Amylin peptide levels are raised in infants of diabetic mothers

Background: Amylin is a novel 37 amino acid peptide hormone that is co-secreted with insulin from the pancreas in response to food intake. As a potent inhibitor of gastric emptying it plays an important role in the control of carbohydrate absorption. Feed intolerance is common in infants of diabetic mothers (IDM). Aims: To establish a normal range of amylin levels in healthy neonates, and to determine whether serum amylin levels are raised in IDM. Methods: A serial sample of 221 infants ⩾28 weeks gestation was enrolled prior to delivery over a 12 month period. Blood samples collected immediately after birth (umbilical cord), and at the routine Guthrie test were analysed for amylin and insulin levels. Results: Amylin levels in umbilical cord (n = 181) and Guthrie samples (n = 33) of healthy infants were 5.7 (3.0–9.1) and 6.9 (2.9–9.0) pmol/l respectively. IDM had significantly raised amylin levels in both cord (n = 31; 32.7 pmol/l, 25.9–48.1) and Guthrie samples (n = 8; 18.1 pmol/l, 15.3–23.6). Amylin correlated positively with insulin (n = 42; r = 0.67; 95% CI 0.4 to 0.81), birth weight (r = 0.22; 95% CI 0.08 to 0.36), and gestation (r = 0.18; 95% CI 0.03 to 0.32). Umbilical cord venous amylin levels showed agreement with arterial cord amylin levels (n = 34, mean bias –0.2, 95% CI 3.1 to –3.6). Conclusions: Amylin levels are significantly increased in the umbilical cord and Guthrie blood samples in IDM

Dexamethasone quantification in dried blood spot samples using LC-MS: The potential for application to neonatal pharmacokinetic studies.

A high-performance liquid chromatography (LC-MS) method has been developed and validated for the determination of dexamethasone in dried blood spot (DBS) samples. For the preparation of DBS samples whole blood spiked with analyte was used to produce 30µl blood spots on specimen collection cards. An 8mm disc was cut from the dried blood spot and extracted using a combination of methanol: water (70:30, v/v) containing the internal standard, triamcinolone acetonide. Extracts were centrifuged and chromatographic separation was achieved using a Zorbax Eclipse Plus C18 column using gradient elution with a mobile phase of acetonitrile and water with formic acid at a flow rate of 0.2ml/min. LC-MS detection was conducted with single ion monitoring using target ions at m/z 393.1 for dexamethasone and 435.1 for the internal standard. The developed method was linear within the tested calibration range of 15-800ng/ml. The overall extraction recovery of dexamethasone from dried blood spot samples was 99.3% (94.3-105.7%). The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. Factors with potential to affect drug quantification measurements such as blood haematocrit, the volume of blood applied onto the collection card and spotting device were investigated. Although a haematocrit related effect was apparent, the assay accuracy and precision values remained within the 15% variability limit with fluctuations in haematocrit of ± 5%. Variations in the volume of blood spotted did not appear to affect the performance of the developed assay. Similar observations were made regarding the spotting device used. The methodology has been applied to determine levels of dexamethasone in DBS samples collected from a premature neonate. The measured concentrations were successfully evaluated using a simple 1 compartment pharmacokinetic model. Requiring only a microvolume (30µl) blood sample for analysis, the developed assay is particularly suited to pharmacokinetic studies involving paediatric populations

Dried blood spots and sparse sampling: A practical approach to estimating pharmacokinetic parameters of caffeine in preterm infants

AIMS: Dried blood spots (DBS) alongside micro‐analytical techniques are a potential solution to the challenges of performing pharmacokinetic (PK) studies in children. However, DBS methods have received little formal evaluation in clinical settings relevant to children. The aim of the present study was to determine a PK model for caffeine using a ‘DBS/microvolume platform’ in preterm infants. METHODS: DBS samples were collected prospectively from premature babies receiving caffeine for treatment of apnoea of prematurity. A non‐linear mixed effects approach was used to develop a population PK model from measured DBS caffeine concentrations. Caffeine PK parameter estimates based on DBS data were then compared with plasma estimates for agreement. RESULTS: Three hundred and thirty‐eight DBS cards for caffeine measurement were collected from 67 preterm infants (birth weight 0.6–2.11 kg). 88% of cards obtained were of acceptable quality and no child had more than 10 DBS samples or more than 0.5 ml of blood taken over the study period. There was good agreement between PK parameters estimated using caffeine concentrations from DBS samples (CL = 7.3 ml h(−1) kg(−1); V = 593 ml kg(−1); t(1/2) = 57 h) and historical caffeine PK parameter estimates based on plasma samples (CL = 4.9–7.9 ml h(−1) kg(−1); V = 640–970 ml kg(−1); t(1/2) = 101–144 h). We also found that changes in blood haematocrit may significantly confound estimates of caffeine PK parameters based on DBS data. CONCLUSIONS: This study demonstrates that DBS methods can be applied to PK studies in a vulnerable population group and are a practical alternative to wet matrix sampling techniques

A test to study the influence of impaction on mandibular third molar development and forensic age estimation in a sample of south Indian children and young adults.

It has been argued that the impaction of the third molars could result in delayed maturation, which, in turn, could affect age estimations in criminal proceedings. In view of this, the present study was undertaken to determine whether the impaction status could delay the chronological process of third molar mineralization in a sample of south Indian children and young adults. The orthopantomograms (OPGs) of 915 children and young adults of south Indian origin aged between 15 and 22 years were evaluated. Mineralisation stage and impaction status were determined for all lower third molars. Descriptive statistics were performed at stages D to H of Demirjian staging system. The results of independent t-test show that the impaction resulted in statistically significant slower mineralization in impacted lower third molars at stages D to F in both sexes. It was ascertained that the mean ages with the impacted lower third molars at stage G were 0.98-1.38 years higher in males and 0.50-0.80 years higher in females than those with non-impacted lower third molars. For stage H, the mean ages were 0.14-0.21 years higher in males and 0.25-0.44 years higher in females. The probabilities of being 18 years and above is higher for non-impacted lower third molars at stages G and H than those with impacted ones. It is concluded that the impaction could result in delayed maturation in the lower third molars of the studied sample. Further studies are warranted in a more diverse sample

Cluster of human parechovirus infections as the predominant cause of sepsis in neonates and infants, Leicester, United Kingdom, 8 May to 2 August 2016.

We report an unusually high number of cases (n = 26) of parechovirus infections in the cerebrospinal fluid (CSF) of neonates and infants admitted with sepsis in the United Kingdom during 8 May to 2 August 2016. Although such infections in neonates and infants are well-documented, parechovirus has not been routinely included in many in-house and commercial PCR assays for CSF testing. Clinicians should consider routine parechovirus testing in young children presenting with sepsis