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.

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.

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.

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.

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.

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.

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.

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.

Perinatal mortality or severe neonatal encephalopathy among normally formed singleton pregnancies according to obstetric risk status:" is low risk the new high risk?" A population-based cohort study.

OBJECTIVE: To evaluate the capacity of the current system of obstetric risk stratification at the outset of pregnancy to predict severe adverse perinatal outcome. STUDY DESIGN: This retrospective cohort study of singleton pregnancies over a five year period (2009-2013) was performed at the Rotunda Hospital, Dublin, Ireland. High-risk or low-risk status was assigned retrospectively to a large consecutive cohort of women with a normally-formed singleton pregnancy on the basis of factors analyzed at the first prenatal hospital visit. The incidence of severe perinatal morbidity and mortality were compared between high- and low-risk groups to determine the predictive utility of risk stratification at the outset of pregnancy for severe perinatal morbidity. RESULTS: During the study period, 41,044 patients registered for prenatal care. 25,702;(63%) were deemed low-risk and 15,342;(37%) high-risk. Low-risk women were statistically more likely to be nulliparous (p < 0.0001) and to have a spontaneous or operative vaginal delivery (p < 0.0001). High-risk women were more likely to be multiparous and to undergo Caesarean delivery (p < 0.0001). The perinatal mortality rate was 3.8 per-1000 in low-risk pregnancies and 6.1 per-1000 in the a priori high-risk group (p = 0.012). The incidence of severe neonatal encephalopathy (NNE) was 1.8 and 0.65 per-1000 in the low and high-risk groups respectively (p = 0.0025). CONCLUSION: Where low-risk status is assigned at registration, neonatal encephalopathy is more prevalent. This data is relevant for the design of prenatal care models and demonstrates that assignment of low obstetric risk on the basis of maternal or pre-pregnancy factors alone may erroneously be interpreted as conferring low-risk status to the fetus.

Rab11 family expression in the human placenta: Localization at the maternal-fetal interface.

Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting. The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. These findings encouraged us to further analyse the localization of these Rabs and their common effector protein, the Rab Coupling Protein (RCP), by immunofluorescence microscopy and to extend this work to normal human placental tissue. The placenta is a highly active exchange interface, facilitating transfer between mother and fetus during pregnancy. As Rab11 proteins are closely involved in transcytosis we hypothesized that the placenta would be an interesting human tissue model system for Rab investigation. By immunofluorescence microscopy, Rab11a, Rab11c(Rab25), Rab14 as well as their common FIP effector RCP showed prominent expression in the placental cell lines. We also identified the expression of these proteins in human placental lysates by Western blot analysis. Further, via fluorescent immunohistochemistry, we noted abundant localization of these proteins within key functional areas of primary human placental tissues, namely the outer syncytial layer of placental villous tissue and the endothelia of fetal blood vessels. Overall these findings highlight the expression of the Rab11 family within the human placenta, with novel localization at the maternal-fetal interface.

Prenatal prediction of significant intertwin birthweight discordance using standard second and third trimester sonographic parameters.

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.

Prenatal detection of major congenital heart disease - optimising resources to improve outcomes.

INTRODUCTION: Congenital heart disease (CHD) is the most common major structural fetal abnormality and the benefits of prenatal detection are well described. The objective of this study was to evaluate the precision of prenatal diagnosis at a single tertiary referral unit over two three year periods (2006, 2007, 2008 and 2010, 2011, 2012), before and after a prenatal screening protocol for CHD was developed to include extended cardiac views, mandatory recall for suboptimal views, and a multidisciplinary Fetal Cardiac clinic was established. There exists a single national centre for paediatric cardiothoracic surgery in Ireland, a situation which facilitates near complete case ascertainment. MATERIALS AND METHODS: Surgery records of the National Children's Cardiac Centre were interrogated for all cases of major congenital heart defects requiring surgical intervention in the first six months of life. Minor procedures such as ligation of a patent ductus arteriosus and isolated atrial septal defect repairs were excluded. Analyses of the Fetal Medicine database at the Rotunda Hospital (a stand-alone tertiary level perinatology centre with 8500 deliveries per year) and the mortality data at the Perinatal Pathology department were conducted. The Cochrane-Armitage trend test was used to determine statistical significance in prenatal detection rates over time. RESULTS: 51,822 women delivered during the study period, and the incidence of major congenital heart disease either that underwent surgical intervention or that resulted in perinatal mortality, was 238/51,822 (0.5%). Prenatal detection of major CHD increased from 31% to 91% (p<0.001). Detection of critical duct-dependant lesions rose from 19% to 100%. CONCLUSION: We attribute the dramatic improvement in prenatal detection rates to the multifaceted changes introduced during the study period. Improved prenatal detection for births that are geographically remote from the National Paediatric Cardiac Centre will require local replication of this prenatal programme.

