649 not find a higher proportion of low serum-folate in the samples taken at booking of women who subsequently delivered babies with major malformations. I report here the 11 c.N.s. malformation cases in that study in greater detail. None of these women had had folic acid!
Gestation at
Type of malformation Anencephaly
booking Serum-folate (wk) (ng/ml) at booking 25
1.9
29 27 15 14
9.5 4.6 4-77 6.22
Parity
Hydrocephaly/ meningocele
Hydrocephaly Meningocele Anencephaly Hydrocephaly/ memngomyelocele Memngomyelocele Anencephaly
0 0 3 0
ponding to C. welchii"). The results were as follows: Group (1) Normal weight Low-birth-weight (2) Special care Lying-in ward (3) Bottle fed Breast fed
(4) Vaginal delivery
Caesarean
section
Total
24 12 24 12 17 18
Encephalocele Occult
spina bifida Anencephaly
9.33 11.22 6.22 7.4 5 7 3.11
2 6 1 0 4 1
The mean booking serum-folate is 6.35ng/ml compared with the mean booking level for all primigravidae in this study of 6.60 (S.D. 2.88) and the multigravid mean of 6.72 (s.D. M8). Only 6 out of 11 women booked before 20 weeks, but since the serum-folate falls as pregnancy advances4 this makes it more clear that there is no difference between these women and those without malformations, since the late bookers would probably have had even higher serum-folate levels at booking. I suggest that this study, which was of a complete year’s bookings in the City of Aberdeen, represents the real situation (i.e., that folic acid deficiency is not the cause of c.N.s. malformation) more reliably than do studies such as that of Smithells et al. where patients were recruited "on a voluntary basis" before 13 weeks. Their "controls" must have included a disproportionate number of women who were receiving more antenatal care than do most women, and whose nutritional state may be different from that of the pregnant population as a whole. Department of Obstetrics University of Aberdeen,
McClung and Toabe9 for use in toxigenicity testing with specific antiserum (Burroughs Wellcome Clostridium perfringens type A). All positive results obtained were also Naglar positive (i.e., toxigenic strains of perfringens type A, corresof
and
Gynaecology,
MARION H. HALL
Aberdeen AB9 2ZD
No. No. positive 76 51 (77%) 27 51 (67%) 69 43 (62%) 34 29 (85%) 75 55 (73%) 28 17 (61%) 74 50 (67%) 29 22 (75%) 103 72 (70%)
In group 3 the breast-fed babies did receive complementary feeds of artificial milk. A mixed diet tends to produce a flora akin to that of an artificially fed baby. 11I The results show that there is a high enough frequency of clostridial colonisation to validate that part of the Pedersen hypothesis. Colonisation is not the same as invasion, however. The lack of difference in the percentage of positive specimens between the low-birth-weight and normal-weight groups and between the special-care baby unit and lying-in ward groups suggests that another factor (or factors) must be sought to explain the peak incidence ofN.E.c. at weights below 1600 g.4 A. D. KINDLEY P. J. ROBERTS Liverpool Maternity Hospital, W. H. TULLOCH Liverpool L7 7B
AMNIOTIC-FLUID ALPHA-FETOPROTEIN IN TURNER SYNDROME
SIR,-There have been conflicting reports about the level of amniotic-fluid a-fetoprotein (A.F.P.) when a fetus has Turner syndrome.’2 We have studied a pregnancy in which Turner syndrome was diagnosed antenatally. The pregnancy was terminated by hysterotomy at 20 weeks’ gestation, and the intact gestation sac was removed (Dr R. Wurm) and transported to the laboratory within an hour. Cord-blood lymphocyte culture confirmed the fetal karyotype to be 45,X.
