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Objective The aim of this study was to evaluate infants, born to women with SARS-CoV-2 detected during pregnancy, for evidence of haematological abnormalities or hypercoagulability in umbilical cord blood. Study design This was a prospective observational case-control study of infants born to women who had SARS-CoV-2 RNA detected by PCR at any time during their pregnancy (n = 15). The study was carried out in a Tertiary University Maternity Hospital (8,500 deliveries/year) in Ireland. This study was approved by the Hospital Research Ethics Committee and written consent was obtained. Umbilical cord blood samples were collected at delivery, full blood count and Calibrated Automated Thrombography were performed. Demographics and clinical outcomes were recorded. Healthy term infants, previously recruited as controls to a larger study prior to the outbreak of COVID-19, were the historical control population (n = 10). Results Infants born to women with SARS-CoV-2 had similar growth parameters (birth weight 3600 g v 3680 g, p = 0.83) and clinical outcomes to healthy controls, such as need for resuscitation at birth (2 (13.3%) v 1 (10%), p = 1.0) and NICU admission (1 (6.7%) v 2 (20%), p = 0.54). Haematological parameters (Haemoglobin, platelet, white cell and lymphocyte counts) in the COVID-19 group were all within normal neonatal reference ranges. Calibrated Automated Thrombography revealed no differences in any thrombin generation parameters (lag time (p = 0.92), endogenous thrombin potential (p = 0.24), peak thrombin (p = 0.44), time to peak thrombin (p = 0.94)) between the two groups. Conclusion In this prospective study including eligible cases in a very large population of approximately 1500 women, there was no evidence of derangement of the haematological parameters or hypercoagulability in umbilical cord blood due to COVID-19. Further research is required to investigate the pathological placental changes, particularly COVID-19 placentitis and the impact of different strains of SARS-CoV-2 (particularly the B.1.1.7 and the emerging Delta variant) and the severity and timing of infection on the developing fetus.

In the prospective multicenter Genesis study, we developed a prediction model for Cesarean delivery (CD) in term nulliparous women. The objective of this secondary analysis was to determine whether the Genesis model has the potential to predict maternal and neonatal morbidity associated with vaginal delivery.The national prospective Genesis trial recruited 2,336 nulliparous women with a vertex presentation between 39 + 0- and 40 + 6-weeks' gestation from seven tertiary centers. The prediction model used five parameters to assess the risk of CD: maternal age, maternal height, body mass index, fetal head circumference and fetal abdominal circumference. Simple and multiple logistic regression analyses were used to develop the Genesis model. The risk score calculated using this model were correlated with maternal and neonatal morbidity in women who delivered vaginally: postpartum hemorrhage (PPH), obstetric anal sphincter injury (OASI), shoulder dystocia, one- and five-minute Apgar score ≤ 7, neonatal intensive care (NICU) admission, cephalohematoma, fetal laceration, nerve palsy and fractures. The morbidities associated with spontaneous vaginal delivery were compared with those associated with operative vaginal delivery (OVD). The likelihood ratios for composite morbidity and the morbidity associated with OVD based on the Genesis risk scores were also calculated.A total of 1,845 (79%) nulliparous women had a vaginal delivery. A trend of increasing intervention and morbidity was observed with increasing Genesis risk score, including OVD (p 0.001), PPH (p 0.008), NICU admission (p 0.001), low Apgar score at one-minute (p 0.001) and OASI (p = 0.009). The morbidity associated with OVD was significantly higher compared to spontaneous vaginal delivery, including NICU admission (p 0.001), PPH (p = 0.022), birth injury (p 0.001), shoulder dystocia (p = 0.002) and Apgar score of7 at one-minute (p 0.001). The positive likelihood ratios for composite outcomes (where the OVD was excluded) increases with increasing risk score from 1.005 at risk score of 5% to 2.507 for risk score of50%.In women who ultimately achieved a vaginal birth, we have shown more maternal and neonatal morbidity in the setting of a Genesis nomogram-determined high-risk score for intrapartum CD. Therefore, the Genesis prediction tool also has the potential to predict a more morbid vaginal delivery.

