604 Archives of Disease in Childhood 1993; 68: 604-605

Antenatal assessment of neurological impairment Arch Dis Child: first published as 10.1136/adc.68.5_Spec_No.604 on 1 May 1993. Downloaded from

W G Taylor, S A Walkinshaw, M A Thomson

Abstract Although intracranial anatomy was normal An unreactive cardiotocograph late in the on repeated examination with no mid-trimester led to a sequence of in- evidence of intracranial calcification, there vestigations that revealed an appropri- remained a strong suspicion ofneurological dys- ately grown , with hepatic function most likely at brain stem level. To calcification, and evidence of intrauterine evaluate fully fetal physiology, two manoeuvres infection. Ultrasound observation and known to alter fetal biophysical parameters were stimulation ofthe fetus with vibration and performed. Vibroacoustic stimulation produces glucose revealed altered neurophysiologi- alteration in fetal behavioural state and a startle cal responses. The profound neurological reaction.1 In this fetus, movements responded impairment was confirmed by detailed normally to stimulation. However, the fetal neonatal investigations. heart rate remained fixed. Fetal breathing (Arch Dis Child 1993; 68: 604-605) movements are related to food ingestion,2 and an oral glucose load followed by a scan one hour The antenatal ultrasound diagnosis and later demonstrated sustained fetal breathing. physiological assessment of a neurologically The prenatal diagnosis was of congenital impaired fetus is discussed with relevance to varicella zoster with hepatic and brain stem neonatal outcome and prognosis. involvement including derangements of the atrioventricular variability (cardioinhibitor effect ofvagus nerve), breathing (phrenic nerve Results ofamniocentesis Case report C4), and possibly swallowing (glossopharyn- and cordocentesis A 23 year old primigravida presented to her geal and vagus nerves). at 27 weeks' gestation with The parents were counselled extensively that pH 7-398 local obstetric unit Carbon dioxide diminished fetal movements. the prognosis was uncertain. Delivery was per- tension 4-65 kPa demonstrated a normal heart rate but with a formed by elective at 39 Oxygen tension 6-67 kPa Base excess -3.4 non-reactive pattern. She was then transferred weeks because of the difficulty of monitoring a Glucose 5 mmol/l utero to On with an heart rate. The infant Haemoglobin 128 g/l in Liverpool Maternity Hospital. fetus unvarying White cells 3-7x 109/1 arrival a repeat cardiotocograph showed little girl weighed 3426 g at birth (50th centile). She Neutrophils 12% and this pattern on rapidly developed marked inspiratory stridor Lymphocytes 85% change (figure) persisted Monocytes 2% continuous monitoring. Ultrasound assessment with pooling of pharyngeal secretions and res- Eosinophils 1% an grown, distress requiring endotracheal in- http://adc.bmj.com/ Platelets 250X 109/1 showed active fetus, appropriately piratory and with normal liquor volume. The liver was tubation. No other neurological features were enlarged with diffuse echodense lesions present but poor muscle bulk was noted in the throughout. Fetal anatomy was otherwise limbs. normal. Umbilical artery Doppler velocimetry Bronchoscopy revealed vocal cord paralysis. gave normal results. A detailed history revealed Contrast swallow and computed tomography maternal varicella zoster infection at 8 weeks' of the neck demonstrated marked pooling of contrast in the indicating significant gestation. In view of the findings, diagnostic pharynx on September 26, 2021 by guest. Protected copyright. amniocentesis and cordocentesis were per- swallowing problems, leading to the diagnosis formed; the results are shown in the table. In the of bulbar palsy. absence of evidence ofhypoxaemia and with the Echocardiography showed a large patent suspicion of congenital varicella zoster virus in- ductus arteriosus with a common origin to the fection, conservative management was pursued. The was 46XX. Examination of for herpes simplex, cytomegalovirus, rubella, and toxoplasma were negative by tissue culture and inoculation. Maternal and fetal blood were negative for antibodies for the same pathogens. However IgM capture (Manchester Public Health Laboratory Service) detected varicella zoster IgM in fetal blood. While viral results were Fetal Centre, serology awaited, Liverpool Maternity cardiotocography was performed and Hospital remained unaltered; there was poor variability W G Taylor and no response to coincident fetal move- S A Walkinshaw M A Thomson ments. On subjective assessment liquor increased. Isolated fetal Correspondence to: volume steadily Dr W G Taylor, Maternity breathing movements were noted but sus- Department, Arrowe Park Hospital, Arrowe Park Road, tained fetal breathing (>30 s) was never Antenatal cardiotocograph at 27 weeks 'gestation showing Upton, Wirral L49 5PE. observed despite prolonged examinations greatly reduced heart rate variability. Arrows indicate fetal Accepted 9 December 1992 (>30 min). activity as nioted by the mother. Antenatal assessment of neurological impairment 605

