Establishment of hormone reference intervals for infants born < 30 weeks' gestation

Objective

Preterm infants, especially those born very preterm (< 32 weeks' gestation), suffer a number of morbidities. Immaturity of the endocrine system and its potential impact on morbidity is the subject of numerous studies. Hormone concentrations are sometimes measured in very preterm infants, however there are little normative data available to be able to interpret the results. The aim of this study was to describe age appropriate hormone reference intervals for babies born less than 30 weeks' gestation.

Study design

Samples were collected at 1, 4, 7, 14, 21, 28 and 42 days after birth from babies born 23–29 weeks' gestation. The serum was analyzed for seven hormones by automated chemiluminescent immunoassay (Siemens Immulite 2000). Results from the 107 infants who survived beyond 40 weeks' corrected gestational age were included in the data analysis.

Results

Cortisol, dehydroepiandrosterone sulfate, growth hormone and progesterone levels were highest during the first seven days with levels up to 10,801 nmol/L; 26.6 μmol/L; 343 mU/L; and > 63.6 nmol/L respectively. Free thyroxine levels were as low as < 2.6 pmol/L for the first 28 days with the nadir at 7 days. Estradiol levels ranged from < 73 to 1626 pmol/L over the six weeks. Reference intervals for IGF-1 could not be established as the levels were below the analyzer's sensitivity. There were no differences in reference intervals between male and female infants.

Conclusions

We describe gestation appropriate reference intervals for six hormones measured in babies born < 30 weeks' gestation. Utilization of these reference intervals permits the correct and timely interpretation of results to the clinician.     

Cognitive outcome at 24 months is more predictive than at 18 months for IQ at 8-9 years in extremely low birth weight children

Background

It is unclear whether developmental assessment later or earlier in childhood is the better predictor of intelligence at 8 years of age. This is an important distinction as many clinical trials assess their final outcomes only in early childhood, assuming the results are valid for later childhood cognitive functioning.

Aims

To compare the ability of developmental assessment at 18 months with 24 months in predicting general intellectual functioning at 8–9 years of age in extremely low birth weight (ELBW, birthweight < 1000 g) children.

Study design

Cohort study.

Subjects

58 ELBW survivors born during 1997 at the Royal Women's Hospital, Melbourne, Australia.

Outcome measures

Cognitive assessments at each of 18 months, 24 months (Mental Developmental Index [MDI]) and 8–9 years (Full Scale IQ) of age, corrected for prematurity were compared by regression analysis and by the κ statistic (agreement beyond chance).

Results

Both the 18-month and the 24-month MDI were significantly predictive of Full Scale IQ at 8–9 years, but more so for the 24-month MDI, with 38% of variance explained compared with 34% of variance explained by the 18-month MDI. The 24-month MDI, expressed as categories of severe, moderate, mild or no developmental delay, was more predictive of categories of severe, moderate, mild or no intellectual impairment at 8–9 years (weighted κ = 0.43, P < 0.001) than was the 18-month MDI (weighted κ = 0.35, P = 0.001).

Conclusions

Cognitive assessment at 24 months is superior to cognitive assessment at 18 months in predicting IQ and intellectual impairment at 8–9 years of age in ELBW children.     

Antenatal magnesium sulphate neuroprotection in the preterm infant

Very preterm infants have high rates of neurological impairments and disabilities. These rates have not diminished as the survival rates have improved. Basic science research suggests that magnesium sulphate before birth can be neuroprotective for the preterm fetus. Some, but not all, observational studies in humans also suggest a protective effect of antenatal magnesium sulphate on cerebral palsy. Four randomised controlled trials of antenatal magnesium sulphate have reported long-term neurological effects in surviving infants, but only one of these was designed specifically to evaluate the long-term effects of treatment. These studies found that, overall, antenatal magnesium sulphate therapy had no significant effect on paediatric mortality or neurological outcomes in the first few years of life, including cerebral palsy, but it was found to lower the rate of motor problems at 2 years of age in one study. The role for antenatal magnesium sulphate therapy as a neuroprotective agent for the preterm fetus is not yet established.     

Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent,selective, melanocortin subtype-4 receptor agonist

Synthetic and natural peptides that act as nonselective melanocortin receptor agonists have been found to be anorexigenic and to stimulate erectile activity. We report the design and development of 1, a potent, selective (1184-fold vs MC3R, 350-fold vs MC5R), small-molecule agonist of the MC4 receptor. Pharmacological testing confirms the food intake lowering effects of MC4R agonism and suggests another role for the receptor in the stimulation of erectile activity.     

Exploring the site of anorectic action of peripherally administered synthetic melanocortin peptide MT-II in rats

Melanotan-II (MT-II), a cyclic heptapeptide, is a potent, non-selective melanocortinergic agonist. When administered centrally or systemically, MT-II elicited a profound inhibitory effect on food intake in rodents, presumably via activation of melanocortin-4-receptor (MC4R). In this study, we sought to investigate whether penetration of MT-II and iodo-MT-II into brain parenchyma is required for the anorectic effect following intravenous (IV) administration. Firstly, both MT-II and iodo-MT-II were effective at suppressing appetite in rats following their IV administration. We next surveyed by in vitro autoradiographic studies the distribution of selective (125)I-MT-II binding sites in multiple brain regions including areas important for feeding regulation such as the hypothalamus and caudal brainstem. Upon IV administration of (125)I-MT-II, significant radioactivity could not be detected in various brain regions by autoradiography except for a group of circumventricular organs (CVOs), which are anatomically situated outside the blood-brain barrier (BBB). The most intensely labeled CVOs include the subfornical organ, median eminence, area postrema and choroid plexus, and accumulation of radioactivity at these sites can be blocked by co-injection of excess unlabeled MT-II. Direct measurement of MT-II in the brain and plasma by LC-MS-MS following IV injection confirmed that the degree of MT-II penetration into the brain is negligible. Furthermore, when given peripherally under conditions that suppressed food intake, MT-II did not result in a detectable induction of c-Fos-like immunoreactivity in brain regions where a significantly elevated c-Fos expression was observed following intracerebroventricular injection of this peptide. Our results indicate that MT-II has a very limited brain penetration capability, and its effect on feeding behavior following systemic administration may be mediated by either the brain regions in close proximity to the CVOs or sites outside of the BBB, including CVOs or other peripheral systems.