Associations between gestational weight gain and adverse neonatal outcomes: a comparison between the US and the Chinese guidelines in Chinese women with twin pregnancies

Background Appropriate gestational weight gain (GWG) is essential for maternal and fetal health. For twin pregnancies among Caucasian women, the Institute of Medicine (IOM) guidelines can be used to monitor and guide GWG. We aimed to externally validate and compare the IOM guidelines and the recently released guidelines for Chinese women with twin pregnancies regarding the applicability of their recommendations on total GWG (TGWG). Method A retrospective cohort study of 1534 women who were aged 18–45 years and gave birth to twins at ≥ 26 gestational weeks between October 2016 and June 2020 was conducted in Guangzhou, China. Women's TGWG was categorized into inadequate, optimal, and excess per the IOM and the Chinese guidelines. Multivariable generalized estimating equations logistic regression was used to estimate the risk associations between TGWG categories and adverse neonatal outcomes. Cohen’s Kappa coefficient was calculated to evaluate the agreement between the IOM and the Chinese guidelines. Results Defined by either the IOM or the Chinese guidelines, women with inadequate TGWG, compared with those with optimal TGWG, demonstrated higher risks of small-for-gestational-age birth and neonatal jaundice, while women with excess TGWG had a higher risk of delivering large-for-gestational-age infants. The agreement between the two guidelines was relatively high (Kappa coefficient = 0.721). Compared with those in the optimal TGWG group by both sets of the guidelines, women classified into the optimal group by the Chinese guidelines but into the inadequate group by the IOM guidelines (n = 214) demonstrated a statistically non-significant increase in the risk of all the adverse neonatal outcomes combined. Conclusions The IOM and the Chinese guidelines are both applicable to Chinese women with twin pregnancies. Supplementary Information The online version contains supplementary material available at 10.1186/s12889-023-15008-z.


Background
Women pregnant with twins are at higher risks of adverse neonatal outcomes than women with singleton pregnancies [1][2][3]. Maternal gestational weight gain (GWG) is a valuable albeit simple indicator for newborn morbidities. However, recognition of abnormal GWG is a challenging task that requires reliable assessment tools.
National guidelines on TGWG for twin pregnancies have not been formulated in many Asian countries including China, although some regional guidelines based on less representative data have been made available [11,12]. Based on data from a regional but relatively large population, the recent Chinese guidelines recommend TGWG of 18.0-26.0 kg for underweight women (PBMI < 18.5 kg/m 2 ), 15.0-25.0 kg for normal-weight women (PBMI 18.5-23.9 kg/m 2 , according to the Chinese criterion), 12.0-21.0 kg for overweight women (PBMI 24.0-27.9 kg/m 2 ), and 9.0-20.0 kg for obese women (PBMI ≥ 28.0 kg/m 2 ) [11]. It is apparent that the Chinese guidelines tend to recommend lower TGWG than do the IOM guidelines, and this is particularly the case for women who would be categorized into different PBMI groups by the inconsistent PBMI cut-offs. It is also notable that the Chinese guidelines include a recommendation for underweight women.
At this stage, it is important to validate and compare the IOM and the Chinese guidelines, which will facilitate decision-making on which guidelines to choose. Here, we reported a retrospective cohort study that was conducted particularly for this purpose.

Study design and data source
A retrospective cohort study was designed to include all women who gave birth to twins between October 2016 and June 2020 in Guangzhou Women and Children's Medical Center, a tertiary medical facility in South China.
Information on demographics, reproductive history, and maternal and neonatal factors relative to the current pregnancies was retrieved from clinical records. Eligible women were those who were aged 18 − 45 years and gave birth to twins at ≥ 26 gestational weeks during the five-year period (n = 1927). Women who delivered stillbirths or births with congenital anomalies (n = 145) were excluded. Women with missing data on the following key variables were excluded: body height, prepregnancy body weight, pre-delivery body weight, and other confounding factors including maternal age, gravidity, parity, historical cesarean section, education level, use of assisted reproductive technology (ART), twin type, pre-existing diabetes/hypertension, gestational diabetes mellitus (GDM), gestational hypertension, and family history of diabetes/ hypertension. These exclusion criteria eventually led to a final cohort of 1534 women for analysis ( Fig. 1).

Ascertainment of total gestational weight gain and adverse neonatal outcomes
Maternal prepregnancy body weight was self-reported at the first prenatal care visit. If possible, missing values on prepregnancy body weight were substituted with body weight measured in the first 12 weeks of gestation. Predelivery body weight was recorded at the admission for hospital delivery. TGWG was calculated as the difference between pre-delivery and prepregnancy body weights. In accordance with the IOM guidelines, we categorized women into inadequate, optimal, and excess TGWG groups. The same groups were formed again using the Chinese guidelines.
This study considered the following adverse neonatal outcomes: small for gestational age (SGA), large for gestational age (LGA), respiratory distress syndrome, neonatal jaundice, and NICU admission. Nationwide surveillance data were used to identify SGA and LGA, which referred to birth weight below the 10th and above the 90th percentile references, respectively [13]. Respiratory distress syndrome was defined as the presence of one of the following signs: tachypnea (respiratory rate > 60 breaths/minute), grunting, nasal flaring, or intercostal retraction [14]. Neonatal Jaundice was diagnosed following the criteria of National Institute for Health and Care Excellence [15].

Statistical analysis
Maternal and neonatal characteristics were described using median and inter-quartile range (IQR) for continuous variables and frequency for categorical variables. Multivariable logistic regressions based on general estimated equations (GEE) were used to estimate the adjusted odds ratios (aORs) of adverse neonatal outcomes for inadequate and excess vs. optimal TGWG after controlling for maternal age, gestational age, PBMI, gravidity, parity, historical cesarean section, educational level, use of ART, twin type, pre-existing diabetes/hypertension, GDM, gestational hypertension, and family history of diabetes/hypertension. Cohen's Kappa coefficient was calculated to evaluate the agreement between the IOM and the Chinse guidelines. Two-sided P-value < 0.05 was considered statistically significant. All the statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria).

Results
The characteristics of the study population are summarized in Table 1. The median maternal age was 31.0 years (IQR 29.0-34.0). A majority of women (85.3%) had a college degree. Nulliparous and primigravid women accounted for 61.0% and 44.3% of the study population, respectively. The prevalence of prepregnancy underweight, normal weight, overweight, and obesity, as defined by Chinese BMI criteria, was 16.0%, 67.5%, 12.9%, and 3.6%, respectively. More than half (54.2%) of women conceived via ART. About 37.7% of parous women had historical cesarean section, 15.4% had family history of diabetes mellitus/hypertension, 1.9% had preexisting diabetes mellitus/hypertension, 24.6% had GDM and 16.5% had gestational hypertension. A majority of women (93.9%) chose cesarean section. The percentages of dichorionic, monochorionic-diamniotic, monoamniotic twin pregnancies were 74.2%, 25.4% and 0.5%, respectively. The median gestational age at delivery was 37.0 weeks (IQR: 35.0-37.0). Of the 3068 twin infants, 1609 (52.4%) were male. We further stratified the study population into inadequate, optimal, and excess TGWG groups using the IOM and the Chinese guidelines and reported their characteristics in Table S1.
Risk associations between TGWG categories and adverse neonatal outcomes are presented in Table 2. Defined by either IOM or the Chinese guidelines, inadequate TGWG, as compared with the optimal TGWG, was associated with statistically significantly increased risks of SGA (aOR CHN Table S2, exclusion of underweight women (n = 245) for the Chinese guidelines did not change the statistical significance of the associations of inadequate Further comparison between the IOM and the Chinese guidelines was made by cross-classifying the TGWG using the two sets of the guidelines after excluding underweight women. Among the remaining 1289 women, a total of 1064 (82.5%) women were classified into the same categories by both sets of the guidelines(Kappa coefficient = 0.721, 95% CI: 0.687-0.755). Two hundred and fourteen (16.6%) women were classified into the optimal group by the Chinese guidelines but into the inadequate group by the IOM guidelines ( Table 3). As shown in Table 4, compared with women in the optimal TGWG group by both sets of the guidelines, those in the optimal group by the Chinese guidelines but in the inadequate group by the IOM guidelines demonstrated a statistically significantly decreased LGA risk (aOR = 0.51, 95% CI: 0.26-0.99) but no statistically significant difference in the risk of any adverse neonatal outcome (aOR = 1.06, 95% CI: 0.81-1.40).

