Decreasing prevalence and time trend of gastroschisis in 14 cities of Liaoning Province: 2006–2015

To identify trends in the prevalence of gastroschisis on the basis of a large population-based observation study with cases identified by the Liaoning Birth Defects Registry including 14 cities over the course of a 10-year period. Data were obtained from the aforementioned registry which was maintained by the Liaoning Women and Children’s Health Hospital, a comprehensive care institution as well as being responsible for the women’s and children’s health care guidance in this province. Gastroschisis prevalence, percent change, annual percent change (APC), and contribution rates of each city were calculated. We observed 747 cases of gastroschisis among 3,248,954 live births, for a prevalence of 2.30 per 10,000 births. The gastroschisis prevalence significantly decreased by 12.63% per year in Liaoning Province. Although the decreasing trends were observed in all these 14 cities, significant results were only observed in Shenyang (APC = −16.31%), Tieling (APC = −20.23%), and Chaoyang (APC = −13.50%). Notably, Tieling, Shenyang, and Yingkou were the three major cities which contributed almost 37.17% of the decreasing trend of gastroschisis in Liaoning Province. In conclusion, our findings demonstrate that the prevalence of gastroschisis has been decreasing during the recent decade among 14 cities in Liaoning Province.

Nevertheless, no formal assessment of this population had been made. Therefore, to address these aforementioned research questions, we examines gastroschisis prevalence among live birth infants in Liaoning Province for the 10-year period from 2006-2015. Table 1 presents the number of live births of each city in Liaoning Province during the 10-year observational period. During this period, the overall number of live births was highest in 2014 (364,400) but lowest in 2015 (298,437). Additionally, when compared with cities, Shenyang, the capital city of this province, had the largest number of live births in each year. In contrast, Benxi had the smallest number of live births.

Results
The prevalence of gastroschisis in each city in Liaoning Province is demonstrated in Table 2. During 2006-2015, 747 gastroschisis cases were detected among 3,248,954 live births (prevalence rate = 2.30 per 10,000 live births). Liaoyang (3.58 per 10,000 live births), Fushun (3.40 per 10,000 live births), and Shenyang (3.14 per 10,000 live births) were the top three leading cities in Liaoning Province. In contrast, Yingkou (1.24 per 10,000 live births), Tieling (1.24 per 10,000 live births), and Anshan (1.43 per 10,000 live births) were the three cities with lowest gastroschisis prevalence. Figure 1 depicts the time trend of gastroschisis prevalence in each city of Liaoning Province during the period of 2006-2015. The overall prevalence significantly decreased by 76.05% from 33.58 to 8.04 per 10,000 live births, or 12.63% per year (Table 3). Among these 14 cities, significant decreasing trends were also observed in three     Table 4 presents the contribution rates of each city of overall decreasing trend of Liaoning Province. Tieling, Shenyang, and Yingkou were the three major cities which contributed almost 37.17% of the decreasing trend of gastroschisis prevalence.

Discussion
To the best of our knowledge, this is the first report describing the time trend of gastroschisis prevalence on the basis of the data from the recent decade in China. Our findings demonstrated prevalence of gastroschisis significantly decreased by 76.05% from 33.58 to 8.04 per 10,000 live births, or 12.63% per year for the 10-year period from 2006 through 2015 in Liaoning Province. Additionally, decreasing trends were observed in all 14 cities of this province.
The overall prevalence of gastroschisis for Liaoning Province in our study during 2006 to 2015 was 2.30 cases per 10,000 live births. This was slightly lower than the reported prevalence in China between 1996 and 2007, which was 2.54 per 10,000 live births 15 . However, compared with the prevalence of gastroschisis (1.6 per 10,000 births) during 1986 to 1987 in China 14 , the prevalence during 2006 to 2015 was significantly higher. Similar patterns were also observed in other countries. For example, on the basis of 25 population-based registries in 15 European countries, Loane et al. 10    Although the decreasing trends were observed in all 14 cities, significant results were only observed in Shenyang (APC = − 16.31%), Tieling (APC = − 20.23%), and Chaoyang (APC = − 13.50%). Additionally, we observed significant geographical variation in prevalence within Liaoning, with some city (e.g. Yingkou) having half the prevalence compared to Shenyang. This difference could not be attributed to the ascertainment of gastroschisis since all the cases were reviewed and confirmed through a group of state-level experts in medical genetics and pediatrics. Possible different development of these cities could possibly explain the differences. Development of a region may be associated with many environmental exposures including maternal age at delivery [18][19][20] , socio-economic status 20,21 , maternal diet and drug use during pregnancy 20,22,23 which were potential risk factors for gastroschisis. Nevertheless, because of the access on the data, we could not test these hypotheses. Herein, future studies are warranted to further investigate these issues.
Our study have several strengthens. First, this report is a population-based observation study describing the time trend of gastroschisis prevalence in all 14 cities of Liaoning Province providing the possibility of comparison between cities. Additionally, this is a relatively longer time period of data as well as accurate results that provided a more recent report on the status of gastroschisis prevalence, with data up to 2015. Of note, previous to the present study, only a few studies have reported the prevalence of gastroschisis in China. Despite the clear strengths of our study, prudence be used when interpreting these findings. First, we have no access to the demographic factors (e.g., maternal age, race/ethnicity) for all live births in Liaoning Province. For example, we could hardly confirm the phenomenon that the prevalence of gastroschisis was especially higher in younger mothers (< 20 years). Additionally, although we were unable to access congenital malformation data in Liaoning Province prior to 2006, our report provided the trend of gastroschisis prevalence on the basis of the recent decade which has been very limited in developing countries. Second, the maximal diagnosis time for gastroschisis cases was the seventh day after birth 15 . We did not include gastroschisis cases confirmed after the seventh day which result in slightly lower prevalence of gastroschisis in the present study than in studies that include longer periods for confirmed diagnoses. However, limited number of cases (n = 4) were diagnosed after that time point in this study during the ten-year observation period.
In summary, a decreasing trend of gastroschisis prevalence was observed in Liaoning Province over the last 10 year which was the most recent and detailed evidence for time trends in the prevalence of gastroschisis in China. The present study not only supports the policy which was proposed by the government but helps them to understand the recent dynamics of gastroschisis prevalence. Since several cities still have relatively higher prevalence of gastroschisis, more prevention work should be carried out in these areas to reduce the risk of gastroschisis.

