The IRELAnD study-investigating the role of early low-dose aspirin in diabetes mellitus: a double-blinded, placebo-controlled, randomized trial.

BACKGROUND: Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials. OBJECTIVE: The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus. STUDY DESIGN: A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months' duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks' gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks' gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis. RESULTS: From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks' gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance. CONCLUSION: In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties.

Critical congenital heart disease: contemporary prenatal screening performance and outcomes in a multi-centre perinatology service.

BACKGROUND: Prenatal detection of critical congenital heart disease (CCHD) optimises perinatal decision-making and neonatal outcomes. The objective of this study was to determine the prenatal screening performance, care pathways and perinatal outcomes for prenatally and postnatally diagnosed cases of CCHD over a four-year period. STUDY DESIGN: This retrospective cohort study in a tertiary centre and its two affiliated secondary sites examined all cases of CCHD, including cases of pregnancy termination and in-utero fetal death, neonatal death and liveborn babies that underwent cardiac catheterization or surgery in the first six weeks of life. Prenatal and postnatal data were ascertained from the first trimester assessment for all patients diagnosed prenatally. Cases requiring intervention that were first identified in the postnatal period were included to determine prenatal detection rates. Follow-up for all cases of CCHD continued to one year of age. RESULTS: In a consecutive cohort of 49,950 pregnancies in a 4-year period 01/2019 to 12/2022, a prenatal diagnosis of CCHD was made in 96 cases, yielding a prevalence of 1.9 per 1000 births. The prenatal detection for right duct-dependant heart pathology and congenital heart block was 100%, 85% for left duct-dependant pathology and 93% for transposition of the great arteries (TGA). In the prenatally diagnosed group, 37% of cases were complicated by extracardiac structural abnormalities, a genetic diagnosis or both. All cases of prenatal detection were identified in the context of routine anatomy screening rather than specialist Fetal Cardiac screening services. Almost half of all pregnancies complicated by CCHD did not undergo neonatal cardiac intervention, by virtue of parental choice determined either prenatally or after birth. An additional eight babies were diagnosed with CCHD in the neonatal period, such that the prenatal detection rate for CCHD was 92% (96/104, 95% CI = 84%-96%). Survival at 1-year for infants deemed suitable for CCHD surgery was 85%. CONCLUSION: In a large unselected population, optimal rates of prenatal detection of critical congenital heart disease can be achieved by a protocolised approach to mid-trimester fetal anatomy ultrasound, underpinned by a programme of sonographer education and training. The cardiac abnormalities most likely to evade prenatal detection are left-sided obstructive lesions.

Assessment of Myocardial Function in Infants of Mothers with Gestational Diabetes Mellitus Using Deformation Imaging over the First Year of Age.

OBJECTIVE: To assess serial myocardial performance and pulmonary vascular resistance (PVR) in infants of mothers with gestational diabetes mellitus (GDM) over the first year of life. STUDY DESIGN: This was a prospective, observational study. Echocardiography was performed at birth, 6 months, and 1 year of age. Pulmonary artery acceleration time and left ventricular (LV) eccentricity index provided surrogate measurements of PVR. Biventricular function was assessed by tissue Doppler imaging and deformation analysis. RESULTS: Fifty infants of mothers with GDM were compared with 50 controls with no difference in gestation (38.9 ± 0.8 weeks vs 39.3 ± 0.9 weeks; P = .05) or birthweight (3.55 ± 0.49 kg vs 3.56 ± 0.41 kg; P = .95). At 1 year of age, the pulmonary artery acceleration time was lower (70 ± 11 vs 79 ± 10; P = .01) in the GDM group. LV global longitudinal strain (24.7 ± 1.9 vs 28.8 ± 1.8 %; P < .01), LV systolic strain rate (1.8 ± 0.2 vs 2.1 ± 0.3 1/s; P < .01), and RV free wall strain (31.1 ± 4.8 vs 34.6 ± 3.9 %; P < .01) were lower in the GDM cohort at 1 year of age (all P values adjusted for gestation, mode of delivery, and maternal body mass index). CONCLUSIONS: Our findings demonstrate higher indices of PVR and lower biventricular function in infants of mothers with GDM compared with controls at each time point assessed in this study over the first year of life.

