Perinatal Outcomes Associated with Early Diabetes Testing in Pregnancies Complicated by Obesity.

OBJECTIVE: This study aimed to determine whether early diabetes testing is associated with differences in perinatal outcomes among pregnant women with obesity (body mass index ≥30 kg/m2). STUDY DESIGN: We conducted a retrospective cohort study of singleton pregnancies from 2012 to 2014 at a large academic medical center which examined the association of diabetes testing (HBA1c, 50 g glucose challenge test, or 100 g oral glucose tolerance test) before 24 weeks with perinatal outcomes using propensity score modeling and logistic regression. RESULTS: Among women with obesity, 790 out of 2,698 (29.3%) underwent early diabetes testing. Propensity score modeling demonstrated that early testing was associated with higher rates of diabetes diagnosis (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.10-2.37, p = 0.01) and a trend toward small for gestational age birth weight (OR: 1.38, 95% CI: 1.00-1.90, p = 0.05) and neonatal composite morbidity (OR: 1.25, 95% CI: 1.00-1.57, p = 0.05) compared with routine testing. Women with inadequate weight gain were more likely a small for gestational age (SGA) infant if they underwent early testing compared with those with routine testing alone (19.8 vs. 11.6%, p = 0.01). CONCLUSION: Early testing targets higher risk women and yields a higher diabetes diagnosis rate, but inadequate weight gain in these women may increase risk SGA birth weight and neonatal morbidity. Randomized clinical trials are urgently needed to assess whether early diabetes testing improves outcomes in women with obesity.

Antibiotic Use in Pregnancy, Abnormal Fetal Growth, and Development of Gestational Diabetes Mellitus.

OBJECTIVE: Antibiotics are commonly used in pregnancy. Prior studies have indicated that antibiotic use in pregnancy may affect birth weight, whereas data in nonpregnant individuals suggest that antibiotic exposure may increase diabetes risk. We evaluated the impact of antibiotic prescriptions during pregnancy on the prevalence of small for gestational age (SGA) and large for gestational age (LGA) birth weight and gestational diabetes mellitus (GDM). STUDY DESIGN: This retrospective cohort study of 12,551 women who delivered at a large academic medical center between 2012 and 2014 assessed the number and type of antibiotic prescriptions prior to GDM testing using the electronic medical record. SGA and LGA birth weight and GDM rates were compared among women who were or were not prescribed antibiotics. RESULTS: Overall, 3,991 (31.8%) of 12,551 patients received at least one antibiotic prescription. After covariate adjustment, no differences existed in risk of SGA (adjusted odds ratio [aOR]: 1; 95% confidence interval [CI]: 0.88-1.15; p = 0.94), LGA (aOR: 1; 95% CI: 0.86-1.17; p = 0.97), or GDM (aOR: 0.90; 95% CI: 0.72-1.13; p = 0.36) between women who were or were not prescribed antibiotics. CONCLUSION: Antibiotic use does not affect the risk of SGA or LGA birth weight or GDM in pregnant women. These results provide reassurance regarding the use of antibiotics when clinically indicated in pregnancy.

Hypertensive disease of pregnancy and maternal mortality.

PURPOSE OF REVIEW: The incidence of hypertensive disorders in pregnancy is increasing and is associated with maternal mortality worldwide. This review provides the obstetrician with an update of the current issues concerning hypertension and maternal mortality. RECENT FINDINGS: Preeclampsia affects about 3% of pregnancies, and all other hypertensive disorders complicate approximately 5-10% of pregnancies in the United States. In industrialized countries, rates of preeclampsia, gestational hypertension, and chronic hypertension have increased as rates of eclampsia have decreased following widespread antenatal care and magnesium sulfate use. Increased maternal mortality is associated with eclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, hepatic or central nervous system hemorrhage, and vascular insult to the cardiopulmonary or renal system. Diagnosis and acute management of severe hypertension is central to reducing maternal mortality. African-American women have a higher risk of mortality from hypertensive disorders of pregnancy compared with Hispanic, American Indian/Alaska Native, Asian/Pacific Islander, and Caucasian women. SUMMARY: Hypertensive disorders in pregnancy are a leading cause of maternal mortality worldwide. The incidence of hypertension in pregnancy continues to increase. Currently, we are unable to determine which patient will develop superimposed preeclampsia or identify subsets of preeclampsia syndrome. Opportunities for research in this area exist to better define treatment aimed at improving maternal outcomes.

Gestational diabetes screening with the new IADPSG guidelines: a cost-effectiveness analysis.

OBJECTIVE: This study investigates the cost effectiveness of gestational diabetes mellitus screening using the new International Association of Diabetes in Pregnancy Study Group (IADPSG) guidelines. STUDY DESIGN: A decision analytic model was built comparing routine screening with the 2-hour (2h) oral glucose tolerance test (OGTT) vs the 1-hour glucose challenge test. All probabilities, costs, and benefits were derived from the literature. Base case, sensitivity analyses, and a Monte Carlo simulation were performed. RESULTS: Screening with the 2h OGTT was more expensive, more effective, and cost effective at $61,503/quality-adjusted life year. In a 1-way sensitivity analysis, the more inclusive IADPSG diagnostic approach remained cost effective as long as an additional 2.0% or more of patients were diagnosed and treated for gestational diabetes mellitus. CONCLUSION: Screening at 24-28 weeks' gestational age under the new IADPSG guidelines with the 2h OGTT is expensive but cost effective in improving maternal and neonatal outcomes. How the health care system will provide expanded care to this group of women will need to be examined.

Rates and predictors of plans for inferior vena cava filter retrieval in hospitalized patients.

BACKGROUND: Use of inferior vena cava (IVC) filters has been increasing over time. However, because of the increased risk of deep vein thrombosis with permanent filters, placement of retrievable filters has been recommended. Little is known about the factors associated with planned retrieval of IVC filters. OBJECTIVE: To describe rates and predictors of plans to retrieve IVC filters in hospitalized patients. DESIGN: We identified all IVC filter placements from 2001-2006 at an academic medical center and reviewed medical charts to obtain data about patient characteristics, filter retrieval plans, and retrieval success rates. Multivariable logistic regression was used to identify independent predictors of planned filter retrieval in patients with retrievable filters. RESULTS: Out of 240 patients who underwent placement of retrievable IVC filters, only 73 (30.4%) had documented plans for filter retrieval. Factors associated with lower rates of planned filter retrieval included a history of cancer [adjusted odds ratio (OR) and 95% confidence interval 0.2 (0.1-0.5)] and not being discharged on anticoagulants [OR 0.1 (0.1-0.3)]. In addition, 36 (21.6%) of patients without retrieval plans had no contraindications to retrieval. Of the 62 patients who underwent attempted filter retrieval, 25.8% of filters could not be successfully removed. CONCLUSIONS: Only 30.4% of patients who underwent placement of a retrievable IVC filter had documented plans for filter removal. Although most patients had justifiable reasons for filter retention, 21.6% of patients had no clear contraindications to filter removal. Efforts to improve rates of filter retrieval in appropriate patients may help reduce the long-term complications of IVC filters.

Role of hippocampal sodium channel Nav1.6 in kindling epileptogenesis.

PURPOSE: Central nervous system plasticity is essential for normal function, but can also reinforce abnormal network behavior, leading to epilepsy and other disorders. The role of altered ion channel expression in abnormal plasticity has not been thoroughly investigated. Nav1.6 is the most abundantly expressed sodium channel in the nervous system. Because of its distribution in the cell body and axon initial segment, Nav1.6 is crucial for action potential generation. The goal of the present study was to investigate the possible role of changes in Nav1.6 expression in abnormal, activity-dependent plasticity of hippocampal circuits. METHODS: We studied kindling, a form of abnormal activity-dependent facilitation. We investigated: (1) sodium channel protein expression by immunocytochemistry and sodium channel messenger RNA (mRNA) by in situ hybridization, (2) sodium current by patch clamp recordings, and (3) rate of kindling by analysis of seizure behavior. The initiation, development, and expression of kindling in wild-type mice were compared to Nav1.6 +/-med(tg) mice, which have reduced expression of Nav1.6. RESULTS: We found that kindling was associated with increased expression of Nav1.6 protein and mRNA, which occurred selectively in hippocampal CA3 neurons. Hippocampal CA3 neurons also showed increased persistent sodium current in kindled animals compared to sham-kindled controls. Conversely, Nav1.6 +/-med(tg) mice resisted the initiation and development of kindling. DISCUSSION: These findings suggest an important mechanism for enhanced excitability, in which Nav1.6 may participate in a self-reinforcing cycle of activity-dependent facilitation in the hippocampus. This mechanism could contribute to both normal hippocampal function and to epilepsy and other common nervous system disorders.

Timing of Gestational Weight Gain and Adverse Perinatal Outcomes in Overweight and Obese Women.

OBJECTIVE: To evaluate whether inadequate or excessive gestational weight gain before the third trimester is associated with adverse pregnancy outcomes, and to evaluate the association of weight gain in the third trimester with fetal growth. METHODS: This was a retrospective cohort study of all eligible overweight and obese women with singleton pregnancies delivered at an academic institution between 2012 and 2014. Our primary exposure was inadequate or excess gestational weight gain during the first and second trimesters. Outcomes included small- (SGA) or large- (LGA) for-gestational-age birth weight as well adverse maternal outcomes and composite neonatal morbidity. Multivariable logistic regression was used to assess the relationship between weight gain and perinatal outcomes, and stratified analyses evaluated the relationship between third trimester weight gain and birth weight category. RESULTS: Of the 5,814 women, 1,280 (22%) had adequate, 1,428 (24.6%) had inadequate, and 3,106 (53.4%) had excessive weight gain in the first and second trimesters. Women with inadequate early gestational weight gain were more likely to deliver an SGA neonate (adjusted odds ratio [aOR] 1.59, 95% CI 1.23-2.06) and less likely to deliver an LGA neonate (aOR 0.73, 95% CI 0.54-0.98), whereas those with excessive early gestational weight gain were less likely to deliver an SGA neonate (aOR 0.66, 95% CI 0.52-0.85) and more likely to deliver an LGA neonate (aOR 1.66, 95% CI 1.32-2.1). Higher weight gain in the third trimester was associated with increased risk for LGA birth weight, but third trimester weight gain was not related to SGA birth weight. CONCLUSION: Early gestational weight gain is associated with birth weight category. Modifying weight gain in the third trimester may limit the risk for LGA birth weight, but higher weight gain in late gestation does not alter the association between inadequate early weight gain and the risk for SGA.

Prolonged antepartum hospitalization: no time for rest.

OBJECTIVE: To characterize sleep patterns among pregnant women undergoing prolonged antepartum hospitalization. STUDY DESIGN: We conducted a prospective cohort study of women undergoing prolonged antepartum hospitalization after 20 weeks' gestation. Women were recruited to wear an Actigraph, complete a sleep log for 7 consecutive days, and complete a sleep survey at the end of the study period. Actigraphy was used to determine rest and sleep intervals, sleep onset latency, and wake time after sleep onset. RESULTS: A total of 40 participants were recruited, and 28 had ≥ 5 nights of data for a total of 177 nights of antepartum sleep data. Mean gestational age was 30 weeks. Median sleep duration was 7.05 h ± 1.71 h. In all, 43.5% of women had an average sleep duration of <7 h per night. In all, 28.2% of the study nights had a bedtime between midnight and 5 am. Going to bed between midnight and 5 am was significantly associated with sleep durations of <7 h (70.7 vs. 32.5%, p < .001). Participants reported an average of 2.4 awakenings per night due to hospital-related events. CONCLUSIONS: Prolonged antepartum hospitalization has a negative impact on sleep duration and quality.

Early Pregnancy Diabetes Screening and Diagnosis: Prevalence, Rates of Abnormal Test Results, and Associated Factors.

OBJECTIVE: To evaluate the prevalence of early diabetes screening in pregnancy, rates of abnormal diabetes test results before 24 weeks of gestation, and factors associated with early diabetes screening. METHODS: This was a retrospective cohort study of all singleton deliveries from 2012 to 2014 among diverse clinical practices at a large academic medical center. We assessed rates of early (less than 24 weeks of gestation) and routine (at or beyond 24 weeks of gestation) diabetes screening, with abnormal test results defined using the Carpenter-Coustan criteria, a 50-g glucose challenge test result greater than 200 mg/dL, or a hemoglobin A1C level greater than 6.5%. Univariate and multivariate analyses were used to evaluate clinical and demographic determinants of screening and diagnosis. RESULTS: Overall, 1,420 of 11,331 (12.5%) women underwent early screening. Increasing body mass index (BMI) category, race, public insurance, history of gestational diabetes mellitus, a family history of diabetes, and chronic hypertension were associated with early screening. Early screening rates rose with increasing BMI category, but only 268 of 551 (48.6%) of women with class III obesity underwent early screening. Among those screened early, 2.0% of normal-weight women, 4.0% of overweight women, 4.2% of class I obese women, 3.8% of class II obese women, and 9.0% of class III obese women had abnormal early test results (P<.001). CONCLUSION: Early diabetes screening is used inconsistently, and many women with risk factors do not undergo early screening. A significant proportion of women with class III obesity will test positive for gestational diabetes mellitus before 24 weeks of gestation, and studies are urgently needed to assess the effect of early diabetes screening and diagnosis on perinatal outcomes in high-risk women.

