Restricted dispersal in a sea of gene flow.

How far do marine larvae disperse in the ocean? Decades of population genetic studies have revealed generally low levels of genetic structure at large spatial scales (hundreds of kilometres). Yet this result, typically based on discrete sampling designs, does not necessarily imply extensive dispersal. Here, we adopt a continuous sampling strategy along 950 km of coast in the northwestern Mediterranean Sea to address this question in four species. In line with expectations, we observe weak genetic structure at a large spatial scale. Nevertheless, our continuous sampling strategy uncovers a pattern of isolation by distance at small spatial scales (few tens of kilometres) in two species. Individual-based simulations indicate that this signal is an expected signature of restricted dispersal. At the other extreme of the connectivity spectrum, two pairs of individuals that are closely related genetically were found more than 290 km apart, indicating long-distance dispersal. Such a combination of restricted dispersal with rare long-distance dispersal events is supported by a high-resolution biophysical model of larval dispersal in the study area, and we posit that it may be common in marine species. Our results bridge population genetic studies with direct dispersal studies and have implications for the design of marine reserve networks.

Apparent systemic 11ß-dehydroxysteroid dehydrogenase 2 activity is increased in preeclampsia but not in intrauterine growth restriction.

OBJECTIVE: The enzyme 11ß-dehydroxysteroid dehydrogenase 2 (11ß-HSD2) converts active cortisol (F) to inactive cortisone (E). A reduced 11ß-HSD2 activity in the placenta has been demonstrated for prematurity, low birth weight, and preeclampsia. We hypothesized that disturbed placental function rather than a maternal response contributes to decreased 11ßHSD2 activity as reflected by a diminished conversion of F to E. Hence, the aim of the present study was to estimate the systemic activity of 11ß-HSD2 throughout gestation and in pregnancies complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR) by calculating maternal serum F/E ratios. METHODS: A total of 188 maternal serum samples were analyzed for nine glucocorticoid metabolites by gas chromatography-mass spectrometry (GC-MS) and F/E ratios were calculated. Study Group A: In a longitudinal set 33 healthy pregnant women were analyzed at three different time points throughout gestation and one postpartum. Study Group B: Cross-sectionally additional 56 patients were enrolled. We compared patients with PE (N = 14) and IUGR (N = 14) with gestational age matched healthy controls (CTRL = 28). RESULTS: Group A: The apparent 11ß-HSD2 activity dropped in the second trimester being restored to first trimester levels (P value = 0.016). Group B: The 11ß-HSD2 activity was high in PE (P value < 0.05) but not in the IUGR group as compared to CTRL. CONCLUSION: The increased apparent serum 11ß-HSD2 activity observed with advancing gestation in normal pregnancy may reflect an elevated general increase in enzyme activity due to a higher placental mass. The high systemic 11ß-HSD2 activity in PE but not in IUGR however suggests an increased F deactivation in maternal tissue in PE rather than in the placenta since placental insufficiency in the absence of PE does not significantly alter F/E ratio.

Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies.

OBJECTIVE: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies. METHODS: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations. RESULTS: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = - 0.47, ρ = - 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR. DISCUSSION: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the changes were most obvious in pregnancies complicated by IUGR and only minor changes were observed in pregnancies where patients had impaired liver function, our data suggests that placental rather than maternal hepatic function strongly determines lipid and steroid levels in pregnancy.

[Pharmacological Thromboprophylaxis during Pregnancy and the Puerperium: Recommendations from Current Guidelines and their Critical Comparison]. / Medikamentöse Thromboembolie-Prophylaxe in Schwangerschaft und Wochenbett: neue Leitlinienempfehlungen & kritischer Leitlinienvergleich.

