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Prospective cohort studies of ZIKV infection during pregnancy

Prospective cohort studies of ZIKV infection during pregnancy
  Brasil et al, 2016[1]
Nielsen-Saines et al, 2019[2]
Hoen et al, 2018[3] Pomar et al, 2018[4] Mulkey et al, 2019[5]
Mulkey et al, 2020[6]
Ospina et al, 2020[7] Coutinho et al, 2020[8]
Site and recruitment period
  • Rio de Janeiro, Brazil
  • September 2015 to May 2016

 

  • French Guiana, Guadeloupe, and Martinique
  • March 2016 to November 2016
  • French Guiana
  • January 2016 to July 2016
  • Barranquilla, Colombia, and Washington, DC
  • June 2016 to June 2017
  • Colombian national surveillance system
  • June 2015 to July 2016
  • Ribeirão Preto, Brazil
  • 2015 to 2016
Study design
  • Longitudinal
  • Longitudinal
  • Longitudinal
  • Longitudinal
  • Surveillance data
  • Longitudinal
Inclusion criteria for pregnant women
  • Symptomatic ZIKV infection with rash confirmed by RT-PCR of blood or urine (rash with onset ≤5 days)
  • Symptomatic ZIKV infection with at least one of the following confirmed by RT-PCR of blood or urine or both: rash, fever, conjunctivitis, arthralgia, or myalgia
  • Symptomatic or asymptomatic ZIKV infection confirmed by RT-PCR in blood or urine or ZIKV IgM
  • Symptomatic ZIKV infection with positive RT-PCR, IgM, IgG, or PRNT for ZIKV
  • Symptomatic ZIKV infection with positive RT-PCR in serum
  • Symptomatic ZIKV infection with positive RT-PCR of blood, urine, amniotic fluid, or placenta
Number of women with confirmed ZIKV infection in pregnancy
  • 244
  • 561
  • 498
  • 82
  • 5926*
  • 511
Number of miscarriages/fetal losses
  • 10 (4.1%)
  • 28 (5.0%)
  • 32 (6.4%)
  • 2 (2.4%)
  • 172 (3.0%)
  • 24 (4.7%)
Loss to follow-up before or immediately after birth or excluded participants
  • 17 (7.0%)
  • 15 (2.7%)
  • 192 (38.6%)
  • 0
  • 253 (4.3%)
  • 209 (42.7%)
Number of neonatal deaths
  • 1 (0.5%)
  • Not reported
  • Not reported
  • 1 (1.2%)
  • 48 (0.9%)
  • 2 (0.4%)
Number of infants with follow-up
  • 216 (88.5%)
  • 527 (93.9%)
  • 279 (56.0%)
  • 80 (97.5%)
  • 0
  • 280 (57.3%)
Median infant follow-up time
  • 18 months (range 7 to 32 months)
  • Birth
  • 3 days of life (range 0 to 7 days)
  • 18 months (range 4 to 18 months)
  • Birth
  • Birth (range 0 to 3 months)
Outcome measure
  • Clinical abnormalities at birth and on follow-up
  • Eye findings
  • Hearing findings
  • Neurodevelopment
  • Clinical findings on the day of birth
  • Clinical findings in the first week of life
  • Neuroimaging findings
  • Neurodevelopment
  • Adverse pregnancy or neonatal outcome reported to surveillance system
  • Pregnancy losses
  • Abnormalities at birth to 3 months of age
Microcephaly
  • 8 (3.7%)
  • 32 (5.8%)
  • 31 (11.4%) of 273 infants
  • 3 (3.7%)
  • 93 (1.6%)
  • 16 (3.1%)
Small for gestational age
  • 10 (4.6%)
  • 53 (10%)
  • 26 (10.2%) of 255 infants
  • Not reported
  • 333 (6.2%)
  • 45 (9.2%)
Preterm infants
  • 28 (13%)
  • Not reported
  • Not reported
  • 5 (6.3%)
  • 409 (7.5%)
  • 45 (9.2%)
Eye abnormalities on funduscopic examination
  • 128 examined (59.3%) and 9 (7%) had abnormalities
  • 39 with neurologic findings (7%)
  • Not reported
  • Not reported
  • 93 (1.6%)
  • 174 examined (35.6%) and 8 (4.6%) had abnormalities
Hearing abnormalities
  • 101 assessed (46.8%) and 13 (12%) had abnormalities
  • Not reported
  • Not reported
  • Not reported
  • Not reported
  • 261 assessed (53.4%) and 1 (0.4%) had an abnormality
Below average neurodevelopment
  • Of 216 children evaluated, 62 (28.7%) had  below average neurodevelopment
  • N/A
  • N/A
  • In 70 children evaluated, decline in neurodevelopment scores noted over time, 33% with abnormal findings
  • N/A
  • N/A
Neurodevelopment tool
  • Bayley-III
  • Hammersmith Infant Neurological Examination
  • N/A
  • N/A
  • Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA)
  • Alberta Infant Motor Scale (AIMS)
  • N/A
  • N/A
ZIKV: Zika virus; RT-PCR: reverse transcription polymerase chain reaction; IgM: immunoglobulin M; IgG: immunoglobulin G; PRNT: plaque reduction neutralization test; N/A: not available.
* 45% of 18,117 pregnant women with symptoms of ZIKV infection tested; 33% of 18,117 positive by RT-PCR.
¶ 1.6% for brain and eye defects combined. Individual microcephaly frequencies or individual eye abnormalities not reported. Eye abnormalities noted on physical inspection (not necessarily funduscopic evaluation).
References:
  1. Brasil P, Pereira JP Jr, Moreira ME, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med 2016; 375:2321.
  2. 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; 25:1213.
  3. Hoen B, Schaub B, Funk AL, et al. Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas. N Engl J Med 2018; 378:985.
  4. 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.
  5. Mulkey SB, Bulas DI, Vezina G, et al. Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure. JAMA Pediatr 2019; 173:52.
  6. 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.
  7. Ospina ML, Tong VT, Gonzalez M, et al. Zika Virus Disease and Pregnancy Outcomes in Colombia. N Engl J Med 2020; 383:537.
  8. Coutinho CM, Negrini S, Araujo D, et al. Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study. BJOG 2020.
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