Sara De Carolis

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Proteinuria and outcome of 444 pregnancies complicated by hypertension

The purpose of this study was to determine the role of proteinuria on pregnancy outcome in 444 hypertensive women with singleton pregnancies. The patients were divided into three hypertensive groups: 98 with chronic hypertension, 199 with nonproteinuric gestational hypertension, and 147 with proteinuric preeclampsia and chronic hypertension with superimposed proteinuric preeclampsia. The presence of increased proteinuria (greater than 0.3 gm/L) predicted an adverse pregnancy outcome. Furthermore, the majority of small-for-gestational-age infants occurred in the group with proteinuric preeclampsia (52%), whereas the rate of small-for-gestational-age infants was 18% and 12% in the group with nonproteinuric gestational hypertension and chronic hypertension, respectively. The group with chronic hypertension did not show any increased risk for fetal outcome. Perinatal mortality rate was extremely poor in the group with proteinuric preeclampsia at 129 per 1000, four times higher than those of the other two groups.

Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case–control study

OBJECTIVE To identify the risk factors associated with pregnancy failure in patients with APS treated with conventional therapy. METHODS A multicentre, case-control study was conducted to compare APS patients with successful and unsuccessful pregnancy outcomes. We retrospectively considered 410 pregnancies of women diagnosed with primary APS. The study focused on 57 unsuccessful pregnancies (considered the study population) and 57 successful pregnancies (considered the control population) matched for age and therapy. All the patients had been treated with conventional protocol treatments including low-dose aspirin and/or heparin. The clinical and laboratory features of the two groups of women diagnosed with APS were compared. RESULTS The independent risk factors for pregnancy failure were: (i) the presence of SLE or other autoimmune diseases [odds ratio (OR) 6.0; 95% CI 1.7, 20.8; P = 0.01]; (ii) history of both thrombosis and pregnancy morbidity (OR 12.1; 95% CI 1.3, 115.3; P = 0.03); and (iii) triple [Immunoglobulin (Ig) G/IgM aCLs plus IgG/IgM anti-β(2) glycoprotein I antibodies plus LA] aPL positivity (OR 4.1; 95% CI 1.0, 16.7; P = 0.05). APS patients diagnosed on the basis of a single positive test and/or history of pregnancy morbidity alone were generally found to have successful pregnancies. CONCLUSION It would seem from these findings that the risk of pregnancy failure in APS women planning to conceive can be stratified on the basis of some specific clinical and laboratory features.

Recurrent spontaneous abortion and intrauterine fetal growth retardation as symptoms of coeliac disease

Women having recurrent miscarriages or intrauterine growth retardation could have subclinical coeliac disease, which can be detected by serological screening tests.

The duration of hypertension in the puerperium of preeclamptic women: Relationship with renal impairment and week of delivery

OBJECTIVE The purpose of the study was to determine whether the duration of hypertension in the puerperium of preeclamptic women was related to certain clinical features of disease severity. STUDY DESIGN We studied 269 singleton pregnancies divided into two groups: 159 with gestational hypertension and 110 with preeclampsia. The normalization time of blood pressure in puerperium was estimated as the interval between the delivery day and the first day when each of two to four self-measurements per day of diastolic blood pressure was observed to be < or = 80 mm Hg for at least 3 consecutive days. RESULTS Normalization time was shorter in gestational hypertension than in preeclampsia (6 +/- 5.5 [means +/- SD] vs 16 +/- 9.5, respectively, p < 0.0001). Normalization time of gestational hypertension showed a significant correlation with uric acid (r = 0.20, p < 0.025); normalization time of preeclampsia displayed significant correlations with the week of delivery (r = -0.34, p < 0.005), uric acid (r = 0.34, p < 0.025), and urea nitrogen (r = 0.29, p < 0.025), respectively. After stratification by parity, in both groups the correlations of normalization time with renal data were observed only among multiparous women, whereas in preeclampsia the link of normalization time with the week of delivery remained highly significant in both subgroups. CONCLUSIONS The differences observed between gestational hypertension and preeclampsia suggest that distinct mechanisms or a different maternal answer to the same mechanism(s), in maintaining high blood pressure in puerperium, are present in the two groups. Normalization time might reflect the recovery time of the endothelial damage in preeclampsia.

European registry of babies born to mothers with antiphospholipid syndrome

Objectives This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the childs immunological profile with their mothers. Methods A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years. Results 134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β2 glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mothers antibodies before 6 months of age (p<0.05). Conclusion Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.

Uterine myomectomy in pregnant women

Objective: To determine whether myomectomy during pregnancy in selected patients improves outcome. Methods: Retrospective analysis of 18 patients who underwent myomectomy between the 6th and 24th week of gestational age. Surgical management of tumors was required on the basis of the characteristics of the myomas and symptoms. The dimensions and site of myomas, symptoms of the patients, time and mode of delivery, and pregnancy outcome were analyzed. Results: One woman was lost to follow-up, and one suffered a miscarriage. The remaining 16 patients delivered healthy babies between the 36th and 41st week; 14 delivered by cesarean section, and 2 vaginally. Conclusion: We suggest that myomectomy during pregnancy may be considered safe in selected patients. Moreover, it permits good pregnancy outcome with healthy babies delivered at term.

Neonatal outcome in hypertensive disorders of pregnancy.

BACKGROUND Hypertensive disorders in pregnancy account for increased perinatal morbidity and mortality when compared to uneventful gestations. AIMS To analyze perinatal outcome of pregnancies complicated by different kinds of hypertension to uncomplicated pregnancies in a series of Italian women and to compare our data with series from other countries. STUDY DESIGN The sample was divided into four groups of hypertensive women: chronic hypertension (CH), gestational hypertension (GH), preeclampsia (PE), and chronic hypertension complicated by preeclampsia (CHPE). One thousand normal pregnancies served as controls. SUBJECTS Neonatal features of the offspring of 965 Italian women with hypertension in pregnancy were evaluated. MEASURES Gestational age, birthweight and the rate of small for gestational age were the outcomes. Perinatal asphyxia and mortality were also assessed. RESULTS Gestational age, the mean of birth weight and birth percentile were significantly lower in all groups with hypertensive complications when compared with controls. The rate of very early preterm delivery (<32 weeks) was 7.8% in CH, 5.9% in GH, 21.2% in PE and 37.2% in CHPE while it was to 1.2% in the control group. The rate of SGA was globally 16.2% in CH, 22.8% in GH, 50.7% in PE, 37.2% in CHPE and 5% in controls. The rate of SGA in PE was much higher than reported in series from other countries. CONCLUSION Comparing our data with those reported from other countries, it is evident that the rate of fetal growth restriction in PE we found in our center, is significantly higher even in the presence of a global lower incidence of PE.

Laboratory criteria of the obstetrical antiphospholipid syndrome - Data from a multicentric prospective European women cohort

A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-beta2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS). We report new data on a prospective multicenter European cohort of 109 pregnant women having APS. Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-beta2-GPI IgM was present in three women. These results suggest that aCL and a-beta2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS. The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.

Predictors of Pregnancy Outcome in Antiphospholipid Syndrome: A Review

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a non-invasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, false-positive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.