Enav Yefet

Glyburide Versus Metformin and Their Combination for the Treatment of Gestational Diabetes Mellitus: A Randomized Controlled Study

OBJECTIVE To compare the efficacy and safety of glyburide versus metformin and their combination for the treatment of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS In this prospective randomized controlled study, we randomly assigned patients with GDM at 13–33 weeks gestation and whose blood glucose was poorly controlled by diet to receive either glyburide or metformin. If optimal glycemic control was not achieved, the other drug was added. If adverse effects occurred, the drug was replaced. If both failed, insulin was given. The primary outcomes were the rate of treatment failure and glycemic control after the first-line medication according to mean daily glucose charts. RESULTS Glyburide was started in 53 patients and metformin in 51. In the glyburide group, the drug failed in 18 (34%) patients due to adverse effects (hypoglycemia) in 6 (11%) and lack of glycemic control in 12 (23%). In the metformin group, the drug failed in 15 (29%) patients, due to adverse effects (gastrointestinal) in 1 (2%) and lack of glycemic control in 14 (28%). Treatment success after second-line therapy was higher in the metformin group than in the glyburide group (13 of 15 [87%] vs. 9 of 18 [50%], respectively; P = 0.03). In the glyburide group, nine (17%) patients were eventually treated with insulin compared with two (4%) in the metformin group (P = 0.03). The combination of the drugs reduced the need for insulin from 33 (32%) to 11 (11%) patients (P = 0.0002). Mean daily blood glucose and other obstetrical and neonatal outcomes were comparable between groups, including macrosomia, neonatal hypoglycemia, and electrolyte imbalance. CONCLUSIONS Glyburide and metformin are comparable oral treatments for GDM regarding glucose control and adverse effects. Their combination demonstrates a high efficacy rate with a significantly reduced need for insulin, with a possible advantage for metformin over glyburide as first-line therapy.

Outcomes From Polyhydramnios With Normal Ultrasound.

OBJECTIVE: To investigate the short- and long-term outcomes of children from pregnancies complicated with polyhydramnios, defined as amniotic fluid index (AFI) >24 cm, and with a normal detailed ultrasound examination. METHODS: This retrospective cohort study examined 134 children aged 4 to 9 years with polyhydramnios and normal detailed ultrasound examination during pregnancy compared with 268 controls with normal AFI and normal detailed ultrasound examination matched for maternal age, year of delivery, gestational week at delivery, and presence or absence of diabetes. The primary outcome was the rate of malformations diagnosed postnatally. Additional outcomes were obstetrics outcomes, genetic syndromes, and neurodevelopment. RESULTS: Polyhydramnios was associated with increased risk for cesarean delivery (CD) and birth weight >90th percentile. This elevation in CD was attributed to increased rate of elective CD due to suspected macrosomia. Polyhydramnios was associated with increased risk for congenital malformations (n = 25 [19%] compared with 27 [10%], respectively; P = .016) without a statistically significant increase in the rate of major malformations (11 [8%] vs. 10 [4%]; P = .057). Genetic syndromes were more prevalent in the polyhydramnios group (5 [3.7%] vs. 2 [0.75%]; P = .043), as were neurologic disorders and developmental delay (9.7% vs. 3%; P = .004). CONCLUSIONS: Despite a normal detailed ultrasound examination, polyhydramnios is associated with increased rate of fetal malformations, genetic syndromes, neurologic disorders, and developmental delay, which may be diagnosed only after birth.

Modifiable risk factors for gestational diabetes recurrence

The literature on risk factors for gestational diabetes mellitus recurrence is inconsistent and sometimes contradictory. The importance of inter-pregnancy interval and parity, remains unclear. We aimed to explore controversial risk factors for gestational diabetes mellitus recurrence, especially the modifiable ones, and to develop a prediction model in a cohort of women with gestational diabetes mellitus. A retrospective, population-based, cross-sectional cohort study was performed. The study included 788 women with gestational diabetes mellitus that delivered between 1991–2012 and had consecutive deliveries at a university affiliated hospital in Israel. Women with pre-existing diabetes were excluded. Factors associated with gestational diabetes mellitus recurrence were examined using log-binomial models to estimate prevalence ratios with 95 % confidence intervals. Multivariate analysis revealed that both inter-pregnancy interval and multiparity were significant risk factors for gestational diabetes mellitus recurrence. Other significant risk factors were maternal age, gestational diabetes mellitus diagnosis week, oral glucose tolerance test values, body mass index gain between pregnancies and insulin use; the latter and multiparity had the strongest effect size (PR ≥ 1.2). Among multiparous women, the association between inter-pregnancy interval and gestational diabetes mellitus recurrence was significantly lower (P = 0.0004) compared with primiparous women (PR = 1.11 [95 % CI 1.09–1.13] versus PR = 1.17 [95 % CI 1.15–1.20], respectively). The model we developed, predicts that reducing the inter-pregnancy interval and weight gain between pregnancies can reduce substantially the risk of gestational diabetes mellitus recurrence. The results suggest that weight gain and inter-pregnancy interval are modifiable risk factors for gestational diabetes mellitus recurrence. Our model could assist physicians in advising women with gestational diabetes mellitus in reducing the risk of recurrent gestational diabetes mellitus during subsequent pregnancies.

