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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.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.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 of7 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 of50%.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.

peer-reviewed Objective Increased fetal size is associated with shoulder dystocia during labor and subsequent need for assisted delivery. We sought to investigate if increased fetal adiposity diagnosed sonographically in late pregnancy is associated with increased risk of operative delivery. Methods This secondary analysis of the Genesis Study recruited 2392 nulliparous women with singleton pregnancy in cephalic presentation, in a prospective, multicenter study, to examine prenatal and intrapartum predictors of Cesarean delivery. Participants underwent ultrasound and clinical evaluation between 39 + 0 and 40 + 6 weeks' gestation. Data on fetal biometry were not revealed to patients or to their managing clinicians. A fetal adiposity composite of fetal thigh adiposity and fetal abdominal wall thickness was compiled for each infant in order to determine whether fetal adiposity > 90th centile was associated with an increased risk of Cesarean or operative vaginal delivery. Results After exclusions, data were available for 2330 patients. Patients with a fetal adiposity composite > 90th centile had a higher maternal body mass index (BMI) (25 ± 5 kg/m2 vs 24 ± 4 kg/m2; P = 0.005), birth weight (3872 ± 417 g vs 3585 ± 401 g; P 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P 90th centile remained a risk factor for Cesarean delivery (P 90th centile was more predictive of the need for unplanned Cesarean delivery than was an estimated fetal weight > 90th centile (odds ratio, 2.20 (95% CI, 1.65–2.94; P 90th centile was not associated with an increased likelihood of operative vaginal delivery when compared with having an adiposity composite ≤ 90th centile (P = 0.37). Conclusions Fetuses with increased adipose deposition are more likely to require Cesarean delivery than are those without increased adiposity. Consideration should, therefore, be given to adding fetal thigh adiposity and abdominal wall thickness to fetal sonographic assessment in late pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. ACCEPTED peer-reviewed

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.

We present a case of third trimester pregnancy complicated by SARS-CoV-2 infection and subsequent reduced fetal movements, resulting in emergency Caesarean delivery with demonstrable placental SARS-CoV-2 placentitis. We show through illustration of this case and literature review that SARS-Co-V-2 placentitis is an uncommon but readily recognisable complication of maternal SARS-CoV-2 infection that may be a marker of potential vertical transmission and that may have the capacity to cause fetal compromise through a direct injurious effect on the placenta., Highlights • We present a pregnancy complicated by SARS-CoV-2 infection and resultant placentitis. • 25% of the parenchyma comprised a deposition similar to perivillous fibrinoid. • Under microscopy, these areas were predominantly a histiocytic intervillositis. • Immunohistochemistry for SARS-CoV-2 showed extensive, strong positive staining. • Reported COVID-19 chronic intervillositis cases depict virus in syncytiotrophoblast.

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.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.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 factors90th 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.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.

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.

ObjectiveEvaluate 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.DesignMulticentre open-label feasibility randomised controlled trial.SettingTwo tertiary maternity hospitals in Dublin, Ireland.Participants546 low-risk nulliparous women completed the study.InterventionsWomen 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.Results546 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).ConclusionLow-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 numberISRCTN (15191778); Post-results.

To examine day care treatment of nausea and vomiting of pregnancy compared with the traditional inpatient management of this condition.We conducted an open-label, single-center, randomized controlled trial to examine the differences between day care and inpatient management of pregnant women with nausea and vomiting of pregnancy. Primary outcome was total number of inpatient nights related to nausea and vomiting of pregnancy.Ninety-eight women were randomized to initial day care management (n=42) or inpatient management (n=56). Results are calculated from the time of randomization until resolution of nausea and vomiting of pregnancy. Women randomized to inpatient care experienced a median (interquartile range) of 2 (1-4) inpatient days compared with 0 (0-2) inpatient days for women randomized to day care (P.001). Women randomized to initial treatment as an inpatient had significantly more median total number of inpatient admissions (one [1-2] compared with zero [0-1] admissions; P.001) compared with women randomized to day care. No significant differences were observed in day care visits (median [interquartile range] one [1-4] compared with two [1-4]; P=.30). Women randomized to inpatient care were as satisfied with their care as those randomized to day care (median [interquartile range]: 67 [57-69] compared with 63 [58-71] Client Satisfaction Questionnaire score; P=.7).Day care treatment of nausea and vomiting of pregnancy reduced hospital inpatient stay and was acceptable to patients.ISRCTN Register, http://www.isrctn.org, ISRCTN05023126.: I.

