Risk Factors for Adverse Pregnancy Outcomes among Zhuang Ethnic Pregnant Women: A Cohort Study in Guangxi, China

Risk factors for adverse pregnancy outcomes among Zhuang ethnic pregnant women are unclear. This study analyzed the incidence and risk factors related to preterm birth (PB), low birth weight (LBW) and macrosomia in Zhuang population. We conducted a prospective cohort study of 9965 Zhuang pregnancy women in Guangxi, China. Information on mothers and newborns was obtained by using questionnaires and referring to medical records. Multivariate logistic regression analyses were used to evaluate the association between related factors and adverse pregnancy outcomes. Our results showed that the incidence of PB, LBW and macrosomia in Zhuang people was 5.55%, 5.64% and 2.19%, respectively. Maternal age ≥36 years (OR=2.22, 95% CI: 1.51–3.27) was related to a higher incidence of PB. Those with pre-pregnancy body mass index (BMI) <18.5 kg/m2 (OR=1.91, 95% CI: 1.45–2.51), and had a female fetus (OR=1.74, 95% CI: 1.36–2.23) were more likely to have LBW infants. Maternal age between 31 and 35 years (OR=1.76, 95% CI: 1.03–2.99) and pre-pregnancy overweight or obesity (OR=1.79, 95% CI: 1.15–2.80) were associated with a higher risk of macrosomia. The protective factors of macrosomia were maternal pre-pregnancy BMI <18.5 kg/m2 (OR=0.30, 95% CI: 0.15–0.60) and female fetus (OR=0.41, 95% CI: 0.28–0.59). Our study provided a reference for maternal and childcare administration among Zhuang population.

Preterm birth (PB), low birth weight (LBW) and macrosomia are common types of adverse pregnancy outcomes. According to an international study of 184 countries, the global incidence of PB was 11.1% in 2010, and it was 7.1% in China [1] . PB remains a global problem associated with perinatal morbidity and adverse health outcomes [2][3][4][5] . It has been reported that the risk factors of PB mainly include the following: maternal age, parity, maternal nutrition during pregnancy, smoking, and gestational diseases [6][7][8] .
LBW and macrosomia have been reported to be the risk factors of newborn illness and diseases in adulthood [9][10][11][12] . One prior study reported that the worldwide prevalence of LBW was 14.6% in 2015 [9] . Some maternal factors such as maternal age, parity, hypertension, and pre-pregnancy body mass index (BMI) have been shown to be related to the risk of LBW [13][14][15][16] . The rate of macrosomia increased over the past several decades in many countries. In China, Shan et al found that the percentages of macrosomia in Beijing increased from 6.6% in 1996 to 9.5% in 2000 and declined to 7.0% in 2010 [17] . While Zhang et al found an overall increase in frequency of macrosomia from 8.9% in 2010 to 10.1% in 2013, in Xi'an, China [18] . Factors associated with macrosomia may include but not limited to parity, BMI, maternal age, and fetal sex [19][20][21] .
It has been reported that ethnic differences also have an impact on pregnancy outcomes. Diabelková et al analyzed the differences in pregnancy outcomes between Roma and non-Roma mothers, and found that the Roma mothers had a higher risk of giving birth to LBW babies [22] . A study from the Xinjiang region in China showed that the incidence of LBW among Uighur, Hazakh and Hui ethnic groups was significantly higher than that of Han ethnic group, while the rate of macrosomia among Uighur was lower than that of Han [23] . China is the largest developing country in the world with 56 ethnic groups. Zhuang is the most populous ethnic minority in China, mostly living in the Guangxi Zhuang Autonomous Region. However, to the best of our knowledge, there were few researches on the incidence and risk factors for adverse pregnancy outcomes in the Zhuang people.
In this study, we investigated and analyzed the incidence and risk factors of three adverse pregnancy outcomes (LBW, PB and macrosomia) in Zhuang ethnic mothers, and provided a reference for maternal and child care administration among the Zhuang population.

