EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies.

OBJECTIVES: aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria ('criteria aPL') and at titres lower than thresholds considered by classification criteria ('low-titre aPL') on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). METHODS: Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. RESULTS: EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-ß2-glycoprotein I (ß2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-ß2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-ß2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-ß2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. CONCLUSION: EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.

The Impact of Twin Birth on Early Neonatal Outcomes.

OBJECTIVE: This study aims to describe the impact of twin birth, chorionicity, intertwin birth weight (BW) discordance and birth order on neonatal outcomes. STUDY DESIGN: We performed a hospital-based retrospective study on 2,170 twins (6.4% of all live births) and 2,217 singletons inborn 2007 to 2011. Data on neonatal characteristics, morbidities, and mortality were collected and compared. Univariate and multiple (adjusted for gestational age [GA] and gender) linear random intercept regression models were used. RESULTS: Overall, 62.3% of twins were born premature. At multiple regression, twins were similar to singletons for neonatal morbidities, but they were more likely to have lower BW and to be born by cesarean delivery. Monochorionic twins had lower GA and BW compared with dichorionic ones and were more likely to develop respiratory distress syndrome (odds ratio [OR], 1.7), hypoglycemia (OR, 3.3), need for transfusion, (OR, 3.4) but not brain abnormalities. Moderate and severe BW discordance were associated with longer length of stay and increased risk for morbidities but not for death. Birth order had no effects. CONCLUSION: Prematurity was the most common outcome in twins and accounted for the apparently increased risk in morbidities. Monochorionicity was confirmed as risk factor for lower GA and neonatal morbidities. BW discordance may play a role in developing neonatal complications and needs to be further investigated.

Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial.

To assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; -1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco.it as EudraCT 2006-004205-26.

Predicting factors for emergency peripartum hysterectomy in women with placenta previa.

PURPOSE: The aim of the study was to identify predictive factors for peripartum hysterectomy in women with placenta previa. METHODS: We retrospectively reviewed all singleton pregnancies with a diagnosis of placenta previa, with the distance between the lower placenta edge and the internal cervical os is ≤2 cm, during the period June 2006-May 2010. Antepartum characteristics of women who did and did not undergo peripartum hysterectomy were compared: they include demographical data, obstetrics history, clinical course of the index pregnancy and sonographic findings. RESULTS: Two-hundred and forty-seven women were selected. peripartum hysterectomy was required in 12 cases (4.9%). A statistically significant increased risk emerged for a history of cesarean section (p < 0.001), major placenta previa (p < 0.001), sonographic suspect of placenta accreta (p < 0.001) and gestational age at delivery <34 weeks' gestation (p < 0.001). These four variables were entered into an unconditioned logistic regression model. The resulting adjusted ORs were 23.1 (95% CI 2.3-235.3, p = 0.008), 14.6 (95% CI 0.6-346.5, p = 0.097), 42.4 (95% CI 5.1-354.5, p = 0.001) and 9.3 (95% CI 1.1-76.9, p = 0.037), respectively. CONCLUSIONS: This study confirms that placenta previa is a condition at substantial risk of peripartum hysterectomy. A history of cesarean section, the sonographic suspect of placenta accreta and gestational age at delivery were found to be independently associated with this risk. Antepartum ultrasonography in particular plays a crucial role in predicting hysterectomy in these cases.

Risk factors for emergency postpartum hysterectomy: the neglected role of previous surgically induced abortions.

The objective of this retrospective case-control study was to identify clinical factors associated with emergency peripartum hysterectomy. Deliveries from January 2003 through October 2009 in this tertiary care obstetrics hospital were reviewed. Cases were women who underwent emergency peripartum hysterectomy. Controls were those who delivered immediately after the cases but in whom hysterectomy was not needed. They were matched to cases in a 5:1 ratio. Thirty-eight cases and 190 controls were selected. Variables found to be significantly associated with emergency postpartum hysterectomy were a stage III-IV placenta previa (p<0.001), previous surgical abortions (p=0.001) and number of fetuses (p=0.039). The corresponding adjusted odds ratios were 40.2 (95% confidence interval 5.6-287.0), 6.0 (95% confidence interval 2.1-17.2) and 7.8 (95% confidence interval 1.1-55.0), respectively. The study confirms the detrimental role of major placenta previa in influencing the risk of postpartum hysterectomy, but also suggests multiple pregnancy and surgical abortion as potential additional risk factors.

Intrapartum prediction of emergency delivery due to non-reassuring fetal status at 40 weeks' gestation in low-risk pregnancies: contribution of Doppler parameters, maternal history, and intrapartum clinical characteristics.

OBJECTIVE: To assess the added value of Doppler parameters, maternal history, and intrapartum clinical characteristics for the prediction of emergency delivery due to non-reassuring fetal status in low-risk pregnancies. METHODS: This was a prospective cohort of low-risk pregnancies undergoing ultrasound assessment at 40 weeks' gestation within 7 days of delivery. The main outcome was emergency cesarean section due to non-reassuring fetal status. The association between Doppler parameters, intrapartum clinical characteristics, and maternal history was performed by logistic regression. The predictive performance of the constructed models was assessed by receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC). RESULTS: From 403 included pregnancies, 18.6% (n = 75) underwent an emergency delivery due to non-reassuring fetal status. The mean gestational age at birth was 40.5 (SD 5) days. Middle cerebral artery pulsatility index (MCA) and cerebroplacental ratio (CPR) were lower in the emergency cesarean section group (1.16 versus 1.30; p < .001, and 1.61 versus 1.78; p = .001, respectively). There was a higher incidence of small-for-gestational-age neonates (20 versus 10.1%; p = .017), lower Apgar scores at the 5th minute (9.7 versus 9.9; p = .006), and NICU admissions (9 versus 3%; p = .016) in the emergency cesarean section group. The base model comprised nulliparity, and the finding of meconium-stained amniotic fluid during labor, achieving an AUC of 66%, while the addition of the MCA Z-score significantly improved the previous model (AUC: 73%; DeLong: p = .008). CONCLUSIONS: In low-risk pregnant woman at term, the addition of MCA Z-score to a previous model comprising maternal history and intrapartum clinical findings, significantly improves the prediction of emergency delivery due to non-reassuring fetal status.

Nasal lavage in pregnant women with seasonal allergic rhinitis: a randomized study.

BACKGROUND: Nasal rinsing appears particularly suitable in the management of pregnant women with seasonal allergic rhinitis since no deleterious effects on the fetus are to be expected. However, to date, no studies have specifically investigated this option. METHODS: Pregnant women with seasonal allergic rhinitis were randomized to intranasal lavage with hypertonic saline solution 3 times daily (n = 22) versus no local therapy (n = 23) during a 6-week period corresponding to the pollen season. Patients were invited to keep a daily record of rhinitis symptoms (rhinorrea, obstruction, nasal itching and sneezing), to record consumption of oral antihistamine and to undergo rhinomanometry. RESULTS: The rhinitis score was similar at study entry but a statistically significant improvement in this score was observed in the study group during all subsequent weeks (p < 0.001 for weeks 2-6). The mean number of daily antihistamines use per patient per week was significantly reduced at weeks 2, 3 and 6 (p < 0.001, p < 0.001 and p = 0.001, respectively). Baseline rhinomanometry performed at week 1 showed similar nasal resistance in the study and control groups. In contrast, a statistically significant difference emerged in the 2 following evaluations. At week 3, nasal resistance in the study and control groups was 0.96 +/- 0.44 and 1.38 +/- 0.52 Pa/ml/s, respectively (p = 0.006). At week 6, it was 0.94 +/- 0.38 and 1.35 +/- 0.60 Pa/ml/s, respectively (p = 0.006). No adverse effect was reported in the active group. CONCLUSIONS: Nasal rinsing is a safe and effective treatment option in pregnant women with seasonal allergic rhinitis.

