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A primary task of a network-based, earthquake early warning system is the prompt event detection and location, needed to assess the magnitude of the event and its potential damage through the predicted peak ground shaking amplitude using empirical attenuation relationships. Most of real-time, automatic earthquake location methods ground on the progressive measurement of the first P-wave arrival time at stations located at increasing distances from the source but recent approaches showed the feasibility to improve the accuracy and rapidity of the earthquake location by using the additional information carried by the P-wave polarization or amplitude, especially with unfavorable seismic network lay-outs. Here, we propose an evolutionary, Bayesian method for the real-time earthquake location which combines the information derived from the differential P-wave arrival times, amplitude ratios and back-azimuths measured at a minimum of two stations. As more distant stations record the P-wave, the posterior pdf is updated and new earthquake location parameters are determined along with their uncertainty. To validate the location method, we performed a retrospective analysis of mainshocks (M > 4.5) occurred during the 2016–2017 Central Italy earthquake sequence by simulating the typical acquisition layouts of in-land, coastal and linear array of stations. Results show that with the combined use of the three parameters, 2–4 s after the first P-wave detection, the method converges to stable and accurate determinations of epicentral coordinates and depth even with a nonoptimal coverage of stations. The proposed methodology can be generalized and adapted to the off-line analysis of seismic records collected by standard local networks.

Seismic sequences are a powerful tool to locally infer geometrical and mechanical properties of faults and fault systems. In this study, we provided detailed location and characterization of events of the 3&ndash, 7 July 2020 Irpinia sequence (southern Italy) that occurred at the northern tip of the main segment that ruptured during the 1980 Irpinia earthquake. Using an autocorrelation technique, we detected more than 340 events within the sequence, with local magnitude ranging between &minus, 0.5 and 3.0. We thus provided double difference locations, source parameter estimation, and focal mechanisms determination for the largest quality events. We found that the sequence ruptured an asperity with a size of about 800 m, along a fault structure having a strike compatible with the one of the main segments of the 1980 Irpinia earthquake, and a dip of 50&ndash, 55&deg, at depth of 10.5&ndash, 12 km and 60&ndash, 65&deg, at shallower depths (7.5&ndash, 9 km). Low stress drop release (average of 0.64 MPa) indicates a fluid-driven initiation mechanism of the sequence. We also evaluated the performance of the earthquake early warning systems running in real-time during the sequence, retrieving a minimum size for the blind zone in the area of about 15 km.

Background To evaluate the trends in AIDS detection and the AIDS-attributed death rate in Brazil between 2007 and 2015 and to determine the population characteristics associated with AIDS detection. Methods Surveillance data including demographics, mode of HIV transmission, AIDS cases, and AIDS-attributed deaths were analysed. A logistic regression model was fitted to assess the trends in AIDS cases by mode of HIV transmission throughout the study period. A segmented Poisson regression model was used to assess changes in the trends of AIDS detection and mortality rates before (2007–2014) and after (2015) the introduction of the Test and Treat Initiative. Results In the segmented Poisson regression, the decline in the AIDS detection rate from 2007 to 2014 was 2.0% annually (i.e., the odds ratio (OR) for annual decline was 0.98 (95% [CI: 0.98–1.00, p-value

Background This study was conducted to determine the seroprevalence of HIV among pregnant women in Brazil and to describe HIV testing coverage and the uptake of antenatal care (ANC). Methods Between October 2010 and January 2012, a probability sample survey of parturient women aged 15-49 years who visited public hospital delivery services in Brazil was conducted. Data were collected from prenatal reports and hospital records. Dried blood spot (DNS) samples were collected and tested for HIV.We describe the agespecific prevalence of HIV infection and ANC uptake with respect to sociodemographic factors. Results Of the 36,713 included women, 35,444 (96.6%) were tested for HIV during delivery admission. The overall HIV prevalence was of 0.38% (95% confidence interval [CI]: 0.31-0.48), and it was highest in: the 30 to 39 year-old age group (0.60% [0.40- 0.88]), in the Southern region of Brazil (0.79% [0.59-1.04]), among women who had not completed primary (0.63% [0.30-1.31]) or secondary (0.67% [0.49-0.97]) school education, and among women who self-reported as Asian (0.94% [0.28-3.10]). The HIV testing coverage during prenatal care was of 86.6% for one test and of 38.2% for two tests. Overall, 98.5% of women attended at least 1 ANC visit, 90.4% attended at least 4 visits, 71% attended at least 6 visits, and 51.7% received ANC during the 1st trimester. HIV testing coverage and ANC uptake indicators increased with increasing age and education level of education, and were highest in the Southern region. Conclusions Brazil presents an HIV prevalence of less than 1% and almost universal coverage of ANC. However, gaps in HIV testing and ANC during the first trimester challenge the prevention of the vertical transmission of HIV. More efforts are needed to address regional and social disparities. Introdução Este estudo foi realizado com o objetivo de determinar a soroprevalência do HIV entre as mulheres grávidas no Brasil e descrever a cobertura de exames de HIV e a integração dos cuidados pré-natais (CPN). Métodos Entre outubro de 2010 e janeiro de 2012, foi realizada uma pesquisa de probabilidade por amostragem direcionada a mulheres grávidas com idade entre 15 e 49 anos, que utilizaram serviços de parto em hospitais públicos do Brasil. Os dados foram coletados a partir de relatórios pré-natais e registros hospitalares. Amostras de sangue foram coletadas e submetidas a exames de HIV. Descrevemos a prevalência da infecção pelo HIV específica de acordo com a idade e a absorção dos CPN em relação a fatores demográficos. Resultados Das 36.713 mulheres incluídas, 35.444 (96,6%) foram submetidas a exames de HIV durante a admissão para o trabalho de parto. A prevalência global de HIV foi de 0,38% (intervalo de confiança [IC] de 95%: 0,31-0,48), e foi maior no grupo com a faixa etária entre 30 e 39 anos de idade (0,60% [0,40-0,88]), da região Sul (0,79% [0,59-1,04]), entre as mulheres com o ensino fundamental incompleto (0,63% [0,30-1,31]) ou ensino médio incompleto (0,67% [0,49-0,97]), e entre as mulheres que se identificam como asiáticas (0,94% [0,28-3,10]). A cobertura do exame de HIV durante os CPN foi de 86,6% para um exame e de 38,2% para dois exames. No geral, 98,5% das mulheres foram atendidas em pelo menos 1 consulta de CPN, 90,4% compareceram a pelo menos 4 consultas, 71% compareceram a pelo menos 6 visitas, e 51,7% receberam CPN durante o 1o trimestre. A cobertura de exames de HIV e os indicadores de captação de CPN aumentaram de forma proporcional ao aumento da idade e do nível de educação, e foram maiores na região Sudeste. Conclusões O Brasil apresenta uma prevalência de menos de 1% e cobertura praticamente universal de CPN. No entanto, as lacunas nos exames de HIV e CPN durante o primeiro trimestre representam um desafio à prevenção contra a transmissão vertical do HIV. São necessários mais esforços a fim de reduzir as disparidades regionais e sociais.

