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. 2022 Feb 24;386(8):757-767.
doi: 10.1056/NEJMoa2101195.

Mortality from Congenital Zika Syndrome - Nationwide Cohort Study in Brazil

Enny S Paixao  1 , Luciana L Cardim  1 , Maria C N Costa  1 , Elizabeth B Brickley  1 , Rita C O de Carvalho-Sauer  1 , Eduardo H Carmo  1 , Roberto F S Andrade  1 , Moreno S Rodrigues  1 , Rafael V Veiga  1 , Larissa C Costa  1 , Cynthia A Moore  1 , Giovanny V A França  1 , Liam Smeeth  1 , Laura C Rodrigues  1 , Mauricio L Barreto  1 , Maria G Teixeira  1
Affiliations

Mortality from Congenital Zika Syndrome - Nationwide Cohort Study in Brazil

Enny S Paixao et al. N Engl J Med. .

Abstract

Background: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited.

Methods: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age.

Results: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome.

Conclusions: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.).

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Conflict of interest statement

Declarations

We declare no competing interests.

Figures

Figure 1
Figure 1. Kaplan-Meier curves showing survival comparing CZS births with non-CZS births up to 36 months of age (A), stratified by head circumference (B) and maternal rash (C).
Figure 1
Figure 1. Kaplan-Meier curves showing survival comparing CZS births with non-CZS births up to 36 months of age (A), stratified by head circumference (B) and maternal rash (C).
Figure 1
Figure 1. Kaplan-Meier curves showing survival comparing CZS births with non-CZS births up to 36 months of age (A), stratified by head circumference (B) and maternal rash (C).
Figure 2
Figure 2. Cox proportional hazards for mortality risk comparing CZS births with non-CZS births up to 36 months of age stratified by gestational age at birth, birth weight and small for gestational age
*CZS: Congenital Zika Syndrome; HR: Hazard Ratio; CI: Confidence Interval * adjusted by maternal age, education, and marital status, ethnicity, number of prenatal appointments, new born sex and year of birth
Figure 3
Figure 3. Causes of death using ICD-10 chapter according to age group by CZS status Brazil, 2015-2018.
CZS: Congenital Zika Syndrome
See this image and copyright information in PMC

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