Discussion
In this retrospective cohort study of Chinese women with twin pregnancies, inadequate/excess TGWG identified by either the IOM or the Chinese guidelines, compared with the optimal TGWG, demonstrated statistically significantly higher risks of adverse neonatal outcomes. Inadequate TGWG according to either set of the guidelines was associated with increased risks of SGA birth and neonatal jaundice, while excess TGWG according to either set of the guidelines was associated with an increased risk of LGA birth. The agreement between the two sets of the guidelines was relatively high (Kappa coefficient = 0.721). Compared with women in the optimal TGWG group by both sets of the guidelines, women in the optimal by the Chinese guidelines but in the inadequate group by the IOM guidelines demonstrated no statistically significant difference in the risk for any adverse neonatal outcome studied.
The association between inappropriate TGWG and adverse neonatal outcomes among twin pregnancies in our study confirmed previous findings. The study of Guan, et al. showed that excess TGWG by IOM references was related to a higher risk of LGA, and inadequate TGWG was associated with increased risks of SGA [16].   A larger cohort study of twin pregnancies in China suggested that inadequate TGWG according to the IOM references was associated with higher risk of SGA in all PBMI groups [11]. The Chinese guidelines we investigated in the present study recommend lower TGWGs than do the IOM guidelines for North American women. Similarly, two studies among Japanese women also recommended lower TGWGs [9,12]. This discrepancy may be explained by the ethnical difference in body size ─ Asian women are relatively short and slim compared with Caucasian women. Chinese women with optimal TGWG according to the Chinese guidelines could be classified as inadequate TGWG by the IOM guidelines because of this discrepancy, and these women accounted for 16.6% of our study population. Additionally, the IOM guidelines for twin pregnancies do not specify the optimal TGWG for underweight women due to lack of data [17]. In China, the prevalence of underweight before pregnancy was estimated to be 12%-17% [11,18,19]. In the present study, 16.0% of women were underweight before pregnancy, highlighting the need to determine the optimal TGWG for these women.
The relatively high agreement between the IOM and the Chinese guidelines and their similar associations with adverse neonatal outcomes suggest that the IOM guidelines are applicable to Chinese twin pregnancies. However, compared with those who were classified as optimal TGWG by both sets of the guidelines, women whose TGWG was classified as optimal by the Chinese guidelines but inadequate by the IOM guidelines did not have an increased risk of any adverse neonatal outcome, suggesting that the Chinese guidelines might be more suitable for Chinese women with twin pregnancies.
The present study was not designed to analyze the association between inappropriate TGWG and maternal prepartum complications such as GDM and preeclampsia. Although some of the previous studies have Table 2 Adjusted risk associations of neonatal outcomes for women with inadequate or excess TGWG vs. women with optimal TGWG, as defined by the Chinese or the IOM guidelines Abbreviations: aOR adjusted odds ratio, ART assisted reproductive technology, CI confidence interval, GDM gestational diabetes mellitus, IOM Institute of Medicine, LGA large for gestational age, NICU neonatal intensive care unit, PBMI prepregnancy body mass index, SGA small for gestational age, TGWG total gestational weight gain a Any adverse outcome was defined as the presence of one or more of the following neonatal outcomes: SGA, LGA, respiratory distress syndrome, neonatal jaundice, and NICU admission b Optimal TGWG was used as the reference c All the models adjusted for the priori defined confounders, including maternal age, gestational age, maternal PBMI, parity, gravidity, education level, twin type, use of ART, historical cesarean section, family history of diabetes mellitus/hypertension, pre-existing diabetes mellitus/hypertension, GDM and gestational hypertension