David M. Tappin a,*, Robert W.A. Girdwood b, Robert Kennedy b,. John Tolland ', Karen Johnstone b, Joan Mackenzie b, Tom Cowan b,. Forrester Cockburn a.
SCREENING Journal Society
of the International
of Neonatal
Screening
Screening3 (1995)2OlL207
An audit of infants ‘unscreened’ by the neonatal screening system in Scotland during 1991 David M. Tappin a,*, Robert W.A. Girdwood b, Robert Kennedy b, John Tolland ‘, Karen Johnstone b, Joan Mackenzie b, Tom Cowan b, Forrester Cockburn a a Department of‘ Child Health, Royal Hospitalfor Sick Children, Yorkhill, Glasgow. Scotland, UK G3 8s b Scottish Inborn Errors Screening Laboratory, StobhiN General Hospital, Glasgow, Scotland, UK ’ Communicable Diseases (Scotland) Unit, Ruchill Hospital, Glasgow, Scotland, UK
Received2 June 1994;revisionaccepted28 November1994 Abstract Introduction: The aim of this study was to assessthe number of infants born in Scotland from whom a newborn screening specimendid not arrive at the screening laboratory. Methods: In a systematic 1 in 8 sample, records on 8379 babies registered as born during 1991, were supplied by the Office of the Registrar General (Scotland). These were matched with records from the neonatal screening laboratory database. For all unmatched records, local health board offices were phoned for evidence of a negative result. Results: Specimensfrom 8324 of these babies were received and tested by the screening laboratory. Of the remaining 55 babies, 34 had died within 24 h of birth, five had returned home (three to England and Wales and two to outside the United Kingdom), four refused for parental objection (three were Jehovah’s Witnesses), and 12 were unscreened. Thus, only 0.14% (12 of 8379 of registered infants (95% Confidence Interval 0.22, 0.06)) were unscreened by the Inborn Errors Screening Program in Scotland during 1991. Discussion: From this study, an estimated 96 infants were unscreened for newborn screening (95% Confidence Interval 39, 143) of 67 032 infants registered as born in Scotland during 1991.At this rate, a caseof congenital hypothyroidism or phenylketonuria would be missed only every 47 and 78 years, respectively, as a result of having been unscreened by the program. Improvement is expected from regular audit now underway. The rate of 0.14% for Scotland is much lower than the rate of 0.82% estimated for unscreened infants in the New York State Newborn Screening Program.
Kq~irorS: Newborn; Screening; Phenylketonuria; Congenital hypothyroidism 1. Introduction
In 1965 Stevenson and Kennedy, at Stobhill Hospital in Glasgow, Scotland, pioneered the use of the Guthrie test, in the United Kingdom (UK), for neonatal * Correspondingauthor. 0925-6164/95/$09.50 0 1995ElsevierScience B.V. All rights reserved SSDl 0925.6164(94)00024-7
202
D.M. Tappin et al.lScreening3
(1995) 201-207
phenylketonuria (PKU) screening [I], In 1968, this method was adopted by the remaining neonatal screening laboratories in the UK. In 1979, a further screening test was added to the neonatal blood sample, to detect excessthyroid stimulating hormone (TSH) for the diagnosis of congenital hypothyroidism [2]. In the UK, the neonatal blood sample is taken by a midwife either in the hospital or, more commonly, after hospital discharge, usually between postnatal days 4 and 7. Blood from a heel prick is impregnated into absorbent paper cards. In Scotland all samples are sent by post to a single laboratory located at Stobhill General Hospital in Glasgow. One reason for missed cases of congenital hypothyroidism and PKU has been lack of a neonatal specimen arriving at the screening laboratory and, therefore, not tested [3-61. This can be due to death before 7 days of age when the sample is often taken, unwillingness of parents to allow their infant to have a blood specimen taken, perhaps for religious reasons, or becausethe parents have not been approached for a specimen. The last reason would constitute an unscreened infant. To track those who might be unscreened in Scotland, a list of negative screening results is routinely sent from the screening laboratory to all health boards. There the list of babies born (from SA4R2discharge notzjications from obstetric units in a health board area), can be compared with negative results from the screening laboratory so that unscreened babies can be uncovered. Once pinpointed, unscreened infants can have a neonatal sample collected and submitted. Despite similar and other back-up systems, neonatal screening programs have missed casesof hypothyroidism and PKU because of non-receipt of specimens [ 31. Previous audit studies have used missed cases of the disorder screened, who later presented clinically, as a measure of completeness of the screening programs. In such studies the frequency of missed cases among all cases identified by neonatal screening was between 0.2% and 3% [3-61. A study of unscreened infants from the New York State Newborn Screening Program used another approach. These investigators randomly selected a sample of 1000 records of live births during 1988 and matched these with newborn screening records. Of the total sample, a screening specimen was not received from 0.82% (95% CI 1.36, 0.26) of infants [7]. All births in Scotland, about 6.5000 per year, are registered by parents at the local office of Births, Deaths and Marriages. Registration information is collated and stored at the Office of the Registrar General in Edinburgh. If all registered births could be matched with newborn specimen cards arriving at the Scottish screening laboratory in Glasgow, casesof congenital hypothyroidism and PKU would not be missed due to non-receipt of a specimen.
