Adverse perinatal outcomes related to pregestational obesity or excessive weight gain in pregnancy

Introduction

Obesity is recognized as a multifactorial global epidemic disease. In almost all countries, it appears to be mainly attributed to factors such as sedentary lifestyle, inadequate diet, and consumption of ultra-processed foods [1], 2]. As the worldwide prevalence of obesity increases, the number of women being affected by the condition, particularly those of reproductive age, also increases significantly [3].

Obesity occurs in 25–30 % of pregnancies in Brazil. Notably, the incidence of pregestational obesity increased from 9.8 to 19.8 % between 2008 and 2018 [4]. According to some studies, the prevalence of excessive weight gain during pregnancy has been increasing, particularly from 34.2 % to 38.7 %during the same period [4], [5], [6], [7], [8]. Maternal obesity and excessive weight gain have also been reported to be associated with the onset of hypertension, development of gestational and type II diabetes mellitus, cardiovascular complications, thromboembolic events, cesarean deliveries, and surgical complications during labor [4], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20].

Women with obesity or excessive weight gain are more likely to give birth to children who are large for gestational age (LGA) or who have macrosomia, congenital malformations, low Apgar score, hypoglycemia, hospitalizations in the neonatal intensive care unit, and who may die [7], 12], 21].

Therefore, the present study aimed to evaluate adverse perinatal outcomes associated with pregestational obesity and excessive weight gain in pregnancy, both alone and in combination.

Subjects and methods

This retrospective cohort included women who had recently given birth and classified them into four groups based on their pregestational body mass index (BMI) and total weight gain during pregnancy. The study was conducted from August to December 2020 at the Darcy Vargas Maternity Hospital (MDV) in Joinville, Santa Catarina State, Brazil.

The study was conducted in accordance with the Declaration of Helsinki 1964 and approved by the institution’s Research Ethics Committee under Opinion No. 4.216.737 and Certificate of Presentation for Ethical Appraisal No. 325126260.0.0000.5363, in accordance with the Resolution No. 466/2012 of the Brazilian National Health Council. A feasibility statement was issued by the institution at which the data were collected. Informed consent was obtained from all individuals included in this study.

Live, single, full-term neonates without chromosomal or structural malformations in women over the age of 18 were included in the study. The exclusion criteria were those who did not consent to participate in the study, those who could not consent due to cognitive or language barriers, and those who were isolated in the postpartum period due to coronavirus disease 2019.

Data were collected using a structured questionnaire. Data regarding complementary and clinical diagnoses were obtained from prenatal care cards and medical records stored in the Micromed^® (MicromedS istemas, Joinville, Brazil) and Olostech^® (OlosTecnologia, Jaraguá do Sul, Brazil) software.

Data regarding pregestational weight (in kilograms) and height (in meters) were obtained from the prenatal care card up to 13 weeks of pregnancy, as recommended by the Brazilian Ministry of Health) [22].

For participants aged ≥20 years, BMI was calculated as follows: the weight of the participant in kilograms divided by the square of their height in meters. Further, it was classified according to the 2000 World Health Organization (WHO) guidelines. Conversely, the BMI of the participants aged<20 years was classified according to the 2007 WHO guidelines.

For calculating the total weight gain (in kilograms) during pregnancy, first, the weight at the end of hospitalization was obtained from the Emergency Department’s medical records; subsequently, the pregestational weight was subtracted from it. Further, the 2009 IOM guidelines were followed for the recommended weight gain [22].

Gestational age was rounded according to the reference values provided by the Brazilian Ministry of Health [22]. Moreover, the newborns were classified according to the reference values provided by the INTERGROWTH-21st project, and for the macrosomia criterion, defined as babies with a birth weight of >4,000 g were considered. The BMI range was determined using a formula to minimize errors related to the calculation. Additionally, double-typing and checking were used to minimize typing mistakes.

Variables were presented as means and standard deviations, medians and interquartile ranges, or percentages, as appropriate. The mean values were compared using analysis of variance (ANOVA) with Tukey’s test and Kruskal-Wallis ANOVA with Dunn’s test. Differences between categorical variables were assessed using the chi-square test. Univariate and multivariate logistic regression analyses were adjusted for the variables of age, previous cesarean delivery, smoking, and alcohol and drug abuse. Adverse perinatal outcomes were classified among the groups according to the patient’s nutritional status and weight gain during pregnancy.

SPSS^® for Windows statistical software (IBM Corporation, Armonk, NY, USA), version 21.0, was used to analyze the collected data. A p-value of <0.05 was considered statistically significant.

Study data are confidential and the responsibility of the researchers, as mandated by Resolution No. 466/2012 of the Brazilian National Health Council.

