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PERINATAL MORTALITY AS INDICATION OF OBSTETRIC CARE
813 also innervated by dopaminergic neurons.’8 These dopaminergic terminals presumably originate from cell bodies situated in the mesencephalon and in the lateral part of the substantia nigra.? Damage of the frontotemporal region might reflect dysfunction of subcortical pathways involving the mesolimbic area, leading to a reduced serotonergic and dopaminergic activity. Metabolism of cerebral serotonin is increased after bilateral destruction of the dorsal noradrenergic pathway at the level of the pontomesencephalic region." It might be that in the acute phase of the diffuse cerebral contusion this pathway is
especially affected. T. C. A. M. VAN WOERKOM A. W. TEELKEN J. M. MINDERHOUD
Department of Neurology, University Hospital, Groningen, Netherlands
PERINATAL MORTALITY AS INDICATION OF OBSTETRIC CARE
SIR,-Controversy over the use of new obstetric techniques was covered extensively in The Lancet during 1976. Clearly we need to test the efficacy of new obstetric techniques by controlled trials. Conclusions drawn from changes in perinatalmortality statistics are hampered by variables such as social characteristics of the population, general health of the mothers, skill and experience of staff, and organisation of obstetric services. However, we decided to see if, by examining
Year
Fig. 2-Perinatal mortality (excluding fetal malformations). Significant increasing trend m ante-partum death-rate (r=0.55, P<0.05), and a significant decreasing trend in intra-partum death-rate (r=+0.79, r<0.02). No year was found sigmficantly different from the others (Z not significant). tal malformation, infection, rhesus incompatibility, gross imshows that the decline in intra-partum mortality in fetuses >2500g was almost solely the result of a fall in anoxic deaths (fig. 4), while the rise in ante-partum mortality in was partly due to an increase in anoxic deaths fetuses <2500g
maturity)
(fig. 3). The results demonstrate the
importance of considering peri-
It::QI
Fig. I-Perinatal mortality. No significant change in total perinatal mortality
rate or
fatal-mal-
tormation rate.
perinatal mortality in useful in the
more
detail, this statistic could be made
of obstetric care. Fetal mortality statistics were collected from the Queen Victoria Memorial Hospital between 1960 and 1974. The definitions and method of analysis will be published elsewhere.’1 Perinatal mortality did not change significantly over this period (fig. 1), but antenatal mortality rose while intra-partum mortality fell (fig. 2). The rise in antenatal mortality was restricted to fetuses weighing <2500g (fig. 3). This was not because fetuses of increasingly smaller size were included in this group. The decline in intra-partum mortality was mainly due to a reduction of mortality in fetuses weighing >2500g (fig. 4). Neonatal mortality which had not altered between 1960 and 1974, showed no other trend when analysed by fetal weight more and less than 2500g. Subdivision of mortality into major causes (anoxia, congeni-
more
assessment
7. Lindvall, O., Björklund, A., Moore, R. Y., Stenevi, U. ibid. 1974, 81, 325. 8 Berger,B., Thierry, A.M., Tassin, J. P., Moyne, M. A. ibid. 1976, 106, 133. 9 Blondaux, C., Buda, M., Petitjean, F., Pujol, J. F. Brain Res. 1975, 88, 425. 1 Anderson, I., Renou, P., Chang, A., Wood, C.Med. J. Aust. (in the press).
Fig. 3-Ante-partum mortality. Significant increase in antt-partum fetal death rate in fetuses weighing less than 2500 g (r=+0.70, P<0.01). —=Total. - - -=Anoxia
only.
Fig. 4—Intra-partum mortality. Significant decrease III intra-partum death-rate of fetuses weighing than 2500 g (r=089, P<0.001). Comparison of deaths before
more
and after 1967,
x’’=25-3, P<0.001.
