Ulla Ashorn

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 womens 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.

Supplementation of Maternal Diets during Pregnancy and for 6 Months Postpartum and Infant Diets Thereafter with Small-Quantity Lipid-Based Nutrient Supplements Does Not Promote Child Growth by 18 Months of Age in Rural Malawi: A Randomized Controlled Trial

BACKGROUND Intrauterine growth restriction may be reduced by supplementing maternal diets during pregnancy, but few studies have assessed the impact of combined prenatal and postnatal interventions on child growth. OBJECTIVE We tested a hypothesis that provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to mothers in pregnancy and 6 mo postpartum and to their infants from 6 to 18 mo of age would promote infant and child growth in the study area in rural Malawi. METHODS We enrolled 869 pregnant women in a randomized trial in Malawi. During pregnancy and 6 mo thereafter, the women received daily 1 capsule of iron-folic acid (IFA), 1 capsule containing 18 micronutrients (MMN), or one 20-g sachet of SQ-LNS [lipid-based nutrient supplements (LNS), containing 21 MMN, protein, carbohydrates, essential fatty acids, and 118 kcal]. Children in the IFA and MMN groups received no supplementation; children in the LNS group received SQ-LNSs from 6 to 18 mo. Primary outcome was child length at 18 mo. RESULTS At 18 mo, the mean length in the IFA, MMN, and LNS groups was 77.0, 76.9, and 76.8 cm (P = 0.90), respectively, and the prevalence of stunting was 32.7%, 35.6%, and 37.9% (P = 0.54), respectively. No intergroup differences were found in the mean weight, head circumference, or midupper arm circumference or the proportions with low z scores for these variables (P > 0.05). Covariate adjustment did not change the analysis results, and the associations between the intervention and child length were not modified by maternal parity, age, or nutritional status (P > 0.10). CONCLUSIONS The findings do not support a hypothesis that provision of SQ-LNSs to women in pregnancy and postpartum and to children from 6 to 18 mo of age would promote child growth in this Malawian study area. This trial was registered at clinicaltrials.gov as NCT01239693.

Provision of 10–40 g/d Lipid-Based Nutrient Supplements from 6 to 18 Months of Age Does Not Prevent Linear Growth Faltering in Malawi

BACKGROUND Complementing infant diets with lipid-based nutrient supplements (LNSs) has been suggested to improve growth and reduce morbidity, but the daily quantity and the milk content of LNSs affect their cost. OBJECTIVE We tested the hypotheses that the change in mean length-for-age z score (LAZ) for infants provided with 10-40 g LNSs/d from ages 6 to 18 mo would be greater than that for infants receiving no dietary intervention at the same age and that provision of LNSs that did not contain milk would be as good as milk-containing LNSs in promoting linear growth. METHODS We enrolled in a randomized single-blind trial 6-mo-old infants who were allocated to 1 of 6 groups to receive 10, 20, or 40 g LNSs/d containing milk powder; 20 or 40 g milk-free LNSs/d; or no supplement until 18 mo of age. The primary outcome was change in LAZ. RESULTS Of the 1932 enrolled infants, 78 (4.0%) died and 319 (16.5%) dropped out during the trial. The overall reported supplement consumption was 71.6% of days, with no difference between the groups (P = 0.26). The overall mean ± SD length and LAZ changes were 13.0 ± 2.1 cm and -0.45 ± 0.77 z score units, respectively, which did not differ between the groups (P = 0.66 for length and P = 0.74 for LAZ). The difference in mean LAZ change in the no-milk LNS group compared with the milk LNS group was -0.02 (95% CI: -0.10, 0.06; P = 0.72). CONCLUSION Our results do not support the hypothesis that LNS supplementation during infancy and childhood promotes length gain or prevents stunting between 6 and 18 mo of age in Malawi. This trial was registered at clinicaltrials.gov as NCT00945698.

