Orofacial Cleft and Poor Birth Health Outcomes: A Populational Cross-Sectional Study

Abstract

Objective

This study aimed to examine whether newborns with orofacial clefts are at increased prevalence of poor birth health outcomes.

Study Design

This is a population-based cross-sectional study, conducted with information from 25,879,282 live births registered in the U.S. Vital Statistics Natality Birth Data from 2017 to 2023. The prevalence ratios and logistic regression models between orofacial cleft status (all, isolated, or nonisolated) and each child's birth health variables (delivery method, maternal morbidity, 5-minute Apgar score, gestational age, birth weight, abnormal conditions, infant breastfed at discharge) were calculated, assuming a p ≤ 0.05 as statistically significant.

Results

The prevalence ratios showed that newborns with orofacial clefts were more susceptible to being born by cesarean section (prevalence ratio [PR] = 1.18, p = 0.000, 95% confidence interval [CI] = 1.16–1.21), having lower birth weight (PR = 2.18, p = 0.000, 95% CI = 2.11–2.25), lower Apgar 5 score (PR = 4.08, p = 0.000, 95% CI = 4.08–4.50), prematurity (PR = 1.55, p = 0.000, 95% CI = 1.50–1.60), experiencing more abnormal conditions at birth (PR = 3.72, p = 0.000, 95% CI = 3.64–3.80), and having more difficulty to be breastfed (PR = 2.16, p = 0.000, 95% CI = 2.11–2.22) than newborns without clefts. These ratios were even higher among those with nonisolated orofacial clefts. Associations were statistic significant even after adjustments.

Conclusion

This study provides evidence that newborns with orofacial clefts are at increased prevalence of poor birth health outcomes.

Key Points

• Orofacial clefts are associated to higher prevalence of birth outcomes.

• Newborns with orofacial clefts were more susceptible to have low birth weight.

• Newborns with orofacial clefts were more susceptible to preterm birth.

Keywords

orofacial cleft - population health - cleft lip - cleft palate

Note

Investigators here had no contact with human subjects and the data used are from an open-access information system, available online, in which the data are disbursed without identifying the subjects.

