Absence of Ductus Venosus: A Comparison of 2 Distinctive Fetal Autopsy Cases and Embryologic Perspectives.

In fetal circulation, oxygenated blood from the placenta flows through the umbilical vein into the ductus venosus (DV), then enters the inferior vena cava, and subsequently reaches the right atrium of the heart. The DV serves as a shunt, allowing this oxygen-rich blood to bypass the liver. The absence of the DV (ADV), also known as agenesis of the DV, is a rare congenital anomaly. Without a DV, blood from the umbilical vein must follow alternative routes to the heart. In ADV cases, blood from the umbilical vein must follow 1 of 2 primary drainage patterns: either an extrahepatic shunt or an intrahepatic shunt. This report details the antenatal ultrasound and postmortem findings of 2 fetuses diagnosed with ADV by prenatal imaging studies. The first case involved a fetus with a persistent right umbilical vein connected directly to the suprahepatic IVC, accompanied by early obliteration of the left umbilical vein and true agenesis of the DV. This fetus also had additional congenital anomalies. In contrast, the second case involved a fetus with a normal left umbilical vein that entered the liver. However, despite an ultrasound diagnosis of "absence" of the DV, a DV was present, though markedly hypoplastic and probably minimally functional or non-functional. In this case, blood from the umbilical vein likely followed an alternate intrahepatic route through the portal and hepatic veins, before reaching the heart (intrahepatic shunt). These contrasting cases emphasize the heterogeneity of vascular anomalies and embryologic origins captured by the term "ADV." Additionally, the terminology of "absence" or "agenesis" may be misleading in some purported ADV cases. Specifically, in the second case, the DV was not absent; it was markedly hypoplastic instead. This also appears to be the first reported case of a hypoplastic DV in a fetus. Both cases underscore the importance of effective collaboration and clear communication between maternal-fetal medicine specialists and pathologists.

Reconsidering Routine Repeat Group and Screens During Pregnancy-Personalizing Pregnancy Care.

The group and screen (G&S) are performed in early pregnancy to identify clinically significant antibodies (CSA) that may necessitate fetal monitoring for hemolysis/anemia or affect RhIg eligibility. Guidelines vary, including differences between RhD-positive and negative patients, but typically, the G&S is repeated at 28 weeks, and sometimes pre-delivery. We reviewed data showing a low risk (0.01%-0.43%) of detecting a new CSA in late gestation (late alloimmunization) and the risk of late alloimmunization causing severe hemolysis/anemia is even lower at <0.01%. Routinely repeating a G&S at 28 weeks and delivery may not be necessary for healthy, low-risk pregnancies.

Maternal, Fetal, and Neonatal Outcomes of Elective Fetal Reduction Among Multiple Gestation Pregnancies: A Systematic Review.

OBJECTIVE: To review the existing literature on fetal and maternal health outcomes following elective pregnancy reduction. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Trials Register. STUDY SELECTION: Studies involving women pregnant with dichorionic twins, trichorionic triplets, or quadra-chorionic quadruplets who underwent elective fetal reduction of 1 or more fetuses to reduce the risks associated with multiple gestation pregnancies. DATA EXTRACTION: The main fetal health outcomes measured were gestational age at delivery, preterm birth, miscarriage, birth weight, and small for gestational age at delivery. The main maternal health outcomes measured were gestational diabetes, hypertensive disorders of pregnancy, and cesarean delivery. DATA SYNTHESIS: Of 7678 studies identified, 24 were included (n = 425 dichorionic twin pregnancies, n = 2753 trichorionic triplet pregnancies, and n = 111 quadra-chorionic quadruplet pregnancies). Fifteen studies (62.5%) did not report maternal health outcomes, while every study reported at least 1 fetal health outcome. Fetal reduction was associated with higher gestational age at birth, lower preterm birth, higher birth weight, and lower rates of small for gestational age infants and intrauterine growth restriction. No consistent pattern was observed for miscarriage and neonatal mortality rates. Following fetal reduction, cesarean delivery rates were lower in most studies. There were no appreciable trends with respect to gestational diabetes or hypertensive disorders of pregnancy. CONCLUSION: Fetal reduction reliably optimizes gestational age at birth and neonatal birth weight. Miscarriage rates and other adverse procedural outcomes did not increase following transabdominal reduction. Further research on maternal outcomes is needed given a paucity of information in the literature.

Perinatal outcome and prognostic factors of fetal megacystis diagnosed at 11-14 week's gestation.

OBJECTIVES: To evaluate aneuploidy rate, prognostic factors, and perinatal outcomes following a diagnosis of fetal megacystis at 11-14 week's gestation. METHODS: A retrospective study of first trimester fetal megacystis from 2010 to 2020 was performed, including ultrasound finding, perinatal outcomes, pathology reports, genetic tests, and neonatal investigations. RESULTS: A total of 98 cases of first trimester fetal megacystis was identified with an overall aneuploidy rate of 12%. There were 54% live births and 46% fetal losses including spontaneous fetal demise and elective termination. Among the 45 fetal losses, 64% had additional structural abnormalities at index ultrasound and final diagnoses were achievable in 64% cases. Among the 53 livebirths, additional ultrasound abnormalities were detected in only 1 fetus and spontaneous resolution of megacystis was detected in 96% of cases. The two cases where fetal megacystis persisted had major postnatal diagnoses: cloacal malformation and megacystis-microcolon-intestinal hypoperistalsis syndrome, respectively. Our data showed LBD ≥ 12 mm was the best individual predictor of adverse perinatal outcome and all 11 cases of lower urinary tract obstruction (LUTO) were diagnosed in fetuses with LBD ≥ 12 mm. CONCLUSIONS: First trimester ultrasound provides important prognostic factors and isolated megacystis <12 mm is associated with a positive outcome.

Placental dichotomy: a hint in twin anemia polycythemia sequence.

BACKGROUND: Monochorionic pregnancies are a significant part of the workload in diagnostic imaging, and must be assessed frequently for the detection of twin-twin transfusion syndrome. Recognizing placental dichotomy at the time of routine fetal cerebral artery Doppler screening is important for alerting the clinician to potential twin anemia polycythemia sequence, an important subset of feto-fetal transfusions. CASE: A 36-year-old multigravid woman with a twin pregnancy delivered at 33 weeks' gestation after fetal distress was identified. Twin anemia polycythemia sequence was diagnosed after delivery. Regular prenatal ultrasound scans had not identified oligo- or polyhydramnios. Retrospective assessment of the ultrasound images of the placenta showed marked dichotomy, with the anemic twin's portion being hyperechogenic. CONCLUSION: Identification of placental dichotomy, in addition to screening with cerebral Doppler flow studies, may lead to earlier identification of twin anemia polycythemia sequence and improved outcomes. 

Contexte : Les grossesses monochorioniques représentent une partie significative de la charge de travail en imagerie diagnostique et doivent fréquemment faire l'objet d'une évaluation aux fins de la détection du syndrome transfuseur-transfusé. Il est important de reconnaître la présence d'une dichotomie placentaire au cours de la tenue d'une étude Doppler régulière de l'artère cérébrale fœtale, et ce, de façon à pouvoir alerter le clinicien quant à la présence possible d'une séquence anémie polyglobulie gémellaire (un sous-ensemble important du syndrome transfuseur-transfusé). Cas : Une multigravide de 36 ans connaissant une grossesse gémellaire a accouché à 33 semaines de gestation, à la suite de l'identification d'une détresse fœtale. Une séquence anémie polyglobulie gémellaire a été diagnostiquée à la suite de l'accouchement. Les échographies prénatales régulières n'avaient pas détecté la présence d'un oligohydramnios ou d'un polyhydramnios. L'analyse rétrospective des images échographiques du placenta a mis au jour la présence d'une dichotomie marquée, la partie relevant du jumeau anémique y apparaissant comme étant hyperéchogène. Conclusion : L'identification de la dichotomie placentaire (s'ajoutant au dépistage au moyen d'études Doppler cérébrales) pourrait mener à l'identification précoce de la séquence anémie polyglobulie gémellaire et à l'amélioration des issues.

