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Linear growth in infants given vitamin E and in controls.

premature infant due to vitamin E deficiency is very rare; onlyeighteen cases have been reported.3,4Because the absorption of oral vitamin E is variable, due

largely to interaction with polyunsaturated fatty acids andiron salts in the gut, my study of the effect on clinical ansemiain premature infants was done with parenteral vitamin E.

Thirty-five infants weighing 2000 g or less were studied overa period of two years at Derby City Hospital. The babies wereallocated sequentially to one of two groups; those who weregiven vitamin E (tocopheryl acetate) at a dose of 125 mg/kgintramuscularly in a divided dose over the first week of life,and those given no vitamin E. Informed consent was obtainedfrom the parents.

At the end of the first week of life, every week thereafter fora total of five weeks, and again at about a year, capillary bloodwas drawn from a heel prick. Coulter counter estimations ofhaemoglobin and total white cell count were made and amanual count of reticulocytes was performed after staining.Weight, crown-heel length, and occipitofrontal head circum-ference were measured weekly. Each infant was studied untilhe was six weeks old or had gone home, whichever was sooner.The severity of complications did not significantly very

between the two groups. Four infants in each group requiredrespiratory support for apncea or respiratory distress syn-drome. One infant in each group had hydrocephalus, appar-ently due to intraventricular haemorrhage. A few infantsshowed mild erythema over the injection site but no infantappeared to become ill as the result of this injection.The measured indices were analysed statistically in a longi-

tudinal manner by analysis of variance. The fall in haemo-.globins at the end of the year were identical, and there was littlevariation over the first six weeks. The other haematologicalvariables also did not reach statistical significance. Measure-ments of weight, length, and head circumsference showed nosignificant difference in the two groups, although there was aconsistent reduction in the weight and linear growth in thoseinfants receiving vitamin E (figure).

This study produced no evidence to support the contentionthat vitamin E reduces the fall of haemoglobin in premature in-fants ; nor does it affect the rate of growth of preterm babies.The routine use of this substance, orally or by intramuscularinjection, in neonatal units cannot be recommended.

Institute of Child Health,Hammersmith Hospital,London W12 0HS MALCOLM I. LEVENE

3. Oski FA, Barness LA. Vitamin E deficiency: A previously unrecognised causeof hemolytic anemia. J Pediat 1967; 70: 211.

4. Ritchie JH, Fish MB, McMasters V, Grossman M. Edema and hemolyticanemia in premature infants. N Engl J Med 1968; 279: 1185.

EFFECT ON THE FETUS OF INDOMETHACIN GIVENTO SUPPRESS LABOUR

SIR,-We are concerned about the use of prostaglandin in-hibitors to suppress premature labour, and report a furthercase of severe neonatal illness almost certainly due to maternalindomethacin.A boy was born at an estimated gestational age of around

34 weeks, weighing 2520 g. Premature labour had been sup-pressed for 5 weeks before delivery by intermittent ritodrineand continuous indomethacin (25 mg three times daily orally).At 34 weeks, labour again started and was allowed to continue.Fetal bradycardia led to emergency caesarean’section. Apgarscores were 5 at 1 min and 8 at 5 min, but apnceic episodesquickly ensued. The liver was enlarged to 5 cm and a systolicmurmur was audible. The infant was nursed in oxygen, and,2 h later, liver enlargement was no longer present; but respira-tory difficulty was more marked and the infant was transferredto a regional hospital with suspected congenital heart-disease.He was cyanosed and had poor peripheral pulses. A systolic

murmur at the left sternal edge was audible but the liver wasnot enlarged. Chest X-ray suggested severe idiopathic respira-tory-distress syndrome. Ventilation with 100% oxygen broughtabout a rapid improvement in blood gases and circulation andpulses became normal. Blood was taken for culture and treat-ment with cloxacillin and gentamicin was started; the bloodculture was sterile. 2 h after the patient’s arrival his blood pHwas 7.38, PaCOz 28 mm Hg, PaOz 271 mm Hg, and inspiredoxygen was reduced to 60%. Shortly after this, the infantdeteriorated; his PaOz fell to 27 mm Hg and the pulse becamevery weak. Inspired oxygen was increased to 100%, and the in-fant gradually improved. An ECG was normal for age andechocardiography excluded significant structural heart-disease.The cardiac murmur had disappeared 24 h later, but the in-fant continued to need ventilation with high pressures and100% oxygen. On several occasions in the subsequent few daysreduction in inspired oxygen induced immediate cyanosis andcirculatory collapse. On the 12th day, oropharyngeal secre-tions showed no phosphatidylglycerol. Ventilation was finallydiscontinued on the 17th day and subsequent progress hasbeen uneventful. The infant required total parenteral nutritionuntil day 17.

