Reaction times, learning, and executive functioning in adults born preterm.

BACKGROUND: This study examines cognitive functioning in adults born across the range of prematurity with appropriate or small for gestational age (SGA) birth weight compared with full-term controls. METHODS: ESTER Preterm Birth Study participants without severe disabilities, comprising 133 early preterm (<34 weeks, 17% SGA), 241 late preterm (34 + 0-36 + 6 weeks, 13% SGA), and 348 full-term subjects, performed the Cogstate® test at a mean age of 23.3 (SD = 1.2) years. Subtests measured paired associate learning, psychomotor function, executive function, spatial memory efficiency, visual memory, attention, working memory, visual learning, and emotional cognition. Data were analyzed with linear regression, full models adjusted for prenatal and postnatal factors and socioeconomic position. RESULTS: Early preterm, late preterm, and full-term participants showed similar abilities in almost all subtests. Early preterm participants had 0.6 fewer moves/10 s (95% CI: -1.0; -0.2, full model) and late preterm and SGA participants had 1.3 fewer moves/10 s (95% CI: -2.1; -0.4) than full-term controls in the Groton Maze Learning Test, indicating weaker spatial memory efficiency. CONCLUSIONS: Adults born across the range of prematurity on average lack major defects in cognitive abilities. Cognitive problems may persist to adulthood only among those born the smallest: very preterm or preterm and SGA. IMPACT: Although preterm birth is a risk for the developing brain, adults born preterm as a group showed similar cognitive performance to their full-term peers. Children born preterm across gestational ages show defects in cognitive domains. With a supportive environment, many of them have the potential to catch up with those born at term. The unfavorable effect of late preterm birth on cognitive functions in childhood may not persist to adulthood; in this study, adults born late preterm showed similar cognitive functioning to adults born full-term. The deficits in cognitive function in adults born preterm detected by earlier studies mainly concern those born the smallest, i.e., very preterm or preterm and small for gestational age.

Prenatal determinants of physical activity and cardiorespiratory fitness in adolescence - Northern Finland Birth Cohort 1986 study.

BACKGROUND: Lower levels of physical activity and cardiorespiratory fitness are key risk factors of chronic adult diseases. Physical activity and cardiorespiratory fitness are predicted by birth weight, but the underlying parental and pregnancy-related factors remain largely unknown. We examined how prenatal determinants are associated with physical activity and cardiorespiratory fitness in adolescence. METHODS: Of the 16-year-old members of the population-based Northern Finland Birth Cohort 1986 (NFBC 1986), 6682 singletons with no major physical disability reported their amount of physical activity outside school hours, and 4706 completed a submaximal cycle ergometer test assessing cardiorespiratory fitness. Physical activity was expressed as metabolic equivalent hours per week (METh/week) and cardiorespiratory fitness as peak oxygen uptake (ml·kg-1·min-1). Prenatal determinants included birth weight, length of gestation, mother's and father's body mass index (BMI), maternal gestational diabetes mellitus (GDM), and maternal hypertension and smoking during pregnancy. Data were analyzed by multiple linear regression. RESULTS: A higher birth weight and longer length of gestation predicted lower levels of physical activity and cardiorespiratory fitness at 16 years, although the association between length of gestation and physical activity was inverse U-shaped. Mother's or father's overweight or obesity before pregnancy were associated with lower levels of their offspring's physical activity and fitness in adolescence. Adjusting for maternal pregnancy disorders and the adolescent's own BMI attenuated the associations with the mother's but not the father's overweight/obesity. Furthermore, maternal GDM predicted lower cardiorespiratory fitness. CONCLUSIONS: A high birth weight and parental overweight/obesity are associated with lower levels of both physical activity and cardiorespiratory fitness in adolescence, while maternal GDM and longer length of gestation are associated with lower cardiorespiratory fitness. Both long and short lengths of gestation predict low physical activity.

Cardiometabolic risk factors in young adults who were born preterm.

