Fetal anomaly diagnosis and termination of pregnancy in Ireland: a service evaluation following implementation of abortion services in 2019.

BACKGROUND: Approximately 3% of pregnancies are diagnosed with a fetal anomaly, of which a proportion is fatal or life-limiting. The introduction of legislation for termination of pregnancy in Ireland in 2019 for conditions "likely to lead to the death of the fetus" made termination of pregnancy for "fatal fetal anomaly" an option for pregnant women in Ireland. OBJECTIVE: This study examined all cases of termination of pregnancy performed for major fetal anomaly over the first 3 years of service implementation, including cases that did not meet the legal criteria, resulting in women traveling outside Ireland for abortion care. STUDY DESIGN: A retrospective service evaluation of tertiary fetal medicine clinics in 2 tertiary maternity hospitals between 2019 and 2021 was undertaken. We compared pregnancies of patients diagnosed with fatal fetal anomaly who underwent termination of pregnancy in Ireland with those of patients who did not meet the legal criteria and hence traveled outside Ireland for termination of pregnancy. RESULTS: Overall, 139 pregnancies met the inclusion criteria; 83 (59.7%) patients had termination of pregnancy in the tertiary maternity hospital (local), and 56 (40.3%) traveled abroad, mainly to the United Kingdom. Demographic characteristics were similar between the 2 groups, as was gestation at diagnosis and delivery. All cases where termination of pregnancy was local were discussed at fetal medicine multidisciplinary meetings, as opposed to 34% of cases of patients who ultimately traveled outside Ireland for termination of pregnancy. The most common indication (25/83; 30.1%) for local termination of pregnancy was trisomy 18, followed by anencephaly. Traveling to obtain abortion care was mainly due to diagnosis of trisomy 21 (30/56; 53.6%), followed by other multiple structural anomalies/syndromes deemed locally as not meeting the legal criteria. CONCLUSION: Legislation for termination of pregnancy for fetal anomaly, restricted to fatal diagnoses, is difficult to implement, requires significant multidisciplinary input, and can lead to limited services for pregnancies diagnosed with major fetal anomalies. Our findings emphasize the impact of legislative barriers to abortion care for fetal anomaly and the need for policies and services that support women's access to termination of pregnancy for fetal anomaly.

The prediction of morbidity related to vaginal delivery in nulliparous women - A secondary analysis from the genesis multicenter trial.

OBJECTIVE: In the prospective multicenter Genesis study, we developed a prediction model for Cesarean delivery (CD) in term nulliparous women. The objective of this secondary analysis was to determine whether the Genesis model has the potential to predict maternal and neonatal morbidity associated with vaginal delivery. STUDY DESIGN: The national prospective Genesis trial recruited 2,336 nulliparous women with a vertex presentation between 39 + 0- and 40 + 6-weeks' gestation from seven tertiary centers. The prediction model used five parameters to assess the risk of CD: maternal age, maternal height, body mass index, fetal head circumference and fetal abdominal circumference. Simple and multiple logistic regression analyses were used to develop the Genesis model. The risk score calculated using this model were correlated with maternal and neonatal morbidity in women who delivered vaginally: postpartum hemorrhage (PPH), obstetric anal sphincter injury (OASI), shoulder dystocia, one- and five-minute Apgar score ≤ 7, neonatal intensive care (NICU) admission, cephalohematoma, fetal laceration, nerve palsy and fractures. The morbidities associated with spontaneous vaginal delivery were compared with those associated with operative vaginal delivery (OVD). The likelihood ratios for composite morbidity and the morbidity associated with OVD based on the Genesis risk scores were also calculated. RESULTS: A total of 1,845 (79%) nulliparous women had a vaginal delivery. A trend of increasing intervention and morbidity was observed with increasing Genesis risk score, including OVD (p < 0.001), PPH (p < 0.008), NICU admission (p < 0.001), low Apgar score at one-minute (p < 0.001) and OASI (p = 0.009). The morbidity associated with OVD was significantly higher compared to spontaneous vaginal delivery, including NICU admission (p < 0.001), PPH (p = 0.022), birth injury (p < 0.001), shoulder dystocia (p = 0.002) and Apgar score of<7 at one-minute (p < 0.001). The positive likelihood ratios for composite outcomes (where the OVD was excluded) increases with increasing risk score from 1.005 at risk score of 5% to 2.507 for risk score of>50%. CONCLUSION: In women who ultimately achieved a vaginal birth, we have shown more maternal and neonatal morbidity in the setting of a Genesis nomogram-determined high-risk score for intrapartum CD. Therefore, the Genesis prediction tool also has the potential to predict a more morbid vaginal delivery.

Feasibility study protocol of a pragmatic, randomised controlled pilot trial: membrane sweeping to prevent post-term pregnancy-the MILO Study.

BACKGROUND: Post-term pregnancy is associated with an increased risk of maternal complications, respiratory distress and trauma to the neonate. Amniotic membrane sweeping has been recommended as a simple procedure to promote the spontaneous onset of labour. However, despite its widespread use, there is an absence of evidence on (a) its effectiveness and (b) its optimal timing and frequency. The primary aim of the MILO Study is to inform the optimal design of a future definitive randomised trial to evaluate the effectiveness (including optimal timing and frequency) of membrane sweeping to prevent post-term pregnancy. We will also assess the acceptability and feasibility of the proposed trial interventions to clinicians and women (through focus group interviews). METHODS/DESIGN: Multicentre, pragmatic, parallel-group, pilot randomised controlled trial with an embedded factorial design. Pregnant women with a live, singleton foetus ≥ 38 weeks gestation; cephalic presentation; longitudinal lie; intact membranes; English speaking and ≥ 18 years of age will be randomised in a 2:1 ratio to membrane sweep versus no membrane sweep. Women allocated randomly to a sweep will then be randomised further (factorial component) to early (from 39 weeks) versus late (from 40 weeks) sweep commencement and a single versus weekly sweep. The proposed feasibility study consists of four work packages, i.e. (1) a multicentre, pilot randomised trial; (2) a health economic analysis; (3) a qualitative study; and (4) a study within the host trial (a SWAT). Outcomes to be collected include recruitment and retention rates, compliance with protocol, randomisation and allocation processes, attrition rates and cost-effectiveness. Focus groups will be held with women and clinicians to explore the acceptability and feasibility of the proposed intervention, study procedures and perceived barriers and enablers to recruitment. DISCUSSION: The primary aim of the MILO Study is to inform the optimal design of a future definitive randomised trial to evaluate the effectiveness (including optimal timing and frequency) of membrane sweeping to prevent post-term pregnancy. Results will inform whether and how the design of the definitive trial as originally envisaged should be delivered or adapted. TRIAL REGISTRATION: ClinicalTrials.gov NCT04307199 . Registered on 12 March 2020.

Spontaneous Human Myometrial Contractility in the Third Trimester of Pregnancy in Relation to Past Mode of Delivery.

OBJECTIVE: It is well established that women with a previous vaginal delivery have higher success rates in relation to vaginal birth after cesarean than those without. The aim of this study was to examine the effect of past mode of delivery on contractile parameters of human myometrium in vitro. STUDY DESIGN: Myometrial strips were excised from 64 women at cesarean delivery (CD) and recordings of spontaneous contractile activity analyzed and compared across three clinical groups: (1) women with no previous delivery (Group 1); (2) women with CD only (Group 2); and (3) women with a history of vaginal delivery and CD (Group 3). RESULTS: Myometrial samples from women in Group 3, women who had a previous vaginal delivery, had a significantly greater maximum amplitude of contractions (p < 0.05), a greater force (mean contractile force) of contractions (p < 0.01), and a faster rate of rise (p < 0.01) and relaxation of contractions (p < 0.05) than those in Groups 1 and 2. CONCLUSION: Many of the functional parameters of human uterine contractions are altered, or enhanced, in the women who have had a previous vaginal delivery, when compared with those without. This may partly explain the clinical differences observed in labor.

Inter-hospital comparison of Cesarean delivery rates should not be considered to reflect quality of care without consideration of patient heterogeneity: An observational study.