Glycosylated haemoglobin as an indicator of diabetes control in pregnancy: A 10-year review of the relationship between HbA1c trends and delivery outcome in type I and type II diabetes.

BACKGROUND: Pregestational diabetes mellitus (PGDM) confers an increased risk of adverse maternal and neonatal outcomes [1,2]. Glycaemic control in the medium and long term is commonly evaluated by examining glycosylated haemoglobin (HbA1c) levels. However, the value of HbA1c in pregnancy may be diminished by increased level of red cell turnover characteristic of pregnancy [3,4]. We sought to examine the impact of HbA1c in the first trimester and pre-delivery, and the within-patient change throughout gestation on mode of delivery and birthweight in pregnancies complicated by a pre-pregnancy diagnosis of type I or type II diabetes. METHODS: A 10-year consecutive cohort of pregnancies complicated by PGDM, from Jan 2010 until Dec 2019, was examined for HbA1c data in the first trimester and within 6 weeks of delivery. Perinatal outcome data, including gestational age at delivery, mode of delivery and birthweight centile, were obtained from hospital records. The Spearman Rank correlation was used to correlate HcA1c levels in the first trimester with birthweight centiles. Non-parametric summaries and rank-based tests, Signed-rank test and Kruskal-Wallis test, were used to compare Hba1c levels. RESULTS: During the 10-year study period, a consecutive cohort of 396 pregnancies that attained a viable gestational age (>24 weeks' gestation) and complicated by pregestational diabetes was identified; representing 81 % of the population of pregestational diabetic pregnancies managed by this service during the study period. The median [IQR] HbA1c levels (mmol/mol) in the first trimester, pre-delivery and the differential across gestation were 51 [19] mmol/mol, 43 [11] mmol/mol and -8 [13] mmol/mol, respectively. A statistically significant reduction in HbA1c levels throughout gestation was observed (p < 0.001). The median [IQR] birthweight centile was 69 [50 - 96]. The distributions in HbA1c levels and birthweight centiles were heavily skewed. No correlation was identified between HbA1c levels and mode of delivery. CONCLUSION: Neither baseline HbA1c levels, pre-delivery values, nor trends across gestation appear to impact birthweight centile or mode of delivery in PGDM. While optimising glycaemic control can affect the long term health of the mother, these indices cannot be relied upon to reflect the impact of glycaemic control on fetal growth aberrations that influence mode of delivery.

Smartphone Apps for Surveillance of Gestational Diabetes: Scoping Review.

BACKGROUND: Developments and evolutions in the information and communication technology sector have provided a solid foundation for the emergence of mobile health (mHealth) in recent years. The cornerstone to management of gestational diabetes mellitus (GDM) is the self-management of glycemic indices, dietary intake, and lifestyle adaptations. Given this, it is readily adaptable to incorporation of remote monitoring strategies involving mHealth solutions. OBJECTIVE: We sought to examine and assess the available smartphone apps which enable self-monitoring and remote surveillance of GDM with a particular emphasis on the generation of individualized patient feedback. METHODS: Five databases were searched systematically for any studies evaluating mHealth-supported smartphone solutions for GDM management from study inception until January 2022. The studies were screened and assessed for eligibility of inclusion by 2 independent reviewers. Ultimately, 17 studies were included involving 1871 patients across 11 different countries. The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) conceptual framework was adhered to for data extraction and categorization purposes. RESULTS: All studies analyzed as part of this review facilitated direct uploading of data from the handheld glucometer to the downloaded patient-facing smartphone app. Glycemic data were captured by all studies and were reassuringly found to be either improved or noninferior to extant models of hospital-based care. Feedback was delivered in either an automated fashion through in-app communication from the health care team or facilitated through bidirectional communication with the app and hospital portal. Although resource utilization and cost-effective analyses were reported in some studies, the results were disparate and require more robust analysis. Where patient and staff satisfaction levels were evaluated, the response was overwhelmingly positive for mHealth smartphone-delivered care strategies. Emergency cesarean section rates were reduced; however, elective cesarean sections were comparatively increased among studies where the mode of delivery was assessed. Most reviewed studies did not identify any differences in maternal, perinatal, or neonatal health when app-based care was compared with usual in-person review. CONCLUSIONS: This comprehensive scoping review highlights the feasibility, reliability, and acceptability of app-assisted health care for the management of GDM. Although further exploration of the economic benefit is required prior to implementation in a real-world clinical setting, the prospect of smartphone-assisted health care for GDM is hugely promising.

