Invasive genetic testing is routinely recommended to investigate aneuploidy as a cause of cystic hygroma in the first trimester. In the context of normal genetic testing, the predicted outcome is impacted by the presence of co-existing structural anomalies, particularly cardiac anomalies. We reviewed the diagnosis and outcome of these patients to establish contemporary outcome data to aid appropriate counseling. This is a retrospective cohort study in a single large maternity hospital. Cases were identified using a fetal anomaly database and an electronic health record system. Data were collected on all patients with a fetal diagnosis of a nuchal translucency > 3mm with septations from 2007 to 2022. Results of chromosomal analysis, pregnancy outcomes and fetal outcomes were collated and described using summary statistics. During the 15-year period, there were over 135,000 deliveries at our center. 677 cases of septated cystic hygroma were diagnosed. Pregnancy outcome was obtained in 97.5% (n=660) of cases, with 92% (621/677) undergoing invasive prenatal or postnatal testing. 39% (247/621) had a normal karyotype. 38% (249/660) of women underwent termination of pregnancy. In-utero demise occurred in 24% (159/660). Structural anomalies were found in 16% (39/247) of those with normal karyotype. In cases of cystic hygroma, normal invasive testing in the absence of structural anomalies carried a livebirth rate of 86% (164/191), in contrast to an overall livebirth rate of 38% (252/660) in all pregnancies affected by cystic hygroma. Cystic hygroma is a significant finding in early pregnancy which confers a risk of aneuploidy of approximately 60% and is associated with adverse pregnancy outcomes. Outcomes of the study demonstrate a high livebirth rate in those with normal invasive testing and fetal echocardiography. This confirms the significance of appropriate counseling regarding confirmatory invasive testing, and highlights the value of follow-up with detailed anatomy ultrasound.

To identify potential cases for fetoscopic endoluminal tracheal occlusion (FETO) in a historical cohort of fetuses with congenital diaphragmatic hernia (CDH).

Data pertaining to outcome in dichorionic(DC) twins complicated by intrauterine growth restriction(IUGR) compared to singleton IUGR are sparse and conflicting. Given the limited evidence to date,we sought to compare perinatal outcome for IUGR in DC twins and singletons by compared data from two large prospective studies - Prospectve Observational Trial to Optimize Paediatric Health in Intrauterine Growth Restriction(PORTO) and Evaluation of Sonographic Predictors of Restricted growth in Twins(ESPRiT). Singleton IUGR data from 1116 pregnancies acquired from the PORTO study database were compared with 308 DC pregnancies with IUGR in at least one twin from the ESPRiT study database. IUGR was defined in both studies as estimated fetal weight(EFW) < 10thcentile. The Hadlock reference was used for centile determination. Both studies were conducted in the same tertiary care centres with dedicated research sonographers. Matching was performed with gestational age at delivery and two-weekly ultrasound examination. The composite outcome for twins is defined as outcome in either DC twin with IUGR. Maternal characteristics were comparable in both groups.Gestational age was prospectively assigned with ultrasound performed before 14 weeks' gestation in all cases(Table 1). The median gestational age and birth weight at delivery was similar in both groups(2200g at 36 weeks' gestation) regardless of the gestational age at which an EFW < 10thcentile was identified. In ultrasound examinations with an EFW < 10thcentile, DC twins with at least one twin with IUGR were at significantly elevated risk of adverse perinatal outcome compared to singleton IUGR, matched for any gestational age at delivery from 26-36 weeks' gestation(Table 2). These data indicate that the growth-restricted fetus in a DC twin gestation is at heightened risk of perinatal morbidity compared to a growth-restricted singleton. This observation should be considered in navigating the intensity of prenatal surveillance and the timing of delivery of a DC twin gestation complicated by fetal growth restriction in either twin.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Objective To evaluate the correlation between umbilical artery (UA) Doppler and its feasibility across categories of maternal body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) in the presence of fetal growth restriction (FGR). Methods A total of 1074 singleton pregnancies with suspected FGR on ultrasound examination between 24(+0) and 36(+0) weeks of pregnancy were reviewed. Evaluation of the UA Doppler was performed at 1- to 2-weekly intervals. Abnormal UA Doppler findings and delivery outcomes were compared between the different maternal BMI categories. Results Increased UA pulsatility index (PI >95th centile) was reported in 81% of obese class II patients (BMI 35-39.9) compared with a 46% incidence in the remaining categories, normal (BMI <24.9), overweight (BMI 25-29.9), and obese class I (BMI 30-34.9) (P = 0.001). In absent or reversed end diastolic flow (AEDF/REDF) we found an increasing incidence across the BMI categories (4%-25%) (P < 0.001). Higher maternal BMI was associated with lower birthweights and higher cesarean section rates. Increasing maternal BMI did not affect successful assessment of UA Doppler. Conclusion There is a positive correlation between increasing maternal BMI and abnormal UA Doppler findings in FGR. Maternal BMI may be considered as an additional risk factor when evaluating UA Doppler for placental insufficiency.

Recent expert consensus advocates a move away from elective Caesarean delivery for the fetus with gastroschisis. We sought to evaluate the mode and timing of delivery for pregnancies complicated by gastroschisis in our unit. This retrospective cohort study assessed all cases of prenatally diagnosed gastroschisis from 2013–2019. Cases were identified from the fetal assessment unit database. Data was compared to the previous 14 years compiled as part of an earlier study. 10 cases of prenatally diagnosed gastroschisis were identified. The mean gestation at delivery was 36+2 with a mean birthweight of 2.6kg. There was one intrauterine fetal demise at 34/40 and one pregnancy termination. Half of the remainder (n = 8) delivered by emergency Caesarean section (CS) and half by vaginal delivery. There were no scheduled elective CS in this cohort. Ultrasound evidence of bowel dilatation was noted in 75% (n = 6). Non-reassuring fetal testing was the indication for caesarean delivery in 75% (n = 3). Only one infant required intubation prior to transfer for surgical repair and this was following a preterm emergency CS. Compared with the preceding 14 years we have reduced our elective CS rate for prenatally diagnosed gastroschisis by 13%. There was no significant difference in 1 and 5 minute Apgar scores across the two time periods. In line with recommendations from the literature, we have demonstrated a change in practice towards attempted vaginal delivery for cases of prenatally diagnosed gastroschisis. This was achieved without any compromise in neonatal care or outcomes.

Introduction Neural tube defects occur in approximately 1/1000 live births in Ireland, with myelomeningocele being the most common form. The current standard management in Ireland involves postnatal closure however access to fetal surgery services is increasing. The Management of Myelomeningocele Study (MOMS) compared prenatal and postnatal closure and showed reduced risk of death, decreased need for ventriculo-peritoneal shunting and improved motor function in the prenatal closure group. We present a case of fetal closure of myelomeningocele referred from our institution. Clinical Case A 33-year-old female presented to the Rotunda for antenatal care in her second pregnancy following in vitro fertilisation abroad. Her first child was born with myelomeningocele and is a wheelchair user. She had been taking folic acid before and throughout this pregnancy. Antenatal ultrasound revealed a lemon-shaped head with Arnold-Chiari malformation, ventriculomegaly and myelomeningocele at L5/S1. Karyotype and microarray from amniocentesis were normal. She was referred to UCH London for fetal surgery consideration and ultimately underwent hysterotomy and closure of fetal myelomeningocele S1-S3 in Leuven, Belgium at 26 weeks gestation. The procedure involved successful closure of the dura and fascial layers, however, primary closure of the skin was not possible and so a silicone dermal regeneration template was applied to the defect. Improvement in head shape, ventricular size and Chiari malformation were noted on subsequent fetal ultrasound throughout the pregnancy. The patient presented with abdominal pain at 35+5 weeks gestation and proceeded to caesarean section. A live born male weighing 3.1 kg was delivered. He was vigorous with good lower limb movements and anal tone. The silicone graft was in position on the sacrum at delivery and peeled away spontaneously revealing a 2cm by 2cm patch of healthy granulating skin. There was no defect or leakage of cerebrospinal fluid. A silicone based wound dressing was applied and the infant was admitted to NICU for management. Enteral feeds were quickly established and postnatal cranial ultrasound was normal. He was transferred to Children’s University Hospital for ongoing multidisciplinary team input. Discussion This case represents the second patient to undergo fetal surgery for spina bifida from our institution, in a new partnership with UCH London and Leuven, Belgium. While the surgery is associated with risks of preterm delivery, intraoperative complications and uterine rupture, the potential for significantly better postnatal outcomes make it an important treatment option for some families and should be considered for discussion in suitable cases as they arise.

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.

We sought to examine rates of induction and cesarean section (CS) in a large cohort of deliveries across three tertiary referral centers over 8 years to explore how induction influences primary CS rates. Indications for primary CS were examined in detail for one of the centers. This is a retrospective analysis of prospectively gathered data carried out at three large maternity hospitals in Dublin from 2006-2014. All cases of inductions and CS for viable births were recorded during this study period and analyzed for trends. From 2006-2014 there were 232,875 viable births across all three sites. For the study population as a whole, the overall rates of induction and CS increased from 22% to 29% (p=0.0001), and 23% to 28% (p=0.0001) respectively. Regarding one center, a significant increase in primary CS (n=13,392, p=0.0001) was identified (Figure 1), the most common indication being an increasing rate of non-reassuring fetal heart monitoring (NRFHM) (25.8% to 32.4% (p=0.0001)(Figure 2)). At this center, the rate of primary CS due to failed induction remained unchanged (4.8->4.5%, p=0.08791) (Figure 3.) Although induction, total and primary CS rates increased over the course of the study period, the rate of primary CS due to failed induction remained surprisingly unchanged. Our data suggest that NRFM is the most common indication for rising primary CS, suggesting increasing numbers of pregnancies at risk of fetal hypoxia in labor. In conclusion, this data challenges the notion that the increasing primary CS rate is associated with a rising trend in induction of labor.

BACKGROUND:The optimum timing of administration of magnesium sulfate (MgSO4) in relation to delivery is not known. The general consensus is to achieve administration to the mother at least 4 hours prior to preterm delivery. OBJECTIVE:To investigate potential predictors of umbilical cord blood magnesium (Mg) concentrations, in particular, timing of antenatal MgSO4 administration in relation to delivery. STUDY DESIGN:A prospective observational study of infants delivered at less than 32 weeks' gestational age. Cord bloods samples were collected at delivery and Mg levels analyzed. RESULTS:Of the 81 included cases, five received no antenatal MgSO4, 65 received a 4 g bolus only, and 11 received a 4 g bolus and 1 g/hour infusion. The median time of bolus administration before delivery was 104 minutes (IQR: 57-215). The mean magnesium level was 0.934 mmol/L in the no antenatal MgSO4 group, 1.018 mmol/L in the bolus only group, and 1.225 mmol/L in the bolus and infusion group (p < .05). In the bolus only group, the highest mean magnesium concentration (1.091 mmol/L) was achieved with administration 1-2 hours before delivery, but the difference was small and not statistically significant. On multiple regression analysis, lower birthweight Z scores and gestational age were independently associated with higher cord blood Mg levels. CONCLUSIONS:In the bolus only group, the highest mean Mg levels were observed with administration 1-2 hours before delivery, but the findings were not statistically significant. Compared to the rest of the cohort, higher Mg levels were found when a bolus was followed by an infusion. Following a MgSO4 bolus, some growth restricted extremely preterm babies may have higher Mg levels than would be otherwise expected.

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: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.

When a fetus is identified with a previable weight but at viable gestation, counseling is often challenging and guarded due to a considerable lack of contemporary outcome data. In an effort to define more realistic expected outcomes, we sought to evaluate the natural history and perinatal outcome of cases of severe early-onset intrauterine growth restriction (IUGR) diagnosed ≥ 24 weeks gestation but with an estimated fetal weight (EFW) <500g. A single center study spanning nine years (2006-2015) was conducted in a large tertiary-referral obstetric hospital. Singleton cases of periviable IUGR referred for a fetal medicine opinion were identified from the centralized obstetric ultrasound database. A comprehensive chart review was performed for obstetric and short and medium-term pediatric outcomes. A total of 88 pregnancies meeting the criteria for inclusion were identified. Incorrect first trimester dating was identified in 11 cases. Of the remaining 77 cases, 27% (n=21) had a structural fetal anomaly, 10% (n=8) had aneuploidy, and 63% (n=48) were both structurally and karyotypically normal. Of the 48 ‘normal’ periviable IUGR cases, 33% (16/48) died in-utero and there was one 1 termination of pregnancy. Of the remaining 31 livebirths, the median gestational age and birth weight at delivery was 31+2 (24+3-37+5) weeks and 1,243 (460-2,390) grams. A total of 81% required neonatal intensive care admission and there were seven early neonatal deaths. In 78% of cases a cesarean delivery (CD) was performed, of which three were classical CD. Overall perinatal survival-to-discharge was 50%. Neurodevelopmental outcome at 1-year was available in 79% of survivors-to-discharge, of which 62% were noted to have a normal developmental outcome. Periviable IUGR is associated with a lower than expected rate of aneuploidy (10%). Half of structurally and genetically normal fetuses will survive to discharge, of which more than 60% will have normal medium-term neurodevelopmental outcome. Contrary to prevailing expectations, we have demonstrated a better than expected perinatal outcome for this particularly high-risk subgroup.Such data will be of benefit in counseling patients in contemporary practice.

The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, "PlaNet", will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice.