- Email: [email protected]
NEONATAL LUPUS SYNDROME: OPTIMISM JUSTIFIED?
640
Letters
to
the Editor
NEONATAL LUPUS SYNDROME: OPTIMISM
JUSTIFIED? 1987 Lancet editorial’
on the neonatal lupus syndrome SiR,—A steroid and therapy to protect the fetus suggested plasma exchange of a mother with Ro (SS-A) antibodies. Barclay and colleagues2 tried this approach in a woman with Ro antibodies and four previous failed pregnancies, the intention being to protect against intrauterine death. Steroids were introduced in week 14 and plasma exchange began in week 25, and the outcome was successful. We have tried this treatment in a similar case but without success. IgG deposition in the fetal heart may provide a clue to the cause of fetal
loss. A 30-year-old woman presented in her fifth pregnancy in April, 1987. Her four previous pregnancies had been unsuccessful (miscarriages at 6 and 7 weeks; placental abruption and uterine death at 26 weeks consequent to "pre-eclampsia"; and death at 48 h after delivery at 27 weeks [birthweight 620 g] for a clinical diagnosis of pre-eclampsia). Post-mortem studies were not helpful, although the heart was not examined microscopically. From 1977 the patient had been treated for hypertension with combinations of chlorthalidone, methyldopa, and labetalol. In 1985 xerophthalmia and a photosensitive rash developed. In 1986 minor renal impairment (plasma creatinine 139 umol/1) was recorded and antinuclear antibodies were present at a titre of 1/80 (the patient was not on methyldopa). Activated partial thromboplastin time (APTT) was normal. At 20 weeks’ gestation the patient’s blood pressure was 150/102 mm Hg when she was on methyldopa and labetalol. She had a malar rash. Plasma creatinine was 98 (imol/1. The DNA binding antibody level was 111 -units (normal below 5) and her Ro antibody titre was 1/160. Cardiolipin antibodies were not detected and APTT and complement C3 and C4 levels were normal. The patient was put on prednisolone 40 mg daily, azathioprine 120 mg daily, and daily 4 litre plasma exchanges for 4 days then twice weekly. Ro antibody titres are shown in the figure. Her blood pressure was controlled at 90/50 to 165/ 100 mm Hg (apart from one transient rise to 200/120 at 23 weeks). The fetal heart rate remained at 125-160/min and fetal movements were consistently felt. Despite reduction in Ro antibody titre, fetal heart sounds disappeared at 25 weeks and an ultrasound scan confirmed fetal death. Necropsy of the 375 g fetus and 64 g placenta revealed no gross abnormality and the cardiovascular system seemed normal. Microscopic examination was normal but immunoperoxidase staining with monoclonal antibodies to IgG (Dako) and polyclonal antibodies to C3 (Dako) revealed diffuse cytoplasmic positivity of all cardiac tissue. Staining with antibodies to IgA and IgM was negative, as was staining of a control heart of a similar gestational age.
Maternal
serum
Antibodies
not
Ro
antibody titres during treatment.
detectable in cord blood after
delivery.
Our patient had long-standing hypertension and some features of active lupus. We used vigorous immunosuppression (adding plasma exchange to the regimen we successfully use during pregnancy in women with a renal transplant) and controlled the blood pressure. The features of active lupus settled promptly and there were no complications apart from minor dyspepsia which responded to a small reduction in the dose of prednisolone. The cause of fetal death is not certain. Taylor and colleagues3 reported Ro antibodies and antibodies reacting with fetal cardiac tissue in mothers of children with complete heart block. They too demonstrated cytoplasmic IgG and complement in all cardiac tissues of two babies. Cardiac antibody deposition may be a factor in intrauterine death associated with Ro antibodies, and our demonstration of such antibodies would be consistent with this although the hypertension may have been important. Frampton and colleagues’ reported plasma exchange and steroid therapy in a pregnant woman with antiphospholipid antibodies. We must temper their recommendations and those of Barclay et aJ2 and your editorial with a note of caution. Despite starting treatment in the 21 st week and achieving a reduction of Ro antibody titre similar to that recorded by Barclay and colleagues, we could not prevent fetal loss. The place of this expensive, hazardous, and psychologically disruptive therapy should be assessed in a controlled trial. Department of Medicine, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP
M. C. VENNING D. J. BURN
Regional Immunology Laboratory, Newcastle upon Tyne
R. M. WARD
Department of Pathology, University of Newcastle upon Tyne
J. A. HENRY
MRC Human Reproduction Group, Newcastle upon Tyne
J. M. DAVISON
1. Editorial. Neonatal lupus syndrome. Lancet 1987; ii: 489. 2. Barclay CS, French MAH, Ross LD, Sokol RJ Successful pregnancy
following
