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Maternal Blood Pressure in Relation to Prenatal Lipid-Based Nutrient Supplementation and Adverse Birth Outcomes in a Ghanaian Cohort: A Randomized Controlled Trial and Cohort Analysis
(ASN, 2021) Abreu, A.M.; Young, R.R.; Buchanan, A.; Lofgren, I.E.; Okronipa, H.E.T.; Lartey, A.; Ashorn, P.; Adu-Afarwuah, S.; Dewey, K.G.; Oaks, B.M.
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.
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
(Public Health Nutrition, 2021) Adu-Afarwuah, S.; Arnold, C.D.; Maleta, K.; Ashorn, P.; Ashorn, U.; Jorgensen, J.M.; Fan, Y.; Nkhoma, M.; Bendabenda, J.; Matchado, A.; Dewey, K.G.
Objectives: Inadequate iodine intake during pregnancy increases the risk of neo natal 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 sup plements (SQ-LNS) with similar nutrient contents as MMN group, plus macronu trients (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 reflect ing 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 require ments. 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 rec ommended dose to pregnant women with relatively high iodine intakes at base line, 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.
Small-Quantity Lipid-Based Nutrient Supplements Do Not Affect Plasma or Milk Retinol Concentrations Among Malawian Mothers, or Plasma Retinol Concentrations among Young Malawian or Ghanaian Children in Two Randomized Trials
(The Journal of Nutrition Community and International Nutrition, 2021) Haskell, M.J.; Young, R.; Adu-Afaruwah, S.; Lartey, A.; Okronipa, H.E.T.; Maleta, K.; Ashorn, U.; Jorgensen, J.M.; Fan, Y-M.; Arnold, C.D.; Allen, L.H.; Ashorn, P.; Dewey, K.G.
Background: Vitamin A (VA) deficiency is prevalent in preschool-aged children in sub-Saharan Africa. Objectives: We assessed the effect of small-quantity lipid-based nutrient supplements (SQ-LNS) given to women during pregnancy and lactation and their children from 6 to 18 mo of age on women’s plasma and milk retinol concentrations in Malawi, and children’s plasma retinol concentration in Malawi and Ghana. Methods: Pregnant women (≤20 wk of gestation) were randomized to receive daily: 1) iron and folic acid (IFA) during pregnancy only; 2)multiplemicronutrients (MMN; 800 μg retinol equivalent (RE)/capsule), or 3) SQ-LNS (800 μg RE/20g) during pregnancy and the first 6 mo postpartum. Children of mothers in the SQ-LNS group received SQ-LNS (400 μg RE/20 g) from 6 to 18 mo of age; children of mothers in the IFA and MMN groups received no supplement. Plasma retinol was measured in mothers at ≤20 and 36 wk of gestation and 6 mo postpartum, and in children at 6 and 18 mo of age. Milk retinol was measured at 6 mo postpartum. VA status indicators were compared by group. Results: Among Malawian mothers, geometric mean (95% CI) plasma retinol concentrations at 36 wk of gestation and 6 mo postpartum were 0.97 μmol/L (0.94, 1.01 μmol/L) and 1.35 μmol/L (1.31, 1.39 μmol/L), respectively; geometric mean (95% CI) milk retinol concentration at 6 mo postpartum was 1.04 μmol/L (0.97, 1.13 μmol/L); results did not differ by intervention group. Geometric mean (95% CI) plasma retinol concentrations for Malawian children at 6 and 18 mo of age were 0.78 μmol/L (0.75, 0.81 μmol/L) and 0.81 μmol/L (0.78, 0.85 μmol/L), respectively, and for Ghanaian children they were 0.85 μmol/L (0.82, 0.88 μmol/L) and 0.88 μmol/L (0.85, 0.91 μmol/L), respectively; results did not differ by intervention group in either setting. Conclusions: SQ-LNS had no effect on VA status of mothers or children, possibly because of low responsiveness of the VA status indicators. J Nutr 2021;151:1029–1037.
Antenatal multiple micronutrient supplementation: call to action for change in recommendation
(ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 2019-11-05) Ahmed, S.; Bourassa, M.W.; Osendarp, S.J.M; Adu-Afarwuah, S.; Ajello, C.; Bergeron, G.; Black, R.; Christian, P.; Cousens, S.; de Pee, S.; Dewey, K.G.; Arifeen, S.E.; Engle-Stone, R.; Fleet, A.; Gernand, A.D.; Hoddinott, J.; Klemm, R.; Kraemer, K.; Kupka, R.; McLean, E.; Moore, S.E.; Neufeld, L.M.; Persson, L-A.; Rasmussen, K.M.; Shankar, A.H.; Smith, E.; Sudfeld, C.R.; Udomkesmalee, E.; Vosti, S.A.