Venous thromboembolism (VTE) is one of the leading causes of maternal deaths worldwide. Due to the increasing number of pregnant women with risk factors, the incidence of VTE has risen over the past decades. Mortality and morbidity of VTE are potentially preventable, since more than two-thirds of these women have identifiable risk factors and may benefit from appropriate thromboprophylaxis. The cornerstones for prevention of VTE are the individual and careful assessment of preexisting and new-onset/transient risk factors during pregnancy as well as before and after delivery and a risk-stratified pharmacological thromboprophylaxis. Current recommendations for thromboprophylaxis must rely on consensus statements and expert opinions. The recently published German AWMF-Guideline 003/001 and the Green-top Guideline No. 37a from the Royal College of Obstetricians and Gynaecologists (RCOG) are discussed. The RCOG Guideline recommends antenatal thromboprophylaxis in women with previous VTE, high-risk thrombophilia or in the presence of ≥ 4 risk factors from the beginning of pregnancy, in women with 3 current risk factors from 28 weeks of gestation. After delivery women with intermediate risk should receive prophylactic LMWH for at least 10 days and women with high risk for 6 weeks postnatally. All women who have had an elective caesarean section and who have>1 additional risk factor should be given prophylactic NMH as well as all women who have had a caesarean section in labour or an emergency caesarean section. At the onset of labour, in case of any vaginal bleeding, prior to scheduled labour induction or at least 12 h before an elective caesarean section, antenatal LMWH prophylaxis should be discontinued. LMWH prophylaxis can be continued 4-6 h after vaginal delivery and 6-12 h after caesarean delivery when women do not have an increased risk of haemorrhage. Current guidelines recommend weight-based LMWH.

Proteoform profiling of peripheral blood serum proteins from pregnant women provides a molecular IUGR signature.

Intrauterine growth restriction (IUGR) is an important cause of perinatal morbidity and mortality and contributes substantially to medically indicated preterm birth; preventing fetal death. Molecular profiling of the mothers' peripheral blood was desired to monitor the health conditions of the fetuses. To develop such a minimally invasive assay, we applied a protein affinity fractionation method to peripheral blood serum samples from pregnant women belonging to either the IUGR or to the control group. Proof-of-principle was shown by relative quantitation analysis of mixtures of intact proteoforms using MALDI-ToF mass spectrometry. The two best differentiating proteins and proteoforms, respectively, were apolipoprotein C-II and apolipoprotein C-III0. Together with three robustly expressed protein proteoforms proapolipoprotein C-II, apolipoprotein C-III1, and apolipoprotein C-III2, which served as landmarks for relative quantitation analysis, they constituted the maternal IUGR proteome signature. Separation confidence of our IUGR proteoform signature reached a sensitivity of 0.73 and a specificity of 0.87 with an area under curve of 0.86 in receiver operator characteristics. SIGNIFICANCE: Identification of IUGR newborns in the case room is required as children are severely diseased and need specialized care during infancy. Yet, at time of birth there is no readily applicable clinical test available. Hence, a molecular profiling assay is highly desired. It needs to be mentioned that current clinical definitions and recommendations for IUGR are unfortunately misleading and are not universally applicable. The most commonly adopted definition is an abdominal circumference (AC) or estimated fetal weight measurement <10th percentile. Although both, the American College of Obstetricians and Gynecologists (ACOG) and the Royal College of Obstetricians and Gynecologists (RCOG) agree that at this cut-off the risk of perinatal morbidity and mortality increases, this definition does not take into account the individualized growth potential of each fetus. In particular its sole use fails to identify larger fetuses that have not achieved their growth potential and may be at risk of adverse outcomes. Also, this definition, when solely applied, will result in the misdiagnosis of IUGR for some constitutionally small fetuses. It needs to be pointed out that the above mentioned criteria can only be determined during pregnancy in case mothers report from early on during pregnancy. We have developed a test that relies on mass spectrometric analysis of the mother's serum protein composition (IUGR signature) which can be determined just ahead of delivery and at date of delivery, respectively using a minimal invasive blood sampling approach. With this manuscript we describe the use of a mass spectrometric profiling method of 30 peripheral blood samples from pregnant women prior to giving birth of either unsuspicious newborns or IUGR-affected infants. We report for the first time that maternal blood sample analysis via affinity mass spectrometry differentiates IUGR infants from controls with high confidence.

[Progesterone for Prevention of Preterm Birth--Evidence-based Indications]. / Progesteron zur Prävention der Frühgeburt--Evidenz-basierte Indikationen.

