Placenta Pathology From Term Born Neonates With Normal or Adverse Outcome.

BACKGROUND: The incidence of umbilical cord or placental parenchyma abnormalities associated with mortality or morbidity of term infants is lacking. METHODS: Placentas of 55 antepartum stillbirths (APD), 21 intrapartum stillbirths (IPD), 12 neonatal deaths (ND), and 80 admissions to a level 3 neonatal intensive care unit (NS) were studied and compared with 439 placentas from neonates from normal term pregnancies and normal outcome after vaginal delivery (NPVD) and with 105 placentas after an elective caesarian sections (NPEC). RESULTS: NPVD and NPEC placentas showed no or one abnormality in 70% and placentas from stillbirth showed two or more abnormalities in 80% of cases. APD placentas more frequently had a low weight and less formation of terminal villi. Hypercoiling was more often present in all study groups. Severe chronic villitis was almost exclusively present in APD placentas. Chorioamnionitis was significantly more frequent in APD, IPD and NS placentas and funisitis was more often observed in IPD and NS placentas. CONCLUSION: Multiple placental abnormalities are significantly more frequent in placentas from term neonates with severe perinatal morbidity and mortality. These placental abnormalities are thought to be associated with disturbed oxygen transfer or with inflammation.

Temporal heterogeneity of placental segmental fetal vascular malperfusion: timing but not etiopathogenesis.

Clinicopathologic correlations of segmental villous avascularity and other histological lesions of segmental fetal vascular malperfusion (SFVM) were analyzed retrospectively to determine whether lesions of various durations reflect different etiopathogeneses. The frequencies of 25 independent clinical and 43 placental phenotypes were statistically compared by ANOVA or Chi-square among 3 groups containing a total of 378 placentas with SFVM: group 1 contained 44 cases of recent SFVM (endothelial fragmentation, villous hypovascularity by CD34 immunostain, and/or stromal vascular karyorrhexis); group 2 contained 264 cases of established SFVM (clusters of avascular villi); and group 3 contained 70 cases of remote SFVM (villous mineralization). Statistically significant differences among the three study groups (p Bonferroni < 0.002) were found in four clinical variables (gestational age, frequencies of macerated stillbirth, induction of labor, and cesarean section) and in five placental variables (frequencies of fetal vascular ectasia, stem vessel luminal vascular abnormalities, diffusely increased extracellular matrix in chorionic villi, chorionic disk extravillous trophoblast microcysts, and excessive extravillous trophoblasts in the chorionic disc). In summary, the absence of statistically significant differences between the study groups regarding the most common causes of SFVM (hypertensive conditions of pregnancy, diabetes mellitus, fetal anomalies, and clinical and pathological features of umbilical cord compromise) is evidence that the three types of SFVM reflect temporal heterogeneity rather than etiopathogenesis. This evidence can be used to date the onset of fetal vascular malperfusion before delivery or stillbirth. The coexistence of different SVFM lesions of various durations indicates ongoing or repeat occurrences of FVM rather than single episodes.

Causes of stillbirths among women from South Africa: a prospective, observational study.

BACKGROUND: About 2·6 million third-trimester stillbirths occur annually worldwide, mostly in low-income and middle-income countries, where the causes of these deaths are rarely investigated. METHODS: We did a prospective, hospital-based, observational study in Soweto, South Africa, to investigate the causes of stillbirths in fetuses of at least 22 weeks' gestational age or with a birthweight of at least 500 g. Maternal clinical information was abstracted from medical records. Investigations included placental macroscopic and histopathological examination and fetal blood culture (including screening for pathogenic bacteria associated with stillbirth). Cases missing one or more of these investigations were considered to have incomplete samples and were excluded from the analysis of cause of stillbirth. Causes of stillbirths were assessed by individual case reviews by at least two obstetricians, and classified with a modified Stillbirth Collaborative Research Network classification system. FINDINGS: Between Oct 9, 2014, and Nov 8, 2015, we enrolled 354 stillbirths (born to 350 women). Among the women with available data, 133 (38%) of 350 had hypertension, median age was 27 years (IQR 23-33), 51 (18%) of 291 were obese, six (2%) of 344 had syphilis, and 94 (27%) of 350 had HIV. 63 (18%) of 341 fetuses showed intrauterine growth restriction. Of 298 cases (born to 294 mothers) with complete samples, the most common causes of stillbirth were maternal medical conditions (64 [21%] cases; among them 56 [19%] with hypertensive disorders and six [2%] with diabetes), placental or fetal infections (58 [19%]; 47 [16%] with fetal invasive bacterial infection), pathological placental conditions (57 [19%]; among them 27 [9%] with fetal membrane and placental inflammation and 26 [9%] with circulatory abnormalities), and clinical obstetric complications (54 [18%]; 45 [15%] with placental abruption). Six (2%) stillbirths were attributed to fetal, genetic, or structural abnormalities. In 55 (18%) cases, no cause of death was identified. The most common bacteria to which stillbirths due to fetal invasive infections were attributed were group B streptococcus (15 [5%] cases), E coli (12 [4%]), E faecalis (six [2%]), and S aureus (five [2%]). INTERPRETATION: Targeted investigation of stillbirths (even without fetal autopsy) can ascertain a cause of stillbirth in most cases. Further studies using such investigations are needed to inform the prioritisation of interventions to reduce stillbirths globally. FUNDING: Novartis and GlaxoSmithKline.

