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Nicole M. Roth, MPH1; Camille Delgado-López, MPH2,3; Lisa D. Wiggins, PhD4; Nancy Nieves Muñoz, EdM2; Sarah B. Mulkey, MD, PhD5,6,7; Leishla Nieves-Ferrer, MS2,3; Kate R. Woodworth, MD1; Glorimar Meléndez Rosario, MPH2,3; Mariam Marcano Huertas2,3; Cynthia A. Moore, MD, PhD1,8; Van T. Tong, MPH1; Suzanne M. Gilboa, PhD1; Miguel Valencia-Prado, MD2 (View author affiliations)

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Infection during pregnancy with Zika virus, a mosquitoborne flavivirus, can cause birth defects and neurodevelopmental abnormalities (1). Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by social and communication impairment and restricted or repetitive patterns of behavior or interests (2); possible associations between antenatal exposure to a limited number of viruses and ASD have been observed (2). The U.S. Zika Pregnancy and Infant Registry (USZPIR)* monitors children born during January 1, 2016–March 31, 2018, to women with laboratory evidence of Zika virus infection during pregnancy. This report used data from USZPIR and the Puerto Rico Autism Registry to estimate the prevalence of ASD diagnoses among children with possible prenatal Zika virus exposure and to describe prenatal characteristics and other outcomes by ASD diagnosis status. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§

Investigation and Outcomes

In Puerto Rico, any child who fails a standardized autism-specific screening, regardless of Zika virus exposure, receives a standardized evaluation at Puerto Rico Children with Special Health Care Needs Pediatric Program and Autism Centers to confirm an ASD diagnosis by Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition** criteria. Those who meet ASD criteria are included in the Puerto Rico Autism Registry.

Among 3,122 children reported to USZPIR in Puerto Rico, 109 (3.5%) had received an ASD diagnosis (Table). When analysis was restricted to 1,968 (63.0%) children who received a social-emotional or ASD-specific screener†† at age ≥18 months, 105 (5.3%) received an ASD diagnosis. No statistically significant differences were identified in the proportions of children with differing evidence of Zika virus exposure,§§ maternal symptoms,¶¶ pregnancy trimester of exposure,*** or Zika-associated birth defects between those with and without an ASD diagnosis. A higher percentage of children with an ASD diagnosis were male compared with those without an ASD diagnosis.

Among the 109 children with an ASD diagnosis, most required substantial or very substantial support in social communication (79.8%) and restricted, repetitive behaviors (77.0%). The median age at ASD diagnosis was 39 months (range = 19–73 months), and 33 (30.3%) children with an ASD diagnosis also had a family member with an ASD diagnosis.

Preliminary Conclusions and Actions

This analysis found that among children with Zika virus exposure reported to USZPIR from Puerto Rico, the prevalence of ASD diagnosis ranged from 3.5% to 5.3%, depending on the denominator. Estimated 2018 prevalence of ASD in general population samples in the continental United States ranged from 1.3% to 4.6% among children aged 4 years (3) and from 2.3% to 4.5% among children aged 8 years (4). A systematic analysis found a prevalence of 723 autism cases per 100,000 population (<1.0%) in Latin America and the Caribbean in 2016 (5).

The findings in this report are subject to at least three limitations. First, follow-up to age 5 years is not yet complete, and ASD can be identified even later in childhood. Second, comparators of ASD prevalence in the general Puerto Rico population are not yet available. As of 2023, Puerto Rico is a participating site for the Autism and Developmental Disabilities Monitoring Network††† to conduct ASD surveillance among children aged 4 and 8 years. Finally, delays in referral of children for evaluation because of the COVID-19 pandemic might have lowered the estimated prevalence of ASD.

Additional information is needed to determine whether an association between Zika virus infection in pregnancy and ASD in children exists. Among children with prenatal Zika exposure, screening was reported for only two thirds. ASD-specific screening is recommended for all children to identify concerns as early as possible and minimize delays in intervention.§§§

Acknowledgments

Staff members who conducted data collection for the Puerto Rico U.S. Zika Pregnancy and Infant Registry and Puerto Rico Autism Registry; Puerto Rico Children with Special Health Care Needs Program.


1Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities, CDC; 2Puerto Rico Department of Health; 3G2S Corporation, Shavano Park, Texas; 4Division of Human Development and Disability, National Center on Birth Defects and Developmental Disabilities, CDC; 5Children’s National Hospital, Washington, DC; 6Department of Neurology, George Washington University School of Medicine & Health Sciences, Washington, DC; 7Department of Pediatrics, George Washington University School of Medicine & Health Sciences, Washington, DC; 8Goldbelt Professional Services, LLC, Chesapeake, Virginia.

References

  1. Mulkey SB, Arroyave-Wessel M, Peyton C, et al. Neurodevelopmental abnormalities in children with in utero Zika virus exposure without congenital Zika syndrome. JAMA Pediatr 2020;174:269–76. https://doi.org/10.1001/jamapediatrics.2019.5204
  2. Shuid AN, Jayusman PA, Shuid N, Ismail J, Kamal Nor N, Mohamed IN. Association between viral infections and risk of autistic disorder: an overview. Int J Environ Res Public Health 2021;18:2817. https://doi.org/10.3390/ijerph18062817
  3. Shaw KA, Bilder DA, McArthur D, et al. Early identification of autism spectrum disorder among children aged 4 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020. MMWR Surveill Summ 2023;72(No. SS-1):1–15. https://doi.org/10.15585/mmwr.ss7201a1
  4. Maenner MJ, Warren Z, Williams AR, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020. MMWR Surveill Summ 2023;72(No. SS-2):1–14. https://doi.org/10.15585/mmwr.ss7202a1
  5. Olusanya BO, Davis AC, Wertlieb D, et al.; Global Research on Developmental Disabilities Collaborators. Developmental disabilities among children younger than 5 years in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Glob Health 2018;6:e1100–21. https://doi.org/10.1016/S2214-109X(18)30309-7
TABLE. Prenatal characteristics and child outcomes among live-born infants with and without a diagnosis of autism spectrum disorder* — U.S. Zika Pregnancy and Infant Registry, Puerto Rico, 2023
Characteristic All children reported to USZPIR
N = 3,122
Children with ASQ:SE-2 or M-CHAT-R/F at age ≥18 mos reported to USZPIR
n = 1,968
With ASD diagnosis Without ASD diagnosis With ASD diagnosis Without ASD diagnosis
No. % (95% CI)§ No. % (95% CI)§ No. % (95% CI)§ No. % (95% CI)§
Total (row %) 109 3.5 (2.9–4.2) 3,013 96.5 (93.1–100) 105 5.3 (4.4–6.5) 1,863 94.7 (90.4–99.1)
Laboratory evidence of Zika virus infection
Possible Zika virus infection 60 55.0 (42.0–70.9) 1,668 55.4 (52.7–58.1) 57 54.3 (41.1–70.3) 944 50.7 (47.5–54.0)
Positive Zika virus NAAT result** 49 45.0 (33.3–59.4) 1,345 44.6 (42.3–47.1) 48 45.7 (33.7–60.6) 919 49.3 (46.2–52.6)
Maternal symptoms††
Signs and symptoms of Zika virus disease 44 40.4 (29.3–54.2) 1,275 42.3 (40.0–44.7) 44 41.9 (30.5–56.3) 863 46.3 (43.3–49.5)
No signs and symptoms of Zika virus disease 65 59.6 (46.0–76.0) 1,738 57.7 (55.0–60.5) 61 58.1 (44.4–74.6) 1,000 53.7 (50.4–57.1)