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.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.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 pH7.20 and a composite of birth injury that included cephalohematoma, fetal laceration, brachial plexus palsy, facial nerve palsy, and fetal fracture.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 at1 hour duration the spontaneous vaginal delivery rate was 63% vs 24% at3 hours (P.001). Operative vaginal delivery increased from 35% at1 hour to 65% at3 hours (P.001). The rate of cesarean delivery increased with duration of the second stage from 1.2% at1 hour to 11% at3 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% at1 hour to 3.4% at3 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.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 labor3 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.

To establish if first or second trimester biometry is a useful adjunct in the prediction of adverse perinatal outcome in twin pregnancy.A consecutive cohort of 1028 twin pregnancies was enrolled for the Evaluation of Sonographic Predictors of Restricted growth in Twins (ESPRiT) study, a prospective study conducted at eight academic centers. Outcome data was recorded for 1001 twin pairs that completed the study. Ultrasound biometry was available for 960 pregnancies. Biometric data obtained between 11 and 22 weeks were evaluated as predictors of a composite of adverse perinatal outcome (mortality, hypoxic ischemic encephalopathy, periventricular leukomalacia, necrotizing enterocolitis, respiratory distress, or sepsis), preterm delivery (PTD) and birthweight discordance greater than 18% (18% BW). Outcomes were adjusted for chorionicity and gestational age using Cox Proportional Hazards regression.Differences in crown-rump length (CRL) were not predictive of adverse perinatal outcome. Between 14 and 22 weeks, a difference in abdominal circumference (AC) of more than 10% was the most useful predictor of adverse outcome, PTD and 18% or more BW discordance in all twins. Overall the strongest correlation was observed for intertwin differences in biometry between 18 and 22 weeks.Biometry in the early second trimester can successfully identify twin pregnancies at increased risk. Intertwin AC difference of greater than 10% between 14 and 22 weeks gestation was the best individual predictor of perinatal risk in all twins. Sonographic biometry in the early second trimester should therefore be utilized to establish perinatal risk, thus allowing prenatal care to be improved.

Background In contemporary practice many nulliparous women require intervention during childbirth such as operative vaginal delivery or cesarean delivery (CD). Despite the knowledge that the increasing rate of CD is associated with increasing maternal age, obesity and larger infant birthweight, we lack a reliable method to predict the requirement for such potentially hazardous obstetric procedures during labor and delivery. This issue is important, as there are greater rates of morbidity and mortality associated with unplanned CD performed in labor compared with scheduled CDs. A prediction algorithm to identify women at risk of an unplanned CD could help reduced labor associated morbidity. Objective In this primary analysis of the Genesis study, our objective was to prospectively assess the use of prenatally determined, maternal and fetal, anthropomorphic, clinical, and ultrasound features to develop a predictive tool for unplanned CD in the term nulliparous woman, before the onset of labor. Materials and Methods The Genesis study recruited 2336 nulliparous women with a vertex presentation between 39+0 and 40+6 weeks' gestation in a prospective multicenter national study to examine predictors of CD. At recruitment, a detailed clinical evaluation and ultrasound assessment were performed. To reduce bias from knowledge of these data potentially influencing mode of delivery, women, midwives, and obstetricians were blinded to the ultrasound data. All hypothetical prenatal risk factors for unplanned CD were assessed as a composite. Multiple logistic regression analysis and mathematical modeling was used to develop a risk evaluation tool for CD in nulliparous women. Continuous predictors were standardized using z scores. Results From a total enrolled cohort of 2336 nulliparous participants, 491 (21%) had an unplanned CD. Five parameters were determined to be the best combined predictors of CD. These were advancing maternal age (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09 to 1.34), shorter maternal height (OR, 1.72; 95% CI, 1.52 to 1.93), increasing body mass index (OR, 1.29; 95% CI, 1.17 to 1.43), larger fetal abdominal circumference (OR, 1.23; 95% CI, 1.1 to 1.38), and larger fetal head circumference (OR, 1.27; 95% CI, 1.14 to 1.42). A nomogram was developed to provide an individualized risk assessment to predict CD in clinical practice, with excellent calibration and discriminative ability (Kolmogorov–Smirnov, D statistic, 0.29; 95% CI, 0.28 to 0.30) with a misclassification rate of 0.21 (95% CI, 0.19 to 0.25). Conclusion Five parameters (maternal age, body mass index, height, fetal abdominal circumference, and fetal head circumference) can, in combination, be used to better determine the overall risk of CD in nulliparous women at term. A risk score can be used to inform women of their individualized probability of CD. This risk tool may be useful for reassuring most women regarding their likely success at achieving an uncomplicated vaginal delivery as well as selecting those patients with such a high risk for CD that they should avoid a trial of labor. Such a risk tool has the potential to greatly improve planning hospital service needs and minimizing patient risk.

Introduction Our study aim was to evaluate standard ultrasound-derived fetal biometric parameters in the prediction of clinically significant intertwin birthweight discordance defined as ≥18%. Material and methods This was a secondary analysis of a prospective cohort study of 1028 unselected twin pairs recruited over a two-year period. Dichorionic twins underwent two-weekly ultrasonographic surveillance from 24 weeks' gestation, with surveillance of monochorionic twins two-weekly from 16 weeks. Ultrasonographic biometric data from 24 to 36 weeks were evaluated for the prediction of an intertwin birthweight discordance threshold ≥18%. Umbilical artery Doppler waveform data was also analyzed to evaluate whether it was predictive of birthweight discordance. Results Of the 956 twin pairs analyzed for discordance, 208 pairs were found to have a clinically significant birthweight discordance ≥18%. All biometric parameters were predictive of significant inter-twin birthweight discordance at low cut-offs, with low discriminatory powers when ROC curves were analyzed. Discordance in estimated fetal weight was predictive of a significant birthweight discordance at all gestational categories with cut-offs between 8 and 11%. A low-discriminatory power and poor sensitivity and specificity were also observed. An abnormal umbilical artery Doppler was predictive of birthweight discordance ≥18% between 28 and 32 weeks' gestation, although with poor sensitivity and specificity. Conclusions Calculation of estimated fetal weight and birthweight discordance between twins allows minimal margin for error. These margins make it difficult to accurately predict those who are at or above the discordance threshold of 18%. These findings highlight that small intertwin discrepancies in weight and biometry should not be overlooked and merit further investigation.

Introduction The number of parents agreeing to autopsy following stillbirth is declining, which has undermined clinicians’ ability to assess causes of intrauterine death and can impact counselling regarding recurrence. Post-mortem radiological imaging is a potential alternative method of investigating perinatal loss. The aim of this study was to assess the role of multi-detector computed tomography (MDCT) in the investigation of stillbirth. Study design Following ethical approval and written consent, parents were offered MDCT of the stillborn infant. MDCT was performed with 3D reconstruction, and images were analysed for image quality, anthropomorphic measurements and pathologic findings. Body part and organ-specific measurements were performed; including head, chest and abdominal circumferences, and muscle and liver mass was also measured. Findings were correlated with obstetric history, post-mortem skeletal survey (plain radiography), and formal autopsy. Results Fourteen third-trimester stillborn infants were scanned. Image quality was moderate to excellent for most body structures. CT was better than plain radiography for imaging skeletal structures and large solid organs and demonstrated a range of pathologies including renal vein thrombosis, mesenteric calcification and skeletal hyperostosis that were not seen on plain radiographs. MDCT did not overlook autopsy findings and provided some additional information. Conclusion This study confirms the feasibility of MDCT in the investigation of third trimester stillbirth. MDCT image quality is acceptable and the examination can demonstrate a range of anatomic and pathologic findings. Initially, its value may be as an important adjunct to conventional autopsy.

Summary. Background: Plasminogen activator inhibitor type 1 (PAI-1) is an important regulator of fibrinolysis. A common deletion polymorphism that results in a sequence of 4G instead of 5G in the promoter region of the gene is associated with a small increase in the risk of venous thromboembolism. Its potential association with adverse pregnancy events remains controversial. Objective: We aimed to assess the impact of the 4G PAI-1 polymorphism on pregnancy outcomes in women who had no prior history of adverse pregnancy outcomes or personal or family history of venous thromboembolism. Patients/methods: This study represents a secondary investigation of a prior prospective cohort study investigating the association between inherited thrombophilias and adverse pregnancy events in Australian women. Healthy nulliparous women were recruited to this study prior to 22 weeks gestation. Genotyping for the 4G/5G PAI-1 gene was performed using Taqman assays in an ABI prism 7700 Sequencer several years after the pregnancy was completed. Pregnancy outcome data were extracted from the medical record. The primary outcome was a composite comprising development of severe pre-eclampsia, fetal growth restriction, major placental abruption, stillbirth or neonatal death. Results: Pregnancy outcome data were available in 1733 women who were successfully genotyped for this polymorphism. The primary composite outcome was experienced by 139 women (8% of the cohort). Four hundred and fifty-nine women (26.5%) were homozygous for the 4G deletion polymorphism, while 890 (51.4%) were heterozygous. Neither homozygosity nor heterozygosity for the PAI-1 4G polymorphism was associated with the primary composite outcome (homozygous OR = 1.30, 95% CI = 0.81–2.09, P = 0.28, heterozygous OR = 0.84, 95% CI = 0.53–1.31, P = 0.44) or with the individual pregnancy complications. Conclusion: The PAI-1 4G polymorphism is not associated with an increase in the risk of serious adverse pregnancy events in asymptomatic nulliparous women.