BACKGROUND:The objective of the present study is to review the literature regarding the management of fertile patients under lithium treatment for bipolar disorder and to report the experience of our Teratology Information Service over the past thirteen years in managing women treated with lithium during preconception, pregnancy and breastfeeding. METHODS:This research focuses on a selective review of the literature and a retrospective survey has been carried out on fertile women under lithium treatment who called our service at A. Gemelli University Hospital in Rome from May 2002 to December 2015. RESULTS:A total of 140 women under lithium treatment called our TIS. A complete follow-up has been performed on 34 patients: 29 called during pregnancy and 5 called during preconception. None of the patients called during breastfeeding, while half of the patients were taking concomitant drugs during pregnancy. One major cardiac malformation (hypoplastic left heart syndrome) has been reported. No minor malformations have been detected. Twenty-one patients delivered a living child, with one premature neonate. Two patients underwent voluntary interruption of pregnancy and six patients had early spontaneous abortion. In one patient, intrauterine growth retardation occurred, but with no adverse neonatal outcomes. Four neonates experienced transient respiratory distress at birth. Two children developed mild to severe language delay, but normal motor development. CONCLUSIONS:Lithium treatment in fertile women is a very delicate topic, where risks and benefits of discontinuing therapy when women plan to become pregnant should be accurately evaluated. Thorough peri-conceptional counselling is crucial for the outcome of pregnancy and for maternal health status during preconception, gestation and breastfeeding.

Objectives To estimate the burden of tuberculosis (TB) in reported AIDS cases, to compare the characteristics of TB/HIV subjects with those without TB and to evaluate survival with or without TB in Brazil. Methods The data source was the linked database between AIDS (2011–2014) and TB (2011–2014) databases from the Notifiable Diseases Information System (SINAN). The sociodemographic, clinical, laboratory results and use of antiretroviral therapy (ART) data were compared by TB occurrence or not. Survival probability was estimated using the Kaplan-Meier method and associated factors were sought using Cox regression. Results The proportion of TB diagnosed from 2011 to 2014 among AIDS cases reported between 2006 and 2014 was 6.3%. Subjects coinfected with TB were predominantly male, older, with lower schooling, with lower CD4 count, higher viral load, and higher proportion of ART initiation than those without TB. 57.5% were diagnosed with HIV before TB, 38.2% as concurrent TB/HIV and 4.3% with TB before HIV. 16,466 reported TB cases were not found in the AIDS database, although registered as HIV-infected in the SINAN TB database between 2011 and 2014. Median survival for PLHIV was 581 days, with 582 for those without TB, significantly higher than 547 for those with TB (log-rank teste, p = 0,001). In the Cox multivariate analysis, male gender [aHR = 1.27 (CI 95% 1.22–1.33)], older age [aHR = 1.020 (CI 95% 1.019–1.022)] and TB coinfection [aHR = 1.97 (CI 95% 1.88–2.07)] were positively associated with adjusted hazard of death, whereas CD4 count 200–499 cells [aHR = 0.21 (CI 95% 0.20–0.22)] and receiving ART [aHR = 0.2 2(CI 95% 0.21–0.23)] reduced the risk of death. Conclusions HIV-infected subjects should be screened for TB at care entry, to minimize diagnosis and treatment delays when active TB is present or to increase the odds of being offered latent TB infection therapy to prevent TB. On the other hand, TB cases should be promptly tested for HIV. All those will contribute to reduce mortality among people living with AIDS.