Trimester with first evidence of exposure§§
1st¶¶ 45 41.3 (30.1–55.2) 1,102 36.6 (34.5–38.8) 44 41.9 (30.5–56.3) 685 36.8 (34.1–39.6)
2nd 42 38.5 (27.8–52.1) 1,129 37.5 (35.3–39.7) 40 38.1 (27.2–51.9) 711 38.2 (35.4–41.1)
3rd 22 20.2 (12.7–30.6) 782 26.0 (24.2–27.8) 21 20.0 (12.4–30.6) 467 25.1 (22.8–27.5)
Child sex
Female 35 32.1 (22.4–44.7) 1,502 49.9 (47.4–52.4) 34 32.4 (22.4–45.3) 909 48.8 (45.7–52.1)
Male 74 67.9 (53.3–85.2) 1,511 50.1 (47.7–52.7) 71 67.6 (52.8–85.3) 954 51.2 (48.0–54.6)
Zika-associated birth defects***
Yes 5 4.6 (1.5–10.7) 118 3.9 (3.2–4.7) 4 3.8 (1.0–9.8) 84 4.5 (3.6–5.6)
No 104 95.4 (78.0–100.0) 2,895 96.1 (92.6–99.7) 101 96.2 (78.4–100.0) 1,779 95.5 (91.1–100.0)
ASD outcomes
Family member with ASD diagnosis
Yes 33 30.3 (20.8–42.5) 31 29.5 (20.0–41.9)
No 58 53.2 (40.4–68.8) 56 53.3 (40.3–69.3)
Unknown 18 16.5 (9.8–26.1) 18 17.1 (10.2–27.1)
Child’s age group when parent first noticed symptoms, mos
<6 6 5.5 (2.0–12.0) 6 5.7 (2.1–12.4)
6–12 27 24.8 (16.3–36.0) 26 24.8 (16.2–36.3)
13–18 31 28.4 (19.3–40.4) 29 27.6 (18.5–39.7)
19–24 19 17.4 (10.5–27.2) 18 17.1 (10.2–27.1)
25–30 5 4.6 (1.5–10.7) 5 4.8 (1.6–11.1)
31–36 10 9.2 (4.4–16.9) 10 9.5 (4.6–17.5)
37–42 3 2.8 (0.6–8.0) 3 2.9 (0.6–8.4)
43–48 3 2.8 (0.6–8.0) 3 2.9 (0.6–8.4)
49–54 2 1.8 (0.2–6.6) 2 1.9 (0.2–6.9)
Unknown 3 2.8 (0.6–8.0) 3 2.9 (0.6–8.4)
Age group of ASD diagnosis, mos
Median (range) 39 (19.0–73.0) 39 (19.0–73.0)
18–25 17 15.6 (9.1–25.0) 17 16.2 (9.4–25.9)
26–33 24 22.0 (14.1–32.8) 22 21.0 (13.1–31.7)
34–41 21 19.3 (11.9–29.5) 21 20.0 (12.4–30.6)
42–49 15 13.8 (7.7–22.7) 15 14.3 (8.0–23.6)
50–57 13 11.9 (6.4–20.4) 12 11.4 (5.9–20.0)
58–65 17 15.6 (9.1–25.0) 16 15.2 (8.7–24.8)
66–73 2 1.8 (0.2–6.6) 2 1.9 (0.2–6.9)
Level of support in social communication†††
Level 1 22 20.2 (12.7–30.6) 22 21.0 (13.1–31.7)
Level 2 47 43.1 (31.7–57.3) 46 43.8 (32.1–58.4)
Level 3 40 36.7 (26.2–50.0) 37 35.2 (24.8–48.6)
Level of support in restrictive, repetitive behaviors†††
Level 1 25 22.9 (14.8–33.9) 24 22.9 (14.7–34.0)
Level 2 64 58.7 (45.2–75) 62 59.0 (45.3–75.7)
Level 3 20 18.3 (11.2–28.3) 19 18.1 (10.9–28.3)

Abbreviations: ASD = autism spectrum disorder; ASQ: SE-2 = Ages and Stages Questionnaires: Social-Emotional, Second Edition; M-CHAT-R/F = Modified Checklist for Autism in Toddlers, Revised with Follow-Up; NAAT = nucleic acid amplification test; USZPIR = U.S. Zika Pregnancy and Infant Registry.
* ASD diagnosis by Diagnostic and Statistical Manual for Mental Disorder, Fifth Edition criteria. https://www.psychiatry.org/psychiatrists/practice/dsm

Suggested citation for this article: Roth NM, Delgado-López C, Wiggins LD, et al. Notes from the Field: Autism Spectrum Disorder Among Children with Laboratory Evidence of Prenatal Zika Virus Exposure — Puerto Rico, 2023. MMWR Morb Mortal Wkly Rep 2023;72:802–804. DOI: http://dx.doi.org/10.15585/mmwr.mm7229a5


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