ABSTRACT
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.
Keywords: birth defects, congenital anomalies, COVID‐19 vaccination in pregnancy, pregnancy, vaccination
1. Background
Concerns about the effect of COVID‐19 vaccines on fetal development contribute to vaccine hesitancy among the pregnant population (Patel et al. 2024). Birth defects originate prenatally and often result in significant morbidity and disability for the affected infant (Centers for Disease Control and Prevention 2008). Birth defect surveillance programs in the United States include birth defects identified through at least 1 year of age (National Birth Defects Prevention Network (NBDPN) 2004). Certain medications, chemicals, and infections during pregnancy can increase the risk of various birth defects (Harris et al. 2017). Therefore, birth defects are an outcome of interest in vaccine safety monitoring for pregnant women, particularly if pregnant women are not included in prelicensure randomized controlled trials.
Studies evaluating the association between COVID‐19 vaccination in pregnancy and birth defects have not found evidence of an association (Calvert et al. 2023; Favre et al. 2023; Goldshtein et al. 2022; Hui et al. 2023; Kharbanda et al. 2024; Magnus et al. 2024; Rowe et al. 2025; Ruderman et al. 2022; Woestenberg et al. 2023). As specific birth defects generally occur in one in 1000 to one in 100,000 live births (National Birth Defects Prevention Network (NBDPN) 2009), some studies were underpowered (< 4000 vaccinated participants) to identify specific birth defects (Favre et al. 2023; Goldshtein et al. 2022; Ruderman et al. 2022; Woestenberg et al. 2023). Further, some studies used only prenatal imaging and/or neonatal health information to ascertain birth defects, which may underestimate prevalences as some birth defects are often identified after the neonatal period (Calvert et al. 2023; Ruderman et al. 2022).
This surveillance evaluation aimed to characterize participant‐reported birth defects among a cohort of US women who received at least one dose of a COVID‐19 vaccine during or just prior to pregnancy from December 2020 to June 2021. We compared the prevalence of specific birth defects to background prevalences reported prior to the availability of COVID‐19 vaccines to identify any potential safety signals. We compared prevalence ratios of specific birth defects among those vaccinated early (pre‐pregnancy and/or first trimester) to those vaccinated in the second and/or third trimesters.
2. Methods
2.1. Data Source and Analytic Cohort
From December 15, 2020, through June 21, 2021, women who reported a pregnancy to V‐safe internet‐based health check‐in surveys (Myers et al. 2023) were screened for eligibility in the CDC COVID‐19 Vaccine Pregnancy Registry (C19VPR), which was developed to monitor the safety of COVID‐19 vaccines in pregnancy at the beginning of the implementation of the US COVID‐19 vaccination program (Gee et al. 2024). At the time of C19VPR eligibility, only first‐generation monovalent index virus vaccines were available (i.e., two‐dose Moderna and Pfizer‐BioNTech mRNA vaccines and the one‐dose Janssen adenoviral‐vector vaccine) (Centers for Disease Control and Prevention 2023). The C19VPR enrolled women who received at least one vaccine dose during pregnancy or just prior to pregnancy (defined as 30 days before the last menstrual period [LMP] associated with the pregnancy). The C19VPR is based on a convenience sample. Of the 65,076 V‐safe participants called via phone to assess eligibility, only 26,121 could be reached. Of these, 23,249 were eligible and enrolled (Madni et al. 2024). Given the timing of C19VPR enrollment and COVID‐19 vaccine availability, for 97% of participants, the registry‐eligible dose (i.e., COVID‐19 vaccine received up to 30 days prior to LMP or during pregnancy) was also the first dose ever received.
From January 2021 through August 2022, C19VPR collected data on COVID‐19 vaccination, medical history, gestational health, fetal health or concerns, pregnancy outcomes, participant postpartum health, and infant health and hospitalizations through interviewer‐led phone surveys. Comprehensive details about C19VPR enrollment and methodology were described previously (Madni et al. 2024). This activity was reviewed by the CDC, deemed public health surveillance, and was conducted consistent with applicable federal law and CDC policy. 1
Among the 23,249 participants enrolled in the C19VPR, 16 participants had two registry‐eligible pregnancies, resulting in 23,265 pregnancies. For the analysis of birth defects, we excluded 3334 (14.3%) pregnancies due to (1) loss to follow‐up resulting in missing pregnancy outcome or infant health data (n = 1203), (2) the pregnancy ending < 20 weeks' gestation (n = 934) as there is poor ascertainment of birth defects prior to this gestational age, (3) multi‐fetal gestation (n = 383), (4) birth defect(s) identification prior to registry‐eligible vaccination (n = 43), or (5) reported COVID‐19 illness during pregnancy (n = 771). The final analytic sample included 19,931 (85.7%) singleton pregnancies from unique participants (i.e., no participant contributed more than one pregnancy to this analysis) (Figure 1). Demographic and clinical characteristics of the 3334 pregnancies excluded from this analysis, which included 3697 fetuses or infants (hereafter referred to as “infants”) are provided in Table S1.
FIGURE 1.
Description of the CDC COVID‐19 Vaccine Pregnancy Registry inclusion and exclusion criteria for the evaluation of participant‐reported birth defects.
2.2. Birth Defect Identification
To ascertain the prevalence of birth defects, at least two CDC clinicians reviewed each participant's responses to questions regarding fetal health concerns, infant health, hospitalizations, and specialist referrals to determine whether the information provided met criteria for a major birth defect, defined as congenital structural abnormalities that have medical, surgical, or cosmetic significance that typically requires medical intervention (WHO 2020). Additional description of the clinical review process was described previously (Madni et al. 2024). The Metropolitan Atlanta Congenital Defects Program (MACDP) 6‐Digit Code Defect List (Centers for Disease Control and Prevention 2024), which is based on the CDC/British Pediatric Association (BPA) coding system, served as the reference and coding system (Centers for Disease Control and Prevention, n.d.). However, as MACDP identifies major birth defects from medical record data, CDC birth defect experts established additional criteria that were applied to the C19VPR participant‐reported information. Identification of major birth defects was based on condition descriptions, treatment, specialist referrals, and timing of diagnosis (e.g., prenatal versus postnatal, age of sign/symptom onset).
Conditions were not classified as major birth defects if the condition: (1) was diagnosed prenatally, could resolve prenatally (e.g., hydronephrosis), and did not have postnatal confirmation available, (2) was vaguely described without additional information, such as treatment (e.g., “a heart problem” with no indication of surgery), (3) could be acquired postnatally (e.g., plagiocephaly) and age of sign/symptom onset was not reported, or (4) was considered a minor birth defect (e.g., anomalies with little or no impact on health or short‐term or long‐term function). For infants with a reported genetic condition (i.e., gene or chromosome anomaly or specific genetic syndrome), the infant was coded as having a genetic condition and any additional birth defects reported were considered to be associated with the genetic condition and not counted separately. This report describes major birth defects identified before 4 months of age from participant‐report (specific MACDP codes are provided in Table S2) and, where available, compares C19VPR birth defect prevalences to existing literature prior to the availability of COVID‐19 vaccines. A list of major birth defects reported among excluded infants is provided in Table S3.
2.3. Statistical Analysis
We examined the distribution of participant demographics, pregnancy characteristics, and health conditions overall and by vaccine manufacturer. Birth defect prevalences were calculated per 10,000 live births; 95% confidence intervals (CI) were estimated using exact methods (Agresti 2018), assuming a binomial distribution. We compared prevalences in the C19VPR to the most recent published estimates using the following prioritization: (1) national (US) estimates (e.g., National Birth Defects Prevention Network, 13 US birth defect surveillance programs), (2) specific US state or metropolitan Atlanta estimates, and (3) European estimates (e.g., European network of population‐based registries for the epidemiological surveillance of congenital anomalies: EUROCAT). Comparator estimates were available for 50 birth defects, and all data sources ascertained and classified defects through medical records and the CDC/BPA coding system, respectively; data sources ranged from 1994 to 2022.