Publication History

Received: 07 February 2025

Accepted: 01 May 2025

Article published online:
21 May 2025

• References

• 1 Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet 2009; 374 (9703): 1773-1785
• 2 Nasreddine G, El Hajj J, Ghassibe-Sabbagh M. Orofacial clefts embryology, classification, epidemiology, and genetics. Mutat Res Rev Mutat Res 2021; 787 (108373): 108373
• 3 Worley ML, Patel KG, Kilpatrick LA. Cleft lip and palate. Clin Perinatol 2018; 45 (04) 661-678
• 4 Denadai R, Lo LJ. The burden of orofacial clefts: global trends and focus on underresourced regions. In: Current Concept in Cleft Surgery. Springer; 2022: 13-20
• 5 Leslie EJ. Genetic models and approaches to study orofacial clefts. Oral Dis 2022; 28 (05) 1327-1338
• 6 Leslie EJ, Marazita ML. Genetics of cleft lip and cleft palate. Am J Med Genet C Semin Med Genet 2013; 163C [phone]
• 7 Reynolds K, Zhang S, Sun B, Garland MA, Ji Y, Zhou CJ. Genetics and signaling mechanisms of orofacial clefts. Birth Defects Res 2020; 112 (19) 1588-1634
• 8 Stuppia L, Capogreco M, Marzo G. et al. Genetics of syndromic and nonsyndromic cleft lip and palate. J Craniofac Surg 2011; 22 (05) 1722-1726
• 9 Khan AMI, Prashanth C, Srinath N. Genetic etiology of cleft lip and cleft palate. AIMS Mol Sci 2020; 7 (04) 328-348
• 10 Kawalec A, Nelke K, Pawlas K, Gerber H. Risk factors involved in orofacial cleft predisposition - review. Open Med (Wars) 2015; 10 (01) 163-175
• 11 Lopes F, Vieira MG. Fatores de risco ambientais e teratogênicos associados às malformações congênitas: um estado do conhecimento Fatores de risco ambientais e teratogênicos associados às malformações congênitas: um estado do conhecimento. RELA Cult 2020; 6: 1-24
• 12 Vieira AR, Orioli IM, Murray JC. Maternal age and oral clefts: a reappraisal. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002; 94 (05) 530-535
• 13 Silva HPVD, Arruda TTS, Souza KSC. et al. Risk factors and comorbidities in Brazilian patients with orofacial clefts. Braz Oral Res 2018; 32: e24
• 14 Wyszynski DF, Sarkozi A, Vargha P, Czeizel AE. Birth weight and gestational age of newborns with cleft lip with or without cleft palate and with isolated cleft palate. J Clin Pediatr Dent 2003; 27 (02) 185-190
• 15 Dolan SM, Gross SJ, Merkatz IR. et al. The Contribution of Birth Defects to Preterm Birth and Low Birth Weight. Vol. 110; 2007.
• 16 Ludorf KL, Benjamin RH, Canfield MA, Swartz MD, Agopian AJ. Prediction of preterm birth among infants with orofacial cleft defects. Cleft Palate Craniofac J 2025; 62 (01) 35-43
• 17 Ludorf KL, Benjamin RH, Canfield M. et al. Low Apgar score and risk of neonatal mortality among infants with birth defects. Am J Perinatol 2024
• 18 Malic CC, Lam M, Donelle J, Richard L, Vigod SN, Benchimol EI. Incidence, risk factors, and mortality associated with orofacial cleft among children in Ontario, Canada. JAMA Netw Open 2020; 3 (02) e1921036
• 19 Wyszynski DF, Wu T. Prenatal and perinatal factors associated with isolated oral clefting. Cleft Palate Craniofac J 2002; 39 (03) 370-375
• 20 Centers for Disease Control and Prevention. User Guide to the 2021 Natality Public Use File; 2021. Accessed September 10, 2024 at: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/Dataset_Documentation/DVS/natality/UserGuide2021.pdf
• 21 Vandenbroucke JP, von Elm E, Altman DG. et al; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Int J Surg 2014; 12 (12) 1500-1524
• 22 Rasmussen SA, Olney RS, Holmes LB, Lin AE, Keppler-Noreuil KM, Moore CA. National Birth Defects Prevention Study. Guidelines for case classification for the national birth defects prevention study. Birth Defects Res A Clin Mol Teratol 2003; 67 (03) 193-201
• 23 Romero DE, Cunha CB. Avaliação da qualidade das variáveis epidemiológicas e demográficas do Sistema de Informações sobre Nascidos Vivos, 2002. Cad Saude Publica 2007; 23 (03) 701-714
• 24 da Silva AM, Calumby RT, Freitas VS. Epidemiologic profile and prevalence of live births with orofacial cleft in Brazil: a descriptive study. Revista Paulista de Pediatria 2023;42;
• 25 da Silva AM, de Lavôr JR, Freitas VS, Vieira AR. Coast-or inland residence and differences in the occurrence of cleft lip and cleft palate. Cleft Palate Craniofac J 2025; 62 (03) 380-384
• 26 Simon L, Hashmi M, Bragg B. Apgar Score. StatPearls Publishing; 2023
• 27 Saraiva JP, Vogt SE, Rocha JDS, Duarte ED, Simão DADS. Association between maternal and neonatal factors and Apgar in usual risk neonates. Rev Rede Enfermagem Nordeste 2018; 19: 3179
• 28 Sung S, Mahdy H. Cesarean Section. StatPearls Publishing; Treasure Island: 2023
• 29 Betran AP, Ye J, Moller AB, Souza JP, Zhang J. Trends and projections of caesarean section rates: global and regional estimates. BMJ Glob Health 2021; 6 (06) 1-8
• 30 Case AP, Colpitts LR, Langlois PH, Scheuerle AE. Prenatal diagnosis and cesarean section in a large, population-based birth defects registry. J Matern Fetal Neonatal Med 2012; 25 (04) 395-402
• 31 International Statistical Classification of Diseases and Related Health Problems- CID10. Accessed September 4, 2023 at: https://cid10.com.br
• 32 World Health Organization. Preterm birth. 2023. Accessed May 30, 2023 at: https://www.who.int/news-room/fact-sheets/detail/preterm-birth
• 33 Shehan JN, Danis III DO, Bains A, Basa K, Marston AP, Levi JR. Cleft palate in newborns diagnosed with prematurity. Otolaryngol Head Neck Surg 2021; 165 (06) 887-894
• 34 Ryu JY, Park TH, Cho BC, Choi KY. The prevalence, risk of premature births, mortality and causes of death of cleft lip with or without palate in South Korea: a nationwide population-based cohort study. Int J Epidemiol 2022; 51 (03) 974-983
• 35 Walker SP, Wachs TD, Gardner JM. et al; International Child Development Steering Group. Child development: risk factors for adverse outcomes in developing countries. Lancet 2007; 369 (9556): 145-157
• 36 Nyarko KA, Lopez-Camelo J, Castilla EE, Wehby GL. Does the relationship between prenatal care and birth weight vary by oral clefts? evidence using South American and United States samples. J Pediatr 2013; 162 (01) 42-9.e1
• 37 Barber EL, Lundsberg LS, Belanger K, Pettker CM, Funai EF, Illuzzi JL. Indications contributing to the increasing cesarean delivery rate. Obstet Gynecol 2011; 118 (01) 29-38
• 38 Eidelman AI. Breastfeeding and cognitive development: is there an association?. J Pediatr (Rio J) 2013; 89 (04) 327-329
• 39 Miller CK. Feeding issues and interventions in infants and children with clefts and craniofacial syndromes. Semin Speech Lang 2011; 32 (02) 115-126
• 40 Beaumont D. A study into weight gain in infants with cleft lip/palate. Paediatr Nurs 2008; 20 (06) 20-23
• 41 Burca NDL, Gephart SM, Miller C, Cote C. Promoting breast milk nutrition in infants with cleft lip and/or palate. Adv Neonatal Care 2016; 16 (05) 337-344
• 42 Grünebaum A, McCullough LB, Orosz B, Chervenak FA. Neonatal mortality in the United States is related to location of birth (hospital versus home) rather than the type of birth attendant. Am J Obstet Gynecol 2020; 223 (02) 254.e1-254.e8
• 43 Boulet SL, Shin M, Kirby RS, Goodman D, Correa A. Sensitivity of birth certificate reports of birth defects in Atlanta, 1995-2005: effects of maternal, infant, and hospital characteristics. Public Health Rep 2011; 126 (02) 186-194
• 44 Salemi JL, Tanner JP, Sampat DP. et al. Evaluation of the sensitivity and accuracy of birth defects indicators on the 2003 revision of the U.S. birth certificate: has data quality improved?. Paediatr Perinat Epidemiol 2017; 31 (01) 67-75
• 45 Vu GH, Warden C, Zimmerman CE. et al. Poverty and risk of cleft lip and palate: an analysis of United States birth data. Plast Reconstr Surg 2022; 149 (01) 169-182
• 46 Heydari MH, Sadeghian A, Khadivi G. et al. Prevalence, trend, and associated risk factors for cleft lip with/without cleft palate: a national study on live births from 2016 to 2021. BMC Oral Health 2024; 24 (01) 36
• 47 World Health Organization (WHO). Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death. 1967;1.