Purpose: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes. Methods: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal–Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology. Results: Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach–Merritt syndrome. Conclusion: In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.

Background-The BRCA1 gene is an important breast cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease.

Background Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. Objective The objective of this study was to determine if genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the OXTR, could explain variation in oxytocin dosing and labor outcomes among women being induced near term. Study Design Pregnant women with a singleton gestation residing in Durham County, NC were prospectively enrolled as part of the Healthy Pregnancy, Healthy Baby cohort study. Those women undergoing an induction of labor at 36 weeks or greater were genotyped for 18 haplotype tagging (ht) single nucleotide polymorphisms (SNPs) in OXTR and 7 htSNPs in GRK6 using TaqMan assays. Linear regression was used to examine the relationship between maternal genotype and maximal oxytocin infusion rate, total oxytocin dose received, and duration of labor. Logistic regression was used to test for association of maternal genotype with mode of delivery. For each outcome, backward selection techniques were utilized to control for important confounding variables and additive genetic models were employed. Race/ethnicity was included in all models due to differences in allele frequencies across populations and Bonferroni correction for multiple testing was used. Results DNA was available from 482 women undergoing induction of labor at 36 weeks or greater. 18 SNPs within OXTR and 7 SNPs within GRK6 were examined. Five SNPs in OXTR showed nominal significance with maximal infusion rate of oxytocin and two SNPs in OXTR were associated with total oxytocin dose received. One SNP in OXTR and two SNPs in GRK6 were associated with duration of labor, one of which met the multiple testing threshold (p=0.0014, rs2731664 [GRK6], mean duration of labor 17.7 hours vs. 20.2 hours vs. 23.5 hours for AA, AC and CC genotypes, respectively). Three SNPs, two in OXTR and one in GRK6, showed nominal significance with mode of delivery. Conclusions Genetic variation in OXTR and GRK6 is associated with the amount of oxytocin required, as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term. With further research, pharmacogenomic approaches may potentially be utilized to develop personalized treatment to improve safety and efficacy outcomes among women undergoing induction of labor.

OBJECTIVE: Oxytocin is a potent uterotonic agent widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. The objective of this study was to determine if genetic variation in the oxytocin receptor gene (OXTR) or in the gene coding GRK6, which regulates desensitization of the OXTR, could explain differences in oxytocin dosing and labor outcomes among women being induced near term. STUDY DESIGN: Pregnant women with a singleton gestation residing in Durham County, NC were prospectively enrolled. DNA was available from 482 women undergoing induction of labor at 36 weeks or greater. 18 haplotype tagging (ht) single nucleotide polymorphisms (SNPs) in the OXTR and 7 htSNPs in GRK6 were genotyped using TaqMan assays. Linear regression was used to examine the relationship between maternal genotype and maximal oxytocin infusion rate, total oxytocin dose received, and duration of labor. Logistic regression was used to test for association of maternal genotype with mode of delivery. For each outcome, backward selection techniques were utilized to control for important confounding variables and additive genetic models were employed. Race/ethnicity was included in all models due to differences in allele frequencies across populations and Bonferroni correction for multiple testing was used. RESULTS: Five SNPs in the OXTR were significantly associated with maximal oxytocin infusion rate and two SNPs in the OXTR were associated with total oxytocin dose received. One SNP in the OXTR and two SNPs in GRK6 were associated with duration of labor, one of which met the multiple testing threshold (p¼0.0014, rs2731664 [GRK6], mean duration of labor 17.7 hours vs. 20.2 hours vs. 23.5 hours for AA, AC and CC genotypes, respectively). Three SNPs, two in the OXTR and one in GRK6, were significantly associated with mode of delivery. (Table) CONCLUSION: Variation in genes coding the OXTR and GRK6 are associated with the amount of oxytocin required, as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term. Pharmacogenomic approaches may potentially be utilized to improve labor outcomes among women undergoing induction of labor.28 First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a nonhuman primate model

Epidemiological studies indicate that obesity is associated with poor outcomes in breast cancer. In our previous work, we demonstrated that a chronic consumption of a high fat diet increases solid tumor growth and metastasis in a spontaneous mammary cancer mouse model. In addition to higher tumor burdens and rates of metastases, mice fed a high fat diet showed elevated levels of adipocyte derived monocyte chemoattractant protein-1 (MCP-1) in the blood. We hypothesized that diet-induced obesity promotes mammary carcinogenesis by inducing an inflammatory and tumor-supportive microenvironment. We further compared chow fed lean MMTV(PyMT) mice with those fed 45.0% (w/w) high fat (HF) to investigate the impact of body adiposity and dietary nutrient overload on levels of MCP-1 in tissue, tumor associated macrophages (TAMs) and for the degree of microvessel density. We analyzed early and late carcinoma stage tumors together with adipose tissue from mice fed HF and control diets in order to identify possible sources of MCP-1 production. MCP-1 levels in tumors of mice differed significantly by cancer stage and diet, with late stage tumors showing more MCP-1 (P<0.05). Moreover, MCP-1 production was elevated in adipose tissue of obese mice compared to lean mice. Tumors and adjacent adipose were stained with CD68 and the numbers of TAMs were quantified. Significantly more TAMs (P<0.05) were found within tumor beds and more crown-like structures were evident in adipose tissue from obese mice at both early and late stage carcinoma. Tumor beds also showed increased microvessel density when stained with CD31. In summary, diet-induced obesity increased levels of MCP-1 in tumors and adipose with more macrophage infiltration and greater vascular density evident in mammary tumor beds. Taken together, these findings suggest that high body adiposity caused by diet-induced changes promote an inflammatory and tumor-supportive microenvironment in breast cancer. NIH P20 RR016440, P30 R032138/GM103488, and P20 RR016477 Citation Format: Emily Ngan, Alessandra Pacilli, Eva Marshall, Kirstie Cutlip, James Coad, Amanda Ammer, Linda Vona-Davis. Diet-induced obesity increases tumor levels of MCP-1, macrophage infiltration and microvessel density in a murine model of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1549. doi:10.1158/1538-7445.AM2013-1549