Abstract
Newborn screening programmes to identify babies at risk of having uncommon but serious medical conditions that can affect normal development are now among the most popular measures for control and treatment of congenital problems. The Newborn Screening Programme in Beijing began in 1981, when a pilot plan was developed that demonstrated the feasibility of its implementation. In 1989 the Beijing Health Department instituted screening for congenital hypothyroidism (CH) and phenylketoneuria (PKU) was included in the programme three years later in 1992. 1 In 1992–1993 the World Health Organisation and the Ministry of Public Health sponsored a co-operative project for neonatal screening in Beijing and six other major Chinese cities. 2
Blood samples were collected between 48 and 72 hours after birth for CH and PKU screening, and sent to the only screening laboratory for testing. While newborn screening is strongly recommended for all babies, participation is voluntary. Parents are asked to provide written consent for the screening test before sample collection. In CH screening, blood thyroid-stimulating hormone (TSH) was quantified by radio-immunoassay (1989–2003) and dissociation enhanced lanthanide fluoroimmunoassay (2004–2010). Reference values used, with the upper cut-off value for TSH, were 20 mU/Land10 mU/L, respectively. PKU screening was originally performed with bacteria inhibition assay (1992–2003), but the laboratory later employed fluorometric methods for the measurement of phenylalanine concentrations (2004–2010). Blood concentrations higher than 120 μmol/L require re-examination using the fluorometric method; concentrations over 240 μmol/L use the bacteria inhibition method.
Throughout this period 1,885,202 newborns were analysed, obtaining initial coverage of 14.01% (this has since increased to 99.16%). There were 547 CH cases diagnosed, resulting in an incidence of one case per 3,447 live births (95% confidence interval 3,180–3,762). Of a total of 1,790,267 newborns screened for PKU, 211 cases were confirmed (including classic PKU and hyperphenylalaninaemia; a baby with a persistently high level of phenylalanine, >1200 μmol/L without treatment, was confirmed as classic PKU), arriving at an incidence of one case per 8,485 live births (95% confidence interval 7,476–9,808) (Table 1).
Methodology results of neonatal screening for metabolism disorders in Beijing
RIA, radio-immunoassay; DELFIA, dissociation enhanced lanthanide fluoroimmunoassay; BIA, bacteria inhibition assay; FLU, fluorometric; PPV, positive predictive value; MS/MS, tandem mass spectrometry; FNR, false-negative rates; FPR, false-positive rates
Of the CH cases diagnosed, 120 (21.94%) were categorized as transient CH, and stopped treatment by age three. Eight (3.79%) patients with PKU died, due either to the decision of parents to discontinue treatment or through other diseases. Of those patients followed up, 176 (88.44%) have done well after feeding with a metabolic formula and low protein diet.
Since 1 June 2009 newborn screening for PKU and CH have been free of charge, and the government has provided free phenylalanine-free aminoacid formula treatment to babies with PKU (the serum pH above 360 umol/L treatment was recommended in China). Each baby with the disease receives the milk powder free for six years, saving families 30,000 yuan (about $USD 4,650) a year as a programme benefit, a significant amount for poor families.
In 2006 the introduction of tandem mass spectrometry (TMS) meant that it was possible to look for a number of different chemicals simultaneously using only a tiny sample of blood. In Beijing, about 35 conditions are now included in this expanded newborn screening programme. 3 Since 2006, the screening services have taken place at the Center for Clinical Laboratory Development, Chinese Academy of Medical Science. Participation in the expanded newborn screening programme is voluntary at a cost of 880 yuan ($USD 130).
Between December 2006 and December 2010, 102,601 neonates were screened under the expanded programme, obtaining initial coverage of 1.24%, which increased to 21.43%. During this period, 24 cases were diagnosed: nine cases of PKU, four cases of methylmalonic aciduria, two cases of maple syrup urine disease, two cases of medium-chain acyl-CoA dehydrogenase deficiency and one case each of propionic acidaemia, multiple acyl-coA dehydrogenase deficiency, Short-chain acyl-CoA dehydrogenase deficiency, tyrosinaemia, Hyperammonemia–Hyperornithinemia–Homocitrullinuria syndrome, carnitine-acylcarnitine translocase deficiency, propionic acidaemia, isovaleric acidaemia, trifunctional protein deficiency. These results yield an incidence of one case per 4,275 live births (95% confidence interval 3,054–7,126), and an average age at diagnosis of 19.2 + 11.4 days (Table 1).