Neonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Statistical Analysis
3. Results
3.1. Study Population
3.2. Multivariable Analysis
3.3. Adverse Prenatal and Early Postnatal Infant Outcomes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BAEPs | Brainstem Auditory Evoked Potentials |
CI | Confidence interval |
CNS | Central Nervous System |
CZS | Congenital Zika Syndrome |
FORMSUS | Formulário do Sistema Único de Saúde (Unified Health System Form) |
GAL | Gerenciador de Ambiente Laboratorial (Laboratory Environment Manager) |
IQR | Interquartile range |
OR | Odds ratio |
PRNT | Plaque Reduction Neutralization Test |
R2 | R squared |
RESP | Registro de Eventos em Saúde Pública (Public Health Events Registry) |
RT-PCR | Real-time reverse transcriptase polymerase chain reaction |
SIM | Sistema de Informações sobre Mortalidade (Mortality Information System) |
SINASC | Sistema de Informações sobre Nascidos Vivos (Live Birth Information System) |
ZIKV | Zika virus |
References
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Signs and Symptoms | ZIKV+ n (%) | ZIKV− n (%) | p-Value 1 |
---|---|---|---|
Rash | 1899 (83.7) | 4477 (79.9) | 0.0001 |
Pruritus | 1391 (61.3) | 2656 (47.4) | <0.001 |
Headache | 636 (28.0) | 1943 (34.7) | <0.001 |
Arthralgia | 596 (26.3) | 2196 (39.2) | <0.001 |
Myalgia | 476 (20.1) | 1670 (29.8) | <0.001 |
Fever | 379 (16.7) | 1862 (33.2) | <0.001 |
Retro-ocular pain | 322 (14.2) | 835 (14.9) | 0.1164 |
Conjunctival hyperemia | 195 (8.6) | 414 (7.4) | 0.2216 |
Edema | 187 (8.2) | 552 (9.6) | 0.0053 |
Conjunctivitis | 90 (4.0) | 210 (3.7) | 0.9846 |
Coryza | 68 (3.6) | 237 (5.3) | 0.0041 |
Cough | 79 (3.5) | 236 (4.2) | 0.0704 |
Diarrhea | 127 (3.0) | 337 (6.0) | 0.2595 |
Lymphadenomegaly | 49 (2.2) | 107 (1.9) | 0.718 |
ZIKV+ | ZIKV− | p-Value 1 | |
---|---|---|---|
Pregnant women | 2269 | 5601 | |
Outcomes | 49 | 44 | <0.001 |
Prevalence | 2.6% | 0.78% | |
1st trimester | |||
Pregnant women | 508 | 1205 | |
Outcomes | 28 | 19 | <0.001 |
Prevalence | 5.5% | 1.6% | |
2nd trimester | |||
Pregnant women | 997 | 1941 | |
Outcomes | 15 | 7 | 0.0015 |
Prevalence | 1.5% | 0.36% | |
3rd trimester | |||
Pregnant women | 764 | 2455 | |
Outcomes | 6 | 18 | 1.0 |
Prevalence | 0.79% | 0.73% |
ZIKV+ n (%) | ZIKV− n (%) | p-Value 1 | |
---|---|---|---|
Total | 2269 | 5601 | |
Age [median (IQR)] | 26 (21–31) | 26 (21–31) | 0.233 * |
Ethnicity/race | |||
White | 945 (44.6) | 2197 (42.8) | 0.168 |
Others | 1176 (55.4) | 2937 (57.2) | |
Missing | 148 | 467 | |
Place of residence | |||
Not urban | 352 (15.5) | 765 (13.7) | <0.001 |
Urban | 1917 (84.5) | 4836 (86.3) | |
Marital status | |||
Single | 1019 (70.0) | 2398 (72.2) | 0.402 |
Married | 411 (28.2) | 872 (26.3) | |
Widowed | 3 (0.2) | 4 (0.1) | |
Divorced | 23 (1.6) | 46 (1.4) | |
Missing | 148 | 467 | |
