Maternal iodine dietary supplements and neonatal thyroid stimulating hormone in Gippsland, Australia.

BACKGROUND AND OBJECTIVES: Pregnant women are at particular risk of iodine deficiency due to their higher iodine requirements. Iodine is known to be essential for normal growth and brain development, therefore neonatal outcomes in mildly iodine deficient areas, such as Gippsland, are a critical consideration. This study aimed to investigate whether iodine supplementation prevented iodine insufficiency as determined by neonatal thyroid stimulating hormone (TSH) screening criteria. METHODS AND STUDY DESIGN: Gippsland-based women aged >=18 years, in their third trimester of pregnancy, provided self-reported information regarding their iodine supplement use and consent to access their offspring's neonatal TSH screening data. 126 women consented to participate, with 111 women completing all components of this study. RESULTS: Only 18.9% of participants followed the National Health and Medical Research Council (NHMRC) recommendation of 150 µg/day iodine supplement, with 42.3% of participants not taking any supplements, or taking supplements with no iodine or insufficient iodine. The remaining women (38.7%) were taking supplements with doses of iodine much higher (200-300 µg) than the NHMRC recommended dose or were taking multiple supplements containing iodine. When correlating iodine intake to their neonates' TSH, no correlation was found. When iodine supplementation usage was categorised as below, equal to, or above NHMRC recommendations there was no significant difference in neonatal TSH. CONCLUSION: This study found that iodine supplementation appeared to prevent maternal iodine insufficiency when measured against neonatal TSH screening criteria.

Lessons learned from 20 years of newborn screening for cystic fibrosis.

OBJECTIVE: To compare three cystic fibrosis (CF) newborn screening strategies used in Victoria since 1989. DESIGN, SETTING AND PARTICIPANTS: Retrospective review of newborn screening and clinical records for people with CF born in Victoria between 1989 and 2008 to compare screening strategies: repeat immunoreactive trypsinogen (IRT) testing (IRT/IRT, 1989-1990), IRT and p.F508del mutation analysis (IRT/p.F508del, 1991-2006) and IRT with analysis of 12 CFTR mutations (IRT/12 mutations, 2007-2008). MAIN OUTCOME MEASURES: Total number of infants screened, people identified with CF (by screening or clinical diagnosis), number of CF-affected terminations of pregnancy, and number of carriers detected. RESULTS: There were 420 people born with CF (live-birth prevalence, 1/3139; 95% CI, 1/2853-1/3462) and 78 CF-affected pregnancy terminations (overall prevalence, 1/2647; 95% CI, 1/2425-1/2896). Of the babies born with CF, 283 (67.4%) were detected by newborn screening alone, 61 (14.5%) had meconium ileus, 33 (7.9%) had a family history of CF, nine (2.1%) were diagnosed antenatally, and 34 (8.1%) were missed by screening (17 missed because IRT level was < 99th percentile, two with repeat IRT level not elevated, 14 without a screened CFTR mutation, and one with missing data). The sensitivities of the protocols were 86.6% for IRT/IRT, 89.9% for IRT/p.F508del, and 95.8% for IRT/12 mutations. Including 12 mutations in the analysis detected one patient who would otherwise have been missed and, had this protocol been implemented from 1989, it would have detected four others. CONCLUSION: Most babies with CF without meconium ileus, a family history or antenatal diagnosis are detected by newborn screening. Despite improved sensitivity with the 12-mutation analysis, most infants detected would have been diagnosed using the IRT/p.F508del protocol.

Effect of tetrahydrobiopterin on Phe/Tyr ratios and variation in Phe levels in tetrahydrobiopterin responsive PKU patients.

BACKGROUND: Whilst a reduction in blood phenylalanine (Phe) levels is essential in patients with PKU, a decrease in Phe/Tyrosine (Tyr) ratio and fluctuations in blood Phe levels over time have been recently associated with improved neuropsychological outcome. The aim of this study was to identify if Tetrahydrobiopterin (BH(4)) offers additional benefit based on the assumption that these 2 factors are beneficial. METHOD: Since 2002, 9 patients identified through NBS as BH(4) responsive (BH(4) group) and 25 non-responsive patients (non-BH(4) group) produced a total of 1384 and 4415 samples, respectively, for analysis. Statistical analysis was performed to compare mean and median Phe levels, Tyr levels and Phe/Tyr ratios in BH(4) and non BH(4) responsive patients. RESULTS: Variations in blood Phe levels were greater in the non-BH(4) group (BH(4): median 338 µmol/L, 95% Confidence Interval (CI) 329-346, mean: 358 µmol/L, CI 350-366; non-BH(4): median 338 µmol/L CI 332-344, mean: 370 µmol/L CI 364-376). Variations in blood Tyr levels were slightly greater in the non-BH(4) group: (BH(4): median 59 µmol/L CI 58-61, mean 67 CI 66-69; non-BH(4): median 62 µmol/L CI 61-63, mean 70 CI 69-71). The variation in Phe/Tyr ratios was greater in the non-BH(4) group (mean 6.12, CI 5.9-6.3) than in the BH(4) group (Mean 5.44, CI 5.3-5.6), particularly at blood Phe levels >600 µmol/L. CONCLUSION: BH(4) responsive patients have smaller variations in blood Phe levels and tighter Phe/Tyr ratios than non-BH(4) responsive patients, particularly at high blood Phe levels. If decreased fluctuations in Phe levels and a decreased Phe/Tyr ratio are indeed neuro-protective, then BH(4) responsiveness is advantageous over diet alone in PKU. Neuropsychological testing in patients who have been treated with BH(4) long term may be able to ascertain the clinical benefit of these biochemical findings.

Increased iodine deficiency in Victoria, Australia: analysis of neonatal thyroid-stimulating hormone data, 2001 to 2006.

OBJECTIVE: To use neonatal thyroid-stimulating hormone (TSH) concentration data to measure the iodine status of the population of the Australian state of Victoria. DESIGN, PARTICIPANTS AND SETTING: Retrospective analysis of the results of 368,552 neonatal heel-prick blood tests for TSH concentration in Victoria in the years 2001-2006. MAIN OUTCOME MEASURES: Iodine deficiency as indicated by a mean percentage of neonatal TSH concentrations > 5 mIU/L of over 3% in accordance with World Health Organization, United Nations Children's Fund and International Council for the Control of Iodine Deficiency Disorder criteria; comparison of findings for the nine Department of Human Services health regions in Victoria. RESULTS: The mean percentage of neonatal TSH concentrations > 5 mIU/L ranged from 4.07% in 2001 to 9.65% in 2006, and this increase was statistically significant (P < 0.001). The populations of all nine Victorian health regions showed increasing iodine deficiency over the study period. Metropolitan populations had higher iodine deficiency than non-metropolitan populations, and this difference was also statistically significant (P < 0.05). These results are consistent with urinary iodine excretion research in Victoria. CONCLUSIONS: The high percentage of elevated TSH concentrations among newborns is of concern and requires ongoing monitoring. Neonatal TSH assay is part of routine screening in Australia, and thus offers an effective and economical method of monitoring population iodine status.

Declining prevalence of cystic fibrosis since the introduction of newborn screening.

