Neither normal nor diseased placentas contain lymphatic vessels

Background

Scant data on placental lymphatic vessels have pointed to the absence of lymphatic circulation. A recent study on mesenchymal dysplasia (MD), however, has identified pathologic lymphangiogenesis using the D2-40 lymphatic marker. These conflicting data have prompted us to investigate whether lymphatic vessels are present in normal developing placentas and in placental disorders characterized by cistern formation.

Design

Seventeen human placentas without significant pathological abnormality ranging from 12 to 39 weeks of gestational age were studied. Cisternal placental disorders were represented by mesenchymal dysplasia (n = 1), partial hydatitiform mole (n = 2), spontaneous abortion (n = 3) and complete hydatiform mole (n = 2). To identify lymphatic vessels, we used lymphatic endothelial markers Prox-1 and D2-40. The pan-endothelial marker CD31 was used to highlight overall placental vasculature and to determine if the lining cells of cisterns were of endothelial origin. Lymphatic marker positivity was assessed in maternal (decidual) as well as in fetal (chorionic villous) vasculature.

Results

No staining with Prox-1 or D2-40 was identified in fetal vessels in developing or term placentas, or in selected cisternal placental disorders, although both markers highlighted a number of thin-walled decidual vessels. Cistern lining cells were negative for Prox-1, D2-40 and CD31. D2-40 consistently marked stromal cells in chorionic villi and highlighted perivascular/pericellular extracellular matrix.

Conclusion

We established that no lymphatic vasculature is present in the chorionic villi during development, at term or in selected edematous placental disorders. The cisternal lining cells are not endothelial cells; most likely they are of stromal cell origin. Lymphangiogenesis is a part of decidual vascular remodeling during gestation.     

First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction

Objective

We test the hypothesis that first-trimester serum analytes, 4-D power Doppler placental vascular indices and uterine artery Doppler (UAD) predicts abnormal placental morphometry in pregnancies with preeclampsia (PE) and fetal growth restriction (FGR).

Study design

Maternal serum analytes (PAPP-A, hCG, ADAM12s, and PP13), bilateral UADs, and placental vascular indices were measured at 11-14 weeks in a nested-case control study within a prospective cohort of women followed from the first-trimester to delivery. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained from 4-D power Doppler histograms. Serum analytes were measured using immunofluorometric assays and values converted to multiples of the median (MoM) for gestational age. Morphometric analysis was performed on placentas from pregnancies complicated by PE (n = 13), gestational hypertension (HBP, n = 7) and FGR (defined as fetal weight <10th percentile with abnormal umbilical artery Doppler: n = 7); and 20 uncomplicated pregnancies. Two pregnancies had both FGR and PE. Each placenta was weighed and random samples taken, and fixed in formalin within 1 h of delivery. Hematoxylin & Eosin stained slides were analyzed by design-based stereology to quantify linear dimensions, surface areas and volumes of placental components. Paired t-test and ANOVA with adjustments for multiple comparisons were used.

Results

The surface areas of terminal and intermediate villi as well as the volume of terminal villi were significantly smaller in placentas from pregnancies complicated by FGR and PE. Compared with the control group the mean PAPP-A (MoM) was lower in the pregnancies with abnormal placenta morphometry (1.1 ± 0.5 versus 0.7 ± 0.5, P = 0.03). The morphometric indices were lower in those pregnancies with low PAPP-A and IUGR compared with preeclampsia.

Conclusion

First-trimester PAPP-A levels are associated with abnormal placental morphometry at delivery in pregnancies with PE and IUGR. These findings may explain the association between adverse pregnancy outcomes and first-trimester PAPP-A.     

Sex specific changes in placental growth and MAPK following short term maternal dexamethasone exposure in the mouse

Objectives

Maternal glucocorticoid (GC) exposure during pregnancy can alter fetal development and program the onset of disease in adult offspring. The placenta helps protect the fetus from excess GC exposure but is itself susceptible to maternal insults and may be involved in sex dependant regulation of fetal programming. This study aimed to investigate the effects of maternal GC exposure on the developing placenta.

Study design and main outcome measures

Pregnant mice were treated with dexamethasone (DEX-1 μg/kg/h) or saline (SAL) for 60 h via minipump beginning at E12.5. Placentas were collected at E14.5 and E17.5 and the expression of growth factors and placental transporters examined by real-time PCR and/or Western blot. Histological analysis was performed to assess for morphological changes.

Results

At E14.5, DEX exposed male and female fetuses had a lower weight compared to SAL animals but placental weight was lower in females only. Hsd11b2 and Vegfa gene expression was increased and MAPK1 protein expression decreased in the placentas of females only. At E17.5 placental and fetal body weights were similar and differences in MAPK were no longer present although HSD11B2 protein was elevated in placentas of DEX females. Levels of glucose or amino acid transporters were unaffected.

Conclusions

Results suggest sex specific responses to maternal GCs within the placenta. Decreased levels of MAPK protein in placentas of female fetuses suggest alterations in the MAPK pathway may contribute to the lower placental weights in this sex. This may contribute towards sex specific fetal programming of adult disease.     

Intercellular adhesion molecule-1 expression in massive chronic intervillositis: Implications for the invasion of maternal cells into fetal tissues

Introduction

Massive chronic intervillositis (MCI), also known as chronic intervillositis of unknown etiology, is a placental lesion associated with massive infiltration of mononuclear cells in the intervillous space, poor perinatal outcome, and high rate of recurrence. Our previous demonstration of increased syncytiotrophoblast (st) intercellular adhesion molecule-1 (ICAM-1) expression in villitis lesions and the finding of extensive monocyte/macrophagic cells in the maternal intervillous space in MCI, led us to further investigate stICAM-1 in MCI.

Materials and methods

A cross-sectional study of placentas from the third trimester of pregnancy (34–41 weeks gestation) was conducted to determine stICAM-1 in MCI (n = 7). MCI stICAM-1 expression was compared to stICAM-1 in villitis (n = 7) and in normal villi from placentas with (n = 7) and without (n = 7) villitis. Maternal cells within villi in MCI were identified in placentas mismatched for maternal/fetal human leukocyte antigen (HLA)-DRw52. Villitis was diagnosed with hematoxylin and eosin staining and antibody to CD3 in serial sections, and ICAM-1 in syncytiotrophoblasts was confirmed with antibodies to ICAM-1 and cytokeratin.

Results

Placentas with MCI had higher stICAM-1 (79.8%) than placentas with villitis (27.1%), normal villi from placentas with villitis (11.5%), and normal villi from placentas without villitis (0.3%). Maternal cells were identified within villi of placentas (n = 5) mismatched (mothers positive, fetuses negative) for HLA-DRw52.

Conclusions

Placentas with MCI have more stICAM-1 than placentas with or without villitis lacking MCI. The finding that MCI and villitis have prominent stICAM-1 and maternal cells in the villi suggests that MCI and villitis could have a similar pathophysiologic mechanism.     

Magnetic resonance imaging relaxation time measurements of the placenta at 1.5 T

Placental insufficiency is a major cause of fetal growth restriction (FGR) and accumulating evidence indicates several aspects of placental morphology are altered in this condition. MRI provides quantitative indices that may be used in non-invasive assessment of the human placenta, such as relaxation time measurements, T1 and T2. We hypothesised that placental relaxation times relate to alterations in placental tissue morphology and hence may be useful in identifying the changes associated with FGR. We report on the first phase of testing this hypothesis, in a study of women in normal pregnancy.

Aims

To assess relaxation time measurements in the placenta in normal pregnancy and correlate these with gestational age and stereological analyses of placental morphology following delivery.

Methods

30 women underwent MRI examination (1.5 T) between 20 and 41 weeks gestation. Placental T1 and T2 measurements were acquired from a mid-depth placental region, co-localised to a structural scan. Fixed, wax-embedded sections of these placentas collected at delivery were stained with hematoxylin/eosin and subjected to stereological analysis.

Results

Placental T1 and T2 show a significant negative correlation with gestation, (Pearson correlation p = 0.01, 0.03 respectively). 17 placentas were analysed stereologically. In the group as a whole there was no significant correlation between T1 and T2 and morphological features. However, in a subset of 7 pregnancies scanned within a week of delivery, a significant positive correlation was observed between the fibrin volume density and the ratio of fibrin: villous volume densities and T2 (Spearman correlation p = 0.02, 0.03 respectively).

Discussion

The correlations between placental T1 and T2 and gestation show that these variables are clearly influenced by changes in placental structure. Fibrin might be a key component but further work is needed to fully elucidate the major structural influences on placental T1 and T2.     

