Sleep Apnea and Fetal Growth Restriction (SAFER)

This study aims to evaluate the association between obstructive sleep apnea (OSA) and fetal growth restriction (FGR) and to assess the role of auto-titrated positive airway pressure (aPAP) as antenatal therapy in these patients. Pregnant patients with diagnosed FGR will be screened for OSA first by screening questionnaire and then by home sleep monitor. Of those patients diagnosed with OSA, half will be assigned to use aPAP each night when sleeping and half will not (standard care).

Study Overview

• Status: Terminated
• Conditions: Obstructive Sleep Apnea; Pregnancy Related; Fetal Growth Restriction
• Intervention / Treatment: Device: S9 VPAP Adapt

Detailed Description

Fetal growth restriction (FGR) affects 5-10% of pregnancies and is one of the leading causes of perinatal morbidity and mortality.

Obstructive sleep apnea (OSA) is a common disorder in which a person's breathing pauses or becomes shallow during sleep. These periods of low oxygen lead stress and inflammation which that may be harmful to both the mother and her fetus. OSA in pregnancy has been associated with poor maternal-fetal outcomes, including low birth weight, preterm delivery, FGR, gestational hypertension/preeclampsia, gestational diabetes and higher rates of neonatal ICU admission.

Auto-titrated positive airway pressure (aPAP) is a machine that gently delivers pressurized air via a mask to keep a patient's airways free of obstruction during sleep. It is currently unclear whether treatment of OSA during pregnancy in women with known FGR can improve fetal and neonatal outcomes.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Jerusalem
    • W. Jerusalem, Jerusalem, Israel, 9112001
      • Hadassah Hebrew University
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • New York
    • Rochester, New York, United States, 14620
      • Rochester University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 50
• Fetal growth restriction (defined as fetal weight <10th percentile based on at least one routine 2nd trimester ultrasound without a subsequent increase to >15th percentile on any ultrasounds prior to enrollment)
• Lower limit of gestational age at enrollment 22+0 weeks.
• Upper limit of gestational age at enrollment: adequate time to complete Stages 1 and 2 and if appropriate to be randomized and receive intervention by no later than 32+0 weeks.
• The absence of 2 minor or 1 major markers of aneuploidy.

Exclusion Criteria:

• Other known cause of fetal growth restriction (including congenital anomalies, intrauterine infection, or multiple gestation)
• Reversed end-diastolic flow in the umbilical artery
• Preexisting diagnosis of OSA being treated with aPAP
• Chronic pulmonary disease (cystic fibrosis, moderate persistent asthma)
• Hemoglobinopathies (sickle cell anemia, thalassemia)
• Maternal craniofacial anomalies
• Premature rupture of membranes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: aPAP; Nightly use of aPAP when sleeping through the date of delivery	Device: S9 VPAP Adapt; Auto-titrated positive airway pressure
NO_INTERVENTION: No aPAP; No use of aPAP (standard of care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth Weight	Weight of child at time of birth	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational Age at Delivery	Gestational age at delivery	1 day

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: University of Rochester; ResMed Foundation; The Hebrew University Hadassah Medical School
• Investigators: Principal Investigator: Alexander Hincker, MD, Washington University in Saint Louis

Publications and helpful links

General Publications

• Nardozza LM, Caetano AC, Zamarian AC, Mazzola JB, Silva CP, Marcal VM, Lobo TF, Peixoto AB, Araujo Junior E. Fetal growth restriction: current knowledge. Arch Gynecol Obstet. 2017 May;295(5):1061-1077. doi: 10.1007/s00404-017-4341-9. Epub 2017 Mar 11.
• Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia--revisited--the bad ugly and good: implications to the heart and brain. Sleep Med Rev. 2015 Apr;20:27-45. doi: 10.1016/j.smrv.2014.07.003. Epub 2014 Jul 24.
• Hincker A, Nadler J, Karan S, Carter E, Porat S, Warner B, Ju YS, Ben Abdallah A, Wilson E, Lockhart EM, Ginosar Y. 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. BMJ Open. 2021 Jun 29;11(6):e049120. doi: 10.1136/bmjopen-2021-049120.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 18, 2019
• Primary Completion (ACTUAL): July 27, 2021
• Study Completion (ACTUAL): July 27, 2021

Study Registration Dates

• First Submitted: September 7, 2019
• First Submitted That Met QC Criteria: September 7, 2019
• First Posted (ACTUAL): September 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: OSA; aPAP; FGR
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Fetal Diseases; Pregnancy Complications; Growth Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Fetal Growth Retardation
• Other Study ID Numbers: 201908162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes