Prediction of cord blood leptin on infant's neurodevelopment: A birth cohort in rural Yunnan, China.

BACKGROUND: Leptin, one of the peptide hormones secreted by adipocytes, plays a vital part in metabolism, but its role in early-life neurodevelopment remains poorly understood. METHODS: We performed leptin analysis on 323 cord blood samples collected from a birth cohort in Yunnan rural area, China, and assessed infants' neurodevelopment at one year of age by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Multiple linear regression and binary logistic regression models were used to explore the associations between cord blood leptin (CBL) concentrations and infants' neurodevelopment and the ability of CBL to predict the probabilities of infants' neurodevelopment delay. RESULTS: Overall, 323 infants were included in this study. The median concentration of CBL was 4.7 ng/ml. The proportion of 1-year-old infants identified as being neurodevelopmental delayed was 34.5%, and delays in cognitive, language, and motor domains were 11.1%, 26.6%, and 13.9%, respectively. Multiple linear regression analyses manifested that the CBL concentration (log10-transformed) was positively correlated with the cognitive, language, and motor composite scores in infants, respectively (ß = 7.76, 95%CI: 3.81-11.71; ß = 6.73, 95%CI: 3.41-10.06; and ß = 6.88, 95%CI: 3.48-10.29, respectively). Binary logistic regression analysis showed that compared with the higher, lower CBL (< 4.7 ng/ml) yielded a 1.41-fold increase in the risk of language development delay (OR = 2.41，95%CI: 1.42-4.09), a 1.49-fold higher risk of motor development delay (OR = 2.49, 95%CI: 1.25-4.96), and a 1.71-fold higher risk of neurodevelopment delay (OR = 2.71, 95%CI: 1.64-4.48) among infants. The prediction models showed that the probabilities of development delay in infants' language, motor, and neurodevelopment increased with the decline of CBL concentrations [rs = -0.63 (95% CI: -0.71, -0.56), rs = -0.46 (95% CI: -0.55, -0.38), rs = -0.55 (95% CI: -0.63, -0.46), respectively]. CONCLUSION: The decline of CBL was associated with the decrease in infants' neurodevelopment scores at one year of age. CBL below 4.7 ng/ml may increase the risk of infants' neurodevelopment delay. The probabilities of infants' neurodevelopment delay increased with the decrease of CBL concentrations. CBL may be a predictor of the probability of children's neurodevelopment delay.

Associations between Cord Blood Leptin Levels and Childhood Adiposity Differ by Sex and Age at Adiposity Assessment.

Lower cord blood leptin levels have been associated with lower and higher adiposity in childhood and associations seem to differ according to the child's age, methods of adiposity assessment and sex. Our aim was to investigate sex-specific associations of cord blood leptinemia with childhood adiposity at birth, 3 and 5 years of age. We measured cord blood leptin using Luminex immunoassays in 520 offspring from the Gen3G cohort. We tested associations between cord blood leptin and body mass index (BMI) z-score, skinfolds thicknesses (SFT), and body composition using dual-energy X-ray absorptiometry, adjusted for confounders. At birth, girls had almost twice as much leptin in cord blood as boys (15.5 [8.9; 25.6] vs. 8.6 [4.9; 15.0] ng/mL; p < 0.0001) as well as significantly greater adiposity. Lower levels of cord blood leptin were associated with higher sum of SFT (ß = −0.05 ± 0.02; p = 0.03) and higher BMI z-score (ß= −0.22 ± 0.08; p = 0.01) in 3-year-old boys only. We did not observe these associations at age 5, or in girls. Our results suggest a sexual dimorphism in the programming of leptin sensitivity and childhood adiposity, but further observational and functional studies are needed to better understand the role of leptin in early life.

Cord blood leptin level and a common variant of its receptor as determinants of the BMI trajectory: The EDEN mother-child cohort.

