Impact of Gestational Weight Gain on Perinatal Outcomes:Appropriateness of IOM Recommendations in Mainland China

Abstract The study was conducted to evaluate the clinical feasibility of Institute of Medicine (IOM) recommendations on gestational weight gain (GWG) in mainland China. 88,297 singleton pregnancies from a nationwide birth registry study were included. GWG per week was calculated and grouped into within, below and above IOM (IOM) guidelines based on rst trimester Chinese body weight index (BMI) status. Univariable and multivariable analyses were performed to determine the relationship between GWG category and perinatal outcomes. We found that excessive GWG was associated with increased risk in pregnancy induced hypertensive disorders (aOR 2.41, 95%CI 2.16-2.69), cesarean section (aOR 1.55, 95%CI 1.47–1.63 for nulliparas, aOR 1.51, 95%CI 1.38–1.65 for multiparas with no prior cesarean section), severe postpartum hemorrhage (aOR 1.15, 95%CI 1.06-1.26), large for gestational neonates (aOR1.76, 95%CI 1.69-1.85) and macrosomia (aOR 1.83, 95%CI 1.72-1.96), while inadequate GWG was correlated with higher risk in placenta abruption (aOR 1.54, 95%CI 1.29-1.85) , fetal distress (aOR 1.19, 95%CI 1.12-1.26), and small for gestational neonates (aOR 1.50, 95%CI 1.41-1.60). Either GWG above or below was associated with increased risk in preterm birth (aOR 1.48, 95%CI 1.38-1.58 for above, aOR 1.47, 95%CI 1.31–1.64 for below), and neonatal asphyxia (aOR 2.28, 95%CI 2.00-2.61 for above, aOR 1.42, 95%CI 1.25-1.61 for below). GWG within IOM recommendations may help prevent various adverse perinatal outcomes and seemed suitable in Chinese population.


Introduction
Inappropriate GWG has remained to be a pronounced problem in both Western and Eastern countries. 1,2,3 Insu cient weight gain has been linked with increased risk of poor fetal growth, 1,4 preterm birth, 1,5,6 and di culty in establishing breastfeeding. 7,8,9 While excessive GWG has been associated with a range of conditions, including gestational diabetes, 10,11 pregnancy-induced hypertension, 1,12,13,14 cesarean birth, 1,15,16 and macrosomia. 1,5,6,10 In 1970, the Institute of Medicine (IOM) reviewed the evidence concerning GWG that achieved optimal pregnancy outcomes, with revised versions published in 1990 and 2009. 17,18 The latest version examined the trade offs between maternal and neonatal outcomes and GWG. In consideration that GWG has found to be differed by maternal pre-pregnancy weight status, 19,20 the recommendations on GWG was based on WHO weight status criteria. 21,22 In Jan 2018, the national prenatal care guideline for Chinese women was o cially published, 23 it accepted the IOM recommendations for Chinese with little sample sized evidence and ignored the difference between Westerners and Chinese in BMI characteristics. 24 Chinese ethics possess a higher rate of body fat compared with Caucasian at the same BMI, 25,26 therefore BMI cutoffs of ≥24 for overweight and≥28 for obesity for Chinese population have been chosen based on the epidemiology evidence. 27 Under different weight status classi cation system, some Chinese women would be classi ed as lower weight status and assigned to larger GWG targets. The appropriateness of recommending the IOM GWG guidelines for Chinese should be evaluated by large population evidence. We aim to assess the suitability of generalizing the IOM recommendations using localized BMI category criteria through evaluating the association between IOM GWG category and perinatal outcomes.