BACKGROUND: The prevention and treatment of preterm birth remains an unsolved problem in modern obstetrics. Progesterone has a variety of actions on the myometrium and the cervix, among others inhibition of myometrial contractility and a cervix strengthening effect by inhibiting the production of proinflammatory cytokines and prostaglandins as well as by reducing the synthesis of proteins, which play a crucial role in initiating labour. Consequently, progesterone may be a promising candidate for the prevention of preterm birth. MATERIAL AND METHODS: We searched PubMed from 1956 to August 2014 using a combination of key words and text words related to preterm birth and progesterone. ('progesterone', progestins, 17-OHPC). The aim of the literature search was to determine evidence-based indications for the use of progesterone in the prevention of preterm birth. RESULTS: (i) Patients with a singleton pregnancy and history of preterm birth should receive vaginal progesterone daily (200 mg capsule or 90 mg containing gel) from 16+0 to 36+0 weeks of gestation (alternatively 250 mg intramuscular 17-OHPC weekly): level of evidence 1a, grade of recommendation ++ . Prophylactic progesterone reduces the incidence of preterm birth <34 and <37 weeks of gestation and perinatal mortality significantly. (ii) Patients with singleton pregnancies and a sonographically short cervix (≤25 mm) before 24 weeks of gestation should receive vaginal progesterone daily (200 mg capsule or 90 mg containing gel) until 36+6 weeks of gestation: level of evidence 1a, grade of recommendation ++ . Prophylactic progesterone leads to a significant reduction in the incidence of preterm birth <28, <33, and <35 weeks of gestation and is associated with a significant reduction of neonatal morbidity. (III) There is a lack of evidence to recommend vaginal progesterone or intramuscular 17-OHPC for primary tocolysis or for "adjunctive" tocolysis (in combination with conventional tocolytic agents). (IV) There is a growing body of evidence that vaginal progesterone (400 mg/day) after successful tocolysis ("maintenance therapy") is a promising option for prolongation of pregnancy: level of evidence 1b, grade of recommendation +. (V) Data from the literature are insufficient to recommend progesterone in patients with preterm rupture of membranes or in the perioperative management of patients requiring transvaginal cervical cerclage. (VI) The vaginal administration of progesterone is well-tolerated by the patients and has only minor maternal side effects, whereas intramuscular injections of 17-OHPC are associated with a significant higher rate of side effects (e. g. local pain, nausea, diarrhoea). It is mandatory to inform patients on the off-label use of progesterone in pregnancy. DISCUSSION: Prophylactic progesterone administration is an evidence-based method for the prevention of preterm birth in women with a previous preterm birth and in pregnant women with a sonographically short cervix (≤25 mm) before 24 weeks of gestation. Vaginal progesterone is favoured over intramuscularly applied 17-OHPC, especially because of the lower rate of maternal side effects. Whether progesterone is an effective approach for the treatment of preterm birth as a tocolytic agent (primary, adjunctive) or for maintenance therapy after arrest of preterm labour has to be shown in further well-designed randomised and controlled trials with adequate statistical power.

Off-label use of misoprostol for labor induction in Germany: a national survey.

OBJECTIVE: Misoprostol is safe and effective for labor induction in viable pregnancies. Little is known about the prevalence of off-label use of misoprostol, and the reasons for using or not using misoprostol for labor induction. As such, a national survey was conducted in Germany to assess reliable data about the use of misoprostol in clinical practice. STUDY DESIGN: A prospective study was performed in 2013 using a standardized survey questionnaire. All registered departments of obstetrics and gynecology in Germany were targeted. RESULTS: Out of 783 questionnaires, 542 (69%) were returned. Three hundred and fifty-five (66%) respondents reported that they use misoprostol for labor induction in viable term pregnancies, and 183 (34%) respondents reported that they never use misoprostol for this indication. The most common reasons given for using misoprostol in labor induction were: effectiveness (40%), good patient acceptance (35%), established/well proven in clinical practice (35%) and cost-effectiveness (32%). The most common reasons given for not using misoprostol were lack of licence (off-label use, 69%) and uncertainty of the legal situation (27%). CONCLUSION: Although misoprostol is not licensed in Germany for obstetric indications, the vast majority of respondents (66%) reported that they use misoprostol for labor induction. The main reasons for not using misoprostol for labor induction in Germany are legal concerns rather than lack of scientific evidence. Cost-effective medications with evidence-based effectiveness and safety should be supported by a clear statement from national medical societies.

