VITAMIN E FOR PREMATURITY

1186 different corticosteroids and different patients or disease Aerosol steroids should be assessed in the same way. University of Western Ontario, Victoria Hospital, London, Ontario, Canada

states.

J. H. TOOGOOD

ORAL REHYDRATION AND MORTALITY FROM DIARRHŒA IN BANGLADESHI VILLAGES

SIR,-Oral rehydration in hospital effectively combats dehydration due to diarrhoea, but it is much more difficult to test this technique in the community. Dr Rahaman and colleagues (Oct. 20, p. 809) are to be congratulated on seizing the opportunity to examine the effect of oral rehydration on mortality from diarrhoea when an isolated community specifically ask for such a service. There are many potential problems in such studies-the effect of surveillance on normal practices, ethical considerations relating to the control therapy, and comparability of the populations. It could be argued that, because one of the two villages asked for help, it was intrinsically different from the other. However, the rapid increase in the use of oral rehydration salt packets by the people of the control village of Bordil during 1978, suggests that they also recognised a good thing when they saw it. I hope the study is continuing for a further period with the introduction of community distribution of rehydration salt packets in the control village. If the diarrhoea mortality in the second village falls to a level similar to that in the first, Rahaman et al. will have even stronger support for their hypothesis. INCIDENCE OF DIARRHGEA IN SECOND YEAR OF

LIFE, PER 1000

CHILDREN

from diarrhoea were supports the observations of many clinicians from Africa and Asia.’It is a pity that those with measles were not reported as a separate group, even though the numbers would be small. It appears encouraging that, during the period when measles was prevalent, the difference in case-fatality rates between the two villages was maintained. If measles affected both populations to a similar extent, this suggests that oral rehydration therapy is beneficial even in measles, a condition which is known to damage the smallbowel mucosa. The suggestion that fatality rates higher during an outbreak of measles

The definition and identification of diarrhoea in this study fairly standard; three or more water stools in 24 h, and surveillance by home visits every 10 days and recall of any illness. However, the incidence of diarrhoea in young children in both these Bangladeshi villages was very low (323 and 277 per 1000 infant years, and 226 and 241 per 1000 toddler years). These figures indicate that less than 1 in 3 infants and 1 in 4 toddlers had an episode of diarrhoea in a year. It is interesting to compare the incidence of diarrhoea in the second year of life from a number of longitudinal studies in different countries (see table). Admittedly the second year is the peak age for diarrhoea in most tropical countries and the Bangladesh figures are either for the first or the subsequent four years, but the difference is striking. The table also indicates how wide are the variations between different countries and studies. are

Edinburgh University, Department of Child Life and Health,

Edinburgh

SIR,-In his comments (Oct. 27, p. 898) on our Oct. 6 paper Dr Baum wonders if bacteria present in unheated milk might harm the baby. He points out that a baby exposed to his own mother’s bacterial flora is very different from a baby exposed to the same bacteria in donor milk from other breast-feeding mothers. The suggestion that there is a feedback mechanism from baby to mother enabling her to manufacture appropriate antibodies1 supports Baum’s argument. However, the ill low birthweight baby to whom much of our bank milk is given is not a suckling baby. We know of no evidence that bacteria in milk differ in pathogenicity whether they are present in the baby’s own mother’s milk or in that of a donor mother. The problem is given a further twist by the fact that a baby on a neonatal unit might be fed heated donor milk until such time as it can be suckled by its own mother. In which case the milk on one day is bacteriologically "safe", yet on the next day the milk may contain an abundance of bacteria. How clean should donor milk be before giving it to low birthweight babies? Our paper was an attempt to answer that question. We believe that human milk is better than milk formult as a food for certain categories of baby cared for on the neonatal unit. Presumably, these advantages rest in the immunological, nutritional, or other physiological properties of human milk. Unfortunately, even precise heat treatment may alter some of the immunological and nutritional properties of milk, and it is most likely that any advantages of breast milk over infant milk formula? will be demonstrated if human milk is given in its least modified form. A study of the safety and practicalities of feeding unheated donor milk using the criteria proposed in our paper is being undertaken in Leicester. Departments of Pædiatrics and Microbiology, Royal Infirmary, Leicester LE1 5WW

1963; 245: 345-77.

