Maternal thrombocytopenia in pregnancy

Thrombocytopenia is a common occurrence in pregnancy. Although pregnancy is associated with physiological changes in platelet count, several pathological conditions cause thrombocytopenia, which can have a significant impact on the mother and the baby. There are diverse etiologies for thrombocytopenia, some of which are unique to pregnancy. This review provides a detailed discussion of the diagnosis and management of the various causes of thrombocytopenia in pregnancy.

Maternal thrombocytopenia in pregnancy

Thrombocytopenia is a common occurrence in pregnancy. Although pregnancy is associated with physiological changes in platelet count, several pathological conditions cause thrombocytopenia, which can have a significant impact on the mother and the baby. There are diverse etiologies for thrombocytopenia, some of which are unique to pregnancy. This review provides a detailed discussion of the diagnosis and management of the various causes of thrombocytopenia in pregnancy.

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Clinical Case Conference 892 Bipolar Disorder and Pregnancy: Maintaining Psychiatric Stability in the Real World of Obstetric and Psychiatric Complications

sulting in relapse and ultimately the reinstatement of medications that had previously maintained the patient&apos;s clinical stability over an extended period. This report describes the complex, real-life issues faced by a woman with bipolar disorder who was determined to do all that she could to conceive and bear a healthy child while remaining psychiatrically well. What will become clear is that using an organized algorithm derived from evidencebased data is complicated by realities confronted on a daily basis in the context of unpredictable but not unexpected variables, such as miscarriage, abnormal or questionable prenatal screening tests, gestational diabetes, and the emergence of fetal decelerations, preterm labor, and psychiatric decompensation. The importance of family dynamics and beliefs, the viability of an available support system, and education regarding preconception planning as well as the risks and benefits of using psychotropic medications during pregnancy will be discussed in the context of real-life events. It should be noted that even when evidence-based decisions are made, clinicians and patients are often faced with newly published data that is inconsistent with prior data. The references cited below reflect both the literature available at the time of this patient&apos;s presentation and the literature published since then. Case Presentation Patient Description &quot;Ms. M&quot; was a 29-year-old Caucasian married woman, gravida 0, with a history of bipolar disorder diagnosed at Bi polar disorder poses uniquely gender-specific challenges for women considering the health and well-being of their unborn children. They struggle with decisions about taking mood stabilizers and other psychiatric medications during pregnancy and whether to breastfeed their babies. Recognizing these concerns, treatment guidelines have been published to provide clinicians and patients with recommendations for moving forward to conceive and bear children in the safest way possible (1-7). While these thoughtful guidelines are based on available perinatal psychopharmacologic data, psychiatrists in tertiary centers for women with reproductive psychiatric concerns have found that in the real world of perinatal psychiatry, strict adherence to these clear and logical guidelines is not always possible. In order to maximize the likelihood that maternal mood and behavioral stability will be maintained, treating bipolar disorder during pregnancy frequently requires polypharmacy with potentially teratogenic medications that may result in adverse side effects for both mother and fetus. Women with bipolar disorder often have complicating comorbid medical conditions such as hypothyroidism and polycystic ovary syndrome that affect their fertility and their psychiatric and medical stability. Routine assessments of prolactin levels are important in bipolar women who require certain neuroleptics for stability. Not infrequently, obstetric complications such as gestational diabetes further complicate psychiatric and obstetric management. Furthermore, despite the severity of bipolar illness, decisions on whether or not to use medications are often based on the patient&apos;s wishes and available data (which are sometimes limited and sparse), re- This article describes complex, real-life issues faced by a woman with bipolar I disorder who wished to bear a healthy child while remaining psychiatrically well. The therapeutic issues include balancing treatment decisions that affect fetal and maternal risks. The authors address the importance of carefully considering the patient&apos;s history of response to medications when evaluating risks to maternal and fetal health. They discuss the role of the psychiatrist as a part of the treatment team faced with unpredictable but not unexpected complexities, such as miscarriage, abnormal or questionable prenatal screening tests, gestational diabetes, and the emergence of fetal decelerations, preterm labor, and psychiatric decompensation. The article presents and evaluates treatment decisions made in the setting of multiple obstetric and psychiatric complications that do not clearly fit published algorithms. The importance of incorporating family and social supports as an integral part of the treatment plan is emphasized