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.

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.

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.

Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial.

BACKGROUND: 2·6 million pregnancies were estimated to have ended in stillbirth in 2015. The aim of the AFFIRM study was to test the hypothesis that introduction of a reduced fetal movement (RFM), care package for pregnant women and clinicians that increased women's awareness of the need for prompt reporting of RFM and that standardised management, including timely delivery, would alter the incidence of stillbirth. METHODS: This stepped wedge, cluster-randomised trial was done in the UK and Ireland. Participating maternity hospitals were grouped and randomised, using a computer-generated allocation scheme, to one of nine intervention implementation dates (at 3 month intervals). This date was concealed from clusters and the trial team until 3 months before the implementation date. Each participating hospital had three observation periods: a control period from Jan 1, 2014, until randomised date of intervention initiation; a washout period from the implementation date and for 2 months; and the intervention period from the end of the washout period until Dec 31, 2016. Treatment allocation was not concealed from participating women and caregivers. Data were derived from observational maternity data. The primary outcome was incidence of stillbirth. The primary analysis was done according to the intention-to-treat principle, with births analysed according to whether they took place during the control or intervention periods, irrespective of whether the intervention had been implemented as planned. This study is registered with www.ClinicalTrials.gov, number NCT01777022. FINDINGS: 37 hospitals were enrolled in the study. Four hospitals declined participation, and 33 hospitals were randomly assigned to an intervention implementation date. Between Jan 1, 2014, and Dec, 31, 2016, data were collected from 409 175 pregnancies (157 692 deliveries during the control period, 23 623 deliveries in the washout period, and 227 860 deliveries in the intervention period). The incidence of stillbirth was 4·40 per 1000 births during the control period and 4·06 per 1000 births in the intervention period (adjusted odds ratio [aOR] 0·90, 95% CI 0·75-1·07; p=0·23). INTERPRETATION: The RFM care package did not reduce the risk of stillbirths. The benefits of a policy that promotes awareness of RFM remains unproven. FUNDING: Chief Scientist Office, Scottish Government (CZH/4/882), Tommy's Centre for Maternal and Fetal Health, Sands.

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.

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

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

Prediction of cesarean delivery in the term nulliparous woman: results from the prospective, multicenter Genesis study.

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.

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

BACKGROUND: Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. OBJECTIVE: The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. STUDY DESIGN: In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. RESULTS: Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7-35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n = 45) of cases remained abnormal and 22% of these (n = 10) had an adverse perinatal outcome. The remaining 48% (n = 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n = 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n = 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n = 42) in the normalizing cerebroplacental ratio group (P value <.001). CONCLUSION: The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome.

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.

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.

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.

Dichorionic twin ultrasound surveillance: sonography every 4 weeks significantly underperforms sonography every 2 weeks: results of the Prospective Multicenter ESPRiT Study.

OBJECTIVE: A 2-week ultrasound scanning schedule for monochorionic twins is endorsed widely. There is a lack of robust data to inform a schedule for the surveillance of dichorionic gestations. We aimed to determine how ultrasound scanning that is performed at 2- or 4-week intervals (or every 4 weeks before 32 weeks' gestation and every 2 weeks thereafter) may impact the prenatal detection of fetal growth restriction (FGR) and ultimately influence timing of delivery. STUDY DESIGN: In a consecutive cohort of 789 dichorionic twin pregnancies that were recruited prospectively for the multicenter Evaluation of Sonographic Predictors of Restricted Growth in Twins study, ultrasound determination of fetal growth and interrogation of umbilical and middle cerebral artery Doppler scans were performed every 2 weeks from 24 weeks' gestation until delivery. Complete delivery and perinatal outcome data were recorded for all pregnancies. Where delivery was prompted by FGR, abnormal umbilical artery Doppler examination or poor biophysical profile and in the absence of ruptured membranes, onset of labor, preeclampsia, or antepartum hemorrhage, the delivery was considered "ultrasound-indicated." For ultrasound-indicated deliveries, detection probabilities for FGR/abnormal umbilical artery Doppler scans/poor biophysical were determined according to the interval between examinations, by the suppression if alternate examination data. RESULTS: Among 789 dichorionic twin pregnancies, 66 pairs (8%) had an "ultrasound indicated" delivery. Detection of FGR was reduced from 88-69%, and detection of abnormal umbilical artery Doppler was reduced from 82-62% when a 4-week ultrasound schedule was simulated. Both of these reductions reached statistical significance. There was a nonsignificant trend toward a reduction in the recording of oligohydramnios with a 4-week interval between examinations. CONCLUSION: This study suggests that the ultrasound surveillance program of every 2 weeks that is recommended currently for monochorionic twins should be extended to dichorionic gestations.