Placenta in intrauterine fetal demise (IUFD): a comprehensive study from a tertiary care hospital.

Background: Intrauterine fetal demise (IUFD) is an unpredictable and challenging obstetric complication. Its etiology is multifactorial with more than 60% attributed to the placental cause. The present study was done with a primary objective of understanding the placental lesions underlying IUFD. Methods: In this retrospective observational study, IUFD cases (>22 weeks) between January 2012 and September 2015 were collected from pathology database. The clinical details with ultrasound findings were collected from mother's charts. The lesions were classified into (A) maternal vascular malperfusion (MVM) including retroplacental hematomas, (B) fetal vascular malperfusion (FVM), (C) inflammatory lesions, and (D) idiopathic. The contributor to fetal death was classified as direct, major, minor, unlikely, or unknown. Placental findings of fetal hypoxia were recorded. Results: The study included 100 cases of IUFD. The mean maternal age was 26 years (18-36 years). Primipara were 46. There were 65 early preterm (PT) (<34 weeks), 20 late PT (34 weeks to <37 weeks) and 15 term (>37 weeks) IUFD. The mean gestation age was 30 weeks. The ratio of male:female fetuses was 1:1.7. Relevant obstetric complications included preeclampsia (n = 39), intrauterine growth restriction (IUGR) (n = 7), pre-gestational diabetes (n = 7), bad obstetric history (n = 6), oligohydramnios (n = 5). The mean placental weight was 256 g. Maternal vascular malperfusion had the highest incidence (30%), followed by combined maternal and FVM (10%). Exclusive inflammatory lesions and FVM were seen in 12 and 6%, respectively. No cause was identified in 18%. Direct contributor to IUFD was identified in 51 cases and major, minor, unlikely contribution in 21, 11 and nine cases, respectively. In nine cases, it was unknown. Lesions indicating fetal hypoxia were noted in 35 cases. In both early and late PT, MVM featured more commonly (23 and 5%). In term placentas, the most common cause was idiopathic. Conclusions: Lesions of MVM were the most common cause of IUFD and served as a direct contributor to fetal demise.

Risk of prematurity and infant morbidity and mortality by maternal fertility status and plurality.

PURPOSE: To evaluate the risk of prematurity and infant mortality by maternal fertility status, and for in vitro fertilization (IVF) pregnancies, by oocyte source and embryo state combinations. METHODS: Women in 14 States who had IVF-conceived live births during 2004-13 were linked to their infant's birth and death certificates; a 10:1 sample of non-IVF births was selected for comparison; those with an indication of infertility treatment on the birth certificate were categorized as subfertile, all others were categorized as fertile. Risks were modeled separately for the fertile/subfertile/IVF (autologous-fresh only) group and for the IVF group by oocyte source-embryo state combinations, using logistic regression, and reported as adjusted odds ratios (AORs) and 95% confidence intervals (CI). RESULTS: The study population included 2,474,195 pregnancies. Placental complications (placenta previa, abruptio placenta, and other excessive bleeding) and prematurity were both increased with pregestational and gestational diabetes and hypertension, among subfertile and IVF groups, and in IVF pregnancies using donor oocytes. Both subfertile and IVF pregnancies were at risk for prematurity and NICU admission; IVF infants were also at risk for small-for-gestation birthweight, and subfertile infants had greater risks for neonatal and infant death. Within the IVF group, pregnancies with donor oocytes and/or thawed embryos were at greater risk of large-for-gestation birthweight, and pregnancies with thawed embryos were at greater risk of neonatal and infant death. CONCLUSIONS: Prematurity was associated with placental complications, diabetes and hypertension, subfertility and IVF groups, and in IVF pregnancies, donor oocytes and/or thawed embryos.

