Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1987 Sep;40(9):1128–1144. doi: 10.1136/jcp.40.9.1128

Clinical biochemistry of the neonatal period: immaturity, hypoxia, and metabolic disease.

R A Harkness 1
PMCID: PMC1141180  PMID: 3312303

Abstract

This review attempts to provide practical information on common problems in the laboratory medicine of newborn infants and also considers unresolved problems in achieving neonatal diagnoses. A common cause of upset in the newborn--intrapartum asphyxia--can now be positively diagnosed. This leaves a small group whom it is necessary to investigate because they may have metabolic disease. The initial investigation of metabolic disease at the district general hospital should be limited to the commoner conditions.

Full text

PDF
1128

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams A., Harkness R. A. Adenosine deaminase activity in thymus and other human tissues. Clin Exp Immunol. 1976 Dec;26(3):647–649. [PMC free article] [PubMed] [Google Scholar]
  2. Anderson J. M., Cockburn F., Forfar J. O., Harkness R. A., Kelly R. W., Kilshaw B. Neonatal spongioform myelinopathy after restricted application of hexachlorophane skin disinfectant. J Clin Pathol. 1981 Jan;34(1):25–29. doi: 10.1136/jcp.34.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson J. R., Linsell W. D., Mitchell F. M. Guidelines on the performance of chemical pathology assays outside the laboratory. Br Med J (Clin Res Ed) 1981 Feb 28;282(6265):743–743. doi: 10.1136/bmj.282.6265.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Applegarth D. A., Toone J. R., MacLeod P. M. Laboratory diagnosis of inborn errors of metabolism in children. Pediatr Pathol. 1983 Jan-Mar;1(1):107–130. doi: 10.3109/15513818309048289. [DOI] [PubMed] [Google Scholar]
  5. Bachmann C., Colombo J. P. Incidence of disorders tested by systematic screening: confidence limits and comparison of programmes. J Inherit Metab Dis. 1982;5(1):3–5. doi: 10.1007/BF01799746. [DOI] [PubMed] [Google Scholar]
  6. Bode J. C., Zelder O., Rumpelt H. J., Wittkamp U. Depletion of liver adenosine phosphates and metabolic effects of intravenous infusion of fructose or sorbitol in man and in the rat. Eur J Clin Invest. 1973 Sep;3(5):436–441. doi: 10.1111/j.1365-2362.1973.tb02211.x. [DOI] [PubMed] [Google Scholar]
  7. Bridger W. A. The Ayerst Award Lecture 1980: the subunits of succinyl coenzyme A synthetase. Can J Biochem. 1981 Jan;59(1):1–8. doi: 10.1139/o81-001. [DOI] [PubMed] [Google Scholar]
  8. Brock D. J. Impact of maternal serum alpha-fetoprotein screening on antenatal diagnosis. Br Med J (Clin Res Ed) 1982 Jul 31;285(6338):365–367. doi: 10.1136/bmj.285.6338.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Burton B. K., Nadler H. L. Clinical diagnosis of the inborn errors of metabolism in the neonatal period. Pediatrics. 1978 Mar;61(3):398–405. doi: 10.1542/peds.61.3.398. [DOI] [PubMed] [Google Scholar]
  10. Chalmers R. A., Purkiss P., Watts R. W., Lawson A. M. Screening for organic acidurias and amino acidopathies in newborns and children. J Inherit Metab Dis. 1980;3(2):27–43. doi: 10.1007/BF02312520. [DOI] [PubMed] [Google Scholar]
  11. Coles E. C., Cotter S., Valman H. B. Increasing prevalence of breast-feeding. Br Med J. 1978 Oct 21;2(6145):1122–1122. doi: 10.1136/bmj.2.6145.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coulombe J. T., Kammerer B. L., Levy H. L., Hirsch B. Z., Scriver C. R. Histidinaemia. Part III: Impact; a prospective study. J Inherit Metab Dis. 1983;6(2):58–61. doi: 10.1007/BF02338972. [DOI] [PubMed] [Google Scholar]
  13. D'Souza S. W., McCartney E., Nolan M., Taylor I. G. Hearing, speech, and language in survivors of severe perinatal asphyxia. Arch Dis Child. 1981 Apr;56(4):245–252. doi: 10.1136/adc.56.4.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Danks D. M. Management of newborn babies in whom serious metabolic illness is anticipated. Arch Dis Child. 1974 Jul;49(7):576–578. doi: 10.1136/adc.49.7.576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Danks D. M. Plan of management for newborn babies in whom metabolic disease is anticipated or suspected. Clin Perinatol. 1976 Mar;3(1):251–259. [PubMed] [Google Scholar]
  16. Darling J. A., Harkness R. A. A method for the group analysis of steroids in milk. Acta Endocrinol (Copenh) 1973 Feb;72(2):391–400. doi: 10.1530/acta.0.0720391. [DOI] [PubMed] [Google Scholar]
  17. Darling J. A., Kelly R. W., Laing A. H., Harkness R. A. The isolation and identification of progesterone obtained from cows' milk during pregnancy. J Endocrinol. 1972 Aug;54(2):347–348. doi: 10.1677/joe.0.0540347. [DOI] [PubMed] [Google Scholar]
  18. Death by a thousand cuts. Br Med J (Clin Res Ed) 1982 Jul 3;285(6334):1–2. [PMC free article] [PubMed] [Google Scholar]
  19. Evans S. E., Durbin G. M. Aspects of the physiological and pathological background to neonatal clinical chemistry. Ann Clin Biochem. 1983 Jul;20(Pt 4):193–207. doi: 10.1177/000456328302000401. [DOI] [PubMed] [Google Scholar]
  20. Fysh W. J., Turner G. M., Dunn P. M. Neurological normality after extreme birth asphyxia. Case report. Br J Obstet Gynaecol. 1982 Jan;89(1):24–26. doi: 10.1111/j.1471-0528.1982.tb04629.x. [DOI] [PubMed] [Google Scholar]
  21. Greer F. R., Reeve L. E., Chesney R. W., DeLuca H. F. Water-soluble vitamin D in human milk: a myth. Pediatrics. 1982 Feb;69(2):238–238. [PubMed] [Google Scholar]
  22. Grivell A. R., Forgie H. J., Fraser C. G., Berry M. N. Effect of feedback to clinical staff of information on clinical biochemistry requesting patterns. Clin Chem. 1981 Oct;27(10):1717–1720. [PubMed] [Google Scholar]
  23. Hallman M. Effect of intraperitoneal chloramphenicol in some mitochondrial enzymes in neonatal rats. Biochem Pharmacol. 1971 Aug;20(8):1797–1809. doi: 10.1016/0006-2952(71)90378-9. [DOI] [PubMed] [Google Scholar]
  24. Hargreaves T., Piper R. F. Breast milk jaundice. Effect of inhibitory breast milk and 3 alpha, 20 abeta-pregnanediol on glucuronyl transferase. Arch Dis Child. 1971 Apr;46(246):195–198. doi: 10.1136/adc.46.246.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Harkness R. A., Coade S. B., Simmonds R. J., Duffy S. Effect of a failure of energy supply on adenine nucleotide breakdown in placentae and other fetal tissues from rat and guinea pig. Placenta. 1985 May-Jun;6(3):199–216. doi: 10.1016/s0143-4004(85)80050-3. [DOI] [PubMed] [Google Scholar]