Study Design and Study Population
This study was approved by the ethical committee of Guangxi Medical University (No. 20140305-001) and conducted under the Helsinki Declaration. Informed consent was obtained from all participants.
The present study was conducted as a part of the prospective Guangxi Zhuang Nationality Birth Cohort study which was initiated in 2015. This ongoing cohort enrolls participants at 13 hospitals in the counties of Jingxi, Longan, Tiandong, Tianyang, Pingguo, Wuming, and Debao, which are located in Guangxi Zhuang Autonomous Region in southern China. Pregnant women, who came for their first prenatal care before 12 gestational weeks, were asked to participate in the study. The eligibility criteria for participants are as follows: (1) the pregnant woman and/or her husband are ethnically Zhuang Chinese; (2) residence in the study area; (3) with an expectation to deliver at the collaborating hospital. Participants were invited to complete a questionnaire by a face-to-face interview. The questionnaire used was designed by epidemiologists. A total of 11 384 pregnant women were enrolled between June 2015 and July 2018. After excluding those who had multiple births (n=549), who gave birth to an infant with a birth defect (n=128), and who was not Zhuang ethnic herself (n=742), a total of 9965 Zhuang ethnic pregnancy women were eventually included in this analysis.

Pregnancy Outcomes
Information about the mothers' disease, history of pregnancy outcomes, and information regarding the infant sex, birth date, birth weight, and gestational age at birth were retrieved from medical records. Gestational age was determined by both the woman's last menstrual period and ultrasound examination. PB was defined as infants born before 37 weeks of gestation [24] . LBW and macrosomia were defined as birthweight < 2500 g and ≥ 4000 g, respectively [9,10] . Trained obstetric nurses measured birth weight immediately after delivery using a calibrated electronic scale.

Data Collection
The face-to-face interviews were conducted with the participants at the first antenatal care visit in the hospital by trained investigators. The interview collected a variety of information, including sociodemographic characteristics (maternal age and occupational status), lifestyle variables (alcohol use during pregnancy, smoking during pregnancy, passive smoking, folic acid intake, cooking fuels, and exercise) and the living conditions (natural ventilation of the house, natural lighting of the house and whether the house was decorated in the last five years). Prepregnancy BMI was calculated as weight (kg)/height (m 2 ).

Statistical Analysis
Categorical data were described as the percentage. All risk factor variables were first examined by univariate analysis to assess the importance of each of them on three adverse pregnancy outcomes. A Bonferroni test was used for Post-hoc pairwise comparison. When a variable was found to be significant at the 0.1 level or was reported to be associated with pregnancy outcomes in previous studies, it was entered into the multivariate model.
The correlation between risk factors and adverse pregnancy outcomes was estimated using logistic regression and expressed as odds ratios (OR) and 95% confidence intervals (CI). A two-tailed value of P<0.05 was considered statistically significant. All statistical analyses were performed by IBM SPSS statistics (version 22.0).

Characteristics of Study Population
A total of 9965 Zhuang ethnic pregnant women were included in the study. The basic characteristics of the pregnant women are shown in table 1. Women enrolled had a mean age of 28.7 years (SD=5.5) and were predominantly non-drinkers and nonsmokers. Over half of infants were male. The incidence of PB, LBW, and macrosomia was 5.55%, 5.64% and 2.19%, respectively.

Univariate and Multiple Analyses of Factors Related to Adverse Pregnancy Outcomes
The associations of maternal and fetal factors with the risk of PB are presented in table 2. In univariate analyses, maternal age ≥ 36 years was associated with an increased risk of PB (OR=1.43, 95% CI: 1.09-1.88), and this association remained statistically significant in multivariate analyses (OR=2.22, 95% CI: 1.51-3.27). No other factors were found to be associated with PB.

