Impaired Intrauterine Growth Research Articles

Exposure to maternal gestational diabetes is associated with higher cardiovascular responses to stress in adolescent indians.

Context:Altered endocrinal and autonomic nervous system responses to stress may link impaired intra-uterine growth with later cardiovascular disease.Objective:To test the hypothesis that offspring of gestational diabetic mothers (OGDM) have high cortisol and cardiosympathetic responses during the Trier Social Stress Test for Children (TSST-C).Design:Adolescents from a birth cohort in India (n = 213; mean age, 13.5 y), including 26 OGDM, 22 offspring of diabetic fathers (ODF), and 165 offspring of nondiabetic parents (controls) completed 5 minutes each of public speaking and mental arithmetic tasks in front of two unfamiliar “evaluators” (TSST-C). Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Heart rate, blood pressure (BP), stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the test using a finger cuff; the beat-to-beat values were averaged for these periods.Results:Cortisol and cardiosympathetic parameters increased from baseline during stress (P < .001). OGDM had greater systolic BP (mean difference, 5.6 mm Hg), cardiac output (0.5 L/min), and stroke volume (4.0 mL) increases and a lower total peripheral resistance rise (125 dyn · s/cm5) than controls during stress. ODF had greater systolic BP responses than controls (difference, 4.1 mm Hg); there was no difference in other cardiosympathetic parameters. Cortisol responses were similar in all three groups.Conclusions:Maternal diabetes during pregnancy is associated with higher cardiosympathetic stress responses in the offspring, which may contribute to their higher cardiovascular disease risk. Further research may confirm stress-response programming as a predictor of cardiovascular risk in OGDM.

Maternal behavior and infant physiology during feeding in premature and term infants over the first year of life.

Little is known about the relationship between maternal behavior and the stability of premature infants' physiologic responses during feeding. In a secondary data analysis, we examined relationships between quality of maternal behavior and cardiorespiratory physiology during feeding in 61 premature and 53 term infants at four times over the first year of life. Measures included heart rate (HR), respiratory rate (RR), and oxygen saturation; Child Feeding Skills Checklist; and Parent-Child Early Relational Assessment. Birthweight, gestational age, and neurodevelopmental risk were covariates. Quality of maternal behavior did not predict infants' physiologic response to feeding. However, birthweight was related to infant feeding physiology among all infants over the first year of life. Stress during fetal life, which may lead to impaired intrauterine growth and low birthweight, may have longitudinal effects on cardiorespiratory functioning of premature infants. Research is needed to further investigate the biological pathways by which maternal-infant interaction supports behavioral and physiologic feeding outcomes of premature infants.

Reduced telomere length is not associated with early signs of vascular aging in young men born after intrauterine growth restriction: a paradox?

The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with early signs of vascular aging and whether telomere length could be a biomarker of this pathway. One hundred and fourteen healthy young men born SGA or after normal pregnancy [appropriate for gestational age (AGA)] were enrolled. Patient data were gathered from questionnaires and clinical exams, including blood pressure (BP) measurement routine laboratory analyses, and carotid intima-media thickness (cIMT). Leukocyte telomere length (LTL) was assessed by quantitative PCR. Birth data were obtained from medical records. The SGA group had significantly higher pulse pressure and cIMT, and a trend to increased SBP and heart rate in comparison to the AGA group. Interestingly, SGA men exhibited a 42% longer LTL than the AGA group. LTL was inversely associated with age, BMI, BP and birth parameters. In multiple regression analysis, BMI was the key determinant of SBP and cIMT. Young men born SGA show early signs of vascular aging. Unexpectedly, in our cohort, the SGA group had longer telomeres than the normal controls. Although longer telomeres are predictive of better health in the future, our findings could indicate a faster telomere attrition rate and probable early onset of cardiovascular risk in SGA participants. Follow-up of this cohort will clarify hypothesis and validate telomere dynamics as indicators of future health risks.

Sexual Dimorphism of Neonatal Lung Development

Gender differences in overall neonatal survival and in short term pulmonary outcome have been reported. Furthermore gender differences in childhood chronic lung disorders have been described all in favor of females. A typical survey on published data regarding gender differences in lung development has been carried out. 1. Structural aspects of lung development: Lung development is regulated by a number of genes, being differently active in the terminal saccular and alveolar period. Gender differences have been described among others for regulation of vascular-endothelial and platelet derived growth factors (VEGF) and platelet-derived growth factor (PDGF), which are active during early lung development with a permissive effect of estrogens mediated by estrogen receptor beta (ER-β). 2. Functional aspects of lung development: Functional components of lung development mainly include surfactant synthesis. Regulation of surfactant protein synthesis was shown to be positively regulated by estrogens, thus favoring lung maturation in females. 3. Lung development and pregnancy complications: Inflammatory alterations induced by LPS lead to larger lung volumes under experimental conditions in females, whereas pulmonary prognosis after impaired intrauterine growth is not affected as clearly by gender. Epidemiological findings indicating an impaired male prognosis in neonatal lung disorders which can at least in part be explained by above described experimental findings. Increased estrogen concentrations in females acting via ER-β may be a key for understanding these findings.

Neonatal Aspects: Is There Continuity?

ABSTRACT During the 9 months between conception and birth, the fetal brain is transformed from instructions in genes to a complex, highly differentiated organ. The human central nervous system (CNS) changes from a microscopic band of embryonic neuroblasts to a 350 gm mass with more than 109 interconnected highly differentiated neurons in the cortex alone. How this extraordinary growth results in sensomotor, cognitive, affective and behavioral development is still unexplored. The development of voluntary, cognitive and purposive activity from fetal to neonatal period is to analyze the developmental transformations of the brain expressed by development of movement patterns from prenatal through postnatal period. As the development of the brain is unique and continuing process throughout the gestation and after birth, it is expected that there is also continuity of fetal to neonatal movements which are the best functional indicator of developmental processes of the brain. Concerning the complexity, voluntary control and stereotype, there are at least four groups of movements: Reflexes, fixed action patterns, rhythmic motor patterns, and directed movements. Substantial indications suggest that spontaneous activity is a more sensitive indicator of brain dysfunction than reactivity to sensory stimuli in reflex testing. It was proved that assessment of general movements in high-risk newborns has significantly higher predictive value for later neurological development than neurological examination. Nutritional stress at critical times during fetal development can have persistent and potentially irreversible effects on organ function. Impaired intrauterine growth and development may antecede insufficient postnatal growth. Thus, it may be a marker of impaired central nervous system integrity because of adverse intrauterine conditions. Unfavorable intrauterine environment can affect adversely fetal growth. There is an association between postnatal growth and neurodevelopmental outcome. Concerning the continuity from fetus to neonate in terms of neurobehavior, it could be concluded that fetus and neonate are the same persons in different environment. While in the womb, fetus is protected from the gravity which is not so important for its neurodevelopment, postnatally the neonate is exposed to the gravity during the labor and from the first moments of autonomous life. Development of motor control is highly dependent on antigravity forces enabling erect posture of infant or young child. These environmental differences should be kept on mind during prenatal as well as postnatal assessment. How to cite this article Stanojevic M. Neonatal Aspects: Is There Continuity? Donald School J Ultrasound Obstet Gynecol 2012;6(2):189-196.

Coronary Flow in Neonates with Impaired Intrauterine Growth

Subclinical myocardial injury has been reported in newborns with fetal weights < 2 SDs for gestational age. Intrauterine growth restriction might affect cardiac function and coronary flow (CF). Seventeen newborns with intrauterine growth restriction and 15 age-matched healthy controls were enrolled in the study. Blood flow in the umbilical artery and maternal uterine artery was assessed using Doppler velocimetry. Cardiac function and left anterior descending coronary artery CF were measured using transthoracic Doppler echocardiography at 1 week of age. The mean growth deviation of the newborns from normal was -2.5 ± 0.2 SDs. Percentage left ventricular shortening fraction was 39 ± 4.3% in patients and 42 ± 4.1% in controls (P= .40), and the mean left ventricular mass index was 86.6 g/m(2) in patients and 73.7 g/m(2) in controls (P < .01). The mean left anterior descending coronary artery diameter was 0.99 ± 0.1 mm in patients and 0.8 ± 0.1 mm in controls (P= .002). The left anterior descending coronary artery flow velocity-time integral was correlated with left ventricular mass index (r= 0.31, P= .007) and with mitral peak E/A ratio (r= 0.74, P= .01). Intrauterine growth restriction was associated with increased peak flow velocity in diastole (34.5 ± 4 vs 19 ± 6 cm/sec in controls, P= .0001), as well as increased CF (37 ± 7.3 vs 8.2 ± 3.0 mL/min in controls, P= .001). CF is significantly increased in neonates with impaired intrauterine growth. Left ventricular mass index is increased, but systolic and diastolic function remains normal. The clinical significance of increased CF is unclear, but it might lead to decreased CF reserve.

