Stillbirth Investigations: An Iconographic and Concise Diagnostic Workup in Perinatal Pathology

Abstract

Introduction Stillbirth is a dramatic event for the parents, health care team, and anyone close to the expectant parents. Multidisciplinary team (MDT) meetings are essential to improve communication in health care. We review the most frequent findings discussed at MDT meetings. Methods A PubMed search was conducted through December 2021 since the inception (1965) using clinical queries with the key terms "stillbirth" AND "investigation" AND "pathology" AND "human." The search strategy included reviews, meta-analyses, randomized controlled trials, clinical trials, and observational studies. This systematic review is based on, but not limited to, the search results. It is the experience of more than 30 years of pediatrics, obstetrics, and pathology staff. Results Two hundred and six articles were screened and complemented through the perusal of congressional activities and personal communications. Pathological findings following perinatal death can be divided into macroscopic, histologic, and placental findings. The placenta is crucial in fetal medicine and is key in determining the cause of stillbirth in a substantial number of events. Perinatal lung disease is essential to evaluate the response of newborns to extrauterine life and address newborns' outcomes appropriately. Conclusions Stillbirth remains one of the less explored areas of medicine, and we can determine the cause in a limited number of cases. Nevertheless, placental pathology is critical in the etiology discovery pathway. Accurate investigations and discussion of photography-supported findings are vital in promoting communication at MDT meetings.

Keywords: Perinatal Investigation; early neonatal illness; intrapartum distress; stillbirth.

Fig. 1

( a ) A neural tube defect of superior type showing an encephalocele ( arrow ) in a preterm baby. ( b ) Epignathus in a late gestation fetus. Epignathus is a form of oropharyngeal teratoma. It arises from the palate and is due to unorganized and uncontrolled differentiation of somatic cells. Although the epignathus is considered benign from the histopathological point of view, it is life-threatening because of its atypical features (size, location, and rate of development) and high risk of airway obstruction occurs. Epignathus is the cause of death in 80 to 100% of the cases recognized at the time of delivery. Gross photograph as a kind contribution of Dr. N. Sarioglu of the Campus Charite, Berlin, Germany. ( c ) Congenital diaphragmatic defects can be incompatible with life. Here is the autopsy view of the thoracic and abdominal cavities of a preterm infant with Wolf–Hirschhorn disease. There is a large defect of the left diaphragm with upward displacement of the abdominal viscera and extreme hypoplasia of both lungs. The female infant weighed 830 g (1,375 ± 281 g) and had a head circumference of 24 cm corresponding to a 26-week gestation fetus. The infant showed bradycardia and no spontaneous breathing. The abdomen was sunken and chest X-ray revealed a diaphragmatic defect, bilateral lung hypoplasia, and a shift of the mediastinum to the right. A chromosomal imbalance with 46, XX, del (4) (pter-p13) was diagnosed, while the parental chromosomes were numerically and structurally normal. ( d ) A preterm infant showing hydroureteronephrosis with megacystis due to urethral posterior valve and dysplasia of the cystourethral connection.

Fig. 2

( a ) The perineal region of this 22 weeks' gestation baby shows a red-brown swelling ( arrow ) on the bottom. ( b ) Histologic examination of the perineal tissue shows a teratoma with cysts of different size and three-layer differentiation (ectodermal, endodermal, and mesodermal). The coccyx is shown in the center of the picture (hematoxylin and eosin staining, 20×). ( c ) Neutrophilic granulocytes in the lumina of a lung at the canalicular stage of differentiation (hematoxylin and eosin staining, 200×). A major lumen is shown ( arrow ). ( d ) Focal inspissation of epithelial squames in the alveolar lumina ( arrow ) of a lung from a baby who died of respiratory failure (hematoxylin and eosin staining, 100×). ( e ) The thickness of the glomerulogenic zone (zone delimitated by the first two arrows from left to right) and its ratio to the definitive zone (zone delimitated by the first arrow and the last arrow from left to right) are very helpful to assess renal maturity (hematoxylin and eosin staining, 40 ×). ( f ) Cystic pseudofollicular change ( arrow ) of the definitive due to focal degeneration of the adrenal cortical cells (hematoxylin and eosin staining, 100×). ( g ) The skin of a baby with restrictive dermopathy, a genodermatosis, shows thickened, hyperkeratotic epidermis, a dermis composed of dense parallel connective tissue, and a thick layer of adipose and fibrous connective tissue in the hypodermis (hematoxylin and eosin staining, 100×). In the inset, there is a tissue section from the same specimen showing no elastic fibers (Elastica van Gieson staining, 100×). ( h ) Normal skin of a baby age-matched to 1 g (hematoxylin and eosin staining, 100×.

Fig. 3

( a ) Owl-eye cell in the lung of a stillborn infant. This feature is characteristic of f infection (hematoxylin an eosin staining, 400×). The inset picture shows positive immunohistochemical detection of cytomegalovirus. ( b ) The liver of a stillborn infant with nucleated erythroid precursors (fetal hepatic hematopoiesis) showing nuclear inclusions ( arrow ). The hepatocytes are not affected (hematoxylin and eosin staining, 400×). ( c ) Immunohistochemical detection of parvovirus B19 in the same liver as shown in ( b ), 100×. ( d ) Infantile Citrobacter pneumonia of an infant with CHARGE syndrome (C: coloboma; H: heart defect; A: atresia of the choanae; R: retardation of psychomotor type; G: genital anomalies; E: ear abnormalities; hematoxylin and eosin staining, 200×). The CHD7 gene of CHARGE syndrome (before gene location the term CHARGE association was used for these children with these anomalies) has been found and is located on chromosome 8.

Fig. 4

( a,b ) Alveolar capillaries are significantly diminished in number and are centrally placed within the alveolar septa, several cell thicknesses away from the pneumocyte-lined air spaces in alveolar capillary dysplasia. ( c,d ) Lung tissue in cases of congenital pulmonary lymphangiectasia with dilated lymphatic channels without lymphatic proliferation. Inset: CD31 immunohistochemical stain in a case of congenital pulmonary lymphangiectasia highlighting dilated lymphatic spaces. The positive CD31 stain in the endothelial lining confirms that the dilated spaces are lymphatic in origin, not artifacts.

Fig. 5

( a ) Plasma cell infiltration of the intervillous space ( arrow ) due to cytomegalovirus infection (hematoxylin and eosin staining, 200×). Inset: Cytomegalovirus detection by immunohistochemistry. ( b ) Perivillitis with encircling of small villi by fibrin and neutrophilic granulocytes ( arrow ; hematoxylin and eosin staining, 200×). ( c ) Marked necrotizing chorioamnionitis with infiltration of the subepithelial tissue ( arrow ; hematoxylin and eosin staining, 200×). ( d ) Amniotic epithelium change (vacuolation, arrow ) associated with omphalocele of the baby (hematoxylin and eosin staining, 400×). ( e ) Massive intervillous fibrin deposition ( arrow ; hematoxylin and eosin staining, 100×). ( f ) Syncytiotrophoblastic hyperplasia ( arrow ) in pregnancy with triploidy (hematoxylin and eosin staining, 100×).