Combined infant and young child feeding with small-quantity lipid-based nutrient supplementation is associated with a reduction in anemia but no changes in anthropometric status of young children from Katanga Province of the Democratic Republic of Congo: A quasi-experimental effectiveness study

Background: Small-quantity lipid-based nutrient supplements (SQ-LNS) are efficacious in controlled settings; data are scarce on the effectiveness utilizing health care delivery platforms. Objective: We evaluated the impact of an infant young child feeding (IYCF)-SQ-LNS intervention on anemia and growth in children aged 6-18 mo in the Democratic Republic of Congo following a quasi-experimental effectiveness design. Methods: An intervention health zone (HZ) received enhanced IYCF including improved counseling on IYCF during pregnancy until 12 mo after birth and daily use of SQ-LNS for infants 6-12 mo; the control HZ received the standard IYCF package. We analyzed data from 2995 children, collected in repeated cross-sectional surveys. We used adjusted difference-in-difference analyses to calculate changes in anemia, iron and vitamin A deficiencies, stunting, wasting, and underweight. Results: Of mothers, 70.5% received SQ-LNS at least once in the intervention HZ, with 99.6% of their children consuming SQ-LNS at least once. The mean number of batches of SQ-LNS (28 sachets per batch, 6 batches total) received was 2.3 ± 0.8 (i.e., 64.4 ± 22.4 d of SQ-LNS). The enhanced program was associated with an 11.0% point (95% CI: -18.1, -3.8; P < 0.01) adjusted relative reduction in anemia prevalence and a mean +0.26-g/dL (95% CI: 0.04, 0.48; P = 0.02) increase in hemoglobin but no effect on anthropometry or iron or vitamin A deficiencies. At endline in the intervention HZ, children aged 8-13 mo who received =3 monthly SQ-LNS batch distributions had higher anthropometry z scores [length-forage z score (LAZ): +0.40, P = 0.04; weight-for-age z score (WAZ): +0.37, P = 0.04] and hemoglobin (+0.65 g/dL, P = 0.007) and a lower adjusted prevalence difference of stunting (-16.7%, P = 0.03) compared with those who received none. Conclusions: The enhanced IYCF-SQ-LNS intervention using the existing health care delivery platform was associated with a reduction in prevalence of anemia and improvement in mean hemoglobin. At endline among the subpopulation receiving =3 mo of SQ-LNS, their LAZ, WAZ, and hemoglobin improved. Future research could explore contextual tools to maximize coverage and intake adherence in programs using SQ-LNS. The integrated IYCF–SQ-LNS program, known locally as the IMIKA program, which stands for “Good Food for the Nourishment of Infant and Young Children” (in Kiswahili), was piloted in 1 HZ in the Katanga Province. The population estimate for the HZ was 129,502 people with an estimated 2525 children aged 6–12 mo. The province was selected for this pilot because the infant and young child health characteristics were poor, but the province was generally less affected by the political instability affecting the rest of the country, which could have disrupted program implementation. The intervention and control HZs were in the same province and in the same district but were noncontiguous in order to avoid program spillover. Despite efforts to select comparable HZs, there were some key differences in the 2 zones, including that the intervention HZ was more rural and depended heavily on agriculture compared with the control HZ, which included more urban areas and a wider range of sources of income. This challenge was accommodated in lieu of selecting nonadjoining HZs with similar demographics but risking substantial program spillover from the intervention to the control HZ. In the control HZ, the population received the usual standard of care provided throughout the DRC based on the Essential Nutrition Actions (ENA). The usual ENA standard of care included the following: 1) iron–folic acid supplementation, antimalarial medication, and individual IYCF counseling during antenatal care visits; 2) individual counseling on IYCF and child health by community health workers (CHWs) during clinic visits; 3) monthly group counseling on IYCF and child health and growth promotion at health clinics; and 4) IYCF counseling during health worker outreach clinics. In the intervention zone, the enhanced IYCF–SQ-LNS/IMIKA program included 3 additional components, briefly as follows: 1) a nutrition education campaign for mothers and pregnant women based on the UNICEF community-based IYCF program tools, 2) the introduction of SQ-LNS (Nutributter® formulation by Nutriset) for daily consumption mixed into complementary foods among children 6–12 mo of age, and 3) reinforcement of the role of CHWs. Training for the enhanced IYCF–SQ-LNS program was based on the UNICEF community-based IYCF program tools with additional modules on the appropriate distribution, storage, and use of SQ-LNS. Training sessions were implemented using a cascade approach. Training for selected CHWs from the HZs occurred at a central location (Lubumbashi). After this, the trained CHWs