588 FETAL RESPONSE TO DRUG WITHDRAWAL

SiR,—There have been several reports of withdrawal symp-

well in advance to allow time for drawal of the drug of dependency.

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in neonates whose mothers were still addicted at delivery. Department of DAVID T. Y. LIU Obstetrics and Gynæcology, These babies appear normal at birth but within 10-36 h ELIZABETH TYLDEN University College Hospital become distressed and require treatment in a neonatal unit.’1 SINA H. TUKEL Medical School, London WC1. It is, therefore, in the infants’ interest that these addicted mothers should be identified and an attempt made to wean them off drugs before delivery. In the past five years 18 known addicts delivered in University College Hospital, London, and ONDINE’S CURSE 11 of these patients were weaned off opiates during pregnancy. readers SIR,Your may interested in a further example It is, however, not generally realised that the fetus may react Ondine’s curse in a young girl. The mythological reference of if or withdrawn adversely drugs are withheld during labour was first applied to three adults who had apnreic periods when rapidly during the antenatal period. Withholding drugs from awake but breathed on command and required mechanical known, or unsuspected, addicts has resulted in a stillbirth and ventilation when asleep.’Ondine, a German water nymph, ina neonatal death in neighbouring hospitals. voked a curse upon her jilted husband so that he would forget to the usually recogDuring labour, fetal distress-not due to breathe (and die) when he fell asleep. nised causes-arising in opiate addicts often appears to be The girl aged 2 years 8 months was admitted with a history relieved by the administration of pethidine or a replacement of recent mild diarrhoea and a family "flu-like" illness. For5 drug such as physeptone. This therapy is now advised in cases she had been intermittently drowsy and prone to sleep. days of opiate dependence. Immediately before admission she became difficult to rouse and We found that during the antenatal period, 24 h urinary cyanosed. During the preceding 9 months the parents had oestrogen production fell for the 48 h after each stepped reducnoticed that "she was blue around the lips" on three occasions tion in drug dosage. Thereafter, the level of maternal oestrogen in the early morning. She was otherwise healthy and had a excretion gradually rose until the drug was reduced again. On normal perinatal history. two occasions drug withdrawal had to be slowed because of Examination revealed a pale, cyanosed child with peripheral precipitate falls in urinary oestriols. limb oedema, puffy face, bounding pulses, and a soft precordial On one occasion, adverse changes in fetal heart-rate were murmur. The cyanosis was reversed by oxygen. Later she observed when external cardiotocography was carried out on became more drowsy with deep cyanosis, papilloedema, and a a patient during an episode of rapid drug withdrawal. A pacranial bruit. tient dependent on pentazocine and dihydrocodeine tartrate Arterial blood gases were Pao2 33 mm Hg, Paco, 56 mm (’DF118’) needed five or six maximal doses of one or other bicarbonate 25 mmol/1; pH 7.20. Electroencephalography Hg; the withdrawal episode fetal tachycardia with drug. During showed generalised slow waves but no focal or paroxysmal feapoor baseline variability and reduced transient changes associscan was normal; right carotid arteriogram E.M.I. tures; ated with fetal movements or Braxton-Hicks contractions were demonstrated a grossly hyperdynamic circulation; electroonly observed. Intramuscular DF118 was administered. A second and nerve-conduction studies were normal, as was myography taken 30 min later showed a to normal fetal return recording the cerebrospinal fluid. Thorough serology and culture failed heart-rate, but poor variability and diminished changes perto reveal a viral agent responsible for a recent encephalitic sisted. episode. Stresses which result in retarded in-utero growth are associAir encephalography 4 months later showed some dilatation ated with a reduced incidence of hyaline-membrane disease. 23 of the cerebral ventricles and a mild degree of cortical atrophy, The offspring of addicts may show evidence of growth disturShe 4 improved dramatically on mechanical ventilation, and bance.’ A lower incidence of hyaline-membrane disease has 7 months after admission she requires ventilation at midday been reported in neonates of animals5 and human mothers and at night when her sleeping respiration becomes inadeaddicted to heroin,67but the concept of fetal stress and materquate. Neurologically she remains normal, and in the daytime nal addiction remains a subject of deliberation.s Glass et a1.8 she is an active child learning new skills. Her only other probfound no difference in cord-blood cortico-steroid levels from lem is water retention if midday ventilation is insufficient. fetuses of addicted mothers and those of controls. Cord-steroid Some patients with Leigh’s subacute necrotising encephalobe influenced the stresses of values, however, may by delivery, myelopathy develop a primary (or central) hypoventilation and the incidence of hyaline-membrane disease need not reflect syndrome ("Ondine’s curse").2 Investigations in this girl have stresses inflicted on the fetus by drug withdrawal.9 revealed certain biochemical similarities to those reported in The above observations suggest the fetus may be subjected several cases of Leigh’s disease-namely, blood pyruvate 99 to "stress" in utero when maternal drug levels are withdrawn mol/1 (normal adult 35-60), blood lactate 3.06 mmol!1 rapidly. Falling maternal urinary oestrogen excretion often in(0-99-1-76), and a positive urine test for thiamine pyrophosdicates fetal compromise, and this falling trend is seen when adenosine triphosphate phosphoryltransferase inhibitor phate cut. It is also not uncommon for drug dosages are severely substance (Prof. J. R. Cooper).3 addicts to report increased fetal movements before their own At least two children with Ondine’s curse and a positive subjective symptoms of withdrawal. Cardiotocographic findurine test have been recorded. One died suddenly in hospital ings suggest evidence that there may also be associated fetal and the neuropathology showed hypothalamic necrosis, brainstress. stem inflammation, but not the typical features of Leigh’s disThe rapid withdrawal of drugs from addicted mothers may ease.4 Clearly a definitive diagnosis in this girl has not been have deleterious effects on their fetuses and should therefore reached especially if one considers Leigh’s disease to be a be avoided. Antenatal drug weaning programmes should be group of different enzyme or coenzyme disorders. This unfortunate child may be unique in presenting at thIs 1. Tylden, B. Adverse Drug Bull, 1973, 38, 120. age with central hypoventilation whilst asleep, yet remains 2. Gluck, L., Kulovich, M. V. Am. J. Obstet. Gynec. 1973, 115, 547. 3. Thomas, D. B. Aust. Pœdiat. J. 1975, 11, 26. developmentally normal and with no features of overt hypo4. Cochm, J. Fedn Proc. 1970, 20, 19. thalamic disease. The neuroradiological evidence of a braic toms

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5. Taeusch, H. W. Jr., Carson, S. H., Wang, N. S., Avery, M. E. J. Pediat. 1973, 82, 869. 6 Sussman, S Amr. J. Dis. Child. 1963, 106, 325. 7. Glass, L., Rajegowda, B. K., Evans, H. G. Lancet, 1971, ii, 685. 8. Glass, L., Rajegowda, B. K., Mukherjee, T. K., Roth, M. M., Evans, H. G. Amr. J. Obstet. Gynec. 1973, 117, 416. 9. Zelson, C., Lee, S. J., Casalino, M. New Engl. J. Med. 1973, 289, 1216.

1. Severinghaus, J. W., Mitchell, R. A. Clin. Res. 1962, 10, 2. Pincus, J. H. Personal communication. 3. Cooper, J. R., Pincus, J. H., Itokawa, Y., Piros, K. New 4.

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Engl. JMed 1970, 283, 793. Pincus, J. H., Cooper, J. R., Piros, K., Turner, V. Neurology, 1974, 24, 885.

Letter: Fetal response to drug withdrawal.

588 FETAL RESPONSE TO DRUG WITHDRAWAL SiR,—There have been several reports of withdrawal symp- well in advance to allow time for drawal of the...
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