Homelessness in pregnancy.

OBJECTIVES: To evaluate the association, if any, of homelessness or refuge accommodation on delivery and short term perinatal outcomes in an Irish tertiary maternity hospital. METHODS: A retrospective cohort study of 133 singleton pregnancies in women reporting to be homeless or living in refuge at their booking antenatal appointment between 2013 and 2022. Analysis compared sociodemographic characteristics and perinatal outcomes in this cohort to a reference population of 76,858 women with stable living arrangements. RESULTS: Women in the homeless/refuge population were statistically more likely to be single (75.2 % vs 39.5 %, p < 0.001), have an unplanned pregnancy (73.7 % vs 27.2 %, p < 0.001), report a history of psychiatric illness (42.9 % vs 22.4 %, p < 0.001), domestic violence (18.8 % vs 0.9 %, p < 0.001) alcohol consumption in pregnancy (3.0 % vs 0.8 %, p < 0.001) or smoking in pregnancy (41.3 % vs 9.7 %, p < 0.001). They were significantly more likely to have a preterm birth (adjusted OR 1.71 (1.01-2.87) p = 0.04). They also had a significantly lower median birth weight compared to the reference population (birthweight 3270 g vs 3420 g, p < 0.001). CONCLUSION: Women in the homeless and refuge population are more likely to experience poorer perinatal outcomes compared to women with stable living arrangements.

A retrospective observational study of labour ward work Intensity: The challenge of maternity staffing.

BACKGROUND: The UK and Ireland are facing significant challenges in the recruitment and retention of midwifery staff. Deficiencies in staffing, training and leadership have been cited as contributory factors to substandard care in both regional and global independent maternity safety reports. Locally, workforce planning is critical to maintaining 'one to one' care for all women in labor and to meet the peaks of daily birthing suite activity. OBJECTIVES: Analyze the variation in work intensity, defined by the mean number and range of births per midwifery working hours. METHODS: Retrospective observational study of birthing suite activity between 2017 and 2020. 30,550 singleton births were reported during the study period; however, 6529 elective Cesarean sections were excluded as these were performed during normal working hours by a separate operating theatre team. The times of 24,021 singleton births were organized into five proposed midwifery working rosters lasting eight or 12 h; A (00.00-07.59), B (08.00-15.59), C (16.00-23.59), D (20.00-0.759) and E (0.800-19.59). RESULTS: The number of births was comparable between the eight-hour and 12-hour work periods with a mean of five to six babies born per roster (range zero to 15). Work periods D and E lasting 12-hours both recorded a mean of eight births (range zero to 18). Hourly births ranged from a minimum of zero to a maximum of five births per hour (greater than seven times the mean), a number that was achieved 14 times during the study period. CONCLUSIONS: The mean number of births is consistent between normal working hours and unsociable 'on-call' periods, however there is an extreme range of activity within each midwifery roster. Prompt escalation plans remain essential for maternity services to manage unexpected increases in demand and complexity. WHAT IS ALREADY KNOWN ON THIS TOPIC: Shortfalls in staffing and inadequate workforce planning have been frequently cited in recent maternity safety reports as barriers to sustainable and safe maternity care. WHAT THIS STUDY ADDS: Our study shows that the mean number of births in a large tertiary center are consistent across day and night rosters. However, there are large fluctuations in activity during which births can exceed the number of available midwives. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: Our study reflects the sentiments of the Ockenden review and APPG report on safe maternity staffing. Investment in services and the workforce to aid recruitment and reduce attrition is essential to establish robust escalation plans, including the deployment of additional staff in the event of extreme service pressures.

The duration of labor in spontaneous preterm deliveries: A retrospective observational study in a tertiary Irish maternity hospital.