To assess whether the prevalence of birth defects was associated with the timing of COVID‐19 vaccination during pregnancy, we categorized participants into three mutually exclusive groups based on gestational age at vaccination. Group 1 included pregnancies of participants vaccinated only early in pregnancy (i.e., all doses received < 14 weeks' gestation, including 30 days before LMP). Group 2 included pregnancies of participants with both early and later vaccination (i.e., one dose < 14 weeks' gestation and one ≥ 14 weeks' gestation). Group 3 included pregnancies of participants with only later vaccination (i.e., all doses ≥ 14 weeks' gestation). We estimated the prevalence ratio and 95% CI for select birth defects by comparing pregnancies in Group 1 to pregnancies in Group 3. For a sensitivity analysis, we also combined Groups 1 and 2, resulting in a group of pregnancies of participants receiving at least one dose < 14 weeks' gestation, and compared these pregnancies to those in Group 3. The timing analysis was restricted to participants who received an mRNA COVID‐19 vaccine (n = 19,376) as these vaccines were received by 97% of our study cohort. Birth defects were included in the timing analysis if (1) at least four cases were reported in Group 1, and (2) the birth defect is known to originate during embryogenesis (first 8 weeks after conception). At least four cases were required in Group 1 because this was the minimum number of cases required to detect a statistically significant increase in prevalence compared to at least one case in Group 3. Four cases in Group 1 compared to one case in Group 3 represent a 10‐fold higher prevalence [prevalence ratio: (4/5093)/(1/12,564) = 9.9; p = 0.04]. Refer to Table S4 for the list of birth defects considered for timing analysis and reasons for exclusions. Prevalence ratios were adjusted for age at pregnancy outcome (< 30 or ≥ 30 years), non‐Hispanic White or other race and ethnicity, and pre‐pregnancy BMI (< 25 or ≥ 25 kg/m2). Receipt of a booster dose of vaccine was not considered in the timing analysis as < 10% of the study population reported receiving a booster dose, and all were received ≥ 19 weeks' gestation. SAS (version 9.4; SAS Institute, Cary, North Carolina, USA) was used for analyses.
3. Results
Of the 19,931 pregnancies included in the analysis, more participants received their registry‐eligible vaccine dose during the second trimester (40.4%) compared to pre‐pregnancy (8.5%), the first trimester (26.3%), or the third trimester (24.8%) (Table 1). Because C19VPR was initiated at the onset of the US COVID‐19 vaccination program, the first COVID‐19 vaccine received was also the registry‐eligible dose for 97% of participants. The most received vaccine by manufacturer was Pfizer‐BioNTech (59.0%), followed by Moderna (38.2%) and Janssen (2.8%). Overall, 37.5% of participants were over 35 years of age, most were non‐Hispanic White (79.5%), and less than half (42.2%) were nulliparous. Pregnancy outcomes included 19,858 live births (99.6%) and 73 non‐live births (0.4%) occurring at ≥ 20 weeks' gestation. Consistent with the phased roll‐out of the COVID‐19 vaccination program that included prioritizing healthcare personnel, 42.5% of participants reported occupation as healthcare personnel. Female sex was reported for 48.2% of the infants.
TABLE 1.
Participant‐reported demographic and clinical characteristics of COVID‐19 vaccines (by manufacturer) received during December 2020–June 2021, CDC COVID‐19 Vaccine Pregnancy Registry (N = 19,931).
| Pfizer‐BioNTech (N = 11,764) | Moderna (N = 7613) | Janssen (N = 554) | Total (N = 19,931) | |
|---|---|---|---|---|
| Timing of registry‐eligible vaccine dose | ||||
| Pre‐pregnancy a | 926 (7.9) | 753 (9.9) | 13 (2.3) | 1692 (8.5) |
| First trimester | 3089 (26.3) | 2045 (26.9) | 116 (20.9) | 5250 (26.3) |
| Second trimester | 4809 (40.9) | 2999 (39.4) | 236 (42.6) | 8044 (40.4) |
| Third trimester | 2940 (25.0) | 1816 (23.9) | 189 (34.1) | 4945 (24.8) |
| Participant age at pregnancy outcome (years) | ||||
| 18–24 | 137 (1.2) | 103 (1.4) | 5 (0.9) | 245 (1.2) |
| 25–29 | 1558 (13.2) | 1094 (14.4) | 80 (14.4) | 2732 (13.7) |
| 30–34 | 5649 (48.0) | 3576 (47.0) | 245 (44.2) | 9470 (47.5) |
| 35–39 | 3760 (32.0) | 2429 (31.9) | 187 (33.8) | 6376 (32.0) |
| 40+ | 659 (5.6) | 408 (5.4) | 36 (6.5) | 1103 (5.5) |
| Missing | 1 (0.0) | 3 (0.0) | 1 (0.2) | 5 (0.0) |
| Race and ethnicity | ||||
| Non‐Hispanic Black | 260 (2.2) | 153 (2.0) | 21 (3.8) | 434 (2.2) |
| Non‐Hispanic White | 9316 (79.2) | 6101 (80.1) | 436 (78.7) | 15,853 (79.5) |
| Hispanic | 1037 (8.8) | 723 (9.5) | 56 (10.1) | 1816 (9.1) |
| Non‐Hispanic American Indian or Alaskan Native | 23 (0.2) | 12 (0.2) | 1 (0.2) | 36 (0.2) |
| Non‐Hispanic Native Hawaiian or Pacific Islander | 10 (0.1) | 6 (0.1) | 0 (0.0) | 16 (0.1) |
| Non‐Hispanic Asian | 825 (7.0) | 417 (5.5) | 23 (4.2) | 1265 (6.3) |
| Non‐Hispanic Multi‐racial | 272 (2.3) | 186 (2.4) | 16 (2.9) | 474 (2.4) |
| Missing | 21 (0.2) | 15 (0.2) | 1 (0.2) | 37 (0.2) |
| Body mass index (kg/m2) | ||||
| < 18.5 | 200 (1.7) | 126 (1.7) | 3 (0.5) | 329 (1.7) |