Fetoplacental vascular alterations associated with fetal growth restriction

Introduction

Placental functional impairment in pregnancies with fetal growth restriction (FGR) can arise from fetoplacental vascular abnormalities. We aimed to compare the micro and macrovasculature of placentas from normal pregnancies with those showing late onset FGR.

Methods

Placental arterial casts (n = 12 normal, 6 FGR) were prepared. Chorionic arterial number and inter-branch length were examined. Microvascular features were quantified in CD34-stained tissue sections obtained by systematic (n = 12 normal, 12 FGR) and targeted (n = 6 normal, 6 FGR) sampling from the placental periphery and centre.

Results

Adjusted for the weight of the placenta or the surface area of the chorionic plate, the number of chorionic arteries was similar in normal and FGR arterial casts. Inter-branch length per unit placental weight was greater in the first generation of arterial branches in FGR (p < 0.05). Villi in FGR placentas were more poorly vascularised, particularly at the periphery and in grossly visible hypovascular regions. Intermediate and terminal FGR villi in these areas exhibited reduced vessel lumens, loss of CD34, and infilling with CD34-negative cells of what appeared to be previously existing vascular spaces.

Conclusion

Differences in chorionic arterial branching patterns between normal and FGR placentas arise from differences in placental size. FGR placentas show microvascular regression and extreme hypovascularity in peripheral areas. These features may well limit the ability of the placenta to meet fetal nutrient requirements late in gestation. Targeted sampling is more effective than systematic random sampling in revealing vascular defects.     

The timing and duration of hypoxia determine gene expression patterns in cultured human trophoblasts

Objective

Exposure of cultured trophoblasts to hypoxia is commonly used to interrogate the molecular mechanisms underlying placental hypoxic injury. We examined the effect of levels, durations, and patterns of hypoxia on gene expression patterns in primary human trophoblasts.

Study design

We exposed primary term human trophoblasts to either standard culture conditions (O₂ = 20%) or to static or alternating levels of oxygen (O₂ = 8%, or O₂ = 0%) either early or late in culture, and analyzed the expression of 34 genes that are known to be regulated in placentas from pregnancies complicated by fetal growth restriction (FGR).

Results

Using multidimensional scale analysis, Euclidean distance, and hierarchical clustering, we found that gene expression patterns in cells exposed to O₂ = 8% were similar to patterns observed in O₂ = 20%, but more distant from patterns in O₂ = 0%. Alternating atmospheric oxygen (8% vs. 0%) yielded intermediate results. Changes in oxygen levels over a longer period had a greater effect on gene expression than short-term changes. Gene expression patterns in cultured trophoblasts did not fully capture expression patterns observed in biopsies from FGR placentas vs. control.

Conclusions

The level, duration, and patterns of hypoxia are critical in determining trophoblast gene expression, and therefore germane for analysis of trophoblast hypoxic injury.     

Pilot study of comparative placental morphometry in pre-eclamptic and normotensive pregnancies suggests possible maladaptations of the fetal component of the placenta

Objective

Adequate maternal, intervillous and fetal blood flow are all necessary for fetal well-being. Compromise to any part of this exchange would be detrimental to pregnancy outcome. Pre-eclampsia is associated with reduced maternal spiral artery flow, resulting in reduced placental perfusion. This in turn creates an ischaemic environment, which may predispose to morphological changes in placental villi. This pilot study sought to assess whether there were morphological alterations in the fetal component of the placenta which could be detrimental to exchange and therefore pregnancy outcome.

Study design

This study utilized morphometric image analysis to examine some features of the fetal component of the placenta in normotensive (NT) and pre-eclamptic (PE) groups. The features examined included: density of placental villi (expressed as percentage of field area occupied by placental tissue); stem vessel carrying capacity (expressed as percentage of stem villus area occupied by vessel lumina); the thickness of the stem arterial walls relative to artery size (expressed as percentage of artery area occupied by arterial wall) and the extent of fibrosis associated with villi (expressed as percentage of field area occupied by fibrosis).

Results

There were significant differences between NT and PE placentae in density of placental villus arrangement NT: 51.89 ± 6.19, PE: 64.78 ± 6.93 (P < 0.001); carrying capacity of stem villi NT: 17.20 ± 11.78, PE: 8.67 ± 8.51 (P < 0.001); relative thickness of stem villi arterial walls NT: 74.08 ± 12.92, PE: 86.85 ± 10.55 (P < 0.001); and extent of fibrosis NT: 0.727 ± 0.310, PE: 1.582 ± 0.707 (P < 0.001).

