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

Abstract

IntroductionFetal 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 analysisThe 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 disseminationThis 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 numberNCT04084990.

Effect of Obstructive Sleep Apnea during Pregnancy on Fetal Development: Gene Expression Profile of Cord Blood

“…These may play a key role in determining lifelong health trajectories that can lead to developmental changes that may increase disease risk, like in cardiovascular and metabolic syndromes [21,22]. The specific underlying mechanisms remain elusive, but genetic and epigenetic changes may play a key role in these processes [8,23]. The hostile intrauterine environment secondary to maternal breathing pauses and nocturnal hypoxia could potentially impact the expression of certain genes, which may affect the metabolism and physiology in the most vulnerable period of life, such as the fetal period, leading to alterations in its growth patterns and to medium and long-term clinical outcomes.…”

Sleep‐disordered breathing and pregnancy outcomes: The impact of maternal oxygen saturation

“…The impact of OSAHS on both the mother and her baby prompted us to assess targeted screening and interventions in the high‐risk population. Based on several preliminary studies, sleep disturbances may impact fetal growth and well‐being 12–14 . As the results on this topic are inconsistent, this area warrants further research.…”

“…Based on several preliminary studies, sleep disturbances may impact fetal growth and well-being. [12][13][14] As the results on this topic are inconsistent, this area warrants further research. Therefore, we consider it essential, both diagnostically and preventively, to characterize the impact of decreased maternal oxygenation, mainly due to the obesity condition placing pregnant patients at higher risk of OSAHS development on pregnancy outcomes.…”