steroid therapy and plasma exchange in a woman with anti-Ro (SS-A) antibodies. Br J Obstet Gynaecol 1987; 94: 369-71. 3 Taylor PV, Scott JS, Gerlis LM, et al. Maternal antibodies against foetal cardiac antigens in congenital complete heart block. N Engl J Med 1986; 315: 667-72 4. Frampton G, Cameron JS, Thom M, Jones S, Rafferty M Successful removal of antiphospholipid antibody dunng pregnancy using plasma exchange and low dose prednisolone. Lancet 1987, ii 1023-24
GASTRIC BYPASS SURGERY AS MATERNAL RISK FACTOR FOR NEURAL TUBE DEFECTS et all described in The Lancet three who had undergone bypass surgery for morbid obesity and subsequently had infants/fetuses with neural tube defects (NTDs). This seemed an excessive incidence given the number of women in the region who had had the operation. Knudsen and Källén2 subsequently reported that of 77 infants identified through the Swedish Birth Registry as having been born to mothers who had undergone bypass surgery for obesity none had NTDs. However, in Haddow’s report the mothers had had gastric bypass surgery, while in Sweden the operation was intestinal bypass. A report in Iowa of three unconfirmed cases of infants with’ NTDs born to women who had gastric bypass surgery for morbid obesity lent support to the findings of Haddow and colleagues and prompted our investigation. 908 women with a history of gastric bypass surgery for obesity were identified by four surgeons specialising in this operation (they were members of the National Bariatric Surgery Registry, Iowa City) and were sent a questionnaire. 511 (57%) responded but only 87 (17% of respondents) had been pregnant after the operation. These 87 women had a combined history of 73 pregnancies (more than 20 weeks’ gestation) before the operation and 110 pregancies after it. The women reported no NTDs among the preoperative pregnancies and 2 NTDs among the later pregnancies. The rate of NTD-affected pregnancies among these gastric bypass patients (2/110 or 1 -8%) represents a 12-fold increase in risk compared with
SiR,—In 1986 Haddow
women
Letters
to
the Editor
NEONATAL LUPUS SYNDROME: OPTIMISM
JUSTIFIED? 1987 Lancet editorial’
on the neonatal lupus syndrome SiR,—A steroid and therapy to protect the fetus suggested plasma exchange of a mother with Ro (SS-A) antibodies. Barclay and colleagues2 tried this approach in a woman with Ro antibodies and four previous failed pregnancies, the intention being to protect against intrauterine death. Steroids were introduced in week 14 and plasma exchange began in week 25, and the outcome was successful. We have tried this treatment in a similar case but without success. IgG deposition in the fetal heart may provide a clue to the cause of fetal
loss. A 30-year-old woman presented in her fifth pregnancy in April, 1987. Her four previous pregnancies had been unsuccessful (miscarriages at 6 and 7 weeks; placental abruption and uterine death at 26 weeks consequent to "pre-eclampsia"; and death at 48 h after delivery at 27 weeks [birthweight 620 g] for a clinical diagnosis of pre-eclampsia). Post-mortem studies were not helpful, although the heart was not examined microscopically. From 1977 the patient had been treated for hypertension with combinations of chlorthalidone, methyldopa, and labetalol. In 1985 xerophthalmia and a photosensitive rash developed. In 1986 minor renal impairment (plasma creatinine 139 umol/1) was recorded and antinuclear antibodies were present at a titre of 1/80 (the patient was not on methyldopa). Activated partial thromboplastin time (APTT) was normal. At 20 weeks’ gestation the patient’s blood pressure was 150/102 mm Hg when she was on methyldopa and labetalol. She had a malar rash. Plasma creatinine was 98 (imol/1. The DNA binding antibody level was 111 -units (normal below 5) and her Ro antibody titre was 1/160. Cardiolipin antibodies were not detected and APTT and complement C3 and C4 levels were normal. The patient was put on prednisolone 40 mg daily, azathioprine 120 mg daily, and daily 4 litre plasma exchanges for 4 days then twice weekly. Ro antibody titres are shown in the figure. Her blood pressure was controlled at 90/50 to 165/ 100 mm Hg (apart from one transient rise to 200/120 at 23 weeks). The fetal heart rate remained at 125-160/min and fetal movements were consistently felt. Despite reduction in Ro antibody titre, fetal heart sounds disappeared at 25 weeks and an ultrasound scan confirmed fetal death. Necropsy of the 375 g fetus and 64 g placenta revealed no gross abnormality and the cardiovascular system seemed normal. Microscopic examination was normal but immunoperoxidase staining with monoclonal antibodies to IgG (Dako) and polyclonal antibodies to C3 (Dako) revealed diffuse cytoplasmic positivity of all cardiac tissue. Staining with antibodies to IgA and IgM was negative, as was staining of a control heart of a similar gestational age.