| 18.5–24.9 | 6182 (52.6) | 3794 (49.8) | 286 (51.6) | 10,262 (51.5) |
| 25.0–29.9 | 2956 (25.1) | 1950 (25.6) | 151 (27.3) | 5057 (25.4) |
| ≥ 30.0 | 2127 (18.1) | 1566 (20.6) | 97 (17.5) | 3790 (19.0) |
| Missing | 299 (2.5) | 177 (2.3) | 17 (3.1) | 493 (2.5) |
| Gravidity | ||||
| 1 | 4042 (34.4) | 2559 (33.6) | 184 (33.2) | 6785 (34.0) |
| 2 | 3862 (32.8) | 2495 (32.8) | 166 (30.0) | 6523 (32.7) |
| 3 | 2120 (18.0) | 1391 (18.3) | 111 (20.0) | 3622 (18.2) |
| 4–14 | 1586 (13.5) | 1077 (14.1) | 79 (14.3) | 2742 (13.8) |
| Missing | 154 (1.3) | 91 (1.2) | 14 (2.5) | 259 (1.3) |
| Parity | ||||
| 0 | 5025 (42.7) | 3159 (41.5) | 223 (40.3) | 8407 (42.2) |
| 1 | 4438 (37.7) | 2902 (38.1) | 167 (30.1) | 7507 (37.7) |
| 2–8 | 1953 (16.6) | 1329 (17.5) | 132 (23.8) | 3414 (17.1) |
| Missing | 348 (3.0) | 223 (2.9) | 32 (5.8) | 603 (3.0) |
| Preexisting diabetes | ||||
| No | 11,514 (97.9) | 7466 (98.1) | 539 (97.3) | 19,519 (97.9) |
| Yes | 113 (1.0) | 73 (1.0) | 6 (1.1) | 192 (1.0) |
| Unknown | 137 (1.2) | 74 (1.0) | 9 (1.6) | 220 (1.1) |
| Pregnancy outcome | ||||
| Live birth | 11,725 (99.7) | 7581 (99.6) | 552 (99.6) | 19,858 (99.6) |
| Stillbirth (≥ 20 weeks) | 31 (0.3) | 20 (0.3) | 2 (0.4) | 53 (0.3) |
| Induced abortion (≥ 20 weeks) | 8 (0.1) | 12 (0.2) | 0 (0.0) | 20 (0.1) |
| Gestational age at outcome | ||||
| < 28 weeks | 45 (0.4) | 37 (0.5) | 1 (0.2) | 83 (0.4) |
| 28 to < 37 weeks | 711 (6.0) | 458 (6.0) | 40 (7.2) | 1209 (6.1) |
| 37 to < 42 weeks | 10,971 (93.3) | 7096 (93.2) | 509 (91.9) | 18,576 (93.2) |
| ≥ 42 weeks | 36 (0.3) | 19 (0.2) | 3 (0.5) | 58 (0.3) |
| Missing | 1 (0.0) | 3 (0.0) | 1 (0.2) | 5 (0.0) |
| Health care personnel | ||||
| No | 6540 (55.6) | 4152 (54.5) | 467 (84.3) | 11,159 (56.0) |
| Yes | 5034 (42.8) | 3357 (44.1) | 73 (13.2) | 8464 (42.5) |
| Declined | 190 (1.6) | 104 (1.4) | 14 (2.5) | 308 (1.5) |
| Census region b | ||||
| Northeast | 2212 (18.8) | 1646 (21.6) | 99 (17.9) | 3957 (19.9) |
| Midwest | 2756 (23.4) | 1743 (22.9) | 130 (23.5) | 4629 (23.2) |
| South | 3965 (33.7) | 2275 (29.9) | 200 (36.1) | 6440 (32.3) |
| West | 2818 (24.0) | 1933 (25.4) | 124 (22.4) | 4875 (24.5) |
| Unknown | 13 (0.1) | 16 (0.2) | 1 (0.2) | 30 (0.2) |
Up to 30 days prior to the last menstrual period associated with the pregnancy.
States and jurisdictions represented in each census region category: Northeast (CT, ME, MA, NH, RI, VT, NJ, NY, PA); Midwest (IN, IL, MI, OH, WI, IA, KS, MN, MO, NE, ND, SD); South (DE, DC, FL, GA, MD, NC, SC, VA, WV, AL, KY, MS, TN, AR, LA, OK, TX); West (AZ, CO, ID, NM, MT, UT, NV, WY, AK, CA, HI, OR, WA).
Seven hundred and fifty infants (3.8%) were determined to have a genetic condition (n = 79) or major birth defect (n = 671), resulting in an overall birth defect prevalence of 377.7 (95% CI 351.6, 405.1) per 10,000 live births. Among the 5209 participants vaccinated only early in pregnancy (i.e., received primary series dose(s) < 14 weeks' gestation, including 30 days before LMP), the overall prevalence of birth defects was 409.8 (95% CI 357.4, 467.5). Ninety‐four different types of major birth defects were identified. Prevalences of all major birth defects identified, organized by organ system, are presented in Table 2 along with 50 comparator estimates available from the literature.
TABLE 2.
Major birth defects by organ system among infants of CDC COVID‐19 Vaccine Pregnancy Registry participants. Participants reported birth defects identified during pregnancy through 3 months of age, January 2021–August 2022.
| Birth defect † | N ‡ | C19VPR prevalence (95% CI) per 10,000 live births | Population‐based prevalence (95% CI) per 10,000 live births ¶¶ |
|---|---|---|---|
| Central nervous system defects | 36 | ||
| Brain reduction anomalies | 4 | 2.0 (0.5, 5.2) | 2.9 (2.5, 3.4) a |
| Corpus callosum anomalies | 4 | 2.0 (0.5, 5.2) | 3.3 (2.7, 3.8) a |
| Dandy Walker anomaly | 2 | 1.0 (0.1, 3.6) | 0.7 (0.6, 0.8) b |
| Hydrocephaly | 7 | 3.5 (1.4, 7.3) | 2.6 (2.4, 2.6) c |
| Microcephaly § | 4 | 2.0 (0.5, 5.2) | 2.0 (1.8, 2.1) c to 8.7 (8.5, 8.9) d |
| Other brain anomalies | 3 | 1.5 (0.3, 4.4) | — |
| Other nervous system anomalies | 4 | 2.0 (0.5, 5.2) | — |
| Spina bifida | 5 | 2.5 (0.8, 5.9) | 3.7 (3.5, 3.8) e |
| Spinal cord anomalies ¶ | 6 | 3.0 (1.1, 6.6) | — |
| Eye defects | 16 | ||
| Cataract or other lens anomalies | 4 | 2.0 (0.5, 5.2) | 1.5 (1.4, 1.6) f |
| Coloboma or anterior or posterior segment anomalies | 4 | 2.0 (0.5, 5.2) | — |
| External eye defects | 8 | 4.0 (1.7, 7.9) | — |
| Other eye anomalies | 1 | 0.5 (0.0, 2.8) | — |
| Orofacial clefts | 24 | ||
| Cleft lip alone †† | 8 | 4.0 (1.7, 7.9) | 3.4 (3.2, 3.6) e |
| Cleft lip with cleft palate | 6 | 3.0 (1.1, 6.6) | 6.5 (6.3, 6.8) e |
| Cleft palate | 10 | 5.0 (2.4, 9.3) | 6.3 (6.0, 6.5) e |
| Ear, face, and neck defects | 18 | ||
| Anomalies of the nose | 2 | 1.0 (0.1, 3.6) | — |
| Face or neck anomalies | 3 | 1.5 (0.3, 4.4) | — |
| Microtia | 7 | 3.5 (1.4, 7.3) | 1.8 (1.7, 1.8) f |
| Pierre Robin sequence ‡‡ | 6 | 3.0 (1.1, 6.6) | 1.0 (0.9, 1.1) c |
| Congenital heart defects | 145 | ||
| Aortic valve stenosis | 1 | 0.5 (0.0, 2.8) | 2.4 (2.3, 2.5) g |
