Euploid First-Trimester Cystic Hygroma: A More Benign Entity than Previously Thought?

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.

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

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

Altered Platelet Function in Intrauterine Growth Restriction: A Cause or a Consequence of Uteroplacental Disease?

Objective A limited number of platelet function studies in intrauterine growth restriction (IUGR) have yielded conflicting results. We sought to evaluate platelet reactivity in IUGR using a novel platelet aggregation assay. Study Design Pregnancies with IUGR were recruited from 24 weeks' gestation (estimated fetal weight < 10th centile) and had platelet function testing performed after diagnosis. A modification of light transmission aggregometry created dose-response curves of platelet reactivity in response to multiple agonists at differing concentrations. Findings were compared with healthy third trimester controls. IUGR cases with a subsequent normal birth weight were analyzed separately. Results In this study, 33 pregnancies retained their IUGR diagnosis at birth, demonstrating significantly reduced platelet reactivity in response to all agonists (arachidonic acid, adenosine diphosphate, collagen, thrombin receptor-activating peptide, and epinephrine) when compared with 36 healthy pregnancy controls (p < 0.0001). Similar results were obtained for cases demonstrating an increasing in utero growth trajectory. When IUGR preceded preeclampsia or gestational hypertension, platelet function was significantly reduced compared with normotensive IUGR. Conclusion Using this comprehensive platelet assay, we have demonstrated a functional impairment of platelets in IUGR. This may reflect platelet-derived placental growth factor release. Further evaluation of platelet function may aid in the development of future platelet-targeted therapies for uteroplacental disease.

Outcome following selective fetoscopic laser ablation for twin to twin transfusion syndrome: an 8 year national collaborative experience.

OBJECTIVE: With the recognition of the role of fetoscopic laser ablation for twin to twin transfusion syndrome (TTTS), there is a requirement for auditable standards for this technically challenging and specialized treatment. The purpose of this study is to report on the perinatal and medium-term neurodevelopmental outcomes following an 8-year national single center experience in the management of TTTS using the selective fetoscopic laser ablation technique. STUDY DESIGN: An audit of all cases of TTTS treated with selective laser ablation by a single national fetal medicine team was performed. Overall perinatal survival and medium-term neurodevelopmental outcomes were reported and correlated with gestational age at diagnosis, placental location, volume of amnio-reduction, Quintero staging and percentage inter-twin growth discordance. Procedure-related complications were recorded. RESULTS: The overall fetal survival for the first 105 consecutive cases of TTTS was 61% (128/210 fetuses). Dual survival occurred in 47% (49/105) of cases, and with a single survival rate of 28% (30/105), perinatal survival of least one infant was achieved in 75% (79/105) of cases. No correlation was found between any clinical or sonographic marker and perinatal outcome, although dual survival was noted to be significantly decreased with increasing Quintero stage (p=0.041). Currently, 86% of survivors have been reported to have a normal medium-term neurological outcome. CONCLUSION: Fetoscopic laser ablation is the established optimal treatment for severe twin to twin transfusion syndrome (TTTS). We report comparable short and medium-term outcomes following the selective fetoscopic technique comparing results from our national program with internationally published single-center outcomes, supporting the efficacy and safety of this treatment at our center.

Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again.

OBJECTIVE: This study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy. STUDY DESIGN: A prospective longitudinal study was performed to evaluate platelet function in a cohort of patients with a history of unexplained RM. Platelet reactivity testing was performed at 4-7 weeks gestation, to compare platelet aggregation between those with a subsequent miscarriage and those who had successful live birth outcomes. Platelet aggregation was calculated using a modified assay of light transmission aggregometry with multiple agonists at different concentrations. RESULTS: In a cohort of 39 patients with a history of RM, 30 had a successful pregnancy outcome while nine had a subsequent miscarriage again. Women with subsequent miscarriage had reduced platelet aggregation in response to adenosine diphosphate (P value 0.0012) and thrombin receptor activating peptide (P value 0.0334) when compared to those with successful pregnancies. Women with subsequent miscarriages also had a trend towards reduced platelet aggregation in response to epinephrine (P value 0.0568). CONCLUSION: Patients with a background history of unexplained RM demonstrate reduced platelet function if they have a subsequent miscarriage compared to those who go on to have a successful pregnancy.