Diagnosis and Treatment of Hypertensive Pregnancy Disorders. Guideline of DGGG (S1-Level, AWMF Registry No. 015/018, December 2013).

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Hypertensive pregnancy disorders contribute significantly to perinatal as well as maternal morbidity and mortality worldwide. Also in Germany these diseases are a major course for hospitalization during pregnancy, iatrogenic preterm birth and long-term cardiovascular morbidity. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. Recommendations: This guideline summarizes the state-of-art for classification, risk stratification, diagnostic, treatment of hypertensive pregnancy disorders.

The Renaissance of Transcervical Balloon Catheters for Cervical Ripening and Labour Induction.

Due to rising rates of labour induction in industrialised countries, safe and effective methods of induction have once again become a focus of interest and research. Prostaglandins are effective for cervical ripening and induction of uterine contractions. They do, however, cause overstimulation of the uterus in up to 20 % of cases, sometimes causing changes in fetal heart rate. Transcervical balloon catheters provide an alternative to prostaglandins for labour induction and have been used for this purpose for almost 50 years. This induction method has experienced a recent renaissance in clinical practice that is reflected in an annually rising number of publications on its use. Balloon catheters allow gentle ripening of the cervix without causing uterine overstimulation. The two catheters available are the Foley catheter (off-label use) and the double balloon catheter, which is licensed for use in induction of labour. Both are as effective as prostaglandins, and do not increase the risk of infection to mother or child. Catheter induction also requires less monitoring compared to prostaglandins resulting in improved patient satisfaction. Balloon catheters provide a useful and promising option to achieve vaginal delivery despite failed prostaglandin induction. Intravenous oxytocin is nevertheless required in up to 85 % of cases for adequate induction/augmentation of contractions. Balloon catheters, vaginal PGE2 and misoprostol are equally effective in the context of an unripe/unfavourable cervix, the rate of uterine hyperstimulation being significantly lower, and the need for oxytocin significantly higher for catheters. Balloon catheters are increasingly being used in combination or sequentially with oral/vaginal misoprostol, although there is currently inadequate published data on the subject. International guidelines recommend the use of balloon catheters for labour induction with an unripe cervix (also following previous caesarean section) as an alternative to prostaglandins, particularly when these are not available or are contraindicated.

Misoprostol for Labour Induction after Previous Caesarean Section - Forever a "No Go"?

Misoprostol in oral or vaginal form is an established method of labour induction worldwide. Its use after previous caesarean section is associated with a high rate of uterine rupture; according to international guidelines it is therefore contraindicated in this setting. However the evidence base for this recommendation comprises case reports, one randomised trial that was discontinued prematurely, and numerous low quality retrospective data analyses published between 1997 and 2004. New insights into e.g. resorption kinetics, dosage and application intervals, dose dependant uterine hyperstimulation rates, as well as increasing clinical experience with misoprostol have lead to a critical reappraisal of these "historical" studies. Accordingly the evidence supporting a ban on vaginal and particularly oral misoprostol for labour induction in the context of a scarred uterus is currently insufficient for a convincing guideline recommendation. In view of the clear advantages of misoprostol over prostaglandin E2 (cheaper, more effective) a retrospective review of registry data should be conducted to determine the incidence of uterine rupture following misoprostol and the circumstances in which it occurs. A prospective, randomised trial could then be conducted on the basis of these findings (e.g. oral misoprostol vs. vaginal prostaglandin E2); known risk factors for uterine rupture including the type of uterine scar would need to be taken into account when selecting patients for vaginal delivery. Until new data from well-designed studies are available, misoprostol will continue to be contraindicated in clinical guidelines for use in labour induction after previous caesarean section.

[Increased risk of stillbirth in older mothers--a rationale for induction of labour before term?]. / Erhöhtes Risiko für Totgeburt bei älteren Müttern - Rationale für Geburtseinleitung vor dem Termin?

The average age of childbearing has risen markedly in Germany and other high-income countries during the past 2 decades. Women aged 35 years or older have an increase in pregnancy complications and in preexisting medical conditions including obesity, diabetes and hypertension as well as a significant increase in the gestational age-related rate of stillbirth compared to younger mothers. Additional individual risk factors for stillbirth are primiparity, body mass index>30 and smoking. After exclusion of risk factors the absolute risk of stillbirth in women aged≥40 years old is 2-fold higher (1 in 503 maternities) at 39/40 weeks of gestation compared to women aged<35 years (1 in 1 020 maternities) at the same gestational age. Women aged 40 years or older have a similar stillbirth risk at 39 weeks of gestation to 25-29-year-olds at 41 weeks gestation. The underlying mechanism for the excess risk of stillbirth in women of advanced maternal age after exclusion of congenital anomalies is unknown. Independent of maternal age the cumulative probability of perinatal death increases from 1.8/1 000 deliveries at 38 weeks of gestation to 9.3/1 000 deliveries at 42 weeks of gestation. Whether on the basis of these data induction of labour at 39 weeks of gestation should be recommended in women of advanced maternal age has recently been discussed in a Scientific Impact Paper of the Royal College of Obstetricians and Gynaecologists. In this context it should be taken into account that the rate of Caesarean sections in women aged 40 years or over is 40%, and, in particular, older nulliparous may request elective Caesaran section rather than elective induction of labour. Recent metaanalyses have shown that elective induction of labour before or after term is not associated with an increase of the Caesarean section rate compared to expectant management. Up to now no randomised controlled trials exist and consequently no -recommendations from current guidelines regarding induction of labour in women of advanced maternal age can be given. In any case, a careful consultation and an individual risk-benefit analysis regarding the obstetric management is mandatory, and the final decision should be made in agreement between the pregnant women and the obstetrician. Currently a randomised controlled trial in the U.K. comparing induction of labour at 39 weeks of gestation with expectant management in nulliparous women aged over 35 years is recruiting, with the aim to determine intrapartum complications and perinatal morbidity and mortality in both managements.

[Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany - Austria - Switzerland)]. / Management der postpartalen Blutung (PPH): Algorithmus der Interdisziplinären D-A-CH-Konsensusgruppe PPH (Deutschland - Österreich - Schweiz).

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

[Active management of the third stage of labour (AMTSL) - the end of a 50 years-dogma?]. / Aktive Leitung der Nachgeburtsperiode - Das Ende eines 50-jährigen Dogmas?

Post-partum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Since more than 50 years AMTSL has been proposed for the prevention of PPH and is still recommended in current guidelines. The 3 key components of AMTSL are the prophylactic administration of oxytocin, clamping and cutting of the umbilical cord immediately after delivery of the baby and controlled cord traction. AMTSL has proven to reduce the rate of severe PPH by 70%. Despite of the long tradition of AMTSL it is still unclear, which of the 3 components significantly contributes to the reduction in PPH. Cochrane analyses and a recent metaanalysis gave strong evidence, that prophylactic oxytocin administration reduces the risk of PPH significantly, however, the optimal dose and mode of application is still a matter of debate.Until a little while ago no randomized controlled studies exist regarding the significance of controlled cord traction and the time of cord clamping in AMTSL. A randomized WHO trial 2012 and the 2013 published TRACOR (Traction of the CORd)-trial from France could clearly demonstrate that controlled cord traction is not associated with a significant reduction in postpartum blood loss and in the risk of severe PPH. A Cochrane analysis 2008 and a recent randomized trial from Sweden came to the conclusion, that there are no significant -differences between early (< 15 s) and delayed (> 1-3 min) cord clamping in the reduction of PPH and severe PPH. Uterine massage after delivery of the placenta, placental cord drainage and umbilical vein injection of uterotonics after delivery of the baby as part of AMTSL are not evidence-based methods. It has taken 50 years since AMTSL was first described for it to become clear that prophylactic oxytocin is the most important and the only evidence-based component of AMTSL. Future guidelines and textbooks should consider these new -findings.

Ballantyne syndrome and congenital anaemia associated with Parvovirus B19 infection: case report and review.

Acute maternal Parvovirus B19 infection affects about 1% of all pregnancies worldwide. Diaplacental transmission of Parvovirus B19 during the second trimester can cause complications like foetal hydrops, premature delivery or foetal loss in about 20-30% of these pregnancies, whereas the majority of maternal infections remain clinically silent. In individual cases, foetoplacental hydrops (of various origins) can trigger a rare form of Preeclampsia in the pregnant woman. The developing maternal oedema in this situation apparently "mirrors" the hydropic state of the foetus. The symptom triad of foetal hydrops, foetoplacental oedema and maternal anasarca defines Ballantyne syndrome. We report a case of Parvovirus-induced Ballantyne syndrome including a 10-year follow-up of mother and child. While the mother recovered rapidly after (preterm) delivery, the infection complicated the first months of life of the neonate. Congenital transfusion-dependent red cell aplasia and cholestatic hepathopathy took a chronic course but resolved under IVIG treatment. Follow-up now finds both the former neonate and the mother entirely recovered. Current knowledge on Ballantyne syndrome as well as perigestational Parvovirus infections including congenital anaemia is briefly reported and pathophysiological hypotheses are discussed.

[Maternal-placental interactions and fetal programming]. / Mütterlich-plazentare Interaktionen und fetale Programmierung.

Pregnancy-related complications not only represent a risk for maternal and fetal morbidity and mortality, but are also a risk for several diseases later in life. Many epidemiological studies have shown clear associations between an adverse intrauterine environment and an increased risk of diabetes, hypertension, cardiovascular disease, depression, obesity, and other chronic diseases in the adult. Some of these syndromes could be prevented by avoiding adverse stimuli or insults including psychological stress during pregnancy, intake of drugs, insufficient diet and substandard working conditions. Hence, all of these stimuli have the potential to alter health later in life. The placenta plays a key role in regulating the nutrient supply to the fetus and producing hormones that control the fetal as well as the maternal metabolism. Thus, any factor or stimulus that alters the function of the hormone producing placental trophoblast will provoke critical alterations of placental function and hence could induce programming of the fetus. The factors that change placental development may interfere with nutrient and oxygen supply to the fetus. This may be achieved by a direct disturbance of the placental barrier or more indirectly by, e. g., disturbing trophoblast invasion. For both path-ways, the respective pathologies are known: while preeclampsia is caused by alterations of the villous trophoblast, intra-uterine growth restriction is caused by insufficient invasion of the extravillous trophoblast. In both cases the effect can be undernutrition and/or fetal hypoxia, both of which adversely affect organ development, especially of brain and heart. However, the mechanisms responsible for disturbances of trophoblast differentiation and function remain elusive.

[Hereditary thrombophilias and placental-mediated pregnancy complications in the II./III. trimester]. / Hereditäre Thrombophilien und Plazenta-medierte Schwangerschaftskomplikationen im II./III. Trimenon.

UNLABELLED: Placental-mediated pregnancy complications (PmC) like preeclampsia, intrauterine growth restriction and placental abruption are common causes of fetal and maternal morbidity and mortality. The high prevalence of hereditary thrombophilias in case-control studies associated with pathological morphological findings of the placenta in these cases gave evidence for the association between hereditary thrombophilias and PmC. However, data from the literature are inconsistent, since subsequent prospective cohort studies could not demonstrate significant associations between inherited thrombophilia and PmC. Because of the multifactorial aetiology of PmC it may be difficult to prove, that hereditary thrombophilias are independent risk factors for PmC. Current guidelines do not recommend screening for inherited thrombophilias in patients with previous PmC. Evidence from current in vitro studies have shown, that heparin has beneficial non-anticoagulatory effects on trophoblast invasion. Retrospective case-control studies and recently published randomised controlled cohort studies have shown, that prophylactic administration of low-molecular-weight heparin (LWH), started in early pregnancy, may lead to a significant reduction in the incidence of PmC in subsequent pregnancies in patients with and without hereditary thrombophilias and previous PmC. CONCLUSION: Large, well-designed multicenter studies are needed to elucidate the role of hereditary thrombophilias in cases of PmC and to confirm the benefit of LWH for subsequent pregnancy outcomes.