BACKGROUND: Cord blood leptin is an indicator of neonatal fat mass and could shape postnatal adiposity trajectories. Investigating genetic polymorphisms of the leptin receptor gene (LEPR) could help understand the mechanisms involved. OBJECTIVES: We aimed to investigate the association of cord blood leptin level and the LEPR rs9436303 polymorphism, with body mass index (BMI) at adiposity peak (AP) and age at adiposity rebound (AR). METHODS: In the EDEN cohort, BMI at AP and age at AR were estimated with polynomial mixed models, for 1713 and 1415 children, respectively. Multivariable linear regression models allowed for examining the associations of cord blood leptin level and LEPR rs9436303 genotype with BMI at AP and age at AR adjusted for potential confounders including birth size groups. We also tested interactions between cord blood leptin level and rs9436303 genotype. RESULTS: Increased leptin level was associated with reduced BMI at AP and early age at AR (comparing the highest quintile of leptin level to the others). Rs9436303 G-allele carriage was associated with increased BMI at AP and later age at AR but did not modulate the association with leptin level. CONCLUSION: These results illustrate the role of early life body composition and the intrauterine environment in the programming of adiposity in childhood.

Cord Blood Adipocytokines and Body Composition in Early Childhood: A Systematic Review and Meta-Analysis.

Childhood obesity is a growing epidemic. Early identification of high-risk groups will allow for the development of prevention strategies. Cord blood adipocytokines have been previously examined as biomarkers predicting future obesity. We conducted a systematic review looking at the association between cord blood leptin and adiponectin with adiposity up to 5 years of age. A literature review was performed between January 1994 and August 2020 using two bibliographic databases (Medline/Pubmed and EMBASE) and was registered on PROSPERO (CRD42017069024). Studies using skinfold thickness and direct methods of assessing body composition in full term neonates were considered. Partial correlation and multiple regression models were used to present the results. Meta-analysis was performed, were possible, using a random effects model. Cochran's Q test was used to assess heterogeneity and I2 statistics to calculate the percentage of variation across studies. The potential for publication bias was assessed using funnel plots. Data from 22 studies were retrieved and reviewed by two independent reviewers. Cord blood leptin was positively associated with adiposity at birth (r = 0.487; 95% CI: 0.444, 0.531) but was inversely related to adiposity up to 3 years of age. The association was not sustained at 5 years. There was a weak positive association between adiponectin in cord blood and adiposity at birth (r = 0.201; 95% CI: 0.125, 0.277). No correlation was found between cord blood adiponectin in young children, but data were limited. This review supports that cord blood leptin and adiponectin are associated with adiposity at birth. The results of this study provide insight into the role of adipocytokines at birth on future metabolic health and their potential use as risk stratification tools.

Does cord blood leptin level mediate the association between neonatal body size and postnatal growth? Results from the EDEN mother-child cohort study.

Background: Leptin is potentially involved in the correction of early postnatal growth of infants having deviated from their genetic trajectory in utero.Aim: To analyse the potential mediating role of cord blood leptin level in the association between neonatal anthropometry and early postnatal growth in the mother-child EDEN cohort.Subjects and methods: We included term newborns with information on leptin, birth weight and length, and weight and length SD-score changes over the first 2 months. The Baron and Kenny method was used to quantify the mediation contribution of leptin in the association between neonatal anthropometry and postnatal growth, considering several confounders. Analyses were stratified to consider sexual dimorphism.Results: A 1 SD higher birth weight was associated with a lower 2-months weight variation of 0.27 (0.18; 0.36) SD and a 0.16 (0.06; 0.26) SD, in boys and girls, respectively. Leptin explained 20% and 25% of these associations, respectively. Leptin did not mediate the association between birth length and birth-to-2 months length variation.Conclusion: Our results suggest that cord blood leptin may not be involved in the negative association between birth length and postnatal length growth but may play a modest mediating role in early postnatal catch-up or catch-down in weight.

High Maternal and Low Cord Blood Leptin Are Associated with BMI-SDS Gain in the First Year of Life.

