Irene Scheimberg

Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement

CONTEXT -The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories. OBJECTIVE -To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community. DATA SOURCES -Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible. CONCLUSIONS -The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.

Evidence of Occurrence of Intradural and Subdural Hemorrhage in the Perinatal and Neonatal Period in the Context of Hypoxic Ischemic Encephalopathy: An Observational Study from Two Referral Institutions in the United Kingdom

The occurrence of subdural hemorrhage (SDH) on the convexities of the cerebral hemispheres is not an unusual finding in the setting of intrauterine, perinatal, or neonatal deaths, the hemorrhage usually presenting either as a thin film over the occipital poles or as a small infratentorial bleed. Working in 2 referral centers with over 30 000 deliveries per year, we routinely examine the dura macroscopically and histologically in nonmacerated fetuses over 24 weeks in gestation and in neonates. This paper describes our experience of intradural hemorrhage (IDH) and SDH associated with hypoxia. Our series comprises 25 fetuses and 30 neonates with obvious macroscopic intradural hemorrhage and hypoxia of varying degrees of severity diagnosed by systematic examination of the brain. Fetal gestational age ranged from 26–41/40 weeks (all no more than 24 hours from intrauterine death), while the 30 neonates lived for between 1 hour and 19 days. Simultaneously with IDH, frank SDH was seen in 2 of 3 of all cases (16 fetuses and 20 neonates). Intradural hemorrhage was more prominent in the posterior falx and tentorium, most likely because of the existence of 2 venous plexus at these sites. Our findings demonstrate that SDH and cerebral hypoxia are common associations of IDH and that SDH (often seen as a thin film of hemorrhage) almost always occurs in association with diffuse falcine IDH. Diffuse IDH with SDH are more frequently associated with severe or moderate hypoxic ischemic encephalopathy (HIE), while mild or early HIE is more common with focal IDH without SDH.

Maternal pancreatic carcinoma metastatic to the placenta: a case report and literature review.

In this article, we report a case of maternal pancreatic carcinoma metastatic to the placenta. The baby is alive and well, with no evidence of tumor metastasis at the age of 1 year. We also present a comprehensive review of all maternal cancers with metastasis to the placenta and/or baby published in the English language.

Nontraumatic Intradural and Subdural Hemorrhage and Hypoxic Ischemic Encephalopathy in Fetuses, Infants, and Children up to Three Years of Age: Analysis of Two Audits of 636 Cases from Two Referral Centers in the United Kingdom

We analyzed the presence or absence of intradural hemorrhage (IDH) and subdural hemorrhage (SDH) and the degree of hypoxic-ischemic encephalopathy (HIE) in the brain of all nonmacerated fetuses of >24 weeks, neonates, and children up to 3 years of age who died of natural causes over a defined period. We looked into the cause of death and the performance of cardiopulmonary resuscitation in our cohort. The IDH was classified as macroscopic or negative/microscopic only; the HIE was classified as absent, indeterminate, or definite. In fetuses, SDH with IDH was present in 22%; IDH alone was present in 31%, and there was no or minimal hemorrhage in 47% of cases. In infants and children SDH with IDH was present in 19%; IDH alone was present in the 32%, and there was no or minimal hemorrhage in 49% of cases. There was a statistically significant correlation between SDH and HIE, especially in infants and children (P < 0.001). When cases were grouped per age, a significant association between age and hemorrhage (P < 0.0001) was demonstrated, SDH being more common in infants ≤1 month corrected age. Intradural hemorrhage can be the source of thin-film SDH in fetuses, infants, and young children. The presence of SDH is associated with hypoxia. Intradural and subdural hemorrhages are more common in autopsies of infants under 1 month corrected age. Although more rare, they can also be found in children between 1 month and 3 years of age in the absence of trauma.

Does Low Vitamin D Have a Role in Pediatric Morbidity and Mortality? An Observational Study of Vitamin D in a Cohort of 52 Postmortem Examinations

Vitamin D is required for calcium absorption and normal bone mineralization; it has a key role in immune regulation against infections and is believed to be involved in immunomodulation in asthma. We did a retrospective analysis of 52 postmortem cases (aged 2 days to 10 years). Seventeen children had vitamin D deficiency (<25 nmol/L); 24 children had vitamin D insufficiency (25–49 nmol/L); 10 children had suboptimal vitamin D levels (50–79 nmol/L); and only 1 child had adequate levels (≥80 nmol/L). Three infants had fractures. Growth plate histology was abnormal in 10 cases with vitamin D deficiency (59%), but radiology was abnormal in only 3 of those cases. Eight infants (33%) with vitamin D insufficiency had abnormal histology, but radiology was normal in all cases. In 3 children hypocalcemia due to vitamin D deficiency was considered accountable for death; they all showed radiological and histological rickets: 2 babies had cardiomyopathy and a 3-year-old had hypocalcemic seizures. Children from all ethnic groups had a high proportion of low vitamin D levels. Vitamin D deficiency (the most common form of pediatric metabolic bone disease) is preventable and treatable. Profound hypocalcemia due to severe vitamin D deficiency can cause unexpected death in babies and young children. Measuring serum vitamin D levels postmortem may provide invaluable information on sudden unexplained death in ‘at-risk’ children. Vitamin D deficiency may be relevant in childhood asthma and in children with multiple infections and babies with bone fractures. Postmortem vitamin D levels are stable and easy to measure.

Recurrent placental massive perivillous fibrin deposition associated with polymyositis: a case report and review of the literature.