Effectiveness of Progestogens as Maintenance Tocolysis and Urogenital Cultures: Secondary Analysis of the PROTECT Trial.

Background In a recently published multicenter randomized controlled trial, we demonstrated that progestogens are not effective as maintenance tocolysis. Objective This study was aimed to evaluate if previous finding may be affected by positive urine culture and/or vaginal swab. Study Design We performed a secondary analysis of the PROTECT trial (NCT01178788). Women with singleton pregnancy between 22 and 31 6/7 weeks' gestation, admitted for threatened preterm labor were considered. At admission, we collected urine culture and vaginal swabs. At discharge, women with a cervical length ≤25 mm were randomized to vaginal progesterone or 17α-hydroxyprogesterone caproate or observation group. We used Chi-square statistics, considering 97.5% CI (confidence interval) and p -value less than 0.025 for significance. Results Urine culture and vaginal swabs were collected in 232 out of 235 patients included in the primary analysis. Overall, 31 out of 232 women (13.4%) had positive urine culture and 60 out of 232 (25.9%) had positive vaginal swab. In women with negative urine culture, a higher rate of preterm birth was found in vaginal progesterone group (27/69, 39.7%) respect with controls (14/68, 20.6%; relative risk [RR] = 1.90; 97.5% CI: 1.01-3.57; p = 0.018). Conclusion Among women with negative urine culture, the rate of preterm birth <37 weeks' gestation was significantly increased in those receiving vaginal progesterone, reinforcing our previous findings in symptomatic women.

Weekly epirubicin in the treatment of gestational breast cancer (GBC).

BACKGROUND: GBC is a rare disease and chemotherapy in this setting lacks a standardized approach. PATIENTS AND METHODS: Patients 16-30 weeks pregnant with locally advanced/metastatic disease or with high risk of recurrence after surgery were evaluated. RESULTS: Twenty patients received weekly epirubicin 35 mg/m(2). Median maternal age was 37 years (23-42). Median gestational age at chemotherapy was 19 weeks. Thirteen patients were treated after surgery while 7 had locally advanced tumours of which one had liver metastases. Mean total epirubicin dose was 420 mg/m(2) with a median number of 12 administrations (4-16). No grade 3-4 toxicities were observed. No foetal adverse events were observed except 1 premature delivery at 28 weeks. Births were induced by caesarean section in 12 patients at a median gestational age of 35 weeks. No malformations were reported except 1 newborn with polycystic kidney. At a median age of 2 years, neurological, cardiological and immunological development was normal in all children as reported by their parents. In 7/20 patients with evaluable disease, five had an objective response. At a median follow-up of 38 months, 17 patients are alive; 14 are disease free. CONCLUSIONS: Weekly epirubicin appears safe and effective with low foetal toxicity and could be considered in GBC.

Decidualized ovarian endometriosis in pregnancy: a challenging diagnostic entity.

BACKGROUND: The hormonal milieu that characterizes pregnancy may determine profound modifications of ovarian endometriomas leading to lesions mimicking malignancy. In this study, we report on our experience and perform a review of the literature on this issue. METHODS: Data from women evaluated at our referral center for prenatal diagnosis were reviewed in order to identify those who were detected with an ovarian endometrioma in pregnancy mimicking malignancy. A review of the literature on this issue (1990-2008) was also performed, using the PubMed database. RESULTS: Three cases were identified at our center. The literature reports on a further 19 cases (11 studies). Sonographic and color Doppler examination consistently documented rapidly growing and abundantly vascularized intracystic excrescences. Conversely, the presence of septations or significant free fluid was never reported. The vast majority of cases underwent surgical removal. Interestingly, in our experience, in a woman who declined surgery and had spontaneous miscarriage at 10 weeks' gestation, the sonographic examination performed 6 weeks after dilatation and curettage revealed an unremarkable typical endometrioma, thus suggesting that it is a transitory transformation. CONCLUSIONS: Pregnancy-related modifications of an ovarian endometrioma leading to the rapid development of vascularized intracystic excrescences are an uncommon but possible event. An expectant management and serial monitoring should first be envisaged in these cases provided that other features of malignancy, such as septations or free fluid, are absent.

