- Email: [email protected]
WEIGHT-GAIN INHIBITION BY LACTOSE IN AUSTRALIAN ABORIGINAL CHILDREN
500 WEIGHT-GAIN INHIBITION BY LACTOSE IN AUSTRALIAN ABORIGINAL CHILDREN A Controlled Trial of Normal and Lactose
Hydrolysed Milk JOHN D. MITCHELL JANETTE BRAND JEANETTE HALBISCH Division of Pœdiatric Gastroenterology, Prince of Wales Children’s Hospital and Schools of Pœdiatrics and Food Technology, University of New South Wales, Kensington; Brewarrina District Hospital, N.S.W. Australia
in 35 slightly undernourished Australian Aboriginal infants was studied in hospital (49 admissions) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder. Infants fed the lactose hydrolysed milk gained 70% more weight than those receiving normal milk. Better weightgains were achieved in those on the lactose hydrolysed milk irrespective of percentage standard weight for age, the presence of diarrhœa on admission to the trial, and stool sugar concentrations. The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world.
Summary
Weight-gain
Introduction IN
Australia, morbidity and mortality
rates in Aborithose in infants and children, are ginals, particularly disturbingly high.1-4 Enteric disease56 and lactose intolerance7 are often found in markedly malnourished Aboriginal children. Abnormality of the small-intestinal mucosa9 and associated low disaccharidase activities, especially lactase,10 are common findings even in Aboriginal infants who are only slightly malnourished." The nutritional consequences of lactose intolerance in association with mild malnutrition are unclear. We used a double-blind feeding trial in hospital to study weightgains in slightly undernourished, Aboriginal infants fed either a normal or a low-lactose milk.
milk (L.H. milk) powder had a lactose content after reconstitution of less than 7.2 g/1. The only difference in the processing of the L.H. milk was the preliminary hydrolysis of lactose to non-lactose sugars (mainly glucose and galactose monomers) by a yeast-derived lactase. Both milks were identically packaged and then coded for use in the trial. All children received a multi-vitamin supplement and older children in both groups were also given a standardised low-lactose solid diet.
lysed
Trial Procedure On admission, children were allotted randomly by code to receive either normal milk or L.H. milk. A record was kept of each child’s weight (daily at 9 A.M. after the morning feed), milk intake, and stool consistency and frequency. The ’Clinitest’ method’z was used to test for the presence of reducing sugars in the stools of all children in whom fluid diarrhoea developed during the trial. A concentration of more than 0-25g/dl reducing sugar in a stool specimen was regarded as indicating severe lactose intolerance and children with such concentrations were transferred to known (declared) L.H. milk. Data from children admitted to hospital for less than three whole days were excluded from the analysis of results, as were data from those children transferred to declared L.H. milk before completing their third day. The "initial" weight was defined as the average of the weights on the first and second morning, and "final" weight was the average of the weights on the penultimate and final mornings. Weight is also expressed as a percentage of the standard weight for age (S.W.F.A.), defined as the 50th percentile for weight at the same age in normal (Caucasian) children in New South Wales." Weightgain (final minus initial weight) is expressed as g kg-I (initial body weight) day-’. Statistical analysis was carried out by Student’s one-tailed t test.
Results 66 admissions satisfied the criteria for entry into the trial. Of these, 17 were excluded; 13 because of the DATA*
ON CHILDREN IN BOTH MILK FEEDING GROUPS
Patients and Methods Patient Selection
The children
Aboriginals of mixed blood from the arid New South Wales surrounding the town of Brewarrina, which has a population of 2000 Caucasians and 1000 Aboriginals. Most of the Aboriginals live on the periphery of the town either in makeshift riverbank housing or within a government housing settlement. All Aboriginal children admitted to the district hospital between December, 1975, and May, 1976, who were less than 3 years of age and not being breast-fed, were considered for inclusion in the trial. The only criterion for exclusion was known hypolactasia, determined by earlier enzyme assay of duodenal biopsy samples. These children were already receiving the trial milk. Readmission of children during the period of the trial was not regarded as reason for exclusion. were
region of western
Trial Milk The two milk preparations were both processed by the same factory (Hunter Valley-Sharpe Pty. Ltd., Hexham, N.S.W.). Normal milk was a full-cream spray dried milk powder with a lactose content after reconstitution of 52 g/1. Lactose hydro-
*Mean±s.E.M. with ranges given in parentheses.
i Children with birth-weights confirmed from maternity-ward records.
child’s hospital stay was less than three days and 4 because of early transfer to declared L.H. milk. Thus, 49 admissions of 36 children remained for analysis in the controlled trial. Children were admitted to the normalmilk group on 25 occasions and to the L.H.-milk group on 24. 2 children had been admitted twice and 1 had been admitted on three occasions to the L.H.-milk group.
501
Both types of milk had been allocated at least once to 6 children during multiple admissions to the trial. 7 children were transferred from the trial to declared L.11. milk. Both groups in the trial were similar in age, S.w.F.A., initial weight, and length of stay in hospital
(see accompanying table).
the L.H. milk (fig. 2). However, only the differences in weight-gains in those with diarrhoea and those with S.W.F.A. <90% were statistically significant. 5 children receiving normal milk and 1 on L.H. milk lost weight during an admission to the trial.
higher
on
Readmission with
Controlled Trial
Weight-gains during admissions for children fed the two different milks are shown in fig. 1. The mean weight-gain (is.E.M.) of 5.40:t0.84 g kg-Iday-’ in the L.H.-milk group was 70% higher than the 3-1 ±0-32 g krl day-’ in children receiving normal milk (P<0025). Although weight was gained more rapidly by the children with lower S.W.F.A.S, those who received L.H. milk gained weight more rapidly than those on normal milk irrespective of their s.w.F.A. Thus, children either above or below the 90% S.W.F.A. gained weight 70% to 80% more rapidly on the L.H. milk (fig. 2). Children with diarrhoea gained weight on the L.H. milk 130% more rapidly than those on normal milk (fig. 2). Even in children without diarrhoea the weight-gain was 60%
Group Crossover (Self Controls)
6 children had been allotted to both milk groups during different admissions. These children represent a small crossover trial group since, by chance, half were allotted to one or other of the milk groups on the first admission. The mean age for the first admission was 0-77years (range 0-15—2-14 years). The mean weightgain during admissions on L.H. milk was 6-01±1-39 g kg"’day-’ and on normal milk it was 2.77+0.87 g kg-l day- ’. This difference (p<0’05) represents a weight-gain by the same individuals which was 120% more rapid while being fed the L.H. milk than while receiving normal milk. Discussion Cow’s milk is thought to be of doubtful nutritional value in aid programmes to developing countries.14-16 Feeding trials in Africal7 and Indonesia11! have strongly suggested that lactose may be harmful in severely malnourished children. Our results, obtained by giving normal cow’s milk or an isocaloric lactose hydrolysate of this milk, confirm that the lactose component can reduce the nutritional value of milk. By Australian standards the Aboriginal children in this study were undernourished. However, to international their mean S.W.F.A. criteria according was well above that regarded as indicating malnutrition. 19 Our findings indicate that the effect of lactose intolerance must be considered when planning nutritional rehabilitation programmes for children with all degrees of nutritional deficiency. Even those children whose weight was above the 90th centile for S.w.F.A., and therefore fell within the normal range, gained weight more rapidly on the L.H. milk. It is likely therefore, that an isolated S.W.F.A. estimation should not be used as the sole criterion for defining those who might be nutritionally disadvantaged by receiving unmodified cow’s milk. Although a falling S.W.F.A. from birth is a more reliable criterion of undernutrition based on weight, such data are often not available. A group of slightly undernourished Aboriginal children from the district of the present trial were investigated by smallbowel biopsy. All had histological evidence of small-gut abnormalities ranging from mild to severe and accompanying variable depression of lactase and other disaccharidase activities."We suggest therefore, that assessment of small-bowel histological integrity and disaccharidase enzyme concentrations may be the most reliable means of predicting the frequency of lactose intolerance in communities before the introduction of unmodified milk. The clinitest method 12 for identification of sugar in stools is widely used to diagnose lactose intolerance in young children. However, in the present trial weightgains were higher on the L.H. milk irrespective of the clinitest result. A negative clinitest result therefore seems to be of little value in excluding lactose intolerance. A fixed increase in blood-glucose is used to define arbitrarily abnormal responses in standard lactose toler-
slightly
vveigrn-gam By/Kg/OUYI
F4. 1—Dtstfibuttoa of weight-gains in undernourished children fed normal and L.H. milk.
Fig. 2-Influence
of % S.W.F.A. and diarrh(ea gains in children on normal or L.H. milk.
mean
weight-
502 Our experience with the clinitest method in this trial suggests that lactose-tolerance tests may, because of their arbitrary delineation, be an equally poor method of excluding sugar intolerance. Although patients with diarrhoea gained weight more rapidly on the hydrolysed milk, those without overt symptoms also showed larger weight-gains than those on normal milk. Simple observation of stools, therefore, should not be relied upon as a means for deciding whether a child will benefit from dietary exclusion of lactose. The number of children who lost weight while being fed normal milk is especially disturbing. Although no serious complications developed in these children, such complications would be more likely to develop in severely malnourished infants with lower protein-calorie reserves.2° The aetiology of the gut mucosal abnormalities and associated lactose intolerance in these Aboriginal children is complex. Effective intervention in the cycle is proving difficult. Efforts are being made to improve the Aboriginals’ socioeconomic condition and an improvement in their nutrition should follow. A wider use of L.H. milk should provide an immediate means of effectively intervening in the cycle of problems related to their malnutrition during infancy. This study has confirmed that lactose intolerance can have important nutritional consequences. Furthermore, our findings indicate that malabsorption of lactose can produce suboptimum weight-gain even in slightly undernourished children. It is likely that the incidence and importance of lactose intolerance in children are underestimated. Our findings should re-emphasise the global implications of aid programmes which use milk produced by a basically lactose-tolerant Western world. Since large-scale hydrolysis of lactose in milk is practicable, the modification of all milk before it is used in international aid programmes should be seriously considered. ance tests.
We thank Dr B. J. Duffy, Professor J. Beveridge, and Professor R. A. Edwards for their advice and encouragement, Mr J. Miller for performing the data analysis; Mr M. Sharpe for his help; Hunter Valley-Sharpe, Pty. Ltd. for the donation of milk; and Dr A. Lopes and the nursing staff of the Brewarrina District Hospital whose continu]Qg assistance and involvement made this study possible.
