Baratto I; Daher S; Frutuoso Lobo T; Aparecida Falbo Guazzelli C

Research Article

J Pediatri Endocrinol. 2019; 4(1): 1029.

Serum Levels and Gestational Curve of Adiponectin and Leptin During Adolescent Pregnancy

Baratto I, Daher S, Frutuoso Lobo T and Aparecida Falbo Guazzelli C*

Department of Obstetrics, Sao Paulo Federal University, Brazil

*Corresponding author: Aparecida Falbo Guazzelli C, R Bandeiras 253 ap 181- Santo Andre, Brazil

Received: April 08, 2019; Accepted: June 14, 2019; Published: June 21, 2019

Abstract

Adiponectin and leptin have a characteristic pattern and play important roles during pregnancy in adults, although little is known about them in adolescent gestation. The objective of this study was to develop a gestational curve for the weekly serum levels of adiponectin and leptin among adolescent pregnant women. Pre-gestational BMI and weight gain were also evaluated and correlated with the serum concentration of these molecules. The study evaluated adolescents with pre-gestational BMI of eutrophy during the evolution of gestation. Peripheral blood samples were collected to evaluate serum adipokine concentrations by the ELISA method. A total of 157 pregnant women participated in the study, totaling 471 blood samples. Serum levels of adiponectin showed significant differences, showing a drop in concentration during gestation (p = 0.0003), we did not observe a correlation between pre-gestational BMI, weight gain and serum levels (p = 0.36; p = 0.10, respectively). With the advancement of gestation, we identified an increase in serum leptin levels (p ‹0.0001), a positive correlation between serum levels and pre-gestational BMI and also between weight gain (p = 0.003; p = 0, 0007, respectively). We conclude that adiponectin decreases with the evolution of pregnancy, however it has no correlation with BMI and weight gain and leptin increases during pregnancy presenting a direct correlation with BMI and weight gain. The pattern of adiponectin and leptin production observed in adolescent pregnant women is similar to that seen in adult pregnant women.

Keywords: Leptin; Adiponectin; Adolescent; Pregnancy; Adipokine

Introduction

Adipokines are proteins secreted by adipose tissue, described as molecules with diverse physiological structures and functions [1,2]. They act as classical cytokines, growth factors and complementary systemic proteins, are involved in the regulation of blood pressure, vascular homeostasis, angiogenesis, lipid and glycemia metabolism [3]. Adiponectin and leptin are the most abundant adipokines synthesized by adipose tissue [4].

Adiponectin exhibits antihyperglycemic, antiatherogenic and anti-inflammatory properties, promotes insulin sensitization, decreases the hepatic production of glucose and increases the action of insulin in the liver [5-7]. Serum levels may vary according to sex, being higher in women [8,9]. Research does not indicate that this difference also occurs with adolescents, but they report lower concentrations between the pubescent and obese [10]. At puberty the levels are significantly lower than those observed in the pre-pubertal period, this is presumed to be a function of the decrease in Insulin Resistance (IR) that occurs at this stage [11,12].

The serum concentration of adiponectin during pregnancy decreases with the advancement and installation of IR, returning to the pre-gravid concentration after delivery. Studies indicate that there is a negative correlation between serum levels and gestational age [5-7,13-15], it seems that during pregnancy, adiponectin acts on the energy balance, on the fatty oxidation of fatty acids, decreasing production glucose and increasing the action of insulin by the liver [13,16,17].

Leptin is involved in inflammatory processes, immune mediated responses, appetite regulation [18], energy storage, modulation of the homeostatic system and regulation of blood pressure, aid in thermogenesis, angiogenesis, insulin secretion by the pancreas, in the production of glucose by the liver and in its uptake through the muscle [19,20-22]. Its synthesis is directly related to the amount of adipose tissue present in the individual’s body, therefore, plasma levels differ in people with the same Body Mass Index (BMI) [23]. In addition to BMI, other factors such as sex, age, fasting, overeating, diet composition and hormones may influence the serum levels of this adipokine [6,7,9,10].

In adults, plasma concentration is higher in females when compared to values found in males [18,28]; in children and adolescents, leptin levels are related to changes in body composition [53-55]. In the gestational period, the major changes in plasma levels of this adipokine occur, being significantly higher [18,29,30]. During pregnancy, leptin plays a key role in regulating placental growth, nutrient transfer, angiogenesis, pulmonary maturation, and trophoblast invasion [31].

Research has shown that blood levels of adiponectin and leptin are related to physiological changes during pregnancy in adult women, but information on the behavior of these molecules in adolescent gestation so far remains unknown.

