Human fetal microglia acquire homeostatic immune-sensing properties early in development.

Microglia, immune cells of the central nervous system (CNS), are important for tissue development and maintenance and are implicated in CNS disease, but we lack understanding of human fetal microglia development. Single-cell gene expression and bulk chromatin profiles of microglia at 9 to 18 gestational weeks (GWs) of human fetal development were generated. Microglia were heterogeneous at all studied GWs. Microglia start to mature during this developmental period and increasingly resemble adult microglia with CNS-surveilling properties. Chromatin accessibility increases during development with associated transcriptional networks reflective of adult microglia. Thus, during early fetal development, microglia progress toward a more mature, immune-sensing competent phenotype, and this might render the developing human CNS vulnerable to environmental perturbations during early pregnancy.

Reciprocal HLA-DR allogenicity between mother and child affects pregnancy outcome parameters.

Successful pregnancy outcome depends on local immunoregulatory mechanisms preventing a detrimental immune response towards the semi-allogeneic fetus. We investigated the influence of HLA-DR (in)compatibility on pregnancy outcome parameters in 480 women. The parameters tested were birth weight, individualized birthweight ratio (IBR), gestational age, and maternal highest diastolic blood pressure. Irrespective of pregnancy complications, maternal-fetal HLA-DR incompatibility resulted in increased IBR. We conclude that reciprocal HLA-DR allogenicity between mother and child positively affect pregnancy outcome parameters.

In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver.

The soluble fms-like tyrosine kinase factor 1 (sFlt-1) is a major contributor to antiangiogenesis during preeclampsia. However, little is known about the effects of sFlt-1 on fetal health. In this study we aim to evaluate the effects of the sFlt-1 concentration during pregnancy on fetal liver physiology. We used adenoviral gene delivery in Sprague-Dawley dams (seven females, 10 weeks old) during mid-gestation (gestational day 8) with adenovirus overexpressing sFlt-1, and age-matched controls (six females, 10 weeks old) with empty adenoviral virus in order to quantify the sFlt-1 concentrations in pregnant dams. Dams exposed to adenoviral sFlt-1 delivery were subdivided into a low (n=4) and high sFlt-1 (n=3) group based on host response to the virus. One-way analysis of variance showed that fetuses (five per dam) exposed to high sFlt-1 concentrations in utero show fetal growth restriction (1.84±0.043 g high sFlt-1 v. 2.32±0.036 g control; mean (M)±s.e.m.; P<0.001), without hypertension or proteinuria in the dams. In continuation, the microarray analysis of the fetal liver of the high sFlt-1 group showed significant enrichment of key genes for fatty acid metabolism and Ppara targets. In addition, using pyrosequencing, we found that the Ppara enrichment in the high sFlt-1 group is accompanied by decreased methylation of its promoter (1.89±0.097 mean % methylation in high sFlt-1 v. 2.26±0.095 mean % methylation in control, M±s.e.m., P<0.02). Our data show that high sFlt-1 concentrations during pregnancy have detrimental effects on the fatty acid metabolism genes and the Ppara targets in the fetal liver.

Delivery or expectant management for prevention of adverse maternal and neonatal outcomes in hypertensive disorders of pregnancy: an individual participant data meta-analysis.

OBJECTIVE: Hypertensive disorders affect 3-10% of pregnancies. Delayed delivery carries maternal risks, while early delivery increases fetal risk, so appropriate timing is important. The aim of this study was to compare immediate delivery with expectant management for prevention of adverse maternal and neonatal outcomes in women with hypertensive disease in pregnancy. METHODS: CENTRAL, PubMed, MEDLINE and ClinicalTrials.gov were searched for randomized controlled trials comparing immediate delivery to expectant management in women presenting with gestational hypertension or pre-eclampsia without severe features from 34 weeks of gestation. The primary neonatal outcome was respiratory distress syndrome (RDS) and the primary maternal outcome was a composite of HELLP syndrome and eclampsia. The PRISMA-IPD guideline was followed and a two-stage meta-analysis approach was used. Relative risks (RR) and numbers needed to treat or harm (NNT/NNH) with 95% CI were calculated to evaluate the effect of the intervention. RESULTS: Main outcomes were available for 1724 eligible women. Compared with expectant management, immediate delivery reduced the composite risk of HELLP syndrome and eclampsia in all women (0.8% vs 2.8%; RR, 0.33 (95% CI, 0.15-0.73); I2  = 0%; NNT, 51 (95% CI, 31.1-139.3)) as well as in the pre-eclampsia subgroup (1.1% vs 3.5%; RR, 0.39 (95% CI, 0.15-0.98); I2  = 0%). Immediate delivery increased RDS risk (3.4% vs 1.6%; RR, 1.94 (95% CI 1.05-3.6); I2  = 24%; NNH, 58 (95% CI, 31.1-363.1)), but depended upon gestational age. Immediate delivery in the 35th week of gestation increased RDS risk (5.1% vs 0.6%; RR, 5.5 (95% CI, 1.0-29.6); I2  = 0%), but immediate delivery in the 36th week did not (1.5% vs 0.4%; RR, 3.4 (95% CI, 0.4-30.3); I2 not applicable). CONCLUSION: In women with hypertension in pregnancy, immediate delivery reduces the risk of maternal complications, whilst the effect on the neonate depends on gestational age. Specifically, women with a-priori higher risk of progression to HELLP, such as those already presenting with pre-eclampsia instead of gestational hypertension, were shown to benefit from earlier delivery. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

The influence of maternal obesity on macrophage subsets in the human decidua.

Obesity is seen as a low grade inflammatory state, and is associated with adverse pregnancy outcomes. Disturbed macrophage characteristics might be essential in obesity associated pregnancy pathology via effects on the regulation of angiogenesis and placental development. This study aims to address the effects of maternal obesity on macrophage subsets in the decidua of women with term uncomplicated pregnancies. Macrophages were isolated from the decidua basalis and decidua parietalis of women with pre-gravid BMI < 25 (control) and BMI > 30 (obese). Macrophages were characterized and quantified using multi-color flow cytometry. Placentas of 10 obese and 10 control women after an uncomplicated term pregnancy were included. The decidua parietalis, but not decidua basalis, showed significantly lower levels of M1-type (HLA-DR+, CD163-) macrophages (p < 0.05) in obese women (4,3% of total macrophages) compared to control women (5,3% of total macrophages). The lower levels of M1 macrophages, considered to be pro-inflammatory, might indicate a mechanism to compensate for the pro-inflammatory environment in obese women to ensure healthy pregnancy outcomes.

Birth weight to placenta weight ratio and its relationship to ultrasonic measurements, maternal and neonatal morbidity: A prospective cohort study of nulliparous women.

INTRODUCTION: Birth weight to placenta weight (BWPW)-ratio is an indicator of the ability of the placenta to maintain adequate nutrient supply to the fetus. We sought to investigate the relationship between BWPW-ratio with fetal growth, utero-placental Doppler and neonatal and maternal morbidity. METHODS: We studied a group of 3311 women recruited to a prospective cohort study of nulliparous women (Rosie Hospital, Cambridge, UK) who delivered a live born infant at term and whose placental weight and birth weight were known. Ultrasonic indices and BWPW ratio were converted to gestational age adjusted z scores. Analysis of continuous variables was by multivariable linear regression. BWPW ratio was also categorized (lowest or highest quintile, both referent to quintiles 2 to 4) and associations with adverse outcomes analyzed using multivariable logistic regression. RESULTS: Lowest quintile of BWPW-ratio was associated (adjusted odds ratio [95% CI], P) with both neonatal morbidity (1.55 [1.12-2.14], 0.007) and maternal diabetes (1.75 [1.18-2.59], 0.005). Highest quintile of BWPW ratio was associated with a reduced risk of maternal obesity (0.71 [0.53 to 0.95], 0.02) and preeclampsia (0.51 [0.31 to 0.84], 0.008), but higher (adjusted z score [95% CI], P) uterine artery Doppler mean pulsatility index (PI) at 20 weeks of gestation (0.09 [0.01-0.18], 0.04) and umbilical artery Doppler PI at 36 weeks of gestation (0.16 [0.07-0.25], <0.001). CONCLUSION: BWPW-ratio is related to ultrasonic measurements and both neonatal and maternal morbidity. Therefore, this ratio may be an indicative marker of immediate and longer term health risks for an individual.

No direct effect of an elective caesarean section on the phenotypic and functional characteristics of maternal peripheral blood T lymphocytes.

PROBLEM: The short term effect of the caesarean delivery on the phenotypic and functional characteristics of the peripheral blood leukocytes of the mother is unknown. METHOD OF STUDY: We determined the composition and activation status of the maternal peripheral blood leukocytes isolated within 4h before and within 24h after elective caesarean delivery with neuraxial anaesthesia. Furthermore, we determined the proliferative and cytotoxic response of these leukocytes to several stimulators. RESULTS: No significant differences in the percentage of CD4+CD25bright and CD8+CD28- T cells or the expression of activation markers FoxP3, CD69 and HLA-DR were observed in peripheral blood drawn before caesarean delivery compared to after caesarean delivery. Also the alloreactive immune responses in samples taken before and after the caesarean delivery were similar. CONCLUSION: Our results show that the phenotype and immune response of maternal peripheral blood T cells obtained before elective caesarean delivery are not different from those obtained after caesarean delivery. This knowledge will facilitate sample collection for future studies on the immune response in term pregnancies.

Caesarean section rates and adverse neonatal outcomes after induction of labour versus expectant management in women with an unripe cervix: a secondary analysis of the HYPITAT and DIGITAT trials.

OBJECTIVE: To evaluate caesarean section and adverse neonatal outcome rates after induction of labour or expectant management in women with an unripe cervix at or near term. DESIGN: Secondary analysis of data from two randomised clinical trials. SETTING: Data were collected in two nationwide Dutch trials. POPULATION: Women with hypertensive disease (HYPITAT trial) or suspected fetal growth restriction (DIGITAT trial) and a Bishop score ≤6. METHODS: Comparison of outcomes after induction of labour and expectant management. MAIN OUTCOME MEASURES: Rates of caesarean section and adverse neonatal outcome, defined as 5-minute Apgar score ≤6 and/or arterial umbilical cord pH <7.05 and/or neonatal intensive care unit admission and/or seizures and/or perinatal death. RESULTS: Of 1172 included women with an unripe cervix, 572 had induction of labour and 600 had expectant management. We found no significant difference in the overall caesarean rate (difference -1.1%, 95% CI -5.4 to 3.2). Induction of labour did not increase caesarean rates in women with Bishop scores from 3 to 6 (difference -2.7%, 95% CI -7.6 to 2.2) or adverse neonatal outcome rates (difference -1.5%, 95% CI -4.3 to 1.3). However, there was a significant difference in the rates of arterial umbilical cord pH <7.05 favouring induction (difference -3.2%, 95% CI -5.6 to -0.9). The number needed to treat to prevent one case of umbilical arterial pH <7.05 was 32. CONCLUSIONS: We found no evidence that induction of labour increases the caesarean rate or compromises neonatal outcome as compared with expectant management. Concerns over increased risk of failed induction in women with a Bishop score from 3 to 6 seem unwarranted. TWEETABLE ABSTRACT: Induction of labour at low Bishop scores does not increase caesarean section rate or poor neonatal outcome.

Comparison of conventional versus three-dimensional ultrasound in fetal renal pelvis measurement and their potential prediction of neonatal uropathies.

OBJECTIVE: To establish a threshold value for fetal renal pelvis dilatation measured by automatic volume calculation (SonoAVC) in the third trimester of pregnancy to predict neonatal uropathies, and to compare these results with conventional antero-posterior (AP) measurement, fetal kidney 3D volume and renal parenchymal thickness. METHODS: In a prospective cohort study, 125 fetuses with renal pelvis AP diameter of ≥5 mm both at 20 weeks of gestation and in the third trimester, underwent an additional 3D volume measurement of the fetal kidney in the third trimester. Receiver operating characteristic (ROC) curves for establishing threshold values for fetal renal pelvis volume, AP measurement, fetal kidney volume and renal parenchymal thickness to predict neonatal uropathies were analyzed. Also, sensitivity, specificity, area under the curve (AUC) and likelihood ratios were calculated. RESULTS: A cut-off point of 1.58 cm³ was identified in the third trimester of pregnancy (AUC 0.865 (95% CI 0.789-0.940), sensitivity 76.3%, specificity 87.4%, LR+ 6.06, LR- 0.27) for measurements with SonoAVC. A cut-off value of 11.5 mm was established in the third trimester of pregnancy (AUC 0.828 (95% CI 0.737-0.918), sensitivity 71.1%, specificity 85.1%, LR+ 4.77, LR- 0.34) for the conventional AP measurement. A cut-off point for fetal kidney volume was calculated at 13.29 cm³ (AUC 0.769 (95% CI 0.657-0.881), sensitivity 71%, specificity 66%, LR+ 2.09, LR- 0.44). For renal parenchymal thickness, a cut-off point of 8.4 mm was established (AUC 0.216 (95% CI 0.117-0.315), sensitivity 31.6%, specificity 32.6%, LR+ 0.47, LR- 2.10). CONCLUSION: This study demonstrates that 3D fetal renal pelvis volume measurements and AP measurements both have a good and comparable diagnostic performance, fetal renal volume a fair accuracy and renal parenchymal thickness a poor accuracy in predicting postnatal renal outcome.

Higher decidual EBI3 and HLA-G mRNA expression in preeclampsia: Cause or consequence of preeclampsia.

The maternal immune system must adapt to tolerate the invasion of the allogeneic feto-placental unit. It is generally accepted that improper adaptation causes pregnancy complications like preeclampsia. The Epstein-Barr virus-induced gene 3 (EBI3) protein is a subunit of immune-modulatory cytokines interleukin 27 (IL-27) and IL-35. EBI3 has been reported to associate with HLA-G. In this small pilot study we find higher decidual EBI3 (p<0.05) and HLA-G (p<0.01) mRNA expression in preeclampsia (n=7) compared to normotensive (n=8) pregnancies. Whether the higher EBI3 and HLA-G mRNA expression is a consequence or cause of preeclampsia remains to be answered. Further research to determine the effects on IL-27 and IL-35 is needed.

The possible role of virus-specific CD8(+) memory T cells in decidual tissue.

The most abundant lymphocyte present in decidual tissue is the CD8(+) T cell. It has been shown that most decidual CD8(+) T cells have an effector-memory phenotype, but expressed reduced levels of perforin and granzyme B compared with the peripheral CD8(+) effector-memory T cells. The specificity of these CD8(+) memory T cells has yet to be determined. One hypothesis is that the decidual memory T cells are virus-specific T cells that should protect the fetus against incoming pathogens. As virus-specific CD8(+) memory T cells can cross-react with human leukocyte alloantigens, an alternative, but not mutually exclusive, hypothesis is that these CD8(+) T cells are fetus-specific. Using virus-specific tetramers, we found increased percentages of virus-specific CD8(+) T cells in decidual tissue compared with peripheral blood after uncomplicated pregnancy. So far, no evidence has been obtained for a cross-reactive response of these virus-specific T cells to fetal human leukocyte antigens. These results suggest that the virus-specific memory T cells accumulate in the placenta to protect the fetus from a harmful infection.

Maternal HLA-C2 and 14 bp insertion in HLA-G is associated with recurrent implantation failure after in vitro fertilization treatment.

The major rate-limiting step in in vitro fertilization (IVF) success appears to be the implantation of the semi-allogeneic embryo into the maternal endometrium. To determine possible risk factors of recurrent failure of embryos to implant, we investigated immunogenetic determinants as level of human leukocyte antigen (HLA) histocompatibility, frequency of killer-cell immunoglobulin-like receptors (KIR) and HLA-C alleles and HLA-G polymorphism. We DNA typed women with recurrent implantation failure (RIF) and their partners for classical HLA Class I, HLA Class II, HLA-G and KIR alleles and compared these results with couples with successful embryo implantation after their first IVF and normal fertile couples. No association was found between RIF and the degree of histocompatibility between partners or sharing of a specific antigen. Also, no significant difference in KIR haplotype or combination of HLA-C group and KIR was observed. We did find a higher frequency of HLA-C2 and a higher frequency of 14 base pair (bp) insertion in HLA-G in women with RIF. Therefore we conclude that the degree of histocompatibility between partners is not a determining factor for the occurrence of RIF. However, presence of the HLA-C2 allotype and the HLA-G allele with a 14 bp insertion is a significant risk factor.

Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring.

Normal placentation relies on an efficient maternal adaptation to pregnancy. Within the decidua, natural killer (NK) cells and dendritic cells (DC) have a critical role in modulating angiogenesis and decidualization associated with pregnancy. However, the contribution of these immune cells to the placentation process and subsequently fetal development remains largely elusive. Using two different mouse models, we here show that optimal placentation and fetal development is sensitive to disturbances in NK cell relative abundance at the fetal-maternal interface. Depletion of NK cells during early gestation compromises the placentation process by causing alteration in placental function and structure. Embryos derived from NK-depleted dams suffer from intrauterine growth restriction (IUGR), a phenomenon that continued to be evident in the offspring on post-natal day 4. Further, we demonstrate that IUGR was accompanied by an overall reduction of global DNA methylation levels and epigenetic changes in the methylation of specific hepatic gene promoters. Thus, temporary changes within the NK cell pool during early gestation influence placental development and function, subsequently affecting hepatic gene methylation and fetal metabolism.

Preservation of human placenta facilitates multicenter studies on the local immune response in normal and aberrant pregnancies.

Our standard procedure for phenotypic and functional analysis of immune cells present in the placenta is to isolate leukocytes from the decidua within five hours of the delivery. However, this results in logistical problems with deliveries at night, weekends or in other medical centers. Collecting placentas after complicated pregnancies is even more difficult owing to the low prevalence and the often unscheduled delivery. The aim was to investigate the possibility of preserving the human placenta before phenotypic and functional analysis of decidual lymphocytes. Placentas were obtained after uncomplicated pregnancy. The tissue was divided into two equal parts: decidual lymphocytes from one part were isolated within five hours according to our standard procedure, whereas the other part was preserved in either Celsior(®), a storage solution for solid organ preservation, or phosphate-buffered saline (PBS) for 24h at 4°C before isolation. Overall, the phenotype and functional capacity of decidual lymphocytes isolated within five hours was comparable to decidual lymphocytes isolated after 24-h preservation in Celsior(®) or PBS. Minor differences were found between decidual lymphocytes isolated within five hours and decidual lymphocytes isolated after 24-h preservation in Celsior(®). The results indicate that PBS is sufficient to preserve the placenta for 24h for phenotypical and functional studies. The ability to preserve the placenta will simplify the procedure for the isolation of decidual lymphocytes and makes it easier to analyze tissue from women who deliver during the night, at weekends or in other hospitals, and possibly even women with complicated pregnancies.

Chorionic plate expression patterns of the maspin tumor suppressor protein in preeclamptic and egg donor placentas.

Maspin is a serine protease inhibitor involved in regulating human placental trophoblast cell migration. Maspin has not been studied in preeclampsia (PE) or relative to the maternal-fetal immunological relationship, both of which may involve altered trophoblast migration. We examined maspin expression in placentas from in vitro fertilization (IVF) and egg donor (ED) pregnancies with and without PE. Exclusive to the chorionic plate, the number of maspin-positive extravillous trophoblasts was significantly decreased in IVF-PE vs. IVF (p = 0.005) and ED vs. IVF (p = 0.013). These data suggest maspin expression may be influenced by PE and/or the immunological dynamics of pregnancy.

Meeting report of the first conference of the International Placenta Stem Cell Society (IPLASS).

The International Placenta Stem Cell Society (IPLASS) was founded in June 2010. Its goal is to serve as a network for advancing research and clinical applications of stem/progenitor cells isolated from human term placental tissues, including the amnio-chorionic fetal membranes and Wharton's jelly. The commitment of the Society to champion placenta as a stem cell source was realized with the inaugural meeting of IPLASS held in Brescia, Italy, in October 2010. Officially designated as an EMBO-endorsed scientific activity, international experts in the field gathered for a 3-day meeting, which commenced with "Meet with the experts" sessions, IPLASS member and board meetings, and welcome remarks by Dr. Ornella Parolini, President of IPLASS. The evening's highlight was a keynote plenary lecture by Dr. Diana Bianchi. The subsequent scientific program consisted of morning and afternoon oral and poster presentations, followed by social events. Both provided many opportunities for intellectual exchange among the 120 multi-national participants. This allowed a methodical and deliberate evaluation of the status of placental cells in research in regenerative and reparative medicine. The meeting concluded with Dr. Parolini summarizing the meeting's highlights. This further prepared the fertile ground on which to build the promising potential of placental cell research. The second IPLASS meeting will take place in September 2012 in Vienna, Austria. This meeting report summarizes the thought-provoking lectures delivered at the first meeting of IPLASS.

Labour and neonatal outcome in small for gestational age babies delivered beyond 36+0 weeks: a retrospective cohort study.

OBJECTIVE: Small for gestational age (SGA) is associated with increased neonatal morbidity and mortality. At present, evidence on whether these pregnancies should be managed expectantly or by induction is lacking. To get insight in current policy we analysed data of the National Dutch Perinatal Registry (PRN). METHODS: We used data of all nulliparae between 2000 and 2005 with a singleton in cephalic presentation beyond 36+0 weeks, with a birth weight below the 10th percentile. We analysed two groups of pregnancies: (I) with isolated SGA and (II) with both SGA and hypertensive disorders. Onset of labour was related to route of delivery and neonatal outcome. RESULTS: Induction was associated with a higher risk of emergency caesarean section (CS), without improvement in neonatal outcome. For women with isolated SGA the relative risk of emergency CS after induction was 2.3 (95% Confidence Interval [CI] 2.1 to 2.5) and for women with both SGA and hypertensive disorders the relative risk was 2.7 (95% CI 2.3 to 3.1). CONCLUSION: Induction in pregnancies complicated by SGA at term is associated with a higher risk of instrumental deliveries without improvement of neonatal outcome. Prospective studies are needed to determine the best strategy in suspected IUGR at term.

Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT).

OBJECTIVE: To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term. DESIGN: Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)). SETTING: Eight academic and 44 non-academic hospitals in the Netherlands between November 2004 and November 2008. PARTICIPANTS: Pregnant women who had a singleton pregnancy beyond 36+0 weeks' gestation with suspected intrauterine growth restriction. INTERVENTIONS: Induction of labour or expectant monitoring. MAIN OUTCOME MEASURES: The primary outcome was a composite measure of adverse neonatal outcome, defined as death before hospital discharge, five minute Apgar score of less than 7, umbilical artery pH of less than 7.05, or admission to the intensive care unit. Operative delivery (vaginal instrumental delivery or caesarean section) was a secondary outcome. Analysis was by intention to treat, with confidence intervals calculated for the differences in percentages or means. RESULTS: 321 pregnant women were randomly allocated to induction and 329 to expectant monitoring. Induction group infants were delivered 10 days earlier (mean difference -9.9 days, 95% CI -11.3 to -8.6) and weighed 130 g less (mean difference -130 g, 95% CI -188 g to -71 g) than babies in the expectant monitoring group. A total of 17 (5.3%) infants in the induction group experienced the composite adverse neonatal outcome, compared with 20 (6.1%) in the expectant monitoring group (difference -0.8%, 95% CI -4.3% to 3.2%). Caesarean sections were performed on 45 (14.0%) mothers in the induction group and 45 (13.7%) in the expectant monitoring group (difference 0.3%, 95% CI -5.0% to 5.6%). CONCLUSIONS: In women with suspected intrauterine growth restriction at term, we found no important differences in adverse outcomes between induction of labour and expectant monitoring. Patients who are keen on non-intervention can safely choose expectant management with intensive maternal and fetal monitoring; however, it is rational to choose induction to prevent possible neonatal morbidity and stillbirth. TRIAL REGISTRATION: International Standard Randomised Controlled Trial number ISRCTN10363217.

Clinical and immunologic aspects of egg donation pregnancies: a systematic review.

BACKGROUND: Egg donation (ED) makes it possible for subfertile women to conceive. Pregnancies achieved using ED with unrelated donors are unique, since the entire fetal genome is allogeneic to the mother. The aims of this review were to evaluate the consequences of ED pregnancies and to place them in the special context of their atypical immunologic relationships. METHODS: This review comprised an online search of English language publications listed in Pubmed/Medline, up to 29 January 2010. Seventy-nine papers met inclusion criteria. Using the literature and the authors' own experience, the relevant data on pregnancy outcome and complications, placental pathology and immunology were evaluated. RESULTS: Multiple studies document that ED pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. The incidence of other perinatal complications, such as intrauterine growth restriction, prematurity and congenital malformations, is comparable to conventional IVF. During pregnancy, both local and systemic immunologic changes occur and in ED pregnancies these changes are more pronounced. There is almost no information in the literature on the long-term complications of ED pregnancies for the mother. CONCLUSIONS: ED pregnancies have a higher risk of maternal morbidity. Owing to the high degree of antigenic dissimilarity, ED pregnancies represent an interesting model to study complex immunologic interactions, as the fully allogeneic fetus is not rejected but tolerated by the pregnant woman. Knowledge of the immune system in ED pregnancies has broader significance, as it may also give insight into immunologic aspects of tolerance in solid organ transplantation.

Elsevier Trophoblast Research Award Lecture: Unique properties of decidual T cells and their role in immune regulation during human pregnancy.

Maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Most studies focus on decidual NK cells and their interaction with fetal trophoblasts, whereas limited data are available on the mechanisms of fetus specific immune recognition and immune regulation by decidual T cells at the fetal-maternal interface. The aim of this review is to describe the phenotypic characteristics of decidual T cell subsets present at the fetal-maternal interface, their interaction with HLA-C expressed by fetal trophoblasts and their role in immune recognition and regulation at the fetal-maternal interface during human pregnancy.