Background In Brazil, due to the rapid increase in programmes for the prevention of mother-to-child transmission (PMTCT), routine programme data are widely available. The objective of this study was to assess the utility of programmatic data to replace HIV surveillance based on the antenatal care (ANC) surveillance survey (SS). Methods We analysed ANC SS data from 219 maternity service clinics. PMTCT variables were extracted from the ANC SS data collection form, which allowed us to capture and compare the ANC SS data and PMTCT HIV test results for each pregnant woman who completed the ANC SS. Both the PMTCT programme and the ANC SS tested for HIV using sequential ELISA and western blot for confirmation. We assessed the completeness (% missing) of the PMTC data included in the ANC SS. Results Of the 36,713 pregnant women who had ANC SS HIV tests performed, 30,588 also underwent PMTCT HIV testing. The HIV prevalence rate from routine PMTCT testing was 0.36%, compared to 0.38% from the ANC SS testing (relative difference −0.05%; absolute difference −0.02%). The relative difference in prevalence rates between pregnant women in northern Brazil and pregnant women central-west Brazil was −0.98 and 0.66, respectively. Of the 29,856 women who had HIV test results from both the PMTCT and ANC SS, the positive percent agreement of the PMTCT versus the surveillance test was 84.1% (95% confidence interval [CI]: 74.8–91.0), and the negative percent agreement was 99.9% (95% CI: 99.9–100.0). The PMTCT HIV testing uptake was 86.4%. The ANC SS HIV prevalence was 0.33% among PMTCT non-refusers and 0.59% among refusers, with a percent bias of −10.80% and a differential prevalence ratio of 0.56. Syphilis and HIV testing results were complete in 98% and 97.6% of PMTCT reports, respectively. The reported HIV status for the women at clinic entry was missing. Conclusions Although there were consistent HIV prevalence estimates from the PMTCT data and the ANC SS, the overall positive percent agreement of 84.1% falls below the World Health Organization benchmark of 94.7%. Therefore, Brazil must continue to reinforce data collection practices and ensure the quality of recently introduced rapid HIV testing before replacing the PMTCT data with surveillance techniques. However, some regions with better results could be prioritized to pilot the use of PMTCT data for surveillance.

Background There are many contradictions about pregnancy and fetal/neonatal outcomes after topical use of timolol alone or timolol in combination with other antiglaucoma medications. Methods Seventy-five pregnant women exposed to antiglaucoma medications were followed prospectively by phone interviews. 27 women used timolol as monotherapy, 48 women used timolol as a part of multidrug therapy. We selected a control group of 187 healthy pregnant women. Results Topical use of timolol alone or timolol in combination with other antiglaucoma medications does not influence pregnancy or fetal/neonatal outcomes. Conclusion Beta-blocker is the first choice treatment for glaucoma in pregnancy but, when necessary, multidrug therapy should not to be excluded.

Summary Introduction Megacystis is a condition of abnormal enlarged fetal bladder for gestational age, which is usually associated with urological malformations that may constitute a life-threatening condition for the baby. Objective The purpose of this study was to assess the prognostic and etiological criteria of fetal megacystis and to describe the neonatal outcome in a large series collected in a single tertiary center. Study design A retrospective observational study was conducted between 2008 and 2012. We reviewed all consecutive cases of fetal megacystis diagnosed during routine ultrasound (US) screening. The following data were collected and analyzed: maternal age, gestational age at diagnosis, prenatal ultrasonographic details of the urinary system, extra-urinary ultrasonographic anomalies, fetal karyotype, pregnancy outcome, postnatal diagnosis, and medical/surgical follow-up. Results Of the 25 fetuses included in this study, 76% were males. The mean gestational age (GA) at diagnosis was 23.1 ± 7.5 weeks (range 12–34), among them only four (16%) were diagnosed during the first trimester. Associated urological malformations were detected in 92% (n = 23) of the cases, while other malformations were detected in 36% (n = 9). Oligohydramnios or anyhydramnios were observed in 52% (n = 13) of the cases. Twelve (48%) fetuses were considered as having poor prognosis for renal function. Vesicocentesis with or without vesico-amniotic infusion were performed in 28% (n = 7) of the cases. Pregnancy outcome was surprisingly good, with only one case of prenatal death and survival rate of 96% (n = 24) of liveborn babies. Posterior urethral valve (PUV) (n = 9, 36%) was the most common etiology of the fetal megacystis, followed by persistent urogenital sinus (n = 2, 8%), Prune belly syndrome (n = 2, 8%) and bilateral vescico-ureteral reflux (VUR) (n = 2, 8%). Surgical or endoscopic procedures were performed in 75% (n = 18) of the cases. Six (24%) newborns presented with moderate/severe respiratory distress that requested invasive assisted ventilation. Three cases (n = 3, 12%) of perinatal death were observed due to severe impaired renal function. After a median follow-up of 29 months renal function was good in 79% (n = 19) of the cases. Conclusions Fetal megacystis may underline a wide range of associated pathologies with the highest prevalence of urinary malformation. Optimal counseling of the involved parents requires a multidisciplinary approach to allow the best management during the pregnancy and the perinatal period. Despite the high risk of renal failure, lung hypoplasia, and severe associated anomalies, the outcome of fetuses with megacystis could be improved thanks to an appropriate perinatal diagnosis and neonatal management.

We present the results of a feasibility study of an earthquake early warning system (EEWS) for the Campania region (southern Italy) using schools as specific targets. The study considered the seismogenic zones as sources of potential earthquakes for the area, the Italian accelerometric network as the recording network for seismic event occurrence, and the performances of the software platform PRESTo Plus for data analysis and processing. We analyze the distribution of lead-times for all possible threatening seismic sources for each municipality in the region under study by extracting the lead-time value corresponding to the 5th, 10th and 25th percentiles of the distributions. We discuss the results for the 5th percentile in order to analyze the worst-case scenario: in the case of a single site, the lead-time is expected to be larger than this value in the 95 % of the cases. Since the population distribution in Campania is uneven and most of the people live nearby the coast, whilst the most destructive earthquakes occur along the Apennine chain, we can conclude that an efficient EEWS can allow most of the schools in the area to undertake some mitigating actions. The testing of the EEWS was carried out in the high school ITIS ‘E. Majorana’, located at Somma Vesuviana, about 80 km from the seismogenic Irpinia region. For this purpose, the Sentinel, an actuator made up of low-cost hardware (i.e., Arduino®), was developed in close cooperation with students and teachers of the school to receive alert messages from the PRESTo Plus platform and warn the school users in case of a seismic event. The EEWS and the Sentinel were successfully tested during some blind drills performed during normal school activities.