Requests for reprints should be addressed to J.D.M., Prince of Wales Children’s Hospital, Randwick, N.S.W. 2031, Australia. REFERENCES 1. Kirke, D. K. Med. J. Aust. 1969, ii, 1005 2. Maxwell, G. M., Elliot, R. B. ibid. p. 716. 3. Edmonds, R., Roberts, R. W., Schlafrig, G. Aust. pœdiat. J. 1970, 6, 76. 4. Gracey, M. ibid. 1976, 12, 180. 5. Jose, D. G., Welch, J. S. Med. J. Aust. 1970, i, 349. 6. Walker, A. C., Harry, J. G. ibid. 1972, i, 904. 7. Elliot, R. B., Maxwell, G. M. ibid. 1967, i, 46. 8. Gracey, M. Aust. N.Z.J. Med. 1973, 3, 576. 9. Walker-Smith, J. A., Reye, R. D. K. ibid. 1971, 4, 377. 10. Harris, M. J., Duffy, B. J., Beveridge, J. Med. J. Aust. 1970, i, 356. 11. Mitchell, J. D., Duffy, B. J. Proceedings of the Vth Asian-Pacific Congress of Gastroenterology, Singapore, May, 1976. 12. Kerry, K. R., Anderson, C. M. Lancet, 1964, i, 981. 13. Charts and Tables of Heights, Masses and Head Circumferences of Infants and Children. Australian Government Publishing Service, Canberra, 1975. 14. Graham, G. G. Pœdiatrics, 1975, 55, 295. 15. Bradfield, R. B., Jelliffe, D. B., Ifekwunigwe, A. Lancet, 1975, ii, 325. 16. Davis, A. E., Bolin, T. Nature, 1967, 216, 1244. 17. Ifekwunigwe, A. E. Am. J. clin. Nutr. 1975, 28, 79. 18. Suharjono, Wila Wirya, I. G. N., Samsudin, Sunoto, Sulaiman, Z., Sutedjo, Pœdiat. Indonesiana, 1975, 15, 255. 19. Lancet, 1970, ii, 302. 20. Lifshitz, F., Coelio-Ramirez, P., Gutierres-Topete, G. J. Pediat. 1970, 77, 595.
BROMOCRIPTINE FOR INDUCTION OF OVULATION IN NORMOPROLACTINÆMIC
POST-PILL ANOVULATION
J. VAN DER STEEG H. J. T. COELINGH BENNINK Department of Obstetrics and Gynœcology, State University H.
Hospital Utrecht,
The Netherlands
with anovulation after disoral contraceptive agents and continuing with normal plasma-prolactin concentrations were treated with bromocriptine. Ovulation and menstruation were restored in 9 of the 13 amenorrhœic and 5 of the 6 oligomenorrhœic patients. The success-rate (74%) indicates that bromocriptine is an effective treatment for post-pill anovulation in normoprolactinæmic women.
Summary
19
women
Introduction BROMOCRIPTINE has
proved to be very effective in the hyperprolactinaemic anovulation.’ Some normoprolactinasmic amenorrhoeic patients have also responded to bromocriptine.23 No particular type of treatment
of
amenorrhcea was identified in those patients who responded to bromocriptine therapy. Oestrogen treatment and oral contraceptives are associated with an increase in plasma-prolactin concentration .4The Eetiology of post-pill amenorrhcea is obscure.6 However, the oestrogen in oral contraceptives in interfering with prolactin metabolism may be an aetiological factor. If post-pill anovulation is related to a disturbance of prolactin metabolism which does not result in hyperprolactinaemia, then normoprolactinsemic patients with post-pill anovulation may respond to treatment with bromocriptine. We studied a group of normoprolactlnxmic patients with post-pill anovulation to determine the effect of bromocriptine in this condition. Patients and Methods Selection
of Patients During the 5-year period 1972-1976 anovulation after discontinuation of oral contraceptives (mainly post-pill amenorrhoea) was diagnosed in 96 patients in our gynaecological endocrinological department. About half of our patients with anovulation had been referred by other specialists after treatment with clomiphene or exogenous gonadotrophins had failed. From these 96 patients we selected a group of 33 patients, who agreed to participate in an intensive endocrinological investigation to analyse the effect of bromocriptine and to test its clinical efficacy in post-pill anovulation. Patients with spontaneous recovery of an ovulatory menstrual cycle, patients
who ovulated or became pregnant after induction of ovulation with clomiphene or exogenous gonadotrophins, and patients who were found to be hyperprolactinaemic in the usual initial screening procedure to determine the cause of the anovulation were excluded. Moreover, several patients were lost to follow-up or refused to take part in the investigation. The following features were common to the remaining 33 patients: 1. Normoprolactinsemia (plasma-prolactin < 15 ng/ml). 2. Anovulation after discontinuation of oral contraceptives for at least 6 months. 3. Complete endocrinological screening had excluded other causes of anovulation. Special care was taken to diagnose hypophyseal adenomas. All patients underwent tomography of the sella turcica and were seen by an ophthalmologist for evaluation of the visual fields. 4. No history of taking another drug, except oral contraceptives, known to interfere with prolactin metabolism.
Hydrolysed Milk JOHN D. MITCHELL JANETTE BRAND JEANETTE HALBISCH Division of Pœdiatric Gastroenterology, Prince of Wales Children’s Hospital and Schools of Pœdiatrics and Food Technology, University of New South Wales, Kensington; Brewarrina District Hospital, N.S.W. Australia
in 35 slightly undernourished Australian Aboriginal infants was studied in hospital (49 admissions) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder. Infants fed the lactose hydrolysed milk gained 70% more weight than those receiving normal milk. Better weightgains were achieved in those on the lactose hydrolysed milk irrespective of percentage standard weight for age, the presence of diarrhœa on admission to the trial, and stool sugar concentrations. The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world.
Summary
Weight-gain
Introduction IN
Australia, morbidity and mortality
rates in Aborithose in infants and children, are ginals, particularly disturbingly high.1-4 Enteric disease56 and lactose intolerance7 are often found in markedly malnourished Aboriginal children. Abnormality of the small-intestinal mucosa9 and associated low disaccharidase activities, especially lactase,10 are common findings even in Aboriginal infants who are only slightly malnourished." The nutritional consequences of lactose intolerance in association with mild malnutrition are unclear. We used a double-blind feeding trial in hospital to study weightgains in slightly undernourished, Aboriginal infants fed either a normal or a low-lactose milk.
milk (L.H. milk) powder had a lactose content after reconstitution of less than 7.2 g/1. The only difference in the processing of the L.H. milk was the preliminary hydrolysis of lactose to non-lactose sugars (mainly glucose and galactose monomers) by a yeast-derived lactase. Both milks were identically packaged and then coded for use in the trial. All children received a multi-vitamin supplement and older children in both groups were also given a standardised low-lactose solid diet.
lysed
Trial Procedure On admission, children were allotted randomly by code to receive either normal milk or L.H. milk. A record was kept of each child’s weight (daily at 9 A.M. after the morning feed), milk intake, and stool consistency and frequency. The ’Clinitest’ method’z was used to test for the presence of reducing sugars in the stools of all children in whom fluid diarrhoea developed during the trial. A concentration of more than 0-25g/dl reducing sugar in a stool specimen was regarded as indicating severe lactose intolerance and children with such concentrations were transferred to known (declared) L.H. milk. Data from children admitted to hospital for less than three whole days were excluded from the analysis of results, as were data from those children transferred to declared L.H. milk before completing their third day. The "initial" weight was defined as the average of the weights on the first and second morning, and "final" weight was the average of the weights on the penultimate and final mornings. Weight is also expressed as a percentage of the standard weight for age (S.W.F.A.), defined as the 50th percentile for weight at the same age in normal (Caucasian) children in New South Wales." Weightgain (final minus initial weight) is expressed as g kg-I (initial body weight) day-’. Statistical analysis was carried out by Student’s one-tailed t test.
Results 66 admissions satisfied the criteria for entry into the trial. Of these, 17 were excluded; 13 because of the DATA*
ON CHILDREN IN BOTH MILK FEEDING GROUPS
Patients and Methods Patient Selection
The children
Aboriginals of mixed blood from the arid New South Wales surrounding the town of Brewarrina, which has a population of 2000 Caucasians and 1000 Aboriginals. Most of the Aboriginals live on the periphery of the town either in makeshift riverbank housing or within a government housing settlement. All Aboriginal children admitted to the district hospital between December, 1975, and May, 1976, who were less than 3 years of age and not being breast-fed, were considered for inclusion in the trial. The only criterion for exclusion was known hypolactasia, determined by earlier enzyme assay of duodenal biopsy samples. These children were already receiving the trial milk. Readmission of children during the period of the trial was not regarded as reason for exclusion. were
region of western
Trial Milk The two milk preparations were both processed by the same factory (Hunter Valley-Sharpe Pty. Ltd., Hexham, N.S.W.). Normal milk was a full-cream spray dried milk powder with a lactose content after reconstitution of 52 g/1. Lactose hydro-
*Mean±s.E.M. with ranges given in parentheses.
i Children with birth-weights confirmed from maternity-ward records.
child’s hospital stay was less than three days and 4 because of early transfer to declared L.H. milk. Thus, 49 admissions of 36 children remained for analysis in the controlled trial. Children were admitted to the normalmilk group on 25 occasions and to the L.H.-milk group on 24. 2 children had been admitted twice and 1 had been admitted on three occasions to the L.H.-milk group.
501
Both types of milk had been allocated at least once to 6 children during multiple admissions to the trial. 7 children were transferred from the trial to declared L.11. milk. Both groups in the trial were similar in age, S.w.F.A., initial weight, and length of stay in hospital
(see accompanying table).
the L.H. milk (fig. 2). However, only the differences in weight-gains in those with diarrhoea and those with S.W.F.A. <90% were statistically significant. 5 children receiving normal milk and 1 on L.H. milk lost weight during an admission to the trial.
higher
on
Readmission with
Controlled Trial
Weight-gains during admissions for children fed the two different milks are shown in fig. 1. The mean weight-gain (is.E.M.) of 5.40:t0.84 g kg-Iday-’ in the L.H.-milk group was 70% higher than the 3-1 ±0-32 g krl day-’ in children receiving normal milk (P<0025). Although weight was gained more rapidly by the children with lower S.W.F.A.S, those who received L.H. milk gained weight more rapidly than those on normal milk irrespective of their s.w.F.A. Thus, children either above or below the 90% S.W.F.A. gained weight 70% to 80% more rapidly on the L.H. milk (fig. 2). Children with diarrhoea gained weight on the L.H. milk 130% more rapidly than those on normal milk (fig. 2). Even in children without diarrhoea the weight-gain was 60%
Group Crossover (Self Controls)
6 children had been allotted to both milk groups during different admissions. These children represent a small crossover trial group since, by chance, half were allotted to one or other of the milk groups on the first admission. The mean age for the first admission was 0-77years (range 0-15—2-14 years). The mean weightgain during admissions on L.H. milk was 6-01±1-39 g kg"’day-’ and on normal milk it was 2.77+0.87 g kg-l day- ’. This difference (p<0’05) represents a weight-gain by the same individuals which was 120% more rapid while being fed the L.H. milk than while receiving normal milk. Discussion Cow’s milk is thought to be of doubtful nutritional value in aid programmes to developing countries.14-16 Feeding trials in Africal7 and Indonesia11! have strongly suggested that lactose may be harmful in severely malnourished children. Our results, obtained by giving normal cow’s milk or an isocaloric lactose hydrolysate of this milk, confirm that the lactose component can reduce the nutritional value of milk. By Australian standards the Aboriginal children in this study were undernourished. However, to international their mean S.W.F.A. criteria according was well above that regarded as indicating malnutrition. 19 Our findings indicate that the effect of lactose intolerance must be considered when planning nutritional rehabilitation programmes for children with all degrees of nutritional deficiency. Even those children whose weight was above the 90th centile for S.w.F.A., and therefore fell within the normal range, gained weight more rapidly on the L.H. milk. It is likely therefore, that an isolated S.W.F.A. estimation should not be used as the sole criterion for defining those who might be nutritionally disadvantaged by receiving unmodified cow’s milk. Although a falling S.W.F.A. from birth is a more reliable criterion of undernutrition based on weight, such data are often not available. A group of slightly undernourished Aboriginal children from the district of the present trial were investigated by smallbowel biopsy. All had histological evidence of small-gut abnormalities ranging from mild to severe and accompanying variable depression of lactase and other disaccharidase activities."We suggest therefore, that assessment of small-bowel histological integrity and disaccharidase enzyme concentrations may be the most reliable means of predicting the frequency of lactose intolerance in communities before the introduction of unmodified milk. The clinitest method 12 for identification of sugar in stools is widely used to diagnose lactose intolerance in young children. However, in the present trial weightgains were higher on the L.H. milk irrespective of the clinitest result. A negative clinitest result therefore seems to be of little value in excluding lactose intolerance. A fixed increase in blood-glucose is used to define arbitrarily abnormal responses in standard lactose toler-
slightly
vveigrn-gam By/Kg/OUYI
F4. 1—Dtstfibuttoa of weight-gains in undernourished children fed normal and L.H. milk.
Fig. 2-Influence
of % S.W.F.A. and diarrh(ea gains in children on normal or L.H. milk.
mean
weight-
502 Our experience with the clinitest method in this trial suggests that lactose-tolerance tests may, because of their arbitrary delineation, be an equally poor method of excluding sugar intolerance. Although patients with diarrhoea gained weight more rapidly on the hydrolysed milk, those without overt symptoms also showed larger weight-gains than those on normal milk. Simple observation of stools, therefore, should not be relied upon as a means for deciding whether a child will benefit from dietary exclusion of lactose. The number of children who lost weight while being fed normal milk is especially disturbing. Although no serious complications developed in these children, such complications would be more likely to develop in severely malnourished infants with lower protein-calorie reserves.2° The aetiology of the gut mucosal abnormalities and associated lactose intolerance in these Aboriginal children is complex. Effective intervention in the cycle is proving difficult. Efforts are being made to improve the Aboriginals’ socioeconomic condition and an improvement in their nutrition should follow. A wider use of L.H. milk should provide an immediate means of effectively intervening in the cycle of problems related to their malnutrition during infancy. This study has confirmed that lactose intolerance can have important nutritional consequences. Furthermore, our findings indicate that malabsorption of lactose can produce suboptimum weight-gain even in slightly undernourished children. It is likely that the incidence and importance of lactose intolerance in children are underestimated. Our findings should re-emphasise the global implications of aid programmes which use milk produced by a basically lactose-tolerant Western world. Since large-scale hydrolysis of lactose in milk is practicable, the modification of all milk before it is used in international aid programmes should be seriously considered. ance tests.
We thank Dr B. J. Duffy, Professor J. Beveridge, and Professor R. A. Edwards for their advice and encouragement, Mr J. Miller for performing the data analysis; Mr M. Sharpe for his help; Hunter Valley-Sharpe, Pty. Ltd. for the donation of milk; and Dr A. Lopes and the nursing staff of the Brewarrina District Hospital whose continu]Qg assistance and involvement made this study possible.
Requests for reprints should be addressed to J.D.M., Prince of Wales Children’s Hospital, Randwick, N.S.W. 2031, Australia. REFERENCES 1. Kirke, D. K. Med. J. Aust. 1969, ii, 1005 2. Maxwell, G. M., Elliot, R. B. ibid. p. 716. 3. Edmonds, R., Roberts, R. W., Schlafrig, G. Aust. pœdiat. J. 1970, 6, 76. 4. Gracey, M. ibid. 1976, 12, 180. 5. Jose, D. G., Welch, J. S. Med. J. Aust. 1970, i, 349. 6. Walker, A. C., Harry, J. G. ibid. 1972, i, 904. 7. Elliot, R. B., Maxwell, G. M. ibid. 1967, i, 46. 8. Gracey, M. Aust. N.Z.J. Med. 1973, 3, 576. 9. Walker-Smith, J. A., Reye, R. D. K. ibid. 1971, 4, 377. 10. Harris, M. J., Duffy, B. J., Beveridge, J. Med. J. Aust. 1970, i, 356. 11. Mitchell, J. D., Duffy, B. J. Proceedings of the Vth Asian-Pacific Congress of Gastroenterology, Singapore, May, 1976. 12. Kerry, K. R., Anderson, C. M. Lancet, 1964, i, 981. 13. Charts and Tables of Heights, Masses and Head Circumferences of Infants and Children. Australian Government Publishing Service, Canberra, 1975. 14. Graham, G. G. Pœdiatrics, 1975, 55, 295. 15. Bradfield, R. B., Jelliffe, D. B., Ifekwunigwe, A. Lancet, 1975, ii, 325. 16. Davis, A. E., Bolin, T. Nature, 1967, 216, 1244. 17. Ifekwunigwe, A. E. Am. J. clin. Nutr. 1975, 28, 79. 18. Suharjono, Wila Wirya, I. G. N., Samsudin, Sunoto, Sulaiman, Z., Sutedjo, Pœdiat. Indonesiana, 1975, 15, 255. 19. Lancet, 1970, ii, 302. 20. Lifshitz, F., Coelio-Ramirez, P., Gutierres-Topete, G. J. Pediat. 1970, 77, 595.
