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Published in: BMC Medicine 1/2021

01-12-2021 | Zika Virus | Research article

In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study

Authors: Rebecca Grant, Olivier Fléchelles, Benoît Tressières, Mama Dialo, Narcisse Elenga, Nicolas Mediamolle, Adeline Mallard, Jean-Christophe Hebert, Noémie Lachaume, Elvire Couchy, Bruno Hoen, Arnaud Fontanet

Published in: BMC Medicine | Issue 1/2021

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Abstract

Background

In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas.

Methods

We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother’s pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development—communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition.

Results

Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference − 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions.

Conclusion

In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age.

Trial registration

ClinicalTrials.gov, NCT02810210. Registered 20 June 2016.
Appendix
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Literature
1.
go back to reference Moore CA, Staples JE, Dobyns WB, et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr. 2017;171(3):288–95.CrossRef Moore CA, Staples JE, Dobyns WB, et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr. 2017;171(3):288–95.CrossRef
2.
go back to reference Shapiro-Mendoza CK, Rice ME, Galang RR, et al. Pregnancy outcomes after maternal Zika virus infection during pregnancy - U.S. territories, January 1, 2016-April 25, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(23):615–21.CrossRef Shapiro-Mendoza CK, Rice ME, Galang RR, et al. Pregnancy outcomes after maternal Zika virus infection during pregnancy - U.S. territories, January 1, 2016-April 25, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(23):615–21.CrossRef
3.
go back to reference Hoen B, Schaub B, Funk AL, et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med. 2018;378(11):985–94.CrossRef Hoen B, Schaub B, Funk AL, et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med. 2018;378(11):985–94.CrossRef
4.
go back to reference Pomar L, Vouga M, Lambert V, et al. Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana. BMJ. 2018;363:k4431.CrossRef Pomar L, Vouga M, Lambert V, et al. Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana. BMJ. 2018;363:k4431.CrossRef
5.
go back to reference Brasil P, Pereira JP Jr, Moreira ME, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med. 2016;375(24):2321–34.CrossRef Brasil P, Pereira JP Jr, Moreira ME, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med. 2016;375(24):2321–34.CrossRef
6.
go back to reference Wheeler AC. Development of infants with congenital Zika syndrome: what do we know and what can we expect? Pediatrics. 2018;141:e20172038.CrossRef Wheeler AC. Development of infants with congenital Zika syndrome: what do we know and what can we expect? Pediatrics. 2018;141:e20172038.CrossRef
7.
go back to reference Rice ME, Galang RR, Roth NM, et al. Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection - U.S. territories and freely associated states, 2018. MMWR Morb Mortal Wkly Rep. 2018;67(31):858–67.CrossRef Rice ME, Galang RR, Roth NM, et al. Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection - U.S. territories and freely associated states, 2018. MMWR Morb Mortal Wkly Rep. 2018;67(31):858–67.CrossRef
8.
go back to reference Lopes Moreira ME, Nielsen-Saines K, Brasil P, et al. Neurodevelopment in infants exposed to Zika virus in utero. N Engl J Med. 2018;379(24):2377–9.CrossRef Lopes Moreira ME, Nielsen-Saines K, Brasil P, et al. Neurodevelopment in infants exposed to Zika virus in utero. N Engl J Med. 2018;379(24):2377–9.CrossRef
9.
go back to reference Nielsen-Saines K, Brasil P, Kerin T, et al. Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children. Nat Med. 2019;25(8):1213–7.CrossRef Nielsen-Saines K, Brasil P, Kerin T, et al. Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children. Nat Med. 2019;25(8):1213–7.CrossRef
10.
go back to reference Einspieler C, Utsch F, Brasil P, et al. Association of infants exposed to prenatal Zika virus infection with their clinical, neurologic, and developmental status evaluated via the general movement assessment tool. JAMA Netw Open. 2019;2(1):e187235.CrossRef Einspieler C, Utsch F, Brasil P, et al. Association of infants exposed to prenatal Zika virus infection with their clinical, neurologic, and developmental status evaluated via the general movement assessment tool. JAMA Netw Open. 2019;2(1):e187235.CrossRef