Term induction of labour in nulliparous women: When to draw the line?

Objective: There exists uncertainty surrounding the most effective and efficient means of inducing labour, particularly in the setting of an unfavourable cervix. This study aims to determine the merit of repeating dinoprostone administration when a single application has failed to render the cervix favourable for amniotomy. Study design: Retrospective analysis of a consecutive cohort of nulliparous women who underwent term induction of labour in a tertiary referral centre in Ireland was conducted over a 12- month period (December 2019 to January 2021). The time-interval from dinoprostone administration to delivery and the incidence of complicated birth, associated with single and sequential dinoprostone dosing, were determined. Comparisons were made using the Chi-square test and logistic regression adjusting for gestational age delivery. Results: 586 nulliparous women underwent term induction of labour during the study period. Administration of a single dose of dinoprostone or amniotomy alone were associated with the greatest prospect of an uncomplicated vaginal birth when compared to sequential dinoprostone dosing. Nonetheless, just one in four nulliparous women undergoing induction of labour experienced an unassisted and uncomplicated vaginal birth. The median [interquartile range] for time interval from induction to delivery or decision for caesarean delivery was 0.4 [0.3-0.6] days in those who underwent amniotomy alone, compared to 1.1 [0.7-1.5] days, 1.8 [1.4-2.2] days and 2.2 [2.0-2.6] days for those with 1, 2 or 3 doses of dinoprostone, respectively (p < 0.001 between all groups; Figure 1). Conclusion: These contemporaneous data indicate that in circumstances where more than a single dose of dinoprostone is required for cervical priming in a nulliparous woman, the incidence of an uncomplicated vaginal delivery decreased from more than half of women to less than one third. Over one third of women who were administered either a single dose of dinoprostone or more than one dose experienced an emergency intrapartum Caesarean delivery or a complicated vaginal birth. These findings are relevant to nulliparous women undergoing induction of labour in the setting of an unfavourable cervix and should be incorporated into shared decision-making consultations, particularly when repeat administration of dinoprostone is being considered.

PCR vs karyotype for CVS and amniocentesis-the experience at one tertiary fetal medicine unit.

PURPOSE: Despite the rise of non-invasive screening tests for fetal aneuploidy, invasive testing during pregnancy remains the definitive diagnostic tool for fetal genetic anomalies. Results are rapidly available with polymerase chain reaction (PCR) tests, but cases have been reported whereby initial results were not confirmed after pregnancy termination and the fetal karyotype was ultimately normal. We sought to examine the potential discordance between PCR and karyotype for fetal aneuploidy. METHODS: The results from all amniocentesis and CVS tests performed over a 6-year period in a large tertiary level fetal medicine unit were reviewed. The results of PCR and karyotype were recorded and discrepancies examined. Pregnancy outcomes were also recorded. RESULTS: A total of 1222 invasive tests were performed (716 amniocentesis and 506 CVS). Within the cohort having amniocentesis, 11 had discrepant results (normal QF-PCR result but with a subsequent abnormal karyotype). There was 1 case among this group which QF-PCR should have identified. Within the CVS group, 7 patients had discrepant results. All had a diploid QF-PCR and would not have been identified as abnormal by it. CONCLUSION: PCR can be reliably used to determine aneuploidy of chromosomes 13, 18, and 21. However, in cases of sex chromosome aneuploidy, its performance is less reliable and warrants waiting for a complete karyotype. Given such discordance, we advise waiting for karyotype for all invasive tests performed in the presence of a normal ultrasound before advising a patient of a diploid QF-PCR result or potentially terminating a normal pregnancy.

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.

Neonatal polycystic kidney disease: a novel variant.

