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Worldwide, 98% of stillbirths occur in low-income countries (LIC), where stillbirth rates are ten-fold higher than in high-income countries (HIC). Although most HIC stillbirths occur prenatally, in LIC most stillbirths occur at term and during labor/delivery. Conditions causing stillbirths include those of maternal origin (obstructed labor, trauma, antepartum hemorrhage, preeclampsia/eclampsia, infection, diabetes, other maternal diseases), and fetal origin (fetal growth restriction, fetal distress, cord prolapse, multiples, malpresentations, congenital anomalies). In LIC, aside from infectious origins, most stillbirths are caused by fetal asphyxia. Stillbirth prevention requires recognition of maternal conditions, and care in a facility where fetal monitoring and expeditious delivery are possible, usually by cesarean section (CS). Of major causes, only syphilis and malaria can be managed prenatally. Targeting single conditions or interventions is unlikely to substantially reduce stillbirth. To reduce stillbirth rates, LIC must implement effective modern antepartum and intrapartum care, including fetal monitoring and CS., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives-The nonstress test is currently the most widely used modality for antenatal surveillance in twin pregnancies, with a quoted false-positive rate of 11%-12%. Our objective was to report our experience with the sonographic portion of the biophysical profile in twin pregnancies as the primary screening modality.Methods-Women with twin pregnancies delivered by a single maternal-fetal medicine practice from 2005 to 2013 were included. We excluded monoamniotic twins. Twin pregnancies began weekly sonography for the biophysical profile starting at 32 to 33 weeks, or earlier if indicated. The nonstress test was performed if the sonographic biophysical profile score was less than 8 of 8. We reviewed biophysical profile scores and outcomes for all patients who delivered at 33 weeks or later to assess the false-positive rate for the biophysical profile, as well as the incidence of intrauterine fetal death (IUFD) after initiation of antenatal surveillance.Results-A total of 539 twin pregnancies were included. The incidence of IUFD per patient was 2 per 539 (0.4%; 95% confidence interval [CI], 0.1%-1.3%), and the incidence of IUFD per fetus was 2 per 1078 (0.19%; 95% CI, 0.05%-0.7%). The overall positive screen rate was 24 per 539 (4.45%; 95% CI, 3.0%-6.5%). The false-positive screen rate, defined as an abnormal biophysical profile that did not diagnose an IUFD or lead to delivery, was 10 per 539 (1.9%; 95% CI, 1.0%-3.4%).Conclusions-In twin pregnancies the use of the sonographic biophysical profile for routine antenatal surveillance has a low false-positive rate, with a very low incidence of IUFD. The sonographic biophysical profile should be considered as a primary mode for antenatal surveillance in twin pregnancies, with a reflex nonstress test for an abnormal score., (© 2015 by the American Institute of Ultrasound in Medicine.)

Bovine tritrichomonosis is a sexually transmitted disease caused by the protozoon Tritrichomonas foetus and characterised by embryonic-death and abortion. During pregnancy, the processes of cell proliferation and death play a crucial role for blastocyst implantation and the subsequent maintenance of early pregnancy, and their misbalance may lead to the abortion. In this study, we aimed to investigate whether cell proliferation and death may be altered during tritrichomonosis. For this purpose, we used pregnant BALB/c mice as an alternative experimental animal model that has successfully reproduced the infection. We analysed the immunohistochemical expression of active caspase-3 and proliferating cell nuclear (PCNA) antigens in the endometrium of infected mice. We found an increase in the number of caspase-3 positive cells in infected mice that were not pregnant at the necropsy. Besides, the number of positive proliferating cells increased in the uterine luminal epithelium of infected animals killed at 5-7 days post coitum (dpc). Pregnant infected mice killed at 8-11 dpc showed higher proliferation than control animals. We suggest that the cytopathic effect induced by T. foetus in the uteri of infected mice may induce the apoptosis of the epithelial cells and, as a result, promote a compensatory proliferative response. The information described here will be helpful to further study the pathogenesis of the bovine tritrichomonosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: With advances in therapy, more neonates with severe congenital anomalies are surviving, albeit some with neurologic disorders, possibly related to antenatal low brain blood flow. This autopsy series reports antenatal brain injury in neonates expiring due to severe anomalies, and provides correlation with umbilical cord blood gas and acid-base analysis., Methods: We identified autopsies of third trimester neonates expiring shortly following delivery due to severe anomalies or malformations. Brain injury classified as "older" included periventricular leukomalacia, gliosis and karyorrhectic neurons, and "recent" included red neurons and reactive glial changes., Results: We identified 22 cases (nine term, 13 preterm). 16 (73%) had brain injury, including 11 with older injury. Cord arterial blood was analyzed in 17, and six had pH <7 or base deficit >12 mmol/L. Four out of 5 (80%) neonates with neuronal necrosis compared to two out of 12 (17%) without had a pH <7 or base deficit >12 mmol/L (p = 0.03). Five out of nine (56%) neonates with white matter injury compared to one out of 8 (13%) without had pH <7 or base deficit >12 mmol/L (p = NS)., Conclusions: Antenatal brain injury is frequent in neonates with severe congenital anomalies. Severely abnormal cord blood analysis results correlate significantly with neuronal necrosis and show a trend toward white matter injury; however, the absence of these abnormal results does not preclude the presence of brain injury.

Objective: To report a recent update on fetuses with right-sided congenital diaphragmatic hernia (RCDH) in the era of fetal surgery., Design: Retrospective review of prospectively collected data., Setting: Fetal treatment centres in Leuven and Barcelona., Population: Consecutive cases of RCDH between 2002 and 2012., Methods: Data on prenatal imaging, genetic testing, pregnancy and neonatal outcomes were extracted from our databases, including structural and genetic anomalies, candidate outcome predictors such as lung size, liver herniation ratio, polyhydramnios, cervical length, preterm prelabour rupture of membranes and gestational age at birth., Main Outcome Measures: Survival and oxygen dependency at discharge., Results: Ten out of 86 fetuses with RCDH had associated abnormalities. Of 76 isolated pregnancies, eight women opted for termination of pregnancy, most with severe hypoplasia and one was lost to follow up. Nineteen pregnancies were expectantly managed and delivered at a mean gestational age of 36.0 ± 3.0 weeks. Survival at discharge was 53% (10/19), one being oxygen dependent. In the fetal surgery group (n = 48), mean gestational age at delivery was 34.5 ± 3.0 weeks. In our recent experience not previously published (n = 23) survival rate was 52 and 39% were oxygen dependent at discharge. Pooling these data with earlier reported observations by our group we observed a 42% survival rate in 57 fetuses. Lung size on magnetic resonance imaging and an interval of >24 hours between reversal of tracheal occlusion and delivery were predictors of outcome., Conclusions: Right-sided CDH seems to have a poorer outcome than that reported for fetuses with left-sided CDH with similar lung size before birth. Survival rates after expectant management with observed/expected lung-to-head ratio values ≤45 and ≤30% were 17 and 0%, respectively. In those undergoing fetal surgery (observed/expected lung-to-head ratio ≤45%) there was an apparent increase (42%)., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: To perform a systematic review and meta-analysis of reported estimates of the association between gestational syphilis (GS) and stillbirth in the Americas region., Methods: Cochrane Library, Embase, LILACS, MEDLINE/PubMed, PLOS, and ScienceDirect were searched for original research studies quantifying the relationship between GS and stillbirth in the region. A final sample of eight studies was selected. A cumulative meta-analysis plus four subgroup meta-analyses of study data on the association between maternal syphilis during pregnancy and stillbirth were conducted. The four meta-analyses were based on 1) definition of cases and the control; 2) syphilis treatment (presence or absence, effective or ineffective); 3) definition of stillbirth as "showing no signs of life at birth"; and 4) definition of stillbirth based on low birth weight and gestational age. Random-effects metaanalyses were used to calculate pooled estimates of stillbirth with exposure to GS, and each subgroup analysis was tested for heterogeneity., Results: Women with GS had increased odds of stillbirth (pooled odds ratio (OR): 6.87; 95% confidence interval: 2.93, 16.08). There was considerable heterogeneity across the eight studies (percentage of variance (I²) = 95). The funnel plot was not statistically significant, pointing to a lack of publication bias. Increased odds of stillbirth among pregnant women with syphilis were also seen in all four subgroup meta-analyses., Conclusions: GS is a major contributing factor for stillbirths in the Americas. Interventions targeting GS are highly cost-effective and, along with high-quality point-of-care testing, should be implemented across the region to help reach the goal of eliminating congenital syphilis.

