Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight

BACKGROUND AND AIMS: Leptin, the ob gene product, plays a key role in the regulation of body fat mass and weight in adult life. The mechanisms by which maternal and fetal/neonatal weight are regulated during human pregnancy and in early postnatal life are poorly understood. High leptin levels are observed in women during gestation and in cord blood at term. We have hypothesized that high leptin levels at term could represent an important feed-back indicator of nutrient supply. Subsequently, leptin could signal adipose tissue status during late gestation and during early neonatal life. SUBJECTS AND METHODS: 51 healthy newborns were studied. Clinical and auxological data (birth length, weight, and iliac, subscapular, biceps and triceps skinfold thickness) were recorded using a standardized data sheet. Venous cord blood was obtained immediately after birth in all neonates. Subsequently, capillary blood was obtained from the heel from some of the newborns when blood had to be obtained because of signs or symptoms of particular problems such as hypoglycaemia or hyperbilirubinaemia, at the following time points: two to four hours after birth in 51 infants, 56-79 h after birth in 47 infants and 99-128 h after birth in 23 of the newborns. The ratio between the sexes (girls/boys) was similar at all time points. The infants that were included in the study were subsequently found to be normal and healthy after analysis of the clinical and biochemical data. A specific ultrasensitive radioimmunoassay was used to measure leptin, while growth hormone and insulin were measured using commercially available immunoassays. RESULTS: Gestational age was 38-42 weeks, maternal age was 21-42 years. Birth weights ranged from 2480 to 4400 g. All newborns and mothers were subsequently found to be healthy. Leptin levels in venous cord blood was 0.16-6.80 microg/l, median 3. 47 microg/l and in capillary blood shortly after birth 0.26-7.03 microg/l, median 3.89 microg/l. 56-79 h after birth leptin levels had fallen dramatically, range 0.02-1.69 microg/l, median 0.26 microg/l, while 99-128 h after birth, leptin concentrations in capillary blood (0.05-2.61 microg/l, median 0.59 microg/l) had significantly increased when compared to the levels at 56-79 h (P < 0.001). There was a significant correlation between leptin levels in umbilical vein and birth weight of the neonates (r = 0.57, P < 0.03). Multistep regression analysis revealed that weight and skinfold thickness accounted for approximately 35-70% of the variation of leptin levels. Insulin and growth hormone, and glucose and bilirubin however, had no major impact on leptin levels. CONCLUSION: High leptin levels are present in cord blood at birth and in capillary blood shortly after birth. Since leptin levels in cord blood correlate with birth weight it is tempting to speculate that in the fetus as in later life leptin is signalling expansion of fat stores. Most importantly, we now report that leptin levels are high in the fetus but decline rapidly and dramatically after birth in healthy neonates. This may be important for the stimulation of feeding behaviour and the acquisition of energy homeostasis in the neonate.     

Comparison of cation-osmotic haemolysis in normal and low birth weight newborns during the first month of life

The present study was designed to compare cation-osmotic haemolysis (COH) in normal versus low birth weight newborns during the first month of postnatal life. COH was assessed in 80 normal (NBW) and 45 low birth weight newborns (LBW). A significant decrease in COH in the solutions with low ionic strength (15.4-30.8 mmol.l-1 NaCl) was found in LBW in the early period after birth when compared with NBW (p<0.01; p<0.001). In the solutions with high ionic strength (123.2-154.0 mmol.l-1 NaCl), COH again was significantly lower in LBW than in NBW neonates (p<0.01; p<0.001). The differences in COH were still present after both two weeks and one month of postnatal life but only in the solutions with the highest ionic strength (138.6-154.0 mmol.l-1 NaCl) (p<0.01; p<0.001). To conclude, our study demonstrates that COH is significantly lower in LBW than in NBW neonates. Furthermore, the latter show still lower values than adults. Finally, the relationship between COH and erythrocyte deformability is discussed.     

Hypothalamic function in women during the first month post-partum

Plasma LRH-immunoreactive substance in puerperal women was very low on days 5 and 10 post-partum and significantly increased between days 10 and 20 post-partum, but remained at a similar level on day 30 post-partum, which was significantly lower than that in eumenorrhoeic women on day 8 or 9 of the normal cycle. Although LRH administration did not significantly increase serum FSH on day 11 post-partum, daily injections of LRH from days 5 through 10 post-partum caused a significantly increased secretion of FSH on day 11 post-partum, both basally and in response to LRH. No significant difference was observed in serum oestradiol and Prl levels on day 11 post-partum between the two groups of women with and without LRH pre-treatment. It is concluded that the amount of hypothalamic LRH secretion may be small during the first month post-partum, and low basal FSH and unresponsiveness of the pituitary to LRH observed in the early puerperium may result from hypothalamic hypofunction.     