Thus, the objective of this study was to evaluate the serum levels of these molecules during the evolution of gestation in adolescents and to develop a gestational curve for weekly serum levels, and to correlate pre-gestational BMI and total weight gain of adolescents with concentrations of these adipokines.

Materials and Methods

This was a prospective cohort study performed with adolescent pregnant women attended in the Adolescent Prenatal Sector of the Paulista School of Medicine from February 2013 to March 2018. The study was submitted to the Research Ethics Committee of the Federal University of São Paulo / Hospital São Paulo, being approved under the consubstantiated opinion nº 1514/11. Included in this study were adolescent eutrophic pregnant women who were being followed in the prenatal sector of adolescents of Escola Paulista de Medicina (EPM) - UNIFESP.

All patients who accepted to participate in the study spontaneously were included in the sample after reading, understanding and signing the informed consent form.

The patients were followed during gestational development, and blood samples were collected during pregnancy (3 samples, one in each trimester). Pregnant women, older than 10 years and younger than 20 years [32], who presented with pre-gestational BMI of eutrophy (18.5-24.9 kg/m²) were included in this study [33]. Those with multiple gestation, or on the use of corticosteroids, antibiotics, immunosuppressant’s and / or anti-inflammatories, and those that evolved with some clinical intercurrence during pregnancy progression, such as gestational diabetes, preeclampsia, intrauterine growth restriction, or (hypertension, diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, rheumatic fever and asthma). BMI was calculated based on the pre-gestational weight and height, being mentioned by the pregnant woman at the first prenatal visit, the nutritional diagnosis was determined according to the Institute of Medicine (IOM) (2009) [33]. Gestational weight gain was determined by the difference between the weight of the patient at the last predelivery visit and the pre-gestational weight.

We collected and stored in dry tube, 8 mL of blood by venipuncture, and serum levels of adiponectin and leptin were evaluated by the ELISA method, and the plasma values of the molecules expressed in ng/mL (nanograms / milliliters) were determined.

The normality tests Skewness and Kurtosis, Kolmogorov-Smirnov and Shapiro-Wilk were applied to evaluate the distribution of the quantitative variables. For analysis of variance between the groups the One-Way ANOVA test was applied to measure those of parametric distributions and the Kruskal-Wallis test was used to analyze the non-parametric ones, followed by Tukey post-tests or Dunn posttest, respectively. For the analysis of categorical variables the chisquare test was adopted. The Pearson test was applied to calculate the correlation coefficients. The level of significance was set at p ‹0.05. Statistical analyzes were performed using standard software (GraphPad Prism, v6.0 for Windows). As we did not find previous studies that allowed to calculate the sample size recommended for this investigation, the proposal was to carry out a study that serves as the basis for future research. Thus, the sample was of convenience, including all the patients attended in the study period who were in agreement with the established parameters.

Results

The study included 157 healthy adolescent pregnant women, totaling 471 blood samples collected between the 9th and 39th gestational week.

The age of the pregnant women included in this study ranged from 12 to less than 20 years, with an average of 16.51 years (standard deviation 1.76), and there was no significant difference between patients grouped by gestational age (p = 0.06; ANOVA One-Way Test). Regarding the race / color of the patients included, there was a statistical difference between those grouped by gestational age (p ‹0.0001; Chi-Square test). The sample included 81 collections of blood from brown adolescents and 76 collections of blood in white adolescents.

The pre-gestational BMI was 22 kg/m² (Interquartile Interval 21,40 - 22,50), presenting a significant difference between the patients included in the study grouped by gestational age (p = 0.004; Kruskal- Wallis test).

We also identified statistical difference regarding smoking and alcohol variables (p ‹0.0001, Chi-square test, both). Our results showed that 4.9% (n = 23) of the sample studied had smoking during gestation and 2.3% (n = 11) of ingesting alcohol.

With the evolution of pregnancy, serum levels of adiponectin presented significant differences, characterized by a drop in concentration (p = 0.0003; Kruskal-Wallis test). The data are presented in (Table 1 and Figure 1).

Table 1: Adiponectin serum concentrations (ng/mL) during the gestational weeks of adolescents attended in the prenatal sector of adolescents of Escola Paulista de Medicina - UNIFESP.




  
    Gestational Week
    N
    Minimum
    25% Interquartile Interval
    Medium
    75% Interquartile Interval
    Maximum
  
  
    9ª
    16
    1726
    2047
    3473
    4331
    6282
  
  
    10ª
    16
    1141
    2507
    3733
    5267
    7295
  
  
    11ª
    15
    1350
    2596
    3786
    6389
    7575
  
  
    12ª
    15
    1058
    2891
    3677
    5263
    6924
  
  
    13ª
    18
    2392
    2958
    3578
    4442
    8879
  
  
    14ª
    16
    1507
    1570
    3149
    3823
    5690
  
  
    15ª
    15
    1258
    1913
    2635
    6579
    14284
  
  
    16ª
    15
    1001
    1514
    2569
    6250
    10943
  
  
    17ª
    15
    1205
    2447
    3735
    5690
    8377
  
  
    18ª
    15
    1205
    2476
    3781
    4483
    6579
  
  
    19ª
    15
    1575
    2964
    3835
    7362
    9697
  
  
    20ª
    15
    1322
    1599
    2998
    3459
    5960
  
  
    21ª
    15
    1526
    2224
    3520
    5784
    10943
  
  
    22ª
    15
    1579
    2152
    3369
    4954
    9697
  
  
    23ª
    15
    1569
    1632
    2363
    5236
    5471
  
  
    24ª
    15
    1233
    3349
    4183
    6940
    8520
  
  
    25ª
    15
    1511
    2569
    3120
    4250
    6199
  
  
    26ª
    15
    1540
    1789
    2286
    4445
    5391
  
  
    27ª
    15
    1278
    2157
    3292
    3697
    5541
  
  
    28ª
    15
    1353
    2458
    3520
    4723
    8588
  
  
    29ª
    15
    1036
    1599
    2362
    3261
    5367
  
  
    30ª
    15
    1169
    1838
    2372
    3336
    4445
  
  
    31ª
    15
    1247
    1831
    2534
    3687
    7287
  
  
    32ª
    15
    1007
    1951
    2326
    3372
    6352
  
  
    33ª
    15
    1252
    1568
    2160
    2470
    5037
  
  
    34ª
    15
    1158
    1336
    2564
    3569
    5348
  
  
    35ª
    15
    1506
    1800
    2963
    3185
    22103
  
  
    36ª
    15
    1621
    1883
    2610
    4789
    9056
  
  
    37ª
    15
    1036
    1659
    1931
    3466
    9754
  
  
    38ª
    15
    1509
    1943
    2964
    3233
    5031
  
  
    39ª
    15
    1504
    1863
    2275
    3103
    3589
  
  
    Kruskal-Wallis    test, p=0,0003.



Table 1: Adiponectin serum concentrations (ng/mL) during the gestational weeks of adolescents attended in the prenatal sector of adolescents of Escola Paulista de
Medicina - UNIFESP.

Figure 1: Adiponectin serum levels (ng/mL) during the gestational weeks of adolescents attended in the prenatal sector of adolescents of Escola Paulista de Medicina - UNIFESP.

    
    
    Figure 1: Adiponectin serum levels (ng/mL) during the gestational weeks of
adolescents attended in the prenatal sector of adolescents of Escola Paulista
de Medicina - UNIFESP.

We did not observe a correlation between the pre-gestational BMI, the weight gain of the pregnant women and the serum levels of adiponectin (p = 0.36, p = 0.10, respectively).

After the Kruskal-Wallis test, we observed that there were no statistical differences in serum adiponectin levels between the gestational weeks of the adolescents included in the study (Dunn’s post-test).

With the advancement of gestational weeks, we identified an increase in serum leptin levels (p ‹0.0001; One Way Test-ANOVA). The results are described in (Table 2 and Figure 2).

Table 2: Serum leptin concentrations (ng/mL) during the gestational weeks of adolescents attended in the prenatal sector of adolescents of the Escola Paulista de Medicina - UNIFESP.




  
    Gestational Week
    N
    Minimum
    Maximum
    Average
    Standard Deviation
  