Polycystic kidney disease (PKD) is a condition typified by multiple renal cysts and renal enlargement. Classification is usually determined by mode of inheritance-autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD). ARPKD frequently presents in fetal life, but here we report a rare case of a family with two siblings diagnosed with ADPKD manifesting in utero with novel genetic findings. During the first pregnancy, enlarged cystic kidneys were noted at the gestational age (GA) of 18 weeks, which became progressively larger and anyhdramnios ensued by GA of 25 weeks. The couple opted to terminate the pregnancy. The second pregnancy similarly presented with bilateral enlarged cystic kidneys, but amniotic fluid remained normal throughout and she delivered at GA of 36 weeks. Genetic testing revealed the fetus to be heterozygous in AD PKD1, which is known to cause ADPKD and heterozygous for a hypomorphic allele for ADPKD of uncertain significance. The fetus was also found to be heterozygous in the AR PKHD1 gene with a variant not previously described in the literature. Where fetal features consistent with ARPKD are identified in the setting of familial ADPKD, this fetal manifestation of ADPKD, resulting from combined variants in the PKD1 gene, should be considered.

Calling into question the future of hyperoxygenation in pregnancy.

Maternal hyperoxygenation has been investigated as a potential diagnostic and therapeutic tool since the 1960s. Since then, it has been applied in many obstetric scenarios, both clinically and in the research setting. It is often administered without any determination of pre-hyperoxygenation maternal or fetal oxygen levels. Studies focussing on maternal oxygen therapy for the treatment of fetal growth restriction have been ongoing for over thirty years and there remains no clear evidence of benefit. Studies investigating the potential diagnostic or therapeutic role of maternal oxygen therapy in the setting of fetal congenital cardiac disease have reported varying success rates and some potentially worrying adverse effects. The purpose of this article is to review the effects of maternal hyperoxygenation on fetal and maternal health and to ascertain the safety of undertaking further clinical trials that employ the use of hyperoxygenation in pregnancy.

Prenatal prediction of neonatal haemodynamic adaptation after maternal hyperoxygenation.

The reactivity of the pulmonary vascular bed to the administration of oxygen is well established in the post-natal circulation. The vasoreactivity demonstrated by the fetal pulmonary artery Doppler waveform in response to maternal hyperoxia has been investigated. We sought to investigate the relationship between the reactivity of the fetal pulmonary arteries to hyperoxia and subsequent neonatal cardiac function in the early newborn period. METHODS: This explorative study with convenience sampling measured pulsatility index (PI), resistance index (RI), acceleration time (AT), and ejection time (ET) from the fetal distal branch pulmonary artery (PA) at baseline and following maternal hyperoxygenation (MH). Oxygen was administered for 10 min at a rate of 12 L/min via a partial non-rebreather mask. A neonatal functional echocardiogram was performed within the first 24 h of life to assess ejection fraction (EF), left ventricular output (LVO), and neonatal pulmonary artery AT (nPAAT). This study was conducted in the Rotunda Hospital, Dublin, Ireland. RESULTS: Forty-six women with a singleton pregnancy greater than or equal to 31 weeks' gestational age were prospectively recruited to the study. The median gestational age was 35 weeks. There was a decrease in fetal PAPI and PARI following MH and an increase in fetal PAAT, leading to an increase in PA AT:ET. Fetuses that responded to hyperoxygenation were more likely to have a higher LVO (135 ± 25 mL/kg/min vs 111 ± 21 mL/kg/min, p < 0.01) and EF (54 ± 9% vs 47 ± 7%,p = 0.03) in the early newborn period than those that did not respond to MH prenatally. These findings were not dependent on left ventricular size or mitral valve (MV) annular diameter but were related to an increased MV inflow. There was no difference in nPAAT. CONCLUSION: These findings indicate a reduction in fetal pulmonary vascular resistance (PVR) and an increase in pulmonary blood flow and left atrial return following MH. The fetal response to hyperoxia reflected an optimal adaptation to postnatal life with rapid reduction in PVR increasing measured cardiac output.

The Role of Aspirin for Preeclampsia Prevention in Women with Diabetes.

