Comparison of radiographic femur measurements in stillbirths and neonatal deaths to ultrasound measurements in ongoing pregnancies.

Identifying growth abnormalities in stillbirths is clinically useful but complicated by maceration. This is an observational study of consecutive postmortem examinations in which femur lengths and gestational age at delivery were collected, along with associated congenital anomalies and extent of fetal maceration. Between 2005 and 2012, 1530 consecutive postmortem examinations were performed and the information recorded. Fragmented fetuses (417), live-born fetuses that survived for more than 24 hours (134), fetuses with any signs of maceration (419), fetuses with known anomalies (98), and records with missing data (249) were excluded. The analyses focused on the remaining 265 nonmacerated stillborn fetuses and infants that survived for less than 24 hours after birth. The relationship between gestational age at delivery and femur length was computed, and a quadratic equation fit the data well between 12 and 40 weeks' gestation (R  =  0.944). Gestational age-specific reference ranges for radiographic femur measurements in stillbirths are equivalent to those for ultrasound-determined measurements in ongoing pregnancies. These reference data may be useful in identifying growth abnormalities in nonmacerated stillborn fetuses.

Current status of paediatric post-mortem imaging: an ESPR questionnaire-based survey.

BACKGROUND: The use of post-mortem imaging, including skeletal radiography, CT and MRI, is increasing, providing a minimally invasive alternative to conventional autopsy techniques. The development of clinical guidelines and national standards is being encouraged, particularly for cross-sectional techniques. OBJECTIVE: To outline the current practice of post-mortem imaging amongst members of the European Society of Paediatric Radiology (ESPR). MATERIALS AND METHODS: We e-mailed an online questionnaire of current post-mortem service provisions to members of the ESPR in January 2013. The survey included direct questions about what services were offered, the population imaged, current techniques used, imaging protocols, reporting experience and intended future involvement. RESULTS: Seventy-one percent (47/66) of centres from which surveys were returned reported performing some form of post-mortem imaging in children, of which 81 % perform radiographs, 51% CT and 38% MRI. Eighty-seven percent of the imaging is performed within the radiology or imaging departments, usually by radiographers (75%), and 89% is reported by radiologists, of which 64% is reported by paediatric radiologists. Overall, 72% of positive respondents have a standardised protocol for radiographs, but only 32% have such a protocol for CT and 27% for MRI. Sixty-one percent of respondents wrote that this is an important area that needs to be developed. CONCLUSION: Overall, the majority of centres provide some post-mortem imaging service, most of which is performed within an imaging department and reported by a paediatric radiologist. However, the populations imaged as well as the details of the services offered are highly variable among institutions and lack standardisation. We have identified people who would be interested in taking this work forwards.

Cerebellar Purkinje cell vulnerability to prenatal nicotine exposure in sudden unexplained perinatal death.

The present study was aimed at supplementing our previous investigations on the morphological features of the Purkinje cells during the autonomic nervous system development, particularly in victims of sudden perinatal death (Sudden Intrauterine Unexplained Death Syndrome and Sudden Infant Death Syndrome), given their crucial role in determining connectivity patterns in the brain as well as in the control of autonomic functions. We highlighted in these pathologies, and precisely in 21 cases of sudden foetal death and 26 cases of sudden infant death, a high percentage of developmental defects of the Purkinje cells such as heterotopia, hypoplasia, hyperplasia, mitotic and/or shrunken features and abnormal neuronal nuclear antigen expression. These alterations can be interpreted as a result of a defective maturation and/or migration of Purkinje cells in foetal cerebellum, likely consequence of exposure to injuries, particularly to maternal cigarette smoke. Interestingly, we observed in sudden perinatal deaths an association with similar developmental defects of both the dentate and the inferior olivary nuclei. This suggests the existence of a Purkinje-Olivo-Dentate network playing a fundamental role in triggering a sudden death mechanism in perinatal life in the presence of specific risk factors.

[Intra-uterine death caused by fetal akinesia]. / Intra-uteriene sterfte door foetale bewegingsarmoede: het belang van diagnostiek na een vruchtdood.

BACKGROUND: When two successive pregnancies end in intra-uterine fetal death (IUFD), the question of whether it is coincidental or if there is an underlying abnormality arises. Although diagnostic investigations into the underlying cause are not always carried out after IUFD, they are recommended by the professional body. CASE DESCRIPTION: A 28-year-old female attended our gynaecology outpatient clinic for a second opinion following two intra-uterine fetal deaths. Her own treating physician was of the opinion that there was no connection between the two IUFDs. After a multidisciplinary evaluation, the phenotype fetal akinesia deformation sequence (FADS) was diagnosed in both cases. This is a rare, clinically and aetiologically heterogeneous group of disorders. Thereafter the patient and her husband were offered specific pre-conception counseling. CONCLUSION: Every IUFD justifies systemic and multidisciplinary investigation to determine any underlying aetiology such as FADS. This may contribute to better pre-conception advice and prenatal individualised diagnostics in a subsequent pregnancy.

Vanishing twins in diamniotic dichorionic in vitro fertilization gestation in mid-second trimester.

The authors report a diamniotic dichorionic twin pregnancy after in vitro fertilization (IVF) in mid-second trimester. The dead fetuses were delivered by cesarean section at the 20th week of gestation. The authors discuss management aspects and review of the literature.

Preoperative prediction of the individualized risk of early fetal death after laser therapy in twin-to-twin transfusion syndrome.

OBJECTIVE: The aim of this study is to evaluate the independent and combined value of gestational age, fetal weight, fetoplacental Doppler, and myocardial performance index for the prediction of individual risk of early (≤7 days) intrauterine fetal death (IUFD) after laser therapy in twin-to-twin transfusion syndrome (TTTS). MATERIAL AND METHODS: A consecutive series of 215 cases of TTTS treated with laser therapy in three centers was prospectively studied. Ultrasound evaluation within 24 h of surgery included estimated fetal weight discordance, umbilical artery, pulsatility index (PI) and diastolic flow evaluation, middle cerebral artery PI and middle cerebral artery peak systolic velocity, ductus venosus PI and atrial flow assessment, and modified myocardial performance index. Logistic regression analysis was used to explore the association of preoperative parameters with IUFD. RESULTS: Intrauterine fetal death occurred in 17 (7.9%) of the recipients and 33 (15.3%) donors (p = 0.016). The only independent predictors of IUFD in recipients was the middle cerebral artery peak systolic velocity >1.5 MoM (OR = 22, p = 0.015), but this event was present in only 3% of recipients. In donors, reverse end diastolic flow in the umbilical artery (OR = 14.748, p = 0.033), estimated fetal weight discordance (OR = 1.054, p = 0.036), and gestational age (OR = 0.757, p = 0.046) were independent predictors. CONCLUSION: In TTTS, preoperative fetal assessment can identify independent risk factors for early post-operative IUFD, particularly in donors.

Thirty-eight cases of acute pancreatitis in pregnancy: a 6-year single center retrospective analysis.

Thirty-eight pregnant inpatients with acute pancreatitis (AP) were retrospectively reviewed from 2006 to 2012 in our hospital. The incidence of pregnancy-associated AP was 2.27‰. Most (78.95%) of the attack occurred in the third trimester. The median of APACHE II score was 6 and severe AP accounted for 31.58% (12 cases). Primary diseases were absent in most cases (57.89%). The most common clinical presentations were abdominal pain (89.47%) and vomiting (68.42%). Pleural effusion and ascites were found only in the third trimester. Elevated white blood cell count, amylase and lipase were commonly found in biochemical examinations. Eleven cases required intensive care in ICU and 21 cases received caesarean section. There were 2 maternal deaths and 12 fetal losses including 4 abortions. It is concluded that AP is a rare entity in pregnancy. The incidence of pancreatitis increases with the gestational age. However, the severity is not necessarily related with the pregnancy trimesters. The diagnosis is based on clinical presentations, laboratory tests and imaging examinations. Although the treatment strategy of a pregnant woman with pancreatitis is similar to the general non-pregnant patient with AP, a multidisciplinary team consisting of gastroenterologist, gastrointestinal surgeon, radiologist, obstetrician, and ICU doctor should be set up.

Post-partum bilateral renal cortical necrosis in antiphospholipid syndrome and systemic lupus erythematosus.

In the presence of systemic lupus erythematosus or related autoimmune disorders, antiphospholipid syndrome (APS) is termed secondary APS. Pregnancy-related renal failure due to SAPS is rarely reported in the literature. We present the case of a young primgravida woman with bilateral renal cortical necrosis due to secondary APS in late pregnancy.

Second trimester fetal death caused by varicella-zoster virus infection.

A 31-year-old woman contracted acute varicella at 13 weeks of gestation. Severe hydrops fetalis, hepatomegaly, and intrauterine fetal death were detected at 16 weeks of gestation by ultrasound examinations. An examination at autopsy, histopathology, and polymerase chain reaction (PCR) provided evidence of varicella-zoster virus (VZV) infection of the fetus. Second trimester intrauterine fetal death caused by mother to fetus infection of VZV is extremely rare.

Post-mortem high-field magnetic resonance imaging: effect or various factors.

PURPOSE: To evaluate image quality and diagnostic accuracy of high-field post-mortem (PM) magnetic resonance imaging (MRI) on fetuses below 20 weeks of gestation before and after the freeze-thaw process. MATERIALS AND METHODS: Nine fetuses were scanned with three different scanning procedures: "fresh", just after termination of pregnancy (TOP), "non-fresh short scan" and "non-fresh long scan" after being kept at -20 °C, followed by a conventional autopsy. The brain, thorax except the heart, heart and abdomen were studied. The qualities of the images for the four different fetal regions and for the three different scanning procedures were reported. Regression analysis was used to investigate the effect on image quality of different factors. Additionally, the diagnostic accuracy was also evaluated. RESULTS: Fetuses at 12.0-19.6 weeks were included. Regression analysis showed that better image quality was correlated to advanced gestation at TOP and scan on fresh fetuses. PM-MRI on fresh fetuses was always diagnostic for the brain and in more than half of cases on non-fresh fetuses and was nearly equally diagnostic for thoracic and abdominal structures. CONCLUSION: High-field PM-MRI seems to offer a quite reliable alternative to the parents declining conventional PM for fetuses before 20 weeks whether these fetuses are freshly scanned or after being frozen.

Fetal alcohol exposure: consequences, diagnosis, and treatment.

Maternal alcohol use during pregnancy is prevalent, with as many as 12% of pregnant women consuming alcohol. Alcohol intake may vary from an occasional drink, to weekly binge drinking, to chronic alcohol use throughout pregnancy. Whereas there are certain known consequences from fetal alcohol exposure, such as fetal alcohol syndrome, other effects are less well defined. Craniofacial dysmorphologies, abnormalities of organ systems, behavioral and intellectual deficits, and fetal death have all been attributed to maternal alcohol consumption. This review article considers the theoretical mechanisms of how alcohol affects the fetus, including the variable susceptibility to fetal alcohol exposure and the implications of ethanol dose and timing of exposure. Criteria for diagnosis of fetal alcohol syndrome are discussed, as well as new methods for early detection of maternal alcohol use and fetal alcohol exposure, such as the use of fatty acid ethyl esters. Finally, current and novel treatment strategies, both in utero and post utero, are reviewed.

Customized growth charts for twin gestations to optimize identification of small-for-gestational age fetuses at risk of intrauterine fetal death.

OBJECTIVE: Customized growth charts developed for singleton pregnancies have been shown to be more effective than population-based ones at identifying small-for-gestational age (SGA) fetuses at risk for intrauterine fetal death (IUFD). We sought to compare the association between SGA and IUFD in twins using customized growth charts designed for twin gestations compared to those designed for singletons. METHODS: This was a retrospective cohort study using a database including singleton and twin pregnancies undergoing ultrasound examination between 16 and 20 weeks' gestation. After excluding preterm births < 34 weeks, congenital anomalies and stillbirths, we identified 51, 150 singleton births. Coefficients for significant physiological and pathological variables affecting birth weight for singletons were derived using backward stepwise multiple regression. The same process was repeated for twin births (1608 pairs), also adjusting for chorionicity. Customized growth charts for each pregnancy were derived using these two regression models for optimal birth weight at term and a proportionality equation. The association between SGA < 10(th) percentile, defined using the twin and singleton-customized charts, and IUFD were compared. Statistical analysis, including calculation of adjusted odds ratios (OR) for IUFD and screening accuracy using each chart, was performed. RESULTS: The derived coefficients for optimal birth weight for twins were different from those for singletons, with lower constants and root mean square error (3422 and 288.9, respectively, in twins vs 3543 and 416 in singletons). Among 3786 twin infants, IUFD was seen in 123 (3.2%). The numbers of fetuses identified as SGA were 575 (15.2%) and 504 (13.3%) by the singleton and twin charts, respectively. Fetuses classified as SGA by the twin-specific customized charts were at a significantly increased risk for IUFD (adjusted OR, 2.3 (95% CI, 1.4-3.5)), whereas those classified as SGA by the singleton-customized charts were not (adjusted OR, 1.2 (95% CI, 0.7-2.0)). CONCLUSION: Customized charts designed specifically for twins are more effective at identifying twin pregnancies at risk for IUFD than are those derived using singleton birth data.

Lifting the lid on unborn lethal Mendelian phenotypes through exome sequencing.

PURPOSE: Mendelian phenotypes in humans vary from benign variants to lethal disorders. Embryonic lethal phenotypes that are similar to what has been known for a long time in mice have remained largely unknown because of the difficulty in arriving at a molecular diagnosis. The purpose of this study is to test whether next generation sequencing can reveal the underlying etiology of recurrent fetal loss. METHODS: We hypothesized that exome sequencing combined with autozygome analysis can reveal the underlying mutation in a family in which recurrent fetal loss was likely to be autosomal recessive in origin. RESULTS: A novel mutation in CHRNA1 was identified. This gene is known to cause multiple pterygium and fetal akinesia syndrome. CONCLUSION: This is the first report of exome sequencing to identify the cause of recurrent fetal loss and reveal the diagnosis of a lethal human phenotype. Our results should inspire a systematic examination of the extent of "unborn" Mendelian phenotypes in humans using next-generation sequencing.