2. Methods
A systematic 1 in 8 sample of records (total 8379) of neonates registered in Scotland as having been born during 1991 was provided by the Registrar General’s Office (RGO). This sample size was selected so that with an unscreened rate of 2%, 95% confidence intervals would be 1.7% and 2.3%. Each record included father’s
D.M. Tuppin et ah/Screening 3 (199.5) 201-207
203
surname, mother’s surname, address, the date of birth of the infant, and the hospital code of birth. Records were imported into DataEase (DataEase UK Limited, 1 Coventry Road, Ilford, Essex, IGl 4QR), a database management software package. Data on all infants screened since 1985 by the Scottish National Inborn Errors Screening Laboratory (Guthrie) at Stobhill Hospital, Glasgow have been recorded on a computer, in Fortran language without standard database punctuation. 81485 records from babies screenedbetween December 1990and March 1992were exported in ASC II format and imported into a second DataEase database. This transfer of information was not perfect and 367 (0.5%) of these records were unrecognizably corrupted. Another 3507 (4.3%) records were partially corrupted. RGO records were matched with newborn screening records by mother’s surname and infant date of birth using an automated technique. Paired records were checked by hand. Unmatched and incorrectly matched RGO records were then searched for individually. This search started with incorrect spelling of the surname (e.g., McDonald instead of MacDonald). Father’s surname was then substituted for the mother’s surname. If address and mother’s or father’s surname matched and the date of birth was absent or incorrect by a few days, a match was still made. In addition, a match was accepted if the hospital of birth, date of birth and address were the same, even if the father or the mother’s surname was corrupted. Pairings with the same date of birth and hospital of birth alone were not accepted. RGO records which were still unmatched were investigated individually by a clerk at the Inborn Errors Screening Laboratory. The office of the health board Regional Medical Officer was telephoned to seewhether a negative newborn screening notification had been received. A second check was made by searching the stored hard copy, produced by data entry from the newborn screening cards. Relative risk (RR) estimations and chi-square analyses were performed by standard statistical techniques using the data presented in this paper and data from the New York State Newborn Screening Program [7]. 3. Results
Initial automated matching by date of birth and mother’s surname allowed 6700 of 8379 records to be paired. However, 264 of these RGO records were incorrectly matched, usually due to common surnames such as McDonald and Smith, leaving 6436 (76%) correctly matched by computer. These mismatches were easily recognized as they often lived in separate parts of Scotland and were born in different hospitals. The 1679 unmatched and the above 264 mismatched RGO records, totalling 24% of the original sample, were individually searched for by DMT in the newborn screening database. All but 235 (2.8%) RGO records could be matched confidently with a record in the newborn screening database (Table 1). The reasons for unmatched and inappropriately matched records by computer were minor errors in spelling of the surname (440/o),father’s surname instead of mother’s (23%), mistakes or corrupted date of birth (21%) and no recognizable record ( 12%). Table 2 shows the outcome of telephoning the office of the Regional Medical
204
D.M. Tappin et al./Screening 3 (1995) 201-207
Table 1 Matching RGO with newborn screening records: automated and individual Automated
Individual
6436 correct Reason for no automated match Father’s surname Corrupted date of birth Spelling errors No matching newborn screening record found
Total RGO records
264 incorrect
454 399 855 235 8379
Table 2 Outcome of telephoning the office of the Regional Medical Officer (RMO) for infants where no matching newborn screening record was found Outcome
Newborn Screening Laboratory
Negative result at RMO Baby died within 24 h of birth Baby returned home outside Scotland RGO record incorrect: wrong year Refusal for religious reasons Refusal for other reasons ‘Unscreened’ (including lost in the post) Total
