Newborn Screening for Congenital Hypothyroidism, Congenital Adrenal Hyperplasia, and Glucose-6-Phosphate Dehydrogenase Deficiency for Improving Health Care in India.

Newborn screening (NBS) aims toward early detection of treatable congenital disorders. From January 2008 through December 2017, 13,376 newborns were screened for congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and glucose-6-phosphate dehydrogenase (G6PD) deficiency at Sir Ganga Ram Hospital, India, by measuring G6PD activity, thyroid-stimulating hormone, and 17-hydroxyprogesterone on dried blood specimens. The birth prevalence of 1:2,000 for CH, 1:2,500 for CAH, and 1:125 for G6PD deficiency indicates the latter as the most prevalent. Performance evaluation of testing reveals a robust screening program with 100% sensitivity and >99% specificity. Hence, we recommend NBS for early diagnosis and treatment to prevent adverse outcomes.

MoM cutoffs for variables, an important tool for multivariate analysis and accurate interpretation of preeclampsia risk in high-risk pregnancy at 11-13+6 weeks gestation.

OBJECTIVE: To determine the diagnostic accuracy of preeclampsia (PE) screening test offered in early pregnancy for the prediction of the risks for early-onset (requiring delivery <32 weeks gestation) and late-onset (requiring delivery ≥32 weeks gestation) disease. METHODS: In a retrospective study of 615 women with singleton pregnancy, the risk for PE was calculated by the combined effect of multiple variables: serum placental growth factor (PLGF) and pregnancy-associated plasma protein-A (PAPP-A), maternal age, parity, ethnicity, mean arterial pressure (MAP), body mass index (BMI), uterine artery-pulsatility index, and previous history of PE or hypertension (HT). The results of the screening test in three different groups of women were validated by pregnancy outcome: (i) control group - without any history of PE/HT; (ii) history of PE without HT; and (iii) history of HT without PE. The performance of the screening test was evaluated for early- and late-onset PE. RESULTS: The multivariate screening effectively identified cases of PE with >97% specificity. The detection rate (DR) was 93.8% for late-onset PE at a false positive rate (FPR) of 2.3% and 44.4% for early-onset PE at an FPR of 0.0%. The incidence of PE was 7% overall, with 1.52% and 5.43% for early- and late-onset PE, respectively. CONCLUSION: The study demonstrated 96.6% diagnostic accuracy of the multi-variable screening test to predict the risk of PE in the first trimester. The negative predictive value (>98%) reinforces the utility of cost-effective noninvasive screening test for the early detection of PE. ABBREVIATIONS: PLGF: Placental growth factor; PAPP-A: Pregnancy-associated plasma protein-A; free ß-HCG: Free beta-human chorionic gonadotropin; BMI: Body mass index; MAP: Mean arterial blood pressure; Ut-PI: Mean uterine artery pressure (left and right uterine artery)-pulsatility index; MoM: Multiple of median; NICE: National Institute for Health and Clinical Excellence.

Inherited metabolic disorders: prenatal diagnosis of lysosomal storage disorders.

OBJECTIVE: To offer accurate prenatal diagnosis of lysosomal storage disorders in early pregnancy. METHOD: Prenatal enzymatic diagnoses of Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandoff, GM1, mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy and Batten diseases were made in uncultured chorionic villi samples by fluorometric/spectrophotometric methods. RESULTS: Of 331 prenatal enzymatic diagnosis, 207 fetuses (67%) were normal and 124 (37%) were affected. The interpretation of affected, normal and carrier fetuses was done using their respective reference ranges as well as % enzyme activity of normal mean. The prenatal molecular confirmation was feasible in 43 biochemically diagnosed fetuses. Of the 207 normal reported fetuses, post natal enzymatic confirmation was done in 23 babies, clinical status of another 165 babies was assessed as unaffected via questionnaire on telephone and 19 were lost to follow-up. In affected pregnancies, 123 opted for termination of which 44 were confirmed enzymatically after abortion. A single false positive was determined to be a carrier by prenatal mutation analysis and carried to term. CONCLUSION: We recommend uncultured chorionic villi for reliable prenatal enzymatic diagnosis of various lysosomal storage disorders on account of the low rate of false positive (0.5%) and false negative (2.2%) results.

Inherited metabolic disorders: Quality management for laboratory diagnosis.

BACKGROUND: The advancements in laboratory technology and knowledge of the mechanisms behind metabolic disorders have facilitated accurate and reliable laboratory testing in screening, diagnosis and treatment of inherited metabolic disorders. Therefore, quality assurance and improvement in diagnostic proficiency have become essential in this area. In most developing countries, standard practices for quality assurance in testing of enzymes, hormones and metabolites involved in these genetic disorders have not been fully implemented. We highlight the benefits of quality assurance and aim to create awareness for greater compliance with the criteria established for quality control to ensure accuracy in biochemical genetic testing. METHODS: Establishing the limit of detection and testing range for each analyte and enzyme are useful as a reference while setting up new assays. To minimize error, %CV should be monitored regularly. Evaluation of proficiency testing performance provides scope to the laboratory for improving testing quality. RESULTS: Low precision seen in lysosomal enzyme assays does not undermine their diagnostic efficacy as differentiation between patients and normal subjects is possible by setting % coefficient of variation cutoffs. CONCLUSIONS: The study will facilitate the collaboration with other screening and diagnostic systems and help in development of new laboratory standards.

Newborn screening: need of the hour in India.

After a review of the current health scene in India, the authors suggest that the Government of India should consider seriously, the introduction of new born screening. As a first step, a central advisory committee should be constituted to recommend what is required to be done to strengthen the infrastructure and the manpower to carry out new born screening, and the disorders to be screened. In the urban hospitals newborn screening (NBS) for three disorders can be easily introduced (congenital hypothyroidism, congenital adrenal hyperplasia and G-6-PD deficiency), while in the rural areas this should begin with congenital hypothyroidism, especially in the sub Himalayan areas. Concurrently, logistic issues regarding diets and special therapies for inborn errors of metabolism should be sorted out, laboratories to confirm the diagnosis should be set up, and a cadre of metabolic physicians should be build up to treat those identified to have inborn errors of metabolism. Once these are established on a firm footing, tandem mass spectrometry should be introduced as it allows the identification of a number of disorders in an affordable manner. The recent improvements and current trends in health care in India have created the necessary infrastructure for adopting NBS for the benefit of infants in India.