Case Report Obstructive Sleep Apnea during Pregnancy Therapy and Implications for Fetal Health"?


Introduction Obstructive sleep apnea (OSA) is a disorder that occurs in 2 to 4070 of the adult population and is characterized by recurrent obstruction of the upper airway during sleep leading to nocturnal hypoxemia and disturbed sleep (1). The occurrence of OSA during pregnancy has been reported in a small number of cases, but the characteristics of maternal respiration have not been fully described (2-5). Nasal continuous positive airway pressure (nCPAP) is the treatment of choice for OSA at the present time (6). Its effects on the fetus, however, have not previously been studied. We report herein the management and outcome of a pregnant woman with severe sleep apnea and the effects of the apneas and nCPAP on fetal heart rate.

SUMMARY A 32 yr-old woman In her last trimester of pregnancy WlS found to have severe obstructive sleep apnea (OSA). The overnight polysomnogram demonstrated an apnea plus hypopnealndex of 159 events per hour. Apneas were associated with severe oxygen desaturatlon to 40% during rapid eye movement sleep, maternal bradycardia, and second degree heart block. External cardlotocography showed normal fetal heart rate reactivity to fetal movements, even during the apneas and episodes of oxygen desaturatlon. Nasal continuous positive airway pressure at a level of 15 cm H 20 effectively treated the apneas and desaturatlon and had no effect on the fetal heart rate. The patient was Induced electively during the 39th wk of pregnancy and gave birth to a newborn with growth retardation. Early recognition and treatment of OSA In pregnancy might prevent problems with fetal development. AM REV RESPIR DIS 1991; 144:461-463

were not dilated or thickened and contracted normally. A fetal ultrasound performed at 16 wk had confirmed the gestational age. All evaluations of fetal health (nonstress test and biophysical profile) were within normal limits. A doppler study to evaluate fetal-placental circulation was unsuccessful at Case Report 36 wk because of the patient's obesity. An overnight polysomnogram with the patient A 32-yr-old obese family practitioner, half pack per day cigarette smoker, was brought to the hoslying on the right side revealed severe OSA with pital during the 36th wk of her pregnancy because an apnea plus hypopnea index of 159 events/hr, of hypersomnolence. She was a primigravida who and the apnea duration ranged from 14 s in nonREM sleep to 40 s in REM sleep. The baseline oxyhad developed diet-controlled gestational diabetes during the first trimester. During the previous 2 gen saturation was 850/0 during nonapneic sleep months, she had noted marked daytime hypersomand decreased to a low value of 40% during REMassociated events (figure 1). The sleep architecture nolence (falling asleep while talking on the phone) and decreased mental acuity. Snoring had been preswas preserved except for a decrease in the proporent for many years but had gotten worse during tion of slow wave sleep (Stages 3 and 4) to 7% of the pregnancy. Being a physician, she thought that the total sleep time. There was marked maternal bradycardia to 30 beats/min during the obstrucshe had developed narcolepsy or hypothyroidism. tive events with episodes of second-degree heart She had no significant past medical or surgical block. External cardiotocography during the materhistory. The patient weighed 155kg (height, 165cm; body nal events and desaturations did not show fetal demass index, 55), having gained 12 kg over the course celerations, with the fetal heart rate remaining in the 120 to 140 beats/min range and showing norof the pregnancy. The blood pressure was 140/88. mal reactivity to fetal movements (figure 2). Physical examination revealed no nasal or pharynThe patient underwent a repeat sleep study for geal abnormalities, and no goiter was palpable. The nCPAP titration with external fetal cardiac monitorlungs were clear. The jugular venous pressure was ing. It was necessary to increase the nCPAP to 15em not increased, and the cardiac examination was norH 20 to alleviate the apneas and maintain the oxymal. There was 3 + pedal edema. Laboratoryevalgen saturation above 90% (titration was carried out uation showed normal blood counts with a hemoglobin of 14.3 g/dl, normal blood chemistry, and with the patient lying on both left and right sides). The fetal heart rate did not show any changes with a normal electrocardiogram. A room air arterial progressive CPAP titration. The patient was unblood gas with the patient awake and supine showed able to tolerate nCPAP at 15 em H 20 and hence pH, 7.38; Pac02,43mmHg; and Pao., 79mmHg. was kept in hospital with nCPAP at 12.5 cm H 20 The free T4 index was 105 nmollL (normal 51 to 169); progesterone, 188 nmollL (normal for preg- , and supplemental oxygen to maintain oxygen satunant women greater than 60 nmoIlL); and testosterration above 90%. 'IWodays after starting therapy, the patient felt much improved and noted resoluone, 8 nmollL (normal 0.5 to 3.1 nmollL for nontion of her hypersomnolence. pregnant women). Pulmonary function tests were The patient was induced electivelyat 39.5 wk with all within the normal range. The ventilatory response oxytocin. The first stage of delivery lasted 6 hand to hypercapnia was not tested at the time because 20 min. The second stage lasted 10 min and was of the pregnancy. An echocardiogram demonstrated complicated by variable decelerations with termimild concentric left ventricular hypertrophy with nal bradycardia of the fetus to 70 beats/min. A low preserved wall motion. The right-sided chambers