We present a case of recurrent massive perivillous fibrin deposition (MPVFD) in a patient with polymyositis (PM). Massive perivillous fibrin deposition occurred in 2 consecutive pregnancies: the 1st ended in an intrauterine death at 34 weeks of gestation, while the 2nd pregnancy resulted in a live-born baby at 32 weeks of gestation. The association between MPVFD and PM has been rarely reported in the literature in the form of case reports of single pregnancies.

Fowler Syndrome Presenting as a Dandy-Walker Malformation: A Second Case Report

Fowler syndrome, also known as proliferative vasculopathy and hydrocephaly-hydranencephaly, is a lethal condition characterized by hydrocephalus associated with progressive destruction of central nervous system tissue as a result of an unusual and characteristic proliferative vasculopathy. The occurrence of Fowler syndrome in consanguineous families and recurrence in both sexes are suggestive of an autosomal recessive transmission. We present the second case of Fowler syndrome presenting as a Dandy-Walker malformation, in a consanguineous family.

Letter to the editor. Lack of evidence for a causal relationship between hypoxic-ischemic encephalopathy and subdural hemorrhage in fetal life, infancy,and early childhood.

To the Editor, We read with great interest the article by Byard and colleagues entitled ‘‘Lack of Evidence for a Causal Relationship Between Hypoxic-Ischemic Encephalopathy and Subdural Hemorrhage in Fetal Life, Infancy, and Early Childhood’’ [1]. We were surprised by the authors’ conclusion categorically ruling out any postmortem evidence of subdural hemorrhage (SDH) in the setting of hypoxicischemic encephalopathy in fetal life, infancy, and early childhood. Of their 82 cases, 59 were either resuscitated sudden infant death syndrome or accidental deaths. The series included only 8 cases of antepartum/intrapartum asphyxia that had been examined at the contributing forensic institutes within a period of up to 17 years. In none of these did they observe macroscopic SDH. As perinatal pathologists working in hospitals with several thousand deliveries per year, we have seen a number of such cases presenting with SDH (Fig. 1). In this we agree with Smith and colleagues, who described focal SDHs on the convexities as not unusual in intrauterine deaths [2]. Smith et al attribute the mechanism of these SDHs to tearing of the bridging veins secondary to excessive moulding, and this may be the mechanism in some cases. However, we have seen SDHs after lowersegment caesarean section, during which such tearing is unlikely to have occurred. A recent paper [3] found asymptomatic intracranial hemorrhage in up to 26% of term neonates born by normal vaginal delivery studied by magnetic resonance imaging. Byard and colleagues do not explain their criteria for including or excluding cases in their series. With respect to the antepartum/ intrapartum asphyxia, we believe the authors have not examined enough cases and therefore suggest it is not safe to conclude that SDH does not occur in nontraumatic intrauterine deaths. Those of us who conduct a high number of pediatric postmortem examinations per year have come across thin-film SDH in young children who have died suddenly in the context of hypoxic-ischemic encephalopathy due to a cardiac malformation (Fig. 2), positional asphyxia, or unsuspected primary pulmonary hypertension. These cases are good examples of the hypoxic-ischemic encephalopathy that may be seen as a corollary of ‘‘natural’’ causes of death.

Anterior Segment Seeding in Eyes With Retinoblastoma Failing to Respond to Intraophthalmic Artery Chemotherapy

IMPORTANCE Anterior chamber seeding following intraophthalmic artery chemotherapy is rarely reported. OBJECTIVES To describe clinicopathologic observations in eyes in which intraophthalmic artery chemotherapy for retinoblastoma failed and to report anterior chamber involvement. OBSERVATIONS A retrospective case series of 12 enucleated eyes (11 patients) with retinoblastoma refractory to intraophthalmic artery chemotherapy between March 1, 2010, and October 31, 2013, at University College London Institute of Ophthalmology and the Retinoblastoma Service, Royal London Hospital. Data analysis was conducted from June 1, 2014, to March 1, 2015. The International Classification of Retinoblastoma groups were B in 1 eye (8%), C in 4 eyes (33%), and D in 7 eyes (58%). Systemic chemotherapy with vincristine sulfate, etoposide, and carboplatin had failed in 10 patients (91%) and 6 eyes (50%) received additional local treatments. In 6 eyes (50%) anterior chamber invasion was clinically detectable. On histopathologic examination, 4 eyes (33%) had no viable retinal tumor; the remainder had poorly differentiated tumor (6 eyes [50%]) or moderately differentiated tumor (2 eyes [17%]). Anterior segment involvement occurred in the ciliary body and/or ciliary muscle (7 eyes [58%]), iris (6 eyes [50%]), and cornea (4 eyes [33%]). CONCLUSIONS AND RELEVANCE Intraophthalmic artery chemotherapy can fail in eyes with retinoblastoma. In contrast to previous reports on outcomes following intraophthalmic artery chemotherapy, our series shows involvement of the anterior segment of the eye, including the ciliary body, iris, and cornea. Careful case selection and follow-up are advised.

Gastroesophageal reflux disease and sudden infant death: mechanisms behind an under-recognized association.

We present 4 cases of sudden infant death in which we believe that gastroesophageal reflux (GOR) was a contributory, if not a causative, factor. Two of our patients had documented GOR reflux disease during life, and all 4 cases showed histologic evidence of GOR. No other cause of death was identified in any of the patients. Gastroesophageal reflux can cause sudden death in a vulnerable infant during a critical period of development through failure of “autoresuscitation” mechanisms.