OBJECTIVE: Contemporary approaches to monitoring quality of care in obstetrics often focus on comparing Cesarean Delivery rates. Varied rates can complicate interpretation of quality of care. We previously developed a risk prediction tool for nulliparous women who may require intrapartum Cesarean delivery which identified five key predictors. Our objective with this study was to ascertain if patient heterogeneity can account for much of the observed variation in Cesarean delivery rates, thereby enabling Cesarean delivery rates to be a better marker of quality of care. MATERIALS AND METHODS: This is a secondary analysis of the Genesis study. This was a large prospective study of 2336 nulliparous singleton pregnancies recruited at seven hospitals. A heterogeneity score was calculated for each hospital. An adjusted Cesarean delivery rate was also calculated incorporating the heterogeneous risk score. RESULTS: A cut-off at the 90th percentile was determined for each predictive factor. Above the 90th percentile was considered to represent 'high risk' (with the exception of maternal height which identified those below the 10th percentile). The patient heterogeneous risk score was defined as the number of risk factors > 90th percentile (<10th percentile for height). An unequal distribution of high-risk patients between centers was observed (p < 0.001). The correlation between the Cesarean delivery rate and the patient heterogeneous risk score was high (0.76, p < 0.05). When adjusted for patient heterogeneity, Cesarean delivery rates became closer aligned. CONCLUSION: Inter-institutional diversity is common. We suggest that crude comparison of Cesarean delivery rates between different hospitals as a marker of care quality is inappropriate. Allowing for marked differences in patient characteristics is essential for correct interpretation of such comparisons.

Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes.

INTRODUCTION: Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two CYP24A1 missense variants. METHODS: The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine. RESULTS: The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted calcium of 3.27 (upper reference limit (URL: 2.30) mmol/L), suppressed iPTH (<6 ng/L), elevated 25(OH)D (264 (URL: 55) nmol/L) and elevated 1,25(OH)D (293 (URL: <280) pmol/L). Ionized calcium was 1.55 (URL: 1.28) mmol/L. Sanger sequencing revealed two heterozygous missense variants in the CYP24A1: p.(Arg439Cys), R439C and p.(Trp275Arg), W275R. The proband's brother and sister had the same genotype. The brother had intermittent hypercalcaemia and hypervitaminosis D. Only the sister had a history of nephrolithiasis. The proband's daughter and two nephews were heterozygous for the R439C variant. The proband and her brother frequently had elevated 25(OH)D:24,25(OH)2D ratios (>50) during follow-up. CONCLUSIONS: W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family.

Concentrations of perfluoroalkyl substances in human milk from Ireland: Implications for adult and nursing infant exposure.

Concentrations of 10 perfluoroalkyl substances (PFASs) were measured in 16 pools of human milk from Ireland. Only four PFASs were detected (PFOA, PFNA, PFHxS and PFOS), with concentrations dominated by PFOA which was detected in all samples at a median of 0.10 ng/mL. Concentrations and the relative abundance of PFASs in human milk from Ireland are within the range reported for other countries. Estimated exposures for nursing infants to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) do not suggest a health concern. A one compartment pharmacokinetic model was used to predict the intakes of PFOS and PFOA required to support the observed concentrations in human milk. This suggests current adult exposure in Ireland to PFOS is below the provisional tolerable weekly intake (TWI) proposed by EFSA. In contrast, the model predicts that the maximum concentration detected in human milk in this study, implies a level of adult exposure that would exceed EFSA's provisional TWI for PFOA. As exposure of the Irish population to PFASs via drinking water, indoor air and dust is well-characterised, current understanding suggests that the major contributor to overall exposure of the Irish population is via the diet and/or less well-studied pathways like dermal uptake from PFAS-containing fabrics and cosmetics.

Emerging and legacy brominated flame retardants in the breast milk of first time Irish mothers suggest positive response to restrictions on use of HBCDD and Penta- and Octa-BDE formulations.