The safety of quinolones in pregnancy.

Quinolones and fluoroquinolones are highly efficient antibiotics. However, concerns regarding possible harmful effects have limited their use during pregnancy. Nevertheless, accumulating clinical data suggest that they may be safe during pregnancy. This review aimed to explore the mechanisms of action of the quinolones and fluoroquinolones, which set the stage for concerns regarding possible teratogenic and mutagenic effects; to clarify the clinical dilemmas that brought forth the necessity in reevaluating the use of those medications during pregnancy; and to review the accumulated data regarding their safety during pregnancy in animal models and humans. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to assess the mechanisms of action that had led to concerns regarding the use of fluoroquinolones during pregnancy, appraise the basic knowledge gained from animal studies about the effects of fluoroquinolones during pregnancy, and analyze the human data on the actual effect of variable fluoroquinolones in pregnancy.

Predictive Value of Second-Trimester Biomarkers and Maternal Features for Adverse Pregnancy Outcomes

Objective: To establish the predictive probability for placenta-associated morbidities using second-trimester α-fetoprotein (AFP), human chorionic gonadotropin (HCG), and maternal features. Patients and Methods: A retrospective database of all singleton deliveries with available second-trimester HCG and AFP results from 2005 to 2012 was built and divided into 0, 1, or 2 elevated markers (defined as ≥2 multiples of the median [MoM]). For each group, we analyzed the risk for adverse obstetric outcome - comprising preeclampsia, placental abruption, and birth weight below the 10th percentile - and the time of delivery in those pregnancies. Additionally, prediction models for adverse obstetric outcome, using logistic regression incorporating AFP, HCG, and other maternal characteristics, were calculated. Results: Among 22,124 women who delivered, 16,197 (73%) had AFP and HCG results. Compared with the group with normal markers, the adverse obstetric outcome rate was mildly increased with elevated HCG or AFP, but it was markedly increased when both markers were elevated (13 vs. 31%, OR 2.9, 95% CI 2.0-4.3). Delivery of newborns with adverse obstetric outcome was earlier with each additional elevated marker. The accuracy of predicting adverse obstetric outcome was improved by using prediction models for women with HCG or AFP ≥1.2 MoM that incorporated maternal age, BMI, parity, and chronic hypertension (C-statistic 61-75%). Conclusion: HCG and AFP combined with other maternal characteristics are useful tools for predicting the risk for adverse obstetric outcome.

The safety of quinolones and fluoroquinolones in pregnancy: a meta‐analysis

Quinolones were contraindicated during pregnancy because of concerns regarding fetal malformations and carcinogenesis in animals. The literature is conflicting regarding their safety in humans.

Postprandial glycemic control during gestational diabetes pregnancy predicts the risk of recurrence

In this study we aimed to explore the significance of glycemic control during gestational diabetes mellitus (GDM) pregnancy in predicting recurrence as this is unknown. A retrospective population-based cohort study of women with first diagnosed GDM pregnancy was conducted. A total of 426 women with 4,226 glucose charts were obtained. Daily glucose values were collected from the glucose charts. Non-parametric (LOWESS) regression was used to present the glucose measurements along the gestational weeks. The analyses revealed that the 2-hour postprandial levels among women with GDM recurrence were substantially higher throughout gestation (PR = 1.89 [95% CI: 1.33, 2.73] for every 20 mg/dl increase). In a multivariable log-binomial regression, the mean postprandial glucose was significantly associated with GDM recurrence (p = 0.017) after adjusting for maternal age, family history of diabetes, insulin use, and inter-pregnancy interval (PR = 1.04 [95% CI: 1.01, 1.07]). The study conclusion is that tighter postprandial glycemic control should be considered. Future studies should explore tighter cutoffs of the 2-hour postprandial glucose.

Labor induction versus expectant management at early term in pregnancies with second trimester elevated human chorionic gonadotropin or alpha fetoprotein

Elevated human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) have been linked to placental dysfunction and associated morbidities. We aimed to compare the induction of labor with expectant management at term in those pregnancies for the prevention of neonatal and maternal morbidities.

Response to Comment on Nachum et al. Glyburide Versus Metformin and Their Combination for the Treatment of Gestational Diabetes Mellitus: A Randomized Controlled Study. Diabetes Care 2017;40:332–337

The comment by Barbour and Davies (1) acknowledges that our study (2) is important given the increasing popularity of oral agents to treat gestational diabetes mellitus (GDM) but raises concerns whether the study design and conclusions can be generalized to other GDM populations. With regard to treatment efficacy before 24 weeks, in our study the success rate of oral treatments before and after 24 weeks was similar: 67% vs. 69% after first-line therapy and 89% vs. 90% for second-line therapy, …

Fixed time interval compared with on‐demand oral analgesia protocols for post‐caesarean pain: a randomised controlled trial

To compare the efficacy, safety and satisfaction from two modes of oral analgesia administration for the treatment of post‐caesarean pain in the first 48 h following surgery: on‐demand versus fixed time interval administration.