A new strategy for a P wave-based, on-site earthquake early warning system has been developed and tested on Japanese strong motion data. The key elements are the real-time, continuous measurement of three peak amplitude parameters and their empirical combination to predict the ensuing peak ground velocity. The observed parameters are compared to threshold values and converted into a single, dimensionless variable. A local alert level is issued as soon as the empirical combination exceeds a given threshold. The performance of the method has been evaluated by applying the approach to the catalog of Japanese earthquake records and counting the relative percentage of successful, missed, and false alarms. We show that the joint use of three peak amplitude parameters improves the performance of the system as compared to the use of a single parameter, with a relative increase of successful alarms of about 35\%. The proposed methodology provides a more reliable prediction of the expected ground shaking and improves the robustness of a single-station, threshold-based earthquake early warning system.

Context: Many women of reproductive age and pregnant women require diagnostic tests involving ionizing radiation. Fetal exposure to radiation worries both the patient and the obstetricians and could lead to inappropriate termination of pregnancy. Evidence Acquisition: To conduct this review of the literature Pub-med was searched. Retrospective studies, reviews of literature, multicentric epidemiological case control studies were reviewed. Official data base Reprotox and The Teratogen Information System Teris were also consulted. Results: Standard diagnostic X ray tests including those of the lower abdomen imply that the dose absorbed by the uterus is in any case less than 0.05 Sv ( = 5 rad). The majority of the studies in literature estimates that 1-2 rad fetal exposure may increase the risk of leukemia of 1.5 - 2.0 over the natural incidence, meaning that 1 in 2,000 children exposed to ionizing radiation in utero will develop leukemia in childhood. Conclusions: At present, no single diagnostic procedure is able to cause damage to the embryo or fetus. There are possible harmful effects for doses above 0.2 - 0.25 Gy (20-25 rad).

Objectives To evaluate the natural history of cystic hygroma (CH) in fetal and neonatal periods to enrich parental counselling. Ultrasonographic characteristics, associated syndromes, chromosomal anomalies, fetal cardiac pathology and life after birth were considered. Study design From May 1985 to September 2010, 207 pregnancies were seen the authors’ centre with suspected vascular–lymphatic fetal malformation: 156 of them had CH. Cases were followed up by telephone interview to determine fetal and neonatal outcomes. Chi-squared test was used for statistical analysis. Results Among the 156 cases of CH, the condition was septated in 75% of cases, associated with other pathologies in 74%, and retronuchal in 88%. Intrauterine regression was seen in 36% of cases, with complete disappearance in 77%. The karyotype was normal in 55% of cases. Follow-up was completed in 85 cases and revealed 54 spontaneous abortions (63%) and 31 live births (37%). Amongst these, 21 out of 31 children had a favourable outcome (68%). A negative embryo–fetal outcome was significantly associated with CH being associated with other pathologies, such as hydrops, retronuchal position and altered karyotype. Spontaneous regression or resolution of CH was associated with live births. Conclusions The management of pregnancies with a diagnosis of fetal CH requires knowledge of natural history of the malformation for appropriate parental counselling.

Spontaneous heterotopic pregnancy is a rare clinical condition in which intrauterine and extrauterine pregnancies occur at the same time. The occurrence of an ovarian heterotopic pregnancy is a singular event as it comprises only 2.3% of all heterotopic pregnancies, extremely rare among women who conceive naturally. A case of a 28-year old patient was treated for spontaneously conceived heterotopic pregnancy. The patient was admitted to our center with lower abdominal pain and amenorrhoea. A transvaginal ultrasound scan showed an ovarian and an intrauterine heterotopic pregnancy. This was managed laparoscopically. Considering spontaneous pregnancies, every physician treating women of reproductive age should be aware of the possibility of heterotopic pregnancy. It can occur in the absence of any predisposing risk factors; only with an early diagnosis and treatment the intrauterine pregnancies will reach viability with a great chance of a favorable obstetric outcome.

A great number of newborns with spina bifida now survive with a growing life expectancy. Support with regard to sexual issues is essential in the management of adolescents with spina bifida, who require specific knowledge of sexual problems related to their disability. Women with spina bifida are usually fertile and need pre-conception counseling. Furthermore, compared to healthy women they have a higher chance of conceiving a child with spina bifida, so they are treated with periconceptional folic acid supplements. In addition pregnancies in women with spina bifida require adequate management of secondary conditions, mainly urological issues, which are exacerbated during pregnancy. This article gives an overview of sexual education, sex functioning and sexual activity among adolescents with spina bifida. Moreover, we aim to support young women with spina bifida, providing pre-conception counseling and practical guidelines essential for the urological management of their pregnancy.

Management of ischemic heart disease in pregnant women is still difficult, as there is little experience with many of the newer treatments such as clopidogrel. The safety of clopidogrel in pregnancy is unknown, especially in combination with aspirin. Its use during gestation has been described in a few case reports. We describe the case of a 36-year-old woman in her 9th week of pregnancy with a history of chronic hypertension, dyslipidemia and CAD, who required antiplatelet treatment. Clopidogrel and aspirin were administrated until one week before delivery and a healthy child was born at 36 weeks of pregnancy by caesarean section, without any complication.

