Preterm Birth and its Association with Altered Renal Sodium Handling in Response to Mental Stress in Young Adults

Background: Early-life programming risk factors such as preterm birth and very low birth weight (VLBW; <1500 g) contribute to later hypertension development, but the underlying mechanisms are not fully developed. Experimental data suggest that altered pressure natriuresis (defined as an increase in renal perfusion pressure to promote sodium excretion) and renal sodium handling may be important contributing mechanisms. Adults with primary hypertension exhibit blunted pressure natriuresis in response to sympathetic arousal, but this has not been described in adults born preterm. We investigated renal sodium excretion relative to the change in blood pressure (BP) in response to stress in a cohort of young adults born preterm with VLBW compared to term-born controls with normal birth weight.

Hypothesis: We hypothesized that young adults born preterm will have a blunted pressure natriuresis response to mental stress compared to those born term.

Methods: In this long-term prospective cohort of 161 individuals aged 18–23 years, 129 (80%) born preterm and 32 (20%) born term, we measured spot urine sodium/creatinine before and after a 30-min mental stress test and non-invasive continuous BP every 2 min prior to and during the stress test. We defined our outcome, pressure natriuresis, urine sodium corrected for creatinine relative to the change in mean arterial pressure (MAP) before and after the stress test, using three estimations: (i) relative change in sodium/creatinine per relative change in MAP; (ii) percent change in sodium/creatinine per percent change in MAP; and (iii) sodium excretion rate per change in MAP. We further defined blunted response as ≤0 for each of these estimations. We used generalized linear models to estimate the association between prematurity and the outcome and tested for effect modification by sex by including an interaction term in each model and stratifying by sex.

Results: The mean age of study participants was 19.8 years (SD 0.9) of whom 56% were female. On unadjusted analyses, the preterm-term difference in the relative change in sodium/creatinine per change in MAP was b=0.11 per mmHg (95% CI: -0.06 to 0.27). When defined as the percent change in urine sodium/creatinine per percent change in MAP, the difference in pressure natriuresis between the two groups was b=42.4% (4.7 to 80.2). Lastly, the difference in sodium excretion rate relative to change in MAP was b=0.08 min/mmHg (-0.03 to 0.18). Across the three measures of pressure natriuresis, the relative risk of blunted response was 1.2 (0.68 to 2.1). Upon assessment of effect modification by sex, percent change in urine sodium/creatinine per percent change in MAP was b=67.6% (-5.78 to 141.0) in males and b=18.9% (-13.8 to 51.7) in females, but all interaction terms were not statistically significant.

Conclusions:Except for percent change in urine sodium/creatinine relative to percent change in MAP, we did not observe a difference in pressure natriuresis in response to mental stress between those born preterm and term. Through preliminary stratified analyses, we observed no evidence of effect modification by sex. Ongoing analyses include investigating other measures of pressure natriuresis and adjusted multivariable models.

Source of mentor’s funding or other support that funded this research: NIDDK T35DK007400; NHLBI K23HL148394, L40HL148910, and R01HL146818; NICHD P01HD047584 and P01HD084227; NCRR M01RR07122 to the Clinical Research Unit of Wake Forest Baptist Medical Center; NCATS UL1TR001420 to the Wake Forest Clinical and Translational Science Award, American Heart Association (14GRNT20480131 and 18TPA34170522), and the Forsyth Medical Center and Wake Forest School of Medicine Department of Pediatrics research funds.