814 natal mortality in detail. This approach gives the obstetrician the opportunity to examine obstetric factors which influence predominantly either ante-partum or intra-partum death-rates (e.g., antenatal and intranatal fetal monitoring), and draws his attention to the possibility that a favourable change in one death-rate may occur at the expense of an unfavourable change in another. For example, an increased use of induction may reduce the stillbirth-rate due to intrauterine asphyxia but increase the postnatal death-rate by making more babies premature. The rise in ante-partum death-rates could not be explained and will be further investigated. At first this rise in fetuses weighing <2500g was attributed to higher referral-rates of smaller fetuses as neonatal intensive care improved and as doctors became more aware of the services available. But analysis of the data showed this not to be true. The fall in intra-partum death-rate in mature fetuses was thought due to a combination of improved health of the population, better obstetric care, and the introduction of fetal diagnostic techniques.1 Department of Obstetrics and Gynæcology, Monash University, Queen Victoria Memorial Hospital, Melbourne, Australia 3000
CARL WOOD
PETER RENOU
FOLATE DEFICIENCY AND INTRAVENOUS NUTRITION on intravenous have been reported.12I would like to add two in which jaundice was a striking feature.
SIR,-Acute folate deficiency in patients
(i.v.) nutrition more cases
Case 1 A 14-year-old boy with spina bifida, who had had an ileal conduit, was admitted with a 2-day history of abdominal pain. At laparotomy a perforated appendix and peritonitis were
dealt with. Postoperatively prolonged paralytic ileus developed and he was given i.v. nutrition and broad-spectrum antibiotics. His abdomen burst and required resuturing on day 5. He later bled from his wound and required 6 units of blood between the 20th-27th postoperative days. In this time he became deeply jaundiced and pancytopenic. Heavy haematuria was controlled by 4 units of platelet concentrate, and he was also given 1 unit of fresh frozen plasma. A coagulation screen was normal apart from an Owren prothrombin activity of 50%. Frequent blood cultures were negative and he had no laboratory evidence of disseminated intravascular coagulation (D.l.C.). The day after the haematuria he became comatose. Calcium folinate 9 mg i.v. daily was started as a last hope; bone-marrow biopsy was not done because the patient was thought to be dying. He rapidly regained consciousness, and his jaundice disappeared in 5 days. Haematological progress was satisfactory.
Case 2 A 74-year-old woman with a history of several months’ vomiting was admitted with a benign cesophageal stricture. The surgery was difficult and she was left postoperatively with a feeding gastrostomy. However, 3 days postoperatively i.v, feeding and i.v. broad-spectrum antibiotics were introduced because of severe diarrhrea. By day 7 she was deeply jaundiced, pancytopenic, and comatose. Bone-marrow examination on day 6 showed grossly megaloblastic and dyserythropoietic haemoposiesis. On calcium folinate 9 mg i.v. daily she made a rapid hasmatological recovery, the marrow was normoblastic 7 days later, and jaundice disappeared. However, much later a wound infection led to fatal gram-negative septicaemia. Necwas refused. The hxmatological and biochemical results are summarised in the table. The presumptive diagnosis in both cases was acute folate deficiency. Serum-folate could not be assayed because of the antibiotic therapy. However, the response to i.v. folate and the conversion of megaloblastic to normal hsEmopoiesis in case 2 point to folate deficiency. In neither case was the peripheral blood macrocytic, and thrombocytopenia, probably an important first sign of acute folate deficiency,2 was investigated in both as a sign of D.I.C., with negative results, before the true diagnosis was suspected. The jaundice was more severe than is usual for uncomplicated megaloblastic anaemia.3 The higher level of bilirubin and more rapid development of jaundice and marrow failure in case 2 may have been indicative of reduced folate stores before operation. The rise in bilirubin and L.D.H. in megaloblastic ansmia has been attributed to ineffective erythropoiesis, and the dyserythropoiesis seen in the marrow of case 2 was very striking. In both cases liver enzymes rose in parallel with the bilirubin, and liver biopsy in case 2 revealed swollen hepatocytes and an unusually high number of mitotic figures. The liver architecture was well preserved and necrosis was not prominent. These appearances are probably the effect of acute folate deficiency; marrow failure secondary to liver disease seems unlikely because marrow appearances and liver function rapidly returned to normal after folic-acid therapy. In other reports the i.v. regimen contained ethanol, and this was thought a prime suspect in precipitating megaloblastic haemopoiesis. These two patients were not given ethanol. Before folate therapy was started both these patients were thought to be dying, and, although patient 2 did die, it was not from folate deficiency. The diagnosis of acute folate deficiency in the postoperative patient on i.v. feeding is important because it is potentially lethal. Folate supplements should normally be given whenever intravenous alimentation lasts more than a very few days.
ropsy
Hæmatology Department, Radcliffe Infirmary,
P.
Oxford OX2 6HE 1. 2.