Conclusion

These significant differences between normotensive and pre-eclamptic placentae suggest possible fetal maladaptations in response to the intervillous ischaemia, compounding the existing maternal compromise to materno-fetal exchange. Further investigations would, however, be necessary in order to make more conclusive deductions.     

The morphometry of materno-fetal oxygen exchange barrier in a baboon model of obesity

Introduction

More than one-fourth of U.S. women are overweight; more than one-third are obese. Maternal obesity has been linked to an increased incidence of stillbirths, fetal macrosomia, fetal intrauterine growth restriction and pre-eclampsia. The placenta plays a key role in the nutrients and oxygen supply to the fetus. The data about structural changes in the placental villous membrane (VM), a major component of the feto-maternal nutrient and oxygen exchange barrier, during obesity are sparse and inconsistent. Our objective was to evaluate the morphometric changes in the placental exchange barrier in a baboon model of obesity.

Materials and methods

The previously described baboon model of maternal obesity was studied. We compared 4 obese to 4 non-obese baboons. Placental stereology with the use of transmission electron microscopy was performed to estimate VM oxygen diffusing capacities and morphometry.

Results

The specific placental oxygen diffusing capacities per unit of fetal weight were similar in baboons and humans. Maternal leptin concentrations correlated negatively with placental basement membrane thickness (r = −0.78, p < 0.05), while fetal leptin levels correlated negatively with endothelial thickness of fetal capillaries (r = −0.78, p < 0.05). The total and specific villous membrane oxygen diffusing capacities were not different between the two groups.

Conclusion

To the best of our knowledge this is the first report of placental oxygen diffusing capacities and placental ultrastructural changes in a baboon model of obesity. Previously reported placental inflammation in maternal obesity is not associated with changes in the VM diffusing capacities and ultrastructure.     

Ontogenic changes in placental transthyretin

Objectives

Before secretion of fetal thyroid hormone at around 16 weeks gestation normal fetal development depends on a constant supply of maternal thyroid hormone (TH), particularly thyroxine (T₄). The detailed mechanisms of transplacental delivery of TH are still uncertain. The TH binding protein, transthyretin (TTR), is produced and secreted by placenta and may play a role in this process. The ontogeny of placental TTR is unknown. Our aim was to study changes in placental TTR in early and late pregnancy.

Study design

We collected placentas from surgically terminated pregnancies between 6 and 17 weeks gestation (n = 44) and from normal term (38-39 weeks) pregnancies following caesarean section (n = 5). Real time-PCR, western blotting and immunohistochemistry were used to determine TTR mRNA and protein levels.

Results

There were highly significant correlations between gestational age and TTR mRNA (r = 0.974; p < 0.0001) and between gestational age and TTR protein (r = 0.901; p < 0.001) levels between weeks 6 and 13 of gestation. TTR expression did not increase between 13 and 17 weeks and was not different at term. Good correlation was observed between TTR mRNA and TTR protein between individual placental samples (r = 0.916; p < 0.0001). A similar trend was observed using immunohistochemical staining of placental paraffin sections.

Conclusions

Our results demonstrate that TTR is expressed in the human placenta from at least 6 weeks gestation. Levels rise during the first trimester at a time when placental oxygen tensions are also rising. We hypothesise that TTR production and secretion by the placenta may facilitate transplacental delivery of TH to the fetus.     

Mother's lifetime nutrition and the size, shape and efficiency of the placenta

Background

Studies have shown that the shape and size of the placenta at birth predict blood pressure in later life. The influences that determine placental morphology are largely unknown. We have examined the role of mother’s body size.

Methods

We studied 522 neonates who were born in a maternity hospital in Mysore, South India. The weight of the placenta and the length and breadth of its surface, were measured after delivery.

Results

Higher maternal fat mass predicted a larger placental surface (p = 0.02), while larger maternal head circumference predicted a more oval placental surface (p = 0.03). Higher maternal fat mass and larger maternal head circumference were associated with greater placental efficiency, indicated by lower ratios of the length (p = 0.0003 and p = 0.0001 respectively) and breadth (p = 0.0002 and p < 0.0001) of the surface to birthweight. In a sub-sample of 51 mothers whose own birthweight was available, higher maternal birthweight was related to lower ratios of the length and breadth of the surface to birthweight (p = 0.01 and 0.002). Maternal height was unrelated to placental size or shape.

