Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;59(4):417-426.
doi: 10.1177/10556656211010060. Epub 2021 Apr 28.

Birth Defect Co-Occurrence Patterns Among Infants With Cleft Lip and/or Palate

Maria Luisa Navarro Sanchez  1 , Renata H Benjamin  1 , Laura E Mitchell  1 , Peter H Langlois  2 , Mark A Canfield  2 , Michael D Swartz  3 , Angela E Scheuerle  4 , Daryl A Scott  5   6 , Hope Northrup  7 , Christian P Schaaf  5   8   9 , Joseph W Ray  10 , Scott D McLean  11 , Han Chen  1   12 , Philip J Lupo  13 , A J Agopian  1
Affiliations

Birth Defect Co-Occurrence Patterns Among Infants With Cleft Lip and/or Palate

Maria Luisa Navarro Sanchez et al. Cleft Palate Craniofac J. 2022 Apr.

Abstract

Objective: To investigate 2- to 5-way patterns of defects co-occurring with orofacial clefts using data from a population-based registry.

Design: We used data from the Texas Birth Defects Registry for deliveries between 1999 and 2014 to Texas residents, including 1884 cases with cleft palate (CP) and 5289 cases with cleft lip with or without cleft palate (CL±P) without a known syndrome. We identified patterns of defects co-occurring with CP and with CL±P observed more frequently than would be expected if these defects occurred independently. We calculated adjusted observed-to-expected (O/E) ratios to account for the known tendency of birth defects to cluster nonspecifically.

Results: Among infants without a syndrome, 23% with CP and 21% with CL±P had at least 1 additional congenital anomaly. Several combinations of defects were observed much more often than expected. For example, the combination of CL±P, congenital hydrocephaly, anophthalmia, and other nose anomalies had an O/E ratio of 605. For both CP and CL±P, co-occurrence patterns with the highest O/E ratios involved craniofacial and brain abnormalities, and many included the skeletal, cardiovascular, and renal systems.

Conclusions: The patterns of defects we observed co-occurring with clefts more often than expected may help improve our understanding of the relationships between multiple defects. Further work to better understand some of the top defect combinations could reveal new phenotypic subgroups and increase our knowledge of the developmental mechanisms that underlie the respective defects.

Keywords: cleft lip; cleft palate; co-occurrence; co-occurring defects; nonsyndromic; orofacial clefts.

PubMed Disclaimer

Conflict of interest statement

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Number of the top 30 birth defect combinations by organ systems involved, among infants with cleft palate (CP). Each count represents 1 birth defect combination with CP (eg, CP + reduction deformities of the brain + other anomalies of nose would be shown in the cell with CNS and ENT overlap). Numbers do not sum to 30 due to combinations not represented in any of these 5 organ systems (eg, CP + unspecified anomalies of genital organs). CNS indicates central nervous system; ENT, ear, nose, and throat.
Figure 2.
Figure 2.
Number of the top 30 birth defect combinations by organ systems involved, among infants with cleft lip with or without cleft palate (CL±P). Each count represents 1 birth defect combination with CL±P (eg, CL±P + congenital hydrocephaly + anophthalmia + other anomalies of nose would be shown in the cell with CNS, eyes, and ENT overlap). CNS indicates central nervous system; ENT, ear, nose, and throat.
See this image and copyright information in PMC

References

    1. Adamson CL, Anderson VA, Nopoulos P, Seal ML, Da Costa AC. Regional brain morphometric characteristics of nonsyndromic cleft lip and palate. Dev Neurosci. 2014;36(6):490–498. - PubMed
    1. Agopian AJ, Evans JA, Lupo PJ. Analytic methods for evaluating patterns of multiple congenital anomalies in birth defect registries. Birth Defects Res. 2018;110(1):5–11. - PubMed
    1. Anchlia S, Rao KS, Bonanthaya K, Anupama B, Nayak IV. Ophthalmic considerations in cleft lip and palate patients. J Maxillofac Oral Surg. 2011;10(1):14–19. - PMC - PubMed
    1. Beaty TH, Yang P, Khoury MJ, Harris EL, Liang KY. Using log-linear models to test for associations among congenital malformations. Am J Med Genet. 1991;39(3):299–306. - PubMed
    1. Benjamin RH, Navarro Sanchez ML, Chen H, Mitchell LE, Langlois PH, Canfield MA, Swartz MD, Scheuerle AE, Scott DA, Northrup H, et al. Co-occurring defect analysis: a platform for analyzing birth defect co-occurrence in registries. Birth Defects Res. 2019; 111(18):1356–1364.. - PMC - PubMed

Publication types

LinkOut - more resources