Association between excessive maternal weight, periodontitis during the third trimester of pregnancy, and infants’ health at birth

Abstract Excessive weight is associated with periodontitis because of inflammatory mediators secreted by the adipose tissue. Periodontal impairments can occur during pregnancy due to association between high hormonal levels and inadequate oral hygiene. Moreover, periodontitis and excessive weight during pregnancy can negatively affect an infant’s weight at birth. Objective This observational, cross-sectional study aimed to evaluate the association between pre-pregnancy overweight/obesity, periodontitis during the third trimester of pregnancy, and the infants' birth weight. Methodology The sample set was divided into 2 groups according to the preconception body mass index: obesity/overweight (G1=50) and normal weight (G2=50). Educational level, monthly household income, and systemic impairments during pregnancy were assessed. Pocket probing depth (PPD) and clinical attachment level (CAL) were obtained to analyze periodontitis. The children’s birth weight was classified as low (<2.5 kg), insufficient (2.5–2.999 kg), normal (3–3.999 kg), or excessive (≥4 kg). Bivariate analysis (Mann-Whitney U test, t-test, chi-squared test) and logistic regression (stepwise backward likelihood ratio) were performed (p<0.05). Results G1 showed lower socioeconomic levels and higher prevalence of arterial hypertension and gestational diabetes mellitus during pregnancy than G2 (p=0.002). G1 showed higher means of PPD and CAL (p=0.041 and p=0.039, respectively) and therefore a higher prevalence of periodontitis than G2 (p=0.0003). G1 showed lower infants’ birth weight than G2 (p=0.0004). Excessive maternal weight and educational levels were independent variables associated with periodontitis during the third trimester of pregnancy (X2[2]=23.21; p<0.0001). Maternal overweight/obesity was also associated with low/insufficient birth weight (X2[1]=7.01; p=0.008). Conclusion The present findings suggest an association between excessive pre-pregnancy weight, maternal periodontitis, and low/insufficient birth weight.


Introduction
Patients with obesity have high levels of proinflammatory adipokines and cytokines that negatively affect the individuals' immunity, thus increasing the inflammatory response. The adipose tissue secretes inflammatory mediators that cause a widespread inflammatory state in the body of the obese patients.
As a result, these patients may have a significant inflammatory response in the periodontal tissues, even in the presence of a normal amount of dental plaque. 1 Pregnancy can also negatively affect a patient's oral condition. During pregnancy hormonal alterations cause physiological and anatomical changes. These changes occur from conception to labor and promote fetal growth and pregnancy maintenance. High levels of progesterone and estrogen cause oral alterations during pregnancy decreasing an individual's immune response. 2 Therefore, with the tooth biofilm formation, the patient's periodontal condition can worsen during this period.
Studies have reported a triangular association between obesity/overweight and periodontal status during pregnancy. 3-10 All studies found a positive association between obesity/overweight and periodontal status; however, they did not use the same classifications for periodontitis and body mass index (BMI), and none of the studies analyzed the association of these factors with infants' health at birth.
The scientific literature highlights the association between periodontitis and adverse delivery outcomes, such as preterm birth and low birth weight. [11][12][13][14][15] In contrast, maternal overweight/obesity is strongly associated with insulin resistance, which, in turn, is related to the gestational diabetes mellitus (GDM), preeclampsia, and macrosomia. [16][17][18][19] However, studies that considered maternal overweight/obesity, periodontitis, and birth weight have not been conducted yet. Therefore, this study aimed to evaluate the association between pre-pregnancy overweight/ obesity, periodontitis during the third trimester of pregnancy, and birth weight.

Methodology
The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines were used to ensure the accurate reporting of this observational, cross-sectional study. 20

Ethical approval
According to the Declaration of Helsinki, this study was approved by the Ethics Committee on Human Research (CAAE 58339416.4.0000.5417). All participants provided written informed consent.

Sample conformation
One hundred women in the third trimester of pregnancy were included in this study and subsequently divided into 2 groups according to and/or patients who were taking medications that could negatively affect their oral health. Furthermore, twin or multiple pregnancies were excluded in this study. Patients who had their infants before the 37 th Association between excessive maternal weight, periodontitis during the third trimester of pregnancy, and infants' health at birth J Appl Oral Sci. 2020;28:e20190351 3/9 gestational week and after the 40 th gestational week were excluded from this study.

General evaluations
Data regarding systemic impairments, such as diabetes mellitus and AH during pregnancy, were obtained from medical records and registered as 0 (absent) or 1 (present). AH in pregnancy was established as ≥140/90 mmHg blood pressure levels. 22 The diagnosis of GDM was based on the International Association of the Diabetes and Pregnancy Study Group protocol, 23   Therefore, initially, the dichotomization of periodontitis (0, no periodontitis; 1, with periodontitis) and low/ insufficient birth weight (0, no low/insufficient birth weight; 1, low/insufficient birth weight) was performed, followed by an inclusion of a maximum of 5 independent variables in the logistic models. Thus, a sample size of 100 was considered representative.

Classifications Definitions
Low birth weight (g) <2,500 Insufficient birth weight (g) 2,500-2,999 Normal birth weight (g) 3,000-3,999 Excessive birth weight (g) ≥4,000 g= grams The Kolmogorov-Smirnov test was applied to verify the normal distribution of the sample. The t-test was used in bivariate analysis to examine the normally distributed quantitative variables. The Mann-Whitney U test was used to examine non-normally distributed quantitative variables and ordinal variables. The chi-squared test was used to examine binomial data. The logistic regression was adapted using the stepwise backward (likelihood ratio) method to analyze the independent variables associated with periodontitis and infants' birth weight (dependent variables). A significance level of 5% was considered statistically significant.
Hosmer-Lemeshow, collinearity, and residual analyses were used to increase our understanding of the logistic regression results.

Results
Initially, 123 patients were selected for this study; out of these, 23 were excluded due to the following reasons: requiring absolute rest (n=3), history of periodontitis before pregnancy (n=2), more than 40 weeks of gestation (n=9), smokers (n=2), underweight (n=3), and under orthodontic treatment (n=4). Therefore, 100 patients were included in this study.
G1 showed a higher pre-pregnancy and gestational BMI than G2 (p<0.0001). Furthermore, G1 had a higher prevalence of hypertension and GDM than that of G2 (p=0.002) ( Table 1).
The groups did not differ regarding daily toothbrushing frequency (p=0.757) and daily use of dental floss (p=0.392). However, they differed in the mean PPD (p=0.041), in the mean CAL (p=0.049), and in the prevalence of periodontitis, which was higher in G1 than in G2 (p=0.0003), with 48% (n=24) and 24% (n=12) of patients classified as having moderate and severe periodontitis respectively. None of the patients in G2 were classified as having severe periodontitis, but 36% (n=18) of the patients were classified as having moderate periodontitis ( Table 1).
The average birth weights for G1 and G2 were 3.06±0.35 kg and 3.33±0.38 kg, respectively. No infants were classified as having excessive birth weight. However, 18 infants in G1 (36%) had a low or insufficient weight, whereas only 4 infants in G2 (8%) had a low or insufficient weight (p=0.0008) ( Table 1).
Binary logistic regression was applied to determine the independent variables related to periodontitis (0,

Discussion
This study contributes to the body of scientific evidence by evaluating the association between prepregnancy overweight/obesity, maternal periodontitis, and low birth weight. We adapted the standardized protocols for nutritional status classification and periodontitis diagnosis. The main findings of this study suggest pre-pregnancy excessive weight is significantly associated with periodontitis during the third trimester of pregnancy. Moreover, overweight/ obesity is associated with a low/insufficient birth weight.
Obesity is a chronic and multifactorial disease and an important risk factor for type 2 diabetes, hypertension, coronary heart disease, osteoarthritis, and metabolic syndrome. 29 In this study, the overweight/obese pregnant women had a higher prevalence of AH and GMD than that of non-overweight/nonobese pregnant women (p=0.022). The presence of adiposity in the body was associated with the visceral accumulation of the adipose tissue, which directly contributes to insulin resistance and becomes more evident during pregnancy. 30 Hypertension, in turn, is related to the vascular inflammation and endothelial disturbance.
The vascular inflammation involves the release of inflammatory cytokines and adipokines that increase the vascular permeability and promote cytoskeletal changes in the endothelial cells, which can disrupt the balance between vasodilation and vasoconstriction.

