Pregnancy and primary Sjögren's syndrome: management and outcomes in a multicentre retrospective study of 54 pregnancies.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most common autoimmune diseases, mainly affecting women during the fourth decade of life. During pregnancy, the presence of anti-Ro/SSa and anti-La/SSb antibodies increases the risk of congenital heart block (CHB). Foetal and pregnancy outcomes in pregnant women with pSS compared with the general population are difficult to evaluate because of confounding factors including age and body mass index (BMI). METHOD: The aim of this case-control study was to analyse the impact of pSS in pregnant women on foetal and pregnancy outcomes. RESULTS: We enrolled 19 women with pSS (54 pregnancies) matched by age and BMI to 216 controls. Patients with pSS delivered significantly earlier (38 weeks + 3 days vs. 39 weeks + 2 days) and experienced more spontaneous abortions [< 22 weeks of gestation (WG)] than the controls [n = 16/54 (30.0%) vs. n = 1/216 (0.4%); p < 0.00001]. Preterm delivery (≤ 37+6 WG) was significantly higher in the pSS group than in the control group (29% vs. 12%, p = 0.04). pSS activity significantly affected the birthweight percentile, which was lower in pregnancies occurring after the diagnosis of pSS than in those occurring before (32.43 ± 21.57 vs. 60.46 ± 27.37; p = 0.008). No case of CHB was observed. CONCLUSIONS: pSS is responsible for an increased risk of spontaneous abortion. The duration of pregnancy is lower in patients with than without pSS, with more premature deliveries. Pregnancies that occur after the onset of the disease result in lower birthweight percentile children than when pSS is not clinically overt.

Is incidental gestational thrombocytopaenia really always safe for the neonate?

It is widely admitted that neonates' platelet counts (PCs) are always normal in babies born to mothers with incidental gestational thrombocytopaenia. However, results of PC determinations at delivery have led us to wonder whether incidental gestational thrombocytopaenia is actually safe for the neonate under all circumstances, and to recommend that for every baby born to a mother with a pregnancy-associated thrombocytopaenia, even in the case of confirmed IGT, platelet counts on umbilical cord blood be closely monitored.

[HELLP syndrome: the ten commandments]. / Le syndrome HELLP: les dix commandements.

The internist has a role to play in the practical approach of HELLP syndrome, a disease which can differ according to its symptoms, course and causes. Any recent epigastric pain during the end of pregnancy must be considered as a symptom of HELLP syndrome. Liver disease together with thrombocytopenia may be present even without any renovascular involvement. The disease can be threatening for the mother and lead to the foetal death. It can be sometimes difficult to be distinguished from thrombotic microangiopathy. Treatment consists mainly in rapid discontinuation of pregnancy. Steroid therapy could allow to simplify anaesthesia procedures and to avoid blood transfusion. Early-onset HELLP syndrome could be a marker a chronic nephropathy or a thrombophilic disorder. The HELLP syndrome is a very demonstrative example of the help the internist can afford to the obstetrician in the management of pregnancy-associated disorders.

[Managing a pregnant woman with a low platelet count]. / Que faire en pratique à la découverte d'une thrombopénie en cours de grossesse?

PURPOSE: The practical management of a pregnant woman with a platelet count below 150 x 10(9) per liter is very simple. KEY POINTS: A spurious thrombocytopenia must be discarded and isolated thrombocytopenia (begnin idiopathic gestational thrombocytopenia and idiopathic thrombocytopenic purpura) must be first differenciated from associated forms. It must be determined if thrombocytopenia appeared recently and therefore is directly specific of pregnancy. Severity is indicated by a very low platelet count and a high speed in lowering. Platelet count of the newborn must always be checked on ombilical cord blood at the time of the birth. Steroid therapy may be needed in some cases of idiopathic thrombocytopenic purpura, lupus or HELLP syndrome. Platelet counts must be checked, in every case, three months after delivery and in case of subsequent pregnancy. CONCLUSION: Low platelet count is a demonstrative example of the help the internist can afford to the obstetrician in the management of pregnancy-associated conditions.

[Smoking cessation and pregnancy]. / Sevrage tabagique et grossesse.

Active and passive smoking during pregnancy induce several deleterious effects that may have a negative impact on pregnancy progress, fetus development and both mother and newborn health. Smoking cessation should be a rule for any woman as soon as the beginning of her pregnancy, or better in anticipation of a pregnancy when contraception is no more taken. Every caregiver must help every pregnant woman who smokes to quit smoking. Smoking cessation interventions in pregnant women must combine a psychological support (mainly with cognitive behavioral therapy) and nicotine replacement therapy, which can also be used during breast feeding. It is recommended to adjust the dosage of nicotine replacement therapy according to the symptoms of under or over dosage at the end of the first week of use. On the other hand, vareniclin and bupropion are contra-indicated during pregnancy or breast-feeding. Electronic cigarette is not advised during pregnancy. Prevention of smoking relapse in postpartum period is essential since a percentage as high as 50% of women having quit during their pregnancy resume smoking during the 6 months following delivery.