The impact of treatment of the fetus by maternal therapy on the fetal and postnatal outcomes for fetuses diagnosed with isolated complete atrioventricular block.

OBJECTIVES: to analyse retrospectively the data of fetuses diagnosed with isolated complete atrioventricular block and efficacy of treatment of the fetus by maternal therapy. MATERIALS: Between 1992 and 2004, we diagnosed complete atrioventricular block in 26 singleton and 2 twins fetuses of 27 pregnant women known to have anti Ro/La antibodies, 11 with autoimmune disease, one patient analysed in 2 pregnancies. At presentation, 20 of the fetuses were compensated and non-hydropic, while 8 had hydrops. Twenty patients were treated with dexamethasone, 2 with associated salbutamol and one mother with isoproterenol. RESULTS: Age at presentation was not different between the hydropic and non-hydropic fetuses. The fetuses with hydrops, however, had a lower mean heart rate at presentation, 48.5 +/- 9.25 with a range from 32 to 60, compared to 59.95 +/- 7.9 beats per minute, with a range from 50 to 80, in the non-hydropic fetuses (p less than 0.002). Equally, after birth the mean heart rate in hydropic fetuses was 42.6 +/- 5.1, with a range from 38 to 50, as opposed to 56.05 +/- 11.8 beats per minute, with a range from 29 to 110, in the non-hydropic fetuses (p less than 0.015), The hydropic fetuses were delivered at 31.7 +/- 3.8 weeks' gestation, with a range from 29 to 38 weeks (p less than 0.003) compared to 35.5 weeks' gestation +/-2.04, with a range from 31 to 38, in the non-hydropic fetuses. Mortality was 37.5% in the hydropic fetuses, versus 5% of those without hydrops (p less than 0.02). Pacemakers were implanted in 22 of 26 infants born alive, at a median of 45 days, with a range from 1 day to 5 years, in those without hydrops during fetal life, and 3 days, with a range from 1 day to 8 months in those afflicted by hydrops, of whom 2 died despite the implant of the pacemaker. The presence and degree of hydrops had a significantly negative predictive value. No significant differences were observed between the treated and non treated cases, albeit that administration of steroids ameliorated rapidly the hydrops in 3 of 5 cases. CONCLUSIONS: The outcome in our cases was mainly dependent on the presence and degree of fetal cardiac failure. Treatment of the fetus by maternal administration of steroids did not result in any regression of the conduction disorder, but had a favourable effect on fetal hydrops.

Impact of different stages of intrauterine inflammation on outcome of preterm neonates: Gestational age-dependent and -independent effect.

OBJECTIVE: To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders. METHODS: This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline's criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates. RESULTS: Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2-3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1-7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1-0.7) and need for surfactant (OR = 0.5, CI: 0.2-0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2-3 only, RC = 6.5 days, CI: 2-11). No other outcome was affected. CONCLUSIONS: IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.

Obstetric risk factors for poor neonatal adaptation at birth.

