[Pancreas structure in fetuses and newborn infants who died in the perinatal period].

In the pancreas of fetuses at weeks 22-40 of prenatal development (n = 111) and of newborn infants who died during the first week of postnatal life (n = 38) the changes were detected that were characterized by exocrine part hypoplasia, retardation of acinar pancreatocyte differentiation, connective tissue outgrowth, pancreatic (Langerhans) islet hyperplasia and hypertrophy. The results of the study have shown that with the increase of the total risk sum of the perinatal period pathology development (expressed in balls), the relative content of the insular part of the organ and the number of large pancreatic islets (larger than 100 microm in diameter) decreased. The morphological features detected in this study indirectly reflect endo-ecologically discomfortable conditions of fetus development within the fetoplacental unit which increase the risk of polyendocrinopathy development and fetal intrauterine growth retardation. These polyendocrinopathies increase further the risk of endocrine disturbance occurence in childhood.

Postmortem ultrasonography of the macerated fetus complements autopsy following in utero fetal demise.

Postmortem evaluation following an in utero fetal demise is essential for determining cause of death and counseling regarding future pregnancies. Severe maceration and fetal size along with patient desires may limit the physician's ability to perform a complete autopsy. In the cases presented, we demonstrate the utility of postmortem ultrasonography as an adjunct to traditional autopsy following fetal demise.

Placental findings in singleton stillbirths.

OBJECTIVE: To compare placental lesions for stillbirth cases and live birth controls in a population-based study. METHODS: Pathologic examinations were performed on placentas from singleton pregnancies using a standard protocol. Data were analyzed overall and within gestational age groups at delivery. RESULTS: Placentas from 518 stillbirths and 1,200 live births were studied. Single umbilical artery was present in 7.7% of stillbirths and 1.7% of live births, velamentous cord insertion was present in 5% of stillbirths and 1.1% of live births, diffuse terminal villous immaturity was present in 10.3% of stillbirths and 2.3% of live births, inflammation (eg, acute chorioamnionitis of placental membranes) was present in 30.4% of stillbirths and 12% of live births, vascular degenerative changes in chorionic plate were present in 55.7% of stillbirths and 0.5% of live births, retroplacental hematoma was present in 23.8% of stillbirths and 4.2% of live births, intraparenchymal thrombi was present in 19.7% of stillbirths and 13.3% of live births, parenchymal infarction was present in 10.9% of stillbirths and 4.4% of live births, fibrin deposition was present in 9.2% of stillbirths and 1.5% of live births, fetal vascular thrombi was present in 23% of stillbirths and 7% of live births, avascular villi was present in 7.6% of stillbirths and 2.0% of live births, and hydrops was present in 6.4% of stillbirths and 1.0% of live births. Among stillbirths, inflammation and retroplacental hematoma were more common in placentas from early deliveries, whereas thrombotic lesions were more common in later gestation. Inflammatory lesions were especially common in early live births. CONCLUSIONS: Placental lesions were highly associated with stillbirth compared with live births. All lesions associated with stillbirth were found in live births but often with variations by gestational age at delivery. Knowledge of lesion prevalence within gestational age groups in both stillbirths and live birth controls contributes to an understanding of the association between placental abnormality and stillbirth. LEVEL OF EVIDENCE: II.

Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and children: from research into clinical practice.

Although post-mortem MRI (PMMR) was proposed as an alternative to conventional autopsy more than a decade ago, the lack of systematic validation has limited its clinical uptake. Minimally invasive autopsy (MIA) using PMMR together with ancillary investigations has now been shown to be as accurate as conventional autopsy in foetuses, newborns and infants and is particularly useful for cerebral, cardiac and genitourinary imaging. Unlike conventional autopsy, PMMR provides a permanent three-dimensional auditable record, with accurate estimation of internal organ volumes. MIA is becoming highly acceptable to parents and professionals, and there is widespread political support and public interest in its clinical implementation in the UK. In the short to medium term, it is desirable that a supraregional network of specialist centres should be established to provide this service within the current National Health Service framework.

Fetal age estimation using MSCT scans of deciduous tooth germs.

Evaluation of fetal age is an essential element in many fields such as anthropology, odontology, paleopathology, and forensic sciences. This study examines the correlation between fetal age, femoral diaphyseal length (considered as the gold standard), and deciduous tooth germs of fetuses aged 22 to 40 weeks amenorrhea (WA) based on computed tomography (MSCT) reconstructions. Qualitative and quantitative studies of femoral and deciduous tooth germ lengths were performed on 81 fetuses (39 females and 42 males). R software was used for statistical analyses. Intra-observer and inter-observer variabilities and the interclass correlation coefficient (ICC) were calculated. Correlation coefficients (R (2)) and linear regression equations were calculated. Intra- and inter-observer variabilities were very satisfactory (intra-observer ICC ≥ 0.96, inter-observer ICC ≥ 0.95). Femoral length was significantly correlated with age (R (2) = 0.9). The correlation coefficient between age and height, width, and dental volume was R (2) ≥ 0.73. Tooth germs were good indicators of fetal age. Our method appears to be reliable and reproducible, and the results of this study agreed with those of the literature. The dental formula provided a precise estimation of fetal age between 25 and 32 WA. Tooth germs were reliable indicators of fetal age, and multislice computed tomography was shown to be an innovative and reliable technology for this purpose.

[Contribution of volume ultrasound in the evaluation and prenatal care of fetal cardiovascular anomalies]. / Apport de l'échographie volumique dans l'évaluation et la prise en charge prénatale anténatale des anomalies cardiovasculaires fœtales.

OBJECTIVES: To highlight the value of 3D ultrasound in the prenatal assessment of fetal cardiovascular abnormalities. PATIENTS AND METHODS: A retrospective offline analysis of volume datasets of fetuses diagnosed with cardiovascular anomalies by 2D ultrasound was performed. RESULTS: Thirty-four fetuses with 38 cardiac malformations were evaluated. Mean gestational age at diagnosis was 26 weeks. Isolated cardiovascular malformations were detected in 23 fetuses. Extracardiac abnormalities were identified in eight fetuses. Ten terminations of pregnancy were performed. CONCLUSION: Offline analysis of cardiovascular anomalies conferred significant diagnostic advantages over 2D ultrasound. 3D ultrasound is a valuable tool for the prenatal diagnosis and the management of congenital heart diseases.

[Evaluation of intrauterine death: importance of examination of fetal, placental and maternal factors]. / Evaluierung des intrauterinen Fruchttods: Stellenwert der Untersuchung fetaler, plazentarer und maternaler Faktoren.

AIMS: Intrauterine death is a multifactorial major complication during pregnancy. In this retrospective analysis the pathological anatomical findings of fetuses and placentas as well as maternal factors were evaluated. MATERIAL AND METHODS: A retrospective screening of post-mortem examinations, corresponding placental examinations and clinical data on maternal status (1998-2008) was carried out. A classification of all findings was made with the ReCoDe system and induced abortions and cases with incomplete data were excluded from the study. RESULTS: A total of 84 pregnancies involving 87 fetuses (9 siblings) were evaluated. The median gestation age was 20 weeks (range 12-41). The evaluation based on the ReCoDe system revealed that intrauterine death was mainly associated with placental diseases (n = 63) and to a lesser extent with fetal malformations (n = 15) or maternal diseases (n = 4). Idiopathic cases were rare (n = 2). CONCLUSIONS: Placental examination is important for explaining intrauterine death because in most cases an association with placental diseases can be found but fetal malformation and maternal diseases must be taken into account.

[Fetal cytomegalovirus infection diagnosed on autopsy: a case report]. / Infection fœtale à cytomégalovirus de diagnostic autopsique: à propos d'un cas.

The cytomegalovirus (CMV) is the most common maternal-fetal transmission infectious disease. The diagnosis of this infection is rarely made on antenatal sonographic signs. Pathological examination could, in this case, make etiologic diagnosis. We report the case of a terminated pregnancy, at the term of 19 weeks of gestation, occurring in a 31-year-old woman. The sonography found a terminated pregnancy with anamnios. Histological examination of samples of fetal internal organs showed intranuclear inclusions, compatible with CMV infection. The main objective of our work is to emphasize the value of histological examination in the diagnosis of fetal death etiology. Moreover, we will discuss the benefit of antenatal screening of CMV maternal infection.

The genetic autopsy.

PURPOSE OF REVIEW: To assess the relevance of perinatal and pediatric autopsies in genetic and metabolic diseases. RECENT FINDINGS: Genetic investigations are an important component of fetal autopsies. Despite the advances in imaging diagnosis, the autopsy can identify abnormalities not seen on ultrasound or MRI, as confirmed in recent comparative studies. This is crucial in the diagnosis of syndromic conditions in which the information may be essential to determine the syndrome. Genetic tests may also have a role in the investigation of intrauterine growth restriction and unexplained stillbirth. New techniques have increased the diagnostic yield, even in cases of macerated fetuses.The genetic autopsy is not limited to fetal loss. Genetic abnormalities underlie many cases presenting as sudden unexpected death in infancy, childhood and adolescence, and the need to obtain appropriate samples for genetic analysis applies not only to fetal autopsies. SUMMARY: Fetal autopsies are still the gold standard in diagnosis of fetal abnormalities. Genetic studies are an important component, not only in cases of congenital malformations, but also in unexplained intrauterine death and sudden unexpected death in infancy, as well as in children and adults.

Placental mesenchymal dysplasia with hepatic mesenchymal hamartoma: a case report and literature review.

Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly and grapelike vesicles resembling a partial molar pregnancy and in most cases, a phenotypically normal fetus. Hepatic mesenchymal hamartoma (HMH) is a benign hamartomatous proliferation of mesenchymal liver tissue. PMD has been associated with HMH. Although rare, in combination, it is known to carry a poorer prognosis than in fetuses without structural abnormalities. There are only a few reported cases of PMD and associated HMH with varying management strategies and outcomes, precluding ascertainment of the most appropriate treatment plan. We present a case of PMD with associated cystic HMH resulting in fetal death. We also reviewed the published literature on this issue and explored possible management strategies to prevent adverse fetal and neonatal outcomes.

Modeling the potential public health impact of prepregnancy obesity on adverse fetal and infant outcomes.

OBJECTIVE: Approximately one-third of US reproductive-aged women are obese, and prepregnancy obesity is a strong risk factor for adverse fetal and infant outcomes. The annual number of preventable adverse fetal and infant outcomes associated with prepregnancy obesity in the U.S. was estimated. DESIGN AND METHODS: Adverse fetal and infant outcomes for which statistically significant associations with prepregnancy obesity had been reported by peer-reviewed meta-analyses, which included fetal deaths and nine different major birth defects, were assessed. The true prevalence of prepregnancy obesity was estimated by multiplying self-reported prepregnancy obesity by a bias factor based on the difference between measured and self-reported obesity in U.S. adult women. A Monte Carlo simulation approach was used to model the attributable fraction and preventable number, accounting for uncertainty in the estimates for: strength of the association with obesity, obesity prevalence, and outcome prevalence. RESULTS: Eliminating the impact of prepregnancy obesity would potentially prevent the highest numbers of four outcomes: fetal deaths (6,990; uncertainty interval [UI] 4,110-10,080), congenital heart defects (2,850; UI 1,035-5,065), hydrocephalus (490; UI 150-850), and spina bifida (405; UI 305-505). If 10% of women with prepregnancy obesity achieved a healthy weight before pregnancy or otherwise mitigated the impact of obesity, nearly 300 congenital heart defects and 700 fetal deaths per year could potentially be prevented. CONCLUSION: This simulation suggests that effective prevention strategies to reduce prepregnancy obesity or the risk associated with obesity could have a measurable impact on infant health in the US.

Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion.

BACKGROUND: Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in missed abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in missed abortion. METHODS: Women with missed abortion (n=27) and healthy controls (n=26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry. RESULTS: Compared with induced abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in missed abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positively correlated with Notch1. CONCLUSIONS: The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in missed abortion.

Perinatal pathologic examination of nonintact, second-trimester fetal demise specimens: the value of standardization.

CONTEXT: Management of second-trimester intrauterine fetal demise via dilation and evacuation results in nonintact specimens for pathologic examination. Surgical pathology examination is often mandated; however, evidence on expected findings and specimen evaluation guidelines are lacking. OBJECTIVES: To assess pathologic findings of nonintact, second-trimester fetal demise specimens, through comparison of anatomic abnormalities identified on standardized perinatal examination to individualized general pathology examinations. DESIGN: Single institution, retrospective chart review of 14- to 24-week gestational size fetal demise cases was conducted from May 2006 to October 2010. Suspected abnormalities, chromosomal and pathologic diagnoses were collected. A general surgical pathology examination occurred between May 2006 and October 2008, while a perinatal pathologist examined specimens between October 2008 and October 2010. Statistical analysis consisted of t tests and χ(2) tests by Stata/SE 12.1. RESULTS: One hundred eighteen specimens were included and mean gestational size was 16.0 weeks (standard deviation, 1.6 weeks). Perinatal pathologic evaluation diagnosed significantly more abnormalities than did general pathologic examination (77.3% [34 of 44] versus 9.5% [7 of 75], P < .001). Forty-eight abnormalities were identified: 77.0% (n = 37) were placental and 23.0% (n = 11) were fetal. Chromosomal analysis was done on 73.7% (n = 87 of 118) with 12.6% (n = 11 of 87) showing abnormalities. Among aneuploid specimens, the perinatal pathologist confirmed abnormalities in 66.7% (n = 4 of 6) of cases while general pathologists confirmed abnormalities in 0% (n = 0 of 5) (P = .02). CONCLUSIONS: Systematic surgical pathology examination of nonintact, second-trimester fetal demise specimens yields increased information on fetal or placental abnormalities, which may be clinically useful. Institutions with high-risk obstetrical practices and dilation and evacuation providers should consider integrating a standardized perinatal checklist into educational and practice guidelines.

[Placental pathology of uteroplacental vascular deficiency]. / Anatomie pathologique de l'insuffisance vasculaire utéroplacentaire.

The indications of the pathological examination of the placenta are mainly represented by uteroplacental vascular deficiency. The clinical context is often evocative, but it can sometimes be solely an intra-uterine growth retardation or an unexplained in utero fetal death. So, the pathological lesions of this uteroplacental vascular deficiency must be well-known to be correctly interpreted, for none of these lesions is truly specific. The pathological diagnosis is based on a group of macroscopic and microscopic arguments. Various physiopathological mechanisms, often imperfectly known, can be at the origin of an uteroplacental vascular insufficiency, but in the current position, the pathological examination does not allow etiopathogenic orientation. The development of the trophoblastic biopsies gives us access to a new material which, in parallel with the cytogenetic analysis, often allows us, in front of an unexplained intra-uterine growth retardation, to direct the diagnosis towards uteroplacental vascular insufficiency. The histological analysis of the chorionic villous sampling taken precociously during pathological pregnancies is thus a major diagnostic contribution. But especially, this analysis gives access to new information which, in the near future, will enable us to better define the pathological evolution of the lesions of hypoxic chorionic villous and to contribute to a better knowledge of this pathology which, under many aspects, still conceals many mysteries.

Prenatal diagnosis, clinical outcomes, and associated pathology in pregnancies complicated by massive subchorionic thrombohematoma (Breus' mole).

