Syphilis, toxoplasmosis, other infections (varicella zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus (STORCH) infections may result in neonatal disease and neurologic sequalae.1 Population-based prevalence rates of STORCH infections among very low birth weight (VLBW) and/or preterm infants in the United States are lacking.
Methods
Vermont Oxford Network (VON) is a voluntary worldwide community of practice. VON members submitted standardized data on live-born infants 401 to 1500 g or 22 to 29 completed weeks’ gestational age who were inborn or transferred to the reporting hospital within 28 days of birth from January 1, 2018, to December 31, 2020.2 Infant data were collected during the initial birth hospitalization. Transferred infants were tracked to determine their ultimate disposition and length of stay. The Institutional Review Board at The University of Vermont determined that use of the VON database for this study was not human subjects research.
A STORCH infection was defined as acquired in utero or during birth from a list that included toxoplasmosis, rubella, syphilis, cytomegalovirus (CMV), herpes simplex, parvovirus B19, Zika, and varicella zoster. Maternal race and ethnicity were determined by personal interview with the mother or review of the birth certificate or medical record, in that order of preference.2 Congenital anomalies included an anomaly on a specific list or, if not on the list, an anomaly that was the primary cause of death or required surgical or medical therapy before discharge.2 Small for gestational age (SGA) was defined as birth weight <10th percentile, and microcephaly was defined as a head circumference less than the third percentile for gestational age and sex.3 Isolated microcephaly was defined as microcephaly without SGA. Statistical analyses were performed by using SAS 9.4 (SAS Institute, Inc, Cary, NC).
Results
Data were reported by 777 hospitals in the United States. Overall, 944 of 128 141, or 7.37 per 1000 VLBW and/or preterm infants were diagnosed with STORCH infections. CMV (3.37 per 1000), syphilis (2.01 per 1000), and herpes simplex (1.82 per 1000) were the infections reported most frequently (Table 1). Eleven infants had >1 infection.
Incidence of Specific STORCH Infections Among VLBW and Preterm Infants, US VON Member Hospitals, 2018–2020
. | No. Infectionsa . | Rate per 1000 (99% CI) . |
---|---|---|
Overall | 956 | 7.37 (6.78–8.01) |
CMV | 432 | 3.37 (2.98–3.82) |
Syphilis | 257 | 2.01 (1.71–2.35) |
Herpes simplex | 233 | 1.82 (1.54–2.15) |
Parvovirus B19 | 16 | 0.12 (0.07–0.24) |
Toxoplasmosis | 10 | 0.08 (0.04–0.17) |
Rubellab | 5 | 0.04 (0.01–0.12) |
Varicella zoster | 2 | 0.02 (0.00–0.08) |
Zika | 1 | 0.01 (0.00–0.07) |
. | No. Infectionsa . | Rate per 1000 (99% CI) . |
---|---|---|
Overall | 956 | 7.37 (6.78–8.01) |
CMV | 432 | 3.37 (2.98–3.82) |
Syphilis | 257 | 2.01 (1.71–2.35) |
Herpes simplex | 233 | 1.82 (1.54–2.15) |
Parvovirus B19 | 16 | 0.12 (0.07–0.24) |
Toxoplasmosis | 10 | 0.08 (0.04–0.17) |
Rubellab | 5 | 0.04 (0.01–0.12) |
Varicella zoster | 2 | 0.02 (0.00–0.08) |
Zika | 1 | 0.01 (0.00–0.07) |
CI, confidence interval.
A total of 933 infants were diagnosed with 1 infection, 10 were diagnosed with 2 infections, and 1 was diagnosed with 3 infections.
Infections might have been suspected; only 2 cases of congenital rubella were reported in the United States during 2018–2019 (Centers for Disease Control and Prevention. Annual statistics from the National Notifiable Diseases Surveillance System [NNDSS]. Available at: https://wonder.cdc.gov/nndss/nndss_annual_tables_menu.asp. Accessed November 22, 2021).
Infants with CMV had the lowest birth weights and were nearly twice as likely to be SGA or microcephalic as infants without infections, although infants with CMV were least likely to have isolated microcephaly (Table 2). Survivors with CMV also had the longest lengths of stay. Only 70.5% of mothers of infants diagnosed with syphilis received any prenatal care, compared with 96.1% of mothers of infants without infections.