| Atrial septal defect | 26 | 13.1 (8.6, 19.2) | 11.5 (10.6, 12.4) h |
| Bicuspid aortic valve | 7 | 3.5 (1.4, 7.3) | — |
| Coarctation of the aorta | 6 | 3.0 (1.1, 6.6) | 5.8 (5.6, 6.0) e |
| Common atrioventricular canal with ventricular septal defect | 1 | 0.5 (0.0, 2.8) | 5.8 (5.6, 6.1) e |
| Coronary artery or sinus anomalies | 2 | 1.0 (0.1, 3.6) | — |
| Double outlet right ventricle | 1 | 0.5 (0.0, 2.8) | 2.4 (2.3, 2.6) e |
| Hypoplastic left heart syndrome | 1 | 0.5 (0.0, 2.8) | 2.6 (2.4, 2.8) e |
| Other anomalies of the aorta | 4 | 2.0 (0.5, 5.2) | — |
| Other heart anomalies | 11 | 5.5 (2.8, 9.9) | — |
| Other pulmonary valve anomalies | 1 | 0.5 (0.0, 2.8) | — |
| Persistent foramen ovale | 2 | 1.0 (0.1, 3.6) | — |
| Persistent right aortic arch | 4 | 2.0 (0.5, 5.2) | — |
| Pulmonary artery stenosis | 1 | 0.5 (0.0, 2.8) | 5.5 (4.8, 6.3) i |
| Pulmonary valve atresia or stenosis | 6 | 3.0 (1.1, 6.6) | 10.4 (10.1, 10.7) e |
| Pulmonary valve or artery atresia, stenosis, or hypoplasia | 2 | 1.0 (0.1, 3.6) | — |
| Shone's complex | 1 | 0.5 (0.0, 2.8) | — |
| Tetralogy of Fallot | 5 | 2.5 (0.8, 5.9) | 4.9 (4.7, 5.1) e |
| Transposition of the great vessels | 1 | 0.5 (0.0, 2.8) | 3.0 (2.8, 3.2) e |
| Tricuspid valve stenosis or hypoplasia | 1 | 0.5 (0.0, 2.8) | 1.8 (1.7, 2.0) e |
| Unspecified aortic valve anomalies | 2 | 1.0 (0.1, 3.6) | — |
| Unspecified defect of septal closure | 8 | 4.0 (1.7, 7.9) | — |
| Vascular ring | 1 | 0.5 (0.0, 2.8) | 1.3 (1.0, 1.6) h |
| Ventricular septal defect | 59 | 29.7 (22.6, 38.3) | 37.5 (35.9, 39.2) h |
| Other circulatory defects | 3 | 1.5 (0.3, 4.4) | — |
| Anomalies of respiratory system | 5 | ||
| Anomalies of the lung | 3 | 1.5 (0.3, 4.4) | — |
| Other respiratory anomalies | 2 | 1.0 (0.1, 3.6) | — |
| Gastrointestinal defects | 41 | ||
| Anal atresia or stenosis | 3 | 1.5 (0.3, 4.4) | 4.6 (4.4, 4.8) e |
| Duodenal or small intestine stenosis or atresia | 3 | 1.5 (0.3, 4.4) | 3.4 (3.3, 3.6) j |
| Esophageal atresia or stenosis | 7 | 3.5 (1.4, 7.3) | 2.4 (2.2, 2.5) e |
| Hirschsprung's disease | 3 | 1.5 (0.3, 4.4) | 1.4 (1.4, 1.5) g |
| Malrotation | 3 | 1.5 (0.3, 4.4) | — |
| Other gastrointestinal anomalies | 4 | 2.0 (0.5, 5.2) | — |
| Pyloric stenosis | 18 | 9.1 (5.4, 14.3) | 16.1 (15.8, 16.4) g |
| Genitourinary defects | 198 | ||
| Anomalies of the urethra | 3 | 1.5 (0.3, 4.4) | — |
| Chordee without hypospadias (males only) | 18 | 9.1 (5.4, 14.3) | — |
| Exstrophy of urinary bladder | 1 | 0.5 (0.0, 2.8) | 0.2 (0.2, 0.2) g |
| Hydronephrosis | 16 | 8.1 (4.6, 13.1) | 14.9 (14.4–15.2) c , §§ |
| Hypospadias (males only) | 67 | 33.7 (26.2, 42.8) | 62.1 (61.4, 62.8) g |
| Kidney agenesis, dysplasia, or hypoplasia | 14 | 7.1 (3.9, 11.8) | 6.5 (6.3, 6.7) g |
| Lobulated, fused, horseshoe, or ectopic kidney | 6 | 3.0 (1.1, 6.6) | 3.5 (3.1, 3.6) c |
| Multicystic kidney | 6 | 3.0 (1.1, 6.6) | 4.0 (3.8, 4.2) c |
| Obstructive defects of the renal pelvis or ureter | 11 | 5.5 (2.8, 9.9) | 14.9 (14.4–15.2) c , §§ |
| Other disorders of sexual development | 1 | 0.5 (0.0, 2.8) | 0.2 (0.2, 0.3) c |
| Other specified anomalies of kidney | 8 | 4.0 (1.7, 7.9) | |
| Ovarian anomalies (females only) | 1 | 0.5 (0.0, 2.8) | — |
| Other penile anomalies (males only) | 16 | 8.1 (4.6, 13.1) | — |
| Patent urachus | 1 | 0.5 (0.0, 2.8) | — |
| Penoscrotal webbing or fusion (males only) | 11 | 5.5 (2.8, 9.9) | — |
| Polycystic kidney | 2 | 1.0 (0.1, 3.6) | — |
| Undescended, absent, or torsion of testicle (males only) | 12 | 6.0 (3.1, 10.6) | — |
| Vesicoureteral reflux | 1 | 5.5 (2.8, 9.9) | — |
| Inguinal hernia | 29 | 14.6 (9.8, 21.0) | — |
| Musculoskeletal defects | 153 | ||
| Clubfoot | 17 | 8.6 (5.0, 13.7) | 18.9 (18.4, 19.3) e |
| Craniosynostosis | 12 | 6.0 (3.1, 10.6) | 5.6 (5.4, 5.7) g |
| Diaphragmatic hernia | 5 | 2.5 (0.8, 5.9) | 3.2 (3.0, 3.4) e |
| Epigastric hernia | 1 | 0.5 (0.0, 2.8) | — |
| Hip dysplasia or dislocation § | 50 | 25.2 (18.7, 33.2) | 6.2 (5.5, 6.8) h to 49.0 (NR) k |
| Limb anomalies, lower | 3 | 1.5 (0.3, 4.4) | — |
| Limb anomalies, upper | 2 | 1.0 (0.1, 3.6) | — |
| Limb deficiencies, lower | 2 | 1.0 (0.1, 3.6) | 2.0 (1.9, 2.1) g |
| Limb deficiencies, upper | 3 | 1.5 (0.3, 4.4) | 4.2 (4.0, 4.3) g |
| Omphalocele | 2 | 1.0 (0.1, 3.6) | 2.6 (2.5, 2.8) e |
| Other musculoskeletal anomalies | 7 | 3.5 (1.4, 7.3) | — |
| Polydactyly +++ | 2 | 1.0 (0.1, 3.6) | 14.2 (13.3, 15.2) h |
| Skull deformations | 8 | 4.0 (1.7, 7.9) | — |
| Syndactyly | 6 | 3.0 (1.1, 6.6) | 3.3 (3.1, 3.4) c |
| Torticollis or fibromatosis coli | 40 | 20.1 (14.4, 27.4) | — |
| Anomalies of the skin | 3 | ||
| Cutis aplasia or other skin anomalies | 3 | 1.5 (0.3, 4.4) | 0.5 (0.4, 0.6) l |
| Amniotic bands | 1 | 0.5 (0.0, 2.8) | 0.2 (0.2, 0.2) c |
| Cancer or neoplasms | 47 | ||
| Cancer | 2 | 1.0 (0.1, 3.6) | — |
| Hemangioma (skin or internal) | 43 | 21.7 (15.7, 29.2) | — |
| Sacral or coccygeal teratoma | 2 | 1.0 (0.1, 3.6) | 0.7 (NR) m |
| Other anomalies | 4 | 2.0 (0.5, 5.2) | — |
Abbreviations: CI, confidence interval; NR, not reported.
Specific MACDP codes included under each condition are provided in Table S2.
