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      Population-Based Surveillance for Birth Defects Potentially Related to Zika Virus Infection — 22 States and Territories, January 2016–June 2017

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      , MPH 1 , , MPH 1 , , , MD 1 , , PhD 1 , , MPH 1 , , DO 1 , , MPH 1 , , MS 1 , , DPhil 2 , , MA 2 , , PhD 3 , 3 , , MD 4 , , MPH 4 , , MPH 5 , , MPH 6 , , MSPH 6 , , MPH 7 , , PhD 8 , , MSN 9 , , MBBS 9 , , MPH 10 , , MPH 10 , , PhD 11 , , MPAff 11 , , MPH 12 , , MS 13 , , MS 13 , , MPH 14 , , MPH 14 , , MS 15 , , MPH 15 , , MD 16 , 16 , , MD 17 , , MPH 17 , , PhD 18 , 18 , , PhD 19 , , MPH 19 , , MPH 20 , , MPH 20 , , MS 21 , , MSCP 21 , , PhD 22 , , MPH 22 , 23 , , PhD 23 , , MPH 1 , , MPH 1 , , MPH 1 , , PhD 24 , , MPH 1 , , PhD 1 , , MD, PhD 1 , , PhD 1
      Morbidity and Mortality Weekly Report
      Centers for Disease Control and Prevention

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          Abstract

          Zika virus infection during pregnancy can cause congenital brain and eye abnormalities and is associated with neurodevelopmental abnormalities ( 1 – 3 ). In areas of the United States that experienced local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy increased in the second half of 2016 compared with the first half ( 4 ). To update the previous report, CDC analyzed population-based surveillance data from 22 states and territories to estimate the prevalence of birth defects potentially related to Zika virus infection, regardless of laboratory evidence of or exposure to Zika virus, among pregnancies completed during January 1, 2016–June 30, 2017. Jurisdictions were categorized as those 1) with widespread local transmission of Zika virus; 2) with limited local transmission of Zika virus; and 3) without local transmission of Zika virus. Among 2,004,630 live births, 3,359 infants and fetuses with birth defects potentially related to Zika virus infection during pregnancy were identified (1.7 per 1,000 live births, 95% confidence interval [CI] = 1.6–1.7). In areas with widespread local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy was significantly higher during the quarters comprising July 2016–March 2017 (July–September 2016 = 3.0; October–December 2016 = 4.0; and January–March 2017 = 5.6 per 1,000 live births) compared with the reference period (January–March 2016) (1.3 per 1,000). These findings suggest a fourfold increase (prevalence ratio [PR] = 4.1, 95% CI = 2.1–8.4) in birth defects potentially related to Zika virus in widespread local transmission areas during January–March 2017 compared with that during January–March 2016, with the highest prevalence (7.0 per 1,000 live births) in February 2017. Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance. State and territorial health departments, in collaboration with CDC, conducted population-based surveillance for birth defects potentially related to Zika virus infection during pregnancy.* As previously described ( 4 ), data from medical records were abstracted for live births and pregnancy losses with any potentially Zika-related birth defect. Clinical expert review of verbatim descriptions was used to confirm case inclusion, and cases were assigned to one of four mutually exclusive categories. † Because the case definition for birth defects potentially related to Zika virus infection has been updated to exclude neural tube defects (NTDs) and other early brain malformations and consequences of central nervous system dysfunction ( 5 ), the prevalence of cases with 1) brain abnormalities and/or microcephaly and 2) eye abnormalities without mention of a brain abnormality are reported. Prevalence estimates for NTDs and other early brain malformations during the study period, compared with brain and eye abnormalities in areas with widespread local transmission, are presented to support the updated case definition. § Prevalence was calculated using the number of monthly live births reported by each jurisdiction. Jurisdictions included in this report submitted data to CDC for the entire period (January 2016–June 2017). Jurisdictions were aggregated by level of local transmission of Zika virus: 1) widespread local transmission of Zika virus (Puerto Rico and the U.S. Virgin Islands); 2) limited local transmission of Zika virus (southern Florida counties and Texas Public Health Region 11); and 3) without local transmission of Zika virus. ¶ Prevalence estimates for birth defects per 1,000 live births were calculated by group for each quarter. A PR (compared with the reference period, January–March 2016) was calculated for each quarter. PRs and CIs were calculated using Poisson regression. SAS (version 9.4; SAS Institute) was used to conduct all analyses. During January 1, 2016–June 30, 2017, among 2,004,630 live births, 3,359 infants and fetuses with a birth defect potentially related to Zika virus infection were delivered to residents of the 22 jurisdictions, including 2,813 (83.7%) with brain abnormalities and/or microcephaly and 546 (16.3%) with eye abnormalities without mention of a brain abnormality (overall prevalence = 1.7 per 1,000 live births; 95% CI = 1.6–1.7) (Table 1). During the reference period, in areas with widespread local Zika transmission, limited local transmission, and without local transmission, prevalences were 1.3, 2.2, and 1.7 per 1,000 live births, respectively (Table 2). TABLE 1 Population-based counts and prevalence of infants and fetuses with birth defects potentially related to Zika virus infection during pregnancy — 22 U.S. jurisdictions,* January 1, 2016–June 30, 