Cognitive functioning in the last year of life as a function of age, gender, and race.

Research has shown that many factors affect cognitive functioning. In this study cognitive functioning was analyzed using proxy reports concerning 17,135 decedents included in the 1993 National Followback Mortality Study conducted for the National Center for Health Statistics. These responses form a representative sample of all U.S. residents over age 15 who died in 1993 (except for those in South Dakota, which did not participate). Decedents had more difficulty understanding where they were than remembering what year it was or in recognizing family members. Logistic regression models found that age, gender, and race were the most important predictors of these basic cognitive functions. Although increasing age was associated with more cognitive difficulties, men had fewer deficits than women and Black Americans tended to have fewer deficits than White Americans. Possible reasons for these findings are discussed as well as some general implications for health service provision.     

Leptin hormonal kinetics in the fed state: effects of adiposity, age, and gender on endogenous leptin production and clearance rates

Leptin is an adipocyte-secreted hormone that regulates energy homeostasis and neuroendocrine function. Replacement therapy with recombinant methionyl human leptin (r-metHuLeptin) improves obesity, insulin resistance, hyperlipidemia, and neuroendocrine dysfunction associated with low-leptin states. We administered three doses of r-metHuLeptin (0.1, 0.3, and 1.0 mg/kg) to healthy subjects to determine r-metHuLeptin pharmacokinetics in the fed state, to determine endogenous leptin production and clearance rates, and to study the effects of age, body mass index, gender, and race on r-metHuLeptin pharmacokinetics. We detected no dose-dependent effects on elimination half-life (t(1/2)), dose-normalized area under the curve (nAUC(0- infinity)), total body clearance (CL), or volume of distribution at steady state. The mean t(1/2), CL, and volume of distribution at steady state of r-metHuLeptin are 3.4 +/- 1.5 h, 79 +/- 16 ml/kg.h, and 150 +/- 39 ml/kg, respectively. Older subjects have a higher nAUC(0- infinity) (P = 0.003) and tend to have a decreased leptin production rate (Rsyn) and CL (P = 0.01). Increased body mass index is associated with higher baseline endogenous leptin levels (P < 0.0001), higher Rsyn (P < 0.0001), and longer t(1/2) (P = 0.008). Females have significantly greater baseline endogenous leptin levels and Rsyn than males (P < 0.0001). In summary, the leptin production rate is increased in females and with increasing adiposity, whereas leptin clearance is decreased with increasing adiposity, and nAUC(0- infinity) is increased with age. Elucidation of leptin pharmacokinetic parameters allows the accurate calculation of exogenous leptin replacement doses for humans in the fed state.     

Hypertension in the first month of life

We reviewed our 10-year experience with neonatal hypertension. Fifty-three cases were identified, which represented 0.7% of all neonatal tertiary care admissions. Causes were identified in 23 (43%) neonates. These included acute tubular necrosis (n = 7), renal vascular abnormalities (n = 8), renal structural abnormalities (n = 4), interstitial nephritis (n = 2), and coarctation of the aorta (n = 2). No cause was identified in 30 (57%) infants. If the two neonates with coarctation are excluded, infants who had normal urinalyses, blood urea nitrogen (BUN), serum creatinine and plasma renin activity (PRA), had non-malignant hypertension that tended to be short-lived and always resolved spontaneously. In contrast, a cause of hypertension was found in 68% of those having an abnormal urinalysis, BUN, serum creatinine or PRA. There were two hypertensive deaths in this group. While the hypertension was usually more prolonged, it still generally resolved spontaneously by 1 year of age or following corrective surgery. Our experience indicates that diagnostic studies can be postponed if the urinalysis, BUN, serum creatinine and PRA are normal and if coarctation of the aorta has been excluded. If these preliminary studies are abnormal, however, a renal cause is likely and further studies are indicated.     

