Sleep Apnea and Fetal Growth Restriction (SAFER) study: protocol for a pragmatic randomised clinical trial of positive airway pressure as an antenatal therapy for fetal growth restriction in maternal obstructive sleep apnoea.

INTRODUCTION: Fetal growth restriction (FGR) is a major contributor to fetal and neonatal morbidity and mortality with intrauterine, neonatal and lifelong complications. This study explores maternal obstructive sleep apnoea (OSA) as a potentially modifiable risk factor for FGR. We hypothesise that, in pregnancies complicated by FGR, treating mothers who have OSA using positive airway pressure (PAP) will improve birth weight and neonatal outcomes. METHODS AND ANALYSIS: The Sleep Apnea and Fetal Growth Restriction study is a prospective, block-randomised, single-blinded, multicentre, pragmatic controlled trial. We enrol pregnant women aged 18-50, between 22 and 31 weeks of gestation, with established FGR based on second trimester ultrasound, who do not have other prespecified known causes of FGR (such as congenital anomalies or intrauterine infection). In stage 1, participants are screened by questionnaire for OSA risk. If OSA risk is identified, participants proceed to stage 2, where they undergo home sleep apnoea testing. Participants are determined to have OSA if they have an apnoea-hypopnoea index (AHI) ≥5 (if the oxygen desaturation index (ODI) is also ≥5) or if they have an AHI ≥10 (even if the ODI is <5). These participants proceed to stage 3, where they are randomised to nightly treatment with PAP or no PAP (standard care control), which is maintained until delivery. The primary outcome is unadjusted birth weight; secondary outcomes include fetal growth velocity on ultrasound, enrolment-to-delivery interval, gestational age at delivery, birth weight corrected for gestational age, stillbirth, Apgar score, rate of admission to higher levels of care (neonatal intensive care unit or special care nursery) and length of neonatal stay. These outcomes are compared between PAP and control using intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Boards at Washington University in St Louis, Missouri; Hadassah Hebrew University Medical Center, Jerusalem; and the University of Rochester, New York. Recruitment began in Washington University in November 2019 but stopped from March to November 2020 due to COVID-19. Recruitment began in Hadassah Hebrew University in March 2021, and in the University of Rochester in May 2021. Dissemination plans include presentations at scientific conferences and scientific publications. TRIAL REGISTRATION NUMBER: NCT04084990.

Obstructive Sleep Apnea in Pregnancy: Assessment of Current Screening Tools.

OBJECTIVE: To estimate the predictive ability of current obstructive sleep apnea (OSA) screening tools and the individual questions in these tools at identifying pregnant women who have OSA. METHODS: A total of 293 third-trimester patients were enrolled between 2010 and 2012, and 248 patients had sleep monitor results. Recruited participants completed a questionnaire consisting of six OSA screening tools and overnight portable sleep monitoring. Predictive ability of the screening tools for OSA compared with results of the diagnosis from overnight sleep monitoring was estimated using the area under receiver operating characteristic curves. RESULTS: Two hundred eighteen (88%) of the patients were OSA-negative, and 30 patients (12%) were OSA-positive based on sleep monitoring results. Compared with OSA-negative patients, OSA-positive patients had greater body mass indices and neck circumferences as well as significantly higher rates of hypertension (chronic and gestational), pregestational diabetes mellitus, asthma, and preeclampsia. The overall predictive ability of the screening tools for OSA was modest (area under receiver operating characteristic curves 0.62-0.695). However, individual components of the questionnaire were strongly associated with OSA. CONCLUSION: We found that none of the studied OSA screening tools accurately detected OSA in pregnant women in the third trimester. We have identified proposed elements of a new screening tool based on promising components from several tools that may more accurately detect patients with OSA. LEVEL OF EVIDENCE: II.

Obstructive sleep apnea screening and postoperative mortality in a large surgical cohort.

OBJECTIVE: A recent investigation at Barnes-Jewish Hospital located in St. Louis, Missouri, found that an estimated 22% of adults presenting for inpatient surgery screened as high risk for obstructive sleep apnea (OSA). Surgical patients with OSA have multiple comorbidities and are at increased risk for perioperative complications. Our objective was to determine if a prior diagnosis of OSA or a positive screen for OSA was associated with increased risk for 30-day and one-year mortality. METHODS: B-J APNEAS (Barnes-Jewish Apnea Prevalence in Every Admission Study) was a prospective cohort study. Unselected adult surgical patients at Barnes Jewish Hospital were prospectively enrolled between February 2006 and April 2010. All patients completed preoperative OSA screening and those who were at risk for OSA according to a combination of the Berlin and Flemons screening tools received targeted postoperative interventions. STOP (loud Snoring, daytime Tiredness, Observed apneas, and high blood Pressure) and STOP-BANG (STOP, plus body mass index [BMI], age, neck circumference, and gender) scores also were obtained. RESULTS: Overall, the sample included 14,962 patients, of whom 1939 (12.9%) reported a history of OSA. All four screening tools identified a high prevalence of undiagnosed patients at risk for OSA (9.5%-41.6%), but agreement among screens was not strong with κ statistic ranging from 0.225 to 0.611. There was no significant difference in 30-day postoperative mortality between patients with possible OSA (based on their history or on a positive OSA screen with any of the four instruments) and the rest of the surgical population. Significant differences in one-year mortality were noted between the low-risk and high-risk groups as identified by the Flemons' (4.96% vs 6.91%; p<0.0001), STOP (5.28% vs 7.57%; p<0.0001) and STOP-BANG (4.13% vs 7.45%; p<0.0001) screens. After adjusting for risk factors, none of the OSA screening tools independently predicted mortality rate up to one year postoperatively. CONCLUSION: Neither a prior diagnosis of OSA nor a positive screen for OSA risk was associated with increased 30-day or one-year postoperative mortality. Differences in 1 year postoperative mortality were noted with three of the screening tools. The results of our study highlight uncertainties and research priorities for the medical community.

Use of recombinant factor VIIa in patients with amniotic fluid embolism: a systematic review of case reports.

BACKGROUND: Patients with amniotic fluid embolism (AFE) (major cardiac and pulmonary symptoms plus consumptive coagulopathy) have high circulating tissue factor concentrations. Recombinant factor VIIa (rVIIa) has been used to treat hemorrhage in AFE patients even though rVIIa can combine with circulating tissue factor and form intravascular clots. A systematic review was done of case reports from 2003 to 2009 of AFE patients with massive hemorrhage who were and were not treated with rVIIa to assess the thrombotic complication risk. METHODS: MEDLINE was searched for case reports of AFE patients receiving rVIIa (rVIIa cases) and of AFE patients who received surgery to control bleeding but no rVIIa (cohorts who did not receive rVIIa). Additional AFE case reports were obtained from the Food and Drug Administration, the Australian and New Zealand Haemostasis Registry, and scientific meeting abstracts. The risk of a negative outcome (permanent disability or death) in rVIIa cases versus cohorts who did not receive rVIIa was calculated using risk ratio and 95% confidence interval. RESULTS: Sixteen rVIIa cases and 28 cohorts were identified who did not receive rVIIa. All patients had surgery to control bleeding. Death, permanent disability, and full recovery occurred in 8, 6, and 2 rVIIa cases and 7, 4, and 17 cohorts who did not receive rVIIa (risk ratio 2.2, 95% CI 1.4-3.7 for death or permanent disability vs. full recovery). CONCLUSION: Recombinant factor VIIa cases had significantly worse outcomes than cohorts who did not receive rVIIa. It is recommended that rVIIa be used in AFE patients only when the hemorrhage cannot be stopped by massive blood component replacement.

The management of accidental dural puncture and postdural puncture headache: a North American survey.

STUDY OBJECTIVE: To evaluate the management of accidental dural puncture (ADP) and postdural puncture headache (PDPH) among obstetric anesthesiologists practicing in North America. DESIGN: Questionnaire survey of individual members of the Society for Obstetric Anesthesia and Perinatology (SOAP). SETTING: University hospital. MEASUREMENTS: In June 2008, a 4-part, 83-item electronic survey was distributed to all North American members of SOAP. It contained questions about respondent demographics, epidural catheter and intrathecal catheter management after ADP, PDPH management, epidural blood patch (EBP) management, and patient follow-up. MAIN RESULTS: Of the 843 United States and Canadian members of SOAP who were surveyed, 160 responses were collected. Respondents reported placing an epidural 75% of the time and an intrathecal catheter 25% of the time following ADP. Common prophylactic and conservative treatment strategies included hydration, caffeine, and opioids by mouth; 76% of respondents leave an intrathecal catheter in place for 24 hours to reduce the frequency of headache. Epidural blood patches are placed by 81% of practitioners less than 24 hours after headache onset. CONCLUSIONS: Protocols for ADP management are rare. There is wide variation in catheter management after dural puncture, measures used to prevent and treat a resultant headache, and EBP management.

Intracranial venous thrombosis in the parturient.

Intracranial venous thrombosis is a rare but potentially fatal complication of pregnancy and the postpartum period. The presenting symptoms can mimic those of a postdural puncture headache and are easily misdiagnosed, especially in a parturient who has undergone regional anesthesia. The incidence of 10-20 per 100,000 is likely higher than reported. The etiology, clinical presentation and course, risk factors, management, and relation of intracranial venous thrombosis to pregnancy are presented. Published case reports and series of intracranial venous thrombosis that have either occurred during the puerperium or involved women of childbearing age after dural puncture are summarized. Finally, the diagnosis and management of intracranial venous thrombosis in parturients, focusing on parturients who have undergone regional anesthesia, is discussed. When intracranial venous thrombosis occurs in a parturient after regional anesthesia, it is often treated as a post-dural puncture headache.

Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture.

Progesterone modulates gamma-aminobutyric acid and excitatory amino acid neurotransmitter systems and has neuroprotective properties in models of hypoxia-ischemia. This study examined the in vitro effects of allopregnanolone, the active progesterone metabolite, in models of N-methyl-D-aspartate (NMDA)-induced necrosis and apoptosis. Cultured NT2 neurons were exposed to 1 mM NMDA. Lactate dehydrogenase (LDH) release was measured 24 h later. NMDA at a concentration of 1 mM produced a 39 +/- 19% release of total LDH. Exposure to 10 microM allopregnanolone prior to NMDA exposure reduced LDH release by 51% (P = 0.0028). NMDA stimulated apoptotic cell changes defined by terminal dUTP nick-end labeling (TUNEL) and 5,5', 6,6'-tetrachloro-1,1,3,3'-tetra ethlybenzimidazolycarbocyanide iodide staining were reduced to baseline values by both 10 microM allopregnanolone and 100 microM MK-801. Pretreatment with allopregnanolone (0-10 microM) reduced the percentage of TUNEL-positive cells in a dose-dependent manner (EC(50) = 2.7 +/- 0.1 nM). Physiologic concentrations of allopregnanolone provided protection against both necrotic and apoptotic injury induced by NMDA excitotoxicity.