Eyal Sivan

Leptin in human pregnancy: The relationship with gestational hormones

OBJECTIVES The aims of the study were (1) to examine the relationship between leptin and placental hormones by measuring serial changes in serum levels of leptin during and after pregnancy and (2) to study the effects of several gestational hormones on leptin release from fully differentiated 3T3-L1 adipocyte cell cultures. STUDY DESIGN Serum levels of leptin were measured throughout pregnancy and at 3 months post partum in 29 healthy women and were also measured in 18 healthy women at delivery by cesarean section and on postpartum day 3. In addition, 3T3-L1 mouse adipocytes were incubated for 24 hours in media containing various reproductive hormones and leptin production was measured. RESULTS Serum leptin levels increased significantly (8.4 +/- 0.9 vs 13.5 +/- 1.5 ng/mL; P <.001) between the first 2 trimesters of pregnancy but not between the second and third trimesters. These changes in leptin did not correlate significantly with changes in body mass index. Leptin levels dropped significantly during the immediate postpartum period, from 34.1 +/- 4.9 at cesarean delivery to 7.3 +/- 1.4 ng/mL on postpartum day 3 (P <.001). Fasting insulin level did not correlate significantly with leptin level during pregnancy but did so during the postpartum period (r = 0.60; P <.05). Leptin secretion from 3T3-L1 adipocytes was increased significantly when cells were cultured with human chorionic gonadotropin (150%, P <.01) and also when they were cultured with estrogen (120%, P <.03). CONCLUSION The data suggest that leptin production by adipose tissue is stimulated by several hormones of pregnancy, which may contribute to the increased leptin levels observed during gestation.

Dietary vitamin E prophylaxis and diabetic embryopathy: Morphologic and biochemical analysis ☆ ☆☆ ★ ★★

OBJECTIVE In this study we sought to determine whether dietary supplementation with vitamin E, a known antioxidant, would reduce the incidence of diabetic embryopathy in an in vivo rat model. STUDY DESIGN Eighty-day-old Sprague-Dawley rats were assigned to one of five groups: two control groups (groups 1 and 2) and three diabetic groups (groups 3, 4, and 5). One group of controls (group 2) and one group of diabetic rats (group 4) received dietary supplements of vitamin E (440 mg/day). The other three groups (groups 1, 3, and 5) received a normal diet only. Group 5 received insulin therapy to control glucose levels. On day 6 of gestation diabetes was induced in groups 3, 4, and 5 with streptozotocin (65 mg/kg). Animals were killed on day 12; embryos were examined for size, protein content, evidence of malformations, and superoxide dismutase activity. RESULTS In both groups (groups 3 and 4) of diabetic rats the mean blood glucose level than was significantly higher in controls. Insulin-treated animals (group 5) had glucose levels that were comparable to those of controls. The unsupplemented diabetic group had a neural tube defect rate of 21.48% +/- 9.6% (percentage of neural tube defects per rat) and a resorption rate of 21.37% +/- 20.39% (percentage of resorptions per rat) as compared with rates in the supplemented diabetic group of 6.92% +/- 4.08% and 2.17% +/- 3.74%, respectively (p < 0.01). Groups 1, 2, and 5 had similar neural tube defect rates (6.63% +/- 5.0%, 5.01% +/- 4.87%, and 3.55% +/- 5.92%, respectively. Vitamin E levels, measured by high-performance liquid chromatography, were significantly higher in maternal serum and embryos in the supplemented groups (p < 0.001) than in controls. Superoxide dismutase activity was reduced in the diabetes groups and was not affected by vitamin E therapy. CONCLUSIONS Supplementation with the antioxidant vitamin E confers a significant protective effect against diabetic embryopathy and may potentially serve as a dietary prophylaxis in the future. We postulate that this protective effect is mediated by a reduction in the oxidative load induced by hyperglycemia.

Maternal serum adiponectin levels during human pregnancy.

Objective:Pregnancy is a unique situation characterized by insulin resistance. The role of adiponectin, an insulin-sensitizing hormone, has not been completely clarified during pregnancy. The aim of this cross-sectional study was to evaluate adiponectin levels during pregnancy and postpartum.Study design:Adiponectin and leptin levels were tested in 80 pregnant women, 20 in each trimester (mean gestational age 10.5±1.9; 19.3±4.9; 39.3±0.8 weeks,) as well as 4 days postpartum.Results:Adiponectin levels during first (13.3±3.6 μg/ml), second (12.6±4.4 μg/ml) and third trimester (11.2±3.7 μg/ml) did not differ and were significantly higher than postpartum levels (8.8±2.1 μg/ml; P<0.0001, P<0.004 and P<0.02, respectively).Conclusion:Despite increased insulin resistance during pregnancy, no significant alterations in adiponectin levels were observed. This may imply that the regulation of adiponectin during gestation is altered. The elevated gestational adiponectin levels are consistent with increased ‘adiponectin resistance’ during pregnancy.

Pregnancy Outcome After Age 50

OBJECTIVE: To evaluate pregnancy complications occurring after age 50. METHODS: We compared the pregnancy outcomes of women aged 50–64 years with those aged 45–49 years and with the general population. RESULTS: During 5 years from January 1, 1999, to June 30, 2004, 123 women aged 45 years and older gave birth. Fifty-five percent were nulliparous, 24 of 123 were aged 50–64 years, and 99 of 123 women were aged 45–49 years. All women older than age 50 conceived via in vitro fertilization with oocyte donation. For these 123 women, the overall mean gestational age at delivery was 37.6±2.6 weeks. The mean birth weight was 2,684±754 g, significantly lower than the general population, and the incidences of multifetal pregnancies, diabetes, and hypertension were high. Women aged 50 years and older were more likely to be hospitalized during pregnancy than women younger than 50 years (63% versus 22%, P<.001). Neonatal outcome was generally good. Women aged 50 years and older gave birth to significantly more low birth weight babies than those younger than age 50 years (61% versus 32%, P=.002). Gestational age and birth weight were both significantly lower for singletons and multiples in women older than age 50 years compared with those younger than age 50 years (gestational age of singletons 36.9 versus 38.4 weeks, P=.005; birth weight of singletons 2,694 versus 3,027 g, P=.019; gestational age of multiples 35.1 versus 36.4 weeks, P=.01; birth weight of multiples 1,976 versus 2,310 g, P=.038, respectively). CONCLUSION: Pregnant women aged 50–64 years have increased risks of preterm birth, low birth weight babies, diabetes mellitus, hypertension, and hospitalization. LEVEL OF EVIDENCE: II-2

Outcome of hysteroscopic resection of submucous myomas for infertility

OBJECTIVE To examine the reproductive outcome after operative hysteroscopic resection of submucous myomas in women for whom no other infertility factor was identified. DESIGN Fifteen infertile women with submucous myomas underwent an intensive workup to exclude other causes of infertility. Operative hysteroscopy for resection of the submucous myomas was performed using a rigid 26 French resectoscope (Karl Storz GmbH & Co., Tuttlingen, Germany). SETTING Academic tertiary referral center. RESULTS The mean +/- SD duration of the procedure was 25.5 +/- 5.6 minutes. No operative or postoperative complications occurred and all patients were discharged within 6 hours. The follow-up period was 12.0 +/- 4.2 months (mean +/- SD). Seven women conceived (pregnancy rate of 47%) and six of them subsequently delivered at term. CONCLUSION The results of this study indicate that operative hysteroscopy achieved a pregnancy rate comparable to myomectomy via laparotomy. These results suggest that operative hysteroscopy is the procedure of choice for the resection of submucous myomas in infertile women.

Fetal thymus size as a predictor of chorioamnionitis in women with preterm premature rupture of membranes.

Emerging evidence indicates that chorioamnionitis is associated with a significant decrease in thymic size at birth in very low birth weight (VLBW) preterm infants. The aim of this study was to determine whether decreased fetal thymus size is associated with histological or clinical chorioamnionitis in patients with preterm premature rupture of membranes (PROM).

Prophylactic Pelvic Artery Catheterization and Embolization in Women with Placenta Accreta: Can It Prevent Cesarean Hysterectomy?

We present the outcome of a relatively large cohort of women with suspected placenta accreta who underwent prophylactic pelvic artery catheterization prior to cesarean section. All pregnant women with suspected placenta accreta who delivered in one tertiary center were included in this retrospective study. All patients underwent an elective cesarean section with prophylactic pelvic artery catheterization of internal iliac arteries through femoral or brachial approach. Thirty women underwent prophylactic catheterization; placenta accreta was clinically confirmed in 25 (83.3%) cases. Embolization was performed in 23 cases (76.6%) and hysterectomy in 2 (8%). Median estimated amount of blood loss was 2000 mL (500 to 9000 mL). There were no major catheterization-related complications. Three women had a subsequent pregnancy and uncomplicated delivery by cesarean section. Prophylactic pelvic artery catheterization and embolization in women with placenta accreta is safe and effective in prevention of hysterectomy and should be considered in woman wishing to preserve fertility.