Subjects
Our study was performed in compliance with the Declaration of Helsinki (as revised in 2013). The retrospective birth registry study protocol was approved by the Ethics Committee of Peking Union Medical College Hospital (reference number PUMCH-JS-1151) under a waiver of informed consent from individual patients. Data were abstracted from the nationwide multicenter birth registry study carried out in 14 representative medical centers (including 2 secondary and 12 tertiary, 7 general hospitals, and 7 maternal and child health care centers) from 10 provinces in the four major economic regions of China from October 1, 2016 to September 30, 2017, Specially assigned clinicians at each hospital were responsible for collecting and reporting information of pregnant women who delivered after 20 weeks of gestation. Complete medical information for each birth, including maternal demographics, medical and obstetrical history, maternal and perinatal outcome information were retrospectively registered into a prospectively designed network-based standardized data acquisition system depending on digital and written form of medical records. The data acquisition system was prospectively designed with clear and detailed eld de nition by information center of National Research for Family Planning Institute. The accuracy and validity of data entered were reviewed and veri ed by a second researcher on a monthly basis. Data entered into the data collection system were ultimately exported from the central network-based database system.
Only ethically Chinese women over 18 years old with a singleton pregnancy who gave birth at 24 or more completed weeks of gestation were included. Women were eligible if they had a height, weight at delivery and either self-reported or recorded rst trimester weight (11-14 gestational weeks), the later was mostly extracted from rst trimester aneuploidy screening reports. Those with extreme values were excluded from analysis (maternal age at delivery older than 60 years old, height outside a range of 120-200 cm, rst trimester weight lower than 25kg, GWG outside of a range of -25-50 kg). In this study, we have used rst trimester BMI instead of pre-pregnancy BMI, in consideration that there has no reliable source of pre-pregnancy weight since most women came to obstetric units only after they became pregnant. BMI (kg/m 2 ) was calculated as the ratio of the weight (kg) at rst trimester divided by height squared (m 2 ). GWG was calculated by weight before delivery minus weight recorded at rst-trimester. In order to account for gestational age at delivery, we use average GWG per week for the second and the third trimester instead of total GWG. The WHO weight status criteria, the corresponding Chinese version and the associated IOM recommended GWG per week for the second and third trimester are listed in table1. but not evaluated as outcomes due to the nutritional counseling and dietary adjustments that occur after such a diagnosis and the consequent effect on GWG. Neonatal outcomes included, preterm birth (PTB), large for gestational age and small for gestational age (LGA and SGA) de ned as birthweight above or below the 90th and 10th centiles of our local population standard chart after adjusting for gender and gestation, 29 macrosomia (birth weight greater than 4000 g), fetal distress was de ned as either meconium stained amniotic uid or persistent abnormal fetal heart rate, and newborn asphyxia de ned as a postnatal Apgar score lower than 7 at ve minute after birth. Preterm birth was considered for medically-indicated PTB and spontaneous PTB (sPTB), the later was further subdivided by whether premature rupture of membrane has occurred, namely, preterm premature rupture of membranes (PPROM) and sPTB without PROM.

Statistical analyses
Maternal demographics and characteristics were assessed and compared between individuals in different GWG categories using the Kruskal-Wallis test for continuous variables and the chi-square test for categorical variables. A multivariate logistic regression of the GWG categories and other variables was performed to estimate the adjusted odds ratio (OR) with 95% CI intervals of the maternal adverse outcomes and neonatal adverse outcomes whereby "within" IOM recommendation was reference. Multinomial logistics for analysis for the risk of each subgroup of preterm birth. Covariates included maternal age, conception method, parity, previous cesarean section, gestational diabetes, pre-gestational diabetes and chronic hypertension. Two-sided test alpha=0.05. Missing values processed censoring. All data analyses were performed using R version 4.0.2 (2020-06-22).

Results
A total of 99,960 women having delivery at or more than 20 completed weeks of gestation were identi ed in the national birth registry database, those non ethically Chinese, with missing data or implausible data concerning GWG or twin pregnancy were excluded. A total of 88,297 singleton pregnancies were therefore available for nal analysis, only 0.2% of them presented in labor without prenatal care. Figure 1 Figure 2b and Figure 3b ) Abbreviations: OR,odds ratio; CI, Confidence interval; PROM, Premature rupture of membrane; LGA, large for gestational age; SGA, small for gestational age.
The analysis was adjusted for maternal age, parity, conception method, chronic hypertension, prior cesarean section, pregestational diabetes, and gestational diabetes.
The bolded values indicate statistical significance.