DISCUSSION
In this large population-based study, we examined the incidence of PB, LBW and macrosomia in Zhuang population, and identified the possible risk factors associated with the three adverse pregnancy outcomes. To the best of our knowledge, this is the first cohort study to investigate the incidence and risk factors for adverse pregnancy outcomes in the Zhuang population. The results of the present study suggested that in Zhuang population, maternal age ≥36 years was related to an increased risk of PB; pre-pregnancy underweight, gestational age <37 weeks, and having a female fetus were associated with the risk of LBW; maternal age between 31-35 years, pre-pregnancy overweight or obesity, and male fetus might be the risk factors of macrosomia.
It has been demonstrated that maternal prepregnancy BMI was associated with the infant birth weight: women with low pre-pregnancy BMI had a higher risk of giving birth to LBW babies; on the other hand, high pre-pregnancy BMI was a risk factor for macrosomia [20,31,32] . The Zhuang women in our study had lower pre-pregnancy BMI (5.91% overweight or obesity) than women in other cohort study (9% overweight or obesity in Shanghai and 11.72% in Ma'anshan) [26,33] . Thus, the higher LBW incidence and the lower macrosomia incidence of Zhuang fetal may be related to the lower pre-pregnancy BMI of their mothers. Furthermore, some researchers suggested that maternal and child health outcomes may vary by health inequalities between different ethnic groups [34] . The factors contributing to health inequalities between ethnic and non-ethnic minority populations are varied and complex, while some studies suggested that the income, education, employment, social policies, health care systems, health behaviors, cultural norms, and maternal and child health service coverage may all play a role [34][35][36] .
Our study showed that mothers with maternal age ≥36 years were more likely to deliver preterm babies. It is consistent with the previous studies [37,38] . Previous evidence showed that the risk of pregnancy outcome would be greater in advanced age due to placental physiological changes of aging [37,39] . It should be noted that the average age of childbearing in China has increased from 26.31 in 2000 to 29.13 in 2010 [38] . Therefore, clinical workers should strengthen the prevention and health care of pregnant women in advanced maternal age to avoid serious adverse pregnancy outcomes.
LBW remains an important public health issue for developing countries [40] . Our study demonstrated that pre-pregnancy BMI <18.5 kg/m 2 , nulliparous, and female fetus were risk factors for LBW. The possible mechanism is as follows. Low pre-pregnancy weight women may not be able to provide adequate nutrients to the fetus, ultimately leading to LBW [41] . Increasing parity is related to a progressive increase in uterine blood flow, which leads to increased birth weight of subsequent offspring [15] . In terms of infant sex, the weight difference between male and female infants may be associated with chromosomes and hormones [42] .
Maternal age between 31-35 years old and prepregnancy overweight or obesity were related to a higher risk of macrosomia, which is consistent with several other studies [43,44] . Both two factors can lead to macrosomia by affecting fetal fat and protein stores [43,44] . We also found that male fetuses were more likely to be macrosomia. This is consistent with differences in fetal growth between males and females [42] . In addition, we found that gestational diabetes mellitus tended to be a risk factor for macrosomia. The excessive shunting of nutrients to the fetus and the acceleration of fetal growth trajectory may contribute to the increased risk of macrosomia in women with gestational diabetes mellitus [45] .
One of the strengths of our study is that the prospective cohort design was used. The information was collected in the early stages of pregnancy, which can reduce the recall bias. In addition, interviews conducted with all participants provided the opportunity to adjust for more potential risk factors for adverse pregnancy outcomes, such as maternal pre-pregnancy BMI, regular exercise, passive smoking, and cooking fuels. However, the study has some limitations. First, some variables have missing data, e.g. pre-pregnancy BMI, passive smoking, natural ventilation of house, and natural lighting of house. Second, maternal nutritional status was not addressed in this study. It is common knowledge that low maternal levels of nutrients are related to adverse effects on fetal development.
In conclusion, the incidence of PB, LBW and macrosomia in Zhuang people was 5.5%, 5.64% and 2.19%, respectively. In Zhuang pregnant women, maternal age ≥36 years was related to a higher incidence of PB. Mothers who were pre-pregnancy underweight, with gestational age <37 weeks, and had a female fetus were more likely to have LBW infants. Maternal age between 31-35 years, pre-pregnancy overweight or obesity, and male fetus were linked to increased risk of macrosomia. Health service at the perinatal stage  [18] should be strengthened for pregnant women with one of these risk factors to reduce the incidence of adverse pregnancy outcomes. The potential mechanism of these risk factors should be studied in future studies.