Evaluating the cost-effectiveness of prenatal surgery for myelomeningocele: a decision analysis.

OBJECTIVE: To determine whether prenatal myelomeningocele repair is a cost-effective strategy compared to postnatal repair. METHODS: Decision-analysis modeling was used to calculate the cumulative costs, effects and incremental cost-effectiveness ratio of prenatal myelomeningocele repair compared with postnatal repair in singleton gestations with a normal karyotype that were identified with myelomeningocele between T1 and S1. The model accounted for costs and quality-adjusted life years (QALYs) in three populations: (1) myelomeningocele patients; (2) mothers carrying myelomeningocele patients; and (3) possible future siblings of these patients. Sensitivity analysis was performed using one-way, two-way and Monte Carlo simulations. RESULTS: Prenatal myelomeningocele repair saves $ 2 066 778 per 100 cases repaired. Additionally, prenatal surgery results in 98 QALYs gained per 100 repairs with 42 fewer neonates requiring shunts and 21 fewer neonates requiring long-term medical care per 100 repairs. However, these benefits are coupled to 26 additional cases of uterine rupture or dehiscence and one additional case of neurologic deficits in future offspring per 100 repairs. Results were robust in sensitivity analysis. CONCLUSION: Prenatal myelomeningocele repair is cost effective and frequently cost saving compared with postnatal myelomeningocele repair despite the increased likelihood of maternal and future pregnancy complications associated with prenatal surgery.

Excitotoxicity as a Common Mechanism for Fetal Neuronal Injury with Hypoxia and Intrauterine Inflammation.

Excitotoxicity is a mechanism of neuronal injury, implicated in the pathogenesis of many acute and chronic neurologic disorders, including perinatal brain injury associated with hypoxia-ischemia and exposure to intrauterine inflammation. Glutamate, the primary excitatory neurotransmitter, signals through N-methyl-d-aspartic acid (NMDA)/α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Proper functioning of both of these receptors, in conjunction with glutamate signaling, is crucial for normal development. However, even a small imbalance can result in perinatal neuronal injury. Therefore, a mechanistic understanding of the role of excitotoxicity and the NMDA/AMPA receptor functions is critical to establishing the pathogenesis of hypoxic-ischemic encephalopathy (HIE) and perinatal brain injury due to exposure to intrauterine inflammation. Evidence from experimental animal models and clinical studies indicates that both oxygen and glucose deficiencies play a major role in fetal neuronal injury. However, the connection between these deficiencies, excitotoxicity, and HIE is not well established. The excitotoxic mechanisms in animal models and humans have many parallels, suggesting that detailed animal studies can elicit clinically relevant discoveries. While current therapies for HIE include hypothermia and other neuroprotective measures, emphasizing prevention of acute injuries, increase of therapeutic time window, and increased neural repair, there are no effective widely used treatment modalities for fetuses and neonates exposed to intrauterine inflammation. Further studies of HIE and intrauterine inflammation (as in cases of preterm birth and chorioamnionitis) will provide a better insight into development of effective therapeutic interventions for these conditions.

The Impact of Maternal Body Mass Index and Gestational Age on the Detection of Uterine Contractions by Tocodynamometry: A Retrospective Study.

OBJECTIVE: To examine the impact of maternal body mass index (BMI) and gestational age (GA) on uterine contraction detection by tocodynamometry. METHODS: Gravidas with preterm labor (PTL) complaints who were evaluated by tocodynamometry, discharged from Labor and Delivery triage, and subsequently readmitted for preterm delivery were studied. Forty-six patients in whom contractions were detected (group 1) were compared to 49 women in whom contractions were not detected (group 2) with respect to BMI and GA at both evaluation and delivery. Multivariable logistic regression was used to adjust for confounders. RESULTS: Group 2 had a higher mean BMI (31.7 vs 26.1, P < .001), were more likely to be obese (57.1% vs 19.6%, P < .001), and were more likely to have been evaluated in the mid-trimester (36.7% vs 17.4%, P = .04) compared to group 1. Independent risk factors for the inability of the tocodynamometer to detect contractions were obesity (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.07-0.46) and evaluation in the mid-trimester (OR 0.33, 95% CI 0.13-0.84). CONCLUSION: Our study provides evidence that the effectiveness of tocodynamometry diminishes with increasing maternal BMI. Efficacy of tocodynamometry is also decreased at earlier GA, most pronounced below 25 weeks. To evaluate women with PTL symptoms in the mid-trimester or symptomatic obese women at any GA, a modality other than tocodynamometry could be valuable to more accurately assess uterine activity.

Perinatal inflammation/infection and its association with correction of metabolic acidosis in hypoxic-ischemic encephalopathy.

OBJECTIVE: To investigate the decreased response to hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE) and infection, we sought to determine the association of fetal inflammation/infection with perinatal metabolic acidosis. STUDY DESIGN: We performed a retrospective cohort study of neonates with suspected HIE started on whole-body hypothermia within 6 h of birth that had a cord gas at delivery and placental pathology performed. Neonates were compared based on the presence of clinical and histologic chorioamnionitis. The cord gas at delivery was compared with the initial arterial gas after birth. RESULTS: In all, 50 out of 67 (74.6%) neonates admitted for therapeutic hypothermia met inclusion criteria. Chorioamnionitis did not affect the cord gas at delivery, but both clinical and histologic chorioamnionitis were associated with a significantly increased metabolic acidosis on the initial neonatal arterial gas. CONCLUSION: Chorioamnionitis, diagnosed both clinically and histologically, is associated with a persistent state of acidosis in neonates with HIE that may contribute to worse neurologic outcomes.

Prematurity: present and future.

The study of preterm labor and prematurity has undergone a major transformation in its approach from an inevitable part of obstetrics with few answers to one in which science has led to knowledge and clinical intervention. Despite these advancements, understanding of preterm labor and prevention of prematurity is still limited. In the current review, we begin the discussion with fetal viability, first from a historical perspective and then from the understanding of this issue from a prospective of various professional organizations. We then present the scope of the problem of preterm birth from various countries including the discrepancy between the US and Europe. We continue with updates on extreme prematurity and outcomes with two longitudinal studies from the past 2 years. We further review available interventions for prematurity and discuss the use of antenatal corticosteroids. First, we examine their use in the context of professional recommendations and then examine the trajectory of their continued use in the late preterm period. We focus on a European-based trial with preliminary results and an ongoing American counterpart. The current knowledge of molecular mechanisms behind preterm labor is presented with a focus on the multiple etiologies of preterm labor, both known and presumed, with updates in the basic science realm. Furthermore, we present up-to-date studies on prediction of preterm birth and prematurity-related morbidity.

An ACOG-affiliated medical student obstetrics and gynecology club.

An ACOG-affiliated obstetrics and gynecology club for medical students was developed at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School to introduce medical students to the specialty early in their careers, to educate them about obstetrician-gynecologists effect on women's health, and to guide them through exploration of the field. With ACOG District III Fellow and Junior Fellow support and collaboration, the club was formed and operational within 6 months. Because of this club students feel included in the district and national organizations by participating in Junior Fellow and Fellow activities. Through Junior Fellow activities, medical students get first-hand exposure to numerous obstetrics and gynecology residency programs. Through workshops and noncredit electives, medical students receive personal mentoring by Fellows and Junior Fellows. Students participate in community projects and from those programs can better understand the needs of women, especially women with inadequate or no health insurance. The collaboration between Junior Fellows, Fellows, and medical students is the most important component in establishing a student-run club affiliated with ACOG. This project has effectively introduced students to the field of women's health early in their careers and could provide a model for implementation at other medical schools.

Circadian cycle-dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation.

Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term electroencephalogram (EEG) biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video/EEG/electromyogram (EMG) analyses. A single LPS injection at E17 was performed in pregnant CD1 dams. Control dams were injected with same volumes of saline (LPS n=10, Control n=8). At postnatal age of P90-100, 24-h synchronous video/EEG/EMG recordings were done using a tethered recording system and implanted subdural electrodes. Behavioral state scoring was performed blind to treatment group, on each 10s EEG epoch using synchronous video, EMG and EEG trace signatures to generate individual hypnograms. Automated EEG power spectrums were analyzed for delta and theta-beta power ratios during wake vs. sleep cycles. Both control and LPS hypnograms showed an ultradian wake/sleep cycling. Since rodents are nocturnal animals, control mice showed the expected diurnal variation with significantly longer time spent in wake states during the dark cycle phase. In contrast, the LPS-treated mice lost this circadian rhythm. Sleep microstructure also showed significant alteration in the LPS mice specifically during the dark cycle, caused by significantly longer average non-rapid eye movement (NREM) cycle durations. No significance was found between treatment groups for the delta power data; however, significant activity-dependent changes in theta-beta power ratios seen in controls were absent in the LPS-exposed mice. In conclusion, exposure to in utero inflammation in CD1 mice resulted in significantly altered sleep architecture as adults that were circadian cycle and activity state dependent.

Androgen replacement in menopause.

Menopause and the years leading to the menopausal transition are associated with significant decline in sex steroid levels. In contrast to the abrupt decline in estrogens at the time of menopause, a fall in the circulating testosterone and the adrenal preandrogens most closely parallel increasing age. Their accelerated decrease occurs in the years preceding menopause. It is now recognized that the decline in androgens plays a significant role in affecting perimenopausal and menopausal symptomatology and quality of life. Loss of circulating levels of androgens affects libido, vasomotor symptoms, mood and well-being, bone structure, muscle mass. Also, it influences cardiovascular profile. In the menopausal female (in whom these symptoms are clearly linked to low levels of bioavailable testosterone levels), hormone replacement therapy may be of benefit. Recently, interest is increasing in the use of androgen replacement not only for women who have undergone premature or surgical menopause but also for those who experience natural menopause and premenopausal loss of libido from diminished free testosterone.