Adults who were born preterm with a very low birth weight have higher blood pressure and impaired glucose regulation later in life compared with those born at term. We investigated cardiometabolic risk factors in young adults who were born at any degree of prematurity in the Preterm Birth and Early Life Programming of Adult Health and Disease (ESTER) Study, a population-based cohort study of individuals born in 1985-1989 in Northern Finland. In 2009-2011, 3 groups underwent clinical examination: 134 participants born at less than 34 gestational weeks (early preterm), 242 born at 34-36 weeks (late preterm), and 344 born at 37 weeks or later (controls). Compared with controls, adults who were born preterm had higher body fat percentages (after adjustment for sex, age, and cohort (1985-1986 or 1987-1989), for those born early preterm, difference = 6.2%, 95% confidence interval (CI): 0.4, 13.2; for those born late preterm, difference = 8.0%, 95% CI: 2.4, 13.8), waist circumferences, blood pressure (for those born early preterm, difference = 3.0 mm Hg, 95% CI: 0.9, 5.1; for those born late preterm, difference = 1.7, 95% CI: -0.1, 3.4), plasma uric acid levels (for those born early preterm, difference = 20.1%, 95% CI: 7.9, 32.3; for those born late preterm, difference = 20.2%, 95% CI: 10.7, 30.5), alanine aminotransferase levels, and aspartate transaminase levels. They were also more likely to have metabolic syndrome (for those born early preterm, odds ratio = 3.7, 95% CI: 1.6, 8.2; for those born late preterm, odds ratio = 2.5, 95% CI: 1.2, 5.3). Elevated levels of conventional and emerging risk factors suggest a higher risk of cardiometabolic disease later in life. These risk factors are also present in the large group of adults born late preterm.

Maternal preeclampsia and bone mineral density of the adult offspring.

OBJECTIVE: Preterm birth at very low birthweight (<1500 g) is associated with cardiometabolic risk factors and reduced bone mineral density in the adult offspring. Preeclampsia is a frequent cause of preterm birth and is also associated with cardiometabolic risk factors in the offspring. Whether it is associated with bone mineral density is not known. STUDY DESIGN: We evaluated skeletal health in participants of the Helsinki Study of Very Low Birthweight Adults: 144 born at very low birthweight and 139 born at term. From the very low birthweight and term offspring a respective 32 and 11 were born from pregnancy complicated by preeclampsia. We measured bone mineral density at age 18.5 to 27.1 years by dual X-ray absorptiometry. RESULTS: Very low birthweight adults exposed to maternal preeclampsia had higher lumbar spine Z score (mean -0.44, compared with -1.07 in very low birthweight unexposed adults, P = .002), femoral neck Z score (-0.05 vs -0.53, P = .003) and whole body bone mineral density Z score (-0.14 vs -0.72, P = .001). Corresponding Z scores for those born at term were -0.02 (preeclampsia) and -0.45 (no preeclampsia) for lumbar spine (P = .2), 0.78 and 0.08 for femoral neck (P = .02) and 0.02 and -0.31 for whole body bone mineral density Z score (P = .08). The results survived adjustment for offspring current height, body mass index, leisure time physical activity, socioeconomic position, smoking, and maternal smoking during pregnancy, and maternal prepregnancy body mass index. CONCLUSION: Young adults exposed to maternal preeclampsia have higher bone mineral density than those not exposed. This difference is seen among those born at very low birthweight and seems also to be present among those born at term.

Offspring's blood pressure and metabolic phenotype after exposure to gestational hypertension in utero.

The aim of the study was to investigate the impact of de novo hypertension in pregnancy, i.e. gestational (non-proteinuric) hypertension (GH) and preeclampsia (PE), on the long-term metabolic outcome of the offspring. Data was obtained from the Northern Finland Birth Cohort 1986 (NFBC 1986), including 9,362 pregnancies and subsequent births between 1985 and 1986. Pregnancies were categorised into three groups: (1) GH with blood pressure (BP) ≥ 140/90 mmHg, (2) PE with BP ≥ 140/90 mmHg and proteinuria, and (3) reference group with normal BP. The final study population included 331 offspring of mothers with GH, 197 with PE and 5,045 offspring of normotensive mothers. The main outcome measures were systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), body mass index (BMI), and serum lipid, glucose and insulin levels of the 16 year-old offspring. The children of mothers with GH had higher BP compared to the reference group (SBP percentage difference 2.7 (95% CI 1.6, 3.8); DBP 3.4 (2.1, 4.6); MAP 3.1 (2.0, 4.1), P < 0.001 for all) and a tendency towards higher cholesterol and apolipoprotein B values. The offspring of mothers with PE had higher DBP and MAP, however after the adjustments this difference disappeared. Maternal de novo hypertension during pregnancy is associated with offspring's elevated blood pressure level already in adolescence. GH may also be associated with unfavourable lipid profile of the offspring.

