Maternal and foetal placental vascular malperfusion in pregnancies with anti-phospholipid antibodies.

OBJECTIVE: The objective of the study was to evaluate the rates of pathological placental lesions among pregnant subjects positive for aPL antibodies. METHODS: We performed a longitudinal case-control study including 27 subjects with primary APS, 51 with non-criteria APS, 24 with aPL antibodies associated with other well-known CTDs enrolled at the end of the first trimester of pregnancy and 107 healthy controls. RESULTS: Compared with controls and after correction for multiple comparisons, primary, non-criteria APS and aPL associated to CTD, subjects had lower placental weight, volume and area. After penalized logistic regression analysis to correct for potential confounders, placental lesions suggesting severe maternal vascular malperfusion (MVM) were more common among primary [odds ratio (OR) 11.7 (95% CI 1.3, 108)] and non-criteria APS [OR 8.5 (95% CI 1.6, 45.9)] compared with controls. The risk of foetal vascular malperfusion (FVM) was higher in primary APS [OR 4.5 (95% CI 1.2, 16.4)], aPL associated with CTDs [OR 3.1 (95% CI 1.5, 6.7)] and non-criteria APS [OR 5.9 (95% CI 1.7, 20.1)] compared with controls. Among clinical and laboratory criteria of APS, first trimester aCL IgG >40 UI/ml [OR 4.4 (95% CI 1.3, 14.4)], LA positivity [OR 6.5 (95% CI 1.3, 33.3)] and a history of pre-eclampsia at <34 weeks [OR 32.4 (95% CI 6.5, 161)] were the best independent first trimester predictors of severe MVM [area under the curve 0.74 (95% CI 0.6, 0.87)]. CONCLUSION: Compared with healthy controls, pregnant subjects with aPL antibodies have an increased risk of placental lesions, suggesting MVM and FVM. First-trimester variables such as aCL IgG >40 UI/ml and a history of pre-eclampsia were significant predictors of both severe MVM and FVM.

Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro-coagulant gene pathway activation.

PROBLEM: The Brown Norway (BN) rat is a model of T-helper 2 immune diseases, and also a model of pregnancy disorders that include placental insufficiency, fetal loss, and pre-eclampsia-like symptoms. The aim of this study was to investigate the plasma proteomic/cytokine profile of pregnant BN rats in comparison to that of the Lewis (LEW) rat strain. METHOD OF STUDY: Plasma proteomics differences were studied at day 13 of pregnancy in pooled plasma samples by differential in-gel electrophoresis, and protein identification was performed by mass spectrometry. Key protein findings and predicted cytokine differences were validated by ELISA using plasma from rats at various pregnancy stages. Proteomics data were used for ingenuity pathway analysis (IPA). RESULTS: In-gel analysis revealed 74 proteins with differential expression between BN and LEW pregnant dams. ELISA studies confirmed increased maternal plasma levels of complement 4, prothrombin, and C-reactive protein in BN compared to LEW pregnancies. LEW pregnancies showed higher maternal plasma levels of transthyretin and haptoglobin than BN pregnancies. Ingenuity pathway analysis revealed that BN pregnancies are characterized by activation of pro-coagulant, reactive oxygen species, and immune-mediated chronic inflammation pathways, and suggested increased interleukin 6 and decreased transforming growth factor-ß1 as potential upstream events. Plasma cytokine analysis revealed that pregnant BN dams have a switch from anti- to pro-inflammatory cytokines with the opposite switch observed in pregnant LEW dams. CONCLUSION: Brown Norway rats show a maternal pro-inflammatory response to pregnancy that likely contributes to the reproductive outcomes observed in this rat strain.

Antiphospholipid antibodies in women with severe preeclampsia and placental insufficiency: a case-control study.

Objective Preterm delivery for preeclampsia or placental insufficiency (PREPI) is a clinical criterion for antiphospholipid syndrome (APS), but no prior prospective studies have used the international classification criteria for APS. Our objective is to determine the proportion of women with PREPI who test positive for aPL using international criteria for antiphospholipid antibody (aPL) assays. Methods We conducted a prospective, case-control study of 148 women delivered < 36 weeks because of PREPI compared to 148 controls. PREPI cases delivered < 36 weeks were compared to matched controls. Cases and controls were tested for aPL. Demographic variables were compared with chi-squared and Wilcoxon-rank-sum statistics. Rates of + aPL were compared using adjusted odds ratios (aORs) for maternal body mass index (BMI) and Caucasian race. Positive aPL (+aPL) was defined as lupus anticoagulant (LA), anticardiolipin (aCL) immunoglobulin G (IgG) (GPL) or immunoglobulin M (IgM) (MPL) ≥ 40, or anti-ß2-glycoprotein I (aß2GPI) IgG (SGU) or IgM (SMU) ≥ 40. Results Controls were more likely to be Caucasian (87% vs 70%, p = 0.006) and had lower BMIs (BMI 26 vs 33, p < 0.001). Positive aPL were found more commonly in cases than controls (11.5% vs 1.4%, aOR 8.9 (95% CI 1.9-41.4)). In + aPL cases, 76% had + LA, 41% had + aCL, and 24% had + aß2GPI. Conclusion Women requiring early delivery for PREPI are more likely to have aPL (and thus APS) than controls. This is the first prospective study using both obstetric definitions and laboratory criteria in accordance with APS international criteria.

RNA Sequencing Exposes Adaptive and Immune Responses to Intrauterine Growth Restriction in Fetal Sheep Islets.

The risk of type 2 diabetes is increased in children and adults who exhibited fetal growth restriction. Placental insufficiency and intrauterine growth restriction (IUGR) are common obstetrical complications associated with fetal hypoglycemia and hypoxia that reduce the ß-cell mass and insulin secretion. In the present study, we have defined the underlying mechanisms of reduced growth and proliferation, impaired metabolism, and defective insulin secretion previously established as complications in islets from IUGR fetuses. In an IUGR sheep model that recapitulates human IUGR, high-throughput RNA sequencing showed the transcriptome of islets isolated from IUGR and control sheep fetuses and identified the transcripts that underlie ß-cell dysfunction. Functional analysis expanded mechanisms involved in reduced proliferation and dysregulated metabolism that include specific cell cycle regulators and growth factors and mitochondrial, antioxidant, and exocytotic genes. These data also identified immune responses, wnt signaling, adaptive stress responses, and the proteasome as mechanisms of ß-cell dysfunction. The reduction of immune-related gene expression did not reflect a change in macrophage density within IUGR islets. The present study reports the islet transcriptome in fetal sheep and established processes that limit insulin secretion and ß-cell growth in fetuses with IUGR, which could explain the susceptibility to premature islet failure in adulthood. Islet dysfunction formed by intrauterine growth restriction increases the risk for diabetes.

Metabolic and immunologic aspects of fetoplacental insufficiency.

PROBLEM: The chronic placental insufficiency is the most common cause of intrauterine hypoxia, retardation of fetal growth, and other threatening conditions. Immune disturbances may occur in the system "mother-placenta-fetus." METHOD OF STUDY: Biochemical blood indicators were studied on an automated biochemical analyzer. Pattern of lymphocyte subpopulations was detected by direct membrane immunofluorescence. RESULTS: Study revealed imbalance of immune parameters, caused by placental insufficiency (increase natural killers (CD16(+) , CD56(+) ), B lymphocytes (CD19(+) CD3(-) ), T and B lymphocytes with HLA-DR(+) antigen, and early activation of immune cells (by CD25(+) ), as well as disorders in apoptotic mechanisms (by CD95(+) )). CONCLUSION: Placental insufficiency leads to abnormalities of the immune system in pregnant, parturient women and maternity patients which were evaluated by localization of activation markers CD25(+) CD95(+) on the CD3(+) , CD4(+) , CD8(+) , CD16(+) , CD56(+) lymphocytes. This is reflected in the change of lymphocyte functions in newborns.

The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is characterized by thrombosis (arterial, venous, small vessel) and/or pregnancy morbidity occurring in patients with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS is the most severe form of the disease, characterized by multiple organ thromboses occurring in a short period and commonly associated with thrombotic microangiopathy (TMA). Similar to patients with complement regulatory gene mutations developing TMA, increased complement activation on endothelial cells plays a role in hypercoagulability in aPL-positive patients. In mouse models of APS, activation of the complement is required and interaction of complement (C) 5a with its receptor C5aR leads to aPL-induced inflammation, placental insufficiency, and thrombosis. Anti-C5 antibody and C5aR antagonist peptides prevent aPL-mediated pregnancy loss and thrombosis in these experimental models. Clinical studies of anti-C5 monoclonal antibody in aPL-positive patients are limited to a small number of case reports. Ongoing and future clinical studies of complement inhibitors will help determine the role of complement inhibition in the management of aPL-positive patients.

Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency.

Defective placentation and subsequent placental insufficiency lead to maternal and fetal adverse pregnancy outcome, but their pathologic mechanisms are unclear, and treatment remains elusive. The mildly hypertensive BPH/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal/fetal interface leads to elevation in local TNF-α levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-α improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation.

Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation.

Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor- or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies.

Antiphospholipid antibody syndrome.

Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss. Thus, obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiologic mechanisms of action of aPLs have been described. This article discusses the diagnostic and obstetric challenges of obstetric APS, proposed pathophysiologic mechanisms of APS during pregnancy, and the management of women during and after pregnancy.

Placental findings in late-onset SGA births without Doppler signs of placental insufficiency.

OBJECTIVES: To describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. METHODS: A series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation. RESULTS: A total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161). DISCUSSION: In most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease. CONCLUSIONS: A significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency.

Levels of cytokines in umbilical cord blood in small for gestational age preterm infants.

INTRODUCTION: Being born small for gestational age (SGA) can be a reference to intrauterine growth retardation (IUGR) and is associated with increased neonatal morbidity and mortality. In pregnancies complicated by IUGR placental insufficiency is thought to be one of the leading underlying pathogenetic mechanisms. As cytokines appear to be implicated in implantation and -placental development, imbalances in cytokine levels may contribute to pregnancy disorders i. e., IUGR. OBJECTIVE: Cord blood cytokine profiles were analyzed in order to characterize differences in cytokine profiles between SGA and appropriate for gestational age (AGA) preterm infants. METHODS: Cytokine concentrations were measured in venous cord blood of preterm infants delivered by caesarean section without previous labour activity and without signs of maternal or fetal infection. RESULTS: 93 preterm infants were enrolled, 29 SGA preterm infants (GA 31.0 (24.6-36.7) weeks; BW 1080 (315-2010) grams) and 63 AGA preterm infants (GA 33.3 (26.0-36.9) weeks; BW 1790 (760-3570) grams). In both groups multiple cytokines could be detected. Significant differences in cytokine levels between the groups were found for G-CSF, IL-12p40 and IL-8, while levels of IL-1a, IL-6, IL-10, IP-10, MCP-1, MCP-3, MIP-1a and TNF-a were not different. CONCLUSIONS: Alteration of cytokine levels in SGA preterm infants may be involved in the pathogenesis of reduced intrauterine growth as well as in the higher morbidity in these infants. Further studies are needed to get more comprehension of the complex function of cytokines in pregnancies complicated by IUGR.

An immunologic basis for placental insufficiency in fetal growth restriction.

OBJECTIVE: We sought to determine whether chronic villitis, an immunologic disease of the placenta, was related to fetal growth restriction. METHODS: Beginning in October 1999, a protocol was instituted that required placentas of high-risk births be submitted for standardized histological examination. Chronic villitis was diagnosed when a lymphohistiocytic infiltrate involving placental villi was present and was graded according to the extent and location of the infiltrate. Fetal growth restriction was defined as weight less than 3rd, 5th, and 10th percentiles. Placental hypoplasia was defined as weight less than 10th percentile. RESULTS: In the 10,204 placental examinations that were performed, low-grade and high-grade chronic villitis was associated with hypoplastic placentas and fetal growth restriction. Infants with placentas with low-grade and high-grade chronic villitis were more likely to require cesarean delivery for nonreassuring fetal heart rate compared with controls (27% and 25% versus 21%; p < 0.05). Fetal acidemia (umbilical artery pH < 7.0) was associated with high-grade chronic villitis compared with controls (4% versus 2%; p < 0.05). CONCLUSION: Chronic villitis was associated with anatomic and functional placental insufficiency manifested as placental hypoplasia, growth restriction, increased risk of cesarean for nonreassuring fetal heart rate, and fetal acidemia. These findings support an immunologic basis for fetal growth restriction.

Intrauterine growth restriction: cytokine profiles of trophoblast antigen-stimulated maternal lymphocytes.

Intrauterine growth restriction (IUGR) is an important perinatal syndrome that poses several serious short- and long-term effects. We studied cytokine production by maternal peripheral blood lymphocytes stimulated by trophoblast antigens. 36 women with a diagnosis of IUGR and 22 healthy women with normal fetal growth were inducted. Peripheral blood mononuclear cells were stimulated with trophoblast antigens and levels of the proinflammatory cytokines IL-6, IL-8, IL-12, IL-23, IFNγ, and TNFα and the anti-inflammatory cytokines IL-4, IL-10, and IL-13 were measured in culture supernatants by ELISA. IL-8 was produced at higher levels by blood cells of the IUGR group than normal pregnant women, while IL-13 was produced at lower levels. IL-8, IFNγ, and TNFα were higher in IUGR with placental insufficiency than in normal pregnancy. IL-12 levels were higher and IL-10 levels were lower in IUGR with placental insufficiency than in IUGR without placental insufficiency. We suggest that a stronger pro-inflammatory bias exists in IUGR as compared to normal pregnancy and in IUGR with placental insufficiency when compared to IUGR without placental insufficiency. Several ratios of proinflammatory to anti-inflammatory cytokines also support the existence of an inflammatory bias in IUGR.

Obstetric antiphospholipid syndrome: an update on pathophysiology and management.

Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids, a group of inner and outer cell membrane antigens found in mammals. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Although obstetric APS was originally reported in association with slow progressive thrombosis and infarction in the placenta, it is most often associated with a poor obstetric outcome. In fact, obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss (RPL). Thus obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiological mechanisms of action of aPLs have been described. The most common histopathological finding in early pregnancy loss has been defective endovascular decidual trophoblastic invasion. Treatment with heparin and aspirin is emerging as the therapy of choice, with ∼75% of treated women with RPL and aPLs having a successful delivery compared with <50% without treatment. This review highlights the diagnostic challenges of obstetric APS, the obstetric complications associated with APS, proposed pathophysiological mechanisms of APS during pregnancy, and the management of women during and after pregnancy.

Dysregulated complement activation as a common pathway of injury in preeclampsia and other pregnancy complications.

The complement system protects the host against invading organisms, initiates inflammation and dispose of immune complexes and the products of inflammatory injury. The complement system provides an important link between the innate and adaptive immune systems. Experimental observations suggest that increased complement activation causes and/or perpetuates inflammation during pregnancy. Recent studies suggest a link between complement activation and preeclampsia. Excessive activation or insufficient regulation of complement recruits leukocytes and unleashes potent inflammatory and anti-angiogenic mediators associated with placental insufficiency and maternal endothelial dysfunction characteristic of preeclampsia. We review the animal and human studies that link complement activation and pathogenic events in preeclampsia, present evidence that activation of the complement system is associated with the development of preeclampsia and provides new targets to prevent its complications.

Elevated antiphospholipid antibody titers and adverse pregnancy outcomes: analysis of a population-based hospital dataset.

BACKGROUND: The primary objective of this study was to determine if elevated antiphospholipid antibody titers were correlated with the presence of preeclampsia/eclampsia, systemic lupus erythematosus (SLE), placental insufficiency, and a prolonged length of stay (PLOS), in women who delivered throughout Florida, USA. METHODS: Cross-sectional analyses were conducted using a statewide hospital database. Prevalence odds ratios (OR) were calculated to quantify the association between elevated antiphospholipid antibody titers and four outcomes in 141,286 women who delivered in Florida in 2001. The possibility that the relationship between elevated antiphospholipid antibody titers and the outcomes of preeclampsia/eclampsia, placental insufficiency, and PLOS, may have been modified by the presence of SLE was evaluated in a multiple logistic regression model by creating a composite interaction term. RESULTS: Women with elevated antiphospholipid antibody titers (n = 88) were older, more likely to be of white race and not on Medicaid than women who did not have elevated antiphospholipid antibody titers. Women who had elevated antiphospholipid antibody titers had an increased adjusted odds ratio for preeclampsia and eclampsia, (OR = 2.93 p = 0.0015), SLE (OR = 61.24 p < 0.0001), placental insufficiency (OR = 4.58 p = 0.0003), and PLOS (OR = 3.93 p < 0.0001). Patients who had both an elevated antiphospholipid antibody titer and SLE were significantly more likely than the comparison group (women without an elevated titer who did not have SLE) to have the outcomes of preeclampsia, placental insufficiency and PLOS. CONCLUSION: This exploratory epidemiologic investigation found moderate to very strong associations between elevated antiphospholipid antibody titers and four important outcomes in a large sample of women.

Examination of distinct fetal and maternal molecular pathways suggests a mechanism for the development of preeclampsia.

In pregnancy, the maternal spiral arteries must widen to nourish the growing fetus. It is this critical step in placental development that is commonly defective in the pathology of preeclampsia. Other features often observed in the placental pathology of preeclampsia include fewer invasive trophoblasts, shallow trophoblast invasion and placental thrombosis and atherotic-like changes. In this review, we propose that there are two distinct pathways, maternal and fetal, which converge on narrow spiral arteries. The unmodified (along the fetal pathway) or blocked (along the maternal pathway) spiral artery, or a combination of the two, may in turn lead to placental insufficiency and induce the maternal cascade of events leading to preeclampsia. We suggest a paradigm for the molecular developmental events that cause preeclampsia through narrow spiral arteries and focus on early events that may cause failed remodeling or blockage of the arteries, which then lead to placental insufficiency and ultimately the hypoxic placenta associated with preeclampsia. We propose that examination of the molecular mechanisms of maternal and fetal pathways that lead to the development of preeclampsia may aid researchers to focus on new potential factors in this molecular basis and ultimately in treatment of this disease.

Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction.

Immune mechanisms have been implicated in placental dysfunction in patients with recurrent miscarriages and intrauterine growth restriction (IUGR), but the mediators are undefined. Here we show that complement activation, particularly C5a, is a required intermediary event in the pathogenesis of placental and fetal injury in an antibody-independent mouse model of spontaneous miscarriage and IUGR, and that complement activation causes dysregulation of the angiogenic factors required for normal placental development. Pregnancies complicated by miscarriage or growth restriction were characterized by inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor 1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation in vivo blocked the increase in sVEGFR-1 and rescued pregnancies. In vitro stimulation of monocytes with products of the complement cascade directly triggered release of sVEGFR-1, which sequesters VEGF. These studies provide the first evidence linking the complement system to angiogenic factor imbalance associated with placental dysfunction, and identify a new effector of immune-triggered pregnancy complications.

Placental pathologic conditions in anticardiolipin antibody positive women whose infants had congenital heart defects.

Anticardiolipin antibodies (ACLA) are present in 10% of women with recurrent pregnancy loss. Other associations with ACLA are arterial and venous thrombosis, cerebral infarction, pulmonary hypertension, preterm delivery, and fetal growth retardation. A previous prospective study of infants of mothers with positive ACLA identified an increased incidence of congenital heart disease in this population. As a follow-up, the placentas of the initial 40 ACLA-positive patients were studied to determine whether there was an increased incidence of infarct or thrombosis compared with that in control subjects matched for maternal age and gestational age within the same 2-year period. The age of ACLA-positive mothers was 30 +/- 5 years versus 29 +/- 5 years in the ACLA-negative mothers. Gestational age was 37 +/- 2 weeks in both groups; placental weight was 553 +/- 169 gm in the ACLA-positive group versus 593 +/- 117 gm in the ACLA-negative group. The birth weight was 2972 +/- 709 gm in infants of ACLA-positive mothers and 2920 +/- 674 gm in infants of ACLA-negative mothers. There was no statistically significant difference between the two groups in gestational age, maternal disease, placental histologic findings, placental weight, type of delivery, or type of ACLA. Twenty-seven ACLA-positive women were receiving prednisone. Chi square analysis showed the ACLA-positive mothers to have more spontaneous abortions (p = 0.02) and to have more children with congenital heart disease (5 ventricular septal defects and 2 atrial septal defects) (p = 0.006). In summary, infants born with congenital heart defects in women positive for ACLA did not have significant placental pathologic conditions when compared with control infants.

[Immunologic aspects of the fetal growth retardation syndrome]. / Ob immunologicheskikh aspektakh sindroma zaderzhki razvitiia ploda.

Serial measurements of allo- and autoimmune lymphocytotoxic antibodies (LCT-AB), circulating immune complexes (CIC) and heterophilic hemolysins were carried out over pregnancy weeks 24-40 in 63 pregnant women with small-for-date fetuses, 63 ones with other pregnancy complications, and in 15 ones with normal pregnancy. The mean allo- and auto-LCT-AB levels remained unchanged over the course of pregnancy and were virtually the same in all the examinees. CIC and heterophilic hemolysin levels were found growing in women with small-for-date fetuses starting from pregnancy week 28, as against the two reference groups. A direct relationship between abnormally high heterophilic hemolysin levels and blood rheology disorders could be traced. The incidence of unfavorable perinatal outcomes was increasing if heterophilic hemolysin levels surpassed 1.1 U optic density and the placenta was thin. These results permit considering the small-for-date fetus syndrome as a manifestation of immunity conflict in pregnancy.