Synthesis and Receptor Binding Studies of α5 GABAAR Selective Novel Imidazodiazepines Targeted for Psychiatric and Cognitive Disorders.

GABA mediates inhibitory actions through various GABAA receptor subtypes, including 19 subunits in human GABAAR. Dysregulation of GABAergic neurotransmission is associated with several psychiatric disorders, including depression, anxiety, and schizophrenia. Selective targeting of α2/3 GABAARs can treat mood and anxiety, while α5 GABAA-Rs can treat anxiety, depression, and cognitive performance. GL-II-73 and MP-III-022, α5-positive allosteric modulators have shown promising results in animal models of chronic stress, aging, and cognitive disorders, including MDD, schizophrenia, autism, and Alzheimer's disease. Described in this article is how small changes in the structure of imidazodiazepine substituents can greatly impact the subtype selectivity of benzodiazepine GABAAR. To investigate alternate and potentially more effective therapeutic compounds, modifications were made to the structure of imidazodiazepine 1 to synthesize different amide analogs. The novel ligands were screened at the NIMH PDSP against a panel of 47 receptors, ion channels, including hERG, and transporters to identify on- and off-target interactions. Any ligands with significant inhibition in primary binding were subjected to secondary binding assays to determine their Ki values. The newly synthesized imidazodiazepines were found to have variable affinities for the benzodiazepine site and negligible or no binding to any off-target profile receptors that could cause other physiological problems.

Symptomatic and neurotrophic effects of GABAA receptor positive allosteric modulation in a mouse model of chronic stress.

Chronic stress is a risk factor for Major Depressive Disorder (MDD), and in rodents, it recapitulates human behavioral, cellular and molecular changes. In MDD and after chronic stress, neuronal dysfunctions and deficits in GABAergic signaling are observed and responsible for symptom severity. GABA signals predominantly through GABAA receptors (GABAA-R) composed of various subunit types that relate to downstream outcomes. Activity at α2-GABAA-Rs contributes to anxiolytic properties, α5-GABAA-Rs to cognitive functions, and α1-GABAA-Rs to sedation. Therefore, a therapy aiming at increasing α2- and α5-GABAA-Rs activity, but devoid of α1-GABAA-R activity, has potential to address several symptomologies of depression while avoiding side-effects. This study investigated the activity profiles and behavioral efficacy of two enantiomers of each other (GL-II-73 and GL-I-54), separately and as a racemic mixture (GL-RM), and potential disease-modifying effects on neuronal morphology. Results confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the α2-, α3-, α5-GABAA-Rs and α5-containing GABAA-Rs, respectively, and separately reduces immobility in the forced swim test and improves stress-induced spatial working memory deficits. Using unpredictable chronic mild stress (UCMS), we show that acute and chronic administration of GL-RM provide pro-cognitive effects, with mild efficacy on mood symptoms, although at lower doses avoiding sedation. Morphology studies showed reversal of spine density loss caused by UCMS after chronic GL-RM treatment at apical and basal dendrites of the PFC and CA1. Together, these results support using a racemic mixture with combined α2-, α3-, α5-GABAA-R profile to reverse chronic stress-induced mood symptoms, cognitive deficits, and with anti-stress neurotrophic effects.

Rates of substance and polysubstance use through universal maternal testing at the time of delivery.

OBJECTIVE: To report substance and polysubstance use at the time of delivery. STUDY DESIGN: A cross-sectional study was performed on mothers consented for universal drug testing (99%) during hospital admission at six delivery hospitals in Cincinnati, Ohio. Mass spectrometry urinalysis detected positivity rates of 46 substances. Rates of positive drug tests for individual and common co-occurring substances measured were reported. RESULTS: 2531 maternal samples were tested (88%) and 33% contained cotinine, 11.3% THC, 7.2% opioids, 3.8% cocaine, and 1.9% methamphetamines. Polysubstance use prevalence was as high as 15%. Among mothers testing positive for methadone or buprenorphine, 93% also tested positive for cotinine and 39% tested positive for a third substance in addition to cotinine. CONCLUSIONS: Substance use at delivery is more prevalent than previously reported. Many mothers testing positive for opioids also test positive for other substances, which may increase overdose risk and exacerbate neonatal opioid withdrawal syndrome (NOWS).

Substance Use and Utilization of Prenatal and Postpartum Care.

