Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, CA.
Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, CA; Department of Pediatrics, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Am J Obstet Gynecol MFM. 2020 Nov;2(4):100237. doi: 10.1016/j.ajogmf.2020.100237. Epub 2020 Sep 21.
Congenital central hypoventilation syndrome is a rare genetic disorder of autonomic regulation of breathing resulting from mutations in the paired-like homeobox gene. Individuals with congenital central hypoventilation syndrome demonstrate an absent or diminished physiological response to hypercapnia and hypoxia that is most severe during sleep and depend on mechanical ventilation to maintain normal gas exchange. Increased disease awareness and availability of paired-like homeobox gene testing has improved congenital central hypoventilation syndrome morbidity and mortality, and patients are now living into adulthood. During pregnancy, delivery, and the postpartum period, women with congenital central hypoventilation syndrome are vulnerable to developing respiratory insufficiency. Currently, there is no standardized approach to monitoring ventilatory status and anticipating the need for changes to existing ventilatory support for women with congenital central hypoventilation syndrome during pregnancy, labor, and delivery.
This study aimed to characterize current practices for monitoring ventilatory status and managing ventilatory needs in women with congenital central hypoventilation syndrome during pregnancy; identify specific circumstances through which ventilation may be compromised during pregnancy, delivery, and postpartum; evaluate utilization of prenatal congenital central hypoventilation syndrome testing; and report any adverse pregnancy outcomes.
We conducted an anonymous cross-sectional survey of women with congenital central hypoventilation syndrome with current or prior pregnancy. The 26-item electronic questionnaire included questions on congenital central hypoventilation syndrome genotype; number and outcome of pregnancies; use of mechanical ventilation; and issues with or adjustments made to ventilation during pregnancy, delivery, and the postpartum period.
We received 10 responses. Three patients were not diagnosed with congenital central hypoventilation syndrome until after pregnancy and delivery. The 7 patients with a preexisting congenital central hypoventilation syndrome diagnosis reported information on 10 total pregnancies. At baseline, patients relied on various types of ventilatory support including positive pressure ventilation via tracheostomy, bilevel noninvasive positive pressure ventilation, and diaphragm pacing by phrenic nerve stimulation. Polysomnography for objective assessment of nocturnal ventilation was not consistently utilized. Changes to baseline ventilatory support were required during 3 out of 10 pregnancies. In addition, 2 patients using diaphragm pacing reported discomfort with pacing during the third trimester or after cesarean delivery, prompting discontinuation of diaphragm pacing. In 1 instance, discontinuation of diaphragm pacing and lack of recognition of need for an alternative support method led to respiratory arrest and need for emergent resuscitation. All patients who were offered prenatal congenital central hypoventilation syndrome testing chose to undergo testing. Of note, 9 out of 10 pregnancies were carried successfully to term and 5 infants were diagnosed with congenital central hypoventilation syndrome.
Women with congenital central hypoventilation syndrome may experience issues maintaining adequate ventilation during pregnancy, necessitating an adjustment of ventilator settings or use of an alternative type of ventilation. Objective assessment of nocturnal ventilation by means of polysomnography is an important part of congenital central hypoventilation syndrome pregnancy care to optimize maintenance of adequate gas exchange. Patients who rely on diaphragm pacing may experience discomfort with pacing during the later stages of pregnancy and after cesarean delivery. Anticipatory guidance and contingency planning for changing ventilatory needs should be discussed early in pregnancy. Prenatal congenital central hypoventilation syndrome testing should be offered to pregnant patients with congenital central hypoventilation syndrome to inform delivery decisions and prepare for the provision of advanced neonatal care.
先天性中枢性通气不足综合征是一种罕见的自主呼吸调节遗传疾病，由同源盒基因配对样基因的突变引起。患有先天性中枢性通气不足综合征的个体对高碳酸血症和缺氧的生理反应缺失或减弱，这种情况在睡眠期间最为严重，并且依赖机械通气来维持正常的气体交换。随着对该病认识的提高和配对样同源盒基因检测的普及，先天性中枢性通气不足综合征的发病率和死亡率有所下降，患者现在可以活到成年。在怀孕期间、分娩期间和产后期间，患有先天性中枢性通气不足综合征的女性易发生呼吸功能不全。目前，对于患有先天性中枢性通气不足综合征的女性在怀孕期间、分娩期间和产后期间监测通气状态和预测对现有通气支持的需求，尚无标准化的方法。
本研究旨在描述目前监测患有先天性中枢性通气不足综合征的女性通气状态和管理其通气需求的方法；确定在怀孕期间、分娩期间和产后期间可能会出现通气受损的具体情况；评估产前先天性中枢性通气不足综合征检测的使用情况；并报告任何不良妊娠结局。
我们对目前或曾经怀孕的患有先天性中枢性通气不足综合征的女性进行了一项匿名横断面调查。这份 26 项的电子问卷包括先天性中枢性通气不足综合征基因型、妊娠次数和结局、机械通气的使用情况以及在怀孕期间、分娩期间和产后期间通气出现问题或需要调整的情况。
我们收到了 10 份回复。有 3 名患者是在怀孕和分娩后才被诊断出患有先天性中枢性通气不足综合征。7 名有先天性中枢性通气不足综合征诊断的患者报告了总共 10 次妊娠。在基线时，患者依赖各种类型的通气支持，包括经气管切开的正压通气、双水平无创正压通气和膈神经刺激的膈神经起搏。客观评估夜间通气的多导睡眠图并未得到一致应用。有 3 次妊娠需要改变基线通气支持。此外，2 名使用膈神经起搏的患者在孕晚期或剖宫产时报告膈神经起搏不适，导致膈神经起搏停止。在 1 例中，膈神经起搏的停止和对需要替代支持方法的认识不足导致了呼吸骤停，需要紧急复苏。所有接受产前先天性中枢性通气不足综合征检测的患者都选择进行了检测。值得注意的是，10 次妊娠中有 9 次成功足月分娩，5 名婴儿被诊断为先天性中枢性通气不足综合征。
患有先天性中枢性通气不足综合征的女性在怀孕期间可能会出现维持足够通气的问题，需要调整呼吸机设置或使用替代类型的通气。通过多导睡眠图进行夜间通气的客观评估是先天性中枢性通气不足综合征妊娠护理的重要组成部分，可优化维持足够气体交换的效果。依赖膈神经起搏的患者可能会在孕晚期和剖宫产术后感到起搏不适。应在妊娠早期就开始讨论对通气需求变化的预期指导和应急计划。应向患有先天性中枢性通气不足综合征的孕妇提供产前先天性中枢性通气不足综合征检测，以告知分娩决策并为提供先进的新生儿护理做好准备。