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 rate of caesarean section (CS) is increasing globally. The nulliparous, term, singleton, vertex presentation, spontaneously labouring woman (Robson Group 1/RG1) is considered low risk for CS. It has been hypothesized that more CS occur at nighttime or at weekends due to doctor fatigue. The European Working Time Directive (EWTD) was implemented in our institution in 2013 to limit doctor working hours, which aimed at reducing fatigue but arguably fractures continuity of care. This study aimed to determine the effect of nocturnal hours and weekend on-call as well as the implementation of EWTD on our RG1 CS rates.This was a population-based study in a tertiary referral centre from 2008-2017. The inclusion criteria for our study were limited to RG1. Data were analysed from an established clinical database, including mode and time of delivery. Descriptive statistics are presented as number and percent for categorical variables. Relative frequencies were tested using chi-squared test. All statistical analyses were performed using SPSS Version 26. Statistical significance was defined as p .05.There were 86,473 deliveries over the 10-year study period. There were 18,761 women in RG1. Overall the RG1 CS rate was 12.9 % (n = 2415). Rates of CS in the RG1 were not statistically different between those delivering on weekdays (12.9 %, n = 1726/13,430) and weekends (12.9 %, n = 689/5,331, OR 0.99, 95 % CI = 0.90-1.09, p = .89). During daytime hours the CS rate was 12.1 % (n = 777/6411) and at nighttime was 13.3 % (n = 1638/12,350, OR 1.10, 95 % CI = 1.01-1.21, p = .03). Comparing the time periods pre and post EWTD implementation, there was a significant increase in CS rates (12.1 % n = 1319/10,873 V 13.9 % n = 1096/7,888, OR 1.17, 95 % CI = 1.07-1.27 p.001). With respect to other modes of delivery in RG1 pre and post EWTD, there was a statistically significant decrease in operative vaginal delivery (OVD) rates (40.1%, n=4,360 V 37.7%, n=2,973, OR 0.90, 95% CI = 0.85-0.95, p = .001) CONCLUSION: This study shows an association between obstetric trainee working practices, RG1 CS and OVD rates; this is most pronounced at night and after the introduction of the EWTD. It is unlikely that obstetric trainee working practices are the only factor related to the increasing CS rate and reduced OVD rate. Consideration should be giving to addressing the needs of obstetric trainees in relation to achieving their competencies with now reduced labour ward exposure. Further study is required to see if alternate arrangements in relation to simulation training could increase the OVD rate and reduce the CS rate.

Objective: Studies summarizing the outcome of first-trimester septated cystic hygroma are generally based on small studies or from multiple centers with limited ascertainment. We reviewed the natural history of a large cohort of such cases from a single tertiary referral center, with the aim being to establish contemporary outcome data, particularly in the setting of normal karyotype. Methods: A retrospective cohort study from 2007 to 2017 was conducted at a single tertiary referral prenatal diagnosis center. Data were analyzed from a prospectively collated fetal anomaly database. Search terms were “increased nuchal translucency (NT),” “cystic hygroma,” and “septated cystic hygroma.” All cases were confirmed to have NT >3 mm with septations. Cases of simple increased NT without septations were excluded. Results: During the study period, over 110,000 pregnancies were delivered at our center, resulting in 410 cases of septated cystic hygroma diagnosed prior to 14 weeks’ gestation. Pregnancy outcome was obtained in 99% (405/410) of cases, with detailed pathology outcome available in 92% (378/410). A total of 87% (351/405) underwent invasive prenatal testing, and postnatal chromosome status was established in further 27 cases. A total of 61% (230/378) had abnormal chromosomal status. Of the 39% (148/378) with normal chromosomal status, only 13% (19/148) had a significant structural fetal abnormality, which included 7 cardiac and 12 noncardiac abnormalities. Overall, the perinatal loss was 62% (253/405). The total survival rate in the setting of euploid cystic hygroma without structural abnormality was 84% (108/129). Conclusions: Counseling regarding outcomes in the setting of first-trimester septated cystic hygroma initially focuses on the strong likelihood of an abnormal karyotype, which occurs in 61% of cases. However, once fetal chromosomal abnormality is excluded, our results demonstrate only a 13% incidence of major structural fetal abnormality, which appears significantly less than previously reported. Normal fetuses have a 77% survival rate. These data represent the largest single-center study of first-trimester cystic hygroma with complete outcome data and therefore will be useful for contemporary patient counseling. Such counseling can be more positive than previously expected, once chromosomal abnormality is first excluded.

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).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.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.The accuracy of the Genesis Cesarean delivery prediction tool is supported by this validation study.