BROMOCRIPTINE FOR INDUCTION OF OVULATION IN NORMOPROLACTINÆMIC
POST-PILL ANOVULATION
J. VAN DER STEEG H. J. T. COELINGH BENNINK Department of Obstetrics and Gynœcology, State University H.
Hospital Utrecht,
The Netherlands
with anovulation after disoral contraceptive agents and continuing with normal plasma-prolactin concentrations were treated with bromocriptine. Ovulation and menstruation were restored in 9 of the 13 amenorrhœic and 5 of the 6 oligomenorrhœic patients. The success-rate (74%) indicates that bromocriptine is an effective treatment for post-pill anovulation in normoprolactinæmic women.
Summary
19
women
Introduction BROMOCRIPTINE has
proved to be very effective in the hyperprolactinaemic anovulation.’ Some normoprolactinasmic amenorrhoeic patients have also responded to bromocriptine.23 No particular type of treatment
of
amenorrhcea was identified in those patients who responded to bromocriptine therapy. Oestrogen treatment and oral contraceptives are associated with an increase in plasma-prolactin concentration .4The Eetiology of post-pill amenorrhcea is obscure.6 However, the oestrogen in oral contraceptives in interfering with prolactin metabolism may be an aetiological factor. If post-pill anovulation is related to a disturbance of prolactin metabolism which does not result in hyperprolactinaemia, then normoprolactinsemic patients with post-pill anovulation may respond to treatment with bromocriptine. We studied a group of normoprolactlnxmic patients with post-pill anovulation to determine the effect of bromocriptine in this condition. Patients and Methods Selection
of Patients During the 5-year period 1972-1976 anovulation after discontinuation of oral contraceptives (mainly post-pill amenorrhoea) was diagnosed in 96 patients in our gynaecological endocrinological department. About half of our patients with anovulation had been referred by other specialists after treatment with clomiphene or exogenous gonadotrophins had failed. From these 96 patients we selected a group of 33 patients, who agreed to participate in an intensive endocrinological investigation to analyse the effect of bromocriptine and to test its clinical efficacy in post-pill anovulation. Patients with spontaneous recovery of an ovulatory menstrual cycle, patients
who ovulated or became pregnant after induction of ovulation with clomiphene or exogenous gonadotrophins, and patients who were found to be hyperprolactinaemic in the usual initial screening procedure to determine the cause of the anovulation were excluded. Moreover, several patients were lost to follow-up or refused to take part in the investigation. The following features were common to the remaining 33 patients: 1. Normoprolactinsemia (plasma-prolactin < 15 ng/ml). 2. Anovulation after discontinuation of oral contraceptives for at least 6 months. 3. Complete endocrinological screening had excluded other causes of anovulation. Special care was taken to diagnose hypophyseal adenomas. All patients underwent tomography of the sella turcica and were seen by an ophthalmologist for evaluation of the visual fields. 4. No history of taking another drug, except oral contraceptives, known to interfere with prolactin metabolism.