BACKGROUND: We calculated prevalences of birth defects among infants of participants in the Centers for Disease Control and Prevention's (CDC) COVID-19 Vaccine Pregnancy Registry (C19VPR). METHODS: C19VPR enrolled women receiving COVID-19 vaccines ≤ 30 days before the last menstrual period or during pregnancy from December 2020 through June 2021. We included 19,931 participants with singleton pregnancies ending ≥ 20 weeks' gestation who did not report COVID-19 illness during pregnancy. Clinicians identified birth defects from participant-reported infant health information up to 4 months after birth. We compared C19VPR birth defect prevalences to published pre-pandemic estimates. For seven defects originating during embryogenesis (cleft lip with/without cleft palate, atrial septal defect, coarctation of the aorta, ventricular septal defect, esophageal atresia or stenosis, hypospadias, kidney agenesis/hypoplasia/dysplasia), we estimated prevalence ratios comparing those vaccinated < 14 weeks' to those vaccinated ≥ 14 weeks' gestation. RESULTS: Participants reported receiving Pfizer-BioNTech vaccines (59.0%), Moderna (38.2%), and Janssen (2.8%) vaccines. Most (65.2%) participants received their first COVID-19 vaccine after the first trimester. The prevalence of major birth defects was 3.8%. Among defects with comparator estimates available (n = 50), 35 were below or within expected ranges. C19VPR prevalences were higher than the comparator confidence interval for 15 defects; however, C19VPR confidence intervals included comparator estimates. Prevalences did not differ by the timing of vaccination for seven defects examined. CONCLUSIONS: Birth defects prevalence estimates among infants born to women receiving COVID-19 vaccines during or just prior to pregnancy were generally similar to pre-pandemic estimates. While there was no strong evidence of associations between vaccination and specific defects, statistical power was low.

The U.S. Centers for Disease Control and Prevention (CDC) developed and implemented the CDC COVID-19 Vaccine Pregnancy Registry (C19VPR) to monitor vaccine safety. Potential participants who received a COVID-19 vaccine in pregnancy or up to 30 days prior to their pregnancy-associated last menstrual period were eligible to participate in the registry, which monitored health outcomes of participants and their infants through phone interviews and review of available medical records. Data for select outcomes, including birth defects, were reviewed by clinicians. In certain cases, medical records were used to confirm and add detail to participant-reported health conditions. This paper serves as a description of CDC C19VPR protocol. We describe the development and implementation for each data collection aspect of the registry (i.e., participant phone interviews, clinical review, and medical record abstraction), data management, and strengths and limitations. We also describe the demographics and vaccinations received among eligible and enrolled participants. There were 123,609 potential participants 18-54 years of age identified from January 2021 through mid-June 2021; 23,339 were eligible and enrolled into the registry. Among these, 85.3 % consented to medical record review for themselves and/or their infants. Participants were majority non-Hispanic White (79.1 %), residents of urban areas (93.3 %), and 48.3 % were between 30 and 34 years of age. Most participants completed the primary series of vaccination by the end of pregnancy (89.7 %). Many participants were healthcare personnel (44.8 %), possibly due to the phased roll-out of the vaccination program. The registry continues to provide important information about the safety of COVID-19 vaccination among pregnant people, a population with higher risk of poor outcomes from COVID-19 who were not included in pre-authorization clinical trials. Lessons learned from the registry may guide development and implementation of future vaccine safety monitoring efforts for pregnant people and their infants.

Studies suggest that pregnant women might be at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) (1,2). This report provides updated information about symptomatic women of reproductive age (15-44 years) with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19. During January 22-October 3, CDC received reports through national COVID-19 case surveillance or through the National Notifiable Diseases Surveillance System (NNDSS) of 1,300,938 women aged 15-44 years with laboratory results indicative of acute infection with SARS-CoV-2. Data on pregnancy status were available for 461,825 (35.5%) women with laboratory-confirmed infection, 409,462 (88.7%) of whom were symptomatic. Among symptomatic women, 23,434 (5.7%) were reported to be pregnant. After adjusting for age, race/ethnicity, and underlying medical conditions, pregnant women were significantly more likely than were nonpregnant women to be admitted to an intensive care unit (ICU) (10.5 versus 3.9 per 1,000 cases; adjusted risk ratio [aRR] = 3.0; 95% confidence interval [CI] = 2.6-3.4), receive invasive ventilation (2.9 versus 1.1 per 1,000 cases; aRR = 2.9; 95% CI = 2.2-3.8), receive extracorporeal membrane oxygenation (ECMO) (0.7 versus 0.3 per 1,000 cases; aRR = 2.4; 95% CI = 1.5-4.0), and die (1.5 versus 1.2 per 1,000 cases; aRR = 1.7; 95% CI = 1.2-2.4). Stratifying these analyses by age and race/ethnicity highlighted disparities in risk by subgroup. Although the absolute risks for severe outcomes for women were low, pregnant women were at increased risk for severe COVID-19-associated illness. To reduce the risk for severe illness and death from COVID-19, pregnant women should be counseled about the importance of seeking prompt medical care if they have symptoms and measures to prevent SARS-CoV-2 infection should be strongly emphasized for pregnant women and their families during all medical encounters, including prenatal care visits. Understanding COVID-19-associated risks among pregnant women is important for prevention counseling and clinical care and treatment.

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.

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.

Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly (1). In February 2016, CDC recommended 1) routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, 2) retesting during the second trimester for women who initially test negative, and 3) testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy (2). To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection* and outcomes in their fetuses and infants, CDC established pregnancy and infant registries (3). During January 1, 2016-April 25, 2017, U.S. territoriesdagger with local transmission of Zika virus reported 2,549 completed pregnancies section sign (live births and pregnancy losses at any gestational age) with laboratory evidence of recent possible Zika virus infection; 5% of fetuses or infants resulting from these pregnancies had birth defects potentially associated with Zika virus infection paragraph sign (4,5). Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries. Identification and follow-up of infants born to women with laboratory evidence of recent possible Zika virus infection during pregnancy permits timely and appropriate clinical intervention services (6).