Examining the effects of second-and third-trimester gestational weight gain rates on the perinatal outcomes among Chinese twin pregnancies: a retrospective cohort study

Gestational weight gain (GWG) is an important indicator for assessing the nutritional status of pregnant women and is closely related to foetal growth and health [1, 2]. Excessive or inadequate weight gain during pregnancy can affect the short- and long-term health of the mother and foetus. Both excessive and inadequate weight gain during pregnancy are associated with adverse pregnancy outcomes. Studies have shown that excessive GWG increases the risk of hypertensive disorders of pregnancy, gestational diabetes, macrosomia, large for gestational age, and caesarean section and even affects the future growth trajectory of the child, with consequences including childhood and adolescent obesity, while inadequate weight gain during pregnancy increases the risk of miscarriage, premature delivery, foetal growth restriction and stillbirth [3‐6]. The Institute of Medicine (IOM) published guidelines on appropriate weight gain ranges during pregnancy in 1990 and revised them in 2009 to establish appropriate weight gain ranges for singleton pregnancies and temporary weight gain ranges for twins based on pre-pregnancy body mass index [1]. The revised guidelines included recommended rates of 2^nd and 3^rdtrimester weight gain in pounds per week for singleton pregnancies but not for twin pregnancies. Compared with singleton pregnancies, twin pregnancies have attracted much attention due to their more complex physiological characteristics and higher incidence of adverse pregnancy outcomes. Numerous studies have been devoted to the study of GWG in twin pregnancies to explore the applicability of the IOM recommendations for twin pregnancies in China, but no consensus has been reached. GWG and adverse events in twin pregnancies are often confounded by the length of gestation. Most studies mainly focus on total weight gain throughout pregnancy, while relatively few studies have been devoted to the relationship between weight gain rates in different trimesters and pregnancy outcomes. It has been clinically observed that GWG is not linear throughout pregnancy, with slower increases in the 1^st trimester and a more uniform rate in the 2^nd and 3^rd trimesters [7]. Therefore, this study aimed to assess the effect of second- and third-trimester rates of GWG on maternal and neonatal outcomes using the 2009 revised IOM guidelines for twin pregnancies. Due to sample size limitations, only the women with twin pregnancies and a normal pre-pregnancy body mass index (BMI) were analysed in this study.

A total of 2399 pregnant women received perinatal care and delivered twins at the Fujian Maternity and Child Health Hospital during the study period from 2014 to 2018. Of these, there were 1226 pregnant women with normal weight. We excluded 29 women as a result of maternal age < 18 or > 45 years, pre-existing diabetes (n = 14), chronic hypertension (n = 5), gestational age under 20 weeks (n = 20),multiple gestations (n = 6), stillbirth of one twin (n = 31), and missing records of gestational age, pre-pregnancy weight or height, or delivery weight (n = 190). There were 931 pregnant women and 1862 infants included (Fig. 1).

The majority of twin-pregnant women in this study had 2^nd and 3^rdtrimester rates of weight gain within the IOM recommendations. That is, 54.3% of women had estimated 2^nd and 3^rd trimester rates of weight gain meeting the recommended rates, 25.9% of women had weight gain less than the recommended rates, and 19.8% of women had rates greater than the recommended rates. Table 1 shows the differences in the baseline characteristics among the three groups. The average maternal age was 30.1 ± 4.3 years, pre-pregnancy BMI was 21.1 ± 1.6, height was 160.4 ± 5.1 cm, and the mean number of years of education was 12.6 ± 3.3 years. Significant differences were found for age, pre-pregnancy BMI, height, and years of education among women with weekly rates of GWG in the 2^nd and 3^rd trimesters less than, within and greater than recommended rates (P < 0.05). There were no significant differences among the three groups in the proportions of nulliparity, monochorionic membrane or infant sex. The gestational age and average birth weight of the infants were significantly different between any two groups(P < 0.001). Women who were excluded from this study due to missing information had similar baseline characteristics as those included (data not shown).

