-2.7) (p = 0.200) in the MMN group. We found no significant differences for other delivery complications. Provision of SQ-LNS to pregnant women may have increased the incidence of CS. The baseline rate was, however, lower than recommended. It is unclear if the higher CS incidence in the SQ-LNS group resulted from increased obstetric needs or more active health seeking and a better supply of services. Trial registered at clinicaltrials.gov, NCT01239693.

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.

Consumption of multiple micronutrients or small-quantity lipid-based nutrient supplements containing iodine at the recommended dose during pregnancy, compared with iron and folic acid, does not affect women's urinary iodine concentration in rural Malawi: a secondary outcome analysis of the iLiNS DYAD trial.

OBJECTIVES: Inadequate iodine intake during pregnancy increases the risk of neonatal morbidity and mortality. We aimed to evaluate whether prenatal supplements containing iodine affect urinary iodine concentrations (UIC) of pregnant women in Malawi. DESIGN: A randomised controlled trial. Pregnant women (n 1391) were assigned to consume 60 mg/d Fe and 400 µg/d folic acid (IFA) or 18 vitamins and minerals including 250 µg/d iodine (MMN) or 20 g/d small-quantity lipid-based nutrient supplements (SQ-LNS) with similar nutrient contents as MMN group, plus macronutrients (LNS) until childbirth. In a sub-study (n 317), we evaluated group geometric mean urinary iodine concentration (UIC) (µg/L) at 36 weeks of gestation controlling for baseline UIC and compared median (baseline) and geometric mean (36 weeks) UIC with WHO cut-offs: UIC < 150, 150-249, 250-499 and ≥500 reflecting insufficient, adequate, above requirements and excessive iodine intakes, respectively. SETTING: Mangochi District, Malawi. PARTICIPANTS: Women ≤20 weeks pregnant. RESULTS: Groups had comparable background characteristics. At baseline, overall median (Q1, Q3) UIC (319 (167, 559)) suggested iodine intakes above requirements. At 36 weeks, the geometric mean (95 % CI) UIC of the IFA (197 (171, 226)), MMN (212 (185, 243)) and LNS (220 (192, 253)) groups did not differ (P = 0·53) and reflected adequate intakes. CONCLUSIONS: In this setting, provision of supplements containing iodine at the recommended dose to pregnant women with relatively high iodine intakes at baseline, presumably from iodised salt, has no impact on the women's UIC. Regular monitoring of the iodine status of pregnant women in such settings is advisable. Clinicaltrials.gov identifier: NCT01239693.

Lipid based nutrient supplements during pregnancy may improve foetal growth in HIV infected women - A cohort study.

OBJECTIVES: Both maternal HIV infection and antiretroviral therapy are associated with adverse birth outcomes. The role of antenatal nutrient supplements with regard to adverse birth outcomes in HIV infected women exposed to antiretroviral therapy is not well known. We assessed the association between HIV and birth outcomes and explored whether antenatal lipid-based nutrient supplements (LNS) modulated this association. METHODS: We analysed a nested cohort of pregnant Malawian women who received daily LNS, multiple micronutrients (MMN) or iron and folic acid (IFA). Birth weight, length-for-age z-score (LAZ) and weight-for-age z-score (WAZ) were analysed as continuous outcomes and proportion of stunting and small-for-gestational age (SGA) as dichotomous outcomes. RESULTS: 134 HIV infected (46 LNS, 39 MMN, 49 IFA) and 833 HIV uninfected (271 LNS, 287 MMN, 275 IFA) women were included. Maternal HIV infection was associated with a lower mean birth weight (-129g (-209, -48), P = 0.002); LAZ (-0.34 (-0.54, -0.13), P = 0.002) and WAZ (-0.21 (-0.40, -0.02), P = 0.041) and a higher risk of stunting (RR (95% confidence interval), 1.87 (1.24, 2.83), P = 0.003) and SGA (1.66 (1.21, 2.26), P = 0.001) in the newborn. If the women received LNS, HIV was not associated with LAZ (mean difference (95%); -0.02 (-0.35, 0.31), P = 0.918) or newborn stunting (RR (95% CI), 0.84 (0.34, 2.03), P = 0.691). However HIV tended to be associated with LAZ if the women received MMN (-0.42 (-0.80, -0.03), P = 0.053); and was significantly associated with LAZ if the women received IFA (-0.52 (-0.89, -0.14), P = 0.021) and with newborn stunting if they received MMN (2.40 (1.15, 4.98), P = 0.029) or IFA (2.40 (1.26, 4.59), P = 0.024). CONCLUSIONS: Further research to investigate the impact of LNS on various aspects of foetal growth in HIV infected women is warranted.

Effects of lipid-based nutrient supplements or multiple micronutrient supplements compared with iron and folic acid supplements during pregnancy on maternal haemoglobin and iron status.