The combined method of diagnosis parvovirus infection during pregnancy by maternal serum enzyme immunoassay and deoxyribonucleic acid isolation parvovirus B19 polymerase chain reaction in amnniotic fluid and fetal cord blood newborns, can diagnose vertical transmission and anticipate a negative effect on the fetus parvovirus. Lack of maternal IgM antibodies in serum due to parvovirus seroconversion during pregnancy does not exclude the persistence of the virus in the fetus. To analyze the diagnostic value of the method for determining the LHP parvovirus B19 DNA in the amniotic fluid, umbilical cord blood of newborns to determine vertical transmission of parvovirus infection when infected mothers B19 during pregnancy.

The perinatal autopsy is an important tool in the investigation of fetal and neonatal death, and a complete understanding of its risks and benefits is necessary for providers of perinatal care. This review, from the perspective of a perinatal pathologist, reports the details of the autopsy procedure, its goals, its value to individual patients and the health care system in general, and its alternatives. Even with new emerging technologies, the conventional perinatal autopsy remains the gold standard for determining the cause of death and the final summary of all pathologic findings. Therefore, the information provided in this review can help providers properly convey information about perinatal autopsy to bereaved families., (Copyright © 2014. Published by Elsevier Inc.)

Objectives: In resource-poor settings, the standard of care to inform labour management is the partograph plus Pinard stethoscope for intermittent fetal heart rate (FHR) monitoring. We compared FHR monitoring in labour using a novel, robust wind-up handheld Doppler with the Pinard as a primary screening tool for abnormal FHR on perinatal outcomes., Design: Prospective equally randomised clinical trial., Setting: The labour and delivery unit of a teaching hospital in Kampala, Uganda., Participants: Of the 2042 eligible antenatal women, 1971 women in active term labour, following uncomplicated pregnancies, were randomised to either the standard of care or not., Intervention: Intermittent FHR monitoring using Doppler., Primary Outcome Measures: Incidence of FHR abnormality detection, intrapartum stillbirth and neonatal mortality prior to discharge., Results: Age, parity, gestational age, mode of delivery and newborn weight were similar between study groups. In the Doppler group, there was a significantly higher rate of FHR abnormalities detected (incidence rate ratio (IRR)=1.61, 95% CI 1.13 to 2.30). However, in this group, there were also higher though not statistically significant rates of intrapartum stillbirths (IRR=3.94, 0.44 to 35.24) and neonatal deaths (IRR=1.38, 0.44 to 4.34)., Conclusions: Routine monitoring with a handheld Doppler increased the identification of FHR abnormalities in labour; however, our trial did not find evidence that this leads to a decrease in the incidence of intrapartum stillbirth or neonatal death., Trial Registration Number: Clinical Trails.gov (1000031587)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Fetal aortic valvuloplasty can be performed for severe midgestation aortic stenosis in an attempt to prevent progression to hypoplastic left heart syndrome (HLHS). A subset of patients has achieved a biventricular (BV) circulation after fetal aortic valvuloplasty. The postnatal outcomes and survival of the BV patients, in comparison with those managed as HLHS, have not been reported., Methods and Results: We included 100 patients who underwent fetal aortic valvuloplasty for severe midgestation aortic stenosis with evolving HLHS from March 2000 to January 2013. Patients were categorized based on postnatal management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses were live-born, and 38 had a BV circulation (31 from birth, 7 converted after initial univentricular palliation). Left-sided structures, namely aortic and mitral valve sizes and left ventricular volume, were significantly larger in the BV group at the time of birth (P<0.01). After a median follow-up of 5.4 years, freedom from cardiac death among all BV patients was 96±4% at 5 years and 84±12% at 10 years, which was better than HLHS patients (log-rank P=0.04). There was no cardiac mortality in patients with a BV circulation from birth. All but 1 of the BV patients required postnatal intervention; 42% underwent aortic or mitral valve replacement. On the most recent echocardiogram, the median left ventricular end-diastolic volume z score was +1.7 (range, -1.3 to +8.2), and 80% had normal ejection fraction., Conclusions: Short- and intermediate-term survival among patients who underwent fetal aortic valvuloplasty and achieved a BV circulation postnatally is encouraging. However, morbidity still exists, and ongoing assessment is warranted., (© 2014 American Heart Association, Inc.)

Patients with heterotaxy syndrome (HS) have a range of anomalies and outcomes. There are limited data on perinatal outcomes after prenatal diagnosis. To determine the factors influencing perinatal and infant outcomes, we analyzed prenatal and postnatal variables in fetuses with HS from 1995 to 2011. Of 154 fetuses with HS, 61 (40%) had asplenia syndrome (ASP) and 93 (60%) had polysplenia syndrome (PSP). In the ASP group, 22 (36%) patients were elected for termination of pregnancy, 4 (10%) had fetal death, and 35 of 39 (90%) continued pregnancies were live born. In the PSP group, 12 (13%) patients were elected for termination of pregnancy, 5 (6%) had fetal death (4 with bradyarrhythmia), and 76 of 81 (94%) continued pregnancies were live born. Bradyarrhythmia was the only predictor of fetal death. In the live-born ASP group, 43% (15 of 35) died, 7 because of pulmonary vein stenosis, 4 postoperatively, and 4 because of noncardiac causes. In the live-born PSP group, 13% (10 of 76) died, 5 postoperatively, 2 from bradyarrhythmia, 1 from a cardiac event, and 2 from noncardiac causes. Pulmonary vein stenosis and noncardiac anomalies were independent risk factors for postnatal death. Only 8% of ASP patients achieved biventricular circulation, compared with 65% of PSP patients. In the live-born cohort, the 5-year survival rate was 53% for ASP and 86% for PSP. In conclusion, most PSP patients are currently alive with biventricular circulation in contrast with few ASP patients. Bradyarrhythmia was the only predictor of fetal death. Pulmonary vein stenosis and noncardiac anomalies were predictors of postnatal death., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine the phenotypic presentation, causes, and outcome of fetal cardiomyopathy (CM) and to identify early predictors of outcome., Background: Although prenatal diagnosis is possible, there is a paucity of information about fetal CM., Methods: This was a retrospective review of 61 consecutive fetal cases with a diagnosis of CM at a single center between 2000 and 2012., Results: Nonhypertrophic CM (NHCM) was diagnosed in 40 and hypertrophic CM (HCM) in 21 fetuses at 24.7 ± 5.7 gestational weeks. Etiologies included familial (13%), inflammatory (15%), and genetic-metabolic (28%) disorders, whereas 44% were idiopathic. The pregnancy was terminated in 13 of 61 cases (21%). Transplantation-free survival from diagnosis to 1 month and 1 year of life for actively managed patients was better in those with NHCM (n = 31; 58% and 58%, respectively) compared with those with HCM (n = 17; 35% and 18%, respectively; hazard ratio [HR]: 0.44; 95% confidence interval [CI]: 0.12 to 0.72; p = 0.007). Baseline echocardiographic variables associated with mortality in actively managed patients included ventricular septal thickness (HR: 1.21 per z-score increment; 95% CI: 1.07 to 1.36; p = 0.002), cardiothoracic area ratio (HR: 1.06 per percent increment; 95% CI: 1.02 to 1.10; p = 0.006), ≥3 abnormal diastolic Doppler flow indexes (HR: 1.44; 95% CI: 1.07 to 1.95; p = 0.02), gestational age at CM diagnosis (HR: 0.91 per week increment; 95% CI: 0.83 to 0.99; p = 0.03), and, for fetuses in sinus rhythm, a lower cardiovascular profile score (HR: 1.45 per point decrease; 95% CI: 1.16 to 1.79; p = 0.001)., Conclusions: Fetal CM originates from a broad spectrum of etiologies and is associated with substantial mortality. Early echocardiographic findings appear useful in predicting adverse perinatal outcomes., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Congenital atrioventricular (AV) block is commonly associated with heterotaxy syndrome; together they have reportedly low survival rates (10-25%). However, information about perinatal outcome and predictors of non-survival after prenatal diagnosis of this association is scarce. Therefore, we studied fetuses with heterotaxy syndrome and bradycardia or AV-block diagnosed between 1995 and 2011, and analyzed pre and post-natal variables. The primary outcome was death and the secondary outcome was pacemaker placement. Of the 154 fetuses with heterotaxy syndrome, 91 had polysplenia syndrome, 22/91(24%) with bradycardia or AV-block. Thirteen (59%) patients had sinus bradycardia at diagnosis, 8 (36%) complete AV block, and 1 (5%) second-degree AV-block. Three patients elected for termination of pregnancy (3/22, 14%), 4 had spontaneous fetal demise (4/22, 18%), and 15 (15/22, 68%) were live-born. Of the fetuses with bradycardia/AV-block, 30% presented with hydrops, 20% had ventricular rates <55 beats/min, and 10% had cardiac dysfunction. Excluding termination of pregnancy, 15/19 fetuses (79%) survived to birth. Among the 15 live-born patients, 4 had bradycardia and 11 had AV-block. A further 3 patients died in infancy, all with AV-block who required pacemakers in the neonatal period. Thus, the 1-year survival rate, excluding termination of pregnancy, was 63% (12/19). Of the remaining 12 patients, 9 required pacemaker. Predictors of perinatal death included hydrops (p < 0.0001), ventricular dysfunction (p = 0.002), prematurity (p = 0.04), and low ventricular rates (p = 0.04). In conclusion, we found a higher survival rate (63%) than previously published in patients with heterotaxy syndrome and AV block or bradycardia diagnosed prenatally. Hydrops, cardiac dysfunction, prematurity and low ventricular rates were predictors of death.

