Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

Perception and experiences of adolescent mothers and communities in caring for their preterm babies: findings from an in-depth study in rural Bangladesh.

BACKGROUND: A significant concern for Bangladesh is the high prevalence of adolescent pregnancy and the associated negative consequences for mother and baby, including a teen-related increased risk of preterm birth (PTB). Bangladesh also has one of the highest incidences of PTB (19%). Despite these high numbers of adolescent pregnancies and PTB, little is reported about the experiences of adolescent mothers in caring for their preterm babies, and the interventions needed to support them. The aim of this study was to explore gaps and opportunities for improved care for preterm babies among adolescent mothers and communities in rural Bangladesh. METHODS: We conducted a qualitative study in rural villages of Baliakandi sub-district of Bangladesh. Data collection involved in-depth interviews with adolescent mothers of premature and term babies, adult mothers with premature babies, and family members (n = 36); focus groups with community members (n = 5); and key informant interviews with healthcare providers (n = 13). Adolescent mothers with term and adult mothers with PTBs were included to elicit similarities and differences in understanding and care practices of PTB. A thematic approach was used for data analysis. RESULTS: We explored two major themes- perceptions and understanding of PTB; care practices and care-seeking for illnesses. We observed gaps and variations in understanding of preterm birth (length of gestation, appearance, causes, problems faced) and care practices (thermal management, feeding, weight monitoring) among all, but particularly among adolescents. Immediate natal and marital-kins were prominent in the narratives of adolescents as sources of informational and instrumental support. The use of multiple providers and delays in care-seeking from trained providers for sick preterm babies was noted, often modulated by the perception of severity of illness, cost, convenience, and quality of services. Health systems challenges included lack of equipment and trained staff in facilities to provide special care to preterm babies. CONCLUSION: A combination of factors including local knowledge, socio-cultural practices and health systems challenges influenced knowledge of, and care for, preterm babies among adolescent and adult mothers. Strategies to improve birth outcomes will require increased awareness among adolescents, women, and families about PTB and improvement in quality of PTB services at health facilities.

Impact of a school-based nutrition educational intervention on knowledge related to iron deficiency anaemia in rural Karnataka, India: A mixed methods pre-post interventional study.

OBJECTIVE: To understand the extent to which adolescent awareness about anaemia and anaemia prevention can be changed by nutrition messages received at school. DESIGN: Mixed-methods pre-post intervention study. SETTING: Three government schools in Bagalkot, Belagavi and Raichur districts of Karnataka, India. POPULATION: Students of grade six and seven and teachers involved in implementing the intervention. METHODS: An educational intervention was co-developed by school teachers and nutrition experts using locally adapted resource materials that consisted of lectures, role play and practical demonstrations. Seven half-hour educational sessions were delivered by school teachers over 7 weeks to 455 students. Pre- and post-intervention tests measured changes in adolescents' knowledge about anaemia. Semi-structured in-depth interviews with teachers and focus groups with students explored their reactions to the intervention. MAIN OUTCOME MEASURES: Knowledge score related to anaemia. RESULTS: The percentage of children with correct scores increased by 7.3-49.0 percentage points for the tested questions after implementation of the intervention. The mean knowledge score increased by 3.67 ± 0.17 (p < 0.01). During interviews, teachers and students highlighted high acceptance of the intervention and materials, an increase in awareness, a positive attitude towards changing behaviour around diet, an increase in the demand for iron and folic acid supplements and improved sharing of messages learned with peers and families. Challenges expressed included need for further training, time limitations and hesitancy in teaching about menstruation and pregnancy. CONCLUSIONS: Educational interventions carried out for adolescents by teachers in schools are effective in improving awareness and attitude related to anaemia and its prevention.

Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase.

BACKGROUND: Ureaplasma, a genus of the order Mycoplasmatales and commonly grouped with Mycoplasma as genital mycoplasma is one of the most common microbes isolated from women with infection/inflammation-associated preterm labor (PTL). Mycoplasma spp. produce sialidase that cleaves sialic acid from glycans of vaginal mucous membranes and facilitates adherence and invasion of the epithelium by pathobionts, and dysregulated immune response. However, whether Ureaplasma species can induce the production of sialidase is yet to be demonstrated. We examined U. parvum-infected vaginal epithelial cells (VECs) for the production of sialidase and pro-inflammatory cytokines. METHODS: Immortalized VECs were cultured in appropriate media and treated with U. parvum in a concentration of 1 × 105 DNA copies/ml. After 24 h of treatment, cells and media were harvested. To confirm infection and cell uptake, immunocytochemistry for multi-banded antigen (MBA) was performed. Pro-inflammatory cytokine production and protein analysis for sialidase confirmed pro-labor pathways. RESULTS: Infection of VECs was confirmed by the presence of intracellular MBA. Western blot analysis showed no significant increase in sialidase expression from U. parvum-treated VECs compared to uninfected cells. However, U. parvum infection induced 2-3-fold increased production of GM-CSF (p = 0.03), IL-6 (p = 0.01), and IL-8 (p = 0.01) in VECs compared to controls. CONCLUSION: U. parvum infection of VECs induced inflammatory imbalance associated with vaginal dysbiosis but did not alter sialidase expression at the cellular level. These data suggest that U. parvum's pathogenic effect could be propagated by locally produced pro-inflammatory cytokines and, unlike other genital mycoplasmas, may be independent of sialidase.

How are hospitals in England caring for women at risk of preterm birth in 2021? The influence of national guidance on preterm birth care in England: a national questionnaire.

BACKGROUND: National guidance (Saving Babies Lives Care Bundle Version 2 (SBLCBv2) Element 5) was published in 2019, with the aim to standardise preterm care in England. We plan to identify how many preterm birth surveillance clinics there are in England, and to define current national management in caring for women who are both asymptomatic and high-risk of preterm birth, and who arrive symptomatically in threatened preterm labour, to assist preterm management both nationally and internationally. METHODS: An online survey comprising of 27 questions was sent to all maternity units in England between February 2021 to July 2021. RESULTS: Data was obtained from 96 units. Quantitative analysis and free text analysis was then undertaken. We identified 78 preterm birth surveillance clinics in England, an increase from 30 preterm clinics in 2017. This is a staggering 160% increase in 4 years. SBLCBv2 has had a considerable impact in increasing preterm birth surveillance clinic services, with the majority (61%) of sites reporting that the NHS England publication influenced their unit in setting up their clinic. Variations exist at every step of the preterm pathway, such as deciding which risk factors warrant referral, distinguishing within particular risk factors, and offering screening tests and treatment options. CONCLUSIONS: While variations in care still do persist, hospitals have done well to increase preterm surveillance clinics, under the difficult circumstances of the COVID pandemic and many without specific additional funding.

Pharmacokinetics and placental transfer of dolutegravir in pregnancy.

Dolutegravir is currently recommended by the WHO as the preferred first-line treatment for all people with HIV, including pregnant women. Estimates indicate that, by 2024, nearly 22 million adults in low- and middle-income countries will have transitioned to dolutegravir-based ART. It is therefore critical that there is a clear appreciation and understanding of the risks that may be associated with in utero exposure to dolutegravir. In this review we consolidate data from studies on dolutegravir and the placenta. The studies have largely focused on the pharmacokinetics and placental transfer of dolutegravir in pregnancy. These include studies on transplacental transfer of dolutegravir, ex vivo placenta perfusion models, physiologically based pharmacokinetic (PBPK) models and animal studies. The data available clearly demonstrate that placental transfer of dolutegravir occurs in moderate to high concentrations. Intracellular placental dolutegravir has been demonstrated in the placental villous tissue. There are limited data suggesting that pregnancy is associated with decreased maternal dolutegravir levels. In addition, PBPK models have great potential in predicting the passage of drugs through the placenta and further contributing towards the elucidation of fetal exposure. The animal studies available demonstrate that in utero dolutegravir exposure can be associated with neural tube defects. Taking into consideration that antiretroviral exposure may be associated with poor placental development or function and increased risk of adverse effects to the fetus, it is crucially important that these risks are evaluated, especially with the rapid scale up of dolutegravir-based ART into national treatment programmes.

Understanding the relationship between social determinants of health and maternal mortality: Scientific Impact Paper No. 67.

Within this document we use the terms pregnant woman and women's health. However, it is important to acknowledge that it is not only people who identify as women for whom it is necessary to access care. Obstetric and gynaecology services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth.

