Hypertension is the primary risk factor for cardiovascular disease that constitutes a serious worldwide health concern and a significant healthcare burden. As the majority of hypertension has an unknown etiology, considerable research efforts in both experimental models and human cohorts has focused on the premise that alterations in the fetal and perinatal environment are key factors in the development of hypertension in children and adults. The exact mechanisms of how fetal programming events increase the risk of hypertension and cardiovascular disease are not fully elaborated; however, the focus on alterations in the biochemical components and functional aspects of the renin–angiotensin (Ang) system (RAS) has predominated, particularly activation of the Ang-converting enzyme (ACE)-Ang II-Ang type 1 receptor (AT1R) axis. The emerging view of alternative pathways within the RAS that may functionally antagonize the Ang II axis raise the possibility that programming events also target the non-classical components of the RAS as an additional mechanism contributing to the development and progression of hypertension. In the current review, we evaluate the potential role of the ACE2-Ang-(1–7)-Mas receptor (MasR) axis of the RAS in fetal programming events and cardiovascular and renal dysfunction. Specifically, the review examines the impact of fetal programming on the Ang-(1–7) axis within the circulation, kidney, and brain such that the loss of Ang-(1–7) expression or tone, contributes to the chronic dysregulation of blood pressure (BP) and cardiometabolic disease in the offspring, as well as the influence of sex on potential programming of this pathway.

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals.

Objectives Preterm birth appears to contribute to early development of cardiovascular disease, but the mechanisms are unknown. Prematurity may result in programming events that alter the renin–angiotensin system. We hypothesized that prematurity is associated with lower angiotensin-(1-7) in adolescence and that sex and obesity modify this relationship. Methods We quantified angiotensin II and angiotensin-(1-7) in the plasma and urine of 175 adolescents born preterm and 51 term-born controls. We used generalized linear models to estimate the association between prematurity and the peptides, controlling for confounding factors and stratifying by sex and overweight/obesity. Results Prematurity was associated with lower plasma angiotensin II (β: −5.2 pmol/l, 95% CI: −10.3 to −0.04) and angiotensin-(1-7) (−5.2 pmol/l, 95% CI: −8.4 to −2.0) but overall higher angiotensin II:angiotensin-(1-7) (3.0 95% CI: 0.9–5.0). The preterm–term difference in plasma angiotensin-(1-7) was greater in women (−6.9 pmol/l, 95% CI: −10.7 to −3.1) and individuals with overweight/obesity (−8.0 pmol/l, 95% CI: −12.2 to −3.8). The preterm–term difference in angiotensin II:angiotensin-(1-7) was greater among those with overweight/obesity (4.4, 95% CI: 0.6–8.1). On multivariate analysis, prematurity was associated with lower urinary angiotensin II:angiotensin-(1-7; −0.13, 95% CI: −0.26 to −0.003), especially among the overweight/obesity group (−0.38, 95% CI: −0.72 to −0.04). Conclusion Circulating angiotensin-(1-7) was diminished whereas urinary angiotensin-(1-7) was increased relative to angiotensin II in adolescents born preterm, suggesting prematurity may increase the risk of cardiovascular disease by altering the renin–angiotensin system. Perinatal renin–angiotensin system programming was more pronounced in women and individuals with overweight/obesity, thus potentially augmenting their risk of developing early cardiovascular disease.

A 42-day tapering course of dexamethasone, which was shown previously to decrease the risk of chronic lung disease in very low birth weight infants, does not increase the risk of the composite outcome of death or major neurodevelopmental impairment.

Objective-To determine if postnatal dexamethasone (DEX) exposure affects pulmonary outcomes at school-age in children born with very low birth weight (VLBW).Study design-Follow-up study of 68 VLBW children who participated in a randomized controlled trial (RCT) of postnatal DEX. Pulmonary function was assessed by spirometry. Current asthma status was obtained from a parent.Results-Sixty-eight % of the placebo group had below normal forced expiratory volume in 1 second (FEV 1 ) compared to 40% of the DEX group (X 2 = 4.84, p=.03), with trends for lower forced vital capacity (FVC) and FEV 1 values in the placebo group. Fifty % of placebo group and 34% of DEX group had below normal FEV 1 /FVC (X 2 =1.59; p =.21). Parent-reported prevalence of asthma did not differ between groups. Logistic regression analysis suggested that the positive effects of DEX on pulmonary function at follow-up were mediated in part by shortened postnatal exposure to mechanical ventilation.Conclusions-Postnatal DEX exposure was associated with higher expiratory flow with no adverse effects on pulmonary outcomes at school-age. The prevalence of asthma and impaired pulmonary function underscore the influence of neonatal illness on health at school age, and stress the importance of repeated follow-up examinations of these children. Keywordsprematurity; chronic lung disease; bronchopulmonary dysplasia; children; corticosteroid; lung function asthma Approximately 1.5% of infants are born prematurely each year with very low birth weight (VLBW) (birth weight < 1501 grams) (1), and about 19-23% of these infants will develop chronic lung disease (CLD) (2,3). A diagnosis of CLD has been associated with greater Address correspondence to: Patricia A. Nixon, Ph.D., Wake Forest University, HES Dept. P.O. Box 7868, Winston-Salem, NC 27109-7868, Phone (336) Fax (336) 758-4680, Email nixonpa@wfu.edu. edited by AJ and WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. hospital readmission rates for respiratory morbidity during the first five years of life (4), increased odds of asthma (4) and respiratory symptoms in childhood (5), and reduced pulmonary function in infancy (6), childhood (7,8), adolescence (9), and young adulthood (10) compared to their VLBW peers without CLD. Systematic reviews indicate that treatment of VLBW infants with corticosteroids, primarily dexamethasone (DEX), in the first few weeks of life significantly decreases duration of ventilator dependence and the incidence of CLD (11-13). The beneficial effects of postnatal corticosteroids on the lung are believed to be related to reduce...