Inverse changes in the serum levels of the soluble leptin receptor and leptin in neonates: relations to anthropometric data.

We aimed to evaluate the role of the soluble leptin receptor (sOB-R), the major leptin-binding protein in blood, for the regulation of growth and development of neonates. Therefore, human arterial and venous cord blood samples were taken from newborns of 45 healthy mothers to investigate correlations with anthropometric data. Furthermore, we compared changes in sOB-R and leptin in neonatal serum between postnatal d 1, 3, and 5. Cord blood levels of leptin (direct correlation) and the molar sOB-R/leptin ratio (inverse correlation) correlated significantly (P < 0.05) with weight, triceps, biceps, iliacal, and subscapular skinfolds at birth as well as on d 3 and 5 of life. During the first week of life, median leptin levels decreased significantly (P < 0.001) from 3.4 ng/ml in venous cord blood to 2.2 ng/ml in venous blood on d 1 after birth to 0.88 ng/ml on d 3 and 0.75 ng/ml on d 5. In contrast and most interestingly, median levels of sOB-R increased significantly (P < 0.001) from 14.5 ng/ml in cord blood to 18.9 ng/ml on d 1, 83 ng/ml on d 3, and 79.4 ng/ml on d 5. Consequently, the molar sOB-R/leptin ratio increased from 0.45 to 1.30 (d 1), 10.5 (d 3), and 13.7 (d 5) during the same period (P < 0.001). We found a remarkable postnatal change in the leptin-sOB-R axis with decreasing leptin and increasing sOB-R levels. Hence, the sOB-R may block leptin function by its competition with the membrane receptor for the ligand. These suppressive effects may be an important stimulus for energy uptake in the first week of life or in other conditions with a high energy demand.

Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight.

The mechanisms by which maternal and fetal weight are regulated during pregnancy are poorly understood. The ob protein, termed leptin, is produced by adipocytes. It is involved in the regulation of body weight by suppressing appetite and stimulating energy expenditure both in humans and rodents. In this study we examined whether leptin concentrations in the mother and the newborn correlate with birth weight, placental weight, and maternal weight at term. Leptin concentrations were measured in amniotic fluid, venous and arterial cord blood, and maternal serum at birth (n = 27) using a specific RIA employing human recombinant leptin for tracer and standard preparation. Gestational age was 38-42 weeks, maternal age was 21-42 yr, mean maternal weight at birth was 80.0 +/- 10.8 kg, and mean body mass index before pregnancy was 23.4 +/- 2.8 kg/m2. The newborns' mean weight was 3450 +/- 580 g, and mean placental weight was 616 +/- 120 g. Serum leptin levels from nonpregnant women ranged between 1.7-18.4 ng/mL, median 5.5 ng/ml (n = 30). Mean leptin concentration in maternal serum at birth was 20.0 +/- 13.2 ng/mL and was higher (P < 0.002) than in arterial cord blood (9.7 +/- 9.4 ng/mL) and venous cord blood (8.9 +/- 8.6 ng/mL). Mean amniotic fluid leptin concentration was 3.6 +/- 2.8 ng/mL. Placental weight correlated inversely with leptin levels in maternal serum at birth (r = -0.49, P < 0.01). In addition, leptin concentrations in venous cord blood correlated significantly with the levels in arterial cord blood (r = 0.98, P < 0.0001), and leptin levels in cord blood correlated positively with birth weight (r = 0.57, P = 0.03) and placental weight (r = 0.50, P < 0.01). In contrast, there was no correlation between maternal serum leptin levels and birth weight. Thus, leptin levels are high in the fetus and in the mother at term. We hypothesize that high leptin levels could represent an important feed-back modulator of substrate supply and subsequently for adipose tissue status during late gestation.

Leptin, the ob gene product, in female health and disease.

Leptin is a recently discovered hormone which is involved in the regulation of body weight. It provides a molecular basis for the lipostatic theory of the regulation of energy balance. White adipose tissue is the main site of leptin synthesis and there is some evidence of ob gene expression in brown fat. Leptin seems to play a key role in the control of body fat stores by coordinated regulation of feeding behaviour, metabolic rate, autonomic nervous system regulation and body energy balance in rodents, primates and humans. Apart from the function of leptin in the central nervous system on the regulation of energy balance, it may well be one of the hormonal factors that signal the body's readiness for sexual maturation and reproduction to the brain. During late pregnancy and at birth when maternal fat stores have been developed leptin levels are high. Leptin could then be a messenger molecule signaling the adequacy of the fat stores for reproduction and maintenance of pregnancy. At later stages of gestation leptin could signal the expansion of fat stores in order to prepare the expectant mother for the energy requirements of full term gestation, labour and lactation. This overview focuses on those topics of leptin research which are of particular interest in reproductive medicine and gynecology.

Influence of hysterectomy on the fibrinolytic activity of plasma of women with intact ovarian function.

Hysterectomies are frequently required operations in gynecology. Several studies have reported an association between premenopausal hysterectomy and the risk of cardiovascular diseases. However, the pathophysiological linkages between these two conditions have not been elucidated. In recent years it has been shown that a decrease in plasma fibrinolytic activity is associated with increased risk of thrombosis. Furthermore, it has been known that the uterus is a very finbrinolytic active organ. In the present study we investigated the hypothesis that hysterectomy may lead to a decrease in plasma fibrinolytic activity, and thereby increase the risk for thromboembolic diseases. Fibrinolytic parameters of plasma were investigated in 26 women before and 6 weeks after premenopausal hysterectomy. Euglobulin lysis time (ELT), a global measure of plasma fibrinolytic activity, and the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were not different before and after hysterectomy. The ELT difference before and after venous occlusion, which is a good indicator for the risk of thrombosis, was also not significantly changed after hysterectomy. Estradiol-17 beta, progesterone, LH, FSH and sex hormone binding globulin displayed no significant changes after hysterectomy. Furthermore, the hormone measurements also indicated that the women were premenopausal. There were no correlations between the hormone values and fibrinolytic parameters. These data indicate that premenopausal hysterectomy does not lead to changes in plasma fibrinolytic activity.

Leptin concentrations in maternal serum and amniotic fluid during the second trimenon: differential relation to fetal gender and maternal morphometry.

Leptin, a hormone produced by adipocytes, provides information on the availability of fat stores to the hypothalamus and acts as an afferent satiety signal regulating appetite and energy expenditure in both rodents and humans [Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432; Sinha MK. Human leptin: the hormone of adipose tissue. Eur J Endocrinol 1997;136:461-4; Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse ob protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546-9; Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-6; Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J, Staels B, Auwern J. Transient increase in obese gene expression after food intake or insulin administration. Nature 1995;377:527-9; Campfield LA, Smith FJ, Burn P. The OB protein (leptin) pathway - a link between adipose tissue mass and central neural networks. Horm Metab Res 1996;28:619-632; Blum WF, Kiess W, Rascher W, editors. Leptin - the voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997]. In addition, leptin is thought to play an important role for reproduction and during gestation [Kiess W, Blum WF, Aubert ML. Leptin, puberty and reproductive function: lessons from animal studies and observations in humans. Eur J Endocrinol 1997;138:1-4; Barash IA, Cheung CC, Wigle DS, Ren H, Kabitting EB, Kuijer JL, Clifton DK, Steiner RA. Leptin is a metabolic signal to the reproductive system. Endocrinology 1996;133:3144-47; Chehab F, Lim M, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genetics 1996;12:318-20; Kiess W, Schubring C, Prohaska F, Englaro P, Rascher W, Attanasio A, Blum WF. Leptin in amniotic fluid at term and at midgestation. In: Blum WF, Kiess W, Rascher W, editors. Leptin - the voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997]. The purpose of this study was to gain more insight into a putative role of leptin during midgestation. Therefore we have measured leptin concentrations in maternal serum and amniotic fluid using a specific radioimmunoassay (RIA) employing human recombinant leptin for tracer and standard preparation [Blum WF, Kiess W, Rascher W, editors, Leptin - The voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997; Blum WF, Englaro P, Heiman M, Attanasio Am, Kiess W, Rascher W. Clinical studies of serum leptin. In: Blum WF, Kiess W, Rascher W. Leptin - The voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997; Blum WF, Englaro P, Heiman M, Attanasio AM, Kiess W, Rascher W. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage and testosterone. J Clin Endocrinol Metab 1997;82:2904-2910]. In addition, estriol, hCG and alphafetoprotein were measured in maternal serum. (ABSTRACT TRUNCATED)

Fibrinolysis and factor XIII in women with spontaneous abortion.

In the present study, parameters of the fibrinolytic system and factor XIII were determined in 26 women with spontaneous abortion and in 21 women with intact pregnancies to gain insight into the role of fibrinolysis in spontaneous abortion. Both groups of women did not significantly differ from each other in age or weeks of pregnancy. There were no differences in euglobulin lysis time (ELT), tissue plasminogen activator (t-PA) antigen, and plasminogen activator inhibitor type 1 (PAI-1) antigen between the study group and the control group. Factor XIII activity was significantly decreased in patients during abortion. In the present study, changes of fibrinolytic parameters measured in teh cubital vein blood of patients with abortion were not observed although local changes in fibrinolytic activity had been associated with spontaneous abortion. The pathophysiological role of the decrease in factor XIII activity observed in the present study remains to be elucidated.

Contamination of human milk in Middle Hesse, Germany--a cross-sectional study on the changing levels of chlorinated pesticides, PCB congeners and recent levels of nitro musks.

Human milk samples from women in Middle Hesse, Germany were chemically analyzed for contamination levels of alpha-, beta- and gamma-HCH, HCB, p,p'-DDE and p,p'-DDT as well as the PCB-congeners no. 28, 31, 49, 52, 101, 118, 138, 153, 156, 170 and 180. Changes in concentrations of these compounds in human milk over an extended time period were studied by comparing samples from 1984/85, 1990/91 and 1995. In addition, concentrations of the nitro-aromatic compounds musk xylene and musk ketone were determined in the 1995 samples. The study showed statistically highly significant (p<0.001) reductions in levels of beta- and gamma-HCH, HCB, p,p'-DDE and p,p'-DDT, in human milk from 1995 compared to samples from 1984/85. A weakly significant reduction (p<0.05) of alpha-HCH was also observed. For low-chlorinated PCB congeners, on the other hand, a highly significant increase of PCB no. 28 was detected and concentrations of congeners no. 31, 49 and 52 remained unchanged. Concentrations of the high-chlorinated congeners no. 101, 138, 153 and 180 dropped (highly significant). A highly significant reduction of PCB no. 118 and 156 occurred between 1990/91 and 1995, but a highly significant increase was found for no. 170. Lower levels of hydrocarbon contamination of human milk samples from 1995 than were found in samples from 1984/85 and 1990/91 can be seen to result partially from voluntary reductions, but primarily reflect restrictive environmental legislation in the Federal Republic of Germany. Mean concentrations of musk xylene and musk ketone in samples from 1995 were 41 microg/kg and 10 microg/kg milk fat, respectively.

Temperature regulation in healthy and resuscitated newborns immediately after birth.

Oxygen consumption (VO2) is a sensitive and reliable indicator of any disturbances of thermoregulatory adaptation in the newborn. This study has been carried out in a attempt to find out, if there is any difference between the thermoregulatory processes of healthy and resuscitated neonates. To this end, both VO2 and rectal temperature (RT) were continuously measured in 31 healthy and 13 resuscitated neonates respectively, within the first 140 postnatal minutes and during 30 minutes from the second until the fifth day of their lives. In the healthy neonates, the VO2 used to decrease over the study period. The high initial VO2 observed postnatally is due to mechanisms of thermoregulation beginning immediately after delivery as soon as the newborn child is exposed to chilly environmental temperatures. The brown adipose tissue (BAT) is supposed to be the essential site of non-shivering thermogenesis (NST). The thermogenetic function of this tissue may be shown by local measuring of temperature. In the resuscitated neonates, VO2 was lower than in the healthy children. Hypoxia results in an ineffective capillary blood supply of the BAT owing to a redistribution of circulating blood volume, thus leading to a disturbance of thermoregulation. Since the activity of the BAT is dependent on oxygen supply hypoxia might be regarded as the limiting factor. In the presence of an isothermal environment, the RT measured in the healthy children differed from those determined in the resuscitated neonates. This clearly shows that thermoregulatory processes may be impaired by a difficult birth.(ABSTRACT TRUNCATED AT 250 WORDS)

[Urine drainage following vaginal gynecologic operations]. / Harnableitung nach vaginalen gynäkologischen Operationen.

