Background
Obesity and overweight have become major health concerns in women of childbearing age, and their prevalence has been increasing worldwide. Data from the Pregnancy Risk Assessment Monitoring System (PRAMS) indicated that 45% of US women who give birth were overweight and obese before pregnancy [
1], while overweight and obesity have affected 6~24% of Chinese women of reproductive age [
2‐
5]. Prepregnancy overweight or obesity has been associated with a number of poor maternal and neonatal outcomes such as higher risk of cesarean delivery, gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preterm birth, macrosomia, and low Apgar scores [
1,
4,
6]. In addition, maternal obesity may also affect the long-term health of their children, such as increasing the risk of obesity, poor body fat distribution, high blood pressure, adverse lipid profile, and insulin resistance in child and adult offspring [
7,
8]. On the other hand, maternal underweight with the prevalence of 11–14% in Chinese pregnant women has been also associated with suboptimal fetal growth, including low birth weight and small-for-gestational age (SGA) [
2‐
4,
6,
9].
Gestational weight gain (GWG) is a potentially modifiable risk factor for a series of adverse pregnancy outcomes which could be reduced by nutrition or exercise interventions during pregnancy [
10]. Recently, a systematic review and meta-analysis estimated that 47% of pregnant women had excessive GWG and 23% had inadequate GWG according to 2009 Institute of Medicine (IOM) recommendations [
11]. Excessive GWG has been associated with increased risk of cesarean delivery, hypertensive diseases of pregnancy, postpartum weight retention, macrosomia, and childhood overweight or obesity for the offspring, whereas insufficient GWG may contribute to low birth weight, preterm birth and failure to initiate breast-feeding [
10,
12,
13]. In addition, some previous epidemiologic studies using total GWG (kg) as the measurement may introduce bias because of neglecting the inherent correlation between GWG and gestational age at delivery [
14,
15]. Moreover, the rate of GWG is constant and its association with pregnancy time is close to be linear in the 2nd and 3rd trimesters [
16], and thus, the rate of GWG in the 2nd and 3rd trimesters would be more preferable for evaluating the association between GWG and pregnancy outcomes. Furthermore, few studies have examined the dose-response relationship between GWG and pregnancy outcomes. To our knowledge, only two studies reported the dose-response relationship between rate of GWG in the 2nd and 3rd trimesters and preterm birth [
15,
17].
Therefore, the purpose of the present study was to examine associations of prepregnancy body mass index (BMI) and rate of GWG in the 2nd and 3rd trimesters with pregnancy outcomes in Chinese urban women, and we also assessed the dose-response relationship between rate of GWG and pregnancy outcomes in the whole population and in women stratified by prepregnancy BMI categories.
Discussion
In this retrospective cohort study of Chinese urban women, 22.6, 27.4 and 50.0% of women had insufficient, adequate and excessive rate of GWG in the 2nd and 3rd trimesters, respectively, and more than 70% of women who were overweight or obese had excessive rate of GWG according to the IOM recommendations. We also found that maternal underweight prepregnancy BMI was associated with higher risk of SGA, while overweight or obese pregnancy BMI was associated with increased odds of cesarean delivery and LGA. After adjusting for potential confounding factors, both insufficient and excessive rates of GWG were associated with higher risk of preterm birth than women with adequate rate of GWG. In addition, insufficient rate of GWG was associated with increased risk of SGA, whereas excessive rate of GWG was associated with higher risk of cesarean delivery and LGA.
One interesting finding of our study is that we observed a U-shaped association of GWG rate with preterm birth by both logistic regression and RCS analysis. Consistent with our findings, a previous study also reported a U-shaped relationship, with both low and high rates of 2nd and 3rd trimester GWG having a positive association with preterm birth among US pregnancy women [
17]. Another study also indicated that the association between rate of GWG and preterm birth was U-shaped in Peruvian women who were normal-weight or overweight before pregnancy [
24]. The potential mechanisms linking insufficient rate of GWG and an elevated risk of preterm birth may involve diminished uteroplacental blood flow, poor expansion of plasma volume, deficiencies in micronutrients, impaired antioxidant activity, infection and inflammation, while excessive rate of GWG may be associated with an increased risk of preterm birth due to induction of a pro-inflammatory state and fluid retention associated with preeclampsia [
24,
25]. Potential mechanisms underlying the association between GWG and preterm birth needed to be further explored in future research.