forceps delivery was performed. Apgar scores were 5, 7, and 8 at 1, 5, and 8 min, respectively. The newborn required 1 min of CPAP. The baby boy was growth retarded, weighing 2,680 g (below 10th percentile), with head circumference of 31 em (below third percentile) and length of 48 em (below 10th percentile). The placenta weighed 640 g (normal "'500 g), with no abnormalities noted. The umbilical vein pH was 7.22 (normal, 7.25 to 7.4). The fetal hemoglobin was 20 g/dl with a hematocrit of 0.70 (normal < 0.65). The neonatal glucose and blood gases were normal. 'IWo weeks postpartum, the patient had lost 10 kg. She underwent a repeat sleep study which showed an apnea plus hypopnea index of 122 events/h with oxygen desaturation to 46%. She required the same nCPAP level to alleviate the apneas and maintain oxygen saturation above 90% as was needed prior to delivery. Repeat pulmonary function tests showed no changes from previous. Repeat progesterone was 1.7 nmollL (normal, 0.3 to 2.2 for the follicular phase); testosterone was 3.5 nmollL (normal, 0.5 to 3.1 nmollL for women); free testosterone was 10.7 pmol/L (normal, 2.4 to 13.2 pmollL for nonpregnant women). The ventilatory response to hyperoxic hypercapnia showed

(Received in original form August 31, 1990and in revised form February 20, 1991) 1 From the Desmond N. Stoker Laboratory and the Departments of Medicine and Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. 2 Supported by the Quebec Lung Association and the Environmental Lung Disease Research Fund. 3 Correspondence and requests for reprints should be addressed to R. D. Levy, M.D., Respiratory Division, Room L4.09, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec, Canada H3A lAI.





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Microphone Fig. 1. Repetitive respiratory disturbances (apneaslhypopneas) are observed during a period of REM sleep. They are characterized by diminution of the amplitude of the rib cage and abdominal movements (respiratory inductive plethysmography) and severe oxygen desaturation (Sao z' pulse oximeter). The events appear central at onset, but evolve into an obstructive pattern with paradoxical rib cage and abdominal movements (inward motion of the rib cage in association with outward motion of the abdomen). The latter portions are associated with maternal bradycardia and snoring (microphone) as airflow is reestablished. (Outward = increased cross-sectional circumference).

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20 sec Fig. 2. Fetal heart rate during maternal REM sleep recorded simultaneously with the polysomnogram illustrated in figure 1 (note different time scales). Normal variability of the heart rate is evident, without fetal deceleration. There were no relationships between the changes in fetal heart rate with maternal respiratory disturbances, oxygen desaturation or maternal bradycardia.

a normal increase in minute ventilation to rising end-tidal PCO] (slope, 3.9 L/mm Hg CO]), but the curve wasshifted to the right w~ th a minute ventilation of 38 L/min at an end-tidal peo] of 60mm Hg.

Discussion We have described the management of a patient with marked obesity and severe OSA during pregnancy. The condition responded well to the application of a combination of nCPAP and oxygen therapy. The prevalence of OSA during pregnancy is unknown, and only a few cases have been described. Conti and coworkers (4) reported a single case, and its description was limited to observations regarding the management of airway complications resulting from oropharyngeal abnormalities. Kowall and colleagues (5) described immediate improvement of the clinical symptomatology in one patient with OSA after nCPAP therapy, as wellas improvement of OSA 3 months postpartum. The effects of OSA and nCPAP therapy on the fe-

tus, however, were not documented. JoelCohen and coworkers (2)described fetal heart rate deceleration and acidemia in association with maternal apneas and desaturation in one of their patients, but this was not consistently demonstrated in two others. Schoenfeld and colleagues suggested OSA as a possible cause of intrauterine growth retardation (3). The characteristics of maternal respiration were not .eported in these latter studies. There are a number of physiologic changes during pregnancy which may be important with r, spect to ventilation and oxygen delivery. The increased abdominal contents, as in obesity, result in decreased expiratory reserve volume and functional residual capacity, thus bringing tidal breathing into the range of the closing volume (7). Increased progesterone levels during pregnancy account for the decreased resting Pacol values and an increased ventilatory response to hypercapnia (7). Circulatory changes include a 15to 30070 increase in cardiac output (8). Tissue oxygen delivery is also altered as the oxyhemoglobin curve