2017 Characteristic Brain abnormalities and/or microcephaly† (n = 2,813 [83.7%]) Eye abnormalities without brain abnormalities§ (n = 546 [16.3%]) Total (N = 3,359 [100%]) Prevalence¶ (95% CI) 1.4 (1.4–1.5) 0.3 (0.3–0.3) 1.7 (1.6–1.7) Eye abnormalities, no. (%) 289 (10.3) — 835 (24.9) Pregnancy outcome** Live birth, no. (%) 2,667 (95.7) 537 (99.3) 3,204 (96.3) Neonatal death (≤28 days), no. (% of live births) 138 (5.2) 9 (1.7) 147 (4.6) Pregnancy loss,†† no. (%) 119 (4.3) 4 (0.7) 123 (3.7) Zika virus laboratory testing for mothers or infants Positive, no. (%) 64 (2.3) 9 (1.6) 73 (2.2) Negative, no. (%) 103 (3.7) 15 (2.7) 118 (3.5) No laboratory testing performed/NA,§§ no. (%) 2,646 (94.1) 522 (95.6) 3,168 (94.3) Abbreviations: CI = confidence interval; NA = not applicable. * 22 U.S. jurisdictions included births that occurred in California (selected counties), Florida (selected southern counties), Georgia (selected metropolitan Atlanta counties), Hawaii, Illinois, Indiana, Iowa, Louisiana, Massachusetts, Minnesota, New Jersey, New York (excluding New York City residents), North Carolina (selected regions), Oklahoma, Puerto Rico, Rhode Island, South Carolina, Texas (Public Health Regions 10, 11), the U.S. Virgin Islands, Utah, Vermont, and Virginia. Total live births = 2,004,630. † Congenital microcephaly (head circumference <3rd percentile for gestational age and sex and documentation of microcephaly or a small head in the medical record), intracranial calcifications, cerebral atrophy, abnormal cortical gyral patterns (e.g., polymicrogyria, lissencephaly, pachygyria, schizencephaly, gray matter heterotopia), corpus callosum abnormalities, cerebellar abnormalities, porencephaly, hydranencephaly, ventriculomegaly/hydrocephaly (excluding “mild” ventriculomegaly without other brain abnormalities), fetal brain disruption sequence (collapsed skull, overlapping sutures, prominent occipital bone, scalp rugae), and other major brain abnormalities. § Microphthalmia/anophthalmia, coloboma, cataract, intraocular calcifications, and chorioretinal anomalies (e.g., atrophy and scarring, gross pigmentary changes, excluding retinopathy of prematurity); optic nerve atrophy, pallor, and other optic nerve abnormalities. ¶ Per 1,000 live births. ** Thirty-two unknown pregnancy outcomes not included. †† Included miscarriages, fetal deaths, and terminations. Not all programs reported pregnancy losses. §§ Included cases where no testing was performed or testing status was unknown. TABLE 2 Prevalence of birth defects potentially related to Zika virus infection* during pregnancy, by level of local transmission of Zika virus and quarter — 22 U.S. jurisdictions, January 1, 2016–June 30, 2017 Characteristic Areas with widespread local transmission† (n = 129 [3.8%]) Areas with limited local transmission§ (n = 340 [10.1%]) Areas without local transmission¶ (n = 2,890 [86.0%]) Prevalence** PR†† (95% CI) Prevalence** PR†† (95% CI) Prevalence** PR†† (95% CI) Quarter Jan–Mar 2016 1.3 Reference 2.2 Reference 1.7 Reference Apr–Jun 2016 2.5 1.9 (0.9–4.0) 2.0 0.9 (0.6–1.3) 1.7 1.0 (0.9–1.1) Jul–Sep 2016 3.0 2.3 (1.1–4.8) 2.0 0.9 (0.6–1.3) 1.7 1.0 (0.9–1.1) Oct–Dec 2016 4.0 3.0 (1.4–6.1) 2.7 1.2 (0.9–1.7) 1.5 0.9 (0.8–1.0) Jan–Mar 2017 5.6 4.1 (2.1–8.4) 1.9 0.8 (0.6–1.2) 1.5 0.9 (0.8–1.0) Apr–Jun 2017 2.0 1.5 (0.7–3.5) 2.1 1.0 (0.7–1.4) 1.5 0.9 (0.8–1.0) Zika virus laboratory testing for mothers or infants Positive, no. (%) 50 (38.8%) 7 (2.1%) 16 (0.6%) Negative, no. (%) 55 (42.6%) 27 (7.9%) 36 (1.3%) No laboratory testing performed/ NA,§§ no. (%) 24 (18.6%) 306 (90.0%) 2,838 (98.2%) Abbreviations: CI = confidence interval; NA = not applicable; PR = prevalence ratio. * Fetuses and infants included those with 1) brain abnormalities and/or microcephaly or 2) eye abnormalities without mention of a brain abnormality included in the brain abnormalities and/or microcephaly category. † Jurisdictions with widespread local transmission of Zika virus during 2016–2017 included Puerto Rico and the U.S. Virgin Islands. Total live births for areas with widespread local transmission = 42,358. § Jurisdictions with limited local transmission of Zika virus during 2016–2017 included southern Florida counties and Texas Public Health Region 11. Total live births for areas with limited local transmission = 156,613. ¶ Jurisdictions without local transmission of Zika virus during 2016–2017 included California (selected counties), Georgia (selected metropolitan Atlanta counties), Hawaii, Illinois, Indiana, Iowa, Louisiana, Massachusetts, Minnesota, New Jersey, New York (excluding New York City residents), North Carolina (selected regions), Oklahoma, Rhode Island, South Carolina, Texas Public Health Region 10, Utah, Vermont, and Virginia. Total live births for areas without local transmission = 1,805,659. ** Per 1,000 live births. †† Compared with reference, January–March 2016. §§ Included cases where no testing was performed or testing status was unknown. The prevalence of birth defects potentially related to Zika virus infection in widespread local transmission areas was significantly higher in three periods during July 2016–March 2017 compared with that during the reference period. Prevalence increased fourfold (PR = 4.1, 95% CI = 2.1–8.4) during January–March 2017 (5.6 per 1,000 live births), compared with that during the reference period (1.3 per 1,000) (Table 2), reaching a peak prevalence of 7.0 per 1,000 live births in February 2017 (Figure). In areas with limited local transmission, there was a 20% (PR = 1.2, 95% CI = 0.9–1.7) increase during October–December 2016 (2.7 per 1,000 live births) compared