The Effects of Pre-Pregnancy Body Mass Index and Weight Gain During Pregnancy on Perinatal Outcomes: A Retrospective Cohort Study

OBJECTIVE: To investigate the effects of pre-pregnancy body mass index and weight gain during pregnancy on perinatal outcomes and delivery mode. STUDY DESIGN: In this retrospective cohort study, 722 pregnant women giving birth between 2018-2019 were screened from our hospital database. First, they were divided into four groups according to their prepregnancy body mass index (low-weight/normal-weight/overweight/obese), and then they were redivided into three groups according to pregnancy weight gain (≤7/8-15/≥16 kg). Prenatal body mass index and pregnancy weight gain were compared concerning maternal-neonatal results and mode of delivery. RESULTS: According to pre-pregnancy body mass index, among the obese pregnant group, gestational diabetes mellitus (p<0.001), preeclampsia (p=0.029), preterm delivery (p=0.011) and cesarean delivery (p=0.061) rates were more common. As the body mass index increases, neonatal intensive care requirement (p=0.0020) and low 1st minute APGAR scores (p=0.019) were detected more frequently. However, as pregnancy weight gain decreased, preterm delivery (p=0.041) increased. Also, birth weight increased (p<0.001) with the weight gain of the pregnant. Pregnant women gaining more than 16 kg were associated either with a lower <2500 g or a higher birth weight risk >4000 g. CONCLUSION: Pre-pregnancy high body mass index is associated with negative obstetric outcomes like gestational diabetes, preeclampsia, preterm delivery, and increased cesarean rates, and poor fetal incidences with a low APGAR score and high neonatal intensive care admission rates.

many complications during pregnancy, especially gestational diabetes and preeclampsia, and are more likely to have a cesarean delivery (1). Excessive pregnancy weight gain may have similar effects, and may affect the ability of the mother's weight loss and the risk of obesity after childbirth, and may have negative effects on her long-term health (2). The longterm effects of maternal obesity and excessive gestational weight gain on a newborn are also of concern. On the other hand, women who are below normal weight when they become pregnant and have inadequate gestational weight gain are at an increased risk for a small birth of the gestational week, which may have both short and long-term results (3).

Introduction
Both pre-pregnancy body mass index (BMI) and gestational weight gain may affect maternal and neonatal outcomes. For example, obese women have an increased risk of In another study on the impacts of gestational weight on pregnancy outcome, data analysis revealed that obese women with low gestational weight gain had a decreased risk for preeclampsia, cesarean section, instrumental delivery, and large for gestational age (LGA) births. There was a 2-fold increased risk for preeclampsia and LGA infants among average and overweight women with excessive weight gain and high gestational weight gain increased the risk for cesarean delivery in all maternal BMI categorization (3).
The present study aimed to investigate the effects of prepregnancy BMI and weight gain during pregnancy on perinatal outcomes and mode of delivery.

Materials and Methods
This retrospective cohort study was conducted between October 2018 and March 2019 in the Gynecology and Obstetrics Clinic of Karabuk University Training and Research Hospital of the Ministry of Health. This study was approved by the local ethics committee of Karabuk University (Ref. No:2020-189). Women with singleton pregnancies who gave birth in the delivery unit of our hospital were included in this study. Pregnant women without adequate records and medical history, births before 24 weeks, multiple pregnancies, pregnant women with severe systemic disease (e.g., diabetes mellitus, chronic hypertension, and chronic kidney failure) were excluded from this study. The records of 722 pregnant women who met these criteria were analyzed retrospectively. Pregnant women were divided into four groups according to the pre-pregnancy BMI; Group 1: Low weight (BMI: ≤18.49 kg/m²), Group 2: Normal weight (BMI: 18.5-24.99 kg/m²), Group 3: Overweight (BMI: [25][26][27][28][29].99 kg/m²), Group 4: obese (BMI: ≥ 30 kg/m²). The pregnant women were also divided into three groups according to the weight gain during pregnancy: Group A: weight gain of seven kg or less in, Group B: weight gain between eight and 15 kilograms, Group C: weight gain of 16 and over kilograms. The groups were compared concerning maternal demographic parameters, obstetric outcomes (preterm delivery, preeclampsia, gestational hypertension, gestational diabetes mellitus, oligohydramnios, and intrauterine growth restriction (IUGR)), and fetal outcomes (birth weight, APGAR scores of newborn babies, and neonatal intensive care admissions). Pregnant women who had a previous cesarean delivery (n=254) and who had cesarean delivery due to malpresentation (n=12) were not included in this subgroup to evaluate the risk of cesarean delivery objectively. The following adverse pregnancy outcomes were evaluated: gestational hypertension (blood pressure >140/90 mmHg on at least two occasions greater than six hours apart without evidence of chronic hypertension), preeclampsia (criteria for gestational hypertension and significant proteinuria), gestational diabetes (at least two abnormal values on the 100-g glucose tolerance test following an elevated 50-g glucose challenge test), preterm premature rupture of membranes (PPROM) (membrane rupture before37 weeks' gestation), preterm delivery (before 37 weeks gestation), IUGR (estimated fetal weight by ultrasound below the 10 th percentile or birth weight below the 10 th percentile for gestational age), birth weight greater than 4000 g, and birth weight less than 2500 g.
Minitab package program and R software were used to perform statistical analyses. Before group comparisons, the compatibility of variables to normal distribution was determined using the Anderson-Darling test. It was determined that the variables did not show normal distribution. To compare groups, the Mann-Whitney U test was used in binary group comparisons, and the Kruskal Wallis test was used in multiple group comparisons. Dunn test was used to determine the different group (or groups) after the Kruskal-Wallis H test. The Chi-Square test was used in the analysis of categorical data. Logistics stepwise regression analysis was performed to analyze the factors that may affect the delivery type. p<0.05 was used as a statistical significance level.

