Pregnancy in congenital central hypoventilation syndrome.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Autonomic function in children with congenital central hypoventilation syndrome and their families.

STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is a genetic disorder characterized by failure of automatic control of breathing in the absence of obvious anatomic lesions. There have been several reports suggesting that CCHS patients display autonomic dysregulation. Pulse arterial tonometry (PAT) is a novel technique that provides noninvasive moment-to-moment measurements of sympathetic tone changes to the cutaneous vascular bed. We hypothesized that autonomic function as measured by PAT would be altered in children with CCHS. DESIGN: Prospective study. SETTING: CCHS Family Conference, Orlando, FL, and the local community in Louisville, KY. PARTICIPANTS: Nineteen CCHS patients and 31 parents as well as 24 control children and 15 adult control subjects. INTERVENTIONS: Children with CCHS and their parents underwent sympathetic challenges (vital capacity sigh and cold hand pressor test) and a test of reactive hyperemia (brachial artery occlusion) while PAT was continuously monitored from the right hand. Control children and control adults underwent the same procedure. MEASUREMENTS AND RESULTS: The maximal change of the PAT signal compared to the preceding baseline was averaged and expressed as percentage change for each of the challenges. The magnitude of sympathetic discharge-induced attenuation of PAT signal following a sigh was reduced in CCHS children compared to control subjects for both the vital capacity sighs and the cold hand pressor test. There were no differences observed in the magnitude of PAT attenuation between parents of children with CCHS and control adults. No differences were observed between either CCHS and control subjects or CCHS parents and adult control subjects for the brachial artery occlusion test. CONCLUSION: CCHS patients show an attenuated response to endogenous sympathetic stimulation, supporting the presence of autonomic nervous system dysfunction as a consistent feature of this condition. No differences were found in parents of children with CCHS compared to control adults, consistent with the finding that CCHS is primarily the result of a de novo gene mutation.

Epidemiologic survey of 196 patients with congenital central hypoventilation syndrome.

This study examined the cross-sectional medical and social characteristics of children diagnosed with congenital central hypoventilation syndrome (CCHS). A detailed questionnaire was mailed to all families with a child with CCHS who are affiliated with a family network or support group. The questionnaire response rate was >75% (n=196). Mean age was 10.22 years +/- 6.6 years (SD) (range, 0.4-38 years), with a 1:1 sex ratio. Multisystem involvement was almost universal among the cohort, with Hirschsprung's disease (HD) present in 16.3%; 61.7% of the children had a tracheotomy, but 14.3% were never tracheotomized, with 77 subjects (39.3%) not having a tracheostomy tube at time of survey. Respiratory support approaches varied but clearly reflected the trend towards earlier and more widespread transition to noninvasive ventilatory modalities. Significant developmental problems were noted, but attendance in regular classes occurred in the majority. Significant deficiencies in routine periodic evaluation and management were reported. In addition, the presence of CCHS was associated with a significant financial and psychosocial burden to the families. In conclusion, a comprehensive survey of 196 CCHS children and their families revealed a cross-sectional picture of substantial medical and psychosocial complexities associated with this disorder, and pointed out substantial inadequacies in routine preventive care that appear to impose stress on the families. The emerging trend of earlier transition to noninvasive ventilatory support warrants future studies. Implementation of recommended guidelines for diagnosis and multidisciplinary follow-up of CCHS should ultimately ameliorate the long-term outcome of this lifelong condition.