Negative result found
178 34 5 2 3 1 12 235
Officer (RMO) for the 235 RGO records not matched. This includes two infants for whom the Office of the Registrar General sent a record which could only be matched with an infant born at the same address with the same surname on the same day and month but in a different year. This was uncovered by the RMO and probably indicates a mistake in data entry at the RGO. In the final analysis, excluding infants whose parents refused neonatal screening, 12 (0.14%) of 8379 registered infants were unscreenedby the Inborn Errors Screening Program in Scotland during 1991, according to our computer matching and followup of unmatched cases(Table 2). RMOs reported that samples had been sent for 5 of these 12 unscreened infants. There was no evident geographical focus of unscreened infants. Thus, the coverage of newborn screening by the Inborn Errors Screening Program in Scotland was 99.86% (95% CI 99.78, 99.94). 4. Discussion
The National Inborn Errors program in Scotland started to screen for PKU on blood taken in the neonatal period during 1965 [ 11. Since then, a number of other
D.M.
Tappin et al/Screening3
(1995)
201-207
205
diseaseshave also been examined and, at present, routine screening also includes tests for congenital hypothyroidism and galactosemia. To date, in Scotland, the Inborn Errors Screening laboratory has succeededin picking up all known casesof PKU, congenital hypothyroidism and galactosemia born after the screening commenced. Once assay techniques were sufficiently sensitive and specific, the main concern was babies for whom a newborn specimen did not arrive at the laboratory. This study has shown that very few infants (0.14%, 96 infants per year; 95% CI 39, 143) are unscreened by the Inborn Errors Screening Program in Scotland. It would take 47 years and 78 years, respectively, to miss a case of congenital hypothyroidism (incidence 1 in 4500 births) or PKU (incidence 1 in 7500 births) becauseof an infant being unscreenedby the neonatal screening system in Scotland. This is a significantly better (chi-square, 15.3, P < 0.0001) rate than the 0.82% unscreened infants estimated in the only other study of this kind performed, the New York study of 1988 [ 71. In that study, the risk of being unscreened in New York was over 5-times greater (RR 5.6,95% CI 2.3, 13.3) than being unscreenedby the Scottish Inborn Errors Screening Program. The design of systematically sampling 1 in 8 RGO records allowed close confidence intervals to be obtained with the suspected 2% ‘missed’ cases reported in other studies [336]. With only 12 infants unscreened (0.14%), an even smaller sample would have given adequate confidence intervals. The Scottish Inborn Errors Screening Laboratory has continued a regular audit program with smaller systematic samples of 1500 infant records from the Registrar General’s Office each quarter year. This analysis of the first quarter in 1992 indicated that 2 of 1500 infants had been unscreened (0.13%). A major problem encountered was to transfer records from Fortran format to a database which could be easily searched. This required an initial step where each record was delimited so that the recipient database could recognize the beginning and end of each field of information and each record. It was impossible to perform this step without corruption of data as records and fields were not of uniform length. Some corruptions allowed matching of records but others could not be matched. This included the 178 babies who had negative results at the Office of the Regional Medical Officer and on hard copy at the neonatal screening laboratory. Minor spelling mistakes accounted for the major workload (44%) of records which were not matched by computer. Especially common in Scotland are the prefixes Mac and Mr. Use of the wrong prefix is difficult to eradicate and may be a transposition error in the Inborn Errors Laboratory or a mistake made by the midwife who took the blood sample. In addition, the data are handwritten on the screening cards. After reading addresses directly from 15000 Guthrie cards, one of the authors (DMT) was surprised that more transcription errors did not occur. Simple spelling mistakes in transcription could be improved by an automated spell-check dictionary of surnames. Mistakes in the date of birth could be reduced by improved computer software. A limit to digits of 01 to 31 for day, 01 to 12 for month and present and previous year for year of birth would eradicate most transcription errors. The Scottish Inborn Errors Screening Laboratory is at present having a major computer