Indomethacin is effective in closing a patent ductus arter-iosus in the neonatal period.’ Intrauterine ductus closure hasbeen demonstrated in fetal bmbs when the mother is given in-domethacin.2 This might result in cardiac failure at birth,3 butthis would be transient if pulmonary blood-flow is increased inthe normal way. However, there is also an effect on pulmonaryvasculature.2,4 Hypertrophy of pulmonary vascular smoothmuscle occurs and may be related to the increased pulmonaryarterial pressure caused by prenatal ductal closure. A conse-quence of this would be persistent fetal circulation, which hasbeen reported after indomethacin therapy. 5,6 If the effect onpulmonary vasculature were to reduce fetal pulmonary arterialflow prenatally, the maturation of the lung might be impaired,as has been shown in fetal lambs.’ 7

1. Heymann MA, Rudolph AM, Silverman NH. Closure of the ductus arter-iosus in premature infants by inhibition of prostaglandin synthesis. NEngl J Med 1976; 295: 530-33.

2. Rudolph AM. Effects of prostaglandins and synthetase inhibitors on the fetalcirculation. In: Anderson A, Beard R, Brudenell JM, Dunn PM, eds. Pre-term labour: Proceedings of the fifth study group of the Royal College ofObstetricians and Gynæcologists, 1977: 231-42.

3. Arcilla RA, Thilenius OG, Ranniger K. Congestive heart failure from sus-pected duct closure in utero. J Pediat 1969; 75: 74-78.

4. Levin DL, Fixler DE, Morriss FC, Tysan J. Morphologic analysis of the pul-monary vascular bed in infants exposed to prostaglandin synthetase inhi-bition. J Pediat 1978; 92: 478-83.

5. Csaba IF, Sulyok E, Eiztl T. Relationship of maternal treatment with indo-methacin to persistence of fetal circulation syndrome. J Pediatr 1978; 92:484.

6. Rubaltelli FF, Chiozza ML, Zanardo V, Cantarutti F. Effect on neonate ofmaternal treatment with indomethacin. J Pediatr 1978; 94: 161.

7. Howat WF, Avery ME, Humphreys PW, Normand ICS, Reid L, Strang LB.Factors affecting pulmonary surface properties in the fetal lamb. Clin Sci1965; 29: 239.

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Although no neonatal morbidity was attributed to indo-methacin in the first forty-eight infants exposed to the drugprenatally,S more recent reports suggest the morbidity may behigh. Five of the ten neonates reported by Casba et al. wereaffected, as were five of the twenty-nine reported by Rubaltelliet al.; three infants died.

Other drugs are available for suppressing premature labour,and obstetricians and paediatricians should be aware of theadditional hazard to which the fetus is exposed if indometha-cin is given to the mother. Aspirin is also a potent prostaglan-din inhibitor and may have a similar effect if ingested in anyquantity in the last trimester of pregnancy.Queen Mother’s Hospital,Yorkhill, Glasgow G3 8SH

B. M. GOUDIE

J. F. B. DOSSETOR

NASAL OBSTRUCTION AND UNEXPECTED INFANTDEATH

SIR,-Dr Shaw (Nov. 3, p. 954) draws attention to the pos-sibility that nasal obstruction may have an important role inunexpected death in infants. We would like to provide somemore information about nasal obstruction that your readers

may not be aware of and put forward a case that changes innasal airway resistance may have a critical role to play in thesudden-infant-death syndrome (SIDS).One factor which has not been introduced into the literature

on SIDS is the cyclic change in nasal resistance, often termedthe nasal cycle. In 80% of normal adults the nasal air flowalternates from one nasal passage to the other over a period ofhours, the total nasal resistance to air flow remaining rela-tively constant. 1,2 Spontaneous variations in the resistance ofeach nasal passage have been observed in infants during thefirst 48 h of life, with airflow alternating from one nasal pass-age to the other over a period of hours.3 The cyclic change innasal resistance is due to the alternate swelling and constric-tion of the erectile tissue in the nasal mucosa and this isbelieved to be regulated by the sympathetic innervation.4 Thenasal cycle is exaggerated with nasal infection or inflammationand under these conditions one side of the nasal passages maybecome completely obstructed for a period of hours.5 It isreasonable to assume that the infant behaves in a similar wayto the adult and that during periods of nasal infection or snuf-fles the respiration may be alternately restricted to one nasalpassage at a time. Any restriction of the air flow through theopen nasal passage could then result in total airway obstruc-tion and there are at least two factors which may precipitatesuch a situation. Any asymmetry of the nasal passages due toan anatomical defect will mean that the total nasal resistanceto air flow will fluctuate during the nasal cycle as the normallylow resistance passage will be periodically obstructed duringthe course of the nasal cycle.

