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Purpose: To evaluate whether or not continuous positive airway pressure (CPAP) treatment in pregnancies complicated by obstructive sleep apnea (OSA) is associated with a decrease in hypertensive disorders of pregnancy., Methods: This was a retrospective cohort study of perinatal outcomes in women who underwent objective OSA testing and treatment as part of routine clinical care during pregnancy. Where diagnostic criteria for OSA were reached (respiratory event index (REI) ≥ 5 events per hour), patients were offered CPAP therapy. Obstetrical outcomes were compared between the control group (no OSA), the group with untreated OSA (OSA diagnosed, not CPAP compliant), and the group with treated OSA (OSA diagnosed and CPAP compliant), with CPAP compliance defined as CPAP use ≥ 4 h, 70% of the time or greater. A composite hypertension outcome combined diagnoses of gestational hypertension (gHTN) and preeclampsia (PreE) of any severity., Results: The study comprised outcomes from 177 completed pregnancies. Our cohort was characterized by obesity, with average body mass indices > 35 kg/m 2 , and average maternal age > 30 years old. CPAP was initiated at an average gestational age of 23 weeks (12.1-35.3 weeks), and average CPAP use was 5.9 h (4-8.5 h). The composite hypertension outcome occurred in 43% of those without OSA (N = 77), 64% of those with untreated OSA (N = 77), and 57% of those with treated OSA, compliant with CPAP (N = 23) (p = 0.034)., Conclusion: Real-world data in this small study suggest that CPAP therapy may modulate the increased risk of hypertensive complications in pregnancies complicated by OSA., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The purpose of this project was to determine the positive predictive value of existing obstructive sleep apnea (OSA) screening tools in clinical use, in a real-world clinical population of gravidae, and to explore the development of a new questionnaire for screening for OSA during pregnancy., Methods: Pregnant people were administered sleep screening questionnaires as part of routine clinical care. These included Facco's four variable OSA screening tool, the STOP-BANG, and the Epworth Sleepiness Scale. Those who screened positive were referred for diagnostic sleep testing, typically with a type III home monitoring device. Here we analyzed the screening responses used by those who completed diagnostic testing to determine the positive predictive value of the existing tools., Results: 159 pregnant people completed diagnostic OSA testing and were included in this analysis. The positive predictive value of Facco's four variable sleep screening tool was 74.3%, STOP-BANG was 75.3%, and the Epworth Sleepiness Scale was 69.8%. Our sample size was insufficient to create a new screening tool., Conclusions: Here we calculated the positive predictive value of Facco's 4 variable screening tool for screening for OSA in pregnancy in a real-world pregnant population. While we were not able to generate a new screening tool for screening for OSA during pregnancy, both STOP-BANG and Facco's four variable tool had positive predictive values over 70% in our population which was characterized by high BMI and advanced maternal age. Increased clinical use of the pregnancy-specific tool may be warranted., Competing Interests: None., (© 2023 The Authors.)

Background: Shift work has been associated with adverse pregnancy outcomes. The objective of this study was to evaluate the association between sleep disturbances and adverse pregnancy outcomes., Methods and Findings: This was a secondary analysis of a prospective study of participants enrolled in a prospective observational study wherein gravidae were screened for sleep apnea (2010-2012). A screening questionnaire with standard sleep apnea questionnaires as well as novel items about shift work and nocturnal sleep duration was administered at a prenatal care visit. Short sleep duration was defined as less than 7 hours. Prolonged sleep duration was defined as greater than 9 hours. In a cohort of 1125 pregnant people, 9.4% reported shift work at the time of screening. Gravidae who reported shift work were more likely than gravidae who reported no shift work to develop preeclampsia (28.3% versus 13.0%, P<0.001), preeclamspsia with severe features (16.0% versus 8.5%, P = 0.010), gestational diabetes (28.3% versus 19.9%, P = 0.041), and a composite of adverse obstetric outcomes (61.3% versus 47.8%, P = 0.008). After adjusting for potentially confounding variables, shift work was associated with an increased risk for preeclampsia with (adjusted relative risk (aRR) 1.70, 95% CI 1.03-2.79, p = 0.036) and without (aRR 2.03, 95% CI 1.43-2.90, p<0.001) severe features, and gestational diabetes mellitus class A1 (aRR 1.47, 95% CI 1.05-2.05, p = 0.023) and class A2 (aRR 1.67, 95% CI 1.13-2.44, p = 0.009). Sleep duration was associated with gestational diabetes (31.3% among those with short sleep duration, 25.2% among those with normal sleep duration and 14.0% among those with prolonged sleep duration, P<0.001) and gestational diabetes class A2 (29.5%, 17.9%, and 10.1%, respectively, P<0.001). Gravidae with prolonged sleep duration experienced less composite adverse pregnancy outcomes at 42.6% compared to 57.4% for those with short sleep duration or 52.5% for those with normal sleep duration, P = 0.002., Conclusions: Shift work and sleep duration are both associated with adverse pregnancy outcomes. Further research on the impact of sleep disturbance on pregnancy outcomes is warranted., Competing Interests: The authors have declared that no competing interests exist.