Education | |||
Elementary school | 289 (19.4) | 627 (18.4) | 0.331 |
High school | 980 (65.6) | 2219 (65.0) | |
Higher school | 224 (15.0) | 566 (16.6) | |
Missing | 776 | 2189 | |
Twin pregnancy | |||
No | 1501 (99.1) | 3413 (98.7) | 0.181 |
Yes | 13 (0.9) | 45 (1.3) | |
Missing | 755 | 2143 | |
Type of labor | |||
Natural | 668 (44.1) | 1596 (46.2) | 0.179 |
Cesarean section | 847 (55.9) | 1862 (53.8) | |
Missing | 754 | 2143 | |
Prenatal consultations | |||
≥6 | 1295 (86.9) | 2920 (85.8) | 0.318 |
<6 | 196 (13.1) | 484 (14.2) | |
Missing | 778 | 2197 | |
Need for hospitalization | |||
No | 1686 (98) | 3810 (97.6) | 0.388 |
Yes | 35 (2) | 94 (2.4) | |
Missing | 548 | 1697 |
Predictors | OR | 95% CI | p-Value |
---|---|---|---|
Exposure to ZIKV during pregnancy | 2.46 | 1.30–4.64 | 0.005 |
Observations: 3463 pregnant women | |||
R2/R2 adjusted: 0.017/0.017 | |||
Exposure to ZIKV during 1st trimester | 4.29 | 1.93–9.53 | <0.001 |
Observations: 915 pregnant women | |||
R2/R2 adjusted: 0.049/0.047 | |||
Exposure to ZIKV during 2nd trimester | 5.29 | 1.08–25.95 | 0.040 |
Observations: 1793 pregnant women | |||
R2/R2 adjusted: 0.042/0.042 | |||
Exposure to ZIKV during 3rd trimester Observations: 915 pregnant women R2/R2 adjusted: 0.049/0.047 | 0.68 | 0.21–2.14 | 0.506 |
ZIKV+ n (%) | ZIKV− n (%) | p-Value 1 | |
---|---|---|---|
Total | 49 | 44 | |
Maternal age [median (IQR)] | 25 (21–29) | 23 (20–31) | 0.600 |
Place of residence | |||
Not urban | 40 (81.6) | 36 (81.8) | 0.982 |
Urban | 9 (18.4) | 8 (18.2) | |
Maternal ethnicity/race | |||
White | 18 (40) | 17 (39.5) | |
Others | 27 (60) | 25 (60.5) | 0.014 |
Missing | 1 | 4 | |
Fetus/newborn sex | |||
Female | 22 (47.8) | 27 (67.5) | 0.066 |
Male | 24 (52.2) | 13 (32.5) | |
Missing | 3 | 4 | |
Newborn birth length | |||
cm [median (IQR)] | 45 (43.2–47.8) | 47 (44–48) | 0.505 |
Newborn birth weight | |||
g [median (IQR)] | 2640 (2402.5–2902.5) | 2637.5 (2120–2957.5) | 0.996 |
Newborn head circumference | |||
cm [median (IQR)] | 30 (28–31) | 29.2 (28–30,1) | 0.460 |
Prematurity | |||
No | 36 (83.7) | 37 (84.1) | 0.164 |
Yes | 3 (7) | 4 (9.1) | |
Not applicable | 4 (9.3) | 3 (6.8) | |
Twinning | |||
No | 49 (100) | 44 (100) | 1 |
Yes | 0 | 0 |
ZIKV+ n (%) | ZIKV− n (%) | p-Value 1 | |
---|---|---|---|
Total | 49 | 44 | |
Fever | |||
Yes | 6 (12.2) | 12 (27.3) | 0.067 |
No | 43 (87.8) | 32 (72.7) | |
Rash | |||
Yes | 46 (93.9) | 35 (79.5) | 0.04 |
No | 3 (6.1) | 9 (20.5) | |
Arthralgia | |||
Yes | 16 (32.7) | 16 (36.4) | 0.707 |
No | 33 (67.3) | 28 (63.6) | |
Headache | |||
Yes | 14 (28.6) | 15 (34.1) | 0.566 |
No | 35 (71.4) | 29 (65.9) | |
Conjunctivitis | |||
Yes | 3 (6.1) | 1 (2.3) | 0.619 |
No | 46 (93.9) | 43 (97.7) | |
Coryza | |||
Yes | 1 (2) | 4 (9.1) | 0.186 |
No | 48 (98) | 40 (90.9) | |
Diarrhea | |||
