[Coronary involvement and nephrotic syndrome in systemic lupus: A case report]. / Atteinte coronarienne et syndrome néphrotique au cours du lupus systémique : à propos d'une observation.

INTRODUCTION: Heart failure during systemic lupus erythematosus has various causes. CASE REPORT: A 29-year-old female presented with a systemic lupus flare and a nephrotic syndrome, followed by cardiogenic shock requiring extra-corporeal membranous oxygenation. Ventricular dysfunction was related to massive myocardial infarction due to an anterior interventricular artery thrombosis and an underlying atheroma. The young age and the absence of chest pain were not suggestive of coronary artery disease initially. Coronary thrombosis was probably favored by the nephrotic syndrome, in which the arterial thrombotic risk is increased. CONCLUSION: Coronary artery disease should be systematically evoked in the presence of ventricular dysfunction in patients with systemic lupus, including when they are young and in the absence of chest pain. Nephrotic syndrome should be identified as a risk factor for arterial thrombosis.

[Pregnancy and antiphospholipid syndrome]. / Grossesse et syndrome des antiphospholipides.

Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patient's medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time.

[Liver disease and pregnancy]. / Pathologies hépatiques et grossesse.

Liver dysfunction during pregnancy can be related or not to pregnancy itself. The purpose of this review is to summarize the possible causes of liver dysfunction during pregnancy and their management. Liver dysfunction during pregnancy can be chronic or acute, independent or specific to pregnancy. Management of liver disease can be different during pregnancy. The knowledge of liver dysfunction during pregnancy is of help for a better management of the mother in order to avoid maternal and fetal mortality and morbidity.

[Maternal adrenal necrosis in the third trimester of pregnancy: a rare complication of antiphospholipid syndrome]. / Nécrose des surrénales maternelles au troisième trimestre de la grossesse dans le cadre d'un syndrome des antiphospholipides: à propos d'un cas.

Adrenal necrosis, a rare life threatening complication of antiphospholipid syndrome, is difficult to diagnose during pregnancy. We report the case of a 33-year-old woman with bilateral adrenal necrosis which started during the third trimester of her second pregnancy. Antiphospholipid syndrome had been diagnosed few years ago, after a thrombotic event. The pregnancy was uneventful until 36 weeks plus five days, when the patient was admitted for bilateral back ache, initially considered as uterine contractions. Labour was induced because pain persisted and was associated with major thrombocytopenia. A healthy infant was delivered vaginally on the second day, adrenal failure was diagnosed based on intense asthenia, persistent severe lumbar pain, low blood sodium and cortisol. Bilateral adrenal oedema was documented by CT scan and MRI. Symptoms resolved following administration of hydrocortisone and fludrocortisone. This case illustrates the difficulty to diagnose adrenal necrosis in the third trimester of pregnancy.

The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome.

OBJECTIVE: To examine the predictive value of clinical examination, laboratory tests and Doppler ultrasound examination in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) pregnancies. METHODS: A prospective study of 116 pregnancies followed in a single tertiary referral centre. Outcomes analysed were fetal/neonatal death and adverse pregnancy outcome. Univariate analysis was performed for: (i) medical and obstetric history; (ii) medical and obstetric clinical examination; (iii) biological data; (iv) Doppler ultrasound examination. Variables significantly associated with the outcomes in the univariate analysis were entered into a logistic regression model. RESULTS: Sixteen out of 116 pregnancies ended in 12 fetal deaths and 4 embryonic losses. Hence, data for 100 pregnancies were analysed. Seven fetal deaths and one neonatal death occurred, associated with abnormal end-diastolic umbilical artery Doppler flow at the second trimester (P < 0.006), a history of thrombophlebitis (P < 0.001) or notched uterine artery and growth restriction at the second trimester (P < 0.002). Multivariate analysis retained abnormal end-diastolic umbilical artery Doppler flow (P = 0.047) and history of thrombophlebitis (P = 0.018) as significant predictors. Thirty-one adverse pregnancy outcomes occurred, associated with notched uterine artery (P < 0.00003), abnormal end-diastolic umbilical artery Doppler flow (P < 0.0006) and fetal growth restriction at the second trimester (P < 0.008), growth restriction (P < 0.00001) and notched uterine artery at the third trimester (P < 0.0008), use of heparin (P < 0.05) and history of thrombophlebitis (P < 0.04). Notched uterine artery at the second trimester remained the only predictor in multivariate analysis (P = 0.001). CONCLUSIONS: Results of the second trimester Doppler ultrasound examination are the best predictors for late pregnancy outcome in SLE and/or APS.

The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women.

OBJECTIVE: To study the characteristics of the haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in the antiphospholipid syndrome (APS) and its influence on the subsequent pregnancies. METHODS: This was a retrospective analysis of 16 episodes of HELLP complicating APS in 15 women. RESULTS: HELLP was complete in 10 cases and partial in six. It occurred during the second trimester in seven cases (the earliest at 18 weeks' gestation), the third trimester in seven cases, and the day following delivery in two cases. Pre-eclampsia was present in six cases and eclampsia in five. Outcome of pregnancies was: live birth (n = 8), stillbirth (n = 2) and fetal death (n = 6). APS was primary in nine women and secondary to systemic lupus erythematosus (SLE) in six. HELLP revealed primary APS in six cases. Seven women were not treated. Low dose aspirin was empirically prescribed in one woman whose APS had been undiagnosed despite a history of two fetal deaths. In the other women, therapy consisted of aspirin (n = 8), low molecular weight heparin with a dose varying between 3000 and 12 000 U daily (n = 5), and high dose immunoglobulin every 4 weeks (n = 2), hydroxychloroquine (n = 4), and prednisone (n = 6). Six women had seven subsequent pregnancies, 3-6 years after the complicated pregnancy. HELLP recurred at 33 weeks' gestation in one woman with SLE treated with prednisone, hydroxychloroquine, aspirin, and enoxaparin, and pregnancy ended in live birth. One woman became pregnant after in vitro fertilisation and embryo transfer, but pregnancy ended in fetal death despite prednisone, hydroxychloroquine, and enoxaparin. Four women had five uneventful pregnancies with 100 mg daily aspirin and heparin. CONCLUSIONS: APS may be revealed by HELLP. In APS, HELLP is associated with pre-eclampsia/eclampsia in most cases and seems to occur earlier than in the general population. Heparin plus aspirin may prevent obstetric complications in the subsequent pregnancies.

[Oocytes in vitro maturation: results and future in humans]. / Maturation in vitro des ovocytes : bilan et perspectives dans l'espèce humaine.

Mature oocytes are rare and highly specialized cells. In vitro maturation of human oocytes is an emerging assisted reproductive technology allowing to produce more mature oocytes without ovarian stimulation. Whereas in vitro maturation is technically more demanding than conventional in vitro fertilization for the laboratory, it carries many potential advantages, for example, in terms of lower treatment heaviness and removal of risk of severe ovarian hyperstimulation syndrome for the patients. Although the technology is still experimental, oocytes in vitro maturation has been successfully used and pregnancies and live births have been reported. Despite these successes, the overall efficiency of in vitro maturation remains low and this procedure must still be improved. The different steps of in vitro maturation process are shown and discussed as well as results in terms of pregnancy and live birth rates.

A study of 75 pregnancies in patients with antiphospholipid syndrome.

OBJECTIVE: To describe a French tertiary referral center experience in the treatment of pregnancies in patients with the antiphospholipid syndrome (APS). METHODS: Retrospective review of the data of 75 consecutive pregnancies in 47 women. RESULTS: After exclusion of induced abortions and pregnancies occurring before APS onset, the prior live birth rate was 7.9%. Forty-nine pregnancies occurred in women with history of vascular thrombosis, 17 with history of thrombocytopenia. Heparin was prescribed in 39 pregnancies, associated with aspirin in 35 cases, and aspirin alone was used in 36 as first-line therapy. Corticosteroids were prescribed in 38 pregnancies. Three pregnancies by in vitro fertilization led to one embryonic loss, one full term birth, and one premature birth. Six pregnancies treated with immunoglobulin ended in one fetal death, 2 premature and 3 full term deliveries. The outcome of the other 66 pregnancies was one embryonic loss, 8 fetal deaths, 16 prematurates, and 38 full term births. Use of corticosteroids correlated with severe prematurity (p = 0.005), preeclampsia (p = 0.014), intrauterine growth retardation (p = 0.005), and presence of disease associated to APS (p = 0.009). After exclusion of one fetal death associated with congenital anomaly, live birth rate was 72.9%. There was a trend for higher rate of fetal survival in patients without history of vascular thrombosis (84.6 vs 66.4%; p = 0.11). CONCLUSION: Obstetrical prognosis in APS was improved by antithrombotic therapy. Studies are needed to define individual risk and specific significance of the various antiphospholipid antibodies, in order to improve the respective indications for aspirin alone or with heparin in women without thrombotic events.