Low-grade, systemic inflammation in adolescents: association with early-life factors, gender, and lifestyle.

Low-grade, systemic inflammation is related to increased risk of cardiovascular disease in adults. The proinflammatory state tracks from adolescence to adulthood. Identifying correlates of inflammation in adolescents could provide opportunities to prevent cardiovascular disease in adulthood. However, population-based data on correlates of inflammation in adolescence are limited. Therefore, the authors studied the associations of early-life factors, gender, and lifestyle with inflammation (measured by high-sensitivity C-reactive protein and leukocyte count) at age 16 years (2001-2002) in the prospective, population-based Northern Finland Birth Cohort 1986 Study (n = 5,240). In females, being born small for gestational age and current use of oral contraceptives were associated with the proinflammatory state. The association of birth size with inflammation was not observed in males. In logistic regression analyses, oral contraceptive use (odds ratio (OR) = 2.83), abdominal obesity (OR = 5.17), and smoking (OR = 2.72) were associated with elevation of both inflammation markers in females; abdominal obesity (OR = 5.72) and smoking (OR = 2.02) were associated in males. Thus, females appear more susceptible to the adverse effects of being born small for gestational age than males. Given the widespread use of oral contraceptives and the potential pathophysiologic consequences of the proinflammatory state, the association of oral contraceptive use with inflammation in adolescence may have public health implications.

Validation of the Hemo_Control instrument for determination of B-haemoglobin concentration in primary health care.

OBJECTIVE: The aim of this study was to evaluate the analytical performance of a new portable haemoglobinometer, Hemo_Control (EKF-diagnostic, GmbH, Germany), which measures haemoglobin concentration in venous and capillary samples. METHOD: The within series and between series imprecision of the Hemo_Control instrument were calculated after measuring the concentration of venous samples under standardized conditions; by experienced laboratory technicians in a hospital laboratory, and venous and capillary samples under conditions similar to where the instrument is intended for use; by personnel at two primary health care centres. The bias of the Hemo_Control instrument was calculated as the difference between its results and results obtained with a Coulter LH 750 instrument traceable to the ICSH reference method. RESULTS: The uncertainty of the Hemo_Control instrument for venous samples was lower than the quality goal of +/- 5% considered acceptable for patient care. High within series imprecision (5.5%) was observed for measurements of capillary blood samples in one of the primary care centres, whereas adequate analytical performance was obtained at the other centre. The Hemo_Control instrument showed negligible bias of +0.8 g/L for both venous and capillary samples in primary health care. CONCLUSION: The observed uncertainty indicates that Hemo_Control is appropriate for near patient testing using venous samples. Capillary samples may be used if sampling skills are adequate.

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.

Cardiovascular risk factors in adolescents born preterm.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

PP083. Maternal pre-eclampsia and bone mineral density of the adult offspring.

INTRODUCTION: Preterm birth at very low birth weight (VLBW; <1500g) is associated with cardiometabolic risk factors and reduced bone mineral density (BMD) in the adult offspring. Pre-eclampsia (PE) is a frequent cause of preterm birth and is also associated with cardiometabolic risk factors in the offspring. Whether it is associated with BMD is not known. OBJECTIVE: To study BMD in adult offspring of mothers with pre-eclampsia. METHODS: We studied participants of the Helsinki Study of Very Low Birth Weight Adults: 144 born at VLBW and 139 born at term. From the VLBW and term offspring a respective 32 and 11 were born from pregnancy complicated by preeclampsia. We measured BMD at age 18-27 years by dual X-ray absorptiometry. We express BMD in Z scores which indicate the difference in SD units from the value expected for sex and age. RESULTS: VLBW adults exposed to maternal pre-eclampsia had higher lumbar spine Z score (mean -0.44 SD units, compared to -1.07 in unexposed VLBW adults, p=0.002) and femoral neck Z score (-0.05 vs. -0.53, p=0.003). Corresponding Z scores for those born at term were -0.02 (PE) and -0.45 (no PE) for lumbar spine (p=0.2), 0.78 and 0.08 for femoral neck (p=0.02). The Table shows mean differences after adjustment for offspring current body size and potential confounders. CONCLUSIONS: Young adults exposed to maternal PE have higher BMD than those not exposed. This suggests that preeclampsia has a long-term protective effect on offspring bone health.