BACKGROUND: Early infant weight development influences metabolic regulation later in life. For the prevention of obesity and metabolic diseases, it is important to understand the underlying mechanisms in detail. OBJECTIVES: This study aims to examine the effects of maternal anthropometric, sociodemographic, and lifestyle factors on maternal and cord blood leptin levels at birth and on the development of body mass index (BMI) standard deviation scores (SDS) in offspring up to 1 year of age. METHODS: Seventy-six mother-child pairs were enrolled in this follow-up analysis in a cross-sectional design. Standardized questionnaires were used to collect information regarding maternal anthropometrics, lifestyle habits, and sociodemographic conditions, and newborn weight, or, rather, BMI-SDS, development during the first year of life. RESULTS: Cord blood leptin (ß = -0.222, p = 0.074), maternal leptin (ß = 0.414, p = 0.001), and female sex of the offspring (ß = 0.385, p = 0.003) explained 29.0% of the variance in BMI-SDS changes in the first year of life. Cord blood leptin was influenced by newborn sex (male; ß = -0.220, p = 0.025) and maternal moderate-intensity physical activity in the third trimester (ß = 0.265, p = 0.007, corr. R2 = 9.2%); maternal leptin was influenced by maternal prepregnancy BMI (ß = 0.602, p < 0.001) and weight gain during pregnancy (ß = 0.247, p = 0.004, corr. R2 = 35.5%). CONCLUSIONS: Higher maternal and lower cord blood leptin levels are associated with a higher BMI-SDS increase during the first year of life. Maternal leptin is influenced by maternal BMI and weight gain during pregnancy, and cord blood leptin is influenced by maternal physical activity; therefore, it can be suggested that an active and healthy maternal lifestyle may play a pivotal and beneficial role in the offspring's weight development.

Associations of cord leptin and cord insulin with adiposity and blood pressure in White British and Pakistani children aged 4/5 years.

Background: Cord leptin and cord insulin concentrations may be important biomarkers of child adiposity and cardiovascular health, especially in populations with an increased long-term risk of type 2 diabetes and cardiovascular diseases. We aimed to determine whether cord leptin and insulin are associated with adiposity and early cardiovascular health at age 4/5, and whether any associations differ between White British and Pakistani children. Methods: Using bi-ethnic cohort data from 6060 mother-offspring pairs (2717 (44.8%) White British, 3343 (55.2%) Pakistani), we examined associations of cord leptin and insulin with adiposity (BMI, skinfold thickness) and systolic and diastolic blood pressure at age 4/5. Results: Cord leptin and insulin were higher in Pakistani compared to White British children (7.4 ng/ml versus 6.7 ng/ml and 4.1 mU/L versus 3.63 mU/L , respectively). Associations with adiposity measurements were similar in both groups and close to the null value. For example, each 10 ng/ml higher cord leptin was associated with a difference in mean childhood BMI of 0.10 kg/m 2 (95% CI 0.01, 0.19) in White British, 0.01 kg/m 2 (95% CI -0.08, 0.10) in Pakistani and 0.04 kg/m 2 (95% CI -0.02, 0.11) in both groups combined.  Associations with systolic and diastolic blood pressure were also close to the null and consistent in both groups. Conclusions: We found no evidence that cord leptin or insulin were likely to be valuable biomarkers for predicting later adiposity and blood pressure in White British or Pakistani children. For now, other factors such as family history and social-economic status may be more useful markers of risk.

Maternal overweight is not an independent risk factor for increased birth weight, leptin and insulin in newborns of gestational diabetic women: observations from the prospective 'EaCH' cohort study.

BACKGROUND: Both gestational diabetes mellitus (GDM) as well as overweight/obesity during pregnancy are risk factors for detrimental anthropometric and hormonal neonatal outcomes, identified to 'program' adverse health predispositions later on. While overweight/obesity are major determinants of GDM, independent effects on critical birth outcomes remain unclear. Thus, the aim of the present study was to evaluate, in women with GDM, the relative/independent impact of overweight/obesity vs. altered glucose metabolism on newborn parameters. METHODS: The prospective observational 'Early CHARITÉ (EaCH)' cohort study primarily focuses on early developmental origins of unfavorable health outcomes through pre- and/or early postnatal exposure to a 'diabetogenic/adipogenic' environment. It includes 205 mother-child dyads, recruited between 2007 and 2010, from women with treated GDM and delivery at the Clinic of Obstetrics, Charité - Universitätsmedizin Berlin, Germany. Recruitment, therapy, metabolite/hormone analyses, and data evaluation were performed according to standardized guidelines and protocols. This report specifically aimed to identify maternal anthropometric and metabolic determinants of anthropometric and critical hormonal birth outcomes in 'EaCH'. RESULTS: Group comparisons, Spearman's correlations and unadjusted linear regression analyses initially confirmed that increased maternal prepregnancy body-mass-index (BMI) is a significant factor for elevated birth weight, cord-blood insulin and leptin (all P < 0.05). However, consideration of and adjustment for maternal glucose during late pregnancy showed that no maternal anthropometric parameter (weight, BMI, gestational weight gain) remained significant (all n.s.). In contrast, even after adjustment for maternal anthropometrics, third trimester glucose values (fasting and postprandial glucose at 32nd and 36th weeks' gestation, HbA1c in 3rd trimester and at delivery), were clearly positively associated with critical birth outcomes (all P < 0.05). CONCLUSIONS: Neither overweight/obesity nor gestational weight gain appear to be independent determinants of increased birth weight, insulin and leptin. Rather, 3rd trimester glycemia seems to be crucial for respective neonatal outcomes. Thus, gestational care and future research studies should greatly consider late pregnancy glucose in overweight/obese women with or without GDM, for evaluation of critical causes and interventional strategies against 'perinatal programming of diabesity' in the offspring.