with that during the reference period (2.2 per 1,000), although the increase was not significant (Table 2). In areas without local transmission, there was also no significant difference in the prevalence of birth defects potentially related to Zika virus infection between the reference period and any of the subsequent quarters (Table 2). In widespread local Zika virus transmission areas, the significant prevalence increase was limited to brain abnormalities and/or microcephaly and eye abnormalities without mention of a brain abnormality; the prevalence of NTDs and other early brain malformations remained flat during the study period (Supplementary Figure, https://stacks.cdc.gov/view/cdc/84198). FIGURE Prevalence of birth defects potentially related to Zika virus infection during pregnancy,* by level of local Zika virus transmission and month — 22 U.S. jurisdictions, January 2016–June 2017 † , § , ¶ * Fetuses and infants included those with 1) brain abnormalities and/or microcephaly or 2) eye abnormalities without mention of a brain abnormality included in brain abnormalities and/or microcephaly category. † Jurisdictions with widespread local transmission of Zika virus during 2016–2017 included Puerto Rico and the U.S. Virgin Islands. § Jurisdictions with limited local transmission of Zika virus during 2016–2017 included southern Florida counties and Texas Public Health Region 11. ¶ Jurisdictions without local transmission of Zika virus during 2016–2017 included California (selected counties), Georgia (selected metropolitan Atlanta counties), Hawaii, Illinois, Indiana, Iowa, Louisiana, Massachusetts, Minnesota, New Jersey, New York (excluding New York City residents), North Carolina (selected regions), Oklahoma, Rhode Island, South Carolina, Texas Public Health Region 10, Utah, Vermont, and Virginia. The figure is a line chart showing the prevalence of birth defects potentially related to Zika virus infection during pregnancy, by level of local Zika virus transmission and month, in 22 U.S. jurisdictions, during January 2016–June 2017. Overall, most cases (3,168 [94.3%]) had no reported laboratory testing of maternal, placental, fetal, or infant specimens. Among the remaining 191 cases, laboratory evidence of confirmed or possible Zika virus infection was reported in at least one specimen for 73 (2.2%) cases, and 118 (3.5%) had negative Zika virus laboratory testing. In widespread local transmission areas, laboratory testing at any time in at least one specimen was reported for 105 of 129 (81.4%) cases; among the 105 cases with laboratory testing, 50 (47.6%) had laboratory evidence of confirmed or possible Zika virus infection. Discussion The peak occurrence of birth defects potentially related to Zika virus infection in areas with widespread local transmission occurred in February 2017, 6 months after the reported peak of the Zika virus outbreak in these areas in August 2016 ( 6 ). This is consistent with other findings regarding the time between the peak of a Zika virus outbreak and recognition of an increase in potentially Zika-related birth defects ( 7 ). Approximately one half (47.6%) of cases with laboratory test results available in areas with widespread local transmission had confirmed or possible laboratory evidence of infection. In areas with limited local transmission, the prevalence increased 20% during October–December 2016, although not significantly; no increase was observed in areas without local transmission. Compared with the previous report ( 4 ), this analysis added seven more jurisdictions (including one with widespread local transmission) and reported 18 months of data from monitoring births potentially affected by the outbreak. The previous report grouped widespread and limited local transmission areas together, reporting a 21% increase in prevalence for these areas combined ( 4 ). Stratification by local transmission levels provides support that the significant increase in prevalence is exclusive to widespread local Zika virus transmission areas. Further, the baseline prevalence of birth defects potentially related to Zika virus infection during the reference period in the 22 jurisdictions is consistent with the baseline prevalence for three jurisdictions before Zika virus was introduced in the Region of the Americas ( 5 ). The findings in this report are subject to at least four limitations. First, results might not be generalizable beyond the included jurisdictions because jurisdictions might differ in population demographics and case-finding methodology. Second, heightened awareness can result in better identification of affected infants. For example, there might have been more extensive implementation of recommendations for eye exams in widespread local transmission areas. Third, categorization of areas with limited local transmission included regions of Florida and Texas that were larger than the actual areas of local transmission, which might mask any increase in Zika-related birth defects in smaller geographic areas where transmission occurred. Finally, the majority of cases did not have Zika virus testing reported. In widespread local transmission areas, approximately three quarters of cases had at least one sample tested, although the relatively high prevalence of negative results could reflect that timing might not have been optimal for detection of Zika virus in many cases. However, nearly half of those tested had laboratory evidence of Zika virus infection. During the Zika virus outbreak, population-based birth defects surveillance programs were adapted to monitor birth defects potentially related to Zika