Cytochrome P450 (CYP2D6) genotype is associated with elevated systolic blood pressure in preterm infants after discharge from the neonatal intensive care unit

Abstract

Objective: To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU).

Study design: A convenience cohort of infants born at <32 weeks gestational age was followed after NICU discharge. We retrospectively identified a subgroup of subjects with ESBP (systolic blood pressure [SBP] >90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables.

Results: Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP=84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids (P=.0002).

Conclusions: ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants.