Cardiometabolic Risk Factors in Young Adults Born Preterm
Cardiometabolic Risk Factors in Young Adults Born Preterm
The characteristics of the study groups are presented in Table 1 . Subjects who were born preterm were approximately 2 times more likely to be obese than were controls (Figure 2 and Table 2 ), which was reflected in their higher mean body mass indices and waist circumferences ( Table 3 ). Waist circumferences, waist-hip ratios, and (with borderline significance for the early preterm group) percentages of body fat were higher in both early and late preterm groups than in the controls; lean body masses were similar ( Table 3 ).
(Enlarge Image)
Figure 2.
Prevalence of hypertension, obesity, metabolic syndrome, and fatty liver index greater than 30 in adults who were born early preterm or late preterm compared with adults born at term (controls), Northern Finland, 2009–2011.
Hypertension was 2 to 3 times more common in adults who were born preterm (Figure 2 and Table 2), although this was not statistically significant for the late preterm group. Adults who were born early preterm had systolic blood pressures that were 3.0 mm Hg higher and diastolic blood pressures that were 2.6 mm Hg higher than did the controls (Table 4). The difference remained statistically significant after adjustment for covariates.
One subject who was born late preterm reported using medication for type 2 diabetes mellitus and was excluded from the analyses of glucose metabolism. Subjects who were born late preterm had higher fasting and 2-hour insulin concentrations and higher indices of homeostatic model assessment for insulin resistance than did the controls (Table 4). These differences were minimally changed after adjustment for parental and prenatal confounders but became attenuated after adjustment for current characteristics. Glucose concentrations were similar in all the groups. Eight (3.3%) of the late preterm subjects and 11 (3.2%) of the controls had impaired glucose tolerance, and 1 (0.4%) subject who was born late preterm was found to have diabetes after taking an oral glucose tolerance test.
Women who were born early preterm had 11.4% (95% confidence interval (CI): 5.6, 16.9) lower HDL-C and 9.7% (95% CI: 4.5, 14.7) lower apolipoprotein A1 concentrations than did women in the control group (Web Table 4 http://aje.oxfordjournals.org/content/181/11/861/suppl/DC1). The differences remained similar after we controlled for covariates. These associations were not present among men (Web Table 4 http://aje.oxfordjournals.org/content/181/11/861/suppl/DC1). There were no differences in triglyceride or total or low-density lipoprotein cholesterol levels. No subjects used lipid-lowering medications.
Of the 711 subjects who had adequate data, 46 (6.5%) fulfilled the criteria of metabolic syndrome. Of the controls, 12 (3.5%) had the syndrome. Among those who were born early preterm, 15 (11.5%) had the syndrome (after adjustment for sex, age, and cohort, odds ratio = 3.7, 95% CI: 1.6, 8.2) (Figure 2 and Table 2). Among those who were born late preterm, 19 (17.9%) had the syndrome (odds ratio = 2.5, 95% CI: 1.2, 5.3) (Figure 2 and Table 2). The results were similar when further adjustments were made for covariates (Table 2).
Subjects who were born preterm were 8 to 13 times more likely to have an intermediate or high fatty liver index, which is a proxy of nonalcoholic fatty liver disease (Figure 2, Table 2 ). Of the individual markers of fatty liver disease, alanine aminotransferase and aspartate transaminase concentrations were higher in those who were born preterm, although this was statistically significant for the late preterm group only ( Table 4 ). Concentrations of plasma uric acid, another marker of metabolic syndrome, were 20.1% higher in the subjects born early and late preterm ( Table 4 ). In addition, plasma albumin and plasma urea concentrations were higher in those born early preterm than in the controls. As for markers of inflammation, the levels of blood leucocytes were higher in those born early preterm ( Table 4 ).
To study whether perinatal conditions that might accompany preterm birth contributed to our findings, we reanalyzed the data by 1) excluding those who were born small for gestational age, 2) excluding those who were born in connection with a pregnancy of multiples, and 3) further adjusting the analyses for maternal gestational diabetes. This did not alter any of the conclusions of the study. We further adjusted the analyses for maternal hypertension in pregnancy. When we adjusted for the variables in model 4, we found that compared with subjects who were not exposed, those who were exposed to maternal hypertension had systolic blood pressures that were 2.6 mm Hg higher and diastolic blood pressures that were 2.0 mm Hg higher. After adjustment for maternal hypertension in addition to other covariates, the differences in systolic and diastolic blood pressures with controls became attenuated to 1.9 (95% CI: −0.3, 4.0) and 1.7 mm Hg (95% CI: 0.1, 3.3), respectively, for early preterm and 0.5 mm Hg (95% CI: −1.2, 2.3) and 0.02 mm Hg (95% CI: −1.1, 1.6), respectively, for subjects born late preterm; this adjustment also attenuated the differences in fat mass and body fat percentage for those who were born early preterm. Further, we reran the analyses that included birth weight standard deviation score by using a birth weight standard based on serial ultrasound measurements of the fetus instead of the commonly used Finnish standard based on newborn measurements. Again, this did not alter our conclusions.
