Young adults with a very low birth weight have higher indexes of insulin resistance and glucose intolerance and higher blood pressure than those born at term.

Respiratory distress syndrome (RDS) and development of bronchopulmonary dysplasia (BPD) are characterized by endothelial cell damage. Persistent pulmonary hypertension of the newborn (PPHN) is a disorder that alters the pulmonary microvasculature. Immunohistochemistry for VEGFA(165), an endothelial cell mitogen, and its receptor Flt-1, was performed on lung tissues from autopsies from four fetuses, three preterm infants, four term infants without primary lung disease, four infants with BPD, and four infants with PPHN. VEGF was measured in tracheal aspirates from 31 preterm infants, 5 intubated term infants without primary lung injury, and 12 infants with PPHN during the first 10 postnatal days, and from 8 infants with BPD. Immunohistochemistry for VEGF and Flt-1 was similar in fetuses, preterm infants, and term infants: for VEGF mostly in bronchial epithelium and alveolar macrophages, and for Flt-1 mostly in vascular endothelial cells and bronchial epithelial cells. In patients with BPD, and PPHN, staining for VEGF and Flt-1 appeared also in Type II pneumocytes. Preterm infants with more severe RDS had lower VEGF than those who recovered. The persistent expression of VEGF and Flt-1 during the fetal and neonatal period supports a physiological role for VEGF in human lung development. The lower pulmonary VEGF in preterm infants with more severe RDS may contribute to the pathophysiology of the acute lung injury. In BPD, the expression of VEGF in alveolar epithelium may represent a compensatory increase after the acute phase of the lung disease. In PPHN, that more cell types express VEGF and Flt-1, and the tendency toward a higher concentration of pulmonary VEGF may represent enhanced production of VEGF in response to impaired endothelial function.

Glucocorticoids rate among the most controversial topics in today's perinatology and neonatology. Many sick preterm infants exhibit signs of adrenal insufficiency, the etiology, diagnostic criteria, and optimal treatment of which are under debate. Moreover, most of these infants are exposed to pharmacological glucocorticoid doses both in utero and after birth. In face of this, surprisingly little is known about the physiological glucocorticoid exposure before early preterm birth. This exposure is highly variable and mainly regulated by the placental enzyme 11 beta-hydroxysteroid dehydrogenase-2 (11 beta-HSD2), which converts excess cortisol (F) to inactive cortisone (E). Impaired activity of this enzyme is common in intrauterine growth restriction and preeclampsia, conditions frequently associated with early preterm birth. To identify clinical determinants associated with decreased placental 11 beta-HSD2 function, we studied 107 small preterm infants [mean birth weight, 1067 g (range, 395-2453 g); gestational age, 28.2 wk (range, 22.4-32.0 wk)] by determining their placental 11 beta-HSD2 activity rate (per milligram protein) and total activity (per placenta) as well as cord vein F and E concentrations. An E/(E+ F) ratio expresses the overall balance of the F/E shuttle. There were positive correlations between relative birth weight and placental 11 beta-HSD2 activity rate (r = 0.30; P = 0.002) and total activity (r = 0.56; P < 0.0001) as well as E/(E+ F) ratio (r = 0.27; P = 0.01) and E concentration (r = 0.32; P = 0.003). Infants with increased umbilical artery resistance had lower total placental 11 beta-HSD2 activity (P = 0.02), E/(E+ F) ratio (P = 0.04), and E concentration (P = 0.0002). Gestational age was inversely associated with placental 11 beta-HSD2 activity rate (r = -0.25; P = 0.009). We conclude that, in small preterm infants, reduced placental 11 beta-HSD2 function is associated with low relative birth weight and severe fetal distress. Whether these conditions are associated with early postnatal adrenal insufficiency or long-term cardiovascular risk remains an important issue for further study.

A dults born very preterm (VP; <32 weeks of gestation) or at very low birth weight (VLBW; <1500 g) have higher blood pressure than their peers born at term.1-10 A recent meta-analysis showed that VLBW or VP adults have on average 3.3 mm Hg higher systolic pressure than controls. 7 Another meta-analysis, including studies in adults born at any degree of prematurity, concluded that the mean difference between adults born preterm and controls was 4.2 mm Hg for systolic and 2.6 mm Hg for diastolic blood pressure. 8 These differences were more pronounced among women (systolic/diastolic 4.9/2.9 mm Hg) but clearly present among men as well (2.0/1.3 mm Hg). 8 These differences are considerable given that, at the population level, a 2 mm Hg reduction in diastolic pressure is estimated to result in a 7% to 14% reduction in mortality from ischemic heart disease and 9% to 19% from stroke with greatest reductions in the youngest age groups. 11Although these meta-analyses have been important in confirming the association between very preterm birth and adult blood pressure, they have, apart from sex, not been able to assess any other risk factors or protective factors for high blood pressure among adults born very preterm. This would be a crucial step in identifying underlying mechanisms, which then could serve as targets for prevention.The higher blood pressure among adults born VLBW/VP could arise from dissimilar conditions that lead to preterm birth or Abstract-Adults born preterm at very low birth weight (VLBW; <1500 g) have higher blood pressure than those born at term.It is not known whether all VLBW adults are at risk or whether higher blood pressure could be attributed to some of the specific conditions underlying or accompanying preterm birth. To identify possible risk or protective factors, we combined individual-level data from 9 cohorts that measured blood pressure in young adults born at VLBW or with a more stringent birth weight criterion. In the absence of major heterogeneity, we performed linear regression analysis in our pooled sample of 1571 adults born at VLBW and 777 controls. Adults born at VLBW had 3.4 mm Hg (95% confidence interval, 2.2-4.6) higher systolic and 2.1 mm Hg (95% confidence interval, 1.3-3.0) higher diastolic pressure, with adjustment for age, sex, and cohort. The difference in systolic pressure was present in men (1.8 mm Hg; 95% confidence interval, 0.1-3.5) but was stronger in women (4.7 mm Hg; 95% confidence interval, 3.2-6.3). Among the VLBW group, blood pressure was unrelated to gestational age, maternal smoking, multiple pregnancy, retinopathy of prematurity, or bronchopulmonary dysplasia. Blood pressure was higher than that of controls among VLBW adults unexposed to maternal preeclampsia. Among those exposed, it was even higher, especially if born appropriate for gestational age. In conclusion, although female sex and maternal preeclampsia are additional risk factors, the risk of higher blood pressure is not limited to any etiologic subgroup of VLBW adults, arguing for vigilance in...