Conclusions

Higher maternal fat mass, reflecting the mother’s current nutritional state, and larger maternal head circumference, reflecting the mother’s fetal/infant growth, are associated with changes in the shape and size of the placental surface and greater placental efficiency. We suggest that these associations reflect effects of the mother’s nutrition at different stages of her lifecourse on the development of the placenta and on materno-placento-fetal transfer of nutrients.     

Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by α1-microglobulin

Background

Preeclamptic women have increased plasma levels of free fetal hemoglobin (HbF), increased gene expression of placental HbF and accumulation of free HbF in the placental vascular lumen. Free hemoglobin (Hb) is pro-inflammatory, and causes oxidative stress and tissue damage.

Methodology

To show the impact of free Hb in PE, we used the dual ex vivo placental perfusion model. Placentas were perfused with Hb and investigated for physical parameters, Hb leakage, gene expression and morphology. The protective effects of α₁-microglobulin (A1M), a heme- and radical-scavenger and antioxidant, was investigated.

Results

Hb-addition into the fetal circulation led to a significant increase of the perfusion pressure and the feto-maternal leakage of free Hb. Morphological damages similar to the PE placentas were observed. Gene array showed up-regulation of genes related to immune response, apoptosis, and oxidative stress. Simultaneous addition of A1M to the maternal circulation inhibited the Hb leakage, morphological damage and gene up-regulation. Furthermore, perfusion with Hb and A1M induced a significant up-regulation of extracellular matrix genes.

Significance

The ex vivo Hb-perfusion of human placenta resulted in physiological and morphological changes and a gene expression profile similar to what is observed in PE placentas. These results underline the potentially important role of free Hb in PE etiology. The damaging effects were counteracted by A1M, suggesting a role of this protein as a new potential PE therapeutic agent.     

Placental pathology in fetal growth restriction

Objectives

One of the causes of intrauterine fetal growth restriction (FGR) can be pathology of the placenta. The aim of this study was to compare macroscopic and microscopic changes of the placentas from intrauterine growth restricted fetuses with those from normally developed fetuses, in order to test the hypothesis that vascular damage due to decreased maternal vascular perfusion may be responsible for FGR.

Study design

Between May 2007 and December 2008 we performed detailed macroscopic and histological examination of singleton placentas of 50 consecutive neonates with fetal growth restriction (FGR group) and compared them to 50 normal fetuses, born next to an FGR case, as a control group.

Results

Gestational age, birth weight, spontaneous delivery rate, mean weight of the placenta and the fetal-placental weight ratio were all lower in the FGR group than in the control group (p < 0.05). Thickening of the villous trophoblastic basal membrane, incidence of villous infarction, presence of thrombi or haematomas and the incidence of villitis were more common in the FGR group than in the controls (p < 0.05). There were, however, no significant differences in perivillous fibrin deposition, stromal fibrosis and cytotrophoblast proliferation between the groups. In FGR women who smoked, intervillous haematomas and villous infarction were more common (p < 0.05) than in controls.

Conclusions

All macroscopic and microscopic pathological changes associated with FGR were directly linked to reduction of placental blood flow. As smoking is a main risk factor for these placental abnormalities these results emphasize the need to persuade women to quit smoking not only during pregnancy, but even better long before pregnancy.     

Regulation by hypoxia of adrenomedullin output and expression in human trophoblast cells

Objectives

Plasma adrenomedullin concentrations are increased in the fetal circulation in acute and chronic hypoxic conditions. The effect of hypoxia in regulating adrenomedullin synthesis and secretion was investigated in human placental trophoblast cells.

Study design

Human trophoblast cells obtained from term placentas (n = 7) were cultured in hypoxic condition (3% oxygen). Cytotrophoblast cells were cultured for up to 48 h and syncytiotrophoblasts for 2, 8 and 24 h. Changes in adrenomedullin output compared to normoxic conditions were measured by radioimmunoassay. Protein expression was evaluated with Western blot and immunocytochemistry.

Results

Hypoxia induced a time-dependent increase in adrenomedullin output and protein expression by placental trophoblast cells.

Conclusions

Hypoxia regulates adrenomedullin secretion and expression by human placenta, thereby promoting increased adrenomedullin concentration in the fetal circulation in clinical circumstances characterized by reduced oxygen levels.     

Effect of young maternal age and skeletal growth on placental growth and development

Objectives

Teenagers are susceptible to delivering small-for-gestational-age infants. Previous studies implicate continued skeletal growth as a contributory factor, and impaired placental development was the primary cause of fetal growth restriction in growing adolescent sheep. The aims of this study were to examine the impact of young maternal age and growth on placental development.

Study design

Placentas were collected from 31 teenagers, of which 12 were growing and 17 non-growing based on knee height measurements. An adult control group (n = 12) was included.

Main outcome measures

Placental weight and morphometric measurements of villous, syncytiotrophoblast, fibrin and vessel areas, as well as indices of proliferation and apoptosis, were analysed in relation to maternal growth and age.

Results

Growing teenagers had a higher birthweight:placental weight ratio than non-growing teenagers (p < 0.05). Villous area, syncytial area, fibrin content, vascularisation and cell turnover did not differ between growing and non-growing teenagers. There were no differences in placental weight or morphometry between adult and teenage pregnancies. Maternal smoking, a potential confounding factor, did not exert a major influence on the placental parameters examined, except for a stimulatory effect on placental proliferation (p < 0.05) and syncytial knot formation (p < 0.05).

Conclusions

We were unable to detect any major differences in placental size or composition between growing and non-growing teenagers. Birthweight:placental weight ratio was higher in growing compared to non-growing teenagers. This suggests that maternal growth may affect placental function rather than development, and is consistent with our recent observations that maternal growth was not detrimental to fetal growth.     

Plasma and placental nitric oxide levels in women with and without pre-eclampsia living at different altitudes

Objective

To investigate the nitric oxide (NO) levels in the plasma and the placentas of pregnant women with pre-eclampsia and women without pre-eclampsia, and to determine the effect of high or low altitude of residence.

Methods

NO was determined by chemoluminescence and group comparisons were performed.

Results

Women with pre-eclampsia (n = 63) had higher plasma NO levels (38.6 ± 17.44 vs 30.6 ± 12.44 µmol/L, P = 0.004) and higher placental NO levels (38.5 ± 17.0 vs 24.3 ± 7.16 ng/mg protein, P < 0.05) compared with women without pre-eclampsia. A similar trend was found when comparisons were made according to altitude of residence. NO levels were significantly higher in the plasma of pre-eclamptic women living at sea level (41.11 ±18.78 vs 28.96 ± 9.57 µmol/L, P = 0.003), and in the placentas of women living at high altitude (39.51 ± 16.98 vs 21.91 ± 6.64 ng/mg protein, P < 0.0001).

Conclusion

Women with pre-eclampsia had higher plasma and placental NO levels and the differences were associated with altitude of residence.     

Pregnancy outcomes and ultrasonographic diagnosis in patients with histologically-proven placental chorioangioma

Objective

To evaluate pregnancy outcome and ultrasound diagnosis in patients with histologically-confirmed placental chorioangioma.

Study design

Placentas with histological diagnosis of chorioangioma were identified and medical charts were reviewed for findings of ultrasound examinations. Pregnancy outcomes were compared with all singleton deliveries without chorioangioma in the same time period.

Main outcome measures

Primary outcome was Neonatal Intensive Care Unit admission rate. Secondary outcome was ultrasound detection rate of chorioangioma.

Results

Among 14,725 singleton deliveries, 23 placentas were diagnosed with chorioangioma (0.16%). The control group included all singleton deliveries without chorioangioma (n = 14702). Neonates in the study group were more likely to be admitted to the Neonatal Intensive Care Unit (OR = 4.45) and to have smaller birth weight (p = 0.006). Only 2 of 7 larger chorioangiomas (≥2 cm) with available ultrasound reports were identified by ultrasound (29% detection rate). All cases demonstrated normal fetal growth and wellbeing.

Conclusion

Chorioangiomas are not always identified by routine prenatal sonography. Even in the absence of ultrasonic abnormalities, neonatal morbidity, as measured by NICU admission rate, is increased.     