right innominate and left carotid arteries. important component of respiratory develop- Arch Dis Child: first published as 10.1136/adc.68.5_Spec_No.604 on 1 May 1993. Downloaded from Cranial computed tomography suggested early ment. A respiratory rhythm generator is well cerebral atrophy; abdominal ultrasound and established and active for at least the last computed tomography confirmed the presence trimester.6 Diaphragmatic movement is an of calcification in liver and spleen. A skeletal integral part of breathing and requires intact survey and ophthalmic examination were phrenic nerves. Breathing increases after food normal. ingestion and is thought to be mediated via She required tracheostomy and fundal plica- fetal chemoreceptors. Fetal breathing activity tion with gastrostomy, as well as surgical liga- is also influenced by the alteration in low volt- tion of the ductus because of cardiac failure. age electrocortical activity, which parallels Despite this she continued to have frequent alteration in plasma glucose.7 Thus in this case episodes of aspiration pneumonia often with a glucose load provided a stimulus to fetal septicaemia, which resulted in obstructive breathing movements possibly by both routes. emphysema, cor pulmonale, and severe failure Fetal breathing movements are associated with to thrive. No immune deficiency was found. rapid eye movement sleep, indicating its influ- At 3 months a bilateral keratitis developed ence by overall neurological activity. from which no virus or organism was isolated, Vibroacoustic stimulation profoundly alters leaving considerable corneal scarring. She died fetal behavioural state causing a shift from IF at 10 months from cardiorespiratory failure, by state to 4F.l In this case such a shift was suffi- which time there was gross developmental cient to produce sustained fetal breathing delay with hypoplasia of the muscles in all movements. Without such additional stimulus, limbs. Varicella zoster virus was not isolated however, sustained fetal breathing was rarely from the infant after birth but varicella zoster seen despite prolonged observation periods. IgG at birth was >200 units. At 1 month it was Normally periods of apnoea are short, but they 193 units. may extend up to two hours beyond 30 weeks' Postmorten examination revealed cardiocir- gestation.2 Hypoxaemia leads to a cessation of culatory failure with ventricular hypertrophy, fetal breathing and a slow recovery on return- extensive on the right and moderate on the left. ing to a normal arterial oxygen tension.8 Fetal There was hepatic engorgement, ascites, blood gases and biochemistry in this case bilateral hydrothorax, and patchy pulmonary excluded factors that are associated with atelectasis. Mild pancreatic fibrosis was depression of fetal respiration. noted. The initiation of swallowing is a complex coordinated movement of tongue, pharynx, and larynx mediated through the glosso- Discussion pharyngeal (IX) and vagus (X) nerves. Poly- The risk of congenital malformation after first hydramnios secondary to neuromuscular trimester primary infection with varicella disease is well described. zoster virus is thought to be very low.3 In the absence of an anatomical anomaly the However, neurological abnormality could postnatal investigations confirmed the ante- http://adc.bmj.com/ possibly occur towards the end of the first natal impression that increased liquor was due trimester after infection. In the 15 mm fetus (6 to impaired fetal swallowing. This case illus- weeks' postconception) all of the primordia of trates the increasing ability of antenatal diag- the cranial nerves are laid down with their stem nosticians using invasive and non-invasive nuclei4 and may then be vulnerable to infec- assessment, not only to make a diagnosis but tion. Intrahepatic calcification was the only also to examine fetal function in such a way to

abnormality exhibited by this fetus antenatally, as to offer insight into the ultimate prognosis. on September 26, 2021 by guest. Protected copyright. as indicative of intrauterine infection, and Such information, however incomplete, should postnatally there were no skin lesions or con- be invaluable in the neonatal period to direct tractions. The subsequent neurological dys- investigations and aid prognostic counselling. function was anticipated after serial ultrasound assessment of biophysical activities. 1 Pillai M, James D. Development of human fetal behavior: a review. Fetal Diagn Ther 1990; 5: 15-32. Fetal heart rate variability is under the com- 2 Patrick J, Campbell K, Carichael L, Natale R, Richardson B. plex control of the developing sympathetic and Pattems of human fetal breathing during the last 10 weeks of . Obstet Gynecol 1980; 56: 24-30. parasympathetic nervous systems and by 3 Rudd P, Peckham C. Infection ofthe fetus and the newborn. chemoreceptors. An animal model has shown Clinics in and gynaecology. Vol 2. London: Bailliere, 1988: 55-71. that atropine induced parasympathetic vagal 4 Hamilton WJ, Mossman HW. Human embryology. 4th ed. blockade reduces mean beat to bear variability Cambridge: W Heffer, 1972: 491-9. 5 Dalton KJ, Dawes GS, Patrick JE. The autonomic nervous by 65%.5 In this case variability was markedly system and fetal heart rate variability. Am Y Obstet Gynecol reduced with failure to respond to alterations 1983; 146: 456-61. 6 Maloney JE, Alcorn D, Bowes G, Wilkinson M. in patterns, strongly suggestive Development of the future respiratory system before birth. of vagal impairment. Semin Perinatol 1980; 4: 251-60. 7 Richardson B, Hohimer AR, Mueggler P, Bissonnette J. Fetal movement is largely under cortical Effects of glucose concentration on fetal breathing move- control, and ultrasound demonstrated that this ments and electrocortical activity in fetal lambs. Am J Obstet Gynecol 1982; 142: 678-83._ _ was normal in appearance and in response to 8 Boddy K, Dawes GS. Fetal breathing. BrMed Bull 1975; 31: vibroacoustic stimulation. Fetal breathing is an 3-7.