Cardiometabolic health in adults born with very low birth weight-a sibling study.

BACKGROUND: Preterm survivors have increased risk for impaired cardiometabolic health. We assessed glucose regulation and cardiometabolic biomarkers in adult very low birth weight (VLBW, <1500 g) survivors, using siblings as controls. METHODS: VLBW-participants were matched with term-born, same-sex siblings. At mean age 29.2 years (SD 3.9), 74 VLBW-adults and 70 siblings underwent a 2-h 75 g oral glucose tolerance test and blood tests for assessment of cardiometabolic biomarkers. RESULTS: Of participants, 23 (31%) VLBW and 11 (16%) sibling-controls met World Health Organization criteria for impaired glucose regulation (OR adjusted for age and sex 2.5, 95% CI: 1.1 to 5.8). Adjusting for age and sex, VLBW-participants showed 9.2% higher 2-h glucose (95% CI: 0.4% to 18.8%) than their siblings. Also, fasting (13.4%, -0.3% to 29.0%) and 2-h free fatty acids (15.6%, -2.4% to 36.9%) were higher in VLBW-participants. These differences were statistically significant only after further adjusting for confounders. No statistically significant differences were found regarding other measured biomarkers, including insulin resistance, atherogenic lipid profiles or liver tests. CONCLUSIONS: VLBW-adults showed more impaired fatty acid metabolism and glucose regulation. Differences in cardiometabolic biomarkers were smaller than in previous non-sibling studies. This may partly be explained by shared familial, genetic, or environmental factors. IMPACT: At young adult age, odds for impaired glucose regulation were 3.4-fold in those born at very low birth weight, compared to same-sex term-born siblings. Taking into consideration possible unmeasured, shared familial confounders, we compared cardiometabolic markers in adults born preterm at very low birth weight with term-born siblings. Prematurity increased risk for impaired glucose regulation, unrelated to current participant characteristics, including body mass index. In contrast to previous studies, differences in insulin resistance were not apparent, suggesting that insulin resistance may partially be explained by factors shared between siblings. Also, common cardiometabolic biomarkers were similar within sibling pairs.

Abdominal adipose tissue and liver fat imaging in very low birth weight adults born preterm: birth cohort with sibling-controls.

Preterm birth at very low birth weight (VLBW, < 1500 g) is associated with an accumulation of cardiovascular and metabolic risk factors from childhood at least to middle age. Small-scale studies suggest that this could partly be explained by increased visceral or ectopic fat. We performed magnetic resonance imaging on 78 adults born preterm at VLBW in Finland between 1978 and 1990 and 72 term same-sex siblings as controls, with a mean age of 29 years. We collected T1-weighted images from the abdomen, and magnetic resonance spectra from the liver, subcutaneous abdominal adipose tissue, and tibia. The adipose tissue volumes of VLBW adults did not differ from their term siblings when adjusting for age, sex, and maternal and perinatal factors. The mean differences were as follows: subcutaneous - 0.48% (95% CI - 14.8%, 16.3%), visceral 7.96% (95% CI - 10.4%, 30.1%), and total abdominal fat quantity 1.05% (95% CI - 13.7%, 18.4%). Hepatic triglyceride content was also similar. VLBW individuals displayed less unsaturation in subcutaneous adipose tissue (- 4.74%, 95% CI - 9.2%, - 0.1%) but not in tibial bone marrow (1.68%, 95% CI - 1.86%, 5.35%). VLBW adults displayed similar adipose tissue volumes and hepatic triglyceride content as their term siblings. Previously reported differences could thus partly be due to genetic or environmental characteristics shared between siblings. The VLBW group displayed less unsaturation in subcutaneous abdominal adipose tissue, suggesting differences in its metabolic activity and energy storage.

Maternal pre-pregnancy overweight and gestational diabetes and dietary intakes among young adult offspring.

BACKGROUND/OBJECTIVES: Maternal pre-pregnancy overweight/obesity and gestational diabetes (GDM) are associated with increased fat deposition in adult offspring. The purpose of this study was to identify if maternal pre-pregnancy overweight (body mass index (BMI) ≥ 25 kg/m2) or GDM are associated with dietary quality or intake in adult offspring. SUBJECTS/METHODS: Participants (n = 882) from two longitudinal cohort studies (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study) completed a validated food-frequency questionnaire at a mean age of 24.2 years (SD 1.3). Diet quality was evaluated by a Recommended Finnish Diet Index (RDI). The study sample included offspring of normoglycaemic mothers with pre-pregnancy overweight/obesity (ONO = 155), offspring of mothers with GDM regardless of BMI (OGDM = 190) and offspring of mothers with normal weight and no GDM (controls; n = 537). RESULTS: Among men, daily energy and macronutrient intakes were similar in ONO and controls. However, after adjusting for current offspring characteristics, including BMI, daily carbohydrate intake relative to total energy intake was higher in ONO-men [2.2 percentages of total energy intake (95% confidence interval 0.4, 4.0)]. In ONO-women, macronutrient intakes relative to total energy intake were similar with controls, while total daily energy intake seemed lower [-587.2 kJ/day (-1192.0, 4.4)]. After adjusting for confounders, this difference was attenuated. Adherence to a healthy diet, as measured by RDI, was similar in ONO and controls [mean difference: men 0.40 (-0.38, 1.18); women 0.25 (-0.50, 1.00)]. In OGDM vs. controls, total energy and macronutrient intakes were similar for both men and women. Also adherence to a healthy diet was similar [RDI: men 0.09 (-0.62, 0.80); women -0.17 (-0.93, 0.59)]. CONCLUSIONS: Our study suggested higher daily carbohydrate intake in male offspring exposed to maternal pre-pregnancy overweight/obesity, compared with controls. Prenatal exposure to GDM was not associated with adult offspring dietary intakes.

Maternal early pregnancy body mass index and diurnal salivary cortisol in young adult offspring.

Background Maternal early pregnancy overweight (body mass index [BMI] 25.0-29.9 kg/m2) and obesity (BMI ≥ 30 kg/m2) are associated with mental and physical health adversities in the offspring. Prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been put forward as one of the mechanisms that may play pathophysiological role. However, evidence linking maternal overweight and obesity with offspring HPA-axis activity is scarce. We studied if maternal early pregnancy BMI is associated with diurnal salivary cortisol, a marker of HPA-axis activity, in young adult offspring. Methods At a mean age of 25.3 (standard deviation [SD) = 0.6) years, 653 Arvo Ylppö Longitudinal Study participants collected saliva samples for cortisol analyses, at awakening, 15 and 30 min thereafter, 10:30AM, 12:00PM, 5:30PM and at bedtime. Maternal BMI was calculated from weight and height verified by a measurement in the first antenatal clinic visit before 12 weeks of gestation derived from healthcare records. Results Per each one kg/m2 higher maternal early pregnancy BMI offspring diurnal average salivary cortisol was -1.4% (95% CI:-2.6, -0.2, pFDR = 0.033) lower, at awakening it was -2.4% (95% CI:-4.0, -0.7, pFDR = 0.025) lower and the morning average salivary cortisol was -2.0% (95% CI:-3.4, -0.5, pFDR=0.017) lower. These associations were independent of the offspring's own young adulthood BMI, and other important covariates. Conclusion Our findings show that young adult offspring born to mothers with higher early pregnancy BMI show lower average levels of diurnal cortisol, especially in the morning. Whether these findings reflect prenatal programming of the offspring HPA-axis activity warrants further investigation.

Gestational Diabetes But Not Prepregnancy Overweight Predicts for Cardiometabolic Markers in Offspring Twenty Years Later.

