Abstract
The timing of umbilical cord and placental thrombosis in the third trimester intrauterine fetal death (TT-IUFD) may be fundamental for medico-legal purposes, when it undergoes medical litigation due to the absence of risk factors. Authors apply to human TT-IUFD cases a protocol, which includes histochemistry and immunohistochemistry (IHC) for the assessment of thrombi’s chronology. A total of 35 thrombi of umbilical cord and/or placenta were assessed: 2 in umbilical artery, 6 in umbilical vein, 15 in insertion, 10 in chorionic vessels, 1 in fetal renal vein, 1 in fetal brachiocephalic vein. Thrombi’s features were evaluated with hematoxylin–eosin, Picro-Mallory, Von Kossa, Perls, and immunohistochemistry for CD15, CD68, CD31, CD61, and Smooth Muscle Actin. The estimation of the age of the thrombi was established by applying neutrophils/macrophages ratio taking into consideration, according to literature, the presence of hemosiderophagi, calcium deposition, and angiogenesis. To estimate an approximate age of fresh thrombi (< 1 day), a non-linear regression model was tested. Results were compared to maternal risk factors, fetal time of death estimated at autopsy, mechanism, and cause of death. Our study confirms that the maternal risk factors for fetal intrauterine death and the pathologies of the cord, followed by those of the placental parenchyma, are the conditions that are most frequently associated with the presence of thrombi. Results obtained with histological stainings document that the neutrophile/macrophage ratio is a useful tool for determining placental thrombi’s age. Age estimation of thrombi on the first day is very challenging; therefore, the study presented suggests the N/M ratio as a parameter to be used, together with others, i.e., hemosiderophagi, calcium deposition, and angiogenesis, for thrombi’s age determination, and hypothesizes that its usefulness regards particularly the first days when all other parameters are negative.
Highlights
According to the World Health Organization (WHO), third trimester intrauterine fetal death (TT-IUFD) is considered the birth of a child showing no signs of life that occurs from the 28th week of pregnancy onwards, whereas many differences can be found between different states
Umbilical cord anomalies, placental dysmaturity, cord turns around the neck or other parts of the fetal body, and maternal risk factors were considered
Morphological analysis of thrombus samples documented that the increase of the number of macrophages was related to a decrease in neutrophils (Fig. 1)
Summary
According to the World Health Organization (WHO), third trimester intrauterine fetal death (TT-IUFD) is considered the birth of a child showing no signs of life that occurs from the 28th week of pregnancy onwards, whereas many differences can be found between different states (http://www.who.int/maternal_child_adolescent/epidemiology/stillbirth/en/). According to the Lancet Ending Preventable Stillbirths study group, late gestation stillbirth rates vary across high-income countries from 1.3 to 8.8/1000 births. These results may further be reduced with correct analysis of risk factors (obesity, advanced maternal age, in vitro fertilization), access to antenatal healthcare, accurate monitoring during pregnancy, improved data from stillbirth autopsies performed by a trained perinatal pathologist, and optimizing bereavement care [3]. Problems related to the frequent lack of consent to autopsy, or to the absence of fetal and/or placenta examination, reduce the possibility to identify the cause of death
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