Severe fetal placental vascular lesions in term infants with neurologic impairment

doi:10.1016/j.ajog.2004.07.030

American Journal of Obstetrics and Gynecology

Volume 192, Issue 2, February 2005, Pages 452-457

https://doi.org/10.1016/j.ajog.2004.07.030 Get rights and content

Objective

This study tests the hypothesis that placental disease can identify antepartum processes that either progress into the intrapartum period or predispose to intrapartum brain injury.

Study design

Lesions that affect large fetal vessels were compared in the placentas of 125 neurologically impaired term infants who were the focus of clinical negligence litigation and 250 consecutive singleton deliveries of ≥36 weeks of gestation.

Results

One or more of 4 severe placental fetal vascular lesions (fetal thrombotic vasculopathy, chronic villitis with obliterative fetal vasculopathy, chorioamnionitis with severe fetal vasculitis, and meconium-associated fetal vascular necrosis) were found in 51% of index cases versus 10% of the comparison group (P <.0001). Prevalence of these lesions in the 64 infants with cerebral palsy was 52% (P <.0001).

Conclusion

Severe fetal placental vascular lesions are correlated highly with neurologic impairment and cerebral palsy. Their nature, duration, and anatomic location make them strong candidates for the antepartum processes that place fetuses at risk for brain injury during the intrapartum period.

Section snippets

Patients

A medicolegal case registry was used to identify 125 index cases with neonatal encephalopathy (NE), CP, or other well-documented related forms of long-term neurologic impairment after singleton birth at ≥36 weeks gestation. Cases from 32 states were entered into the registry without patient identifiers and represent, with 1 exception, births that occurred after 1990. Approximately 80% of cases were reviewed at the request of defense attorneys and 20% for plaintiffs. Infants with major

Results

Mean maternal age, mean infant birth weight for gestational age (Z-score), and the proportion of infants who were male were similar in the 125 index cases with neurologic impairment and the 250 children in the comparison group (Table I). Gestational age at delivery was slightly but significantly higher (39.5 ± 1.6 weeks vs 39.1 ± 1.4 weeks) in the index cases, in part because of a higher proportion of mothers delivering after 42 weeks (8% vs 4% in comparison group). Index cases were born more

Comment

The primary finding of this study is that more than one half of placentas from children referred for medicolegal consultation to evaluate possible causes of neurologic impairment had severe fetal vascular lesions. This represents a >5-fold increase compared with term placentas that were sent for pathologic evaluation in a university hospital setting. The similar prevalence in cases with or without NE and the lack of variation with respect to umbilical artery pH values and 5-minute Apgar scores