virus infection during pregnancy. Use of population-based birth defects surveillance programs and the U.S. Zika Pregnancy and Infant Registry provide an example of a complementary approach in ascertaining both exposures and outcomes to better monitor new and emerging threats during pregnancy and impact on infants ( 8 ). Birth defects surveillance was important for identifying infants with birth defects potentially related to Zika virus infection whose mothers were not tested during pregnancy or were not tested at a time when infection could be detected. Health departments can use these data to inform referral services for affected infants and program planning. These findings underscore the important role of birth defects surveillance programs in preparing for emerging public health threats to pregnant women and infants. Summary What is already known about this topic? In states and territories with documented local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy increased 21% during the second half of 2016 compared with that in the first half. What is added by this report? In U.S. territories with widespread local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection increased fourfold during January–March 2017 compared with January–March 2016. What are the implications for public health practice? During the Zika virus outbreak, birth defects surveillance programs adapted to rapidly identify Zika-related birth defects regardless of laboratory evidence. These data provide more complete information on all infants affected and allow planning for care.

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          Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection — U.S. Territories and Freely Associated States, 2018

          Introduction Zika virus infection during pregnancy causes serious birth defects and might be associated with neurodevelopmental abnormalities in children. Early identification of and intervention for neurodevelopmental problems can improve cognitive, social, and behavioral functioning. Methods Pregnancies with laboratory evidence of confirmed or possible Zika virus infection and infants resulting from these pregnancies are included in the U.S. Zika Pregnancy and Infant Registry (USZPIR) and followed through active surveillance methods. This report includes data on children aged ≥1 year born in U.S. territories and freely associated states. Receipt of reported follow-up care was assessed, and data were reviewed to identify Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection. Results Among 1,450 children of mothers with laboratory evidence of confirmed or possible Zika virus infection during pregnancy and with reported follow-up care, 76% had developmental screening or evaluation, 60% had postnatal neuroimaging, 48% had automated auditory brainstem response-based hearing screen or evaluation, and 36% had an ophthalmologic evaluation. Among evaluated children, 6% had at least one Zika-associated birth defect identified, 9% had at least one neurodevelopmental abnormality possibly associated with congenital Zika virus infection identified, and 1% had both. Conclusion One in seven evaluated children had a Zika-associated birth defect, a neurodevelopmental abnormality possibly associated with congenital Zika virus infection, or both reported to the USZPIR. Given that most children did not have evidence of all recommended evaluations, additional anomalies might not have been identified. Careful monitoring and evaluation of children born to mothers with evidence of Zika virus infection during pregnancy is essential for ensuring early detection of possible disabilities and early referral to intervention services.
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            Preliminary Report of Microcephaly Potentially Associated with Zika Virus Infection During Pregnancy - Colombia, January-November 2016.

            In Colombia, approximately 105,000 suspected cases of Zika virus disease (diagnosed based on clinical symptoms, regardless of laboratory confirmation) were reported during August 9, 2015-November 12, 2016, including nearly 20,000 in pregnant women (1,2). Zika virus infection during pregnancy is a known cause of microcephaly and serious congenital brain abnormalities and has been associated with other birth defects related to central nervous system damage (3). Colombia's Instituto Nacional de Salud (INS) maintains national surveillance for birth defects, including microcephaly and other central nervous system defects. This report provides preliminary information on cases of congenital microcephaly identified in Colombia during epidemiologic weeks 5-45 (January 31-November 12) in 2016. During this period, 476 cases of microcephaly were reported, compared with 110 cases reported during the same period in 2015. The temporal association between reported Zika virus infections and the occurrence of microcephaly, with the peak number of reported microcephaly cases occurring approximately 24 weeks after the peak of the Zika virus disease outbreak, provides evidence suggesting that the period of highest risk is during the first trimester of pregnancy and early in the second trimester of pregnancy. Microcephaly prevalence increased more than fourfold overall during the study period, from 2.1 per 10,000 live births in 2015 to 9.6 in 2016. Ongoing population-based birth defects surveillance is essential for monitoring the impact of Zika virus infection during pregnancy on birth defects prevalence and measuring the success in preventing Zika virus infection and its consequences, including microcephaly.
