Effect of 12-month intervention with lipid-based nutrient supplement on the physical activity of Malawian toddlers: A randomised, controlled trial

Physical activity is beneficial for children’s well-being. The effect of dietary supplementation on children’s physical activity in food-insecure areas remains little studied. We examined the effects of a lipid-based nutrient supplement (LNS) on children’s objectively measured physical activity in a randomised, controlled, outcome-assessor-blinded trial. Mothers of the children received one capsule daily of Fe-folic acid (IFA), one capsule containing eighteen micronutrients (MMN) or one 20 g sachet of LNS (containing twenty-two MMN, protein, carbohydrates, essential fatty acids and 494 kJ (118 kcal)) during pregnancy and for 6 months thereafter. Children in the IFA and MMN groups received no supplementation, and these groups were collapsed into a single control group; children in the LNS group received 20 g LNS from 6 to 18 months. We measured physical activity with accelerometers over 1 week at 18 months. The main outcome was mean vector magnitude counts/15 s. Of the 728 children at the beginning of child intervention at 6 months, 570 (78 %) provided sufficient data for analysis. The mean accelerometer counts for the 190 children in the LNS group and for the 380 children in the control group were 303 (sd 59) and 301 (sd 56), respectively (P for difference=0·65). LNS, given to mothers during pregnancy and 6 months postpartum and to their infants from 6 to 18 months of age, did not increase physical activity among 18-month-old children. The study was conducted in a semi-urban and rural area of Mangochi District, Southern Malawi. This area has high prevalence of chronic infant undernutrition( 34 ). The activity sub-study was a part of a larger trial, iLiNS-DYAD-M, details of which have been published earlier( 35 ). In brief, iLiNS-DYAD-M was a randomised, single-blind, parallel-group controlled trial testing the health effects of supplementing maternal diet during pregnancy and lactation and infant diet from 6 to 18 months of age with LNS. This study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving human subjects were approved by the College of Medicine Research and Ethics Committee, University of Malawi, and by the Ethics Committee of Pirkanmaa Hospital District, Finland. We performed the trial according to Good Clinical Practice guidelines. Written or thumb-printed informed consent was obtained from all subjects. The maternal enrolment took place through the antenatal clinics in Mangochi district hospital, Malindi hospital and Lungwena health centre. We included mothers whose ultrasound scan confirmed pregnancy of ≤20 completed gestation weeks. Detailed maternal inclusion and exclusion criteria were published previously( 35 ). For the physical activity sub-study, we recruited all participants who came to the last clinic visit of the main trial at the age of 18 months when they were still receiving the intervention. Those children who had moved out of the study area or whose guardian did not give consent for the sub-study were excluded. Data collection was conducted between January 2013 and March 2014. The details of the randomisation procedure can be found in an earlier publication( 35 ). In brief, a researcher not involved in the data collection created randomisation slips in blocks of nine and sealed the slips in opaque, numbered envelopes. Eligible pregnant women were requested to choose one of the top six envelopes in a stack. The contents of the envelope indicated her participant number and group allocation. We used single-masked procedures for the LNS intervention; that is, field workers who delivered the supplements knew which mothers were receiving LNS. The research assistants measuring activity and anthropometric outcomes were kept blinded to the group allocation until the end of data collection. The researchers doing the analyses were blinded until the data were cleaned and the statistical analysis plan published online (www.ilins.org and online Supplementary Material S1). The trial included three study groups( 35 ), which were collapsed into two groups for the purpose of this analysis. Children in the LNS group received 20 g of small-quantity LNS (20 g LNS) daily from 6 to 18 months of age. Their mothers had received 20 g of LNS during pregnancy and lactation (20 g LNS-P&L), daily during pregnancy and for 6 months thereafter. Both the 20 g milk containing LNS and 20 g LNS-P&L included twenty-two vitamins and minerals, 10 g fat (including linolenic acid and α-linolenic acid) and 2·6 g protein( 33 , 36 ). The main ingredients of the LNS were peanuts, vegetable oil, milk powder, and a vitamin and mineral mix. The 20 g daily ration of LNS would provide the RDA of most micronutrients for a healthy, breast-feeding infant( 36 ). LNS was produced and packed in individual 20 g foil sachets by Nutriset S.A.S. Children in the control group did not receive supplementation, but their mothers had received either (a) one capsule daily of Fe-folic acid until delivery (60 mg Fe+400 µg folic acid) and one daily tablet of Ca (200 mg), akin to placebo, from delivery to 6 months postpartum (original Fe-folic acid (IFA) group) or (b) one tablet of multiple micronutrients (containing Fe-folic acid and sixteen additional micronutrients( 36 )) daily through pregnancy and 6 months postpartum (original micronutrients (MMN) group). Because of the absence of difference in child outcomes between the original IFA and MMN groups in our previous analyses( 33 , 35 ), and because children in these groups received no intervention from 6 to 18 months, we collapsed the IFA and MMN groups into a single control group. Data collectors made weekly home visits to collect information on supplement use and fortnightly visits to deliver the supplements. Guardians were advised to divide the daily LNS ration into two equal proportions, mixed with porridge. As a result of a new quality assurance procedure in the supplement production, there was a brief interruption