Arnon Wiznitzer

Gestational diabetes: the need for a common ground

Gestational diabetes mellitus is a substantial and growing health concern in many parts of the world. Certain populations are especially vulnerable to developing this condition because of genetic, social, and environmental factors. Gestational diabetes has serious, long-term consequences for both baby and mother, including a predisposition to obesity, metabolic syndrome, and diabetes later in life. Early detection and intervention can greatly improve outcomes for women with this condition and their babies. Unfortunately, screening and diagnostic tests are not uniform worldwide, which could lead not only to underdiagnosis but also undermanagement of the illness. Here, we report the controversies surrounding the causes, screening, diagnosis, management, and prevention of gestational diabetes, and give specific recommendations for research studies to address the major issues of this medical condition.

Effect of bariatric surgery on pregnancy outcome.

To compare the perinatal outcomes of women who delivered before with women who delivered after bariatric surgery.

The safety of metoclopramide use in the first trimester of pregnancy.

BACKGROUND In various countries, metoclopramide is the antiemetic drug of choice in pregnant women, but insufficient information exists regarding its safety in pregnancy. METHODS We investigated the safety of metoclopramide use during the first trimester of pregnancy by linking a computerized database of medications dispensed between January 1, 1998, and March 31, 2007, to all women registered in the Clalit Health Services, southern district of Israel, with computerized databases containing maternal and infant hospital records from the district hospital during the same period. We assessed associations between the use of metoclopramide in pregnancy and adverse outcomes for the fetus, adjusting for parity, maternal age, ethnic group, presence or absence of maternal diabetes, smoking status, and presence or absence of peripartum fever. RESULTS There were 113,612 singleton births during the study period. A total of 81,703 of the infants (71.9%) were born to women registered in Clalit Health Services; 3458 of them (4.2%) were exposed to metoclopramide during the first trimester of pregnancy. Exposure to metoclopramide, as compared with no exposure to the drug, was not associated with significantly increased risks of major congenital malformations (5.3% and 4.9%, respectively; odds ratio, 1.04; 95% confidence interval [CI], 0.89 to 1.21), low birth weight (8.5% and 8.3%; odds ratio, 1.01; 95% CI, 0.89 to 1.14), preterm delivery (6.3% and 5.9%; odds ratio, 1.15; 95% CI, 0.99 to 1.34), or perinatal death (1.5% and 2.2%; odds ratio, 0.87; 95% CI, 0.55 to 1.38). The results were materially unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis. CONCLUSIONS In this large cohort of infants, exposure to metoclopramide in the first trimester was not associated with significantly increased risks of any of several adverse outcomes. These findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy.

Association of lipid levels during gestation with preeclampsia and gestational diabetes mellitus: a population-based study

OBJECTIVE The study evaluates lipids profile changes during gestation in pregnancies with and without preeclampsia and/or gestational diabetes. STUDY DESIGN Lipid profiles were assessed between year prior and after pregnancy in 9911 women without cardiovascular comorbidities. RESULTS Lipid levels during gestation varied substantially with a nadir following conception and a peak at delivery. Compared to preconception levels total cholesterol levels increased from 164.4 mg/dL to 238.6 mg/dL and triglycerides (TGs) from 92.6 mg/dL to 238.4 mg/dL. The composite endpoint (gestational diabetes mellitus or preeclampsia) occurred in 1209 women (12.2%). Its prevalence increased with levels of TG-from 7.2% in the group with low TGs (<25th percentile adjusted for the gestational month) to 19.8% in the group with high TGs (>75th percentile), but was not associated with high-density lipoprotein levels. In multivariate analysis higher TGs levels, but not low high-density lipoprotein, were associated with the primary endpoint. CONCLUSION Lipid levels change substantially during gestation. Abnormal levels of TGs are associated with pregnancy complications.

Dietary polyunsaturated fatty acid prevents malformations in offspring of diabetic rats.

OBJECTIVE The purpose of the current study was to determine whether a dietary source of arachidonic acid could serve as a pharmacologic prophylaxis to obviate the teratogenic effects of hyperglycemia. STUDY DESIGN Eighty-day-old Sprague-Dawley rats were mated, and after conception were randomly allocated to five groups: two groups were nondiabetic normal controls and three groups had diabetes experimentally induced with streptozocin. Of the two control groups, one was fed a normal diet (group 1) and the other group (group 2) received a normal diet and 1.0 ml of safflower oil, a polyunsaturated fatty acid known to increase serum arachidonic acid levels. In the three diabetic groups (groups 3, 4, and 5) glucose levels were allowed to remain > 350 mg/dl by withholding daily insulin therapy. Group 3 received a normal diet without supplementation; group 4 received a normal diet plus normal saline solution sham feedings, whereas group 5 received a normal diet supplemented with 1.0 ml of safflower oil. The oral agents (normal saline solution and polyunsaturated fatty acid) were administered with a tuberculin syringe. RESULTS Diabetic rats not receiving insulin therapy and receiving normal diets produced offspring with malformation rates of 20% compared with control rates of 4.8%. Supplemental normal saline solution or safflower oil given orally to controls did not alter the growth or malformation rates. These rates were similarly unaffected in the diabetic rats receiving oral supplementation of normal saline solution. However, with safflower oil supplementation to diabetic rats the incidence of neural tube defects was decreased from 20.0% to 7.6% (p < 0.0001). An inverse relationship was observed between the malformation rate and the serum arachidonic acid level: 17.83 (SD 5.84 micrograms/ml) in the nondiabetic controls, with a malformation rate of 4.8%, versus 14.18 (SD 2.58 micrograms/ml) in the diabetic rats, with a malformation rate of 20.0% (p < 0.05). With safflower oil supplementation serum levels of arachidonic increased from 14.18 +/- 2.58 micrograms/ml to 19.99 +/- 7.99 micrograms/ml (p < 0.05); this was associated with a concomitant decline in the malformation rate. CONCLUSION These data demonstrate that diabetic embryopathy is associated with a deficiency state in essential fatty acid, corroborating our previous in vitro findings. Furthermore, the use of a dietary polyunsaturated fatty acid that specifically increases arachidonic levels significantly reduced the incidence of diabetic embryopathy. These findings may serve as a basis for developing strategies of pharmacologic prophylaxis against diabetes-induced congenital malformations.

Pregnancy outcome of asthmatic patients: A population-based study

Objective. To investigate pregnancy outcome of asthmatic patients. Methods. A retrospective population-based study comparing all singleton pregnancies in women with and without asthma was conducted. Patients lacking prenatal care (less than three visits in prenatal care facilities) were excluded from the study. Deliveries occurred during the years 1988–2002. Stratified analysis, using a multiple logistic regression model was performed to control for confounders. Results. During the study period 139 168 singleton deliveries occurred, of which 1.4% in asthmatic patients (n = 963). Using a multivariate analysis, with backward elimination, the following complications were significantly associated with maternal asthma: diabetes mellitus (OR = 1.8, 95%CI 1.5–2.0, p < 0.001), fertility treatments (OR = 1.6, 95%CI 1.3–2.1, p < 0.001), intrauterine growth restriction (IUGR) (OR = 1.5, 95%CI 1.1–1.9, p = 0.004), hypertensive disorders (OR = 1.5, 95%CI 1.2–1.7, p < 0.001) and premature rupture of membranes (OR = 1.2, 95%CI 1.1–1.5, p = 0.013). Higher rates of cesarean deliveries were found among asthmatic patients as compared to the controls (17.1% vs. 11.4%, p < 0.001). This association persisted even after controlling for possible confounders such as failure to progress in labor, mal-presentations, IUGR, etc. No significant differences regarding low Apgar scores (less than 7) at 1 and 5 minutes were noted between the groups (3.9% vs. 4.4%, p = 0.268 and 0.4% vs. 0.6%, p = 0.187, respectively). Likewise, the perinatal mortality rate was similar among patients with and without asthma (1.3% vs. 1.3%, p = 0.798). Conclusion. Pregnant women with asthma are at an increased risk for adverse maternal outcome. This association persists after controlling for variables considered to co-exist with maternal asthma. However, perinatal outcome is favorable. Careful surveillance is required in pregnancies of asthmatic patients, for early detection of possible complications.

Gonadotropin-releasing hormone specific binding sites in uterine leiomyomata

Gonadotropin-releasing hormone (GnRH) analogs can cause regression of uterine leiomyomata. This effect is thought to be mediated by the inhibition of gonadotropin release and steroid synthesis. In the present study we examined the possibility that these analogs may also act directly on uterine leiomyomata. Specific binding sites for GnRH are present in myoma membranes, as 125I-Buserelin binding was displaced with equal efficiency by the superagonists, Buserelin and D-Trp6-GnRH, and by the antagonist Organon 30276, but not by unrelated peptides such as thyrotropin releasing hormone and oxytocin. A nonlinear Scatchard curve obtained for Buserelin specific binding suggests the presence of at least two binding sites, one of which exhibits a relatively high affinity for GnRH analogs (Kd of approximately 10(-8) M). Western blotting with a specific GnRH receptor antibody revealed the presence of a 60 kDa protein in myoma membranes. This protein has a similar molecular weight to the purified pituitary GnRH receptor. These results indicate, for the first time, the presence of specific binding sites for GnRH in uterine leiomyomata, suggesting a direct effect of GnRH analogs on this tissue.