Material and Methods
Study population and data source. Liaoning Women and Children's Health Hospital is one of the sole obstetrical and gynecological hospitals for the province of Liaoning. It has also been a comprehensive care institution and has been in charge of the women's and children's health care guidance. Data from 2006 to 2015 were retrieved from the maternal and child health certificate registry of Liaoning Province which was maintained by this hospital. Hospital-delivered live birth and stillbirth infants were all included in this registry as the monitored subjects. This registry covers all 14 cities of the province (Shenyang, Dalian, Anshan, Fushun, Benxi, Dandong, Jinzhou, Yingkou, Fuxin, Liaoyang, Panjing, Tieling, Chaoyang, Huludao), with approximately 42 million inhabitants. The maximal diagnosis time for a congenital malformation case was the seventh day after birth 15 .
The details procedures of data collection were described in previous report 15 . Briefly, a 'Birth Defects Register Form' was used to collect the related information on the infants with gastroschisis. Once a gastroschisis case was identified and confirmed at the monitored hospital, the mother of the infant was interviewed by a trained obstetric or pediatric specialist in order to complete the aforementioned register form. Subsequently, the 'Birth Defects Register Form' was first submitted to the local maternal and child health facility and then to the provincial maternal and child health hospital, which is Liaoning Women and Children's Health Hospital. The data of these cases were reviewed and confirmed by a group of state-level experts in medical genetics and pediatrics 15 .
Gastroschisis is defined as a congenital malformation characterized by visceral herniation usually through a right side abdominal wall defect to an intact umbilical cord and not covered by a membrane, and excludes a hypoplasia of the abdominal muscles, a skin-covered umbilical hernia, or an omphalocele (www.icbdsr.org). Infants with gastroschisis with or without other birth defects were included as cases. However, infants with gastroschisis and an abdominal wall disruption with a phenotype consistent with either an amniotic band sequence or limb body wall complex or a recognized single gene disorder or chromosomal abnormality, such as Down syndrome, were excluded from this study 15 . If a case was reported as both gastroschisis and omphalocele or eversion of viscera, then the monitored hospital was asked to confirm the data and collect relevant information again, such as photographs and detailed descriptions, which were finally ascertained by state-level medical geneticists. For suspected gastroschisis cases that were diagnosed through prenatal ultrasound scans, case ascertainment after termination or examination after the birth were requested. Therefore, seven hundred and forty-seven cases were identified. Additionally, the total number of live births in the study window was 3,248,954.
The data quality control was described in detail in previous literature 15 . In brief, according to the program manual to ensure high quality data, the disease diagnosis, data collection, data checking, and medical records were verified by the expert group at each level. In addition, an independent retrospective survey was organized by the experts to find deficiencies and inaccuracies in the data 15 . Statistical analysis. Gastroschisis prevalence were calculated for nine 1-year time intervals from 2006 to 2015. The annual percentage change for gastroschisis prevalence was used to quantify the time trends [24][25][26][27] . A regression line was fitted to the natural logarithm of the rates, weighted by the number of cases, i.e. y = α + β x + ε , where y = ln (rate) and x = calendar year, and then the APC was calculated as 100 × (e β − 1). The 95% confidence interval (CI) of the APC was calculated by the methods for population-based cancer statistics recommended by the National Cancer Institute 28 . All analyses were conducted using SPSS for Windows (version 22, SPSS Inc, Chicago, IL, USA). All statistical tests were two-sided, and P-values less than 0.05 were considered statistically significant.