The denominator was the total number of live births (n = 19,858), except if indicated as females only (n = 9599) or males only (n = 10,160). Birth defect categories shown in bold include all specific birth defects listed directly below. Each infant was counted only once within a bolded category and once under each specific birth defect that was reported; therefore, the number of infants in the subcategories may sum to more than the total in the bolded category.
For microcephaly and hip dysplasia, a range of prevalences is presented because these defects lack standardized definitions, resulting in wide ranges of prevalences reported in the literature.
Excludes infants with spina bifida.
One infant with cleft lip was also reported to have holoprosencephaly and is also counted under other brain anomalies.
Two infants with Pierre Robin sequence were also reported to have cleft palate and are also counted under cleft palate.
The published rate available combines hydronephrosis and obstructive defects of the renal pelvis or ureter; the combined rate for C19VPR was 13.1 (8.0, 18.1), n = 26. One infant was reported to have both hydronephrosis and an obstructive defect of the ureter.
Population‐based estimates of polydactyly among non‐Hispanic White infants 11.4 (10.0, 12.8) h .
Footnotes include references and the years in which surveillance was conducted to obtain estimates.
(Morris et al. 2019), 2005–2014.
(Santoro et al. 2019), 2002–2015.
(EUROCAT 2024), 2018–2022.
(Cragan et al. 2016), 2009–2013.
(Stallings et al. 2024), 2016–2020.
(Stallings et al. 2018), 2011–2015.
(Texas Department of State Health Services 2024), 1999–2020.
(Kucik et al. 2012), 1994–2005.
(Reller et al. 2008), 1998–2005.
(Lupo et al. 2017), 2010–2014.
(Woodacre et al. 2016), 1998–2008.
(Coi et al. 2023), 1998–2017.
(Hambraeus et al. 2016), 2000–2013.
The C19VPR prevalence was either below or within the expected range for 35 of the 50 birth defects with a comparator estimate. Fifteen birth defects had a prevalence higher than the upper CI from the literature (i.e., Dandy Walker anomaly, hydrocephaly, cataract or other lens anomalies, cleft lip alone, microtia, Pierre Robin sequence, atrial septal defect, esophageal atresia or stenosis, exstrophy of urinary bladder, kidney agenesis, dysplasia or hypoplasia, other disorders of sexual development, craniosynostosis, cutis aplasia or other skin anomalies, amniotic bands, sacral or coccygeal teratoma). Comparator estimates were within the C19VPR CI for all birth defects except the Pierre Robin sequence. CIs around the C19VPR estimate for Pierre Robin sequence (3.0 per 10,000 live births, 95% CI: 1.1, 6.6) barely exclude the comparator point estimate (1.0 per 10,000 live births, 95% CI: 0.9, 1.1). Of note, five of the six participants were vaccinated after the first trimester (i.e., after the time at which Pierre Robin sequence begins).
Sixty‐four infants (0.3%) had more than one major birth defect identified. CDC birth defect experts manually reviewed these cases (JDC, CAM). For 21 infants, the multiple birth defects were related (e.g., multiple heart defects) or sequelae of an underlying defect (e.g., vesicoureteral reflux with hydronephrosis, spina bifida with club foot). For 43 infants, the birth defects belonged to more than one organ system or developmental process, and of these, two had a pattern consistent with VACTERL association. Among the two infants with patterns of VACTERL association, one participant received both doses of the COVID‐19 vaccine prior to or at 2 weeks' gestation, and the other participant received both doses after 24 weeks' gestation. The comparator point estimate for VACTERL association (0.5 per 10,000, 95% CI: 0.4, 0.5) (EUROCAT 2024) was within the C19VPR CI (1.0 per 10,000 live births, 95% CI: 0.1, 3.6).
Seven birth defects met inclusion criteria for the timing analysis: cleft lip with or without cleft palate, atrial septal defect, coarctation of the aorta, ventricular septal defect, esophageal atresia or stenosis, hypospadias, and kidney agenesis/hypoplasia/dysplasia. For C19VPR participants in Group 1 (early vaccination only), prevalences of all seven birth defects were higher than, but not statistically different from those in Group 3 (later vaccination only) (Table 3). Results were similar when combining Group 1 and Group 2 (at least one early dose) to those in Group 3. We explored alternative gestational week cut points, such as all doses received < 10 weeks' gestation versus all doses received ≥ 10 weeks' gestation, but results were not meaningfully different; thus standard trimester cut points were used (data not shown).
TABLE 3.
Prevalence of select infant birth defects among CDC COVID‐19 Vaccine Pregnancy Registry participants by timing of COVID‐19 vaccination. Participants reported birth defects identified during pregnancy through 3 months of age, January 2021–August 2022.
| Group assignment based on timing of COVID‐19 vaccination(s) during pregnancy a | Group 1 only early (n = 5093) | Group 2 both early and later (n = 1720) | Group 3 only later (n = 12,564) | Comparison of Group 1 to Group 3 | Comparison of Groups 1 and 2 to Group 3 | |||
|---|---|---|---|---|---|---|---|---|
| Dose(s) received only 30 days prior to LMP to < 14 weeks' gestation | Two doses received, one < 14 weeks' gestation and one ≥ 14 weeks' gestation | Dose(s) received ≥ 14 weeks' gestation | ||||||
| Birth defect | n | Prevalence (95% CI) per 10,000 | n | Prevalence (95% CI) per 10,000 | n | Prevalence (95% CI) per 10,000 | Adjusted prevalence ratio (95% CI) b | Adjusted prevalence ratio (95% CI) b |
| Orofacial clefts | ||||||||
| Cleft lip with/without cleft palate | 4 | 7.9 (0.2, 15.6) | 3 | 17.4 (0.0, 37.2) | 7 | 5.6 (1.5, 9.7) | 1.44 (0.42, 4.91) | 1.88 (0.65, 5.41) |
| Congenital heart defects | ||||||||
| Atrial septal defect | 10 | 19.6 (7.5, 31.8) | 4 | 23.3 (0.5, 46.0) | 12 | 9.6 (4.2, 15.0) | 2.04 (0.88, 4.72) | 2.15 (0.98, 4.72) |
| Coarctation of the aorta | 4 | 7.9 (0.2, 15.6) | 0 | — | 2 | 1.6 (0.0, 3.8) | 4.82 (0.88, 26.33) | 3.61 (0.68, 19.03) |
| Ventricular septal defect | 22 | 43.2 (25.2, 61.2) | 5 | 29.1 (3.6, 54.5) | 32 | 25.5 (16.7, 34.3) | 1.67 (0.97, 2.87) | 1.52 (0.92, 2.53) |
| Gastrointestinal defects | ||||||||
| Esophageal atresia or stenosis | 4 | 7.9 (0.2, 15.6) | 1 | 5.8 (0.0, 17.2) | 2 | 1.6 (0.0, 3.8) | 4.92 (0.90, 26.83) | 4.64 (0.90, 24.06) |
| Genitourinary defects | ||||||||
| Hypospadias (males only c ) | 18 | 68.1 (36.8, 99.5) | 9 | 103.6 (36.3, 170.9) | 39 | 61.3 (42.1, 80.5) | 1.10 (0.63, 1.92) | 1.23 (0.75, 2.00) |
| Kidney agenesis, dysplasia, or hypoplasia | 6 | 11.8 (2.6, 21.2) | 1 | 5.8 (0.0, 17.2) | 7 | 5.6 (1.5, 9.7) | 2.15 (0.72, 6.42) | 1.86 (0.65, 5.38) |
Abbreviations: CI, confidence interval; SD, standard deviation.