PURPOSE: To identify obstetric risk factors of delivering a neonate with poor neonatal adaptation at birth. MATERIAL AND METHODS: Nested case-control study. Poor neonatal adaptation was defined for presence of at least: umbilical cord artery pH <7.10, base deficit ≥12 mmol/L, Apgar score at 1' ≤5. Controls were selected from the same population and matched with cases. The association between clinical parameters and poor neonatal adaptation was analyzed by logistic regression. RESULTS: One hundred and thirty three women (2.1% of all live births) with a neonate presenting a poor neonatal adaptation were matched with 133 subsequent controls. Significant contributions for the prediction of poor neonatal adaptation were provided by maternal age ≥35 years (p ≤ .001, odds ratio (OR) 3.9 [95%CI: 2.3-6.8]), nulliparity (p ≤ .001, OR 3.3 [95%CI: 1.8-6]), complications during pregnancy (p = .032, OR 2.2 [95%CI: 1.1-4.4]), gestational age at delivery <37 weeks (p = .008, OR 5.2 [95%CI: 1.5-17.8]) and cardiotocography category II or III (p ≤ .001, OR 36.3 [95%CI: 16.5-80.1]). The receiver operative characteristic curve was 0.91 [95%CI: 0.87-0.95], and detection rates 82.7% and 89.5% at 10% and 20% of false positive rates, respectively. CONCLUSIONS: Several obstetric risk factors before and during labor can identify a subgroup of newborns at higher risk of a poor neonatal adaptation at birth.

Progestogens for Maintenance Tocolysis in Women With a Short Cervix: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of progestogens for maintenance tocolysis in women undelivered after their first preterm labor episode. METHODS: Women with singleton pregnancies between 22 0/7 and 31 6/7 weeks of gestation with arrested preterm labor and a cervical length 25 mm or less at hospital discharge were eligible. Patients with a previous preterm birth were excluded. In a randomized controlled trial conducted in five university hospitals, women were randomized to receive vaginal progesterone (200 mg per day) or intramuscular 17α-hydroxyprogesterone caproate (341 mg per week) or to an observation groups (control group). The primary outcome was the proportion of women with preterm birth at less than 37 weeks of gestation. A sample size of 160 per group (n=480) was planned to compare vaginal progesterone and 17α-hydroxyprogesterone caproate groups with those in the control group. The sample size estimation was based on the hypothesis that the risk of experiencing preterm birth in the control group would be 30% and that 17α-hydroxyprogesterone caproate or progesterone would decrease this risk to 15%. A P value of <.025 was defined as statistically significant. At planned interim analysis (n=254), the trial was stopped for futility. RESULTS: Between July 2010 and June 2015, 257 women were eligible and 254 were subsequently randomly assigned to vaginal progesterone (n=86), 17α-hydroxyprogesterone caproate (n=87), or observation (n=81). Nineteen (8%) were excluded from the analysis because they either dropped out or information was missing, leaving 235 women available for analysis. Demographic characteristics were similar across groups. The preterm birth rate did not differ significantly between groups: 23% in the 17α-hydroxyprogesterone caproate group, 39% in the vaginal progesterone group, and 22% in the women in the control group (P=.949 for 17α-hydroxyprogesterone caproate compared with the women in the control group and P=.027 for vaginal progesterone compared with women in the control group). CONCLUSION: The use of progestogens for maintenance tocolysis in women with a short cervix did not reduce the rate of preterm birth. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01178788.

Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview.

The term chorioamnionitis is used to refer to an intrauterine infection/inflammation occurring between the maternal tissues and the fetal membranes (choriodecidual space) or in the fetal annexes (chorioamniotic membranes, amniotic fluid, umbilical cord). Histological examination of the placenta is the gold standard for diagnosis. However, clinical, biochemical and microbiological criteria are also used to define the disease. The literature contains a large body of evidence showing that chorioamnionitis is the leading cause of very preterm birth and, therefore, contributes significantly to neonatal morbidity and mortality. In recent decades, numerous studies have attempted to establish whether, and to what extent, intrauterine infection/inflammation might negatively affect the short- and long-term outcome of preterm infants. The question is still unanswered. The discrepancy observed across studies can be attributed largely to the use of different inclusion and exclusion criteria, diagnostic criteria and methods, and to whether or not potential confounding factors, such as gestational age were considered. Anyhow, the association between chorioamnionitis and severe prematurity requires serious efforts by researchers to clarify the mechanisms linking intrauterine infection/inflammation with preterm birth, and thus to identify strategies that may guide clinicians' diagnostic and therapeutic choices, with regard to both mothers and infants.