Small-quantity, lipid-based nutrient supplements provided to women during pregnancy and 6 mo postpartum and to their infants from 6 mo of age increase the mean attained length of 18-mo-old children in semi-urban Ghana: a randomized controlled trial

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.

Acceptability of three novel lipid‐based nutrient supplements among Malawian infants and their caregivers

We tested the acceptability of three new lipid-based nutrient supplements (LNSs) in two independent phases among 18 8-12-month-old healthy rural Malawians and their caregivers. In phase 1, acceptability was assessed by offering three new LNSs in random order, and an LNS already determined to be acceptable, Nutributter(®), each added to 30 g of warm maize porridge over three consecutive days. In phase 2, infants from each village were provided one of the new supplements for a 2-week home-use trial. Outcome measures included the amount consumed, time completion of the dose and the maternal rating of likeability on a 5-point scale. The supplements were rated acceptable if consumption was over 50% of the offered dose in phase 1. The mean (95% confidence interval) proportion of the LNS test meals consumed under direct observation was 88% (82-94%) for LNS-10gM, 90% (84-95%) for LNS-20gM, 87% (79-95%) for LNS-20gNoM, and 86% (83-90%) for Nutributter. The median (25th and 75th centile) time (minutes) for completing the offered test meal was 4 (2, 7) for LNS-10gM, 5 (3, 6) for LNS-20gM, 4 (3, 8) for LNS-20gNoM and 4 (2, 6) for Nutributter. During both phases, almost all caregivers rated all study foods very likeable for themselves and their children, with mean scores slightly lower among the caregivers than among the infants. In the home-use phase, the test foods were almost exclusively used by the study participants with minimal sharing with siblings and other household members. Some infants were reported to prefer the new investigational products over traditional complementary food. Considering that the novel LNS was largely acceptable. Efficacy trials are now needed to assess their impact on child growth and development.

Feeding patterns and behaviors during home supplementation of underweight Malawian children with lipid-based nutrient supplements or corn-soy blend

The way caregivers use supplementary food for undernourished children and integrate it into feeding patterns may influence the benefits achieved by supplementation. We studied feeding patterns and behaviors in 170 underweight 6-17-month-olds who received either lipid-based nutrient supplements (LNS) (n=85) or corn-soy blend (CSB) (n=85) during a 12-week intervention trial in southern Malawi. Observational data were collected during one 11h home visit per participant. Differences were assessed by study group and by mode of serving LNS. Associations between selected caregiver behaviors and child growth were also tested. We found no difference between the CSB and LNS groups in mean number of feeding episodes per day or mean daily feeding time. Caregivers fed the child with a spoon, washed their hands before feeding, and there were leftovers significantly more often in the CSB than LNS group and when LNS mixed with porridge and plain LNS were compared. This suggests that differences between the groups were linked to the mode of serving LNS. Presence of leftovers was negatively associated with change in childs WAZ. Programs promoting LNS in Malawi should consider behaviors related to mode of serving and provide advice to caregivers in order to minimize leftovers during supplement use.

Feeding patterns of underweight children in rural Malawi given supplementary fortified spread at home

Fortified spread (FS), containing dry food particles embedded in edible fat, offers a convenient means for nutrition rehabilitation. To describe how caregivers feed FS to their undernourished children at home, and how FS use affects other feeding patterns, we conducted a longitudinal observational study in rural Malawi. Sixteen 6- to 17-month-old underweight children (weight-for-age z-score < -2.0; -3.0 < weight-for-height z-score < 0) received FS for 12 weeks. Twelve-hour observations were conducted before supplementation and during weeks 1, 4, 8 and 12 of FS use. FS was fed to children about two times per day; each serving was 15-20 g. The spread was first used mainly alone as a between-meal snack, and then became integrated into the typical complementary feeding pattern by being mixed with porridge. Introduction of FS reduced the number of plain porridge meals, but did not decrease the total number of meals or breastfeeds per day and did not change the daily mean time caregivers spent on feeding. Children accepted the FS well, but more FS was wasted when it was offered mixed with porridge than when given alone (23.6% vs. 1.2%, 95% CI for the difference 13.2% to 31.6%). FS supplementation is feasible for community-based nutrition interventions in Malawi because it easily becomes part of the feeding routine, does not replace other foods and does not take extra caregiver time. To limit wastage, caregivers should be advised to serve FS plain or to mix it with only a small quantity of porridge.

Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi

BACKGROUND Maternal and infant undernutrition is associated with poor infant development; however, few studies have examined the impact of combined pre- and postnatal dietary supplementation on infant development. OBJECTIVE Our objective was to determine whether provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to mothers during pregnancy and the first 6 mo postpartum, and to children aged 6-18 mo, improves infant development in Malawi. DESIGN We randomly assigned 869 pregnant women to receive one of the following daily: an iron and folic acid (IFA) capsule, a multiple micronutrient (MMN) capsule containing 18 micronutrients, or a 20-g sachet of SQ-LNSs containing 22 vitamins and minerals, protein, carbohydrates, essential fatty acids, and 118 kcal. Children in the lipid-based nutrient supplement (LNS) group only received SQ-LNSs from 6 to 18 mo of age. We monitored the acquisition of 11 developmental milestones monthly by maternal report; observed the attainment of 7 motor milestones at 6, 12, and 18 mo of age; and conducted a comprehensive assessment of motor, language, and socioemotional development and executive function at 18 mo of age. The primary analysis was by intention-to-treat. RESULTS By maternal report, children in the LNS group achieved walking alone (B = 0.53; 95% CI: 0.11, 0.94; P = 0.034) and waving goodbye (B = 0.60; 95% CI: 0.12, 1.08; P = 0.040) earlier than the IFA group and standing with assistance earlier than the MMN group (B = 0.51; 95% CI: 0.12, 0.89; P = 0.029). By researcher observation, there was a trend (P = 0.052) for a greater percentage of children in the LNS group (58%) to walk alone at age 12 mo than in the IFA (49%) and MMN (49%) groups. At age 18 mo, there were no significant differences between groups in any scores. CONCLUSION Although provision of SQ-LNSs to pregnant women and infants in Malawi may affect the age of acquisition of certain developmental milestones, it did not affect our assessments of motor, language, socioemotional, or executive function skills at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT01239693.

Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes

Preterm birth is a major cause of neonatal mortality and morbidity worldwide. Bacterial infection and the subsequent inflammatory response are recognised as an important cause of preterm birth. It is hypothesised that these organisms ascend the cervical canal, colonise placental tissues, cause chorioamnionitis and in severe cases infect amniotic fluid and the foetus. However, the presence of bacteria within the intrauterine cavity does not always precede chorioamnionitis or preterm birth. Whereas previous studies observing the types of bacteria present have been limited in size and the specificity of a few predetermined organisms, in this study we characterised bacteria found in placental tissues from a cohort of 1391 women in rural Malawi using 16S ribosomal RNA gene sequencing. We found that specific bacteria found concurrently on placental tissues associate with chorioamnionitis and delivery of a smaller newborn. Severe chorioamnionitis was associated with a distinct difference in community members, a higher bacterial load and lower species richness. Furthermore, Sneathia sanguinengens and Peptostreptococcus anaerobius found in both matched participant vaginal and placental samples were associated with a lower newborn length-for-age Z-score. This is the largest study to date to examine the placental microbiome and its impact of birth outcomes. Our results provide data on the role of the vaginal microbiome as a source of placental infection as well as the possibility of therapeutic interventions against targeted organisms during pregnancy.

Association between maternal dental periapical infections and pregnancy outcomes: results from a cross-sectional study in Malawi.

Maternal infections are associated with intrauterine growth restriction (IUGR) and preterm birth (PTB). Dental infections are common in low‐income settings, but their contribution to adverse pregnancy outcomes is unknown. We studied the epidemiology of dental periapical infections among pregnant women and their association to foetal growth restriction and the duration of pregnancy in a rural sub‐Saharan African population.