CONTEXT: Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m2] might adversely affect offspring cardiometabolic health. OBJECTIVE: To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. DESIGN: Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). SETTING: Province of Uusimaa and Northern Finland. PARTICIPANTS: At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI <25 kg/m2 (controls; n = 556). MAIN OUTCOME MEASURES: We assessed the cardiometabolic biomarkers from blood and measured the blood pressure at rest and heart rate. RESULTS: Compared with the controls, the OGDM and ONO groups had greater fasting glucose (1.6%; 95% CI, 0.1% to 3.1%; and 2.3%; 95% CI, 0.5% to 4.3%, respectively) and insulin (12.7%; 95% CI, 4.4% to 21.9%; and 8.7%; 95% CI, 0.2% to 17.8%). These differences attenuated to nonsignificance when adjusted for confounders and/or current offspring characteristics, including BMI or body fat percentage. The OGDM group had lower SHBG (men, -12.4%; 95% CI, -20.2% to -3.9%; women, -33.2%; 95% CI, -46.3% to -16.8%), high-density lipoprotein (-6.6%; 95% CI, -10.9% to -2.2%), and apolipoprotein A1 (-4.5%; 95% CI, -7.5% to -1.4%). These differences survived the adjustments. The heart rate and other biomarkers were similar among the groups. CONCLUSIONS: Adult offspring of mothers with GDM have increased markers of insulin resistance and a more atherogenic lipid profile. These were only partly explained by confounders or current offspring adiposity. Maternal prepregnancy overweight/obesity was associated with impaired offspring glucose regulation, which was explained by confounders and/or current adiposity.

Leisure Time Physical Activity in Young Adults Born Preterm.

OBJECTIVE: To evaluate the amount of self-reported physical activity in young adults born prematurely compared with those born at term. STUDY DESIGN: Unimpaired participants of the Preterm Birth Study (Preterm Birth and Early Life Programming of Adult Health and Disease) birth cohort study were studied at age 23.3 ± 1.2 (SD) years: 118 born early preterm (<34 weeks), 210 late preterm (34-36 weeks), and 311 born at term (≥37 weeks, controls). The participants completed a validated 30-item, 12-month physical activity questionnaire. The annual frequency and total volume of conditioning and nonconditioning leisure time physical activity and commuting physical activity were calculated and the data analyzed by means of linear regression. RESULTS: Adults born early preterm reported a 31.5% (95% CI, 17.4-43.2) lower volume of leisure time physical activity (in metabolic equivalents [MET] h/year) and had a 2.0-fold increased OR (1.2-3.3) of being in the least active quintile than controls. Lower amounts of conditioning, nonconditioning, and commuting physical activity all contributed to the difference. In addition, early preterm participants undertook less vigorous physical activity (≥6 MET). No differences in physical activity were found between the late preterm and control groups. Adjustments for potential early life confounders and current mediating health characteristics did not change the results. CONCLUSIONS: Young adults born early preterm engage less in leisure time physical activities than peers born at term. This finding may in part underlie the increased risk factors of cardiometabolic and other noncommunicable diseases in adults born preterm. Low physical activity is a risk factor for several noncommunicable diseases and amenable to prevention.

Objectively measured physical activity and sedentary time in young adults born preterm-The ESTER study.

BACKGROUND: Young adults born preterm have higher levels of cardio metabolic risk factors and they report less physical activity than their peers born at term. Physical activity provides important cardio metabolic health benefits. We hypothesized that objectively measured physical activity levels are lower and time spent sedentary is higher among preterm-born individuals compared with controls. METHODS: We studied unimpaired participants of the ESTER birth cohort study at age 23.3 y (SD: 1.2): 60 born early preterm (<34 wk), 108 late preterm (34-36 wk), and 178 at term (controls). Physical activity and sedentary time were measured by hip-worn accelerometer (ActiGraph). RESULTS: As compared with controls' (mean physical activity, 303 counts per minute (cpm; SD 129)), physical activity was similar among adults born early preterm (mean difference = 21 cpm, 95% CI -61, 19) or late preterm (5 cpm, -27, 38). Time spent sedentary was also similar. Adjustments for early life confounders or current mediating characteristics did not change the results. CONCLUSION: In contrast to our hypothesis, we found no difference in objectively measured physical activity or time spent sedentary between adults born preterm and at term. The previously reported differences may be limited to physical activity captured by self-report.

Diurnal Cortisol Patterns and Dexamethasone Suppression Test Responses in Healthy Young Adults Born Preterm at Very Low Birth Weight.