The Implementation of Preeclampsia Screening and Prevention (IMPRESS) Study.

BACKGROUND: Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. OBJECTIVE: This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. STUDY DESIGN: This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. RESULTS: Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. CONCLUSION: This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.

Parietal bone agenesis and athelia in retinoic acid embryopathy: An expansion of the phenotype.

BACKGROUND: Retinoic acid signaling plays a critical role during embryogenesis and requires tight regulation. Exposure to exogenous retinoic acid during fetal development is known to have teratogenic effects, producing a recognizable embryopathy. CASE: We describe a case of retinoic acid embryopathy secondary to maternal isotretinoin use until the ninth week of gestation and expand the phenotype to include the rare features of parietal bone agenesis and athelia. Histology of the parietal region showed fibrous tissue with no intramembranous ossification. The fetus also had multiple craniofacial dysmorphisms, thymic agenesis, and transposition of the great arteries with double outlet right ventricle and subaortic perimembranous ventricular septal defect. Neuropathology revealed enlarged ventricles with agenesis of the cerebellar vermis, focal duplication of the central canal and scattered parenchymal ependymal rests, and possible cerebral heterotopias with associated abnormal neuronal lamination. A chromosomal microarray was normal. CONCLUSION: Parietal bone agenesis and athelia are both rare congenital anomalies not previously reported in retinoic acid embryopathy. However, retinoic acid or its degrading enzyme has been demonstrated to exert effects in both of these developmental pathways, offering biological plausibility. We propose that this case may represent an expansion of the phenotype of retinoic embryopathy.

Antenatal predictors of outcome in prenatally diagnosed congenital diaphragmatic hernia (CDH).

BACKGROUND: Pulmonary hypoplasia is the main cause of mortality in isolated congenital diaphragmatic hernia (CDH) and its prediction is paramount when counseling parents. We sought to identify antenatal parameters that predicted neonatal mortality in CDH. METHOD: Search was conducted in MEDLINE, EMBASE, Cochrane Database of Systematic reviews, PubMed, Scopus, and Web of Science on the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e LHR), total fetal lung volume (TFLV), o/e TFLV, percentage predicted lung volume (PPLV) and degree of liver herniation to predict neonatal morbidity and mortality in fetuses with CDH. Primary outcome was perinatal survival and secondary was the use of extracorporeal membrane oxygenation (ECMO). RESULTS: Until April 2016, 1067 articles were found, of which 22 were included in our meta-analysis. This showed that the odds of survival with LHR <1.0 and liver herniation on ultrasound were 0.14 (CI 0.10-0.27) and 0.21 (CI 0.13-0.35) respectively. Mean LHR, o/e LHR, absolute TFLV, o/e TFLV, PPLV and liver herniation all predicted survival, however o/e LHR and o/e TFLV performed best in this prediction. When the longest diameter measurement method was used, the o/e TFLV (summary area under curve (AUC) 0.8) was slightly superior to o/e LHR (summary AUC 0.78). This difference disappeared when LHR was measured by the trace method. The most discriminatory threshold for O/E LHR and O/E TFLV was 25%. LHR <1 was predictive of extracorporeal life support (ECLS) use. CONCLUSION: O/E LHR, o/e TFLV (thresholds of 25%) and liver herniation are good predictors of mortality in CDH. LEVEL OF EVIDENCE: Level II Type of study: Systematic review and meta-analysis.

Guidelines for the use of recombinant activated factor VII in massive obstetric haemorrhage.

Recombinant activated factor VII (rFVIIa) is emerging as a novel therapy for the treatment of life or fertility-threatening post-partum haemorrhage (PPH) unresponsive to standard therapy that in some cases may prevent the need for peripartum hysterectomy. The level of evidence to date for use of rFVIIa in PPH is limited to case reports and case series with one nonrandomised study. No high-quality randomised controlled trials have been published at this stage, precluding a quality systematic review. Guidelines have been published for the use of rFVIIa in non-obstetric haemorrhage, though to date none are available for PPH. A multidisciplinary group of Australian and New Zealand clinicians from the fields of obstetrics, anaesthesia and haematology, who have both clinical experience in and/or knowledge of rFVIIa was convened by the manufacturer. This group produced an opinion and guideline based on their experience and the published international literature on the use of rFVIIa. This is intended to be used as a guideline and algorithm for the use of rFVIIa, though any use should be tailored to local practice and resources.

An audit of outcome in intravascular transfusions using the intrahepatic portion of the fetal umbilical vein compared to cordocentesis.

INTRODUCTION: Maternal red cell alloimmunization is a potential cause of perinatal morbidity and mortality. The outcome of severe disease has been transformed by the use of in-utero and particularly, fetal intravascular transfusion. In the majority of instances this is performed by cordocentesis. However, this cohort study represents the experience in a large tertiary referral centre in performing fetal intravascular transfusions via the intrahepatic vein (IHV). METHODS: Over an 8-year period, 1997-2004, 221 in-utero transfusions (IUT) were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age of the cohort was 31 years (range 19-43). The median gestation at initial IUT was 25 weeks (interquartile range (IQR) 23-29 weeks). RESULTS: A median number of three IUT were performed in each fetus (IQR 2-5) with a median haemoglobin at first fetal blood sampling of 7.3 g% (IQR 4.6-8.8 g%) (73% < or =5 SD and 27% < or =2 SD). Of the total intravascular transfusions, 170 were performed via the IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%). There were 'transient' bradycardias complicating 4.1% of all transfusions and amniorrhexis following 1.4%. 92% of babies were live born at a median gestation of 34 weeks (range 21-38) with a birth weight centile of 50 (range 3-90). There was no significant difference in intravascular transfusion complication rate when the procedure was performed via the IHV (7.6%) as compared to cord root puncture (3.0%) (Fisher's exact test, p < 0.47). CONCLUSION: IUT performed by fetal IHV puncture is safe and carries no excess morbidity when performed for severe rhesus disease.

Prenatal diagnosis of congenital disorder of glycosylation type Ia (CDG-Ia) by cordocentesis and transferrin isoelectric focussing of serum of a 27-week fetus with non-immune hydrops.

Blood was obtained by cordocentesis from a fetus with non-immune hydrops demonstrated by ultrasound scanning at 27 weeks' gestation. Abnormalities of serum transferrin isoelectric focussing (IEF) were identified, characteristic of a congenital disorder of glycosylation type I (CDG-Ia). A diagnosis of CDG-Ia was confirmed by enzyme analysis of cultured amniocytes. This is the first report of CDG-Ia diagnosed by serum analysis in a fetus. Previous reports have warned that diagnostic abnormalities do not appear in serum until several weeks after birth. The sensitivity of cordocentesis transferrin IEF is unknown but is less than 100% effective because cases have been diagnosed postnatally after normal prenatal or neonatal studies. Enzyme analysis or mutation analysis is required for diagnosis of congenital disorder of glycosylation (CDGs) regardless of whether a diagnostic transferrin pattern is identified prenatally. The analysis of a small sample of serum, from cordocentesis, performed to check for fetal anemia, simplified the investigation, diagnosis, and genetic counselling of a case of non-immune hydrops detected at 27 weeks' gestation. This might be a useful test for other cases in these circumstances, as fetal blood is usually collected to check for anemia.