Objective
To study associations between placental histopathology and stillbirth as well as neonatal outcome in a population born extremely preterm.
Design
Prospective cohort study.
Setting
Stockholm, ...Sweden.
Population
167 infants born <27 gestational weeks during 2004–2007.
Methods
One senior perinatal pathologist, blinded to outcome data, evaluated all placental slides.
Main outcome measures
Intrauterine fetal death, small‐for‐gestational age, major neonatal morbidity (intraventricular hemorrhage ≥grade 3, retinopathy of prematurity ≥grade 3, necrotizing enterocolitis, cystic periventricular leukomalacia or severe bronchopulmonary dysplasia) and neonatal mortality. Additional outcome variables were Apgar score at 5 min, sepsis, and treated patent ductus arteriosus.
Results
Accelerated villous maturation was associated with a decreased risk for Apgar score <7 at 5 min (p = 0.041). Fetal thrombosis and low placental weight were associated with an increased risk for both intrauterine fetal death (p < 0.001 and p = 0.011, respectively) and small‐for‐gestational age (p < 0.001 and p < 0.001, respectively).
Conclusion
Placental histology may have prognostic value as it appears to be associated with intrauterine fetal death, as well as with being small‐for‐gestational age and assignment of a low Apgar score at birth.
ABSTRACT
Objective. To correlate placental histopathology, in particular ischemic changes, with the clinical severity of preeclampsia. Design. A blinded retrospective study. Setting. One Swedish ...hospital. Sample. One hundred and fifty‐seven women with severe (n= 116) or mild (n= 41) preeclampsia and 157 normotensive women matched according to gestational‐age. Methods: One senior pathologist, blinded to clinical data and group, examined all histological slides. In the statistical analyses, adjustment for gestational week was done when appropriate. Main outcome measures. Placental histopathological findings. Results: Amount of infarction increased with the severity of preeclampsia (p < 0.001). Infarction involving ≥5% of the placental tissue was seen in 39.7% of severe preeclampsia, 17.1% of mild preeclampsia and 5.1% of non‐preeclampsia. When comparing placentas in severe preeclampsia, mild preeclampsia and non‐preeclampsia, there was an increase in the presence of any infarction (80.2%, 61.0%, vs. 20.4%). Also, there was a difference in the presence of decidual arteriopathy (35.3%, 22.0%, vs. 3.8%) and accelerated villous maturation (71.6%, 53.3%, vs. 12.6%). We found no difference in intervillous thrombosis, abruption placenta or placental weight in relation to gestational week. Conclusions. In pregnancies with mild or severe preeclampsia, a large proportion of the placentas had histological signs of pathology, in particular signs of ischemia. The pathology was similar, but more pronounced in severe compared to mild preeclampsia, suggesting mild and severe preeclampsia to have similar underlying etiology.
Objective: To ascertain whether the protective effect of smoking during preeclampsia (PE) can be visualized in the placenta.
Methods: The study cohort consisted of placentas (n = 523) from ...pregnancies complicated by PE, delivered at Karolinska University Hospital in Stockholm during the period 2000-2009. Of the women included in the study, 488 were non-smokers and 35 were smokers at first visit to maternity care. Outcome variables were placental infarctions and decidual arteriopathy.
Results: Infarctions (affecting ≥5% of the placental tissue) were found in 15.6% of the placentas from non-smokers and in 25.7% of the placentas from smokers (OR 1.88: CI 0.84-4.16, p = 0.12). Decidual arteriopathy was found in 27.5% of the placentas from non-smokers and in 40.0% of the placentas from smokers (1.76: CI 0.87-3.56, p = 0.12). When diagnosed histopathologically, placental abruption was found in 15.4% among non-smokers and in 17.1% among smokers (1.14: CI 0.46-2.84, p = 0.98). Those differences did not show any statistical significance.
Conclusion: No significant differences concerning placental infarctions, decidual arteriopathy or abruption were found between preeclamptic placentas from non-smokers compared to smokers.