Preeclampsia, gestational hypertension and subsequent hypothyroidism.

OBJECTIVES: To evaluate the effect of preeclampsia (PE) and gestational hypertension (GH) on subsequent hypothyroidism. Recent studies suggest that women with PE have increased risk for reduced thyroid function, but the association between PE and GH with overt hypothyroidism has not been examined. STUDY DESIGN: Two prospective population-based cohort studies, the Northern Finland Birth Cohorts 1966 and 1986, followed women who had PE (N=955), GH (N=1449) or were normotensive (N=13531) during pregnancy. Finnish national registers were used to confirm subsequent hypothyroidism. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) estimated hypothyroidism risk when comparing women with PE or GH with normotensive women. MAIN OUTCOME MEASURES: Primary hypothyroidism during follow-up of 20-40 years. RESULTS: The subsequent prevalence of hypothyroidism was higher among women with PE (4.0%) and GH (4.5%) compared with normotensive women (3.5%), but the risk increase was not significant (aHR for PE 1.13, 95%CI 0.80-1.59 and aHR for GH 1.11, 95%CI 0.85-1.45). Subgroup analysis among nulliparous women revealed a significant association between late PE and subsequent hypothyroidism (aHR 1.82, 95%CI 1.04-3.19). Early or recurrent PE were not associated with hypothyroidism (aHR 0.93, 95%CI 0.46-1.81 and aHR 1.35, 95%CI 0.63-2.88, respectively). CONCLUSIONS: Overall, PE or GH during pregnancy was not significantly associated with subsequent hypothyroidism in Finnish women after 20-40 years of follow-up. However, late PE in nulliparous women was associated with a 1.8-fold increased risk of subsequent hypothyroidism, a finding that merits further study in other populations.

Prepregnancy overweight and gestational diabetes as determinants of subsequent diabetes and hypertension after 20-year follow-up.

CONTEXT: Overweight is a strong risk factor for gestational diabetes (GDM), and both states indicate increased risk for subsequent metabolic syndrome. Data separating effects of overweight and GDM on risk for metabolic diseases are limited. OBJECTIVE: The aim of the study was to evaluate prepregnancy overweight and GDM as determinants of risk for subsequent diabetes and hypertension. DESIGN: Population-based data from the Northern Finland Birth Cohort 1986 were compounded with register-based data on diagnosis of diabetes and hypertension. SETTING: The study was conducted in Northern Finland. PARTICIPANTS: We studied: 1) normal-weight women with GDM (n = 70); 2) overweight women with GDM (n = 54); 3) normal-weight (n = 768) and 4) overweight (n = 250) women with risk factors for GDM but normal oral glucose tolerance test results; and 5) women with no risk factors for GDM (n = 5341). MAIN OUTCOME MEASURES: We measured cumulative incidence of diabetes and hypertension, hazard ratio (HR), and population-attributable fraction (PAF) for determinants of risk. RESULTS: The cumulative incidence of diagnosed diabetes and hypertension in the whole study population was 1.3 and 7.5%, respectively. Concomitant overweight and GDM indicated high risks for diabetes (HR, 47.24; PAF, 15.8%) and hypertension (HR, 9.16; PAF, 4.4%). Even when the OGTT in pregnancy was normal, prepregnancy overweight associated with risks for diabetes (HR, 12.63; PAF, 22.2%) and hypertension (HR, 2.86; PAF, 6.0%). In normal-weight women, GDM indicated risk for diabetes (HR, 10.61; PAF, 5.2%) but not for hypertension. CONCLUSIONS: Prepregnancy overweight is an essential risk factor for subsequent diabetes and hypertension, especially when combined with GDM.