Loralei L. Thornburg

Gabapentin, estrogen, and placebo for treating hot flushes : A randomized controlled trial

OBJECTIVE: To compare the efficacy of gabapentin, estrogen, and placebo in the treatment of hot flushes. METHODS: We performed a randomized, double-blind, placebo-controlled trial of 60 postmenopausal women to assess the efficacy of estrogen and gabapentin in the treatment of moderate-to-severe hot flushes. Participants were randomly assigned to receive either 0.625 mg/d of conjugated estrogens (n = 20), placebo (n = 20), or gabapentin titrated to 2,400 mg/d (n = 20) for 12 weeks. Participants recorded frequency and severity of baseline hot flushes on a hot flush diary for 2 weeks before randomization and for 12 weeks after randomization. The primary outcome measure was the weekly hot flush composite score, which takes into account both severity and frequency of hot flushes. Secondary outcome measures were differences in pre- and posttreatment scores pertaining to depression (Zung Depression Scale) and other climacteric symptoms (Greene Climacteric Scale). RESULTS: Intention-to-treat analysis showed that the reduction in the hot flush composite score for both estrogen (72%, P = .016) and gabapentin (71%, P = .004) was greater than the reduction associated with placebo (54%) at the conclusion of the 12th week. The extent of reduction in hot flush composite score, however, was not significantly different between estrogen and gabapentin (P = .63). No differences were seen between groups in the Zung Depression Scale, or in any of the Greene Climacteric subscales except for the Somatic Symptom cluster, which was significantly greater in the gabapentin arm than in the placebo arm. Despite a lack of group differences in adverse events, the Headache, Dizziness, and Disorientation cluster appeared with greater frequency in the gabapentin group. Estimation of the number needed to harm in this cluster suggests that these symptoms may occur with every fourth patient treated with gabapentin. CONCLUSION: Despite the small scale of this study, gabapentin appears to be as effective as estrogen in the treatment of postmenopausal hot flushes. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT 00276081. LEVEL OF EVIDENCE: I

Hypertension in pregnancy and women of childbearing age.

Hypertension in women of childbearing age is a challenging medical problem with increasing prevalence. Essential hypertension remains the most common diagnosis in young women. Reproductive goals and possible teratogenic effects must be considered when initiating therapy. Hypertensive disorders of pregnancy are frequent causes of maternal/fetal morbidity and mortality, the most common being preeclampsia/eclampsia. Pregnant patients should be screened routinely. Early recognition and prompt care from a multidisciplinary service, including obstetrics, cardiology, and intensive medicine, are required to prevent deleterious outcomes. Hypertensive disorders of pregnancy reflect endometrial endothelial dysfunction/abnormalities and systemic endothelial dysfunction, which might predict future cardiovascular disease in these young women, prompting early preventive measures.

Effect of second-trimester and third-trimester rate of gestational weight gain on maternal and neonatal outcomes.

OBJECTIVE: To estimate the effect of second- and third-trimester rate of gestational weight gain on pregnancy outcomes using the revised Institute of Medicine guidelines. METHODS: This is a retrospective cohort study of singleton live births in upstate New York between January 2004 and December 2008. Women were grouped by prepregnancy body mass index (BMI) and rates of second- and third-trimester gestational weight gain were calculated. Women were then classified as having less than, within, or greater than recommended rates of gain. Maternal and neonatal outcomes were assessed based on rate of weight gain within each BMI class. RESULTS: Of 73,977 women meeting inclusion criteria, 4% were underweight, 48% normal weight, 24% overweight, and 24% obese: 13% class I, 6% class II, and 5% class III, respectively. After controlling for potential confounding variables, less than recommended rates of second- and third-trimester weight gain were associated with increased odds of small-for-gestational-age neonates in all BMI groups except obese classes II and III. Greater than recommended rates of weight gain were associated with increased odds of large-for-gestational-age neonates in all BMI groups and increased odds of cesarean delivery in all BMI groups with the exception of underweight and obese class III women. CONCLUSION: Suboptimal second- and third-trimester rates of gestational weight gain in the most obese women, even with net weight loss, do not increase the odds of small-for-gestational-age neonates. Excessive rates of gestational weight gain increase the odds of large-for-gestational-age neonates regardless of BMI. LEVEL OF EVIDENCE: II

Fetal anatomic evaluation in the overweight and obese gravida

To evaluate the rate of completion of anatomic surveys of fetuses in overweight and obese gravid patients as compared with normal controls.

Inflammatory cytokines and antioxidants in midtrimester amniotic fluid: correlation with pregnancy outcome

OBJECTIVE Elevated interleukin-6 (IL-6) level in midtrimester amniotic fluid is associated with preterm delivery. We hypothesized that, in patients with elevated IL-6, vitamin C and alpha-fetoprotein may provide protection from spontaneous preterm delivery through antioxidant functions. STUDY DESIGN Antioxidant potential of alpha-fetoprotein was assessed in vitro. Amniotic fluid was collected from a prospective cohort of patients who underwent midtrimester amniocentesis. In patients with IL-6 >600 pg/mL, alpha-fetoprotein, vitamin C, tumor necrosis factor-alpha, tumor necrosis factor receptors, and antioxidant capacity were compared between subjects with spontaneous preterm and term deliveries. RESULTS Alpha-fetoprotein demonstrated 75% the antioxidant capacity of albumin in vitro. Of 388 subjects, 73 women had elevated IL-6 levels. Among these subjects, alpha-fetoprotein, but not vitamin C, was significantly lower in 9 women with preterm birth. Antioxidant capacity correlated with vitamin C and tumor necrosis factor receptors, but not with alpha-fetoprotein or pregnancy outcome. CONCLUSION Amniotic fluid alpha-fetoprotein, but not vitamin C, may protect against preterm birth in patients with elevated midtrimester IL-6 levels.

Fetal nuchal translucency thickness evaluation in the overweight and obese gravida

To evaluate the time required and failure rate for completion of nuchal translucency thickness (NT) measurements with increased maternal body mass index (BMI).

Ultrasound screening for fetal aneuploidy using soft markers in the overweight and obese gravida

To determine the completion rate of ultrasound surveys for aneuploidy markers by maternal body mass index (BMI).

Perinatal outcomes in type 2 diabetic patients compared with non-diabetic patients matched by body mass index

Objective: Given that both type 2 diabetes and obesity are associated with adverse pregnancy outcomes and often coexist, we sought to determine if outcomes in type 2 diabetic patients are related to the presence of diabetes or to maternal obesity. Methods: This retrospective cohort study examined perinatal outcomes of type 2 diabetic and nondiabetic patients matched by prepregnancy body mass index January 2000 to July 2008. Chi-square, Fisher’s exact test, Mann-Whitney U and t-tests were used to compare groups. The association between type 2 diabetes and adverse perinatal outcomes was evaluated through logistic regression with adjustment for potential confounders. Results: 213 pairs of type 2 and non-diabetic patients were compared. Diabetic patients had overall worse composite pregnancy, delivery, fetal, and neonatal outcomes. Specifically, diabetic patients had higher rates of preeclampsia, poly- and oligohydramnios, cesarean delivery, shoulder dystocia, postpartum hemorrhage, preterm delivery, LGA infant, fetal anomaly, and neonatal hypoglycemia, hyperbilirubinemia, RDS, sepsis, intubation, and admission to the NICU. Diabetes remained a significant predictor of adverse delivery, fetal and neonatal composite outcomes when adjusted for confounders in logistic regression. Conclusions: Type 2 diabetic patients have a higher incidence of adverse perinatal outcomes than nondiabetic patients independent of obesity.

Risk factors for wound complications in morbidly obese women undergoing primary cesarean delivery

Objective: To determine factors influencing separation and infectious type wound complications (WCs) in morbidly obese women undergoing primary cesarean delivery (CD). Methods: Retrospective cohort study evaluating infectious and separation WC in morbidly obese (body mass index [BMI] > 35 kg/m2) women undergoing primary CD between January 1994 and December 2008. Chi-square, Fisher’s exact and Student’s t tests used to assess associated factors; backward logistic regression to determine unadjusted and adjusted odds ratios. Results: Of 623 women, low transverse skin incisions were performed in 588 (94.4%), vertical in 35 (7%). Overall WC rate was 13.5%, which varied by incision type (vertical 45.7% vs. 11.6% transverse; p < 0.01), but not BMI class. Incision type and unscheduled CD were associated with infection risk, while incision type, BMI, race and drain use were associated with wound separation. Conclusion: In morbidly obese women both infectious and separation type WC are more common in vertical than low transverse incisions; therefore transverse should be preferred.

Antepartum Obstetrical Complications Associated with Obesity

Obesity is a major risk factor for many obstetrical complications, including pre-eclampsia, gestational diabetes, indicated preterm birth, macrosomia, and stillbirth. Clinicians should be aware of the unique obstetrical management considerations related to obesity, including recommendations for alterations in prenatal care. In addition, obese gravidas commonly have underlying medical conditions that can impact pregnancy and must be appreciated to optimize care. Obese women should be educated about these risks, ideally before pregnancy. Awareness of the complications that can arise for these women and potential changes in management offer opportunities to improve both prenatal and lifelong health.