Vaccine doses include only first‐generation monovalent index virus mRNA vaccines (Moderna or Pfizer‐BioNTech) available from December 15, 2020, through June 21, 2021. During this time, two doses of an mRNA vaccine were recommended for adults with Dose 2 occurring about 4 weeks after Dose 1. Birth defects included in the timing analysis had to meet the following criteria: (1) at least four cases were reported in Group 1 as this was the minimum number of cases required to have sufficient statistical power to detect a significant increase in risk from Group 3 with 95% confidence, and (2) the origin of the birth defect is established to occur during the period of embryogenesis (first 8 weeks after conception). Mean gestational age at first vaccination conferring registry eligibility was 2.7 (SD 4.4), 12.1 (2.0), and 25.3 (6.8) for Group 1, Group 2, and Group 3, respectively.
Adjusted for age at pregnancy outcome (< 30 or ≥ 30 years), non‐Hispanic White versus other race or ethnicity, and BMI (< 25 or ≥ 25 kg/m2), except esophageal atresia or stenosis, which was adjusted for BMI only as all with this defect were younger than 30 and non‐Hispanic White. p > 0.05 for all prevalence ratios.
Denominator for males only: Group 1, n = 2643; Group 2, n = 869; Group 3, n = 6359.
4. Discussion
The overall prevalence of participant‐reported major birth defects in the C19VPR (3.8%) was similar to estimates published prior to the COVID‐19 pandemic and COVID‐19 vaccine availability (3%–5%) (Centers for Disease Control and Prevention 2008; Texas Department of State Health Services 2024). Prevalence of participant‐reported birth defects among only those who were vaccinated early in pregnancy (4.1%) was also within the published background rate. Prevalences of specific birth defects reported in the C19VPR were also similar.
Our study relied on participant‐report of birth defects in response to phone surveys that included structured and open‐ended interview questions about fetal and infant health, given the need to rapidly implement surveillance as COVID‐19 vaccines were administered during pregnancy. Validation studies comparing maternal‐report of infant birth defects to clinician‐report have observed close agreement (> 80%), but studies were limited in sample size (e.g., < 900 infants with and without birth defects) (Freedman and Koren 2002; Maas et al. 2024; van Gelder et al. 2017). Agreement was highest among infants categorized as having no birth defects or categorized as having at least one major birth defect, but among infants categorized as having a minor defect, mothers were more likely to report minor conditions as major birth defects (Maas et al. 2024; van Gelder et al. 2017). Among the other studies that examined COVID‐19 vaccination and birth defects, methods for identifying birth defects included participant‐report (Woestenberg et al. 2023), health administrative data or electronic health records (Calvert et al. 2023; Goldshtein et al. 2022; Hui et al. 2023; Kharbanda et al. 2024; Magnus et al. 2024; Rowe et al. 2025), or targeted diagnostic testing (Favre et al. 2023; Ruderman et al. 2022). Similar to our findings, these studies observed no increase in prevalences of birth defects among infants of women receiving COVID‐19 vaccines in pregnancy. Consistency of results, despite the use of varying identification methods, suggests that the general patterns of findings from these studies are robust.
We found no significant difference in birth defect prevalences between early and later vaccination groups, though prevalences tended to be higher among those vaccinated early. It is important to acknowledge that these results are subject to biases that overestimate prevalence ratios. First, the ability to identify birth defects in utero increases with gestational age (identification bias). We excluded infants with birth defects identified prior to vaccination; thus, those vaccinated later during pregnancy were more likely to be excluded. In fact, among 43 pregnancies excluded because a birth defect was identified prior to vaccination, 13 were known to have at least one of the seven birth defects included in the timing analysis. Thus, it was not that these birth defects did not exist; they were excluded because the objective of our study was to examine birth defects after vaccination. Had this exclusion criteria not been applied, we would have overestimated the prevalence of birth defects associated with vaccination, but prevalence ratios would have been attenuated. Second, pregnancies with fetal birth defects have a higher risk of ending prior to 14 weeks of gestation (i.e., spontaneous or induced abortion), and thus would not have had the opportunity to be included in the later vaccination group (survival bias). Due to limitations of the timing analysis, results should be interpreted with caution. Mitigation of these biases would have required recruitment of a registry cohort prior to pregnancy with standardized birth defect screening throughout pregnancy regardless of the timing of vaccination.
This report benefits from several strengths. First, the C19VPR cohort includes nearly 20,000 vaccinated participants, providing a sample twice the size of most other studies investigating the risk of birth defects in infants of women who received a COVID‐19 vaccine during pregnancy. Second, the collection of specific COVID‐19 vaccine and pregnancy timing data allowed us to account for the timing of vaccination relative to pregnancy. Third, we included all pregnancy outcomes occurring ≥ 20 weeks' gestation, which enabled us to increase sensitivity by including birth defects among non‐live births.
Limitations should be noted. First, our study cohort was a convenience sample of pregnant women who were, on average, older than the US pregnant population (Osterman et al. 2023). This may explain our observed prevalence of Pierre Robin sequence being higher than the population‐based comparator estimate, as Pierre Robin sequence has been attributed to genetic syndromes or anomalies associated with advanced maternal age (Santoro et al. 2021). Further, C19VPR participants were early vaccine recipients, nearly 80% were non‐Hispanic White, and more than a third were health care personnel, suggesting that our results could differ from those obtained from a nationally representative sample of pregnant women. Second, with few cases identified for each birth defect, prevalence estimates and ratios should be interpreted with caution, as CIs are wide enough for estimates to be considered statistically unstable (Parker et al. 2017). Third, because vaccination was required for registry eligibility, we did not have a concurrent group of unvaccinated pregnant women for comparison. Therefore, we could not directly assess the association between COVID‐19 vaccination and birth defects in our cohort. We relied on published background estimates to make comparisons, which were only available for a subset of the birth defects. Background estimates may not be directly comparable due to differences in case definitions, case ascertainment (e.g., medical records rather than participant‐report), periods of follow‐up, and demographic makeup of cohorts (Kucik et al. 2012; Woodacre et al. 2016). Our analysis is based on birth defects identified up to 4 months after birth, while existing birth defect surveillance systems in the United States typically include birth defects identified through at least 1 year after birth. Thus, we may have underestimated the prevalence of some birth defects. Lastly, this study does not examine vaccination early in pregnancy and birth defects among pregnancies ending at less than 20 weeks' gestation, as ascertainment of birth defects during early pregnancy is limited.
CDC's Advisory Committee on Immunization Practices continues to recommend COVID‐19 vaccines for all pregnant women, given the risks of SARS‐CoV‐2 infection in pregnancy (Badell et al. 2022; Fleming‐Dutra et al. 2023; Kharbanda et al. 2021; Lipkind et al. 2022; Zauche et al. 2021). Though live vaccines are contraindicated in pregnancy due to a theoretical possibility of attenuated viruses crossing the placental barrier during fetal development, non‐live vaccines are routinely recommended in pregnancy (e.g., Tdap, influenza) (Keller‐Stanislawski et al. 2014; Kroger et al. 2024). COVID‐19 vaccines are not live vaccines. Despite recommendations, hesitancy surrounding vaccination during pregnancy persists due to perceived safety concerns (Badell et al. 2022). Post‐marketing monitoring for birth defects is critical to evaluate the safety of COVID‐19 vaccines because pregnant women were excluded from pre‐licensure randomized controlled trials. Findings from this report can inform clinical guidelines and patient health decisions.
Author Contributions
All authors attest they meet the ICMJE criteria for authorship.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Table S1.