Gestational hypertensive disease in twin pregnancy: Influence on outcomes in a large national prospective cohort.

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.

Neuro-developmental outcome of a large cohort of growth discordant twins.

UNLABELLED: Our aims were to study the effect of birthweight growth discordance (≥20%) on neuro-developmental outcome of monochorionic and dichorionic twins and to compare the relative effects of foetal growth discordance and prematurity on cognitive outcome. We performed a cross-sectional multicentre prospective follow-up study from a cohort of 948 twin pregnancies. One hundred nineteen birthweight-discordant twin pairs were examined (24 monochorionic pairs) and were matched for gestational age at delivery with 111 concordant control pairs. Participants were assessed with the Bayley Scales between 24 and 42 months of age. Analysis was by paired t test for intra-twin pair differences and by multiple linear regression. Compared to the larger twin of a discordant pair, the smaller twin performed significantly worse in cognition (mean composite cognitive score difference = -1.7, 95% confidence interval (CI) = 0.3-3.1, p = 0.01) and also in language and motor skills. Prematurity prior to 33 weeks' gestation, however, had a far greater impact on cognitive outcomes (mean cognitive composite score difference = -5.8, 95% CI = 1.2-10.5, p = 0.008). CONCLUSION: Birthweight growth discordance of ≥20% confers an independent adverse effect on long-term neuro-development of the smaller twin. However, prior to 33 weeks' gestation, gestational age at birth adversely affects cognitive development to a greater extent than foetal growth discordance.

The effect of maternal subclinical hypothyroidism on IQ in 7- to 8-year-old children: A case-control review.

BACKGROUND: In Ireland, pregnant women are not routinely screened for subclinical hypothyroidism (SCH). AIM: Our objective was to compare the intelligence quotient (IQ) of children whose mothers had been diagnosed with SCH prenatally with matched controls using a case-control retrospective study. MATERIALS AND METHODS: In a previous study from our group, 1000 healthy nulliparous women were screened anonymously for SCH. This was a laboratory diagnosis involving elevated TSH with normal fT4 or normal TSH with hypothyroxinaemia. We identified 23 cases who agreed to participate. These were matched with 47 controls. All children underwent neurodevelopmental assessment at age 7-8. Wechsler Intelligence Scale for Children IV assessment scores were used to compare the groups. Our main outcome measure was to identify whether there was a difference in IQ between the groups. RESULTS: From the cohort of cases, 23 mothers agreed to the assessment of their children as well as 47 controls. The children in the control group had higher mean scores than those in the case group across Verbal Comprehension Intelligence, Perceptual Reasoning Intelligence, Working Memory Intelligence, Processing Speed Intelligence and Full Scale IQ. Mann-Whitney U-test confirmed a significant difference in IQ between the cases (composite score 103.87) and the controls (composite score 109.11) with a 95% confidence interval (0.144, 10.330). CONCLUSIONS: Our results highlight significant differences in IQ of children of mothers who had unrecognised SCH during pregnancy. While our study size and design prevents us from making statements on causation, our data suggest significant potential public health implications for routine prenatal screening.

Comparison of outcomes of twins conceived spontaneously and by artificial reproductive therapy.

OBJECTIVE: To compare the outcomes of twin pregnancies conceived by artificial reproductive techniques (ART) with those of spontaneous conception. STUDY DESIGN: In this multicenter prospective trial, comparisons were made between methods of conception in twin pregnancies, for maternal and perinatal outcomes. RESULTS: Of 1001 twin pairs, 763/1001 (72.7%) were spontaneously conceived and 238/1001(27.3%) were conceived by ART. There were no significant differences between the two groups with respect to obstetric complications. There were 13 per 1000 (20/1504; 1%) perinatal deaths in the spontaneously conceived group and 6 per 1000 (3/466; 0.6%) in the ART group (p = 0.8141). We found no differences in gestational age at delivery (median 36.9 versus 37.0 weeks), birth weight (median 2520 g versus 2538 g), or in a composite measure of adverse perinatal outcome (17% versus 15%) between the groups. CONCLUSION: There were no differences in the rate of adverse obstetric or perinatal outcomes between twins conceived naturally compared with twins conceived by assisted conception.