The impact of malaria parasites on the placenta and perinatal outcome at Korle Bu teaching hospital, Accra, Ghana: a case control study

Objective: Malaria remains a complex and overwhelming health problem affecting vulnerable groups such as pregnant women and their infants in Ghana. Malaria during pregnancy does not only pose a threat to the mother but can cause serious structural damages to the placenta and subsequently affect the pregnancy outcome. The aim of the study was to investigate the impact of Plasmodium parasites on the placenta and perinatal outcome of women delivering at Korle Bu Teaching Hospital. A better understanding of the impact of malaria parasites on the placenta morphology and prenatal outcome is crucial for better management of pregnant women and their babies. Methods: The study involved testing blood collected from postpartum placentas and examining the placental tissue for Plasmodium parasites, after which they were classified as study group (Plasmodium positive) or control (Plasmodium negative). The patients in the study group with similar gestational and maternal age were matched with patients from the control group. The morphological characteristics of the placenta and the perinatal outcome of the two patient groups were compared using an unpaired t-test. Results: Sixteen (16, 13.6%) out of 118 women tested positive for Plasmodium parasites on the maternal side of the placenta by both rapid diagnostic test and microscopy and /or tested positive for malarial parasite during pregnancy, whiles the rest (102, 86.4%) had no history of malaria in the index pregnancy and tested negative. The mean placenta weight was significantly reduced in the study group (difference: -102.0g; 95% Confidence Interval [CI]: 424.4g, 486.6g) who delivered during early term (p=0.02). Patients in the study group, who delivered during late term, had a significantly reduced mean placenta diameter (difference: -2.5cm; 95% CI: 20.0cm, 21.4cm) (p=0.003) and delivered infants with lower mean birth weight (difference: - 0.693kg; 95 CI: 3.268kg, 3.475kg) (p<0.001). Conclusion: Malaria during pregnancy does not only pose a threat to the mother but to the fetus and our results add evidence that malaria parasites cause alterations to certain morphological characteristics of the placenta which subsequently affect the birth weight as the pregnancy progresses to late term

Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review of the Literature.

As outcomes of patients with sickle cell anemia improve and survival into adulthood with good quality of life and expectation of long-term survival becomes more common, challenges have developed, including issues related to reproduction. Pregnancy is frequently complicated in patients with sickle cell anemia with mortality up to 4.0%. Here we report maternal perinatal mortality in two women with sickle cell anemia who died post-partum due to acute chest syndrome (ACS), caused by bone marrow fat embolism and review the literature pertinent to this subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple complications. At 30 weeks' gestation she developed hemolysis associated with poor placental function necessitating delivery by C-section. The fetus was delivered successfully but she died due to multi organ failure after delivery. Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year-old woman with uncomplicated sickle cell anemia who presented with pre term labor and crisis, then ACS and fetal distress. The infant was delivered successfully but the patient died after cardiovascular collapse. Autopsy results showed fat and bone marrow embolization as the cause of death. Pregnancy continues to be high risk for patients with sickle cell anemia including those with mild disease. Maternal perinatal mortality could be unpredictable due to serious complications of sickle cell disease. More studies to assess maternal perinatal mortality are needed.

Rethinking placental pathology in the PSANZ classification of unexplained stillbirth at term.

BACKGROUND: Approximately 30 per cent of stillbirths are currently classified 'unexplained' using the Perinatal Society of Australia and New Zealand (PSANZ) classification system in New Zealand. This unexplained category includes deaths with placental pathology even though the importance of placental pathology and its causal relationship to stillbirth is well described. AIMS: To determine whether unexplained stillbirths in New Zealand classified using PSANZ criteria can be more usefully classified based on placental pathology. METHODS: Audit of the classification of cause of death among 'unexplained antepartum death' at term by perinatal pathologist review of postmortem and/or placental pathology reports using the current PSANZ Perinatal Death Classification (PDC)10 classification and a proposed 'significant placental pathology' subclassification. The main outcome measure was a change in cause of death from unexplained term stillbirth to an alternative PSANZ classification or to significant placental pathology subcategory. RESULTS: In total, 177 unexplained stillbirths with a postmortem and/or placental pathology report in New Zealand between 2007 and 2013 inclusive were reviewed. Twenty-three cases (13%) had significant placental pathology that could have been a direct cause of the stillbirth. A further seven cases (4%) were misclassified and could be better classified within another PDC category. CONCLUSIONS: A classification system incorporating placental pathologies which are recognised by the current literature to be causative of stillbirth would better describe stillbirths at term in New Zealand. This would benefit parental counselling and follow-up in subsequent pregnancies. A standard approach to reporting placental pathology would benefit clinicians. Education on placental pathology for clinicians working with parents experiencing stillbirth and multidisciplinary approach to classification is also recommended.