Objective: To study modalities and complications of intrauterine exchange transfusion (IUET) for the management of severe fetal anaemia., Study Design: Retrospective study of all IUET procedures performed between January 1999 and January 2012 at a regional centre. Characteristics of each procedure were studied to identify risk factors for complications. Survival rates according to the different aetiologies of anaemia were evaluated., Results: In total, 225 IUET procedures were performed in 96 fetuses. Major indications were feto-maternal erythrocyte alloimmunization (n=80/96, 83.3%) and parvovirus B19 infection (n=13/96, 13.5%). Twenty-six percent of the fetuses (25/96) had hydrops fetalis before the first IUET. Intrauterine fetal death occurred after 2.7% (6/225) of procedures, premature rupture of the membranes occurred after 0.9% (2/225) of procedures, and emergency caesarean section was required after 3.6% (8/225) of procedures. Fetal bradycardia [odds ratio (OR) 37, 95% confidence interval (CI) 8.3-170; p<0.01] and gestational age up to 32 weeks (OR 3.67; 95% CI, 1.07-12.58; p=0.038] were significantly associated with complications after IUET. Complications occurred in 17.7% of pregnancies (17/96) and 7.5% of IUET procedures (17/225). The overall survival rate in the study cohort was 87.5% (84/96): 90% (72/80) in the alloimmunization group and 76.9% (10/13) in the parvovirus-infected group (NS)., Conclusion: IUET has a higher complication rate than simple intrauterine transfusion, and should be performed by well-trained specialists., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Background: We sought to describe current outcomes and risk factors for mortality for fetuses diagnosed with absent pulmonary valve syndrome (APV). Fetuses with APV were divided into two cohorts, those with underlying tetralogy of Fallot (TOF/APV) and those without underlying TOF and either an intact ventricular septum or small ventricular septal defect (APV/IVS)., Methods: The fetal echocardiographic database was reviewed from January 1, 2001, until June 1, 2010, and all subjects with a diagnosis of APV were included. Multiple clinical and fetal echocardiographic measurements were recorded. Statistical analysis was performed by χ2 analysis and t tests. Survival analysis was performed by Kaplan-Meier analysis. Significant relationships between variables were explored by regression analysis. Significance was set at p=0.05., Results: The cohort consisted of 15 fetuses with TOF/APV and 6 fetuses with APV/IVS. There were no fetal demises in either cohort. Survival to birth was 71% in the TOF/APV cohort and 83% in the APV/IVS cohort (p=0.62). Of subjects born alive, survival was 80% for both cohorts (p=0.95). However, in the APV/IVS cohort, transplantation-free survival was only 20%. Underlying single-ventricle physiology strongly predicted those who underwent heart transplantation (p=0.003, R2=0.50). For the entire APV cohort, left ventricular dysfunction (p=0.005, R2=0.41) and a higher pulmonary artery valve-to-aortic valve ratio (p=0.02, R2=0.34) predicted mortality., Conclusions: Postnatal outcomes continue to improve for fetuses with APV syndrome. Left ventricular dysfunction and higher pulmonary artery valve-to-aortic valve ratio accurately predict postnatal mortality for fetuses with APV., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Primary hydrothorax is a rare congenital anomaly with outcomes ranging from spontaneous resolution to fetal demise. We reviewed our experience with fetuses diagnosed with primary hydrothorax to evaluate prenatal management strategies., Methods: We reviewed the records of patients evaluated for fetal pleural effusions at our Fetal Treatment Center between 1996 and 2013. To define fetuses with primary hydrothorax, we excluded those with structural or genetic anomalies, diffuse lymphangiectasia, immune hydrops, and monochorionic diamniotic twin gestations., Results: We identified 31 fetuses with primary hydrothorax, of whom 24 had hydrops. Hydropic fetuses were more likely to present with bilateral effusions. Of all fetuses with primary hydrothorax, 21 had fetal interventions. Survival without hydrops was 7/7 (100%), whereas survival with hydrops depended on whether or not the patient had fetal intervention: 12/19 (63%) with intervention and 1/5 (20%) without intervention. Premature delivery was common (44%) among those who had fetal intervention., Conclusions: Fetal intervention for primary hydrothorax may lead to resolution of hydrops, but preterm birth and neonatal demise still occur. Understanding the pathophysiology of hydrops may provide insights into further prenatal management strategies, including targeted therapies to prevent preterm labor., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The goal of the work was a comparative analysis of intrauterine therapy among pregnant women with diagnosed fetal uropathy and unilateral hydronephrosis., Methods: The study was conducted on a group of 98 pregnant women hospitalized at the Department of Gynecology Fertility and Fetal Therapy Polish Mother's Memorial Hospital between 2006-2012. The study group included 77 cases of fetal obstructive uropathy (79%) and 21 cases of unilateral hydronephrosis (21%). Both groups have been analyzed in terms of prognosis. Follow-up has been conducted and results have been statistically analyzed., Results: In 11% of cases of obstructive uropathy therapy early complications were observed. The remaining 89% of the patients delivered at a later date, of which 54% after 34 weeks of pregnancy The average weight of a newborn was 2645g and Apgar score - 7.45. 73% of newborns were discharged home in good condition, with preserved diuresis., Conclusions: 1. The use of intrauterine therapy has a positive effect on fetal condition and newborn postnatal state. 2. Unilateral hydronephrosis group was characterized by a significantly longer duration of pregnancy higher birth weight, Apgar score, and greater survival of newborns. 3. In the group of obstructive uropathy survival improvement was achieved and dieresis was preserved Intrauterine interventions were associated with a low risk of complications.

Single-twin demise can pose substantial risks for the surviving co-twin, including increased risk of fetal loss, preterm delivery, neurovascular injury, and end-organ damage. In this chapter, we summarise recently published research on the causes of single twin demise, the pathophysiology of injury to the surviving co-twin, and the evidence for current management strategies. The gestation at which single intrauterine fetal demise occurs, and the chorionicity of the multiple pregnancies, are the two most important factors when considering the risks to the surviving twin. Management should include fortnightly ultrasound scans for growth, umbilical artery Doppler studies, and liquor volume. In monochorionic twins, more complex Doppler assessment with middle cerebral artery Doppler velocimetry and a magnetic resonance imaging of the survivor's brain at least 3 weeks after single intrauterine fetal demise occurs should be carried out to look for evidence of neurological morbidity. With no other obstetric complications, dichorionic pregnancies can be delivered at term. Monochorionic pregnancies are more difficult to manage, and are often delivered between 34 and 36 weeks., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Anatomopathologic studies have failed to define the fetal inflammatory response syndrome (FIRS) as a cause of fetal death. Here, liver fragments of perinatal autopsies were collected at a university hospital from 1990 to 2009 and classified according to the cause of death, perinatal stress, and gestational age (GA) of the fetus. IL-6, TNF-α, and C-reactive protein (CRP) expression were immunostained, respectively, with primary antibody. Cases with congenital malformation, ascending infection, and perinatal anoxia showed increased IL-6, CRP, and TNF-α, respectively. Prematures presented higher expression of IL-6 whereas term births showed higher expression of CRP. Cases classified as acute stress presented higher expression of IL-6 and TNF-α and cases with chronic stress presented higher expression of CRP. GA correlated negatively with IL-6 and positively with CRP and TNF-α. Body weight correlated negatively with IL-6 and positively with CRP and TNF-α. Despite the diagnosis of FIRS being clinical and based on serum parameters, the findings in the current study allow the inference of FIRS diagnosis in the autopsied infants, based on an in situ liver analysis of these markers.