[Obstructive Sleep Apnea Syndrom during pregnancy: prevalence of main symptoms and relationship with Pregnancy Induced-Hypertension and Intra-Uterine Growth Retardation]. / Le syndrome d'apnées du sommeil pendant la grossesse: prévalence des symptômes cliniques et corrélation avec la pathologie vasculaire gravidique.

OBJECTIVE: To investigate the frequency of main symptoms of Obstructive Sleep Apnea Syndrom (OSAS) and their relationship with Pregnancy Induced-Hypertension (PIH) as well as Intrauterine Growth Retardation (IGR) as suggested by recent studies. METHODOLOGY: Four hundred (and) thirty-eight enquiry forms completed during post-partum period were analysed, after exclusion of multiple pregnancies. Collected data were demographic characteristics, obstetrical events, sleep disorders during last trimester, screening of snoring and vigilance troubles with an Epworth score. RESULTS: Forty-five percentages of the patients reported to have habitual snoring during pregnancy. Among these, 85% were non-snorers before pregnancy. Daytime somnolence concerned 84,5% of the population with an Epworth score significatively increased (P<0,0001). The prevalence of PIH was found to be 4,5%, with two apparently independent risk factors: the body mass index (OR=1,1) and an association between snoring and increased vigilance trouble (OR=2,6). No statistical difference was found concerning IGR. CONCLUSIONS: SAS symptoms are frequent during pregnancy and snoring appears to be linked with PIH. However, polysomnographic data are not yet sufficient to explain pathophysiological mechanisms and find relevant diagnostic markers during pregnancy.

[How to manage a patient with chronic arterial hypertension during pregnancy and the postpartum period]. / Conduite à tenir chez une hypertendue artérielle chronique pendant la grossesse et le postpartum.

The management of chronic arterial hypertension during pregnancy and postpartum requires first to estimate the risk of the pregnancy, linked with the severity of hypertension, with cardiac and renal involvement, with its cause as well as with the background (obesity, diabetes, possible history of placental vascular pathology). On a very practical approach, antihypertensive drug has to be started or increased if systolic pressure reaches or exceeds 160 mmHg or if diastolic pressure reaches or exceeds 105 mmHg. Below this level, there are no evidence-based medicine data, but it seems reasonable to treat if pressure increases over 150/100 mmHg (140/90 mmHg in case of ambulatory monitoring). Excessive pressure figures control must be avoided as much as insufficient ones: in practice, it is necessary to decrease the treatment dose if figures are below 130/80 mmHg. Three antihypertensive drugs are consensually recommended today: alphametyldopa, calcium-channel blockers and labetalol. Monotherapy is most often sufficient; if needed, two of these drugs can easily be associated, and even three if necessary. Converting enzyme inhibitors and angiotensin receptor II antagonists should not be prescribed to pregnant women. Betablockers and diuretics are not recommended. Whatever is the antihypertensive drug used, it is necessary to detect the signs of bad placenta blood circulation with uterine Doppler ultrasound and regular controls of fetal growth, and to check for appearance of proteinuria, defining then over-imposed pre-eclampsia needing immediate admission to the maternity. After delivery, lacatation suppresion with bromocriptin should not be prescribed.

Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators.

Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity.

[Immune thrombocytopenia and pregnancy: State of knowledge and unanswered questions]. / Purpura thrombopénique immunologique et grossesse : état des connaissances actuelles et questions encore sans réponse.

Pregnancy is a common problem in women with immune thrombocytopenia (ITP). It could be a source of anxiety for the patients and their family, nurses and medical doctors and many questions are unresolved in this setting. Most of published recommendations were based on experts' opinion rather than on evidence-based medicine and randomized studies. The objectives of this article are to remind the known recommendations and to discuss the unresolved questions and the prospective.

[Thrombosis risk during pregnancy after history of cerebral venous thrombosis]. / Risque thrombotique des grossesses après un épisode de thrombose veineuse cérébrale.

