Growth patterns of children with congenital Zika syndrome in Brazil: a matched-cohort study.

BACKGROUND: Children born with congenital Zika syndrome typically present with structural abnormalities and neurological impairments that can disrupt postnatal growth. We aimed to evaluate longitudinal anthropometric trajectories of children with congenital Zika syndrome compared with children without congenital Zika syndrome in Brazil.

METHODS: In this matched-cohort study, we used Brazilian administrative data on singleton livebirths from Jan 1, 2015, to Dec 31, 2018, with follow-up routine primary care health data from birth to age 5 years. We excluded children with missing or inconsistent information about sex, type of pregnancy, birthweight, gestational age, date of birth, and anthropometric measurements. Cases of congenital Zika syndrome were obtained from the Brazilian Ministry of Health's Public Health Event Registry. For children classified with congenital Zika syndrome, we excluded those with a diagnosis of congenital syphilis or toxoplasmosis. An exactly matched comparison group of children with a similar likelihood of exposure to the Zika virus was selected. Descriptive statistics was used to compare anthropometric characteristics among children with congenital Zika syndrome and microcephaly, children with congenital Zika syndrome without microcephaly, and children without congenital Zika syndrome. Using mixed-effects models, we estimated mean trajectories of length or height (cm), weight (kg), and BMI (kg/m2) for these three groups. Multi-state models, stratified by microcephaly status and sex, were applied to compare transitions between nutritional status (based on WHO growth indicators) over time.

FINDINGS: We analysed growth measurements for 1268 children with congenital Zika syndrome and 6340 matched controls. Measurements indicative of stunting (length-for-age and height-for-age Z score <-2), underweight (weight-for-age Z score <-2), malnutrition (BMI-for-age Z score <-2), and wasting (weight-for-length and weight-for-height Z score <-2) were more frequent among children with congenital Zika syndrome and microcephaly (1676 [49·2%] of 3408, 1623 [39·3%] of 4126, 743 [21·8%] of 3408, and 839 [24·6%] of 3408, respectively) and children with congenital Zika syndrome but no microcephaly (924 [30·5%] of 3028, 857 [24·0%] of 3577, 566 [18·7%] of 3028, and 602 [19·9%] of 3028, respectively) than among children without congenital Zika syndrome (3489 [11·0%] of 31 836, 1355 [3·5%] of 38 172, 1490 [4·7%] of 31 836, and 1410 [4·4%] of 31 836, respectively; all p<0·0001). At age 5 years, adjusted mean height was 6·61 cm less in children with congenital Zika syndrome and microcephaly and 4·21 cm less in those without microcephaly than matched controls. In transition models, the 6-month probability of recovery from severe stunting (≥-6 SD to <-3 SD) among children with congenital Zika syndrome with microcephaly was 0·32 (95% CI 0·27-0·37) in males and 0·24 (0·20-0·29) in females. The transition probabilities increased among children with congenital Zika syndrome and no microcephaly (0·47 [95% CI 0·40-0·53] in males and 0·37 [0·30-0·44] in females). By contrast, the transition probabilities were at least 0·75 among all children without congenital Zika syndrome. Expected first passage times, representing the expected time to transition from one nutritional state to another, also indicated slower recovery in children with congenital Zika syndrome.

INTERPRETATION: A substantial and persistent burden of growth impairment in children with congenital Zika syndrome highlights the need for sustained growth monitoring and targeted nutritional interventions to support long-term health in this population.

FUNDING: Wellcome Trust, Brazilian Ministry of Health.

TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.