Results
Among 722 pregnant women included in this study, 105 (14.55%) were obese, 193 (26.73%) were overweight, 378 (52.35%) were normal weight, and 46 (6.37%) were in the low BMI group (Table I). Further classification revealed that 126 (17.45%) of the pregnant women gained <8kg, 423 (58.58%) gained 8-15kg and 173 (23.96%) gained 16 kg or more during pregnancy (Table II). The education level in the obese group was lower than the normal BMI group (being a high school and university graduate 34.27% vs. 57.67%). Obese and overweight women were a little older and their parity was higher than normal weight. As the BMI of the pregnancy increased, the mean weight gains during pregnancy decreased.
In obese pregnant group, gestational diabetes mellitus (p<0.001), preeclampsia (p=0.029), preterm delivery (p=0.011) and cesarean delivery (p=0.061) were more common. As the BMI increases, neonatal intensive care requirement (p=0.002) and low minute 1 APGAR score (p=0.019) were detected more frequently. There was no difference between groups concerning oligohydramnios and IUGR rates ( Table I). As weight gain decreased during pregnancy, preterm delivery (p=0.041) was found more frequently. As weight gain increased during pregnancy, birth weight increased (p<0.001), and pregnant women with weight gain above 16 kg (Group C) were associated with lower rates to have a newborn with a birth weight less than 2500 g. On the other hand, higher rates to have a newborn with a birth weight over 4000 g were more common, but the rates of cesarean, preeclampsia, gestational diabetes mellitus, oligohydramnios, and IUGR were similar (Table II). The logistic regression analysis was performed for the data that might affect the mode of delivery, and we found that the cesarean rates increased as the BMI increased (p=0.026).    Table III showed the results of the groups and subgroups grouped by pre-pregnancy BMI and weight gain during pregnancy, respectively. Preterm birth, gestational diabetes mellitus, preeclampsia, and 1st minute low APGAR score rates were insignificantly higher in Group 4C included patients who were obese and excessive weight gain during pregnancy (≥16 kg) than all other groups. In Group 2, pre-pregnancy normal weight group, the rate of preterm delivery increased as weight gain decreased during pregnancy (p=0.008) (Table III).

