Prenatal growth and early postnatal influences on adult motor cortical excitability.

OBJECTIVE: Suboptimal prenatal growth may adversely influence motor neurophysiologic development and predispose the individual to greater risk of neurodegenerative disorders in later life. We investigated the influences of prenatal growth and the postnatal environment on motor cortical function in young adults. METHODS: Transcranial magnetic stimulation was used to construct corticospinal stimulus-response curves for 35 young adults (mean age: 28 +/- 0.5 years; 19 males) born >or=37 weeks' gestation. Birth weight centile was calculated relative to maternal size, parity, ethnicity, gender, and gestation. Handgrip strength and dexterity were measured separately. Regression analyses assessed the influence of prenatal (birth weight centile and gestation) and postnatal (socioeconomic indices and maternal education) factors on corticospinal parameters, strength, and dexterity scores. RESULTS: Lower birth weight was associated with increased interhemispheric asymmetry in motor threshold and increased cortical stimulus-response curve slope. A shorter gestation predicted a larger area under this curve in the right hand. High motor threshold was predicted by greater environmental adversity in early postnatal life, but not by prenatal factors. Higher birth weight centile and lower motor threshold were associated with greater educational achievement. CONCLUSIONS: Poor in utero growth and mild prematurity are associated with altered corticospinal excitability in adulthood. An early postnatal environment with less early postnatal socioeconomic disadvantage and having a mother with a completed high school education partly ameliorates this. While altered cortical development has some functional consequences already evident in early adulthood, it may have a later, additional adverse impact on aging-related changes in motor function.

Gender differences in the relationship between leptin, insulin resistance and the autonomic nervous system.

OBJECTIVES: Leptin, an important hormonal regulator of body weight, has been shown to stimulate the sympathetic nervous system (SNS) in vitro although the physiological relevance remains unclear. Increased SNS activity has been implicated in the pathogenesis of insulin resistance and an increased cardiovascular risk. We have therefore investigated the relationship between leptin, insulin resistance and cardiac autonomic activity in healthy young adults. 130 healthy men and women age 20.9 years were studied. Insulin sensitivity was assessed using the IVGTT and minimal model with simultaneous measures of leptin. Cardiac autonomic activity was assessed using spectral analysis of heart rate variability. RESULTS: Women showed significantly higher fasting leptin, heart rate and cardiac sympathetic activity, and lower insulin sensitivity. Men showed inverse correlations between insulin resistance and heart rate, and between insulin resistance and cardiac sympatho-vagal ratio. Women, in contrast, showed no SNS relationship with insulin resistance, but rather an inverse correlation between leptin and the sympatho-vagal ratio, suggesting that leptin in women is associated with SNS activity. The correlation remained significant after adjustment for BMI and waist-to-hip ratio (beta=-0.33 and p=0.008). CONCLUSION: Insulin resistance and SNS activity appear to be linked, although the relationship showed marked gender differences, and the direction of causality was unclear from this cross-sectional study. Leptin appears to exert a greater effect on the SNS in women, possibly because of their greater fat mass.

A common mitchondrial DNA variant is associated with thinness in mothers and their 20-yr-old offspring.

A common mitochondrial (mt)DNA variant that is maternally inherited, the 16189 variant, is associated with type 2 diabetes and thinness at birth. To elucidate the association of the variant with thinness, we studied the 16189 variant in a well-characterized Australian cohort (n = 161) who were followed up from birth to age 20 yr. PCR analysis and mtDNA haplotyping was carried out on DNA from 161 offspring from consecutive, normal, singleton pregnancies followed from birth to age 20 yr. The 16189 mtDNA variant was present in 14 of the 161 20 yr olds (8.7%). Both the mothers with the 16189 variant and their 20-yr-old offspring were thinner than those without. Median (interquartile range) BMI was 21.9 kg/m(2) (20.4 to 22.9) in mothers with the variant compared with 23.5 (21.4 to 26.6) in those without (P = 0.013) and 22.2 (21.1 to 23.8) in 20 yr olds with the variant compared with 22.7 (20.8 to 25.6) in those without (P = 0.019). The 16189 variant was also associated with a high placental weight and high placental-to-birth weight ratio (P = 0.051 and P = 0.0024, respectively). Insulin sensitivity was normal in 20 yr olds with the 16189 variant. This contrasts with 20 yr olds who did not have the variant but who had been thin or small at birth and who had normal BMI and normal placental-to-birth weight ratio, but were insulin resistant. This study suggests that the 16189 mtDNA variant is associated with maternally inherited thinness in young adults. This may be mediated by effects on mtDNA replication and, thence, placental function. Further research is required to confirm these hypotheses.

Size at birth and cardiovascular responses to psychological stressors: evidence for prenatal programming in women.

BACKGROUND: Epidemiological studies have repeatedly shown inverse associations between size at birth and blood pressure in later life. There is some evidence to suggest that exaggerated blood pressure responses to psychological stressors are a forerunner of sustained hypertension. OBJECTIVE: To determine whether individuals who were smaller at birth have greater blood pressure and heart rate responses to psychological stressors. DESIGN: Prospective cohort study. METHODS: A total of 104 men and 79 women (mean age 26.3 years) were recruited from the Adelaide Family Heart Study cohort. Blood pressure was monitored continuously throughout the study using a Portapres and participants undertook a series of three stress tests: Stroop, mirror drawing and public speech. The stress response was defined as the increment from baseline to the mean blood pressure during the three tasks. RESULTS: In women, a 1 kg increase in birthweight was associated with an 8.7 mmHg (95% confidence interval: 3.6-13.8, P = 0.001) reduction in the systolic and a 4.1 mmHg (1.6-6.6, P = 0.002) reduction in the diastolic response to stress. The heart rate response to stress was also inversely related to birthweight. These results remained significant after correction for gestational age and other potential confounding factors. Similar results were found for birth length and head circumference. There were no such relationships in men. CONCLUSIONS: This study provides the first human evidence that cardiovascular responses to psychological stressors may be programmed antenatally and suggests a potential mechanism linking reduced fetal growth with raised blood pressure and cardiovascular disease in later life.