Expectant management versus multifetal pregnancy reduction in dichorionic triamniotic (DCTA) triplets: Single centre experience.

OBJECTIVES: In trichorionic triplet pregnancies, multifetal pregnancy reduction (MFPR) reduces the risk of preterm birth, neonatal morbidity and mortality without increasing miscarriage. A similar benefit has been suggested in dichorionic triamniotic (DCTA) pregnancy, but multiple methods are currently used. This study investigates if the method of reduction used in DCTA triplet pregnancy influences the evidence of benefit from MFPR. METHODS: This is a retrospective cohort study of DCTA pregnancies between 2010 and 2019 who attended a single UK fetal medicine tertiary referral center. Cohorts were defined based on MFPR decision and method. The primary outcome was offspring survival until neonatal discharge. The secondary outcomes included miscarriage, preterm birth, livebirth, rates of small for gestational age (SGA) neonates, ans maternal morbidity. To evaluate the differences in neonatal survival until discharge we used Cox proportional regression to calculate hazard rates (HR) and 95% confidence intervals (CI). Differences in secondary outcomes were compared using univariate analysis. RESULTS: The study reports the outcomes for 83 DCTA pregnancies. MFPR to DCDA twins was chosen in 19 pregnancies (14 radiofrequency ablation, RFA; 5 intrafetal laser, IFL); in 9 pregnancies selective reduction to a singleton was performed by KCl injection. The rate of pregnancies in with ≥ 1 fetus born alive was not different between groups (p = 0.90). However, the number of expected neonates alive at discharge from hospital was highest in the RFA group (89%, HR 0.28, 95% CI 0.21-0.87, p = 0.02). Rates of premature delivery before 32 weeks (p = 0.02), low birth weight (p < 0.001) and birthweight < 10th percentile (p = 0.01) were all elevated in the expectant management group, compared to women who opted for reduction. There was no difference in miscarriage between groups. CONCLUSIONS: Our study suggests that MFPR by RFA, an established and widely available procedure, is of benefit in promoting neonatal survival until discharge in DCTA triplets.

Etiology and perinatal outcome of periviable fetal growth restriction associated with structural or genetic anomaly.

OBJECTIVE: To investigate the etiology and perinatal outcome of periviable fetal growth restriction (FGR) associated with a structural defect or genetic anomaly. METHODS: This was a retrospective study of singleton pregnancies seen at a referral fetal medicine unit between 2005 and 2018, in which FGR (defined as fetal abdominal circumference ≤ 3rd percentile for gestational age) was diagnosed between 22 + 0 and 25 + 6 weeks of gestation. The study group included pregnancies with periviable FGR associated with a genetic or structural anomaly (anomalous FGR), while the control group consisted of structurally and genetically normal pregnancies with periviable FGR (non-anomalous FGR). Results of genetic testing, TORCH screen and postmortem examination, as well as perinatal outcome, were investigated. RESULTS: Of 255 pregnancies complicated by periviable FGR, 188 were eligible; of which 52 (28%) had anomalous FGR and 136 (72%) had non-anomalous FGR. A confirmed genetic abnormality accounted for 17/52 cases (33%) of anomalous FGR, with trisomy 18 constituting over 50% (9/17; 53%). The most common structural defects associated with FGR were central nervous system abnormalities (13/35; 37%). Overall, 12 (23%) cases of anomalous FGR survived the neonatal period. No differences were found in terms of perinatal survival between pregnancies with anomalous and those with non-anomalous FGR. CONCLUSIONS: Most pregnancies complicated by anomalous FGR were associated with a structural defect. The presence of an associated genetic defect was invariably lethal, while those with a structural defect, in the absence of a confirmed genetic abnormality, survived into infancy in over 90% of cases, with an overall one in three chance of perinatal survival. These data can be used for counseling prospective parents. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Developing and testing an algorithm for automatic segmentation of the fetal face from three-dimensional ultrasound images.