11.
go back to reference Wheeler AC, Toth D, Ridenour T, et al. Developmental outcomes among young children with congenital Zika syndrome in Brazil. JAMA Netw Open. 2020;3(5):e204096.CrossRef Wheeler AC, Toth D, Ridenour T, et al. Developmental outcomes among young children with congenital Zika syndrome in Brazil. JAMA Netw Open. 2020;3(5):e204096.CrossRef
13.
go back to reference Bjarnadóttir E, Stokholm J, Chawes B, et al. Determinants of neurodevelopment in early childhood - results from the Copenhagen prospective studies on asthma in childhood (COPSAC2010) mother-child cohort. Acta Paediatr. 2019;108(9):1632–41.CrossRef Bjarnadóttir E, Stokholm J, Chawes B, et al. Determinants of neurodevelopment in early childhood - results from the Copenhagen prospective studies on asthma in childhood (COPSAC2010) mother-child cohort. Acta Paediatr. 2019;108(9):1632–41.CrossRef
14.
go back to reference Koutra K, Chatzi L, Roumeliotaki T, et al. Socio-demographic determinants of infant neurodevelopment at 18 months of age: Mother-Child Cohort (Rhea Study) in Crete, Greece. Infant Behav Dev. 2012;35(1):48–59.CrossRef Koutra K, Chatzi L, Roumeliotaki T, et al. Socio-demographic determinants of infant neurodevelopment at 18 months of age: Mother-Child Cohort (Rhea Study) in Crete, Greece. Infant Behav Dev. 2012;35(1):48–59.CrossRef
15.
go back to reference Monk C, Georgieff MK, Osterholm EA. Research review: maternal prenatal distress and poor nutrition - mutually influencing risk factors affecting infant neurocognitive development. J Child Psychol Psychiatry. 2013;54(2):115–30.CrossRef Monk C, Georgieff MK, Osterholm EA. Research review: maternal prenatal distress and poor nutrition - mutually influencing risk factors affecting infant neurocognitive development. J Child Psychol Psychiatry. 2013;54(2):115–30.CrossRef
16.
go back to reference Flamand C, Fritzell C, Matheus S, et al. The proportion of asymptomatic infections and spectrum of disease among pregnant women infected by Zika virus: systematic monitoring in French Guiana, 2016. Euro Surveill. 2017;22(44):17–00102.CrossRef Flamand C, Fritzell C, Matheus S, et al. The proportion of asymptomatic infections and spectrum of disease among pregnant women infected by Zika virus: systematic monitoring in French Guiana, 2016. Euro Surveill. 2017;22(44):17–00102.CrossRef
17.
go back to reference Hoen B, Carpentier M, Gaete S, et al. Kinetics of Anti-Zika Virus Antibodies after Acute Infection in Pregnant Women. J Clin Microbiol. 2019;57(11):e01151-19.CrossRef Hoen B, Carpentier M, Gaete S, et al. Kinetics of Anti-Zika Virus Antibodies after Acute Infection in Pregnant Women. J Clin Microbiol. 2019;57(11):e01151-19.CrossRef
18.
go back to reference Pasquier C, Joguet G, Mengelle C, et al. Kinetics of anti-ZIKV antibodies after Zika infection using two commercial enzyme-linked immunoassays. Diagn Microbiol Infect Dis. 2018;90(1):26–30.CrossRef Pasquier C, Joguet G, Mengelle C, et al. Kinetics of anti-ZIKV antibodies after Zika infection using two commercial enzyme-linked immunoassays. Diagn Microbiol Infect Dis. 2018;90(1):26–30.CrossRef
19.
go back to reference Matheus S, Talla C, Labeau B, et al. Performance of 2 commercial serologic tests for diagnosing Zika virus infection. Emerg Infect Dis. 2019;25(6):1153–60.CrossRef Matheus S, Talla C, Labeau B, et al. Performance of 2 commercial serologic tests for diagnosing Zika virus infection. Emerg Infect Dis. 2019;25(6):1153–60.CrossRef
20.
go back to reference Flamant C, Branger B, Nguyen The Tich S, et al. Parent-completed developmental screening in premature children: a valid tool for follow-up programs. Plos One. 2011;6(5):e20004.CrossRef Flamant C, Branger B, Nguyen The Tich S, et al. Parent-completed developmental screening in premature children: a valid tool for follow-up programs. Plos One. 2011;6(5):e20004.CrossRef
21.
go back to reference Squires J, Bricker D. Ages & stages questionnaires®, third edition (ASQ®-3): a parent-completed child monitoring system. Baltimore: Paul H. Brookes Publishing Co., Inc.; 2009. Squires J, Bricker D. Ages & stages questionnaires®, third edition (ASQ®-3): a parent-completed child monitoring system. Baltimore: Paul H. Brookes Publishing Co., Inc.; 2009.
22.
