Villitis of unknown aetiology: Its incidence and significance in placentae from a British population

doi:10.1016/S0143-4004(84)80019-3

Placenta

Volume 5, Issue 5, September–October 1984, Pages 395-402

https://doi.org/10.1016/S0143-4004(84)80019-3 Get rights and content

Summary

A histological study of 1000 randomly selected placentae from women delivered in Manchester, UK, revealed 136 cases of villitis; this is a higher incidence than that recorded in Australia and North America but lower than that noted in South America. There were no obvious clinical differences between mothers whose placentae showed a villitis and those in a control group whose placentae were free of villitis. As in other studies, there was an association between the presence of a villitis, particularly severe villitis, and fetal intrauterine growth retardation. The nature of this association cannot, however, be clarified until the aetiology of villitis is determined.

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Cited by (107)

Association of distinct features of villitis of unknown etiology histopathology and fetal growth restriction diagnosis in a retrospective cohort from Eastern Ontario
2022, Placenta
Citation Excerpt :
This form of placental pathology is referred to as villitis of unknown etiology (VUE). VUE is an independent predictor of small-for-gestational age (SGA) infants [adjusted odds ratio (aOR) 2.35, 95% CI (1.55, 3.56)] [9], and is associated with other neonatal complications including preterm delivery [10], fetal growth restriction (FGR) [9,11] and intra-uterine fetal death (IUFD) [11–13]. In the Canadian context, VUE affects approximately 9% of placentas submitted for pathology evaluation following third trimester delivery [14], while globally there is a wider range, with case rates as high as 37% [7,9,15].
Villitis of unknown etiology (VUE) is associated with fetal growth restriction (FGR) and adverse short-term neonatal outcomes. No investigation to date has found which VUE features are driving the association with FGR diagnosis.
A retrospective cohort study of placenta pathology specimens (2013–2017) was conducted. Independent variables of interest were: VUE distribution (focal vs diffuse), location (basal vs non-basal), and grade (high vs low). The primary outcome was FGR, and secondary outcomes were neonatal intensive care unit (NICU) admission, NICU length of stay, Apgar scores <7 at 1, 5, and 10-min, and recurrence rate of villitis in subsequent pregnancies. Association between VUE characteristics and our primary outcome were investigated using logistic regression. Secondary outcomes were explored with regression analyses and recurrence rate of VUE for members of the cohort with a recorded subsequent pregnancy was calculated.
One hundred and twenty seven placentas were included. Adjusted models showed no difference in the odds of FGR between high-grade versus low-grade VUE [aOR 1.25 95% CI (0.50, 3.26), p = 0.6], focal/multi-focal vs diffuse cases [aOR 1.03 95% CI (0.28, 4.34), p = >0.9], and basal vs non-basal VUE [aOR 0.06 95% CI (0.00, 1.10), p = 0.058]. After adjusting for prematurity <37 weeks, there were lower odds of NICU admission in basal vs non-basal cases [aOR 0.25, 95% CI (0.06, 0.90), p = 0.048). There was no difference in the odds of neonates presenting with Apgar <7 for the distinct VUE histopathology features. Three cases had recurrent VUE, resulting in a 6.8% [95% CI (3.02%, 10.61%)] recurrence rate. All recurrent cases were high-grade and identified with basal localization.
There are no statistical associations between distinct VUE features and FGR diagnosis, however location of villitis may be associated with worse neonatal outcomes. Villitis of any type (severity, degree, location) could potentially drive insufficient placental function and poor fetal growth.
The etiology of preeclampsia
2022, American Journal of Obstetrics and Gynecology
Preeclampsia is one of the “great obstetrical syndromes” in which multiple and sometimes overlapping pathologic processes activate a common pathway consisting of endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. This article reviews the potential etiologies of preeclampsia. The role of uteroplacental ischemia is well-established on the basis of a solid body of clinical and experimental evidence. A causal role for microorganisms has gained recognition through the realization that periodontal disease and maternal gut dysbiosis are linked to atherosclerosis, thus possibly to a subset of patients with preeclampsia. The recent reports indicating that SARS-CoV-2 infection might be causally linked to preeclampsia are reviewed along with the potential mechanisms involved. Particular etiologic factors, such as the breakdown of maternal-fetal immune tolerance (thought to account for the excess of preeclampsia in primipaternity and egg donation), may operate, in part, through uteroplacental ischemia, whereas other factors such as placental aging may operate largely through syncytiotrophoblast stress. This article also examines the association between gestational diabetes mellitus and maternal obesity with preeclampsia. The role of autoimmunity, fetal diseases, and endocrine disorders is discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention.
Chronic Villitis of unknown etiology (VUE): Obstetrical features, outcome and treatment
2021, Journal of Reproductive Immunology
Villitis of unknown etiology (VUE) is characterized by lympho-histiocytic infiltrates, which are predominant within the villous stroma. VUE can be of low grade i.e. affecting less than 10 contiguous villi or high grade with either patchy or diffuse subgroups (the later concerning more than 30 % of distal villi). Several other placental lesions could be associated with VUE, in particular in diffuse subgroups, such as diffuse perivillous fibrin deposition and chronic intervillositis. One of the most characteristic features of VUE is the late onset of fetal growth restriction after 32 weeks of gestation, and earlier detection of villitis should first raise an infectious origin. High grade VUE has been associated with fetal growth restriction, prematurity, fetal deaths, recurrent pregnancy loss, central nervous system injury and is characterized by relatively high risk of recurrence (25–50 %). Prospective and well-designed studies are necessary to determine the real prevalence of these adverse pregnancy events associated with VUE. Data about the management of VUE are extremely scarce and thus no recommendation based on the literature review could be actually done.
