Clinical trial NCT02086448: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP)
Official title: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obese
Pregnancy
Sleep Disordered Breathing
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2014-03-13
Enrollment: 242
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to better understand how sleep apnea, a common sleep disorder in which a person has one or more pauses in breathing or shallow breaths while sleeping, may affect pregnancy and to determine the effect of Continuous Positive Airway Pressure (CPAP), a treatment that uses mild air pressure to keep the airways open during sleep, for pregnant women with sleep apnea.

Detailed description: Emerging data support a link between sleep disordered breathing (SDB) and adverse pregnancy outcomes, particularly preeclampsia. Furthermore, SDB, which is characterized by intermittent nocturnal hypoxia-reoxygenation as well as sleep disruption, results in endothelial dysfunction and metabolic dysregulation, the same biological pathways that have been associated with adverse pregnancy outcomes. Obesity is a well-known risk factor for both adverse pregnancy outcomes and SDB, and has been associated with the same aforementioned biological aberrations. Therefore, obesity complicates the definition of a causal relationship between SDB and pregnancy outcomes. While some classic cardiovascular risk factors (prehypertension) are certainly relevant in pregnancy, there are also well-established risk factors that are unique to pregnancy (uterine vascular stiffness, placental angiogenic factors). The interplay between SDB, obesity and these unique cardiovascular risk factors remains undefined, and this proposal aims to address this knowledge gap. Without this data, our ability to understand how we can mitigate these risks through the use of therapeutic interventions for SDB, such as CPAP (continuous positive airway pressure), is compromised. To further address this knowledge gap, we will make use of the placenta's ability to accumulate evidence of damage over time and provide a record of maternal vascular health throughout gestation. Numerous placental lesions deriving from maternal vascular disease have been identified and can be readily detected on placental pathology. These lesions can provide a measure of the severity of hypoxic stress experienced by the fetus during gestation.

The investigators' central hypothesis is that SDB is an effect modifier that increases maternal cardiovascular risk and placental hypoxic injury in obese pregnant women, and that CPAP treatment during pregnancy will result in an improved cardiovascular risk and placental profile. To test this hypothesis the investigaotrs will identify a cohort of obese women both with and without SDB. The investigators will examine SDB's impact on maternal vascular stiffness (uterine artery Doppler), angiogenesis (pregnancy specific angiogenic factors e.g., sFLT-1) and metabolism (insulin resistance) across pregnancy (Aim 1). The investigators will perform a randomized controlled trial of autotitrating- CPAP verses sham-CPAP in pregnancy to examine the impact of CPAP treatment during pregnancy on cardiovascular risk (Aim 2) and will explore the interplay between SDB, CPAP and evidence of maternal vascular disease and chronic fetal hypoxia by evaluating the placental profile of obese women with and without SDB (Aim 3).

Eligibility criteria: Inclusion Criteria:

* women between 14 0/7 and 20 6/7 weeks gestation at the time of their initial PSG assessment.
* Pregnancy and current BMI \>=30
* Self-reported frequent snoring (\>=3x/week over past month) or self-reported non-snorer.

Exclusion Criteria:

* diagnosis of pregestational diabetes.
* self-report a history of sleep apena and who are using or were receommended by a physican to use a PAP device already
* twins

Primary outcomes:
measure: Uterine Artery Doppler Mean Pulsatility Index -by Ultrasound
timeFrame: early pregnancy (14-16 weeks gestation)
measure: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1)/ Placental Growth Factor (PlGF) Ratio-blood Measurement
timeFrame: early pregnancy (14-16 weeks gestation)
measure: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)-Blood Measurement of Glucose and Insulin
timeFrame: early pregnancy (14-16 weeks gestation)
measure: Uterine Artery Doppler Mean Pulsatility Index -by Ultrasound
timeFrame: late pregnancy (28-32 weeks gestation)
measure: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1)/ Placental Growth Factor (PlGF) Ratio-blood Measurement
timeFrame: late pregnancy (28-32 weeks gestation)
measure: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)-Blood Measurement of Glucose and Insulin
timeFrame: late pregnancy (28-32 weeks gestation)
Secondary outcomes:
measure: Placental Histology and Immunohistochemistry
timeFrame: After delivery (expected 37-40 weeks gestation)
Other outcomes:
measure: Mean Arterial Blood Pressure (mmHg) Angiogenic Domain
timeFrame: early pregnancy (14-16 weeks gestation)
measure: Pregnancy Outcome Data
timeFrame: At time of delivery (expected 37-40 weeks gestation)
measure: Mean Arterial Blood Pressure (mmHg) Angiogenic Domain
timeFrame: late pregnancy (28-32 weeks gestation)
measure: Soluble Endoglin (sEng ,pg/mL)-Blood Measurement
timeFrame: early pregnancy (14-16 weeks gestation)
measure: Soluble Endoglin (sEng , pg/mL)-Blood Measurement
timeFrame: late pregnancy (28-32 weeks gestation)
Locations:
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of the UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Francesca Facco, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Onslow ML, Wolsk J, Wisniewski S, Patel S, Gallaher M, Hubel C, Cashmere DJ, Facco FL. The association between sleep-disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity. J Clin Sleep Med. 2023 Jan 1;19(1):97-109. doi: 10.5664/jcsm.10254.