The Impact of Self-Monitoring of Blood Olucose on Self-Efficacy and Pregnancy Outcomes in Women With Diet-Controlled Gestational Diabetes:

PURPOSE The purpose of this study was to examine the effects of self-monitoring of blood glucose (SMBG) on feelings of self-efficacy, dietary compliance, and pregnancy outcomes in women with diet-controlled gestational diabetes mellitus (GDM). METHODS Fifty-eight women with GDM and a fasting blood glucose level <95 mg/dL were randomly assigned to 2 groups. The experimental group measured their blood glucose levels 4 times daily using a reflectance meter with memory. Metabolic status was assessed in the control group by periodic monitoring at prenatal visits. Otherwise the management protocol was identical for both groups. The Diabetes Empowerment Scale was completed at study entry and at 37 weeks gestation to assess feelings of self-efficacy. Dietary compliance was assessed at each visit. RESULTS Both groups of women achieved excellent glucose control; only 1 woman in each group required insulin therapy. There were no significant differences with regard to feelings of self-efficacy, dietary compliance, birth weight, gestational age at delivery, Apgar scores, and neonatal complications. Rates of macrosomia, delivery by cesarean section, and occurrence of birth trauma were similar. CONCLUSIONS SMBG appears to have little effect on maternal feelings of self-efficacy, dietary compliance, or pregnancy outcomes in women with diet-controlled GDM.

Impact of fetal reduction on the incidence of gestational diabetes.

OBJECTIVE To estimate the rate of gestational diabetes in triplet pregnancies and to assess the impact of fetal reduction on the incidence of this complication. METHODS One hundred eighty‐eight consecutive triplet pregnancies referred to the Sheba Medical Center between 1994 and 1998 were included. One hundred three of these pregnancies continued as triplets, whereas 85 women elected to undergo fetal reduction to twins. The incidence of gestational diabetes (based on the criteria of Carpenter and Coustan) and other outcome variables were compared between the two groups. Student t‐tests and χ2 analysis were used as appropriate. RESULTS Mean (±SD) maternal age was 29.2 ± 4.8 in the triplet group and 29.3 ± 4.1 in the reduction group. The groups had similar median parity (1.6 ± 1.1 in the triplet group and 1.5 ± 0.7 in the reduction group). The rate of gestational diabetes was significantly higher in the triplet group than in the reduction group (22.3% vs 5.8%). A lower birth weight (1764 ± 448 g vs 2208 ± 526 g) and an earlier gestational age at delivery (33.4 ± 2.8 weeks vs 36.0 ± 2.8 weeks) were observed in the triplet group compared with the reduction group. CONCLUSION The number of fetuses in multifetal pregnancies influences the incidence of gestational diabetes. These findings support the hypothesis that an increase in placental mass and, thus, an increase in diabetogenic hormones play a role in the etiology of gestational diabetes.

Adiponectin and Leptin Concentrations in Dichorionic Twins with Discordant and Concordant Growth

CONTEXT Discordant twin gestation, in which one fetus is growth restricted, is a unique model that can elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. OBJECTIVE The objective of the study was to determine the cord blood adiponectin and leptin concentrations and evaluate their association with birth weight in dichorionic twins, with and without growth discordance. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURE: In this cross-sectional study, arterial cord blood adiponectin and leptin concentrations were determined in two groups of newborns: 1) discordant twins, in which one of the twins is growth restricted (small for gestation age and abnormal umbilical arteries Doppler) and the other is appropriate for gestation age (AGA) (n = 14 pairs); and 2) concordant twins, in which both twins are AGA (n = 15 pairs). RESULTS Results were: 1) within the discordant twins group, the median adiponectin concentration was significantly lower in the growth-restricted newborns than in their cotwins (P = 0.004); 2) within the concordant twin group, there was no significant difference in the median cord blood adiponectin concentration between the two AGA twins; 3) the median leptin concentration did not differ between the twins pairs in both study groups; 4) a positive correlation between cord blood adiponectin concentrations and both birth weight (r = 0.7, P < 0.001) and gestational age (r = 0.6, P < 0.02) was found only in the small-for-gestational-age newborns; 5) linear regression model revealed that birth weight is independently associated with circulating adiponectin concentration. CONCLUSIONS Low circulating adiponectin concentrations, previously reported in adults, children, and infants who were born small for gestational age, characterize fetuses with growth restriction and are independently associated with birth weight.