go back to reference Robins D, Fein D, Barton M, Green J. The Modified Checklist for Autism on Toddlers: an initial study investigating the early detection of autism and pervasive developmental disorders. J Autism Dev Disord. 2001;31(2):131–44.CrossRef Robins D, Fein D, Barton M, Green J. The Modified Checklist for Autism on Toddlers: an initial study investigating the early detection of autism and pervasive developmental disorders. J Autism Dev Disord. 2001;31(2):131–44.CrossRef
23.
go back to reference Fenson L, Marchman VA, Thal DJ, Dale PS, Reznick JS, Bates E. MacArthur-Bates communicative development inventories. 2nd ed. Baltimore: Paul H. Brookes; 2007. Fenson L, Marchman VA, Thal DJ, Dale PS, Reznick JS, Bates E. MacArthur-Bates communicative development inventories. 2nd ed. Baltimore: Paul H. Brookes; 2007.
24.
go back to reference World Health Organization Multicentre Growth Reference Study Group. Assessment of sex difference and heterogeneity in motor milestone attainment among populations in the WHO Multicentre Growth Reference Study. Acta Paediatr Oslo Nor 1992. 2006;450:66–75. World Health Organization Multicentre Growth Reference Study Group. Assessment of sex difference and heterogeneity in motor milestone attainment among populations in the WHO Multicentre Growth Reference Study. Acta Paediatr Oslo Nor 1992. 2006;450:66–75.
25.
go back to reference Boucher O, Simard MN, Muckle G, et al. Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants. Neurotoxicology. 2013;35:162–8.CrossRef Boucher O, Simard MN, Muckle G, et al. Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants. Neurotoxicology. 2013;35:162–8.CrossRef
26.
go back to reference Pierrat V, Marchand-Martin L, Arnaud C, et al. Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks’ gestation in France in 2011: EPIPAGE-2 cohort study. BMJ. 2017;358:j3448.CrossRef Pierrat V, Marchand-Martin L, Arnaud C, et al. Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks’ gestation in France in 2011: EPIPAGE-2 cohort study. BMJ. 2017;358:j3448.CrossRef
27.
go back to reference Yeung EH, Sundaram R, Ghassabian A, et al. Parental obesity and early childhood development. Pediatrics. 2017;139(2):e20161459.CrossRef Yeung EH, Sundaram R, Ghassabian A, et al. Parental obesity and early childhood development. Pediatrics. 2017;139(2):e20161459.CrossRef
28.
go back to reference Liu S, Wang Z, Zhao C, et al. Effects of early comprehensive interventions on child neurodevelopment in poor rural areas of China: a moderated mediation analysis. Public Health. 2018;159:116–22.CrossRef Liu S, Wang Z, Zhao C, et al. Effects of early comprehensive interventions on child neurodevelopment in poor rural areas of China: a moderated mediation analysis. Public Health. 2018;159:116–22.CrossRef
29.
go back to reference Chowdhury R, Taneja S, Bhandari N, et al. Vitamin-D status and neurodevelopment and growth in young north Indian children: a secondary data analysis. Nutri J. 2017;16(1):59.CrossRef Chowdhury R, Taneja S, Bhandari N, et al. Vitamin-D status and neurodevelopment and growth in young north Indian children: a secondary data analysis. Nutri J. 2017;16(1):59.CrossRef
30.
go back to reference Ostradrahimi A, Salehi-Pourmehr H, Mohammad-Alizadeh-Charandabi S, et al. The effect of perinatal fish oil supplementation on neurodevelopment and growth of infants: a randomized controlled trial. Eur J Nutr. 2018;57(7):2387–97.CrossRef Ostradrahimi A, Salehi-Pourmehr H, Mohammad-Alizadeh-Charandabi S, et al. The effect of perinatal fish oil supplementation on neurodevelopment and growth of infants: a randomized controlled trial. Eur J Nutr. 2018;57(7):2387–97.CrossRef
31.
go back to reference Noeder M, Logan BA, Struemph KL, et al. Developmental screening in children with CHD: ages and stages questionnaires. Cardiol Young. 2017;27(8):1447–54.CrossRef Noeder M, Logan BA, Struemph KL, et al. Developmental screening in children with CHD: ages and stages questionnaires. Cardiol Young. 2017;27(8):1447–54.CrossRef
Metadata
Title
In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study
Authors
Rebecca Grant
Olivier Fléchelles
Benoît Tressières
Mama Dialo
Narcisse Elenga
Nicolas Mediamolle
Adeline Mallard
Jean-Christophe Hebert
Noémie Lachaume
Elvire Couchy
Bruno Hoen
Arnaud Fontanet
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2021
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-020-01888-0

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