Placental fetal thrombotic vasculopathy is associated with neonatal encephalopathy

doi:10.1016/j.humpath.2004.02.014

Human Pathology

Volume 35, Issue 7, July 2004, Pages 875-880

https://doi.org/10.1016/j.humpath.2004.02.014 Get rights and content

Abstract

Neonatal encephalopathy (NE) remains an important cause of morbidity and mortality in the term infant, and many cases have an antepartum, rather than an intrapartum, etiology. Chronic processes such as thrombosis result in changes in the placenta. We sought to determine whether histopathological examination of the placenta in cases of NE, focusing on these changes, could identify significant antenatal processes that are not recognized by clinical assessment alone. Infants born at term with NE were identified retrospectively over a 12-year period. Placental tissue from deliveries during the study period was available for reexamination. Controls were selected from a cohort of 1000 consecutive deliveries on which clinical and pathological data were collected as part of an earlier study. Bivariate and multivariate analyses of clinical and pathological factors for cases and controls were used to test for an independent association with NE. Clinical and placental data was collected on 93 cases of NE and 387 controls. The placental features of fetal thrombotic vasculopathy (FTV), funisitis (signifying a fetal response to infection), and accelerated villous maturation were independently associated with NE. Of the clinical factors studied, meconium-stained liquor and abnormal cardiotocograph were independently associated. There were no independently associated clinical antenatal factors. Placental features of infection, thrombosis, and disturbed uteroplacental flow are significant independent factors in the etiology of NE in this study. Acute and chronic features suggest that NE may result from acute stress in an already compromised infant. The absence of significant clinical antenatal factors supports the value of placental examination in the investigation of infants with NE.

Section snippets

Patient selection: controls

This was a retrospective study, and patients were selected from records held at a tertiary referral maternity center. As part of an earlier protocol, placental tissue samples had been collected from 1000 consecutive deliveries. We selected from this group all live-born, singleton, term (≥37 completed weeks of gestation) infants. Those with congenital anomalies, with neonatal illness necessitating admission to the neonatal intensive care unit, or with incomplete data were excluded, leaving 816

Clinical factors

There were 93 infants with NE. Six infants (6.5%) were classified as grade 1 NE, 79 (85%) as grade 2 NE, and 8 (8.6%) as grade 3 NE. There was follow-up on 90 cases: 3 had a non-CP neurologic diagnosis, and 17 (18.8%) were ultimately diagnosed as having CP. Of these CP cases, none had grade 1 NE, 12 had grade 2 (16% of grade 2 NE cases), and 5 had grade 3 (62.5% of grade 3 NE cases).

All preconceptual and antenatal clinical factors, with the exception of viral illness during pregnancy, were more

Discussion

NE is associated with a poor outcome in 39% of cases, as defined by death, CP, or significant developmental delay.17 The pathogenesis of NE has been thought of as primarily hypoxic-ischemic, with the insult to the neonatal brain occurring acutely during the birth process. However, evidence for perinatal brain injury in term infants with subsequent CP is lacking in the majority of cases.9 In a large multivariate analysis of antenatal and perinatal factors relevant to CP, the inclusion of

Acknowledgements

The authors acknowledge the assistance of Dr. Ronan Conroy, Dept of Biostatistics, Royal College of Surgeons in Dublin, Ireland.

