878 the occurrence of cerebral atrophy in a baby whose delivery had been normal and who had no evidence of other intrauterine infection combine to suggest that the brain damage was caused by Coxsackie B2. Presumed viral infections during pregnancy should be investigated more fully, and infants born after such maternal illnesses should be carefully followed up. I thank Dr T. C. Noble and Dr Elizabeth
White, Newcastle General
Hospital, for their help. Department of Family and Community Medicine, University of Newcastle upon Tyne, and General Practice, Durham
Ryton, Co.
J. RICHARDSON
FLOPPY-INFANT SYNDROME AND MATERNAL DIAZEPAM AND/OR NITRAZEPAM case (July 30, p. 244) is alarming, unexpected in view of what is known of the metabolism of diazepam in pregnancy. Cree et al.’ showed that administration of diazepam to the mother during labour can produce primary or secondary apnoea, hypotonia, poor sucking, risk of aspiration of feeds, and hypothermia. These complications were almost entirely restricted to infants whose mothers had been given more than 30 mg of diazepam in the 15 h before delivery. In two of their cases additional long-term low-dose diazepam (5 mg three times a day) seemed to contribute considerably to the infant’s sedation, with high concen-
SIR,-Dr Gillberg’s
though
not
trations in cord blood relative to those in maternal blood. Dr Gillberg’s case is valuable in stressing that low-dose long-term diazepam therapy alone can produce the same clinical effects without the help of a bolus at the time of delivery. I have seen two similar cases. A 28-year-old mother had had five early miscarriages and a 38-week stillbirth 2 years previously. She had been given diazepam 5 mg three times a day throughout her latest pregnancy. In addition she was admitted for bed rest for the last 9 weeks of pregnancy, during which time she took nitrazepam 10 mg every night. Elective cxsarean section at 38 weeks produced a male infant of 2610 g who, though floppy, did not require intubation. He was admitted to the special-care nursery where he remained floppy and unresponsive. He was nursed in an incubator and had two striking colour changes in the first 3 days. He was unable to suck and required tube feeding for 96 h. He gradually improved and was discharged home suckling successfully on day 10. Had this child not been admitted to the special-care nursery he might have died on a postnatal ward of an apnceic episode. In the absence of other factors it was concluded that the sedation was due to a combination of diazepam and nitrazepam. Blood concentrations were not measured. A further case suggests that nitrazepam alone can produce a similar syndrome. A 29-year-old mother was admitted for bed rest for the last 8 weeks of her pregnancy after removal of a Shirodkar suture. She took nitrazepam 10 mg every night as part of the ward routine. She had 9 full-term normal delivery with a male infant of birth-weight 2980 g, and intubation was not required. However, she found that her baby was very sleepy and reluctant to breast feed, and she described how her baby had been slapped across the face in an effort to wake him up. On examination on day 3 the infant was indeed noted to be excessively sleepy and unresponsive, with no other cause being found apart from 100 mg pethidine given intramuscularly to the mother during labour. Sedation hindered the establishment of breast-feeding and caused the mother great distress. The baby was discharged on day 7. Dr Haram’s case (Sept. 17, p. 612) is in no way reassuring. His infant was passive and hypotonic, had a colour change on a postnatal ward, and required admission to a special-care nur1. Cree,
J. E., Mayer, J., Hailey, D. M. Br. med. J. 1973, iv, 251.
sery for 3
days. Administration throughout pregnancy might produce fetal tolerance and increase a baby’s ability to metabolise the drug. Indeed, a withdrawal syndrome has been des-
cribed in the newborn.2 But my first case had been exposed to diazepam throughout the pregnancy yet he was sedated. There is a general lack of awareness of the hazards of longterm diazepam in pregnancy. Unfortunately, many women on diazepam will continue to take the drug by repeat prescriptions even when they become pregnant, and the liberal use of diazepam and nitrazepam on general medical and surgical wards seems to extend to antenatal wards. Where severe psychiatric disturbance makes prescription essential the psediatric staff should be alerted. In all but the mildest cases a period in a special-care nursery is desirable because of the danger of apnoea. Apart from the danger, the sedated infant will have less chance of being breast fed, and his participation in the process of mother-child bonding will be impaired. Children’s Department, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
A. N. P. SPEIGHT
CIMETIDINE IN TREATMENT OF PANCREATIC INSUFFICIENCY
SIR,-Of the methods of preventing destruction of pancreatic
extracts during gastric transit suggested in your editorial (July 9, p. 73) we believe the most promising to be the use of H2-receptor blockers. Theoretically these drugs should inhibit gastric secretion sufficiently to prevent inactivation of orally ingested pancreatic enzymes. Regan, Saunders, and their col-
leagues3.4 have described the use of cimetidine and metiamide
Faecal fat excretion in patients on tidine or on cimetidine alone.
pancreatin
alone
or
2. Renerterin, J. L., Bhett, K. J. Pediat. 1977, 90, 123. 3. Regan, P. T. and others Clin. Res. 1976, 24, 567. A. 4. Saunders, J H. B., Drummond, S., Wormsley, K. G., Br. 418.
with cime-
medJ 1977, i,
879
adjunct to treatment of pancreatic insufficiency. We have tried this combined treatment in six patients. The patients, all males with pancreatic insufficiency (five having had a subtotal pancreatectomy) and an average age of 43 (range 34-58), had steatorrhoea (>5 g of faecal fat in 24 h. All were taking and had been taking for several months, different amounts of pancreatic extracts in powder form (8-20 g of the commercially available preparation, ’Pancreasmit’). On this regimen and with fat intake restricted to no more than 25g per meal the steatorrhaea had been managed satisfactorily (see figure). We measured faecal fat excretion5 for three consecutive 72 h periods during which each patient received his usual dosage of pancreatin or pancreatin plus cimetidine (1g daily) or cimetidine only (1 g daily). Faecal fat excretion fell significantly (p
White, Newcastle General
Hospital, for their help. Department of Family and Community Medicine, University of Newcastle upon Tyne, and General Practice, Durham
Ryton, Co.
J. RICHARDSON
FLOPPY-INFANT SYNDROME AND MATERNAL DIAZEPAM AND/OR NITRAZEPAM case (July 30, p. 244) is alarming, unexpected in view of what is known of the metabolism of diazepam in pregnancy. Cree et al.’ showed that administration of diazepam to the mother during labour can produce primary or secondary apnoea, hypotonia, poor sucking, risk of aspiration of feeds, and hypothermia. These complications were almost entirely restricted to infants whose mothers had been given more than 30 mg of diazepam in the 15 h before delivery. In two of their cases additional long-term low-dose diazepam (5 mg three times a day) seemed to contribute considerably to the infant’s sedation, with high concen-
SIR,-Dr Gillberg’s
though
not
trations in cord blood relative to those in maternal blood. Dr Gillberg’s case is valuable in stressing that low-dose long-term diazepam therapy alone can produce the same clinical effects without the help of a bolus at the time of delivery. I have seen two similar cases. A 28-year-old mother had had five early miscarriages and a 38-week stillbirth 2 years previously. She had been given diazepam 5 mg three times a day throughout her latest pregnancy. In addition she was admitted for bed rest for the last 9 weeks of pregnancy, during which time she took nitrazepam 10 mg every night. Elective cxsarean section at 38 weeks produced a male infant of 2610 g who, though floppy, did not require intubation. He was admitted to the special-care nursery where he remained floppy and unresponsive. He was nursed in an incubator and had two striking colour changes in the first 3 days. He was unable to suck and required tube feeding for 96 h. He gradually improved and was discharged home suckling successfully on day 10. Had this child not been admitted to the special-care nursery he might have died on a postnatal ward of an apnceic episode. In the absence of other factors it was concluded that the sedation was due to a combination of diazepam and nitrazepam. Blood concentrations were not measured. A further case suggests that nitrazepam alone can produce a similar syndrome. A 29-year-old mother was admitted for bed rest for the last 8 weeks of her pregnancy after removal of a Shirodkar suture. She took nitrazepam 10 mg every night as part of the ward routine. She had 9 full-term normal delivery with a male infant of birth-weight 2980 g, and intubation was not required. However, she found that her baby was very sleepy and reluctant to breast feed, and she described how her baby had been slapped across the face in an effort to wake him up. On examination on day 3 the infant was indeed noted to be excessively sleepy and unresponsive, with no other cause being found apart from 100 mg pethidine given intramuscularly to the mother during labour. Sedation hindered the establishment of breast-feeding and caused the mother great distress. The baby was discharged on day 7. Dr Haram’s case (Sept. 17, p. 612) is in no way reassuring. His infant was passive and hypotonic, had a colour change on a postnatal ward, and required admission to a special-care nur1. Cree,
J. E., Mayer, J., Hailey, D. M. Br. med. J. 1973, iv, 251.
sery for 3
days. Administration throughout pregnancy might produce fetal tolerance and increase a baby’s ability to metabolise the drug. Indeed, a withdrawal syndrome has been des-
cribed in the newborn.2 But my first case had been exposed to diazepam throughout the pregnancy yet he was sedated. There is a general lack of awareness of the hazards of longterm diazepam in pregnancy. Unfortunately, many women on diazepam will continue to take the drug by repeat prescriptions even when they become pregnant, and the liberal use of diazepam and nitrazepam on general medical and surgical wards seems to extend to antenatal wards. Where severe psychiatric disturbance makes prescription essential the psediatric staff should be alerted. In all but the mildest cases a period in a special-care nursery is desirable because of the danger of apnoea. Apart from the danger, the sedated infant will have less chance of being breast fed, and his participation in the process of mother-child bonding will be impaired. Children’s Department, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
A. N. P. SPEIGHT
CIMETIDINE IN TREATMENT OF PANCREATIC INSUFFICIENCY
SIR,-Of the methods of preventing destruction of pancreatic
extracts during gastric transit suggested in your editorial (July 9, p. 73) we believe the most promising to be the use of H2-receptor blockers. Theoretically these drugs should inhibit gastric secretion sufficiently to prevent inactivation of orally ingested pancreatic enzymes. Regan, Saunders, and their col-
leagues3.4 have described the use of cimetidine and metiamide
Faecal fat excretion in patients on tidine or on cimetidine alone.
pancreatin
alone
or
2. Renerterin, J. L., Bhett, K. J. Pediat. 1977, 90, 123. 3. Regan, P. T. and others Clin. Res. 1976, 24, 567. A. 4. Saunders, J H. B., Drummond, S., Wormsley, K. G., Br. 418.
with cime-
medJ 1977, i,
879
adjunct to treatment of pancreatic insufficiency. We have tried this combined treatment in six patients. The patients, all males with pancreatic insufficiency (five having had a subtotal pancreatectomy) and an average age of 43 (range 34-58), had steatorrhoea (>5 g of faecal fat in 24 h. All were taking and had been taking for several months, different amounts of pancreatic extracts in powder form (8-20 g of the commercially available preparation, ’Pancreasmit’). On this regimen and with fat intake restricted to no more than 25g per meal the steatorrhaea had been managed satisfactorily (see figure). We measured faecal fat excretion5 for three consecutive 72 h periods during which each patient received his usual dosage of pancreatin or pancreatin plus cimetidine (1g daily) or cimetidine only (1 g daily). Faecal fat excretion fell significantly (p