BACKGROUND: Early life stress, such as painful and stressful procedures during neonatal intensive care after preterm birth, can permanently affect physiological, hormonal and neurobiological systems. This may contribute to altered programming of the hypothalamic-pituitary-adrenal axis (HPAA) and provoke changes in HPAA function with long-term health impacts. Previous studies suggest a lower HPAA response to stress in young adults born preterm compared with controls born at term. We assessed whether these differences in HPAA stress responsiveness are reflected in everyday life HPAA functioning, i.e. in diurnal salivary cortisol patterns, and reactivity to a low-dose dexamethasone suppression test (DST), in unimpaired young adults born preterm at very low birth weight (VLBW; <1500 g). METHODS: The participants were recruited from the Helsinki Study of Very Low Birth Weight Adults cohort study. At mean age 23.3 years (2.1 SD), 49 VLBW and 36 controls born at term participated in the study. For cortisol analyzes, saliva samples were collected on two consecutive days at 0, 15, 30 and 60 min after wake-up, at 12:00 h, 17:00 h and 22:00 h. After the last salivary sample of the first study day the participants were instructed to take a 0.5 mg dexamethasone tablet. RESULTS: With mixed-effects model no difference was seen in overall diurnal salivary cortisol between VLBW and control groups [13.9% (95% CI: -11.6, 47.0), P = 0.31]. Salivary cortisol increased similarly after awakening in both VLBW and control participants [mean difference -2.9% (29.2, 33.0), P = 0.85]. Also reactivity to the low-dose DST (awakening cortisol ratio day2/day1) was similar between VLBW and control groups [-1.1% (-53.5, 103.8), P = 0.97)]. CONCLUSIONS: Diurnal cortisol patterns and reactivity to a low-dose DST in young adulthood were not associated with preterm birth.

Physical Fitness in Young Adults Born Preterm.

BACKGROUND: Young adults born preterm have higher levels of cardiometabolic risk factors than their term-born peers. Muscular and cardiorespiratory fitness have important cardiometabolic and other health benefits. We assessed muscular, cardiorespiratory, and self-rated fitness in preterm-born young adults. METHODS: We studied unimpaired participants of the ESTER (Ennenaikainen syntymä ja aikuisiän terveys [Preterm Birth and Early-Life Programming of Adult Health and Disease]) birth cohort study at age 23.3 (SD: 1.2) years: 139 born early preterm (EPT; <34 weeks), 247 late preterm (LPT; 34-36 weeks), and 352 at term (control group). We measured muscular fitness with the number of modified push-ups performed in 40 seconds and maximal handgrip strength of the dominant hand, cardiovascular fitness with heart rate at the end of a 4-minute step test, and self-rated fitness. Data were analyzed with linear regression. RESULTS: Young adults born EPT (-0.8; 95% confidence interval: -1.5 to -0.1; adjusted for gender, age, and source cohort) and LPT (-0.8; -1.4 to -0.3) performed fewer modified push-ups than controls. Handgrip strength was 23.8 (0.9-46.8) N lower in EPT participants. Cardiorespiratory fitness, measured by submaximal step test, was similar. On a self-rated fitness scale (1-5), the EPT adults reported 0.2 (0.0-0.4) lower scores than controls. After adjustment for early-life confounders, the results remained. They attenuated after further adjustment for mediating factors. CONCLUSIONS: Young adults born EPT and LPT had lower muscular fitness than controls, which may predispose them to cardiometabolic and other chronic diseases. Adults born EPT also perceived themselves as less fit than controls.

Insulin sensitivity and secretory response in adults born preterm: the Helsinki Study of Very Low Birth Weight Adults.

CONTEXT: Preterm birth is associated with an increased risk of type 2 diabetes in adult life. The mechanisms are poorly known. OBJECTIVE: We studied insulin sensitivity and secretion in adults born preterm at very low birth weight (VLBW; < 1500 g). DESIGN: Longitudinal Birth Cohort Study (Helsinki Study of Very Low Birth Weight Adults). SETTING: The study was conducted at Uusimaa, Finland. PARTICIPANTS: One hundred seven adults born at VLBW and 100 controls born at term not small for gestational age (SGA), group-matched for sex, age, and birth hospital. The mean age was 25.0 years. MAIN OUTCOME MEASURES: We performed a 14-sample intravenous glucose tolerance test and calculated insulin sensitivity (Si), insulin secretory response (AIR), and disposition index, by Minimal Model (Minmod Millennium®). RESULTS: Compared with controls, VLBW adults had lower Si (mean difference -11.9%, 95% CI -22.1 to -0.4%, adjusted for sex, age, and body mass index) and higher AIR (19.9%; 4.4-37.7%). The association with Si attenuated when further adjusted for height, parental diabetes, parental education, smoking, maternal smoking, hormonal contraception, and physical activity, but the association with AIR remained. Disposition index was similar. There was no difference between the 40 VLBW adults born SGA and the remaining VLBW adults. CONCLUSIONS: Adults born preterm at VLBW have lower insulin sensitivity than their term-born peers with a similar body size. In young adulthood, this remains compensated by higher insulin secretion. We suggest that this represents an early stage in the pathway leading to type 2 diabetes. Our results underline the importance of a healthy lifestyle and prompt vigilance in the screening of type 2 diabetes and impaired glucose tolerance in adults born preterm.

Objectively measured physical activity in young adults born preterm at very low birth weight.

Unimpaired adults born preterm at very low birth weight (<1500 g) consistently have lower conditioning physical activity than those born at term. We used wrist-worn accelerometers to measure objectively physical activity in 57 very low birth weight and 47 control subjects aged 25 years. We found no difference in any physical activity measures.

Adrenalin, noradrenalin and heart rate responses to psychosocial stress in young adults born preterm at very low birthweight.

OBJECTIVE: Adults born preterm at very low birthweight (VLBW; ≤ 1500 g) have high levels of cardiovascular risk factors and altered responses to psychosocial stress including higher blood pressure and lower cortisol. Our aim was to investigate adrenalin (A), noradrenalin (NA) and heart rate (HR) responses to psychosocial stress in adults born preterm at VLBW. DESIGN AND PARTICIPANTS: We studied 50 young adults, aged 19-27 years, born at VLBW and 39 term-born controls, group-matched for age, sex and birth hospital. They underwent a standardized psychosocial stress test, the Trier Social Stress Test (TSST). MEASUREMENTS: During TSST, A, NA (baseline and 0, 10 and 90 min after stress) and HR were measured. Data were analysed with mixed-effects and linear regression models, adjusted for age, sex, body mass index, hormonal contraception, time of day and highest parental educational attainment. RESULTS: Baseline concentrations, peak after stress, increments and area under the curve for A and NA were similar in VLBW and control groups. In women, NA concentrations were 27.7% lower (95% CI; 3.1-52.2) in VLBW compared with control women; in men, there was no significant difference. A concentrations were similar for VLBW and control groups in both sexes. Mean HR at baseline, task and HR reactivity was also similar in VLBW and control groups. CONCLUSIONS: Very low-birthweight women seem to have a lower NA response to stress compared with term-born peers. If replicated, this could be a protective characteristic for cardiovascular diseases.

Blunted hypothalamic-pituitary-adrenal axis and insulin response to psychosocial stress in young adults born preterm at very low birth weight.

BACKGROUND: Young adults born preterm at very low birth weight (VLBW, ≤1500 g) have higher levels of cardiovascular risk factors, including impaired glucose regulation, than their term-born peers. This could be mediated through altered hypothalamic-pituitary-adrenal axis (HPAA) response to stress. OBJECTIVE: To compare HPAA, glucose and insulin responses provoked by psychosocial stress in VLBW subjects versus a comparison group of term-born controls. DESIGN AND PARTICIPANTS: We studied 54 unimpaired young adults, aged 19-27 years, born at VLBW and a comparison group of 40 adults born at term, group-matched for age, sex and birth hospital, from one regional centre in southern Finland. The participants underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). MEASUREMENTS: In conjunction with TSST, we measured salivary cortisol, plasma ACTH, cortisol, glucose and insulin. Data were analysed with mixed-effects model and multiple linear regression analyses. RESULTS: Baseline concentrations for cortisol, ACTH, insulin and glucose were similar in VLBW and comparison groups. During TSST, analysed with mixed-effects model, overall concentrations of plasma cortisol were 17·2% lower (95% CI; 3·5 to 28·9) in the VLBW group. The VLBW group also had lower salivary (P = 0·04) and plasma cortisol (P = 0·02) responses to TSST. Insulin and glucose concentrations correlated with changes in cortisol concentrations. Accordingly, VLBW subjects had 26·5% lower increment in insulin (95% CI; 9·8-40·1). Analyses were adjusted for age, sex, body mass index, hormonal contraception, menstrual cycle phase, time of day and parental education. CONCLUSIONS: VLBW adults have lower HPAA responses to psychosocial stress than term-born controls. This is accompanied by a lower insulin response.

