Epidemiology of birth defects based on surveillance data from 2011–2015 in Guangxi, China: comparison across five major ethnic groups

The World Health Organization estimates that approximately 260,000 deaths (7% of all neonatal deaths) globally were caused by birth defects (BD) s in 2004 [1]. It is estimated that the prevalence rates of BDs is 4.7% in the developed countries, 5.6% in the middle-income countries, and 6.4% in the low-income countries [1, 2]. China is a middle-income country with the largest population in the world. With 16 million births annually, it is expected that there are 0.9 million BDs each year in China [3]. Based on the most recent surveillance data in 2011, BDs have become the second most common cause of infant deaths in China (the leading cause being premature/low birth weight) [3‐5]. BDs are the main causes of spontaneous abortion, stillbirth, perinatal death, infant death and congenital disability. BDs also affect the child’s and the family’s quality of life and carry a significant economic burden to the family and the society, particularly in the setting of China’s one-child and recently two-child policy since 2013 [3, 6, 7].

The causes of BDs are complex and multifactorial. Nearly 50% of BDs cannot be ascribed to a specific cause [8, 9]. In 1964, after the thalidomide tragedy, several countries including the Great Britain, Israel, and Finland started conducting BD surveillance [10‐14]. The Chinese Ministry of Health started the BD surveillance systems in 1986 [15‐17]. The surveillance was initially paper-based data reporting method, that was replaced by an electronic, web-based reporting system developed by the National Office for Maternal and Child Health Surveillance in 1998 [18]. The quality of birth defect monitoring varies in different parts of the world, and may vary even within the same country or region [19, 20]. In China, the emphasis placed on monitoring for BDs is higher and more comprehensive in Eastern China than in Midwestern China [3].

Guangxi is one of the western provinces of China, and the Chinese minorities account for majority of the population in Guangxi province (37.2%) [21]. Liuzhou is the most representative city in Guangxi, for its geographic (population of 3.8 million), economic (region’s industrial center), composition of population (large ethnic minority groups), and culture and customs within the ethnicities [22]. There are fifty-six (56) ethnic groups in China, and more than thirty ethnic groups reside in Liuzhou. The largest ethnic group in Liuzhou is Han (48.9%), followed by Zhuang (35.2%), Miao (6.4%), Dong (6.3%), Yao (1.9%), and Mulao (0.8%) [21, 23, 24]. The Chinese ethnic groups have their own, different languages, culture, customs and living environments. The epidemiology of BDs among various Chinese ethnic groups has not been described in the literature. Since the etiology of BDs could be multi-factorial involving genetic factors, environmental factors and their interactions, it is crucial to understand the difference in BD phenotypes among Chinese ethnic groups. Therefore, our study aims to provide further insights on BDs among the different Chinese ethic groups in Liuzhou. The information gained may allow clinicians to provide proper counselling to families, allow public health officials to appropriately plan targeted interventions, and may provide the foundation for further etiologic and epidemiologic studies.

Our study performed a comprehensive analysis of ethnic differences in the perinatal infant prevalence of BDs in Liuzhou, Guangxi, China over a 5 year time period. The average prevalence rate of total perinatal infants’ BDs was 25.2 per 1000 PIs in the past 5 years, with an upward trend increasing by 1.49% on average each year. The ethnic distribution in our study sample was consistent with the ethnic distribution in Liuzhou, Guangxi as reported in the 2012 Chinese population census [21, 23].

The average prevalence rate (25.2 per 1000 PIs) was higher than 20.2/1000, which was reported in a prior analysis of BDs in perinatal children in Guangxi from 2001 to 2010 [26]. The upward trend in the prevalence rate of BDs has been noted commonly in recent epidemiologic BD studies in China [3, 18, 25‐28]. The upward trend in BD epidemiology is potentially explained by several factors. Firstly, there is continued development of laws and regulations in Maternal and Child Health Care that have led to increased focus on BD surveillance and there is now full development of a government-led online BD surveillance system for the entire country. There is continued improvement in the overall health awareness of the country along with significant national financial support used in projects targeting tertiary prevention against BDs (pre-marital medical examination, pre-pregnancy care, genetic counselling, family planning, education on optimal reproductive age, and folic acid supplementation), along with the wider use of prenatal diagnosis techniques and the timely and effective diagnosis (e.g., Thalassemia carrier screening in pre-marital and pre-pregnancy check-up; primary health care ultrasound screening; nationwide newborn screening for congenital hypothyroidism, G6PD deficiency, phenylketonuria and galactosemia), and treatment and rehabilitation of the children who are born with defects (surgical operation for cleft lip with/without palate and congenital heart disease) [3].

Our average prevalence rate was the highest among similar studies in various regions of China, such as Hunan (191.84 per 10,000 PIs) from 2005 to 2014; Inner Mongolia (156.1 per 10,000 PIs) from 2005 to 2008; and overall China (145.43 per 10,000 PIs) in 2009 [18, 25, 29]. Our rate was lower than that reported from the United States (29.2 per 1000 PIs) in 2008, and the reported from the Korea (548.3 per 10,000 births, from 2009 to 2010), but higher than the reported from BDs in southern Vietnam (60.2 per 10,000 live births) [30‐32]. Actually Hunan, Inner Mongolia and most of the other similar studies in China use a BD monitoring period between 28 weeks of gestation and 7 days after birth; [25, 29] but in the United State the live birth hospitalizations are used in the 2008 Nationwide Inpatient Sample [30, 31]. Li et al. found that the prevalence rate of BDs rose to 291.4 per 10,000 births from 244.2 per 10,000 births after including less than 28 week BDs in analysis of Guangdong BDs in 2007 [28]. Similarly, a study by Wang et al. showed that in a hospital-based survey from the prenatal 20th gestational week to postnatal 7 days, the prevalence of BDs was 232.7 per 10,000 births, which was significantly lower than that from the population-based survey (232.7 vs. 347.4 per 10,000 births, P < 0.001) [27]. In summary, the survey monitoring period and survey sample (hospital-based vs. population-based survey) did impact the prevalence rate and the raw number of BDs epidemiology.

The causes of BDs are complex, including a variety of risk factors such as: advanced maternal age, exposures during the pregnancy, geographical location exposures, and race and ethnicity [2, 8, 33]. There are 56 ethnicities in China. Han is the biggest population comprising about 91.5%, and the second largest ethnicity is Zhuang, comprising around 1.3% [21]. Overall, the prevalence rates of BDs among the ethnic minorities in China are not well known. Guangxi is characterized as one of the five autonomous regions in China for their relatively large populations of ethnic minorities (called the “Guangxi Zhuang Autonomous Region”). In our study, we analyzed the ethnic distribution of total BDs and differences of BD prevalence across major ethnic groups. Overall, we found that ethnic minority groups including Zhuang, Yao, Miao, Dong and all others had a lower prevalence rate in BDs as compared to Han, and the difference in the risk was statistically significant. This finding is consistent with the finding from a population-based survey in Inner Mongolia, China conducted from 2005 to 2008, which showed that ethnic Mongols (147.8, 1/10000) were less likely to have BDs than Han Chinese (155.9, 1/10000) [29]. In several studies from the United States there were observed racial differences in the risk of BDs which were postulated to be related to genetic susceptibilities, cultural or social experiences that could modify exposures, or the combinations of genetic susceptibilities and environmental exposures [30, 34‐36]. Does this mean ethnic groups in China have different genetic and partially-genetic causes of BDs or that the BDs could be due to their different life-style and environment exposures? Further epidemiologic study will be required to answer these questions.

Most previous Chinese studies showed that prevalence rates of overall BDs were different between rural and urban environments. For example, in the Inner Mongolia study, in the analysis of BDs in the Xinjiang multi-ethnic region, and in the government BDs Prevention Report in 2012, all concluded that a higher incidence of BDs in rural areas than urban areas [3, 29, 37]. However, in the study conducted in Guangxi from 2001 to 2010 in the epidemiology of BDs based on a BDs surveillance system from 2005 to 2014 in Hunan and the analysis of BDs in Hunan 2009, the prevalence of overall BDs in urban areas was significantly higher than that in rural areas [25, 26, 38]. These differences in results likely relate to socio-economic status, level of education, access to health care, exposure to environmental pollution and the life pressures which may be different between urban and rural areas. These factors may have direct or indirect impact on maternal exposures and could impact the prevalence rate of BDs [18, 29, 38, 39]. Future studies from our center will attempt to correlate more information on residential location of the perinatal infant and any relation to ethnicity as a risk factor for the development of BDs.

The top six BD categories covered most BDs (86.8%) in our study. In a study of BDs in Guangxi from 2001 to 2010, the top six BDs were Schridde syndrome, polydactylism, congenital heart disease (CDH), total cleft lip, ear anomaly and hypospadias. This contrasted to the top six in our study which included musculoskeletal BDs as number one, and then cardiovascular, craniofacial, urogenital, other BDs, and neurologic BDs [26].

Thalassemia gene carriers in Guangxi comprise more than 20% of the population [7], which was the major cause of Schridde syndrome. This is a type of haemoglobin-hemolytic disease and was included in other BDs in our analysis. The most serious Schridde syndromes were almost all electively terminated before gestations of 28 weeks in recent years as a result of improvement in the premarital medical examination and at the level of prenatal diagnosis in Guangxi. Even as our study included gestation less 28 weeks, it still resulted in a lower prevalence of Schridde syndrome (15.27 vs. 29.57, per 10,000 PIs) compared to 2001–2010 in Guangxi [26].

The prevalence of CDH was increasing in our report, which is consistent with outcomes of other current studies from within China; and this would likely be due to the use of fetal ultrasound in antenatal care examinations and the improved surveying system online in China supported by the national finances in Maternal and Child Health Care System [3, 18, 28, 40].

Our study found ethnic differences in the overall risk of BDs and types of BDs. To our knowledge, this is the first report of ethnic differences in the epidemiology of BDs in a hospital-based surveying system with internal quality controls in Guangxi, China. Our study provided a comprehensive description of ethnic differences in the risk of BDs in the most representative city (e.g., geography, composition of population) in Guangxi.