Problem Considered: Obstructive sleep apnea (OSA) is underdiagnosed during pregnancy, but there is strong theoretical and some empiric evidence that treatment may improve obstetric outcomes. Barriers to screening, testing, and treatment are common during pregnancy. The goal of this described intervention was to reduce these barriers and improve detection of OSA in pregnancy., Methods: Representatives from sleep medicine and perinatology established a cross-disciplinary, collaborative Sleep Pregnancy Clinic offering a streamlined referral process for multimodal screening, testing, and treatment of OSA during pregnancy. This is a retrospective analysis of data from the clinic's first 19 months., Results: Between June 2017 and December 2018, 134 pregnant women were referred for OSA testing. Sixty-three (47.0%) completed objective sleep testing, and 38 (60.3%) of the women who completed testing met diagnostic criteria for OSA. This intervention resulted in a statistically significant increase in the number of diagnostic sleep apnea tests performed (average 22.4 tests per year pre-intervention, 77 per year post-intervention [ P  = 0.0012])., Discussion and Conclusions: Despite a streamlined referral pipeline, completion rates of OSA testing in pregnant women remained below 50%. However, the overall number of women referred and who completed testing increased significantly during this time period. Of those who completed testing, the majority were diagnosed with OSA. Since starting this clinic, we have created resources to familiarize patients with the equipment and worked to reduce other barriers. Assessment of these interventions and the impact of treatment on obstetric outcomes is ongoing, as is assessment of reasons women do not complete diagnostic testing., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Cholinergic neurons elaborate a hemicholinium-3 (HC-3) sensitive choline transporter (CHT) that mediates presynaptic, high-affinity choline uptake (HACU) in support of acetylcholine (ACh) synthesis and release. Homozygous deletion of CHT (-/-) is lethal shortly after birth (Ferguson et al. 2004), consistent with CHT as an essential component of cholinergic signaling, but precluding functional analyses of CHT contributions in adult animals. In contrast, CHT+/- mice are viable, fertile and display normal levels of synaptosomal HACU, yet demonstrate reduced CHT protein and increased sensitivity to HC-3, suggestive of underlying cholinergic hypofunction. We find that CHT+/- mice are equivalent to CHT+/+ siblings on measures of motor co-ordination (rotarod), general activity (open field), anxiety (elevated plus maze, light/dark paradigms) and spatial learning and memory (Morris water maze). However, CHT+/- mice display impaired performance as a result of physical challenge in the treadmill paradigm, as well as reduced sensitivity to challenge with the muscarinic receptor antagonist scopolamine in the open field paradigm. These behavioral alterations are accompanied by significantly reduced brain ACh levels, elevated choline levels and brain region-specific decreased expression of M1 and M2 muscarinic acetylcholine receptors. Our studies suggest that CHT hemizygosity results in adequate baseline ACh stores, sufficient to sustain many phenotypes, but normal sensitivities to physical and/or pharmacological challenge require full cholinergic signaling capacity.

In cholinergic neurons, the presynaptic choline transporter (CHT) mediates high-affinity choline uptake (HACU) as the rate-limiting step in acetylcholine (ACh) synthesis. It has previously been shown that HACU is increased by behaviorally and pharmacologically-induced activity of cholinergic neurons in vivo, but the molecular mechanisms of this change in CHT function and regulation have only recently begun to be elucidated. The recent cloning of CHT has led to the generation of new valuable tools, including specific anti-CHT antibodies and a CHT knockout mouse. These new reagents have allowed researchers to investigate the possibility of a presynaptic, CHT-mediated, molecular plasticity mechanism, regulated by and necessary for sustained in vivo cholinergic activity. Studies in various mouse models of cholinergic dysfunction, including acetylcholinesterase (AChE) transgenic and knockout mice, choline acetyltransferase (ChAT) heterozygote mice, muscarinic (mAChR) and nicotinic (mAChR) receptor knockout mice, as well as CHT knockout and heterozygote mice, have revealed new information about the role of CHT expression and regulation in response to long-term alterations in cholinergic neurotransmission. These mouse models highlight the capacity of CHT to provide for functional compensation in states of cholinergic dysfunction. A better understanding of modes of CHT regulation should allow for experimental manipulation of cholinergic signaling in vivo with potential utility in human disorders of known cholinergic dysfunction such as Alzheimer's disease, Parkinson's disease, schizophrenia, Huntington's disease, and dysautonomia.