Diet and nutrient intake in young adults born preterm at very low birth weight.

OBJECTIVE: To assess dietary intake in young adults born preterm at very low birth weight (VLBW) (≤ 1500 g). STUDY DESIGN: We studied 151 young adults aged 19-27 years who were born at VLBW and 156 term-born controls, group-matched for age, sex, and birth hospital. Participants completed a 3-day food record, which was checked by a nutritionist. Food and nutrient intakes were calculated with use of a dietary analysis program. Data were analyzed by multiple linear regression, adjusted for age, sex, body mass index, height, living at parental home, daily smoking, and highest parental education. RESULTS: Compared with controls, VLBW subjects had lower mean (SD) daily intake of vegetables, fruits, and berries (183 [150] g vs 241 [168] g, P = .002] and milk products (343 [242] g vs 427 [316] g, P = .003). Energy intake from carbohydrates, protein, and fat was similar, as was salt intake. VLBW participants had lower daily intake of calcium (858 [389] mg vs 1080 [514] mg, P < .0001), vitamin D (3.7 [2.6] µg vs 4.4 [3.6] µg, P = .02), and cholesterol (189 [74] mg vs 227 [105] mg, P = .002], whereas intake of essential fatty acids was higher (4.3 [1.5] mg vs 4.0 [1.5] mg, P = .01). CONCLUSIONS: Lower consumption of vegetables, fruits, berries, and milk products combined with lower calcium and vitamin D intake in VLBW participants offers a target for reducing the risk of osteoporosis and cardiovascular diseases in persons of VLBW.

Lower conditioning leisure-time physical activity in young adults born preterm at very low birth weight.

BACKGROUND: Adults born preterm at very low birth weight (VLBW, <1500 g) have elevated levels of risk factors for cardiovascular diseases and type 2 diabetes. Preliminary observations suggest that this could partly be explained by lower rates of physical activity. The aim of this study was to assess physical activity in healthy young adults born preterm at very low birth weight compared with term-born controls. METHODOLOGY/PRINCIPAL FINDINGS: We studied 94 unimpaired young adults, aged 21-29 years, born at VLBW and 101 age-, sex-, and birth hospital-matched term-born controls from one regional center in Southern Finland. The participants completed a validated 30-item 12-month physical activity questionnaire and the NEO-Personality Inventory based on the Big Five taxonomy, the most commonly used classification of personality traits. Yearly frequency, total time, total volume and energy expenditure of conditioning and non-conditioning leisure-time physical activity (LTPA) and commuting physical activity were compared between VLBW and term-born subjects. A subset of participants underwent dual-energy x-ray absorptiometry for body composition measurement. Data were analyzed by multiple linear regression. Compared with controls, VLBW participants had lower frequency [-38.5% (95% CI; -58.9, -7.7)], total time [-47.4% (95% CI; -71.2, -4.1)], total volume [-44.3% (95% CI; -65.8, -9.2)] and energy expenditure [-55.9% (95% CI; -78.6, -9.4)] of conditioning LTPA when adjusted for age, sex, body mass index, smoking, parental education and personality traits. Adjusting for lean body mass instead of body mass index attenuated the difference. There were no differences in non-conditioning LTPA or commuting physical activity. CONCLUSIONS/SIGNIFICANCE: Compared with term-born controls, unimpaired VLBW adults undertake less frequent LTPA with lower total time and volume of exercise resulting in lower energy expenditure. Differences in personality that exist between the VLBW and term-born groups do not seem to explain this association.