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Placental fetal vascular malperfusion, neonatal neurologic morbidity, and infant neurodevelopmental outcomes: a systematic review and meta-analysis
2023, American Journal of Obstetrics and Gynecology
This study aimed to evaluate the association of placental fetal vascular malperfusion lesions with neonatal brain injury and adverse infant neurodevelopmental outcomes.
PubMed and Medline, Scopus, and Cochrane databases were searched from inception to July 2022.
We included cohort and case-control studies reporting the associations of fetal vascular malperfusion lesions with neonatal encephalopathy, perinatal stroke, intracranial hemorrhage, periventricular leukomalacia, and infant neurodevelopmental and cognitive outcomes.
Data were analyzed by including fetal vascular malperfusion lesions as an exposure variable and brain injuries or neurodevelopmental impairment as outcomes using random-effects models. The effect of moderators, such as gestational age or study type, was assessed by subgroup analysis. Study quality and risk of bias were assessed by applying the Observational Study Quality Evaluation method.
Out of the 1115 identified articles, 26 were selected for quantitative analysis. The rates of neonatal central nervous system injury (neonatal encephalopathy or perinatal stroke) in term or near-term infants were more common among fetal vascular malperfusion cases (n=145) than among controls (n=1623) (odds ratio, 4.00; 95% confidence interval, 2.72–5.90). In premature deliveries, fetal vascular malperfusion lesions did not influence the risk of intracranial hemorrhage or periventricular leukomalacia (odds ratio, 1.40; 95% confidence interval, 0.90–2.18). Fetal vascular malperfusion–associated risk of abnormal infant neurodevelopmental outcome (314 fetal vascular malperfusion cases and 1329 controls) was modulated by gestational age being higher in term infants (odds ratio, 5.02; 95% confidence interval, 1.59–15.91) than in preterm infants (odds ratio, 1.70; 95% confidence interval, 1.13–2.56). Abnormal infant cognitive development and mental development were more common among fetal vascular malperfusion cases (n=241) than among controls (n=2477) (odds ratio, 2.14; 95% confidence interval, 1.40–3.27). The type of study (cohort vs case-control) did not influence the association between fetal vascular malperfusion and subsequent infant brain injury or abnormal neurodevelopmental outcome.
The findings of cohort and case-control studies indicate a considerable association between fetal vascular malperfusion placental lesions and increased risk of brain injury in term neonates, and neurodevelopmental impairment in both term and preterm infants. A diagnosis of placental fetal vascular malperfusion should be taken into consideration by both pediatricians and neurologists during the follow-up of infants at risk of adverse neurodevelopmental outcomes.
Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease
2023, American Journal of Obstetrics and Gynecology
The importance of a fully functioning placenta for a good pregnancy outcome is unquestioned. Loss of function can lead to pregnancy complications and is often detected by a thorough placental pathologic examination. Placental pathology has advanced the science and practice of obstetrics and neonatal-perinatal medicine by classifying diseases according to underlying biology and specific patterns of injury. Many past obstacles have limited the incorporation of placental findings into both clinical studies and day-to-day practice. Limitations have included variability in the nomenclature used to describe placental lesions, a shortage of perinatal pathologists fully competent to analyze placental specimens, and a troubling lack of understanding of placental diagnoses by clinicians. However, the potential use of placental pathology for phenotypic classification, improved understanding of the biology of adverse pregnancy outcomes, the development of treatment and prevention, and patient counseling has never been greater. This review, written partly in response to a recent critique published in a major obstetrics-gynecology journal, reexamines the role of placental pathology by reviewing current concepts of biology; explaining the most recent terminology; emphasizing the usefulness of specific diagnoses for obstetrician-gynecologists, neonatologists, and patients; previewing upcoming changes in recommendations for placental submission; and suggesting future improvements. These improvements should include further consideration of overall healthcare costs, cost-effectiveness, the clinical value added of placental assessment, improvements in placental pathology education and practice, and leveraging of placental pathology to identify new biomarkers of disease and evaluate novel therapies tailored to specific clinicopathologic phenotypes of both women and infants.
Neonatal Encephalopathy
2023, Avery's Diseases of the Newborn
Neonatal encephalopathy describes a constellation of neurologic findings that are the final common pathway of many potential disease processes. The clinical picture of neonatal encephalopathy can be of primary neurological origin or secondary to congenital or acquired diseases.
Affected newborns may present immediately after birth or within the first few weeks of age. Presenting findings may be subtle or obvious, ranging from poor feeding to seizures, encephalopathy, respiratory failure, and shock. Magnetic resonance imaging techniques have improved diagnostic and prognostic capabilities for numerous types of diseases causing neonatal encephalopathy. Hypoxic-ischemic encephalopathy (HIE) is the most common cause of acute neonatal encephalopathy and accounts for 24% of neonatal death worldwide. Other common neurologic causes include genetic epilepsies, arterial ischemic stroke, and cerebral sinovenous thrombosis.
Inborn errors of metabolism presenting in the newborn period commonly are associated with neurologic symptoms, either secondary to accumulation of toxic metabolites, or the inability to meet the high energy demand of the brain. Infectious and genetic causes are also commonly found when evaluating a newborn with encephalopathy. Survivors of neonatal encephalopathy are at significant risk for moderate to severe long-term disabilities, including motor problems, epilepsy, language, cognition, hearing, or vision impairment, as well as neuropsychological difficulties.
Placental pathology
2022, Reproductive and Developmental Toxicology
Placental pathology: Pathways leading to or associated with perinatal brain injury in experimental neurology, special issue: Placental mediated mechanisms of perinatal brain injury
2022, Experimental Neurology
Perinatal brain injury is a multifactorial process. In utero placental physiology plays a major role in neuroprotection and the normal development of the fetal central nervous system. Advances in placental pathology have clarified several specific mechanisms of injury and the histologic lesions most strongly associated with them. This review provides an updated summary of the relevant placental anatomy and physiology, the specific placental pathways leading to brain injury, the revised Amsterdam classification system for placental pathology, and the known associations of specific placental lesions with subtypes of adverse neurologic outcomes.
Acute and Chronic Placental Abnormalities in a Multicenter Cohort of Newborn Infants with Hypoxic–Ischemic Encephalopathy
2021, Journal of Pediatrics
To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic–ischemic encephalopathy (HIE) and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE.
Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system.
Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (−15.9 vs −14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P < .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P < .001) than those without acute abnormalities.
Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.
ClinicalTrials.gov: NCT02811263

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^☆: Supported in part by the National Maternity Hospital Laboratory Research and Development Fund, Dublin, Ireland.

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Original contributionPlacental fetal thrombotic vasculopathy is associated with neonatal encephalopathy☆

Abstract

Section snippets

Patient selection: controls

Clinical factors

Discussion

Acknowledgements

Hum Pathol

Hum Pathol

Hum Pathol

Neurol Clin

J Pediatr

Am J Obstet Gynecol

Placenta

J Pediatr

Hypoxic ischemic encephalopathyclinical aspects

Developmental outcomes of newborn encephalopathy in term infants

Indian J Pediatr

Antepartum risk factors for newborn encephalopathyThe Western Australian case control study

BMJ

Placental lesions associated with cerebral palsy and neurological impairment following term birth

Arch Pathol Lab Med

Original contribution
Placental fetal thrombotic vasculopathy is associated with neonatal encephalopathy☆