Orofacial clefts (OFCs) are among the most common human congenital malformations worldwide, and the majority of OFCs are non-syndromic (1). Although most OFCs are not fatal, children born with non-syndromic cleft lip, with or without cleft palate (NSCL/P), may have low intelligence and/or impaired speech/language development (2). In addition, OFCs also impose significant social, financial, and public health burdens. Periconceptional folic acid (FA) supplementation could help reduce the risk of neural tube defects (NTDs) (3) and other selected structural birth defects, including OFCs (4). However, the effect on different subtypes of OFCs has not been thoroughly evaluated. Similarly, the effect of policy changes, including the change from mandatory pre-marital health examination to voluntary examinations, release of the two-child population policy, and the subsequent update to the ongoing three-child policy, have not yet been explored. The current study examined the trend of OFCs in 5 counties based on data from a population-based birth-defect surveillance system in a high prevalence area of northern China from 2000 to 2020. The prevalence of OFCs in the 5 counties in Shanxi Province decreased significantly in the past two decades. Periconceptional supplementation with FA may have contributed to the decline in OFC prevalence.
The data used in the current study came from a population-based birth-defect surveillance system in Shanxi Province. Details of the system have been described in our previous publication (3). In summary, all livebirths or stillbirths of 28 or more complete gestational weeks and pregnancy terminations at any gestational age following the prenatal diagnosis of birth defects among pregnant women who reside in five counties located in Shanxi Province (Pingding, Shouyang, Taigu, Xiyang, and Zezhou) for more than 1 year were included. OFCs were coded Q35–37 according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) as different types of birth defect collected in the system (Table 1). The birth prevalence of OFCs by year, period, type, and gestational week’s group was compared using chi-squared tests. Two-tailed P≤0.05 was considered statistically significant. All statistical analyses were performed using SPSS Statistics for Windows (Version 24.0. IBM Corp., Armonk, NY, USA).
ICD-10 code Gestational weeks <28 weeks ≥28 weeks Total n Prevalence, 1/10,000 n Prevalence, 1/10,000 n Prevalence, 1/10,000 Cleft palate (Q35) 4 0.13 98 3.24 102 3.38 Cleft lip (Q36) 38 1.26 249 8.24 287 9.50 Cleft lip with cleft palate (Q37) 48 1.59 275 9.10 323 10.69 Total 90 2.98 622 20.59 712 23.57
Table 1. Prevalence of orofacial clefts (OFCs) by subtype and gestational weeks in 5 counties of Shanxi Province, 2000–2020.
From 2000 to 2020, a total of 302,101 births and 712 cases of OFCs were recorded in the system, resulting in a total prevalence of 23.57/10,000 births. The proportion of perinatal OFCs with ≥28 gestational weeks accounted for 100% in 2000 and 41.7% in 2020 (Figure 1A) while the proportion of pre-perinatal OFCs with <28 gestational weeks accounted for 0% in 2000 and 58.3% in 2020. The perinatal prevalence decreased dramatically, from more than 30/10,000 in 2002 to merely 5.9/10,000 in 2020 (chi-squared: 39.922, P<0.05) (Figure 1B). The decreasing trend in overall OFCs was also reflected in decreasing frequency of OFCs detected at perinatal stage (Figure 2A) (chi-squared: 120.001, P<0.05). While the pre-perinatal OFCs showed an upward trend during the past two decades due to early detection.Figure 1. Orofacial clefts (OFCs) by gestational week and year in 5 counties, Shanxi Province, China, 2000–2020. (A) Proportion of OFCs; (B) Prevalence of OFCs. Note: Perinatal prevalence (cases of 28 or more gestational weeks), pre-perinatal prevalence (cases before 28 gestational weeks), and total prevalence (all cases regardless of gestational age) were calculated. Significant time points and corresponding population policy and public strategies are as follows: 2003, canceled mandatory pre-marital physical check-ups; 2009, national campaign for FA supplementation; 2012, population policy transition; and 2016, release of universal two-child policy.Figure 2. Prevalence of orofacial clefts (OFCs) by period in 5 counties of Shanxi Province, 2000–2020. (A) pooled OFCs by gestational weeks; (B) OFCs by subtype. Note: Perinatal prevalence (cases of 28 or more gestational weeks), pre-perinatal prevalence (cases before 28 gestational weeks), and total prevalence (all cases regardless of gestational age) were calculated. The 6 periods were divided according to population policy and public strategy, i.e., 2000–2003 (Period before voluntary pre-marital physical check-ups), 2004–2008 (Period of voluntary pre-marital physical check-ups and before FA supplementation), 2009–2011 (Period of after FA supplementation), 2012–2015 (Period of population policy transition), 2016–2018 (Period of universal two-child policy), and 2019–2020.
Cleft lip with cleft palate was the most common type among all OFCs, followed by cleft lip alone, and isolated cleft palate was the third most common type. The rate of cleft lip with cleft palate was 10.69 per 10,000 births and accounted for 45% of OFCs in this population. The prevalence of OFCs detected at the perinatal stage (20.59/10,000) was higher than that detected at pre-perinatal stage (2.98/10,000) (Table 1).
Among all types of OFCs, the prevalence of cleft lip decreased the most (Figure 2B): from 15.15 per 10,000 live births between 2000–2003 to 9.35 per 10,000 live births between 2009–2011; from 6.26 per 10,000 live births between 2016–2018 to 3.08 per 10,000 live births between 2019–2020; an overall reduction of 80% in the past 2 decades (Overall reduction, chi-squared: 28.526, P<0.05). Cleft lip with cleft palate increased from 6.19 per 10,000 live births to as high as 13.70 per 10,000 live births between 2000–2011 and decreased to 7.18 per 10,000 live births between 2019–2020 (Overall reduction, chi-squared: 21.356, P<0.05). Cleft palate showed a decreasing trend from 7.04 to 0.87 per 10,000 live births during the first decade and slightly increased to 2–3 per 10,000 live births after that (Overall reduction, chi-squared: 34.837, P<0.05).