Patrick J. Twomey

Maternal Blood Lipid Profile during Pregnancy and Associations with Child Adiposity: Findings from the ROLO Study

Background The in-utero environment affects fetal development; it is vital to understand how maternal diet during pregnancy influences childhood body composition. While research indicates that triglycerides in hyperglycaemic women may increase birth weight, little is known about this relationship in euglycemic women. This study examines the relationship between maternal blood lipid status and infant adiposity up to 2 years of age. Methods Data from 331 mother-child pairs from the ROLO longitudinal birth cohort study was analysed. Maternal dietary intakes were recorded and fasting blood lipids, leptin and HOMA were measured in early and late pregnancy and cord blood. Infant anthropometric measurements and skin-fold thicknesses were recorded at birth, 6 months and 2 years. Correlation and regression analyses were used to explore associations between maternal blood lipid status and infant adiposity. Results All maternal blood lipids increased significantly during pregnancy. Maternal dietary fat intake was positively associated with total cholesterol levels in early pregnancy. Late pregnancy triglycerides were positively associated with birth weight (P = 0.03) while cord blood triglycerides were negatively associated with birth weight (P = 0.01). Cord HDL-C was negatively associated with infant weight at 6 months (P = 0.005). No other maternal blood lipids were associated with infant weight or adiposity up to 2 years of age. Conclusion Maternal and fetal triglycerides were associated with birth weight and cord HDL-C with weight at 6 months. Thus, maternal lipid concentrations may exert in-utero influences on infant body composition. There may be potential to modulate infant body composition through alteration of maternal diet during pregnancy.

Analytical performance specifications for external quality assessment – definitions and descriptions

Abstract External Quality Assurance (EQA) is vital to ensure acceptable analytical quality in medical laboratories. A key component of an EQA scheme is an analytical performance specification (APS) for each measurand that a laboratory can use to assess the extent of deviation of the obtained results from the target value. A consensus conference held in Milan in 2014 has proposed three models to set APS and these can be applied to setting APS for EQA. A goal arising from this conference is the harmonisation of EQA APS between different schemes to deliver consistent quality messages to laboratories irrespective of location and the choice of EQA provider. At this time there are wide differences in the APS used in different EQA schemes for the same measurands. Contributing factors to this variation are that the APS in different schemes are established using different criteria, applied to different types of data (e.g. single data points, multiple data points), used for different goals (e.g. improvement of analytical quality; licensing), and with the aim of eliciting different responses from participants. This paper provides recommendations from the European Federation of Laboratory Medicine (EFLM) Task and Finish Group on Performance Specifications for External Quality Assurance Schemes (TFG-APSEQA) and on clear terminology for EQA APS. The recommended terminology covers six elements required to understand APS: 1) a statement on the EQA material matrix and its commutability; 2) the method used to assign the target value; 3) the data set to which APS are applied; 4) the applicable analytical property being assessed (i.e. total error, bias, imprecision, uncertainty); 5) the rationale for the selection of the APS; and 6) the type of the Milan model(s) used to set the APS. The terminology is required for EQA participants and other interested parties to understand the meaning of meeting or not meeting APS.

Why are clinical practice guidelines not followed

Abstract Clinical practice guidelines (CPG) are written with the aim of collating the most up to date information into a single document that will aid clinicians in providing the best practice for their patients. There is evidence to suggest that those clinicians who adhere to CPG deliver better outcomes for their patients. Why, therefore, are clinicians so poor at adhering to CPG? The main barriers include awareness, familiarity and agreement with the contents. Secondly, clinicians must feel that they have the skills and are therefore able to deliver on the CPG. Clinicians also need to be able to overcome the inertia of “normal practice” and understand the need for change. Thirdly, the goals of clinicians and patients are not always the same as each other (or the guidelines). Finally, there are a multitude of external barriers including equipment, space, educational materials, time, staff, and financial resource. In view of the considerable energy that has been placed on guidelines, there has been extensive research into their uptake. Laboratory medicine specialists are not immune from these barriers. Most CPG that include laboratory tests do not have sufficient detail for laboratories to provide any added value. However, where appropriate recommendations are made, then it appears that laboratory specialist express the same difficulties in compliance as front-line clinicians.

Validating the association between plasma tumour necrosis factor receptor 1 levels and the presence of renal injury and functional decline in patients with Type 2 diabetes

AIMSnElevated plasma soluble tumour necrosis factor receptor 1 (TNFR1) predicts long-term progression of chronic kidney disease. We investigated the association between elevated TNFR1 and the presence of renal disease in patients with Type 2 diabetes mellitus registering a haemoglobin A1c (HbA1c) >48mmol/mol despite medical therapy.nnnMETHODSnUsing sensitivity, specificity and regression analyses we interrogated the association between plasma TNFR1 and presence of chronic kidney disease as assessed by the presence of microalbuminuria and/or an estimated glomerular filtration rate of less than 60ml/min/1.73m2 (stages 3-5 chronic kidney disease). The association of TNFR1 with C-reactive protein and leptin-adiponectin ratio as plasma markers of systemic inflammation and adipose stress respectively was also investigated.nnnRESULTSnUpper quartile TNFR1 is independently associated with elevated urinary albumin-creatinine ratios, reductions in eGFR and strongly predicts the presence of stages 3-5 chronic kidney disease in regression modelling. Elevated TNFR1 levels are associated with increased plasma C-reactive protein and augmented leptin-adiponectin ratio.nnnCONCLUSIONSnOur study confirms plasma TNFR1 as a surrogate of renal structural and functional impairment in patients with type 2 diabetes mellitus. Association of TNFR1 with markers of systemic inflammation and adipose stress indicates that TNFR1 may be a biomarker of these processes as components of the pathogenesis of diabetic kidney disease.

Maternal and fetal blood lipid concentrations during pregnancy differ by maternal body mass index: findings from the ROLO study

BackgroundPregnancy is a time of altered metabolic functioning and maternal blood lipid profiles change to accommodate the developing fetus. While these changes are physiologically necessary, blood lipids concentrations have been associated with adverse pregnancy outcomes such as gestational diabetes, pregnancy-induced hypertension and high birth weight. As blood lipids are not routinely measured during pregnancy, there is limited information on what is considered normal during pregnancy and in fetal blood.MethodsData from 327 mother-child pairs from the ROLO longitudinal birth cohort study were analysed. Fasting total cholesterol and triglycerides were measured in early and late pregnancy and fetal cord blood. Intervals were calculated using the 2.5th, 50th and 97.5th centile. Data was stratified based on maternal body mass index (BMI) measured during early pregnancy. Differences in blood lipids between BMI categories were explored using ANOVA and infant outcomes of macrosomia and large-for-gestational-age (LGA) were explored using independent student T-tests and binary logistic regression.ResultsAll maternal blood lipid concentrations increased significantly from early to late pregnancy. In early pregnancy, women with a BMIxa0<xa025xa0kg/m2 had lower concentrations of total cholesterol compared to womenxa0with a BMI ofxa025–29.9xa0kg/m2 (Pxa0=xa00.02). With triglycerides, womenxa0in the obese category (BMIxa0>xa030xa0kg/m2) had higher concentrations than both women in thexa0normal-weight and overweight category in early and late pregnancy (Pxa0<xa00.001 and Pxa0=xa00.03, respectively). In late pregnancy, triglyceride concentrations remained elevated in womenxa0in the obese category compared to women in thexa0normal-weightxa0category (Pxa0=xa00.01). Triglyceride concentrations were also elevated in late pregnancy in mothers that then gave birth toxa0infants with macrosomia and LGA (Pxa0=xa00.01 and Pxa0=xa00.03, respectively).ConclusionBlood lipid concentrations increase during pregnancy and differ by maternal BMI. These intervals could help to inform the development of references for blood lipid concentrations during pregnancy.Trial registrationROLO Study - ISRCTN54392969. Date of registration: 22/04/2009.

Laboratory trend in vitamin D status in Ireland: Dual concerns about low and high 25OHD

Serum 25-hydroxyvitamin D (25OHD) is the pre-eminent estimate of vitamin D status that we have been measuring in a hospital laboratory setting since the 1970s. We previously evaluated the trend in 25OHD results in our laboratory from 1993 to 2013. Using a time series analysis of monthly average 25OHD results the trend was modelled, and this was used to forecast monthly average 25OHD from 2014 to 2016. In this study, all 25OHD results from 2014 to 2016 were retrieved (nu2009=u200967,922) and trimmed to 40,307 results after duplicates were excluded. The average monthly actual 25OHD was almost identical to the average monthly forecast 25OHD (pu2009=u20090.028) with a strong correlation between the actual 25OHD and forecast 25OHD (ru2009=u20090.69, pu2009<u20090.001). This upward trend is attributed to higher oral intake of vitamin D. We have a dual concern: policies to prevent hypovitaminosis D must be offset by strategies to avert hypervitaminosis D.

Congenital hypophosphataemia in adults: determinants of bone turnover markers and amelioration of renal phosphate wasting following total parathyroidectomy

Congenital hypophosphataemia (CH) is a collection of disorders that cause defective bone mineralisation manifesting with rickets in childhood and osteomalacia in adulthood. Bone turnover markers (BTMs) are surrogate measures of metabolic bone disease severity. We explored the utility of BTMs in 27 adults with CH: 23 had X-linked hypophosphataemia (XLH), of whom 2 were hypoparathyroid post-total parathyroidectomy (PTx); 2 had autosomal dominant hypophosphataemic rickets (ADHR), and 2 had none of the known mutations. We measured the renal tubular maximum reabsorption rate of phosphate (TmP/GFR), C-terminal fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), ionised calcium, 1,25-dihydroxyvitamin D [1,25(OH)2D], and a panel of BTMs: serum bone-specific alkaline phosphatase (bone ALP), osteocalcin (Oc), total procollagen type I amino-terminal propeptide (PINP), and carboxy-terminal telopeptide of type I collagen (CTX); and urine amino-terminal telopeptides of type I collagen (uNTX). After excluding 2 patients with XLH and PTx, the frequency of abnormal elevation in BTMs was: bone ALP (96%); CTX (72%); PINP (52%); uNTX (48%); Oc (28%). The strongest association with bone ALP was TmP/GFR. Those patients receiving phosphate supplements and alfacalcidol had significant elevation in CTX. The 2 patients with XLH and PTx had normalisation of TmP/GFR and near normalisation of BTMs post-operatively, despite marked elevation in both C-terminal and intact FGF23. In conclusion, BTMs in our CH patients indicated that most have abnormalities consistent with osteomalacia and many have mild secondary hyperparathyroidism; and the normalisation of TmP/GFR after total PTx in 2 cases of XLH remains unexplained, but possible causes are speculated.

Five Year Follow-Up of a Low GI Dietary Randomised Controlled Trial in Pregnancy - No Long-Term Maternal Effects of a Dietary Intervention

To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post‐intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes.

Opinion: redefining the role of the physician in laboratory medicine in the context of emerging technologies, personalised medicine and patient autonomy (‘4P medicine’)

The role of clinical pathologists or laboratory-based physicians is being challenged on several fronts—exponential advances in technology, increasing patient autonomy exercised in the right to directly request tests and the use of non-medical specialists as substitutes. In response, clinical pathologists have focused their energies on the pre-analytical and postanalytical phases of Laboratory Medicine thus emphasising their essential role in individualised medical interpretation of complex laboratory results. Across the European Union, the role of medical doctors is enshrined in the Medical Act. This paper highlights the relevance of this act to patient welfare and the need to strengthen training programmes to prevent an erosion in the quality of Laboratory Medicine provided to patients and their physicians.

Could accreditation bodies facilitate the implementation of medical guidelines in laboratories

Abstract Several studies have shown that recommendations related to how laboratory testing should be performed and results interpreted are limited in medical guidelines and that the uptake and implementation of the recommendations that are available need improvement. The EFLM/UEMS Working Group on Guidelines conducted a survey amongst the national societies for clinical chemistry in Europe regarding development of laboratory-related guidelines. The results showed that most countries have guidelines that are specifically related to laboratory testing; however, not all countries have a formal procedure for accepting such guidelines and few countries have guideline committees. Based on this, the EFLM/UEMS Working Group on Guidelines conclude that there is still room for improvement regarding these processes in Europe and raise the question if the accreditation bodies could be a facilitator for an improvement.