To investigate the possibility that antinuclear antibodies (ANA) are involved in recurrent pregnancy loss (RPL).Case-control study carried out on 294 women (194 cases and 100 controls) in two University hospitals. The presence, the serum titers and the indirect immunofluorescence (IIF) patterns of ANA were determined in women with RPL and in control women.Antinuclear antibodies at titers ≥ 1:80 were detected in 97 (50%) women with RPL and in 16 (16%) control women. Elevated ANA titers (≥1:180) were detected only in RPL women, whereas all control women had ANA titers no greater than 1:80. No differences could be detected in the IIF patterns between RPL and control women. No differences in ANA positivity could be detected according to the type (primary or secondary) or number (2 versus ≥3) of losses.ANA could be of some value in identifying women with RPL with potential, although still not fully defined, immune abnormalities.

Objective Heparin-binding epidermal growth factor–like growth factor (HB-EGF) plays a role in blastocyst implantation and is down-regulated in preeclampsia and in hypertensive pregnancy disorders associated with defective extravillous trophoblast invasion. Defective placentation and severe preeclampsia are also features of the antiphospholipid syndrome (APS). The purpose of this study was to investigate whether abnormal HB-EGF expression plays a pathogenic role in antiphospholipid antibody (aPL)–mediated defective placentation. Methods HB-EGF expression in placental tissue was evaluated by Western blotting and messenger RNA analysis in normal and APS placentae. Polyclonal IgG fractions or monoclonal β2-glycoprotein I–dependent aPL and their respective controls were investigated for the following 4 features: their binding to human trophoblast monolayers, as determined by cell enzyme-linked immunosorbent assay (ELISA); their effect on HB-EGF expression by Western blotting in trophoblast cell extracts as well as by ELISA as a protein secreted in the culture supernatants; their inhibitory effect on in vitro trophoblast invasiveness, as evaluated by Matrigel assay; and their inhibitory effect on matrix metalloproteinase (MMP) levels, as measured by gelatin zymography. Experiments were also performed in the presence of serial concentrations of heparin or recombinant HB-EGF. Results Placental APS tissue displayed reduced expression of HB-EGF. Polyclonal and monoclonal aPL bound to trophoblast monolayers and significantly reduced the in vitro synthesis and secretion of HB-EGF. Heparin inhibited aPL binding and restored HB-EGF expression in a dose-dependent manner. Addition of recombinant HB-EGF reduced the in vitro aPL-induced inhibition of Matrigel invasiveness as well as MMP-2 levels. Conclusion These preliminary findings suggest that the reduction of aPL-mediated HB-EGF represents an additional mechanism that is responsible for the defective placentation associated with APS and that heparin protects from aPL-induced damage by inhibiting antibody binding.

To evaluate, in pregnant women at high risk for gestational diabetes (GDM), the longitudinal changes of adiponectin, carbohydrate and lipid metabolism, and to assess their independent value as risk factors for the development of GDM. Fifty women at beginning of pregnancy were studied. Adiponectin, insulin sensitivity (homeostasis model assessment, HOMA) and lipid panel were measured at 1st, 2nd and 3rd trimesters of pregnancy. Twelve patients developed GDM. In both groups, GDM and normal glucose tolerance (NGT), adiponectin decreased from 1st to 2nd and 3rd trimesters by about 5 and 20% (GDM, p0.05), and of about 17 and 25% in NGT (p0.05), respectively. Values observed in NGT were similar to those of GDM (F = 9.401; p = 0.238). The Cox regression model identified as the strongest independent risk factor for GDM HOMA over 1.24 (RR = 14.12) at 1st trimester, fasting glycaemia over 87 mg/dl (RR = 42.68) triglycerides over 158 mg/dl (RR = 5.87) and body mass index (BMI) over 27 kg/m(2) (RR = 4.38) at 2nd trimester. Adiponectin in high-risk women is characterised by a constant reduction throughout gestation, irrespective of the development of GDM. HOMA, fasting glycaemia, triglycerides and BMI, but not adiponectin are independent predictors of GDM.

Objective The aim of this study was to evaluate if the Internet provides evidence-based information to women seeking information about teratogenic risk factors and women's risk perception. Furthermore, we evaluated the possible risk related to teratogen exposure in the study sample and analysed age, gravidity, educational level, geographic location, marital status and type of exposure compared to a control group made up of women who did not use the Internet to search for teratogen-related information. Study design Between October 2008 and June 2009, a questionnaire was administered to pregnant women calling our Teratology Information Service concerning a suspected teratogenic exposure. Results Fifty-seven percent ( n = 116) of callers had used the Internet to find medical information about their exposure, while 43% ( n = 87) had not. Internet users had a medium-high level of education and consulted the Internet because of its convenience, usually early in their pregnancy. We verified the accuracy of the information the women obtained from the Internet and found that 59.5% ( n = 69) of women received evidence-based answers; 18.1% ( n = 21) were informed that their exposure was dangerous when it was not; 4.3% ( n = 5) were wrongly reassured; and the rest ( n = 18) were not able to interpret the data they found or found no relevant information. Conclusions Internet use during pregnancy is a widespread phenomenon as the Internet offers the opportunity to share apprehensions and doubts with other women, but it can often lead to increased and unjustified anxiety. Medical information published on websites cannot be considered a substitute for informed medical advice, and patients should not take any action before consulting with a health care professional.

