Obstetrical Complications, Obstructive Sleep Apnea of Adult, Preeclampsia
Conditions
Keywords
CPAP, Apnea, pregnancy
Brief summary
A randomized controlled trial of 1,500 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.
Detailed description
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 1,500 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.
Interventions
DEVICEContinuous Positive Airway Pressure
Autotitrating CPAP with weekly contact, incentives for compliance and initial sleep advice counseling
OTHERSleep Advice Control
Initial sleep advice counseling alone
Sponsors
The George Washington University Biostatistics Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
This study is an unmasked randomized controlled multi-center clinical trial.
Intervention model description
Women who are between 14 weeks 0 days and 21 weeks 5 days with a singleton gestation and obstructive sleep apnea (OSA) will be randomized to one of two arms at participating MFMU Network clinical center: * Autotitrating CPAP with weekly contact, incentives for compliance and initial sleep advice counseling * Initial sleep advice counseling alone
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Singleton gestation. Twin gestation reduced to singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 14 weeks project gestational age. 2. Gestational age at randomization between 14 weeks 0 days and 21 weeks 6 days based on clinical information and evaluation of the earliest ultrasound. 3. 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. Chronic renal disease with serum creatinine \>1.3 mg/dL because the primary outcome would be pre-determined. 8. Antiphospholipid antibody syndrome, because it would compromise the primary outcome diagnosis. 9. 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. 10. Active vaginal bleeding (more than spotting) at the time of randomization. 11. Known chromosomal, genetic, major malformations or fetal demise, or planned termination of pregnancy because inclusion would compromise evaluation of secondary neonatal outcomes. 12. Known major uterine malformations associated with adverse pregnancy outcomes. 13. Current use of opiates (heroin, methadone, or other daily opioid use) due to inaccuracy of the home sleep test and inefficiency of CPAP. 14. Active drug use, alcohol use, or unstable psychiatric condition. 15. Participation in another interventional study that influences preeclampsia, hypertensive disorders of pregnancy, or GDM. 16. Prenatal care or delivery planned at a non-network center where access to the complete electronic medical record will not be available to research staff. 17. Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnosis of Hypertensive Disorders of Pregnancy | Up to 14 days postpartum | Subjects are considered to have the primary outcome if they meet the criteria for eclampsia, HELLP, atypical HELLP, preeclampsia, superimposed preeclampsia or antepartum gestational hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gestational diabetes | As soon as possible after randomization between 14 weeks, 0 days and 21 weeks, 6 days gestation | Gestational diabetes by oral GTT criteria performed after randomization |
| Preterm birth | Preterm delivery up to and less than 37 weeks gestation | Preterm birth less than 34 weeks and less than 37 weeks |
| Cesarean Delivery | At the time of delivery | Delivery by cesarean section |
| Maternal morbidity composite | Within 6 weeks postpartum | Maternal morbidity composite defined as the occurrence of one of the following: * Maternal death * Transfusion of ≥ 4 units of PRBC within 6 weeks postpartum * ICU admission within 6 weeks postpartum |
| Maternal adverse cardiovascular outcome composite | By 6 weeks postpartum | Maternal adverse cardiovascular outcome composite defined as the occurrence of one or more of the following: * Venous thromboembolism * New onset heart failure with ejection fraction (EF) \< 40% * Cerebrovascular accident * Myocardial infarction * New onset atrial fibrillation |
| Fetal or Neonatal Death | through 72 hours postpartum | Antepartum, intrapartum, or neonatal death |
| Neonatal respiratory support | within 72 hours of delivery | Intubation, continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) for ventilation or cardiopulmonary resuscitation |
| Birth weight | Immediately post birth | 1. Small for gestational age defined as \< 5th percentile weight for gestational age, assessed specifically by sex and race of the infant based on United States birth certificate data 2. Large for gestational age defined as greater than the 90th percentile for gestational age. 3. Macrosomia defined as birthweight \> 4000 grams |
| Neonatal encephalopathy | within 72 hours of delivery | Neonatal encephalopathy as defined by the NICHD Neonatal Research Network criteria |
| Neonatal Seizures | 72 hours post birth | Neonatal seizure activity confirmed by central review |
| Shoulder dystocia | During delivery | Shoulder dystocia during delivery |
| Birth trauma | During delivery | Bone fractures, brachial plexus palsy, other neurologic injury, retinal hemorrhage, or facial nerve palsy |
| Intracranial hemorrhage | Within 72 hours post delivery | Intraventricular hemorrhage grades III and IV, subgaleal hematoma, subdural hematoma, or subarachnoid hematoma |
| Hyperbilirubinemia | Within 72 hours post delivery | Hyperbilirubinemia requiring phototherapy or exchange transfusion |
| Hypoglycemia | Within 72 hours post delivery | glucose \< 35 mg/dl requiring IV therapy |
| NICU Stay | Greater than or equal to 72 hours post birth | Neonatal Intensive Care Unit stay |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRebecca Clifton, PhD
The George Washington University Biostatistics Center
STUDY_DIRECTORMonica Longo, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
STUDY_CHAIRFrancesca Facco, MD
Magee Women's Hospital of UPMC
Outcome results
None listed