Search

Antiphospholipid syndrome is defined by the presence of thrombosis and/or obstetrical adverse events (≥3 recurrent early miscarriage or fetal death or a prematurity34 weeks of gestation) associated with persistent antiphospholipid antibodies. The pregnancy outcome has been improved by the conventional treatment (aspirin 100mg/day with low molecular weight heparin [LMWH] from 30 to 75% of uncomplicated pregnancies. In PROMISSE study, 19% of pregnancies had at least one obstetrical adverse event despite treatment (maternal, fetal or neonatal complications) in relation with APS. In the European registry of babies born from APS mothers, maternal and foetal adverse events were observed in 13% of cases, with prematurity in 14% despite treatment. The presence of lupus erythematosus, a history of thrombosis, presence of lupus anticoagulant and APL triple positivity are considered as factors associated with unfavorable obstetrical outcome. Hydroxychloroquine (HCQ) has anti-inflammatory and anti-thrombotic properties. Studies in vitro have shown that HCQ is able to restore the placental expression of Annexin V, which has an anticoagulant effect and to prevent the placental injury induced by APL. HCQ used for lupus erythematosus decrease the thrombotic risk and its value for thrombotic APS has been raised in an open labelled French study. In European retrospective study, the addition of HCQ to conventional treatment improved refractory obstetrical APS. Its use during the pregnancy of patients with lupus erythematosus, the evidence of good safety during the pregnancy and follow-up of children born to mothers exposed to HCQ demonstrate an overall good safety profile for mothers and the fetus. This clinical trial is designed to assess the interest of the addition of hydroxychloroquine to conventional treatment in APS during the pregnancy.

Chronic intervillositis is a rare condition, which is associated with severe obstetrical outcome and high recurrence rate. Obstetrical adverse events are intrauterine growth restriction, recurrent early miscarriages, intrauterine deaths and prematurity by placental insufficiency. The determination of the extension and the intensity of the chronic intervillositis are not currently standardized. High rates of recurrence have been described, but actually there is no reliable predictive biomarker. No treatment is currently validated, but the use of immunomodulatory drugs could be justified by the possible autoimmune or allo-immune origin. The treatment should be particularly discussed in patients with recurrent and severe obstetrical adverse events and in the presence of severe and massive histological lesions.

The placenta has generated many beliefs over centuries and in all ethnicities. Considered in our society as a surgical waste, it is elsewhere contemplated for its mysterious protective powers, viewed as the seat of the soul, disposed of, burnt or even buried. However, once time is taken for its examination, the placenta tells a story. Of interest is the similarity observed between placental vascular disease in hypertensive pregnancy and atherosclerosis in coronary artery disease for example. Hypertension in pregnancy is frequent and associated with increased adverse obstetrical outcomes, and long-term risk of cardiovascular and kidney disease. This article will discuss the role of placental histopathology in hypertensive pregnancies, its indicative value for long-term cardiovascular risk in mothers and for subsequent pregnancy.De tout temps, le placenta a fait l’objet de croyances. Simple déchet anatomique dans nos sociétés, il est ailleurs le siège de l’âme, brûlé, jeté, enterré. Pourtant, si l’on prend la peine de l’examiner, le placenta nous raconte une histoire. En effet, on observe un mimétisme entre les atteintes artérielles placentaires des grossesses hypertensives et les lésions d’artériosclérose de la coronaropathie par exemple. Les grossesses hypertensives sont fréquentes, associées à court terme à un risque accru de complications obstétricales, et à long terme de maladies cardiovasculaires et rénales. Cet article se propose de discuter l’utilité de l’examen du placenta en cas d’hypertension, de sa valeur indicative sur la survenue d’événements cardiovasculaires à long terme chez la mère, et du risque sur le déroulement d’une grossesse ultérieure.

