|Year : 2020 | Volume
| Issue : 3 | Page : 891-897
Causal relationship between cord blood leptin level and different patterns of birth weight
Ahmed A Khattab1, Dalia M El-Lahony1, Wafaa M Abo El-Fotoh1, Osama T Abd El-Fattah2
1 Pediatrics Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Pediatrics Department, Ministry of Health, Menoufia, Egypt
|Date of Submission||15-Feb-2019|
|Date of Decision||07-Mar-2019|
|Date of Acceptance||10-Mar-2019|
|Date of Web Publication||30-Sep-2020|
Osama T Abd El-Fattah
Source of Support: None, Conflict of Interest: None
To estimate the cord blood leptin level in different patterns of birth weight.
Birth weight is a strong predictor of both neonatal mortality and morbidity. Umbilical cord blood leptin has been consistently shown to be positively associated with birth weight. It has been widely accepted as a marker of neonatal adiposity.
Patients and methods
A case–control study was conducted on 60 neonates who were divided into 20 small for gestational age (SGA), 20 appropriate for gestational age (AGA), and 20 large for gestational age (LGA). All neonates were recruited from the gynecology and obstetrics department at Menoufia University Hospital and Shebin El-Kom Teaching Hospital, Egypt, during 1 June till 25 November 2018. Full history, physical examination, and cord leptin level were examined in all neonates.
Most patients of SGA group were males (60%), whereas females were the most frequent in AGA (60%) and LGA (80%) groups. LGA had significantly higher cord leptin (53.58 ± 19.75 ng/ml) than AGA (20.99 ± 12.8 ng/ml) and SGA (5.77 ± 8.27 ng/ml) groups (P < 0.005). It was significantly higher in AGA group than SGA group (P = 0.014). Cord leptin was significantly positive correlated with birth weight in SGA (P < 0.01) and AGA groups (P = 0.013) and BMI in SGA group only (P = 0.026).
Umbilical cord leptin level was significantly higher in LGA and AGA groups than SGA group. Umbilical cord leptin level was positively correlated with birth weight in SGA, AGA, and LGA groups. However, it was not correlated with sex of neonates in all studied groups.
Keywords: appropriate for gestational age, birth weight, leptin, large for gestational age, neonates, small for gestational age
|How to cite this article:|
Khattab AA, El-Lahony DM, Abo El-Fotoh WM, Abd El-Fattah OT. Causal relationship between cord blood leptin level and different patterns of birth weight. Menoufia Med J 2020;33:891-7
|How to cite this URL:|
Khattab AA, El-Lahony DM, Abo El-Fotoh WM, Abd El-Fattah OT. Causal relationship between cord blood leptin level and different patterns of birth weight. Menoufia Med J [serial online] 2020 [cited 2020 Nov 26];33:891-7. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/891/296700
| Introduction|| |
Birth weight remains one of the most important measures of the health status of a population and is a strong predictor of both neonatal mortality and morbidity. It can reflect fetal growth rates in the antenatal period. Fetal growth is a complex process that is influenced by multiple factors and has far-reaching health implications . Several hormones are believed to have a regulatory role. However, the relative contribution of many hormones remains speculative at best and usually controversial . Leptin is a circulating polypeptide hormone expressed abundantly in the adipose tissue that regulates body weight and energy expenditure through a negative feedback signal between the adipose tissue and the hypothalamic centers of satiety . Both fetal and placental productions of leptin have been demonstrated, but the different contribution of these two compartments to umbilical leptin circulating levels is difficult to evaluate . The role of leptin as an intrauterine growth modulator has been a subject of controversy. Healthy pregnant women have significantly higher serum leptin levels than healthy nonpregnant ones . Cord blood leptin concentrations have also been shown to be inversely associated with weight gain in infancy and with BMI in early childhood . Higher circulating fetal and maternal leptin levels and the presence of leptin and leptin receptors in fetal and placental tissues indicate that leptin is potentially a growth factor. However, the strong correlation between leptin and birth weight may merely reflect fetal adiposity and may not be related to fetal growth . The aim of this study was estimate the serum leptin level in different patterns of birth weight to find the causal association between cord leptin concentration and birth weight.
