Impact of Deferred Cord Clamping on Mortality and Severe Neurologic Injury in Twins Born at <30 Weeks of Gestation.

OBJECTIVE: To determine whether deferred cord clamping (DCC) compared with early cord clamping (ECC) was associated with reduction in death and/or severe neurologic injury among twins born at <30 weeks of gestation. STUDY DESIGN: We performed a retrospective cohort study including all liveborn twins of <30 weeks admitted to a tertiary-level neonatal intensive care unit (NICU) in Canada between 2015 and 2018 using the Canadian Neonatal/Preterm Birth Network database. We compared DCC ≥30 seconds vs ECC <30 seconds. Our primary outcome was a composite of death and/or severe neurologic injury (severe intraventricular hemorrhage grade III/IV and/or periventricular leukomalacia). Secondary outcomes included neonatal morbidity and health care utilization outcomes. We calculated aORs and ß coefficients for categorical and continuous variables, along with 95% CI. Models were fitted with generalized estimated equations accounting for twin correlation. RESULTS: We included 1597 twins (DCC, 624 [39.1%]; ECC, 973 [60.9%]). Death/severe neurologic injury occurred in 17.8% (n = 111) of twins who received DCC and in 21.7% (n = 211) of those who received ECC. The rate of death/severe neurologic injury did not differ significantly between the DCC and ECC groups (aOR 1.07; 95% CI, 0.78-1.47). DCC was associated with reduced blood transfusions (adjusted ß coefficient, -0.49; 95% CI, -0.86 to -0.12) and NICU length of stay (adjusted ß coefficient, -4.17; 95% CI, -8.15 to -0.19). CONCLUSIONS: The primary composite outcome of death and/or severe neurologic injury did not differ between twins born at <30 weeks of gestation who received DCC and those who received ECC, but DCC was associated with some benefits.

Committee Opinion No. 418: The Complete 11-14 Week Prenatal Sonographic Examination.

OBJECTIVE: Sonography during the first trimester provides an opportunity to assess a pregnancy in its early stage. This document provides an opinion about the implementation and content of prenatal sonographic examinations at 11-14 weeks gestation in Canada. TARGET POPULATION: Pregnant women at 11-14 weeks gestation. BENEFITS, HARMS, AND COSTS: The 11-14 week prenatal sonographic examination can provide important information that may contribute to pregnancy management. It can be used to confirm viability, establish gestational age, determine the number of fetuses, assess the adnexa/ovaries, and, in a multiple pregnancy, assess chorionicity and amnionicity. Scanning also offers an opportunity to detect fetal abnormalities and perform aneuploidy screening by measuring the nuchal translucency thickness. It may be valuable in screening for preeclampsia and other obstetrical disorders (by combining uterine artery Doppler scanning with other bio-clinical markers) and for invasive placentation. There are no physical harms to mother or fetus from offering a routine 11-14 week prenatal sonographic examination, and there are no extra costs for patients. EVIDENCE: Articles related to routine 11-14 week prenatal sonography were identified in a search of EMBASE and MEDLINE using the search terms first trimester ultrasound, nuchal translucency, and 11-14 week ultrasound. The search included all articles published on the topic until May 2019. Abstracts were reviewed by one author, and articles deemed relevant were then reviewed in full to determine whether to include them in the study. Articles that were not in English and articles that did not pertain to 11-14 week prenatal sonography were excluded. INTENDED AUDIENCE: This document is intended for sonographers, midwives, family physicians, obstetricians, and maternal-fetal medicine specialists.

Cell specific patterns of methylation in the human placenta.

Epigenetic processes, such as DNA methylation, are known to regulate tissue specific gene expression. We explored this concept in the placenta to define whether DNA methylation is cell-type specific. Cytotrophoblasts and fibroblasts were isolated from normal midtrimester placentas. Using immunocytochemistry, we demonstrated 95% purity for cytotrophoblasts and 60-70% for fibroblasts. We compared DNA methylation profiles from cytotrophoblasts, fibroblasts and whole placental villi using bisulfite modified genomic DNA hybridized to the Illumina Methylation27 array. Euclidean cluster analysis of the DNA methylation profiles showed 2 main clusters, one containing cytotrophoblasts and placenta, the other fibroblasts. Differential methylation analysis identified 442 autosomal CpG sites that differed between cytotrophoblasts and fibroblasts, 315 between placenta and fibroblasts and 61 between placenta and cytotrophoblasts. Three candidate methylation differences were validated by targeted pyrosequencing assays. Pyrosequencing assays were developed for CpG sites less methylated in cytotrophoblasts than fibroblasts mapping to the promoter region of the beta subunit of human chorionic gonadotropin 5 (CGB5), as well as 2 CpG sites mapping to each of 2 tumor suppressor genes. Our data suggest that epigenetic regulation of gene expression is likely to be a key factor in the functional specificity of cytotrophoblasts. These data are proof of principle for cell-type specific epigenetic regulation in placenta and demonstrate that the methylation profile of placenta is mainly driven by cytotrophoblasts.

Abdominal bloating: an under-recognized endometriosis symptom.

OBJECTIVE: To explore the association between the symptom of abdominal bloating and the diagnosis of endometriosis. METHODS: Twenty-six patients with endometriosis diagnosed by laparoscopy and 25 women without endometriosis were recruited to a case-control study. Subjects completed detailed questionnaires regarding perception of abdominal bloating, bloating-related symptoms, and effect on lifestyle. Abdominal girth was measured three times daily for one whole menstrual cycle, as were ratings of perceived abdominal bloating severity and discomfort. Experiences of abdominal and gastrointestinal symptoms were compared. RESULTS: A significantly larger proportion of women with endometriosis than control subjects experienced abdominal bloating (96% vs. 64%). In women with abdominal bloating, the following were more common in those who had endometriosis: associated severe discomfort (30% vs. 0%), wearing loose clothes during bloating (87% vs. 38%), and simultaneous hand swelling (30% vs. 6%). The experiences of cyclically related diarrhea and constipation were more frequent with endometriosis. While there were significant changes in bloating and discomfort ratings across the menstrual cycle, there was a trend towards a difference between the control subjects and unmedicated endometriosis groups only in how the pattern of bloating severity fluctuated across the cycle. Lower abdominal girth measurements changed significantly across menstrual cycle phases. Control and unmedicated endometriosis groups differed significantly in girth changes across the menstrual cycle, controls experiencing much less variation. Compared with the unmedicated endometriosis group, women receiving hormonal treatment had higher bloating severity ratings and discomfort scores, but there was no objective difference in abdominal girth. CONCLUSION: Painful abdominal bloating appears to be common in women with endometriosis and causes considerable symptomatic distress.