Association Between Pre-Pregnancy Body Mass Index and Labor Induction Success Rates: A Case Control Study

Introduction

Obesity is described as excessive fat accumulation [1]. A large meta-analysis of more than 100 000 patients showed that almost 47% of pregnant women gained more weight than recommended. Data from the Basic Health Research Survey (Riskesdas) in 2018 showed that the prevalence of overweight, obesity, and central obesity among adult Indonesians was 13.6%, 21.8%, and 31%, respectively [1]. The prevalence of obesity doubled in a decade, from 2007 to 2018 (10.5% to 21.8%). The high prevalence of adult women with obesity in Java is a concern in obstetrical morbidity [1,2]. The body mass index (BMI) has been categorized according to Asian parameters. Underweight is categorized as a BMI less than 18.5 kg/m2; normal weight, a BMI from 18.5 to 22.9 kg/m2; overweight, a BMI from 23.0 to 24.9 kg/m2; and obesity, a BMI of more than 25 kg/m2 [3]. The recommended ranges of weight gain for pregnancy are 12.5 to 18.5 kg for women with underweight, 11.5 to 16 kg for women with normal weight, 7 to 11.5 kg for women with overweight, and 5 to 9 kg for women with obesity [4]. An increase in pre-pregnancy BMI is associated with delayed labor, higher required dose of oxytocin, higher rate of vaginal delivery failure, and higher rate of cesarean delivery [5]. Obesity is associated with several pregnancy complications, such as gestational diabetes (odds ratio [OR] 2.83), gestational hypertension/preeclampsia (OR 2.68), and maternal depression (OR 1.43). Also, the onset of labor is delayed in women with obesity (>41 weeks gestation), particularly with BMI >35 kg/m2, and with the onset of preterm spontaneous labor in women with underweight. The cervical dilatation in healthy women with obesity was slower than that of women with normal weight (OR 3.9), and women with obesity had a higher risk for cesarean delivery (OR 3.2) [6]. Regarding parity, a study showed nulliparous women with obesity have higher risk of cesarean delivery and longer labor duration than do nulliparous women without obesity [5].

Human labor is described by 4 myometrial phases, namely quiescence, preparation (activation), labor (contraction), and recovery (involution). The preparation phase is associated with contractile-associated proteins including oxytocin receptor (OXTr), PGFr, and connexin-43. The active phase is associated with synchronization of uterine contractility. The main roles of oxytocin stimulation include effects on the hypothalamus-hypophysis adrenal axis, fetus, and placenta. During labor, myocyte contraction is coordinated by the fundus uterus as a pacemaker, then spreading toward the cervix [6]. Oxytocin is synthesized in peripheral tissues, such as the uterus, placenta, amnion, corpus luteum, testis, and heart. It was suggested that oxytocin acts as a luteotropic hormone opposing luteolytic action of PGF2-alpha. Therefore, to initiate labor, it is essential to get sufficient PGF2-alpha to overcome luteotropic action of oxytocin in late gestation. A persistent stimulation can be desensitized by numerous mechanisms. It was said that the exposure of oxytocin in myometrial cells for up to 20 h resulted in a 10-fold reduction of oxytocin-binding capacity [7].

OXTr belongs to G-protein-coupled receptors, which have several effects, such as acting as voltage-regulator of the calcium channel and subsequent myosin light-chain kinase activator. It was reported that OXTr is mainly in cells of the nervous system, mammary gland cells, and uterus during pregnancy. It was also suggested that OXTr gene disruption can occur through various unexplored molecular mechanisms. Interestingly, a study showed there was a variant of individual polymorphisms of OXTr. Therefore, proper labor is not simple, but a complexity of regulation of physiological processes [8]. The affinity of OXTr requires magnesium and cholesterol. A high affinity of oxytocin binding was obtained with liposomes, which contain an amount of cholesterol. Therefore, cholesterol acts as a modulator and stabilizes the affinity state for agonists and antagonists. A metal ion, like magnesium, is known to increase the response target cell of oxytocin [7].

Adipose, the largest endocrine and paracrine organ, contributes to adipokine, cytokine, and chemokine release, which are physiological and therapeutic targets in uterine contraction. Calcium channels are crucial for myometrial contraction. Adrenergic receptors, such as beta-2 for relaxation and alpha-1 or alpha-2 as potential tocolytics, are responsible for uterine contractility. Prostaglandins, especially PGE1, like misoprostol, are used for labor induction [9]. A study showed the effect of oxytocin desensitization on oxytocin-induced myometrial contractility in women with advanced maternal age and morbid obesity. There was reduced uterine contractility of oxytocin-naive and oxytocin-pretreated samples in vitro [10]. Recent data suggest that the dysregulation of leptin, adiponectin, and kisspeptin alter myometrial contractility. The decrease of leptin was suggested to have relaxing myometrial effects. Although there was not available information, the decrease of adiponectin receptor (t-cadhelin/adiponectin-binding-protein) suggested an effect on uterine contractility. Also, the increase of kisspeptin suggested steroid hormone alteration, which is inducing hypogonadotropic-hypogonadism [9].