NEONATAL NECROTISING ENTEROCOLITIS
SIR,-Neonatal necrotising enterocolitis (N.E.C.) has lately been the subject of a hypothesiss an editorialand a letter7 in The Lancet. Pedersen et al.5 suggested that necrotising enterocolitis could be caused by clostridial invasion of bowel damaged by anoxia. They commented that clostridial colonisation of the neonatal intestine had not been examined in detail. They cited a survey of breast-fed babies in rural Guatemala who, in their first week, had mainly an anaerobic flora. We have examined the faeces of 103 babies on their fifth day of life. This day was chosen because the mean time of onset of the N.E.c. is day 4.8 These babies were unselected-some coming from a lying-in ward and some from the special-care baby unit. The weight, type of delivery, type of feed, and ward of origin of each baby was noted. Fsces were cultured anaerobically on blood and neomycin blood agar plates as well as in Robertson’s cooked-meat medium for 24 h at 37°C. The Robertson’s cooked-meat samples were then subcultured and reincubated anaerobically. The plates were examined for clostridia at each stage. A half antitoxin Naglar plate was prepared by the method 4
Hall, M. H., Pirani, B. B. K., Campbell, D. Br. J. Obstet. Gynœc. 1976, 83,
132 5 Pedersen, P. V. Lancet, 1976, ii, 715. 6 ibid 1977, i, 459. 7 Flynn, D. H., and others, ibid. p. 545. 8 Mizrahi, A., and others. J. Pediat. 1965,
66, 697.
Fetus with Turner syndrome after ated from left cervical pouch.
30 ml of fluid had been aspir-
During collection of amniotic fluid from the sac one of the large fetal cervical pouches was inadvertently punctured, and 30 ml of clear amber liquid which looked like amniotic fluid was obtained without difficulty. Subsequent inspection of the 9. McClung, S. L., Toabe, R. J. Bact. 1947, 53, 139. 10. Cowan, S. T. Manual for Identification of Medical Bacteria; p. 67. London, 1974. 11. Fraser Williams, R. in Scientific Foundations of Pædiatrics (edited by J. A. Davis and J. Dobbing); chap. 44. London, 1974. 1. Hunter, A., Hammerton, J. L., Baskett, T., Lyons, E. Lancet, 1976, i, 596. 2. Seller, M. J. ibid. p. 807.
Gestation at
Type of malformation Anencephaly
booking Serum-folate (wk) (ng/ml) at booking 25
1.9
29 27 15 14
9.5 4.6 4-77 6.22
Parity
Hydrocephaly/ meningocele
Hydrocephaly Meningocele Anencephaly Hydrocephaly/ memngomyelocele Memngomyelocele Anencephaly
0 0 3 0
ponding to C. welchii"). The results were as follows: Group (1) Normal weight Low-birth-weight (2) Special care Lying-in ward (3) Bottle fed Breast fed
(4) Vaginal delivery
Caesarean
section
Total
24 12 24 12 17 18
Encephalocele Occult
spina bifida Anencephaly
9.33 11.22 6.22 7.4 5 7 3.11
2 6 1 0 4 1
The mean booking serum-folate is 6.35ng/ml compared with the mean booking level for all primigravidae in this study of 6.60 (S.D. 2.88) and the multigravid mean of 6.72 (s.D. M8). Only 6 out of 11 women booked before 20 weeks, but since the serum-folate falls as pregnancy advances4 this makes it more clear that there is no difference between these women and those without malformations, since the late bookers would probably have had even higher serum-folate levels at booking. I suggest that this study, which was of a complete year’s bookings in the City of Aberdeen, represents the real situation (i.e., that folic acid deficiency is not the cause of c.N.s. malformation) more reliably than do studies such as that of Smithells et al. where patients were recruited "on a voluntary basis" before 13 weeks. Their "controls" must have included a disproportionate number of women who were receiving more antenatal care than do most women, and whose nutritional state may be different from that of the pregnant population as a whole. Department of Obstetrics University of Aberdeen,