Serum hepcidin levels,iron status,and HFE gene alterations during the first year of life in healthy Spanish infants

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7?±?1.5 to 52.0?±?1.5 ng/mL; p?<?0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8?±?1.5 vs 37.9?±?1.3 ng/mL, p?<?0.018, and 54.3?±?1.5 vs 44.0?±?1.4 ng/mL, p?<?0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p?=?0.046 and p?=?0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.     

Respiratory mechanics of the piglet during the first month of life.

Piglets at 3, 14, and 30 days of age were studied to assess the postnatal changes in lung, chestwall, and total respiratory system compliance associated with normal growth. Static deflation compliance of the lung and total respiratory system increased significantly with age; there was no change in chestwall compliance. When normalized for body weight or lung volume, all measures of compliance tended to decrease with postnatal age. Measures of lung and chestwall compliance obtained with an end-inspiratory occlusion technique were less than the static compliance measures, but demonstrated the same relative changes with postnatal maturation. Chestwall compliance at 3 days of age was only 1.3 times greater than lung compliance and there was no significant change in this ratio with postnatal age. In contrast to the trend for the human infant, the piglet's chestwall at 3 days of age is stiff relative to the lung and does not become stiffer with age over the first 4 weeks of life.     

Adult life span as a function of age at maturity

A regression analysis was made of age at first reproduction in female mammals, as a function of body weight, using the data of Wootton. Data on maximal life span, also expressed as a function of body weight, were used to calculate “adult” life span, wherever possible, by subtracting the cognate value for age at first reproduction. Then a regression analysis of adult life span as a function of age at first reproduction was made. In both cases global regression lines (i.e., for whole data sets) were computed by standard least squares and by a robust method, as well as local regression lines for subgroups classified by taxonomic and ecological criteria. The slopes of the various regression lines were found to vary widely as a function of the method of classification. This result argues against the notion that the ratio of life history variables is a constant, or that one life history variable is likely to be a simple function of another. The results for bats are anomalous, in that age at first reproduction appears to be independent of body weight (over about two orders of magnitude). It is concluded that a full understanding of life history variables, such as maximal life span and age at maturity, is likely to depend on combined physiological, ecological, and evolutionary insights.     

Relationship of serum leptin concentration with age, gender, and biomedical parameters in healthy, non-obese subjects

It is known that the circulating levels of leptin, the adipocyte hormone implicated in the control of energy balance, are correlated with fat body mass (FBM), although the influences of other physiological conditions are not fully understood. We investigated the relationships of serum leptin concentration with age, gender, and 36 hormone-metabolic parameters in a sample of a well defined healthy population (n=246; age range 20-93 years), and in subgroups of lean individuals according to their body mass index (BMI), within similar age range and gender distribution. Only insulin secretion (positively) and testosteronemia (negatively, in males) show direct correlations. The other relationships are not significant but throughout collaborating variables, such as serum lipids, especially through FBM, lean body mass (LBM) through insulin secretion, and gender through FBM. In males, LBM correlates with insulin secretions, s-IGF-1 and with s-testosterone. The relationship between insulin secretion and LBM persists up to advanced age. From the present study it may be concluded that the positive relationship of leptin with insulin secretion and the negative one with testosterone, indicate direct implications of leptin in insulin signaling, as well as in male sexual development. Finally, the fact that the amount of secreted insulin depends on LBM and the latter on testosterone and IGF-1, indicates the importance of muscle mass in the control of insulin secretion.     

Adrenal status during the first month of life in mature and premature human infants

Measurements of 17-hydroxyprogesterone (17-OHP) in blood collected onto filter paper after heel puncture by lancet and steroid metabolites in random collections of urine, were made in human infants born from 25 weeks of gestation onwards. The concentration of 17-OHP in blood eluted from filter paper samples was inversely related to both gestational age and birth weight. In mature infants, 17-OHP concentrations fell rapidly soon after birth, whereas concentrations remained high over the first month of life in infants born earlier than 33 weeks of gestation. Sulphated urinary steroids were identified as having a 3 beta-hydroxy-5-ene structure and although the pattern of excretion was similar in mature and premature infants, significantly higher concentrations were found in the premature group. Steroid metabolites normally present when concentrations of circulating 17-OHP are increased due to 21-hydroxylase deficiency were not detectable in urine samples collected from infants born prematurely. Where direct comparison of 17-OHP in blood spots and urinary steroid metabolites was possible, the concentrations of 17-OHP in blood samples paralleled 3 beta-hydroxy-5-ene steroid metabolites in urine. The results suggest that a circulating cross-reacting 3 beta-hydroxy-5-ene steroid may be responsible for increased concentrations of 17-OHP in infants born prematurely. Increased concentrations of both 17-OHP in blood spots and steroid sulphates in urine were associated with stress in premature, but not in more mature, infants suggesting that in infants born prematurely postnatal stress may delay adrenal maturation.     