Another finding of our study is that insufficient rate of GWG was associated with higher risk of SGA. In concordance with our results, the forementioned PRAMS cohort also reported that inadequate GWG in underweight and normal prepregnancy BMI groups was associated with increased risk for SGA infants [
26]. A large-scale retrospective study conducted in Japanese women found that poor GWG was associated with a higher frequency of SGA [
6]. Another retrospective cohort study focusing on Taipei women also demonstrated that GWG below the guideline increased the risk of SGA in women with prepregnancy underweight or normal weight [
4]. In contrast to a previous study suggesting that GWG below recommendations was associated with a four-fold risk of SGA in US obese women [
27], our study demonstrated that insufficient rate of GWG was associated with SGA among women who were prepregnancy underweight or normal weight rather than overweight/obese women. Differences in findings may be partly due to ethnicity disparities. Although factors associated with low GWG and high risk of SGA are largely unknown, several studies inferred that ethnicity, inflammation and preeclampsia might be risk factors for poor fetal growth [
28].
The positive associations of prepregnancy BMI and rate of GWG with increased risk of LGA have reported in different populations [
4,
6,
11,
26], which is in line with our study. A retrospective cohort study conducted in Taiwanese women also reported that overweight or obese women were at risk for LGA, compared with the women of normal weight, and GWG above the guideline was associated with higher rates of LGA [
4]. Another study also revealed that excess GWG was associated with a higher frequency of LGA in Japanese women [
6]. Similar to that reported by a recent systematic review and meta-analysis [
11], we also found the strongest association between insufficient rate of GWG and lower risk of LGA in underweight women. It might be partly explained by the association of baseline maternal BMI and GWG with changes in the hormonal milieu, including insulin resistance, suggested by animal studies [
29].
In addition, we also found that prepregnancy overweight/obesity was associated with an elevated risk of cesarean delivery, which was in accordance with the findings of previous studies [
6,
30‐
32]. The association between overweight/obese and increased risk of cesarean delivery might partly due to excess pelvic soft tissue which can lead to a relative obstruction of the birth canal, and decreased rates of cervical dilation and subsequent increased rate of inductions after labor had started [
31,
33]. However, the relationship between rate of GWG and cesarean delivery is still controversial. A prospective cohort study conducted in the Netherlands reported that 1st trimester rate of GWG increased odds of cesarean delivery (OR = 1.19, 95% CI 1.10–1.29), while rate of 2nd and 3rd trimester GWG was not associated with cesarean delivery [
30]. Another retrospective cohort study among Hispanic women indicated that rate of GWG in the 3rd trimester was associated with a 1.24 odds of cesarean delivery, whereas excessive rate of GWG in the 1st and 2nd trimester was not associated with higher risk of cesarean delivery [
31]. In the current study, we observed that rate of GWG in the 2nd and 3rd trimesters was associated with increased risk of cesarean delivery. Prior studies indicated that excessive GWG might contribute to risk of cesarean delivery through an increase in child birth weight, and an elevated rate of preeclampsia independent of prepregnancy BMI [
31,
33].
The main strengths of this study include a relatively large sample size, using rate of GWG in the 2nd and 3rd trimesters to control for the effect of length of pregnancy on pregnancy outcomes, adjusting for potential confounding factors comprehensively, and utilizing RCS analysis to assess dose-response relationships of GWG rate with adverse pregnancy outcomes. Our study has several limitations. First, our data included only Chinese Han population, and it is unclear whether the results can be extrapolated to women of other ethnic groups. Second, we did not record GWG for different trimesters of pregnancy, so we were unable to examine associations of pregnancy outcomes with rate of GWG in different trimesters. Finally, we did not differentiate spontaneous and induced preterm birth, and did not distinguish between emergency and elective cesarean deliveries.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.