To characterize abnormal growth processes and their associated cardiovascular abnormalities in SGA fetuses using Individualized Growth Assessment (IGA).This longitudinal investigation utilized a SGA cohort [EFW and BW10th percentile] derived from the PORTO study. Fetuses categorized by their Fetal Growth Pathology Score [FGPS1] patterns [Pattern 2 {Pattern 2 was usually characterized by a single, growth abnormality (67% of cases) of variable magnitude that occurred within two weeks of delivery {median onset age: 37.6 weeks}. The incidence of UA abnormalities was low (25%) while those of MCA and DV/MPI were high {60%, 42%}. Most neonates were of normal size (67%) and delivered at term (67%).Pattern 3 had an initial progressive growth restriction phase, followed by constant but abnormally low growth. Growth pathology had an early onset (median age: 31.6 weeks), was moderate but persistently abnormal. The incidences of cardiovascular abnormalities were moderate [30-50%]. Most neonates were abnormally small (80%) but delivered at term (90%).Pattern 5 had an initial progressive phase with an early onset [onset age {median}: 31.6 weeks]. However, this process was arrested and returned toward normal. Growth pathology magnitudes were minor as were the incidences of cardiovascular abnormalities. Neonatal size was usually normal and all fetuses delivered at term.Characteristics of SGA Growth Restricted, Patterns 2, 3 and 5 are clearly different from those found in SGA Normal or SGA Growth Restricted Pattern 1 groups. They also differed from one another, indicating that growth restriction can manifest itself in several different ways. Pattern 2 is similar to "late" growth restriction reported previously. Patterns 3 and 5 are novel and have been designated as "adaptive" and "recovering" types of growth restriction.

To characterize growth processes and their associated cardiovascular abnormalities in SGA fetuses with normal growth and progressive growth restriction patterns as defined by Individualized Growth Assessment (IGA).A SGA cohort (EFW and BW10th percentile) was derived from the PORTO study that included 47 fetuses with normal growth outcome (SGA Normal) and 34 fetuses with progressive growth restriction (SGA Growth Restricted, Pattern 1). Composite fetal size parameters were used to quantify growth pathology at individual third trimester time points (individual composite Prenatal Growth Assessment Score {icPGAS}) and calculated cumulatively during the third trimester (Fetal Growth Pathology Score 1{FGPS1}). Paired Doppler evaluations of the umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and myocardial performance index (MPI) were used to detect cardiovascular anomalies. Outcome variables were birth age and birth weight.Ranking fetuses with respect to the severity of the 3rd trimester growth pathology (-FGPS1) revealed three subgroups in each of these two groups. In SGA Normal, no (51%), minimal (19%) or minor (30%) growth abnormalities were present. Although vascular flow abnormalities occurred without growth abnormalities (UA: 38%; MCA: 35%), they increased with minor growth disturbances (UA: 64%; MCA: 50%). All fetuses delivered at term and in only 7 cases (minor growth abnormalities subgroup) were the neonates abnormally small based on IGA criteria. In SGA Growth Restricted, Pattern 1, the progression of growth restriction was slow (47%), moderate (21%) and rapid (32%). Corresponding median -FGPS1 values were -1.34%, -2.67% and -4.88%, respectively. The median age of onset was 33.6, 29.7 and 29.7 weeks in these three subgroups. UA abnormalities occurred infrequently in the first two subgroups but were found in all cases of rapidly progressing pathology. Similar results were found for the MCA and DV + MPI Doppler parameters (rapid progression: MCA = 50%; DV + MPI = 50%). Premature delivery occurred less frequently with slow progression but was nearly 100% in the moderately and rapidly progressive subgroups.Negative FGPS1 growth restriction patterns can be used to classify SGA fetuses. Subgroups, based on ranked -FGPS1 values in both SGA Normal and SGA Growth Restricted Pattern 1 groups had marked differences in cardiovascular abnormalities and neonatal outcomes. The characteristics of these two groups are consistent with small, normally growing fetuses and fetuses with "early" growth restriction, respectively.

Objective To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. Study Design This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. Results Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67–0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1–13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6–104.6), and male gender (OR: 2.5, CI: 1.4–4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78–0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. Conclusion IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. Key Points

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

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

Background Antenatal exposure to intra-uterine inflammation results in precocious Haptoglobin (Hp) expression (switch-on status). We investigated the relationships between foetal Hp expression at birth with newborn and childhood outcomes. Methods We evaluated cord blood samples from 921 newborns of women at imminent risk for preterm delivery randomised to either placebo (n = 471, birth gestational age (GA) median [min-max]: 31 [24–41] weeks) or magnesium sulphate (n = 450, GA 31 [24–42] weeks]). Primary outcome was infant death by 1 year and/or cerebral palsy (CP) ≥ 2 years of corrected age. Adjusted odd ratios (aOR) for neonatal and childhood outcomes were calculated controlling for GA, birth weight, sex, and magnesium exposure. Findings Primary outcome occurred in 2.8% of offspring. Newborns were classified in three pre-defined categorisation groups by cord blood Hp switch status and IL-6 levels: inflammation-nonexposed (Category 1, n = 432, 47%), inflammation-exposed haptoglobinemic (Category 2, n = 449, 49%), and inflammation-exposed anhaptoglobinemic or hypohaptoglobinemic (Category 3, n = 40, 4%). Newborns, found anhaptoglobinemic or hypohaptoglobinemic (Category 3) had increased OR for intraventricular haemorrhage (IVH) and/or death (aOR: 7.0; 95% CI: 1.4–34.6, p = 0.02) and for CP and/or death (aOR: 6.27; 95% CI: 1.7–23.5, p = 0.006) compared with Category 2. Foetal ability to respond to inflammation by haptoglobinemia resulted in aOR similar to inflammation-nonexposed newborns. Hp1-2 or Hp2-2 phenotypes protected against retinopathy of prematurity (aOR = 0.66; 95% CI 0.48–0.91, p = 0.01). Interpretation Foetal ability to switch-on Hp expression in response to inflammation was associated with reduction of IVH and/or death, and CP and/or death. Foetuses unable to mount such a response had an increased risk of adverse outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT00014989

