ORCID Profile
0000-0002-5142-4239
Current Organisations
Auckland District Health Board
,
The University of Auckland
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Publisher: Wiley
Date: 31-01-2021
DOI: 10.1111/CEN.14422
Publisher: MDPI AG
Date: 03-05-2022
DOI: 10.3390/IJNS8020030
Abstract: A national protocol for structured follow-up and texting of repeat newborn bloodspot screening (NBS) s le requests was introduced. Repeat s les are needed where the initial s le is inadequate or the result borderline-positive. This protocol aimed to improve the timeliness and completeness of receipt of repeat NBS s les. Under the structured protocol, all repeat s le requests were phoned or texted to the lead maternity carer (LMC), in addition to the standard written report issued. Weekly text reminders were sent until 4 weeks or the s le was received. National data were monitored following implementation of the protocol. The proportion of repeat s les received within 10 days of request improved after the introduction of the protocol, from 35.0% in 2013 to 81.4% in 2020 (p 0.001). The proportion of requests lost to follow-up decreased, from 4.1% in 2013 to 1.3% in 2020 (p 0.001). A structured NBS follow-up protocol that included SMS text messaging led to an earlier and more complete receipt of repeat s les. This is likely due to practitioners receiving the request more quickly, as well as the laboratory adopting a consistent approach to repeated reminders. SMS text messages are a useful adjunctive method for screening programmes to communicate with health care providers.
Publisher: MDPI AG
Date: 21-10-2022
DOI: 10.3390/IJNS8040056
Abstract: Between 2005 and 2021, 49 cases of classical congenital adrenal hyperplasia were diagnosed in New Zealand, 39 were detected in newborns and 10 were not detected by screening. Currently, for every case of CAH detected by screening, 10 false-positive tests are encountered. Second-tier liquid chromatography-tandem mass spectrometry (LCMSMS) has the potential to improve screening sensitivity and specificity. A new laboratory protocol for newborn screening for CAH was evaluated. Birthweight-adjusted thresholds for first- and second-tier 17-hydroxyprogesterone, second-tier 21-deoxycortisol and a steroid ratio were applied to 4 years of newborn screening data. The study was enriched with 35 newborn screening specimens from confirmed CAH cases. Newborn screening was conducted on 232,542 babies, and 11 cases of classical CAH were detected between 2018 and 2021. There were 98 false-positive tests (specificity 99.96%, PPV = 10.1%) using the existing protocol. Applying the new protocol, the same 11 cases were detected, and there were 13 false-positive tests (sensitivity 99.99%, PPV = 45.8%, (X2 test p 0.0001). Incorporating the retrospective specimens, screening sensitivity for classical CAH was 78% (existing protocol), compared to 87% for the new protocol (X2 test p = 0.1338). Implementation of LCMSMS as a second-tier test will improve newborn screening for classical CAH in New Zealand.
Publisher: Wiley
Date: 21-10-2017
DOI: 10.1111/CEN.13250
Abstract: The aim of this study was to assess the performance of the revised New Zealand (NZ) newborn screening TSH cut-offs for congenital hypothyroidism (CHT). Screening data over 24 months were obtained from the NZ newborn metabolic screening programme, which utilizes a 2-tier system of direct clinical referral for infants with markedly elevated TSH, and second s les from those with mild TSH elevation. We evaluated the impact of a reduced TSH threshold (50 to 30 mIU/l blood) for direct notification and a lower cut-off (15 to 8 mIU/l blood) applied to second s les and babies older than 14 days. In 2013 and 2014, 117 528 infants underwent newborn screening for CHT. Fifty-two CHT cases were identified by screening (47 general newborn population, five repeat testing in low-birth-weight infants) and one case was missed. Thirty-two infants with screening TSH ≥30 mIU/l were directly referred at a median of 9 days (5-14) and 15 with TSH 15-29 mIU/l were referred after a second s le at a median of 20 days (9-52, P < 0·001). All directly referred infants were confirmed as CHT cases with no earlier referrals as a result of the reduced threshold. The lower TSH cut-off applied to second s les lead to the identification of six extra cases of CHT (15% increase) from seven extra clinical referrals. The NZ screening programme achieved a 15% increase in CHT case detection for minimal increase in workload or anxiety for families of healthy infants. A further decrease in the threshold for direct referral may allow earlier diagnoses.
Publisher: MDPI AG
Date: 10-05-2022
DOI: 10.3390/IJNS8020033
Abstract: Screening for severe combined immunodeficiency (SCID) was added to the New Zealand national newborn screening programme in December 2017. Documentation pertaining to the application to add SCID to the panel and screening results over the first three years were reviewed. Screening evaluation metrics were shown to differ according to site of collection (babies in a neonatal intensive care unit vs. the community), definition of a positive test (out-of-range result vs. result leading to a further action on baby), and screening target/case definition (primary SCID vs. non-SCID T-cell lymphopenia). Our experience demonstrates both the value of close clinical involvement during the implementation phase of SCID screening and that the use of standard definitions will facilitate international comparison.