Those are a few mechanisms which contribute to uterine contractility during labor. Oxytocin is released in many ways. First, fetus head pressure to the cervix will activate the Ferguson reflex. Second, high levels of estrogen make OXTr more sensitive. Third, prostaglandin synthesis that is released will activate a specific type of OXTr. Also, the supraoptic nucleus and paraventricular nucleus in the hypothalamus sends axon collateral to various brain regions, including the median eminence, amygdala, hippocampus, cingulate, and frontal cortex. It is suggested that the oxytocin system in the brain has an implication in decreasing the oxytocin level according to behavioral and physiological functions [11].

A few studies have shown different conclusions [1,2,4]. First, uterine contractility is less contracted in women with obesity than in those without obesity, as measured by myometrial strips. Similarly, the women with obesity had more prolonged labor than did women without obesity, but both groups had a similar strength of uterine contraction during labor, as measured by intrauterine pressure assessment. Second, OXTr gene expression did not correlate with maternal BMI by linear regression. It showed OXTr gene expression varies through different regions of the uterus, where the fundal has greater amounts than the lower uterine segment. It seems that dysfunction of labor in women with obesity is independent of myometrial OXTr gene and protein expression. Variations of cholesterol level in cell membranes affect OXTr binding, signaling, and desensitization. It is unknown whether obesity or dietary cholesterol affects the myometrial cell membrane, which could alter OXTr alteration [12].

Therefore, this study aimed to investigate the association between BMI in pre-pregnancy and outcomes from labor induction in 248 women admitted during 1 year at Margono Soekarjo General Hospital in Purwokerto, Indonesia.

Material and Methods

ETHICS COMMITTEE APPROVAL:

The research was approved by the Ethics Committee of Prof. Dr. Margono Soekarjo General Hospital Purwokerto, Indonesia (approval number 420/03562).

DECLARATION OF PATIENT CONSENT:

The authors certify that the patients gave their consent for clinical information to be reported in the journal and understand that names will not be published.

STUDY DESIGN AND SETTINGS:

This was a case-control study conducted for 1 year from March 2023 to March 2024 at Prof. Dr. Margono Soekardjo General Hospital.

STUDY POPULATION:

Pregnant women at any gestational age were enrolled in the study. Patients with relevant clinical samples were admitted on the same day. BMI was calculated as body weight (kg) before pregnancy divided body height squared (m²). All pregnant women who were inducted for labor were divided into groups of those with successful in labor and those without. The induction of labor procedure implementation and outcomes were based on The International Federation of Gynecology and Obstetrics. Women who were successful in giving birth by induction either by oxytocin or misoprostol induction were the control group and women who failed in giving birth by induction were the case group. The BMI of the case and control groups were recorded before pregnancy. BMI was categorized with Asian parameters, as follows: underweight as BMI less than 18.5 kg/m²; normal weight, BMI 18.5 to 22.9 kg/m²; overweight, BMI 23.0 to 24.9 kg/m²; and obesity, BMI more than 25 kg/m². BMI was measured with validated scales.

Exclusion criteria were pregnant women with multiple gestations, history of chronic disease (renal disease, diabetes, and chronic hypertension), history of other infections (premature rupture of membranes, dental intrauterine fetal death infections, respiratory infection such as tuberculosis and pneumonia, and other forms of infection), intrauterine fetal restriction, intrauterine fetal death, and fetal congenital (cephalic and renal abnormalities), as shown in Figure 1.

SAMPLE SIZE ESTIMATION:

This study used total sampling in the years 2023 and 2024 at Margono Hospital. The total number of pregnant women delivered that year after being excluded based on exclusion criteria was 248.

STATISTICAL METHODS:

We used ORs to analyze correlation and chi-square to analyze for significance of the correlation between the basal mass index of patients with success or failure of induction on delivery. Statistical analysis was performed using SPSS (IBM SPSS Statistics for Windows, Version 29.0.; IBM Corp, Armonk, NY, USA).

DATA COLLECTION:

The data were collected from registered pregnant women coming from polyclinic or maternal emergency departments who were hospitalized for giving birth and induced for labor at Margono Hospital, Central Java, Indonesia from October 2023 to March 2024.

Results

PATIENT CHARACTERISTICS:

This study included 248 patients: 197 patients with obesity in pregnancy and 51 patients without. Table 1 outlines obstetric and clinical characteristics based on patients who failed induction of delivery. Notably, in both groups, failure of induction occurred in pregnant women mostly aged 20 to 35 years. There was no significant difference in characteristics between groups.

STATISTICAL RESULTS:

Table 2 summarizes the correlation between obesity and the risk of failure of induction in pregnancy (OR 3.78, 95% CI 1.53–9.31, P=0.002). The results showed that patients with obesity found during pregnancy have 3.78 times higher risk of failure of induction in pregnancy.

Discussion

CONFOUNDING FACTORS:

This study considered potential confounding factors in the association between obesity and induction failure. History of other infections, history of chronic disease, intrauterine fetal restriction, intrauterine fetal death, and congenital fetal abnormalities (cranial and renal) were confounders due to the link to obesity and failure induction, necessitating statistical adjustment. Those confounders are excluded from the samples.

Conclusions

To conclude, there was a statistically significant correlation between BMI in pre-pregnancy and increased risk of labor induction failure. Pregnant women with obesity had higher odds of labor induction failure to those without. There was a 3.78 times risk of labor induction failure for those who had obesity before pregnancy, compared with women without obesity before pregnancy. Therefore, for clinical impact, pregnant women with and without obesity have to observe their body weight increase during pregnancy, with the maximal additional body weight following the recommendations.