Characteristics of VLBW and Preterm Infants With and Without STORCH Infections, US VON Member Hospitals, 2018–2020
. | CMV (n = 424) . | Syphilis (n = 253) . | Herpes Simplex (n = 227) . | Additionala (n = 40) . | None (n = 127 197) . |
---|---|---|---|---|---|
Maternal characteristics, n (%) | |||||
Maternal race and ethnicity | |||||
Blackb | 141 (33.8) | 109 (43.3) | 82 (36.3) | 12 (30.0) | 39 380 (31.3) |
Hispanic | 98 (23.5) | 67 (26.6) | 42 (18.6) | 7 (17.5) | 24 647 (19.6) |
Whiteb | 142 (34.1) | 66 (26.2) | 98 (43.4) | 16 (40.0) | 51 501 (40.9) |
Asian or Pacific Islanderb | 24 (5.8) | 2 (0.8) | 1 (0.4) | 2 (5.0) | 6411 (5.1) |
American Indian or Alaska Nativeb | 3 (0.5) | 4 (1.6) | 1 (0.4) | 3 (7.5) | 1008 (0.8) |
Otherb | 10 (2.4) | 4 (1.6) | 2 (0.9) | 0 (0.0) | 2789 (2.2) |
Prenatal care | 411 (97.6) | 177 (70.5) | 216 (95.2) | 37 (92.5) | 121 782 (96.1) |
Multiple gestation | 59 (13.9) | 38 (15.0) | 35 (15.4) | 6 (15.0) | 30 588 (24.0) |
Vaginal delivery | 101 (23.8) | 82 (31.9) | 83 (36.6) | 10 (25.0) | 34 341 (27.0) |
Infant characteristics | |||||
Birth wt, median (Q1, Q3), g | 896 (660, 1248) | 1190 (928, 1380) | 1100 (790, 1335) | 1081 (750, 1373) | 1085 (790, 1330) |
Gestational age, median (Q1, Q3), wk | 28 (25, 31) | 29 (27, 30) | 28 (26, 30) | 28 (26, 30) | 28 (26, 30) |
1-min Apgar score, median (Q1, Q3) | 5 (3, 7) | 5 (3, 7) | 6 (3, 7) | 3 (1, 7) | 5 (3, 7) |
Male sex, n (%) | 239 (56.4) | 120 (47.4) | 110 (48.5) | 16 (40.0) | 64 305 (50.6) |
Congenital anomaly, n (%) | 45 (10.6) | 19 (7.5) | 7 (3.1) | 8 (20.0) | 7956 (6.3) |
SGA, n (%) | 182 (43.4) | 38 (15.2) | 30 (13.3) | 10 (25.0) | 24 378 (19.5) |
Microcephaly, n (%) | 117 (30.7) | 29 (12.2) | 21 (9.9) | 6 (15.8) | 10 612 (9.1) |
Isolated microcephaly among those with microcephaly, n (%) | 9 (7.7) | 8 (27.6) | 9 (42.9) | 3 (50.0) | 1992 (18.8) |
Outcomes | |||||
Survivors, n (%) | 363 (87.3) | 223 (89.91) | 185 (82.2) | 31 (77.5) | 110 415 (87.4) |
Total length of stay among survivors, median (Q1, Q3), d | 81 (50, 121) | 64 (48, 95) | 68 (47, 99) | 74 (53, 98) | 66 (45, 96) |
. | CMV (n = 424) . | Syphilis (n = 253) . | Herpes Simplex (n = 227) . | Additionala (n = 40) . | None (n = 127 197) . |
---|---|---|---|---|---|
Maternal characteristics, n (%) | |||||
Maternal race and ethnicity | |||||
Blackb | 141 (33.8) | 109 (43.3) | 82 (36.3) | 12 (30.0) | 39 380 (31.3) |
Hispanic | 98 (23.5) | 67 (26.6) | 42 (18.6) | 7 (17.5) | 24 647 (19.6) |
Whiteb | 142 (34.1) | 66 (26.2) | 98 (43.4) | 16 (40.0) | 51 501 (40.9) |
Asian or Pacific Islanderb | 24 (5.8) | 2 (0.8) | 1 (0.4) | 2 (5.0) | 6411 (5.1) |
American Indian or Alaska Nativeb | 3 (0.5) | 4 (1.6) | 1 (0.4) | 3 (7.5) | 1008 (0.8) |
Otherb | 10 (2.4) | 4 (1.6) | 2 (0.9) | 0 (0.0) | 2789 (2.2) |
Prenatal care | 411 (97.6) | 177 (70.5) | 216 (95.2) | 37 (92.5) | 121 782 (96.1) |
Multiple gestation | 59 (13.9) | 38 (15.0) | 35 (15.4) | 6 (15.0) | 30 588 (24.0) |
Vaginal delivery | 101 (23.8) | 82 (31.9) | 83 (36.6) | 10 (25.0) | 34 341 (27.0) |
Infant characteristics | |||||
Birth wt, median (Q1, Q3), g | 896 (660, 1248) | 1190 (928, 1380) | 1100 (790, 1335) | 1081 (750, 1373) | 1085 (790, 1330) |
Gestational age, median (Q1, Q3), wk | 28 (25, 31) | 29 (27, 30) | 28 (26, 30) | 28 (26, 30) | 28 (26, 30) |
1-min Apgar score, median (Q1, Q3) | 5 (3, 7) | 5 (3, 7) | 6 (3, 7) | 3 (1, 7) | 5 (3, 7) |
Male sex, n (%) | 239 (56.4) | 120 (47.4) | 110 (48.5) | 16 (40.0) | 64 305 (50.6) |
Congenital anomaly, n (%) | 45 (10.6) | 19 (7.5) | 7 (3.1) | 8 (20.0) | 7956 (6.3) |
SGA, n (%) | 182 (43.4) | 38 (15.2) | 30 (13.3) | 10 (25.0) | 24 378 (19.5) |
Microcephaly, n (%) | 117 (30.7) | 29 (12.2) | 21 (9.9) | 6 (15.8) | 10 612 (9.1) |