went back to train other CHWs in their respective health area (aire de sante) within each HZ. CHWs in the intervention area were provided with motor bikes as both as an incentive and a way to improve their access to remote communities. Motor bike distribution did not occur in the comparison HZ. While both the intervention HZ and the comparison HZ received counseling, the intervention HZ included outreach counseling by CHWs on IYCF and SQ-LNS, in addition to facility-based counseling, while the comparison HZ received only facility-based counseling and no SQ-LNS distribution or counseling. A full description of the enhanced IYCF–SQ-LNS program is detailed elsewhere (27). Informed consent was obtained from each mother/caregiver, and for illiterate participants it was administered in the presence of a literate adult household member. The Ministry of Health and the National Statistics Office in Lubumbashi in DRC reviewed and approved the protocol for the impact evaluation. The University of Lubumbashi School of Public Health ethics committee approved this evaluation. Before launching the program, formative research was conducted on the acceptability, appropriate use, marketing, and behavior change strategies needed to support the introduction of an enhanced IYCF–SQ-LNS intervention. The formative data collection included a month-long acceptability trial in 2010, which confirmed the SQ-LNS were well accepted (26). Focus groups with caregivers of young children and key informant interviews with mothers, fathers, and health workers were conducted to develop product packaging and messaging pertaining to the SQ-LNS and to assess the knowledge, attitudes, practices, and barriers to optimal IYCF practices. The product was locally branded as “Kulabora” in Swahili, which translates to “eating better.” The enhanced IYCF program had comprehensive counseling and educational components that targeted all mothers and their children (up to 12 mo of age) and pregnant women in the intervention catchment area, but not the comparison HZ, as detailed elsewhere (27). This was achieved by developing information, education, and communication materials and messages and tailored key messages, which were reinforced through various channels in the intervention site. The 4 key messages were as follows: 1) put your baby to the breast within an hour of giving birth; 2) only give breast milk (no water or other foods) to your baby until they are 6 mo of age; 3) from 6 mo of age, continue to breastfeed and give solid foods enriched with fish, caterpillars/insects, and eggs, even when you provide Kulabora; and 4) wash your hands with soap or ash before preparing food, eating, giving food to your baby, and after using the toilet. These messages were included in flipchart teaching aids, during educational sessions, other in-person interactions, on posters, on the Kulabora packaging, and in radio spots. The IMIKA program also strengthened the role of CHWs who formed an integral part of IYCF counseling and, for SQ-LNS, the monthly distribution, as well as counseling on the appropriate storage and use of SQ-LNS. Mothers of children 6–12 mo of age in the intervention zone were expected to receive 4 strips of 7 sachets of SQ-LNS (i.e., a monthly totaling 28 sachets, which we refer to as a batch) at their nearest health facility during their monthly clinic visits or for very-hard-to-access areas through outreach services by health center staff. Each child was eligible to receive 6 batches, 1/mo from 6–12 mo of age. Each of the 7 sachets detailed pictorially how to use SQ-LNS (Kulabora) and included a key message: 1) give 1 packet per child per day, 2) wash your child's hands with soap and water before feeding, 3) breastfeed your child before giving food, 4) put a small amount of food that you think your child will eat in a separate bowl, 5) mix the Kulabora into the food, 6) feed the food mixed with the Kulabora to your child, and 7) Kulabora is for children from 6 to 12 mo of age. In September 2012, the enhanced IYCF counseling started, and Kulabora distribution started in May 2013 and continued until after the completion of all evaluation data collection, ending approximately March 2015. Three rounds (February 2013, July 2013 and February 2014) of lot-quality assurance surveys (LQASs) (28) were conducted in all 13 health areas in the intervention zone. This was an additional effort to monitor the enhanced intervention package put in place to check if the program was functioning reasonably well before going to the effort of conducting the endline survey. Health areas/posts were graded on 21 benchmark questions that ranged from SQ-LNS stocks, staff training, health worker activities, program coverage in terms of SQ-LNS, and group counseling. A pass or fail grade was assigned if a predefined coverage target was achieved or not. Corrective action was implemented in low-performing health centers as needed. A pre-post, quasi-experimental effectiveness study design was used to evaluate the IMIKA program. Repeated serial cross-sectional baseline and endline surveys were conducted in the intervention and the comparison HZs. The baseline survey was conducted in October 2011 and the endline survey in October–November 2014 in both sites. Caregivers of children 6.0–11.9 mo of age were expected to receive monthly distributions of SQ-LNS for a maximum of 6 distributions per child. The endline survey occurred in October–November 2014, 6 mo prior to the end of the SQ-LNS supply, which was expected to last until March 2015. The baseline and endline surveys followed a 2-stage cluster-sampling design. In the first stage, 30 clusters were randomly selected from each HZ (60 total) using probability-proportional-to-population-size sampling. The enumeration team made a list of all children aged 6.0–17.9 mo in each selected cluster, and 22 children from each cluster were randomly selected. There was no replacement for any reason. The same clusters were used for the baseline and the endline data collection, but different households and children were randomly selected, as the children selected in the baseline sample had aged out of the intervention. The estimated sample size provided 80% power to detect a relative decline in the prevalence of anemia and ID of 15% and 20%, respectively, at an ɑ of 0.05. The enhanced IYCF–SQ-LNS intervention was designed for pregnant women and children aged <12 mo. However, the age range for the evaluation was children aged 6–18 mo, even though those >12 mo would have aged out of the program. This was done in order to reduce the difficulties and costs associated with identifying enough children within a much narrower age band and because the expectation was that any effects would persist among those children who had aged out of the program. Due to cost, and typical reduction in health care–seeking behavior of mothers of children >1 y of age, it was not possible to expand the age range of the intervention. Trained enumerators asked caregivers questions pertaining to household sociodemographic characteristics and knowledge, attitudes, experiences, and behaviors relating to nutrition, IYCF, anemia, and SQ-LNS. The enumerators asked mothers to recall various breastfeeding practices for the selected child aged 6–18 mo, such as how soon after birth breastfeeding was initiated, whether the child was breastfed yesterday, and when water and complementary foods were first introduced. Also, at baseline and endline, a 24-h recall of all the foods and drinks (including meals and snacks) children consumed in the previous day and night was collected in accordance with the standard WHO/UNICEF IYCF indicators approach (29). In the endline survey only, mothers were asked about exposure to specific parts of the IMIKA program, such as familiarity with their CHW, participation in group counseling sessions, and awareness of radio messages on IYCF. Extensive information was also collected on the use of the SQ-LNS, including how it was consumed (mixed or eaten alone), if the child liked the SQ-LNS, any changes (both positive and negative) since the child started consuming the SQ-LNS, and how many monthly batches had been collected from the nearest health facility. After the questionnaire was completed, anthropometric measures of the children were taken by trained enumerators following standardized protocols (30). Weight was measured using electronic Seca® 874 scales to the nearest 10 g. Length was measured using a wooden Shorr® measuring board to the nearest millimeter. Age was calculated using date of birth from either a child health card or birth certificate (if available) and the date of survey. If no reliable proof of age was available, age was estimated in months using a local events calendar or by mother/caregiver report. A capillary blood specimen was collected in a 500-μL Microtainer® with EDTA through a finger prick. One drop of blood from the Microtainer® was used for the evaluation of hemoglobin by the photometric method using the HemoCue® 301 hemoglobin system (HemoCue® AB). One drop was used to test for malaria using a malaria antigen (HRP2/pLDH) combo rapid test kit for Plasmodium falciparum and Plasmodium vivax. The Microtainers® were stored in a cool box during the day and transported to a central laboratory in each zone where they were processed at the end of the day. The Microtainers® were centrifuged at 3500 rpm for 10 min at room temperature using a fixed-speed centrifuge, and the plasma was pipetted into cryovial tubes and PCR tubes. The processed specimens were then frozen and stored at −20°C. At the end of the survey, the specimens were shipped to Germany, where the VitMin Laboratory used an ELISA to assess serum ferritin (SF), sTfR, retinol binding protein (RBP), C-reactive protein (CRP), and ɑ1-acid glycoprotein (AGP) (31). Descriptive statistics are presented as percentages. Statistical significance was set at P < 0.05, and all analyses were adjusted for clustering with Taylor series variance estimation. Analyses were conducted with SAS version 9.4 (SAS Institute). Child anthropometric variables were converted into z scores [length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ)] based