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.

The influence of maternal body mass index on fetal weight estimation in twin pregnancy.

OBJECTIVE: Sonographic estimated fetal weight (EFW) is important in the management of high-risk pregnancies. The possibility that increased maternal body mass index (BMI) adversely affects EFW assessments in twin pregnancies is controversial. The aim of this study was to investigate the effect of maternal BMI on the accuracy of EFW assessments in twin gestations prospectively recruited for the ESPRiT (Evaluation of Sonographic Predictors of Restricted growth in Twins) study. STUDY DESIGN: One thousand one twin pair pregnancies were recruited. After exclusion, BMI, birthweights, and ultrasound determination of EFW (within 2 weeks of delivery) were available for 943 twin pairs. The accuracy of EFW determination was defined as the difference between EFW and actual birthweight for either twin (absolute difference and percent difference). Cells with less than 5% of the population were combined for analysis resulting in the following 3 maternal categories: (1) normal/underweight, (2) overweight, and (3) obese/extremely obese. RESULTS: Analysis of the 3 categories revealed mean absolute variation values of 184 g (8.0%) in the normal/underweight group (n = 531), 196 g (8.5%) in the overweight group (n = 278), and 206 g (8.6%) in the obese/extremely obese group (n = 134) (P = .028, which was nonsignificant after adjustment for multiple testing). Regression analysis showed no linear or log-linear relationship between BMI and the accuracy of EFW (P value for absolute difference = .11, P value for percentage difference = .27). CONCLUSION: Contrary to a commonly held clinical impression, increasing maternal BMI has no significant impact on the accuracy of EFW in twin pregnancy.

Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia.   Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders.

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.

Subclinical hypothyroidism as a risk factor for placental abruption: evidence from a low-risk primigravid population.

BACKGROUND: Subclinical thyroid hypofunction in pregnancy has been shown to have an association with neurodevelopmental delay in the offspring. It is unclear whether obstetric factors may account for this observation. AIMS: To establish the prevalence of subclinical hypothyroidism (SCH) in a low-risk primigravid population and to explore its association with obstetric sequelae. MATERIALS AND METHODS: Nine hundred and fifty-three primigravid women had thyroid hormone indices analysed in the early second trimester. Delivery and neonatal outcomes were available for 904 women who met the criteria for inclusion in the study. Women with subclinical hypothyroidism (thyroid-stimulating hormone (TSH) values at or above the 98th percentile with a normal free thyroxine (fT4)) or isolated maternal hypothyroxinaemia (fT4 level at or below the second percentile with a normal-range TSH) were compared with biochemically euthyroid controls. Chi-squared test and analysis of variance were used for statistical analysis. RESULTS: The prevalence of SCH or isolated maternal hypothyroxinaemia was 4%. Positivity for antithyroid peroxidase (TPO) or antithyroglobulin (ATG) antibodies correlated with SCH status (P = 0.02). Placental abruption was observed more commonly in the setting of either SCH or isolated maternal hypothyroxinaemia when compared with euthyroid controls (P = 0.02 and 0.04, respectively). CONCLUSIONS: Subclinical hypothyroidism and isolated maternal hypothyroxinaemia are associated with placental abruption. The observation of these effects in this healthy low-risk population lends weight to the case for antenatal screening for diminished thyroid reserve.

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.