Inflammatory mediators secreted by the patients'
adipose tissue are also involved in this process and in the exacerbate vasoconstriction, causing an increase in blood pressure. 3 A lower socioeconomic level has previously been shown to be associated with periodontitis and obesity. 4,8,31 In this study, pregnant women with excessive weight had lower educational levels (p=0.034) and lower monthly household incomes (p=0.011) compared with pregnant women with nonexcessive weight (Table 1). This can be explained by the fact that individuals with lower socioeconomic status show inadequate eating behaviors because they are reliant on cheaper foods that have more calories and lower nutritive content, resulting in overweight and obesity. 4,8,31 The association between periodontitis and lower socioeconomic levels exists because the patients who have both conditions have lesser access to healthcare services and lesser access to oral hygiene education programs. 8 However, in this study, the groups did not differ in the daily toothbrushing frequency or in the daily use of dental floss. Both the BMI increase and the lower educational levels were considered as independent variables of periodontitis according to the final logistic regression model ( Table   2).
The association between obesity and periodontitis can be explained by the fact that the adipose tissue of the patients with excessive weight secretes Association between excessive maternal weight, periodontitis during the third trimester of pregnancy, and infants' health at birth J Appl Oral Sci. 2020;28:e20190351 7/9 inflammatory mediators, such as the tumor necrosis factor alpha, the interleukin 6, and the C-reactive protein, which can make the host more susceptible to inflammation. 1,4,32 Therefore, patients with overweight/ obesity can have higher levels of inflammation anddestruction of the periodontium, even in the presence of a normal amount of bacterial plaque, compared with patients with normal weight.
Periodontal impairments can also occur during pregnancy due to profound disturbances in the In contrast, women diagnosed with periodontitis during pregnancy are more likely to have preterm births and infants with low birth weight than women not diagnosed with periodontitis during pregnancy. [11][12][13][14][15]33,35 Two pathogenic mechanisms are The first study that suggested oral bacteria influenced the pregnancy outcomes was reported by Collins, et al. 36 (1994). It highlighted that injecting pregnant hamsters with Porphyromonas gingivalis led to intrauterine growth retardation and to smaller fetuses, together with increased levels of proinflammatory mediators [interleukin 1 beta (IL-1b) and prostaglandin E2 (PGE2)] in the amniotic fluid.
However, studies that evaluate the association of these factors while considering the presence of periodontitis have not been conducted yet. In this study pregnant women with excessive weight had infants with low/insufficient birth weight (p=0.0008), in addition to the higher prevalence of periodontitis.
Therefore, periodontitis seems to be significantly associated with infants' health at birth. Nevertheless, according to the logistic regression related to infant's weight at birth, overweight/obesity was the independent variable that persisted on the final logistic model, while the presence of periodontitis prevailed until model 4 of the logistic regression (p=0.226, Table   3). The authors hypothesize that periodontitis could be one of the variables to remain until the final logistic model in a future larger sample study. The findings of our study are in contrast with those that sought to assess the association between pre-pregnancy overweight/obesity and birth weight. It is hypothesized that inflammatory mediators (e.g., IL-1b and PGE2) are directly associated with low birth weight. 36 The inflammatory mediators secreted by the adipose tissue in overweight individuals 1,32 may also play a key role in the higher prevalence of underweight infants due to the indirect effect of the pro-inflammatory markers.
Future prospective studies with larger samples must be conducted to better understand the association between maternal overweight/obesity, periodontitis, and birth weight based on this indirect effect. T h i s study has some limitations. A longitudinal study with a larger sample size is required to further understand the association between maternal overweight/obesity, periodontitis, and birth weight. Additionally, this study considered obese and overweight patients in the same group. Future prospective studies are required to evaluate the effect of obesity only on periodontitis during pregnancy and the subsequent birth weight.
Moreover, future studies should collect the participants' visual dental plaque data to ensure the comparison between groups regarding the quality of oral hygiene habits.
Despite the limitations of this study, it is considered relevant to better understand the association between periodontitis, overweight/obesity during pregnancy, and low birth weight. This is notable as no previously published studies consider maternal systemic health, periodontal condition during pregnancy, and infants' health at birth. Conclusion These findings suggest an association between e xc e s s i ve p r e -p r e g n a n c y w e i g h t , m a t e r n a l periodontitis, and low/insufficient birth weight.
Additionally, periodontitis seems to be associated with the patient's socioeconomic status, and this should be considered during the comprehensive and multidisciplinary care of the overweight/obese pregnant women.