The brominated flame retardants (BFRs) hexabromocyclododecane (HBCDD), eight polybrominated diphenyl ethers (PBDEs), and decabromodiphenyl ethane (DBDPE) were measured in 16 pools of human milk from Ireland. Concentrations of BDEs-47, -99, -100, -153, and HBCDD were significantly lower (p < 0.05) than those in Irish human milk collected in 2011. In contrast, concentrations of BDE-209 in our study exceeded those in 2011, and while decabromodiphenyl ethane (DBDPE) was not detected in 2011 it was detected in 3 of our samples. This suggests increased use of DBDPE and that while restrictions on the Penta- and Octa-BDE formulations are reducing human exposure, those on Deca-BDE use have yet to reduce body burdens. Estimated exposures for nursing infants to all target BFRs do not suggest a health concern. A one compartment pharmacokinetic model was used to predict body burdens arising from BFR intakes via air, dust and diet. While for most targeted BFRs, predicted and observed body burdens derived from our human milk data compared reasonably well; predicted BDE-209 and DBDPE values were substantially lower than observed. This suggests exposure pathways not included in the model like dermal uptake from fabrics may be important, and highlights knowledge gaps about the human half-lives and bioavailability of these contaminants.

Low-Temperature Pack Aluminization Process on Pipeline Steel To Inhibit Asphaltene Deposition.

Asphaltene deposition in petroleum refineries is known to be problematic as it reduces efficiency and may lead to structural failure or production downtime. Though several successful approaches have been utilized to limit deposition through the addition of dispersants and inhibitors to petroleum, these methods require constant intervention and are often expensive. In this study, we demonstrate an innovative technique to engineer the surface chemistry of pipeline steels to inhibit asphaltene deposition. Pack aluminization, a standard industrial-scale chemical vapor deposition process, is employed at a low temperature of 600 °C to aluminize API 5L X65 high strength pipe steel substrates. The results showed deposit-free steel surfaces after high-pressure and high-temperature fouling experiments. The improvement is attributed to the formation of an aluminide intermetallic phase of Fe2Al5, which changes the native oxide chemistry to favor alumina over hematite. The continuous passivating oxide scale, acting as a protective barrier, mitigates asphaltene deposition and sulfidic corrosion. Because this process is based on alloying the surface of the steel and is not a coating with a weakly adhered interface, it is not prone to delamination, and it can be re-formed when damaged within the aluminized region. The combination of low-cost processing and improved antifouling characteristics makes surface chemistry modification of steel a promising preventative approach against asphaltene deposition.

Effects of maternal parity on response of human myometrium to oxytocin and ergometrine in vitro.

OBJECTIVE: The aim of this study was to compare the effects of oxytocin and ergometrine on the intrinsic contractile parameters of human uterine smooth muscle at term between primiparous and multiparous women. STUDY DESIGN: Myometrial biopsies were obtained from women undergoing planned caesarean section at term. The biopsies were dissected into eight uniform strips and mounted in tissue baths for isometric recording. The strips were challenged with increasing concentrations of oxytocin and ergometrine. Parameters of contractile activity, including mean contractile force (MCF) and maximum amplitude of contractions (MAMP) were recorded and analysed. Results were compared between primiparous (Group 1) and multiparous (Group 2) women. RESULTS: Myometrial biopsies were obtained from n = 11 donors (88 tissue strips), of which n = 5 were Group 1 and n = 6 were Group 2. In relation to oxytocin, the MAMP value observed was significantly greater in Group 2 than in Group 1 (151 ±â€¯18mN vs 67 ±â€¯14mN, P < 0.01). Regarding ergometrine, the MCF response was greater in Group 2 samples (24 ±â€¯10 mN) than that in Group 1 (18 ±â€¯2mN) (P < 0.05). CONCLUSION: Our findings highlight that women in a first pregnancy have a decreased response to both oxytocin and ergometrine in an in vitro setting when compared with women in a subsequent pregnancy, and this may have clinical implications regarding the management of postpartum haemorrhage in this cohort.

Graphene-aramid nanocomposite fibres via superacid co-processing.

The development of graphene-polymer nanocomposite materials has been hindered by issues such as poor colloidal stability of graphene in liquid media, weak interactions between graphene and the host polymers as well as the lack of scalable and economical graphene synthesis routes. Chlorosulfonic acid (CSA) can spontaneously disperse graphene without the need for mechanical agitation, chemical functionalisation or surfactant stabilisation,1 however is incompatible with most polymers and organic materials. Here, we demonstrate how poly(p-phenylene terephthalamide) (PPTA) - the polymer which constitutes Kevlar - can be co-processed with graphene in CSA and wet-spun into nanocomposite fibres with minimal aggregation of graphene.

Comment on: Synthesis of New Azo Compounds Based on N-(4-Hydroxyphenyl)maleimide and N-(4-Methylphenyl)maleimide. Molecules 2010, 15, 7498-7508.

The synthesis of (E)-phenylazo-3-N-(4-hydroxyphenyl)maleimide (1) using a procedure previously reported in Molecules is deemed to be erroneous. A detailed re-investigation of the earlier work suggests that the spectral data for key intermediates and the final product, (1), was mis-assigned. We conclude that compound (1) was not synthesized, but rather an unusual ring opening reaction of the maleimide unit of the starting material, N-(4-hydroxyphenyl)maleimide (2) leading to the generation of (Z)-4-((4-hydroxyphenyl)amino)-4-oxobut-2-enoic acid, (3) was observed instead. Examination of the original experimental data reveals systematic errors in the reporting of all of the combustion microanalytical data. Overall, the present investigation suggests that errors in the interpretation of spectral data, falsification of analytical data and selective editing of experimental results raise questions over the veracity of the work presented in the original paper.

PARROT Ireland: Placental growth factor in Assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a Stepped Wedge Cluster Randomised Control Trial Research Study Protocol.

INTRODUCTION: Women presenting with suspected pre-eclampsia are currently triaged on the basis of hypertension and dipstick proteinuria. This may result in significant false positive and negative diagnoses resulting in increased morbidity or unnecessary intervention. Recent data suggest that placental growth factor testing may be a useful adjunct in the management of women presenting with preterm pre-eclampsia. The primary objective of this trial is to determine if the addition of placental growth factor testing to the current clinical assessment of women with suspected preterm pre-eclampsia, is beneficial for both mothers and babies. METHODS AND ANALYSIS: This is a multicentre, stepped wedge cluster, randomised trial aiming to recruit 4000 women presenting with symptoms suggestive of preterm pre-eclampsia between 20 and 36+6 weeks' gestation. The intervention of an unblinded point of care test, performed at enrolment, will quantify maternal levels of circulating plasma placental growth factor. The intervention will be rolled out sequentially, based on randomisation, in the seven largest maternity units on the island of Ireland. Primary outcome is a composite outcome of maternal morbidity (derived from the modified fullPIERS model). To ensure we are not reducing maternal morbidity at the expense of earlier delivery and worse neonatal outcomes, we have established a co-primary outcome which will examine the effect of the intervention on neonatal morbidity, assessed using a composite neonatal score. Secondary analyses will examine further clinical outcomes (such as mode of delivery, antenatal detection of growth restriction and use of antihypertensive agents) as well as a health economic analysis, of incorporation of placental growth factor testing into routine care. ETHICS AND DISSEMINATION: Ethical approval has been granted from each of the seven maternity hospitals involved in the trial. The results of the trial will be presented both nationally and internationally at conference and published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02881073.

Maternal parity and functional contractility of human myometrium in vitro in the third trimester of pregnancy.

OBJECTIVE: It is well established that the duration of the first and second stages of labor are shorter in parous women than in their nulliparous counterparts, a phenomenon not well understood. The aim was to examine the effect of maternal parity on contractile parameters of human myometrium. DESIGN: Myometrial strips were excised from n = 74 women at cesarean delivery and recordings of contractile activity analyzed and compared across three clinical groups: 1. No previous delivery (P0); 2. One previous delivery (P1); 3. Greater than one previous delivery (P>1). RESULTS: There was a trend towards greater mean contractile force in the P>1 group than the P1 and P0 groups (P = 0.412). Frequency of contractions was less in the P1 group than in the P0 and P>1 groups(P = 0.027). No differences were observed in relation to all other parameters. CONCLUSION: Excluding frequency, no intrinsic differences were observed in the functional parameters of human uterine contractions in relation to parity.

Defining the upper limit of the second stage of labor in nulliparous patients.

BACKGROUND: Increased duration of the second stage of labor provides clinical challenges in decision-making regarding the optimal mode of delivery that minimizes maternal and neonatal morbidity. OBJECTIVE: In a large cohort of uncomplicated nulliparous singleton cephalic labors, we sought to examine the effect of increasing duration of second stage on delivery and perinatal outcome. STUDY DESIGN: The GENESIS Study recruited 2336 nulliparous patients with vertex presentation in a prospective double-blinded study to examine prenatal and intrapartum predictors of delivery. Metrics included maternal demographics, duration of second stage, mode of delivery, and associated maternal and neonatal outcomes. Indicators of morbidity included third- or fourth-degree tear, postpartum hemorrhage, neonatal intensive care unit admission, low Apgar scores, cord pH <7.20 and a composite of birth injury that included cephalohematoma, fetal laceration, brachial plexus palsy, facial nerve palsy, and fetal fracture. RESULTS: Of 2336 recruited nulliparous participants, 1872 reached the second stage of labor and had complete data for analysis. Increased maternal age (P=.02) and birthweight (P<.001) were found to be associated with a longer second stage. Increasing second stage duration was found to impact on mode of delivery, such that at <1 hour duration the spontaneous vaginal delivery rate was 63% vs 24% at >3 hours (P<.001). Operative vaginal delivery increased from 35% at <1 hour to 65% at >3 hours (P<.001). The rate of cesarean delivery increased with duration of the second stage from 1.2% at <1 hour to 11% at >3 hours (P<.001). The rates of third- or fourth-degree tear increased with second stage duration (P=.003), as did postpartum hemorrhage (P<.001). The composite neonatal birth injury rate increased from 1.8% at <1 hour to 3.4% at >3 hours. The maximum rate of birth injury was 6.5% at 2-3 hours (P<.001). Multiple logistic regression analysis that controlled for maternal age and birthweight confirmed that operative vaginal delivery, perineal trauma, postpartum hemorrhage, and neonatal birth injury remained significantly more likely with increasing second stage duration. CONCLUSION: In a prospective cohort of nulliparous pregnancies, increasing duration of second stage of labor was associated with increased rates of operative vaginal and cesarean delivery. Although almost 90% of term nulliparous women with a second stage of labor >3 hours will succeed in achieving a vaginal birth, this success comes at a maternal morbidity cost, with a 10% risk of severe perineal injury and an increasing rate of significant neonatal injury.

The Impact of Aspirin on Ultrasound Markers of Uteroplacental Flow in Low-Risk Pregnancy: Secondary Analysis of a Multicenter RCT.

OBJECTIVE: This article evaluates the effect of low-dose aspirin on uterine artery (UtA) Doppler, placental volume, and vascularization flow indices in low-risk pregnancy. STUDY DESIGN: In this secondary analysis of the TEST randomized controlled trial, low-risk nulliparous women were originally randomized at 11 weeks to: (1) routine aspirin 75 mg; (2) no aspirin; and (3) aspirin based upon the preeclampsia Fetal Medicine Foundation screening test. UtA Doppler, three-dimensional (3D) placental volume, and vascularization flow indices were assessed prior to and 6 weeks postaspirin commencement. RESULTS: A total of 546 women were included (aspirin n = 192, no aspirin n = 354). Between first and second trimesters, aspirin use was not associated with a change in UtA Doppler, placental volume, or vascular flow indices. There was no significant difference in the change in UtA Doppler pulsatility index (PI) Z-scores or notching (PI Z-score -0.2 vs. -0.2, p = 0.17), nor was there a significant change in placental volume Z-score and vascular flow indices (volume Z-score change: 0.74 vs. 0.62, p = 0.34). CONCLUSION: Low-dose aspirin commenced at 11 weeks in low-risk women does not appear to improve uterine and placental perfusion or placental volume. Any perceived effect on uteroplacental vasculature is not reflected in changes in placental volume nor uteroplacental flow as assessed by two-dimensional and 3D ultrasound.

Preeclampsia Prevention Using Routine Versus Screening Test-Indicated Aspirin in Low-Risk Women.

The objective was to evaluate whether routine aspirin 75 mg is more cost-effective than the Fetal Medicine Foundation screen-and-treat approach for preeclampsia prevention in low-risk nulliparous women. A health economic decision analytical model was devised to estimate the discounted net health and cost outcomes of routine aspirin versus Fetal Medicine Foundation screening test-indicated aspirin for a cohort of 100 000 low-risk nulliparous women. Both strategies were compared with no intervention. A subanalysis also compared disaggregated components of the algorithm. The analysis used data from hospital administration, literature, and a randomized controlled trial. Sensitivity analyses assessed the impact of aspirin adherence, test cost, and accuracy on study results. Presumed rates of preeclampsia were 3.75% with no intervention versus 0.45% with aspirin use. Results found that routine aspirin was the preferred strategy, in terms of greater health gains and larger cost savings. It provided 163 quality-adjusted life-years relative to no intervention, whereas the screen-and-treat policy achieved 108 quality-adjusted life-years. Routine aspirin would result in an estimated cost saving of €14.9 million annually relative to no intervention, whereas screen-and-treat approach would result in a smaller cost saving of €3.1 million. When the analysis was extended to consider alternative screen-and-treat strategies, routine aspirin remained the optimally cost-effective approach. In conclusion, routine aspirin use in low-risk nulliparous women has a greater health gain and cost saving compared with both the Fetal Medicine Foundation and other screen-and-treat approaches.

Trial of feasibility and acceptability of routine low-dose aspirin versus Early Screening Test indicated aspirin for pre-eclampsia prevention (TEST study): a multicentre randomised controlled trial.

OBJECTIVE: Evaluate the feasibility and acceptability of routine aspirin in low-risk women, compared with screening-test indicated aspirin for the prevention of pre-eclampsia and fetal growth restriction. DESIGN: Multicentre open-label feasibility randomised controlled trial. SETTING: Two tertiary maternity hospitals in Dublin, Ireland. PARTICIPANTS: 546 low-risk nulliparous women completed the study. INTERVENTIONS: Women underwent computerised randomisation to: Group 1-routine aspirin 75 mg from 11 until 36 weeks; Group 2-no aspirin and; Group 3-aspirin based on the Fetal Medicine Foundation screening test. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Proportion agreeing to participate; (2) compliance with protocol; (3) proportion where first trimester uterine artery Doppler was obtainable and; (4) time taken to issue a screening result. Secondary outcomes included rates of pre-eclampsia and small-for-gestational-age fetuses. RESULTS: 546 were included in the routine aspirin (n=179), no aspirin (n=183) and screen and treat (n=184) groups. 546 of 1054 were approached (51.8%) and enrolled. Average aspirin adherence was 90%. The uterine artery Doppler was obtained in 98.4% (181/184) and the average time to obtain a screening result was 7.6 (0-26) days. Of those taking aspirin, vaginal spotting was greater; n=29 (15.1%), non-aspirin n=28 (7.9%), OR 2.1 (95% CI 1.2 to 3.6). Postpartum haemorrhage >500 mL was also greater; aspirin n=26 (13.5%), no aspirin n=20 (5.6%), OR 2.6 (95% CI 1.4 to 4.8). CONCLUSION: Low-risk nulliparous women are open to taking aspirin in pregnancy and had high levels of adherence. Aspirin use was associated with greater rates of vaginal bleeding. An appropriately powered randomised controlled trial is now required to address the efficacy and safety of universal low-dose aspirin in low-risk pregnancy compared with a screening approach. TRIAL REGISTRATION NUMBER: ISRCTN (15191778); Post-results.

Vaginal birth after caesarean section: Current status and where to from here?

Vaginal birth after caesarean (VBAC) delivery remains a controversial topic, and one for which there is a lack of robust data to guide clinicians and parturients regarding their best option for mode of delivery in a subsequent pregnancy. In many developed countries the trend observed in recent years is that of progressively reduced VBAC rates, and hence increased use of elective repeat caesarean section (ERCS). This factor has contributed, more than any other, to the disproportionately high caesarean section (CS) rates in many countries. With current CS rates varying between 30 and 50% in the developed world, a previous CS is the cited primary indication in approximately 30%. To compound matters, there are huge variations in the reported VBAC rates between different countries, regions and even institutions. This review has focused on the recent trends in VBAC attempt, success and overall rates internationally, with inclusion of figures for a period of 25 years from a single Irish institution. An analysis of the reported factors that influence VBAC success, or failure, is presented. The complex task of estimating risk, both perinatal and maternal, for women who pursue VBAC or ERCS, is included in this review. Finally, the current evidence base for clinical practice pertaining to VBAC is outlined, with inclusion of commentary regarding the future for this difficult area of obstetric practice.