OBJECTIVES: Newborn screening for cystic fibrosis (CF) facilitates early diagnosis and genetic counselling for parents of affected infants. Many parents elect to use prenatal testing for subsequent pregnancies, and this may affect the prevalence of CF. The aim of this study was to assess the evidence for changes in the live-birth prevalence of CF since the introduction of newborn screening for CF. METHODS: The authors reviewed the records of the Victorian newborn screening programme and the clinical records of the three centres caring for patients with CF in Victoria, Australia, in order to determine the live-birth prevalence of patients with CF; before (1979-1988) and after (1989-2006) the introduction of newborn screening. The authors reviewed the records of the Victorian Clinical Genetics Service to ascertain the number and outcome of prenatal tests for CF (1979-2006). Live births in Victoria were obtained from the state birth register. FINDINGS: Between 1979 and 1988, the live-birth prevalence of CF was 3.96 (95% CI 3.48 to 4.49) per 10 000 live births. Following the introduction of newborn screening (1989-2006) the live-birth prevalence of CF was 3.28 (95% CI 2.97 to 3.63) per 10 000 live births, representing a reduction of 17% (95% CI 2% to 29%, p=0.025). In the prescreening period, there were 10 prenatal tests, which identified three affected pregnancies, all of which were terminated. In the later period, there were 304 prenatal tests (mean 17/year), of which 76 were affected, and 70 of these pregnancies were terminated. CONCLUSION: The authors observed a modest reduction in the live-birth prevalence of CF since the introduction of newborn screening. This is principally due to at-risk couples detected by newborn screening electing to use prenatal testing on subsequent pregnancies.

Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome.

OBJECTIVES: To map prenatal screening and diagnostic testing pathways in Victorian pregnant women during 2003 to 2004; measure the impact of prenatal diagnostic testing uptake on the effectiveness of prenatal screening for Down syndrome; and assess factors influencing uptake of diagnostic testing following screening. METHODS: State-wide data collections of prenatal screening and diagnostic tests were linked to all Victorian births and pregnancy terminations for birth defects. RESULTS: Overall, 52% of women had a prenatal test (65 692/126 305); screening (44.9%), diagnostic testing (3.9%), or both (3.2%). Uptake of diagnostic testing was 71.4% (2390/3349) after an increased risk screen result, and 2.5% (1381/54 286) after a low risk result. Variation in uptake of diagnostic testing reduced the effectiveness of the screening program by 11.2%: from 87.4% (sensitivity - 125/143) to 76.2% (prenatal diagnoses of Down syndrome - 109/143). In both the increased and low risk groups, uptake was influenced by absolute numerical risk, as well as by the change in numerical risk from a priori risk. CONCLUSIONS: This comprehensive follow-up demonstrates clearly that numerical risk is being used to aid in decision making about confirmatory diagnostic testing. Collectively, these fundamental individual decisions will impact on the overall effectiveness of screening programmes for Down syndrome.

Using record linkage and manual follow-up to evaluate the Victorian maternal serum screening quadruple test for Down's syndrome, trisomy 18 and neural tube defects.

OBJECTIVES: The Genetic Health Services Victoria maternal serum screening (MSS) quadruple test has been available to pregnant women in Victoria since 1996. The objectives of this study were to follow up the pregnancies screened by MSS between July 1998 and June 2000 and to determine the performance characteristics of the test for Down's syndrome, trisomy 18 and neural tube defects (NTDs). METHODS: MSS results were matched to pregnancy outcome information from the Perinatal Data Collection Unit and Birth Defects Register, using automated probabilistic record linkage. For unmatched pregnancies, manual follow-up was carried out by contacting referring doctors and hospitals, resulting in a very high follow-up rate of 99.2% (18,989/19,143). RESULTS: The sensitivity of MSS for Down's syndrome was 85% (23/27-95%CI 72-99%) with a falsepositive rate (FPR) of 6.8% (risk threshold >or= 1 in 250). While using a fixed 5% FPR, the sensitivity for Down's syndrome was slightly lower (78%). The sensitivity for trisomy 18 was 44% (4/9 - 95% CI 12-77%) with a FPR of 0.5% (risk threshold of >or= 1 in 200). 11 of the 15 (73 - 95%CI 51-97%) cases of open NTDs were detected from screening, with a 1% FPR (risk threshold alpha-fetoprotein [AFP] >or=2.5 MoM). All cases of anencephaly had increased AFP levels. CONCLUSION: Probabilistic record linkage and manual follow-up is an efficient method for ascertainment of pregnancy outcomes, with a higher follow-up rate than that reported in similar studies. MSS should remain an available option for all pregnant women in Victoria, with test characteristics comparable with other recent reports of the quadruple test.