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.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.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.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 Warburg effect, defined as increased glycolysis and decreased oxidative phosphorylation, occurs in murine macrophages following LPS stimulation and is required for activation. There are differences between human and murine macrophage metabolic responses to stimulation, with peak metabolite concentrations occurring earlier in humans than mice. Complex changes occur in the human immune system with age, resulting in the very young and the very old being more susceptible to infections. Anti-bacterial immune responses in umbilical cord immune cells are considered deficient but there is a paucity of data on the role that metabolism plays. We hypothesized that metabolic responses in human macrophages occur early during activation. In addition, we hypothesized that umbilical cord derived macrophages have an altered immunometabolic response compared with adult macrophages. We demonstrate that adult and cord blood monocyte derived macrophages (MDM) immediately increase glycolysis in response to stimulation with LPS or Mycobacterium tuberculosis (Mtb), however only adult MDM decrease oxidative phosphorylation. At 24 hours post stimulation, glycolysis remains elevated in both adult and cord blood MDM, oxidative phosphorylation remains unchanged in the cord blood MDM and has normalized in the adult MDM stimulated with Mtb. However, LPS stimulated adult MDM have increased oxidative phosphorylation at 24 hours, illustrating differences in metabolic responses to different stimuli, time-dependent variation in responses and differences in macrophage metabolism in adults compared with umbilical cord blood. We compared the phenotype and function of macrophages derived from adult or cord blood. Cord blood MDM secreted less TNF following Mtb stimulation and more IL-6 following LPS stimulation compared with adult MDM. Our findings demonstrate that whilst cord blood MDM exhibit an immediate increase in glycolytic flux in response to stimulation, similar to adult MDM, cord blood MDM do not concomitantly decrease oxygen consumption. This indicates that adult macrophages shift to Warburg metabolism immediately after stimulation, but cord blood macrophages do not. Understanding the differences in the metabolic profiles of macrophages over a human lifetime will enable the translation of immunometabolism into effective immuno-supportive therapies that could potentially be targeted at vulnerable populations, such as the very old and the very young.

OBJECTIVE We have shown previously that third-trimester growth in small fetuses (estimated fetal weight (EFW) 10th percentile are also variable but in different ways. METHODS This was a study of 191 cases with EFW 10th percentile (appropriate-for-gestational-age (AGA) cohort), derived from the PORTO study. Composite size parameters were used to quantify growth pathology at individual third-trimester timepoints (individual composite prenatal growth assessment score (-icPGAS)). The fetal growth pathology score 1 (-FGPS1), calculated cumulatively from serial -icPGAS values, was used to characterize third-trimester growth patterns. Vascular-system evaluation included umbilical artery (UA) and middle cerebral artery (MCA) Doppler velocimetry. Outcome variables were birth age (preterm/term delivery) and BW (expressed as growth potential realization index for weight (GPRIWT ) and percentile). The findings from the AGA cohort were compared with those from small fetuses (EFW