We examined the effect of three types of prenatal supplements containing different amounts of iron on haemoglobin (Hb) and iron status (zinc protoporphyrin [ZPP] and soluble transferrin receptor [sTfR]) in late pregnancy among 1,379 women in rural Malawi. Participants were recruited at ≤20 gestational weeks (gw) and randomly assigned to consume daily (1) 60-mg iron and folic acid (IFA); (2) 20-mg iron plus 17 micronutrients in a capsule (MMN); or (3) lipid-based nutrient supplement (LNS; 118 kcal) with 20-mg iron plus 21 micronutrients, protein, and fat. We analysed differences between intervention groups in mean Hb, ZPP, and sTfR at 36 gw, and the proportion with anaemia (Hb < 100 g L-1 ) and iron deficiency (ZPP > 60 µmol mol-1 haem or sTfR > 6 mg L-1 ) at 36 gw. Women in the IFA group had higher Hb at 36 gw than women in the LNS group (P = 0.030) and higher iron status (lower ZPP and sTfR) than women in both the LNS (P < 0.001 for both ZPP and sTfR) and MMN (P = 0.025 and P = 0.046) groups. Results for anaemia and iron deficiency showed similar trends. Further research is needed to elucidate the appropriate amount of iron to improve Hb and iron status, while improving birth outcomes.

Providing lipid-based nutrient supplement during pregnancy does not reduce the risk of maternal P falciparum parasitaemia and reproductive tract infections: a randomised controlled trial.

BACKGROUND: Maternal infections are associated with maternal and foetal adverse outcomes. Nutrient supplementation during pregnancy may reduce the occurrence of infections by improving maternal immunity. We aimed to investigate the impact of small-quantity lipid-based nutrient supplement (SQ-LNS) on the occurrence of Plasmodium falciparum parasitaemia during pregnancy and trichomoniasis, vaginal candidiasis and urinary tract infection (UTI) after delivery. METHODS: Pregnant Malawian women enrolled in the iLiNS-DYAD trial receiving daily supplementation with SQ-LNS, multiple micronutrients (MMN) or iron & folic acid (IFA) from <20 gestation weeks (gw) were assessed for P. falciparum parasitaemia at 32 gw using rapid diagnostic testing (RDT), at 36 gw using polymerase chain reaction (PCR) and at delivery using both RDT and PCR; and at one week after delivery for trichomoniasis and vaginal candidiasis using wet mount microscopy and for UTI using urine dipstick analysis. The prevalence of each infection by intervention group was estimated at the prescribed time points and the global null hypothesis was tested using logistic regression. Adjusted analyses were performed using preselected covariates. RESULTS: The prevalence of P. falciparum parasitaemia was 10.7% at 32 gw, 9% at 36 gw, and 8.3% by RDT and 20.2% by PCR at delivery. After delivery the prevalence of trichomoniasis was 10.5%, vaginal candidiasis was 0.5%, and UTI was 3.1%. There were no differences between intervention groups in the prevalence of any of the infections. CONCLUSION: In this population, SQ-LNS did not influence the occurrence of maternal P. falciparum parasitaemia, trichomoniasis, vaginal candidiasis or UTI. TRIAL REGISTRATION: Identifier: NCT01239693 (10 November 2010).

The impact of lipid-based nutrient supplement provision to pregnant women on newborn size in rural Malawi: a randomized controlled trial.

BACKGROUND: Small birth size, often associated with insufficient maternal nutrition, contributes to a large share of global child undernutrition, morbidity, and mortality. We developed a small-quantity lipid-based nutrient supplement (SQ-LNS) to enrich the diets of pregnant women. OBJECTIVE: The objective was to test a hypothesis that home fortification of pregnant women's diets with SQ-LNS would increase birth size in an African community. DESIGN: We enrolled 1391 women with uncomplicated pregnancies (<20 gestational weeks) in a randomized controlled trial in Malawi. The women were provided with one daily iron-folic acid (IFA) capsule, one capsule containing multiple micronutrients (MMNs), or one 20-g sachet of SQ-LNS (LNS, containing 118 kcal, protein, carbohydrates, essential fatty acids, and 21 micronutrients). Primary outcomes were birth weight and newborn length. Secondary outcomes included newborn weight, head and arm circumference, and pregnancy duration. Analysis was by intention to treat. RESULTS: The mean ± SD birth weight and newborn length were 2948 ± 432, 2964 ± 460, and 3000 ± 447 g (P = 0.258) and 49.5 ± 2.4, 49.7 ± 2.2, and 49.9 ± 2.1 cm (P = 0.104) in the IFA, MMN, and LNS groups, respectively. For newborn weight-for-age, head circumference, and arm circumference, the point estimate for the mean was also highest in the LNS group, intermediate in the MMN group, and lowest in the IFA group, but except for midupper arm circumference (P = 0.024), the differences were not statistically significant. The prevalence of low birth weight (<2500 g) was 12.7%, 13.5%, and 12.1% (P = 0.856), respectively; newborn stunting (length-for-age z score < -2) was 19.2%, 14.0%, and 14.9% (P = 0.130), respectively; and newborn small head circumference (head circumference-for-age z score < -2) was 5.8%, 3.0%, and 3.1% (P = 0.099), respectively. The associations between the intervention and the outcomes were not modified by maternal parity, age, or nutritional status (P > 0.100). CONCLUSION: The study findings do not support a hypothesis that provision of SQ-LNS to all pregnant women would increase the mean birth size in rural Malawi. The trial was registered at clinicaltrials.gov as NCT01239693.