Maternal
serum
Antibodies
not
Ro
antibody titres during treatment.
detectable in cord blood after
delivery.
Our patient had long-standing hypertension and some features of active lupus. We used vigorous immunosuppression (adding plasma exchange to the regimen we successfully use during pregnancy in women with a renal transplant) and controlled the blood pressure. The features of active lupus settled promptly and there were no complications apart from minor dyspepsia which responded to a small reduction in the dose of prednisolone. The cause of fetal death is not certain. Taylor and colleagues3 reported Ro antibodies and antibodies reacting with fetal cardiac tissue in mothers of children with complete heart block. They too demonstrated cytoplasmic IgG and complement in all cardiac tissues of two babies. Cardiac antibody deposition may be a factor in intrauterine death associated with Ro antibodies, and our demonstration of such antibodies would be consistent with this although the hypertension may have been important. Frampton and colleagues’ reported plasma exchange and steroid therapy in a pregnant woman with antiphospholipid antibodies. We must temper their recommendations and those of Barclay et aJ2 and your editorial with a note of caution. Despite starting treatment in the 21 st week and achieving a reduction of Ro antibody titre similar to that recorded by Barclay and colleagues, we could not prevent fetal loss. The place of this expensive, hazardous, and psychologically disruptive therapy should be assessed in a controlled trial. Department of Medicine, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP
M. C. VENNING D. J. BURN
Regional Immunology Laboratory, Newcastle upon Tyne
R. M. WARD
Department of Pathology, University of Newcastle upon Tyne
J. A. HENRY
MRC Human Reproduction Group, Newcastle upon Tyne
J. M. DAVISON
1. Editorial. Neonatal lupus syndrome. Lancet 1987; ii: 489. 2. Barclay CS, French MAH, Ross LD, Sokol RJ Successful pregnancy
following
steroid therapy and plasma exchange in a woman with anti-Ro (SS-A) antibodies. Br J Obstet Gynaecol 1987; 94: 369-71. 3 Taylor PV, Scott JS, Gerlis LM, et al. Maternal antibodies against foetal cardiac antigens in congenital complete heart block. N Engl J Med 1986; 315: 667-72 4. Frampton G, Cameron JS, Thom M, Jones S, Rafferty M Successful removal of antiphospholipid antibody dunng pregnancy using plasma exchange and low dose prednisolone. Lancet 1987, ii 1023-24
GASTRIC BYPASS SURGERY AS MATERNAL RISK FACTOR FOR NEURAL TUBE DEFECTS et all described in The Lancet three who had undergone bypass surgery for morbid obesity and subsequently had infants/fetuses with neural tube defects (NTDs). This seemed an excessive incidence given the number of women in the region who had had the operation. Knudsen and Källén2 subsequently reported that of 77 infants identified through the Swedish Birth Registry as having been born to mothers who had undergone bypass surgery for obesity none had NTDs. However, in Haddow’s report the mothers had had gastric bypass surgery, while in Sweden the operation was intestinal bypass. A report in Iowa of three unconfirmed cases of infants with’ NTDs born to women who had gastric bypass surgery for morbid obesity lent support to the findings of Haddow and colleagues and prompted our investigation. 908 women with a history of gastric bypass surgery for obesity were identified by four surgeons specialising in this operation (they were members of the National Bariatric Surgery Registry, Iowa City) and were sent a questionnaire. 511 (57%) responded but only 87 (17% of respondents) had been pregnant after the operation. These 87 women had a combined history of 73 pregnancies (more than 20 weeks’ gestation) before the operation and 110 pregancies after it. The women reported no NTDs among the preoperative pregnancies and 2 NTDs among the later pregnancies. The rate of NTD-affected pregnancies among these gastric bypass patients (2/110 or 1 -8%) represents a 12-fold increase in risk compared with
SiR,—In 1986 Haddow
women