Isolated microcephaly among those with microcephaly, n (%) | 9 (7.7) | 8 (27.6) | 9 (42.9) | 3 (50.0) | 1992 (18.8) |
Outcomes | |||||
Survivors, n (%) | 363 (87.3) | 223 (89.91) | 185 (82.2) | 31 (77.5) | 110 415 (87.4) |
Total length of stay among survivors, median (Q1, Q3), d | 81 (50, 121) | 64 (48, 95) | 68 (47, 99) | 74 (53, 98) | 66 (45, 96) |
Q1, first quartile; Q3, third quartile.
Because of small numbers, rubella, parvovirus B19, toxoplasmosis, Zika, and varicella zoster were combined in the “additional” group. Eleven infants with >1 infection are also in this group.
Non-Hispanic.
Infants with STORCH infections had similar rates of survival (86.3%) as infants without STORCH infections (87.4%).
Discussion
Prevalence of STORCH infections was 7.37 per 1000 among VLBW and/or preterm infants. In a population of VLBW and/or preterm infants in California from 2005 to 2016, prevalence of CMV infection was 2.7 per 1000,4 lower than that in the current study.
In this cohort, a large proportion of infants with CMV were SGA or microcephalic. In a study using health care data from 2000 to 2015 in the United States, congenital CMV diagnosis was associated with a sevenfold increased birth prevalence of microcephaly.5 A report from a single center found the yield of routinely testing infants who were SGA for STORCH infections was extremely low.6 A survey of neonatologists found that the most frequent reasons for pursuing STORCH testing were pathologic findings of physical and ophthalmologic examinations, such as microcephaly.7
In 2019, the VON VLBW database included >90% of US live births, making this study nearly population-based and the largest report of STORCH infections among VLBW and/or preterm infants. VON does not have population-based data on moderate preterm, late preterm, or term populations. We do not know whether NICUs performed universal screening for STORCH infections or routine testing based on clinical criteria, such as SGA or microcephaly, so we have underestimated the true prevalence. We do not know what tests were used to diagnose STORCH infections. Understanding testing practices may be important to assess differences in ascertainment and to develop strategies to increase identification of STORCH infections. STORCH infection tests may not be covered by health insurance; therefore, identifying high-risk populations in which testing is cost-effective is an important public health issue. These data may be useful to monitor trends and identify health disparities in STORCH infections among infants in the United States.
Acknowledgments
We thank our colleagues who submit data to VON on behalf of infants and their families. The centers contributing data to this study are listed in Supplemental Table 3.
FUNDING: No external funding.
Dr Edwards conceptualized and designed the study, conducted the analyses, drafted the initial manuscript, and reviewed and revised the manuscript; Ms Greenberg conducted the analyses and reviewed and revised the manuscript; Drs Ehret, Soll, Lanzieri, and Horbar conceptualized and designed the study and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
References
Competing Interests
FINANCIAL DISLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
POTENTIAL CONFLICT OF INTEREST: Drs Edwards and Ehret receive salary support from Vermont Oxford Network (VON). Ms Greenberg is a VON employee. Dr Soll is vice president, director of clinical trials and follow-up, and director of Cochrane at VON and an unpaid member of the VON Board of Trustees. Dr Horbar is the president and chief executive and chief scientific officer of VON and an unpaid member of the VON Board of Trustees; and Dr Lanzieri has indicated she has no potential conflicts of interest to disclose.
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