  
    9ª
    16
    9,6
    59,75
    24,29
    14,83
  
  
    10ª
    16
    9,57
    45,9
    22,11
    10,09
  
  
    11ª
    15
    11,29
    98,01
    38,46
    30,29
  
  
    12ª
    15
    5,83
    95,65
    40,10
    32,56
  
  
    13ª
    18
    11,48
    103,3
    29,91
    22,45
  
  
    14ª
    16
    5,59
    54,48
    26,12
    15,27
  
  
    15ª
    15
    2,15
    65,16
    24,51
    16,51
  
  
    16ª
    15
    5,29
    82,23
    32,91
    22,24
  
  
    17ª
    15
    7,74
    43,74
    18,47
    10,69
  
  
    18ª
    15
    7,73
    38,06
    19,54
    8,867
  
  
    19ª
    15
    8,84
    55,34
    28,1
    11,16
  
  
    20 ª
    15
    11,56
    96,91
    38,42
    23,87
  
  
    21ª
    15
    12,85
    54,45
    28,34
    11,01
  
  
    22ª
    15
    12,15
    54,46
    24,37
    11,97
  
  
    23ª
    15
    7,18
    55,45
    33,53
    15,64
  
  
    24ª
    15
    3,42
    46,22
    20,01
    13,26
  
  
    25ª
    15
    4,76
    61,51
    21,84
    17,05
  
  
    26ª
    15
    11,7
    48,05
    31,00
    12,96
  
  
    27ª
    15
    4,47
    51,06
    26,15
    13,98
  
  
    28ª
    15
    1,31
    40,67
    24,89
    11,11
  
  
    29ª
    15
    11,05
    69,42
    31,59
    16,25
  
  
    30ª
    15
    4,67
    87,76
    39,67
    23,52
  
  
    31ª
    15
    11,88
    83,12
    40,42
    23,78
  
  
    32ª
    15
    4,49
    77,36
    39,57
    22,15
  
  
    33ª
    15
    11,04
    160,2
    39,30
    39,22
  
  
    34ª
    15
    7,56
    68,42
    30,62
    17,49
  
  
    35ª
    15
    12,38
    85,75
    45,52
    21,32
  
  
    36ª
    15
    2,87
    77,51
    42,39
    22,37
  
  
    37ª
    15
    14,17
    79,61
    40,15
    16,93
  
  
    38ª
    15
    19,63
    85,75
    49,93
    22,51
  
  
    39ª
    15
    11,07
    85,5
    34,75
    20,57
  
  
    ANOVA One-Way Test, p <0,0001.



Table 2: Serum leptin concentrations (ng/mL) during the gestational weeks of adolescents attended in the prenatal sector of adolescents of the Escola Paulista de
Medicina - UNIFESP.

Figure 2: Serum levels of Leptin (ng/mL) during the gestational weeks of adolescents attended in the prenatal sector of adolescents of Escola Paulista de Medicina - UNIFESP.

    
    
    Figure 2: Serum levels of Leptin (ng/mL) during the gestational weeks of
adolescents attended in the prenatal sector of adolescents of Escola Paulista
de Medicina - UNIFESP.

After the One-Way ANOVA test, we observed statistical differences regarding serum leptin levels between some gestational weeks (compared to two, Tukey’s post-test). We identified differences in the comparisons between the 17^th to the 38^th, the 18^th to the 38^th, the 24^th to the 38^th and the 25^th to the 38^th.

We identified a positive correlation between pre-gestational BMI and the weight gain of pregnant women with serum leptin levels (p = 0.003, p = 0.0007, respectively).

Discussion

This study performed with adolescent pregnant women evaluated the serum profile of adiponectin (ng/mL) and leptin (ng/mL) during the course of pregnancy (9^th to 39^th gestational weeks). Through the values found, a gestational curve was developed with the serum concentrations for these molecules.

In pregnancy, adiponectin acts on the development of the inflammatory response in the maternal-fetal unit. This reaction is physiological and needs to be modulated so that an adequate evolution of the pregnancy occurs. The involvement of this protein in local and systemic inflammatory reactions is already well known [34].

The literature indicates that this molecule presents specific behavior in pregnant women, but, unlike other adipokines, its serum concentration tends to reduce with the progression of gestation [13,17,35,36]. There appears to be a negative correlation between adiponectin and gestational age [14,15]. Similar results were observed in our study with adolescents.

Some authors have reported that plasma levels of adiponectin decrease gradually with the advancement of pregnancy because its concentration reduces as the fat tissue increases [13-15,37], but these values return to normal soon after delivery [13]. Studies have reported that the serum concentration of adiponectin at certain periods of gestation in healthy women may be altered from the first trimester [36-38]. Some studies indicate a correlation between IR and adiponectin concentration in adult pregnant women [39-42].

In similar studies, researchers demonstrated significant differences during pregnancy progression in adults, where they observed a reduction in the serum concentration of adiponectin when they compared the first to the third trimester [6,37,39,43].

Our results show that the behavior of adiponectin in the evolution of gestation in adolescents is similar to what the literature indicates in pregnancy for adults.

When we observed the serum levels of adiponectin (ng/mL) during gestational weeks we found that the concentration of this molecule tends to be higher at the beginning of gestation (median 3473 ng/mL) than at the end of pregnancy (median 2275 ng/mL).

In this study, we observed a peak serum adiponectin concentration at the 24th gestational week. Our hypothesis is that this alteration is related to the installation of IR, however we do not find other studies that support this hypothesis in the literature.