To report about a case of complicated late postpartum eclampsia where neonatal low birth weight could be considered a predictive factor of placental sufferance.A 25-year-old woman, without medical or familiar history for hypertension or cerebrovascular diseases, underwent a normal spontaneous delivery with neonatal birth weight of 2340 g (9th percentile). Eight days later the patient presented sudden headache and generalized tonic-clonic seizures.Blood hypertension and alterations in laboratory studies were detected; a diagnosis of late postpartum eclampsia was made. A CT scan showed subarachnoid hemorrhage (Hunt and hess grade I, Fisher grade III). Serial cerebral angiograms did not show any intracranial vascular malformations; epilepsy and hypertension were successfully medically treated; and a repeat CT examination showed the gradual resolution of subarachnoid hemorrhage. Headache progressively disappeared.Low neonatal birth weight could be linked to placental dysfunction and considered as a predictive factor for the onset of postpartum preeclampsia/eclampsia. We recommend a careful clinical and laboratory management of puerperium up to the first month postpartum, in particular in cases of "sine causa" neonatal low birth weight.

All the recent data about the physiology of the fetus and its active role into the womb allow us to consider the fetus as a biological protagonist in the intrauterine environment. This capacity can be detected during both the embryonic and the fetal period. The pre-implantation blastocyst is biologically autonomous, because it can provide nutriments for itself during the trip from the oviduct to the site of implantation [1] and has an active role in the choice of the implantation site [2].

Rubella is the first virus demonstrated as a teratogen. There is a high risk to develop congenital rubella syndrome (CRS) if the infection occurs in the first part of pregnancy, particularly in women without specific immunological protection. Specific therapies to prevent CRS are not available. Many developed countries have specific vaccination programs and maternal rubella is rare. However, in developing countries or where campaigns of rubella surveillance and preconceptional vaccination are inadequate, there are still cases of CRS registered despite primary possibilities of prevention. Maternal infection is not indicative of vertical transmission in 100% of cases, and damage does not necessarily occur in all cases of fetal infection. This is the reason why an adequate prenatal counselling is mandatory, particularly in cases of proven maternal infection. Advanced prenatal diagnostic techniques, invasive or not, should be offered to the women especially in order to distinguish the cases without fetal damage. Prevention of voluntary interruption of pregnancy for the latter or in case of maternal false IgM rubella antibody positivity or IgM "chronic carrier" patients is mandatory. World wide, the aim is to perform an adequate primary prevention through vaccination of childbearing age women without specific immunological protection.

The authors report a positive experience in controlling severe postpartum hemorrhage after cesarean section performed for placenta praevia by using an inflated intrauterine balloon and avoiding any further invasive surgery.

Cancer complicates approximately 1 in 1000 pregnancies. In pregnancy management, whether the benefits outweigh the risks derived from therapy must be carefully considered.Thirty-two pregnant patients with the diagnosis of malignancy were followed. The indications and timing for surgery, chemotherapy, radiotherapy or delayed treatment were decided according to the malignancy characteristics and gestational age. The patient's consent was obtained before every decision.The rate of live births, premature deliveries, foetal abnormalities and neonatal deaths was 97%, 82%, 9% and 3%, respectively. Three women (9%) died during puerperium because of disease progression.The cancer treatment took into full consideration the specific condition of each pregnant patient. A good rate of live births was observed, even if a high rate of preterm delivery occurred. The management of malignancy required a team of experts in order to optimise every available choice for maternal health and neonatal well-being.

OBJECTIVES. We sought to verify the association between maternal intrahepatic cholestasis of pregnancy (ICP) and neonatal respiratory distress syndrome (RDS) and to determine how bile acids levels alter the risk of developing neonatal RDS. METHODS. We extracted data from our divisional database about all of the newborns born during the years 2000–2004. We compared 77 neonates born from pregnancies complicated by ICP with 427 neonates in the same range of gestational age born from noncomplicated pregnancies. We studied maternal bile acids levels immediately before delivery in mothers with ICP and measured bile acid levels during the first 24 hours of life in their newborns. RESULTS. The incidence of RDS in newborns from cholestatic pregnancies was twice that the reference population (28.6% vs 14%). The multivariate analysis showed that the risk of RDS in these newborns was ∼2.5 times higher than in control infants. Within the ICP group, maternal and neonatal bile acid levels of infants affected by RDS were not significantly higher than those of healthy infants. The multivariate analysis showed that a low gestational age was the most important risk factor, but the probability of respiratory distress syndrome also increased by 2‰ for every additional micromole of the interaction term “neonatal by maternal bile acids level.” CONCLUSIONS. Maternal ICP is significantly associated with the occurrence of RDS in the newborn. We hypothesize that bile acids can produce surfactant depletion in the alveoli reverting the reaction of phospholipase A2. This hypothesis could potentially be confirmed by bronchoalveolar lavage study.

Objective To determine pregnancy and neonatal outcome after the failure of levonorgestrel as an emergency contraceptive. Design A retrospective observational cohort study. Setting Telephone consultations concerning reproductive risk factors conducted by Telefono Rosso-Teratology Information Service, Catholic University of Sacred Heart, Rome, Italy. Patient(s) Women exposed to levonorgestrel (36 cases) compared with a control group (80 cases). Intervention(s) Teratological counseling. Main Outcome Measure(s) The rate of congenital anomalies, the prepartum or peripartum complications, and the pregnancy outcomes. Result(s) Twenty-five exposed newborns with length and weight identical to that of the control group were shown to be without increased risk of congenital malformation. No statistical differences were observed in terms of spontaneous or legal abortion and pregnancy and neonatal complications, and there was no ectopic pregnancy in either group. Conclusion(s) Although the sample size was small, in our experience, the failure of levonorgestrel as an emergency contraceptive was not associated with an increased risk of major congenital malformations, prepartum or peripartum complications, or an adverse pregnancy outcome.