Publisher: Springer Berlin Heidelberg
Date: 08-12-2017
DOI: 10.1007/8904_2016_25
Publisher: Wiley
Date: 2019
DOI: 10.1002/JIMD.12030
Abstract: When screening for carnitine uptake disorder (CUD), the New Zealand (NZ) newborn screening (NBS) service identified infants as screen-positive if they had initial and repeat free carnitine (C0) levels of less than 5.0 μmol/L. Since 2006, the NBS service has identified two infants with biochemical and genetic features consistent with neonatal CUD and nine mothers with features consistent with maternal CUD. A review of the literature suggests that these nine women reflect less than half the true prevalence and that CUD is relatively common. However, the NZ results (two infants) suggest a very low sensitivity and positive predictive value of NBS. While patients presenting with significant disease due to CUD are well described, the majority of adults with CUD are asymptomatic. Nonetheless, treatment with high-dose oral L-carnitine is recommended. Compliance with oral L-carnitine is likely to be poor long term. This may represent a specific risk as treatment could repress the usual compensatory mechanisms seen in CUD, such that a sudden discontinuation of treatment may be dangerous. L-carnitine is metabolized to trimethylamine-N-oxide (TMAO) and treated patients have extremely high plasma TMAO levels. TMAO is an independent risk factor for atherosclerosis and, thus, caution should be exercised regarding long-term treatment with high-dose carnitine of asymptomatic patients who may have a biochemical profile without disease. Due to these concerns, the NZ Newborn Metabolic Screening Programme (NMSP) initiated a review via a series of advisory and governance committees and decided to discontinue screening for CUD.
Publisher: American Academy of Pediatrics (AAP)
Date: 12-2007
Abstract: OBJECTIVE. The objective of this study was to examine the major constituent of nonesterified fatty acids in children with respect to auxologic parameters, insulin sensitivity, and lipid levels, because nonesterified fatty acid levels are elevated in obesity and are important in the development of comorbidities. METHODS. Fasting blood s les were obtained from 73 children (43 girls 49 obese median [range] age: 11.4 [0.9–17.6] years). Concentrations of the major circulating nonesterified fatty acids (myristate, palmitate, oleate, stearate, and arachidate) were determined by gas chromatography mass spectrometry, alongside measurement of insulin, adiponectin, and lipid profiles. RESULTS. The sum of all nonesterified fatty acids was significantly higher in obese versus normal-weight children, although gender (but not age or puberty) was an important determinant, with the difference remaining significant only in boys. Overall, obese children had higher concentrations of myristate, palmitate, and oleate but not stearate or arachidate. Age was an important determinant of myristate and arachidate, whereas gender proved more important for palmitate and stearate. Fasting insulin concentrations were not associated with either total nonesterified fatty acid concentrations or any of the in idual nonesterified fatty acids, although a positive correlation was found between adiponectin and total nonesterified fatty acid concentrations that was independent of obesity status and that seemed mediated by changes in palmitate and stearate. Serum total cholesterol and low-density lipoprotein (but not high-density lipoprotein) levels seemed to correlate positively with circulating concentrations of palmitate, oleate, and stearate, whereas serum triacylglycerols correlated with myristate, palmitate, and oleate concentrations. CONCLUSIONS. Nonesterified fatty acid concentrations are elevated in obese children, primarily as a result of increases in myristate, palmitate, and oleate. Independent effects of nonesterified fatty acids on circulating adiponectin levels and lipid parameters were observed, although we found no relationship between nonesterified fatty acid concentrations and the insulin resistance identified with obesity.
Publisher: Wiley
Date: 21-09-2022
DOI: 10.1002/JMD2.12339
Abstract: Newborn screening (NBS) for classical galactosaemia (CG) facilitates early diagnosis and treatment to prevent life‐threatening complications, but remains controversial, and screening protocols vary widely between programmes. False‐negatives associated with first‐tier screening of total galactose metabolites (TGAL) are infrequently reported however, newborns with TGAL below the screening threshold have not been systematically studied. Following the diagnosis of CG in two siblings missed by NBS, a retrospective cohort study of infants with TGAL just below the cut‐off (1.5 mmol/L blood) was conducted. Children born in New Zealand (NZ) from 2011 to 2019, with TGAL 1.0–1.49 mmol/L on NBS were identified from the national metabolic screening programme (NMSP) database, and clinical coding data and medical records were reviewed. GALT sequencing was performed if CG could not be excluded following review of medical records. 328 infants with TGAL 1.0–1.49 mmol/L on NBS were identified, of whom 35 had ICD‐10 codes relevant to CG including vomiting, poor feeding, weight loss, failure to thrive, jaundice, hepatitis, Escherichia coli urinary tract infection, sepsis, intracranial hypertension and death. CG could be excluded in 34/35, due to documentation of clinical improvement with continued dietary galactose intake, or a clear alternative aetiology. GALT sequencing in the remaining in idual confirmed Duarte‐variant galactosaemia (DG). In conclusion, undiagnosed CG appears to be rare in those with TGAL 1.0–1.49 mmol/L on NBS however, our recent experience with missed cases is nevertheless concerning. Further work is required to establish the optimum screening strategy, to maximize the early detection of CG without excess false‐positives.
