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Abstract

Background

Congenital malformations remain a major cause of under-five mortality in the United States, yet contemporary long-term trends and demographic disparities have not been comprehensively evaluated. This study examined national patterns in congenital malformation-related mortality among U.S. children under 5 years from 1999 to 2023.

Methods

Mortality data were obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER) Database, focusing on congenital malformations-related deaths among children aged under 5 years between 1999 and 2023 in the U.S. Cases were identified using ICD-10 codes from Q00 to Q89.9.

Results

This comprehensive analysis included a total of 143,931 deaths, demonstrating significant trends and disparities. The overall age-adjusted mortality rate (AAMR) declined from 34.70 (95% CI: 33.86–35.54) in 1999 to 25.95 (95% CI: 25.21–26.68) in 2023, showing an average annual percentage change (AAPC) of −1.21 (95% CI: −1.50 to −1.02). Mortality was higher in males than in females. Across all races, the least decline was noted among NH American Indian or Alaska Natives. Non-metropolitan areas exhibited higher overall AAMR (34.80 [95% CI: 34.33–35.27]) compared to metropolitan areas (29.02 [95% CI: 28.85–29.19]).

Conclusion

The overall AAMR decreased from 1999 to 2023, with significantly higher deaths among males, rural regions and Alaskan Natives. These findings demonstrate an overall decline in mortality but persistent demographic and geographic inequities, highlighting the need for targeted public health and policy interventions to improve outcomes for vulnerable pediatric populations.

Keywords

congenital malformations epidemiology under-five children public health demography mortality

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References

Rosano

Botto

Botting

, et al. Infant mortality and congenital anomalies from 1950 to 1994: an international perspective. J Epidemiol Community Health 2000; 54: 660–666. https://doi.org/10.1136/jech.54.9.660

Agha

Williams

Marrett

, et al. Determinants of survival in children with congenital abnormalities: a long-term population-based cohort study. Birth Defects Research Part a Clinical and Molecular Teratology 2006; 76: 46–54. https://doi.org/10.1002/bdra.20218

LPS

Kadandale

, et al. Consanguinity and chromosomal abnormalities. Int J Anat Res 2017; 5: 4531–4537. https://doi.org/10.16965/ijar.2017.393

Christianson

Howson

Modell

. Global report on birth defects. March of Dimes Birth Defects Foundation, 2006.

EUROCAT Central Registry . EUROCAT special report: congenital anomalies are a major group of mainly rare diseases. 2012.

Liu

Joseph

Wen

. Trends in fetal and infant deaths caused by congenital anomalies. Semin Perinatol 2002; 26: 268–276. https://doi.org/10.1053/sper.2002.34776

Lee

K-S

Khoshnood

Chen

, et al. Infant mortality from congenital malformations in the United States, 1970-1997. Obstet Gynecol 2001; 98: 620–627. https://doi.org/10.1016/s0029-7844(01)01507-1

Temtamy

. A genetic epidemiological study of malformations at birth in Egypt. East Mediterr Health J 1998; 4: 252–259. https://doi.org/10.26719/1998.4.2.252

Egbe

Lee

, et al. Effect of race on the prevalence of congenital malformations among newborns in the United States. Ethn Dis 2015; 25: 226–231.

10.

Multiple cause of death data on CDC WONDER 2026. https://wonder.cdc.gov/mcd.html.

11.

Ingram

Deborah D

Franco

Sheila J

. 2013 NCHS Urban-Rural Classification Scheme for Counties. Vital and health statistics. Series 2, Data evaluation and methods research. 2014; 166: 1–73. https://pubmed.ncbi.nlm.nih.gov/24776070/, 24776070.

12.

Anderson

Rosenberg

. Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep 1998; 47(3): 1–16. https://www.ncbi.nlm.nih.gov/pubmed/9796247

13.

Joinpoint Regression Program . Version 5.2.0.0. April, 2024; statistical research and applications branch. National Cancer Institute.

14.

Kim

Fay

Feuer

, et al. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med 2000; 19(3): 335–351. https://doi.org/10.1002/(SICI)1097-0258(20000215)19:33.0.CO;2-Z

15.

Pitt

Morris

. European trends in mortality in children with congenital anomalies: 2000–2015. Birth Defects Research 2021; 113: 958–967. https://doi.org/10.1002/bdr2.1892

16.

Kang

Cao

Jing

, et al. Global, regional, and national incidence and mortality of congenital birth defects from 1990 to 2019. Eur J Pediatr 2023; 182: 1781–1792. https://doi.org/10.1007/s00431-023-04865-w

17.