Background: Congenital lower urinary tract obstruction (LUTO) is a disease associated with high perinatal mortality and childhood morbidity. Fetal vesicoamniotic shunting (VAS) bypasses the obstruction with the potential to improve outcome., Objective: To determine the effectiveness, cost-effectiveness and patient acceptability of VAS for fetal LUTO., Design: A multicentre, randomised controlled trial incorporating a prospective registry, decision-analytic health economic model and preplanned Bayesian analysis using elicited opinions. Patient acceptability was evaluated by interview in a qualitative study., Setting: Fetal medicine departments in the UK, Ireland and the Netherlands., Participants: Pregnant women with a male singleton fetus with LUTO., Interventions: In utero percutaneous VAS compared with conservative care., Main Outcome Measures: The primary outcome was survival to 28 days. Secondary outcome measures were survival and renal function at 1 year of age, cost of care and cost per additional life-year and per disability-free survival at the end of 1 year., Results: The trial stopped early with 31 women randomised because of difficulties in recruitment. Of those randomised to VAS and conservative management, 3/16 (19%) and 2/15 (13%), respectively, did not receive their allocated intervention. Based on intention-to-treat analysis, survival at 28 days was higher if allocated VAS (50%) than conservative management (27%) [relative risk (RR) 1.88, 95% confidence interval (CI) 0.71 to 4.96, p = 0.27]. At 12 months survival was 44% in the VAS arm and 20% in the conservative arm (RR 2.19, 95% CI 0.69 to 6.94, p = 0.25). Neither difference was statistically significant. Of survivors at 1 year, two in the VAS arm had no evidence of renal impairment and four in the VAS arm and two in the conservative arm required medical management. One baby in the conservative arm had end-stage renal failure at 1 year. VAS was more expensive because of additional surgery and intensive care. VAS cost £15,500 per survivor at 1 year and £43,900 per disability-free year. Elicited expert opinions showed uncertainty in the effect of VAS at 28 days. In a Bayesian analysis combining elicited opinion with the results, uncertainty of the benefit of VAS remained (RR 1.31, 95% credible interval 0.84 to 2.18). The acceptability study identified visualisation of the fetus during ultrasound scanning, perceiving a personal benefit, and altruism as positive influences on recruitment. Fear of the VAS procedure and the perceived severity of LUTO influenced non-participation. The need for more detailed information about the condition and its implications during pregnancy and following delivery was a further important finding of this research. Recruitment was hampered by logistical and regulatory difficulties, a lower incidence of LUTO and lower antenatal diagnosis rate [estimated to be 3.34 (95% CI 2.95 to 3.72) per 10,000 total births and 47%, respectively, in an associated epidemiological study] and high termination of pregnancy rates. In the registry women also demonstrated a clear preference for conservative management., Conclusions: Survival to 28 days and 1 year appears to be higher with VAS than with conservative management, but it is not possible to prove benefit beyond reasonable doubt. Notably, prognosis in both arms for survival and renal function is poor. VAS was substantially more costly and unlikely to be regarded as cost-effective based on the 1-year data. Parents should be counselled about the risks of pregnancy loss with or without VAS insertion. The National Institute for Health and Care Excellence interventional procedures guidance (IPG 202) should be updated to reflect this new evidence. Babies in the PLUTO trial should be followed up long term for the different outcomes., Trial Registration: ISRCTN53328556., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 17, No. 59. See the NIHR Journals Library website for further project information.

Background: San Diego Hospice and the Institute for Palliative Medicine created one of the earliest perinatal palliative care programs in the country. Only four studies have reported outcomes for pregnant women referred to perinatal palliative care services for potentially lethal prenatal diagnoses., Objectives: To learn: (1) who is referred for perinatal palliative care at San Diego Hospice; (2) what happens after referral to perinatal palliative care; and (3) what happens after delivery for this population., Design: This was an exploratory retrospective electronic chart review of all patients referred to a home perinatal palliative program., Results: Sixty-six women were referred to the San Diego Hospice and the Institute for Palliative Care home perinatal palliative care program between October 2006 and August 2012. Mean age was 31 years. The majority of women were Hispanic, Christian/Catholic, married, with full prenatal care, and previous children. Average gestational age at referral was 27 (18-39] weeks. Thirty-two cases were referred for Trisomy 13, Trisomy 18, or anencephaly. Palliative care services were given over a mean 45 (0-132) days and 3 (0-12) visits prior to delivery. Most women completed a birth plan prior to delivery, chose palliative treatment only, and made final arrangements with the palliative team. Forty-one deliveries resulted in a liveborn infant. Twelve liveborn infants survived past 72 hours and were admitted to pediatric hospice care., Conclusions: One-third of women met with the palliative care team only once or twice prior to delivery, indicating a need for earlier referral to provide more comprehensive palliative care.

Congenital malformations are a known cause of intrauterine death; of them, congenital heart diseases (CHDs) are accountable for the highest fetal and neonatal mortality rates. They are strongly associated with other extracardiac malformations and an early fetal mortality. Two hundred and twenty fves cases of CHDs are presented. Of them, 155 were isolated CHDs (group A) and 70 were associated with extracardiac malformations, chromosomal disorders, or genetic syndromes (group B). The overall mortality in group B was higher than that observed in group A (p <0.01). Prenatal mortality was similar in both groups: A: 8.4% (13 out of 155); B: 15.7% (11 out of 70). Postnatal mortality was A: 16.8% (26 out of 155) (p <0.01), OR: 0.52 (95% CI: 0.16-1.7); B: 32.9% (23 out of 70) (p <0.01), OR: 0.41 (95% CI: 0.20-0.83). Heart diseases associated with extracardiac abnormalities had a higher mortality rate than isolated congenital heart diseases in the period up to 60 weeks of postmenstrual age (140 days post-term). No differences were observed between both groups of patients in terms of prenatal mortality.

Objective: The aim of this study is to report the short-term morbidity of congenital diaphragmatic hernia at a tertiary referral center in Karachi, Pakistan., Methods: It is a retrospective cohort study of fetuses with congenital diaphragmatic hernia from January 2001 to December 2011. This includes all cases with prenatal diagnosis and those presenting in the postnatal period. This study analyses the survival of these cases and assesses the prognostic factors associated with the mortality of this condition., Results: During the 11 year study period, 65 cases of diaphragmatic hernia were identified. Among these, 41 cases were diagnosed in the antenatal period while the rest of the 24 presented in the postnatal period. Fifty-eight out of the 65 (89%) were born alive. Only 38% of these survived beyond 28 days of life. Factors like antenatal diagnosis and birthweight significantly influenced the outcome while mode of delivery, site of lesion and gestational age at delivery did not affect the prognosis., Conclusion: The overall mortality of congenital diaphragmatic hernia remains high. Survival rate of isolated hernia was substantially higher than those who had associated anomalies. The data from this study will provide the basis for counseling women in our setup.

Background: Sacrococcygeal teratoma is the most common neonatal tumor. Fetuses with large tumors may develop hydrops from a high cardiac output state (HCOS) and progress rapidly to fetal demise. We postulate that the prenatal solid tumor volume index (STVI), or the ratio of solid tumor volume to the estimated fetal weight (EFW), has greater impact than the total tumor volume in outcome prediction., Methods: A retrospective chart review of all sacrococcygeal teratoma patients (n = 38) between 2005 and 2012 was conducted. Total tumor volume and percent of solid component were calculated by magnetic resonance imaging and then normalized by dividing them by either head circumference or EFW. Outcomes measured were survival, hydrops or high cardiac output state, defined as a combined ventricular output of >625 mL/min/kg with abnormal Doppler or echocardiogram findings., Results: Thirty-one patients were included in the study. All deaths (n = 7) had either high cardiac output state or hydrops. At a total tumor volume/EFW >0.16, the patient was 17 times more likely to develop HCOS/hydrops (P = 0.001) with 81.25% sensitivity and 86.67% specificity. At a STVI >0.09, the patient was 120 times more likely to develop HCOS/hydrops (P < 0.0001) with 81.25% sensitivity and 100% specificity., Conclusions: While total tumor volume aids in stratifying patients into high risk categories, STVI (solid tumor volume/EFW) is a better predictor of adverse outcomes. This data will allow us to identify patients who are high risk for cardiac compromise and guide appropriate therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Congenital heart defects (CHD) are the most prevalent congenital disease, with 45% of deaths resulting from a congenital defect due to a cardiac malformation. Clinically significant CHD permit survival upon birth, but may become immediately life threatening. Advances in surgical intervention have significantly reduced perinatal mortality, but the outcome for many malformations is bleak. Furthermore, patients living while tolerating a CHD often acquire additional complications due to the long-term systemic blood flow changes caused by even subtle anatomical abnormalities. Accurate diagnosis of defects during fetal development is critical for interventional planning and improving patient outcomes. Advances in quantitative, multidimensional imaging are necessary to uncover the basic scientific and clinically relevant morphogenetic changes and associated hemodynamic consequences influencing normal and abnormal heart development. Ultrasound is the most widely used clinical imaging technology for assessing fetal cardiac development. Ultrasound-based fetal assessment modalities include motion mode (M-mode), two dimensional (2D), and 3D/4D imaging. These datasets can be combined with computational fluid dynamics analysis to yield quantitative, volumetric, and physiological data. Additional imaging modalities, however, are available to study basic mechanisms of cardiogenesis, including optical coherence tomography, microcomputed tomography, and magnetic resonance imaging. Each imaging technology has its advantages and disadvantages regarding resolution, depth of penetration, soft tissue contrast considerations, and cost. In this review, we analyze the current clinical and scientific imaging technologies, research studies utilizing them, and appropriate animal models reflecting clinically relevant cardiogenesis and cardiac malformations. We conclude with discussing the translational impact and future opportunities for cardiovascular development imaging research., (Copyright © 2013 Wiley Periodicals, Inc.)