INTRODUCTION: Few data have been published about the prognosis of a pregnancy following an episode of venous cerebral thrombosis (CVT), and far less about preventive strategy. METHODS: This is a retrospective study of a case series of 11 pregnancies in six women who had previously presented a CVT. RESULTS: The first pregnancies after CVT occurred on average 58 months later. Prevention with aspirin or heparin was administered in ten cases during pregnancy, and in all the cases with heparin in postpartum. No recurrence of CVT was observed. A minor pulmonary embolism was diagnosed in postpartum in one case. CONCLUSION: Prognosis of a pregnancy after a CVT seems to be favourable if a sufficient delay after CVT is respected. Although no results of controlled trials are available, prophylaxis with heparin is probably reasonable as benefit seems higher than risks and is strongly advised during the postpartum period.

Enhancement of hypoxemia by right-to-left atrial shunting in severe asthma.

We report two cases of severe hypoxemia due to right-to-left shunt in acute asthmatic patients. During acute asthma, the transmural right atrial pressure can be higher than left atrial pressure during inspiration and then induce a right-to-left shunt through inter-atrial communication leading to hypoxemia. Contrast echography as well as Doppler analysis can easily confirm the diagnosis.

Intoxication by benzodiazepines: studies with diazepam used as a model compound suggest an interaction with red blood cells calmodulin dependent (Ca2+, Mg2+) ATPase.

20 patients under therapy or intoxicated by benzodiazepines were studied. A partial inhibition of (Ca2+, Mg2+)ATPase on 'B' membranes (CaM rich membranes) was evident in 2 cases. A total inhibition of (Ca2+, Mg2+) ATPase on both 'B' and 'A' (CaM depleted) membranes was noted in 1 case: the patient who was severely intoxicated had pronounced hemolysis. As an attempt to elucidate the mechanism of this action, the effect of diazepam chosen as model compound was studied on 'B' and 'A' membranes prepared from normal human RBC previously incubated with diazepam. A high concentration of diazepam, corresponding to a 20-fold therapeutic level results in a 50% inhibition of the maximal activity of the enzyme on 'B' membranes. It may be speculated from these experiments that the effect of high concentration of benzodiazepines on CaM dependent (Ca2+, Mg2+) ATPase leads to accelerated RBC destruction.

Maternal Herpes simplex virus type 2 encephalitis following Cesarean section.

Herpes simplex virus type 2 (HSV-2) encephalitis is rare especially during pregnancy. In immunocompetent patients, HSV-2 meningitis (contrary to HSV-1 meningitis) is usually mild, without encephalitis. We report a rare case of maternal HSV-2 encephalitis following Cesarean section. The woman had no symptomatic genital lesion, and the infant was not infected. The route of meningeal infection (neuronal or hematogenous) is discussed.

Comparison of the prevalence of alcohol, cannabis and other drugs between 900 injured drivers and 900 control subjects: results of a French collaborative study.

A collaborative case-control study was conducted in France in order to determine the prevalence of alcohol, cannabinoids, opiates, cocaine metabolites, amphetamines and therapeutic psychoactive drugs in blood samples from drivers injured in road accidents and to compare these values with those of a control population. Recruitment was performed in emergency departments of six university or general hospitals and comprised 900 drivers involved in a non-fatal accident and 900 patients (controls) who attended the same emergency units for a non-traumatic reason. Drivers and controls were matched by sex and age. Alcohol was determined by flame ionization-gas chromatography, drugs of abuse (DOA) by gas chromatography-mass spectrometry with the same analytical procedures in the six laboratories, and medicines by high performance liquid chromatography with diode array detection. Blood alcohol concentration exceeding 0.5 g/l (i.e. the legal French threshold) was found in 26% of drivers and 9% of controls. In the 18-27 years age range, alcohol was the only toxic found in blood samples of 17% drivers and 5% controls, leading to an odds-ratio (OR) of 3.8. A significant relationship was found between alcohol blood concentrations and OR values. All age groups confounded, the main active substance of cannabis, Delta(9) tetrahydrocannabinol (THC), was found in 10% of drivers and 5% of controls. In the less than 27 years old, THC (>1 ng/ml) was detected alone in the blood of 15.3% drivers and of 6.7% controls, giving OR=2.5, whereas there was no link between THC blood concentrations and OR value. THC was found alone in 60% of cases and associated with alcohol in 32%, with OR=4.6 between drivers and controls for this association. The difference in morphine prevalence between drivers (2.7%) and controls (0.03%) was highly significant (P<0.001), with OR=8.2. The number of positive cases for amphetamines and cocaine metabolites was too low for reaching any interpretation. The most frequently observed psychoactive therapeutic drugs were by far benzodiazepines, that were found alone in 9.4% of drivers and 5.8% of controls, which led to OR=1.7 (P<0.01). This study demonstrates a higher prevalence of opiates, alcohol, cannabinoids and the combination of these last two compounds in blood samples from drivers involved in road accidents than in those from controls, which suggests a causal role for these compounds in road crashes.