Insulin resistance and epigenetic regulation: insights from human studies and prospects for future research.

In this study, we review the current knowledge and recent insights on the role of epigenetic factors in the development of human insulin resistance (IR)- and metabolic syndrome (MS)-related phenotypes, and attempt to lay a framework to consider IR as a potentially reversible incapacity to control metabolic homeostasis that is strongly influenced by the interplay between external and internal cues. We summarize the evidence on how tissue-specific epigenetic markers participate either by activating or repressing the gene expression programs to modulate IR- and MS-associated traits. Some additional data are provided about how the exploration of DNA methylation markers in peripheral blood mononuclear cells potentially offers appealing information about the impact of epigenetics in the pathogenesis of IR. Clues about the relation between IR and impaired intrauterine growth explained by fetal metabolic programming and epigenetic modifications are shown, including novel findings about the impact of histone modifications. For instance, we observed that specific epigenetic factors in genes associated with mitochondrial biogenesis may be associated with birth weight. Furthermore, some prospective ideas about the functional consequences of genetic variation modulated by allele-specific epigenetic markers and its impact on MS susceptibility are also illustrated. Finally, we summarize the current knowledge of epigenetics as the biological rationale for potential therapeutic intervention in IR and MS.

Coronary Flow in Neonates with Impaired Intrauterine Growth

Background: Subclinical myocardial injury has been reported in newborns with fetal weight below 2 standard deviations for gestational age. Our aim was to investigate whether impaired intrauterine growth affects cardiac function and coronary flow (CF). Subjects and Methods: Seventeen newborns with impaired intrauterine growth and fifteen age-matched healthy controls were enrolled in the study. Fetal growth was assessed by fetometry. Doppler velocimetry of the umbilical artery and maternal uterine arteries blood flow was assessed. Cardiac function and left anterior descending artery (LAD) coronary flow were measured by transthoracic Doppler echocardiography at one week of age. Results: The mean growth deviation of the newborns from normal was -2.5± 0.2SD. The left ventricular mass and left ventricular shortening fraction was similar in patients and controls. The mean LAD diameter was 0.99±0.1 mm in patients and 0.8±0.1 in controls, p=0.002. LAD flow velocity time integral (VTI)/min correlated with left ventricular mass (R = 0.46, p=0.0001) and with mitral peak E-wave velocity (R = 0.74, p< 0.01). Impaired intrauterine growth was associated with increased peak flow velocity in diastole; 34.5±4 cm/s and 19±6 cm/s in controls, p = 0.0001 as well as increased CF; 37±7.3 ml/min and 8.2±3.0 ml/min in controls, p = 0.001. Conclusions: Coronary flow is significantly increased in neonates with impaired intrauterine growth. The left ventricular mass and systolic and diastolic functions remain normal. The clinical significance of the increase of CF is unclear but increased basal flow might lead to a decreased coronary flow reserve.