BACKGROUND: Preterm deliveries account for 10% of all births, and are the most important cause of neonatal mortality globally. Despite their frequency, there is a paucity of information known about usual patterns of preterm labor, as previous studies which critically defined the normal progression of labor excluded preterm gestations. OBJECTIVE: To compare the durations of the first, second and third stages of spontaneous preterm labor in nulliparous and multiparous women at varying preterm gestations. METHODS: A retrospective observational study was undertaken of women admitted in spontaneous preterm labor from January 2017 to December 2020 with viable singleton gestations between 24 and 36 + 6 weeks' gestation who then proceeded to have a vaginal delivery. There were 512 cases following exclusion of preterm inductions of labor, instrumental vaginal deliveries, provider-initiated pre-labor Caesarean sections and emergency intrapartum Caesarean sections. The data was then examined to determine our outcomes of interest including the durations of the first, second and third stages of preterm labor, analyzing results by parity and gestation. For comparison, we reviewed data of term spontaneous labors and spontaneous vaginal deliveries during the same study period, identifying 8339 cases. FINDINGS: 97.6% of participants achieved a spontaneous cephalic vaginal delivery with the remainder undergoing an assisted breech birth. 5.7% of gestations delivered spontaneously between 24 + 0 and 27 + 6 weeks, with most births at gestations greater than 34 weeks (74%). The second stage duration (mean 15 vs 32 vs 32 mins respectively) was significantly different across the three gestation periods (p < 0.05), but was notably much quicker in extremely preterm labors. The first and third stage durations were similar between all gestational age groups with no statistically significant differences in results. There was a significant influence of parity on the first and second stages of labor, with multiparous women progressing more quickly than nulliparae (p < 0.001). CONCLUSION: The duration of spontaneous preterm labor is described. Multiparous women progress more quickly in the first and second stages of preterm labor than nulliparous women.

ERBIN deficiency links STAT3 and TGF-ß pathway defects with atopy in humans.

Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these congenital disorders have been associated with either increased TGF-ß activity or impaired STAT3 activation, suggesting that these pathways might intersect and that their disruption may contribute to atopy. In this study, we show that STAT3 negatively regulates TGF-ß signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation and SMAD2/3 binding protein. Individuals with dominant-negative STAT3 mutations (STAT3mut ) or a loss-of-function mutation in ERBB2IP (ERBB2IPmut ) have evidence of deregulated TGF-ß signaling with increased regulatory T cells and total FOXP3 expression. These naturally occurring mutations, recapitulated in vitro, impair STAT3-ERBIN-SMAD2/3 complex formation and fail to constrain nuclear pSMAD2/3 in response to TGF-ß. In turn, cell-intrinsic deregulation of TGF-ß signaling is associated with increased functional IL-4Rα expression on naive lymphocytes and can induce expression and activation of the IL-4/IL-4Rα/GATA3 axis in vitro. These findings link increased TGF-ß pathway activation in ERBB2IPmut and STAT3mut patient lymphocytes with increased T helper type 2 cytokine expression and elevated IgE.

Piriformis pyomyositis, an unusual presentation of leg pain post partum--case report and review of literature.

Piriformis pyomyositis is defined as a subacute infection of skeletal muscles associated with systemic infectious symptoms. In the literature it rarely occurs postpartum. We report a case of piriformis pyomyositis involving a parturient and review the published cases available in the literature.

A spoonful of sugar makes the melanoma go: the role of heparan sulfate proteoglycans in melanoma metastasis.

Heparan sulfate proteoglycans (HSPGs) have been shown to regulate signaling in many systems and are of increasing interest in cancer. While these are not the only sugars to drive melanoma metastasis, HSPGs play important roles in driving metastatic signaling cascades in melanoma. The ability of these proteins to modulate ligand-receptor interactions in melanoma has been quite understudied. Recent data from several groups indicate the importance of these ligands in modulating key signaling pathways including Wnt and fibroblast growth factor (FGF) signaling. In this review, we summarize the current knowledge regarding the structure and function of these proteoglycans and their role in melanoma. Understanding how HSPGs modulate signaling in melanoma could lead to new therapeutic approaches via the dampening or heightening of key signaling pathways.

The cannabinoid receptor inverse agonist AM251 regulates the expression of the EGF receptor and its ligands via destabilization of oestrogen-related receptor α protein.

BACKGROUND AND PURPOSE: AM251 is an inverse agonist of the cannabinoid 1 receptor (CB(1)R) that can exert 'off-target' effects in vitro and in CB(1)R knock-out mice. AM251 is also potent at modulating tumour cell growth, suggesting that growth factor-mediated oncogenic signalling could be regulated by AM251. Since dysregulation of the EGF receptor has been associated with carcinogenesis, we examined AM251 regulation of EGF receptor (EGFR) expression and function. EXPERIMENTAL APPROACH: The various biological functions of AM251 were measured in CB(1)R-negative human cancer cells. Pharmacological and genetic approaches were used to validate the data. KEY RESULTS: The mRNA levels for EGFR and its associated ligands, including HB-EGF, were induced several fold in PANC-1 and HCT116 cells in response to AM251. This event was associated with enhanced expression of EGFR on the cell surface with concomitant increase in EGF-induced cellular responses in AM251-treated cells. Exposure to XCT790, a synthetic inverse agonist of the orphan nuclear oestrogen-related receptor α (ERRα), also induced EGFR and HB-EGF expression to the same extent as AM251, whereas pretreatment with the ERRα-selective agonist, biochanin A, blunted AM251 actions. AM251 promoted the degradation of ERRα protein without loss of the corresponding mRNA. Knock-down of ERRα by siRNA-based approach led to constitutive induction of EGFR and HB-EGF levels, and eliminated the biological responses of AM251 and XCT790. Finally, AM251 displaced diethylstilbestrol prebound to the ligand-binding domain of ERRα. CONCLUSIONS AND IMPLICATIONS: AM251 up-regulates EGFR expression and signalling via a novel non-CB(1)R-mediated pathway involving destabilization of ERRα protein in selected cancer cell lines.

How effective is amniotomy as a means of induction of labour?

BACKGROUND: Amniotomy or artificial rupture of membranes is routinely used for induction of labour. AIMS: To assess the efficacy of amniotomy alone for induction. METHODS: A retrospective descriptive study of 3,586 cases of amniotomy for induction of labour between July 1996 and December 1999. RESULTS: In total, 26,670 women delivered in the National Maternity Hospital during the study period. Of these 4,928 women required induction of labour and 72.8% of these (n = 3,586) underwent amniotomy only for induction of labour. Spontaneous labour occurred in 90.1% of the women who underwent amniotomy within 24 h. Oxytocin as an induction agent was employed in 9.8% of cases. Overall, 80.5% of the women had a spontaneous delivery, 7.3% had a ventouse delivery, 4.3% had a forceps delivery, and 7.9% underwent a caesarean section. In total, 90.5% of multips and 63.4% of primips had a spontaneous vaginal delivery. CONCLUSIONS: Amniotomy is a simple, safe and effective method of induction of labour.

The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma.

Tyrosine kinase receptors represent targets of great interest for cancer therapy. Here we show, for the first time, the importance of the orphan tyrosine kinase receptor, ROR2, in melanoma progression. Using melanoma tissue microarrays, we show that ROR2 is expressed predominantly in metastatic melanoma. As ROR2 has been shown to specifically interact with the non-canonical Wnt ligand, Wnt5A, this corroborates our earlier data implicating Wnt5A as a mediator of melanoma metastasis. We show here that increases in Wnt5A cause increases in ROR2 expression, as well as the PKC-dependent, clathrin-mediated internalization of ROR2. WNT5A knockdown by siRNA decreases ROR2 expression, but silencing of ROR2 has no effect on WNT5A levels. ROR2 knockdown does, however, result in a decrease in signaling downstream of Wnt5A. Using in vitro and in vivo metastasis assays, we show that ROR2 is necessary for the Wnt5A-mediated metastasis of melanoma cells. These data imply that ROR2 may represent a novel target for melanoma therapy.

Conservative management of placenta accreta.

Two case reports of conservative management of placenta accreta in primiparous women are reported. Initial attempts to evacuate the uterus via manual removal and routine oxytocics were unsuccessful. The patients were counselled regarding further management options, surgical (hysterectomy), radiological guided arterial embolisation, medical (methotrexate, prostaglandins, mifepristone) and conservative ("watchful waiting"). After a long discussion regarding the risks of haemorrhage and infection and emergency hysterectomy, both patients opted for a conservative approach and were discharged from hospital with the placenta still in situ. The patients were followed with weekly clinical and ultrasonic assessment. One patient had a spontaneous evacuation 43 days postnatally and the second 80 days postnatally. The fertility of both women was conserved but neither have attempted further pregnancy to date.

Resuscitation at the limits of viability--an Irish perspective.

BACKGROUND: Advances in neonatal care continue to lower the limit of viability. Decision making in this grey zone remains a challenging process. OBJECTIVE: To explore the opinions of healthcare providers on resuscitation and outcome in the less than 28-week preterm newborn. DESIGN/METHODS: An anonymous postal questionnaire was sent to health care providers working in maternity units in the Republic of Ireland. Questions related to neonatal management of the extreme preterm infant, and estimated survival and long-term outcome. RESULTS: The response rate was 55% (74% obstetricians and 70% neonatologists). Less than 1% would advocate resuscitation at 22 weeks, 10% of health care providers advocate resuscitation at 23 weeks gestation, 80% of all health care providers would resuscitate at 24 weeks gestation. 20% of all health care providers would advocate cessation of resuscitation efforts on 22-25 weeks gestation at 5 min of age. 65% of Neonatologists and 54% trainees in Paediatrics would cease resuscitation at 10 min of age. Obstetricians were more pessimistic about survival and long term outcome in newborns delivered between 23 and 27 weeks when compared with neonatologists. This difference was also observed in trainees in paediatrics and obstetrics. CONCLUSION: Neonatologists, trainees in paediatrics and neonatal nurses are generally more optimistic about outcome than their counterparts in obstetrical care and this is reflected in a greater willingness to provide resuscitation efforts at the limits of viability.

Comparative study on the outcome of obstetric cholestasis.

OBJECTIVES: The aim of this study was to determine the characteristics and outcomes of obstetric cholestasis (OC) and the significance of measuring total bile acid (TBA) to aid diagnosis. METHODS: This study was conducted over a 27-month period at a tertiary referral maternity hospital (>8000 deliveries annually). In the study period, 753 women presented with pruritus of no specific origin. This group was divided into OC (TBA > or =6 micromol/L, N=151) and idiopathic pruritus of pregnancy (TBA <6 micromol/L, N=602). The latter group served as controls. Data were collected retrospectively and analyzed using SPSS 11.4 for Windows (SPSS Inc., Chicago, IL, USA). RESULTS: Patients were matched for age, ethnicity, parity, and smoking status, sex of baby, and Apgar scores at 1 and 5 minutes. OC was noted to be higher in twin pregnancies. Twice as many mothers in the OC group were induced compared to controls. Of the OC group, 18.0% delivered preterm versus 7.7% of controls. Of the mothers with OC, 48.3% had a TBA in the range of 11-39.9 micromol/L, 21.2% had a TBA >40 micromol/L, and the remaining 30.5% had a TBA between 6 and 10.9 micromol/L. Of the OC group with preterm delivery, all had a raised TBA >11 micromol/L. CONCLUSIONS: The presence of OC increases preterm delivery, both idiopathic and iatrogenic. Increasing induction, admission to the neonatal intensive care unit, and low birth weight were also noted. A TBA cut-off value of >11 micromol/L will more accurately aid the diagnosis of OC in the absence of raised liver function test results, reducing the over-diagnosis of this condition.

Solvent-detergent plasma as replacement therapy in a pregnant patient with factor V deficiency.

This case illustrates the successful treatment of factor V deficiency in pregnancy using solvent-detergent plasma.