The aetiology distribution of birth defects based on the China Birth Cohort Study

Birth defects, which comprise a series of severe congenital abnormalities, impose a significant burden on society, families and individuals. Consequently, it is crucial to identify the underlying causes of birth defects and reduce their occurrence. Although an increasing number of risk factors for birth defects have been identified, few associations can be established as causal. Furthermore, the distribution of aetiology related to birth defects remains unclear. This study aims to analyse birth defect cases from the China Birth Cohort Study (CBCS) to elucidate the aetiological profile of these conditions.

A total of 3873 abnormal cases were recorded in the CBCS from November 2017 to August 2021. Abnormal fetuses (including both live births and foetal losses) were diagnosed by obstetricians, ultrasound specialists and geneticists based on prenatal screening and clinical examinations. The causes of birth defects were categorised into chromosomal anomalies, genetic anomalies, environmental exposures and twinning. Chromosomal and genetic anomalies were identified through genetic screening. Data on exposure, including the substances involved and the duration of exposure, were reviewed to determine whether environmental factors contributed to the birth defects.

After excluding cases with minor malformations, a total of 2123 birth defect cases were reviewed. The most common birth defects among the included cases were congenital heart disease, polydactyly, trisomy 21 and cleft palate with cleft lip. Of these, only 22.4% (475/2123) had identifiable causes. Specifically, 415 cases were attributed to chromosomal anomalies, while 31 cases were diagnosed as monogenic disorders. Additionally, 23 cases were linked to environmental exposures, and 6 cases were associated with twinning. The proportions of birth defect cases with known causes were significantly higher in the spontaneous abortion group (12/27, 44.4%), the therapeutic abortion group (314/1044, 30.1%) and perinatal death group (13/36, 36.1%) compared with live births (136/1016, 13.4%).

Nearly 80% of birth defect cases in the CBCS lack a clear identifiable cause. Therefore, translating statistical associations between risk factors and birth defects into causal relationships is both necessary and important.