ObjectivesThis study examined the natural history, including incidence and prevalence, of SARS-CoV-2 antibodies serially up to 6 months post infection in Irish Healthcare Workers (HCWs) at an academic tertiary maternity hospital, during the first pandemic peak from March to September 2020.DesignThis single centre observational study profiled SARS-CoV-2 incidence and infection using viral RNA detected using oro/nasopharyngeal swabs accompanied by serological assessment of study participants for the presence of S SARS-CoV-2 antibodies. Participant demographics were also collected alongside information on clinical symptoms and time to recovery. Real time polymerase-chain-reaction (RT-PCR) for viral RNA SARS-CoV-2 detection was performed using the Allplex™ SARS-CoV-2 three gene target 2019-nCoV assay (SeeGene Inc., Rep. of Korea) or the Xpert Xpress SARS-CoV-2 assay on the GeneXpert platform (Cepheid, USA). Blood samples were obtained at the time of initial swab and at up to 4 time points thereafter, for the serological assessment of antibodies against both the spike and nucleocapsid protein antigens of SARS-CoV-2. Serological response was measured using the Captia™ Anti-SARS-CoV-2 (IgG) ELISA (Trinity Biotech) as part of a clinical performance evaluation. Two other testing methods were also used; the Anti-SARS-CoV-2 ELISA (IgG) assay (EuroImmun) and the Abbott Anti-SARS-CoV-2 IgG 75 kit on the Architect™ i2000SR instrument (Abbott Laboratories).SettingAcademic Tertiary Maternity Hospital in Dublin, Ireland.ParticipantsWe invited symptomatic and asymptomatic healthcare workers employed at the Rotunda Maternity Hospital to participate in the CAST study.Main Outcome MeasuresThe CAST study aimed to examine incidence and clinical symptoms of SARS-CoV-2 in HCWs and to determine the presence and longevity of antibodies in this group. We also sought to examine the clinical utility of the Captia™ Anti-SARS-CoV-2 (IgG) ELISA (Trinity Biotech) and to compare it to the current “accepted” gold standard platform in Ireland.ResultsBy July 2020, 398 molecular tests had been completed on symptomatic staff with clinical suspicion of SARS-CoV-2 infection. In this cohort, 14% (n=54/398) had SARS-CoV-2 RNA detected by RT-PCR. The CAST study enrolled 137 HCWs with 86 participants symptomatic at time of swab collection and a further 51 asymptomatic control participants. SARS-CoV-2 RNA was detected in 52% (n=45/86) symptomatic study participants and serological positivity was confirmed in 98% (n=44/45) of those participants. Asymptomatic SARS-CoV-2 RNA infection was detected in 4% (n=2/51) of control participants with a seropositivity rate in this group of 8% (n=4/51). We demonstrated that 95% of SARS-CoV-2 PCR positive participants have detectable levels of antibodies at 100 days post infection, which persisted in 91% of participants at day 160+. Ongoing symptoms up to six months post infection were present in 50% of study participants with positive PCR and serology results. These data will be important to consider for long-term workforce planning in a healthcare setting, as the ongoing pandemic continues.FundingThe CAST study was supported by the Rotunda Hospital and Trinity Biotech.

Background Background Population-based data on SARS-CoV-2 infection in pregnancy and assessment of passive immunity to the neonate, is lacking. We profiled the maternal and fetal response using a combination of viral RNA from naso-pharyngeal swabs and serological assessment of antibodies against SARS-CoV-2. Methods This multicentre prospective observational study was conducted between March 24th and August 31st 2020. Two independent cohorts were established, a symptomatic SARS-CoV-2 cohort and a cohort of asymptomatic pregnant women attending two of the largest maternity hospitals in Europe. Symptomatic women were invited to provide a serum sample to assess antibody responses. Asymptomatic pregnant women provided a nasopharyngeal swab and serum sample. RT-PCR for viral RNA was performed using the Cobas SARS-CoV-2 6800 platform (Roche). Umbilical cord bloods were obtained at delivery. Maternal and fetal serological response was measured using both the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche), Abbott SARS-CoV-2 IgG Assay and the IgM Architect assay. Informed written consent was obtained from all participants. Results Ten of twenty three symptomatic women had SARS-CoV-2 RNA detected on nasopharyngeal swabs. Five (5/23, 21.7%) demonstrated serological evidence of anti-SARS-CoV-2 IgG antibodies and seven (30.4%, 7/23) were positive for IgM antibodies. In the asymptomatic cohort, the prevalence of SARS-CoV-2 infection in RNA was 0.16% (1/608). IgG SARS-CoV-2 antibodies were detected in 1·67% (10/598, 95% CI 0·8%-3·1%) and IgM in 3·51% (21/598, 95% CI 2·3–5·5%). Nine women had repeat testing post the baseline test. Four (4/9, 44%) remained IgM positive and one remained IgG positive. 3 IgG anti-SARS-CoV-2 antibodies were detectable in cord bloods from babies born to five seropositive women who delivered during the study. The mean gestation at serological test was 34 weeks. The mean time between maternal serologic positivity and detection in umbilical cord samples was 28 days. Conclusion Using two independent serological assays, we present a comprehensive illustration of the antibody response to SARS-CoV-2 in pregnancy, and show a low prevalence of asymptomatic SARS-CoV2. Transplacental migration of anti-SARS-CoV-2 antibodies was identified in cord blood of women who demonstrated antenatal anti-SARS-CoV-2 antibodies, raising the possibility of passive immunity.

Objective We profile the maternal and fetal response to SARS-CoV-2 infection in symptomatic and asymptomatic pregnant women and make an assessment of passive immunity to the neonate, Design Multicentre prospective study. Setting Dublin, Ireland Methods RT-PCR for viral RNA via a nasopharyngeal swab was performed using the Cobas SARS-CoV-2 6800 platform. Maternal, and fetal serological antibody response, via umbilical cord bloods, was measured using both the Elecsys® immunoassay, Abbott SARS-CoV-2 IgG Assay and the IgM Architect assay. Main outcome Measure Prevalence of RT PCR positive SARS-CoV-2. Assessment of IgM and IgG anti-SARS-CoV-2 serology antibodies. Results Ten of twenty three symptomatic women had SARS-CoV-2 RNA in a nasopharyngeal swab. Five (5/23, 21.7%) demonstrated serological evidence of anti-SARS-CoV-2 IgG antibodies and seven (30.4%, 7/23) were positive for IgM antibodies. In the asymptomatic cohort, the prevalence of SARS-CoV-2 infection in RNA was 0.16% (1/608). IgG SARS-CoV-2 antibodies were detected in 1·67% (10/598, 95% CI 0·8%-3·1%) and IgM in 3·51% (21/598, 95% CI 2·3–5·5%). Nine women had repeat testing between post baseline. Four (4/9, 44%) remained IgM positive, one IgG positive. IgG anti SARS-CoV-2 antibodies were detectable in cord bloods from babies born to five seropositive women who delivered during the study. Conclusion Using two independent serological assays, we present a comprehensive illustration of the antibody response to SARS-CoV-2 in pregnancy, and show a low prevalence of asymptomatic SARS-CoV-2. Transplacental migration of anti-SARS-CoV-2 antibodies was identified in cord blood of women who demonstrated antenatal anti-SARS-CoV-2 antibodies, raising the possibility of passive immunity.

Pre-eclampsia (PET) affects 2-3% of all pregnancies, rising to 5-7% in nulliparous women. This study aimed to investigate the prevalence of PET over a 13-year period.A retrospective review was performed over a 13-year period (2004-2016) via interrogation of the annual clinical reports of The Rotunda Hospital, Dublin.There was a fall in the overall incidence of PET (nulliparous and multiparous), from a peak of 3.8% in 2007 to 1.5% in 2015. Comparing the first and second halves of the study time-period this decrease was statistically significant (In our institution, we have shown a decrease in preeclampsia rates over a 13-year period. While the reason for this trend remains unclear, a similar trend has been observed in another tertiary unit and additional research is required to explain the etiology behind these observations.

Contemporary approaches to monitoring quality of care in obstetrics often focus on comparing Cesarean Delivery rates. Varied rates can complicate interpretation of quality of care. We previously developed a risk prediction tool for nulliparous women who may require intrapartum Cesarean delivery which identified five key predictors. Our objective with this study was to ascertain if patient heterogeneity can account for much of the observed variation in Cesarean delivery rates, thereby enabling Cesarean delivery rates to be a better marker of quality of care.This is a secondary analysis of the Genesis study. This was a large prospective study of 2336 nulliparous singleton pregnancies recruited at seven hospitals. A heterogeneity score was calculated for each hospital. An adjusted Cesarean delivery rate was also calculated incorporating the heterogeneous risk score.A cut-off at the 90th percentile was determined for each predictive factor. Above the 90th percentile was considered to represent 'high risk' (with the exception of maternal height which identified those below the 10th percentile). The patient heterogeneous risk score was defined as the number of risk factors90th percentile (10th percentile for height). An unequal distribution of high-risk patients between centers was observed (p 0.001). The correlation between the Cesarean delivery rate and the patient heterogeneous risk score was high (0.76, p 0.05). When adjusted for patient heterogeneity, Cesarean delivery rates became closer aligned.Inter-institutional diversity is common. We suggest that crude comparison of Cesarean delivery rates between different hospitals as a marker of care quality is inappropriate. Allowing for marked differences in patient characteristics is essential for correct interpretation of such comparisons.