OBJECTIVES: Prenatal and postpartum care for women with substance use is important due to increased risk of poor health outcomes. The influence of substance use on perinatal care utilization is not well characterized, especially postpartum care. The objective of this study was to examine the effect of substance use during pregnancy on prenatal and postpartum care utilization in a nationally representative sample and to identify maternal characteristics associated with inadequate prenatal and postpartum care among women with substance use. METHODS: Pregnancy Risk Assessment Monitoring System data (2016-2018) from 8 states were used for this study. Logistic regression models adjusted for complex survey weights and confounder variables were used to estimate the odds of not receiving adequate prenatal care and postpartum care. Weighted Rao-Scott chi-square tests were used to examine maternal characteristics associated with care utilization among women who reported substance use during pregnancy. RESULTS: The study included 15,131 women, with 5.3% who reported illicit substance use during pregnancy. In multivariable models, substance use was associated with an increase in the odds of not receiving adequate prenatal care (OR 1.69, CI 1.32, 2.17) and not receiving postpartum care (OR: 1.47, CI 1.10, 1.95). Among women who reported substance use, depression and smoking status were associated with not receiving adequate prenatal or postpartum care. CONCLUSIONS: Substance use during pregnancy is independently associated with disparities in prenatal and postpartum care access. Future studies are needed to identify how barriers lead to care inequalities and importantly, to identify strategies to improve care utilization.

Handling Techniques to Reduce Stress in Mice.

Laboratory animals are subjected to multiple manipulations by scientists or animal care providers. The stress this causes can have profound effects on animal well-being and can also be a confounding factor for experimental variables such as anxiety measures. Over the years, handling techniques that minimize handling-related stress have been developed with a particular focus on rats, and little attention to mice. However, it has been shown that mice can be habituated to manipulations using handling techniques. Habituating mice to handling reduces stress, facilitates routine handling, improves animal wellbeing, decreases data variability, and improves experimental reliability. Despite beneficial effects of handling, the tail-pick up approach, which is particularly stressful, is still widely used. This paper provides a detailed description and demonstration of a newly developed mouse-handling technique intended to minimize the stress experienced by the animal during human interaction. This manual technique is performed over 3 days (3D-handling technique) and focuses on the animal's capacity to habituate to the experimenter. This study also shows the effect of previously established tunnel handling techniques (using a polycarbonate tunnel) and the tail-pick up technique. Specifically studied are their effects on anxiety-like behaviors, using behavioral tests (Elevated-Plus Maze and Novelty Suppressed Feeding), voluntary interaction with experimenters and physiological measurement (corticosterone levels). The 3D-handling technique and the tunnel handling technique reduced anxiety-like phenotypes. In the first experiment, using 6-month-old male mice, the 3D-handling technique significantly improved experimenter interaction. In the second experiment, using 2.5-month-old female, it reduced corticosterone levels. As such, the 3D-handling is a useful approach in scenarios where interaction with the experimenter is required or preferred, or where tunnel handling may not be possible during the experiment.

The Palmaris Longus and Its Association with Carpal Tunnel Syndrome.

Background The palmaris tendon inserts into the palmar fascia and is positioned in close association with the transverse carpal ligament. Loading of this tendon has been demonstrated to increase carpal tunnel pressures. Purpose The purpose of this study was to determine if a relationship exists between the palmaris tendon, carpal tunnel syndrome (CTS), and handedness. The sensitivity, specificity, positive predictive value, and negative predictive value for Schaeffer's test were calculated. Methods A retrospective review of patient charts undergoing endoscopic carpal tunnel release was performed. Rates of palmaris longus agenesis (PLA) were compared to a population matched data set. Statistical analysis was performed using a one-proportion z -test. Schaeffer's test for the palmaris longus tendon was performed on all patients and compared to intraoperative confirmation. Results A total of 520 carpal tunnel releases were performed in 389 consecutive patients. The frequency of PLA in this surgical cohort was significantly lower compared to the population matched dataset. No correlation between handedness and laterality of CTS or PLA was found. Schaeffer's test was evaluated to yield sensitivity (93.6%), specificity (100%), positive predictive value (100%), and negative predictive value (50.8%). Conclusion The palmaris tendon was more prevalent in a population of patients undergoing carpal tunnel release. These findings can be used to provide further insight into the pathophysiology of CTS. While Schaeffer's test was accurate in detecting the palmaris longus tendon, a negative test was frequently incorrect. Further imaging is recommended in patients with a negative Schaeffer's test when the palmaris longus is desired for surgical utilization. Level of Evidence This is a Level III, prognostic study.

A statewide quality improvement (QI) initiative for better health outcomes and family stability among pregnant women with opioid use disorder (OUD) and their infants.

A collaborative led by state health and human service agencies, academic leaders, and stakeholders tested interventions to expand use of medication assisted treatment (MAT) through a maternal medical home (MMH) model that coordinated behavioral health and prenatal care with social supports for pregnant women with opioid use disorder (OUD) enrolled in Medicaid. The program was anchored in four clinical organizations with distinct models of care: community behavioral health, residential behavioral health, hospital-based obstetrical practice, and co-located obstetrical and behavioral health. A modified version of the Institute for Healthcare Improvement Breakthrough Series Model for Improvement was implemented using monthly performance data feedback to conduct small tests of change and improve care. Administrative data from the state's Medicaid, vital statistics, and child welfare systems were linked to evaluate the impact of MOMS on 252 mother-infant dyads compared to a sample of 846 Medicaid beneficiaries with OUD in the third trimester of pregnancy. MOMS participation was associated with increased likelihood of MAT in trimesters one, two and three (AOR = 2.30, 4.40, 2.75, respectively), behavioral health counseling during trimesters two and three (AOR = 3.75 and 2.07, respectively), retention in MAT during postpartum months one through three and four through six (AOR = 2.86, 2.40, respectively), and marginally lower out-of-home placement of infants born to mothers with OUD (AOR = 0.66). Within the MOMS program, greater participation in behavioral health treatment and MAT (χ2(3) ≥ 12.09) was observed in the co-located behavioral health/obstetrical care practice site compared to behavioral health-led and obstetrical provider-led sites.

Statewide Quality Improvement Initiative to Reduce Early Elective Deliveries and Improve Birth Registry Accuracy.

OBJECTIVE: To evaluate the success of a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data accuracy rapidly and at scale in Ohio. METHODS: Between February 2013 and March 2014, participating hospitals were involved in a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data. This initiative was designed as a learning collaborative model (group webinars and a single face-to-face meeting) and included individual quality improvement coaching. It was implemented using a stepped wedge design with hospitals divided into three balanced groups (waves) participating in the initiative sequentially. Birth registry data were used to assess hospital rates of nonmedically indicated inductions at less than 39 weeks of gestation. Comparisons were made between groups participating and those not participating in the initiative at two time points. To measure birth registry accuracy, hospitals conducted monthly audits comparing birth registry data with the medical record. Associations were assessed using generalized linear repeated measures models accounting for time effects. RESULTS: Seventy of 72 (97%) eligible hospitals participated. Based on birth registry data, nonmedically indicated inductions at less than 39 weeks of gestation declined in all groups with implementation (wave 1: 6.2-3.2%, P<.001; wave 2: 4.2-2.5%, P=.04; wave 3: 6.8-3.7%, P=.002). When waves 1 and 2 were participating in the initiative, they saw significant decreases in rates of early elective deliveries as compared with wave 3 (control; P=.018). All waves had significant improvement in birth registry accuracy (wave 1: 80-90%, P=.017; wave 2: 80-100%, P=.002; wave 3: 75-100%, P<.001). CONCLUSIONS: A quality improvement initiative enabled statewide spread of change strategies to decrease early elective deliveries and improve birth registry accuracy over 14 months and could be used for rapid dissemination of other evidence-based obstetric care practices across states or hospital systems.

Risk Factors for Brachial Plexus Birth Injury.

Over the course of decades, the incidence of brachial plexus birth injury (BPBI) has increased despite advances in healthcare which would seem to assist in decreasing the rate. The aim of this study is to identify previously unknown risk factors for BPBI and the risk factors with potential to guide preventative measures. A case control study of 52 mothers who had delivered a child with a BPBI injury and 132 mothers who had delivered without BPBI injury was conducted. Univariate, multivariable and logistic regressions identified risk factors and their combinations. The odds of BPBI were 2.5 times higher when oxytocin was used and 3.7 times higher when tachysystole occurred. The odds of BPBI injury are increased when tachysystole and oxytocin occur during the mother's labor. Logistic regression identified a higher risk for BPBI when more than three of the following variables (>30 lbs gained during the pregnancy, stage 2 labor >61.5 min, mother's age >26.4 years, tachysystole, or fetal malpresentation) were present in any combination.

Using a State Birth Registry as a Quality Improvement Tool.