Acknowledgments
We would like to thank the participants for participating in the CDC COVID‐19 Vaccine Pregnancy Registry and the members of the C19VPR Team for their support and contributions. We would also like to thank Abt Associates, who helped coordinate the enrollment and completion of phone surveys for registry participants.
Funding: The authors received no specific funding for this work.
CDC COVID‐19 Vaccine Pregnancy Registry team: Jenna Chambless MSN, Shana Godfred‐Cato DO, Kendra Norris MSN, Tara Johnson MPH, MS.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Endnotes
See, for example, 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. §241(d); 5 U.S.C. §552a; 44 U.S.C. §3501 et seq.
Contributor Information
Christine K. Olson, Email: pregregadmin@cdc.gov.
CDC COVID‐19 Vaccine Pregnancy Registry team:
Jenna Chambless, Shana Godfred‐Cato, Kendra Norris, and Tara Johnson
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
References
- Agresti, A. 2018. Statistical Methods for the Social Sciences. 5th ed. Pearson. [Google Scholar]
- Badell, M. L. , Dude C. M., Rasmussen S. A., and Jamieson D. J.. 2022. “COVID‐19 Vaccination in Pregnancy.” BMJ 378: e069741. 10.1136/bmj-2021-069741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Calvert, C. , Carruthers J., Denny C., et al. 2023. “A Population‐Based Matched Cohort Study of Major Congenital Anomalies Following COVID‐19 Vaccination and SARS‐CoV‐2 Infection.” Nature Communications 14, no. 1: 107. 10.1038/s41467-022-35771-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Centers for Disease Control and Prevention . 2008. “Update on Overall Prevalence of Major Birth Defects—Atlanta, Georgia, 1978–2005.” MMWR. Morbidity and Mortality Weekly Report 57, no. 1: 1–5. https://www.ncbi.nlm.nih.gov/pubmed/18185492. [PubMed] [Google Scholar]
- Centers for Disease Control and Prevention . 2023. “COVID‐19 Timeline.” https://www.cdc.gov/museum/timeline/covid19.html.
- Centers for Disease Control and Prevention . 2024. “Birth Defects Tracking.” https://www.cdc.gov/birth‐defects/tracking/index.html.
- Centers for Disease Control and Prevention . n.d. “The Metropolitan Atlanta Congenital Defects Program (MACDP).” https://www.cdc.gov/birth‐defects/tracking/index.html#cdc_generic_section_5‐the‐metropolitan‐atlanta‐congenital‐defects‐program‐macdp.
- Coi, A. , Barisic I., Garne E., et al. 2023. “Epidemiology of Aplasia Cutis Congenita: A Population‐Based Study in Europe.” Journal of the European Academy of Dermatology and Venereology 37, no. 3: 581–589. 10.1111/jdv.18690. [DOI] [PubMed] [Google Scholar]
- Cragan, J. D. , Isenburg J. L., Parker S. E., et al. 2016. “Population‐Based Microcephaly Surveillance in the United States, 2009 to 2013: An Analysis of Potential Sources of Variation.” Birth Defects Research Part A: Clinical and Molecular Teratology 106, no. 11: 972–982. 10.1002/bdra.23587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EUROCAT . 2024. European Platform on Rare Disease Registration: Prevalence Charts and Table, 2018–2022. European Commission. https://eu‐rd‐platform.jrc.ec.europa.eu/eurocat/eurocat‐data/prevalence_en. [Google Scholar]
- Favre, G. , Maisonneuve E., Pomar L., et al. 2023. “Risk of Congenital Malformation After First Trimester mRNA COVID‐19 Vaccine Exposure in Pregnancy: The COVI‐PREG Prospective Cohort.” Clinical Microbiology and Infection 29, no. 10: 1306–1312. 10.1016/j.cmi.2023.06.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fleming‐Dutra, K. E. , Zauche L. H., Roper L. E., et al. 2023. “Safety and Effectiveness of Maternal COVID‐19 Vaccines Among Pregnant People and Infants.” Obstetrics and Gynecology Clinics of North America 50, no. 2: 279–297. 10.1016/j.ogc.2023.02.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freedman, B. , and Koren G.. 2002. “Reliability of Maternal Reporting in Identifying Major Congenital Malformations.” Veterinary and Human Toxicology 44, no. 3: 180–181. [PubMed] [Google Scholar]
- Gee, J. , Shimabukuro T. T., Su J. R., et al. 2024. “Overview of U.S. COVID‐19 Vaccine Safety Surveillance Systems.” Vaccine 42, no. 3: 125748. 10.1016/j.vaccine.2024.02.065. [DOI] [PubMed] [Google Scholar]
- Goldshtein, I. , Steinberg D. M., Kuint J., et al. 2022. “Association of BNT162b2 COVID‐19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes.” JAMA Pediatrics 176, no. 5: 470–477. 10.1001/jamapediatrics.2022.0001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hambraeus, M. , Arnbjornsson E., Borjesson A., Salvesen K., and Hagander L.. 2016. “Sacrococcygeal Teratoma: A Population‐Based Study of Incidence and Prenatal Prognostic Factors.” Journal of Pediatric Surgery 51, no. 3: 481–485. 10.1016/j.jpedsurg.2015.09.007. [DOI] [PubMed] [Google Scholar]
- Harris, B. S. , Bishop K. C., Kemeny H. R., Walker J. S., Rhee E., and Kuller J. A.. 2017. “Risk Factors for Birth Defects.” Obstetrical & Gynecological Survey 72, no. 2: 123–135. 10.1097/ogx.0000000000000405. [DOI] [PubMed] [Google Scholar]
- Hui, L. , Marzan M. B., Rolnik D. L., et al. 2023. “Reductions in Stillbirths and Preterm Birth in COVID‐19‐Vaccinated Women: A Multicenter Cohort Study of Vaccination Uptake and Perinatal Outcomes.” American Journal of Obstetrics and Gynecology 228, no. 5: 581–585. 10.1016/j.ajog.2022.10.040. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keller‐Stanislawski, B. , Englund J. A., Kang G., et al. 2014. “Safety of Immunization During Pregnancy: A Review of the Evidence of Selected Inactivated and Live Attenuated Vaccines.” Vaccine 32, no. 52: 7057–7064. 10.1016/j.vaccine.2014.09.052. [DOI] [PubMed] [Google Scholar]
- Kharbanda, E. O. , DeSilva M. B., Lipkind H. S., et al. 2024. “COVID‐19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births.” JAMA Pediatrics 178: 823–829. 10.1001/jamapediatrics.2024.1917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kharbanda, E. O. , Haapala J., DeSilva M., et al. 2021. “Spontaneous Abortion Following COVID‐19 Vaccination During Pregnancy.” JAMA 326, no. 16: 1629–1631. 10.1001/jama.2021.15494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kroger, A. , Bahta L., Long S., and Sanchez P.. 2024. “General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP).” https://www.cdc.gov/vaccines/hcp/acip‐recs/general‐recs/downloads/general‐recs.pdf.
- Kucik, J. E. , Alverson C. J., Gilboa S. M., and Correa A.. 2012. “Racial/Ethnic Variations in the Prevalence of Selected Major Birth Defects, Metropolitan Atlanta, 1994–2005.” Public Health Reports 127, no. 1: 52–61. 10.1177/003335491212700106. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lipkind, H. S. , Vazquez‐Benitez G., DeSilva M., et al. 2022. “Receipt of COVID‐19 Vaccine During Pregnancy and Preterm or Small‐for‐Gestational‐Age at Birth—Eight Integrated Health Care Organizations, United States, December 15, 2020–July 22, 2021.” MMWR. Morbidity and Mortality Weekly Report 71, no. 1: 26–30. 10.15585/mmwr.mm7101e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lupo, P. J. , Isenburg J. L., Salemi J. L., et al. 2017. “Population‐Based Birth Defects Data in the United States, 2010–2014: A Focus on Gastrointestinal Defects.” Birth Defects Research 109, no. 18: 1504–1514. 10.1002/bdr2.1145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maas, V. Y. F. , Ederveen E. G. T., van Rijt‐Weetink Y. R. J., Woestenberg P. J., Bergman J. E. H., and Conijn M.. 2024. “A Comparison of Infants' Birth Defects Self‐Reported by Mothers With Data Provided by General Practitioners: Data From the Dutch Pregnancy Drug Register.” Birth Defects Research 116, no. 1: e2276. 10.1002/bdr2.2276. [DOI] [PubMed] [Google Scholar]
- Madni, S. A. , Sharma A. J., Zauche L. H., et al. 2024. “CDC COVID‐19 Vaccine Pregnancy Registry: Design, Data Collection, Response Rates, and Cohort Description.” Vaccine 42, no. 7: 1469–1477. 10.1016/j.vaccine.2023.11.061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magnus, M. C. , Soderling J., Ortqvist A. K., et al. 2024. “COVID‐19 Infection and Vaccination During First Trimester and Risk of Congenital Anomalies: Nordic Registry Based Study.” British Medical Journal 386: e079364. 10.1136/bmj-2024-079364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morris, J. K. , Wellesley D. G., Barisic I., et al. 2019. “Epidemiology of Congenital Cerebral Anomalies in Europe: A Multicentre, Population‐Based EUROCAT Study.” Archives of Disease in Childhood 104, no. 12: 1181–1187. 10.1136/archdischild-2018-316733. [DOI] [PubMed] [Google Scholar]
- Myers, T. R. , Marquez P. L., Gee J. M., et al. 2023. “The V‐Safe After Vaccination Health Checker: Active Vaccine Safety Monitoring During CDC'S COVID‐19 Pandemic Response.” Vaccine 41, no. 7: 1310–1318. 10.1016/j.vaccine.2022.12.031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- National Birth Defects Prevention Network (NBDPN) . 2004. “Chapter 3 Case Definition.” In Guidelines for Conducting Birth Defects Surveillance, edited by Sever L. E. and Sever L. E.. National Birth Defects Prevention Network, Inc. https://www.nbdpn.org/guidelines.php#NSBDS. [Google Scholar]
- National Birth Defects Prevention Network (NBDPN) . 2009. “Population‐Based Birth Defects Surveillance Data From Selected States, 2002–2006.” Clinical and Molecular Teratology 85, no. 12: 939–1055. 10.1002/bdra.20638. [DOI] [PubMed] [Google Scholar]
- Osterman, M. J. K. , Hamilton B. E., Martin J. A., Driscoll A. K., and Valenzuela C. P.. 2023. “Births: Final Data for 2021 (NCHS National Vital Statistics Reports), Issue.” https://stacks.cdc.gov/view/cdc/122047. [PubMed]
- Parker, J. D. , Talih M., Malec D. J., et al. 2017. “National Center for Health Statistics Data Presentation Standards for Proportions.” Vital and Health Statistics 2, no. 175: 1–22. https://www.ncbi.nlm.nih.gov/pubmed/30248016. [PubMed] [Google Scholar]
- Patel, A. , Puglisi J. L., Patel S., and Tarn D. M.. 2024. “COVID‐19 Vaccine Acceptance in Pregnant Women in the United States: A Systematic Review and Meta‐Analysis.” Journal of Women's Health 33, no. 4: 453–466. 10.1089/jwh.2023.0498. [DOI] [PubMed] [Google Scholar]
- Reller, M. D. , Strickland M. J., Riehle‐Colarusso T., Mahle W. T., and Correa A.. 2008. “Prevalence of Congenital Heart Defects in Metropolitan Atlanta, 1998–2005.” Journal of Pediatrics 153, no. 6: 807–813. 10.1016/j.jpeds.2008.05.059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rowe, S. L. , Sullivan S. G., Munoz F. M., et al. 2025. “COVID‐19 Vaccination During Pregnancy and Major Structural Birth Defects.” Pediatrics 155, no. 4: e2024069778. 10.1542/peds.2024-069778. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruderman, R. S. , Mormol J., Trawick E., et al. 2022. “Association of COVID‐19 Vaccination During Early Pregnancy With Risk of Congenital Fetal Anomalies.” JAMA Pediatrics 176, no. 7: 717–719. 10.1001/jamapediatrics.2022.0164. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Santoro, M. , Coi A., Barišić I., et al. 2019. “Epidemiology of Dandy‐Walker Malformation in Europe: A EUROCAT Population‐Based Registry Study.” Neuroepidemiology 53, no. 3–4: 169–179. 10.1159/000501238. [DOI] [PubMed] [Google Scholar]
- Santoro, M. , Coi A., Barišić I., et al. 2021. “Epidemiology of Pierre‐Robin Sequence in Europe: A Population‐Based EUROCAT Study.” Paediatric and Perinatal Epidemiology 35, no. 5: 530–539. 10.1111/ppe.12776. [DOI] [PubMed] [Google Scholar]
- Stallings, E. B. , Isenburg J. L., Mai C. T., et al. 2018. “Population‐Based Birth Defects Data in the United States, 2011–2015: A Focus on Eye and Ear Defects.” Birth Defects Research 110, no. 19: 1478–1486. 10.1002/bdr2.1413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stallings, E. B. , Isenburg J. L., Rutkowski R. E., et al. 2024. “National Population‐Based Estimates for Major Birth Defects, 2016–2020.” Birth Defects Research 116, no. 1: e2301. 10.1002/bdr2.2301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Texas Department of State Health Services . 2024. Texas Birth Defects Registry Annual Report: Birth Defects Among 1999–2020 Deliveries. Texas Department of State Health Services. https://www.dshs.texas.gov/sites/default/files/birthdefects/annualreport/1999‐2020‐TBDR‐Annual‐Report.pdf. [Google Scholar]
- van Gelder, M. , Vorstenbosch S., Derks L., Te Winkel B., van Puijenbroek E. P., and Roeleveld N.. 2017. “Web‐Based Questionnaires to Assess Perinatal Outcome Proved to Be Valid.” Journal of Clinical Epidemiology 90: 136–143. 10.1016/j.jclinepi.2017.07.004. [DOI] [PubMed] [Google Scholar]
- WHO . 2020. Birth Defects Surveillance: A Manual for Programme Managers. 2nd ed. WHO. Licence: CC BY‐NC‐SA 3.0 IGO. https://www.who.int/publications/i/item/9789240015395. [Google Scholar]
- Woestenberg, P. J. , de Feijter M., Bergman J. E. H., Lutke L. R., Passier A., and Kant A. C.. 2023. “Maternal First Trimester COVID‐19 Vaccination and Risk of Major Non‐Genetic Congenital Anomalies.” Birth Defects Research 115, no. 18: 1746–1757. 10.1002/bdr2.2251. [DOI] [PubMed] [Google Scholar]
- Woodacre, T. , Ball T., and Cox P.. 2016. “Epidemiology of Developmental Dysplasia of the Hip Within the UK: Refining the Risk Factors.” Journal of Children's Orthopaedics 10, no. 6: 633–642. 10.1007/s11832-016-0798-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zauche, L. H. , Wallace B., Smoots A. N., et al. 2021. “Receipt of mRNA Covid‐19 Vaccines and Risk of Spontaneous Abortion.” New England Journal of Medicine 385, no. 16: 1533–1535. 10.1056/NEJMc2113891. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.