Results

During the data collection period, 2,604 births were reported at MDV. The study cohort included 1,666 women who gave birth at MDV during the study period and met the inclusion criteria, representing 64 % of births from August to December 2020. Notably, group 1, i.e., the reference group, was the largest and included participants who had neither prenatal obesity nor excessive weight gain during pregnancy. It included participants with low weight and insufficient weight gain (3.6 %) and those who were eutrophic or overweight (45.9 %). Group 2 included participants with pregestational obesity but without excessive weight gain during pregnancy, accounting for 11.4 % of the study cohort. Group 3 included participants without pregestational obesity but with excessive weight gain, accounting for 31.9 % of the study cohort. Finally, group 4 included participants with pregestational obesity and excessive weight gain, accounting for 10.7 % of the study cohort. None of the participants were excluded during the study period.

Table 1 presents the analyzed characteristics of the participants in the three study groups (Groups 2, 3, and 4) compared to the reference group. The groups differed in terms of age of the participants, number of pregnancies, number of vaginal deliveries, number of prenatal consultations, and drug use. However, these groups did not differ in terms of skin color, number of terminated pregnancies, employment, marital status, smoking, or alcohol consumption.

Table 2 shows a comparison of the neonatal characteristics of participants in the three study groups vs. those in the reference group. In this analysis, the groups differed in terms of birth weight, classification on the basis of birth weight, presence of macrosomia, and type of birth. However, they did not differ in terms of tears, episiotomy, use of forceps in vaginal delivery, or Apgar score.

Table 3 presents a summary of the outcomes analyzed. Factors associated with adverse perinatal outcomes were identified using a logistic regression model adjusted for the following confounding factors: age, previous cesarean delivery, smoking, and alcohol and drug use. The variables selected for analysis were the presence of GDM, the presence of PIH, form of delivery, and LGA newborns.

Discussion

Obesity is a global epidemic with an increasing prevalence in women of reproductive age. The same applies to excessive weight gain during pregnancy. Our analyses revealed that both conditions (alone and in combination) are closely correlated with the perinatal outcomes assessed in this study.

Several studies have reported an association of pregestational obesity and excessive weight gain during pregnancy with GDM, PIH, cesarean deliveries, LGA newborns, and postpartum weight retention, which are risk factors for maternal and neonatal morbidity and mortality [4], 10], 11], [13], [14], [15], [16], [17], [18], [19, 23], 24].

In our study population, the prevalence of pregestational obesity was 22.1 %, whereas the prevalence of excessive weight gain during pregnancy was 42.6 %. Similar results were found by Mastroeni et al. and Goldstein et al. [7], 8].

In a recent study by Carrilho et al. on a Brazilian population [4], which used data from the Brazilian National Food and Nutrition Surveillance System, between 2008 and 2018, the prevalence of pregestational obesity increased from 9.8 to 19.8 % and that of excessive weight gain in pregnancy increased from 34.2 to 38.7 %. Notably, the highest incidence of excessive weight gain in pregnancy was observed in patients without pregestational obesity, but most adverse events were more significant in patients with both pregestational obesity and excessive weight gain in pregnancy [7], 15], [25], [26], [27], [28], [29], [30].

Regarding the analyzed outcomes, the prevalence of GDM is known to range from 3 to 25 % among all pregnancies in Brazil, depending on the diagnostic criteria. The present study reported a prevalence of 20.7 % of the total sample [31].

Insulin resistance due to pregnancy hormones is known to favor the development of GDM [18]. In the present study, the risk of GDM was significant in group 2, (OR=3.6; 95 % CI: 35 2.5–5.2) and in group 4 (OR=1.9; 95 % CI: 1.3–2.9). This finding indicates that pregestational BMI increases the risk of GDM independent of excessive weight gain during pregnancy, which is consistent with the findings of other studies [13], 14], 19], 31], 32].

Regarding the recent evidence, a previous study reported that pregestational obesity is also associated with a greater risk of developing GDM (OR=2.6; 95 % CI: 1.7–4.1) [18]. Chen et al. [13] found an OR of 2.2 for developing GDM (95 % CI: 2.0–2.3), which is consistent with the findings of our study. Further, a study by Ferreira et al. (2020) on a Brazilian population, reported that pregestational obesity increases the risk of developing GDM by 7.5 times (95 % CI: 1.8–30.8) [33].

To the best of our knowledge, one of the most comprehensive studies was performed by Santos et al. [14], who evaluated 39 cohorts in Europe, North America, and Oceania, with a total of 265,270 births, and found an association between pregestational BMI and excessive weight gain during pregnancy with a greater risk of developing GDM in the presence of both conditions (OR=7.8;95 % CI: 6.4–9.6).

In Brazil, the prevalence of hypertension among pregnancy complications is 10 %. The present study found a prevalence of 9 %, which is consistent with the relevant literature. Although the pathogenesis of hypertensive disorders remains incompletely understood, obesity during pregnancy is considered a predisposing factor for these disorders [23], [34], [35], [36].

One of the main hypotheses for the occurrence of hypertensive disorders is related to placental dysfunction and a systemic inflammatory response in pregnancy, which may be influenced by inadequate weight gain during pregnancy [37]. Furthermore, hypertensive disorders are the leading causes of maternal and neonatal morbidity and mortality, accounting for 10–15 % of these outcomes [36].

