We report the existence of a 'placental clock', which is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women we have demonstrated that placental secretion of corticotropin-releasing hormone (CRH) is a marker of this process and that measurement of the maternal plasma CRH concentration as early as 16-20 weeks of gestation identifies groups of women who are destined to experience normal term, preterm or post-term delivery. Further, we report that the exponential rise in maternal plasma CRH concentrations with advancing pregnancy is associated with a concomitant fall in concentrations of the specific CRH binding protein in late pregnancy, leading to a rapid increase in circulating levels of bioavailable CRH at a time that coincides with the onset of parturition, suggesting that CRH may act directly as a trigger for parturition in humans.

Structural remodeling of myocardium after infarction plays a critical role in functional adaptation. Diffusion tensor magnetic resonance imaging (DTMRI) provides a means for rapid and nondestructive characterization of the three-dimensional fiber architecture of cardiac tissues. In this study, microscopic structural changes caused by MI were evaluated in Fischer 344 rats 4 wk after infarct surgery. DTMRI studies were performed on 15 excised, formalin-fixed rat hearts of both infarct (left anterior descending coronary artery occlusion, n = 8) and control (sham, n = 7) rats. Infarct myocardium exhibited increased water diffusivity (41% increase in trace values) and decreased diffusion anisotropy (37% decrease in relative anisotropy index). The reduced diffusion anisotropy correlated negatively with microscopic fiber disarray determined by histological analysis (R = 0.81). Transmural courses of fiber orientation angles in infarct zones were similar to those of normal myocardium. However, regional angular deviation of the diffusion tensor increased significantly in the infarct myocardium and correlated strongly with microscopic fiber disarray (R = 0.86). These results suggest that DTMRI may provide a valuable tool for defining structural remodeling in diseased myocardium at the cellular and tissue level.

OBJECTIVE—There is conflicting evidence regarding the benefit of intravenous insulin therapy on mortality following acute myocardial infarction (AMI). The goal of the current study was to determine whether improved glycemic control, achieved through an insulin/dextrose infusion with a variable rate of insulin, reduces mortality among hyperglycemic patients with AMI. RESEARCH DESIGN AND METHODS—Subjects suffering AMI with either known diabetes or without diabetes but blood glucose level (BGL) ≥7.8 mmol/l were randomized to receive insulin/dextrose infusion therapy for at least 24 h to maintain a BGL <10 mmol/l or conventional therapy. RESULTS—A total of 240 subjects were recruited. Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8 vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs. 6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h, mortality was lower among subjects with a mean BGL ≤8 mmol/l, compared with subjects with a mean BGL >8 mmol/l (2 vs. 11% at 6 months, P = 0.02). CONCLUSIONS—We did not find a reduction in mortality among patients who received insulin/dextrose infusion therapy. However, it remains possible that tight glycemic control with insulin therapy following AMI improves outcomes.

Obesity in women of reproductive age is increasing at an unprecedented rate in western societies. Maternal obesity is associated with an unequivocal increase in maternal and fetal complications of pregnancy. Excessive maternal weight gain in pregnancy also appears to be an independent risk factor, regardless of prepregnancy weight. Few guidelines exist regarding appropriate weight gain in pregnancy in obese women. We review the association of maternal obesity with pregnancy complications. We also suggest that appropriate diet and lifestyle intervention can enable women with severe prepregnancy obesity to safely achieve quite strict targets for limited weight gain in pregnancy.

The prevalence of sufficient physical activity was found to be low and strongly related to social support and self-efficacy. This is an important group to whom diabetes prevention strategies can be targeted.

OBJECTIVEVitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a doubleblind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy. RESEARCH DESIGN AND METHODSWomen with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat. RESULTSThere was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women (P = 0.25). Neonatal cord 25OHD was higher in HD offspring (46 6 11 vs. 29 6 12 ng/mL, P < 0.001), and deficiency was more common in LD offspring (24 vs. 10%, P = 0.06). Post hoc analysis in LD women showed an inverse relationship between pretreatment 25OHD and both fasting and 2-h blood glucose level on OGTT (both P < 0.001). Baseline 25OHD remained an independent predictor after multiple regression analysis. CONCLUSIONSHD vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.Vitamin D deficiency has become a common problem globally. It has been estimated that one billion people worldwide are vitamin D deficient (1). In the U.S., vitamin D deficiency is prevalent across populations of all age-groups (2). Even in a country with high ultraviolet exposure like Australia, the prevalence of vitamin D deficiency (25-hydroxyvitamin D [25OHD] level ,20 ng/mL [,50 nmol/L]) was 31% among

Women's ability to follow a healthy lifestyle is embedded in their psychological wellbeing and the social and cultural context of their lives. The study highlights the need for a holistic approach that ensures personal support and access to services as well as lifestyle specific programs.

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