Another important factor influencing the nasal resistance isthe sleeping position, as the nasal passage on the side on whichone sleeps usually has a high resistance due to engorgement ofthe erectile tissue caused by pressure on the jugular vein.6 Thesleeping position of an infant or any anatomical asymmetry of

8. Zuckerman H, Reiss U, Rubenstein I. Inhibition of human premature laborby indomethacin. Obstet Gynecol 1974; 44: 787-92.

1. Heetderks DL. Observations on the reaction of normal nasal mucosa mem-brane. Am J Med Sci 1927; 174: 231.

2. Eccles R. The central rhythm of the nasal cycle. Acta Otolaryng 1978; 86:464-68.

3. Lacourt G, Polgar G. Interaction between nasal and pulmonary resistancein new born infants. J Appl Physiol 1971; 30: 870-73.

4. Eccles R. The domestic pig as an experimental animal for studies on thenasal cycle. Acta Otolaryng 1978; 85: 431-36.

5. Robinson JM. The lymph pump mechanism of the nose and paranasalsinuses. Laryngoscope 1950; 60: 489-509.

6. Rundcrantz H. Postural variations of nasal patency. Acta Otolaryng 1969;68: 435-43.

the nasal passages may therefore be critical in determining theresistance to air flow during the normal cyclic changes in nasalresistance and these factors may cause periods of total airwayobstruction when the nasal cycle is exaggerated during aperiod of snuffles.A simple method of determining the extent of any unilateral

nasal obstruction in the infant is to hold a cold silver surfacenear to the nose and note the areas of condensation on the mir-ror. Such observations could provide further useful informa-tion in determining the significance of nasal obstruction inSIDS.

Department of Physiology,University College Cardiff,Cardiff CF1 1XL

R. ECCLESK. S. J. ECCLES

PaO2 BY SKIN ELECTRODE

SIR,-The letter by Dr Rooth and colleagues (Sept. 22, p.157) focuses on the influence of circulatory indicators ontranscutaneous oxygen tension (tcP02).We mounted a Radiometer TCM 1 TC electrode operated

at 43°C on the dorsum of 18 feet of sixteen volunteers aged22-34 years who were supine. Local hypotension was inducedby raising the feet stepwise to 40 cm. The average mean arter-ial blood pressure in the morning was 96±9 mm Hg (± SD)(at the arm). The reduction in blood-pressure during foot ele-vation was calculated from the column of blood between theheart and the measuring oosition.The tcPOz of the feet when at heart level was 49±14 mm

Hg. In every experiment the tcPOz decreased steadily as thefoot was raised (see figure). For individuals (feet) the rate of

Relative tcPO (value at test position divided by value at heartlevel) and mean arterial blood-pressure during foot elevation.

Mean and SEM. Significance of deviation from 1.00 is indicated by:*p<0.05, **p<0001.

variation ranged from 0-1% to 3-1%; the average change intcPO was 1 2%/mm Hg change in mean arterial pressure.

In 6 feet the energy consumption of the tcPOz electrodesnecessary to maintain a constant temperature of 42&deg;C wasrecorded. The total consumption, corrected for energy lost toambient air and tissue, was used as an indicator of blood flowin the heated tissue beneath the electrode. Corrected in this

way the energy consumption fell significantly during foot ele-vation and was linearly correlated to tcPOz. Furthermore, theblood flow in the heated tissue beneath the electrode did notshow autoregulation (the ability to maintain constant bloodflow despite variations in perfusion pressure’). Autoregulationwas demonstrated simultaneously in normal non-heated skin 5cm from the tcP02 electrode by xenon-133 washout technique.Our results show-that normal blood flow regulation is

extinct under the heated tcPO electrode, that blood flow in

1. Henriksen O, Nielsen SL, Paaske WP. Autoregulation of blood flow inhuman adipose tissue. Acta Physiol Scand 1973; 89: 531-37.