Aims: Increased uterine artery pulsatility index (PI) is associated with adverse pregnancy outcomes. The aim of the study was to determine the role of uterine artery PI at 18-24 and 30-34 weeks, gestation in predicting adverse pregnancy outcomes., Material and Methods: Color Doppler assessment of the uterine arteries was carried out in 435 consecutive women attending an antenatal clinic at 18-24 weeks and in 134 women at 30-34 weeks. The 95th percentiles of the mean uterine PI and the presence or the absence of bilateral notches was recorded. Using the reference range, performance characteristics in the prediction of pregnancy outcomes were calculated. Association of mean PI at 30-34 weeks with pregnancy outcomes also was studied. The adverse pregnancy outcomes were defined as any or the combination of pre-eclampsia, fetal growth restriction, intrauterine fetal death, preterm delivery and placental abruption., Results: The women with adverse pregnancy outcomes had significant higher mean PI (1.27 +/- 0.55 vs. 0.99+/-0.32; p=0.003) and higher prevalence of bilateral notch (20% vs. 4.6%, p=0.001) than those with normal outcomes. The mean (+/-SD) PI in women with severe adverse outcome was 1.66+/-0.66 vs. 1.0+/-0.32 in women with normal pregnancy outcome (p=0.002). For a screen positive rate of 10.6% (mean PI>95th percentile for gestational age and/or bilateral notches), the sensitivity for predicting an adverse outcome was 33.3%. The sensitivity increased to 60% for predicting a severe adverse outcome. Increased resistance in the third trimester was also associated with an adverse pregnancy outcome., Conclusion: Increased uterine artery PI in second and third trimester of pregnancy is associated with an increased risk of adverse pregnancy outcomes.

Study Question: Does neonatal outcome including congenital malformations in children born after ICSI with epididymal and testicular sperm [testicular sperm extraction (TESE)/percutaneous epididymal sperm aspiration (PESA)/testicular sperm aspiration (TESA) (TPT)] differ from neonatal outcome in children born after ICSI with ejaculated sperm, IVF and natural conception (NC)?, Summary Answer: Children born after TPT have similar neonatal outcome, including total malformation rates, as have children born after ICSI and IVF with ejaculated sperm. Testing for variance over the four groups may indicate smaller differences in specific malformation rates with TPT as the highest risk group., What Is Known Already: Regarding neonatal outcome as well as congenital malformations in children born after TPT, studies are few, with limited sample size, heterogeneous and often performed without relevant control groups., Study Design, Size, Duration: Population-based cohort study including all Danish children born after TPT and fresh embryo transfer in Denmark from 1995 to 2009. Children born after transfer of frozen-thawed embryos were excluded. Control groups of children conceived by ICSI with ejaculated sperm, IVF and NC were identified by cross-linkage of the Danish IVF Register, Medical Birth Register (MBR) and National Hospital Discharge Register (HDR)., Participants/materials, Setting: The study group consisted of 466 children born after TPT, while the control groups consisted of 8967 (ICSI with ejaculated sperm), 17 592 (IVF) and 63 854 (NC) children. Neonatal outcomes and congenital malformations were analysed for singletons and twins separately. Risk estimates for low birthweight (LBW, <2500 g) and preterm birth (PTB, <37 gestational weeks) were adjusted for maternal age, parity, child gender and year of childbirth. The study group was identified from the Danish national database on children born after TPT. Control groups were obtained from the IVF register and the MBR. All information included in the study was retrieved from the national registers., Main Results and the Role of Chance: Considering singletons and twins as one group, the sex ratio (♂/♀) was significantly lower for children born after TPT (0.89) compared with conventional IVF (1.11; P = 0.017) but did not differ significantly when compared with ICSI with ejaculated sperm (0.94) and NC (1.05). The mean birthweight (BW) for singletons did not differ significantly between groups when including only first-born children. The mean gestational age (GA) in the TPT singletons (279 ± 12 days) was significantly higher compared with IVF (276 ± 18 days; P = 0.02), but similar to ICSI with ejaculated sperm and NC singletons when including only first-born children (277 ± 16 days and 279 ± 14 days, respectively). Rate of stillbirths, perinatal and neonatal mortality in the group of TPT singletons did not differ significantly from any of the control groups. Comparable results were found for the TPT twin group, except for perinatal mortality, which was significantly lower in the TPT group compared with naturally conceived twins. The adjusted risk of LBW was significantly higher for TPT versus NC singletons [adjusted odds ratio (AOR) = 0.67 (0.48-0.93)]; however AOR for PTB was similar in the two groups. Regarding twins, similar adjusted risks were observed for PTB and LBW between the TPT and all three control groups. Significantly more Caesarean sections were performed after IVF (27.3% for singletons) and ICSI (25.1% for singletons) with ejaculated sperm compared with the TPT group (16.4% for singletons). The total rate of congenital malformations in the TPT group was 7.7% and did not differ significantly from any of the control groups. However, singleton TPT boys showed an increased rate of cardiac malformations (3.6%) compared with singleton boys after IVF (1.4%; P = 0.04) and NC (1.1%; P = 0.02). Considering the level of male infertility as a continuum over the four groups, tests for variance in the rate of cardiac malformations in singleton boys, and undescended testicles for singleton as well as twin boys were each significantly increased from NC to IVF to ICSI to TPT (P < 0.001). The rate of hypospadias showed the same pattern, but the TPT group did not differ significantly compared with the control groups., Limitations, Reasons for Caution: One of the limitations is that the TPT group could not be classified according to testicular or epididymal sperm, as these data were not available in the IVF register. Another limitation is that registry-based studies are encumbered with the risk of reporting or coding errors or missing data due to insufficient coding. However, the quality of data on congenital malformations in HDR has, in other studies, been validated and found acceptable for epidemiological research, and furthermore, recordings on study and control groups are performed similarly., Wider Implications of the Findings: Accumulating data show that TPT treatment is equally safe as conventional ICSI and IVF treatment and as NC with regard to neonatal outcome including congenital malformation., Study Funding/potential Competing Interests: This study is supported by Laboratory of Reproductive Biology, Scientific Unit, Horsens Hospital. No competing interests declared.

Objectives: High perinatal autopsy rates are necessary for institutional management protocols and national policy-making. This study reviews perinatal autopsy rates and factors affecting these rates at the University Hospital of the West Indies., Method: All perinatal deaths (stillborn infants > or = 24 weeks gestation or 500 g; early neonatal deaths ie 0-7 days old) at the University Hospital of the West Indies, between January 2002 and December 2008, were reviewed retrospectively, using the annual perinatal audit records. The annual autopsy rates were calculated and the reasons why autopsies were not done examined., Results: The average stillbirth (SB) autopsy rate was 59.6% (range 51.9 - 76.7%), while that for early neonatal deaths (ENDs) was 47.9% (range 34.4 - 63.2), with an overall average perinatal autopsy rate of 54.0% (range 42.2 - 62.2). Autopsies were requested in 79.3% and 51.7% of SBs and ENDs, respectively. Of those requested, 81.7% were done (75.2% stillbirths; 92.5% ENDs). In the ENDs, failure to request an autopsy was predominantly noted in premature infants weighing < 1000 g (75.2% of those not requested). In stillbirths, the reasons for failure to request were largely unknown with failure to gain permission accounting for only 20.3% of these cases., Conclusions: The average annual perinatal autopsy rate at the University Hospital of the West Indies between 2002 and 2008 was 54.0%. This is below the internationally recommended rate of 75%. Failure to request an autopsy was the most significant factor contributing to this. The reasons for this are not entirely clear and require further study.

Objective: To evaluate the rate and consequences of a late or missed diagnosis of fetal and neonatal alloimmune thrombocytopenia (FNAIT)., Design: Retrospective analysis of prospectively collected data of a national cohort., Setting: National referral centre for fetal therapy in the Netherlands., Population: Twenty-six women with pregnancies complicated by FNAIT and at least one previous pregnancy with a thrombocytopenic child., Methods: Retrospective analysis of data from our electronic FNAIT database. In a consecutive cohort managed between July 2008 and July 2010, timing of first diagnosis of FNAIT was correlated to severity and outcome in the subsequent pregnancies., Main Outcome Measures: Occurrence of delayed diagnosis of FNAIT, and possibly associated intracranial haemorrhage (ICH)., Results: In four of 26 pregnancies, timely diagnostic testing for FNAIT was not performed despite fetal or neonatal thrombocytopenia or ICH. Down syndrome, dysmaturity and birth trauma were perceived to be the cause of the thrombocytopenia/ICH. In two of these four subsequent, untreated pregnancies, severe fetal ICH occurred. The other 22 women were treated for FNAIT using intravenous immunoglobulin, all children are alive and well., Conclusions: All neonates with thrombocytopenia at birth should be evaluated for FNAIT. Missing this diagnosis can have severe consequences for subsequent pregnancies., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

This study analyzed 156 cases of fetal hydrocephalus treated at Osaka National Hospital from 1992 to 2011 to review current methods for diagnosing and treating fetal hydrocephalus, and for estimating its clinical outcome. This was a retrospective study of a single institute (Osaka National Hospital). Of 156 cases in total, 37% were diagnosed as isolated ventriculomegaly, 50% as another type of malformation (36 cases of myelomeningocele, six of holoprosencephaly, three of Dandy-Walker syndrome, one case of Joubert syndrome, 12 of arachnoid cyst, nine of encephalocele, three of atresia of Monro and eight of corpus callosum agenesis, and 13% as secondary hydrocephalus. Diagnoses were made between 13 and 40 weeks of gestation (average 27 weeks). Diagnosis was made before 21 weeks of gestation in 24% of cases, from the first day of 22 weeks to the sixth day of 27 weeks in 27%, and after the first day of 28 weeks in 49%. With the exclusion of 17 aborted cases and 40 cases in which the patients were too young to evaluate or lost during follow-up, the final outcome was analyzed for 90 cases. Of these, 17% of the patients died, 21% showed severe retardation, 13% moderate retardation, 26% mild retardation, and 23% showed a good outcome. The long-term outcome was mostly influenced by the basic disease and accompanying anomaly. The time of diagnosis showed no correlation with outcome. Hydrocephalus associated with arachnoid cyst, atresia of Monro, and corpus callosum agenesis, and hydrocephalus due to fetal intracranial hemorrhage, resulted in good outcomes. By contrast, holoprosencephaly, hydrocephalus associated with encephalocele, syndromic hydrocephalus, and hydrocephalus due to fetal virus infection led to poor outcomes. For accurate diagnosis and proper counseling, established protocols are important for the diagnosis and treatment of fetal hydrocephalus, including not only fetal sonography, fetal magnetic resonance imaging, and TORCH (toxoplasma, rubella, cytomegalovirus, herpes simplex) screening test, but also chromosomal and gene testing., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Hepatoblastoma is an uncommon fetal neoplasm that may represent an isolated malignancy or a component of a familial cancer or syndromic diagnosis., Case: A large fetal liver mass was detected on routine ultrasound examination of a 23-year-old woman with thyroid nodules and hypertension. Inferior vena cava compression prompted delivery; postnatal biopsy revealed hepatoblastoma. Maternal thyroid biopsy revealed papillary carcinoma. Neonatal and maternal cytomolecular analysis revealed APC gene disruption at 5q22.2. Pedigree analysis exposed multigenerational colon cancer and thyroid cancer, which in conjunction with genetic testing is consistent with familial adenomatous polyposis., Conclusion: This is a novel means of familial adenomatous polyposis diagnosis. Obstetricians and perinatologists should be alert for familial cancer or syndromic diagnoses presenting as fetal neoplasms.

Quantify steatosis, fibrosis, and focuses of extramedullary erythropoiesis (ER) in the liver and report it to the causes of death in the perinatal. Morphologic analysis of steatosis', percentage of fibrosis, and ER of 467 perinatal autopsies. Cases with hypoxia/perinatal anoxia and ascending infection showed higher percentage of fibrosis. The number of ER was significantly higher among premature infants and in cases with infection. Our results contribute to a better quality of perinatal care through clinical demonstration of which injuries are associated with them, what may help in early diagnosis of these alterations in children who survive.

Objectives: To compare prospectively maternal acceptance of fetal and neonatal virtuopsy with that of conventional autopsy and to determine the confidence with which magnetic resonance (MR) virtuopsy can be used to diagnose normality/abnormality of various fetal anatomical structures., Methods: MR and/or computed tomography virtuopsy and conventional autopsy were offered to 96 women (102 fetuses/neonates) following termination of pregnancy (TOP), intrauterine fetal death (IUFD) or neonatal death. Multivariable logistic regression analysis was used to investigate the effect on maternal acceptance of virtuopsy and/or conventional autopsy of the age of the mother, gestational age at TOP or delivery after IUFD, order of pregnancy, parity, religion, type of caregiver obtaining consent and reason for death. When parents consented to both MR virtuopsy and conventional autopsy of fetuses ≥ 20 weeks of gestation or neonates, the confidence with which MR virtuopsy could be used to diagnose normality/abnormality of various anatomical structures was determined on a scale in which conventional autopsy was considered gold standard. On autopsy we classified fetuses/neonates as having either 'normal' or 'abnormal' anatomical structures; these groups were analyzed separately. At virtuopsy, we indicated confidence of diagnosis of normality/abnormality of every anatomical structure in each of these two groups defined at autopsy, using a scale from 0 (definitely abnormal) to 100 (definitely normal)., Results: Of the 96 women, 99% (n = 95) consented to virtuopsy and 61.5% (n = 59) to both conventional autopsy and virtuopsy; i.e. 36 (37.5%) consented to virtuopsy alone. Maternal acceptance of conventional autopsy was independently positively related to singleton pregnancy, non-Moslem mother, earlier gestation at TOP or delivery afer IUFD and a maternal-fetal medicine specialist obtaining consent. Thirty-three fetuses ≥ 20 weeks of gestation had both conventional autopsy and MR virtuopsy, of which 19 had a full autopsy including the brain. In fetuses with normal anatomical structures at conventional autopsy, MR virtuopsy was associated with high diagnostic confidence (scores > 80) for the brain, skeleton, thoracic organs except the heart, abdominal organs except the pancreas, ureters, bladder and genitals. In fetuses with abnormal anatomical structures at autopsy, MR virtuopsy detected the anomalies with high confidence (scores < 20) for these same anatomical structures. However, in three cases, virtuopsy diagnosed brain anomalies additional to those observed at conventional autopsy., Conclusion: MR virtuopsy is accepted by nearly all mothers while conventional autopsy is accepted by about two-thirds of mothers, in whom refusal depends mainly on factors over which we have no control. Although conventional autopsy remains the gold standard, the high acceptance of virtuopsy makes it an acceptable alternative when the former is declined., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To determine if postmortem examinations of fetuses and infants change the diagnosis obtained at prenatal ultrasound and affect counseling of future pregnancies, and if there has been a change over recent years in the accuracy of prenatal ultrasound diagnosis., Methods: This was a retrospective review of 455 autopsies of fetuses and infants with developmental anomalies performed at Trondheim University Hospital between 1995 and 2004 and with a prenatal ultrasound examination performed at a tertiary referral center. The routine ultrasound examinations were performed by specially trained midwives and obstetricians, referral scans by fetal medicine experts and autopsies by consultant pathologists with experience in perinatal pathology. The results of this study were also compared with those of a previous similar study performed between 1985 and 1995, with fetuses and infants coming from the same population and diagnosed at the same center., Results: Of all cases analyzed during the study period, there was complete agreement between prenatal ultrasound and postmortem findings in 84% (384/455), i.e. prenatal ultrasound diagnoses were supplemented by postmortem examinations in 16% (71/455). Autopsy findings in four of these cases influenced further counseling. There was agreement regarding the main diagnosis in 98% (445/455) of cases. In the previous 10-year period, there was complete agreement in 75% and the main diagnosis was correct in 90% of cases. These differences between the two time periods were statistically significant (P = 0.0004 and P < 0.0001, respectively). The most frequent defects involved the central nervous system, heart and urinary tract. For these defects, detection rates for the main diagnoses were significantly better in 1995-2004 compared with in the previous 10-year period (P = 0.0125, P = 0.0111 and P = 0.0241, respectively)., Conclusion: The accuracy of prenatal sonographic detection of developmental anomalies has increased in recent years. However, postmortem examination is still necessary to verify or improve the prenatal diagnosis and may influence future counseling., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: The autopsy and clinical information on children dying with anti-SSA/Ro-associated cardiac manifestations of neonatal lupus (cardiac NL) were examined to identify patterns of disease, gain insight into pathogenesis and enhance the search for biomarkers and preventive therapies., Methods: A retrospective analysis evaluating reports from 18 autopsies of cardiac NL cases and clinical data from the Research Registry for Neonatal Lupus was performed., Results: Of the 18 cases with autopsies, 15 had advanced heart block, including 3 who died in the second trimester, 9 in the third trimester and 3 post-natally. Three others died of cardiomyopathy without advanced block, including two dying pre-natally and one after birth. Pathological findings included fibrosis/calcification of the atrioventricular (AV) node, sinoatrial (SA) node and bundle of His, endocardial fibroelastosis (EFE), papillary muscle fibrosis, valvular disease, calcification of the atrial septum and mononuclear pancarditis. There was no association of pathology with the timing of death except that in the third-trimester deaths more valvular disease and/or extensive conduction system abnormalities were observed. Clinical rhythm did not always correlate with pathology of the conduction system, and the pre-mortem echocardiograms did not consistently detect the extent of pathology., Conclusion: Fibrosis of the AV node/distal conduction system is the most characteristic histopathological finding. Fibrosis of the SA node and bundle of His, EFE and valve damage are also part of the anti-Ro spectrum of injury. Discordance between echocardiograms and pathology findings should prompt the search for more sensitive methods to accurately study the phenotype of antibody damage.

Objective: To determine outcomes for babies with congenital diaphragmatic hernia (CDH) diagnosed prenatally and postnatally presenting to a tertiary unit., Method: Fetal medicine database and neonatal surgical unit admission books were reviewed to identify cases of CDH over a 12-year period (Jan 1998- Dec 2009)., Results: A total of 132 cases of CDH were diagnosed prenatally and 39 cases diagnosed postnatally. Mean gestation at diagnosis was 22 weeks (range 13-37 weeks). Karyotyping was abnormal in 15.9%; abnormal karyotype in 3.6% of fetuses without other structural anomalies compared with 38.9% when other anomalies were identified. In 45 cases (34.1%) pregnancy was terminated. Two stillbirths occurred (2.3% of ongoing pregnancies). One hundred twenty-four babies were live born, of whom 98 babies underwent surgery. Survival to discharge of all live born babies was 72.6%; survival following surgery was 91.8%. Birthweight had a significant effect on survival (odds ratio 0.22, 95% confidence intervals 0.08-0.66). Survival for live born babies prenatally diagnosed was significantly lower (65.9%) than those diagnosed postnatally (92.3%)., Conclusion: Abnormal karyotype was more common when CDH was associated with other anomalies. In multivariate analysis, lower birthweight and prenatal diagnosis had a significant impact on survival. Only prenatally diagnosed CDH survival figures should be utilised in prenatal counselling., (© 2012 John Wiley & Sons, Ltd.)

Objective: Primary fetal pleural effusions are rare. If severe, thoracoamniotic shunting is needed. Our objective was to study the management and outcomes of pleural effusions in our unit., Methods: Retrospective analysis of primary fetal hydrothorax between 1991 and 2010., Results: Of 41 cases, 23 (56%) were hydropic, and 27 (66%) required shunting. Overall, 2 (4.8%) were diagnosed with a chromosomal condition and 4 (9.6%) with a congenital condition (3 Noonan syndrome, 1 mild structural cardiac defect). There were 5 terminations of pregnancy (TOP), 3 in utero deaths and 33 liveborn neonates (80%). Intact survival rate was 44% (12/27) among those shunted, 56% (23/41) among all cases and 70% (23/33) among all liveborn neonates. Most (87.5%) neonatal deaths occurred in newborns delivered before 34 weeks of gestation. The survival rate was higher in nonhydropic compared with hydropic fetuses (85% vs 47%). There were no procedure-related fetal losses. One in utero death was complicated by fatal maternal amniotic embolism., Conclusion: Fetuses with pleural effusions should undergo expert prenatal workup. Hydropic fetuses and those with massive effusions are candidates for thoracoamniotic shunting., (© 2012 John Wiley & Sons, Ltd.)

Objective: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death., Study Design: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed., Results: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95% CI: 1.3-13.5)., Conclusion: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To review the procedure-related complication rates following fetal blood sampling and intrauterine red cell transfusion for anaemic fetuses at a single tertiary center., Design: A retrospective study of 114 intrauterine transfusions., Setting: A single tertiary referral fetal medicine center at Queen Charlotte's and Chelsea Hospital, Imperial College London, London, UK., Sample: All cases (114) undergoing fetal blood sampling and intrauterine transfusion between January 2003 and May 2010., Methods: Early procedure-related complications (severe fetal bradycardia requiring either abandonment of the procedure or emergency delivery, fetal death, preterm labor or rupture of membranes) were investigated by review of computerized records and individual chart review., Main Outcome Measures: Live birth rate, perinatal mortality, procedure-related fetal bradycardia, preterm labor and procedure-related spontaneous rupture of membranes., Results: The majority of cases (77.8%) were due to red cell alloimmunization, with anti-D being the commonest cause. The live birth rate was 93.5%, with a procedure-related fetal death rate of 0.9%. The preterm labor rate (<37 weeks' gestation) was 3.5% only occurring in patients undergoing multiple (>3) fetal transfusions. Complications in this series did not appear to be increased the earlier the gestation at which the first transfusion took place., Conclusions: Despite a reduction in the number of cases requiring intrauterine therapy for fetal anemia, contemporary outcomes appear to be good if not improving. It is important that the experience required to manage these cases should be concentrated in fewer centers to maximize good perinatal outcome., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Purpose of Review: Parvovirus B19 infection is often considered a mild and self-limiting disease of minor clinical importance. This review aims to raise awareness of recently discovered potentially devastating consequences of this infection in pregnancy, and provides updated guidelines on diagnosis and management., Recent Findings: In contrast to previous beliefs, parvovirus B19 infection during any stage of pregnancy may not only cause fetal death, but may also result in severe and irreversible neurological sequelae in survivors. Improved diagnostic techniques allow more reliable and earlier diagnosis of fetal disease., Summary: Clinicians need to be aware of the risk of adverse outcome of parvovirus B19 infection in pregnancy, and sometimes the long interval between exposure and fetal symptoms. Accurate diagnosis using PCR and weekly ultrasound checks ups with Doppler measurement of middle cerebral artery flow velocity up to 20 weeks postexposure may improve detection of fetal disease. More timely treatment likely results in improved outcome.

Objective: We sought to better define echocardiographic predictors of perinatal mortality in fetuses with Ebstein's anomaly (EA) or tricuspid valve dysplasia (TVD)., Method: Parameters included measured chamber size, the presence of hydrops, and Doppler recordings of the left ventricular (LV) myocardial performance index (MPI)., Results: Between 1 January 2000 and 31 December 2008, 21 fetuses were diagnosed with either EA (17) or TVD (4). Five fetuses were lost to follow-up, and 12 of 16 fetuses were born live (75%). Survivors were found to have smaller right atrial area index scores when compared with non-survivors (1.025 ± 0312 vs 1.502 ± 0.105, respectively, p = 0.013) and were less likely to present with hydrops (0% survivors vs 75% of non-survivors, p < 0.01). LV MPI sub-analysis revealed a shorter combined isovolemic contraction and relaxation time for non-survivors compared wth survivors (46.5 ± 8.2 ms vs 82.3 ± 21.2 ms, respectively, p = 0.004) although no difference was observed for LV ejection times or overall LV MPI between survivors and non-survivors., Conclusion: Physiologic analysis of left ventricular function via the LV Tei index and its component measurements demonstrates potentially novel insights into hemodynamic derangements and their association with outcomes in patients with EA/TVD., (© 2012 John Wiley & Sons, Ltd.)

Over more than 50 years, the nocuous effects of smoking in pregnancy on the fetus are well known. In the first years of science the focus was primarily on restricted fetal growth while in more recent years over 10.000 studies investigated the incomparably big sum of detrimental effects for the unborn's health. In this statement we want to present the recent scientific findings on this topic. The statement is aimed to show all doctors who treat pregnant women the present situation and evidence. In the beginning we give a short overview about the epidemiological situation in Europe. Then we present step by step the health effects with regards to pathophysiology and clinics. Furthermore the reader will learn about possibilities for smoking cessation in pregnancy. The problem of passive-smoking in pregnancy will be dealt with in a separate chapter. At present there is strong evidence that pregnant smoking has a detrimental effect on birth-weight, placenta-associated disease, stillbirth, sudden infant death syndrome (SIDS), childhood overweight, clefts, lung function, asthma, cardiovascular diseases and mental developmental disorders. These factors can be summarized by the term Fetal Tobacco Syndrome. There is supply for more studies for less investigated health effects. Pregnancy is a chance to stop smoking as most women show a high motivation in this period. Hence doctors of all disciplines should inform pregnant women about the detrimental effects of smoking on their unborn child and show them possibilities for smoking cessation.

Complications act as stress-inducers during pregnancy so the fetus can develop functional compensatory mechanisms or morphologic changes. The cases analyzed are with congenital malformations or acute stress; chronic included cases with ascending infection (AI) and perinatal hypoxia/anoxia (PHA). The hematoxylin-eosin (H&E) was done to analyze the vacuolization, and the immunohistochemistry to the phagocytosis. The discreet standard of vacuolization was observed in 52.6% of the cases, 22.1% moderate, and 25.3% severe. The number of macrophages was higher in PHA. Changes in these organs are closely related to the cause of death and to the period during which the harmful agent.

Postmortem examination remains the gold standard for the correct diagnosis of many diseases and for unraveling unexplained causes of death. This paper reports on the poor utilization of autopsy services and encourages parents/caregivers and practitioners to perform postmortem examinations on deceased neonates in sub-Saharan Africa. In a retrospective study, the records of 1093 neonates (653 males and 440 females, ratio 1.5∶1) who died at the University of Benin Teaching Hospital and who were brought to the mortuary between 2006 and 2010 were reviewed to determine the utilization of and factors influencing postmortem examination. Sixty-two percent of the neonates died within the 1st week of life, and only 9 (0.8%) underwent a postmortem examination. Findings in the 9 postmortem studies performed on 7 males and 2 females provided additional information on the causes of death. The religious beliefs that neonates should not be subjected to postmortem study and beliefs that dead neonates are taboo and a punishment by the gods for past wrongdoings influenced 511 (46.8%) parents/caregivers to refuse postmortem analysis. The practitioners did not request postmortem study in 281 (25.7%) of the cases. The utilization of postmortem examination was marginal in this setting. We advocate the need for public enlightenment campaigns to modify the attitudes of parents/caregivers toward the postmortem study of deceased neonates. Policies should be formulated to mandate postmortem examinations of deceased neonates to enhance insight into neonatal disease, unravel unexplained causes of death, and improve the standard of neonatal care in this subregion.

Objectives: To evaluate the accuracy and probabilities of different fetal ultrasound parameters to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH)., Methods: Between January 2004 and December 2010, we evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right-sided). The following parameters were evaluated: gestational age at diagnosis, side of the diaphragmatic defect, presence of polyhydramnios, presence of liver herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung volume/fetal weight ratio (US-FLW), observed/expected contralateral and main pulmonary artery diameter (o/e-ContPA and o/e-MPA) ratios and the contralateral vascularization index (Cont-VI). The outcomes were neonatal death and severe postnatal pulmonary arterial hypertension (PAH)., Results: Neonatal mortality was 64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/e-LHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/e-ContPA, o/e-MPA and Cont-VI were associated with both neonatal death and severe postnatal PAH (P < 0.001). Receiver-operating characteristics curves indicated that measuring total lung volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI was the most accurate ultrasound parameter to predict neonatal death and severe PAH (P < 0.001)., Conclusions: Evaluating total lung volumes is more accurate than is measuring only the contralateral lung size. Evaluating pulmonary vascularization (Cont-VI) is the most accurate predictor of neonatal outcome. Estimating the probability of survival and severe PAH allows classification of cases according to prognosis., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To assess the use and efficacy of in-utero pleurodesis for experimental treatment of bilateral fetal chylothorax., Methods: This was a study of 78 fetuses with bilateral pleural effusion referred to three tertiary referral centers in Taiwan between 2005 and 2009. Fetuses were karyotyped following amniocentesis and the lymphocyte ratio in the pleural effusion was determined following thoracocentesis. Forty-nine (62.8%) fetuses had a normal karyotype and were recognized to have fetal chylothorax; of these, 45 underwent intrapleural injection of 0.1KE OK-432 per side per treatment. We evaluated clinical (hydrops vs. no hydrops) and genetic (mutations in the reported lymphedema-associated loci: VEGFR3, PTPN11, FOXC2, ITGA9) parameters, as well as treatment outcome. Long-term survival was defined as survival to 1 year of age., Results: The overall long-term survival rate (LSR) was 35.6% (16/45); the LSR for non-hydropic fetuses was 66.7% (12/18) and for hydropic fetuses it was 14.8% (4/27). If we included only fetuses with onset of the condition in the second trimester, excluding those with onset in the third trimester, the LSR decreased to 29.4% (10/34). Notably, 29.6% (8/27) of hydropic fetuses had mutations in three of the four loci examined., Conclusions: OK-432 pleurodesis appeared to be an experimental alternative to the gold-standard technique of thoracoamniotic shunting in non-hydropic fetal chylothorax. In hydropic fetuses, pleurodesis appeared less effective., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To assess outcome in twin pregnancies according to chorionicity., Methods: A cohort was retrieved from local ultrasound databases at 14 obstetric departments in Denmark, comprising all twin pregnancies with two live fetuses scanned between weeks 11 and 14 in the period 1 January 2004 to 31 December 2006. Outcome data were retrieved from the National Board of Health., Results: Among 2038 twin pregnancies, 1757 (86.2%) were dichorionic (DC) and 281 (13.8%) were monochorionic diamniotic (MC). In MC pregnancies, the rate of spontaneous fetal loss in both second and third trimesters was more than threefold higher than the comparable rate in DC pregnancies: 6.0% vs. 1.9% for at least one fetus in the second trimester (P < 0.001) and 2.1% vs. 0.7% in the third trimester (P = 0.03). In 98.4% of DC pregnancies and in 91.1% of MC pregnancies, at least one infant was liveborn. Amongst pregnancies with two live fetuses at 24 weeks, the proportion with two live infants at 28 days after delivery was 97.5% and 95.1%, respectively., Conclusions: The increased incidence of fetal loss in MC pregnancies compared with DC pregnancies predominantly occurs before 24 weeks' gestation. After this stage, although the risk of intrauterine fetal death is still higher in MC than in DC pregnancies, if both fetuses are alive at 24 weeks, the chance of a woman having two live infants 1 month after delivery is similar in MC and DC pregnancies., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Background: Intermittent fetal heart rate (FHR) monitoring during labor using an acoustic stethoscope is the most frequent method for fetal assessment of well-being in low- and middle-income countries. Evidence concerning reliability and efficacy of this technique is almost nonexistent., Objectives: To determine the value of routine intermittent FHR monitoring during labor in the detection of FHR abnormalities, and the relationship of abnormalities to the subsequent fresh stillbirths (FSB), birth asphyxia (BA), need for neonatal face mask ventilation (FMV), and neonatal deaths within 24 h., Methods: This is a descriptive observational study in a delivery room from November 2009 through December 2011. Research assistants/observers (n = 14) prospectively observed every delivery and recorded labor information including FHR and interventions, neonatal information including responses in the delivery room, and fetal/neonatal outcomes (FSB, death within 24 h, admission neonatal area, or normal)., Results: 10,271 infants were born. FHR was abnormal (i.e. <120 or >160 beats/min) in 279 fetuses (2.7%) and absent in 200 (1.9%). Postnatal outcomes included FSB in 159 (1.5%), need for FMV in 695 (6.8%), BA (i.e. 5-min Apgar score <7) in 69 (0.7%), and deaths in 89 (0.9%). Abnormal FHR was associated with labor complications (OR = 31.4; 95% CI: 23.1-42.8), increased need for FMV (OR = 7.8; 95% CI: 5.9-10.1), BA (OR = 21.7; 95% CI: 12.7-37.0), deaths (OR = 9.9; 95% CI: 5.6-17.5), and FSB (OR = 35; 95% CI: 20.3-60.4). An undetected FHR predicted FSB (OR = 1,983; 95% CI: 922-4,264)., Conclusions: Intermittent detection of an absent or abnormal FHR using a fetal stethoscope is associated with FSB, increased need for neonatal resuscitation, BA, and neonatal death in a limited-resource setting. The likelihood of an abnormal FHR is magnified with labor complications., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: To describe a series of complex fetal anemia cases, detail the appropriate investigations and management, and review the literature., Methods: Four cases of non-red cell alloimmunization or infective cases of fetal anemia are presented., Results: Of the four cases presented, one was a neonatal death, one pregnancy was terminated, one case was diagnosed with Diamond Blackfan anemia, and one case was due to recurrent feto-maternal hemorrhages despite negative Kleihauer tests., Conclusions: Non-alloimmune causes of fetal anemia can be difficult to manage. Some cases require repeated and frequent intrauterine transfusions. The perinatal mortality and preterm delivery rates are increased, and some cases require considerable long-term treatment including regular transfusions. We present our experience of a series of non-immune fetal anemia managed in a tertiary unit, review the literature, and suggest appropriate management.