McClung and Toabe9 for use in toxigenicity testing with specific antiserum (Burroughs Wellcome Clostridium perfringens type A). All positive results obtained were also Naglar positive (i.e., toxigenic strains of perfringens type A, corresof
and
Gynaecology,
MARION H. HALL
Aberdeen AB9 2ZD
No. No. positive 76 51 (77%) 27 51 (67%) 69 43 (62%) 34 29 (85%) 75 55 (73%) 28 17 (61%) 74 50 (67%) 29 22 (75%) 103 72 (70%)
In group 3 the breast-fed babies did receive complementary feeds of artificial milk. A mixed diet tends to produce a flora akin to that of an artificially fed baby. 11I The results show that there is a high enough frequency of clostridial colonisation to validate that part of the Pedersen hypothesis. Colonisation is not the same as invasion, however. The lack of difference in the percentage of positive specimens between the low-birth-weight and normal-weight groups and between the special-care baby unit and lying-in ward groups suggests that another factor (or factors) must be sought to explain the peak incidence ofN.E.c. at weights below 1600 g.4 A. D. KINDLEY P. J. ROBERTS Liverpool Maternity Hospital, W. H. TULLOCH Liverpool L7 7B
AMNIOTIC-FLUID ALPHA-FETOPROTEIN IN TURNER SYNDROME
SIR,-There have been conflicting reports about the level of amniotic-fluid a-fetoprotein (A.F.P.) when a fetus has Turner syndrome.’2 We have studied a pregnancy in which Turner syndrome was diagnosed antenatally. The pregnancy was terminated by hysterotomy at 20 weeks’ gestation, and the intact gestation sac was removed (Dr R. Wurm) and transported to the laboratory within an hour. Cord-blood lymphocyte culture confirmed the fetal karyotype to be 45,X.
NEONATAL NECROTISING ENTEROCOLITIS
SIR,-Neonatal necrotising enterocolitis (N.E.C.) has lately been the subject of a hypothesiss an editorialand a letter7 in The Lancet. Pedersen et al.5 suggested that necrotising enterocolitis could be caused by clostridial invasion of bowel damaged by anoxia. They commented that clostridial colonisation of the neonatal intestine had not been examined in detail. They cited a survey of breast-fed babies in rural Guatemala who, in their first week, had mainly an anaerobic flora. We have examined the faeces of 103 babies on their fifth day of life. This day was chosen because the mean time of onset of the N.E.c. is day 4.8 These babies were unselected-some coming from a lying-in ward and some from the special-care baby unit. The weight, type of delivery, type of feed, and ward of origin of each baby was noted. Fsces were cultured anaerobically on blood and neomycin blood agar plates as well as in Robertson’s cooked-meat medium for 24 h at 37°C. The Robertson’s cooked-meat samples were then subcultured and reincubated anaerobically. The plates were examined for clostridia at each stage. A half antitoxin Naglar plate was prepared by the method 4
Hall, M. H., Pirani, B. B. K., Campbell, D. Br. J. Obstet. Gynœc. 1976, 83,
132 5 Pedersen, P. V. Lancet, 1976, ii, 715. 6 ibid 1977, i, 459. 7 Flynn, D. H., and others, ibid. p. 545. 8 Mizrahi, A., and others. J. Pediat. 1965,
66, 697.
Fetus with Turner syndrome after ated from left cervical pouch.
30 ml of fluid had been aspir-
During collection of amniotic fluid from the sac one of the large fetal cervical pouches was inadvertently punctured, and 30 ml of clear amber liquid which looked like amniotic fluid was obtained without difficulty. Subsequent inspection of the 9. McClung, S. L., Toabe, R. J. Bact. 1947, 53, 139. 10. Cowan, S. T. Manual for Identification of Medical Bacteria; p. 67. London, 1974. 11. Fraser Williams, R. in Scientific Foundations of Pædiatrics (edited by J. A. Davis and J. Dobbing); chap. 44. London, 1974. 1. Hunter, A., Hammerton, J. L., Baskett, T., Lyons, E. Lancet, 1976, i, 596. 2. Seller, M. J. ibid. p. 807.