632 Cardiac Evaluation of Neonates with Impaired Intrauterine Growth

Background and aims. We investigated the relationship between the cardiac function and coronary flow in neonates with impaired intrauterine growth.Methods. Fetal growth was assessed by fetometry and Doppler velocimetry of the umbilical artery blood flow. Impaired fetal growth was defined as an estimated fetal weight less than mean -2SD from the normal gestational age related fetal weight. Cardiac function and left anterior descending artery (LAD) flow parameters were measured by transthoracic Doppler echocardiography in 14 newborns at one week of age when the ductus arteriosus was closed. Gestational age- and age-matched healthy newborns, appropriate for gestational age (N=15) served as controls.Results. The mean pulsatility index was 0.97 and the mean birth weight 2.2 (range 2.1 to 2.4) kg. The left ventricular shortening fraction was normal 39±4.3%. Aortic velocity time integral/minute as a measure of systolic LV function correlated to LAD PFVd, r=0.54, p< 0.0001. LAD peak flow velocity in diastole (PFVd) correlated to left ventricular mass (r=0.46, p=0.0001). The mean LAD diameter was 0.99±0.09 mm. Impaired intrauterine growth was associated with an increase of PFVd (mean 34.5±4, controls 19±6 mm/s, p=0.0001) and coronary flow (7.3±2, and 4.8±2 ml/min respectively, p=0.04). LAD velocity time integral per minute correlated to mitral peak E-wave (r=0.74, p< 0.01).Conclusions. Basal coronary flow and peak flow velocity appear to be significantly increased in these neonates with intrauterine growth impairment, which leads to decreased coronary flow reserve. LAD flow parameters were linearly related to LV systolic and diastolic functions and to LV mass.

Intrauterine Growth Patterns in Fetal Gastroschisis

The objective of this study was to evaluate patterns of intrauterine growth in fetal gastroschisis. This was a retrospective review of prenatally diagnosed cases of fetal gastroschisis delivered at the University of North Carolina Hospital from January 2000 to January 2007. Fetal growth (biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight) and amniotic fluid volume were evaluated by gestational age. Gastroschisis was diagnosed in 83 pregnancies; outcomes were available in 71 fetuses. The mean gestational age at diagnosis was 17 weeks and 1 day. The mean gestational age at delivery was 35 weeks and 4 days. Mean birth weight was 2306 g. As early as the second trimester, all morphometric measures demonstrated impaired in utero growth, with growth curves shifted to the right of the 50th percentile when compared with a standard population. Estimated fetal weight below the 10th percentile was suspected in 23% of pregnancies, and birth weight at less than the 10th percentile occurred in 47% of neonates. Amniotic fluid volumes remained stable throughout gestation. Fetuses with gastroschisis display impaired intrauterine growth, which is noted in the midsecond trimester of pregnancy and does not appear to progress throughout gestation.

Effect of Exposure to Selective Serotonin Reuptake Inhibitors In Utero on Fetal Growth: Potential Role for the IGF-I and HPA Axes

To investigate the possible effect of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) on somatic growth and on hormones of the hypothalamic-pituitary-adrenal (HPA) and insulin-like growth factor (IGF)-I axes, we compared the anthropometric parameters and hormonal profile of 21 SSRI-exposed infants and 20 matched controls. The SSRI group was characterized by lower crown-heel length (p < 0.01), smaller head circumference (p = 0.08), and higher percentage of infants with birth weight, birth length, and head circumference below the 10th percentile (p < 0.045, p = 0.08, p < 0.04, respectively), in addition to a significantly lower cord blood level of cortisol (p < 0.03) and higher level of thyroid-stimulating hormone (TSH) (p < 0.004). Infants exposed to citalopram had a lower cord blood IGF-I level than infants exposed to paroxetine (p < 0.001) and controls (p < 0.003). Placental IGF-I receptor (IGF-IR) expression was significantly higher in the SSRI group than in controls (p < 0.01). Urine 5-hydroxyindoleacetic acid (5-HIAA) level was negatively correlated with birth weight (r = -0.71, p < 0.025) and with dehydroepiandrosterone (DHEA) level (r = -0.71, p < 0.025). The Finnegan score was correlated with dehydroepiandrosterone sulfate (DHEAS) (r = 0.8, p < 0.005) and cortisol (r = 0.62, p = 0.05). Fetal exposure to SSRIs causes impaired intrauterine growth accompanied by alterations in the IGF-I and HPA axes. The findings may raise concern regarding maternal use of SSRIs during pregnancy.

Birth weight and adult lung function: a within-pair analysis of twins followed up from birth

The aim of the study was to evaluate whether there is any association between intrauterine growth and later lung function or bronchial reactivity in early adulthood in line with Barker's hypothesis. Nineteen twin pairs with disproportionate intrauterine growth pattern were followed up from birth: either one of the pairs had intrauterine growth retardation (birth weight <2 SD) or the within-pair birth weight difference was >1.3 SD. Flow-volume spirometry, followed by isocapnic hyperventilation of cold air, was performed at the ages of 8-16 and 14-22 years in 1993 and 1999. Wilcoxon's matched-pairs analysis was used to compare smaller and larger twin pairs. In 1993, there were no significant differences between the groups in either spirometry or cold air challenge. In 1999, such a difference was found in forced expiratory volume % (FEV%) and forced expiratory flow (FEF) at 25%-75%, the smaller twin pairs having lower values. In 1993, nine subjects reacted to cold air (>9% decrease in FEV in 1 second). In 1999, only four subjects reacted to cold air, and they all belonged to the group of smaller twins (P=0.04). Lung function evaluated by FEV% and FEF25-75 was lower and responses to cold air were more common at the median age of 16 years in twins with impaired intrauterine growth.

