Background

Adequate knowledge about the safety of consumption of small-quantity lipid-based nutrient supplements (SQ-LNSs) is needed.

Objective

We aimed to test the hypothesis that SQ-LNS consumption is noninferior to control with respect to child morbidity.

Methods

Women (n = 1320) ≤20 wk pregnant were assigned to iron and folic acid until delivery with no supplementation for offspring; or multiple micronutrient supplements until 6 mo postpartum with no supplementation for offspring; or SQ-LNSs until 6 mo postpartum, and SQ-LNSs for offspring (6 mg Fe/d) from 6 to 18 mo of age [the lipid-based nutrient supplement (LNS) group]. We assessed noninferiority (margin ≤20%) between any 2 groups during 0-6 mo of age, and between the non-LNS and LNS groups during 6-18 mo of age for caregiver-reported acute respiratory infection, diarrhea, gastroenteritis, fever/suspected malaria, poor appetite, and "other illnesses."

Results

During 0-6 mo of age, 1197 infants contributed 190,503 infant-days. For all morbidity combined, overall mean incidence (per 100 infant-days) was 3.3 episodes, overall mean prevalence (percentage of infant-days) was 19.3%, and the 95% CIs of the incidence rate ratio (IRR) and longitudinal prevalence rate ratio (LPRR) between any 2 groups were ≤1.20. During 6-18 mo, there were 240,097 infant-days for the non-LNS group and 118,698 for the LNS group. For all morbidity combined, group mean incidences were 4.3 and 4.3, respectively (IRR: 1.0; 95% CI: 1.0, 1.1), and mean prevalences were 28.2% and 29.3%, respectively (LPRR: 1.0; 95% CI: 1.0, 1.1). Noninferiority was inconclusive for diarrhea, fever/suspected malaria, and poor appetite.

Conclusions

SQ-LNS consumption does not increase reported overall child morbidity in this population compared with the 2 other treatments.This trial was registered at clinicaltrials.gov as NCT00970866.

Little is known about the impact of small-quantity lipid-based nutrient supplements (SQ-LNSs) on maternal morbidity. This secondary outcome analysis aimed to compare morbidity symptoms among women in two trials evaluating the efficacy of SQ-LNSs. From enrolment (≤20-week gestation) to 6 months postpartum, Ghanaian (n = 1320) and Malawian (n = 1391) women were assigned to consume daily: 60 mg iron and 400 µg folic acid until childbirth and placebo thereafter (iron and folic acid [IFA] group); or multiple micronutrients (MMN); or 20 g/day SQ-LNSs. Within country, we used repeated measures logistic regression and analysis of variance models to compare group differences in the period prevalence and percentage of days of monitoring when women had fever, gastrointestinal, reproductive, and respiratory symptoms during the second and third trimesters of pregnancy (n ~ 1243 in Ghana, 1200 in Malawi) and 0-3 and 3-6 months postpartum (n ~ 1212 in Ghana, 730 in Malawi). Most outcomes did not differ significantly among groups, with the following exceptions: in Ghana, overall, the prevalence of vomiting was lower in the LNS (21.5%) than MMN (25.6%) group, with the IFA group (23.2%) in-between (p = 0.046); mean ± SD percentage of days with nausea was greater in the LNS (3.5 ± 10.3) and MMN (3.3 ± 10.4) groups than the IFA (2.7 ± 8.3) group (p = 0.002). In Malawi, during 3-6 month postpartum, the prevalence of severe diarrhoea was greater in the LNS (8.1%) than the MMN (2.9%) group, with IFA (4.6%) in-between, p = 0.041). We conclude that the type of nutrient supplement received during pregnancy and lactation generally does not influence morbidity symptoms in these settings. Clinicaltrials.gov identifiers: NCT00970866; NCT01239693.