Maternal and perinatal outcome of patients with preterm labor and meconium-stained amniotic fluid

Objective To determine the clinical significance of meconium-stained amniotic fluid (AF) observed at amniocentesis in patients with preterm labor. Methods A nested case-control study was constructed based on the color of AF during amniocentesis. Forty-five women admitted with preterm labor and meconium-stained AF were matched for gestational age at admission and compared with 135 women with preterm labor and clear AF. All AF samples were cultured for aerobic and anaerobic bacteria and mycoplasma. Results The rates of positive AF cultures for microorganisms, overall preterm birth (before 36 weeks), preternt birth before 32 weeks, and clinical chorioamnionitis were all significantly higher in patients with meconium-stained AF than in those with clear AF (positive AF cultures, 38 versus 11%, P < .001; preterm delivery before 36 weeks, 73 versus 41%, P < .001; preterm delivery before 32 weeks, 51 versus 17%, P < .001; and clinical chorioamnionitis, 22 versus 6%, P = .003). In contrast, no significant differences were observed between groups with respect to maternal age, gravidity, parity, abruptio placentae, placenta previa, fetal distress, cesarean rate, or puerperal morbidity. Conclusion Patients with preterm labor and meconiumstained AF had higher rates of microbial invasion of the amniotic cavity, clinical chorioamnionitis, and premature deliveries than those with clear AF.

Pregnancy and perinatal outcome in epileptic women: A population-based study

Objective. To investigate the pregnancy outcome of patients with epilepsy. Study design. A population-based study comparing all singleton pregnancies of patients with and without epilepsy was performed. Patients lacking prenatal care were excluded from the analysis. Deliveries occurred between the years 1988 and 2002 in a tertiary medical center. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders. Results. During the study period 139 168 singleton deliveries occurred in our medical center. Of these, 220 (0.2%) were of patients with epilepsy. With the exception of gestational diabetes mellitus (GDM), no other significant differences regarding maternal outcomes were noted between the groups. However, a higher rate of congenital malformations was noted among the epileptic population (7.7% vs. 3.8%; p < 0.001). Also, a higher rate of cesarean deliveries (CD) was found among epileptic women (17.3% vs. 11.55%, p = 0.008). This association was persistent after controlling for possible confounders, using a multivariable analysis (OR = 1.5, 95% CI 1.1–2.3; p = 0.05). Conclusion. The course of pregnancy of patients with epilepsy is favorable, except for higher rates of cesarean deliveries, GDM, and congenital malformations.

Acute antepartum pyelonephritis in pregnancy: a critical analysis of risk factors and outcomes

OBJECTIVE To test the incidence and sonographic parameters of pyelonephritis during pregnancy, and to examine risk factors and pregnancy outcomes of women with acute antepartum pyelonephritis. STUDY DESIGN A retrospective population-based study comparing all singleton pregnancies of patients with and without acute antepartum pyelonephritis was performed. Patients lacking prenatal care as well as multiple gestations were excluded from the study. Multiple logistic regression models were used to control for confounders. RESULTS Out of 219,612 singleton deliveries in 1988-2010, 165 women (0.07%) suffered from acute antepartum pyelonephritis. Abnormal sonographic findings were found in 85.7% of the patients with pyelonephritis. Pyelonephritis was significantly associated with nulliparity (46.1% vs. 24.4%, p<0.001), younger maternal age (26.3 ± 6.0 vs. 28.6 ± 5.8 years, p<0.001), intrauterine growth restriction (IUGR) (6.7% vs. 2.1%, p<0.001), placental abruption (3.6% vs. 0.7%, p<0.001), low 1 min Apgar scores (10.3% vs. 6.0%, p<0.05), urinary tract infection (UTI) (4.2% vs. 0.4%, p<0.001) and preterm delivery (less than 37 weeks gestation; 20.0% vs. 7.8%; p<0.001). Using a multivariable analysis, independent risk factors for acute antepartum pyelonephritis were nulliparity (OR 2.0; 95% C.I 1.4-2.9; p<0.001), UTI (OR 10.3; 95% C.I 4.8-22.1; p<0.001) and younger maternal age (OR 0.96; 95% C.I 0.93-0.99; p=0.009). Using another multivariable analysis, with preterm delivery as the outcome variable, acute antepartum pyelonephritis was found as an independent risk factor for preterm delivery (OR 2.6; 95% C.I 1.7-3.9; p<0.001). CONCLUSION Acute antepartum pyelonephritis is associated with adverse perinatal outcomes and specifically is an independent risk factor for preterm delivery.