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              Population-Based Surveillance of Birth Defects Potentially Related to Zika Virus Infection — 15 States and U.S. Territories, 2016

              Zika virus infection during pregnancy can cause serious birth defects, including microcephaly and brain abnormalities ( 1 ). Population-based birth defects surveillance systems are critical to monitor all infants and fetuses with birth defects potentially related to Zika virus infection, regardless of known exposure or laboratory evidence of Zika virus infection during pregnancy. CDC analyzed data from 15 U.S. jurisdictions conducting population-based surveillance for birth defects potentially related to Zika virus infection.* Jurisdictions were stratified into the following three groups: those with 1) documented local transmission of Zika virus during 2016; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents; and 3) less than one case of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents. A total of 2,962 infants and fetuses (3.0 per 1,000 live births; 95% confidence interval [CI] = 2.9–3.2) ( 2 ) met the case definition. † In areas with local transmission there was a non-statistically significant increase in total birth defects potentially related to Zika virus infection from 2.8 cases per 1,000 live births in the first half of 2016 to 3.0 cases in the second half (p = 0.10). However, when neural tube defects and other early brain malformations (NTDs) § were excluded, the prevalence of birth defects strongly linked to congenital Zika virus infection increased significantly, from 2.0 cases per 1,000 live births in the first half of 2016 to 2.4 cases in the second half, an increase of 29 more cases than expected (p = 0.009). These findings underscore the importance of surveillance for birth defects potentially related to Zika virus infection and the need for continued monitoring in areas at risk for Zika. In 2016, as part of the emergency response to the Zika virus outbreak in the World Health Organization’s Region of the Americas, population-based birth defects surveillance systems monitored fetuses and infants with birth defects potentially related to Zika virus infection using a standard case definition and multiple data sources. Medical records were abstracted for data on birth defects, congenital infections, pregnancy outcome, head circumference, vital status, and Zika laboratory test results, irrespective of maternal Zika virus exposure or infection. Verbatim text describing the birth defects was reviewed to identify those that met the case definition. Infants and fetuses were aggregated into four mutually exclusive categories: those with 1) brain abnormalities or microcephaly; 2) NTDs; 3) eye abnormalities without mention of a brain abnormality included in the two previously defined categories; and 4) other consequences of central nervous system (CNS) dysfunction, specifically joint contractures and congenital sensorineural deafness without mention of brain or eye abnormalities included in another category. Because the evidence linking NTDs and congenital Zika virus infection is weak, prevalence estimates per 1,000 live births were calculated both overall and excluding NTDs for each quarter in 2016; CIs were calculated using Poisson regression ( 1 , 2 ). All 15 U.S. jurisdictions ¶ included in this report had existing birth defects surveillance systems that were rapidly adapted to monitor birth defects potentially related to Zika virus infection. These jurisdictions provided data on live births and pregnancy losses occurring from January 1–December 31, 2016. The jurisdictions were stratified into the following three groups: those with 1) confirmed local Zika virus transmission during 2016**; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents (i.e., “higher” Zika prevalence) †† ; and 3) less than one case per 100,000 residents of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC (i.e., “lower” [low or no travel-associated] Zika prevalence) §§ ( 3 ). Overall, 2,962 infants and fetuses with birth defects potentially related to Zika virus infection were identified (3.0 per 1,000 live births; CI = 2.9–3.2) (Table), including 1,457 (49%) with brain abnormalities or microcephaly, 581 (20%) with NTDs, 262 (9%) with eye abnormalities without mention of a brain abnormality, and 662 (22%) with other consequences of CNS dysfunction without mention of brain or eye abnormalities. Among the 2,962 infants and fetuses with defects potentially related to Zika virus infection, there were 2,716 (92%) live births. Laboratory evidence of possible Zika virus infection in maternal, placental, infant, or fetal specimens was present in 45 (1.5%) cases; 96 (3.2%) had negative tests for Zika virus, and 2,821 (95.2%) either had no testing performed or no results available. TABLE Population-based counts of cases of infants and fetuses with birth defects potentially related to Zika virus infection and prevalence per 1,000 live births — 15 U.S. jurisdictions,* 2016 Characteristic Brain abnormalities or microcephaly† (N = 1,457; 49%) Neural tube defects and other early brain malformations§ (N = 581; 20%) Eye abnormalities¶ (N = 262; 9%) Consequences of CNS dysfunction** (N = 662; 22%) Total (N = 2,962; 100%) Prevalence per 1,000 live births (95% CI) 1.5 (1.4–1.6) 0.60 (0.55–0.65) 0.27 (0.24-0.30) 0.68 (0.63–0.74) 3.0 (2.9–3.2) Eye abnormalities No. (%) 144 (9.9) 24 (4.1) — 0 430 (14.5) Consequences of CNS dysfunction No. (%) 133 (9.1) 77 (13.3) 12 (4.6) — 884 (29.8) Pregnancy outcome†† Live