Stillbirth and intrauterine fetal death: factors affecting determination of cause of death at autopsy.

OBJECTIVES: There have been several attempts to classify cause of death (CoD) in stillbirth; however, all such systems are subjective, allowing for observer bias and making comparisons between systems challenging. This study aimed to examine factors relating to determination of CoD using a large dataset from two specialist centers in which observer bias had been reduced by classifying findings objectively and assigning CoD based on predetermined criteria. METHODS: Detailed autopsy reports from intrauterine deaths in the second and third trimesters during 2005-2013 were reviewed and findings entered into a specially designed database, in which CoD was assigned using predefined objective criteria. Data regarding CoD categories and factors affecting determination of CoD were examined. RESULTS: There were 1064 intrauterine deaths, including 246 early intrauterine fetal deaths (IUFD) (< 20 weeks), 179 late IUFDs (20-23 weeks) and 639 stillbirths (≥ 24 weeks' gestation). Overall, around 40% (n = 412) had a clear CoD identified, whilst around 60% (n = 652) were classified as 'unexplained', including around half with identified risk factors or lesions of uncertain significance, with the remaining half (n = 292 (45%)) being entirely unexplained. A stepwise increase in the proportion of unexplained deaths was observed with increasing maceration. Black and Asian women had significantly greater proportions of deaths due to ascending infection, whilst women aged over 40 years had significantly increased placenta-related CoDs. There was no significant difference in CoD distribution according to maternal body mass index or with increasing postmortem interval. Around half of those with an identifiable CoD could be identified from clinical review and external fetal examination or imaging, with most of the remainder being determined following placental examination. CONCLUSIONS: Based on objective criteria, many intrauterine deaths throughout gestation remain unexplained despite autopsy examination. The rate of unexplained death varies from around 30% to 60% depending on interpretation of the significance of features. CoD determination is dependent on both the classification system used and subjective interpretation, such that variation in the proportion of 'unexplained' cases is based largely on speculation regarding mechanisms of death. Novel methods to determine objectively the mechanism of death at postmortem examination are required. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death.

OBJECTIVES: Placental abnormalities are a common cause of death in stillbirth, ranking second only to unexplained deaths, though there is wide variation in the proportion attributed to placental disease. In clinical practice, interpretation of the significance of placental findings is difficult, since many placental features in stillbirths overlap with those in live births. Our aim was to examine objectively classified placental findings from a series of > 1000 autopsies following intrauterine death in order to evaluate the role of placental histological examination in determining the cause of death. METHODS: As part of a larger study evaluating several aspects of autopsy findings in intrauterine death, a dedicated database was used to collate antenatal and postmortem examination details for all cases examined between 2005 and 2013 at two tertiary specialist centers in London, UK. Histological findings for placentas were evaluated in relation to the final cause of death. RESULTS: Among 1064 intrauterine deaths, 946 (89%) cases had the placenta submitted for examination as part of the autopsy. Of these, 307 (32%) cases had the cause of death assigned to abnormalities of the placenta, cord or membranes. Around one third of stillbirths (≥ 24 weeks) had some isolated placental histological abnormality identified, many of uncertain significance, a significantly greater proportion than in cases of second-trimester intrauterine fetal demise (P < 0.0001). The cause of death was ascending infection in 176/946 (19%) cases, peaking at 22 weeks' gestation, with significantly more black mothers having ascending infection compared with other ethnicities (P < 0.0001). Maternal vascular malperfusion was the largest category of placental abnormalities in stillbirth, with peak prevalence in the early third trimester. There were 18 (2%) cases with specific histological abnormalities, including chronic histiocytic intervillositis and massive perivillous fibrin deposition. CONCLUSIONS: Placental pathologies represent the largest category of cause of intrauterine death. Placental histological examination is the single most useful component of the autopsy process in this clinical setting. A minority of cases are associated with specific placental pathologies, often with high recurrence rates, that can be diagnosed only on microscopic examination of the placenta. Many deaths remain unexplained, although placental histological lesions may be present which are of uncertain significance. A rigorous, systematic approach to placental pathology research and classification may yield better understanding of the significance of placental findings and reduce the rate of unexplained intrauterine deaths. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Explaining Fetal Death--What Are the Contributions of Fetal Autopsy and Placenta Examination?

The aim of our study was to categorize fetal deaths by different diagnostic groups and see to what extent an autopsy of a presumably normal fetus contributes to the final diagnosis and how many unexplained fetal deaths remain unexplained after examination of the placenta. We reviewed autopsy reports of 351 fetuses with a gestational age of 12 or more weeks at the Department of Pathology and Medical Genetics at St Olavs Hospital during the years 2001 through 2010. In our records, 38.5% (135 of 351) of the deaths were due to noninfectious placenta causes, 31.6% (111 of 351) were caused by infections, and 29.9% (105 of 351) of the fetal deaths remained unexplained after autopsy. We also found that an inconclusive report was more common early in pregnancy. The incidence of fetal loss due to circulatory disturbances in the placenta increased toward term. Infections were evenly distributed in intrauterine fetal deaths, although in spontaneous abortions, they were more frequent during the second trimester. For both explained and unexplained deaths, we observed a bimodal distribution, with peaks in the early second trimester and late third trimester toward term.

LMWH to prevent placenta-mediated pregnancy complications: an update.

Placenta-mediated pregnancy complications, including preeclampsia, placental abruption, intrauterine growth restriction/small for gestational age and recurrent or late pregnancy loss, affect over 5% of pregnancies and can result in significant maternal and perinatal morbidity and mortality. These complications have been suggested to at least partly arise from placental insufficiency, possibly as a result of inappropriate coagulation activation. This association has led to the hypothesis that anticoagulant therapy, such as low molecular weight heparin, might reduce their occurrence. The following review will attempt to summarize the extensive research that has been performed to date exploring this hypothesis and provide guidance on the current and future role of low molecular weight heparin in women at risk for placenta-mediated pregnancy complications. A case will be made to question the widely adopted practice of prescribing low molecular weight heparin to women with prior placenta-mediated pregnancy complications and suggest possible areas for future research.

Outcome of pregnancy following second- or third-trimester intrauterine fetal death.

OBJECTIVE: To investigate the outcomes of a pregnancy after a second- or third-trimester intrauterine fetal death (IUFD). METHODS: A prospective observational study was conducted at Trousseau Hospital (Paris, France) between 1996 and 2011. The first ongoing pregnancy in women who had had a previous IUFD was monitored. Management of their treatment was according to a standardized protocol. Recurrence of fetal death was the main outcome criterion. RESULTS: The subsequent pregnancies of 87 women who had experienced at least one previous IUFD were followed up. The cause of previous IUFD was placental in 50 (57%) women, unknown in 19 (22%), adnexal in 12 (14%), metabolic in 2 (2%), and malformative in 4 (5%). Three (3%) participants had another stillbirth. Overall, obstetric complications occurred in 34 (39%) pregnancies (including 22 [25%] preterm births, 5 [6%] small for gestational age, and 6 [7%] maternal vascular complications). Obstetric complications were significantly more common among women whose previous stillbirth had been due to placental causes than among those affected by other causes (P=0.02). CONCLUSION: Most pregnancies after IUFD resulted in a live birth; however, adverse obstetric outcomes were more common when the previous stillbirth was due to placental causes.

Ischemic placental disease and risks of perinatal mortality and morbidity and neurodevelopmental outcomes.

Preeclampsia, intrauterine growth restriction, and placental abruption are serious obstetrical complications that constitute the syndrome of ischemic placental disease and account for a disproportionate degree of perinatal morbidity and mortality. We review the risks of stillbirth and neonatal and infant mortality in relation to ischemic placental disease, focusing on population-based studies. We also review the risks of neonatal morbidity and neurodevelopmental outcomes in relation to ischemic placental disease. A synthesis of the findings of the relevant studies relating ischemic placental disease to adverse perinatal outcomes underscores two important observations. First, despite the low prevalence of each of the three obstetrical complications, all are associated with increased risks of adverse perinatal and infant outcomes, as well as neurodevelopmental deficits. Second, the burden of increased perinatal risks appears strongest during the preterm period. Efforts to reduce the risks of ischemic placental disease remain critically important and developing effective clinical interventions will be a target worthy for consideration.

Long-term maternal morbidity and mortality associated with ischemic placental disease.

Ischemic placental disease can have long-term maternal health implications. In this article, we discuss the three conditions of ischemic placental disease (preeclampsia, fetal growth restriction, and abruption placenta) and its associated long-term maternal morbidity. Retrospective observational studies comparing pregnancies complicated by ischemic placental disease to uncomplicated pregnancies suggest an increased long-term risk of hypertension, cardiovascular death, metabolic syndrome, and cerebrovascular disease. This association is much stronger in women who had an indicated-preterm delivery due to ischemic placental disease. It is important to adequately counsel women who are diagnosed with these conditions about their future health risks. Increased awareness of the potential health risks and multidisciplinary collaboration remains paramount to instituting the appropriate screening and preventative strategies (i.e., behavior modification) for affected women.

Identification of causes of stillbirth through autopsy and placental examination reports.

The autopsy and placental histopathological examination results following fetal deaths were analyzed retrospectively in an attempt to explain the stillbirths that occurred from 1996 to 2010 at the Department of Obstetrics and Gynecology, University of Szeged. One hundred and forty fetal deaths were recorded in that period, i.e. a rate of 4.69 stillbirths per 1000 deliveries. The postmortem examination provided the exact cause of the fetal death in 57.9% of the cases. The most common causes were a placental insufficiency (46.9%) and an umbilical cord complication (25.9%). In the first half of the third trimester, a placental insufficiency predominated as the cause of stillbirth, whereas mainly umbilical cord complications occurred around term. In spite of the availability of the autopsy and histopathological examination results, the proportion of unexplained stillbirths in our sample was relatively high. A considerable proportion of stillbirth cases could probably be prevented by more effective screening of a placental insufficiency.

Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death.

OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.

Association between antibodies to Coxiella burnetii in bulk tank milk and perinatal mortality of Danish dairy calves.

BACKGROUND: Coxiella burnetii is a well-known cause of placentitis and subsequent abortion in ruminants, but there are no reports on the relationship with perinatal mortality. The study was performed to determine the influence of level and change of bulk tank milk (BTM) antibodies to C. burnetii on two outcomes associated with parturition in cattle: a) stillbirth; and b) stillbirth and neonatal mortality combined (perinatal death). METHODS: Twenty-four Danish dairy herds were tested repeatedly for antibodies to C. burnetii in BTM using a commercial ELISA. Samples were collected monthly from July 2008 to July 2009. Information on the 2,362 calvings occurring in the study period was obtained from the Danish Cattle Database. Two multilevel logistic regression models were created for the two outcomes stillbirth and perinatal mortality. One model included the level of BTM antibodies in a specified period before or after the outcome had occurred. The other model included the change in antibodies over time. These predictors were included both at herd and animal level. Furthermore, all models included parity and breed. RESULTS: The individual monthly BTM antibody levels were highly correlated within herds. Consequently, changes in BTM antibody levels were not found to be associated with neither risk of stillbirth nor the risk of perinatal mortality. However, the risk of stillborn calves and perinatal death was higher with high level of BTM antibodies 8 to 9 months after the incident, but not outside this period. CONCLUSION: We conclude that the level of antibodies to C. burnetii in BTM may be associated with perinatal mortality, but the association was not persistent and should be investigated further.

Perinatal genomics: Current research on genetic contributions to preterm birth and placental phenotype.

Significant maternal, fetal, and newborn morbidity and mortality can be attributed to complications of pregnancy. There are direct links between perinatal complications and poor fetal/newborn development and impaired cognitive function, as well as fetal, newborn, and maternal death. Many perinatal complications have pathophysiologic mechanisms with a genetic basis. The objective of this chapter is to focus on perinatal genomics and the occurrence of two specific complications: preterm birth and dysfunctional placental phenotype. This chapter includes discussions of genetic variation, mutation and inheritance, gene expression, and genetic biomarkers in relation to preterm birth, in addition to the impact of maternal tobacco smoke exposure on placental phenotype. The concept of epigenetics is also addressed, specifically the regulation of gene expression in the placenta and fetal origins of adult health and disease. There is great potential for nurse-researchers to make valuable contributions to perinatal genomics investigations, but this requires perseverance, increased genetics-based understanding and skills, as well as multidisciplinary mentorship.