We examined the impact on depression at 6 months postpartum of maternal supplementation with small-quantity lipid-based nutrient supplement (SQ-LNS) compared to supplementation with iron and folic acid (IFA) or multiple micronutrients (MMN). In this partially double-blinded randomized controlled trial, pregnant women ≤20 weeks gestation (n = 1320) were recruited from antenatal clinics and randomly assigned to receive either (1) SQ-LNS during pregnancy and for 6 months postpartum, or (2) IFA during pregnancy only, or (3) MMN during pregnancy and for 6 months postpartum. Maternal depressive symptoms were measured at 6 months postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Women who scored 12 or more on the EPDS were considered to show symptoms of depression. One thousand one hundred fifty-one women were included in this analysis (LNS = 382, IFA = 387 and MMN = 382). Characteristics of the three groups were similar at baseline, and there were no significant differences between women who were included in the analysis (n = 1151) and those who were not (n = 169). At 6 months postpartum, 13% of the women overall showed symptoms of depression, and this did not differ by group (LNS = 13.1%, IFA = 11.2% and MMN = 14.7%. P = 0.36). The median (25, 75 percentile) EPDS score did not differ by group (LNS 4.0 (1.0, 8.0), IFA 4.0 (1.0, 8.0), MMN 5.0 (2.0, 9.0), P _transformed = 0.13). Adjustment for covariates did not alter these findings. Maternal supplementation with SQ-LNS compared to MMN or IFA did not affect postnatal depressive symptoms in this sample of Ghanaian women.

Background: It is unclear whether maternal supplementation with small-quantity lipid-based nutrient supplements (SQ-LNSs; 118 kcal/d) affects maternal weight.Objective: We compared several secondary anthropometric measures between 3 groups of women in the iLiNS (International Lipid-based Nutrient Supplements)-DYAD trial in Ghana.Methods: Women (n = 1320; <20 wk of gestation) were randomly assigned to receive 60 mg Fe + 400 μg folic acid/d (IFA), 18 vitamins and minerals/d [multiple micronutrients (MMNs)], or 20 g SQ-LNSs with 22 micronutrients/d (LNS) during pregnancy and a placebo (200 mg Ca/d), MMNs, or SQ-LNSs, respectively, for 6 mo postpartum. Weight, midupper arm circumference (MUAC), and triceps skinfold (TSF) thickness at 36 wk of gestation and 6 mo postpartum were analyzed, as were changes from estimated prepregnancy values. We assessed the adequacy of estimated gestational weight gain (GWG) by using Institute of Medicine (IOM) and International Fetal and Newborn Growth Standards for the 21st Century (INTERGROWTH-21st) guidelines.Results: The estimated prepregnancy prevalence of overweight or obesity was 38.5%. By 36 wk of gestation, women (n = 1015) had a mean ± SD weight gain of 7.4 ± 3.7 kg and changes of -1.0 ± 1.7 cm in MUAC and -2.8 ± 4.1 mm in TSF thickness. The LNS group had a lower prevalence of inadequate GWG on the basis of IOM guidelines (57.4%) than the MMN (67.2%) but not the IFA (63.1%) groups (P = 0.030), whereas the prevalence of adequate (26.9% overall) and excessive (10.4% overall) GWG did not differ by group. The percentages of normal-weight women (in kg/m²: 18.5 < body mass index < 25.0; n = 754) whose GWG was less than the third centile of the INTERGROWTH-21st standards were 23.0%, 28.7%, and 28.5% for the LNS, MMN, and IFA groups, respectively (P = 0.36). At 6 mo postpartum, the prevalence of overweight or obesity was 45.3%, and the risk of becoming overweight or obese did not differ by group.Conclusion: SQ-LNS supplementation is one potential strategy to address the high prevalence of inadequate GWG in women in settings similar to Ghana, without increasing the risk of excessive GWG. This trial was registered at clinicaltrials.gov as NCT00970866.