Background Operative vaginal delivery (OVD), either vacuum or forceps, can be used to expedite vaginal delivery. While rates of OVD have been reducing worldwide, rates in Ireland remain high. The Robson Ten Group Classification System (TGCS) was originally created to compare rates of caesarean delivery between healthcare units, although no similar system exists for the analysis of OVD. Aims We sought to examine rates of OVD using the TGCS in an effort to understand which patient groups make significant contributions to the overall rate of OVD. Materials and methods This is a retrospective cohort study of all women delivering in a tertiary-level university institution in Dublin, Ireland, from 2007 to 2016. Mode of delivery for all patients was extracted from contemporaneously recorded hospital records. Rates of OVD were analysed according to the TGCS, and the contribution of each group to the overall hospital population was calculated. Results There were 86 191 deliveries of women in our institution, of which 19.3% (16 673/86 191) had an OVD. Women in Group 1 (singleton, cephalic, nulliparous women at term in spontaneous labour) contributed the most to the overall rate of OVD, accounting for almost half of all OVDs (46.1% (7679/16 673)). Nulliparous women with a singleton, cephalic fetus at term who were induced (Group 2) were more likely to have an OVD than similar patients who laboured spontaneously (Group 1). Conclusion OVD accounts for almost one in five deliveries in our population and is predominately performed in nulliparous women. These groups may be the subject of interventions to lower rates of OVD. The Robson TGCS is a freely available tool to hospitals and birthing centres to facilitate comparison of rates of OVD on local and national levels.

Background: Pregnant women represent a vulnerable population at higher risk of complications of infectious diseases. Data regarding the consequences of the emerging pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy are scarce. Recent evidence suggests that pregnant women might be at higher risk of severe disease, while exposed fetuses and newborns could suffer from preterm birth, growth restriction and neonatal infections. Methods: We developed an international web registry to allow structured data collection. Pregnant women at any stage during gestation tested for SARS-CoV-2 infection were enrolled. Maternal, obstetrical and neonatal outcomes were recorded. Findings: 1033 pregnant women tested for SARS-CoV-2 were included, among which 926 tested positive and 107 tested negative. Positive pregnant women were at higher risk of severe maternal outcomes compared to negative women [aRR 5.6, 95% CI 1.4-22.7]. Risk factors for severe maternal outcomes among positive women were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. No difference in term of obstetrical and neonatal outcomes were observed between positive and negative women. Positive pregnant women with severe maternal outcomes were at higher risk of cesarean sections [70.7% (n=53/75)], preterm deliveries [62.7% (n= 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. A positive neonatal SARS-CoV-2 test was observed in 2.9% (n=11/384) of newborns with an available test at birth. Interpretation: Pregnant women, particularly those with associated comorbidities, seem to be at higher risk of severe complications of SARS-CoV-2 infection. Preliminary data regarding obstetrical and neonatal outcomes among women with a mild disease are reassuring. Funding Statement: None. Declaration of Interests: The authors declare that we have no conflicts of interest. Ethics Approval Statement: The study was approved by both the Swiss Ethical Board (CER-VD-2020-00548) and the local ethics boards at each participating center.

Background: Recent evidence suggests that pregnant women might be at higher risk of severe disease associated with the emerging pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while exposed fetuses/newborns could suffer from preterm birth, growth restriction and neonatal infections. The magnitude of this increased risk and specific risk factors for severity remains unclear. Methods: We performed a case control study comparing pregnant women with severe coronavirus disease 19 (case) to pregnant women with a milder form (controls) enrolled in COVI-Preg international registry cohort between from March 24 to July 26, 2020. Risk factors for severity, obstetrical, fetal and neonatal outcomes were assessed. Findings: A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented a severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of cesarean sections [70.7% (n=53/75)], preterm deliveries [62.7% (n= 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. Interpretation: Pregnant women, particularly those with associated comorbidities, seem to be at higher risk of severe complications of SARS-CoV-2 infection. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease; complications include cesarean sections, prematurity and neonatal admission to the intensive care unit. Funding Statement: None. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The study was approved by both the Swiss Ethical Board (CER-VD- 2020-00548) and the local ethics boards at each participating center.

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.

This is a transcript of a scientific conference on the subject of prenatal surgery for spina bifida. It represents the views of three patients, an obstetrician, a postnatal neurosurgeon, a neonatologist, a paediatric neurologist, two surgeons who practice open spina bifida foetal surgery, a fetoscopic surgeon and an obstetrician experienced in randomised trials and systematic reviews. Implications for current practice and recommendations for future research are also discussed in detail.

Objectives: Screening and diagnosis of gestational diabetes (GDM) has been a source of controversy. The prevalence has increased in line with an obesity epidemic and a trend towards delayed child-bearing. Treatment of even modest glycaemic impairment in pregnancy has been shown to be beneficial in preventing its clinical sequalae. However the cumbersome nature and timing of the oral glucose tolerance test coupled with debate around universal versus risk factor based screening have been problematic. This group aimed to investigate a panel of biomarkers which have shown promise in the literature to predict GDM from the first trimester in a group of high risk women. Methods: Serum samples were drawn on 248 women deemed at risk of GDM before 15 weeks' gestation to measure C-reactive protein, sex hormone binding globulin, adiponectin and 1,5 anhydroglucitol. Patients underwent an oral glucose tolerance test as per IADPSG criteria at 28 weeks' gestation. Multiple logistic regression was used to examine the link between incidence of GDM and early pregnancy serum biomarkers. Results: Adiponectin levels in the first trimester are independently linked to the risk of GDM. Serum adiponectin

Objectives We aimed to firstly identify the different haemodynamic profiles amongst nulliparous women who develop either gestational hypertension (GH), pre-eclampsia (PE), normotensive fetal growth restriction (FGR) versus unaffected pregnancies using non-invasive cardiac output monitoring (NICOM®). Our second primary objective was to assess the ability of NICOM® derived variables to predict the evolution of PE, GH and FGR. Study design Low risk nulliparous women were enrolled in a single center prospective observational study. NICOM® assessments were performed at 14, 20 and 28 weeks’ gestation and data was obtained on cardiac output (CO), total peripheral resistance (TPR), indexed TPR (adjusted for maternal body surface area; TPRi), stroke volume (SV), indexed SV (adjusted for maternal body surface area; SVi) and heart rate (HR). Logistic regression was used to model GH, PE and FGR with NICOM® measurements as predictors. Linear, non-linear and interaction terms were assessed using the Akaike Information Criterion. Results The haemodynamic profile of pregnancies complicated by uteroplacental disease- GH (n = 18), PE (n = 6) and FGR (n = 24) were compared to 318 healthy unaffected pregnant controls. Women with evolving PE have a different haemodynamic profile to those developing either GH or FGR. The best independent predictors for the evolution of uteroplacental disease at 14 weeks’ gestation were CO in the prediction of FGR (AUC = 0.61; p 0.002), TPR in the prediction of GH (AUC = 0.63; p Conclusions NICOM® derived maternal haemodynamic profile at 14 weeks’ gestation has the novel potential to identify pregnancies which will ultimately develop uteroplacental disease.

Platelet function in pregnancy is poorly understood. Previous studies of platelet function in pregnancy have used non-physiological assays of platelet function with conflicting results. This study using a physiological assay of platelet function investigated platelet interactions with von Willebrand Factor (VWF) in blood from healthy pregnant women and healthy non-pregnant controls. Blood samples (200 µl) from third-trimester pregnancies (n = 21) and non-pregnant controls (n = 21) were perfused through custom-made parallel-plate flow chambers coated with VWF under arterial shear (1,500 s−1). Multi-parameter measurements of platelet interactions with the immobilized VWF surface were recorded by digital-image microscopy and analysed using custom-designed platelet-tracking software. Platelet interactions with VWF decreased in healthy third-trimester pregnant participants relative to controls. This effect is most likely due to haemodilution which occurs physiologically during pregnancy. Interestingly, platelets in blood from pregnant participants translocated more slowly on VWF under arterial-shear conditions. These decreases in platelet translocation speed were independent of haemodilution, suggesting intrinsic changes in platelet function with pregnancy.

Background Fetal growth restriction (FGR) accounts for a significant proportion of perinatal morbidity and mortality. The cerebroplacental ratio (CPR) is gaining much interest as a useful tool in differentiating the “at-risk” fetus in both FGR and appropriate for gestational age (AGA) pregnancies. The Prospective Observational Trial to Optimize Pediatric Health in FGR (PORTO) group, have previously demonstrated that the presence of this ‘brain-sparing’ effect is significantly associated with adverse perinatal outcomes in the FGR cohort. However, data about neurodevelopment in children from pregnancies complicated by FGR are sparse and conflicting. Objective The aim of the PORTO NeuroDevelopmental Assessment Study (PANDA) was to determine whether children born after FGR pregnancies are at additional risk of adverse early childhood developmental outcomes compared to children born small for gestational age (SGA). The objective of this secondary analysis was to describe the role of CPR in the prediction of adverse early childhood neurodevelopmental outcome. Materials and Methods Participants were prospectively recruited from the Perinatal Ireland multicenter observational PORTO study cohort. FGR was defined as birth weight Results Assessments were performed on 198 SGA children; 136 FGR children with abnormal UA Doppler and normal CPR and 41 FGR children with both abnormal UA Doppler and CPR. At three years of age, while there were no differences in head circumference, children who also had an abnormal CPR had persistently shorter stature (p=0.005) and lower weight (p=0.18). Children from FGR affected pregnancies demonstrated poorer neurodevelopmental outcome than their SGA counterparts. FGR pregnancies with an abnormal CPR had significantly poorer neurological outcome at three years of age across all measured variables (Tables 1 & 2). Conclusion We have demonstrated that growth restricted pregnancies with a CPR