Background Birth registry data are universally collected, generating large administrative datasets. However, these data are typically not used for quality improvement (QI) initiatives in perinatal medicine because the quality and timeliness of the information is uncertain. Objective We sought to identify and address causes of inaccuracy in recording birth registry information so that birth registry data could support statewide obstetrical quality initiatives in Ohio. Study Design The Ohio Perinatal Quality Collaborative and the Ohio Department of Health Vital Statistics used QI techniques in 15 medium-sized maternity hospitals to identify and remove systemic sources of inaccuracy in birth registry data. The primary outcome was the rate of scheduled deliveries without medical indication between 370/7 and 386/7 weeks at participating hospitals from birth registry data. Results Inaccurate birth registry data most commonly resulted from limited communication between clinical and medical record staff. The rate of scheduled births between 370/7 and 386/7 weeks' gestation without a documented medical indication as recorded in the birth registry declined by 35%. Conclusion A QI initiative aimed at increasing the accuracy of birth registry information demonstrated the utility of these data for surveillance of perinatal outcomes and has led to ongoing efforts to support birth registrars in submitting accurate data.

A Statewide Progestogen Promotion Program in Ohio.

OBJECTIVE: To promote use of progestogen therapy to reduce premature births in Ohio by 10%. METHODS: The Ohio Perinatal Quality Collaborative initiated a quality improvement project in 2014 working with clinics at 20 large maternity hospitals, Ohio Medicaid, Medicaid insurers, and service agencies to use quality improvement methods to identify eligible women and remove treatment barriers. The number of women eligible for prophylaxis, the percent prescribed a progestogen before 20 and 24 weeks of gestation, and barriers encountered were reported monthly. Clinics were asked to adopt protocols to identify candidates and initiate treatment promptly. System-level changes were made to expand Medicaid eligibility, maintain Medicaid coverage during pregnancy, improve communication, and adopt uniform data collection and efficient treatment protocols. Rates of singleton births before 32 and 37 weeks of gestation in Ohio hospitals were primary outcomes. We used statistical process control methods to analyze change and generalized linear mixed models to estimate program effects accounting for known risk factors. RESULTS: Participating sites tracked 2,562 women eligible for treatment between January 1, 2014, and November 30, 2015. Late entry to care, variable interpretation of treatment guidelines, maintenance of Medicaid coverage, and inefficient communication among health care providers and insurers were identified as treatment barriers. Births before 32 weeks of gestation decreased in all hospitals by 6.6% and in participating hospitals by 8.0%. Births before 32 weeks of gestation to women with prior preterm birth decreased by 20.5% in all hospitals, by 20.3% in African American women, and by 17.1% in women on Medicaid. Births before 37 weeks of gestation were minimally affected. Adjusting for risk factors and birth clustering by hospital confirmed a program-associated 13% (95% confidence interval 0.3-24%) reduction in births before 32 weeks of gestation to women with prior preterm birth. CONCLUSION: The Ohio progestogen project was associated with a sustained reduction in singleton births before 32 weeks of gestation in Ohio.

A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.

Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs), including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK) or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease.

Intrauterine fetal demise after prenatal diagnosis of congenital heart disease: assessment of risk.

OBJECTIVES: Elective deliveries in fetal congenital heart disease (CHD) attempt to balance fetal and neonatal risk with the goal of optimizing overall outcome. However, the magnitude of the risk for intrauterine fetal demise (IUFD) is unclear. This study aimed to (1) determine the rate of IUFD and (2) identify fetal risk factors associated with IUFD. METHODS: Retrospective review of pregnancies complicated by CHD between 1998 and 2010. Data were collected regarding pregnancy outcome, extracardiac anomalies (ECA), genetic and cardiac diagnoses, severity of valve regurgitation, gestational age at birth and birth weight. Fisher's exact test and odds ratios were used to compare outcomes between groups. RESULTS: A total of 501 pregnancies analyzed resulted in 445 live births, 22 IUFD, 16 terminations and 18 unknown outcomes. Amongst IUFD, 27% had a genetic diagnosis, 50% had an ECA and 27% had severe valve regurgitation. IUFD odds increased threefold with ECA and sevenfold with severe valve regurgitation. IUFD occurred in 1.2% without risk factors. CONCLUSIONS: IUFD in fetuses with CHD is associated with ECA, genetic syndromes and severe valve regurgitation. In absence of these fetal characteristics, the occurrence of IUFD is low, although it remains higher than in fetuses without CHD.