There is little information on whether prenatal multiple micronutrient (MMN) supplements containing iodine affect women's iodine status. In the International Lipid-based Nutrient Supplements DYAD-Ghana trial, we aimed to assess women's urinary iodine concentration (UIC, μg/L) during pregnancy, as one of the planned secondary outcomes. Women (n = 1,320) <20 weeks of gestation were randomized to consume 60 mg iron and 400 μg folic acid per day (iron and folic acid [IFA]); 18 vitamins and minerals including 250 μg iodine per day (MMN); or 20 g/day of small-quantity lipid-based nutrient supplements (LNS) with the same and additional 4 vitamins and minerals as the MMN (LNS). In a subsample (n = 295), we tested differences in groups' geometric mean UICs at 36 weeks of gestation controlling for baseline UIC and compared the geometric means (approximately median UICs) with the World Health Organization (WHO) cut-offs: median UIC <150, 150-249, and ≥500 reflecting low, adequate, and excessive iodine intakes, respectively. At baseline, overall median UIC was 137. At 36 weeks of gestation, controlling for baseline UIC, geometric mean (95% confidence interval) UICs of the MMN (161 [133, 184]) and LNS (158 [132, 185]) groups did not differ; both values were significantly greater (overall p = .004) than that of the IFA group (116 [101, 135]). The median UICs of the MMN and LNS groups were within the WHO "adequate" range, whereas that of the IFA group was below the WHO adequate range. In this setting, supplementation during pregnancy with small-quantity LNS or MMN providing iodine at the WHO-recommended dose, compared with IFA, increases the likelihood of adequate iodine status.

Background

Interventions are needed to address iron deficiency in low-income settings.

Objective

This secondary outcome analysis aimed to compare the hemoglobin (Hb) and iron status [zinc protoporphyrin (ZPP)] of children born to women enrolled in the iLiNS-DYAD trial in Ghana.

Methods

Women ≤20 wk pregnant (n = 1320) were assigned to receive 60 mg Fe/d and 400 µg folic acid/d until delivery and placebo thereafter, and no supplementation for infants (IFA group); or multiple micronutrients containing 20 mg Fe/d until 6 mo postpartum and no supplementation for infants (MMN); or small-quantity lipid-based nutrient supplements (SQ-LNSs) containing 20 mg Fe/d until 6 mo postpartum, and SQ-LNSs for infants from 6 to 18 mo of age (LNS). We compared infants' Hb (g/L) and ZPP (µmol/mol heme) at 6 and 18 mo of age.

Results

At 6 mo of age, groups did not differ in mean ± SD Hb (overall: 113 ± 9.9 g/L) or geometric mean (95% CI) ZPP [overall: 62.6 (60.6, 64.7)]. At 18 mo of age, mean ± SD Hb (overall: 112 ± 10.4 g/L) did not differ significantly between groups, whereas geometric mean (95% CI) ZPP was lower (P = 0.031) in the LNS group [53.9 (50.7, 57.3)] than the IFA [60.4 (56.7, 64.3)] but not the MMN [58.8 (55.6, 62.2)] group. Further, the LNS group, compared with the IFA and MMN groups combined, had a lower prevalence of elevated (>70) ZPP (27.5% compared with 35%; P = 0.02) and a marginally lower prevalence of anemia (38.7% compared with 44.9%; P = 0.06). These results generally remained unchanged when controlling for prespecified covariates or correcting for inflammation.

Conclusions

In this setting, providing SQ-LNSs or multiple micronutrients with 20 mg Fe/d, compared with iron (60 mg/d) and folic acid, to pregnant women does not affect their infants' Hb or iron status at 6 mo of age, but maternal and infant supplementation with SQ-LNSs increases infants' iron status at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT00970866.

We examined hemoglobin (Hb, g/L), iron status (zinc protoporphyrin, ZPP, µmol/mol heme, and transferrin receptor, TfR, mg/L) and inflammation (C-reactive protein, CRP and alpha-1 glycoprotein, AGP) in pregnant Ghanaian women who participated in a randomized controlled trial. Women (n = 1320) received either 60 mg Fe + 400-µg folic acid (IFA); 18 micronutrients including 20-mg Fe (MMN) or small-quantity lipid-based nutrient supplements (SQ-LNS, 118 kcal/d) with the same micronutrient levels as in MMN, plus four additional minerals (LNS) daily during pregnancy. Intention-to-treat analysis included 349, 354 and 354 women in the IFA, MMN and LNS groups, respectively, with overall baseline mean Hb and anemia (Hb <100) prevalence of 112 and 13.3%, respectively. At 36 gestational weeks, overall Hb was 117, and anemia prevalence was 5.3%. Compared with the IFA group, the LNS and MMN groups had lower mean Hb (120 ± 11 vs. 115 ± 12 and 117 ± 12, respectively; P < 0.001), higher mean ZPP (42 ± 30 vs. 50 ± 29 and 49 ± 30; P = 0.010) and TfR (4.0 ± 1.3 vs. 4.9 ± 1.8 and 4.6 ± 1.7; P < 0.001), and greater prevalence of anemia (2.2% vs. 7.9% and 5.8%; P = 0.019), elevated ZPP (>60) [9.4% vs. 18.6% and 19.2%; P = 0.003] and elevated TfR (>6.0) [9.0% vs. 19.2% and 15.1%; P = 0.004]. CRP and AGP concentrations did not differ among groups. We conclude that among pregnant women in a semi-urban setting in Ghana, supplementation with SQ-LNS or MMN containing 20 mg iron resulted in lower Hb and iron status but had no impact on inflammation, when compared with iron (60 mg) plus folic acid (400 µg). The amount of iron in such supplements that is most effective for improving both maternal Hb/iron status and birth outcomes requires further evaluation. This trial was registered at ClinicalTrials.gov as: NCT00970866.

Background

Previous studies show an association between maternal plasma and salivary cortisol and preterm birth but have been primarily conducted in high-income countries. It is unknown whether salivary cortisol is a risk factor for preterm birth in Ghana. Our objective was to determine whether maternal salivary cortisol during pregnancy was associated with pregnancy duration and preterm delivery in Ghana.

Methods

We conducted a cohort study of 783 pregnant women in Ghana. We measured salivary cortisol at baseline (mean 16 wk), 28 wk., and 36 wk. gestation. Pregnancy duration was determined primarily by ultrasound. We used adjusted linear regression models to examine the association between cortisol and pregnancy duration and Poisson regression models to determine the risk of preterm delivery among women with high cortisol at baseline or 28 wk. gestation.

Results

Mean pregnancy duration was 39.4 ± 1.8 wk. and 6.6% had a preterm delivery. Mean maternal cortisol increased throughout pregnancy, from 4.9 ± 2.7 nmol/L at baseline (16 wk) to 6.4 ± 3.2 nmol/L at 28 wk. and 7.9 ± 3.0 nmol/L at 36 wk. gestation. In adjusted analyses, higher cortisol concentrations at baseline (β = - 0.39, p = .002) and 28 wk. (β = - 0.49, p = .001), but not 36 wk. (β = - 0.23, p = .084) were associated with a shorter pregnancy duration. Women with high cortisol at baseline (> 6.3 nmol/L) had an increased relative risk of preterm delivery (RR (95% CI): 1.96 (1.13, 3.40)), but the association between high cortisol at 28 wk. and preterm delivery was not significant. There was a significant interaction with fetal sex (p-for-interaction = 0.037): among women carrying male fetuses, high cortisol at baseline increased the risk of preterm delivery threefold (3.18 (1.51, 6.71)) while there was no association (1.17 (0.50, 2.74)) among women carrying female fetuses.

Conclusion

Higher maternal cortisol is associated with a shorter pregnancy duration and an increased risk of preterm delivery. Subgroup analysis by fetal sex revealed that this association is evident primarily among women carrying male fetuses. Future studies of cortisol and preterm delivery should include consideration of fetal sex as a potential effect modifier.