V., Wardrop, C. A. J., Tennant, G. B., Hughes, L. E. Lancet, 1975, ii, 640. Ibbotson, R. M., Colvin, B. T., Colvin, M. P. Br. med. J. 1975, ii, 145.
Heatley,
R.
3. Chanarin, I. The
Megaloblastic Anæmias. Oxford,
1969.
J. GREEN
especially affected. T. C. A. M. VAN WOERKOM A. W. TEELKEN J. M. MINDERHOUD
Department of Neurology, University Hospital, Groningen, Netherlands
PERINATAL MORTALITY AS INDICATION OF OBSTETRIC CARE
SIR,-Controversy over the use of new obstetric techniques was covered extensively in The Lancet during 1976. Clearly we need to test the efficacy of new obstetric techniques by controlled trials. Conclusions drawn from changes in perinatalmortality statistics are hampered by variables such as social characteristics of the population, general health of the mothers, skill and experience of staff, and organisation of obstetric services. However, we decided to see if, by examining
Year
Fig. 2-Perinatal mortality (excluding fetal malformations). Significant increasing trend m ante-partum death-rate (r=0.55, P<0.05), and a significant decreasing trend in intra-partum death-rate (r=+0.79, r<0.02). No year was found sigmficantly different from the others (Z not significant). tal malformation, infection, rhesus incompatibility, gross imshows that the decline in intra-partum mortality in fetuses >2500g was almost solely the result of a fall in anoxic deaths (fig. 4), while the rise in ante-partum mortality in was partly due to an increase in anoxic deaths fetuses <2500g
maturity)
(fig. 3). The results demonstrate the
importance of considering peri-
It::QI
Fig. I-Perinatal mortality. No significant change in total perinatal mortality
rate or
fatal-mal-
tormation rate.
perinatal mortality in useful in the
more
detail, this statistic could be made
of obstetric care. Fetal mortality statistics were collected from the Queen Victoria Memorial Hospital between 1960 and 1974. The definitions and method of analysis will be published elsewhere.’1 Perinatal mortality did not change significantly over this period (fig. 1), but antenatal mortality rose while intra-partum mortality fell (fig. 2). The rise in antenatal mortality was restricted to fetuses weighing <2500g (fig. 3). This was not because fetuses of increasingly smaller size were included in this group. The decline in intra-partum mortality was mainly due to a reduction of mortality in fetuses weighing >2500g (fig. 4). Neonatal mortality which had not altered between 1960 and 1974, showed no other trend when analysed by fetal weight more and less than 2500g. Subdivision of mortality into major causes (anoxia, congeni-
more
assessment
7. Lindvall, O., Björklund, A., Moore, R. Y., Stenevi, U. ibid. 1974, 81, 325. 8 Berger,B., Thierry, A.M., Tassin, J. P., Moyne, M. A. ibid. 1976, 106, 133. 9 Blondaux, C., Buda, M., Petitjean, F., Pujol, J. F. Brain Res. 1975, 88, 425. 1 Anderson, I., Renou, P., Chang, A., Wood, C.Med. J. Aust. (in the press).
Fig. 3-Ante-partum mortality. Significant increase in antt-partum fetal death rate in fetuses weighing less than 2500 g (r=+0.70, P<0.01). —=Total. - - -=Anoxia
only.
Fig. 4—Intra-partum mortality. Significant decrease III intra-partum death-rate of fetuses weighing than 2500 g (r=089, P<0.001). Comparison of deaths before
more
and after 1967,
x’’=25-3, P<0.001.
814 natal mortality in detail. This approach gives the obstetrician the opportunity to examine obstetric factors which influence predominantly either ante-partum or intra-partum death-rates (e.g., antenatal and intranatal fetal monitoring), and draws his attention to the possibility that a favourable change in one death-rate may occur at the expense of an unfavourable change in another. For example, an increased use of induction may reduce the stillbirth-rate due to intrauterine asphyxia but increase the postnatal death-rate by making more babies premature. The rise in ante-partum death-rates could not be explained and will be further investigated. At first this rise in fetuses weighing <2500g was attributed to higher referral-rates of smaller fetuses as neonatal intensive care improved and as doctors became more aware of the services available. But analysis of the data showed this not to be true. The fall in intra-partum death-rate in mature fetuses was thought due to a combination of improved health of the population, better obstetric care, and the introduction of fetal diagnostic techniques.1 Department of Obstetrics and Gynæcology, Monash University, Queen Victoria Memorial Hospital, Melbourne, Australia 3000
CARL WOOD
PETER RENOU
FOLATE DEFICIENCY AND INTRAVENOUS NUTRITION on intravenous have been reported.12I would like to add two in which jaundice was a striking feature.
