Department of Neurology, University of Massachusetts Medical School, 55 Lake Ave N, Worcester, MA 01655, USA.
Pediatrics. 2010 Oct;126(4):e779-87. doi: 10.1542/peds.2010-0084. Epub 2010 Sep 13.
Apnea of prematurity (AOP) is a disturbance in respiratory rhythm defined by idiopathic pauses in breathing that reduce blood oxygen levels and/or heart rate. It is a major clinical problem among preterm infants.
The primary goal of this study was to estimate the genetic susceptibility to AOP in a cohort of preterm twins. A secondary aim was to identify risk factors associated with AOP in this cohort.
A single-center, retrospective study (2000-2008) was performed by using data from 317 premature twin pairs (<36 weeks' gestational age). Heritability estimates were determined by comparing intrapair AOP concordance between 56 monozygotic and 161 dizygotic twin pairs by using structural equation modeling. Risk factors of AOP among a cohort of 543 premature twins were assessed by using mixed-effects logistic regression.
The heritability of AOP was 87% (95% confidence interval [CI]: 0.64-0.97) among same-gender twins. A gender-dependent model revealed that genetic factors accounted for 99% of the variance in male twins (95% CI: 0.89-1.00) and 78% of the variance in female twins (95% CI: 0.49-0.94). Significant risk factors for AOP were low gestational age (P<.001), cesarean delivery (P=.017), and conception through assisted reproductive technologies (P=.008).
These findings suggest that AOP has an important genetic basis underlying this developmental-related disorder of respiratory control. Future genomic studies may provide information on pathophysiological mechanisms that underlie AOP.
早产儿呼吸暂停（AOP）是一种呼吸节律紊乱，表现为呼吸暂停，导致血氧水平和/或心率降低。它是早产儿的一个主要临床问题。
本研究的主要目的是评估早产儿双胞胎队列中 AOP 的遗传易感性。次要目的是确定该队列中与 AOP 相关的危险因素。
采用单中心回顾性研究（2000-2008 年），使用 317 对早产双胞胎（<36 周胎龄）的数据。通过结构方程模型比较 56 对同卵双胞胎和 161 对异卵双胞胎的 AOP 内对一致性，来确定遗传率估计值。通过混合效应逻辑回归评估 543 例早产儿队列中 AOP 的危险因素。
同性别双胞胎中 AOP 的遗传率为 87%（95%置信区间[CI]：0.64-0.97）。性别依赖性模型显示，遗传因素在男性双胞胎中占 99%（95% CI：0.89-1.00），在女性双胞胎中占 78%（95% CI：0.49-0.94）。AOP 的显著危险因素为低胎龄（P<.001）、剖宫产（P=.017）和辅助生殖技术受孕（P=.008）。
这些发现表明，AOP 是一种与呼吸控制发育相关的疾病，其发生具有重要的遗传基础。未来的基因组研究可能会提供与 AOP 相关的病理生理机制的信息。