The literature shows that, unlike other hormones secreted by adipose tissue, serum adiponectin levels decrease as adiposity increases, being inversely correlated with obesity, IR and metabolic syndrome [2,44].

In relation to leptin, our study showed a significant increase (p = 0.0001) with the evolution of pregnancy, suggesting that this change can be gradually observed. The literature shows that plasma concentrations of leptin increase during pregnancy in adults, concluding that this is a condition in which hyperleptinemia is observed [18,45-47].

Researchers studying serum levels of leptin in adult pregnant women found that the plasma concentration had a significant increase between the first and third trimester of gestation with postpartum decline [46]. During pregnancy, the concentration of leptin in maternal serum is higher than that observed in non-pregnant women [29].

Our results were similar to those presented in recent studies with adult pregnant women [45,49,50]. Serum levels of leptin present changes during pregnancy, this increase occurs in pregnant women with and without obstetric complications. Elevation in serum concentration during the course of pregnancy has been extensively investigated with the main purpose of elucidating a possible relationship to clinical intercurrences such as preeclampsia, gestational diabetes, intrauterine growth restriction and low birth weight [19,28,45,46,51-55].

Studies have shown that serum leptin concentration during pregnancy with clinical complications appears to be related to hyperleptinemia [28,45,46,51-55], and that women who experience spontaneous or recurrent miscarriage appear to have lower plasma levels such a molecule [56,57].

Our results are similar to those observed in gestation of adult women [45,52]. Serum leptin concentrations begin to rise from the onset of pregnancy and are higher than that of non-pregnant women throughout pregnancy [23].

The literature indicates that leptin values are directly related to the amount of adipose tissue present in the body, since the plasma concentration differs in people with the same BMI [23].

It is known that gestation is characterized by metabolic and endocrine adaptations of the maternal organism, including increased body weight and adipose tissue. Thus elevated serum leptin levels during pregnancy are related to weight gain and BMI, as well as changes in hormone levels that may stimulate the secretion of this molecule (eg, insulin) [59]. Our results are similar to those performed with adult pregnant women, where a positive correlation was observed between maternal plasma leptin concentration and anthropometric data at both the beginning and the end of gestation. This association suggests that body weight and, probably, adiposity gain are important factors for the increase in circulating leptin levels [58,60]. Thus, based on our study we can affirm that in adolescent pregnant there is an increase in the plasma concentration of leptin and reduction in adiponectin during the course of gestation. In adolescents we observed similar results to those observed for the adult pregnant woman, thus showing that these molecules have the same behavior independent of the age group. The continuity of this research may contribute to elucidate the doubts about the behavior of adipokines in the progression of gestation, but it is worth noting that until now the literature does not present a gestational curve with the values determined for adults and/or adolescents.

Conclusion

With the evolution of pregnancy, serum levels of adiponectin (ng / mL) presented a reduction in blood concentration, with significant differences (p = 0.0003). When we compared the serum values of adiponectin from two to two gestational weeks, we did not observe a statistically significant alteration, evidencing a progressive decrease. No correlation was observed between the pre-gestational BMI and the weight gain of the pregnant women and the plasma levels of adiponectin (ng/mL) (p = 0.36, p = 0.10, respectively).

With the evolution of pregnancy, serum levels of leptin (ng/ mL) showed an increase in blood concentration, with significant differences (p ‹0.0001). The serum concentration of leptin (ng/mL) presented statistically significant differences when we compared the 17^th, 38^th, 18^th, 38^th, 24^th, 38^th and 25^th, 38^th. We observed a positive correlation between the pre-gestational BMI and the weight gain of the pregnant women and the serum concentration of leptin (ng/mL) (p = 0.003; p = 0.0007, respectively).

The pattern of adiponectin and leptin production observed in adolescent pregnant women is similar to that seen in adult pregnant women.

Acknowledgements

Author contributions

Indiomara Baratto – Performed the laboratories tests, collected the data, collaborated in patient recruitment, made clinical contribuitions, wrote the manuscript.

Silvia Daher – designed the study analyzed the data and performance the statistical analysis

Thalita Frutuoso Lobo – performed the laboratories tests and the statistical analysis

Cristina Aparecida Falbo Guazzelli – designed the study, collected the data, collaborated in patient recruitment, wrote and corrected the manuscript.

References

Download PDF

Citation: Baratto I, Daher S, Frutuoso Lobo T and Aparecida Falbo Guazzelli C. Serum Levels and Gestational Curve of Adiponectin and Leptin During Adolescent Pregnancy. J Pediatri Endocrinol. 2019; 4(1): 1029.

Instruction for Authors

Submit Your Article