The acceptability of cervical electrical impedance spectroscopy within a multi-modal preterm birth screening package: a mixed methods study.

BACKGROUND: Reducing the rate of preterm birth is a cornerstone of global efforts to address child mortality, however existing screening tests offer imperfect prediction. Cervical electrical impedance spectroscopy (EIS) is a novel technique to quantify the ripening changes which precede labour. Mid-trimester EIS measurements have been shown to accurately predict preterm birth in asymptomatic women. This study aimed to comprehensively evaluate the acceptability of cervical EIS to low and high-risk women as part of a package of screening tests performed during a larger prospective trial. METHODS: In this parallel convergent mixed methods study, 40 women completed questionnaires before and after screening tests (EIS, cervical length measurement and fetal fibronectin quantification). Quantitative outcomes were anxiety levels before and after screening (Spielberger State Trait Anxiety Inventory, STAI-6), pain (Short Form McGill Pain Questionnaire) and ratings of EIS device appearance and test acceptability (visual analogue scales). Twenty-one women (11 high-risk, 10 low-risk) also attended a semi-structured qualitative interview. Interviews were recorded and transcribed, then thematic analysis was performed. A convergence coding matrix was constructed to enable triangulation of quantitative and qualitative results. RESULTS: High risk women demonstrated a significant reduction in anxiety following screening (mean STAI-6 score 34.5 vs. 29.0, p = 0.002). A similar trend was observed among low-risk participants. Ratings of pain, EIS device appearance and procedural acceptability did not differ between groups. Mean pain ratings were low (visual analogue scale 0.97 and 1.01), comparing favourably to published evaluations of conventional screening tests. Qualitative analysis provided insight into both the physical consequences and emotional experiences of screening. Additional determinants of the screening experience included device design, pre-existing perspectives on intimate examination, attitudes to knowledge in pregnancy and interaction with clinical staff. Finally, a range of practical considerations regarding wider use of EIS were identified, with valuable complementary detail regarding acceptability for use in antenatal care. CONCLUSIONS: Cervical EIS is well tolerated and acceptable to both low and high-risk women when performed as part of a multi-modal screening package. These results provide useful insights to inform the design of future study and screening protocols.

The Tommy's Clinical Decision Tool, a device for reducing the clinical impact of placental dysfunction and preterm birth: protocol for a mixed-methods early implementation evaluation study.

BACKGROUND: Disparities in stillbirth and preterm birth persist even after correction for ethnicity and social deprivation, demonstrating that there is wide geographical variation in the quality of care. To address this inequity, Tommy's National Centre for Maternity Improvement developed the Tommy's Clinical Decision Tool, which aims to support the provision of "the right care at the right time", personalising risk assessment and care according to best evidence. This web-based clinical decision tool assesses the risk of preterm birth and placental dysfunction more accurately than current methods, and recommends best evidenced-based care pathways in a format accessible to both women and healthcare professionals. It also provides links to reliable sources of pregnancy information for women. The aim of this study is to evaluate implementation of Tommy's Clinical Decision Tool in four early-adopter UK maternity services, to inform wider scale-up. METHODS: The Tommy's Clinical Decision Tool has been developed involving maternity service users and healthcare professionals in partnership. This mixed-methods study will evaluate: maternity service user and provider acceptability and experience; barriers and facilitators to implementation; reach (whether particular groups are excluded and why), fidelity (degree to which the intervention is delivered as intended), and unintended consequences. Data will be gathered over 25 months through interviews, focus groups, questionnaires and through the Tommy's Clinical Decision Tool itself. The NASSS framework (Non-adoption or Abandonment of technology by individuals and difficulties achieving Scale-up, Spread and Sustainability) will inform data analysis. DISCUSSION: This paper describes the intervention, Tommy's Clinical Decision Tool, according to TiDIER guidelines, and the protocol for the early adopter implementation evaluation study. Findings will inform future scale up. TRIAL REGISTRATION: This study was prospectively registered on the ISRCTN registry no. 13498237 , on 31st January 2022.

Mechanistic Insights into Immune Suppression and Evasion in Bacterial Vaginosis.

The immunological response to bacterial vaginosis (BV) remains poorly understood and recurrent BV is still a major public health burden especially in the pregnant population. This article reviews the potential mechanisms by which BV-associated bacteria suppress and circumvent the host and microbial defence responses, and propagate their survival/dominance without overt inflammation. We discuss the composition of cervicovaginal mucosal barrier and the mechanism by which BV circumvents host defence: the degradation of the mucosal barrier and immunoglobulin A (IgA); the BV-associated organism Gardnerella vaginalis haemolysin (vaginolysin); diminished IgA response against vaginolysin; mucosal sialic acid degradation, foraging and depletion; inhibition of IL-8-induced neutrophilic infiltration; and metabolite-induced incapacitation of neutrophil and monocyte chemotaxis. We also highlight the tolerance/resistance to both host and antimicrobial molecules mounted by BV-associated biofilms. A plausible role of sialic acid-binding immunoglobulin-like lectins (SIGLECS) was also suggested. Sialidase, which is often produced by G. vaginalis, is central to the immunosuppression, relapse and recurrence observed in BV, although it is supported by other hydrolytic enzymes, vaginolysin and immunomodulatory metabolites.

Cervical Tissue Hydration Level Monitoring by a Resonant Microwave Coaxial Probe.

Cervical tissue hydration level is one of the most important parameters to monitor in the early diagnosis of preterm birth. Electrical-impedance-spectroscopy-based techniques are often used, but they suffer from limited accuracy. Open microwave coaxial probes have been widely used as a broadband dielectric characterization technique for human tissue samples due to their versatility, but with limited accuracy due to their nonresonant nature. In this work, a resonant microwave open coaxial probe with multiple harmonic resonances is proposed as a sensing platform for tissue-hydration-level monitoring. The mechanical design was analyzed and verified by finite-element full 3D electromagnetic simulation and experiments. Dominant sources of errors and the ways to mitigate them were discussed. In vitro experiments were carried out on human cervix samples to verify the precision and accuracy by comparing the results to a commercial skin-hydration sensor. The proposed sensor shows mean fractional frequency shift of (3.3 ± 0.3) × 10-4 per unit % over the entire data. This translates into an absolute frequency shift (ΔfN) of 252 ± 23 kHz/%, 455 ± 41 kHz/%, and 647 ± 57 kHz/% at second, fourth, and sixth harmonic resonance, respectively.

Shifting Social Norms and Adolescent Girls' Access to Sexual and Reproductive Health Services and Information in a South African Township.

Despite policy on adolescent sexual and reproductive health (SRH) services and education, teen pregnancies remain common in South Africa. Social norms and cultural resistance are a well-documented challenge for SRH program implementation in South Africa, and beyond. To gain insight on the complex picture of adolescents' access to SRH information and services in a peri-urban township, we explored this topic from a diversity of perspectives, carrying out 86 interviews to capture perceptions of adolescents, their parents, community members, and health professionals. Our research shows that despite the taboo nature of the issue of adolescent SRH, individual positions on adolescent access to SRH services and information are shifting and diverse, and are influenced by factors other than cultural norms. This research serves as a reminder to avoid simplistic reference to "culture" as a way of explaining health-related behaviors and people's responses to health challenges.

The effect of COVID-19 on maternal newborn and child health (MNCH) services in Bangladesh, Nigeria and South Africa: call for a contextualised pandemic response in LMICs.

Global response to COVID-19 pandemic has inadvertently undermined the achievement of existing public health priorities and laregely overlooked local context. Recent evidence suggests that this will cause additional maternal and childhood mortality and morbidity especially in low- and middle-income countries (LMICs). Here we have explored the contextual factors influencing maternal, neonatal and children health (MNCH) care in Bangladesh, Nigeria and South Africa amidst the pandemic. Our findings suggest that between March and May 2020, there was a reduction in utilisation of basic essential MNCH services such as antenatal care, family planning and immunization due to: a) the implementation of lockdown which triggered fear of contracting the COVID-19 and deterred people from accessing basic MNCH care, and b) a shift of focus towards pandemic, causing the detriment to other health services, and c) resource constraints. Taken together these issues have resulted in compromised provision of basic general healthcare. Given the likelihood of recurrent waves of the pandemic globally, COVID-19 mitigation plans therefore should be integrated with standard care provision to enhance system resilience to cope with all health needs. This commentary suggests a four-point contextualised mitigation plan to safeguard MNCH care during the pandemic using the observed countries as exemplars for LMIC health system adaptations to maintain the trajectory of progress regarding sustainable development goals (SDGs).

Acute Villitis and Intravascular Microorganisms in Fetal Vessels: A Case Report and Literature Review of an Unusual Histopathological Finding.

Optimal management of intrauterine infection to avoid serious adverse perinatal outcomes entails prompt administration of antibiotics and consideration of early delivery of the fetus to remove the focus of infection. We report an unusual case of preterm chorioamnionitis which did not improve with sensitive antibiotics, or delivery of the fetus, and ultimately required an emergency hysterectomy to save the mother's life. Interestingly, subsequent histopathological analysis of the post-hysterectomy specimen did not reveal myometrial necrosis or infectious microorganisms. The placental pathological examination, on the other hand, showed evidence of necrotising chorioamnionitis accompanied by a rarely reported lesion: acute villitis with abundant intravascular Escherichia coli, a finding which is strongly associated with fetal demise and adverse maternal outcomes.

Postnatal pelvic floor muscle stiffness measured by vaginal elastometry in women with obstetric anal sphincter injury: a pilot study.

INTRODUCTION AND HYPOTHESIS: Vaginal childbirth is associated with pelvic floor muscle (PFM) damage in a third of women. The biomechanics prediction, detection and management of PFM damage remain poorly understood. We sought in this pilot study to determine whether quantifying PFM stiffness postnatally by vaginal elastometry, in women attending a perineal trauma clinic (PTC) within 6 months of obstetric anal sphincter injury, correlates with their antecedent labour characteristics, pelvic floor muscle damage, or urinary/bowel/sexual symptoms, to inform future definitive prospective studies. METHODS: In this pilot study, we measured postnatal PFM stiffness by vaginal elastometry in 54 women. A subset of participants (n = 14) underwent magnetic resonance imaging (MRI) to define any levator ani (LA) muscle defects from vaginal childbirth. We investigated the association of PFM stiffness with demographics, labour and delivery characteristics, clinical features and MRI evidence of LA damage. RESULTS: Raised maternal BMI was associated with reduced pelvic floor stiffness (r = -0.4; p < 0.01). Higher stiffness values were associated with forceps delivery for delayed second stage of labour (n = 14) vs non-forceps vaginal delivery (n = 40; 630 ± 40 N/m vs 500 ± 30 N/m; p < 0.05), and a non-significant trend towards longer duration of the second stage of labour. Women with urinary, bowel or sexual symptoms (n = 37) demonstrated higher pelvic floor stiffness values than those without (570 ± 30 N/m vs 450 ± 40 N/m; p < 0.05). CONCLUSIONS: A history of delayed second stage of labour and forceps delivery was associated with higher PFM stiffness values in the postnatal period. Whether high pelvic muscle stiffness antenatally is a risk factor for instrumental vaginal delivery and LA avulsion is unknown.

Differential cytokine and metabolite production by cervicovaginal epithelial cells infected with Lactobacillus crispatus and Ureaplasma urealyticum.

INTRODUCTION: We sought to quantify targeted metabolites (d-lactate, pyruvate, urea, ammonia) and the cytokine IL-8 produced by human cervicovaginal epithelial cells co-cultured with Ureaplasma urealyticum (a preterm birth-associated bacterium) or Lactobacillus crispatus (a healthy vaginal commensal associated with term birth). METHODS: Concentrations of d-lactate, pyruvate, urea and ammonia measured by enzyme-based spectrophotometry and IL-8 by ELISA were determined and compared between monolayer-cultured HeLa cells (ATCC 35241) infected with strains of U. urealyticum (ATCC 27618, 0.5 mL = 3640 CFU/mL, U. urealyticum) or L. crispatus (ATCC 33820, MOI = 10,000, 1000 and 100, L. crispatus) and incubated in 5% CO2 at 37 °C for 24 h. Uninfected HeLa cells (Hc) were used as controls and cytotoxicity was determined by the amount (optical density) of lactate dehydrogenase (LDH) released by the dead HeLa cells. RESULTS: The amount of LDH released by untreated Hc (P = 0.002) and U. urealyticum-infected cells (P < 0.0001) was higher than those of L. crispatus-infected cells, with U. urealyticum-infected cells recording the highest % cytotoxicity and L. crispatus-infected cells MOI 10,000 (Lc10,000) the least (P < 0.0001). Though there was no significant difference in the concentration of urea between the samples, U. urealyticum-infected cells showed higher ammonia compared to other samples (p = 0.03). In contrast, all L. crispatus samples had higher d-lactate than untreated Hc (p = 0.01) and U. urealyticum-infected cells (P = 0.01). Also, Lc10,000 had the highest d-lactate (p = 0.001) and lowest pyruvate (P = 0.04, excluding UU) compared to other samples. Furthermore, U. urealyticum-infected cells produced the highest IL-8 (P = 0.01) compared to other samples, with Lc10,000 producing undetectable levels. CONCLUSION: Infection of cervicovaginal epithelial cells by U. urealyticum stimulates production of ammonia from urea and induces elevated IL-8 production possibly leading to significantly higher cytotoxicity. In contrast, L. crispatus appeared protective against HeLa cell inflammation and death, producing more d-lactate and less IL-8, consistent with a role for L. crispatus in promoting vaginal floral health and reducing infection/inflammation-associated preterm birth.

Is portable foetal electrocardiogram monitor feasible for foetal heart rate monitoring of small for gestational age foetuses in the home environment.

Small-for-gestational-age (SGA) foetuses are at greater risk of complications than normal foetuses. Studies have demonstrated that foetal electrocardiogram (ECG) device (Monica-AN24) can be employed for monitoring foetal heart rate (FHR). However, its reliability and acceptability has not been assessed in SGA foetuses. This study was aimed at: (a) determining the acceptability of wearing the device more than once, (b) investigating the reliability of acquiring successful FHR data at different gestation. Patients with singleton non-anomalous foetus >24 weeks gestation and an estimated foetal weight below tenth percentile were recruited. Thirty-five women wore the device once. Twenty-four of these wore second time (68.6%). Overall, success-rate of FHR signals was 48.6% and increased to 68.8% beyond 34 weeks gestation. Foetal ECG is a promising method for monitoring SGA foetus >34 weeks gestation. Compared to day recordings, foetal signals were more reliable at night. Further studies are required before its clinical utility can be ascertained. IMPACT STATEMENT What is already known on this subject? Pregnancies that are affected by small-for-gestational-age (SGA) foetus pose a major public health problem and are associated with increased perinatal morbidity and mortality. There is no consensus on the optimal timing of delivery. Current methods employed for monitoring SGA foetuses include ultrasound scans for foetal-biometry and Doppler assessments. However, they provide a snapshot of information on foetal well-being, restrict patient mobility and cannot be employed over long-time periods. It is plausible that ambulatory foetal-ECG device that enable monitoring over a longer time period may better inform decisions about the timing of delivery. What do the results of this study add? Trans-abdominal foetal-ECG is a promising method of monitoring SGA foetus in the home setting with a success rate of acquiring reliable foetal heart rate (FHR) data over 90% at night time. What are the implications of these findings for clinical practice and/or further research? Overall, the study approved the concept of long-term home monitoring and has highlighted the facilitators and barriers to wearing the monitor in clinical care. These observations can be used to undertake robust research to assess the use of foetal-ECG monitor singly or in conjunction with current monitoring techniques for optimal foetal surveillance.

Imbalanced Angiogenesis in Peripartum Cardiomyopathy　- Diagnostic Value of Placenta Growth Factor.

BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16-22] and 98 [IQR 78-126] ng/mL, respectively; P<0.001) and the sFlt-1/PlGF ratio was lower (9.8 [6.6-11.3] and 1.2 [0.9-2.8], respectively; P<0.001). The sFlt-1/PlGF ratio was lower in PPCM than in normal deliveries (1.2 [0.9-2.8] vs. 94.8 [68.8-194.1], respectively; P<0.0001). The area under the curve for PlGF (cut-off value: 50ng/mL) and/or the sFlt-1/PlGF ratio (cut-off value: 4) to distinguish PPCM from either normal delivery or AHF was >0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3-1.7] and 0.3 [IQR 0.3-1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101-4,050] ng/mL; P<0.001). CONCLUSIONS: Plasma of PPCM patients shows imbalanced angiogenesis. High PlGF and/or low sFlt-1/PlGF may be used to diagnose PPCM.

Second Harmonic Generation microscopy reveals collagen fibres are more organised in the cervix of postmenopausal women.

BACKGROUND: During labour, the cervix undergoes a series of changes to allow the passage of the fetoplacental unit. While this visible transformation is well-described, the underlying and causative microscopic changes, in which collagen plays a major role, are poorly understood and difficult to visualise. Recent studies in mice and humans have shown that Second Harmonic Generation (SHG) microscopy, a non-destructive imaging technique, can detect changes in the cervical collagen. However, the question of whether SHG can identify changes in the arrangement of cervical collagen at different physiological stages still needs addressing. Therefore, this study aimed to compare the cervical collagen alignment between pre- and postmenopausal women using SHG and to generate proof-of-concept data prior to assessing this technique in pregnancy. METHODS: Cervical biopsies from premenopausal (n = 4) and postmenopausal (n = 4) multiparous women undergoing hysterectomy for benign conditions were cross-sectionally scanned using an upright confocal microscope. SHG images were collected in Z-stacks and qualitatively evaluated using semi-quantitative scoring (0-3 in ascending degree of alignment) by assessors who were unaware of the classification of the SHG images, and quantitatively, using 2D Fourier transformation analysis. The dominant orientation and difference in dispersion of collagen fibres in each z-stack (X ± SD) was calculated and compared between groups. RESULTS: Qualitatively, collagen fibres appeared more organised in postmenopausal women, [premenopausal: median 0, range (0-1), postmenopausal: median 1.25, range (1-3); X 2 (df = 5) = 19.35, p = 0.002]. Quantitatively, there was a statistically significant difference in collagen fibre dispersion between premenopausal (5.39° ± 12.68°) and postmenopausal women (-1.58° ± 8.24°), [Welch's t-test (245.54) = 5.54, p < 0.01], with no significant differences in dispersion within each group [premenopausal, Welch's F (7, 57.23) = 1.84, p = 0.098; postmenopausal, Welch's F (7, 57.28) = 1.39, p = 0.23]. CONCLUSION: These results suggest an increased alignment of cervical collagen in postmenopausal women which may result in increased stiffness and reduced compliance, confirm that SHG microscopy can provide qualitative and quantitative information about cervical collagen orientation without sample preparation, and support further research to explore SHG as a means of assessing cervical remodelling to predict the timing of term and preterm labour.

Deprivation and poor psychosocial support are key determinants of late antenatal presentation and poor fetal outcomes--a combined retrospective and prospective study.

BACKGROUND: Published guidelines emphasise the need for early antenatal care to promote maternal and neonatal health. Inadequate engagement with antenatal care is associated with adverse pregnancy outcomes including maternal death. The factors that influence the uptake and utilisation of maternity care services are poorly understood. We retrospectively explore a large maternity database of births in a large referral UK hospital to capture the socio-demographic factors that influence late pregnancy booking, and then prospectively compare the stress and social support status of consenting early and late-booking women. METHODS: Retrospective socio-demographic and clinical outcome data on 59,487 women were collected from the maternity database record of births between 2002 and 2010 at the Jessop Wing Hospital, Sheffield UK. In a follow-on prospective survey between October 2012 and May 2013 a convenience cohort of early and late bookers for antenatal care were then studied using validated scales for fetomaternal attachment, stress and anxiety, and social support. RESULTS: In our retrospective study, pregnancy during the teenage years, higher parity, non-white ethnic background, unemployment and smoking were significantly associated with late access to antenatal services and poor fetal outcomes (P < 0.001). However, late booking per se did not predict adverse fetal outcomes, when socio-demographic factors were accounted for. A high index of multiple deprivation (IMD) score remained independently associated with late booking when confounding factors such as ethnicity and employment status were controlled for in the model (P = 0.03). Our prospective data demonstrated that women who book late were more likely to be unmarried (OR: 3.571, 95 % CI: 1.464-8.196, p = .005), of high parity (OR: 1.759, 95 % CI: 1.154-2.684, P = 0.009), and have lower social support than early bookers (P = 0.047). CONCLUSIONS: Of the many complex sociocultural factors that influence the timing of maternal engagement with antenatal care, multiple deprivation and poor social support remain key factors. Improving access to prenatal care requires in-depth exploration of the relationship between maternal psychosocial health indices, social support mechanisms and engagement with antenatal care. Findings from these studies should inform interventions aimed at improving access to care.