Continuous Positive Airway Pressure (CPAP) for Sleep Apnea in Pregnancy

Emerging data support a link between sleep disordered breathing (SDB) and adverse pregnancy
outcomes. In particular, women with obstructive sleep apnea (OSA) appear to be at increased
risk of both hypertensive disorders of pregnancy and gestational diabetes. In the
non-pregnant population, OSA is typically treated with continuous positive airway pressure
(CPAP) during sleep and has been shown to reduce blood pressure in hypertensive patients.
Unfortunately, data on whether maternal and neonatal outcomes could be improved with
treatment of OSA during pregnancy are extremely limited. This study aims to address this
knowledge gap.

A randomized controlled trial of 2,700 women to assess whether treatment of obstructive sleep
apnea with continuous positive airway pressure (CPAP) in pregnancy will result in a reduction
in the rate of hypertensive disorders of pregnancy.

Inclusion Criteria:

1. Nulliparous (no prior delivery at or after 20 weeks 0 days of gestation).

2. Singleton gestation. Twin gestation reduced to singleton, either spontaneously or
therapeutically, is not eligible unless the reduction occurred before 14 weeks project
gestational age (see Section 3.4.2).

3. Gestational age at randomization between 16 weeks 0 days and 21 weeks 6 days based on
clinical information and evaluation of the earliest ultrasound as described in
Gestational Age Determination in Section 3.4.2

4. Diagnosis with mild to moderate OSA as defined by an AHI score ≥ 5 and <30.

Exclusion Criteria:

1. Previously prescribed, current or planned therapy for sleep apnea.

2. Age < 18 years, because the rate of sleep apnea in this population is extremely low.

3. Inability to sleep in a stable place with access to the CPAP machine at least 5 nights
per week.

4. Asthma requiring systemic steroid therapy for more than 14 days within the past 6
months because this population is expected to be unresponsive to CPAP therapy.

5. Current use of prescribed sleeping pills for insomnia.

6. Chronic medical conditions requiring oxygen supplementation (e.g. pulmonary fibrosis,
pulmonary hypertension, cystic fibrosis) because this population is expected to be
unresponsive to CPAP therapy.

7. Current use of antihypertensive medication because of the difficulty in diagnosing
superimposed preeclampsia.

8. Chronic renal disease with serum creatinine >1.3 mg/dL because the primary outcome
would be pre-determined.

9. Antiphospholipid antibody syndrome, because it would compromise the primary outcome
diagnosis.

10. History of medical complications such as:

1. Active liver disease (acute hepatitis, chronic active hepatitis, persistently
abnormal liver enzymes)

2. Thrombocytopenia with platelet count <100,000 because of the difficulty in
assessing the primary outcome.

11. Active vaginal bleeding (more than spotting) at the time of randomization.

12. Known chromosomal, genetic, major malformations or fetal demise, or planned
termination of pregnancy because inclusion would compromise evaluation of secondary
neonatal outcomes.

13. Known major uterine malformations associated with adverse pregnancy outcomes.

14. Current use of opiates (heroin, methadone, or other daily opioid use) due to
inaccuracy of the home sleep test and inefficiency of CPAP.

15. Active drug use, alcohol use, or unstable psychiatric condition.

16. Participation in another interventional study that influences preeclampsia,
hypertensive disorders of pregnancy, or GDM.

17. Prenatal care or delivery planned at a non-network center.