Placental structure and inflammation in pregnancies associated with obesity

Background

Pre-gravid obesity is associated with increased morbidity and mortality for both mother and offspring. Recent studies have demonstrated a heightened inflammatory response both systemically and locally within the adipose and placental tissue in women with pre-gravid obesity, which may play a role in mediating the adverse pregnancy outcomes. The aim of this study was to characterise the maternal and placental inflammatory status and investigate associated changes in placental structure in obese women.

Methods

The pro-inflammatory status of a cohort of 47 non-obese (BMI 20-25 kg/m²) and 33 obese (≥30 kg/m²) women was characterised by measuring maternal circulating levels and placental gene expression of pro-inflammatory cytokines, and quantifying immune cell populations within the placenta. The effect of pre-gravid obesity on placental structure was investigated by examining placental maturity, vessel density, the formation of syncytial knots and sprouts, and the degree of fibrin deposition, chorangiosis and muscularisation of vessel walls.

Results

Maternal obesity was associated with significantly greater IL-1β (p < 0.05), IL-8 (p < 0.05), MCP-1 (p < 0.001) and CXCR2 (p < 0.05) mRNA expression within the placenta and higher circulating maternal levels of IL-6 (3.30 ± 0.38 vs. 1.77 ± 0.15 pg/ml) (p < 0.001) compared with non-obese women. There were no differences in the number of CD14⁺, CD68⁺ cells or neutrophils within the placental villi of non-obese and obese women. However there were significantly higher numbers of neutrophils within the interstitial space (p < 0.05). Greater muscularity of placental vessel walls was associated with maternal obesity (p = 0.03), however no other associated structural changes were observed.

Conclusions

Our findings show that although pre-gravid obesity was associated with greater expression of placental pro-inflammatory cytokines and higher circulating IL-6 in pregnancy, there were no major differences in immune cell populations within the placental villi and only a greater degree of muscularity in the vessel walls.     

Immunohistochemical expression of Annexin A5 in preeclamptic placentas

Objective

To study the expression of Annexin A5 (A5) in relation to preeclampsia using immunohistochemical Tissue Microarray (TMA) technique.

Study design

Case-control study of 66 singleton preeclamptic (PE) patients matched for gestational age (GA) at delivery with 63 normotensive controls with normally grown fetuses. Immunohistochemical expression of A5 and other population characteristics were compared between the two groups using Chi-square, One-way ANOVA, Spearman’s Correlation, and Linear Regression.

Results

The two groups were similar for maternal age and rate of corticosteroid administration, but differed for nulliparity, Body Mass Index (BMI), blood pressure, presence of placental histological lesions, and placental weight. Expression of A5 was similar in PE and controls (p = 0.10); however it was found to be lower in PE cases complicated by fetal growth restriction (FGR, n = 34) compared with matched controls (n = 55) (p = 0.04). An inverse correlation was found between A5 and GA in cases but not in controls (p = 0.04 vs p = 0.71). The association was even more significant in the subgroup of PE complicated by FGR (p = 0.02). A5 expression was not influenced by blood pressure, proteinuria, or placental weight.

Conclusions

Annexin A5 expression seems to be related only to FGR and not to PE or its clinical severity.     

Effects of famine on placental size and efficiency

Background

Placental growth responds to maternal influences including diet. We have examined placental size, shape and efficiency among babies born around the time of the 5-month wartime famine in Holland 1944-1945.

Methods

We examined the birth records of 2414 term singleton babies born in Amsterdam during 1943-1947. The records included the size of the baby and the thickness of the placental surface, together with its length and breadth which we used to calculate its area and volume.

Results

Compared to babies born before the famine babies who were in utero during the famine had smaller placental areas. Babies whose mothers conceived after the famine ended also had smaller placental areas. Famine was associated with a 19 cm² decrease in area. Babies who were in mid-late gestation during the famine were 160 g lighter than would have been predicted from their placental area (p < 0.001). Babies who were in early gestation during the famine, or who were conceived after it had ended were 102 g heavier than would have been predicted from their placental area (p < 0.001). These latter babies were either longer or had larger head circumferences depending on when the mother experienced the famine. Among babies who were in early gestation during the famine the reduction in placental area was greater in boys than girls (p for interaction 0.03).

Conclusion

Famine impaired the normal processes of placentation, even among babies who were conceived after it had ended. In babies who were in mid-late gestation during the famine, the placenta was less efficient. In babies who were in early gestation during the famine, or who were conceived after it had ended, the placenta was more efficient. The placentas of boys and girls responded differently to famine.