SIR,-Acute folate deficiency in patients
(i.v.) nutrition more cases
Case 1 A 14-year-old boy with spina bifida, who had had an ileal conduit, was admitted with a 2-day history of abdominal pain. At laparotomy a perforated appendix and peritonitis were
dealt with. Postoperatively prolonged paralytic ileus developed and he was given i.v. nutrition and broad-spectrum antibiotics. His abdomen burst and required resuturing on day 5. He later bled from his wound and required 6 units of blood between the 20th-27th postoperative days. In this time he became deeply jaundiced and pancytopenic. Heavy haematuria was controlled by 4 units of platelet concentrate, and he was also given 1 unit of fresh frozen plasma. A coagulation screen was normal apart from an Owren prothrombin activity of 50%. Frequent blood cultures were negative and he had no laboratory evidence of disseminated intravascular coagulation (D.l.C.). The day after the haematuria he became comatose. Calcium folinate 9 mg i.v. daily was started as a last hope; bone-marrow biopsy was not done because the patient was thought to be dying. He rapidly regained consciousness, and his jaundice disappeared in 5 days. Haematological progress was satisfactory.
Case 2 A 74-year-old woman with a history of several months’ vomiting was admitted with a benign cesophageal stricture. The surgery was difficult and she was left postoperatively with a feeding gastrostomy. However, 3 days postoperatively i.v, feeding and i.v. broad-spectrum antibiotics were introduced because of severe diarrhrea. By day 7 she was deeply jaundiced, pancytopenic, and comatose. Bone-marrow examination on day 6 showed grossly megaloblastic and dyserythropoietic haemoposiesis. On calcium folinate 9 mg i.v. daily she made a rapid hasmatological recovery, the marrow was normoblastic 7 days later, and jaundice disappeared. However, much later a wound infection led to fatal gram-negative septicaemia. Necwas refused. The hxmatological and biochemical results are summarised in the table. The presumptive diagnosis in both cases was acute folate deficiency. Serum-folate could not be assayed because of the antibiotic therapy. However, the response to i.v. folate and the conversion of megaloblastic to normal hsEmopoiesis in case 2 point to folate deficiency. In neither case was the peripheral blood macrocytic, and thrombocytopenia, probably an important first sign of acute folate deficiency,2 was investigated in both as a sign of D.I.C., with negative results, before the true diagnosis was suspected. The jaundice was more severe than is usual for uncomplicated megaloblastic anaemia.3 The higher level of bilirubin and more rapid development of jaundice and marrow failure in case 2 may have been indicative of reduced folate stores before operation. The rise in bilirubin and L.D.H. in megaloblastic ansmia has been attributed to ineffective erythropoiesis, and the dyserythropoiesis seen in the marrow of case 2 was very striking. In both cases liver enzymes rose in parallel with the bilirubin, and liver biopsy in case 2 revealed swollen hepatocytes and an unusually high number of mitotic figures. The liver architecture was well preserved and necrosis was not prominent. These appearances are probably the effect of acute folate deficiency; marrow failure secondary to liver disease seems unlikely because marrow appearances and liver function rapidly returned to normal after folic-acid therapy. In other reports the i.v. regimen contained ethanol, and this was thought a prime suspect in precipitating megaloblastic haemopoiesis. These two patients were not given ethanol. Before folate therapy was started both these patients were thought to be dying, and, although patient 2 did die, it was not from folate deficiency. The diagnosis of acute folate deficiency in the postoperative patient on i.v. feeding is important because it is potentially lethal. Folate supplements should normally be given whenever intravenous alimentation lasts more than a very few days.
ropsy
Hæmatology Department, Radcliffe Infirmary,
P.
Oxford OX2 6HE 1. 2.
V., Wardrop, C. A. J., Tennant, G. B., Hughes, L. E. Lancet, 1975, ii, 640. Ibbotson, R. M., Colvin, B. T., Colvin, M. P. Br. med. J. 1975, ii, 145.
Heatley,
R.
3. Chanarin, I. The
Megaloblastic Anæmias. Oxford,
1969.
J. GREEN