Design considerations for point-of-care clinical trials comparing methadone and buprenorphine treatment for opioid dependence in pregnancy and for neonatal abstinence syndrome.

RATIONALE: In recent years, the U.S. has experienced a significant increase in the prevalence of pregnant opioid-dependent women and of neonatal abstinence syndrome (NAS), which is caused by withdrawal from in-utero drug exposure. While methadone-maintenance currently is the standard of care for opioid dependence during pregnancy, research suggests that buprenorphine-maintenance may be associated with shorter infant hospital lengths of stay (LOS) relative to methadone-maintenance. There is no "gold standard" treatment for NAS but there is evidence that buprenorphine, relative to morphine or methadone, treatment may reduce LOS and length of treatment. DESIGN: Point-of-care clinical trial (POCCT) designs, maximizing external validity while reducing cost and complexity associated with classic randomized clinical trials, were selected for two planned trials to compare methadone to buprenorphine treatment for opioid dependence during pregnancy and for NAS. This paper describes design considerations for the Medication-assisted treatment for Opioid-dependent expecting Mothers (MOMs; estimated N = 370) and Investigation of Narcotics for Ameliorating Neonatal abstinence syndrome on Time in hospital (INFANTs; estimated N = 284) POCCTs, both of which are randomized, intent-to-treat, two-group trials. Outcomes would be obtained from participants' electronic health record at three participating hospitals. Additionally, a subset of infants in the INFANTs POCCT would be from mothers in the MOMs POCCT and, thus, potential interaction between medication treatment of mother and infant could be evaluated. CONCLUSION: This pair of planned POCCTs would evaluate the comparative effectiveness of treatments for opioid dependence during pregnancy and for NAS. The results could have a significant impact on practice.

Gene regulatory network of renal primordium development.

Animal development progresses through the stepwise deployment of gene regulatory networks (GRN) encoded in the genome. Comparative analyses in different species and organ systems have revealed that GRN blueprints are composed of subcircuits with stereotypical architectures that are often reused as modular units. In this review, we report the evidence for the GRN underlying renal primordium development. In vertebrates, renal development is initiated by the induction of a field of intermediate mesoderm cells competent to undergo lineage specification and nephric (Wolffian) duct formation. Definition of the renal field leads to the activation of a core regulatory subcircuit composed of the transcription factors Pax2/8, Gata3 and Lim1. These transcription factors turn on a second layer of transcriptional regulators while also activating effectors of tissue morphogenesis and cellular specialization. Elongation and connection of the nephric duct to the cloaca (bladder/urethra primordium) is followed by metanephric kidney induction through signals emanating from the metanephric mesenchyme. Central to this process is the activation and positioning of the glial cell line-derived neurotrophic factor (Gdnf)-Ret signaling pathway by network subcircuits located in the mesenchyme and epithelial tissues of the caudal trunk. Evidence shows that each step of the renal primordium developmental program is regulated by structured GRN subunits organized in a hierarchical manner. Understanding the structure and dynamics of the renal GRN will help us understand the intrinsic phenotypical variability of congenital anomalies of the kidney and urinary tract and guide our approaches to regenerative medicine.

Changes in the indications for scheduled births to reduce nonmedically indicated deliveries occurring before 39 weeks of gestation.

OBJECTIVE: To estimate the change in indications for scheduled deliveries during the Ohio Perinatal Quality Collaborative's initiative to decrease scheduled deliveries for nonmedical indications before 39 weeks of gestation. METHODS: Documented indications for scheduled deliveries between 36 0/7 and 38 6/7 weeks were categorized as: strong medically accepted reasons for delivery; intermediate acceptability; and unnecessary before 39 weeks. We describe each of these indication categories as a proportion of all deliveries in the participating hospitals between October 2008 and December 2009. RESULTS: The percentage of scheduled deliveries that were unnecessary before 39 weeks or had intermediate indications decreased over time (P=.03). There were 145 fewer with intermediate reasons and 265 fewer that were unnecessary when the first 4 months of the project were compared with the last 4 months. Strong medical indications as a percentage of all deliveries did not change significantly over time (P=.99). CONCLUSION: Our quality collaborative reduced scheduled deliveries of medically unnecessary and intermediate indications for delivery at 36 0/7 and 38 6/7 weeks. However, scheduled deliveries with strong medical indication did not change significantly over time. LEVEL OF EVIDENCE: III.

