Statistical analysis
wasting
REGRESSION, WASTING, SECONDARY
In the absence of dependency between the effects of the pre- and postnatal interventions (see below), a sample size of 588 children per study arm (All analyses in this study were documented a priori in the MISAME-III statistical analysis plan, which was published in the study website on November 3, 2020 (The analysis strategy to evaluate the effects of BEP supplementation on infant outcomes was established based on the presence or absence of dependency (i.e., statistically significant interaction at Group differences in growth and nutritional status of infants at the age of 6 months (also at 9 and 12 months in a subsample) were estimated by fitting linear regression models for the continuous outcomes and linear probability models with robust variance estimation for the binary outcomes. Poisson regression models with robust variance estimation were fitted to estimate risk ratios between study arms in terms of the number of months infants received EBF and the number of months infants were diagnosed with wasting during the 6 months postpartum. All models contained the health center and randomization block as fixed effects to account for any possible clustering by the study design. Adjusted models further included prespecified known prognostic factors of the study outcomes such as maternal age, height, body mass index (BMI), MUAC, hemoglobin concentration, gestational age, and parity at study enrollment. Our main analysis followed a modified intention-to-treat (mITT) principle in which all infants who had birth anthropometry measurements were included in the analyses at 6 months. For this purpose, we conducted multiple imputations of missing data using chained equations under the “missing-at-random assumption.” Fifty imputations of missing data were conducted to estimate the regression coefficients. We further assessed the robustness of our findings by conducting sensitivity analyses such as a complete cases analysis (i.e., by including only infants with available measurements at 6 months) and a per-protocol analysis (i.e., by including only participants with BEP adherence of at least 75%).As a secondary analysis, we modelled growth trajectories of infants from birth to 6 months, which continued up to 9 and 12 months on a subsample of infants. Mixed effects models with a random intercept for the individual infant and a random slope for the age of the child (in months) were fitted to estimate group differences on average monthly changes in LAZ, WLZ, WAZ, MUAC, and head circumference. We explored the best model fit for our data by assessing different potential relationships of the study outcomes with time, by visual inspection of graphs and comparing model fit indices (AIC and BIC). We applied linear models (WLZ and WAZ), quadratic model (LAZ), and restricted cubic spline models with 6 knots (MUAC and head circumference) according to the model fit. Fixed effects in the model included the main effect of group, time, and group by time interaction, which the later estimates difference between groups on monthly changes in the outcomes. All models included the clustering indicators (i.e., health center and randomization block), whereas adjusted models additionally included the aforementioned known maternal prognostic factors of infant growth.Furthermore, we explored potential intervention effect modification on the primary outcome LAZ at 6 months by prespecified subgroup factors, such as maternal BMI (<18.5 kg/mThe longitudinal prevalence rates of common childhood morbidities during the 6 months follow-up were calculated using “the total number of days that the outcome was reported” as numerator, and “the total days observed or assessed” as denominator. We used Poisson regression models with robust variance estimation to estimate risk ratios comparing study arms by the occurrence of morbidity outcomes.Finally, to inform on the potential effect of the combination of the pre- and postnatal BEP interventions, we conducted supplementary analysis using a four intervention arms approach evaluating LAZ and stunting at 6 months and LAZ trajectories from birth to 12 months comparing the control group for both intervention periods (IFA/IFA) against each of the prenatal only BEP (BEP/IFA), the postnatal only BEP (IFA/BEP), and the combination of the pre- and postnatal BEP (BEP/BEP) groups.