Hofbauer cells are placental macrophages found in chorionic villous stroma; they express classic monocyte/macrophage markers, such as CD68. Little is known about their participation in placental ...disease and immunologic interactions at the placental interface. The aim of this study was to quantify the amount of Hofbauer cells in placentas complicated, or not, by chorioamnionitis and in placentas from different gestational ages. Fifty-eight 2nd-and 3rd-trimester placentas with the histologic diagnosis of acute chorioamnionitis were compared with 42 control placentas matched according to gestational age. Immunohistochemistry evaluation was performed with a monoclonal anti-CD68 antibody. Five areas of each placenta were photographed and 5 investigators, with the help of a computerized image analysis program, independently evaluated the number of CD68+ cells. Our results showed that there are significantly fewer CD68+ cells per villous area in placentas diagnosed with chorioamnionitis than in those of controls (P < 0.001). Moreover, there was a significant overall decrease in the number of these cells in 3rd as compared with 2nd trimester placentas (P = 0.02), as well as in placentas from term as compared to preterm pregnancies (P = 0.004). Our data indicate that CD68+ Hofbauer cells may be involved in placental infection and possibly associated with the developmental maturation of the fetoplacental unit.
Objective: To study associations between placental histopathology and neonatal outcome in preeclampsia (PE). Study design: The cohort consisted of 544 singleton pregnancies complicated by PE and ...managed at Karolinska University Hospital, Stockholm, Sweden during 2000-2009. Evaluation of placental histopathology was made by one senior perinatal pathologist, blinded to outcome. Clinical outcome was obtained from prospectively collected medical registry data and medical records. Main outcome measures were intrauterine fetal death, smallness for gestational age, admission to neonatal unit, major neonatal morbidity (defined as presence of intraventricular hemorrhage grade 3, retinopathy of prematurity grade 3, necrotizing enterocolitis, cystic periventricular leucomalacia and/or severe bronchopulmonary dysplasia) and neonatal mortality. Logistic regression analyses including gestational age were performed. Results: Abnormal placental weight, both low (adjusted odds ratio (OR) 95% confidence interval 5.2 1.1-24, p = 0.03) and high (adjusted OR 1048 21-51 663, p < 0.001) for gestational age, was associated with major neonatal morbidity in preterm infants. Accelerated villous maturation was less prevalent in intrauterine fetal death pregnancies (adjusted OR 0.18 0.04-0.77, p = 0.02). Decidual arteriopathy increased the odds for admission to neonatal care (adjusted OR 2.7 1.1-6.5, p = 0.03). Infarction involving 5% of the placenta was associated with intrauterine fetal death and small for gestational age infants (adjusted OR's 75 5.5-1011, p = 0.001 and 3.2 1.7-5.9, p < 0.001; respectively). No relations between histological variables and neonatal mortality could be found. Conclusion: Placental pathology in PE reflects adverse perinatal events and deviant placental weight predicts adverse neonatal outcome in preeclamptic women delivering preterm. Placental investigation without delay can contribute to neonatal risk assessment.
The aim of the present study was to evaluate the histopathology in placentas from patients with severe preeclampsia with and without hemolysis, elevated liver enzymes, and low platelets (HELLP) ...syndrome. An additional aim was to compare the prevalence of infants born small for gestational age in the 2 groups. The study is retrospective and includes 178 women who have been diagnosed at the Karolinska University Hospital Huddinge or at the Free University Medical Center between 2000 and 2005 with severe preeclampsia. A total of 96 women had severe preeclampsia without signs of HELLP (preeclampsia group), whereas 82 fulfilled the criteria for having HELLP syndrome (HELLP group). Infarction (P=0.014), intervillous thrombosis (P<0.001), and abruption (P=0.002) were more common in the preeclampsia group than in the HELLP group. There was no statistically significant difference in the frequency of accelerated villous maturation (P=0.61), decidual arteriopathy (P=0.27), or chorioamnionitis (P=0.61). Furthermore, there was a higher mean placental weight, adjusted for gestational age, in the Swedish HELLP material than in the preeclampsia group (P<0.001). Finally, mothers in the preeclampsia group gave birth significantly more often to small for gestational age babies than mothers suffering from HELLP syndrome (P<0.001). The histopathologic profile and the range of placental lesions were partly different in the preeclampsia and HELLP patients. Considering the central role that placenta seems to have in preeclampsia, the present result might suggest that different underlying pathogenetic mechanisms and courses can be in play in patients with preeclampsia and HELLP syndrome.
Problem
Pre‐eclampsia (
PE
), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to ...endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of
PE
is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in
PE
pregnancy promotes
NK
cell activation, suggested to be important in
PE
pathogenesis. In line with this suggestion, we studied
NK
cell cytotoxicity in peripheral blood of
PE
patients and controls and the
mRNA
expression of cytokines and of the
NKG
2D receptor and its ligands
MICA
/B and
ULBP
1‐3 in
PE
‐ and normal placenta.
Method of study
The cytotoxic capacity of peripheral blood
NK
cells was analyzed using K562 target cells. The cytokine
mRNA
profiles and the
mRNA
expression of the
NKG
2D receptor and its ligands
MICA
/B and
ULBP
1‐3 in
PE
placenta were assessed and compared to those in normal placenta using real‐time quantitative
RT
‐PCR.
Results
The cytotoxicity of peripheral blood
NK
cells was upregulated in
PE
cases. Further, we found an enhanced inflammatory cytokine
mRNA
response combined with a dysregulated regulatory response and a significant
mRNA
overexpression of
NKG
2D receptor and its ligands
MICA
/B and
ULBP
in
PE
placenta.
Conclusion
The destruction of chorionic villi observed in
PE
placenta might be conveyed by an enhanced local cytotoxic response through the
NKG
2D receptor‐ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.
Hofbauer cells are placental macrophages found in chorionic villous stroma; they express classic monocyte/macrophage markers, such as CD68. Little is known about their participation in placental ...disease and immunologic interactions at the placental interface. The aim of this study was to quantify the amount of Hofbauer cells in placentas complicated, or not, by chorioamnionitis and in placentas from different gestational ages. Fifty-eight 2nd- and 3rd-trimester placentas with the histologic diagnosis of acute chorioamnionitis were compared with 42 control placentas matched according to gestational age. Immunohistochemistry evaluation was performed with a monoclonal anti-CD68 antibody. Five areas of each placenta were photographed and 5 investigators, with the help of a computerized image analysis program, independently evaluated the number of CD68(+) cells. Our results showed that there are significantly fewer CD68(+) cells per villous area in placentas diagnosed with chorioamnionitis than in those of controls (P < 0.001). Moreover, there was a significant overall decrease in the number of these cells in 3rd as compared with 2nd trimester placentas (P = 0.02), as well as in placentas from term as compared to preterm pregnancies (P = 0.004). Our data indicate that CD68(+) Hofbauer cells may be involved in placental infection and possibly associated with the developmental maturation of the fetoplacental unit.
Preeclampsia (PE) is a major cause of maternal and fetal morbidity and mortality. The maternal symptoms are diverse and the neonates are often born premature and growth-restricted. Today the survival ...of premature infants has increased, but the neonatal complications including morbidity and long-term developmental deficits are still common.The etiology and pathophysiological mechanisms in PE are still not known, but it seems as if a central part of the pathogenesis is associated with an unsuccessful implantation of the placenta into the uterus. The only cure is to deliver the mother, which is often a difficult decision in regard to prematurity of the fetus, when the disease has begun early in pregnancy.In our first and second studies, we examined the placental pathology in relation to the maternal symptoms and severity of disease. The first study showed that there was a correlation between the severity of symptoms and the placental pathology. Further, the pathological picture was similar in mild and severe PE, but differed in relation to controls. To summarize, mild PE seems to be part of the PE spectrum, and not a normal physiological development of pregnancy, in contrast to what has previously been claimed.The second study showed that placental pathology differed in severe PE with and without HELLP syndrome (hemolysis, elevated liver enzymes and low platelets), which is a disease regarded as a PE subtype, although the clinical picture is different from classical PE. This indicates that other mechanisms might be involved in the HELLP syndrome.In the third and fourth studies, we examined the placental pathology in relation to perinatal, neonatal and childhood outcome. In the third study, we investigated the relation between placental pathology and perinatal and neonatal outcome in a cohort of PE patients and found that placental pathology was associated with adverse outcome. In the fourth study, in which we studied infants born extremely premature, we also found correlations between placental pathology and perinatal and neonatal outcome.In the fourth study, we also explored possible relations between placental pathology and neurologic and developmental outcome of the child at the age of 2.5 years. We found a significant association between placental infarction and cerebral palsy (CP), and tendencies between several pathological findings and developmental outcome.Overall, we have shown that the underlying pathologies in mild and severe PE probably are similar, whereas HELLP syndrome might have a different etiology. In addition, we have found associations between placental pathology and outcome of the offspring.
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