Pregnancy in congenital central hypoventilation syndrome

Abstract

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.