in LNS delivery during the trial implementation. Because of this episode, 121 children missed receiving LNS for a period that ranged from 1 to 41 d between 1 August and 11 September 2012. Further details on this episode were published earlier( 35 ). Apart from malaria, which was treated with lumefantrine/artemether at the study clinic, the participants’ medical conditions were treated in Malawi’s national health system, with the study team reimbursing the participants for all medical costs. Physical activity was measured over 1 week with the ActiGraph GT3X+ (ActiGraph LLC), a small accelerometer that records accelerations in three different axes: vertical, antero-posterior and medio-lateral( 26 , 37 ). While at the clinic, research assistants instructed the guardians to secure the accelerometer on the child’s right hip using an elastic belt and to allow the child to wear the device continuously throughout the day and night and to remove it only if the child showed signs of discomfort. At the maternal enrolment visit, trained anthropometrists measured the mothers’ weight with digital scales (SECA 874 flat scale; Seca GmbH & Co.) and height with stadiometers (Harpenden stadiometer; Holtain Limited). Research assistants obtained maternal age and years of schooling by interviewing mothers at the enrolment visit. Household food insecurity was assessed with the Household Food Insecurity Access Scale (HFIAS)( 38 ). On the basis of the length of follow up and the number of supplement doses delivered home and returned unused, the mean adherence (proportion of days when the children consumed LNS supplements) was 77 %( 33 ). Children’s date of birth was verified by the research assistants who visited the child soon after birth( 35 ). At the clinic visits at 6 and 18 months of age, research anthropometrists measured participants’ weight in triplicate to the nearest 20 g using an electronic infant-weighing scale (SECA 381 baby scale; Seca GmbH & Co) and length to the nearest 1 mm using a high-quality length board (Harpenden Infantometer; Holtain Limited). We calculated length-for-age z-score (LAZ) and weight-for-length z-score (WLZ) using the WHO 2006 Child Growth Standards( 39 ). Research assistants observed the children to assess their ability to walk at 18 months of age. Guardians were interviewed on how much the children were being carried by others, and children who were reportedly being carried 1 h or more every day or almost every day were classified as carried. We analysed data using Stata/IC software, version 12.1 (StataCorp.). We set the level of statistical significance at 0·05 for all analyses. All the analyses were based on the principle of modified intention to treat; that is, we included all participants randomly assigned in the analyses, with the exception that two participants whose group allocations were incorrectly transcribed and assigned during enrolment were included in the group corresponding to the actual intervention they received throughout the trial. We considered physical activity data to be missing if the actual onset of measurement was over 30 d from the planned date. There were two reasons for this choice: children were no longer receiving intervention at this stage and improved motor skills at older age could result in accelerometer readings different from those of children at 18 months of age. The data reduction was done similarly to our earlier study( 31 ): we excluded the first and the last days of measurement as incomplete days, night time between 20.00 and 05.00 hours, and strings of ≥20 min of zeroes( 11 ). Participants with ≥4 d( 27 ) with ≥6 h( 40 ) of accelerometer data were included in the analyses. We set epoch length at 15 s( 11 , 41 , 42 ). We used daily mean vector magnitude (VM) counts/15 s as the main outcome. The VM counts were calculated by taking the square root of the sum of squared activity counts of each of the three axes. Secondary outcomes included mean vertical axis counts/15 s, percentage of time in moderate-to-vigorous physical activity (MVPA), percentage of time being sedentary and percentage of active children. We calculated mean VM and vertical axis counts/15 s by averaging mean counts/15 s of each day over all valid days for each of the participants. The percentage of time spent in MVPA was defined using validated cutoff points of vertical axis activity counts ≥419 counts/15 s( 25 ) and percentage of time being sedentary as vertical axis activity counts ≤48 counts/15 s( 25 ). The proportion of active children was calculated according to the guidelines of the US National Association for Sports and Physical Education as those children whose mean time in MVPA over all valid days was ≥90 min/d( 43 ). We used Fisher’s exact test to test for differences in the rate of loss to follow up between groups. We tested the hypothesis that physical activity of infants in the intervention group would be greater than that of infants in the control group for each activity outcome using Student’s t test, and the hypothesis that a greater proportion of children in the intervention group would reach 90 min of MVPA/d with a log-binomial regression model. We also drew kernel density plots for each of the outcomes. As a secondary analysis for assessing the mean VM counts in the intervention and control groups, we built a regression model adjusting for eight pre-specified variables (LAZ at 6 months, WLZ at 6 months, sex, season of activity measurement, birth order, maternal education, maternal age and HFIAS score) and for child carrying (carried v. not). We also performed a sensitivity analysis by testing the differences in mean VM counts between the three original groups, LNS, IFA and MMN, with ANOVA. The sample size was originally calculated in accordance with the main objective of the trial: 288/group to detect an effect size of 0·3 of LNS on child length. The sample size of about 190 LNS and 380 control participants for this sub-study offered about 80 % power to detect an effect size of 0·25 sd in continuous outcomes at 5 % two-sided type I error rate.