Application of the screening test principles to screening for neonatal hypoglycemia.

Severe and prolonged neonatal hypoglycemia can cause brain injury, while the long-term consequences of mild or transitional hypoglycemia are uncertain. As neonatal hypoglycemia is often asymptomatic it is routine practice to screen infants considered at risk, including infants of mothers with diabetes and those born preterm, small or large, with serial blood tests over the first 12-24 h after birth. However, to prevent brain injury, the gold standard would be to determine if an infant has neuroglycopenia, for which currently there is not a diagnostic test. Therefore, screening of infants at risk for neonatal hypoglycemia with blood glucose monitoring does not meet several screening test principles. Specifically, the long-term neurodevelopmental outcomes of transient neonatal hypoglycemia are not well understood and there is no direct evidence from randomized controlled trials that treatment of hypoglycemia improves long-term neurodevelopmental outcomes. There have been no studies that have compared the long-term neurodevelopmental outcomes of at-risk infants screened for neonatal hypoglycemia and those not screened. However, screening infants at risk of hypoglycemia and treating those with hypoglycaemic episodes to maintain the blood glucose concentrations ≥2.6 mmol/L appears to preserve cognitive function compared to those without episodes. This narrative review explores the evidence for screening for neonatal hypoglycemia, the effectiveness of blood glucose screening as a screening test and recommend future research areas to improve screening for neonatal hypoglycemia. Screening babies at-risk of neonatal hypoglycemia continues to be necessary, but as over a quarter of all infants may be screened for neonatal hypoglycemia, further research is urgently needed to determine the optimal method of screening and which infants would benefit from screening and treatment.

Antenatal glucocorticoids: where are we after forty years?

Since their introduction more than forty years ago, antenatal glucocorticoids have become a cornerstone in the management of preterm birth and have been responsible for substantial reductions in neonatal mortality and morbidity. Clinical trials conducted over the past decade have shown that these benefits may be increased further through administration of repeat doses of antenatal glucocorticoids in women at ongoing risk of preterm and in those undergoing elective cesarean at term. At the same time, a growing body of experimental animal evidence and observational data in humans has linked fetal overexposure to maternal glucocorticoids with increased risk of cardiovascular, metabolic and other disorders in later life. Despite these concerns, and somewhat surprisingly, there has been little evidence to date from randomized trials of longer-term harm from clinical doses of synthetic glucocorticoids. However, with wider clinical application of antenatal glucocorticoid therapy there has been greater need to consider the potential for later adverse effects. This paper reviews current evidence for the short- and long-term health effects of antenatal glucocorticoids and discusses the apparent discrepancy between data from randomized clinical trials and other studies.

Low dose transdermal oestradiol suppresses gonadotrophin secretion in breast-feeding women.

The object of the study was to investigate the effect on gonadotrophin secretion of a small increase in oestradiol concentration. A total of 13 fully breast-feeding women (12 weeks post-partum) underwent serial blood sampling at 10 min intervals for 12 h on 2 different days; day 1 untreated and day 5 after 3 days of treatment with transcutaneous oestradiol (100 micrograms/day). On both days bolus gonadotrophin-releasing hormone (GnRH; 10 micrograms i.v.) was given after a 10 h baseline period. In six of the subjects, a naloxone infusion was administered during the second study day. Application of transdermal oestradiol raised the oestradiol concentration within the normal follicular phase range. The mean luteinizing hormone (LH) concentration on day 5 was found to be significantly lower than that on day 1 (P < 0.05). The LH response to GnRH was, however, significantly higher on day 5 than day 1 (P < 0.001). The mean follicle stimulating hormone (FSH) concentration on day 5 was also significantly lower than that on day 1 (P < 0.01), while the peak concentration after GnRH was unchanged. When the opioid antagonist naloxone was infused after oestradiol treatment, the subjects with low pre-study oestradiol concentrations exhibited no effect on LH concentration, while in the subjects with higher oestradiol concentrations the LH concentration was increased. It was concluded that the administration of small doses of oestradiol caused a significant fall in gonadotrophin concentration in breast-feeding women.(ABSTRACT TRUNCATED AT 250 WORDS)

Three year follow up of patients with raised blood pressure identified at health checks in general practice.

OBJECTIVE: To assess the extent of three year follow up of blood pressure, weight, and smoking habit in patients with raised blood pressure identified at health checks. DESIGN: Retrospective audit of medical and nursing records. SETTING: Three general practices in Oxfordshire. PATIENTS: 386 of 448 patients with raised blood pressure (diastolic greater than or equal to 90 or systolic greater than or equal to 160 mm Hg) identified from 2935 patients aged 35-64 attending health checks in 1982-4. MEASUREMENTS AND MAIN RESULTS: All records of blood pressure, weight, and smoking habit in the medical record were abstracted for three years after the initial health check. All 42 patients with an initial diastolic blood pressure greater than or equal to 105 mm Hg and 316 of 344 patients with an initial pressure of 90-104 mm Hg had at least one further measurement of their blood pressure. Follow up of smoking habit and of weight was less complete with only half of the 100 smokers and 67 of the 87 obese patients (body mass index greater than or equal to 30) having any documented follow up of these risk factors. Annual follow up in the second and third years occurred in 228/297 (76.8%) and 232/320 (72.5%) in patients with blood pressure greater than 95 mm Hg at the beginning of each year. For patients who smoked annual follow up in these years occurred in fewer than a third and for those who were obese in just over half. On the assumption that those not followed up had not changed, at the end of three years the proportion of patients with diastolic blood pressure greater than or equal to 100 mm Hg had fallen from 61 patients (15.8%) to 31 (8.1%); the proportion of smokers had fallen from 103 (26.7%) to 94 (24.4%); and the proportion of obese patients had fallen from 87 (22.5%) to 79 (20.5%). CONCLUSIONS: These changes were modest and in the absence of a control group cannot be attributed necessarily to health checks. Although the standard of follow up was better than in previously reported studies of the management of hypertension, the results emphasise the need to develop formal protocols for dietary and antismoking interventions and to evaluate formally the effectiveness (and cost effectiveness) of health checks.

The role of laminin and the laminin/fibronectin receptor complex in the outgrowth of retinal ganglion cell axons.

Chick embryo retinal ganglion cell (RGC) axons grow to the optic tectum along a stereotyped route, as if responding to cues distributed along the pathway. We showed previously that, in culture, RGCs from embryonic Day 6 retina are responsive to the neurite-promoting effects of the extracellular matrix glycoprotein laminin and that this response is lost by RGCs at a later stage of development. Here we report that, before axon outgrowth is initiated in vivo, laminin, is expressed along the optic pathway at nonbasal lamina sites that are accessible to the growth cones of RGC axons. The distribution of laminin within the pathway is consistent with its localization at the end-feet of neuroepithelial cells that line the route, and it continues to be expressed at these marginal sites during the first week of embryonic development. At later stages, concomitant with the loss of response by RGCs in culture, laminin becomes restricted to basal laminae at the retinal inner limiting membrane and pial surface of the optic pathway. Neurofilament-positive RGC axons bind a monoclonal antibody, JG22, which recognizes the laminin/fibronectin receptor complex, and continue to do so throughout embryonic development. We show that, in vitro, the JG22 antigen expressed by RGCs appears to function as a laminin receptor, by demonstrating that JG22 antibody blocks neurite outgrowth on a substrate of laminin. These findings are consistent with the possibility that laminin defines a transient performed pathway specifically recognized by early RGC growth cones as they navigate toward their central target.