A case of antenatal cerebral haemorrhage resulting from maternal alloimmunisation against fetal platelets.

Prenatal thrombocytopenia is a rare event and is generally due to fetal infection. In very rare cases, fetal thrombocytopenia is induced by maternal IgG directed against the fetal platelets. This alloimmunisation could lead to in utero bleeding. We now report such a case, in which fetal thrombocytopenia was complicated by a huge temporal lobe haematoma. Such a prenatal event is rare: only eight cases have been published, with only one pathologically confirmed case. Our patient is the second one in which neuropathological examination demonstrated prenatal intracerebral bleeding.

Pregnancy in past or present lupus nephritis: a study of 32 pregnancies from a single centre.

OBJECTIVE: To study maternal and fetal outcome in women with past or present histologically proven systemic lupus erythematosus (SLE) nephritis. METHOD: Retrospective study of 32 pregnancies in 22 women with past or present histologically proven SLE nephritis in a single French centre. RESULTS: Pregnancy (25 planned and 7 not planned) occurred in a mean (SD) of 8 (5) years after SLE diagnosis and 6 (4) years after renal disease onset. Seven occurred in women with antiphospholipid syndrome. At pregnancy onset, all but one woman had creatininaemia below 100 micromol/l, five had proteinuria >0.5 g/day, none had hypertension. Twelve pregnancies occurred in women previously treated with immunosuppressant drugs. Treatment comprised prednisone (n=31), hydroxychloroquine (n=11), aspirin (n=22), heparin (n=12), and azathioprine in one patient with steroid resistant nephrotic syndrome disclosing SLE. No therapeutic abortion was done. During pregnancy or the postpartum period, or both, proteinuria >0.5 g/day occurred in 10 women (five related to pre-eclampsia, four to renal flare, one to stable nephrotic syndrome). One flare consisted of mild arthralgias. Pregnancy outcome comprised one feto-maternal death in SLE disclosed by pregnancy, five embryonic losses, two fetal deaths, and 18 premature (one neonatal death) and six full term births. No criterion appeared to influence fetal survival significantly. At long term, one patient died during an SLE flare, three women had renal relapses. At the last visit, all had creatininaemia below 100 micromol/l except one woman with creatinine level 115 micromol/l, nine had proteinuria >0.5 g/day, and one was treated for hypertension. CONCLUSION: Pregnancy need not be discouraged in women with a history of SLE nephritis with normal or mildly impaired renal function. Deterioration of renal function rarely occurs. However, these pregnancies are at high risk of pre-eclampsia and prematurity.

Pregnancy in patients with Wegener's granulomatosis: report of five cases in three women.

Five cases of pregnancy occurring in three women with previously diagnosed Wegener's granulomatosis are described. The disease was diffuse in one case and localised in the other. Initial treatment consisted of a combination of corticosteroids and intravenous cyclophosphamide in two women, and methotrexate in one. Four pregnancies ended in live births despite pre-eclampsia in two cases. One therapeutic abortion was induced because of encephalocele. Comparable reported cases were reviewed to examine the implications of immunosuppressive treatment on the fetus. A relapse occurred during pregnancy in 40% of the cases, but in 25% if only pregnancies beginning during inactive disease were taken into account. No other indicator for maternal and fetal outcome was obvious. Pregnancy should be planned after complete disappearance of disease activity. In the case of a relapse a combination of immunosuppressive drugs and corticosteroids should be chosen rather than corticosteroids alone because the outcome of pregnancy is poor in cases of undertreatment. Prematurity remains common.

[Materno-fetal platelet allo-immunization revealed by in utero intracerebral fetal hemorrhage: proposed management for the next pregnancy]. / Allo-immunisation plaquettaire materno-foetale decouverte devant une hémorragie intracérébrale foetale in utero: proposition de prise en charge pour la grossesse suivante.