Pre-eclampsia (P-EC) is a multisystem disorder exclusive to pregnancy. It complicates ~2 to 8% of all pregnancies and remains a major cause of maternal mortality. P-EC is characterized by a profound hypercoagulable state. The delicate hemostatic balance that must be maintained in the uteroplacental circulation during pregnancy makes this system vulnerable to perturbation. An abnormal hemostatic pattern occurs within the uteroplacental circulation in P-EC compared with normal pregnancy. Much recent research has focused on the epidemiological link between inherited thrombophilia and P-EC. The data suggest a weak statistical association, indicating an improbable primary role in the pathogenesis. Without clear evidence, low molecular weight heparins have been widely used to reduce recurrence of P-EC in thrombophilia-positive women. This practice now should be reviewed. Future research needs to focus on improving our basic scientific understanding of the role of the hemostatic system in human placentation.

The demographics of the obstetric population in Ireland are increasingly changing due to immigration patterns. As the obstetric population becomes more ethnically diverse, the challenge for health professionals is to provide more appropriate, culturally-specific care. This observational study compared birth plan preferences among Irish and Nigerian pregnant women. Included in this study were 113 Nigerian women and 519 Irish women attending the Unified Maternity Services in Cork. A questionnaire was used to assess patients' attitudes toward varying aspects of obstetric care. Differences between the two study populations were seen across all aspects of care. Among other differences, Nigerian women booked at a later gestation compared to their Irish counterparts (33.8 weeks vs. 20.8 weeks respectively, P < 0.001), preferred to have a vaginal delivery (90.7% vs. 64.2%) and an analgesia-free birth (39.6% vs. 5.8%). This study demonstrates a need to recognize the cultural variations in preferences for pregnancy and childbirth in order to provide culturally-specific care.

There is currently inconsistent evidence and clinical guidance on how to best manage a pregnancy complicated by reduced fetal movements. This novel, web-based, anonymous questionnaire evaluated 96 assessment and management approaches from doctors working in obstetrics in the Republic of Ireland who were presented with a clinical scenario of a primigravida concerned about reduced fetal movements at 39+3 weeks' gestation. This study identified a lack of clinical practice guidelines available in maternity hospitals in the Republic of Ireland. We demonstrated that almost all clinicians applied more than one assessment method and that most incorporated a cardiotocograph into their assessment. There was a low uptake of simple symphysio-fundal height measurement and high usage of kickcharts. The minority of clinicians admitted or induced their patients. This survey identified the need for national and international guidelines to ensure safe antepartum care and delivery.

Objective Early elective termination of pregnancy is the most common outcome of a diagnosis of anencephaly in developed countries. Experience and expertise with management of ongoing pregnancies is limited. We aimed to investigate the natural history of these pregnancies from diagnosis to delivery and to determine timing of death. Method A retrospective review of cases of anencephaly diagnosed between 2003 and 2009 in tertiary-referral university teaching hospitals in Cork. Results The majority of cases (25/26; 96%) were diagnosed prenatally at a median gestation of 21+2 weeks (range 13+4–32+4). The median maternal age was 30 years (range 17–41) and 50% were primigravidae. Seven pregnancies were complicated by polyhydramnios and four deliveries were complicated by shoulder dystocia. The median gestation at delivery was 35 weeks (range 22+5–42+6); 69% of labours were induced at a median gestation of 34 weeks. Six women (6/26; 23%) had a pre-labour intrauterine fetal death and nine women (9/26; 35%) had an intrapartum fetal death. Median neonatal survival time was 55 min (range 10 min to 8 days). Six parents donated neonatal organs for transplantation. Conclusion This study provides useful information for health professionals caring for patients with a diagnosis of anencephaly. The majority of these infants die prior to delivery but short-term survival is possible. Copyright © 2010 John Wiley & Sons, Ltd.

SummaryProtein S, protein C and antithrombin are important regulators of coagulation. While deficiencies of these proteins have been linked to adverse pregnancy outcomes, testing for these deficiencies during pregnancy is limited by the use of non-pregnant reference ranges and a limited understanding of the changes that occur during pregnancy. Although several small studies have previously reported on the activity of these proteins during pregnancy, potentially important changes have been overlooked by continuing to compare the activity during pregnancy with non-pregnant reference ranges. In the current study, we investigated the activity of protein S, protein C and antithrombin during the first half of pregnancy in 440 otherwise asymptomatic women who went on to have uncomplicated singleton pregnancies. Consistent with previous studies, we found that antithrombin activity remained unchanged, while protein S activity decreased significantly to a mean level of 46%. We did not observe a progressive decrease in protein S during the second trimester as several studies have suggested previously. In contrast, we observed a potentially biologically significant increase in protein C activity throughout the first 22 weeks of pregnancy. Given the physiological role of protein C, we postulate that this increase may play a role in maintaining early pregnancy through both an anticoagulant and an inflammatory regulation pathway.

OBJECTIVE: To estimate the association between five commonly inherited thrombophilia polymorphisms and adverse pregnancy outcomes in women who had no prior history of adverse pregnancy outcomes or personal or family history of venous thromboembolism. METHODS: Healthy nulliparous women (n2,034) were recruited to this prospective cohort study before 22 weeks of gestation. Genotyping for factor V Leiden, prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and thrombomodulin polymorphism was performed. Clinicians caring for women were blinded to the results of thrombophilia tests. The primary composite outcome was the development of severe preeclampsia, fetal growth restriction, placental abruption, stillbirth, or neonatal death. RESULTS: Complete molecular results and pregnancy outcome data were available in 1,707 women. These complications were experienced by 136 women (8.0%). Multivariable logistic regression demonstrated two statistically significant findings. Women who carried the prothrombin gene mutation had an odds ratio of 3.58 (95% confidence interval [CI] 1.20–10.61, P.02) for the development of the composite primary outcome. Homozygous carriers of the MTHFR 1298 polymorphism had an odds ratio of 0.26 (95% CI 0.08–0.86, P.03). None of the other polymorphisms studied showed a significant association with the development of the primary outcome in this cohort of women. CONCLUSION: Prothrombin gene mutation confers an increased risk for the development of adverse pregnancy outcomes in otherwise asymptomatic, nulliparous women, whereas homozygosity for MTHFR 1298 may protect against these complications. The majority of asymptomatic women who carry an inherited thrombophilia polymorphism have a successful pregnancy outcome. (Obstet Gynecol 2010;115:5–13) LEVEL OF EVIDENCE: II

Pleiotrophin (PTN) is a heparin-binding protein with multiple activities in cell growth, migration and differentiation mediated through multiple receptors. In mammals, PTN expression in trophoblast is found exclusively in the human and in some of the apes in which an endogenous retrovirus upstream of the first coding exon generates a phylogenetically new trophoblast-specific promoter associated with exon UV3. To understand the functions of ERV promoter-mediated trophoblastic PTN expression in pregnancy, we correlated the expression of PTN and its receptors anaplastic lymphoma kinase (ALK), receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta), and Syndecan-1 and Syndecan-3 (SDC1 and SDC3) with key developmental processes in first-trimester human placentation. In an extensive survey of cell lines and primary tissues, we found that trophoblastic transcription of PTN is initiated exclusively from the ERV promoter, whereas decidual expression is initiated at the phylogenetically ancient U1 exon-associated promoter. Using immunohistochemistry, we found that different patterns of overlapping expression of PTN and its receptors occur in different trophoblast subtypes. Notably, a role in angiogenesis is supported by expression of PTN and its receptors in villous mesenchyme, fetal macrophages and villus core fetal vessels. PTN staining of extravillous cytotrophoblasts and the syncytial microvillous membrane is consistent with increasing levels of PTN, as measured by ELISA, in the maternal bloodstream as pregnancy progresses.

Aim: Inherited thrombophilic polymorphisms have been linked to pregnancy-related thromboembolism and other adverse pregnancy outcomes. As there are limited data on the prevalence of these polymorphisms in Australian populations, we aimed to assess this in an antenatal population. Methods: Healthy nulliparous women (n = 2031) were recruited to this study. The women had no past or family history of venous thromboembolism. Women were excluded if they or a family member was known to be a carrier of any thrombophilic marker. Genotyping from venous blood for the factor V Leiden, prothrombin 20210A, MTHFR 677 and 1298 and thrombomodulin C1418T polymorphisms was undertaken. Results: Key findings were that 107 of 2019 (5.30, 95% confidence interval 4.36–6.37%) women tested were heterozygous carriers of factor V Leiden and one was homozygous (0.05, 0–0.27%); 2.43% of women were heterozygous carriers of the prothrombin gene mutation (1.80–3.20%) while no women were homozygous for this mutation; 11.62% (10.22–13.02%) and 9.98% (8.67–11.29%) were homozygous for the MTHFR 677 and 1298 polymorphisms, respectively, and 3.43% (2.63–4.22%) of women were homozygous for the thrombomodulin polymorphism. Conclusions: The prevalence of these polymorphisms is consistent with previously published data in Caucasian populations. These data will provide the basis for further assessment of the relationship between poor pregnancy outcome and these inherited thrombophilic polymorphisms in an asymptomatic antenatal population.

Objective Gestational hypertensive disease (GHD) is associated with pregnancy-related complications and poor maternal and fetal outcomes in singleton pregnancies. We sought to examine the influence of GHD in a large prospective cohort of twin pregnancies. Study design The ESPRIT study was a national multicenter observational cohort study of 1028 structurally normal twin pregnancies. Each pregnancy underwent sonographic surveillance with two-week ultrasound from 24 weeks for dichorionic and from 16 weeks for monochorionic gestations. Characteristics and demographics as well as labour and delivery outcome data were prospectively recorded. Perinatal mortality, admission to the neonatal intensive care unit (NICU) and a composite of morbidity of respiratory distress syndrome, hypoxic ischaemic encephalopathy, periventricular leukomalacia, necrotising enterocolitis and sepsis were documented for all cases. Outcomes for patients with documented GHD (pre-eclampsia and gestational hypertension) were compared with those without GHD. Results Perinatal outcome data were recorded for 977 patients. Women with GHD had a higher body mass index (27.1 ± 6.4 vs 25.2 ± 4.5, P < 0.0001) than those without and were more likely to be nulliparous (65% (59/92) vs 46% (407/885), P = 0.001). Both groups had similar mean birthweights, but those with GHD were more likely to have a birthweight discordance ≥18% (35% (32/92) vs 20% (179/885), P = 0.001). Rates of caesarean delivery were higher in those twin pregnancies affected by GHD, and while the rate of composite morbidity was similar in both groups, twins in the GHD group had higher rates of NICU admission. Conclusion In twin gestations, gestational hypertension independently confers an increased risk for emergency caesarean delivery, birthweight discordance and NICU admission, such that intensive maternal–fetal monitoring is justified when hypertension develops in a twin pregnancy.

Objective To assess the comparative cost effectiveness of day care over inpatient management of nausea and vomiting of pregnancy (NVP). Study design A cost utility analysis was performed using a decision analytical model in which a Markov model was constructed. The Markov model was primarily populated with data from a recently published randomised controlled trial. Which included pregnant women presenting to Cork University Maternity Hospital, a tertiary referral maternity hospital, seeking treatment for NVP. Costs and outcomes were estimated from the perspective of the Irish health service (HSE) and patients. A probabilistic sensitivity analysis, using a Monte Carlo simulation, was also performed. A Bayesian Value of Information analysis was used to estimate the value of collecting additional information. Results When both the healthcare provider and patient's perspective was considered, day care management of NVP remained less costly (mean €985; 95% C.I. 705–1456 vs. €3837 (2124–8466)) and more effective (9.42; 4.19–12.25 vs. 9.49; 4.32–12.39 quality adjusted life years) compared with inpatient management. The Cost Effectiveness Acceptability Curve indicates the probability that day care management is 70% more cost effective compared to inpatient management at a ceiling ratio of €45,000 per QALY, indicating little decision uncertainty. The Bayesian Value of Information analysis indicates there is value in collecting further information; the Expected Value of Perfect Information (EVPI) is estimated to be €5.4 million. Conclusion Day care management of NVP is cost effective compared to inpatient management.

Differences in the prevalence of thrombophilias in different ethnic populations have been demonstrated. Because the Australian population includes many different ethnic groups, we sought to assess the effect of ethnicity in our Australian prenatal population on the prevalence of thrombophilic polymorphisms. Asymptomatic, nulliparous women (n = 1,129) recruited for a large prospective study were included in this analysis. These women had no personal or family history of venous thromboembolism and were not known to be carrying an inherited or acquired thrombophilia. Ethnicity was determined at recruitment, and women were categorized as being of Northern European, Southern European, Middle Eastern, Asian, or Other ethnicity. These women underwent genotyping for the following polymorphisms: factor V Leiden G1691A, prothrombin gene A20210G mutation, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and thrombomodulin C1418T. The factor V Leiden allele was seen significantly more frequently in patients of Middle Eastern background compared to those of Northern European and Asian ethnicity (p < 0.05). The prothrombin gene mutation was seen significantly more frequently in patients of Southern European ethnicity compared to those of Northern European or Asian ethnicity (p < 0.05). The MTHFR C677T allele (mutant) was significantly less common in those of Asian ethnicity compared to patients of Northern European and Southern European ethnicity (p < 0.0005). There were no significant differences seen with the MTHFR A1298C polymorphism. The mutant thrombomodulin allele was seen significantly more frequently in Asian women compared to Northern European, Southern European, or Middle Eastern women (p < 0.005). There are important ethnic differences in the prevalence of thrombophilic polymorphisms in the Australian prenatal population.

The objective of this study was to evaluate the acceptability of the SpaceLabs 90207 ambulatory blood pressure monitor among pregnant women.Patients participating in research projects involving ambulatory blood pressure monitoring (ABPM) in pregnancy (N = 110) were asked to complete a questionnaire relating to patient satisfaction on completion of the monitoring period. The first part of the questionnaire involved rating on a visual Likert scale (0-10) whether they found the monitor heavy, noisy, cumbersome, disturbing, or embarrassing to wear. The second part of the questionnaire addressed whether cuff inflation caused significant sleep disturbance or physical discomfort.The mean (SD) and range of the Likert scores are reported. The number of patients reporting sleep disturbance or physical discomfort was calculated. Logistic regression was used to examine which factors were significant predictors of discontinuing monitoring.The mean (SD) responses measured by the Liken scores were: finding the monitor heavy 3.2 (2.3); comfortable 4.8 (2.3); straightforward to use 8.8 (1.8); cumbersome 3.8 (2.3); disturbing 4.5 (2.7); noisy 1.6 (2.2); and embarrassing to wear 1.7 (2.1). Difficulty initiating sleep was reported by 28.8% of patients, and a further 56.3% reported difficulty maintaining sleep due to the monitor. Sleep disturbance was found to be the strongest predictor [r = 0.52; OR 1.68 (1.23, 2.27), p = 0.0009] for the 15% of patients discontinuing the monitoring.While pregnant women tolerate the noise, weight, inconvenience, and disturbance associated with ambulatory blood pressure monitoring (ABPM) well, sleep disturbance is a major cause of dissatisfaction and noncompliance. Future studies should evaluate critically the number of nocturnal blood pressure assessments required, and should allow for a withdrawal rate of approximately 15% when performing sample size calculations for ABPM studies in pregnancy.

Haemostasis is a complex and dynamic equilibrium involving pro-coagulants, the natural anticoagulation system and fibrinolysis. Normal human pregnancy is associated with profound alterations to the process of haemostasis such that the pro-coagulant effect becomes dominant. There are very few studies which have attempted to elucidate the adaptations that take place in the uteroplacental circulation where the haemostatic system faces the conflicting tasks of maintaining blood fluidity during pregnancy while preparing for the haemostatic challenge of delivery. It is hypothesised that excessive thrombosis within the uteroplacental circulation provides the mechanistic basis for the reported associations between the inherited thrombophilias and major pregnancy complications. The evidence underpinning this widely quoted hypothesis is weak.

Methods Twenty-four-hour ambulatory blood pressure monitoring was performed on 40 women (20 hypertensive, 20 normotensive) on a hospitalised and nonhospitalised day. Mean blood pressure differences were calculated for the awake, sleeping and 24-hour periods on both days. Results Mean heart rate was higher at home (1.79, p = 0.04) than in hospital, but there were no significant differences in mean systolic (1.30 mmHg, p = 0.06), diastolic (0.78 mmHg, p = 0.21) or mean arterial blood pressure (0.81 mmHg, p = 0.19) between the hospitalised and non hospitalised day for the group overall. Nevertheless, the range of individual responses was wide (-8.5 mmHg to 15.4 mmHg mean arterial blood pressure). Hypertensive women receiving antihypertensive therapy had significantly greater differences in mean arterial blood pressure between the hospital and non-hospital day when compared to the rest of the group (5.8 mmHg, compared to 3.3 mm Hg, p = 0.02). Conclusions Although hospitalisation does not significantly lower blood pressure in pregnant women as a group, women receiving antihypertensive therapy demonstrate significant differences in blood pressure between hospital and home. Based on conventional blood pressure measurements alone, these women may be at risk of either under treatment, or over treatment, of blood pressure.

The authors wanted to determine the prevalence of limited health literacy, and the relation between health literacy and beliefs about medicines, in an obstetric population. A survey was administered in Cork University Maternity Hospital, Cork, Ireland. The Rapid Estimate of Adult Literacy in Medicine and the general section of the Beliefs About Medicines Questionnaire were used. Of 404 women, 15.3% (n=62) displayed limited health literacy. Age and health literacy were significantly associated with one another, as were health literacy and level at which participants completed formal education. In the general harm domain, level of education and health literacy were associated with stronger beliefs: M=11.85, SD=2.81 vs. M=9.75, SD=2.11; F(3)=13.69, p.001. In the general overuse domain, those with limited literacy scored higher compared with those with adequate health literacy: M=12.48, SD=2.73 versus M=11.51, SD=2.63 (p=.01). These associations remained despite controlling for age (and education) in multivariable analyses. More than 1 in 7 had limited health literacy; these women may benefit from educational initiatives. Limited health literacy is associated with a more negative perception of medicines in this cohort.

Objective To construct monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin reference ranges for umbilical artery (UA) pulsatility index (PI), UA resistance index (RI), fetal middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and cerebroplacental ratio (CPR) from 24 weeks' to 38 weeks' gestation and compare these with published normal values for singleton pregnancies. Methods This prospective multicenter cohort study included 1028 unselected twin pairs recruited over a 2-year period. Participants with dichorionic twins underwent fortnightly ultrasound surveillance from 24 weeks' gestation, with monochorionic twins being followed every 2 weeks from 16 weeks until delivery. A total of 7536 fetal Doppler examinations in 618 twin pregnancies were included in the analysis, with reference ranges for MCDA and DCDA pregnancies constructed for each of the Doppler indices using multilevel modeling. Results UA-PI and UA-RI appear to be higher in twins than in singletons, and MCA-PI and MCA-PSV appear to be lower. The CPR also appears to be lower in twins than in singletons. Similar MCA indices were observed in MCDA and DCDA twins. Conclusion We have established longitudinal reference ranges for UA-PI and UA-RI, MCA-PI and MCA-PSV and CPR in twin pregnancies, which appear to differ from those in singleton pregnancies. The derived twin-specific reference ranges may be more appropriate in the surveillance of these high-risk pregnancies. Applying the singleton CPR cut-off of ≤ 1.0 may lead to a large number of false-positive diagnoses of cerebral redistribution in twin fetuses. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain.

Pre-eclampsia is usually defined on the basis of new onset hypertension and albuminuria developing after 20 weeks of pregnancy. There are difficulties with measurement of these variables. Conventional sphygmomanometry remains the gold standard for blood-pressure measurement. The value of ambulatory blood-pressure measurement has yet to be established. Oedema is now omitted from all definitions of pre-eclampsia, although the finding of widespread severe oedema of sudden onset should not be ignored for clinical purposes. Definitions of pre-eclampsia based solely on hypertension and proteinuria ignore the wide clinical variability in this syndrome. Women with no proteinuria but who do have hypertension and other features such as severe headache or other symptoms, thrombocytopenia, hyperuricaemia, disordered liver function, and fetal compromise are likely to have pre-eclampsia. This notion is accepted in the new Australasian definition of pre-eclampsia and more than hinted at in the new American College of Obstetricians and Gynecologists' definition. Definitions used for clinical purposes should be as safe as practical; they are likely to include a considerable number of false positives. Most research studies are weakened if patients without the disease are included. Therefore, a separate stringent research definition of pre-eclampsia we also suggest.