Chronic villitis: Refining the risk ratio of recurrence using a large placental pathology sample
2021, Placenta
Chronic villitis is an inflammatory lesion that affects 5–15% of placentas and is associated with adverse pregnancy outcomes. Chronic villitis may also recur; however, studies estimating recurrence are based on small samples and estimates of recurrence range from 10 to 56%.
We utilized data from placentas submitted to pathology at a Chicago hospital between January 2009 and March 2018. During the study period, 883 patients had two placentas submitted to pathology. We estimated the risk of recurrent chronic villitis, adjusted for maternal and pregnancy characteristics. We also evaluated whether prevalence of small for gestational age infant differed for those with recurrent chronic villitis and we investigated whether placental pathology worsened in the second study pregnancy among those with recurrent chronic villitis.
The overall prevalence of recurrent chronic villitis in the study sample was 11.5%. Among those with chronic villitis in the first pregnancy, 54% developed chronic villitis in the second pregnancy, corresponding to an adjusted risk ratio of 2.36 (95% confidence interval: 1.92, 2.91). Recurrent chronic villitis was not associated with increased prevalence of small for gestational infant as compared with non-recurrent villitis. Among those with recurrent chronic villitis, high-grade chronic inflammation and fetal vascular malperfusion were more common in the second pregnancy as compared with the first.
Our results suggest that those with chronic villitis in the first pregnancy are over twice as likely to develop chronic villitis in the second pregnancy and that chronic inflammation and fetal vascular malperfusion may worsen among those with recurrent chronic villitis.
Placenta pathology in recipient versus donor oocyte derivation for in vitro fertilization in a setting of hypertensive disorders of pregnancy and IUGR
2021, Placenta
Assisted reproductive technology including in vitro fertilization (IVF) and oocyte donation (OD) may increase risk for placenta-mediated diseases. Comprehensive analysis of histopathological placental lesions according to source of oocytes used in the IVF procedure – recipient derived (RD-IVF) vs oocyte donation (OD-IVF), has not been conducted in a population with a hypertensive disorder of pregnancy (HDP) and/or intrauterine growth restriction (IUGR).
A retrospective cohort study of archived placenta specimens from RD-IVF and OD-IVF pregnancies affected by HDP and/or IUGR was conducted with blinded histopathological placental examination. Three categories of lesions were differentiated and defined as main outcomes: maternal vascular malperfusion (MVM), chronic inflammation, and fetal vascular malperfusion (FVM). To determine the relationship between conception method and placental lesions, multivariable regressions were performed with maternal age, gestational age, HDP, birth and placental weight percentiles as model covariates.
115 placentas were included 83 (72.2%) RD-IVF, 32 (27.8%) OD-IVF. Adjusted OR (aOR) for conception method was 5.05 (95%CI 0.58–43.90, p=0.142) for MVM, 1.87 (95%CI 0.68–5.15, p=0.228) for chronic inflammatory and 0.61 (95%CI 0.15–2.37, p=0.471) for FVM lesions. Multiple gestation demonstrated borderline association with MVM (aOR=0.24, 95%CI 0.04–1.51, p=0.129) and total pathology score (aRR=0.79, 95%CI 0.62–1.01, p=0.058). Subgroup analysis suggested greater odds of villitis of unknown etiology (VUE) for OD-IVF (aOR=2.98, 95%CI 1.12–7.93, p=0.029).
Source of oocyte derivation demonstrated no evidence of association with main outcomes in cases of HDP and/or IUGR. Subgroup analysis demonstrated increased rates of inflammatory lesions for OD-IVF. Multiple gestation may be associated with decreased MVM and total lesions.
Chapter 32 - Placental Correlates of Unanticipated Fetal Death
2018, Diagnostic Gynecologic and Obstetric Pathology
Examination of the placenta is a critical component in evaluating the etiology of intrauterine demise. This is particularly true as pregnancy progresses, as the cause of demise beyond the first trimester is less likely to be due to intrinsic fetal disease and more likely due to “errors of the intrauterine environment”; that is, as a result of causes extrinsic to the fetus. As a general principle, the longer intrauterine stressors that ultimately result in demise are present, the more likely that placental “footprints” of those stressors will (1) accrue and (2) be detectable by gross or microscopic examination. This chapter lists segregated specific mechanisms of demise based on the timing of evolution from onset to demise. Of relevance are the following concepts, the literature for which remains in evolution. These concepts pertain largely to subacute and chronic intrauterine pathologies, although superimposed acute manifestations of preexisting disorders can add to the overall burden of fetal stress and concomitant risk for untoward fetal/neonatal outcome. (1) As a general rule, the more advanced or extensive a pathologic process, the greater the potential risk for untoward fetal/neonatal outcome. (2) Threshold criteria are accruing for identifying the severity/extent of specific placental lesions that herald an increased risk of untoward outcome. (3) The coexistence of separate pathologic processes, each of which can have fetal/neonatal implications, compounds their cumulative effects in at least an additive, if not multiplicative manner. (4) The same processes that lead to unexpected fetal demise can also result in neonatal morbidity and mortality.

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Villitis of unknown aetiology: Its incidence and significance in placentae from a British population

Summary

American Journal of Obstetrics and Gynecology

Placenta

The human placental villitides: a review of chronic intrauterine infection

Current Topics in Pathology