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To assess brain development in fetuses with congenital diaphragmatic hernia (CDH) using a fetal Total Maturation Score (fTMS).
This is a retrospective cohort study using data from a single-center clinical registry. Neonates with an antenatal diagnosis of CDH between 2014 and 2020 and prenatal brain magnetic resonance imaging (MRI) (n = 48) were included. We compared our study sample with historical healthy controls (n = 48). The relationship between fTMS and gestational age (GA), as well as the association between fTMS and key prenatal variables and placental pathologic findings, were evaluated.
Compared with healthy controls, neonates with CDH had a significant delay in fTMS (P value <.001). Within the CDH cohort, there was no significant difference in fTMS based on CDH severity, intrathoracic liver position, right vs left CDH, sex, presence of abnormal echocardiogram findings, treatment with extracorporeal membrane oxygenation (ECMO), or in-hospital mortality. Placentas of neonates with CDH had a high proportion of fetal vascular malperfusion (56%) and chronic inflammation (67%), and relatively large placentas had a protective effect on prenatal brain maturation (P value = .025).
Prenatal brain maturation in neonates with CDH is delayed. Placental pathology may influence fetal brain development. The etiology and clinical impact of prenatal brain immaturity in neonates with CDH warrant further investigation.
Placental pathologic features in obesity
2023, Placenta
Obesity in pregnancy is associated with adverse long-term consequences both in the mother and in offspring. Maternal obesity induces a metabolic-inflammatory state that could impact on placental function and could mediate the adverse outcomes. The purpose of this study was to compare the major placental histological characteristics of non-diabetic obese women to lean controls, focusing on uncomplicated pregnancies.
Prospective case-control study comparing placental histopathological features between 122 non-diabetic obese women and 185 non-obese controls. The analysis was performed on overall subjects, then uncomplicated pregnancies from both groups were analyzed. Placenta pathologic findings were recorded according to standard classification.
Both in overall analysis and among the subset of subjects with an uncomplicated pregnancy, obese subjects had higher risks of maternal vascular malperfusion (MVM) (respectively OR=2.2, 95%CI =1.3–3.7 and OR=4.2, 95%CI=2.1–8.5), fetal vascular malperfusion (FVM) (respectively OR=6.3, 95%CI=3.1–12.5 and OR=7.2, 95%CI=3–17.2), maternal and fetal inflammatory response placental lesions and villitis (VUE) (respectively OR=2.5, 95%CI=1.1–5.6 and OR=10.8, 95%CI=3.3–35.3) compared to controls. Among uncomplicated pregnancies and after adjustment for confounders, first trimester BMI was significantly associated with overall MVM, overall FVM, maternal inflammatory, fetal inflammatory response and VUE.
Placentas from obese women showed a significantly higher risk of maternal and fetal vascular and inflammatory placental lesions, both in overall population and in the subgroup with uncomplicated pregnancies. The metabolic and inflammatory dysfunctions typical of obesity could have an impact on placental development and function, which could be a mediator of the detrimental effects of obesity on pregnancy outcome and on future health of the offspring.
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.
Does maternal vitamin D status influence placental weight or vascular and inflammatory pathology? Secondary analysis from the Kellogg Pregnancy Study
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Positive effects of vitamin D (vitD) supplementation on comorbidities of pregnancy (COP) have been explored; however, few studies have elucidated the pathophysiology behind the development of these COP and the potential relationship with derangements in placental development and morphology. Additionally, it is known that placentas weighing 10th-90th % for gestational age are associated with better outcomes. Therefore, the objective of this study was to assess the impact of resulting circulating serum 25(OH)D concentrations associated with intake of high or low doses of supplementary vitD on placental development and morphology in women who participated in a randomized double blind, placebo-controlled trial of vitD supplementation. We hypothesized that if maternal serum 25(OH)D concentration (vitD status marker) is insufficient/deficient, then placental weight and % for gestational age (GA) will be smaller and will correlate with increased vascular and inflammatory placental pathologic findings.
The findings of the present study are a secondary analysis of data generated from a previously reported randomized controlled trial (RCT), the Kellogg Vitamin D Pregnancy Study. Pregnant women (n = 297) in this RCT (January 2013 - April 2018) were randomly assigned to 400 IU vs. 4400 IU vitD/day (10–14 weeks’ gestational age) and followed to delivery. 132 placentas were analyzed by pathologists blinded to treatment, and the 2016 Amsterdam Consensus Criteria were used to categorize grouping/grading of placental pathology and weight. Total [25(OH)D] was measured using radioimmunoassay (ng/mL). Chi-square and Student’s t-test were used to show the difference in maternal characteristics by treatment group and by placental weight. Chi-square analysis was used to determine differences between the percent pathology findings by treatment group. Students t-test was used to determine the differences in vitD status and the frequency of placental lesions. Association between [25(OH)D] area under the curve (AUC) and placental morphology were determined in a regression model that included maternal BMI ≥ 30 kg/m², race/ethnicity, and vitD treatment group allocation. Data were analyzed using SAS v9.4 (Cary, NC) and statistical significance was indicated by p < 0.05.
The percent pathology findings by treatment group were not significantly different for each of the placental pathology categories as defined by the 2016 Amsterdam Consensus Criteria including placental weight. However, when using 25(OH)D as a biomarker for vitD status, linear regression model showed maternal serum [25(OH)D] AUC was significantly associated with greater placental weight (p = 0.023). Logistic regression models showed mothers with BMI ≥ 30 kg/m² had larger placental weight (p = 0.046), and Hispanic and white/Caucasian mothers had greater placental weights than Black American mothers (p = 0.025). When placentas ≥ 90th % for GA, n = 7, were removed from the placental pool, Pearson correlation still showed a positive association between maternal serum 25(OH)D AUC and placental weight (p = 0.011). In a second linear regression model of placentas ≥ 90th % for GA (n = 7) vs. placentas < 90th % (n = 108), maternal serum 25(OH)D AUC was significantly greater in those placentas ≥ 90th % (p = 0.03); however, this was not associated with increased perinatal mortality.
suggest increasing maternal serum [25(OH)D] via vitamin D supplementation during pregnancy did not adversely affect placental morphology; trends showed those in the treatment group had fewer placental lesions. Placental weight was found to be significantly associated with [25(OH)D] AUC, which represents maternal vitamin D status over the course of pregnancy; 7 placentas ≥ 90th % for GA were not associated with perinatal mortality.
Meconium-stained amniotic fluid
2023, American Journal of Obstetrics and Gynecology
Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.
Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions
2023, Fertility and Sterility
To assess obstetric outcomes and placental findings in pregnancies attained by in vitro fertilization (IVF) in patients with diminished ovarian reserve (DOR).
Retrospective cohort study.
University-affiliated tertiary hospital.
DOR, defined as an antral follicle count (AFC) of 6 or less (DOR group), compared with patients with no DOR and an antral count above 6 (control group).
Live singleton births after IVF between 2009 and 2017.
Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, as categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes.
A total of 110 deliveries of patients with DOR were compared with 772 controls. Maternal age was higher in the DOR group than in the control group (36.3 ± 4.4 years vs. 35.3 ± 4.1 years, P=.02). Patients with DOR were more likely to have a diagnosis of endometriosis (P=.02) and less likely to have a diagnosis of male factor (P<.001), ovulation disorder (P<.001), or tubal factor (P=.04), or a transfer of a blastocyte (P=.007). After adjustment for confounders, pregnancies in the DOR group were notable for a significantly higher rate of preeclampsia (8.1% vs. 2.7%, adjusted odds ratio: 3.05, 95% confidence interval: 1.33–6.97). On placental examination, DOR was associated with a higher rate of fetal vasculopathy (P=.01) and multiple fetal vascular malperfusion lesions (P=.03), and a lower rate of circummarginate insertion (P=.01) and intervillous thrombosis (P=.02).
DOR, specifically defined as an AFC of 6 or less, is associated with a higher incidence of preeclampsia and multiple placental fetal vascular lesions.
Reserva ovárica disminuida es un factor de riesgo para preeclampsia y lesiones de malperfusión placentaria.
Evaluar los resultados obstétricos y hallazgos placentarios en embarazos obtenidos por fertilización in vitro (FIV) en pacientes con reserva ovárica disminuida (DOR).
Estudio de cohorte retrospectivo.
Hospital terciario afiliado a la universidad.
DOR, definida como un recuento de folículos antrales (AFC) de 6 o menos (grupo DOR), en comparación con pacientes sin DOR y un recuento antral superior a 6 (grupo control).
nacidos vivos únicos después de FIV entre 2009 y 2017.
Los resultados primarios fueron los hallazgos placentarios, incluidos los anatómicos, inflamatorios, malperfusión vascular y lesiones de maduración de las vellosidades, categorizadas según la clasificación del Consenso del Grupo del Taller sobre Placenta de Ámsterdam. Resultados secundarios incluyeron resultados obstétricos y perinatales.
Se compararon un total de 110 partos de pacientes con RDO con 772 controles. La edad materna fue mayor en el grupo DOR que en el grupo control (36,3 ± 4,4 años frente a 35,3 ± 4,1 años, p = 0,02). Los pacientes con DOR eran más propensos a tener un diagnóstico de endometriosis (p = 0,02) y menos probabilidades de tener un diagnóstico de factor masculino (p < 0,001), trastorno de la ovulación (p < 0,001), factor tubárico (P=.04), o transferencia de un blastocito (P=.007).
Después del ajuste por factores de confusión, los embarazos en el grupo DOR se destacaron por una tasa significativamente mayor de preeclampsia (8,1 % frente a 2,7 %, razón de probabilidad ajustada: 3,05, intervalo de confianza del 95 %: 1,33–6,97). En el examen de la placenta, DOR se asoció con una tasa más alta de vasculopatía fetal (P = 0,01) y múltiples lesiones de mala perfusión vascular fetal (p = 0,03), y menor tasa de inserción circunmarginada (p = 0,01) y trombosis intervellosa (p = 0,02).
DOR, definida específicamente como un AFC de 6 o menos, se asocia con una mayor incidencia de preeclampsia y múltiples lesiones vasculares fetales placentarias.