  26. Harkness R. A., Coade S. B., Walton K. R., Wright D. Xanthine oxidase deficiency and 'Dalmatian' hypouricaemia: incidence and effect of exercise. J Inherit Metab Dis. 1983;6(3):114–120. doi: 10.1007/BF01800741. [DOI] [PubMed] [Google Scholar]
  27. Harkness R. A., Darling J. A., Bain A. D., Syme J. Plasma lecithin-cholesterol acyltransferase deficiency in a child with terminal pulmonary hyaline membrane disease. Arch Dis Child. 1973 Nov;48(11):906–910. doi: 10.1136/adc.48.11.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Harkness R. A., Geirsson R. T., McFadyen I. R. Concentrations of hypoxanthine, xanthine, uridine and urate in amniotic fluid at caesarean section and the association of raised levels with prenatal risk factors and fetal distress. Br J Obstet Gynaecol. 1983 Sep;90(9):815–820. doi: 10.1111/j.1471-0528.1983.tb09321.x. [DOI] [PubMed] [Google Scholar]
  29. Harkness R. A., Lawrence C. R., Renshaw A., Barr I. C., Brown S. S., Rinsler M. G. Assessment of the performance and clinical utility of a ward side-room bilirubinometer. Ann Clin Biochem. 1983 May;20(Pt 3):149–152. doi: 10.1177/000456328302000304. [DOI] [PubMed] [Google Scholar]
  30. Harkness R. A., Lund R. J. Cerebrospinal fluid concentrations of hypoxanthine, xanthine, uridine and inosine: high concentrations of the ATP metabolite, hypoxanthine, after hypoxia. J Clin Pathol. 1983 Jan;36(1):1–8. doi: 10.1136/jcp.36.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Harkness R. A., Simmonds R. J., Coade S. B., Lawrence C. R. Ratio of the concentration of hypoxanthine to creatinine in urine from newborn infants: a possible indicator for the metabolic damage due to hypoxia. Br J Obstet Gynaecol. 1983 May;90(5):447–452. doi: 10.1111/j.1471-0528.1983.tb08942.x. [DOI] [PubMed] [Google Scholar]
  32. Harkness R. A., Simmonds R. J., Coade S. B. Purine transport and metabolism in man: the effect of exercise on concentrations of purine bases, nucleosides and nucleotides in plasma, urine, leucocytes and erythrocytes. Clin Sci (Lond) 1983 Mar;64(3):333–340. doi: 10.1042/cs0640333. [DOI] [PubMed] [Google Scholar]
  33. Harkness R. A., Taylor N. F., Bowman P. R., Gordon H., Cummins M., Valman H. B. The causes of low oestrogen excretion in pregnancy: the development of diagnostic methods for the antenatal detection of familial congenital adrenocortical hypoplasia. Clin Endocrinol (Oxf) 1980 May;12(5):453–460. doi: 10.1111/j.1365-2265.1980.tb02735.x. [DOI] [PubMed] [Google Scholar]
  34. Harkness R. A., Taylor N. F., Crawfurd M. A., Rose F. A. Recognising placental steroid sulphatase deficiency. Br Med J (Clin Res Ed) 1983 Jul 2;287(6384):2–3. doi: 10.1136/bmj.287.6384.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Harkness R. A., Thistlethwaite D., Darling J. A., Skakkeback N. E., Corker C. S. Neutral 17beta-hydroxysteroid oxidoreductase deficiency in testes causing male pseudohermaphroditism in an infant. J Inherit Metab Dis. 1980;2(3):51–54. doi: 10.1007/BF01801718. [DOI] [PubMed] [Google Scholar]
  36. Harkness R. A., Whitelaw A. G., Simmonds R. J. Intrapartum hypoxia: the association between neurological assessment of damage and abnormal excretion of ATP metabolites. J Clin Pathol. 1982 Sep;35(9):999–1007. doi: 10.1136/jcp.35.9.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Holton J. B. Diagnosis of inherited metabolic diseases in severely ill children. Ann Clin Biochem. 1982 Nov;19(6):389–395. doi: 10.1177/000456328201900601. [DOI] [PubMed] [Google Scholar]
  38. Hällgren R., Niklasson F., Terent A., Akerblom A., Widerlöv E. Oxypurines in cerebrospinal fluid as indices of disturbed brain metabolism. A clinical study of ischemic brain diseases. Stroke. 1983 May-Jun;14(3):382–388. doi: 10.1161/01.str.14.3.382. [DOI] [PubMed] [Google Scholar]
  39. Jennett R. J., Warford H. S., Kreinick C., Waterkotte G. W. Apgar index: a statistical tool. Am J Obstet Gynecol. 1981 May 15;140(2):206–212. doi: 10.1016/0002-9378(81)90109-5. [DOI] [PubMed] [Google Scholar]
  40. KNOWLES J. A. EXCRETION OF DRUGS IN MILK--A REVIEW. J Pediatr. 1965 Jun;66:1068–1082. doi: 10.1016/s0022-3476(65)80094-4. [DOI] [PubMed] [Google Scholar]
  41. Kloner R. A., Ganote C. E., Whalen D. A., Jr, Jennings R. B. Effect of a transient period of ischemia on myocardial cells. II. Fine structure during the first few minutes of reflow. Am J Pathol. 1974 Mar;74(3):399–422. [PMC free article] [PubMed] [Google Scholar]
  42. Krieger I., Nigro M., Taqi Q. Screening for metabolic disease in a metropolitan hospital. Am J Dis Child. 1982 Feb;136(2):125–128. doi: 10.1001/archpedi.1982.03970380037009. [DOI] [PubMed] [Google Scholar]
  43. Kruus S., Bergström L., Suutarinen T., Hyvönen R. The prognosis of near-drowned children. Acta Paediatr Scand. 1979 May;68(3):315–322. doi: 10.1111/j.1651-2227.1979.tb05013.x. [DOI] [PubMed] [Google Scholar]
  44. Kulski J. K., Smith M., Hartmann P. E. Perinatal concentrations of progesterone, lactose and alpha-lactalbumin in the mammary secretion of women. J Endocrinol. 1977 Sep;74(3):509–510. doi: 10.1677/joe.0.0740509. [DOI] [PubMed] [Google Scholar]
  45. Lauritzen C., Lehmann W. D. The significance of steroid hormones for the development of hyperbilirubinaemia and icterus in the newborn infant. J Endocrinol. 1967 Oct;39(2):183–188. doi: 10.1677/joe.0.0390183. [DOI] [PubMed] [Google Scholar]
  46. Leonard J. V., Clayton B. E., Colley J. R. Use of biochemical profile in children's hospital: results of two controlled trials. Br Med J. 1975 Jun 21;2(5972):662–665. doi: 10.1136/bmj.2.5972.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Levin S. D., Brown J. K., Harkness R. A. Cerebrospinal fluid hypoxanthine and xanthine concentrations as indicators of metabolic damage due to raised intracranial pressure in hydrocephalic children. J Neurol Neurosurg Psychiatry. 1984 Jul;47(7):730–733. doi: 10.1136/jnnp.47.7.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Mason J. K., Harkness R. A., Elton R. A., Bartholomew S. Cot deaths in Edinburgh: infant feeding and socioeconomic factors. J Epidemiol Community Health. 1980 Mar;34(1):35–41. doi: 10.1136/jech.34.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Mathew P. M., Wharton B. A. Investigation and management of neonatal jaundice: a problem-orientated case record. Arch Dis Child. 1981 Dec;56(12):949–953. doi: 10.1136/adc.56.12.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Meberg A., Saugstad O. D. Hypoxanthine in cerebrospinal fluid in children. Scand J Clin Lab Invest. 1978 Sep;38(5):437–440. doi: 10.1080/00365517809108448. [DOI] [PubMed] [Google Scholar]
  51. Murphey W. H., Patchen L., Guthrie R. Screening tests for argininosuccinic aciduria, orotic aciduria, and other inherited enzyme deficiencies using dried blood specimens. Biochem Genet. 1972 Feb;6(1):51–59. doi: 10.1007/BF00485965. [DOI] [PubMed] [Google Scholar]
  52. Murphy J. F., Hughes I., Verrier Jones E. R., Gaskell S., Pike A. W. Pregnanediols and breast milk jaundice. Arch Dis Child. 1981 Jun;56(6):474–476. doi: 10.1136/adc.56.6.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. O'Connor M. C., Harkness R. A., Simmonds R. J., Hytten F. E. Raised hypoxanthine, xanthine and uridine concentrations in meconium stained amniotic fluid and during labour. Br J Obstet Gynaecol. 1981 Apr;88(4):375–380. doi: 10.1111/j.1471-0528.1981.tb01000.x. [DOI] [PubMed] [Google Scholar]
  54. O'Connor M. C., Harkness R. A., Simmonds R. J., Hytten F. E. The measurement of hypoxanthine, xanthine, inosine and uridine in umbilical cord blood and fetal scalp blood samples as a measure of fetal hypoxia. Br J Obstet Gynaecol. 1981 Apr;88(4):381–390. doi: 10.1111/j.1471-0528.1981.tb01001.x. [DOI] [PubMed] [Google Scholar]
  55. Pampiglione G., Chaloner J., Harden A., O'Brien J. Transitory ischemia/anoxia in young children and the prediction of quality of survival. Ann N Y Acad Sci. 1978 Nov 17;315:281–292. doi: 10.1111/j.1749-6632.1978.tb50346.x. [DOI] [PubMed] [Google Scholar]
  56. Pang S., Murphey W., Levine L. S., Spence D. A., Leon A., LaFranchi S., Surve A. S., New M. I. A pilot newborn screening for congenital adrenal hyperplasia in Alaska. J Clin Endocrinol Metab. 1982 Sep;55(3):413–420. doi: 10.1210/jcem-55-3-413. [DOI] [PubMed] [Google Scholar]
  57. Raine D. N. Management of inherited metabolic disease. Br Med J. 1972 May 6;2(5809):329–336. doi: 10.1136/bmj.2.5809.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Rao G. S., Rao M. L., Breuer H. Partial purification and kinetics of oestriol 16 alpha-glucuronyltransferase from the cytosol fraction of human liver. Biochem J. 1970 Jul;118(4):625–634. doi: 10.1042/bj1180625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Reibel D. K., Rovetto M. J. Myocardial ATP synthesis and mechanical function following oxygen deficiency. Am J Physiol. 1978 May;234(5):H620–H624. doi: 10.1152/ajpheart.1978.234.5.H620. [DOI] [PubMed] [Google Scholar]
  60. Rose F. A. Review: the mammalian sulphatases and placental sulphatase deficiency in man. J Inherit Metab Dis. 1982;5(3):145–152. doi: 10.1007/BF01800170. [DOI] [PubMed] [Google Scholar]
  61. Rosenfeld R. S., Arias I. M., Gartner L. M., Hellman L., Gallagher T. F. Studies of urinary pregnane-3 alpha,20 beta-diol during pregnancy, post-partum, lactation and progesterone ingestion. J Clin Endocrinol Metab. 1967 Dec;27(12):1705–1710. doi: 10.1210/jcem-27-12-1705. [DOI] [PubMed] [Google Scholar]
  62. STIEHM E. R., RYAN J. BREAST-MILK JAUNDICE. REPORT OF EIGHT CASES AND EFFECT OF BREAST FEEDING ON INCIDENCE AND SEVERITY OF UNEXPLAINED HYPERBILIRUBINEMIA. Am J Dis Child. 1965 Mar;109:212–216. [PubMed] [Google Scholar]
  63. Salle B. L., David L., Chopard J. P., Grafmeyer D. C., Renaud H. Prevention of early neonatal hypocalcemia in low birth weight infants with continuous calcium infusion: effect on serum calcium, phosphorus, magnesium, and circulating immunoreactive parathyroid hormone and calcitonin. Pediatr Res. 1977 Dec;11(12):1180–1185. doi: 10.1203/00006450-197712000-00003. [DOI] [PubMed] [Google Scholar]
  64. Scriver C. R., Levy H. L. Histidinaemia. Part I: Reconciling retrospective and prospective findings. J Inherit Metab Dis. 1983;6(2):51–53. doi: 10.1007/BF02338970. [DOI] [PubMed] [Google Scholar]
  65. Simmonds R. J., Coade S. B., Harkness R. A., Drury L., Hytten F. E. Nucleotide, nucleoside and purine base concentrations in human placentae. Placenta. 1982 Jan-Mar;3(1):29–38. doi: 10.1016/s0143-4004(82)80015-5. [DOI] [PubMed] [Google Scholar]
  66. Smith A. D., Shenkin A., Dryburgh F. J., Morgan H. G. Emergency biochemistry services--are they abused? Ann Clin Biochem. 1982 Sep;19(Pt 5):325–328. doi: 10.1177/000456328201900501. [DOI] [PubMed] [Google Scholar]
  67. Smith J. A., King R. J. The metabolism of testosterone by tissue from normal and neoplastic mouse breast. J Endocrinol. 1966 Jul;35(3):281–287. doi: 10.1677/joe.0.0350281. [DOI] [PubMed] [Google Scholar]
  68. Soyka L. F. Developmental pharmacology of the methylxanthines. Introduction. Semin Perinatol. 1981 Oct;5(4):303–304. [PubMed] [Google Scholar]
  69. Steendijk R. Diagnostic and aetiologic features of idiopathic and symptomatic growth hormone deficiency in the Netherlands. A survey of 176 children. Helv Paediatr Acta. 1980 May;35(2):129–139. [PubMed] [Google Scholar]
  70. Swanström S., Bratteby L. E. Hypoxanthine as a test of perinatal hypoxia as compared to lactate, base deficit, and pH. Pediatr Res. 1982 Feb;16(2):156–160. doi: 10.1203/00006450-198202000-00016. [DOI] [PubMed] [Google Scholar]
  71. Swarbrick E. T., Kingham J. G., Price H. L., Blackshaw A. J., Griffiths P. D., Darougar S., Buckell N. A. Chlamydia, cytomegalovirus, and Yersinia in inflammatory bowel disease. Lancet. 1979 Jul 7;2(8132):11–12. doi: 10.1016/s0140-6736(79)90176-4. [DOI] [PubMed] [Google Scholar]
  72. Taylor N. F. Review: placental sulphatase deficiency. J Inherit Metab Dis. 1982;5(3):164–176. doi: 10.1007/BF01800173. [DOI] [PubMed] [Google Scholar]
  73. Van der Molen H. J., Hart P. G., Wijmenga H. G. Studies with 4-14C-lynestrenol in normal and lactating women. Acta Endocrinol (Copenh) 1969 Jun;61(2):255–274. doi: 10.1530/acta.0.0610255. [DOI] [PubMed] [Google Scholar]
  74. Vogt M. T., Farber E. On the molecular pathology of ischemic renal cell death. Reversible and irreversible cellular and mitochondrial metabolic alterations. Am J Pathol. 1968 Jul;53(1):1–26. [PMC free article] [PubMed] [Google Scholar]
  75. Weatherall J. A. A review of some effects of recent medical practices in reducing the numbers of children born with congenital abnormalities. Health Trends. 1982 Nov;14(4):85–88. [PubMed] [Google Scholar]
  76. Wickizer T. M., Brilliant L. B., Copeland R., Tilden R. Polychlorinated biphenyl contamination of nursing mothers' milk in Michigan. Am J Public Health. 1981 Feb;71(2):132–137. doi: 10.2105/ajph.71.2.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Wijmenga H. G., Van der Molen H. J. Studies with 4-14C-mestranol in lactating women. Acta Endocrinol (Copenh) 1969 Aug;61(4):665–677. doi: 10.1530/acta.0.0610665. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES