Heritability of apnea of prematurity: a retrospective twin study.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Bloch-Salisbury
Elisabeth
E
Department of Neurology, University of Massachusetts Medical School, 55 Lake Ave N, Worcester, MA 01655, USA. elisabeth.salisbury@umassmed.edu
Hall
Mei Hua
MH
Sharma
Priya
P
Boyd
Theonia
T
Bednarek
Francis
F
Paydarfar
David
D
D001049:Apnea / Q000209:etiology / Q000235:genetics*; D004200:Diseases in Twins / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000209:etiology / Q000235:genetics*; D008297:Male; D012307:Risk Factors; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic