Quantitative assessment of placental morphology may identify specific causes of stillbirth

Abstract

BackgroundStillbirth is frequently the result of pathological processes involving the placenta. Understanding the significance of specific lesions is hindered by qualitative subjective evaluation. We hypothesised that quantitative assessment of placental morphology would identify alterations between different causes of stillbirth and that placental phenotype would be independent of post-mortem effects and differ between live births and stillbirths with the same condition.MethodsPlacental tissue was obtained from stillbirths with an established cause of death, those of unknown cause and live births. Image analysis was used to quantify different facets of placental structure including: syncytial nuclear aggregates (SNAs), proliferative cells, blood vessels, leukocytes and trophoblast area. These analyses were then applied to placental tissue from live births and stillbirths associated with fetal growth restriction (FGR), and to placental lobules before and after perfusion of the maternal side of the placental circulation to model post-mortem effects.ResultsDifferent causes of stillbirth, particularly FGR, cord accident and hypertension had altered placental morphology compared to healthy live births. FGR stillbirths had increased SNAs and trophoblast area and reduced proliferation and villous vascularity; 2 out of 10 stillbirths of unknown cause had similar placental morphology to FGR. Stillbirths with FGR had reduced vascularity, proliferation and trophoblast area compared to FGR live births. Ex vivo perfusion did not reproduce the morphological findings of stillbirth.ConclusionThese preliminary data suggest that addition of quantitative assessment of placental morphology may distinguish between different causes of stillbirth; these changes do not appear to be due to post-mortem effects. Applying quantitative assessment in addition to qualitative assessment might reduce the proportion of unexplained stillbirths.Electronic supplementary materialThe online version of this article (doi:10.1186/s12907-016-0023-y) contains supplementary material, which is available to authorized users.

Pregnancy outcome in mothers over the age of 35

“…At a microscopic level, trophoblast proliferation is reduced and the presence of syncytial nuclear aggregates (also termed syncytial knots) in increased (17). These changes are also seen in post-term pregnancies and in FGR stillbirths (21)(22)(23), thus these observations are consistent with a hypothesis of accelerated placental ageing in mothers ≥35 years of age, which could explain the increased risk of stillbirth from 40 weeks' gestation seen at 42 weeks' gestation in women <35 years of age (9).…”

The prediction of fetal death with a simple maternal blood test at 24-28 weeks: a role for angiogenic index-1 (PlGF/sVEGFR-1 ratio)

“…The pathologic processes implicated in fetal death include: infection 65–84 , placental abruption, 5, 37, 70, 85–92 vascular lesions of the placenta, 28, 35, 93–100 preeclampsia, 41, 101–105 fetal growth restriction 9, 106–114 , maternal anti-fetal rejection, 35, 115–120 metabolic disorders, 121–133 genetic disorders, 80, 131, 134–137 umbilical cord accident, 97, 138–145 trauma 146–148 , and placental senescence 22 ; however, most of the 47,000 stillbirths reported from developed countries in 2015 149 were classified as unknown etiology. It is currently believed that the causes of fetal loss change with gestational age: chromosomal abnormalities 150–153 and infection 75 are the most common causes during the first half of pregnancy, placental causes (abruption or vascular abnormalities) 154–156 , and maternal anti-fetal rejection 118 become the most common causes after 26 weeks until term 14 , after which the etiology of in most cases, especially after 40 weeks, is unknown 14 .…”

Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death

“…Whilst previous studies have reported on placental findings in autopsies following intrauterine death, our current findings are based on a large dataset with predefined objective criteria for classification of cause of death. This dataset also allows exploration of the relationship between gestational age, across the full range of second‐ and third‐trimester intrauterine deaths, and placental findings.…”

“…Improved understanding of the mechanisms of intrauterine death require scientifically rigorous, objective criteria in order to separate truly pathological placental findings from incidental features that may overlap extensively with those of normal populations. Recent research demonstrates that a quantitative approach to placental morphology and placentally derived hormones may help to better identify lesions of pathological significance.…”