International audience; We report a case of an unusual chorangioma in a 26-year-old gravida 2, para 1 female. The clinical course was complicated by premature birth at 34weeks' gestation. The baby presented with congenital cardiac and renal malformations. The tumor was 11cm in size, separated from the main placental mass and exhibited atypical histologic characteristics such as fibromatous areas, high cellularity, nuclear atypia and high mitotic index. These histologic features must not be interpreted as malignancy

In France, egg donation is covered by Social insurance among women43 years old. Because of shortage of egg donor, women aged 43 years or more cannot resort to egg donation in French infertility centers, leading them to turn to the foreign centers having practices different and less regulated than in France. We are thus brought to take care of the pregnancy and of the delivery of these women. Our objective was to estimate if the perinatal risks are more important after egg donation abroad than in case of egg donation in a French center.Retrospective study between January, 2010 and April, 2013, comparing women having had an egg donation to Cochin then having delivered in the maternity hospital of their choice (n=88) and the women having had an egg donation abroad then having delivered in the Port-Royal maternity (n=121). First, the modalities of egg donation were compared between the Cochin hospital and the foreign centers. Second, the obstetric and perinatal outcomes were compared between both groups, then by stratifying according to the type of pregnancy (singleton or multiple).Among women having had an egg donation abroad, the age of the donor was lower (25.7 vs. 31.7, P=0.001), the average number of embryos transferred higher (2.1±0.6 vs. 1.7±0.5, P=0.001) and the rate of multiple pregnancies higher (47.9% vs. 9.1%, P=0.001) than among women having had an egg donation at Cochin. We observed after egg donation abroad compared to egg donation at Cochin, a birth weight significantly lower (2678±745g vs. 3045±682g, P=0.001) and a prevalence of intrauterine growth retardation higher (11.1% vs. 4.2%, P=0.04). Among singletons, abnormal placentation was more frequent in case of egg donation abroad (17.5% vs. 5.1%, P=0.02). In case of twin pregnancy, we highlighted very high rates of complications, without significant difference according to the place where egg donation was practiced.We observed an increased risk of intrauterine growth retardation after egg donation abroad, which could essentially be explained by the association between advanced maternal age and multiple gestation. For other obstetric and perinatal complications, the differences between both groups were less important than expected, but very high in both groups, whether the egg donation was realized in France or abroad. The complications seem mainly due to the multiple gestations, justifying the transfer of a single embryo whenever possible.

In normal pregnancies, the earliest stages of development take place in a low oxygen (O

To describe management and screening for high-risk patients concerning post-partum hemorrhage (PPH) and antenatal management for severe anemia, thrombopenia, bleeding disorders and anticoagulant therapy.Bibliographic search restricted to French and English languages using Medline database and recommendations of medical societies.The appropriate place for delivery should be chosen after multidisciplinary concertation based on level of risk (especially past-history of severe PPH and bleeding disorder) and easy access to blood products (Professional Consensus). Prevention for severe anemia is mainly based on oral iron supplementation (grade B). Explorations are required in case of thrombopenia100Giga/L (grade C). Patients with bleeding disorder require the assistance of a physician skilled in hemostasis for perinatal management (grade C). Preventive anticoagulant therapy has no impact on PPH risk and perimedullar analgesia is usually authorized 12hours after last injection (grade C). Curative anticoagulant therapy slightly increases PPH risk and perimedullar analgesia is authorized only after 24hours since last injection (Professional Consensus).Prenatal identification of high-risk patients concerning PPH implies multidisciplinary concertation to determine the most appropriate birthplace where technical and human resources are available.

To provide recommendations regarding the use of arterial embolization in the management of post partum hemorrhage.A literature search was conducted using the Pubmed, Medline and Embase databases and the Cochrane Library (study period 1979 to June 2014).Selective embolization of both uterine arteries without microcatheter is recommended (professional consensus). Embolization should be performed using gelatin sponge pledgets rather than gelatin sponge slurry or powder (grade C). Control of hemorrhage can be expected in 70 to 100% of cases after embolization (EL3). Control of hemorrhage is obtained in 85 to 100% of cases (EL3). Arterial embolization is recommended in case of uterine atony after failure of uterotonic drugs particularly after vaginal delivery, in case of cervical hemorrhage, vaginal thrombus of cervico-vaginal tear in case of failed surgical repair or if surgery is not feasible (grade C). Pseudoaneurysm of the uterine artery is a good indication for embolization. Major complications related to embolization are reported in 5% of cases (EL4). The presence of coagulation disorders is not a contraindication to embolization (professional consensus). Embolization remains feasible after failed arterial ligations (selective or proximal) or after hysterectomy even if technically more challenging (professional consensus). Embolization can be performed in case of post partum hemorrhage related to abnormal placentation (professional consensus). Prophylactic embolization with the placenta left in place is not routinely recommended (professional consensus). The systematic preoperative placement of arterial occlusion balloons is not recommended in the management of abnormal placentation (professional consensus). Secondary post partum hemorrhage is a good indication for arterial embolization (grade C). After embolization, fertility can be spared (EL3). The risk of recurrent post partum hemorrhage does not seem different after arterial ligations or arterial embolization (EL3).