It has been reported that the incidence of twin pregnancies has been increasing worldwide with the changing concept of fertility and the development and popularization of assisted reproductive technology. The fact that twin pregnancies are more complex physiological processes than singleton pregnancies [13], coupled with the importance of the impact of GWG on perinatal outcomes, makes it important to examine the recommendations of the IOM guidelines on pregnancy outcomes. Previous studies have focused mainly on the effect of total GWG on pregnancy outcomes, in which gestational age may be a major confounding factor. One study found that total GWG was positively correlated with pregnancy length in all BMI groups [14]. That is, women with shorter gestational ages had a shorter timeframe to gain weight and may suffer adverse pregnancy outcomes such as preterm birth, which may lead to false correlations between GWG and pregnancy outcomes [15]. To this end, we introduced weight gain rates as study variables to evaluate the associations between GWG rates in the 2^nd and 3^rdtrimesters and perinatal outcomes among Chinese twin gestations. The 2009 IOM recommended an appropriate weight gain rate for singleton pregnancies in the 2^nd and 3^rdtrimesters of pregnancy, but there was no clear recommendation for twin pregnancies, so our study was of some value for the recommendation of weight gain rates for twin pregnancies in the 2^nd and 3^rdtrimesters of pregnancy.

In this retrospective study, the findings showed that maternal and neonatal outcomes were affected by the rate of 2^nd and 3^rd trimester weight gain. We found that a weight gain rate greater than the recommendations in the 2^nd trimester was associated with a decreased risk of preeclampsia, while the weight gain rate in the 3^rd trimester directly affected the incidence of adverse pregnancy outcomes. On the one hand, a weight gain rate in the 3^rd trimester below the recommendations was associated with significant increases in gestational diabetes mellitus, intrahepatic cholestasis syndrome, pre-labour rupture of membranes, average twin birth weight < 2500 g, neonatal respiratory distress syndrome and a lower rate of caesarean section and preeclampsia. On the other hand, a weight gain rate in the 3^rd trimester greater than the recommendations was associated with a higher rate of gestational hypertension and premature delivery and preeclampsia. Previous studies have demonstrated that inadequate weight gain during pregnancy was a risk factor for preterm birth, and our results suggested that a low or high weight gain rate in the 3^rd trimester was related to an increased risk of preterm birth. The results of the study by Carnero A M et al. [16] and Shamshirsaz AA et al. [17] also showed that both very low and very high weight gain rates were associated with an increased incidence of premature delivery [16]. This finding may also be a reason why many international studies are now questioning the current IOM guidelines for twin pregnancies. Notably, in our study, we found that a low weight gain rate in the 3^rd trimester was associated with an increased incidence of gestational diabetes mellitus, which may be contrary to clinical findings. The conflicting results could be due to medical nutritional therapy guidance and intervention by obstetricians based on their experience in managing the nutritional status of pregnant women who were gaining too much weight or who had been diagnosed with gestational diabetes mellitus. These pregnant women adhered to a strict diet and increased their exercise habits, ultimately resulting in a low weight gain rate in the 3^rd trimester or even weight gain rates below the guideline recommended range. Conversely, women who were not diagnosed with gestational diabetes mellitus may be less likely to follow a diet or exercise programme, which could lead to more weight gain. This result was similar to the findings of domestic and foreign academics who noted decreased odds of gestational diabetes mellitus in women with excessive rates of weight gain and increased odds of gestational diabetes mellitus in women with suboptimal rates of weight gain in the 2^nd trimester and 3^rd trimester, due to the nutritional counselling and dietary adjustments that occur after such a diagnosis and the consequent effect on gestational weight gain [18, 19]. In addition, it has been reported that excessive weight gain in the 1^st trimester was related to an increased risk of gestational diabetes mellitus, regardless of pre-pregnancy weight [20]. We did not consider weight gain in the 1^st trimester, which may lead to an inconsistency between our findings and those of some studies [21].These inconsistencies also suggest that we should not neglect weight management in the 1^st trimester of pregnancy.