Discussion
In this analysis of 88,297 singleton pregnancies, we found associations between not achieving gestational weight gain goals recommended by IOM and several adverse maternal and neonatal outcomes including cesarean birth, PROM, PIH, postpartum hemorrhage, PTB, LGA, SGA, macrosomia, fetal distress and newborn asphyxia.
Our ndings corresponds to other studies including a recent meta analysis of GWG and pregnancy outcomes that included 1,309,136 women. 1 Speci cally, the study showed that insu cient GWG was related to SGA (OR  16 However, we found in our study that the impact of excessive GWG on the risk of PIH in Chinese seems to be larger than in the Westerners (aOR 2.44, 95%CI 2.26-2.64), and the prevalence of GDM was 12.7%. Although it is not possible to perform statistical comparison based on these gures. As it is well known that body fat percentage in Chinese is higher than that in Caucasian at the same GWG category, the metabolic mechanism leading to PIH and GDM may manifest that a lower cutoff at 24 kg/m 2 for de ning overweight and 28 kg/m 2 for de ning obese in Chinese would be more applicable for risk assessment.
In addition to common perinatal outcomes associated with poor GWG control and well described in previous studies, we also explored the possible relationship with premature rupture of membrane (PROM) and placenta abruption. In particular, inadequate GWG was associated with higher risk in PROM (aOR 1.15, 95%CI 1.11-1.20) and placenta abruption (aOR 1.54, 95%CI 1.29-1.85), indicating that nutritional factors or underlying social economic factors may play a role in the pathogenesis of these conditions. 30 Considerably fewer studies have evaluated the speci c correlation between GWG and preterm birth subgroup (medically-indicated PTB, PPROM and sPTB without PROM) and gestational week distribution. 31,32,33 In our study, we found that excessive GWG had greater in uence on total PTB than insu cient GWG (aOR 1.  37 the author managed to develop GWG charts of Chinese women based on the same BMI classi cation system in our study, and found that the IOM recommended ranges fell within the 25th and 75th percentiles for underweight and normal weight women but fell below the 50th percentile for overweight and obese women. Neither aforementioned studies included data relating to postpartum outcomes. Elevating the upper limit of the GWG ranges may lead to long-term adverse outcomes, including postpartum weight retention childhood obesity, and adolescent cardiometabolic risk. 38,39,40,41 Nonetheless, a meta-analysis of Westerners from 25 pooled cohort studies including 196,670 participants revealed that GWG ranges associated with the lowest risks for any adverse outcome were roughly comparable with the IOM ranges for underweight, normal weight, and overweight, and were lower for all obesity grades. 42 A cohort study, the INTERGROWTH-21st Project, 43 reported that the weight gain pattern in normal weight women who came from eight geographically diverse urban areas, including China, was strikingly similar, indicates that separate GWG charts for women from different racial groups are not necessary. The researchers speculating that the racial differences reported are more likely caused by social economical or lifestyle factors than true biological differences in nutrient absorption among uncomplicated women. 44,45,46 Until now, the IOM recommendations was well-accepted in China, Our data showed that GWG within IOM recommendations may help prevent various adverse perinatal outcomes. Given the risks of a GWG outside of the IOM recommendations, as documented in this population based study whereby only 44.1% of women achieved a optimal GWG targets. Appropriate management of GWG, by way of lifestyle instructions in diet, exercise and other health behaviours, 47 will assists in promoting maternal and neonatal health.
This study has several limitations. First, the analyses did not account for potential confounding factors, such as medical insurance type or hospital type. Second, rst trimester pregnancy BMI, instead of pre-pregnancy BMI, was used to classify women. This introduces the possibility of mis-classi cation bias. We did not assume that women gained a standard weight during rst trimester which ignored individual difference.
However, it is not feasible to measure the pre-pregnancy weight in clinical practise and self-reported prepregnancy weight is generally unreliable. Noted strengths included prospectively designed and well de ned net-work based data acquisition system with detailed information on perinatal outcomes. The sample size was the largest concerning Chinese ethics before submission and spanned the four main ecnomic zones of China and is representative. With rigorous ascertainment of outcomes and calculation of GWG to account for the duration of pregnancy. The results presented as incidence rates and adjusted odds ratio is readily for clinical counseling.

Conclusion
Inadequate and excessive GWG both remained to be a big issue in Chinese pregnant population, IOM guidelines is applicable in predicting adverse outcomes and maintaining appropriate GWG is essential in preventing adverse maternal and neonatal outcomes.