Fetal Outcome of Sleep Disordered Breathing During Pregnancy
Fetal Outcome of Sleep Disordered Breathing During Pregnancy
Sleep disordered breathing (SDB) is a frequent disorder characterized by some combination of
 repeated events of partial or complete upper airway obstruction during sleep, disruption of
 normal ventilation, hypoxemia, and sleep fragmentation. When untreated, SDB is associated
 with serious cardiovascular and neurobehavioral morbidities. Many physiologic changes that
 occur during pregnancy may compromise the respiratory system and place women at risk for
 developing SDB. Indeed, snoring has been reported in up to 46% of pregnant women. Preliminary
 evidence suggests that SDB is associated with the hypertensive conditions of pregnancy and
 that oxidative stress and endothelial dysfunction are mechanisms important in the development
 of both conditions. Moreover, early reports in animals and in humans suggest that maternal
 SDB may affect the developing fetus and that the intermittent hypoxia and increased
 sympathetic activity induced by SDB could potentially contribute to adverse maternal-fetal
 outcome. However, previous reports have focused on crude and non specific measures of fetal
 outcome such as birth weight and APGAR (Appearance, Pulse, Grimace, Activity, Respiration)
 score and currently there is no data on the mechanisms underlying the adverse effect of
 maternal SDB on the fetus and the newborn infant.

 Hypothesis: SDB during pregnancy imposes a risk to the developing fetus and the newborn
 infant through mechanisms mediated by maternal hypoxia.

 Objectives:

 1. To prospectively investigate the incidence and severity of SDB during pregnancy using an
 objective tool, i.e., overnight polysomnography (PSG) or at-home sleep study using
 portable device in a large cohort of pregnant women.

 2. To examine the effect of maternal SDB on fetal and neonatal outcome. Methods: 300 women
 in the third trimester of a singleton uncomplicated pregnancy, who attend a low risk
 obstetric surveillance will be recruited. Hundred women hospitalized at the Antenatal
 department due to pregnancy related hypertensive disorder, intrauterine growth
 restriction (IUGR), diabetes mellitus or premature labor will also be recruited. In
 addition, 200 women of a singleton uncomplicated pregnancy will be recruited during
 labor at the delivery room. All participants will be asked to complete a designated
 sleep questionnaire. Based on the questionnaires, women in the third trimester will
 undergo a sleep study. Medical records review will be conducted after delivery and will
 include information of maternal blood pressure, labor duration, route of delivery,
 infant birth weight and APGAR score. Placentas will be collected immediately after
 delivery from all women. Cord blood will be obtained immediately after delivery and will
 be analyzed. Post-natal neurobehavioral evaluation will be conducted. Data analysis will
 be performed on 4 population subgroups: (1) Sleep study proven SDB, (2) Sleep study
 proven non-SDB, (3) SDB per questionnaire, (4) non-SDB per questionnaire. Comparisons of
 fetal outcome measures according to group assignment will be performed. In addition, the
 association between the severity of SDB based on sleep studies (degree of hypoxemia,
 degree of sleep fragmentation, amount of respiratory events) and outcome measures will
 be performed.
Sleep questionnaire: The questionnaire is based on validated questionnaires and includes
 information on snoring, sleep pauses and daytime sleepiness.Completed questionnaires will be
 reviewed weekly, and women with either severe daytime sleepiness or self reported frequent
 snoring or any degree of sleep apnea will be contacted and be requested to undergo clinical
 evaluation and an overnight polysomnography (estimated - 100 women). This evaluation will
 consist of an in-depth sleep related and general medical history and physical examination
 including body mass measurements (height, weight, neck circumference).

 Tissue and umbilical cord blood collection: Placentas will be evaluated by a single
 pathologist. The pathologist will be blind to the medical and perinatal history but not to
 gestational age. Each placenta will be examined using a criteria previously reported.

 Cord blood will be obtained at birth from the double clamped umbilical vein and will be
 processed immediately for fetal blood gases analysis. Immediately following delivery, 5 mL of
 blood will be obtained from the umbilical cord of all babies.

 Neuro-behavioral evaluation of the newborn will be conducted at the first 48 hours of life.
Inclusion Criteria:

 -  Women in the third trimester of a singleton uncomplicated pregnancy, who attend a low
 risk obstetric surveillance (for group 1).

 -  Women with related hypertensive disorder, IUGR, diabetes mellitus, or premature labor
 (group 2).

 -  Women of a singleton uncomplicated full term pregnancy at labor (group 3).

 -  Newborns of women from group 1 and 2 (group 4).

 Exclusion Criteria:

 -  Multiple pregnancies.

 -  Maternal chronic medical conditions.

 -  Prematurity.

 -  Congenital abnormalities.

 -  Fetal distress.