is shifted to the right (9). During pregnancy, oxygensaturation is generally wellmaintained during sleep, and the frequency of central apneas and hypopneas is decreased as compared with the nonpregnant state (to). No obstructive apneas were observed in this latter study of normal pregnant women. The effects of pregnancy on the severity of preexistent OSA are unknown. Our patient had severe OSA associated with marked oxygen desaturation. A supine arterial blood gas showed no hypoxemia while awake, but a Pacol of 43 mm Hg, which indicates relative alveolar hypoventilation for a pregnant woman (7). This suggests that resetting of the central chemoreceptors has taken place and that the factors generally resulting in alveolar hyperventilation during pregnancy have been overwhelmed. Berthon-Jones and Sullivan (11) have demonstrated a rightward shift of the ventilatory response to rising COl in hypercapnic patients with OSA that may improve after CPAP treatment. Our patient's response, however, remained abnormal even after 4 wk of treatment with nCPAP. The absence of a substantial change in the severity of the sleep apnea in the postpartum period, despite weight loss of 10 kg and normalization of testosterone level, suggests that the pregnancy itself did not playa major role in the pathogenesis of OSA in our patient. Feto-placental circulatory interactions have been studied primarily in animal models. In sheep, acute reduction of oxygen delivery to the fetus in the presence of maternal hypoxemia or umbilical cord compression causes decreased fetal heart rate, increased fetal blood pressure, and decreased fetal respiratory movements (12-14). In humans, JoelCohen and coworkers (2) described fetal cardiac decelerations during maternal apneas; however, this was not clearly demonstrated in all patients and was not seen in our patient. Chronic hypoxemia results in fetal polycythemia in an animal model (15), but the heart rate and respiratory movements return to baseline (15, 16). Conditions associated with chronically reduced maternal oxygenation in humans, such as cyanotic heart disease, parenchymal lung disease, and living at high altitude may result in intrauterine growth retardation (17). The situation with OSA, however, is different because the oxygen saturation may be well maintained during the daytime, and nocturnal hypoxemia is intermittent. Intrauterine growth retardation in cases of maternal OSA has previously been reported (3). Our patient's newborn was polycythemic and growth retarded despite the presence of gestational diabetes, which tends to result in large neonates. The intermittent hypoxemia likely accounts for these findings, but this remains to be substantiated because there are many other causes of intrauterine growth retardation including hormonal imbalances, malnutrition, and smoking. No follow-up of the newborns of patients with OSA has been described. Whether or not psychomotor retardation becomes manifest later in life in this


group is unknown at the present time; however, this is a frequent sequela of intrauterine growth retardation. Nasal CPAP is presently thought to be the treatment of choice for OSA (6). Its acute effects on the fetus have not previously been described. There are two mechanisms by which nCPAP might adversely affect fetal well-being. First, nCPAP could lead to a reduction in maternal cardiac output with resultant decrease in oxygen delivery to the fetus. Continuous positive airway pressure may theoretically reduce the cardiac output by increasing intrathoracic pressure and, hence, reducing the gradient favoring venous return (18). In 'ubjects with normal cardiac function, venous return and cardiac output appear to be maintained during nCPAP therapy (19). In patients with heart disease, however, the effects ofnCPAP on hemodynamics are variable (20,21).The other potential mechanism by which nCPAP could compromise fetal well-being ·ould be by increasing abdominal pressure with resultant compression of the maternal inferior vena cava. This could occur either by direct transmission of increased intrathoracic pressure through the diaphragm or by recruitment of expiratory abdominal muscles (22). We found that nCPAP at pressures up to 15em H 2 0 , irrespective of which side the mother slept on, did not compromise the fetal heart rate. However, the significance of the stability of the fetal heart rate during nCPAP is uncertain since fetal heart rate has a poor predictive value and low sensitivity for compromised fetal health (23). In conclusion, our observations, in conjunction with others previously reported, suggest that obstructive sleep apnea during pregnancy may have deleterious effects on the fetus. Large prospective studies would be useful to confirm this impression. In the interim, it is reasonable that mothers at high risk for OSA should undergo diagnostic overnight polysomnography, Nasal CPAP is effective therapy and appears safe for the fetus, but caution should be taken in this situation because other factors such as gestational age and the presence of preexistent heart disease

463 or preeclampsia may influence the effects of nCPAP. Thus, fetal monitoring is indicated to assure that therapy is not adversely affecting fetal health. Although improvement in fetal growth has not as yet been demonstrated with long term use of nCPAP, alleviation of maternal OSA and associated intermittent desaturation may have a beneficial effect on fetal development.

Acknowledgment The writers thank Dr. R. Brouillette for helpful comments as well as A. Olha, Dr. J. Walsh, andR. Wilson for expert technical assistance.

