A total of 2,374 pregnancies with meeting inclusion were reported to CDC by December 31, 2021 (Supplemental 2). The median age of pregnant people was 27 years (interquartile range [IQR]: 22–32) (Table 1). Among pregnant people with known trimester of ZIKV exposure (n = 2106, 88.7%), 38.9% had possible Zika exposure detected in the first, 38.0% in the second, and 23.1% in the third trimester. One-quarter (n = 653) were reported as symptomatic; the most common symptoms reported were rash (80.6%), fever (43.6%), and joint pain (44.3%). Similar demographics, trimester of possible ZIKV exposure, and symptoms were reported among the subset with NAAT-confirmed infection (n = 423, 17.8%).
Table 1
Characteristics of pregnant people with any laboratory evidence of Zika virus infection and a subset with nucleic acid amplification test (NAAT)-confirmed Zika virus infection, U.S. Zika Pregnancy and Infant Registry, U.S. States and DC
| Total n (%) N = 2377 | NNAT-confirmed n (%) N = 423 |
Maternal age (years) | 2347 | 421 |
Median (IQR) | 27 (22–32) | 27 (22–32) |
< 20 | 307 (13.1) | 55 (13.1) |
20–24 | 507 (21.6) | 91 (21.6) |
25–29 | 620 (26.4) | 113 (26.8) |
30–34 | 518 (22.1) | 92 (21.9) |
35–39 | 317 (13.5) | 54 (12.8) |
≥ 40 | 78 (3.3) | 16 (3.8) |
Unknown/Not Reported | 30 (1.3) | 2 (0.5) |
Delivery Type | 1737 | 272 |
Vaginal | 1141 (65.7) | 177 (65.1) |
Caesarean section | 596 (34.3) | 95 (34.9) |
Unknown/Not Reported | 641 (27.0) | 151 (35.7) |
Plurality | 2248 | 371 |
Singleton | 2212 (98.4) | 366 (98.7) |
Multiple | 36 (1.6) | 5 (1.3) |
Unknown (lost to follow-up) | 0 | 0 |
Trimester with first evidence of Zika exposurea | 2106 | 391 |
First (< 14 weeks) | 819 (38.9) | 162 (41.4) |
Second (14–27 weeks) | 800 (38.0) | 171 (43.7) |
Third (≥ 28 weeks) | 487 (23.1) | 58 (14.8) |
Unknown/Not reported | 271 (11.4) | 32 (7.6) |
Symptoms reportedb | 653 | 235 |
Rash | 526 (80.6) | 213 (90.6) |
Fever | 285 (43.6) | 92 (39.1) |
Joint pain | 289 (44.3) | 105 (44.7) |
Conjunctivitis | 172 (26.3) | 69 (29.4) |
Headache | 27 (4.1) | 10 (4.3) |
Myalgia | 36 (5.5) | 8 (3.4) |
Otherc | 10 (1.5) | 8 (3.4) |
Abbreviations: NAAT, nucleic acid amplification test; IQR, interquartile range |
a Symptom onset date, travel dates to endemic region, or date of earliest laboratory evidence of Zika virus infection were used to calculate trimester of exposure. |
bNot mutually exclusive |
cOther symptoms reported to USZPIR are chills/rigors, flu-like symptoms, diarrhea, eye pain, and nausea or vomiting. |
Among 2,374 pregnancy outcomes, there were 2,248 (94.7%) live births (36 multiples) and 126 pregnancy losses (76.2% <20 weeks and 23.8% ≥20 weeks) (Table 2). Overall, 9.9% (n = 214) of infants were born preterm (< 37 weeks), including 18.0% (22/122) of infants with ZBD and 8.9% (192/2126) of infants without ZBD. Overall, 5.4% (122) live-born infants had a ZBD; 91.8% (n = 112) had brain abnormalities or microcephaly (63 cases with only microcephaly), 23.0% (n = 28) had eye abnormalities (10 cases with eye abnormalities only), and 14.8% (n = 18) had both brain and eye abnormalities. Ten percent (n = 225) of live-born infants were born SGA, including 50.8% of infants with ZBD (62/122) and 7.7% of infants without ZBD (163/2126). There were 20 infant deaths reported (11 with ZBD and 9 without ZBD). Of these, 60.0% (n = 12) of deaths occurred in the neonatal period (≤ 28 days), 30.0% (n = 6) in the postneonatal period (29–364 days), and 10.0% (n = 2) were ≥ 1 year of age.
