Lena Macara

Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilical artery is associated with maldevelopment of the placental terminal villous tree

OBJECTIVE Our purpose was to evaluate the structure of placental terminal villi and their capillaries in pregnancies complicated by intrauterine growth restriction with absent end-diastolic flow velocity in the umbilical artery. STUDY DESIGN Glutaraldehyde-perfusion-fixed villous tissue and a plastic cast of the vessels in at least two cotyledons were prepared from 10 cases with intrauterine growth restriction and 9 gestational age-matched control placentas. The structure and dimensions of 20 terminal capillary loops per cast were determined by scanning electron microscopic examination, and their appearances were correlated with the peripheral villi of the perfusion-fixed villous tissue. RESULTS Capillary loops in the growth-restricted cases were sparse in number and significantly longer than in the control cases (218 microns [72] vs 137 microns [30], mean and SD, p < 0.05). They exhibited fewer branches (4.0 [1.9] per loop vs 6.1 [2.2], p < 0.05) and a majority of loops were uncoiled (79% vs 18%, p < 0.05). The villous tissues from the growth-restricted cases demonstrated elongated villi, consistent with the cast findings. The trophoblast surface was wrinkled and in some areas covered by fibrin plaques. CONCLUSIONS The terminal villous compartment of the placenta appears to be maldeveloped in preterm intrauterine growth restriction pregnancies where absent end-diastolic flow velocity is demonstrated in the umbilical artery before delivery. These findings are consistent with an increase in fetoplacental vascular impedance at the capillary level and may account for the impaired gas and nutrient transfer in this disorder.

Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery Doppler waveforms.

The abnormal umbilical artery Doppler waveform represented by absent end-diastolic flow velocity (AEDFV) identifies a group of preterm small-for-gestational age fetuses that are at high risk of perinatal death due to chronic fetal hypoxia. The placental ischaemia that results from inadequate trophoblast invasion of spiral arterioles leads to an assumption of placental villous hypoxia, though an alternative explanation is that the placenta fails to adequately transfer oxygen to the fetus from the intervillous space. Because oxygen transport takes place within the terminal villi, we undertook the first detailed studies of villous ultrastructure structure and immunohistochemistry in order to determine the likely origin of fetal hypoxia in this condition. Terminal villi were examined ultrastructurally using transmission electron microscopy and by immunohistochemical localization of matrix molecules (laminin and collagens I, III and IV) and a marker of cell proliferation (MIB-1), in 16 small-for-gestational age pregnancies with AEDFV in the umbilical artery [deemed to have intrauterine growth restriction (IUGR)] and in 16 gestation age-matched controls. Terminal villi from the IUGR cases were smaller in diameter (P < 0.02) and had several abnormal features in comparison with the controls; increased syncytial nuclei (P < 0.01), reduced cytotrophoblast nuclei (P < 0.01), thickened basal lamina (P < 0.01), and increased stromal deposition of collagens and laminin. The amount of proliferating cytotrophoblast was reduced in the IUGR group (P < 0.014) and the degree of capillary erythrocyte congestion within terminal villous capillaries was increased (P < 0.001). Several of the structural differences in the terminal villi of the IUGR group such as reduced cytotrophoblast proliferation and stromal fibrosis are incompatible with the prevailing view of placental hypoxia in IUGR. Rather thickening of the basal lamina and congestion of the capillaries by erythrocytes are predicted to limit oxygen transfer from the intervillous space to the fetus and may represent an equilibration of oxygen tension between intervillous space and the terminal villi. Despite the known reduction in uteroplacental blood flow in IUGR, fetoplacental blood flow is compromised to a far greater extent in the presence of AEDFV such that maternal blood leaving the placenta has a higher oxygen content than under normal circumstances.

The cell adhesion molecule, VCAM‐1, is selectively elevated in serum in pre‐eclampsia: does this indicate the mechanism of leucocyte activation?

Objective To determine whether circulating levels of cell adhesion molecules, markers of endothelial damage and leucocyte activation, were increased in pre‐eclampsia.

Adaptive angiogenesis in placentas of heavy smokers

Smoking in pregnancy increases perinatal morbidity and mortality, suggesting impaired placental function, though placental weight is increased. We used scanning electron microscopy to show adaptive angiogenesis in term placental villi from smokers (n=4) and non-smokers (n=4). These images may aid communication of the dangers of smoking in pregnancy.

Elaboration of stem villous vessels in growth restricted pregnancies with abnormal umbilical artery Doppler waveforms

Objective To assess the elaboration of placental stem villous vessels from pregnancies complicated by intrauterine growth restriction (IUGR) with absent end–diastolic flow velocity detected prior to delivery in the umbilical artery.

Control of the fetoplacental circulation

This year marks the 250th anniversary of the discovery by William Hunter of the existence of two distinct circulations within the human placenta. Until relatively recently the placenta has been viewed with “respect” – a passive structure which occasionally elicited fear and anxiety if implanted either too low or too deep. More recently our understanding of perinatal physiology, blood flow regulation and epidemiological data linking prenatal events with adult disease has created renewed interest in the placenta. This review will focus on the regulation of fetal blood flow in the placenta, the possible mechanisms whereby it may be deranged and why this might be relevant to adult disease.

Inter‐assay variation in antiphospholipid antibody testing

We evaluated inter‐assay variation in anticardiolipin antibody status, comparing three centres, and using different assays among 36 women with recurrent miscarriage and 26 controls. There was no more agreement between the laboratories than would be predicted on the basis of chance for IgM and only fair agreement among the laboratories for IgG. None of the tests were significantly more likely to be positive in the cases compared with the controls.

Pathological basis for abnormal umbilical artery doppler waveforms in pregnancies complicated by intrauterine growth restriction

Summary The abnormal umbilical artery Doppler waveform represented by absent enddiastolic flow velocity (AEDFC) identifies a group of preterm fetuses with intrauterine growth restriction (IUGR) at high risk of perinatal death due chronic hypoxia from compromised umbilical artery blood flow. Initial studies of AEDFV placentae suggested a loss of small stem arterioles, though by immunohistochemical localization with an antibody to α-smooth muscle actin, we were unable to demonstrate any selective loss of even the smallest vessels in the 10–25 μM post-fixation diameter range. Further studies of villous ultrastructure and immunohistochemical localization of matrix molecules (laminin and collagens I, III and IV) demonstrated evidence of villous fibrosis and trophoblast aging. Parallel scanning electron microscopy studies demonstrated reduced numbers of malformed peripheral villi, whose capillaries were elongated and only poorly branched. Several of the structural differences in the terminal villi of this IUGR group, such as reduced cytotrophoblast proliferation and stromal fibrosis, are incompatible with the prevailing view of placental hypoxia in preterm IUGR with AEDFV. Reduced numbers of malformed terminal vili would be predicted to both increase capillary vascular impedance, and compromise placental gas exchange. Despite the known reduction in uteroplacental arterial blood flow in IUGR with AEDFV in the umbilical arteries, there is a greater fall in extraction of oxygen from the intervillous space: as such that maternal blood leaving the placenta has a higher content than under normal circumstances. Our data challenge the presumption of “placental hypoxia” in this subset of preterm IUGR pregnancies complicated by AEDFV in the umbilical arteries, which has both scientific and clinical implications.