Do Birth Outcomes Predicted by Occipital Position Inform Definitions of Occiput Posterior and Occiput Transverse?

Fetal head position significantly influences birth outcomes, with higher rates of complications observed when the fetal head is in the Occiput Posterior (OP) position compared to Occiput Transverse (OT) or Occiput Anterior (OA) positions. There is no consensus in the current literature on the precise rotational point at which the fetal occiput shifts from posterior to transverse, reducing clarity in both scientific and clinical communication. Different studies employ varying definitions of these positions, which affects management decisions. This study aims to determine if a definable threshold exists between the directly posterior and directly transverse positions that correlates with different birth outcomes, thereby proposing a consistent and clinically useful definition for OP versus OT. We analyzed ultrasound data from 570 patients at full dilatation from five previous studies, correlating the angle of the fetal occiput (noted on a clock-face) with birth outcomes. Adverse outcomes were defined as cesarean delivery, instrumental vaginal delivery, significant postpartum hemorrhage (500 ml or more), obstetric anal sphincter injury, five-minute Apgar scores <7, arterial cord pH <7, base excess less than -12, or neonatal intensive care unit admission. The analysis was conducted using SAS version 9.4. The study found a continuous relationship between the fetal occipital angle and adverse birth outcomes without a distinct threshold separating OP from OT positions. No clear inflection point was demonstrated in pregnancy outcomes between OT and OP. The relationship between the angle of occiput position and pregnancy outcomes was continuous: the closer the fetal head was to directly OP, the higher the likelihood of adverse outcomes. Given the lack of a clear cut-off and to improve consistency in future research, we recommend dividing the occiput position into four quadrants of 90 degrees each. This classification could standardize reporting and potentially improve clinical decision-making regarding fetal position during labor.

Transverse position. Using rotation to aid normal birth-OUTcomes following manual rotation (the TURN-OUT trial): a randomized controlled trial.

BACKGROUND: The fetal occiput transverse position in the second stage of labor is associated with adverse maternal and perinatal outcomes. Prophylactic manual rotation in the second stage of labor is considered a safe and easy to perform procedure that has been used to prevent operative deliveries. OBJECTIVE: This study aimed to determine the efficacy of prophylactic manual rotation in the management of the occiput transverse position for preventing operative delivery. We hypothesized that among women who are at ≥37 weeks' gestation with a baby in the occiput transverse position early in the second stage of labor, manual rotation compared with a "sham" rotation will reduce the rate of operative delivery. STUDY DESIGN: A double-blinded, parallel, superiority, multicenter, randomized controlled clinical trial in 3 tertiary hospitals was conducted in Australia. The primary outcome was operative (cesarean, forceps, or vacuum) delivery. Secondary outcomes were cesarean delivery, serious maternal morbidity and mortality, and serious perinatal morbidity and mortality. Outcomes were analyzed by intention to treat. Proportions were compared using χ2 tests adjusted for stratification variables using the Mantel-Haenszel method or Fisher exact test. Planned subgroup analyses by operator experience and technique of manual rotation (digital or whole hand rotation) were performed. The planned sample size was 416 participants (trial registration: ACTRN12613000005752). RESULTS: Here, 160 women with a term pregnancy and a baby in the occiput transverse position in the second stage of labor, confirmed by ultrasound, were randomly assigned to receive either a prophylactic manual rotation (n=80) or a sham procedure (n=80), which was less than our original intended sample size. Operative delivery occurred in 41 of 80 women (51%) assigned to prophylactic manual rotation and 40 of 80 women (50%) assigned to a sham rotation (common risk difference, -4.2% [favors sham rotation]; 95% confidence interval, -21 to 13; P=.63). Among more experienced proceduralists, operative delivery occurred in 24 of 47 women (51%) assigned to manual rotation and 29 of 46 women (63%) assigned to a sham rotation (common risk difference, 11%; 95% confidence interval, -11 to 33; P=.33). Cesarean delivery occurred in 6 of 80 women (7.5%) in the manual rotation group and 7 of 80 women (8.7%) in the sham group. Instrumental (forceps or vacuum) delivery occurred in 35 of 80 women (44%) in the manual rotation group and 33 of 80 women (41%) in the sham group. There was no significant difference in the combined maternal and perinatal outcomes. The trial was terminated early because of limited resources. CONCLUSION: Planned prophylactic manual rotation did not result in fewer operative deliveries. More research is needed in the use of manual rotation from the occiput transverse position for preventing operative deliveries.

Persistent occiput posterior position outcomes following manual rotation: a randomized controlled trial.

BACKGROUND: Persistent occiput posterior position in labor is associated with adverse maternal and perinatal outcomes. Prophylactic manual rotation from the occiput posterior position to the occiput anterior position in the second stage of labor is considered a safe and easy to perform procedure that in observational studies has shown promise as a method for preventing operative deliveries. OBJECTIVE: This study aimed to determine the efficacy of prophylactic manual rotation in the management of occiput posterior position for preventing operative delivery. The hypothesis was that among women who are at least 37 weeks pregnant and whose baby is in the occiput posterior position early in the second stage of labor, manual rotation will reduce the rate of operative delivery compared with the "sham" rotation. STUDY DESIGN: A double-blinded, parallel, superiority, multicenter, randomized controlled clinical trial in 4 tertiary hospitals was conducted in Australia. A total of 254 nulliparous and parous women with a term pregnancy and a baby in the occiput posterior position in the second stage of labor were randomly assigned to receive either a prophylactic manual rotation (n=127) or a sham rotation (n=127). The primary outcome was operative delivery (cesarean, forceps, or vacuum delivery). Secondary outcomes were cesarean delivery, combined maternal mortality and serious morbidity, and combined perinatal mortality and serious morbidity. Analysis was by intention to treat. Proportions were compared using chi-square tests adjusted for stratification variables using the Mantel-Haenszel method or the Fisher exact test. Planned subgroup analyses by operator experience and by manual rotation technique (digital or whole-hand rotation) were performed. RESULTS: Operative delivery occurred in 79 of 127 women (62%) assigned to prophylactic manual rotation and 90 of 127 women (71%) assigned to sham rotation (common risk difference, 12; 95% confidence interval, -1.7 to 26; P=.09). Among more experienced operators or investigators, operative delivery occurred in 46 of 74 women (62%) assigned to manual rotation and 52 of 71 women (73%) assigned to a sham rotation (common risk difference, 18; 95% confidence interval, -0.5 to 36; P=.07). Cesarean delivery occurred in 22 of 127 women (17%) in both groups. Instrumental delivery (forceps or vacuum) occurred in 57 of 127 women (45%) assigned to prophylactic manual rotation and 68 of 127 women (54%) assigned to sham rotation (common risk difference, 10; 95% confidence interval, -3.1 to 22; P=.14). There was no significant difference in the combined maternal and perinatal outcomes. CONCLUSION: Prophylactic manual rotation did not result in a reduction in the rate of operative delivery. Given manual rotation was associated with a nonsignificant reduction in operative delivery, more randomized trials are needed, as our trial might have been underpowered. In addition, further research is required to further explore the potential impact of operator or investigator experience.

A pilot exploratory investigation on pregnant women's views regarding STan fetal monitoring technology.

BACKGROUND: Women's views are critical for informing the planning and delivery of maternity care services. ST segment analysis (STan) is a promising method to more accurately detect when unborn babies are at risk of brain damage or death during labour that is being trialled for the first time in Australia. This is the first study to examine women's views about STan monitoring in this context. METHODS: Semi-structured interviews were conducted with pregnant women recruited across a range of clinical locations at the study hospital. The interviews included hypothetical scenarios to assess women's prospective views about STan monitoring (as an adjunct to cardiotocography, (CTG)) compared to the existing fetal monitoring method of CTG alone. This article describes findings from an inductive and descriptive thematic analysis. RESULTS: Most women preferred the existing fetal monitoring method compared to STan monitoring; women's decision-making was multifaceted. Analysis yielded four themes relating to women's views towards fetal monitoring in labour: a) risk and labour b) mobility in labour c) autonomy and choice in labour d) trust in maternity care providers. CONCLUSIONS: Findings suggest that women's views towards CTG and STan monitoring are multifaceted, and appear to be influenced by individual labour preferences and the information being received and understood. This underlies the importance of clear communication between maternity care providers and women about technology use in intrapartum care. This research is now being used to inform the implementation of the first properly powered Australian randomised trial comparing STan and CTG monitoring.

A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer.

Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences contain multiple regulatory motifs and hence are capable of influencing expression of host genes. TEs are known to be released from epigenetic repression and can become transcriptionally active in cancer. Such activation could also lead to lineage-inappropriate activation of oncogenes, as previously described in lymphomas. However, there are few reports of this mechanism occurring in non-blood cancers. Here, we re-analyzed whole transcriptome data from a large cohort of patients with colon cancer, compared to matched normal colon control samples, to detect genes or transcripts ectopically expressed through activation of TE promoters. Among many such transcripts, we identified six where the affected gene has described role in cancer and where the TE-driven gene mRNA is expressed in primary colon cancer, but not normal matched tissue, and confirmed expression in colon cancer-derived cell lines. We further characterized a TE-gene chimeric transcript involving the Interleukin 33 (IL-33) gene (termed LTR-IL-33), that is ectopically expressed in a subset of colon cancer samples through the use of an endogenous retroviral long terminal repeat (LTR) promoter of the MSTD family. The LTR-IL-33 chimeric transcript encodes a novel shorter isoform of the protein, which is missing the initial N-terminus (including many conserved residues) of Native IL-33. In vitro studies showed that LTR-IL-33 expression is required for optimal CRC cell line growth as 3D colonospheres. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in colon cancer.

Does ST analysis have a place in electronic fetal monitoring?

Intrapartum cardiotocography (CTG) has a high false-positive rate. This has contributed to the rapid increase in obstetric interventions without a strong improvement in perinatal outcomes. We explore the role of ST analysis (STAN®) as an adjunct to CTG in identifying fetal asphyxia during labor. We conclude that STAN® reduces the rate of fetal blood sampling and instrumental vaginal deliveries, and has the potential to reduce the number of Australian operative interventions without compromising neonatal outcome.

Transverse occiput position: Using manual Rotation to aid Normal birth and improve delivery OUTcomes (TURN-OUT): A study protocol for a randomised controlled trial.

BACKGROUND: Fetal occiput transverse position in the form of deep transverse arrest has long been associated with caesarean section and instrumental vaginal delivery. Occiput transverse position incidentally found in the second stage of labour is also associated with operative delivery in high risk cohorts. There is evidence from cohort studies that prophylactic manual rotation reduces the caesarean section rate. This is a protocol for a double blind, multicentre, randomised, controlled clinical trial to define whether this intervention decreases the operative delivery (caesarean section, forceps or vacuum delivery) rate. METHODS/DESIGN: Eligible participants will be ≥37 weeks pregnant, with a singleton pregnancy, and a cephalic presentation in the occiput transverse position on transabdominal ultrasound early in the second stage of labour. Based on a background risk of operative delivery of 49%, for a reduction to 35%, an alpha value of 0.05 and a beta value of 0.2, 416 participants will need to be enrolled. Participants will be randomised to either prophylactic manual rotation or a sham procedure. The primary outcome will be operative delivery. Secondary outcomes will be caesarean section, significant maternal mortality and morbidity, and significant perinatal mortality and morbidity. Analysis will be on an intention-to-treat basis. Primary and secondary outcomes will be compared using a chi-squared test. A logistic regression for the primary outcome will be undertaken to account for potential confounders. This study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, Sydney, Australia, (protocol number: X110410). DISCUSSION: This trial addresses an important clinical question concerning a commonly used procedure which has the potential to reduce operative delivery and its associated complications. Some issues discussed in the protocol include methods of assessing risk of bias due to inadequate masking of a procedural interventions, variations in intervention efficacy due to operator experience and the recruitment difficulties associated with intrapartum studies. TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry (identifier: ACTRN12613000005752 ) on 4 January 2013.

Persistent Occiput Posterior position - OUTcomes following manual rotation (POP-OUT): study protocol for a randomised controlled trial.

BACKGROUND: Occiput posterior position is the most common malpresentation in labour, contributes to about 18% of emergency caesarean sections and is associated with a high risk of assisted delivery. Caesarean section is now a major contributing factor to maternal mortality and morbidity following childbirth in developed countries. Obstetric intervention by forceps and ventouse delivery is associated with complications to the maternal genital tract and to the neonate, respectively. There is level 2 evidence that prophylactic manual rotation reduces the caesarean section rate and assisted vaginal delivery. But there has been no adequately powered randomised controlled trial. This is a protocol for a double-blinded, multicentre, randomised controlled clinical trial to define whether this intervention decreases the operative delivery (caesarean section, forceps or vacuum delivery) rate. METHODS/DESIGN: Eligible participants will be (greater than or equal to) 37 weeks' with a singleton pregnancy and a cephalic presentation in the occiput posterior position on transabdominal ultrasound early in the second stage of labour. Based on a background risk of operative delivery of 68%, then for a reduction to 50%, an alpha value of 0.05 and a beta value of 0.2, 254 participants will need to be enrolled. This study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, Sydney, Australia, and protocol number X110410. Participants with written consent will be randomised to either prophylactic manual rotation or a sham procedure. The primary outcome will be operative delivery (defined as vacuum, forceps and/or caesarean section deliveries). Secondary outcomes will be caesarean section, significant maternal mortality/morbidity and significant perinatal mortality/morbidity. Analysis will be by intention-to-treat. Primary and secondary outcomes will be compared using a chi-squared test. A logistic regression for the primary outcome will be undertaken to account for potential confounders. The results of the trial will be presented at one or more medical conferences. The trial will be submitted to peer review journals for consideration for publication. There will be potential to incorporate the results into professional guidelines for obstetricians and midwives. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry ACTRN12612001312831 . Trial registered 12 December 2012.

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma.

Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences harbor multiple regulatory motifs and hence are capable of influencing expression of host genes. In response to environmental changes, TEs are known to be released from epigenetic repression and to become transcriptionally active. Such activation could also lead to lineage-inappropriate activation of oncogenes, as one study described in Hodgkin lymphoma. However, little further evidence for this mechanism in other cancers has been reported. Here, we reanalyzed whole transcriptome data from a large cohort of patients with diffuse large B-cell lymphoma (DLBCL) compared with normal B-cell centroblasts to detect genes ectopically expressed through activation of TE promoters. We have identified 98 such TE-gene chimeric transcripts that were exclusively expressed in primary DLBCL cases and confirmed several in DLBCL-derived cell lines. We further characterized a TE-gene chimeric transcript involving a fatty acid-binding protein gene (LTR2-FABP7), normally expressed in brain, that was ectopically expressed in a subset of DLBCL patients through the use of an endogenous retroviral LTR promoter of the LTR2 family. The LTR2-FABP7 chimeric transcript encodes a novel chimeric isoform of the protein with characteristics distinct from native FABP7. In vitro studies reveal a dependency for DLBCL cell line proliferation and growth on LTR2-FABP7 chimeric protein expression. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in cancer and suggest that LTR2-FABP7 may contribute to the pathogenesis of DLBCL in a subgroup of patients.

When should women be recruited to intrapartum research projects? A retrospective review.

OBJECTIVE: To review and describe the impact of varied recruitment processes in two intrapartum studies. DESIGN: Retrospective review of one prospective cohort study and one pilot randomized controlled trial. SETTING: Australian tertiary referral hospital. POPULATION: Women with term, cephalic singleton pregnancies. METHODS: Recruitment processes in one observational and one interventional study examining the management of occipitoposterior position in labor were reviewed. Data concerning recruitment and serial attrition for these studies were collected. The value of allowing consent in early labor in addition to consent in the antenatal period was assessed. MAIN OUTCOME MEASURE: Relative proportions of women participating compared with the numbers approached and recruited. RESULTS: One in 48 women approached about the observational study agreed to participate and then had a fetus in occipitoposterior position. One in 33 women in the intervention study were eventually randomized. Women approached in early labor were more likely to agree to participate (77% vs. 58%; p < 0.0001), more likely to have an ultrasound scan during labor (40% vs. 15%; p < 0.0001) and more likely to be randomized to intervention (4% vs. 1.5%; p = 0.02). CONCLUSION: Intrapartum research is associated with low rates of recruitment and these rates may be improved by asking women to provide informed consent during labor rather than the antenatal period. It is important to consider ways to facilitate randomized controlled trials involving women in labor to advance evidence-based care in this environment. This should include prospective research that seeks to define the best approach to patient recruitment.