In a retrospective study covering 161 patients, postoperative discharge of urine by means of a suprapubic catheter (SPC) and a transurethral indwelling catheter (TIC) following vaginal hysterectomy with reconstructive surgery were compared. The incidence of urinary tract infections differed clearly in the two groups, though not significantly (SPC 20.9%, TIC 37.2%). The SPC has clear advantages, causing fewer micturition difficulties and being more readily accepted. Isolated complications such as macrohematuria, bladder tamponade, and blocking of the catheter represent disadvantages of the SPC as compared to the TIC.

[Cardiotocographic findings in silent uterine rupture]. / Kardiotokographische Befunde bei stiller Uterusruptur.

A silent hysterorrhexis in the expulsion phase and a second silent hysterorrhexis in the absence of labor, with the amniotic sac intact and the os uteri one centimeter wide were detected by external cardiotocography. In both cases there was a sudden loss of oscillation and suddenly persistent fetal bradycardia after the cardiotocogram had previously been normal. These findings are in agreement with the six cases of cardiotocographically documented silent hysterorrhexis published hitherto.

Oxygen consumption, heart rate, respiratory rate and rectal temperature in healthy newborns during the first two hours after birth.

A report is made on the continuous registration of oxygen consumption, heart rate, respiratory rate and rectal temperature in 32 neonates during the first two hours of life. A short account of the registration technique is given. A comparative study shows, that oxygen consumption, heart rate and respiratory rate fall during the period of observation, whereas the rectal temperature rises. 26 out of the 32 neonates demonstrated a approximately linear fall of each of the oxygen consumption values during the period of observation. There is a similar relationship, which is statistically verified, between the oxygen uptake and heart rate. Oxygen consumption and heart rate can be correlated with each other after the first 60 minutes of life. This close and direct relationship between the oxygen consumption and the heart rate, an important parameter of the heart and circulatory system, stresses clearly the importance of the continuous registration of oxygen consumption for monitoring the general condition of the neonate. A change from this situation means a risk for the neonate which must be clarified by blood-gas analysis. A continuous registration of oxygen uptake for the surveillance of the neonate includes numerous vital functions and appears to be a more suitable parameter than single parameters which include only partial functions. The application of the method is simple and safe for the infant.

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.

Longitudinal analysis of maternal serum leptin levels during pregnancy, at birth and up to six weeks after birth: relation to body mass index, skinfolds, sex steroids and umbilical cord blood leptin levels.

Leptin is an important regulator of body fat mass and energy expenditure during adult life. The mechanisms by which maternal and fetal weight are regulated during pregnancy are poorly understood. In order to gain more insight into a potential role of leptin during gestation, a prospective, longitudinal study was carried out to measure leptin concentrations in maternal serum of 29 healthy women during pregnancy up to 6 weeks after birth and also in umbilical cord blood of their newborns. Leptin concentrations were measured using a specific RIA. In addition, estradiol, testosterone, and sex hormone binding globulin were determined using commercially available RIAs. The mothers' skinfolds were determined at four sites using a Holtain caliper. Leptin levels increased continuously during pregnancy and reached 25.8 +/- 14.7 ng/ml at 38-40 weeks. At birth, leptin concentrations were 23.5 +/- 15.4 ng/ml. Three days after delivery a significant decrease of leptin levels to 10.6 +/- 6.0 ng/ml was observed. Six weeks after birth the leptin concentration in maternal serum was 13.8 +/- 8.6 ng/ml. At birth, maternal serum levels were significantly higher than levels in cord blood and did not correlate with leptin levels in cord blood or neonatal weight. Furthermore, leptin levels did not correlate with maternal sex steroids and sex hormone binding globulin levels. At 6-8 weeks of pregnancy, maternal leptin serum levels correlated significantly with BMI (r = 0.81). The correlation coefficients (leptin vs. BMI) dropped with increasing gestational age and at birth only a poor correlation persisted (r = 0.50). Six weeks after birth there was again a high correlation between leptin levels in maternal serum and BMI (r = 0.76). Subscapular skinfold thickness was correlated to leptin concentrations in maternal serum during the whole period of the investigation. In conclusion, maternal leptin levels continuously increased from 6-8 weeks up to 38-40 weeks of pregnancy. Maternal leptin levels decreased dramatically after birth. Six weeks after delivery, leptin levels were comparable to the values measured at the beginning of pregnancy. We hypothesize that leptin might play an important role during pregnancy and fetal development.