| Participants and Methods|| |
A case–control study was conducted on 60 neonates who were divided into 20 small for gestational age (SGA), 20 appropriate for gestational age (AGA) and 20 large for gestational age (LGA). All neonates were recruited from the Gynecology and Obstetrics Department (neonatal resuscitation room). The sample was recruited immediately after birth at Menoufia University and Shebin El-Kom Teaching Hospital, Egypt, during the period of 1 June till 25 November 2018. The study was approved by the Ethical Committee of Menoufia Faculty of Medicine, and an informed consent obtained from all patient's guardian before the start of the study. Inclusion criteria were both sexes, age immediately after birth, and the following birth weights: AGA: a birth weight was considered to be appropriate for gestational age if the birth weight was between the 10th and 90th percentiles for the infant's gestational age and sex; SGA: infants who are at or below the 10th percentile in birth weight, for the infants of the same gestational age and sex; and LGA: infants who are at or above the 90th percentile in birth weight, for the infants of the same gestational age and sex.
Chromosomal anomalies, major congenital anomalies, smoker or alcoholic mother, birth asphyxia, neonatal sepsis, and refusal of parental consent were the exclusion criteria.
All cases were subjected to full history taking, including age of mother, maternal illness, date of last menstrual period, and maternal drug intake; natal history, including mode of delivery, gestational age, Apgar score, and resuscitation measures; postnatal history, including activity, suckling, and incubation; complete clinical examination, stressing on general examination and general look; vital signs [respiratory rate, heart rate, temperature and blood pressure); anthropometric measures (weight, height, head circumference and abdominal girth with calculation of BMI (kg/m 2)]; assessment of maturity using the new Ballard score (it is a set of procedures developed to determine gestational age through neuromuscular and physical assessment of a newborn infant, the neuromuscular criteria depend mainly upon muscle tone and the physical ones rely on anatomical changes) ; and systemic examination, including chest and heart examination, complete abdominal examination, and full neurological examination.
Laboratory investigations included complete blood count, quantitative CRP, and cord blood leptin.
Method of sampling
Sample size was calculated using computer sample block randomization type. Samples were obtained during routine investigations. A 5-ml venous blood sample was taken from cord blood immediately after the separation of the placenta. Blood was left to clot and then centrifuged for 10 min at 5000 rpm. The sera were separated and stored at −20°C until the time of the assay. Venous blood was drained by sterile syringes and put in a tube containing dipotassium EDTA reagent. The sample were shaken gently and analyzed by Medonic 20 (Sweden).
Measurement of cord blood leptin
It was done using DRG Leptin ELISA kits (EIA-2395) RUO, (DRG International, Inc. Global Headquarters 841 Mountain Avenue Springfield, NJ 07081, USA). The enzymatic reaction is stopped chemically, and the color intensity is read at 450 nm in an ELISA reader. From the absorbance of the samples and those of a calibration curve, the concentration of leptin is determined by interpolation.
Results were tabulated and statistically analyzed using a personal computer using Microsoft Excel 2016 and SPSS version 21 (SPSS Inc., Chicago, Illinois, USA). Statistical analysis was done using descriptive, for example, percentage, mean and SD, and analytical, for example, χ2, F test, Mann–Whitney test, and Pearson's correlation coefficient (r). A P value less than 0.05 was considered statistically significant.
| Results|| |
Results showed that there was no statistically significant difference between the studied groups regarding the age of the mothers of studied neonates. However, BMI of the mothers was significantly higher in LGA (30.17 ± 3.92 kg/m 2) than SGA (24.09 ± 1.92 kg/m 2) and AGA (26.15 ± 2.38 kg/m 2) groups. Moreover, it was higher in AGA than SGA group. There was a significant difference among the studied groups regarding mode of delivery, with the exception between SGA and AGA. Most of the studied group infants were delivered by cesarean section (40 neonates) than normal vaginal delivery (20 neonates). Moreover, there was a significant difference among the studied groups regarding history of diabetic mellitus [Table 1]. The study shows that most (60%) of SGA group patients were males, whereas females were the most frequent in AGA (60%) and LGA (80%) groups. Birth weight was significantly higher in LGA group (4.24 ± 0.14 kg) than SGA (2.15 ± 0.37 kg) and AGA (3.21 ± 0.38 kg) groups. Moreover, head circumference was significantly higher in LGA (35.33 ± 0.52 cm) group than SGA (30.41 ± 1.46 cm) and AGA (33.35 ± 1.46 cm) groups [Figure 1]. Length and BMI of neonates were significantly higher in LGA group than SGA and AGA groups. Moreover, length and BMI were higher in AGA group than SGA group [Table 2]. Analyzing complete blood count, platelets were significantly higher in AGA (280 ± 104 × 103) group than SGA (221 ± 73.11 × 103/μl) and LGA (267 ± 94.0 × 103/μl) groups (P < 0.05). Moreover, it was higher in LGA (267 ± 94.0 × 103/μl) group than SGA (221 ± 73.11 × 103/μl) group (P = 0.018). However, there was no significant difference among SGA, AGA, and LGA groups regarding haemoglobin% and total leukocytes count [Table 3]. The results of cord leptin showed a highly significant difference among SGA, AGA and LGA groups regarding cord leptin (ng/ml). It was significantly higher in LGA (53.58 ± 19.75 ng/ml) than AGA (20.99 ± 12.8 ng/ml) and SGA (5.77 ± 8.27 ng/ml) groups (P < 0.05). Moreover, cord leptin was significantly higher in AGA group more than SGA group (P = 0.014; [Table 3]). Additionally, cord leptin was significantly positively correlated with birth weight in SGA (r = 0.880, P < 0.01) and AGA groups (r = 0.668, P = 0.013) and no correlation in LGA group. Cord leptin was significantly positively correlated with BMI in SGA group only (r = 0.664, P = 0.026; [Figure 2]), and no correlation was found in AGA and LGA groups [Table 4]. Our results show the best cutoff points for cord leptin level to be 71.25 ng/ml, and at that point, its sensitivity to diagnose the different patterns of birth weight is 30.8%, and specificity is 62.4%.
|Table 1: Comparison between the studied groups regarding age and BMI and maternal risk factors of studied neonates|
Click here to view
|Figure 1: Distribution of the studied groups regarding birth weight and head circumference of the studied neonates.|
Click here to view
|Table 2: Comparison between the studied groups regarding clinical data and anthropometric measurements|
Click here to view
|Table 3: Comparison between the studied groups regarding complete blood count findings and serum cord leptin concentration|
Click here to view
|Figure 2: Correlation between cord leptin and BMI in small-for-gestational-age group.|
Click here to view
|Table 4: Correlation between serum leptin in the studied groups in comparison with different parameters|
Click here to view
| Discussion|| |
In this study, there were no statistical significant differences among the studied groups regarding the age of the mothers of studied neonates. However, BMI of the mothers was statistical significantly higher in LGA than SGA and AGA groups. Moreover, it was higher in AGA than SGA group. This comes in agreement with Chaoimh et al.  who found the same result that BMI of the mothers was significantly higher in LGA than SGA and AGA groups. Moreover, Christou et al.  found that, as expected, weight, length, and BMI were significantly higher in LGA compared with AGA infants. In this study, there was a significant difference among the studied groups regarding mode of delivery with the exception between SGA and AGA. This agrees with Wells et al.  who found the same results. Our results disagree with Christou et al.  who found that the distribution of vaginal deliveries and cesarean sections was not significantly different between the LGA group and the AGA group. In this study, there was significant difference among the studied groups regarding the history of maternal diabetes mellitus, which is higher in LGA group more than AGA and SGA groups. This agrees with Byström et al.  who concluded that gestational diabetes mellitus has a strong association with increase birth weight. Moreover, Tyrrell et al.  stated that genetically elevated maternal BMI and elevated blood glucose levels were potentially causally associated with higher offspring birth weight. In this work, there was no statistically significant difference among the studied groups regarding their sex. These findings agree with Tung et al.  who revealed that there were no significant differences in birth weight and BMI between male and female neonates. In addition, Wolf et al.  found that males were the most frequent in AGA (47 cases) and LGA (36 cases) than in SGA (12 cases) group. However, females were frequent by AGA (35 cases), LGA (34 cases) and SGA (11 cases). In this study, there was a highly significant difference among SGA, AGA, and LGA groups regarding their anthropometric measurements. Birth weight, head circumference, length, and BMI of neonates were significantly higher in LGA group than SGA and AGA groups, correspondingly. This agrees with Wolf et al.  who found that head circumference, length, and BMI were higher in LGA than AGA and SGA. Moreover, Christou et al.  found that birth weight was significantly increased in LGA group than AGA group. In the same line, mean head circumference was significantly increased in LGA group than AGA. In addition, Kuhle et al.  found that BMI and HC are ∼0.25 SD units larger in LGA compared with AGA infants. Our results disagree with Ramy et al.  who found that there was no significant difference in maternal and their neonates' measurements, age, parity, birth weight, head circumference, length, and BMI between SGA, AGA and LGA groups. This result showed that platelets were significantly higher in AGA group than SGA and LGA. It was also higher in LGA group than SGA group. However, there was no significant difference among SGA, AGA and LGA groups regarding haemoglobin% and total leukocytes count. These results agree with Nayak et al.  who found highest levels of platelets in AGA and lowest in the SGA group. Moreover, Decsi et al.  found no difference in serum hemoglobin level between SGA and preterm newborn with comparably low birth weight. Ramy et al.  found significant differences in platelets count among the three study groups, with the highest mean platelet in the SGA group compared with the other two groups. In this study, we found that cord leptin (ng/ml) was significantly higher in LGA (53.58 ± 19.75 ng/ml) than AGA (20.99 ± 12.8 ng/ml) and SGA (5.77 ± 8.27 ng/ml) groups. This may be owing to high adipose tissue, which was present more in LGA than AGA and SGA. Moreover, cord leptin was significantly higher in AGA group more than SGA group. This agrees with Palcevska-Kocevska et al.  who found that there was a significant difference between leptin levels in AGA and LGA newborns (1.93 ± 0.84 vs. 3.12 ± 1.50 ng/ml). Valūnienė et al.  found that SGA infants had significantly lower levels of cord leptin compared with AGA infants. In addition, Piphetti et al.  stated that SGA newborns had significantly reduced cord leptin concentration as compared with LGA and AGA. This study revealed that cord leptin level was significantly positively correlated with birth weight in SGA (P < 0.001) and AGA (P = 0.013) groups. Previous studies have reported significant positive correlation between leptin concentration and fetal weight, indicating that leptin is a potential growth factor ,,,,,. This study revealed that cord leptin level was not significantly correlated with sex of neonates in SGA, AGA and LGA groups, which agrees with Considine et al.  who found that there was no sex effect on leptin levels in human. In addition, Mouzaki et al.  reported that there was no sex difference of leptin levels in cord blood at term in contrast to the situation in the adult, where consistently higher levels of leptin are found in serum from female than from male individuals. However, Tung et al.  revealed that female neonates had significantly higher levels of umbilical cord leptin than males. This study revealed that serum leptin level was significantly positive correlated with BMI in SGA group only (P = 0.026), and no correlation was found in AGA and LGA groups. These results agree with Palchevska et al.  who observed a positive correlation between BMI and concentration of leptin and adiponectin in SGA group. Our results disagree with Karakosta et al.  who found that newborn with high cord blood leptin exhibit lower weight, height, and BMI at birth. Moreover, Brunner et al.  reported inverse associations between cord blood leptin and BMI in early life and have suggested that early-life leptin concentrations may play a role in the development of obesity. Our results shows the best cutoff point for cord leptin level is 71.25 ng/ml, and at that point, its sensitivity to diagnose the different patterns of birth weight is 30.8% and specificity is 62.4%.
| Conclusion|| |
Our data indicate that birth weight is independently associated with leptin concentrations in cord blood of newborns. Umbilical cord leptin level was significantly positive correlation with birth weight in SGA, AGA, and LGA groups, and this suggests that leptin may be involved in as-yet-unknown mechanisms that regulate fetal growth. However, it was not correlation with sex of neonates in the studied groups.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Elhddad ASA, Lashen H. Birth weight in relation to fetal and maternal leptin and insulin: a systematic review and meta-analysis. 2012; 1:1-14.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 2015; 372
Clapp IIIJF, Kiess W. Cord blood leptin reflects fetal fat mass. J Soc Gynecol Investig 2008; 5
Molvarec A, Szarka A, Walentin S, Beko G, Karádi I, Prohászka Z, et al
. Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia. Reprod Biol Endocrinol 2011; 9
Brunner S, Schmid D, Huttinger K, Much D, Bruderl M, Sedlmeier EM, et al
. Effect of reducing the n-6/n-3 fatty acid ratio on the maternal and fetal leptin axis in relation to infant body composition. Obesity (Silver Spring) 2014; 22
Karakosta P, Chatzi L, Plana E, Margioris A, Castanas E, Kogevinas M. Leptin levels in cord blood and anthropometric measures at birth: a systematic review and meta-analysis. Paediatr Perinat Epidemiol 2011; 25
Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard Score, expanded to include extremely premature infants. J Pediatr 2009; 119
Chaoimh C, Murray DM, Kenny LC, Irvine AD, Hourihane J, Kiely M. Cord blood leptin and gains in body weight and fat mass during infancy. Eur J Endocrinol 2016; 175
Christou H, Connors JM, Ziotopoulou M, Hatzidakis V, Papathanassoglou E, Ringer SA, et al
. Cord blood leptin and insulin-like growth factor levels are independent predictors of fetal growth. J Clin Endocrinol Metab 2001; 86
Wells JC, Dumith SC, Ekelund U, Reichert FF, Menezes AM, Victora CG, et al
. Associations of intrauterine and postnatal weight and length gains with adolescent body composition: prospective birth cohort study from Brazil. J Adolesc Health 2012; 51
Byström M, Liu A, Quinton AE, Champion BL, Mann K, Peek M, Nanan RKH. Gestational diabetes independently increases birth length and augments the effects of maternal BMI on birth weight: a retrospective cohort study. Front Pediatr 2014; 2
Tyrrell J, Richmond RC, Palmer TM, Feenstra B, Rangarajan J, Metrustry S, et al
. Genetic evidence for causal relationships between maternal obesity-related traits and birth weight. JAMA 2016; 315
Tung W, Lin S, Hwang Y, Wu C, Wang Y, Tsai WH. Association of cord plasma leptin with birth size in term newborns. Pediatr Neonatol 2009; 50
:255 − 260.
Wolf HJ, Ebenbichler CF, Huter O, Bodner J, Lechleitner M, Foger B, et al
. Fetal leptin and insulin levels only correlate in large-for-gestational age infants. Eur J Endocrinol 2000; 142
Kuhle S, Ashley-Martin J, Maguire B, Hamilton DC. Percentile curves for skinfold thickness for Canadian children and youth. PeerJ 2016; 4
Ramy N, Zakaria M, El Kafoury M, Kamal M. Cord blood lipid profile in relation to anthropometric measures of newborns. Kasr Al Ainy Med J 2017; 23
Nayak CD, Agarwal V, Nayak DM. Correlation of cord blood lipid heterogeneity in neonates with their anthropometry at birth. Indian J Clin Biochem 2013; 28
Decsi T, Erhardt E, Márkus A, Burus I, Molnár D. Plasma lipids, phospholipid fatty acids and indices of glycaemia in 10-year-old children born as small-for-gestational-age or preterm infants. Acta Paediatr 1999; 88
Palcevska-Kocevska S, Aluloska N, Krstevska M, Shukarova-Angelovska E, Kojik L, et al
. Correlation of serum adiponectin and leptin concentrations with anthropometric parameters in newborns. Srp Arh Celok Lek 2012; 140
Valūnienė M, Verkauskienė R, Boguszewski M, Dahlgren J, Lašienė D, Lašas L, et al
. Leptin levels at birth and in early postnatal life in small- and appropriate-for-gestational-age infants. Medicina 2007; 43
Piphetti M, Tommaselli A, D'Elia A, Di Carlo C, Mariano A, Di Carlo A, et al
. Maternal serum and umbilical cord blood leptin concentrations with fetal growth restriction. Obstet Gynecol 2003; 102
Hassink SG, de Lancey E, Sheslow DV, Opentanoue I, Considine RV, Caro JF et al
. Placental leptin: an important new growth factor in intrauterine and neonatal development? Pediatrics 2011; 100
Koistinen HA, Koivisto VA, Andersson S, Karonen SL, Kontula K, Oksanen L, et al
. Leptin concentration in cord blood correlates with intrauterine growth. J Clin Endocrinol Metab 1997; 82
Ong KK, Ahmed ML, Sherriff A, Woods KA, Watts A, Golding J, Dunger DB. Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. J Clin Endocrinol Metab 2009; 84
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al
. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334
Mouzaki A, Panagoulias I, Raptis G, Farri-Kostopoulou E. Cord blood leptin levels of healthy neonates are associated with IFN-γ production by cord blood T-cells. PLoS One 2012; 7
Palchevska S, Krstevska M, Shukarova E, Aluloska N, Jakimoska M, Kocevski D, et al
. Comparing preterm and term newborns serum adiponectin and leptin concentrations and their correlations with anthropometric parameters. Maced J Med Sci 2012; 5
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]