We appreciate the comments by Devakumar et al .1 and agree that there are still some unanswered questions regarding the long‐term impact of multiple micronutrient supplementation (MMS) during pregnancy. However, in their assessment, Devakumar and colleagues ignore the significant benefits shown in the individual patient data (IPD) meta‐analysis, which strongly influenced our task force's conclusions. Rather, their comments focus only on the birth size data from the Cochrane reviews.2, 3 In the IPD meta‐analysis, which included data from nearly 113,000 pregnancies, the authors found that, in addition to reducing the risk of low birthweight, MMS significantly reduces the risk of preterm birth (RR = 0.93 (0.87–0.98), random effects).2 The Cochrane review also states that MMS “probably led to a slight reduction in preterm births” on the basis of data from 91,425 participants with moderate quality evidence (RR = 0.95 (0.90–1.01)
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
(Maternal & Child Nutrition, 2020-02-05) Adu-Afarwuah, S.; Adams, K.P.; Mridha, M.K.; Oaks, B.M.; Matias, S.L.; Arnold, C.D.; Kumordzie, S.M.; Okronipa, H.; Ocansey, M.E.; Dewey, K.G.
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
Supplementation with Small-Quantity Lipid-Based Nutrient Supplements Does Not Increase Child Morbidity in a Semiurban Setting in Ghana: A Secondary Outcome Noninferiority Analysis of the International Lipid-Based Nutrient Supplements (iLiNS)–DYAD Randomized Controlled Trial
(The Journal of Nutrition Community and International Nutrition, 2019-10-11) Adu-Afarwuah, S.; Young, R.R.; Lartey, A.; Okronipa, H.; Ashorn, P.; Ashorn, U.; Oaks, B.M.; Dewey, K.G.
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 0–6mo of age, and between the non-LNS and LNS groups during 6–18mo 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), andmean prevalences were 28.2% and 29.3%, respectively (LPRR: 1.0; 95% CI: 1.0, 1.1). Noninferioritywas 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.
Maternal and child factors associated with child body fatness in a Ghanaian cohort
(Public Health Nutrition, 2019-07-25) Adu-Afarwuah, S.; Kumordzie, S.M.; Okronipa, H.; Arimond, M.; Ocansey, M.E.; Young, R.R.; Bentil, H.J.; Tamakloe, S.M.; Oaks, B.M.; Dewey, K.G.
Objective: We aimed to identify factors (child diet, physical activity; maternal BMI) associated with body composition of Ghanaian pre-school children. Design: Longitudinal analysis of the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana randomized trial, which enrolled 1320 pregnant women at ≤20 weeks’ gestation and followed them and their infants until 6 and 18 months postpartum, respectively. At follow-up, child age 4–6 years, we collected data on body composition (by 2H dilution), physical activity and diet, extracted dietary patterns using factor analysis, and examined the association of children’s percentage body fat with maternal and child factors by regression analysis. Setting: Eastern Region, Ghana. Participants: Children 4–6 years of age. Results: The analysis included 889 children with percentage body fat and dietary data at follow-up. We identified two major dietary patterns, a snacking and a cooked foods pattern. Percentage body fat was positively associated (standardized β (SE)) with maternal BMI at follow-up (0·10 (0·03); P = 0·003) and negatively associated with physical activity (−0·15 (0·05); P = 0·003, unadjusted for child gender), but not associated with the snacking (0·06 (0·03); P = 0·103) or cooked foods (−0·05 (0·07); P = 0·474) pattern. Boys were more active than girls (1470 v. 1314 mean vector magnitude counts/min; P < 0·0001) and had lower percentage body fat (13·8 v. 16·9 %; P < 0·0001). Conclusions: In this population, maternal overweight and child physical activity, especially among girls, may be key factors for addressing child overweight/ obesity. We did not demonstrate a relationship between the dietary patterns and body fatness, which may be related to limitations of the dietary data available.
The association of early linear growth and haemoglobin concentration with later cognitive, motor, and social–emotional development at preschool age in Ghana
(Matern Child Nutrition, 2019-05-01) Adu‐Afarwuah, S.; Ocansey, M.E.; Kumordzie, S.M.; Okronipa, H.; Young, R.R.; Tamakloe, S.M.; Oaks, B.M.; Arimond, M.; Dewey, K.G.; Prado, E.L.
It is important to identify the periods during childhood when exposure to environmental risk factors results in long‐term neurodevelopmental deficits. Stunting and anaemia may be sensitive indicators of exposure to such risks. In a prospective cohort enrolled before birth, we investigated the association of developmental scores at 4– 6 years with (a) birth length and linear growth during three postnatal periods and (2) haemoglobin (Hb) concentration at three time points. Children were participants in a follow‐up study of a randomized controlled trial of nutritional supplementation in Ghana. At 4–6 years, cognitive, motor, and social–emotional developments were assessed using standard tests adapted for this population. We estimated the associations of length‐for‐age z‐score (LAZ) at birth and postnatal linear growth (n = 710) and Hb (n = 617) with developmental scores in regression models, using multistage least squares analysis to calculate uncorrelated residuals for postnatal growth. Cognitive development at 4–6 years was significantly associated with LAZ at birth (β = 0.12, 95% CI = 0.05, 0.19), ΔLAZ from 6 to 18 months (β = 0.16, 95% CI = 0.04, 0.28), and Hb at 18 months (β = 0.13, 95% CI = 0.06, 0.20), but not with ΔLAZ during 0– 6 months, ΔLAZ from 18 months to 4–6 years, Hb at 6 months, or Hb at 4– 6 years. No evidence of associations with motor or social–emotional development were found. These results suggest that in similar contexts, the earlier periods prior to birth and up to 18 months are more sensitive to risk factors for long‐term cognitive development associated with LAZ and Hb compared with later childhood. This may inform the optimal timing of interventions targeting improved cognitive development.
The effects of supplementing maternal and infant diets with lipid-based nutrient supplements on physical activity and sedentary behaviour at preschool age in Ghana
(British Journal of Nutrition, 2019-09-16) Adu-Afarwuah, S.; Ocansey, M.E.; Pulakka, A.; Young, R.R.; Kumordzie, S.M.; Okronipa, H.; Oaks, B.M.; Dewey, K.G.; Prado, K.L.
Evidence on whether nutritional supplementation affects physical activity (PA) during early childhood is limited. We examined the long-term effects of lipid-based nutrient supplements (LNS) on total PA, moderate-to-vigorous PA (MVPA) and sedentary behaviour (SB) of children at 4–6 years using an accelerometer for 1 week. Their mothers were enrolled in the International Lipid-based Nutrient Supplement-DYAD randomised controlled trial in Ghana, assigned to daily LNS or multiple micronutrients (MMN) during pregnancy through 6 months postpartum or Fe and folic acid (IFA) during pregnancy and placebo for 6 months postpartum. From 6 to 18 months, children in the LNS group received LNS; the other two groups received no supplements. Analysis was done with intention to treat comparing two groups: LNS v. non-LNS (MMNþ IFA). Of the sub-sample of 375 children fitted with accelerometers, 353 provided sufficient data. Median vector magnitude (VM) count was 1374 (interquartile range (IQR) 309), and percentages of time in MVPA and SB were 4·8 (IQR 2) and 31 (IQR 8) %, respectively. The LNS group (n 129) had lower VM (difference in mean −73 (95 % CI −20, −126), P = 0·007) and spent more time in SB (LNS v. non-LNS: 32·3 v. 30·5 %, P = 0·020) than the non-LNS group (n 224) but did not differ in MVPA (4·4 v. 4·7 %, P = 0·198). Contrary to expectations, provision of LNS in early life slightly reduced the total PA and increased the time in SB but did not affect time in MVPA. Given reduced social-emotional difficulties in the LNS group previously reported, including hyperactivity, one possible explanation is less restless movement in the LNS group
Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries
(Annals of the New York Academy of Sciences, 2019-05-27) Adu-Afarwuah, S.; Bourassa, M.W.; Osendarp, S.J.M.; Ahmed, S.; Ajello, C.; Bergeron, G.; Black, R.; Christian, P.; Cousens, S.; de Pee, S.; Dewey, K.G.; Arifeen, S.E.; Engle-Stone, R.; Fleet, A.; Gernand, A.D.; Hoddinott, j; Klemm, R.; Kraemer, k; Kupka, R.; McLean, E.; Moore, S.E.; Neufeld, L.M.; Persson, L.A.; Rasmussen, K.M.; Shankar, A.H.; Smith, E.; Sudfeld, C.R.; Udomkesmalee, E.; Vosti, S.A.
Inadequate micronutrient intakes are relatively common in low- and middle-income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost-effectiveness of MMS compared with IFA. Recent meta-analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual-participant data meta-analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost-effective method to reduce the risk of adverse birth outcomes.

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