Materno-fetal platelet allo-immunization causes fetal or neonatal thrombocytopenia and sometimes severe intracerebral bleeding. The HPA-1s antigen is most generally implicated. This accident can occur during the first pregnancy with a major risk of severe recurrence during the next pregnancy. These women require specific care in a specialized center although no consensus has been reached on management of second pregnancies. Proposed treatments include immunoglobulins and/or corticosteroids, fetal blood puncture and unique or iterative platelet transfusions.

[Evaluation of the association of a serum marker and second trimester ultrasonography for the screening of trisomy 21 in women of less than 38 years. Prospective study of 5,163 patients]. / Evaluation de l'association marqueur sérique et échographie du deuxième trimestre pour le dépistage de la trisomie 21 chez les femmes de moins de 38 ans. Etude prospective chez 5,163 patientes.

OBJECTIVES: Use of serum markers alone for trisomy 21 screening programs leads to a high rate of amniocentesis. Adding a second parameter (ultrasonography during the second trimester) might reduce this rate yet retain satisfactory sensitivity. This work was conducted to evaluate the pertinence of associating serum hCG level between 16 and 17 weeks gestation and morphological ultrasonography between 18 ans 20 weeks gestation. METHOD: A prospective study was conducted in 5,163 pregnant women aged over 38 years. A morphological ultrasonography was performed in all patients whose hCG level > 1/150 indicated a risk. An amniocentesis was proposed if an anomaly was detected at ultrasonography. RESULTS: Serum hCG was above the risk threshold retained in 11.9% of the patients and among these patients at least one anomaly was detected at ultrasonography in 12%. An amniocentesis was performed in 1.4% of all patients. The positive predictive value of the screening test was 20%. CONCLUSION: Combining a serum marker and ultrasonography during the second trimester allows a reduction in the rate of amniocentesis compared with screening with serum markers alone. Sensitivity for detecting trisomy 21 remains satisfactory.

Can we advise ovulation induction in patients with SLE?

The prognosis of systemic lupus erythematosus (SLE) has greatly improved during the last two decades, now allowing most patients to have a very long survival including a satisfactory quality of life. Initially considered contraindicated in SLE due to its overwhelming risks, pregnancy is nowadays allowed in a majority of patients, and fair results are usually obtained under appropriate management (1-3). Consequently, patients thought to have infertility ask the question of a possible therapy, i.e. ovulation induction (OI) associated or not with in vitro fertilization (IVF). Considering the importance of estrogens in the pathogenesis of the disease, the use of such procedures raise several questions in SLE. Though data remain to date extremely scarce, the theoretical and practical aspects of OI in SLE will be briefly reviewed here.

Outcome of planned pregnancies in systemic lupus erythematosus: a prospective study on 62 pregnancies.

We conducted a prospective study in order to determine planned pregnancy outcome in systemic lupus erythematosus followed in a tertiary referral centre. Pregnancy was authorized if disease was inactive on 20 mg/day prednisone or less for at least 1 yr. Upon the diagnosis of pregnancy, systematic corticosteroids consisting of 10 mg/day prednisone or more were started. In the case of antiphospholipid antibodies, 100 mg/day aspirin was added, replaced by heparin in the pre-partum period. In the case of antiphospholipid syndrome complicated by previous thrombotic events or fetal losses despite aspirin, heparin was prescribed. One woman with a history of atrioventricular block was treated with dexamethasone. Patients were monitored by medical and obstetrical examination, and laboratory tests carried out at least monthly and a quarterly echography. Among 62 pregnancies in 38 women, lupus flare was observed in 27% of the cases, 6% of which occurred in the post-partum period. Flares were moderate except in one renal involvement in a woman with prior diffuse proliferative glomerulonephritis. Therapy was not modified in half of the cases. Pregnancy ended in early spontaneous abortion not related to lupus flare (n = 10), stillbirth (n = 2). induced abortion (n = 2), preterm birth (n = 29) and full-term birth (n = 19). Caesarean section was performed in nine cases. A severe infection occurred in two premature neonates. Another premature neonate was growth retarded. Two children had cutaneous neonatal lupus. No child died, neither had atrioventricular block. Stillbirth and severe prematurity were more common in mothers with antiphospholipid syndrome. After exclusion of early spontaneous and induced abortions, the live birth rate was 96%, that is close to the French general population. The main problem remains a high rate of prematurity, but without maternal or neonatal death.

Psychological reactions after multifetal pregnancy reduction: a 2-year follow-up study.

This study had two objectives. Firstly we assessed the effects of multifetal pregnancy reduction on the mothers' emotional well-being and the relationship with the children during the 2 years following intervention. Secondly at 2 years we compared mothers who had a reduction with mothers who had not and had delivered triplets. The comparisons focused on the mothers' health and their relationship with the children. Women having had a reduction in two hospitals in Paris, between May 1992 and June 1993, were contacted just after intervention for a prospective study. In all, 18 women were included. At 1 and 2 years, 10 women participated. At 2 years, 10 additional women were included. The answers of these 20 mothers were compared to those of 11 consecutive mothers of 2 year old triplets, assessed by the same psychologist in a previous prospective study. Semi-structured interviews were conducted at home. The mothers' social characteristics, their parity, the children's condition at birth and 4 months were very similar between the reduction and triplet groups. One year after birth one-third of the women in the reduction group reported persistent depressive symptoms related to the reduction, mainly sadness and guilt. The others made medical and rational comments expressing no emotion. At 2 years all but two women seemed to have overcome the emotional pain associated with the reduction. The comparison with mothers of triplets indicated that the mothers' anxiety and depression, and difficult relationship with the children were less acute in the reduction group. These results presented some limitations, since a high number of women who miscarried or refused to participate in the follow-up were not assessed at 1 and 2 years. However, a majority of women who participated in the study 2 years after intervention seemed able to accept a multifetal pregnancy reduction to achieve parental goals.

[Krukenberg tumor during pregnancy with maternal and fetal virilization: a difficult diagnosis. A case report]. / Tumeur de Krukenberg associée à la grossesse avec virilisation maternelle et foetale: un diagnostic difficile. A propos d'un cas.

We present a case of maternal and fetal virilization caused by an androgen-secreting ovarian tumor. Biopsy at caesarean section was required to determine the etiology (Krukenberg tumor) and orient diagnosis to a primary cancer (gastric adenocarcinoma).

A male fetus with aqueductal stenosis and four accessory spleens. A case report with a tentative genetic explanation.

A male fetus presenting with prenatal hydrocephalus is reported. The fetus died during labor. Pathological examination disclosed four accessory spleens without any abnormalities of the situs. Hydrocephalus was secondary to aqueductal stenosis. Histological features of the aqueduct were consistent with a developmental defect. The association of such malformations has already been reported and could be explained by common regulatory mechanisms which control the splenic and neural tube development.

[Planned pregnancy program in systemic lupus erythematosus]. / Programme de planification de la grossesse au cours du lupus érythémateux disséminé.

OBJECTIVES: Maternal and fetal risk is high during pregnancy for young women with systemic lupus erythematosus. We analyzed outcome after a planned pregnancy program for these patients. METHODS: Between 1982 and 1994, 58 pregnancy were planned in 34 women with systemic lupus. Nine of them had renal and 5 central nervous system involvement; antiphospholipid syndrome was present in 8; steroid therapy was given in 24, immunosuppressors in 2 and plasma exchange in 1. At diagnosis of pregnancy, prednisone was prescribed (at least 10 mg/d), associated with aspirin in all non-symptomatic patients with antiphospholipid antibodies followed by heparin at pre partum. Heparin was used in case of antiphospholipid syndrome. Women with anti-SSA or B antibodies and no past history of congenital atrioventricular block were not given any specific treatment. RESULTS: An acute lupus flare-up occurred in 27% of the cases including 6% in post partum. The flare-up was mild in all cases and treatment had to be changed in half of the cases. There were 9 early abortions, 1 induced abortion for congenital malformation, 2 fetal deaths, 28 premature deliveries and 18 term deliveries. Cesarean section was indicated in 8 cases. Severe neonatal infection occurred in 2 premature infants and 1 other was growth retarded. Cutaneous neonatal lupus was observed in 2 infants. No atrioventricular blocks occurred. CONCLUSION: Fetal death or very premature birth were more frequent in patients with antiphospholipid syndrome. When pregnancy is planned in women with systemic lupus erythematosus, live birth rate reaches 96% after exclusion of early and therapeutic abortions. This rate is close to the rate in the general population. The high rate of premature birth is the main risk, but there were no maternal nor neonatal deaths.