Serial echocardiography during the first 3 mth of life in normal neonates.

Echocardiography was performed in 13 normal neonates on the first day of life and repeated after 1 wk, 1 mth and 3 mth. Measurements were made of cardiac chamber size and wall thickness, mitral, tricuspid and pulmonary valve motion, right and left ventricular systolic time intervals, and of fractional left ventricular shortening (%deltaS) and mean velocity of circumferential fibre shortening (mean Vcf). During the study there was a relative decrease in right ventricular cavity size and wall thickness with an increase in the pulmonary valve EF slope, indicating a fall in pulmonary artery pressure with regression of the right ventricle. Left ventricular size and thickness increased while LVET became longer, possibly the consequence of an increasing left ventricular afterload. There was not a significant change in %deltaS and mean Vcf during the study period. The greatest change from right to left ventricular preponderance occurred between 1 wk and 1 mth of life and was accompanied by changes in the mean frontal QRS axis of the electrocardiogram. The study shows that significant changes occur in the echocardiogram during the first 3 mth of life; neonatal echocardiograms should be interpreted not only in relation to the baby's weight, but also to its age.     

Reduced lung function in healthy preterm infants in the first months of life

RATIONALE: Preterm delivery has been associated with a higher incidence of respiratory morbidity even in infants that do not have significant respiratory disease during the neonatal period. Reduced flows have been reported in children and adolescents born prematurely. OBJECTIVE: The aim of this study was to assess lung function in healthy preterm infants in the first months of life. METHODS: Preterm infants with less than 48 h of supplemental oxygen were recruited. Lung function was assessed by the raised-volume rapid thoracic compression in the first months of life. The control group consisted of full-term infants without a history of respiratory diseases. MEASUREMENTS AND MAIN RESULTS: Sixty-two preterm (29 male) and 27 full-term (10 male) infants were tested. Adjusting for length, age, and sex, we found a mean significant reduction of 92 ml/s (22%) in FEF(50), 73 ml/s (21%) in FEF(25-75), and 19 ml (28%) in FEV(0.5) in the preterm group. These differences in expiratory flows remained significant using another model that adjusts for lung volume (p < 0.01 for FEF(50), FEF(25-75), and FEV(0.5), and p < 0.05 for FEF(75)). In the preterm group, after adjusting for length, male sex, lower gestational age, and increased weight were significantly and independently associated with reduced flows. CONCLUSIONS: Our findings confirm that prematurity is independently associated with reduced lung function and that this is detectable in the first months of life. Male sex, lower gestational age, and weight are important predictors for reduced expiratory flows in this group.     

Changes in serum albumin, transferrin and amino acid indices during the first month of life in small-for-date infants

Total serum proteins, albumin, albumin/globulin ratio, and plasma-free amino acids have been determined in 12 small-for-date infants and in 14 normal infants at birth, at 1 week and at 1 month after birth. All infants were fed ad libitum with an adapted infant formula providing 1.9 g protein and 74 kcal/100 ml. Total serum proteins and albumin but not transferrin were low at birth in small-for-date infants, reaching normal values after 1 week of feeding. Serum globulins were low from birth to 1 week in small-for-date infants but they were normal after 1 month. Values for classical amino acid malnutrition indices suggest a state of protein-energy malnutrition which disappeared after 1 week of feeding.     

Circulating ghrelin levels as function of gender,pubertal status and adiposity in childhood

Ghrelin, a natural GH secretagogue, exerts remarkable endocrine and non-endocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated to insulin secretion, enhanced in anorexia and reduced in obesity. Ghrelin levels in childhood have never been evaluated. We measured morning ghrelin levels after overnight fasting in 29 healthy lean children (NC) and in 36 obese children (OBC). The results were compared with those recorded twice in 3 different sessions in healthy lean adults (NA). In NA ghrelin levels showed good within-subject reproducibility without gender-related differences. Ghrelin levels in NC [(median; 25 degrees -75 degrees centile): 426.0; 183.0-618.0 pg/ml] were similar to those in NA (380.5; 257.7-551.7 pg/ml). Ghrelin levels in OBC (229.5; 162.5-339.5 pg/ml) were lower (p<0.03) than in NC (426.0; 183.0-618.0 pg/ml). Both in NC and in OBC, ghrelin levels were independent of gender and pubertal status. In all children, ghrelin levels were negatively associated (p<0.05) to weight excess (r=-0.24), insulin (r=-0.28) and IGF-I (r=-0.4) levels. In conclusion, these findings demonstrate that morning ghrelin levels after overnight fasting show good within-subject reproducibility, and are similar in both sexes and do not vary from childhood to adulthood. In childhood, circulating ghrelin levels are reduced in obese subjects being negatively correlated to overweight and insulin secretion.     

Thyroid function in seventy-five healthy preterm infants thirty to thirty-five weeks of gestational age: a prospective and longitudinal study during the first year of life.

Thyroid function was evaluated in 75 healthy preterm infants, 30-35 weeks of gestational age. Serum thyrotropin (TSH), thyroxine (T(4)), triiodothyronine (T(3)), free T(4) (immunochemoluminescence) and reverse triiodothyronine (rT(3)) (radioimmunoassay) were measured in the mother and in the cord at delivery and in the preterm infants at 1 hour, 24 hours, 1 week, 3 weeks, 2 months, 4 months, 6 months, and 12 months of postnatal age. These values were compared to those of healthy full-term infants of the same postnatal age (22 at 24 hours from our hospital and from previously reported data at others times). Mean 24-hour TSH values were significantly lower (p < 0.001) in preterm than in full-term infant populations (12.38 +/- 6.13 microIU/mL versus 22.02 +/- 13.28 microIU/mL); however, all TSH values of preterm infants were in the range of the full-term values. Mean 24-hour free T(4) values were similar in preterm and full-term infants (1.88 +/- 0.46 ng/dL versus 2.01 +/- 0.54 ng/dL) and all preterm infants had free T(4) values within the range of those of full-term infants at 24 hours. Mean T(4) and T(3) values were significantly lower in preterm than in full-term neonates at 1 hour and 24 hours of age. Mean 24-hour rT(3) values were significantly higher in preterm than in full-term newborns. From 1 week onwards, all thyroid function values were in the same range in both populations. In conclusion, individual thyroid function was similar in healthy preterms and full-terms from the first 24 hours of life. Normative data in preterm infants during the first year of life applying the latest luminescence techniques currently used worldwide are reported.     

Postnatal growth and circulating ACTH and cortisol concentrations during the first month of life in cloned lambs

Recent studies have indicated that there is a decrease in perinatal survival of apparently normal animals produced by somatic-cell nuclear transfer. Here we report that the cortisol and adrenocorticotrophic hormone (ACTH) profiles of cloned lambs in the first 4 weeks of life are significantly different to that of control lambs. The growth of cloned lambs however was not different to controls. These findings demonstrate that endocrine development may be altered in apparently "normal" clones.     

Nasal airway dimensions and lung function in awake,healthy neonates

Possible relations between nasal airway dimensions and measures of lung function are not well established. It has been suggested that a major part of airway resistance is found in the nose. However, little is known about the shape of tidal flow volume (TFV) loops in relation to nasal caliber. We therefore investigated whether lung function assessed by tidal breathing in healthy newborn infants was affected by nasal airway dimensions. Nasal airway dimensions were measured in 17 healthy newborn babies (mean age, 2.7 days) by acoustic rhinometry before and immediately after lung function measurements. Lung function was evaluated by TFV loops and passive respiratory mechanics (single-breath occlusion technique), first with both nostrils open, and subsequently immediately after occlusion of the larger of the two nostrils, causing at least a 50% reduction in nasal minimum cross-sectional area (MCA). Neither the TFV expiratory ratios (time and volume to reach peak flow to total time and volume, respectively [t_PTEF/t_E and V_PTEF/V_E, respectively]), nor resistance or compliance of the total respiratory system differed significantly regardless of whether one or both nostrils were open. With one nostril closed there were no significant effects on any of the measured lung function parameters. We conclude that in healthy awake neonates reducing the cross-sectional area of nasal dimensions by 50% does not affect TFV loops or passive respiratory mechanics. Pediatr. Pulmonol. 1998; 25:99–106. © 1998 Wiley-Liss, Inc.