References 1. Guilleminault C. Clinical features and evaluation of obstructive apnea. In: Kryger MH, Roth T, Dement WC, eds. The principles and practice of sleep medicine, 1st ed. Philadelphia: W.B. Saunders, 1989; 552-8. 2. Joel-Cohen SJ, Schoenfeld A. Fetal response to periodic sleep apnea: a new syndrome in obstetrics. Eur J Obstet Gynecol Reprod Riol 1978; 812:77-81. 3. Schoenfeld A, Ovidia A, Freedman S. (''''structive sleep apnea (OSA)-implications in mat. rnalfetal medicine. A hypothesis. Moo Hypotheses ~ ')89; 30:51-4. 4. Conti M, Izzo V, Muggiasca ML, Tiengo M. Sleep apnoea syndrome in pregnancy: a case report. Eur J Anaesthesiol 1988; 5:151-4. 5. Kowall J, Clark ro, Nino-Murcia G, Powell N. Precipitation of obstructive sleep apnea during pregnancy. Obstet Gynecol 1989; 74:453-5. 6. Sullivan CE, Issa FG, Berthon-Jones M, McCauley VB, Costas LJV. Home treatment of obstructive sleep apnea with continuous positive airway pressure applied through a nose mask. Bull Eur Physiopathol Respir 1984; 20:49-54. 7. Weinberger SE, Weiss ST, Cohen WR, Weiss JW, J ohnson ST. Pregnancy and the lung. Am Rev Respir Dis 1980; 121:559-81. 8. Ueland K, Novy MJ, Peterson EN, Metcalfe MD. Maternal cardiovascular dynamics. IV. The influence of gestational age on the maternal cardiovascular response to posture and exercise. Am JObst Gynecol 1969; 104:856-64. 9. Kambam JR, Handte RE, Brown WR, Smith BE. Effect of pregnancy on oxygen dissociation (abstract). Anesthesiology 1983; 59:A395. 10. Brownell LG, West P, Kryger MH. Breathing

during sleep in normal pregnant women. Am Rev Respir Dis 1986; 133:38-41. 11. Berthon-Jones M, Sullivan CEo Time course of change in ventilatory response to CO z with longterm CPAP therapy for obstructive sleep apnea. Am Rev Respir Dis 1987; 135:144-7. 12. Jensen A, Wolfang K, Kastendiek E. Fetal sympathetic activity, transcutaneous POz, and skin blood flow during repeated asphyxia in sheep. J Dev Physiol 1987; 9:337-46. 13. Koos BJ, Sameshina H, Power 00. Fetal breathing, sleep state, and cardiovascular responses to graded hypoxia in sheep. J Appl Physiol 1987; 62:1033-9. 14. Itskovitz J, Lagamma EF, Rudolph AM. Effects of cord compression on fetal blood flow distribution and o, delivery. Am J Physiol1987; 252: Hl00-9. 15. Koos BJ, Kintanaka T, Matsuda R, Gilbert RD, Longo LD. Fetal breathing adaptation to prolonged hypoxemia in sheep. J Dev Physio11988; 10:161-6. 16. Boddy K, Dawes GS, Fisher R, Pinter S, Robinsr. .I d. Foetal respiratory movements, electrocordeal and cardiovascular responses to hypoxemia and hypercapnia in sheep. J Physiol 1974; 243: 599-618. 17. Crawford CS. The growth retarded newborn. In: Bolognese RJ, Schwarz RH, Shhneider J, eds. Perinatal medicine. Baltimore: Williams and Wilkins, 1982; 501-26. 18. Abboud N, Rehder K, Rodarte JR, Hyatt RE. Lung volumes and closing capacity with continuous positive airway pressure. Anesthesiology 1975; 42:138-42. 19. Leech JA, Ascah K, Non-invasive hemodynamic studies of applied nasal CPAP in normal volunteers. Chest 1989; 96:114s. 20. Takasaki Y, Orr D, Popkin J, Rutherford R, . Liu P, Bradley DT. Effect of nasal continuous positive airway pressure on sleep apnea in congestive heart failure. Am Rev Respir Dis 1989;140:1578-84. 21. Podszus T, Becker H, Peter JH, Von Wichert P. Left ventricular function under nCPAP ventilation. Eur Respir J 1989; (Suppl 2:785S). 22. Urbscheit N, Bishop B, Bachopen H. Immediate effects of continuous positive pressure breathing on abdominal expiratory activity, minute ventilation and end-tidal PCOz of conscious man. Phys Ther 1973; 53:258-65. 23. Thacker SB, Berkelman RL. Assessing the diagnostic accuracy and efficacy of selected antepartum fetal surveillance techniques. Obstet Gynecol Surv 1986; 41:121-41.

Obstructive sleep apnea during pregnancy. Therapy and implications for fetal health.

A 32 yr-old woman in her last trimester of pregnancy was found to have severe obstructive sleep apnea (OSA). The overnight polysomnogram demonstrated ...
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