Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials

. 2021 Sep 29;114(Suppl 1):68S–94S. doi: 10.1093/ajcn/nqab276

Study-level effect modifiers	Individual-level effect modifiers
• Geographic region (WHO region: African vs. South-East Asia Region)• Anemia burden (country-specific, closest in time to the study: <60% vs. ≥60%)²• Malaria prevalence (country-specific, closest in time to the study: <10% vs. ≥10%)³• Inflammation prevalence (study-specific:, elevated CRP ≤25% and/or elevated AGP ≤50% vs. elevated CRP >25% and/or elevated AGP >50%)⁴• Water quality (study-specific: <75% vs. ≥75% prevalence of improved drinking water)⁵• Sanitation (study specific: <50% vs. ≥50% prevalence of improved sanitation)⁶• Duration of child supplementation (study target: >12 mo vs. ≤12 mo)• Iron dose in the SQ-LNS product (9 mg/d vs. <9 mg/d)⁷• Child age at baseline or endline• Frequency of contact for intervention delivery or outcome assessments during the study (weekly vs. monthly)• Compliance (average percentage compliance in LNS group ≥80% vs. <80%)⁸	• Maternal BMI (<20 kg/m² vs. ≥20 kg/m²)• Maternal age (<25 y vs. ≥25 y)• Maternal education (no formal or incomplete primary vs. complete primary or greater)• Child sex (female vs. male)• Child birth order (first born vs. later born)• Child baseline acute malnutrition (WLZ <−2 SD or MUAC <125 mm vs. WLZ ≥−2 SD and MUAC ≥125 mm; if MUAC not measured, WLZ <−2 SD vs. WLZ ≥−2 SD)• Child baseline anemia status (Hb ≥110 g/L vs. <110 g/L); iron outcomes only• Child high-dose vitamin A supplementation (receipt within 6 mo before outcome assessment vs. nonreceipt)• Child inflammation at time of outcome assessment (CRP ≤5 mg/L and AGP ≤1 g/L vs. not)• Household socioeconomic status (< study median vs. ≥ study median)⁹• Food security (moderate-to-severe food insecurity vs. mild food insecurity to secure)• Water quality (unimproved vs. improved)⁶• Sanitation (unimproved vs. improved)⁷• Season at the time of outcome assessment (rainy vs. dry)¹⁰

Study-level effect modifiers

Individual-level effect modifiers

• Geographic region (WHO region: African vs. South-East Asia Region)• Anemia burden (country-specific, closest in time to the study: <60% vs. ≥60%)²• Malaria prevalence (country-specific, closest in time to the study: <10% vs. ≥10%)³• Inflammation prevalence (study-specific:, elevated CRP ≤25% and/or elevated AGP ≤50% vs. elevated CRP >25% and/or elevated AGP >50%)⁴• Water quality (study-specific: <75% vs. ≥75% prevalence of improved drinking water)⁵• Sanitation (study specific: <50% vs. ≥50% prevalence of improved sanitation)⁶• Duration of child supplementation (study target: >12 mo vs. ≤12 mo)• Iron dose in the SQ-LNS product (9 mg/d vs. <9 mg/d)⁷• Child age at baseline or endline• Frequency of contact for intervention delivery or outcome assessments during the study (weekly vs. monthly)• Compliance (average percentage compliance in LNS group ≥80% vs. <80%)⁸

• Maternal BMI (<20 kg/m² vs. ≥20 kg/m²)• Maternal age (<25 y vs. ≥25 y)• Maternal education (no formal or incomplete primary vs. complete primary or greater)• Child sex (female vs. male)• Child birth order (first born vs. later born)• Child baseline acute malnutrition (WLZ <−2 SD or MUAC <125 mm vs. WLZ ≥−2 SD and MUAC ≥125 mm; if MUAC not measured, WLZ <−2 SD vs. WLZ ≥−2 SD)• Child baseline anemia status (Hb ≥110 g/L vs. <110 g/L); iron outcomes only• Child high-dose vitamin A supplementation (receipt within 6 mo before outcome assessment vs. nonreceipt)• Child inflammation at time of outcome assessment (CRP ≤5 mg/L and AGP ≤1 g/L vs. not)• Household socioeconomic status (< study median vs. ≥ study median)⁹• Food security (moderate-to-severe food insecurity vs. mild food insecurity to secure)• Water quality (unimproved vs. improved)⁶• Sanitation (unimproved vs. improved)⁷• Season at the time of outcome assessment (rainy vs. dry)¹⁰

AGP, α-1-acid glycoprotein; CRP, C-reactive protein; Hb, hemoglobin; LNS, lipid-based nutrient supplement; MUAC, midupper arm circumference; SQ, small-quantity; WASH, water, sanitation, and hygiene; WLZ, weight-for-length z score.

Country-specific prevalence of anemia among children 6–59 mo old, based on national surveys (see Supplemental Table 3); cutoff chosen based on the median across trials.

Country-specific prevalence of malaria, based on the World Malaria Report 2018 (see Supplemental Table 3) (51); cutoff chosen based on the median across trials.

⁴

Elevated CRP defined as >5 mg/L, elevated AGP defined as >1 g/L. Based on data at outcome assessment because baseline data were not available for all trials; cutoff chosen based on the median across trials.

⁵

Improved water source includes piped water, boreholes or tubewells, protected dug wells or springs, rainwater, and packaged or delivered water (see Supplemental Table 3) (95); based on baseline data, excluding arms that received WASH interventions; cutoff chosen at approximately the median across trials.

⁶

Improved sanitation includes flush/pour flush to piped sewer system, septic tanks, or pit latrines; ventilated improved pit latrines, composting toilets, or pit latrines with slabs (see Supplemental Table 3) (96); based on baseline data, excluding arms that received WASH interventions; cutoff chosen based on the median across trials.

⁷

Study-specific (see Supplemental Tables 2 and 3).

⁸

Study-specific, because reported based on a study-defined indicator (see Supplemental Table 3); cutoff chosen based on the median across trials.

⁹

Based on a study-defined, study-specific assets index.

¹⁰

Rainy compared with dry, based on study- and child-specific average rainfall during the month of measurement and 2 mo prior (see Supplemental Methods and Supplemental Table 4).