births No. (%) 1,387 (95.2) 427 (73.5) 257 (98.1) 645 (97.4) 2,716 (91.7) Neonatal death (≤28 days) No. 89 92 8 30 219 Pregnancy loss §§ No. (%) 65 (4.5) 149 (25.6) 5 (1.9) 16 (2.4) 235 (7.9) Zika virus laboratory testing for infants or mothers Positive No. (%) 29 (2.0) 4 (0.69) 10 (3.8) 2 (0.30) 45 (1.5) Negative No. (%) 65 (4.5) 20 (3.4) 3 (1.1) 8 (1.2) 96 (3.2) No testing performed/NA¶¶ No. (%) 1,363 (93.5) 557 (95.9) 249 (95.0) 652 (98.5) 2,821 (95.2) Abbreviations: CI = confidence interval; CNS = central nervous system; NA = not available. * 15 U.S. jurisdictions: Florida (selected southern counties), Georgia (selected metropolitan Atlanta counties), Hawaii, Iowa, Illinois, Massachusetts, New Jersey, New York (excluding New York City), North Carolina (selected regions), Puerto Rico, Rhode Island, South Carolina, Texas (Public Health Regions 1, 3, 9, and 11), Utah, and Vermont. Total live births = 971,685. † Brain abnormalities or microcephaly (congenital microcephaly [head circumference <3rd percentile for gestational age and sex], intracranial calcifications, cerebral atrophy, abnormal cortical gyral patterns [e.g., polymicrogyria, lissencephaly, pachygyria, schizencephaly, gray matter heterotopia], corpus callosum abnormalities, cerebellar abnormalities, porencephaly, hydranencephaly, ventriculomegaly/hydrocephaly [excluding “mild” ventriculomegaly without other brain abnormalities], fetal brain disruption sequence [collapsed skull, overlapping sutures, prominent occipital bone, scalp rugae], other major brain abnormalities). § Neural tube defects and other early brain malformations (anencephaly/acrania, encephalocele, spina bifida, and holoprosencephaly). ¶ Structural eye abnormalities (microphthalmia/anophthalmia, coloboma, cataract, intraocular calcifications, and chorioretinal anomalies [e.g., atrophy and scarring, gross pigmentary changes, excluding retinopathy of prematurity]); optic nerve atrophy, pallor, and other optic nerve abnormalities. ** Consequences of CNS dysfunction (arthrogryposis, club foot with associated brain abnormalities, congenital hip dysplasia with associated brain abnormalities, and congenital sensorineural hearing loss). †† 11 unknown pregnancy outcomes not included. §§ Includes miscarriages, fetal deaths, and terminations. ¶¶ Includes cases linked to lab data where no testing was performed or there was unknown testing status. The prevalence of reported birth defects cases potentially related to Zika virus infection increased in jurisdictions with confirmed local transmission, from 2.8 per 1,000 live births (182 cases) during the first half of 2016 to 3.0 per 1,000 live births (211 cases) during the second half (CI = 2.4-3.2 and CI = 2.6–3.4, respectively; p = 0.10). In “higher” Zika prevalence jurisdictions, the monitored birth defects prevalence was 3.0 per 1,000 live births in both the first (753 cases) and second (775 cases) halves of 2016. In “lower” prevalence jurisdictions, the monitored birth defects prevalence declined significantly from 3.4 per 1,000 live births (549 cases) during the first half of 2016 to 3.0 (492 cases) per 1,000 live births during the second half (CI = 3.2–3.7 and CI = 2.8–3.3, respectively; p = 0.002) (Figure 1). FIGURE 1 Prevalence of birth defects cases potentially related to Zika virus infection, by Zika virus transmission characteristics and quarter —15 U.S. jurisdictions, 2016* , †,§ * Local transmission jurisdictions included Florida (selected southern counties), Puerto Rico, and Texas (Public Health Region 11). † Higher travel-related Zika prevalence jurisdictions had one or more case of confirmed symptomatic travel-associated Zika virus disease reported to CDC per 100,000 residents. These jurisdictions included Georgia (selected metropolitan Atlanta counties), Massachusetts, New Jersey, New York (excluding New York City), Rhode Island, South Carolina, Texas (Public Health Regions 1, 3, and 9), and Vermont. § Low or no travel-related Zika prevalence jurisdictions had less than one case of confirmed symptomatic travel-associated Zika virus disease reported to CDC per 100,000 residents. These jurisdictions included Hawaii, Illinois, Iowa, North Carolina (selected regions), and Utah. The figure above is a line graph showing the number of birth defects cases per 1,000 live births potentially related to Zika virus infection, by three groups of jurisdictions with varying prevalence and quarter, among 15 U.S., jurisdictions, in 2016. When NTDs were excluded, the prevalence of birth defects potentially related to Zika virus infection in jurisdictions with local Zika transmission increased 21%, from 2.0 per 1,000 live births (CI = 1.7–2.4) to 2.4 (CI = 2.1–2.8) (Figure 2). This increase indicated there were 29 more infants and fetuses with birth defects than were expected in areas with local transmission in the second half of 2016 (169 observed cases compared with 140 expected, p = 0.009). The prevalence of birth defects excluding NTDs in “higher” prevalence jurisdictions did not change (2.4 per 1,000 live births) and the prevalence in the “lower” prevalence jurisdictions significantly decreased from 2.8 per 1,000 live births (CI = 2.5–3.0) to 2.4 (CI = 2.2-2.7). Among 393 infants and fetuses with birth defects potentially related to Zika virus infection in areas with local transmission, 32 (8.1%) had laboratory evidence of possible Zika virus infection in a maternal, placental, infant, or fetal sample, 59 (15.0%) had negative Zika virus test results, and 302 (76.81%) had no testing performed or no results available. FIGURE 