Birth length is the strongest predictor of linear growth status and stunting in the first 2 years of life after a preconception maternal nutrition intervention: the children of the Women First trial

Abstract

Background: The multicountry Women First trial demonstrated that nutritional supplementation initiated prior to conception (arm 1) or early pregnancy (arm 2) and continued until delivery resulted in significantly greater length at birth and 6 mo compared with infants in the control arm (arm 3).

Objectives: We evaluated intervention effects on infants' longitudinal growth trajectory from birth through 24 mo and identified predictors of length status and stunting at 24 mo.

Methods: Infants' anthropometry was obtained at 6, 12, 18, and 24 mo after the Women First trial (registered at clinicaltrials.gov as NCT01883193), which was conducted in low-resource settings: Democratic Republic of Congo, Guatemala, India, and Pakistan. Longitudinal models evaluated intervention effects on infants' growth trajectory from birth to 24 mo, with additional modeling used to identify adjusted predictors for growth trajectories and outcomes at 24 mo.

Results: Data for 2337 (95% of original live births) infants were evaluated. At 24 mo, stunting rates were 62.8%, 64.8%, and 66.3% for arms 1, 2, and 3, respectively (NS). For the length-for-age z-score (LAZ) trajectory, treatment arm was a significant predictor, with adjusted mean differences of 0.19 SD (95% CI: 0.08, 0.30; P < 0.001) and 0.17 SD (95% CI: 0.07, 0.27; P < 0.001) for arms 1 and 2, respectively. The strongest predictors of LAZ at 24 mo were birth LAZ <-2 and <-1 to ≥-2, with adjusted mean differences of -0.76 SD (95% CI: -0.93, -0.58; P < 0.001) and -0.47 SD (95% CI: -0.56, -0.38; P < 0.001), respectively. For infants with ultrasound-determined gestational age (n = 1329), the strongest predictors of stunting were birth LAZ <-2 and <-1 to ≥- 2: adjusted relative risk of 1.62 (95% CI: 1.39, 1.88; P < 0.001) and 1.46 (95% CI: 1.31, 1.62; P < 0.001), respectively.

Conclusions: Substantial improvements in postnatal growth are likely to depend on improved intrauterine growth, especially during early pregnancy.

Keywords: birth length; breastfeeding; growth; infant growth; maternal height; preconception; stunting.

FIGURE 1

All sites unadjusted longitudinal growth outcomes from birth to 24 mo by treatment arm among the longitudinal analysis subset. Data derived from Supplemental Table 1. *Indicates unadjusted pairwise comparisons between arm 1 compared with arm 3 were significant. ^#Indicates unadjusted pairwise comparisons between arm 2 compared with arm 3 were significant. Total participants by arms 1, 2, and 3, n = 755, 808, and 774, respectively. After excluding extreme invalid measurements as determined by expert manual review and accounting for biologically implausible z- scores based on WHO standards (9), the 24-mo longitudinal analysis subset includes all live-born infants with birth length measurements measured by 7 d (168 h) of age on portable length boards and consented to the offspring follow-up study. Arm 1 maternal participants received the study supplement starting at least 3 mo prior to conception and continued through delivery; arm 2 started the study supplement at the end of the first trimester and continued through delivery; arm 3 (control) did not receive study supplement. Sample sizes of offspring according to treatment arm were 755, 808, and 774 for arms 1, 2, and 3, respectively. LAZ, length-for-age z-score; WAZ, weight-for-age z-score; WLZ, weight-for-length z- score.

FIGURE 2

Predictors of length-for-age z-score (LAZ) (2A) and stunting (2B) at 24 mo for infants with gestational age determined by first-trimester ultrasound. Cross-sectional analyses with linear (robust Poisson) regression for continuous (binary) outcomes were used to identify the major predictors of linear growth status at 24 mo. Gestational age was determined by first-trimester ultrasound and z-scores were derived from INTERGROWTH-21st fetal growth charts (10). Total participants n = 1329; by arms 1, 2, 3: n = 438, 478, 413, respectively; by site: Guatemala n = 439, India n = 487, Pakistan n = 403. Model included adjustment for arm, site, cluster, and interaction between site and cluster. *Birth LAZ <–1 to ≥–2. Adj RR, adjusted RR; Educ, education; Ht, height; IG, INTERGROWTH-21st standards; LAZ, length-for-age z-score; Mat, maternal; Pat, paternal; PTB, preterm birth; SES, socioeconomic status; SGA, small for gestational age.