Study for umbilical cord plasma leptin in gestational diabetes and normal pregnancy / 대한산부인과학회지

OBJECTIVE: To compare umbilical cord plasma leptin level between infants of mothers with gestational diabetes and infants of control subjects and to evaluate the regulation of leptin in GDM. METHODS: Leptin concentrations were measured in cord blood at birth using a specific radioimmunoassay employing human recombinant leptin (Human Leptin RIA kit; Linco Research, Inc. USA). We compared cord plasma leptin level between gestational diabetes (n=18 women) and control pregnancies (n=21 women). RESULTS: Maternal weight, fetal birth weight, Ponderal index and placental weight were significant variables among the demographic variables. There was statistical difference in cord plasma leptin level between infants of mothers with gestational diabetes and infants of control subjects (Control subjects: 4.8 [3.7-7.9]ng/mL, GDM women: 8.0 [6.6-11.9]ng/mL, P=0.022). There was also statistical difference in the ratio between cord plasma leptin level and birth weight (Control subjects: 0.001 [0.001-0.002]ng/mL/gm, GDM women: 0.002 [0.002-0.003]ng/mL/gm (P=0.022)), and between cord plasma leptin level and Ponderal index (Control subjects: 0.280 [0.217-0.579], GDM women: 0.605 [0.452-1.005], (P=0.008)). There was no difference in gender. CONCLUSION: We found significant difference in umbilical cord plasma leptin level and adjusted leptin level for fetal birth weight, Ponderal index and placental weight between infants of mothers with gestational diabetes and infants of control subjects. It is suggested that umbilical cord plasma leptin is produced by fetal fat tissue, but it is more complicatedly regulated by placenta and other factors in gestational diabetes.

Serum Leptin in Cord Blood and Its Relation with Birth Weight and Metabolic Parameters / 대한내분비학회지

BACKGROUND: Leptin, produced in the adipose tissue, is involved in the regulation of body weight. The release of the leptin is increased in obese adults even in children. This study investigated whether the serum leptin in cord blood was related to babys birth weight and metabolic parameters. METHODS: 71 pairs of singleton pregnancy babies and their mother were studied. Babies are classified in LGA (large for gestational age), AGA (appropriate for gestational age), SGA (small for gestational age) three groups. After delivery, cord blood and maternal venous blood samples were drawn. We measured the plasma leptin, insulin-like growth factor (IGF)-1, insulin and proinsulin in cord and maternal serum. RESULTS: The concentration of leptin from cord blood was increased in LGA babies and decreased in SGA babies compued with the level in AGA babies. There was positive correlatian (r=0.55, p<0.01) between the plasma leptin level in cord and birth weight. There were positive correlatian between both the plasma proinsulin (r=0.37, p<0.01) and IGF-1 (r=0.32, p<0.01) and birth weight, too. But there was no difference between female and male baby's cord blood leptin level. In multiple regression analysis, cord blood leptin level was found independent factor related to birth weight ( p=0.001) CONCLUDION : The plasma leptin, proinsulin and IGF-1 is correlates to the birth weight. These data provide evidence that leptin and proinsulin are highly related to the nutritional status already during the fetal periods, and effect on the intrauterine fetal growth.