The dynamic changes in the pattern of liver function tests in pregnant obese women
Affiliations: Department of Obstetrics and Gynecology, ‘Polizu’ Clinical Hospital, 011061 Bucharest, Romania, Department of Dermatology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, ‘Dunarea de Jos’ University, 800008 Galati, Romania, Department of Morphology, University of Medicine and Pharmacy, 410028 Oradea, Romania, Department of Diabetes, Nutrition, Metabolic and Internal Diseases, University of Medicine and Pharmacy, 410033 Oradea, Romania
- Published online on: July 13, 2021 https://doi.org/10.3892/etm.2021.10418
- Article Number: 986
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The World Health Organisation (WHO) defined obesity as one of the most dangerous and yet neglected public health issues which threaten to overwhelm even the most developed countries (1). The association between obesity and a higher cancer risk is mainly due to anthropometric parameters and lifestyle factors which activate different biological mechanisms. Anthropometric parameters are BMI, weight increase, and the amount of body fat, particularly visceral fat. Lifestyle factors include sedentary habits and diet parameters, such as a hypercaloric and/or low-quality diet (2). Obesity during pregnancy is an independent risk factor for long-term female malignancies such as ovarian and breast cancer (3). As with obesity, cancer has been acknowledged worldwide as a leading disease with respect to the total number of fatalities, which are mostly caused by late diagnosis (4). Regarding breast cancer prevention, one important aspect lies in the use of screening methods such as mammography. Concerning this, the major issue is related to the filter used in mammographies in that the filters must have homogen mass densities, to ensure the uniform exposure of the patient's breast (5). Cancer is characterized by uncontrolled cell division. Numerous solutions to this include the use of cytostatic agents and the development of theoretical models that describe the use of electrostatic fields in in this regard (6,7). Therefore, it is imperative to put effort into both cancer treatment as well as cancer prevention. Of importance is that there are no approved clinical guidelines for managing obesity during pregnancy (8,9).
The main objective of this study was to emphasize the impact of obesity on hepatic function in pregnant women by analysing the functional tests used in current practice. A further aim was to identify possible predictors of liver damage by analyzing specific anthropometric data (10). There was also a focus on visceral fat which is associated with a number of conditions, including cardiovascular disease, and insulin resistance during the process of visceral adipose tissue collection in the abdominal cavity and surrounding of the internal organs (11).
Materials and methods
This study is descriptive, observational and retrospective and is based on the observation sheets found in the database of the Institute for the Health of the Mother and Child, the Obstetrics Gynecology Department of Polizu Hospital. Patients who presented for consult each trimester of pregnancy were included. The general demographic data considered included age, body mass index (BMI), area of origin, and anthropometric data: Abdominal circumference and a complete set of paraclinical data from which we extracted these specific liver tests: Aspartate aminotransferase (AST), alanine transferase (ALT), direct bilirubin (BD), serum albumin and gamma-glutamyl transferase (GGT) (6-9). In order to reduce the possibility of bias and to increase the reproducibility of the study the normal values of these parameters were produced: Direct bilirubin <1.2 ml/dl, AST <35 µ/l, ALT <35 µ/l, albumin 3.5-4.5 µ/l, GGT <36 µ/l (12-18). It should be considered that AST and ALT levels were monitored dynamically, over several days, describing the variation pattern of the AST value and respecting the cubic model with a significance value of P=0.01. This study was approved by the ethics commission of the National Institute for Maternal and Child Health-Alessandrescu Rusescu on December 5, 2019 with reference number 17852/07.11.2019.
Given the main end-point of this study, which is the comparison of liver function tests during pregnancy in patients with normal weight and overweight/obese, the size of the patient groups should be sufficient to meet this aim (19,20). For this estimation the program MedCalc 14.1 (sampling-comparison of two means test) was used. A significance level of 0.05 was employed to avoid a type 1 (α level-two sided) error and 0.1 to avoid a type 2 (β) error. Thus, 157 patients (66 in group A and 91 in group B) were included in order to guarantee the detection of a 30% difference between the averages of the two groups with a computing power equal to 90%. Written informed consent was obtained from all the patients.
For the statistical analysis of the data, the program MedCalc 14.1 (Stata Corp.) was used as follows: The t-test for independent variables to compare the differences between two means, one-way-repeated measures ANOVA for comparing the differences between three or more means using the Bonferroni correction as post hoc test, and the Pearson or Spearman correlation coefficient depending on observing the Gaussian distribution of data. For all analysis, the confidence interval was 95%; thus, P<0.05 was considered to indicate statistical significance.
The present study included 157 patients divided into two groups, distributed as follows: Group A: 66 obese pregnant women (BMI >25 kg/m2) and group B: 91 patients with normal weight (BMI <25 kg/m2).
AST and ALT levels
Comparative analysis of the AST level in the two groups according to the trimester of pregnancy. When comparing the AST level, it can be observed that obese patients (group A) tend to have higher values in all trimesters, but no difference compared with group B was statistically significant (only in the first trimester is a slight difference detectable between the two groups P=0.1) (Table I and Fig. 1). Comparative analysis of the ALT level in the two groups according to the trimester of pregnancy revealed no statistically significant differences in the comparative analysis between the two groups of ALT (Fig. 2).
Comparative analysis of the AST level in the two groups according to the trimester of pregnancy.
Comparative analysis of the ALT level in the two groups according to the trimester of pregnancy.
Comparative analysis of the AST and ALT levels in the two groups according to the pregnancy trimester.
GGT, albumin and BD levels
Comparative analysis of the GGT level in the two groups was conducted according to the pregnancy trimester. The values of the GGT are higher in the group of obese patients compared to the normoponderous patients, this difference being best underlined in the third trimester (Table II and Fig. 3).
Comparative analysis of the GGT level in the two groups according to the pregnancy trimester.
Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-scores in obese and non-obese patients.
Comparative analysis of the albumin level in the two groups according to the pregnancy trimester was also performed (Fig. 4). The level of albumin remains constant at the lower limit of the normal value of 3.5 µ/l regardless of the nutritional status. There is no statistically significant difference between the two groups.
Comparative analysis of the albumin level in the two groups according to the pregnancy trimester.
Comparative analysis of the BD level in the two groups according to the pregnancy trimester was carried out. As in the case of albumin, direct bilirubin tends to be constant throughout pregnancy, with no statistically significant difference between the group of obese patients and the group of norm-weight patients (Fig. 5 and Table II).
Comparative analysis of the BD level in the two groups according to the pregnancy trimester.
Correlation of circumference and AST
The correlation between the abdominal circumference in the first trimester and the value of aspartate transferase was assessed. In practice, in a patient with a larger abdominal circumference in the first trimester, higher levels of AST were evident (Table III).
Correlation between abdominal circumference in the first trimester and the value of aspartate transferase.
ALT and AST
Measurement of serum ALT and AST were the most useful tests for routine diagnosis of liver disease. The effects of pregnancy on serum levels of ALT and AST are considered somewhat controversial. In some studies, there was a slight increase in ALT and/or AST during the second and third trimesters. However, in most published studies, serum ALT and AST levels did not change during pregnancy (21,22).
Results of the present study showed that obese pregnant women tend to have higher values of hepatic transaminases during all 3 trimesters of pregnancy compared to normal weight pregnant women, even though it was not statistically significant. However, it should be considered that AST and ALT levels were monitored dynamically, over several days; thus, it is necessary to describe the variation pattern of the AST value (23-29). It respects the cubic model with a significance value of P=0.01, which shows that during our follow-up, the AST values tended to increase during Q2, followed by a definite decrease. However, the AST values in Q3 are higher than those in Q1 (Table I and Fig. 1). In addition, there were no significant statistical differences in the comparative analysis between the two groups regarding AST values. The evolution trend was linear with a significance level of P=0.05 (Fig. 2).
The GGT values of were higher in the group of obese patients (group A) compared to the normoponderous patients, this difference being particularly highlighted in the third trimester (Table II and Fig. 3).
Both albumin and direct bilirubin levels have relative constant values throughout pregnancy, with albumin levels remaining close to the lower normal limits (3.5 µ/l). However, none of these values indicated statistical significance.
Given the fact that the only liver function test that varies between the two groups is AST, we performed a Pearson correlation analysis; the data studied concerns the Gaussian distribution. Thus, a directly proportional result and a significant Pearson correlation (r=0.19; P=0.012) were obtained. Furthermore, a larger abdominal circumference is associated with higher levels of AST during T1 pregnancy (Table III and Fig. 6).
Correlation between abdominal circumference in the first trimester and the value of aspartate transferase.
In conclusion, obesity during pregnancy does not markedly influence the patient's liver function. However, patients with greater abdominal circumference are prone to developing a slight hepatic cytolysis syndrome during pregnancy. The functional tests of the liver that we used in the present study agree with the results provided by the specialized studies.
This study, together with the efforts in article publishing were self-founded.
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
CODT analyzed and interpreted the patients' data regarding the hepatic function by comparing the functional tests used in current practice and critically revised the manuscript for its content. FS analyzed and interpreted the patients' data regarding the hepatic function by comparing the functional tests used in current practice and is the corresponding author. AC identified the possible predictors of liver damage and wrote the manuscript. AT revised the literature data and analyzed specific anthropometric patient data. ARP researched the papers that were included as references. AIM designed the experiments and critically revised the manuscript and approved the current form of the article in order to be submitted to the journal. All authors read and approved the final manuscript.
Ethics approval and consent to participate
This study was approved by the ethics commission of the National Institute for Maternal and Child Health ‘Alessandrescu Rusescu’ on December 5th, 2019 with ref. no. 17852/07.11.2019. Written informed consent was provided by the patients.
Patient consent for publication
The patients have given written informed consent for the publication of the data.
The authors declare that they have no competing interests.
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