206
D.M. Tappin et al.lScreening 3 (1995) 201-207
upgrade. This will facilitate record entry reducing false data and will allow audit to be performed directly with the newborn screening database. The other common reason for manual data matching was a change of surname. If parents are unmarried, accounting for 27% in Scotland during 1991 [S], the district midwife who collects the neonatal sample in the mother’s home may use either the mother’s or the father’s surname on the card. The Registrar General sent records with both mother’s and father’s surnames. Initial automated matching was performed using mother’s surname, so if parents were unmarried and father’s surname was used, an automatic match was not made by computer. In Scotland, for every baby whose specimen card arrives at the Inborn Errors Screening Laboratory at Stobhill Hospital in Glasgow, a result is sent out to the local Health Board. There the list of babies born (from SMR2 discharge notifications from obstetric units in a health board area) can be compared with negative results from the screening laboratory so that unscreened babies can be detected. These negative reports are not sent out immediately, and it is a labor intensive job to match the two sets of data one by one. A fear has always existed at the screening laboratory that babies are left unscreened. For this reason and in line with general audit, this study aimed to determine how many babies were left unscreened by the program. This study has sparked great interest from Health Boards. We found no geographical focus of unscreened infants. In the main, extremely good systemsare in place to make sure that each infant born in a health board area in Scotland has a newborn screening result. Five of the 12 unscreened casesseemto have had samples sent. We conclude that these five samples were lost in transit to the Inborn Errors Screening Laboratory. These five specimens should have been discovered by the negative reporting system and are still, therefore, classed as unscreened. The low number of unscreened infants is a credit to midwives, health visitors, the neonatal screening laboratory and health board clerical staff. Continued cooperation with future audit should allow this good performance to continue.
Acknowledgements
This audit would not have been possible without the help of the clerical staff at the offices of the Health Board Regional Medical Officers throughout Scotland. We would like to thank all midwives, health visitors, clerical and scientific staff whose hard work makes the Inborn Errors Screening Program in Scotland so successful. The Medical Research Council supported all aspects of this study (MRC No. 8908795C).
References [l]
Stevenson JS, Kennedy R. The Guthrie test for phenylketonuria 1965-1973. Health Bulletin 1974; 6: 245.
and allied diseases in Scotland
D. M. Tappin et al. /Screening 3 ( 1995) 201-207
207
[2] Sutherland RM, Ratcliffe JG, Kennedy R, Stevenson JS, Patrick MJ, Ferguson-Smith MA. Neonatal screening for hypothyroidism in Scotland: results of a pilot study. Scottish Med J 1981; 26: 229. [3] MRC Steering Committee for the MRC/DHSS Phenyketonuria Register. Routine neonatal screening for phenyketonuria in the United Kingdom 196478. Br Med J 1981; 282: 1680. [4] Pitt D, Connelly J, Wilcken IFB, et al. Genetic screening of newborn in Australia: results for 1981, Med J Aust 1983; 1: 333. [5] Holtzman C, Slazyk WE, Corder0 JF, Hannon WH. Descriptive epidemiology of not tested cases of phenylketonuria and congenital hypothyroidism. Pediatrics 1986; 78: 553. [6] Fisher DA. Effectiveness of newborn screening programs for congenital hypothyroidism: prevalence of not tested cases.Pediatr Clin NA 1987; 34: 881. [7] Pass KA, Schedlbauer LM, MacCubbin PA, Glebatis DM. Comparison of newborn screening records and birth certificates to estimate bias in newborn HIV serosurveys. Am J Public Health 1991; 81 (Suppl.): 22. [ 81 General Register Office Population Estimates Scotland. Government Statistics Service, Her Majesty’s Stationary Office 1991; S2.5.