L. CARROLL M. OSMAN D. P. DAVIES A. S. MCNEISH

VITAMIN E FOR PREMATURITY

J Clin Nutr 1977; 30: 1215-27.

5. Parkin JM. A longitudinal study of village children in Uganda: pattern of illness during the second year of life. In Owor R, Ongom VL, Kirya BG, eds. The child in the African environment: Growth, development and survival. Nairobi East Africa Literature Bureau, 1975: 193-95. 6. Mitler FJW, Court SDM, Walton WS, Knox EG. Growing up in Newcastleupon-Tyne. London: Oxford University Press, 1960.

WILLIAM A. M. CUTTING

BACTERIOLOGY OF RAW BREAST MILK

1. Morley DC. Severe measles in the tropics. Br Med J 1969; i: 363-65. 2. Mata LJ, Kromal RA, Urrutia JJ, Garcia B. Effect of infection on food intake and the nutrition state: perspectives as viewed from the village. Am 3. Fullerton P. Malnutrition and infection: an examination of the effects of diarrhœal disease and other infections on the growth of children up to three years of age (utilising unpublished data from Morley DC and Woodland M). Dissertation for DTPH, University of London, 1978. 4. Gordon JE, Chitkara ID, Wyon JB. Weanling diarrhoea. Am J Med Sci

EH9 1UW

to

SIR,-The practice of giving vitamin E (tocopherol) routinely premature infants has spread from the United States to Eur-

ope. Vitamin E reduces the hxmolysis in vitro of neonatal erythrocytesbut its efficacy in reducing the fall in haemoglobin leading to the anxmia of prematurity has not been consistently demonstrated. Furthermore acute haemolysis in the LA, Ahlsted S, Carlsson B, et al. New knowledge immunoglobulins. Acta Pædiat Scand 1978; 67: 577-82.

1. Hanson

in human milk

2. Graeber JE, Williams ML, Oski FA. The use of intramuscular vitamin E the premature infant. J Pediat 1977; 90: 282.

in

1187 EFFECT ON THE FETUS OF INDOMETHACIN GIVEN TO SUPPRESS LABOUR

Linear

growth in infants given

vitamin E and in controls.

to vitamin E deficiency is very rare; only have been reported.3,4 Because the absorption of oral vitamin E is variable, due largely to interaction with polyunsaturated fatty acids and iron salts in the gut, my study of the effect on clinical ansemia in premature infants was done with parenteral vitamin E. Thirty-five infants weighing 2000 g or less were studied over a period of two years at Derby City Hospital. The babies were allocated sequentially to one of two groups; those who were given vitamin E (tocopheryl acetate) at a dose of 125 mg/kg intramuscularly in a divided dose over the first week of life, and those given no vitamin E. Informed consent was obtained from the parents. At the end of the first week of life, every week thereafter for a total of five weeks, and again at about a year, capillary blood was drawn from a heel prick. Coulter counter estimations of haemoglobin and total white cell count were made and a manual count of reticulocytes was performed after staining. Weight, crown-heel length, and occipitofrontal head circumference were measured weekly. Each infant was studied until he 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 required respiratory support for apncea or respiratory distress syndrome. One infant in each group had hydrocephalus, apparently due to intraventricular haemorrhage. A few infants showed mild erythema over the injection site but no infant appeared to become ill as the result of this injection. The measured indices were analysed statistically in a longitudinal manner by analysis of variance. The fall in haemo-. globins at the end of the year were identical, and there was little variation over the first six weeks. The other haematological variables also did not reach statistical significance. Measurements of weight, length, and head circumsference showed no significant difference in the two groups, although there was a consistent reduction in the weight and linear growth in those infants receiving vitamin E (figure). This study produced no evidence to support the contention that vitamin E reduces the fall of haemoglobin in premature infants ; nor does it affect the rate of growth of preterm babies. The routine use of this substance, orally or by intramuscular injection, in neonatal units cannot be recommended.

