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Despite all the research published in the last three decades on screening and prevention of preeclampsia (PE), this condition remains one of the main causes of maternal and perinatal morbidity and mortality, both in low and high-income countries. It affects 2-8% of all pregnancies, being responsible for one out of five maternal deaths and 15% of all premature deliveries1. An ideal screening test requires identification of women at high-risk of developing severe and early-onset forms of the disease, a high detection rate (DR) with an acceptable false-positive rate (FPR), and the availability of an effective preventive measure2.

Hematopoiesis has previously been observed in the human yolk sac, in placental villi and in the embryonic aorta. Here, our immunocytological study at 24 and 35 days showed packed erythroblasts in the placental vessels, mitotic figures and anti-Ki-67 reactions within these cells. Morphologically, the erythroblasts and vessels were similar to those found in the yolk sac during primitive hematopoiesis. In addition, numerous extravascular erythroblasts were found in the villous core. Positive reactions were obtained in erythroblasts using antibodies against glycophorin-A, GATA-2 and C-kit that characterize the hematopoietic cells. However, erythroblasts did not react with anti-CD34 and anti-CD45. In this respect, they differ from the hematopoietic cell clusters observed in the aorta of the human embryo. The staining for glycophorin-A was maintained in erythroblasts at 6-7 weeks and 12-14 weeks. Anti-GATA-2 reaction was decreased in erythroblasts and appeared in the perivillous cytotrophoblast. Anti-C-kit signal was detected in endothelial cells at 6-7 weeks and switched to stromal and perivascular cells at 12-14 weeks. By term, anti-GATA-2 staining was still present in the trophoblast and appeared in vessels while anti-C-kit was negative. For the leukocytes marker CD15, a staining was found in the endothelium at 35 days, 6-7 and 12-14 weeks and in leukocytes at term. CD45 antibody decorated the leukocytes at 12-14 weeks and at term. Erythroblasts undergo a primitive hematopoiesis in the early placental vessels that may be of value for the embryo in a period of low oxygen environment.

In the first weeks of pregnancy, columns of endovascular cytotrophoblastic plugs develop in the lumen of spiral arteries. Morphologic data show that these plugs become loosened as soon as the end of the second month and the intervillous circulation of maternal blood is likely to be established progressively between the 8th and 12th weeks. The disorganization of the musculo-elastic layers of these vessels provokes a dramatic decrease in vascular tone in the uteroplacental circulation. These modifications appear to govern the establishment of a low-pressure blood flow in the placenta, and hence determine the quality of uteroplacental circulation and normal fetal growth. Placental bed biopsies in women with pre-eclampsia and in a proportion of pregnancies with intrauterine growth retardation have shown that these physiologic changes were absent in the myometrial segments of spiral arteries. Recently, colour Doppler was used to assess intervillous and spiral artery flow in early pregnancy, confirming in vivo free intervillous flow at 12 weeks and a progressive significant decrease in spiral artery resistance with advancing gestation during the first trimester. However, certain data at an earlier gestational age are still contradictory. Particularly, the exact nature of the contents of the intervillous space before 8 weeks, and whether or not this fluid can be considered maternal blood, remains controversial.

The implantation of the human embryo is a double paradox, immunological and biological. The immunological paradox is that it consists of a heterologous graft in which the uterine immune system (via the cytokines) and the embryo's antigenicity (HLAG) collaborate to make possible both implantation and the maintenance of the pregnancy. The biological paradox arises because several different mechanisms must be successively implemented for these two epithelia to fuse and then for one to allow invasion by the other (that is, the for the endometrium to be decidualized by the trophoblast): preparation of the endometrium throughout the menstrual cycle under the influence of estrogens and then progesterone, with the involvement of growth factors (EGF, TGF and IGF), neoangiogenesis (estradiol, FGF and VEGF), recognition by the trophoblastic cells of the various components of the decidua and of the extracellular matrix (integrins and cadherin) and the progressive invasion of the decidua, to the depth of the spiral arteries (by the trophoblastic secretion of metalloproteases). A defective or excessive trophoblastic invasion can result in complications of pregnancy: early spontaneous miscarriage, preeclampsia and growth retardation of vascular origin in the case of defects, placenta accreta or percreta in the case of excess.

To analyze the evolution of the management of delivery and neonatal care in a population of children with correctable malformations born in Parisian maternity hospitals during the period 1985-1994.Data were collected by the Paris Registry of Congenital Anomalies from 400,000 births recorded in Parisian maternity hospitals over a 10-year period. Chromosomal anomalies were excluded. The evolution between the first period (1985-1989) and the second (1990-1994) was analyzed for the following indicators in the management of liveborn children: place of delivery; frequency of prenatal diagnosis; transfer to intensive care units, and mortality.More than 60% of the births of malformed children took place in public maternity hospitals where better management is offered. Most of them were prenatally diagnosed, except for esophageal and anorectal atresia for which the rate of prenatal diagnosis was low. For malformations with poor prognoses (diaphragmatic and abdominal wall anomalies), the rate of deliveries in public maternity hospitals reached about 90%, mostly in those with intensive care units. The evolution between the two periods was characterized by a quicker transfer to intensive care units, during the first day of life for most cases. Lethality during the first day, which was already low during the first period, decreased further. The early neonatal mortality rate decreased for cardiac anomalies, but not significantly. The prognosis remained poor for diaphragmatic anomalies: 49% of liveborn children died during the first week of life.

The efficacy of low-dose aspirin in preventing fetal growth retardation was tested in a randomised, placebo-controlled, double-blind trial. A secondary aim was to find out whether dipyridamole improves the efficacy of aspirin. 323 women at 15-18 weeks' amenorrhoea were selected at twenty-five participating centres on the basis of fetal growth retardation and/or fetal death or abruptio placentae in at least one previous pregnancy. They were randomly allocated to groups receiving placebo, 150 mg/day aspirin, or 150 mg/day aspirin plus 225 mg/day dipyridamole, for the remainder of the pregnancy. In the first phase of the trial all actively treated patients (n = 156) were compared with the placebo group (n = 73). Mean birthweight was significantly higher in the treated than in the placebo group (2751 [SD 670] vs 2526 [848] g; difference 225 g [95% CI 129-321 g], p = 0.029) and the frequency of fetal growth retardation in the placebo group was twice that in the treated group (19 [26%] vs 20 [13%]; p less than 0.02). The frequencies of stillbirth (4 [5%] vs 2 [1%]) and abruptio placentae (6 [8%] vs 7 [5%]) were also higher in the placebo than in the treated group. The benefits of aspirin treatment were greater in patients with two or more previous poor outcomes than in those with only one. In the second analysis, of aspirin only (n = 127) vs aspirin plus dipyridamole (n = 119), no significant differences were found. There was no excess of maternal or neonatal side-effects in the aspirin-treated patients.

Context: Long-term studies of tolerance to perinatal exposure to antiretroviral nucleoside reverse transcriptase inhibitors are required, in view of the potential genotoxicity of some of these molecules. Objective: To evaluate the incidence of cancers in uninfected children born to HIV-infected mothers. Method: Cancers were detected in a nationwide prospective cohort of children born to HIV-infected mothers by standardized questionnaire during the prospective follow-up period of 2 years; thereafter, they were detected by spontaneous pharmacovigilance declaration and by crosschecking data with the national registries of childhood cancer. Standardized incidence ratio for incidence comparisons with general population. Results: Ten cases of cancer were detected among the 9127 exposed HIV-uninfected children (median age: 5.4 years, 53 052 person-years of follow-up). The overall incidence did not differ significantly from that expected for the general population: 10 cases observed versus 8.9 and 9.6 expected depending on whether 1990–1999 or 2000–2004 national rates were used as reference [standardized incidence ratio of 1.1 (0.3–1.5) and 1.0 (0.5–1.9)]. Five cases of central nervous system cancer were observed (standardized incidence ratio of 3.1 [1.0–7.2] P = 0.05 and 2.4 [0.8–5.6], P = 0.12). The relative risk of cancer for children exposed to didanosine–lamivudine combination was higher than that for zidovudine monotherapy [hazard ratio: 13.6 (2.5–73.9)]. Conclusion: This study did not evidence an overall increase in cancer risk in nucleoside reverse transcriptase inhibitor exposed children until 5 years of age. Results suggesting associations with specific nucleoside reverse transcriptase inhibitor combinations need further investigations. A longer surveillance, including differential analysis of the different cancer sites and various nucleoside reverse transcriptase inhibitors administered is warranted.

The women treated for CIN2-3 remain at a substantially increased risk of recurrences, which persists longer than 10 years. The women treated for a CIN2-3 are more likely to develop invasive cancer and the risk is two to five times greater than that of the general population. The main objective of the follow-up of patients treated for high-grade CIN is in one hand, to detect and treat the recurrences and on the other hand, to determine a subpopulation presenting a high risk of recurrence which should be followed-up more intensively. At present, frequent follow-up with cytology and colposcopic evaluation of the cervix is the preferred strategy recommended in France by Anaes. Both, the cytology and the colposcopy don't have a very good sensitivity. HPV test is more sensitive compared to cytology or colposcopy in detecting CIN treatment failures. It would be more prudent to use a strategy involving both the cytology and HPV test. Both the sensitivity and the negative predictive value of combined cytology and HPV testing in detecting a residual disease or recurrence are around 100%. Women presenting negative results of both tests, could, then be considered at a low risk of recurrence and their surveillance should be the same as that of the screening of the general population. In case of positivity a more intensive follow-up should be organized.

Spontaneous uterine rupture is a life threatening event, and the diagnosis is difficult in an unscarred uterus. Many factors can help prevent the catastrophic consequences.A 38-year-old multipara in labor was admitted at 39.5 weeks of gestation. Ultrasound suggested a macrosomic fetus but the cervix was well dilated. Labor was immediately monitored. Two hours later, the fetus developed progressive heart rate decelerations. While evaluating the unexplained anomaly, epigastric pain and vaginal bleeding prompted emergency cesarean delivery. The uterine tear was repaired with good evolution but the infant died a few days later.The association of multiparity, uterine distension and active labor could be considered as risk factors of uterine rupture in cases of unexplained anomalies in an unscarred uterus, making a catastrophic event preventable.

After a pregnancy, there is a transitory increase in the risk of breast cancer. During the pregnancy, the number of mammary epithelial cells increases massively. This increase seems partly due to the expansion of stem cells and proliferating intermediate cells. This proliferation of epithelial cells is accompanied by angiogenesis and by recruitment of stromal cells, as well as changes of the extracellular matrix. During any pregnancy, there is cell trafficking between mother and foetus. Hematopoietic or mesenchymal foetal stem cells are transferred in maternal circulation and could be used by the tumor as support cells and take part in the tumoral development. The study of the mechanisms of this specific oncogenesis may help to develop chemoprevention strategies.

Trophoblast invasion in uterine pregnancy is fine-tuned for the remodelling of the uterine wall and its vascularization. Tubal pregnancy, which occurs in a limited number of patients, involves a dramatic trophoblast invasion in a context of a poor decidualization. By studying the histology of the extravillous trophoblast (EVC) in the anchoring villi, the Ki67 labelling, the location of several adhesion markers (cytokeratin-7, alpha1, alpha6, alphaV, beta1, beta4 integrin subunits and E-cadherin, V/E-cadherin), metalloproteinases (MMP-2, 9 and11), NOS2 and 3, we aimed to detect the specificity of tubal compared to intrauterine pregnancies. No difference could be observed between meso or anti-salpingial trophoblast proliferation or invasion using Ki67. Cytokeratin-7 allowed detection of spindle-shape EVCs and we identified some decidualized stromal cells. Integrins alpha1, beta1 and alphaV, and V/E-cadherin were expressed mainly in the distal EVC correspondingly to intrauterine pregnancy, with a poor expression of alpha1. Integrins alpha6 and beta4, E-cadherin were detected in the distal EVC in contrast to uterine pregnancy. MMP-2, 9, 11 were also shown in distal EVC. NOS2 and 3 labelled the perivascular EVC and NOS3 the endothelial cells of the tubal vessels. These changed distributions of adhesion molecules and MMP together with that of the basic and inducible NOS expressions could be related to mechanical effects in superficial implantation or to a failure of decidualization in tubal pregnancies.

Placental tight and gap junctions and their adhesion molecules were studied by immunochemistry and electron microscopy in early and term placentas in order to clarify their pattern of expression during placental development. Early syncytio-cytotrophoblast contained tight junctions with occludin and gap junctions with connexins 40 and 43. At term, endothelial cells from arterioles had tight and gap junctions following each other. Occludin, claudins 3 and 5 were found at the paracellular clefts of endothelial cells together with connexins 32, 40 and 50. Stromal cells had mixed tight and gap junctions with connexins 32, 43, 50. Capillaries demonstrated interendothelial tight junctions with claudins 3 and 5, and small gap junctions. Taken together these observations showed that the numerous tight and gap junctions of the early placental syncytio-cytotrophoblast are observed in the foetal arterioles and capillaries in the term placenta. We conclude that the tightness of the placenta due to the junctions lying in the syncytio-cytotrophoblast in early pregnancy is maintained by the foetal endothelial layer in term pregnancy, with significant developmental changes of their transmembrane proteins.

With the progress of foetal ultrasonography, diagnosis of foetal tumors can be made before birth. We report five cases of prenatally detected neuroblastoma of the adrenal glands. Diagnosis was made during the third trimester in all cases. At birth no clinical sign related to the tumor was present, and urinary catecholamines were within normal ranges. On ultrasound scans the tumor was cystic in 1 case, solid in 2 cases and of mixed echogenicity in 2 cases. All children were operated on without pre or postoperative chemotherapy. In each setting the tumor was a stage I neuroblastoma according to the Evans classification. All children are alive and disease-free with a follow-up of 32 months at 14 years.

To evaluate the accuracy of MR imaging combined with sonography for the diagnosis of persistent adnexal masses during pregnancy.From January 1999 to November 2003, nine patients with a persistent adnexal masse were included in this retrospective study. All patients underwent both transvaginal and transabdominal sonography combined with MR imaging. Accuracy of imaging techniques was evaluated by comparison with histology.Adnexal masse was detected by systematic sonography in six women whereas three patients were symptomatic. Mean gestational age at the diagnosis was 17 weeks of amenorrhea (range 5-36). Mean tumor size was 96 mm (range 2-15). Two patients underwent a surgery during pregnancy; one for acute abdominal pain related to an adnexal torsion and the second for suspicion of malignancy. One patient underwent a caesarean delivery for obstetrical reasons. In all patients, benign ovarian tumours were found. For eight patients the diagnosis suspected by imaging techniques was confirmed by histology.The combination of sonography and MR imaging allows diagnosing accurately adnexal masses during pregnancy.

The purpose of this work was to report labor and birth management practices for term breech presentation in France and Belgium in 2001-2002 and to describe indications for cesarean sections (before labor, emergency situations) in breech presentations.The PREMODA cohort is a survey population which included 19408 deliveries, 8108 of which were term breech presentations.Infants were delivered by cesarean section before labor (59.1%), emergency cesarean section during labor (18.4%) or vaginally (22.5%). The decision for cesarean section before labor was empirical (breech presentation) in 44.3% of the cases. Half of the cesarean sections performed during labor (n=704, 49.3%) were planned C-sections. Overall, 67.8% of the breech presentations were delivered during planned cesarean sections (before or during labor). When vaginal delivery was attempted, the rate of vaginal birth was 70%.These early results reveal a high rate of cesarean section as well as differences in inter-regional practices. Considering all cesarean sections performed before labor, the most frequent indication was an empirical decision because of the breech presentation. An increased rate of planned cesarean section does not reduce the rate of vaginal delivery when attempted.

It is common practice to prescribe supplementation for pregnant women, but is it useful? We detail here the main deficiencies and their risks. We conclude that low-dose iron and folic acid, vitamin D and iodine supplementation is indicated for women living in France. Other systematic supplementations are not necessary outside pathological situations.

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane and proliferate to form aggregates called trophoblast cell columns (TCCs). They subsequently invade the decidua and differentiate into interstitial and endovascular trophoblasts. The influence of the decidua on EVT differentiation is controversial. We therefore compared the pattern of trophoblast differentiation marker expression in viable intrauterine and tubal pregnancies, as decidual cell markers (prolactin [PRL] and insulin-like growth factor binding Protein-1 [IGFBP1]) were only expressed in endometrial implantation sites. Extravillous trophoblast differentiation in anchoring villi from uterine and ectopic pregnancies exhibited a comparable phenotypical switch: alpha6 integrin subunit, E-cadherin, EGF receptor, Ki 67 and connexin 40 were localized in the proximal part of the TCC, while alpha5beta1 and alpha1 integrins, c-erb B2, hPL and HLA-G were expressed by invasive cytotrophoblasts. The cyclin-dependent kinase inhibitors p16 and p57 were mainly detected in invasive cytotrophoblasts some distance from the columns. However, the TCC was markedly longer in tubal pregnancy than in intrauterine pregnancy. These findings suggest that the decidua is not necessary to trigger EVT invasion, but that it is likely to limit the extent of the TCC and to accelerate the onset of EVT migration.

Cell differentiation markers on placental villi from the first trimester of human pregnancy have been studied by indirect immunofluorescence. Fluorescence labelling with antibodies against CD34 and CD31 was conspicuous in the vascular cells. The vascular paracellular clefts were labelled by anti-cadherin-5. A few vascular cells exhibited a positive reaction for von Willebrand factor, high-molecular-weight melanoma-associated-antibody and alpha-sm-actin compared to term pregnancy, indicating changes in protein expression during vascular differentiation. The poor anti-collagen IV reaction and the absence of a sm-myosin fluorescent signal observed around the vessels confirned the immaturity of the vessels. In contrast, strong reactions have previously been obtained with the latter antibodies in similar locations using term placental villi. A labelling was observed for antibodies against alpha3 and alpha5 integrins in these immature placental vessels suggesting cell-matrix interactions with specific domains of laminin or fibronectin. The vascular cells were also stained by anti-CD26. Surprisingly, the fetal vascular cells exhibited immunostainings in common with the villous cytotrophoblast (CD26) or the syncytiotrophoblast (cadherin-5) and cell islands cytotrophoblast (CD31, cadherin-5, alpha3 and alpha5 integrin subunits). These observations suggested a two step process for fetal vasculogenesis in the villi: i/ the formation of peripheral vessels induced by growth factors or cytokines derived from the nearby trophoblast, ii/ the development of muscular vessels due to growth factors or cytokines production induced by circulatory changes.

Uterus septus is the most frequent congenital uterine anomalies caused by insufficient resorption of the müllerian ducts. Retrospective statistical analysis shows that the uterine septa have the worst reproductive outcome with a high incidence of early abortions. It is well recognized that it increased the incidence of recurrent (or = 3) miscarriages (79% among 1,601 pregnancies), reproductive failure and obstetric complications. A septate uterus does not seem to be an infertility factor. On the other hand, the incidence of unexplained infertility was significantly higher (40%) in the patients with secondary infertility; thus, a contribution from the uterine septum in delayed conception of these patients cannot be excluded. Hysteroscopic surgery has replaced conventional abdominal route. Hysteroscopic metroplasty improves obstetrical prognosis in women with septate uterus, and it's advantages are easiness, low morbidity rate, without the hysterotomy's consequences like adnexial adhesions. Metroplasty is indicated in women with a history of miscarriages (2 or more), which decreased to 15%, in patients with an unexplained infertility, and in women in whom assisted reproductive treatment is being contemplated. Combined with laparoscopy, the hysteroscopic metroplasty is the gold standard for assessing uterine septa, especially in these infertile women. Laparoscopy also is required to complete the diagnostic work up of infertility, and provides an opportunity to treat any coexisting pelvic pathology.

Fetal cells exist in maternal blood and can be utilized for prenatal diagnosis. These cells are present from the sixth week of gestation, with frequency increasing as gestation advances, to many years after the birth. Enrichment of trophoblast cells, erythroblasts and lymphocytes was performed with various density gradient techniques and either magnetic activated or fluorescent activated sorting techniques. The abnormalities were detected by fluorescent in-situ hybridation (FISH) with chromosome-specific DNA probes for the detection of trisomy 21, trisomy 18, Klinefelter syndrome 47 XXY, or by polymerase chain reaction (PCR) for the detection of fetal sex, certain Mendelian disorders (as beta-globin mutations), HLA polymorphisms and fetal Rhesus D blood type. However others studies were necessary to determine the sensitivity and specificity of this technique as a noninvasive alternative to conventional methods of prenatal cytogenetic diagnosis.

The etiology and pathogenesis of intrauterine fetal death, preeclampsia or fetal growth retardation remain still unknown in many cases. However, placental thrombosis and/or infarction might lead to inadequate maternal-fetal circulation. So, the relevance of an additional thrombotic risk factor that enhances the physiological hypercoagulable state of gestation has been suggested in the development of these adverse outcomes of pregnancy. Several genetic mutations are newly recognized associated with an increased frequency of venous thrombosis: mutation of adenine to guanine at nucleotide 506 in the factor V gene, mutation of cytosine at nucleotide 677 in the methylenetetrahydrofolate gene and mutation of guanine to adenine at nucleotide 20210 in the prothrombin gene. In this issue, a review of literature has allowed us to evaluate the prevalence of these genetic predisposing thrombotic factors with the development of obstetrical complications. Furthermore, therapeutic approach is considered.

An increasing number of sickle cell disease patients are deciding to bear children. The high risk of fetal and maternal complications in pregnant sickle cell disease patients mandates multidisciplinary management. Risks include spontaneous abortion, vasculorenal syndrome, fetal growth retardation, and fetal death in utero. The rates of cesarean section, maternofetal infection, and maternal death are higher than in the population at large. The diagnosis should be made prior to conception or during early pregnancy. Frequent visits with the obstetrician, hematologist, and anesthesiologist/intensivist are mandatory. Exchange transfusion or blood transfusion may be indicated in patients with a history of serious obstetrical or hematologic complications. Risks are highest in late pregnancy, during delivery, and in the postpartal period. However, the entire pregnancy is a high-risk period that warrants close monitoring.

The presence of the R506Q mutation of the factor V gene is associated with an increased risk of thromboembolism, particularly during pregnancy. Recently, its involvement in the development of obstetrical complications, such as preeclampsia and fetal losses, has been evoked. The resulting factor VQ506 (factor V Leiden) has arginine 506 replaced by glutamine at the factor Va cleavage site for activated protein C (APC) which induces APC-resistance. During pregnancy, an acquired resistance to APC is observed without the presence of the factor V Leiden mutation which leads to an inappropriate realization of the more expensive DNA analysis. This resistance is at least partly explained by an increase of the factor VIII. In this study, we have compared three reagents: the original test Coatest APC Resistance (Chromogenix) and two modified tests using factor V depleted plasma: Coatest APC Resistance V (Chromogenix) and Accélérimat (BioMérieux). The last test is not influenced by the factor VIII by the adjunction of activated factor X. For each test, the coefficient of discrimination, between carrier and non-carrier of the R506Q mutation of the factor V gene, has been determined on 43 pregnant women (33 non-carriers and 11 heterozygotes) and 51 unselected non pregnant patients with clinically suspected thrombosis (40 non-carriers and 11 heterozygotes). The predilution of the patient's plasma with factor V deficient plasma (Coatest APC Resistance V and Accélérimat) enhances the discrimination between carriers and non-carriers in both groups. However, using Coatest APC Resistance V, a significant difference of results is observed between the two populations in the non-carriers patients. Thus, Accelerimat is probably more efficient than Coatest APC Resistance for the detection of the factor VQ506 during pregnancy.

Preeclampsia, clinically defined by arterial hypertension, oedema and proteinuria is a frequently occurred complication of pregnancy. This disease seems to be linked to oxidative stress within placenta. The local accumulation of lipid peroxides, resulting from free radicals production increase altered prostacyclin/thromboxane synthesis. Increased production of lipid peroxides, thromboxane and/or cytokines triggered vascular and organic dysfunctions observed in preeclampsia. Changes in lipoprotein metabolism, namely increase in plasma very low density lipoproteins concentrations (VLDL) and oxidized low density lipoproteins (LDL) concentrations could participate to endothelial dysfunctions observed during preeclampsia.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary disease. Genetic molecular methods can make the diagnosis of at least three different types of ADPKD. ADPKD concerns young people and complications such as hypertension and decreased renal function occur more frequently if onset is early, if it is a type 1, and if the patient is a woman. The pregnant woman with autosomal dominant cystic disease is at particular high risk of obstetrical complications. Prenatal diagnosis is possible.

A prospective study was conducted in three maternity wards to compare the medical outcomes and the costs of two screening strategies for the detection of fetal/neonatal alloimmune thrombocytopenia (FMAIT). A total of 2066 primiparas and 6081 newborns were included. Fifty-two primiparous women with HPA-1b phenotype were found, and 45 were followed during pregnancy. Four women developed antibodies, and two fetuses exhibited FMAIT; therefore, the prevalence of anti-HPA-1a was 2 per 1000, and the prevalence of FMAIT 1 per 1000. Forty-eight thrombocytopenic newborns were found out of a total of 5632 blood samples. Five were HPA-1a children whose mothers were HPA-1b. The cost-effectiveness of screening all primiparous women was $45,000 and of screening all newborns is $18,000-per anti-HPA-1a alloimmunization diagnosed. Costs per fetal death or disability averted were $500,000 for the primiparous strategy and $225,000 for the newborn strategy. In conclusion, screening newborns for neonatal alloimmune thrombocytopenia is more cost-effective than screening primiparous women.

Preeclampsia is characterized by maternal hypercoagulable state and intravascular coagulation, microthromboses in several organs, and impairment of uteroplacental circulation. Excessive fibrin deposition occurs in the placenta, suggesting that disorders of placental coagulation and fibrinolysis physiologic systems may have a role in hemostasis activation. Term placentas were collected from 17 hypertensive/preeclamptic women and from 17 healthy pregnant women, and processed for both histologic and hemostasis studies. Placental fibrinoid deposition was visualized by cresyl-violet staining and quantified by histomorphometric analysis. The content in hemostasis factors was measured on extracts from homogenized placentas treated by a nonionic detergent. The percentage of villi with fibrinoid deposits was higher in the diseased placentas than in controls: 13.2 +/- 11.2 versus 6.75 +/- 2.7% (p0.001) for the total amount of deposits; 4.8 +/- 6.7 versus 1.5 +/- 1.0% (p = 0.04) for perivillous fibrinoid deposits, which are considered as histologic markers of intraplacental fibrin. The content in type 2 plasminogen activator inhibitor (PAI-2) antigen was higher in the diseased placentas than in controls: 124 +/- 8 versus 104 +/- 6 ng/mg placental protein (p = 0.046); there was a negative correlation between PAI-2 antigen and thrombomodulin activity (r = -0.57, p = 0.02) in the diseased placentas. No significant differences were found between the two groups for placental procoagulant tissue factor and anticoagulant thrombomodulin activities, and for the content in plasminogen activators and PAI-1 antigens. Placental antifibrinolytic potential is increased in pregnancy-induced hypertension and preeclampsia. This change, and the association of the highest PAI-2 placental concentrations with the lowest concentrations of thrombomodulin, may contribute to the prethrombotic state and to the excessive placental perivillous fibrin deposition observed in these situations.

Among a series of 100 cases of retroplacental hematomas we performed vaginal cesareans in 15 and present here the technical difficulties, solutions and indications of this procedure in case of in utero fetal death. Criteria for choosing vaginal cesarean were: term les than 32 weeks, biparietal diameter80 mm, fetal weight2500 g. The main difficulty was the disproportion between the size of the fetus and the cervical orifice due to insufficient anterior trachelotomy. Possible solutions are posterior trachelotomy or craniotomy. This procedure is rapid and causes little blood loss and important advantage in case of impaired hemostasis.

Several trials have been published about the usefulness of early uterine Doppler waveform in the prediction of pre-eclampsia and intrauterine growth retardation in nulliparous or low risk patients. We reviewed 3 trials introducing aspirin therapy in patients selected by an early abnormal uterine Doppler waveform. In one trial, serum alpha fetoprotein above 2.5 median at 16 weeks was used as a first selection criterion. In two studies, the incidence of pre-eclampsia was significantly decreased in aspirin treated groups: McParland's trial (odds ratio: 0.08; 95% CI:0.01-0.63) and Campbell's preliminary report (odds ratio: 0.15; 95% CI:0.02-0.91). In contrast, the rate of intra-uterine growth retardation was found similar in aspirin and placebo treated patients. To clarify the usefulness of aspirin therapy in patients with early abnormal uterine Doppler in improving maternal and fetal outcome, other prospective large studies are needed.