2 Prevalence of birth defects cases* potentially related to Zika virus infection in U.S. jurisdictions with documented local transmission of Zika virus, † by defect type and quarter, 2016 *Fetuses and infants were aggregated into the following four mutually exclusive categories: those with 1) brain abnormalities with or without microcephaly (head circumference at delivery <3rd percentile for sex and gestational age); 2) NTDs and other early brain malformations; 3) eye abnormalities among those without mention of a brain abnormality included in the first two categories; and 4) other consequences of central nervous system dysfunction, specifically joint contractures and congenital sensorineural deafness, among those without mention of brain or eye abnormalities included in another category. † Jurisdictions with local transmission of Zika virus included Florida (selected southern counties), Puerto Rico, and Texas (Public Health Region 11). The figure above is a line graph showing the number of birth defects cases per 1,000 live births in three U.S. jurisdictions with documented local transmission of Zika virus, by defect type and quarter, in 2016. Discussion Leveraging existing birth defects surveillance systems permitted rapid implementation of surveillance for birth defects potentially related to Zika virus infection early during the U.S. Zika virus outbreak. The prevalence of birth defects strongly linked to Zika virus infection increased significantly in areas with local Zika virus transmission (29 more than were expected in the second half of 2016 compared with observed prevalence in the first half). This finding underscores the importance of surveillance for birth defects potentially related to Zika virus infection and the need for continued monitoring in areas at risk for Zika transmission and exposure. An increase in birth defects potentially related to Zika was only observed in jurisdictions with local Zika virus transmission, and this difference was significant when NTDs were excluded. Brain and eye abnormalities and consequences of CNS dysfunction have been most consistently described in cases of congenital Zika infection, whereas the evidence supporting a possible association between NTDs and Zika virus infection during pregnancy is weak ( 1 , 2 ). In jurisdictions with “lower” (low or no travel-associated) Zika prevalence, the reason for the significant decrease in prevalence of birth defects potentially related to Zika (both including NTDs and excluding NTDs) is not clear. However, birth defects surveillance data typically are not final until approximately 24 months after the end of the birth year, and this release of data only 12 months after the end of the birth year likely resulted in less complete ascertainment of birth defects in late 2016 compared with early 2016. Further case ascertainment from the final quarter of 2016 is anticipated in all jurisdictions. In addition, the peak occurrence of birth defects potentially related to Zika virus infection is expected to have occurred in the 2017 birth cohort because the peak of Zika virus transmission occurred in Puerto Rico in August 2016, and local transmission of Zika virus was identified in southern Florida in June 2016 and in southern Texas in November 2016 ( 4 – 7 ). The overall prevalence of the birth defects in this analysis (3.0 per 1,000 live births) was similar to a previously published baseline prevalence of birth defects potentially related to Zika virus infection from 2013–14 (2.9 per 1,000 live births; 95% CI = 2.7–3.1) ( 8 ). The findings presented here included data from an additional 12 jurisdictions, which covers a larger birth cohort totaling nearly 1 million live births, representing approximately one fourth of the total live births in the U.S. states and territories. The findings in this report are subject to at least three limitations. First, the three jurisdictions with local Zika virus transmission differed from one another in the scope and timing of identified local transmission of Zika virus. Whereas Puerto Rico experienced a widespread outbreak that began in early 2016, local transmission in Texas was not confirmed until November 2016. In addition, jurisdictions with local transmission also had a high prevalence of travel-related Zika virus disease in 2016 ( 3 ), which could have contributed to the observed increased prevalence in birth defects. Second, increased awareness of birth defects potentially related to Zika virus infection in areas with local transmission might have resulted in increased efforts focused on rapid and complete identification of these birth defects cases during the second half of 2016. However, a significant increase in NTD prevalence was not observed. Although more complete ascertainment might partially explain the increased prevalence observed in areas with local transmission, it is unlikely that it would lead to a significant change, given the longstanding, mature surveillance systems, the standardized case review process, and no observable change in the prevalence of NTDs. Finally, jurisdictions in this analysis might differ in population demographics and systematic case-finding methodology, contributing to differences in observed prevalences among the three groups ( 9 ). A comparison of the prevalences in the first and second halves of the year was used to partially control for regional differences and monitor trends for those specific jurisdictional groups rather than to compare one group with another. Collaboration between state and territorial Zika pregnancy and