Bardi

Bergman

JEH

Bouman

, et al. Effect of prenatal screening on trends in perinatal mortality associated with congenital anomalies before and after the introduction of prenatal screening: a population‐based study in the northern Netherlands. Paediatr Perinat Epidemiol 2021; 35: 654–663. https://doi.org/10.1111/ppe.12792

18.

Y-F

Zhou

K-Y

Fang

, et al. Efficacy of prenatal diagnosis of major congenital heart disease on perinatal management and perioperative mortality: a meta-analysis. World Journal of Pediatrics 2016; 12: 298–307. https://doi.org/10.1007/s12519-016-0016-z

19.

Moges

Chanie

Anteneh

, et al. The effect of folic acid intake on congenital anomalies. A systematic review and meta-analysis. Front Pediatr 2024; 12: 1386846. https://doi.org/10.3389/fped.2024.1386846

20.

Kancherla

Botto

Rowe

, et al. Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acid. Lancet Global Health 2022; 10: e1053–e1057. https://doi.org/10.1016/s2214-109x(22)00213-3

21.

Chmielewska

Barratt

Townsend

, et al. Effects of the COVID-19 pandemic on maternal and perinatal outcomes: a systematic review and meta-analysis. Lancet Global Health 2021; 9: e759–e772. https://doi.org/10.1016/s2214-109x(21)00079-6

22.

McCann

Sinno

Ramadhan

, et al. COVID-19 disruptions of food systems and nutrition services in Ethiopia: evidence of the impacts and policy responses. Ann Glob Health 2023; 89: 30. https://doi.org/10.5334/aogh.3980

23.

Black

Yefet

, et al. Sex differences in surgically correctable congenital anomalies: a systematic review. J Pediatr Surg 2020; 55: 811–820. https://doi.org/10.1016/j.jpedsurg.2020.01.016

24.

Rouatbi

Farhat

Heying

, et al. Myocardial expression of estrogen Receptor-MRNA is associated with lower markers of post-operative organ damage in young patients with congenital cardiac defect. Front Pediatr 2021; 9: 729198. https://doi.org/10.3389/fped.2021.729198

25.

Monardo

Bryskin

, et al. Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase. Prostate Cancer Prostatic Dis 2009; 13: 39–46. https://doi.org/10.1038/pcan.2009.24

26.

Zhao

Zou

Lei

, et al. Gender differences in infant mortality and neonatal morbidity in mixed-Gender twins. Sci Rep 2017; 7: 8736. https://doi.org/10.1038/s41598-017-08951-6

27.

World Health Organization: WHO . Newborn mortality. https://www.who.int/news-room/fact-sheets/detail/newborn-mortality. 2024.

28.

Miana

Manuel

Antoniali

, et al. COVID-19 pandemic implications in paediatric and congenital heart surgery in Brazil. Cardiol Young 2021; 32: 31–35. https://doi.org/10.1017/s1047951121001608

29.

Coley

Zapata

Schwei

, et al. More than a “number”: perspectives of prenatal care quality from mothers of color and providers. Womens Health Issues 2017; 28: 158–164. https://doi.org/10.1016/j.whi.2017.10.014

30.

Sonenberg

Mason

. Maternity care deserts in the US. JAMA Health Forum 2023; 4: e225541. https://doi.org/10.1001/jamahealthforum.2022.5541

31.

Schwartz

Evans

Burns

, et al. Social inequities impact infant mortality due to congenital heart disease. Public Health 2023; 224: 66–73. https://doi.org/10.1016/j.puhe.2023.08.021

32.

Gressler

Lewis

. Changes in maternal morbidity and infant outcomes following state-level abortion bans post-Dobbs: a comparative interrupted time series study. BMC Public Health 2025; 25: 2265. https://doi.org/10.1186/s12889-025-23468-8

33.

Gemmill

Franks

Anjur-Dietrich

, et al. US abortion bans and infant mortality. JAMA 2025; 333: 1315–1323. https://doi.org/10.1001/jama.2024.28517

34.

Chatterjee

. Causes and consequences of rural hospital closures. J Hosp Med 2022; 17: 938–939. https://doi.org/10.1002/jhm.12973

35.

Coates

Probst

Sarwal

, et al. The impact of rural hospital closures and mergers on health system ecologies: a scoping review. Med Care Res Rev 2025; 82: 359–375. https://doi.org/10.1177/10775587251355671

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