Live imaging of the developing mouse mesonephros.

Embryonic development is a highly dynamic process involving complex tissue interactions and movements. Recent progress in cell labeling, image acquisition, and image processing technologies has brought the study of embryo morphogenesis to another level. It is now possible to visualize in real time the dynamic morphogenetic changes occurring in vivo and to reconstitute and quantify them in 4D rendering. However, extended live embryo imaging remains challenging in terms of embryo survival and minimization of phototoxicity. Here, we describe a procedure to image the developing mesonephros for up to 16 h in intact mouse embryos. This method can easily be adapted to the imaging of other structures at similar developmental stages.

Antenatal steroids for treatment of fetal lung immaturity after 34 weeks of gestation: an evaluation of neonatal outcomes.

OBJECTIVE: To estimate whether antenatal corticosteroids given after fetal lung immaturity in pregnancies at 34 weeks of gestation or more would improve neonatal outcomes and, in particular, respiratory outcomes. METHODS: We compared outcomes of 362 neonates born at 34 weeks of gestation or more after fetal lung maturity testing: 102 with immature fetal lung indices were treated with antenatal corticosteroids followed by planned delivery within 1 week; 76 with immature fetal lung indices were managed expectantly; and 184 were delivered after mature amniocentesis. Primary outcomes were composites of neonatal and respiratory morbidity. RESULTS: Compared with corticosteroid-exposed neonates those born after mature amniocentesis had lower rates of adverse neonatal (26.5% compared with 14.1%, adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27-0.96) and adverse respiratory outcomes (9.8% compared with 3.3%, adjusted OR 0.33, 95% CI 0.11-0.98); newborns born after expectant management had significantly less respiratory morbidity (1.3% compared with 9.8%, adjusted OR 0.11, 95% CI 0.01-0.92) compared with corticosteroid-exposed newborns. CONCLUSION: Administration of antenatal corticosteroids after immature fetal lung indices did not reduce respiratory morbidity in neonates born at 34 weeks of gestation or more. Our study supports prolonging gestation until delivery is otherwise indicated. LEVEL OF EVIDENCE: II.

Using improvement science to increase accuracy and reliability of gestational age documentation.

Our aim was to improve the reliability of recording gestational age (GA) in the mother's obstetric record, as this record is used for clinical management, research databases, and eventual transmission to the Ohio Department of Health birth certificates. We performed a prospective cohort study, including all hospital births. We began quality improvement interventions in October 2009. Improvement test cycles were targeted to four working groups, including nursing staff, community obstetric providers, and the process itself. Test cycle results were evaluated to determine which successful interventions could spread further. Rates of process outcome measurements were compared by statistical process control and univariate analysis pre- and postintervention. During the preintervention period, the median daily GA reliability was 25%. To date, over 30 small sample size tests of change have been completed. Of 8795 births studied, significant improvement in GA accuracy/completeness was detected (median postintervention = 78%, p < 0.01). Increased communication of and completion of the prenatal record, in addition to GA recording in high-risk groups, such as premature infants, were also achieved (all p < 0.01). GA reliability can be increased using standardized improvement science methods. Better communication of GA will enable better clinical decisions and foster population-based perinatal research.

Long-term maternal depression after expectant management of early preterm birth.

OBJECTIVE: This study was undertaken to determine factors that affect depression after delivery of infants at the limits of viability. We hypothesized that expectantly managed mothers would have lower risk of depression several years after delivery. STUDY DESIGN: Charts were reviewed for deliveries in the calendar years 2003 through 2005 with a diagnosis of preterm labor, premature rupture of membranes or cervical insufficiency admitted at a gestation between 20 and 25(6/7) weeks. Surveys were sent that included the Edinburgh Postnatal Depression Scale and questions regarding care around the time of delivery. RESULTS: A total of 176 patients met inclusion criteria. Of those, 36 consented and returned surveys. Of patients who were expectantly managed, none (0%) screened positive for depression, while 11 (38%) patients who were not expectantly management screened positive (p=0.08). Between 36 and 72 returned surveys would be needed for this to be significant, using p<0.05. Survey results indicated that 75% of respondents agreed hospitalization was traumatic, 78% would still attempt to delay birth, 97% would accept tocolysis, 89% agreed their child functioned similar to other children, and 77% were happy with how physicians handled their care. CONCLUSION: Expectant management may be associated with lower risk of depression. Larger studies evaluating psychosocial effects of interventions are justified.