Epidemiology, genes and the environment: lessons learned from the Helsinki Birth Cohort Study

Nonoptimal growth during fetal life and infancy is associated with an increased risk of coronary heart disease and type 2 diabetes later in life. This early pattern of growth is associated with an increased disease risk especially when followed by a relative gain in body size later in childhood. Genetic factors are closely involved in growth and disease pathogenesis and gene-early life environmental interactions will be described affecting adult health outcomes. This overview will primarily focus upon findings from the Helsinki Birth Cohort Study consisting of 15846 subjects born 1924-1944 on whom growth data and information on adult health are available.

The global increase in diabetes: Unique issues for mothers and children

It is now well documented that obesity and diabetes mellitus (DM) are increasing globally in epidemic proportions across all age groups. As a result, type 2 DM is for the first time being seen frequently in children and young adults in many populations. An increase in the incidence of gestational diabetes mellitus (GDM) has also been well documented in Australia and the United States, and there are some data suggesting the same trend in India. However, universal screening for GDM is not practiced in many areas of the world, making it difficult to estimate its true prevalence. The increase in type 2 DM in youth has implications beyond the burgeoning number of persons affected. First, the younger the patient at onset of disease, the greater is the lifetime risk of developing complications of diabetes and/or cardiovascular disease. Secondly, intrauterine exposure to the metabolic environment of maternal diabetes, or GDM, is associated with increased risk of obesity and altered glucose homeostasis (impaired fasting glucose, impaired glucose tolerance and type 2 DM) in the offspring, beginning in childhood and probably reflected in more GDM in the next generation as well. In addition, impaired intrauterine growth (undernutrition) is associated with a similar childhood phenotype and similar adult chronic disease risks. Thus, alterations in the intrauterine metabolic environment may be important contributing factors to the ongoing epidemics of obesity and type 2 diabetes.

Intrauterine environmental and genetic influences on the association between birthweight and cardiovascular risk factors: studies in twins as a means of testing the fetal origins hypothesis

Evidence has accumulated that low birthweight is associated with several risk factors for cardiovascular disease. However, it is not known whether or not these associations are due to a programmed response to intrauterine malnutrition or genetic factors influencing both birthweight and cardiovascular risk factors. Twin studies offer a unique opportunity to distinguish between intrauterine and genetic origins of the association between birthweight and cardiovascular risk. In our twin cohort, low birthweight was associated with insulin resistance, lower HDL and shorter height within both dizygotic and monozygotic twin pairs, suggesting that these associations are, at least in part, independent of genetic factors. In contrast, low birthweight was associated with blood pressure, total and LDL cholesterol, fibrinogen and sympathetic activation within dizygotic twin pairs, but not within monozygotic twin pairs. These differences between dizygotic and monozygotic twins suggest that these associations are, at least in part, due to genetic factors. Therefore, both intrauterine environmental and genetic factors appear to play a role in the association between birthweight and cardiovascular risk factors. In the future, strategies may be developed targeted at improving or preventing impaired intrauterine growth. However, the effects of interventions that comprise changes in environment within the normal range may be limited due to the possible important role of genetic factors.