OBJECTIVES: To review the association between ultrasound findings, placental pathology, and prognosis in pregnancies complicated by massive subchorionic thrombohematoma (MTH)/Breus' mole. METHOD: We identified 14 cases of MTH from January 2004 to December 2012. MTH was defined by >1 cm thickness hematoma and extensive (≥50%) involvement of the fetal surface of the placenta. Patient information, details of initial presentation, and perinatal outcome were obtained from the manual and electronic chart records. Ultrasound findings were related to pregnancy outcomes and associated placental pathology. Participants were stratified on the basis of birth outcome into survivors (live births, n = 7) and nonsurvivors (neonatal deaths or intrauterine fetal deaths/termination of pregnancy, n = 7). RESULTS: All 14 cases of MTH were suspected on ultrasound and confirmed by pathology assessment. All cases in the nonsurvivor group had abnormal umbilical artery (UA) Doppler waveforms compared with none in the survivors (p = 0.02). All cases in the nonsurvivor group had extreme preterm deliveries (p = 0.02). Birth weight was significantly reduced in the nonsurvivor group (p = 0.001), and 5/7 cases were diagnosed with severe intrauterine growth restriction, compared with none in the survivor group (p = 0.02). CONCLUSION: Massive subchorionic thrombohematoma/Breus' mole may be diagnosed in the second trimester by ultrasound assessment of the placenta. Normal fetal growth and UA Doppler waveforms are associated with perinatal survival.

Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study.

BACKGROUND: Post-mortem MRI is a potential diagnostic alternative to conventional autopsy, but few large prospective studies have compared its accuracy with that of conventional autopsy. We assessed the accuracy of whole-body, post-mortem MRI for detection of major pathological lesions associated with death in a prospective cohort of fetuses and children. METHODS: In this prospective validation study, we did pre-autopsy, post-mortem, whole-body MRI at 1·5 T in an unselected population of fetuses (≤24 weeks' or >24 weeks' gestation) and children (aged <16 years) at two UK centres in London between March 1, 2007 and Sept 30, 2011. With conventional autopsy as the diagnostic gold standard, we assessed MRI findings alone, or in conjunction with other minimally invasive post-mortem investigations (minimally invasive autopsy), for accuracy in detection of cause of death or major pathological abnormalities. A radiologist and pathologist who were masked to the autopsy findings indicated whether the minimally invasive autopsy would have been adequate. The primary outcome was concordance rate between minimally invasive and conventional autopsy. FINDINGS: We analysed 400 cases, of which 277 (69%) were fetuses and 123 (31%) were children. Cause of death or major pathological lesion detected by minimally invasive autopsy was concordant with conventional autopsy in 357 (89·3%, 95% CI 85·8-91·9) cases: 175 (94·6%, 90·3-97·0) of 185 fetuses at 24 weeks' gestation or less, 88 (95·7%, 89·3-98·3) of 92 fetuses at more than 24 weeks' gestation, 34 (81·0%, 66·7-90·0) [corrected] of 42 newborns aged 1 month or younger, 45 (84·9%, 72·9-92·1) of 53 infants aged older than 1 month to 1 year or younger, and 15 (53·6%, 35·8-70·5) of 28 children aged older than 1 year to 16 years or younger. The dedicated radiologist or pathologist review of the minimally invasive autopsy showed that in 165 (41%) cases a full autopsy might not have been needed; in these cases, concordance between autopsy and minimally invasive autopsy was 99·4% (96·6-99·9). INTERPRETATION: Minimally invasive autopsy has accuracy similar to that of conventional autopsy for detection of cause of death or major pathological abnormality after death in fetuses, newborns, and infants, but was less accurate in older children. If undertaken jointly by pathologists and radiologists, minimally invasive autopsy could be an acceptable alternative to conventional autopsy in selected cases. FUNDING: Policy research Programme, Department of Health, UK.