Leflunomide is a pyrimidine synthesis inhibitor with proven teratogenic and fetotoxic effects in animal studies, and its active metabolite is detectable in plasma up to 2 years after discontinuation of the drug.1–3 For this reason the fetus could have in utero exposure to leflunomide up to 2 years after the end of treatment unless an oral cholestyramine regimen, 8 g three times daily for 11 days, is administered to obtain undetectable plasmatic levels.1–3 Leflunomide has been classified as pregnancy category X by the Federal Drug Administration and the manufacturer recommends that for women of childbearing age “treatment with leflunomide must not be started until pregnancy is excluded and it has been confirmed that reliable contraception is being used”.1,4 Label instructions about paternal exposure recommend a …

Background: Antiphospholipid antibodies reacting with s2-glycoprotein I (s2GPI) have been associated with recurrent fetal loss and pregnancy complications. Objective: To investigate whether specific mutations in the phospholipid binding site of s2GPI might affect its binding to trophoblast and in turn the anti-s2GPI antibody induced functional effects. Methods: s2GPI adhesion to trophoblast was evaluated as human monoclonal IgM or polyclonal IgG anti-s2GPI antibody binding to trophoblast monolayers cultured (1) in complete medium; (2) in serum-free medium; (3) after serum starvation in the presence of purified human s2GPI; or (4) in the presence of s2GPI with single or multiple mutations in the amino acid loop Cys281-Lys-Asn-Lys-Glu-Lys-Lys-Cys288. The effect of anti-s2GPI binding to trophoblast was evaluated as chorionic gonadotropin (hCG) mRNA expression, and protein release by RT-PCR and radioimmunoassay, respectively. Results: s2GPI adhesion to trophoblast and its consequent recognition by the specific antibodies were inversely proportional to the mutation number in the phospholipid binding site. Anti-s2GPI antibodies reduced gonadotropin release, hormone dependent hCG mRNA expression, and protein synthesis in the presence of s2GPI, while the addition of the mutants or the absence of s2GPI had no effect. Conclusions: s2GPI binds to trophoblast in vitro through its fifth domain, as reported for endothelial cells, and can be recognised by anti-s2GPI antibodies; the antibody binding downregulates trophoblast hCG synthesis and secretion. Such a mechanism might contribute to defective placentation in women with fetal loss associated with the antiphospholipid syndrome.

Objective: To examine the effect of antiphospholipid antibodies on trophoblast expression of adhesion molecules. Design: Primary cytotrophoblast cell cultures. Setting: Department of Obstetrics and Gynecology, Catholic University, Rome, Italy. Patient(s): Five normal pregnant women underwent uncomplicated vaginal delivery at 36 weeks of gestation. Intervention(s): IgG antibodies were isolated from a patient with antiphospholipid syndrome and from a normal control subject, using protein-G Sepharose columns. Cytotrophoblast cells were dispersed in bicarbonate buffer containing trypsin and DNAse I. Main Outcome Measure(s): We investigated the effects of antiphospholipid antibodies on trophoblast adhesion molecules (α1 and α5 integrins, E and VE cadherins), both at the protein and mRNA levels. Result(s): The α1 and α5 integrins were present in trophoblast cells from 24 hours of culture. Treatment with IgG that were obtained from the patient with antiphospholipid syndrome significantly decreased α1 integrin and increased α5 integrin at both the mRNA and protein levels. Furthermore, IgG with antiphospholipid antibodies activities induced VE-cadherin down-regulation and the E-cadherin up-regulation at protein and mRNA levels compared with control IgG or untreated cells. Conclusion(s): The results suggest that the inadequate trophoblastic invasion, induced by antiphospholipid antibodies, can be the result of abnormal trophoblast adhesion molecules expression.

The pathogenic role of anti-annexin V antibodies remains unclear. Anti-annexin V antibodies are frequently associated with higher incidences of intrauterine fetal loss, preeclampsia, and arterial and venous thrombosis. The present study investigated the in vitro ability of anti-annexin V antibody to bind human trophoblast cells, to affect trophoblast gonadotropin secretion and invasiveness, and to induce placental apoptosis. Cytotrophoblast cells were dispersed in Ringer bicarbonate buffer containing trypsin and DNase I, filtered, and layered over a Percoll gradient in Hanks balanced salt solution. In the case of monoclonal anti-annexin V antibody, the highest binding was found when the cells displayed the greatest amount of syncytium formation. Anti-annexin V antibody, but not its negative control, induced trophoblast apoptosis and significantly reduced trophoblast gonadotropin secretion. These findings suggest that recognition by anti-annexin V antibody of adhered annexin V on trophoblast cell structures might represent a potential pathogenic mechanism by which these antibodies can cause defective placentation.

A 25 year-old patient in her third pregnancy presented with acute polyhydramnios at 24 weeks' gestation, which was the same time as in the two previous pregnancies. In both she had preterm premature rupture of membranes, preterm delivery and neonatal deaths. In the third pregnancy, amnioreductions combined with medical treatment resulted in the birth by Caesarean section of a normally formed live male at 31 weeks of pregnancy. Acute recurrent polyhydramnios is an extremely rare condition of unknown aetiology. We hypothesized that amniotic prolactin plays a role in this pathology. It was measured serially in amniotic fluid and high levels were found.