on the WHO 2006 growth standards (32). Biologically implausible values (BIVs; i.e., WAZ −6 < WAZ > +5, LAZ −6 < LAZ > +5, WLZ −5 < WLZ > +5) were flagged and excluded from subsequent analyses (32). Six BIVs or 0.23% of observations were excluded. Key outcome measures included anthropometric z-score indices (LAZ, WLZ, and WAZ) and nutritional biomarkers (hemoglobin, SF, sTfR, and RBP). Each outcome was assessed as a continuous variable as well as a categorical indicator. Anemia was defined according to WHO classifications as anemic (hemoglobin <11.0 g/dL) and “severe or moderate anemia” for hemoglobin <10.0 g/dL (33). Moderate and severe anemia were combined to a single category due to the low prevalence of severe anemia. All clusters in both HZs were located <1000 m so hemoglobin concentration was not adjusted for altitude. ID was defined as SF <12 µg/L. RBP concentrations of less than the 0.7-µmol/L cutoff were used to define vitamin A deficiency. SF, sTfR, and RBP biomarkers were adjusted for inflammation using the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) regression correction technique (34–36). We used an additive difference-in-difference (DiD) (37–39) modeling technique to test and quantify program impact and the associations between the integrated IYCF and SQ-LNS and program indicators between the 2 HZs in pre- and post-surveys. Generalized linear mixed models (GLMMs) with cluster as a random effect were used to examine associations. The DiD effects, their 95% CI, and P values were obtained from GLMMs that accounted for HZ (intervention vs. control) and time (endline vs. baseline) and included an interaction term between HZ and time for quantifying program impact. This use of DiD from mixed models to quantify program impact allowed interpretation of average program effect for an average child within each cluster and was well suited for our design of repeated serial cross-sectional data of different children (38, 39). Two separate GLMMs were used to explore these associations, i.e., 1) continuous and 2) categorical variable outcome analysis. It was determined a priori that the multivariable DiD models would adjust for the following confounding covariates: child's sex and age; maternal age, education, and ethnicity; urban versus rural; household's primary source of income; household asset tertile (from a cumulative count of all household possessions); the presence of another child <5 y old in the household; and malaria test positive status of the index child. Further, multivariate mixed linear models were used to calculate prevalence differences (PDs; %) for binary program indicators that were measured at endline only in both HZs. Rao-Scott chi-square test was used to compare differences in proportions for selected categorical indicators and a design-based t test was used for continuous variables as appropriate. Additionally, in the intervention HZ, program exposure also included the SQ-LNS intervention component, which was captured in a variety of indicators. Components included “mother received SQ-LNS for her child at least once,” number of times SQ-LNS received, and mothers who received 1 batch (28 SQ-LNS sachets) at the last distribution, among several other variables. We evaluated the potential dose–response effect of the SQ-LNS among children 8 to 13 mo old in the intervention HZ who were eligible to receive ≥3 monthly SQ-LNS distributions (3 × 28 sachets) and eligible to receive LNS within the last month. This 8–13-mo age group was selected because SQ-LNS were distributed during routine monthly health facility visits; however, timely introduction of solid foods/complementary feeding at 6 mo in the villages in both HZs was low, ∼27% (27). Children who were only 6 or 7 mo old would have had no or limited time to consume SQ-LNS sachets as they would have received only 1 or 2 batch distributions at maximum, whereas children aged 13 mo would have recently finished SQ-LNS intake and have had a high potential exposure to SQ-LNS over the prior 6 mo. Hence, the 8–13-mo age range enabled us to identify a subpopulation of children most likely to have sufficient program exposure to expect a biological impact. For this dose–response analysis we created 3 categories of Kulabora exposure: 1) no SQ-LNS received, 2) low exposure (received 1–2 batches of SQ-LNS), and 3) higher exposure for ≥3 mo of distribution of SQ-LNS batches, equivalent to ≥50% of the total SQ-LNS sachets. GLMM was used to estimate relative differences in program indicators across the 3 categories of SQ-LNS exposure. In the intervention HZ, we also quantified adjusted PDs of indicators between endline and baseline. We note that adjusted prevalence or mean difference estimates were all calculated from estimable functions of marginals (i.e., least-square means) (40) that accounted for potential confounding covariates. Therefore, estimates might not approximate the value obtained from algebraic subtraction of crude differences in prevalences (or means) and are also subject to missing covariates in the full GLMM.