In the present study, the risk of developing PIH was significant in group 3, comprising participants without pregestational obesity but with excessive weight gain during pregnancy (OR=1.7; 95 % CI: 1.1–2.6), and in group 4, comprising participants with both conditions (OR=3.1; 95 % CI: 1.9–5.2). In the study by Hillesund et al. [38], excessive weight gain during pregnancy was also associated with an OR of 1.3 for developing PIH (95 % CI: 1.2–1.5).

A recent study by Santos et al. [14] assessed the risks related to both pregestational obesity and excessive weight gain during pregnancy, and they found an OR of 4.5 for the development of PIH (95 % CI: 3.9–5.4). This finding is consistent with that of the present study for group 4, which found an OR of 3.1 (95 % CI: 1.9–5.2).

Cesarean deliveries account for approximately 70 % of all births in Brazil. However, in the present study, the prevalence of vaginal delivery was 57 % compared to 43 % of cesarean deliveries in the entire sample. In countries with high cesarean delivery rates, like Brazil, the effect of maternal BMI and weight gain during pregnancy on these rates may be less evident compared to those on populations with lower cesarean delivery rates. In contrast, in other studies, both pregestational obesity and excessive weight gain during pregnancy increased the risk of cesarean deliveries [11], [38], [39], [40], [41].

In Brazil, the prevalence of LGA births ranges from 4.1 to 30.1 %, depending on the adopted classification. The present study found a prevalence of 14.8 % of the analyzed sample for LGA newborns. Further, the study by Mastroeni et al. [7] found a prevalence of 24.4 % of the analyzed sample for LGA newborns.

Significant differences were found among the study groups 2, 3, and 4 in terms of LGA newborns, with an OR of 2.0, 2.6, and 3.2 in groups 2, 3, and 4, respectively. Notably, the results for group 3 were consistent with the results of the study by Morais et al. [11], which found an OR of 2.9 (95 % CI: 1.4–6.0) for LGA newborns in women with excessive weight gain during pregnancy. However, some studies reported that pregestational obesity increases the risk for LGA births by four times [42].

The neonatal complications found in the present study strongly suggest that pregestational obesity and excessive weight gain during pregnancy are significant risk factors for LGA births, suggesting a clear correlation between maternal weight and newborn weight at birth. These results are consistent with those of other relevant studies [10], 11], 14], 15], 18], 19], 25], 27].

Compared to normal-weight newborns, LGA newborns have two times greater risk of mortality in the first 28 days of life. Moreover, LGA newborns are more likely to develop obesity in childhood and adulthood, with severe consequences on public health [1], 43].

Finally, a meta-analysis published in JAMA in 2019 [44], which included studies involving 196,670 participants, reported that both pregestational BMI and excessive weight gain in pregnancy are associated with all the adverse events. However, pregestational BMI was more strongly associated with adverse events than total weight gains during pregnancy, with ORs of 1.3 (95 % CI: 1.27–1.29) and 1.0 (95 % CI: 1.03–1.05), respectively. Conversely, the present study suggests that excessive weight gain during pregnancy is more closely related to PIH, which is associated with higher maternal and fetal morbidity and mortality rates.

Few studies used the combination of pregestational BMI and excessive weight gain to predict the greatest risk of the adverse events analyzed in the present study; however, most of these studies separately evaluated outcomes for pregestational obesity or excessive weight gain during pregnancy. In addition to maternal and neonatal conditions related to obesity and excessive weight gain, it is important to assess the effectiveness of interventions aimed at controlling these issues. recent studies indicate that intervention strategies, such as dietary changes, exercise programs, and behavioral modifications, show varying success rates; some dietary interventions may be less effective if not accompanied by exercise programs or behavioral changes.

The DALI study, mentioned by van Poppel et al. [45], showed that sedentary behavior negatively affects leptin levels in umbilical cord blood and should therefore be avoided to improve perinatal outcomes. Evidence indicates that integrated strategies that address both diet and physical activity are more effective than isolated interventions in preventing excessive weight gain and its associated consequences.

Therefore, integrated interventions that include dietary, physical, and behavioral components appear to be more effective in controlling weight during pregnancy and mitigating the risks associated with pre-pregnancy obesity and excessive weight gain. The combination of these approaches can significantly reduce associated complications and improve overall perinatal outcomes.

Weight gain control during pregnancy can be modified by interventions. Thus, it is advisable to rigorously monitor weight and adjust the diet and lifestyle if weight gain is excessive, particularly during the first trimester and in women with high BMI before pregnancy. The risk of developing GDM was greater in the study groups that included patients with pregestational obesity, whereas the risk of developing PIH was greater in the groups that included patients with excessive weight gain during pregnancy. Correlation with LGA newborns was found in all three study groups when compared with the reference group; however, the type of delivery was not influenced by pregestational obesity or excessive weight gain during pregnancy.