Table 2
Pregnancy outcomes among people with any laboratory evidence and a subset with nucleic acid amplification test (NAAT)-confirmed Zika virus infection - U.S. Zika Pregnancy and Infant Registry, U.S. States and DC.
| Total n (%) N = 2374 | NAAT-confirmed n (%) N = 423 |
Pregnancy outcome | 2374 | 423 |
Live births | 2248 (94.7) | 371 (87.7) |
Pregnancy loss | | |
<20 weeks’ gestation | 96 (4.0) | 39 (9.2) |
≥20 weeks’ gestation | 30 (1.3) | 12 (2.8) |
Gestational age of outcomea | 2159 | 362 |
Term (≥ 37 weeks) | 1945 (90.1) | 326 (90.1) |
Preterm (< 37 weeks) | 214 (9.9) | 36 (9.9) |
Missing | 89 (4.0) | 9 (2.4) |
Small-for-gestational agea,b | 2134 | 354 |
Overall | 225 (10.5) | 64 (17.3) |
Birth defectsa | 2248 | 372 |
Any Zika-associated birth defectsc | 122 (5.4) | 38 (10.0) |
Any eye abnormalities | 28 (1.2) | 10 (2.6) |
Eye abnormalities only (without brain abnormalities and/or microcephaly) | 10 (0.4) | 1 (0.3) |
Any brain abnormalities and/or microcephaly with or without eye abnormalities | 112 (4.9) | 37 (9.9) |
Brain abnormalities and/or microcephaly without eye abnormalities | 94 (4.2) | 28 (7.5) |
Microcephaly only without reported brain or eye abnormalities | 75 (3.3) | 24 (6.4) |
Brain abnormalities without microcephaly or eye abnormalities | 19 (0.8) | 4 (1.1) |
Brain and/or microcephaly and eye abnormalities | 18 (0.8) | 9 (2.4) |
Infant and child deathd | 1638 | 289 |
Overall | 20 (1.2) | 5 (1.7) |
Neonatal (< 28 days) | 12 (60) | 4 (80) |
Postneonatal infant (≥ 28 days to 364 days) | 6 (30) | 0 (0) |
Child (≥ 1 year) | 2 (10) | 1 (20) |
Abbreviations: NAAT, nucleic acid amplification test |
aAmong live births |
b Defined as weight < 10th percentile for sex and gestational age according to INTERGROWTH-21st |
c The case definition for Zika-associated birth defects has been previously described 3,16 |
d Limited to live born infants not lost to follow-up prior to 12 months of age. |
ay axis shows percentage of children presenting with each abnormality among those with any neurologic sequelae. |
b The case definition for Zika-associated birth defects (ZBDs) has been previously described 3,16 |
aDenominator for each domain is all children with any notation of developmental data for each time point. |
b The case definition for Zika-associated birth defects (ZBDs) has been previously described 3,16 |
aConfirmed developmental delay: submitted specialist assessment, receipt of therapy, or multiple notations of delay with supportive neuroimaging findings. |
bPossible developmental delay: failing ≥ 1 domain on a validated screener at ≥ 1 time point, or ≥ 2 domains noted as abnormal at ≥ 2 time points but not reported as a validated screener. |
c The case definition for Zika-associated birth defects (ZBDs) has been previously described 3,16 |
Overall, 1,881 (83.7%) children had at least one follow-up examination (> 14 days of age) reported to USZPIR; of these, 91.6% had visits reported < 6 months, 62.4% between 6–11 months, 60.1% between 12–17 months, 44.8% between 18–23 months, and 37.4% 24-<36 months of age. Among children with ZBD and follow-up data (N = 112), 44.6% (n = 50) had neurologic sequelae. Among these 50, the most common sequelae were tone abnormalities (80.0%), and seizures (30.0%) (Fig. 1), with similar frequencies seen among children in the NAAT-confirmed population (data not shown). Twenty-six (1.5%, n = 26/1769) children without ZBD had neurologic sequelae, most frequently body tone abnormalities (34.6%) and hearing impairment (15.4%).
Among the 1,881 children with follow-up data reported, there were 1,848 with at least one visit with information reported about development. The proportion of visits with reported information about development decreased with increasing age from 92.7% at < 6 months to 38.9% at 24-<36 months of age (Supplemental 2). Reported information on development decreased from 85.3–50.5% for children with ZBD and from 93.2–38.1% for children without ZBD. Among children with ZBD and information on development (n = 109), developmental domain abnormalities were > 25% in children by 6 months of age (Fig. 2). The frequency of reported abnormalities noted across multiple domains was 9.7% by age < 6 months and was highest at 41.7% by age 18–23 months for children with ZBD. Among children without ZBD (N = 1739), the frequency of reported developmental abnormalities was < 20% across all domains and all age intervals. Language domain abnormalities were the most frequently reported by age > 12 months and was 16.0% at the 24-<36 months age interval.
Documentation of a validated developmental screening tool or developmental assessment ranged from 4.9% (n = 2/41) for children 6–11 months to 45.5% (n = 25/55) for children 24-<36 months with ZBD and 5.2% − 33.5% (n = 57/1101 to 222/663, respectively) for the same timepoints for children without ZBD. A secondary analysis comparing data from validated screening tool and non-validated/unknown screening tools did not demonstrate any meaningful differences by developmental domain.
Among the 109 children with ZBD and developmental follow up, 51 (46.8%) had confirmed or possible developmental delay (42 [38.5%] confirmed and a further 9 [8.3%] possible). Gross and fine motor delays were most frequently reported among children with ZBD and confirmed developmental delay; more than one-third had delays noted across multiple domains (Fig. 3). Among children without ZBD and with developmental follow up (n = 1739), confirmed or possible developmental delay was noted among 7.4% (n = 129) (28 [1.6%] confirmed and 101 [5.8%] possible).