Energy restriction initiated at different gestational ages has varying effects on maternal weight gain and pregnancy outcome in common marmoset monkeys (Callithrix jacchus)

With relatively high fertility and short lifespan, marmoset monkeys (Callithrix jacchus) may become useful primate models of prenatal nutritional effects on birth condition and adult disease risk. The present study determined the effects of energy restriction to 75% of expected ad libitum consumption during mid- (day 66) or late (day 99) gestation on maternal weight, fetal growth and pregnancy outcomes in this species. Mid-restriction reliably induced the loss of pregnancy before term, at 92 d, on average. Of the late-restricted pregnancies, four of seven were normal term length while three were preterm deliveries, at 101, 117 and 132 d. Control females had a mean mid-pregnancy weight gain of 0.67 g/d while mid-restricted females lost -0.65 g/d, on average. Control pregnancies averaged a 1.06 g/d gain during late pregnancy, while energy-restricted females lost -0.67 g/d, on average. Restriction-related weight change was highly variable, ranging from +0.55 to -2.56 g/d for mid-restriction pregnancies and from +0.79 to -3.91 g/d for late-restriction pregnancies. For mid-restriction pregnancies, the number of restriction days was best explained by linear weight change and total weight loss while the number of restriction days in late pregnancy was best explained by linear weight change alone. In late-restriction pregnancies, smaller females had higher daily weight losses. Restrictions did not induce litter-size reduction or growth restriction in those infants that were delivered at term but the size of aborted fetuses suggested that at least some pregnancies lost preterm may have involved impaired intra-uterine growth.

Glucose and Insulin Metabolism in Twins: Influence of Zygosity and Birth Weight

AbstractSeveral epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake — indicating glucose intolerance and insulin resistance — among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.

Glucose and insulin metabolism in twins: influence of zygosity and birth weight.

Several epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.

Gestational age and arterial characteristics at 29 years of age in the Atherosclerosis Risk in Young Adults (ARYA) study.

P28 Background: Several studies have indicated that prenatal condition may affect cardiovascular risk factors and thereby risk of cardiovascular morbidity and mortality. Based on these findings it has been suggested that impaired intra-uterine growth leads to increased risk of atherosclerosis. Data directly relating prenatal factors to vascular changes are limited and restricted to older individuals. In the ARYA study we evaluated whether birth characteristics are associated with subclinical atherosclerosis in young adults. Methods: The ARYA-study is a cohort study of 750 men and women aged 27-30 years. Information on birth characteristics (gestational age, birth weight, birth length) was obtained from the municipal health service medical files. At baseline, information on cardiovascular risk factors was obtained by questionnaire and measurements during two visits at the research centre. Arterial characteristics were non-invasively assessed by measuring common carotid intima-media thickness (CIMT) at both carotid arteries and by measuring aortic stiffness by pulse wave velocity (PWV). At present, data on 204 subjects are available for analysis. Linear regression analysis was applied and results are adjusted for age, gender, smoking and family history. Results: This sub-analysis comprised of 204 young adults (47% men) with a mean age of 29.2 (0.5). Mean gestational age was 39.8 (1.8) weeks, birth weight 3420 (539) gram, birth length 51.0 (2.5) cm, CIMT 0.51 (0.05) mm and mean PWV 6.2 (1.0) m/s. With increasing gestational age (in weeks), CIMT decreased with 0.006 mm [CI: -0.010, -0.002], whereas PWV decreased with 0.112 m/s [CI: -0.217, -0.008]. These associations were independent of birth weight. Conclusion: This preliminary analysis of the ARYA-study indicates that decreased gestational age relates to subclinical atherosclerosis already in young adulthood.

Fetal nutrition and adult disease

Recent research suggests that several of the major diseases of later life, including coronary heart disease, hypertension, and type 2 diabetes, originate in impaired intrauterine growth and development. These diseases may be consequences of "programming," whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology, and metabolism. Evidence that coronary heart disease, hypertension, and diabetes are programmed came from longitudinal studies of 25,000 UK men and women in which size at birth was related to the occurrence of the disease in middle age. People who were small or disproportionate (thin or short) at birth had high rates of coronary heart disease, high blood pressure, high cholesterol concentrations, and abnormal glucose-insulin metabolism. These relations were independent of the length of gestation, suggesting that cardiovascular disease is linked to fetal growth restriction rather than to premature birth. Replication of the UK findings has led to wide acceptance that low rates of fetal growth are associated with cardiovascular disease in later life. Impaired growth and development in utero seem to be widespread in the population, affecting many babies whose birth weights are within the normal range. Although the influences that impair fetal development and program adult cardiovascular disease remain to be defined, there are strong pointers to the importance of the fetal adaptations invoked when the maternoplacental nutrient supply fails to match the fetal nutrient demand.