Thromboembolic prophylaxis with danaparoïd (Orgaran) in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widal's disease.

There is no consensus concerning thromboembolic prophylaxis in high-risk pregnant women with a previous history of heparin-induced thrombocytopenia. An alternative anticoagulant therapy is danaparoïd, whereas unfractioned and low-molecular-weight heparin therapy is contraindicated. We report a case of successful thrombosis prophylaxis using danaparoïd in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia during a previous pregnancy and Widal's disease.

[Acute intermittent porphyria associated with hyperaldosteronism and inappropriate antidiuretic hormone secretion syndrome]. / Porphyrie aiguë intermittente associée à un hyperaldostéronisme et à un syndrome de sécrétion inappropriée d'hormone anti-diurétique.

Acute intermittent porphyria, the most commun acute porphyria in France, is an autosomal dominant disorder of heme biosynthesis. The basic biochemical defect is reduced activity of the enzyme porphobilinogen deaminase. Clinical evolution is characterized by acute attacks, with a severe prognosis due to acute abdominal pain and risk of neurological complications, induced by drug intake, infection, alcohol intake or unknown factors. We report the case of a patient with an inappropriate antidiuretic secretion syndrome and secondary hyperaldosteronism associated with acute intermittent porphyria and polyradiculoneuritis syndrome. This syndrome was found to be induced a delayed reaction to thiopental. A favorable response was achieved with heme-arginate treatment.

[Occlusion of the middle cerebral artery after induction of ovulation with gonadotropins]. / Occlusion de l'artère cérébrale moyenne lors d'une induction de l'ovulation par les gonadotrophines.

A case of occlusion of the middle cerebral artery during a treatment with gonadotropin is reported. Such cases are unusual when one considers that these treatments are widely used. They occur after a markek ovarian hyperstimulation syndrome. Treatment is purely preventive with clinical, laboratory and ultrasonic examinations before injection of beta-HCG.

[Respiratory disorders during sleep in the pregnant woman]. / Troubles respiratoires au cours du sommeil de la femme enceinte.

Sleep disordered breathing can occur during pregnancy due to the development of hormonal changes and respiratory function abnormalities that perturb patency of the upper airways. Habitual snoring has been described in 25 p. 100 of the women during the third trimester of pregnancy. The incidence of sleep apnea hypopnea syndrome is unknown due to the lack of longitudinal epidemiological data, and results of the main studies are in favor of upper airway resistance syndrome. However, these sleep-related breathing disorders are more frequently associated with maternal and fetal complications such as maternal hypertension, pre eclampsia and intrauterine growth restriction. This article points out the importance of such associations because of the efficacy of continuous positive airway pressure on the regression of these nocturnal respiratory and vascular complications.

C-reactive protein levels at the onset of labour and at day 3 post-partum in normal pregnancy.

OBJECTIVES: To record maternal serum C-reactive protein levels during normal onset of labour and normal puerperium and to evaluate if inflammation or infection could be predicted during these two periods when serum C-reactive protein is increased. METHODS: Eighty-five pregnant women were enrolled in a longitudinal prospective study and had a blood sample to assess serum C-reactive protein levels on admission to the labour ward for normal onset of labour and at day three post-partum. Inclusion criteria were no previous history, a normal single pregnancy, normal vaginal delivery and an uneventful post-partum course. Twelve non-pregnant women of the same age constitued a control group. An automatic Behring Nephelometer was used to measure serum C-reactive protein concentrations. The Student's t-test (significance p < 0.05) was used for statistical analysis. FINDINGS: C-reactive protein was significantly increased during the onset of labour (4.10 +/- 2.79 mg/L) and reached very high levels during the post-partum period (24.07 +/- 18.28 mg/L) compared to the standard normal serum C-reactive protein level in a population of non-pregnant women of the same age (2.39 +/- 0.07 mg/L). INTERPRETATION: Increased serum C-reactive protein has been reported to be a marker for subclinical infection during pregnancy in various situations including premature labour and premature rupture of membranes and for complications occurring during puerperium such as thrombophlebitis, thromboembolism or endometritis. This interpretation depends on which upper limit is considered as abnormal. Because serum C-reactive protein was raised during the onset of labour, values of less than 10 mg/L could not be considered as a marker for infection during this period. Elevated serum concentrations of estrogen, progestogen and prostaglandins during labour might be one explanation for those physiological changes. Normal vaginal delivery could be compared to a surgical procedure and tissue injury consecutive to vaginal birth as reflected by a dramatic increase in C-reactive protein. More studies using nephelometry are needed to determine normal and upper values of C-reactive protein during pregnancy.