Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

Iodine status of teenage girls on the island of Ireland.

PURPOSE: The trace element iodine is a vital constituent of thyroid hormones. Iodine requirements increase during pregnancy, when even mild deficiency may affect the neurocognitive development of the offspring. Urinary iodine concentration (UIC) is the means of assessing iodine status in population surveys; a median UIC of 100-199 µg/L is deemed sufficient in a non-pregnant population. Milk is the main dietary source of iodine in the UK and Ireland. METHODS: We surveyed the iodine status of 903 girls aged 14-15 years in seven sites across the island of Ireland. Urine iodine concentration was measured in spot-urine samples collected between March 2014 and October 2015. Food group intake was estimated from iodine-specific food-frequency questionnaire. Milk-iodine concentration was measured at each site in summer and winter. RESULTS: The median UIC overall was 111 µg/L. Galway was the only site in the deficient range (median UIC 98 µg/L). All five of the Republic of Ireland sites had UIC ≤ 105 µg/L. In the two sites surveyed twice, UIC was lower in summer vs winter months [117 µg/L (IQR 76-165) vs 130 µg/L (IQR 91-194) (p < 0.01)]. Milk samples collected from Galway and Roscommon had a lower mean iodine concentration than those from Derry/Londonderry (p < 0.05). Milk intake was positively associated with UIC (p < 0.001). CONCLUSIONS: This is the largest survey of its kind on the island of Ireland, which currently has no iodine-fortification programme. Overall, the results suggest that this young female population sits at the low end of sufficiency, which has implications if, in future, they enter pregnancy with borderline status.

The GH-2004 project: the response of IGF1 and type III pro-collagen to the administration of exogenous GH in non-Caucasian amateur athletes.

CONTEXT: The GH-2000 team proposed a method based on IGF1 and type III pro-collagen (P-III-P) to detect exogenously administered GH. As previous studies involved predominantly white European athletes, it is important to assess whether the response of these markers to recombinant human GH (rhGH) differs with ethnicity. OBJECTIVE: To examine the response of serum IGF1 and P-III-P and GH-2000 score to rhGH in non-Caucasian amateur athletes. DESIGN: Double-blind placebo-controlled rhGH administration study. SETTING: Wellcome Trust Clinical Research Facility, Southampton General Hospital. SUBJECTS: The study included 31 male and 14 female amateur athletes of different ethnicities. Intervention The subjects were assigned to treatment with placebo or 0.1 IU/kg per day (low dose) or 0.2 IU/kg per day (high dose) rhGH for 28 days. Blood was collected weekly during treatment and on days 35, 42 and 84 during the washout period. Serum IGF1 and P-III-P were measured, and GH-2000 score was calculated. RESULTS: IGF1, P-III-P and GH-2000 score rose in response to both low- and high-dose GH in both men and women. When compared with the Caucasian volunteers of the previous GH-2000 study, mean baseline and placebo-treated P-III-P and GH-2000 score were lower in GH-2004 men and women. Post-GH, however, peak IGF1 or P-III-P did not differ between studies but the peak GH-2000 score was lower in GH-2004 men. There was no difference between studies in the maximal change in IGF1, P-III-P and GH-2000 score in response to GH in either gender. CONCLUSIONS: These data do not support a significant ethnic effect on the peak or maximal response to rhGH.

Moving one step closer to catching the GH cheats: The GH-2004 experience.

Growth hormone is abused by athletes for its anabolic and lipolytic properties. The detection of GH abuse is challenging because it is an endogenous hormone whose concentration varies widely in any one day. The GH-2000 project proposed a test based on the measurement of IGF-I and type III pro-collagen (P-III-P). When the results of the GH-2000 project were presented to an expert workshop, the method was supported but it was felt that several issues needed to be resolved before the method could be adopted. The first was a potential effect of ethnicity as most subjects in the GH-2000 were white Europeans and the second was a possible effect of injury as P-III-P is a marker of soft tissue turnover. The GH-2004 project was conceived to address these concerns. The GH-2004 project has shown that while there are minor differences in IGF-I and P-III-P between ethnicities, these are small and do not affect the performance of the test. Injury leads to a small rise in P-III-P but again this is not of sufficient magnitude to affect the performance of the test. The GH-2004 project has provided further support for the marker approach as a means of detecting GH abuse in athletes. As WADA have not developed their own immunoassays, however, further work is needed to validate newer commercial assays measuring IGF-I and P-III-P to establish reliable conversion factors to the original GH-2000 units to allow the published formulae to be used.

Influence of ethnicity on IGF-I and procollagen III peptide (P-III-P) in elite athletes and its effect on the ability to detect GH abuse.

CONTEXT: A method based on the two GH dependent markers, IGF-I and procollagen III peptide (P-III-P) has been proposed to detect exogenously administered GH. As previous studies involved predominantly white European elite athletes, it is necessary to validate the method in other ethnic groups. OBJECTIVE: To examine serum IGF-I and P-III-P in elite athletes of different ethnicities within 2 h of competing at national or international events. DESIGN: Cross-sectional observational study. SETTING: National and International sporting events. SUBJECTS: 1085 elite athletes of different ethnicities. INTERVENTION: Serum IGF-I and P-III-P were measured and GH-2000 discriminant function score was calculated. Effect of ethnicity was assessed. RESULTS: In men, IGF-I was 21.7 +/- 2.6% lower in Afro-Caribbeans than white Europeans (P < 0.0001) but there were no differences between other ethnic groups. In women, IGF-I was 14.2 +/- 5.1% lower in Afro-Caribbeans (P = 0.005) and 15.6 +/- 7.0% higher in Orientals (P = 0.02) compared with white Europeans. P-III-P was 15.2 +/- 3.5%, 26.6 +/- 6.6% and 19.3 +/- 5.8% lower in Afro-Caribbean (P < 0.0001), Indo-Asian (P < 0.0001) and Oriental men (P = 0.001), respectively, compared with white European men. In women, P-III-P was 15.7 +/- 4.7% lower in Afro-Caribbeans compared to white Europeans (P =0.0009) but there were no differences between other ethnicities. Despite these differences, most observations were below the upper 99% prediction limits derived from white European athletes. All GH-2000 scores lay below the cut-off limit proposed for doping. CONCLUSIONS: The GH-2000 detection method based on IGF-I and P-III-P would be valid in all ethnic groups.

A determination of the pre-analytical storage conditions for insulin like growth factor-I and type III procollagen peptide.

OBJECTIVE: IGF-I and type III procollagen (P-III-P) have been proposed as markers to detect GH abuse. This study aims to determine whether the pre-analytical storage temperature or delayed centrifugation affect the measured IGF-I and P-III-P concentrations. DESIGN: Observational study. SETTING: Wellcome Trust Clinical Research Facility, Southampton. SUBJECTS: Nineteen healthy volunteers. INTERVENTION: Blood was collected into bottles containing a clotting agent, lithium heparin or EDTA. One sample from each group was centrifuged and stored at -80 degrees C (control sample). The remaining samples from each group were stored as either serum or whole blood at 4 degrees C or room temperature for up to five days prior to storage at -80 degrees C. OUTCOME MEASURES: IGF-I and P-III-P. RESULTS: The storage temperature or timing of centrifugation did not appear to affect IGF-I concentration. In contrast, the measured P-III-P concentration rose by 6.5-7% per day in clotted and lithium heparin samples when stored as whole blood (p<0.006) or serum (6.2-6.5% per day) at room temperature (p<0.001). P-III-P did not change when the samples were stored at 4 degrees C. Although collection into EDTA inhibited the rise in P-III-P, the baseline measured values were significantly higher than in other media and spiking experiments demonstrated that EDTA exerted a significant matrix effect on the assay. CONCLUSION: While the optimum collection method is immediate centrifugation and storage at -80 degrees C, it would seem acceptable to store serum or clotted blood samples at 4 degrees C, but not ambient temperature, for up to five days. It is incumbent on the anti-doping authorities to provide facilities to allow this.

The effect of sports injury on insulin-like growth factor-I and type 3 procollagen: implications for detection of growth hormone abuse in athletes.

CONTEXT: A method to detect exogenously administered growth hormone (GH) based on the measurement of two GH-dependent markers, IGF-I and type 3 procollagen (P-III-P) has been proposed. Skeletal or soft tissue injury may alter these markers. Elevations in either of these proteins after injury might lead to a false accusation of doping with GH. OBJECTIVE: The objective of the study was to assess the effect of musculoskeletal or soft tissue injury on IGF-I and P-III-P concentrations in amateur and elite athletes and assess the effect of injury on the proposed GH detection method. DESIGN: This was a longitudinal observational study after sporting injury. SETTING: The study was conducted at Southampton General Hospital and British Olympic Medical Centre. SUBJECTS: Subjects included elite and amateur athletes after an injury. INTERVENTION: Interventions included measurement of IGF-I and P-III-P and application of the GH-2000 discriminant function score up to 84 d after an injury as well as classification of injury by type and severity. OUTCOME MEASURES: IGF-I and P-III-P concentration and ability to detect GH abuse in athletes without the risk of false accusation because of an injury were measured. RESULTS: There was no change in IGF-I concentration after an injury. By contrast, P-III-P concentrations rose by 41.1 +/- 16.6%, reaching a peak around 14 d after an injury. The rise in P-III-P varied according to injury type and severity. This rise had a trivial effect on the GH-2000 discriminant function score, and no subject reached the threshold needed for a doping offense. CONCLUSIONS: Although there was a rise in P-III-P after injury, this was insufficient to invalidate the GH-2000 detection method based on IGF-I and P-III-P concentrations.

Challenges in detecting the abuse of growth hormone in sport.

BACKGROUND: Growth hormone (GH) is reputed to be in widespread use in the sporting arena as a performance-enhancing agent and is on the list of banned substances published by the World Anti-Doping Agency. The detection of GH abuse poses many challenges. Unlike many substances of abuse, such as synthetic anabolic steroids, GH is a naturally occurring substance; therefore, demonstration of exogenous administration must rely on detecting concentrations in excess of an established reference interval. The purpose of this review is to discuss the methodologies being developed to detect GH abuse. METHODS: We undertook a comprehensive search using multiple electronic databases and hand searches of reference lists of articles. The data for this review reflect our academic interests and experience through work on the GH-2000 and GH-2004 projects. RESULTS: Two approaches have been taken to detect GH abuse. The first is based on assessment of the effect of exogenous GH on pituitary GH isoforms, and the second is based on measurement of markers of GH action. The advantages of each approach and the difficulties encountered with each technique, as well as future concepts in detection, are discussed. CONCLUSION: Although there are substantial challenges for the detection of GH, methodologies now exist to detect GH abuse with reasonable sensitivity and specificity.