Adolescents and adults born as small preterm infants show more pronounced risk factors of cardiovascular disease. Whether similar risks apply across all degrees of preterm birth is poorly known.
We studied the association between preterm birth and cardiovascular risk factors in 6642 16-year-old adolescents of the population-based Northern Finland Birth Cohort 1986. Of these, 79 (1.2%) were born at <34 gestational weeks (early preterm), 238 (3.6%) at 34 to 36 weeks (late preterm), and 6325 at term (controls).
Girls born early preterm had 6.7 mm Hg (95% confidence interval: 3.1–10.2) higher systolic blood pressure (BP) and 3.5 mm Hg (1.1–5.8) higher diastolic BP, but no difference in serum lipid levels compared with control girls. Boys showed no differences in BP, but boys born early preterm had 6.7% (0.2%–13.7%) higher total cholesterol, 11.7% (2.1%–22.3%) higher low-density lipoprotein cholesterol, and 12.3% (3.1%–22.4%) higher apolipoprotein B concentrations. The differences were similar (BP) or stronger (lipids) when adjusted for maternal smoking, birth weight SD score, parental education, pubertal stage, BMI, and lifestyle. There were similar associations with length of gestation as a continuous variable. Accordingly, mean differences between late preterm and controls were in the same direction but weaker, although most were not statistically significant.
Preterm birth was associated with elevated BP in adolescent girls and an atherogenic lipid profile in boys. Because these associations were strongest among those born early preterm, our findings are consistent with a dose-response relationship between shorter length of gestation and cardiovascular risk factors.
Dear Editor,
we have read with great interest the commendable article by Sipola- Leppanen and Colleagues, who have demonstrated that young adults who have been born preterm show an increase in their systemic blood pressure (girls) and atherogenic lipid profile (boys). The Authors have suggested the presence of a dose-response relationship between shorter length of gestation and cardiovascular risk factors [1].
As pioneer in this field, our research group had already demonstrated a similar alteration in a group of young adults who have been born extremely preterm. The majority of them were girls. In this study group, both systolic blood pressure and endothelial dysfunction -the latter expressed as arterial stiffness and measured by means of a previously validated method (flow mediated dilation)- appear to be increased in comparison with healthy controls born at term [2,3].
Furthermore, in our sample size the underlying alteration responsible of these findings are the high levels of asymmetric dimethylarginine , an endogenous strong inhibitor of nitric oxide synthesis. The renal excretion of asymmetric dimethylarginine appears to be inversely related with intrauterine growth restriction - expressed as birth weight- as well [2,4].
In a previous report it has been demonstrated that asymmetric dimethylarginine is involved also in hypercholesterolemia, via the LDL- induced gene expression of protein arginine N-methyltransferases, thus leading to atherosclerosis [5].
By a practical point of view, these findings suggest to adult cardiologists to consider prematurity at birth and/or intrauterine growth restriction as novel risk factors, being in former preterm subjects present an early circulatory dysfunction that might predispose to future cardiovascular adverse events in adulthood.
References
1. Sipola-Leppanen M, Vaarasmaki M, Tikanmaki M, Hovi P, Miettola S, Ruokonen A, Pouta A, Jarvelin MR, Kajantie E. Cardiovascular risk factors in adolescents born preterm. Pediatrics 2014; 134: e1072-1081
2. Bassareo PP, Fanos V, Puddu M, Demuru P, Cadeddu F, Balzarini M, Mercuro G. Reduced brachial flow-mediated vasodilation in young adult ex extremely low birth weight preterm: a condition predictive of increased cardiovascular risk? J Matern Fetal Neonatal Med 2010; 23(S3): 121-124
3. Bassareo PP, Puddu M, Flore G, Deidda M, Manconi E, Melis A, Fanos V, Mercuro G. Could ADMA levels in young adults born preterm predict an early endothelial dysfunction? Int J Cardiol 2012; 159: 217-219
4. Bassareo PP, Fanos V, Puddu M, Flore G, Mercuro G. Advanced intrauterine growth restriction is associated with reduced excretion of asymmetric dimethylarginine. Early Hum Dev 2014;90:173-176
5. Boger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B, Tsikas D, Bode-Boger SM. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res 2000;87:99-105
Conflict of Interest:
None declared
A recent1 Finnish Birth Cohort study found that adolescents born early preterm (EPT) have increased risk factors of cardiovascular disease than those born at term; girls had higher blood pressure which translates to 16% higher mortality from coronary heart disease and 26% higher mortality from stroke; and boys had higher lipid profile. They concluded that there was a dose-response relationship between shorter length of gestation and cardiovascular risk factors.
The definitions of term (infants 37 weeks 0 days or later) and EPT infants (less than 34 weeks gestational age, GA) in this study are inconsistent and lead to confusion interpreting the results. In the methods, the authors describe the control group of 'term' infants as infants greater than 37 weeks GA, which is an inaccurate definition1 as their term control group includes post-term (42 weeks 0 days or later) infants1. Interestingly, they then reran comparisons excluding the post term infants, however, the definition they used for post term infants is 42 weeks and 1 day or later. This also is an inaccurate definition as the American College of Obstetrics and Gynecology (ACOG) defines post term as infants between 42 weeks 0 days and beyond1. Therefore, the comparisons that they reran in the statistical methods, should have excluded infants who completed 42 weeks GA (42 0/7 gestation or later). In other words, the 'term' control group should only include infants 37 0/7-41 6/7 weeks GA2 for statistical accuracy.
Also, when describing the global burden of prematurity, the authors describe infants born 'at 32-36 weeks GA' as moderately preterm (MPT) to contribute up to 80% of preterm infants in Europe. In the methods, however, the authors categorized infants born 'at or before 33weeks 6days' to be described as EPT infants. This overlapping definition varies from the ACOG which describes babies born 'less than 32 weeks' to be early preterm infants and the National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) which recommended using the terminology, MPT for infants 32 0/7 - 33 6/7 weeks GA and late preterm (LPT), for infants born between 34 and 37 completed weeks GA (34 0/7 - 36 6/7 weeks GA)3 . The WHO, on the other hand, describes infants (32 to less than 37 weeks) as moderate to late preterm and infants (28 to less than 32 weeks) as very preterm and those infants (less than 28 weeks) to be extremely preterm4 . It is important for the authors to use consistent terminology when describing EPT infants in their study population. Adhering to standard definitions is critical because their study group (infants less than 34 weeks) includes 32 0/7 - 33 6/7 weeks (MPT) 5 infants in the EPT group. This is extremely confusing and the MPT infants should be excluded from the EPT group for accurate analysis. Use of internationally accepted definitions for preterm, term and post- term infants is imperative for accurate interpretation of outcomes and the global burden of prematurity.
References
1. ACOG Committee Opinion No 579: Definition of term pregnancy. Obstet Gynecol. 2013;122(5):1139-40
2. Chabra S. "Concept of gestational age in completed weeks: lost in translation". Obstetrics and Gynecology 119, no.1 (2012), 183-4
3. Engle WA, Tomashek KM, Wallman C, et al. "Late-preterm infants: a population at risk. Committee on Fetus and Newborn, American Academy of Pediatrics". Pediatrics 120, no.6 (2007):1390-401.
4. Joy E Lawn, Michael G Gravett, Toni M Nunes, Craig E Rubens, Cynthia Stanton and the GAPPS Review Group. Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data. BMC Pregnancy Childbirth. 2010; 10(Suppl 1): S1.
5. Raju TN. Moderately preterm, late preterm and early-term infants: research needs. Clin Perinatol 2013; 40(4):791-7
Conflict of Interest:
None declared