John Gillan

Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement

CONTEXT -The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories. OBJECTIVE -To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community. DATA SOURCES -Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible. CONCLUSIONS -The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.

Abnormal Pulmonary Bombesin Immunoreactive Cells in Wilson-Mikity Syndrome (Pulmonary Dysmaturity) and Bronchopulmonary Dysplasia

Wilson-Mikity syndrome (WMS) is a disorder of uncertain origin. It is sometimes considered a variant of bronchopulmonary dysplasia (BPD), but it lacks the characteristic microscopic stigmata of destruction and fibrosis caused by the barotrauma and oxygen toxicity of ventilator support. Conventional clinical and autopsy studies of WMS have failed to identify the underlying pathophysiology. This study evaluated bombesin-containing pulmonary neuroendocrine (PNE) cells in eight WMS cases, seven cases of BPD, and five controls, using the immunoperoxidase technique. The PNE cells were quantified by established morphometric techniques. The percentage of airways containing PNE cells in WMS (mean, 85.56%) was similar to that in the controls (mean, 82.6%) but significantly greater than that in BPD (mean, 21.28%) (p < .001). Measurement of intraepithelial PNE cell cytoplasm within the bombesin-immunopositive airways demonstrated apparent PNE cell hyperplasia in both WMS and BPD. Prominent numbers of PNE cells were also present in the respiratory bronchioles and alveolar units in WMS. The increased PNE cells in WMS may reflect chronic hypoxia from hypoventilation and or autonomic dysfunction. The profile in BPD may reflect a similar pathophysiology but complicated by ventilator-induced injury to airway epithelium.

Placental cord insertion and birthweight discordance in twin pregnancies: results of the national prospective ESPRiT Study

OBJECTIVE The purpose of this study was to evaluate the impact of noncentral placental cord insertion on birthweight discordance in twins. STUDY DESIGN We performed a multicenter, prospective trial of twin pregnancies. Placental cord insertion was documented as central, marginal, or velamentous according to a defined protocol. Association of the placental cord insertion site with chorionicity, birthweight discordance, and growth restriction were assessed. RESULTS Eight hundred sixteen twin pairs were evaluated; 165 pairs were monochorionic, and 651 pairs were dichorionic. Monochorionic twins had higher rates of marginal (P = .0068) and velamentous (P < .0001) placental cord insertion. Noncentral placental cord insertion was more frequent in smaller twins of discordant pairs than control pairs (29.8% vs 19.1%; P = .004). Velamentous placental cord insertion in monochorionic twins was associated significantly with birthweight discordance (odds ratio, 3.5; 95% confidence interval, 1.3-9.4) and growth restriction (odds ratio, 4; 95% confidence interval, 1.1-14.3). CONCLUSION Noncentral placental cord insertion contributes to birthweight discordance in monochorionic twin pregnancies. Sonographic delineation of placental cord insertion may be of value in antenatal assessment of twin pregnancies.

Parvovirus infects cardiac myocytes in hydrops fetalis.

Parvovirus infection during pregnancy is an important cause of hydrops fetalis. It is attributed to anemia caused by viral-induced destruction of red blood cells. Infection of other organs has been reported including the heart, liver, and lungs. Few of these reports, however, convincingly demonstrate virions within the functional parenchyma of the tissue. This is of particular concern regarding myocardium in the context of hydrops fetalis which is, in part, due to cardiac failure. The problem in routine pathology practice is that most fetuses with the infection are macerated. This, in part, probably explains the paucity of published information on cardiac involvement. This study examined five cases of fatal hydrops fetalis with variable maceration with serologically proven parvovirus B19 infection. Transmission electron microscopy of cardiac tissue demonstrated intranuclear virions in both erythroid precursor cells and in cardiac myocytes in three of these cases. In each of these, immunogold electron microscopy provided confirmatory evidence of parvovirus infection. Virions were not identifiable where maceration had caused disintegration of nuclei in the myocytes. In addition, virions were absent in the three negative control cases where retroplacental hemorrhage was confirmed as the cause of death.This study suggests that parvovirus infection of cardiac myocytes may play a more important role in causing hydrops fetalis than previously realized. It also demonstrates that maceration should not discourage the use of electron microscopy.

Placental pathology, birthweight discordance, and growth restriction in twin pregnancy: results of the ESPRiT Study.

OBJECTIVE We sought to evaluate the association between placental histological abnormalities and birthweight discordance and growth restriction in twin pregnancies. STUDY DESIGN We performed a multicenter, prospective study of twin pregnancies. Placentas were examined for evidence of infarction, retroplacental hemorrhage, chorangioma, subchorial fibrin, or abnormal villus maturation. Association of placental lesions with chorionicity, birthweight discordance, and growth restriction were assessed. RESULTS In all, 668 twin pairs were studied, 21.1% monochorionic and 78.9% dichorionic. Histological abnormalities were more frequent in placentas of smaller twins of birthweight discordant pairs (P = .02) and in placentas of small for gestational age infants (P = .0001) when compared to controls. The association of placental abnormalities with both birthweight discordance and small for gestational age was significant for dichorionic twins (P = .01 and .0001, respectively). No such association was seen in monochorionic twins. CONCLUSION In a large, prospective, multicenter study, we observed a strong relationship between abnormalities of placental histology and birthweight discordance and growth restriction in dichorionic, but not monochorionic, twin pregnancies.

Morphometric Assessment of the Oxygen Diffusion Conductance in Placentae from Pregnancies Complicated by Intra-uterine Growth Restriction

The morphometric oxygen diffusive conductance (D(p)) of the placenta provides a measure of the efficiency of oxygen transfer between the mother and the developing fetus. Any change in the D(p)may point towards possible adaptation in the light of altered oxygen transfer. Placentae from normal (n=40) and small for gestational age SGA (n=24) pregnancies were analysed using stereological techniques. Each placenta was uniform randomly sampled and tissue samples processed to wax infiltration and embedding using conventional histological preparatory methods. A combination of stereological techniques and physiological constants were used to estimate the partial conductances across the five major tissue compartments involved in oxygen transfer. There was a significant reduction in both fetal birthweight and placental weight in the SGA group when compared with controls. A decrease in both chorionic (S(cv)) and fetal capillary (S(fc)) surface area was also observed in SGA placentae when compared with controls (P>0.001). Villous membrane harmonic thickness (T(vm)) was reduced in the SGA placentae (2.33 microm) when compared with controls (2.67 microm P=0.019). This resulted in a reduction in the minimum D(p)in SGA placentae when compared with controls (P=0.023). Adjusting for fetal weight resulted in no difference in the specific diffusive conductance. Changes in T(vm)in SGA placentae combined with changes in basic surface areas were insufficient to maintain overall D(p)values comparable with control placentae.

The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population

Objective. To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population. Methods. This study involves prospective recruitment of 1011 low-risk primigravids with placental ultrasound at 22–24 weeks and 36 weeks. Detailed postnatal review of all mothers and infants was undertaken. Retrospective analysis of ultrasound and clinical outcome data was performed. Results. Eight hundred ten women with complete outcome data were available. Anterior placentation was statistically associated with intrauterine growth restriction (IUGR) and preterm birth and fundal placentation was significantly associated with a higher incidence of pregnancy-induced hypertension and infants with a birthweight less than the 9th centile. Placental infarcts in the third trimester was significantly increased in cases complicated by pre-eclampsia (PET) and in cases with fetal acidosis. Placental calcification was associated a 40-fold increase in the incidence of IUGR. Placental lakes in the second trimester were more prevalent in patients with threatened miscarriage. Increased placental thickness was associated with a higher rate of fetal acidosis. The Grannum grade of the placenta was higher with threatened first or second trimester loss, PET and in infants born less than 9th centile for gestation. Conclusion. Placental site and architecture impact on the incidence of maternal and fetal disease.

Trophoblast basement membrane haemosiderosis in the placental lesion of fetal artery thrombosis : a marker for disturbance of maternofetal transfer ?

The placental lesion of fetal artery thromboses is characterized by collapse and obliteration of chorionic vasculature, an increase in stromal connective tissue and syncytial knots, with a thickening of trophoblast basement membrane. An additional feature, not previously described in association with the lesion, is linear trophoblast basement membrane haemosiderosis. Thirty-five such lesions were examined for this feature which was identified in 32. Random tissue sections of placentae from cases of intrauterine death showed a similar basement membrane haemosiderosis and were used as positive controls. None of 20 normal control cases examined demonstrated the feature. Electron microscopy demonstrated electron-dense bodies within the basement membrane. Spectrographic analyses confirmed the presence of iron within these deposits. The significance of this finding lies not so much in the fact that it is an additional finding in fetal artery thrombosis but rather in the underlying pathophysiology.

Chronic reduction in fetal blood flow is associated with placental infarction

The placenta receives two arterial blood supplies, i.e. one maternal and one fetal. It has been suggested that placental infarction should occur only if both blood supplies are compromised (Wigglesworth, 1984). This hypothesis has not been tested. Haemosiderosis of the trophoblast basement membrane (TBMH) has recently been identified as a feature of fetal artery thrombosis and suggested as a marker of impaired fetal blood flow which is identifiable in both viable and necrotic tissue. We examined 50 placental infarcts for evidence of TBMH, both grossly and microscopically. These were compared with four types of control tissue. Eleven placentae from cases of prolonged intrauterine death, in which this feature was first described, and 35 fetal artery thromboses were used as positive controls and 20 placentae from uncomplicated pregnancies were available as negative controls. Non-infarcted tissue adjacent to infarcts served as an internal negative control. Non-infarcted tissue adjacent to infarcts served as an internal negative control. Microscopically, 36 per cent of infarcts showed TBMH in at least 5 per cent of villi within the lesion and 60 per cent of infarcts showed at least one cluster of villi with the feature. These findings point to a disturbance in fetal blood flow intimately associated with but pre-dating the placental infarction. These findings represent the first experimental evidence to support Wigglesworths theory and suggest that reduction in fetal blood flow prior to thrombosis of maternal vessels contributes to the pathophysiology of placental infarction.

The Value of Neonatal Autopsy

Background and Objective: Neonatal autopsy rates were in decline internationally at the end of the last century. Our objective was to assess the current value of neonatal autopsy in providing additional information to families and healthcare professionals. Methods: We conducted a review of neonatal autopsies performed in a tertiary perinatal centre over an 11-year period. Primary outcomes measured were the annual neonatal autopsy rates and concordance rates between clinical and autopsy diagnoses of the primary cause of death. Secondary outcomes were the clinical, genetic and audit value of the examinations. Findings were used to inform the consent process, and the effect this had on institutional post-mortem rates was assessed over the subsequent 5-year period. Results: There was a marked decline in the annual neonatal autopsy rate from 73% in 1994 to 48% in 2004. 164 cases met the inclusion criteria for review. Complete concordance for cause of death was reached in 91% of cases. Previously unsuspected or unconfirmed clinical conditions, other than the primary cause of death, were uncovered at autopsy in 85 cases. Detailed information on inheritable conditions was obtained in 45 cases. Findings with perceived ‘audit value’ for clinical practice were identified in 29 cases. The dissemination of this information to staff and families contributed to the stabilisation of the consent rate in the following 5-year period. Conclusion: Neonatal autopsy remains a valuable diagnostic tool as it provides critical clinical and audit information for healthcare professionals and families.