Discussion
Obesity is determined in women with BMI ≥30 kg/m 2 (9) and based on this cut-off value, different classes have been introduced to determine risk category as Class I (BMI 30.0 to 34.9 kg/m 2 ), class II (BMI 35.0 to 39.9 kg/m 2 ), and class III (BMI ≥40 kg/m 2 ). All these cut-off values and classifications were established for the non-pregnant population and do not adapt well to the pregnant population. Thus, it is crucial to consider pregnant women to be obese or non-obese based on their pre-pregnancy BMI. In our study, we assessed the impacts of both pre-pregnancy BMI and weight gain during pregnancy on perinatal outcomes to overcome inconsistency in the classification of BMI in pregnant women. Obesity was shown to be modestly increased the risk of early pregnancy loss. In a systematic review, including six retrospective studies, in 28,538 women (10), obesity was associated with the risk of miscarriage. Additional data confirmed this increased risk in this population and revealed that obese women with a history of recurrent miscarriage were at increased risk of future pregnancy loss compared with women with a normal BMI (11). However, both reviews had high heterogeneity for the included studies. Given that we aimed to assess both maternal and neonatal outcomes, we did not include pregnant women with early miscarriages. Another pregnancy complication that was mostly discussed in the literature is gestational diabetes. The risk of developing gestational diabetes mellitus (GDM) was significantly higher in obese women than in the general obstetric population (12,13), and this risk increased with increasing maternal weight and BMI (14,15). In a systematic review of studies on pre-pregnancy BMI and risk of GDM, the prevalence of GDM increased by 0.92 percent for every 1 kg/m2 increase in BMI (16). As we presented in our results, maternal BMI was also an independent risk factor for both preeclampsia and gestational hypertension (17)(18)(19)(20)(21)(22)(23). Consistently, a very well-organized systematic review of 13 cohort studies comprising nearly 1.4 million women revealed that the risk of preeclampsia doubled with each five to seven kg/m2 increase in pre-pregnancy BMI (20). In our study population, pre-pregnancy BMI was associated with preeclampsia.
Several pregnancy complications may lead to an iatrogenically increased rate of premature deliveries, and prematurity is the main risk factor for neonatal deaths. Pre-pregnancy obesity is also associated with hypertension, preeclampsia, and diabetes and indirectly increases the risk of medically indi-   cated preterm delivery. In a systematic review on this issue, overweight and obese women were at an increased risk of induced preterm birth compared with women of normal BMI (24). There is some evidence that pre-pregnancy obesity may also prolong pregnancy (25), but the mechanism has not been determined yet. Although obesity was shown to be a risk factor for prolonged labor, the duration of the second stage of labor did not appear to be affected by increasing BMI (26,27).
As a consequence of all these pregnancy complications, obesity was also a risk factor for both elective and emergency cesarean delivery (28). Obesity-related pregnancy complications, such as higher infant birth weight, increased frequency of preterm and post-term delivery, were reported to be major confounders for the excess risk of cesarean delivery (29).
The Committee on Nutritional Status during Pregnancy and Lactation of the Institute of Medicine analyzed all published data regarding the relationship between pre-pregnancy weight, weight gain during pregnancy, and pregnancy outcome. Based on that analysis, some recommendations have been introduced for healthy gestation (30). These recommendations aimed to prepare pregnant to deliver a term live-born infant with a birth weight between 3000 and 4000 g. Recommendations for gestational weight gain were established based on pre-pregnancy body mass index. Therefore, it was suggested that determining BMI before pregnancy should be an integral part of the physical examination of pregnant women. Studies have suggested that women with class II or III obesity might benefit from lower weight gain target ranges than women with class I obesity (31)(32)(33). In our study, we found negatively correlated pre-pregnancy BMI and weight gain during pregnancy.
Gestational weight gain above suggested values has been associated with an increased risk of macrosomia and large for gestational age (LGA) infants, a cesarean delivery (34), pregnancy-related hypertension (gestational hypertension, preeclampsia) (35)(36)(37)(38)(39), and gestational diabetes (40). A systematic review revealed that high gestational weight gain was associated with a lower risk of preterm birth and small for gestational age, higher risk of LGA and macrosomia, and cesarean delivery compared with women whose gestational weight gain within the recommended range (34).
In a recently published study conducted on the Turkish population, the authors showed that gestational mean weight gain was 10.7 kg in the group with gestational diabetes, whereas it was 7.9 kg in the control group. In this study, prepregnancy body weights were also significantly different between the two groups (72 kg vs. 60 kg, p<0.001). Predictive values of pre-pregnancy weight and gestational weight gains for gestational diabetes were well documented in this study; however, no data were presented regarding pregnancy complications and outcomes (41). Our study had a higher number of pregnant to evaluate these differences compared to that study.
There were also some limitations in our study. The retrospective nature of this study was the main limitation. We could not evaluate the other possible risk factors that might be associated with gestational diabetes and preeclampsia, such as family history and previous pregnancy outcomes. The patients were divided into subgroups according to their prepregnancy BMI and weight gain during pregnancy. The patient distribution between the subgroups was not similar. Additionally, the higher number of patients may be the strength of the current study.
In conclusion, pre-pregnancy high BMI is associated with negative obstetric outcomes, such as gestational diabetes, preeclampsia, preterm delivery and increased cesarean rates, and poor fetal outcomes with low APGAR score and high neonatal intensive care admission rate. The findings suggest that there is a strong relationship between weight gain during pregnancy and birth weight. It should be ensured that candidates who are overweight and obese should be directed to weight control by considering the risks of pregnancy and management should be individualized.