Background

It is unknown whether prenatal lipid-based nutrient supplements (LNSs) affect blood pressure (BP). Associations between hypertension and birth outcomes using recently updated BP cutoffs are undetermined.

Objectives

We aimed to assess the impact of LNSs on maternal hypertension and associations between hypertension and birth outcomes.

Methods

Pregnant Ghanaian women at ≤20 weeks of gestation (n = 1320) were randomly assigned to receive daily 1) iron and folic acid (IFA), 2) multiple micronutrients (MMN), or 3) LNSs until delivery. BP was measured at enrollment and 36 weeks of gestation. We analyzed the effect of LNSs on BP using ANOVA and associations between hypertension [systolic BP (SBP) ≥130 mm Hg or diastolic BP (DBP) ≥80 mm Hg] and birth outcomes by linear and logistic regressions.

Results

Mean ± SD SBP and DBP were 110 ± 11 and 63 ± 8 mm Hg at 36 weeks of gestation and did not differ by supplementation group (SBP, P > 0.05; DBP, P > 0.05). At enrollment, higher DBP was associated with lower birth weight and shorter gestation; women with high DBP had greater risk of low birth weight (LBW) [risk ratio (RR): 2.58; 95% CI: 1.09, 6.08] and preterm birth (PTB) (RR: 3.30; 95% CI: 1.47, 7.40). At 36 weeks of gestation, higher SBP was associated with lower birth weight, length, and head circumference and shorter gestation; higher DBP was associated with lower birth weight and length; and women with high DBP had greater risk of LBW (RR: 3.39; 95% CI: 1.32, 8.69). Neither high SBP nor hypertension were associated with birth outcomes at either time point.

Conclusions

Daily provision of LNSs does not affect maternal hypertension, compared with IFA and MMN. Higher SBP and DBP are associated with a shorter gestation and smaller birth size; however, only high DBP is associated with LBW and PTB. The new BP cutoffs may help identify pregnancies at risk of adverse birth outcomes.This trial was registered at clinicaltrials.gov as NCT00970866.

Background

Childhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life.

Objective

We evaluated the efficacy of small-quantity, lipid-based nutrient supplements (SQ-LNSs) provided during pregnancy, lactation, and infancy on attained size by 18 mo of age.

Design

In this partially double-blind, individually randomized trial, 1320 women at ≤20 wk of gestation received standard iron and folic acid (IFA group), multiple micronutrients (MMN group), or SQ-LNS (LNS group) daily until delivery, and then placebo, MMNs, or SQ-LNS, respectively, for 6 mo postpartum; infants in the LNS group received SQ-LNS formulated for infants from 6 to 18 mo of age (endline). The primary outcome was child length by 18 mo of age.

Results

At endline, data were available for 85% of 1228 infants enrolled; overall mean length and length-for-age z score (LAZ) were 79.3 cm and -0.83, respectively, and 12% of the children were stunted (LAZ <-2). In analysis based on the intended treatment, mean ± SD length and LAZ for the LNS group (79.7 ± 2.9 cm and -0.69 ± 1.01, respectively) were significantly greater than for the IFA (79.1 ± 2.9 cm and -0.87 ± 0.99) and MMN (79.1 ± 2.9 cm and -0.91 ± 1.01) groups (P = 0.006 and P = 0.009, respectively). Differences were also significant for weight and weight-for-age z score but not head or midupper arm circumference, and the prevalence of stunting in the LNS group was 8.9%, compared with 13.7% in the IFA group and 12.9% in the MMN group (P = 0.12). In analysis based on actual supplement provided at enrollment, stunting prevalences were 8.9% compared with 15.1% and 11.5%, respectively (P = 0.045).

Conclusion

Provision of SQ-LNSs to women from pregnancy to 6 mo postpartum and to their infants from 6 to 18 mo of age may increase the child's attained length by age 18 mo in similar settings. This trial was registered at clinicaltrials.gov as NCT00970866.