Antiphospholipid antibodies (aPL) are associated with poor obstetric outcome, such as recurrent abortions, fetal death, growth retardation, and early preeclampsia (1). Passive transfer of whole immunoglobulin fractions from aPL-positive sera has been found to induce fetal loss and growth retardation in pregnant naive mice, suggesting a direct pathogenetic role (2–4). Although it has been assumed that aPL are directed against anionic PL, current advances in the field suggest that antibodies to PL-binding plasma proteins, such as β2-glycoprotein I (β2GPI), can be detected in standard aPL assays (5). Antibodies specific for β2GPI have been identified and found to be associated with the clinical manifestations of the antiphospholipid syndrome (APS) (6–22). The in vivo immunohistologic demonstration of β2GPI on trophoblast surfaces (23,24) and the induction of fetal loss by anti-β2GPI antibodies in experimental animal models (25,26) suggested a role of anti-β2GPI antibodies in fetal loss. Moreover, even murine and human aPL monoclonal antibodies (mAb) specifically reacting with anionic PL in the absence of any plasma cofactor have been shown to produce fetal loss, growth retardation, placental deposition, and necrosis in experimental animal models (3,27,28). Although experimental models have emphasized the role of thrombotic phenomena in placental tissue (4,27), studies in humans have shown that thrombotic events cannot account for all of the histopathologic findings in placentae from women with the APS (29,30). The possibility of direct villous and extravillous trophoblastic damage by aPL through the recognition of phosphatidylserine (PS) exposed during syncytium formation has been suggested (31). Reported direct effects of aPL on trophoblasts have included inhibition of the intercytotrophoblast fusion process (31), of human chorionic gonadotropin (hCG) or placental lactogen secretion (31,32), and/or of trophoblast invasiveness (31). Furthermore, whole IgG fractions from APS patient sera or xenogenic murine anti-PS mAb have been shown to displace annexin V from trophoblasts (and endothelial cell surfaces in the case of human IgG), thus creating conditions favorable to procoagulant state in vitro (31,33). The purpose of the present study was to investigate the in vitro ability of IgG from sera containing high levels of aPL to bind human trophoblast cells and to affect hCG secretion and invasiveness. Furthermore, to identify whether specific effects were related to individual antibody subpopulations, human mAb reacting with β2GPI or with anionic PL in the absence of any plasma cofactor were investigated for their ability to reproduce the binding to trophoblast cell membranes and the modulation of hormone secretion as well as invasiveness. From our results, it appears that trophoblast cells might represent one target for circulating aPL reacting with β2GPI and/or with “pure” anionic PL (whose binding is independent of any plasma cofactor) and that such antibodies affect trophoblast differentiation–related activities.

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

To elucidate the mechanism of metabolic adaptation of women with polycystic ovary syndrome (PCOS) during pregnancy, the endocrino-metabolic features of a group of PCOS patients with or without gestational diabetes were studied longitudinally during the three trimesters of gestation. Oral glucose tolerance test (OGTT, 100 g) and hyperinsulinaemic-euglycaemic clamp were performed throughout the study. Plasma concentrations of insulin and glucose were determined by radioimmunoassay and glucose oxidase technique, respectively. Five of 13 PCOS patients developed gestational diabetes (GD) at the third trimester (PCOS-GD), while the other eight patients did not develop any alteration of glucose metabolism (PCOS-nGD). Both fasting glucose and insulin plasma concentrations did not change significantly during pregnancy and no difference was seen between the two groups. On the contrary PCOS-GD group early exhibited higher values of area under the curve (AUC) for glucose and insulin response to OGTT with respect to those found in PCOS-nGD group. This difference was already significant in the first gestational trimester. Moreover insulin sensitivity value (M) was significantly lower in the first trimester of gestation in PCOS-GD as compared with that found in PCOS-nGD group. However, as gestation proceeded, M value decreased in PCOS-nDG group and the difference from PCOS patients developing gestational diabetes was not sustained into the second and third trimesters. Both groups had similar body mass index values and AUC insulin increase from first to third trimester of gestation. It is concluded that early alteration of insulin sensitivity and secretion constitute specific risk factors in PCOS patients for the development of abnormalities of glucose tolerance.

This study aims at observing and comparing the antigen expression of some fetal T- and B-lymphocyte subpopulations in Rh-isoimmunization, which determines anemic hypoxia in the fetus, and nonimmune fetal hydrops (NIFH) which, even if there are some etiological factors involved, causes hipoxic hypoxia in the fetus. Twelve fetuses were studied by way of 30 fetal blood samples obtained by ultrasound-guided cordocentesis between the 20th and 36th gestational week. Twenty-four blood samples in all where taken from the eight fetuses with Rh-isoimmunization. Six blood samples were obtained from the four fetuses with NIFH. The lymphocyte phenotypes studied by monoclonal antibodies and flow cytometry were the following: CD3, CD4, CD8, expression of T-lymphocyte subpopulations; BsIg, CD19, expression of B-lymphocyte subpopulations. We observed a near-normal maturation process in fetuses with Rh isoimmunization, whereas in fetuses with NIFH we observed inhibition and/or delayed expression of T-lymphocytes. An early and increased B-lymphocyte activation marked a cooperation between the two systems in the early gestational periods.

Objective: To evaluate the influence of body mass on the hypothalamic-pituitary-adrenal (HPA)-axis response to naloxone in polycystic ovary syndrome (PCOS). Design: Controlled clinical study. Setting: Academic research environment. Patient(s): Ten lean and 10 obese women with PCOS compared with 7 lean and 8 obese control subjects matched for body mass index. Intervention(s): Each patient received an IV bolus of naloxone at a dosage of 125 μg/kg. Main Outcome Measure(s): Samples were collected 30 minutes before and 0, 15, 30, 60, 90, and 120 minutes after injection: ACTH and cortisol levels were measured in all plasma samples. Result(s): No significant differences were found in the ACTH and cortisol responses to opioid blockade between lean women with PCOS and lean as well as obese control subjects; conversely, obese patients with PCOS showed a higher ACTH and cortisol responses to naloxone compared with all other groups. Conclusion(s): Hypothalamic-pituitary-adrenal–axis abnormalities of PCOS may be central in origin and abdominal obesity seems to play a key role in the HPA-axis hyperactivity of women with PCOS when naloxone is administered.