Publisher: Wiley
Date: 07-01-2016
DOI: 10.1007/S10545-015-9911-Z
Abstract: Very long chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM #201475) has been increasingly diagnosed since the advent of expanded newborn screening (NBS). Elevated levels of tetradecenoyl-L-carnitine (C14:1) in newborn screening blood spot s les are particularly common in New Zealand, however this has not translated into increased VLCADD clinical presentations. A high proportion of screen-positive cases in NZ are of Maori or Pacific ethnicity and positive for the c.1226C > T (p.Thr409Met) ACADVL gene variant. We performed a retrospective, blinded, case-control study of 255 cases, born between 2006 and 2013, with elevated NBS C14:1 levels between 0.9 and 2.4 μmol/L, below the NZ C14:1 notification cut-off of 2.5 μmol/L. Coded healthcare records were audited for cases and age- and ethnicity- matched controls. The clinical records of those with possible VLCADD-related symptoms were reviewed. The follow-up period was 6 months to 7 years. Two of 247 cases (0.8 %) had possible VLCADD-like symptoms while four of 247 controls (2 %) had VLCADD-like symptoms (p = 0.81). Maori were overrepresented (68 % of the cohort vs 15 % of population). Targeted analysis of the c.1226 locus revealed the local increase in screening C14:1 levels is associated with the c.1226C > T variant (97/152 alleles tested), found predominantly in Maori and Pacific people. There was no increase in clinically significant childhood disease, irrespective of ethnicity. The study suggests that children with elevated C14:1, between 0.9-2.4 μmol/L, on NBS are at very low risk of clinically significant childhood disease. A minimally interventional approach to managing these patients is indicated, at least in the New Zealand population.
Publisher: MDPI AG
Date: 28-01-2020
DOI: 10.3390/IJNS6010006
Abstract: The positive predictive value of newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency was % in New Zealand. This is despite a bloodspot second-tier immunoassay method for 17-hydroxyprogesterone measurement with an additional solvent extract step to reduce the number of false positive screening tests. We developed a liquid chromatography tandem mass spectrometry (LCMSMS) method to measure 17-hydroxyprogesterone in bloodspots to replace our current second-tier immunoassay method. The method was assessed using reference material and residual s les with a positive newborn screening result. Correlation with the second-tier immunoassay was determined and the method was implemented. Newborn screening performance was assessed by comparing screening metrics 2 years before and 2 years after LCMSMS implementation. Screening data analysis demonstrated the number of false positive screening tests was reduced from 172 to 40 in the 2 years after LCMSMS implementation. The positive predictive value of screening significantly increased from 1.71% to 11.1% (X2 test, p 0.0001). LCMSMS analysis of 17OHP as a second-tier test significantly improves screening specificity for CAH due to 21-hydroxylase deficiency in New Zealand.
Publisher: The Endocrine Society
Date: 31-05-2021
Abstract: The positive predictive value of newborn screening for congenital adrenal hyperplasia (CAH) in New Zealand is approximately 10%. The use of a second tier liquid chromatography-tandem mass spectrometry bloodspot steroid profile test with birth weight– or gestational age–adjusted screening cutoffs may result in further screening improvements. Three years of newborn screening data with additional second-tier steroid metabolites was evaluated (n = 167 672 births). Data from babies with a negative screening test and confirmed CAH cases were compared. First- and second-tier steroid measurements were correlated with both birth weight and gestational age. Analysis of variance was used to determine birth weight and gestational age groups. Screening cutoffs were determined and applied retrospectively to model screening performance. First-tier immunoassay data correlated better with gestational age than with birth weight, but there was no difference with second-tier steroid measurements. Four distinct birth weight and gestational age groups were established for 17-hydroxyprogesterone and a steroid ratio measurement. Application of 97.5th percentile second-tier birth weight– or gestational age–adjusted cutoffs would result in 10 positive tests over the period of the study with 8 true-positive screens and 2 false-positive tests. The positive predictive value of screening would be increased from 10.8% to 80%. The use of either birth weight– or gestational age–adjusted cutoffs for second-tier screening tests can significantly reduce the false positive rate of newborn screening for CAH in New Zealand without loss in screening sensitivity.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mark de Hora.