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General Obstetrics and Gynecology: ObstetricsSevere fetal placental vascular lesions in term infants with neurologic impairment

Objective

Study design

Results

Conclusion

Section snippets

Patients

Results

Comment

No-fault cerebral palsy insurance: an alternative to the obstetrical malpractice lottery

J Health Polit Policy Law

Cerebral palsy and clinical negligence litigation: a cohort study

BJOG

A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement

BMJ

Changing panorama of cerebral palsy in Sweden: VIII, prevalence and origin in the birth year period 1991-94

Acta Paediatr

Origin and timing of brain lesions in term infants with neonatal encephalopathy

Lancet

Hemorrhagic endovasculitis of the placenta: a clinicopathologic entity associated with adverse pregnancy outcome

Compr Ther

Origins of cerebral palsy

Am J Dis Child

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

Arch Pathol Lab Med

Meconium-induced umbilical cord vascular necrosis and ulceration: a potential link between the placenta and poor pregnancy outcome

Obstet Gynecol

Fetal thrombotic vasculopathy: the clinical significance of extensive avascular villi

Hum Pathol

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants: Developmental Epidemiology Network Investigators

Pediatr Res

Practice guideline for examination of the placenta

Arch Pathol Lab Med

Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns

Pediatr Dev Pathol

Myocytes of chorionic vessels from placentas with meconium associated vascular necrosis exhibit apoptotic markers

Hum Pathol

Neonatal morphometry: relation to obstetric, pediatric, and menstrual estimates of gestational age

Am J Dis Child

Cerebral palsy and neonatal encephalopathy

Arch Dis Child

Cerebral palsy and intrauterine growth in single births: European collaborative study

Lancet

Fetal deprivation and placental pathology: concepts and relationships

Perspect Pediatr Pathol

General Obstetrics and Gynecology: Obstetrics
Severe fetal placental vascular lesions in term infants with neurologic impairment