Yes | 4 (8.2) | 2 (4.5) | 0.68 |
No | 45 (91.8) | 42 (95.5) | |
Retro-ocular pain | |||
Yes | 7 (14.3) | 5 (11.4) | 0.675 |
No | 42 (85.7) | 39 (88.6) | |
Edema | |||
Yes | 2 (4.1) | 5 (11.4) | 0.249 |
No | 47 (95.9) | 39 (88.6) | |
Myalgia | |||
Yes | 14 (28.6) | 10 (22.7) | 0.52 |
No | 35 (71.4) | 34 (77.3) | |
Lymphadenomegaly | |||
Yes | 2 (4.1) | 0 | 0.496 |
No | 47 (95.9) | 44 (100) | |
Pruritus | |||
Yes | 33 (67.3) | 20 (45.5) | 0.033 |
No | 16 (32.7) | 24 (54.5) | |
Cough | |||
Yes | 0 | 1 (2.3) | 0.473 |
No | 49 (100) | 43 (97.7) | |
Fetal loss | |||
Yes | 4 (9.1) | 5 (10.2) | 1 * |
No | 40 (90.9) | 44 (89.8) |
ZIKV+ n (%) | ZIKV− n (%) | p-Value 1 | |
---|---|---|---|
Total | 49 | 44 | |
CNS abnormalities: | |||
Intracranial calcifications | 26 (74.3) | 15 (75) | 1 |
Ventriculomegaly | 23 (65.7) | 19 (95) | 0.033 |
Posterior fossa malformations | 6 (17.1) | 5 (25) | 0.723 |
Reduced brain volume | 6 (17.1) | 4 (20) | 1 |
Corpus callosum malformations | 6 (17.1) | 3 (15) | 1 |
Cortex dysplasia | 6 (17.1) | 1 (5) | 0.379 |
Lissencephaly | 4 (11.4) | 3 (15) | 1 |
Pachygyria | 3 (8.6) | 1 (5) | 1 |
Hydrops fetalis | 1 (2.9) | 0 | 1 |
Cystic hygroma + encephalocele | 0 | 1 (5) | 0.775 |
Semilobar holoprosencephaly | 0 | 1 (5) | 0.775 |
Physical examination findings: | |||
Arthrogryposis | 4 (8.2) | 0 | 0.154 |
Congenital foot deformities | 1 (2) | 1 (2.3) | 1 |
Esophageal atresia | 1 (2) | 0 | 1 |
Cleft lip and palate | 0 | 1 (2.3) | 0.957 |
Myelomeningocele | 0 | 1 (2.3) | 0.957 |
Ophthalmologic examination: | |||
Optic nerve hypoplasia | 4 (44.4) | 3 (30) | 0.514 |
Incomplete vascularization | 1 (11.1) | 0 | 0.279 |
Pigmentary abnormalities | 2 (22.2) | 0 | 0.115 |
Retinal coloboma | 0 | 2 (20) | 0.156 |
Chorioretinal atrophy | 0 | 1 (10) | 0.329 |
Chorioretinitis | 0 | 1 (10) | 0.329 |
Microphthalmia | 0 | 1 (10) | 0.329 |
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Martins, M.M.; Medronho, R.d.A.; Raymundo, C.E.; Prata-Barbosa, A.; da Cunha, A.J.L.A. Neonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro. Viruses 2025, 17, 208. https://doi.org/10.3390/v17020208
Martins MM, Medronho RdA, Raymundo CE, Prata-Barbosa A, da Cunha AJLA. Neonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro. Viruses. 2025; 17(2):208. https://doi.org/10.3390/v17020208
Chicago/Turabian StyleMartins, Marlos Melo, Roberto de Andrade Medronho, Carlos Eduardo Raymundo, Arnaldo Prata-Barbosa, and Antonio José Ledo Alves da Cunha. 2025. "Neonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro" Viruses 17, no. 2: 208. https://doi.org/10.3390/v17020208
APA StyleMartins, M. M., Medronho, R. d. A., Raymundo, C. E., Prata-Barbosa, A., & da Cunha, A. J. L. A. (2025). Neonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro. Viruses, 17(2), 208. https://doi.org/10.3390/v17020208