PURPOSE OF REVIEW: A diagnosis of type I or type 2 diabetes confers heightened risk for virtually every obstetric and perinatal complication, with the incidence of superimposed preeclampsia representing a particularly high-risk scenario. Over the past three decades, studies have investigated the role of aspirin in preeclampsia prevention, yielding some promising results for certain at-risk groups, yet unconvincing evidence of benefit among women with pre-pregnancy diabetes. The purpose of this review is to present the current evidence base for aspirin use in pregnancy as a means of mitigating preeclampsia risk in the setting of pregestational type I or type 2 diabetes. RECENT FINDINGS: Meta-analysis data examining low-dose aspirin for preeclampsia prevention in at-risk and low-risk women has demonstrated modest benefit, but subanalyses of cohorts with diabetes have failed to demonstrate a beneficial effect. Evidence is emerging that indicates a benefit only among women who initiate aspirin therapy prior to 16 weeks' gestation, and uncertainty exists surrounding the effective dose. In light of equipoise surrounding the potential role of aspirin for prevention of preeclampsia in women with diabetes, current research is targeted at determining clinical efficacy of aspirin in this high-risk obstetric population.

Reducing emergency cesarean delivery and improving the primiparous experience: Findings of the RECIPE study.

OBJECTIVE: The ability to predict the need for emergency Cesarean delivery holds the potential to facilitate birth choices. The objective of the RECIPE study (Reducing Emergency Cesarean delivery and Improving the Primiparous Experience) was to externally validate a Cesarean delivery risk prediction model. This model, developed by the Genesis study, identified five key predictive factors for emergency Cesarean delivery: maternal age, maternal height, BMI, fetal head circumference (HC) and fetal abdominal circumference (AC). STUDY DESIGN: This prospective, observational study was conducted in two tertiary referral perinatal centers. Inclusion criteria were as follows: primiparous women with a singleton, cephalic presentation fetus in the absence of fetal growth restriction (FGR), oligohydramnios, pre-eclampsia, pre-existing diabetes mellitus or an indication for planned Cesarean delivery. Between 38 + 0 and 40 + 6 weeks' gestational age, participants attended for prenatal assessment that enabled the determination of an individualized risk calculation for emergency Cesarean delivery during labour based on maternal height, BMI, fetal HC and AC, with crucially both participants and care providers being blinded to the resultant risk prediction score. Labor, delivery and postnatal outcomes were ascertained. Calibration and receiver operator curves were generated to determine the predictive capacity for emergency Cesarean delivery of the Genesis risk prediction model in this cohort. RESULTS: 559 primiparous participants were enrolled from May 2017 to April 2019, of whom 142 (25 %) had an emergency Cesarean delivery during labour. Participants with a low predicted risk score (<10 %) had a mean predicted rate of 8% (+/- standard deviation of 2%) and a similarly low actual observed rate of Cesarean delivery (8%). Participants with a high predicted risk (>50 %) had a mean predicted Cesarean delivery rate of 64 % (+/- standard deviation of 9%) and also had a high actual observed Cesarean delivery rate (62 %). The calibration curve and receiver operating characteristic curve demonstrated that this validation study had comparable discriminatory power for emergency Cesarean delivery to that described in the original Genesis study. The Area Under the Curve (AUC) in Genesis was 0.69, whereas the AUC in RECIPE was 0.72, which reflects good predictive capacity of the risk prediction model. CONCLUSION: The accuracy of the Genesis Cesarean delivery prediction tool is supported by this validation study.

The RECIPE study: reducing emergency Caesareans and improving the Primiparous experience: a blinded, prospective, observational study.

BACKGROUND: The RECIPE study aims to validate a risk prediction model for intrapartum caesarean delivery which has been developed by our group. The Genesis study was a prospective observational study carried out by the Perinatal Ireland Research Consortium across 7 clinical centres in Ireland between October 2012 and June 2015. Genesis investigated a range of maternal and fetal parameters in a prospective blinded study of 2336 singleton pregnancies between 39 + 0-41 + 0 weeks' gestational age. This resulted in the development of a risk prediction model for Caesarean Delivery in nulliparous women at term. The RECIPE study now proposes to provide external validation of this risk prediction tool. METHODS: In order to externally validate the model, we aim to include a centre which was not involved in the original study. We propose a trial of risk-assignment for intrapartum caesarean amongst nulliparous women with a singleton pregnancy between 38 + 0 and 40 + 6 weeks' gestational age who are planning a vaginal birth. Results of the risk prediction tool will be concealed from participants and from midwives and doctors providing labour care.. Participants will be invited for an ultrasound scan and delivery details will be collated postnatally. The principal aim of this study is to externally validate the risk prediction model. This prediction model holds the potential to accurately identify nulliparous women who are likely to achieve an uncomplicated vaginal birth and those at high prospect of requiring an unplanned caesarean delivery. DISCUSSION: Validation of the Genesis prediction model would enable more accurate counselling for women in the antenatal setting regarding their own likelihood of requiring an intrapartum Caesarean section. It would also provide valuable personalised information to women about the anticipated course of their own labour. We believe that this is an issue of national relevance that will impact positively on obstetric practice, and will positively empower women to make considered, personalised choices surrounding labour and delivery.

Can sonographic assessment of pulmonary vascular reactivity following maternal hyperoxygenation predict neonatal pulmonary hypertension? (HOTPOT study protocol).

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a condition that occurs in 0.5-7 per 1000 live births and can result in significant cardiovascular instability in the newborn. It occurs when there is a failure of the normal circulatory transition in the early newborn period. Recent studies have shown that fetal pulmonary vasculature reacts to maternal hyperoxygenation (MH). The aim of the study is to assess if the in-utero response to MH can predict pulmonary hypertension in the early newborn period. METHODS: We will perform a prospective cohort study. It will evaluate the use of fetal echocardiographic Doppler assessment of the pulmonary vasculature prior to and following MH to predict fetuses that may develop pulmonary hypertension in the neonatal period. The study will be undertaken in the Rotunda Hospital, Dublin, Ireland. A fetal ultrasound and echocardiography will be performed on fetuses in the third trimester. Blood flow velocity waveforms will be recorded during periods of fetal quiescence. Pulsatility index (PI), Resistance index (RI), Peak systolic (PSV) and end diastolic velocity (EDV), time-averaged velocity (TAV), acceleration time (AT), and ejection time (ET) will be measured within the fetal distal pulmonary artery (PA). The acceleration-to-ejection time ratio (AT: ET) will be used to assess pulmonary vascular resistance (PVR). Doppler measurements will be taken at baseline and repeated immediately following MH for 10 min (O2 100% v/v inhalational gas) at a rate of 12L/min via a partial non-rebreather mask. Doppler waveform measurements from the umbilical artery (UAD), middle cerebral artery (MCA) ductus arteriosus (DA), aortic isthmus (AoI) and ductus venosus (DV) will also be obtained. After birth, a comprehensive neonatal functional echocardiogram will be performed within the first 24 hours of life. DISCUSSION: This study proposes to validate methods described to date in investigating the fetal pulmonary vascular response to MH, with expansion of the study subjects to include fetuses at risk of PPHN. Evaluation of the different at-risk subgroups will be informative in relation to the fetal circulatory adaptation close to term. Prediction of neonatal pulmonary hypertension may help guide the pharmacological and neonatal ICU strategies that optimise postnatal survival.

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.

Investigating the role of early low-dose aspirin in diabetes: A phase III multicentre double-blinded placebo-controlled randomised trial of aspirin therapy initiated in the first trimester of diabetes pregnancy.

BACKGROUND: Preeclampsia, preterm birth and low birth weight represent key contributing factors to perinatal morbidity and mortality. Pregnancies complicated by type 1 and type 2 diabetes are at increased risk of these complications, which are purported to be largely attributed to placental dysfunction. Studies investigating a potential role for aspirin therapy in optimizing perinatal outcome have consistently failed to demonstrate a benefit among women with pre-existing diabetes, and yet widespread aspirin administration has become common practice in many centres. This study seeks to examine the effect of aspirin therapy, administered from the first trimester until 36 weeks gestation, on perinatal outcome in women with established pre-pregnancy diabetes. Our hypothesis is that aspirin therapy will reduce complications mediated by placental dysfunction, and improve perinatal outcomes. METHODS: This phase III double-blinded, placebo-controlled randomized clinical trial will be conducted in seven tertiary-level perinatology centres in Ireland. Consenting participants who meet all eligibility criteria will be allocated randomly to either aspirin 150 mg once daily or matching placebo, commenced between 11 + 0 and 13 + 6 weeks. Allocation will take place electronically using software by Clininfo with randomization tables provided by the trial biostatistician. The primary outcome will be a composite clinical measure of placental dysfunction (preeclampsia, preterm birth before 34 weeks, birthweight below the 10th centile or perinatal mortality). This trial has been set up such that it is parallel in design and is a superiority study. No participants have been recruited yet. The trial has been registered with Eudra Clinical Trials - EudraCT Number 2018-000770-29. Funding for this trial was granted by the Health research Board (HRB) 1/9/2017(DIFA-2017-026). DISCUSSION: Aspirin therapy has been investigated for the prevention of preeclampsia owing to its reduction on thromboxane production. Previous studies have failed to demonstrate a beneficial effect of aspirin on perinatal outcome amongst women with type I or type II diabetes. It is plausible that the failure to observe benefit to date, among the limited aspirin studies that have included participants with diabetes, may be a consequence of aspirin initiation too late in pregnancy to exert any effect on placentation. We believe that if aspirin is to be used for the prevention of placental dysfunction, it must be initiated before the second active phase of trophoblast invasion, which takes place from 14 weeks' gestation onwards. No randomized trials investigating the role of aspirin in prevention of preeclampsia in pregnancies complicated by diabetes have previously initiated treatment in the first trimester, the gestational period at which it is most likely to exert an effect on placentation.

Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state.

BACKGROUND: Supplemental oxygen is administered to pregnant women in many different clinical scenarios in obstetric practice. Despite the accepted uses for maternal hyperoxygenation, the impact of hyperoxia on maternal hemodynamic indices has not been evaluated. As a result, there is a paucity of data in the literature in relation to the physiological changes to the maternal circulation in response to supplemental oxygen. OBJECTIVE: The hemodynamic effects of oxygen therapy are under-recognized and the impact of hyperoxygenation on maternal hemodynamics is currently unknown. Using noninvasive cardiac output monitoring which employs transthoracic bioreactance, we examined the effect of brief hyperoxygenation on cardiac index, systemic vascular resistance, blood pressure, stroke volume, and heart rate in pregnant mothers during the third trimester, compared with those effects observed in a nonpregnant population subjected to the same period of hyperoxygenation. STUDY DESIGN: Hemodynamic monitoring was performed in a continuous manner over a 30-minute period using noninvasive cardiac output monitoring. Hyperoxygenation (O2 100% v/v inhalational gas) was carried out at a rate of 12 L/min via a partial non-rebreather mask for 10-minutes. Cardiac index, systemic vascular resistance, stroke volume, heart rate, and blood pressure were recorded before hyperoxygenation, at completion of hyperoxygenation, and 10 minutes after the cessation of hyperoxygenation. Two-way analysis of variance with repeated measures was used to assess the change in hemodynamic indices over time and the differences between the 2 groups. RESULTS: Forty-six pregnant and 20 nonpregnant women with a median age of 33 years (interquartile range, 26-38 years) and 32 years (interquartile range, 28-37 years) were recruited prospectively, respectively (P=.82). The median gestational age was 35 weeks (33-37 weeks). In the pregnant group, there was a fall in cardiac index during the hyperoxygenation exposure period (P=.009) coupled with a rise in systemic vascular resistance with no recovery at 10 minutes after cessation of hyperoxygenation (P=.02). Heart rate decreased after hyperoxygenation exposure and returned to baseline by 10 minutes after cessation of therapy. There was a decrease in stroke volume over the exposure period, with no change in systolic or diastolic blood pressure. In the nonpregnant group, there was no significant change in the cardiac index, systemic vascular resistance, stroke volume, heart rate, or systolic or diastolic blood pressure during the course of exposure to hyperoxygenation. CONCLUSION: Hyperoxygenation during the third trimester is associated with a fall in maternal cardiac index and a rise in systemic vascular resistance without recovery to baseline levels at 10 minutes after cessation of hyperoxygenation. The hemodynamic changes that were observed in this study in response to hyperoxygenation therapy during pregnancy could counteract any intended increase in oxygen delivery. The observed maternal effects of hyperoxygenation call for a reevaluation of the role of hyperoxygenation treatment in the nonhypoxemic pregnant patient.

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.