In this study, we found a higher incidence of neonatal respiratory distress syndrome, average twin birth weight < 2500 g and intrahepatic cholestasis syndrome in pregnant women whose weight gain rate in the 3^rd trimester was below the recommendations. We considered that neonatal respiratory distress syndrome may be a secondary association with preterm birth. There are few studies on the symptoms of intrahepatic cholestasis and gestational weight gain, and our results suggested a statistical association; however, the causal association may need to be fully understood, as it has been shown that intrahepatic cholestasis leads to a loss of appetite and nausea, which may have an impact on gestational weight gain, implying that cholestasis may be the cause of lower rates of weight gain rather than lower rates of GWG being the cause of cholestasis. Further studies should be conducted with detailed data on GWG and the timing of signs or symptoms to understand the cause and consequence [22].

For gestational hypertensive disorders, our findings showed that a weight gain rate greater than the recommendation was associated with lower odds of preeclampsia in the 2^nd trimester and higher odds of gestational hypertension and preeclampsia in the 3^rd trimester. Luke B’s research showed no difference in the weight gain rate in the first half of pregnancy between pregnant women diagnosed with preeclampsia and those without preeclampsia in the second half of pregnancy [23]. The reason for these inconsistencies might be our limited sample size and the limitations of a single-centre study. Domestic and foreign academics have also not reached consensus on the relationship between weight gain in twin pregnancies and hypertensive disorders of pregnancy due to confusion regarding whether weight gain was the cause of or the result of preeclampsia. It may be that pregnancy comorbidities may affect gestational weight gain [14, 24, 25]; for example, gestational diabetes and preeclampsia affect total weight gain during pregnancy [26, 27].

Maternal weight gain in the second half of pregnancy was mainly associated with an increase in foetal weight and placental factors and an increase in maternal body weight and was most closely related to the growth and development of the foetus, especially in the 2^nd trimester [28]. In this study, weight gain in the 2^nd trimester had little effect on perinatal outcomes and no statistically significant difference was found on perinatal outcomes when stratifying 3^rd trimester weekly weight gain less than or greater than the IOM recommendations by weekly weight gain greater than, within or less than IOM recommendations in the 2^nd trimester. The finding may be explained as follows: first, by the difference in study population as we included women with a normal pre-pregnancy body mass index due to sample size limitations; second, our use of an assumed average weight gain in the 1^st trimester may have resulted in misclassification of exposure, biasing associations toward the null; and third, by other differences that may have been due to the more complex physiological changes that occur in twin pregnancy, which cannot be explained reasonably at present, as further exploration is needed to clarify the mechanisms of physiological changes in twin pregnancy. Even so, physicians should be encouraged to address weight gain throughout the pregnancy and intervene in cases where weight gain falls outside of recommendations.

There were some limitations in this study. First, it was a retrospective study, and it was impossible to consider all potential confounding variables, such as the use of assisted reproductive technology, race/ethnicity of pregnant women, and tobacco use, which may lead to confounding bias. The study data were drawn from data of women with twin pregnancies receiving perinatal care at one hospital, possibly leading to poor representation of the general population. Second, the limited sample size led to limitations in analysing underweight, overweight, and obese women, and the small sample size might result instatistically significant differences in demographic characteristics. Additionally, as the weight gain in twin pregnancies was not linear [29], we were unable to eliminate the correlation between pregnancy length and total weight gain by calculating the weight gain rates [30]. Therefore, our computational approach may introduce some bias, and thus, our study may not be sufficient to assess the associations of certain outcomes.

Future prospective and multicentre studies are warranted. All pregnant women received similar prenatal care and monitoring, which reduces the possibility of sampling bias and contributes to the generalizability of the results, thus clarifying the trajectory of weight gain in twin pregnancies and making the findings more clinically useful.

In summary, suboptimal and excessive rates of 2^nd and 3^rd trimester gestational weight gain were associated with adverse pregnancy outcomes in normal weight women, especially in the 3^rd trimester. Our findings are useful to help obstetricians understand the key periods of maternal weight gain and provide clinical recommendations to anticipate perinatal outcomes of twin pregnancies. Further prospective and multicentre studies are required to explore alternate ranges of GWG rates in twin pregnancies to reduce adverse perinatal outcomes.