Abnormal placental invasion, more or less severe, are linked to a decidual alteration. In antenatal screening, those complications can be detected by ultrasound and magnetic resonance. However, in half of the cases, those disorders are discovered incidentally only during delivery. The conservative treatment, consisting in leaving partially or totally the abnormal placenta in situ, seems to be a good alternative to immediate hysterectomy. The aims of this study were to evaluate the benefits of abnormal placental invasion antenatal screening, as weel as the short and medium term morbidity of conservative treatments, depending on the severity of those disorders. A retrospective study was performed on 47 cases of confirmed abnormal placental invasion which had a conservative treatment between 2001 and 2012 at the Port Royal Maternity. Those 47 cases included 29 placenta accreta, 1 placenta increta and 17 placenta percreta. Twenty-four (51,4%) patients benefited from antenatal screenning including the most severe cases (17 placenta percreta). Among them, 76,5% of women with placenta percreta had a secondary hysterectomy secondarily (13/17) compared to 14,3% of those with placenta accreta (1/7). The two main indications for hysterectomy were hemorrhage and infection. None of the 23 patients who had no antenatal screening had secondary hysterectomy and all had simple placenta accreta. The long term complications, such as sepsis, renal failure, phlebitis and pulmonary embolism, concerned 85,7% of women with initial placenta percreta. Among the 30 patients with placenta accreta or increta, only two had complications after conservative treatment. In conclusion, conservative treatment seems to be a good option in less severe forms of placental invasion disorders (accreta and increta), and would not be responsible for a high maternal morbidity in these women. On the other hand, larger studies are needed to study the link between conservative treatments and the absence of subsequent morbidity.; Les troubles de l'invasion placentaire, plus ou moins sévères, surviennent en raison d'une altération de la décidue. L'échographie et l'IRM sont les deux outils permettant un dépistage anténatal de ces complications, cependant, la découverte d'une telle anomalie reste fortuite lors de l'accouchement dans la moitié des cas environ. Le traitement conservateur, qui consiste à laisser partiellement ou totalement in situ la partie placentaire anormalement insérée, semble être une bonne alternative à l'hystérectomie d'emblée. Le but de cette étude était d'évaluer les avantages d'un dépistage anténatal de ces anomalies ainsi que la morbidité à court et à long terme d'un traitement conservateur en fonction de la gravité du TIP. Nous avons étudié de façon rétrospective 47 cas de TIP confirmés ayant bénéficié d'un traitement conservateur entre 2001 et 2012 à la Maternité de Port Royal. Au total, nous avons dénombré 29 cas de placenta accreta, 17 cas de placenta percreta et un seul cas de placenta increta. 24 patientes ont bénéficié d'un dépistage anténatal (51,1%) et tous les TIP les plus sévères (soit les 17 cas de placenta percreta) en faisaient partie. Sur ces 24 patientes, 76,5% des femmes ayant un placenta percreta ont eu une hystérectomie secondaire (13 sur 17) contre 14,3% des femmes ayant un placenta accreta (1/7). Les deux indications principales étaient les métrorragies et l'infection. Aucune des patientes n'ayant pas bénéficié d'un dépistage anténatal n'a eu d'hystérectomie secondaire et toutes avaient un placenta accreta simple. Les complications à long terme, comme le sepsis, l'insuffisance rénale ou les phlébites et embolies pulmonaires, concernaient dans 85,7% des femmes ayant un placenta percreta initialement. Parmi les 30 femmes de notre étude ayant un placenta accreta, seules deux ont eu des complications secondaires au traitement conservateur. En conclusion, le traitement conservateur semble être une bonne option dans les cas de TIP les moins sévères (accreta, increta) et n'entraînerait pas, chez ses femmes, une morbidité importante. En revanche, dans les cas de placenta percreta, de plus larges études seraient nécessaires.

To evaluate the placental pathological patterns in intrauterine growth restriction (IUGR) in order to determinate which placental lesions are linked to clinically significant anomalies and to predict the child outcome and the mother risk of recurrence.Bibliographic review using the Medline and PubMed databases.Placental studies designed in order to provide macroscopic and microscopic information about the mechanism of IUGR are not numerous and retrospective; files are most of the time very small. Meta-analyses are an exception. Maternal vascular underperfusion is admitted to be the most frequent etiology of IUGR. None of the associated placental lesions is pathognomonic but the combination of a number of placental changes is. Low placental weight and microscopic lesions are more frequent than gross anomalies. Other pathophysiological groups of placental pathologies are reported to be linked to fetal growth restriction: umbilical cord anomalies, fetal thrombotic vasculopathy, chronic villitis of unknown etiology and chronic histiocytic intervillositis. Some placental lesions have been reported associated with infants with neurologic impairment and can be as different as vascular lesions, villitis of unknown origin with stem villi vasculopathy, fetal thrombotic vasculopathy or umbilical cord anomalies. However, there is no direct link between a type of placental pathology and the infant's adverse outcome or his neurological risk. The maternal risk of recurrence is not easily predictable except for the chronic histiocytic intervillositis in which the estimated recurrence rate is very high.Placental morphological findings can play a critical role in explaining the IUGR. They always need to be correlated with clinical findings.

Of all the gestational trophoblastic tumors, the gestational choriocarcinomas have the worst prognosis and the most uncommon. We report a case diagnosed on a full-term placenta, discovered incidentally. The patient, gravida 2, para 1, delivered a hypotrophic infant at 38 weeks gestation. The placenta was examined in the laboratory to perform anatomo-pathological examination in order to explain the growth retardation. This study revealed the presence of an intraplacental choriocarcinoma. Disease staging was negative for both mother and child, and beta-HCG levels remained at zero. These two factors are rather good prognosis for choriocarcinoma. With this observation, we highlight the added-value of placental examination, which seems essential for any fetal pathology, pathological pregnancy and intrapartum complications. Anatomo-pathological examination must be meticulous and systematized in order to not overlook an intraplacental tumor.

We report the case of a newborn presenting with anemia, thrombopenia, intrauterine growth restriction (IUGR), and hepatic hemangioma revealing placental mesenchymal dysplasia.This rare disease is not always diagnosed during pregnancy. Placental chorioangioma is responsible (in the absence of lethal complications in utero) for IUGR, anemia, neonatal thrombopenia, and hepatic or cutaneous hemangiomas. The early search for hemangiomas with ultrasound scanning could be useful to predict cardiac failure by left-to-right shunt.

The placenta is essential for fetal development but its in vivo study, including the study of placental perfusion is still very limited to date. MRI is a safe examination that offers new perspectives for the study of placental function that is altered in many conditions (IUGR, preeclampsia…) and placental anatomy (placenta accreta…). The different MRI sequences (DCE, IVIM, BOLD, ASL…) are new tools that may soon allow us to assess precisely placental function and anatomy, in vivo and non-invasively.

The indications of the pathological examination of the placenta are mainly represented by uteroplacental vascular deficiency. The clinical context is often evocative, but it can sometimes be solely an intra-uterine growth retardation or an unexplained in utero fetal death. So, the pathological lesions of this uteroplacental vascular deficiency must be well-known to be correctly interpreted, for none of these lesions is truly specific. The pathological diagnosis is based on a group of macroscopic and microscopic arguments. Various physiopathological mechanisms, often imperfectly known, can be at the origin of an uteroplacental vascular insufficiency, but in the current position, the pathological examination does not allow etiopathogenic orientation. The development of the trophoblastic biopsies gives us access to a new material which, in parallel with the cytogenetic analysis, often allows us, in front of an unexplained intra-uterine growth retardation, to direct the diagnosis towards uteroplacental vascular insufficiency. The histological analysis of the chorionic villous sampling taken precociously during pathological pregnancies is thus a major diagnostic contribution. But especially, this analysis gives access to new information which, in the near future, will enable us to better define the pathological evolution of the lesions of hypoxic chorionic villous and to contribute to a better knowledge of this pathology which, under many aspects, still conceals many mysteries.

In a regional study of preterm infants born before 35weeks of gestation, the aim was to propose a new classification of preterm births into three groups, and to describe the pregnancy complications and fetal disorders in each group.In two areas covered by a perinatal network, all preterm births, live births and stillbirths, which occurred between 22 and 34 completed weeks were recorded over a 21-month period. Each case was classified either in the medically-indicated preterm birth (I) group, or in the accepted spontaneous preterm birth (ASp) group or in the non-accepted spontaneous preterm birth (NASp) group.One thousand and sixty cases of preterm births were included; among them, 981 were live births or ended with per partum infant death. Forty-nine percent of these births were medically indicated, 32 % were ASp and 19 % were NASp. The distribution of pregnancy complications and fetal disorders differed between preterm birth groups: ischemic placental diseases were present in 38,2 % of medically-indicated births; preterm premature rupture of membranes occurred twice more often in I and ASp preterm births than in NASp preterm births.This classification is based on the medical decision; it allows to compare medical practices in given obstetrical situations. It appears to be reproducible and easy to use.

Is preeclampsia a new cardiovascular and end-stage renal diseases risk marker? Preeclampsia is a major obstetrical problem leading to high maternal and perinatal morbidity and mortality worldwide. It is characterized by hypertension and proteinuria occurring after 20 weeks of gestation. Increasing evidence indicates that preeclampsia is not just a pregnancy disease that resolves at the time of delivery, but represent a risk marker of cardiovascular and end-stage renal diseases later in life. The underlying link between preeclampsia and cardiovascular disease is unclear. Women with early onset/severe preeclampsia, recurrent preeclampsia, or preeclampsia with onset as a multipara appear to be at highest risk of cardiovascular disease later in life, including during the premenopausal period.

We report a case of placental metastasis of melanoma in a 30-year-old woman, without fetal involving, the child being healthy after 5 months of follow-up. Placental or fetal metastasis of maternal cancer are rare, but melanoma is remarkable by its metastatic potential among the cancers of the woman in age to procreate. Thirty cases of placental or foetal metastasis of melanoma have been reported. The fetal involvement seems to be always associated with at least a microscopic invasion of the placenta, that is why systematic microscopic examination of the placenta in case of maternal cancer needs to be encouraged. The other predictive factors of fetal involvement seem multiple and complex. The follow-up of the children arisen from a mother affected by a cancer must be close even if, in case of metastasis in children, the prognosis is very poor.

Placental mesenchymal dysplasia (PMD) is a recently described entity. Because of the presence of an embryo and a multicystic placenta, it has been initially misinterpreted as a partial mole on ultrasound as well as on gross examination. However, careful microscopic examination, cytogenetic analyses, molecular studies and follow-up of children allowed to better understand this placental abnormality, allowing an antenatal diagnosis. Our purpose was to describe ultrasonographic, macroscopic and microscopic features in PMD on the basis of a literature review and our own experience. We also detailed clinical presentation, complications of pregnancy and fetopathologic associations. We discussed ethiopathogenic hypotheses as well as differential diagnoses.

Placental chorioangioma is a benign vascular tumor. Lesions larger than 4 cm may cause fetal and maternal complications. Its association with disseminated neonatal hemangiomatosis is rarely described. We report a case of a large chorioangioma associated with an hydrops foetalis and disseminated neonatal hemangiomatosis. The relationship between placental chorioangioma and hemangioma is briefly discussed.

From June 2003 to May 2004 we carried out a comparative study of two malaria prophylaxis regimens for pregnant women. The purpose was to compare the efficacy of two regimens using chloroquine (CQ) or sulfadoxine-pyrimethamine (SP) during pregnancy and delivery in a village located in an endemic area of Mali. The study was carried out in Faladié (District of Kati) located 80 km from Bamako. Prophylaxis was administered during the second and third trimesters of pregnancy (except the 9th month for SP). A total of 301 pregnant women were enrolled including 150 in the CQ group and 151 in the SP group. At the onset of the study, the two groups were comparable with regard to socio-demographic and malaria factors. At the time of delivery, malaria infection was reduced by 43.3% in the CQ group (P10-6), and by 79.1% in the SP group (p10-6). The anemia rate was reduced by 57.5% in the CQ group (Ch2 of McNemar = 0.017), and by 74.8% in the SP group (Ch2 of McNeamar = 0.025). The incidence of placental infection was 20.6 % in the CQ group versus 8.3 % in the SP group (p = 4.10-3). Overall 16.7% of newborns presented low birth weight at delivery including 70.4% in the CQ group. The findings of this study suggest that intermittent presumptive treatment using SP is more effective than intermittent presumptive treatment using CQ in protecting both the mother and newborn against intra-uterine malaria transmission and its consequences.

Smoking remains an important topic. It is estimated that at present half the children born in France have been, or will be, exposed to the toxic effects of passive smoking. This paper aims to review the evidence of the effects of passive smoking, both intra and extra-uterine.Extra-uterine passive smoking is implicated in numerous respiratory (asthma, allergy, infections...) and non respiratory diseases (neoplastic, dental, ophthalmic, digestive, cardio-vascular and infective). Intra-uterine exposure is even more dangerous and leads to abnormalities of the pregnancy (placental abnormalities, prematurity...), of the foetus (behavioural problems, malformations) and long term problems for the unborn child. Passive smoking is responsible for pulmonary morphological abnormalities (pulmonary hypoplasia, reduction in elasticity, increased deposition of collagen and alteration of alveolar structure) and functional disorders (reduced compliance, increased airways resistance, bronchial hyperreactivity). Finally it causes a disturbance of respiratory control, promoting all the factors responsible for sudden cot death.The ill effects of passive smoking fully justify efforts to inform and persuade the medical profession of its duty to fight this scourge.

The Developmental Origins of Human Adult Disease are thought to be secondary to a perturbation of the embryonic or fetal development, which leads to metabolic disorders such as diabetes or hypertension at adulthood. Maternal undernutrition or overnutrition, repeated glucocorticosteroids administered to the mother, or placental dysfunction are the most frequently considered causal factors. Therefore, it is necessary that the obstetrician is aware of these phenomena, as this knowledge may contribute to the prevention of adult diseases. Little is known yet, on the pathophysiological or epigenetic mechanisms that lead to theses observations, and more studies are needed both in humans and animal models.

The large placental chorioangioma is a non-trophoblastic vascular tumor of placenta which size is more than 4 cm. It's a rare tumor, the incidence is between 1/3500 and 1/9000 birth. We analyze, on base of our case and from a literature review, the ultrasonography aspects of this tumor: we bring out also the physiological mechanisms of maternal and fetal complications and finally we detail the therapeutic possibilities. Chorioangioma appears in ultrasound scan like a thoroughly limited hypo-echogenic zone The vascular origin of the tumor can be confirmed by color Doppler. A left-right shunt effect results from arterio-venous communications and causes backwardness growth and fetal death in-utero The fetus is exposed to anemia and microangiopathic thrombopenia The maternal complications are: hydramnios, abruption placenta, premature ruptured membrane. Therapeutic possibilities are reduced: In several fetal anemia, blood transfusion can be done. Some techniques for tumor devascularization are be tried by someone.

To assess the value of para-clinical exams prescribed in case of in utero foetal death, to result in the establishment of a new algorithm of diagnostic tests.A retrospective analysis on a series of 106 stillbirths gathered between September 1989 and December 1998 in the obstetrical and gynaecological department of the Lausanne University Hospital which is a tertiary centre. Stillbirth was defined as foetal death occurring as from the date of foetal viability. Thus, only pregnancies from 24 weeks and onwards were included in this series. We excluded all stillbirths occurring during medical termination of pregnancy and cases with incomplete data files. The Fretts' classification was used. The different exams asked by the physician were screened and we analysed their pertinence to determine the aetiological diagnosis for each case. The search for significant risk factors was also taken into account. We compared our management of in utero foetal death with data from the literature to propose a new algorithm.The aetiology of in utero foetal death could be attributed in ninety percent of the cases. The principal causes were in utero growth retardation (19.8%), foetal congenital and chromosomal anomalies (18.9%), infections (15.1%), placental abruption (7.5%), preeclampsia (5.6%), maternal diabetes (3.8%). The remaining 18.9% are divided in to miscellaneous causes. In 10.4% of the cases we could not find any explanation to the death of the foetus. The exams that yielded the most information when done were: foetal autopsy which was abnormal in 92.7%, placental investigation which was abnormal in 93% and the babygramme (X-ray of the foetal skeleton) which was abnormal in 53%. Maternal serology for infections was informative in 6.6% of the cases.We present here a protocol for the diagnostic management of stillbirth which is differentiated according to the circumstances surrounding the event. This should prove useful to reduce superfluous tests.

The purpose of this paper was to update and analyse all the reported cases of placental metastasis. These tumours are rare and seem to complicate aggressive or disseminated malignant melanomas, leukaemias, breast cancers and lung cancers. Maternal prognosis is poor. The risk factors of cancer in the newborn are unknown. In a pregnant woman with a history of malignancy, a systematic histological examination of the placenta for evidence of metastasis is required. Close observation and follow-up of the infant has to be recommended, especially in case of placental involvement. To estimate the incidence of placental metastases and to improve knowledge of their natural history, the creation of registries of malignancies associated with pregnancy is required.

The vascular placental pathology (VPP) is associated with many etiologies. Some are the consequence of a maternal genetic or acquired predisposition. Others are associated with a chronic maternal disease (hypertension, lupus, obesity, diabetes, ...). Finally, some others are associated with placental implantation leading to fetal ischemia (multiple pregnancy, chorioangioma, primiparity, feto-placental hydrops) or to environmental (altitude) or nutritional factors (famine and specific alimentary depressions). We classify these factors into three categories according to the risk level (moderate, significant and elevated). While any of these factors can increase the risk of VPP, no one is sufficiently sensitive or specific in predict inevitable onset of VPP. In most cases VPP results from a combination of two (or more) risk factors. The risk factors of VPP classified as moderate include age (or = 35 years), increased blood pressure during the second trimester of pregnancy, a new paternity, dietetic factors or environmental factors, smoking and controlled diabetes (class B, C), or inactive systemic diseases. Risk is significantly elevated among obese (BMIor = 25), primiparous women, women with a past familial history (first degree) of preeclampsia or eclampsia, cocaine use or association of tobacco and caffeine use, increased placental mass (associated with twin pregnancy, fetal hydrops or molar pregnancy), uncontrolled diabetes, lupus, active scleroderma. Risk is considered to be high among patients with chronic hypertension, women with a past history of preeclampsia, diabetes (class D, F, R), patients with active systemic disease or with antiphospholipid antibodies or women with lupus or renal lesions and/or proteinuria as well as chronic kidney disease resulting in proteinuria, hypertension and renal insufficiency. Finally, the risk of VPP is considered to be increased in the presence of acquired thrombophilia. It remains moderate in the presence of isolated genetic thrombophilia, except in forms presenting with multiple genetic mutations or associated with an hyperhomocysteinemia. A "high-risk group" is defined among women with past history of deep venous thromboembolic events outside pregnancy, or with a past history of placental vascular pathology (intra-uterine death, placental abruptio, severe and precocious placental, intra-uterine growth retardation, early and repetitive fetal loss) and who, in addition, present with acquired thrombophilia (antiphospholipid antibodies, thrombocytemia), unique homozygous genetic thrombophilia, amultiple genetic thrombophilia or unique heterozygous genetic thrombophilia associated with hyperhomocysteinemia. Prophylactic treatment of acquired thrombophilia and of the multiple genetic forms or associated with hypercysteinemia is a logical rationale, particularly among women with a past history of placental vascular pathology, or with a past history of venous thromboembolic events. On the contrary, prophylaxis using low-molecular-weight heparin in the event of asymptomatic genetic thrombophilic mutations and for women without a past history of deep venous thromboembolism or vascular placental pathology remains controversial.

The purpose is to identify maternal and prenatal risks factors for placental vascular disorders. We excluded biologic and epidemiological data which are discussed in another chapter. Maternal risks factors are pre-existing vascular systemic diseases. Systemic lupus erythematosus (antiphospholipid antibodies are studied in another chapter) is a classical disease associated with unfavorable outcome, particularly when the disease is not quiescent and if the patient has a history of previous poor outcome. Obstetricians' awareness of the influence of inflammatory bowel diseases on pregnancy and fetal outcome is quite poor. These diseases, if they are not quiescent, can induce deleterious perinatal effects. Type 1 or even type 2 diabetes mellitus increases the risk of preeclampsia or hypertension in pregnancy, particularly when there is poor glycemic control early in pregnancy. The duration of type 1 diabetes affects the outcome of pregnancy more than type 2. Smoking during pregnancy is associated with many adverse events including spontaneous abortion, low birth weight and placental abruption. There are data about the dose-response relationship between the number of cigarettes smoked per day and the risk of abortion. Smoking during pregnancy is also protective against preeclampsia and this apparent paradox suggests the complexity of what is called vascular placental pathology. There is a significant relationship between pejorative perinatal vascular outcome and the non quiescence of renal disease. Mid-trimester uterine artery Doppler combining bilateral notches and increased uterine resistance index is the best criterion to predict the placental vascular risk of the pregnancy. Some promising studies suggest the feasibility of uterine Doppler ultrasound screening early in the pregnancy during the first trimester. Large studies are required to confirm this practice. Uterine artery Doppler in combination with other tests (elevated maternal serum hCG or ambulatory 24-hour blood pressure monitoring at 22 weeks gestation) could be a more efficient predictor of vascular complications. A large-scale evaluation is necessary before recommendations can be made. Multiple pregnancies increase the risk of preeclampsia 2- or 3-fold (RR 2.62; 95% CI: 2.03-3.38). A history of preeclampsia is the strongest predictor of unfavorable outcome for the second pregnancy.

First trimester recurrent fetal loss and severe second or third trimester placental vascular disorders are still frequently unexplained. Acquired biological thrombophilia (antiphospholipid syndrome, essential thrombocythemia) are known risk factors. Genetic thrombophilia may represent a new risk factor for placental vascular diseases, but reported data are conflicting. Combined hereditary thrombophilias are indeed a moderate risk factor, but even in these cases most pregnancies are normal giving healthy live birth children. Whether hereditary thrombophilia is associated with recurrent severe placental vascular disorders is unknown.

Thrombophilia may represent a new risk factor for placental vascular disorders. Thromboprophylaxis with low doses of heparin and aspirin may be discussed in order to reduced adverse obstetric outcomes. No randomized controlled trials are currently published in the literature. Thromboprophylaxis may be unwarranted in asymptomatic women because of the lack for an association between thrombophilia and pregnancy outcome. Women with antiphospholipid syndrome are at high risk for pregnancy loss and maternal complications. Pregnancy in women with antiphospholipid syndrome appears to be improved by thromboprophylaxis, but adverse obstetric outcome may occur despite treatment. Thromboprophylaxis is recently reported in women with previous poor obstetric outcomes. These preliminary observational studies are still insufficient to recommend a large diffusion for thromboprophylaxis. Prevention for adverse outcomes with a low fixed dose of heparin may only be discussed in women with previous late fetal loss or intrauterine fetal death.

Placental vascular diseases consist of obstetrical pathologies assumed to be linked to placental ischemia. Preeclampsia, defined as the association of hypertension, proteinuria and edema, occur in 3% of deliveries, in a non-selected population. Eclampsia, defined as the occurrence of convulsions in preeclamptic women, occur in 5 per 10,000 deliveries. Risk factors for preeclampsia are: preeclampsia in the previous pregnancy, maternal age20 years, multiple pregnancies, and nulliparity. Placenta abruption, defined as premature separation of the placenta before delivery, occur in 5 to 15 per 1,000 deliveries. Risk factors are smoking, infertility, and preeclampsia or placental abruption in the previous pregnancy. Stillbirth, defined as fetal death between 24 weeks of gestation and delivery, occur in 1.5 per 1,000 deliveries, with a higher frequency in case of placental abruption, intrauterine growth restriction or preeclampsia.

Hereditary thrombophilia as antiphospholipid syndrome (APS) may represent a new risk factor for placental vascular diseases.General screening for biological abnormalities related to thrombophilia is poorly associated with placental vascular diseases and therefore, may be unwarranted. Women with an history of thrombotic diseases may be at risk for late fetal loss or preeclampsia. Adverse obstetric outcomes are particularly high despite anticoagulation regimens in patients with APS. A high frequency for biological abnormalities related to thrombophilia was detected in pregnancies complicated by late fetal loss in comparison with controls. However, no beneficial strategy prevention was clearly reported and therefore, a selective testing was actually debated for these patients.Searching for acceptable treatment alternatives in patients with APS in order to reduce the high rate for pregnancy complications which may be persistent despite anticoagulation regimens. To determine by controlled studies the role for a prophylactic low molecular weight heparin regimens in patients with haemostatic abnormalities and previous pregnancy complications.