infant registries and birth defects surveillance systems provides a model for using the complementary approach of a prospective, exposure-based surveillance and conventional disease-based surveillance to respond to an emerging public health threat. The U.S. Zika Pregnancy and Infant Registry ¶¶ can provide an early alert mechanism regarding clinical characteristics and manifestations of infants and fetuses with potential congenital infection; over 7,000 pregnancies with laboratory evidence of Zika virus infection have been reported, and CDC is monitoring pregnancy and infant adverse outcomes (https://www.cdc.gov/pregnancy/zika/data/pregnancy-outcomes.html). Established birth defects surveillance systems can adapt to monitor other emerging pregnancy, infant, and newborn outcomes of concern beyond structural birth defects, including functional problems such as hearing loss, and can provide additional clinical information through standardized data collection and clinical review. Finally, birth defects surveillance systems can provide an important mechanism for facilitating timely access to services among infants with birth defects and serve as a resource for assessing subsequent health and developmental outcomes among these children. The unique contributions of ongoing birth defects surveillance and the U.S. Zika Pregnancy and Infant Registry are both critical to optimally monitoring pregnant women and infants from the threat of Zika virus infection and implementing appropriate prevention efforts ( 10 ). Summary What is already known about this topic? Data collected from three U.S. population-based birth defects surveillance systems from 2013 and 2014, before the introduction of Zika virus infection in the World Health Organization’s Region of the Americas, showed a baseline prevalence of birth defects potentially related to congenital Zika virus infection of 2.9 per 1,000 live births. Based on 2016 data from the U.S. Zika Pregnancy and Infant Registry, the risk for birth defects potentially related to Zika virus infection in pregnancies with laboratory evidence of possible Zika virus infection was approximately 20-fold higher than the baseline prevalence. What is added by this report? This report provides the first comprehensive data on the prevalence of birth defects (3.0 per 1,000 live births) potentially related to Zika virus infection in a birth cohort of nearly 1 million births in 2016. A significant increase in birth defects strongly related to Zika virus during the second half of 2016 compared with the first half was observed in jurisdictions with local Zika virus transmission. Only a small percentage of birth defects potentially related to Zika had laboratory evidence of Zika virus infection, and most were not tested for Zika virus. What are the implications for public health practice? Whereas the U.S. Zika Pregnancy and Infant Registry monitors women with laboratory evidence of possible Zika virus infection during pregnancy and their congenitally exposed infants, population-based birth defects surveillance systems make a unique contribution by identifying and monitoring all cases of these birth defects regardless of exposure or laboratory testing or results. Continued surveillance for birth defects potentially related to Zika virus infection is important because most pregnancies affected by Zika virus ended in 2017. These data will help communities plan for needed resources to care for affected patients and families and can serve as a foundation for linking and evaluating health and developmental outcomes of affected children.
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                Journal
                MMWR Morb Mortal Wkly Rep
                MMWR Morb. Mortal. Wkly. Rep
                WR
                Morbidity and Mortality Weekly Report
                Centers for Disease Control and Prevention
                0149-2195
                1545-861X
                24 January 2020
                24 January 2020
                : 69
                : 3
                : 67-71
                Affiliations
                Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities, CDC; Illinois Department of Public Health; Massachusetts Department of Public Health; California Department of Public Health; Indiana State Department of Health; New York State Department of Health; Virginia Department of Health; Minnesota Department of Health; New Jersey Department of Health; Florida Department of Health; Texas Department of State Health Services; Utah Department of Health; Oklahoma State Department of Health; North Carolina Department of Health and Human Services; South Carolina Department of Health and Environmental Control; Louisiana Department of Health; Puerto Rico Department of Health; University of Iowa, Iowa City; Georgia Department of Public Health; Rhode Island Department of Health; Hawaii Department of Health; Vermont Department of Health; U.S. Virgin Islands Department of Health; Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC.
                Author notes
                Corresponding author: Samantha M. Olson, ylz8@ 123456cdc.gov , 404-718-4285.
                Article
                mm6903a3
                10.15585/mmwr.mm6903a3
                7367037
                31971935
                bc308231-b3c2-48ab-a86f-ad89ef7345e9

                All material in the MMWR Series is in the public domain and may be used and reprinted without permission; citation as to source, however, is appreciated.

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