Results
Obesity and Body Composition
The characteristics of the study groups are presented in Table 1 . Subjects who were born preterm were approximately 2 times more likely to be obese than were controls (Figure 2 and Table 2 ), which was reflected in their higher mean body mass indices and waist circumferences ( Table 3 ). Waist circumferences, waist-hip ratios, and (with borderline significance for the early preterm group) percentages of body fat were higher in both early and late preterm groups than in the controls; lean body masses were similar ( Table 3 ).
(Enlarge Image)
Figure 2.
Prevalence of hypertension, obesity, metabolic syndrome, and fatty liver index greater than 30 in adults who were born early preterm or late preterm compared with adults born at term (controls), Northern Finland, 2009–2011.
Blood Pressure
Hypertension was 2 to 3 times more common in adults who were born preterm (Figure 2 and Table 2), although this was not statistically significant for the late preterm group. Adults who were born early preterm had systolic blood pressures that were 3.0 mm Hg higher and diastolic blood pressures that were 2.6 mm Hg higher than did the controls (Table 4). The difference remained statistically significant after adjustment for covariates.
Glucose Metabolism
One subject who was born late preterm reported using medication for type 2 diabetes mellitus and was excluded from the analyses of glucose metabolism. Subjects who were born late preterm had higher fasting and 2-hour insulin concentrations and higher indices of homeostatic model assessment for insulin resistance than did the controls (Table 4). These differences were minimally changed after adjustment for parental and prenatal confounders but became attenuated after adjustment for current characteristics. Glucose concentrations were similar in all the groups. Eight (3.3%) of the late preterm subjects and 11 (3.2%) of the controls had impaired glucose tolerance, and 1 (0.4%) subject who was born late preterm was found to have diabetes after taking an oral glucose tolerance test.
Lipid Profile
Women who were born early preterm had 11.4% (95% confidence interval (CI): 5.6, 16.9) lower HDL-C and 9.7% (95% CI: 4.5, 14.7) lower apolipoprotein A1 concentrations than did women in the control group (Web Table 4 http://aje.oxfordjournals.org/content/181/11/861/suppl/DC1). The differences remained similar after we controlled for covariates. These associations were not present among men (Web Table 4 http://aje.oxfordjournals.org/content/181/11/861/suppl/DC1). There were no differences in triglyceride or total or low-density lipoprotein cholesterol levels. No subjects used lipid-lowering medications.
Metabolic Syndrome
Of the 711 subjects who had adequate data, 46 (6.5%) fulfilled the criteria of metabolic syndrome. Of the controls, 12 (3.5%) had the syndrome. Among those who were born early preterm, 15 (11.5%) had the syndrome (after adjustment for sex, age, and cohort, odds ratio = 3.7, 95% CI: 1.6, 8.2) (Figure 2 and Table 2). Among those who were born late preterm, 19 (17.9%) had the syndrome (odds ratio = 2.5, 95% CI: 1.2, 5.3) (Figure 2 and Table 2). The results were similar when further adjustments were made for covariates (Table 2).
Other Biochemical Markers of Metabolic Syndrome
Subjects who were born preterm were 8 to 13 times more likely to have an intermediate or high fatty liver index, which is a proxy of nonalcoholic fatty liver disease (Figure 2, Table 2 ). Of the individual markers of fatty liver disease, alanine aminotransferase and aspartate transaminase concentrations were higher in those who were born preterm, although this was statistically significant for the late preterm group only ( Table 4 ). Concentrations of plasma uric acid, another marker of metabolic syndrome, were 20.1% higher in the subjects born early and late preterm ( Table 4 ). In addition, plasma albumin and plasma urea concentrations were higher in those born early preterm than in the controls. As for markers of inflammation, the levels of blood leucocytes were higher in those born early preterm ( Table 4 ).
Associations of Perinatal Factors
To study whether perinatal conditions that might accompany preterm birth contributed to our findings, we reanalyzed the data by 1) excluding those who were born small for gestational age, 2) excluding those who were born in connection with a pregnancy of multiples, and 3) further adjusting the analyses for maternal gestational diabetes. This did not alter any of the conclusions of the study. We further adjusted the analyses for maternal hypertension in pregnancy. When we adjusted for the variables in model 4, we found that compared with subjects who were not exposed, those who were exposed to maternal hypertension had systolic blood pressures that were 2.6 mm Hg higher and diastolic blood pressures that were 2.0 mm Hg higher. After adjustment for maternal hypertension in addition to other covariates, the differences in systolic and diastolic blood pressures with controls became attenuated to 1.9 (95% CI: −0.3, 4.0) and 1.7 mm Hg (95% CI: 0.1, 3.3), respectively, for early preterm and 0.5 mm Hg (95% CI: −1.2, 2.3) and 0.02 mm Hg (95% CI: −1.1, 1.6), respectively, for subjects born late preterm; this adjustment also attenuated the differences in fat mass and body fat percentage for those who were born early preterm. Further, we reran the analyses that included birth weight standard deviation score by using a birth weight standard based on serial ultrasound measurements of the fetus instead of the commonly used Finnish standard based on newborn measurements. Again, this did not alter our conclusions.