premature infant due

eighteen

cases

Institute of Child Health, Hammersmith Hospital, London W12 0HS

MALCOLM I. LEVENE

deficiency: A previously unrecognised cause of hemolytic anemia. J Pediat 1967; 70: 211. 4. Ritchie JH, Fish MB, McMasters V, Grossman M. Edema and hemolytic anemia in premature infants. N Engl J Med 1968; 279: 1185. 3. Oski FA, Barness LA. Vitamin E

SIR,-We are concerned about the use of prostaglandin inhibitors to suppress premature labour, and report a further case of severe neonatal illness almost certainly due to maternal indomethacin. A boy was born at an estimated gestational age of around 34 weeks, weighing 2520 g. Premature labour had been suppressed for 5 weeks before delivery by intermittent ritodrine and 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. Apgar scores were 5 at 1 min and 8 at 5 min, but apnceic episodes quickly ensued. The liver was enlarged to 5 cm and a systolic murmur was audible. The infant was nursed in oxygen, and, 2 h later, liver enlargement was no longer present; but respiratory difficulty was more marked and the infant was transferred to 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 was not enlarged. Chest X-ray suggested severe idiopathic respiratory-distress syndrome. Ventilation with 100% oxygen brought about a rapid improvement in blood gases and circulation and pulses became normal. Blood was taken for culture and treatment with cloxacillin and gentamicin was started; the blood culture was sterile. 2 h after the patient’s arrival his blood pH was 7.38, PaCOz 28 mm Hg, PaOz 271 mm Hg, and inspired oxygen was reduced to 60%. Shortly after this, the infant deteriorated; his PaOz fell to 27 mm Hg and the pulse became very weak. Inspired oxygen was increased to 100%, and the infant gradually improved. An ECG was normal for age and echocardiography excluded significant structural heart-disease. The cardiac murmur had disappeared 24 h later, but the infant continued to need ventilation with high pressures and 100% oxygen. On several occasions in the subsequent few days reduction in inspired oxygen induced immediate cyanosis and circulatory collapse. On the 12th day, oropharyngeal secretions showed no phosphatidylglycerol. Ventilation was finally discontinued on the 17th day and subsequent progress has been uneventful. The infant required total parenteral nutrition until day 17. Indomethacin is effective in closing a patent ductus arteriosus in the neonatal period.’ Intrauterine ductus closure has been demonstrated in fetal bmbs when the mother is given indomethacin.2 This might result in cardiac failure at birth,3but this would be transient if pulmonary blood-flow is increased in the normal way. However, there is also an effect on pulmonary vasculature.2,4 Hypertrophy of pulmonary vascular smooth muscle occurs and may be related to the increased pulmonary arterial pressure caused by prenatal ductal closure. A consequence of this would be persistent fetal circulation, which has been reported after indomethacin therapy. 5,6 If the effect on pulmonary vasculature were to reduce fetal pulmonary arterial flow prenatally, the maturation of the lung might be impaired, 7 as has been shown in fetal lambs.’ 1.

Heymann MA, Rudolph AM, iosus in premature infants

Silverman NH. Closure of the ductus arterby inhibition of prostaglandin synthesis. N

Engl J Med 1976; 295: 530-33. Rudolph AM. Effects of prostaglandins and synthetase inhibitors on the fetal circulation. In: Anderson A, Beard R, Brudenell JM, Dunn PM, eds. Preterm labour: Proceedings of the fifth study group of the Royal College of Obstetricians and Gynæcologists, 1977: 231-42. 3. Arcilla RA, Thilenius OG, Ranniger K. Congestive heart failure from suspected duct closure in utero. J Pediat 1969; 75: 74-78. 4. Levin DL, Fixler DE, Morriss FC, Tysan J. Morphologic analysis of the pulmonary vascular bed in infants exposed to prostaglandin synthetase inhibition. J Pediat 1978; 92: 478-83. 5. Csaba IF, Sulyok E, Eiztl T. Relationship of maternal treatment with indomethacin to persistence of fetal circulation syndrome. J Pediatr 1978; 92: 2.

484. 6. Rubaltelli FF, Chiozza ML, Zanardo V, Cantarutti F. Effect on neonate of maternal 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 Sci

1965; 29: 239.