Acute and Chronic Placental Abnormalities in a Multicenter Cohort of Newborn Infants with Hypoxic-Ischemic Encephalopathy.

Published on Jun 16, 2021in The Journal of Pediatrics4.406
· DOI :10.1016/J.JPEDS.2021.06.023
Lina F. Chalak25
Estimated H-index: 25
(UTSW: University of Texas Southwestern Medical Center),
Raymond W. Redline66
Estimated H-index: 66
(University Hospitals of Cleveland)
+ 22 AuthorsEllen M. Bendel-Stenzel8
Estimated H-index: 8
(Mayo Clinic)
OBJECTIVE 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. STUDY DESIGN 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 (HEAL) 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. RESULTS Complete placental pathologic examination was available for 321/500 (64%) trial participants. Placental abnormalities were identified in 273/321 (85%) and were more common in infants ≥ 40 weeks of gestation (93% vs. 81%, p=0.01). 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=0.049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs. 38.0, p<0.001) and higher rates of clinically diagnosed chorioamnionitis (25% vs 2%, P < .001) than those without acute abnormalities. CONCLUSION Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.
#1Yvonne W. Wu (UCSF: University of California, San Francisco)H-Index: 55
#2Amy M. Goodman (UCSF: University of California, San Francisco)H-Index: 7
Last. Raymond W. Redline (Case Western Reserve University)H-Index: 66
view all 11 authors...
Newborns with hypoxic–ischemic encephalopathy (HIE) may exhibit abnormalities on placental histology. In this phase II clinical trial ancillary study, we hypothesized that placental abnormalities correlate with MRI brain injury and with response to treatment. Fifty newborns with moderate/severe encephalopathy who received hypothermia were enrolled in a double-blind, placebo-controlled trial of erythropoietin for HIE. A study pathologist reviewed all available clinical pathology reports to determ...
#1Yi Yuan Zhou (Case Western Reserve University)H-Index: 1
#2Sanjita Ravishankar (Case Western Reserve University)H-Index: 4
Last. Raymond W. Redline (Case Western Reserve University)H-Index: 66
view all 4 authors...
Indications for placental submission are variable. Established guidelines are largely based on expert opinion, and there is a need for more evidence-based criteria. A 10-year database of term placentas was used to evaluate indications significantly associated with placental pathology. Lesions in 5 categories were separated into high- and low-grade subgroups. Two additional high-grade lesions were also evaluated. Indications associated with high-grade placental lesions were chronic monitoring abn...
#1Sanjita Ravishankar (Case Western Reserve University)H-Index: 4
#2Raymond W. Redline (Case Western Reserve University)H-Index: 66
The placenta can serve as a valuable source of information about maternal and fetal conditions during the pregnancy; however, the abilities to perform a preliminary gross examination and interpret a placental pathology report are variable among obstetricians. This article discusses the indications for placental submission to pathology; the essentials of gross examination, including elements that should be performed in the delivery suite; and the most common and clinically relevant histologic fin...
#1Adrienne BinghamH-Index: 2
#2Fusun GundoganH-Index: 16
Last. Abbot R. LaptookH-Index: 79
view all 4 authors...
To determine if pre-specified placental abnormalities among newborns with hypoxic–ischemic encephalopathy (HIE) differ compared to newborns admitted to a NICU without encephalopathy. Retrospective case–control study of newborns with HIE (2006–2014) and controls matched for birth year, gestational age, weight, and gender. One pathologist reviewed archived placental sections using pre-specified criteria. Sixty-seven newborns had HIE, 46 had available placentas and were matched with 92 controls. HI...
#3Karin B. Nelson (NIH: National Institutes of Health)H-Index: 73
Objective We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy. Study design Case–control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were co...
#1Lina F. ChalakH-Index: 25
#2Samantha Latremouille (McGill University)H-Index: 5
Last. Guilherme M. Sant'Anna (McGill University)H-Index: 19
view all 5 authors...
Abstract A review of the conundrum called mild hypoxic-ischemic encephalopathy (HIE) is provided. During the past decades, the definition of HIE has evolved to accommodate the short window of time required for the initiation of therapeutic hypothermia. Also, neurological evaluations have changed with the use of simpler staging systems that can be applied within the first 6 h of life. In this review, we discuss the challenges in the identification of newborns with “mild HIE” within 6 h after birt...
#1Sandra E. Juul (UW: University of Washington)H-Index: 56
#2Bryan A. Comstock (UW: University of Washington)H-Index: 40
Last. Yvonne W. Wu (UCSF: University of California, San Francisco)H-Index: 55
view all 8 authors...
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and erythropoietin (Epo) has the potential to provide additional neuroprotection. OBJECTIVES: The aim of this study was to review the current incidence, mechanism of injury, and sequelae of HIE, a...
#1Seetha Shankaran (WSU: Wayne State University)H-Index: 91
#2Abbot R. Laptook (Brown University)H-Index: 79
Last. Rosemary D. Higgins (NIH: National Institutes of Health)H-Index: 87
view all 33 authors...
Importance Hypothermia for 72 hours at 33.5°C for neonatal hypoxic-ischemic encephalopathy reduces death or disability, but rates continue to be high. Objective To determine if cooling for 120 hours or to a temperature of 32.0°C reduces death or disability at age 18 months in infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants Randomized 2 × 2 factorial clinical trial in neonates (≥36 weeks’ gestation) with hypoxic-ischemic encephalopathy at 18 US centers in the Eunic...
#1Lina F. Chalak (UTSW: University of Texas Southwestern Medical Center)H-Index: 25
Although therapies in addition to whole-body cooling are being developed to treat the neonate at risk for hypoxic-ischemic encephalopathy, we have no quickly measured serum inflammatory or neuronal biomarkers to acutely and accurately identify brain injury or to follow the efficacy of therapy. This review covers inflammatory serum biomarkers in the setting of birth asphyxia that can help assess the degree or severity of encephalopathy at birth and neurodevelopmental outcomes. These biomarkers st...
Cited By1
#1Fatema Al Amrani (Sultan Qaboos University)
#2Guillaume Sébire (Montreal Children's Hospital)H-Index: 10
Last. Christine Saint-Martin (Montreal Children's Hospital)H-Index: 13
view all 5 authors...
Abstract: null null Background null Identifying antepartum versus intrapartum timing and the cause of neonatal encephalopathy (NE) often remains elusive due to our limited understanding of the underlying pathophysiological processes and lack of appropriate biomarkers. null null null Objectives null This retrospective observational study describes a case series of term newborns with NE who displayed a recognizable magnetic resonance imaging (MRI) pattern of immediately post-natal brain abnormalit...
#1Raymond W. Redline (Case Western Reserve University)H-Index: 66
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...
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