The Impact of maternal obesity and race/ethnicity on perinatal outcomes: Independent and joint effects.

OBJECTIVE: Independent and joint impacts of maternal race/ethnicity and obesity on adverse birth outcomes, including pre-eclampsia, low birth weight, and macrosomia, were characterized. METHODS: Retrospective cohort study of all 2007 California births was conducted using vital records and claims data. Maternal race/ethnicity and maternal body mass index (BMI) were the key exposures; their independent and joint impact on outcomes using regression models was analyzed. RESULTS: Racial/ethnic minority women of normal weight generally had higher risk as compared with white women of normal weight (e.g., African-American women, pre-eclampsia adjusted odds ratio [aOR] 1.60, 95% confidence interval [CI]: 1.48-1.74 vs. white women). However, elevated BMI did not usually confer additional risk (e.g., pre-eclampsia aOR comparing African-American women with excess weight with white women with excess weight, 1.17, 95% CI: 0.89-1.54). Obesity was a risk factor for low birth weight only among white women (excess weight aOR, 1.24, 95% CI: 1.04-1.49 vs. white women of normal weight) and not among racial/ethnic minority women (e.g., African-American women, 0.95, 95% CI: 0.83-1.08). CONCLUSIONS: These findings add nuance to our understanding of the interplay between maternal race/ethnicity, BMI, and perinatal outcomes. While the BMI/adverse outcome gradient appears weaker in racial/ethnic minority women, this reflects the overall risk increase in racial/ethnic minority women of all body sizes.

Pregnancy risks associated with obesity.

Obesity has increased dramatically in the United States over the last several decades, with approximately 40% of pregnant women now considered overweight or obese. Obesity has been shown to be associated with numerous poor pregnancy outcomes, including increased rates of preeclampsia, gestational diabetes, fetal macrosomia, stillbirth, postterm pregnancy, and increased rates of cesarean delivery. Many of these complications have been found to increase even further with increasing body mass index in a dose-response fashion. In this review, the association of obesity with maternal, fetal, and pregnancy outcomes is discussed as are the recommendations for caring for the obese gravida.

Obesity in pregnancy: a big problem and getting bigger.

UNLABELLED: Obesity has increased dramatically in the United States over the last several decades, with approximately 40% of women now considered overweight or obese. Obesity has been shown to be associated with poor pregnancy outcomes, including increased rates of cesarean delivery, preeclampsia, gestational diabetes, fetal macrosomia, stillbirth, and postterm pregnancy. In this review, we discuss the association of obesity with maternal, fetal, and pregnancy outcomes as well as the recommendations for care of the obese gravida. TARGET AUDIENCE: Obstetricians and gynecologists and family physicians. LEARNING OBJECTIVES: After completing the CME activity, physicians should be better able to describe the maternal, neonatal, and intrapartum complications associated with obesity in pregnancy and implement additional changes to prenatal care appropriate for the obese gravida.

Early treatment suppresses the development of spike-wave epilepsy in a rat model.

PURPOSE: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood. METHODS: We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij) rats, an established model of human absence epilepsy. Oral ethosuximide was given from age p21 to 5 months, covering the usual period in which seizures develop in this model (age approximately 3 months). Two experiments were performed: (1) cortical expression of ion channels Nav1.1, Nav1.6, and HCN1 (previously shown to be dysregulated in WAG/Rij) measured by immunocytochemistry in adult treated rats; and (2) electroencephalogram (EEG) recordings to measure seizure severity at serial time points after stopping the treatment. RESULTS: Early treatment with ethosuximide blocked changes in the expression of ion channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this model. In addition, the treatment led to a persistent suppression of seizures, even after therapy was discontinued. Thus, animals treated with ethosuximide from age p21 to 5 months still had a marked suppression of seizures at age 8 months. DISCUSSION: These findings suggest that early treatment during development may provide a new strategy for preventing epilepsy in susceptible individuals. If confirmed with other drugs and epilepsy paradigms, the availability of a model in which epileptogenesis can be controlled has important implications both for future basic studies, and human therapeutic trials.