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.

SUMMARYPurpose: 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 ∼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.

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 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 +/− medtg 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 +/− medtg 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.

Objective This study investigates the cost-effectiveness of gestational diabetes mellitus (GDM) screening using the new IADPSG guidelines. Study Design A decision analytic model was built comparing routine screening with the 2h OGTT vs. the 1-hour GCT. 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 GTT was more expensive, more effective, and cost-effective at $61,503/QALY. In a one-way sensitivity analysis, the more inclusive IADPSG diagnostic approach remained cost-effective as long an additional 2.0% or more of patients were diagnosed and treated for GDM. Conclusion Screening at 24-28 weeks GA under the new IADPSG guidelines with the 2h GTT 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.

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Objective We characterized independent and joint impacts of maternal race/ethnicity and obesity on adverse birth outcomes, including preeclampsia, low birthweight (LBW), and macrosomia. Methods Retrospective cohort study of all 2007 California births using vital records and claims data. Maternal race/ethnicity and maternal BMI were the key exposures; we analyzed their independent and joint impact on outcomes using regression models. Results Racial/ethnic minority women of normal weight generally had higher risk as compared to white women of normal weight (e.g., African-American women, preeclampsia aOR, 1.60, 95% CI: 1.48 – 1.74, versus white women). However, elevated BMI did not usually confer additional risk (e.g., preeclampsia aOR comparing African-American women with morbid obesity to white women with morbid obesity; 1.17, 95% CI: 0.89 – 1.54). Obesity was a risk factor for LBW only among white women (morbid obesity aOR, 95% CI: 1.24, 1.04 – 1.49, versus white women of normal weight), and not among racial/ethnic minority women (e.g., African-American women, 0.95, 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.

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.

has been reviewed by the Editorial Board and by special expert referees. Although it is judged not acceptable for publication in Obstetrics & Gynecology in its present form, we would be willing to give further consideration to a revised version. If you wish to consider revising your manuscript, you will first need to study carefully the enclosed reports submitted by the referees and editors. Each point raised requires a response, by either revising your manuscript or making a clear and convincing argument as to why no revision is needed. To facilitate our review, we prefer that the cover letter include the comments made by the reviewers and the editor followed by your response. The revised manuscript should indicate the position of all changes made. We suggest that you use the "track changes" feature in your word processing software to do so (rather than strikethrough or underline formatting). Your paper will be maintained in active status for 21 days from the date of this letter. If we have not heard from you by Jan 25, 2019, we will assume you wish to withdraw the manuscript from further consideration. REVIEWER COMMENTS: Reviewer #1: This manuscript has a purpose to "evaluate the impact of insufficient or excessive gestational weight gain in the first and second trimester on adverse perinatal outcomes, and whether weight gain in the third trimester modifies these risks." This was a retrospective, cohort study using an institutional database, which the authors validated by randomly selecting 300 subjects and manually confirming data in the database. 1. Could the authors please include a 'Precis' for their manuscript? 2. The authors describe BMI and suggested gestational weight gain for the different categories for overweight and obese. Could the authors construct a table with the WHO definition of all the various BMI categories (underweight, normal, overweight, obese) in one column and suggested weight gain for each category in an adjacent column and reference in text? 3. How was gestational age determined? How accurate was determination of gestational age? Was gestational age at birth determined by the Pediatricians with a Ballard score? 4. The authors note that they performed a validation survey by manually abstracting a randomly selected group of 300 charts. How was randomization performed? Why did they select a n=300 charts to validate their database? Reviewer #2: Slight revision-please change "fetal gender" to "fetal sex" in line 145 [gender is a social construct, sex is a biologic construct]. Reviewer #3: This is a retrospective cohort study of over 5000 obese women that examined their weight gain as of 24-28 weeks and relationship to adverse pregnancy outcomes. The manuscript is well written. Line 72: IOM is now the National Academy of Medicine Line 77: "weight gain 11 pounds" I think is missing 'less than' as in weight gain less than 11 pounds