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.

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.

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.

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.

Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis.

OBJECTIVE: The development of osteoarthritis (OA) may be caused by activation of hypertrophic differentiation of articular chondrocytes. Healthy articular cartilage is highly resistant to hypertrophic differentiation, in contrast to other hyaline cartilage subtypes, such as growth plate cartilage. The purpose of this study was to elucidate the molecular mechanism responsible for the difference in the propensity of human articular cartilage and growth plate cartilage to undergo hypertrophic differentiation. METHODS: Whole-genome gene-expression microarray analysis of healthy human growth plate and articular cartilage derived from the same adolescent donors was performed. Candidate genes, which were enriched in the articular cartilage, were validated at the messenger RNA (mRNA) and protein levels and examined for their potential to inhibit hypertrophic differentiation in two models. In addition, we studied a possible genetic association with OA. RESULTS: Pathway analysis demonstrated decreased Wnt signaling in articular cartilage as compared to growth plate cartilage. This was at least partly due to increased expression of the bone morphogenetic protein and Wnt antagonists Gremlin 1, Frizzled-related protein (FRP), and Dkk-1 at the mRNA and protein levels in articular cartilage. Supplementation of these proteins diminished terminal hypertrophic differentiation without affecting chondrogenesis in long-bone explant cultures and chondrogenically differentiating human mesenchymal stem cells. Additionally, we found that single-nucleotide polymorphism rs12593365, which is located in a genomic control region of GREM1, was significantly associated with a 20% reduced risk of radiographic hip OA in 2 population-based cohorts. CONCLUSION: Taken together, our study identified Gremlin 1, FRP, and Dkk-1 as natural brakes on hypertrophic differentiation in articular cartilage. As hypertrophic differentiation of articular cartilage may contribute to the development of OA, our findings may open new avenues for therapeutic intervention.

Triggers and appropriateness of red blood cell transfusions in the postpartum patient--a retrospective audit.

BACKGROUND AND OBJECTIVE: Despite published guidelines, a proportion of red blood cell (RBC) transfusions seem unnecessary. To evaluate the indications for and the appropriateness of RBC transfusions in the postpartum patient, we performed a retrospective audit over a 1-year period in two Dutch hospitals. STUDY DESIGN AND METHODS: Observational study of transfused obstetric patients, admitted in 2006 to the Departments of Obstetrics of a university and a general hospital, was carried out. Relevant clinical and laboratory data were recorded. The appropriateness of RBC transfusions was assessed using the national and age-based transfusion guidelines for the general population; for the studied group the transfusion threshold haemoglobin (Hb) value was 6.4 g/dl for non-massive and 8.1 g/dl for massive blood loss. From these we derived target Hb levels. RESULTS: Ninety patients received one or more RBC units within 48 h of delivery. Mean pretransfusion Hb level was 6.9 [SD 1.2] g/dl. Median number of transfusions was 2. Mean Hb level at discharge was 9.7 [SD 1.1] g/dl. Taking threshold Hb and the derived target Hb level into account, 68% (n = 61) of the patients may have received one or more RBC units inappropriately. Of 311 RBC units transfused, 143 units (46%) were possibly inappropriate, partly due to over-transfusion. CONCLUSION: A significant proportion of postpartum RBC transfusions are possibly inappropriate, partly due to over-transfusion. If current guidelines would be more specific, in particular, with respect to the target Hb levels, the total amount of RBC transfusions may be considerably decreased.

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.

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.

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.

Comparison of macrophage phenotype between decidua basalis and decidua parietalis by flow cytometry.

The two regions of the maternal decidua, decidua basalis and decidua parietalis, differ in the extent of trophoblast invasion and consequently in cytokines and other biological mediators, extracellular matrix and cellular components. Our aim was to compare the phenotypic features of macrophages from the two decidual regions across a broad gestational age range. We isolated macrophages by enzymatic digestion from healthy decidua samples obtained after elective abortions, at 9-18-week and at 19-23-weeks, or after term deliveries (caesarean sections at term and spontaneous term vaginal deliveries). Macrophages were analysed by flow cytometry applying the same instrument settings to all the samples to allow semi-quantitative comparison of the expression of a particular marker between different samples. We found higher expressions of CD80, CD86 and HLA-DR, suggestive of a more activated phenotype of decidual macrophages, at early/mid pregnancy than at term. Marginal differences were found between term decidual macrophages obtained after spontaneous vaginal deliveries or caesarean sections which imply that the parturient process is not associated with decidual macrophage activation. The expressions of CD105, DC-SIGN and MMR were the strongest in decidua basalis of mid pregnancy and indicate the importance of decidual macrophages in tissue homeostasis at the uteroplacental interface.

[Delayed cord clamping in the interest of the newborn child]. / Late afnaveling in het belang van het pasgeboren kind.

The importance of delayed cord clamping, both for the preterm and for the term newborn, for the prevention ofneonatal anaemia (during the neonatal period and/or at the age of3 months) and furthermore to reduce the need of blood transfusions, has recently been demonstrated in controlled clinical studies and meta-analyses. Physiological and pathophysiological factors also provide a rationale for delayed cord clamping: neonatal blood volume may increase by 32% if cord clamping is delayed until the umbilical cord has completely stopped pulsating. A slow transition, involving closure of the ductus arteriosus and the foramen ovale cordis and gradual filling of the neonatal systemic circulation, contributes to the opening of the alveoli due to perfusion of the alveolar capillaries. No disadvantages, such as polycythaemia or hyperbilirubinaemia, have been described with regard to preterm neonates, whereas the incidence of intracranial haemorrhages is reduced. Also for the mother, no disadvantages of late clamping have been determined. As a standard procedure, the baby's umbilical cord should not be clamped until at least 3 minutes have passed. One should wait at least 30 seconds during the birth of children for whom a more active approach is necessary. Of all people, these children will benefit from a good Hb level.

[Need for blood transfusion in premature infants in 2 Dutch perinatology centres particularly determined by blood sampling for diagnosis]. / Bloedtransfusiebehoefte bij prematuren in 2 Nederlandse perinatologische centra sterk bepaald door bloedafname voor diagnostiek.

OBJECTIVE: Determination of factors related to the need for transfusion in premature infants. DESIGN: Descriptive. METHOD: The need for transfusion in premature infants was determined in 2 academic centres: University Medical Center Utrecht and Leiden University Medical Center, The Netherlands. The data had been acquired in another study. The factors under study were: hospital, pregnancy duration, birth weight, gender, time of clamping of the umbilical cord, total volume of blood sampled for diagnostic purposes, number of days of mechanical ventilation, total duration of admission and duration of the admission to the Neonatal Intensive care unit. Both hospitals followed the national interdisciplinary practice guideline 'Blood transfusion'. RESULTS: The total volume ofsampled blood for diagnosis, the duration of the mechanical ventilation and the admission period were related to a greater need for transfusion. On the other hand, the chance of transfusions diminished with longer pregnancy duration or increased birth weight. The difference in need for blood transfusion between both centres was significant. The total volume of transfused erythrocytes showed a strong correlation with the volume sampled for diagnostic procedures. CONCLUSION: Anaemia in neonates is strongly related to the amount of blood taken for diagnostic procedures. Alternatives for blood transfusions in premature infants, and consequently for the reduction of the number of donors per child, are to be sought in delayed clamping of the umbilical cord, use of erythropoietin and use ofautologous umbilical cord blood.

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.

Differential distribution of CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in decidua and maternal blood during human pregnancy.

During pregnancy several maternal and fetal mechanisms are established to prevent a destructive immune response against the allogeneic fetus. Despite these mechanisms, fetus specific T-cells persist throughout gestation but little is known about the regulation of these T-cells. Recently, CD4(+)CD25(+) regulatory T-cells have been identified in human decidua. Human decidua forms the maternal part of the fetal-maternal interface and is subdivided in two distinct regions: the decidua (d.) basalis and the decidua (d.) parietalis. The aim of this study was to determine the distribution of specific T-cell subsets in d. basalis and d. parietalis in early and term pregnancy, with a special emphasis on the presence of CD4(+)CD25(bright) (regulatory) T-cells and CD8(+)CD28(-) (suppressor) T-cells. In addition, we compared phenotypic characteristics of decidua derived T-cell subsets with maternal peripheral blood (mPBL) T-cells and T-cells from non-pregnant controls. We identified significantly higher percentages of CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in decidua compared to peripheral blood suggesting an important role for these T-cell subsets locally at the fetal-maternal interface. The major differences in T-cell subset distribution and the presence of additional phenotypic differences between T-cells in d. basalis, d. parietalis and mPBL may reflect specific immunomodulatory functions of these T-cell subsets at these different sites during pregnancy.

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.

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.

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.

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.

Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

OBJECTIVE: Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. METHODS: Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. RESULTS: Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). CONCLUSION: If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

[Breech presentation at term: the caesarean section that is routinely advised is ultimately not safe for the child]. / Aterme stuitligging: standaard geadviseerde keizersnede uiteindelijk niet veiliger voor het kind.

Recently, the results have become available on both the neonatal and the maternal outcome of deliveries after randomisation in the Term breech trial. At 2 years, in contrast to the original results in which perinatal death and serious neonatal morbidity were higher in the planned vaginal delivery group, no differences were evident in the combined outcdme variable, including death after delivery and neurodevelopmental delay. There were also no apparent differences between the two groups in neurodevelopmental abnormalities as screened by the ASQ postal enquiry. These are the most important findings that should be discussed with the parents during counselling regarding the mode of delivery of a foetus in breech presentation.