Dynamics and significance of placebo response in primary dysmenorrhea.

A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double-blind study on placebo versus antiprostaglandin agents (naproxen and pirprofen). To evaluate the placebo effect and its duration, the treatment was given for 4 successive cycles. Whereas the antiprostaglandin agents were effective in most of the patients (in 80% of the pirprofen group and 85.7% of the naproxen group) and this efficacy was maintained throughout the study, a favorable response to placebo was observed in 84% in the first cycle, 29% in the second, 16% in the third and 10% in the fourth. The incidence of side effects was similar in the placebo and the active treatment groups (35.4% vs. 37.5%). It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics (mental or conditioning theories). However, this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms.

A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia.

OBJECTIVE: To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition. STUDY DESIGN: Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up. RESULTS: The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%). CONCLUSION: These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR.

Update on the current recommendations and outcomes in pregnant women with antiphospholipid syndrome.

Pregnancy morbidity is part of the clinical spectrum of the antiphospholipid syndrome (APS), a chronic autoimmune condition serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents are the mainstay of the treatment of obstetric APS. However, there is an ongoing debate about the optimal management of women with most severe aPL-mediated obstetric complications, women not fulfilling APS criteria and those with refractory disease. Unfortunately, the literature cannot provide definite answers to these controversial issues, being flawed by many limitations. The evidence supporting the recommended therapeutic management of different aPL-related obstetrical clinical manifestations is presented, with a critical appraisal of each approach.

Pregnancy in women with Alport syndrome.

BACKGROUND: Little is known about pregnancy in women with Alport syndrome (AS), as only four cases have been reported in the literature. We herein describe the course of pregnancy in two sisters with overt forms of AS. CASES: Both women were diagnosed as having autosomal recessive AS. Before pregnancy, their renal function and their blood pressure were normal, and proteinuria values were below 2 g/24 h. Both patients faced a progressive and remarkable increase in proteinuria during pregnancy, with subsequent hypoproteinemia. The clinical condition worsened, particularly in the first case, who was managed with some success with a combination of diuretics. She delivered at 32 weeks of pregnancy. The second patient was less challenging and she delivered at 36 weeks. Proteinuria returned to pre-pregnancy levels in both cases, after delivery. CONCLUSION: Management of pregnant women with overt AS is challenging and worsening of renal disease has to be expected. The use of diuretic therapy may be of benefit.

Predictive factors for neonatal survival in women with periviable preterm rupture of the membranes.

OBJECTIVE: To identify clinical, hematological or instrumental factors available at the time of the diagnosis that may predict neonatal survival in periviable preterm premature rupture of the membranes (PROM). METHODS: We report on a cohort (n = 85) of women with periviable PROM (14-23.6 weeks' gestation) occurring over a 10-year period in a single institution. The main outcome chosen was the survival rate beyond the neonatal period. Variables considered were those available at 24 h after admission. RESULTS: The overall survival rate was 49%. In the multivariate analysis, significant contributions for the prediction of neonatal survival were provided by four variables: genetic amniocentesis-related cause of PROM (p < 0.001), gestational age at PROM (p = 0.019), CRP > 1 mg/dl within 24 h after admission (p = 0.042) and oligohydramnios (largest vertical pocket ≤2 cm) (p = 0.041). The corresponding adjusted odds ratio (OR)s were 73.9 (95% CI: 7.9-694.7), 1.5 (95% CI: 1.1-2.0) per week, 0.26 (95% CI: 0.07-0.95) and 0.20 (95% CI: 0.04-0.93), respectively. CONCLUSIONS: Genetic amniocentesis-related cause of PROM, gestational age at PROM, C-reactive protein >1 mg/dl and oligohydramnios are significantly associated with survival in women with periviable PROM. The evaluation of these few and easily available variables may help physicians and patients in the decision-making process of this demanding condition.