Fetal craniofacial abnormalities are challenging to detect and diagnose on prenatal ultrasound (US). Image segmentation and computer analysis of three-dimensional US volumes of the fetal face may provide an objective measure to quantify fetal facial features and identify abnormalities. We have developed and tested an atlas-based partially automated facial segmentation algorithm; however, the volumes require additional manual segmentation (MS), which is time and labour intensive and may preclude this method from clinical adoption. These manually refined segmentations can then be used as a reference (atlas) by the partially automated segmentation algorithm to improve algorithmic performance with the aim of eliminating the need for manual refinement and developing a fully automated system. This study assesses the inter- and intra-operator variability of MS and tests an optimized version of our automatic segmentation (AS) algorithm. The manual refinements of 15 fetal faces performed by three operators and repeated by one operator were assessed by Dice score, average symmetrical surface distance and volume difference. The performance of the partially automatic algorithm with difference size atlases was evaluated by Dice score and computational time. Assessment of the manual refinements showed low inter- and intra-operator variability demonstrating its suitability for optimizing the AS algorithm. The algorithm showed improved performance following an increase in the atlas size in turn reducing the need for manual refinement.

A descriptive pilot study of mitochondrial mutations & clinical phenotype in fibromyalgia syndrome.

BACKGROUND & OBJECTIVES: : Fibromyalgia syndrome (FMS) is one of the most common chronic pain conditions of unknown aetiology. Mitochondrial dysfunction has been reported in FMS with some studies reporting the presence of mitochondrial mutation namely A3243G, which also causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. This pilot study was conducted to assess this mutation and also detect large deletions in mitochondrial DNA (mtDNA) in patients with FMS. METHODS: : Thirty female patients with FMS participated and 30 matched controls were included. Genomic DNA was subjected to polymerase chain reaction (PCR) amplification using specific primers followed by restriction digestion with Apa I enzyme to detect the specific A3243G mtDNA mutation. Long-range PCR was done in two sets to detect the large deletions in the mtDNA. Biochemical parameters including thyroid-stimulating hormone and vitamin D levels were also looked at. RESULTS: : None of the patients were found to carry the common mutation or large deletions. Low vitamin D level was a common finding. Hypothyroidism was found in a few patients. INTERPRETATION & CONCLUSIONS: : Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.

Are fetuses that fail to achieve their growth potential at increased risk of intrapartum compromise?

OBJECTIVE: The true growth potential of a fetus is difficult to predict but recently a new definition, independent of fetal weight, using cerebroplacental (cerebro-umbilical) ratio (CPR) < 0.6765 multiples of the median (MoM), was reported. We applied this definition to a cohort of low-risk pregnancies recruited prospectively to determine if fetuses with CPR < 0.6765 are at increased risk of developing signs of intrapartum fetal compromise. METHODS: Recruitment to this prospective observational study took place between March 2011 and March 2014. All women with low-risk singleton pregnancies at term were eligible. Women with known or suspected placental dysfunction were excluded, as were women with fetuses with an estimated fetal weight < 10(th) centile. All participants underwent ultrasound examination prior to active labor (≤ 4 cm cervical dilatation), during which fetal biometry as well as umbilical artery and fetal middle cerebral artery blood flow were assessed. Following delivery, intrapartum and neonatal outcomes were compared between fetuses that had a CPR < 0.6765 MoM and those that had a CPR ≥ 0.6765 MoM. RESULTS: In total, 775 women were recruited. Fetuses with CPR < 0.6765 MoM were significantly more likely to require Cesarean delivery because of presumed fetal compromise (P < 0.001). These fetuses were also at increased risk of compromise at any time during labor and were less likely to be delivered vaginally, spontaneously or otherwise, than were those with CPR ≥ 0.6765 MoM. CPR < 0.6765 MoM gave a positive predictive value (PPV) for Cesarean delivery because of presumed fetal compromise of 36.7% and a negative predictive value of 88.7%, with a sensitivity of 18% and a specificity of 95.4%. CONCLUSION: Fetuses that failed to achieve their growth potential (defined as CPR < 0.6765 MoM) were at increased risk of intrapartum compromise and were less likely to be delivered vaginally. However, a low negative predictive value was observed for fetal compromise and further studies are required to support the translation of this technique into clinical practice.

Diaphragmatic hernia: a postnatal complication of anomalous drainage of the umbilical vein.

The ductus venosus (DV) connects the portal venous system to the inferior vena cava. Rarely, the umbilical venous drainage is anomalous, either connecting to the portal sinus within the liver or having an extrahepatic connection, bypassing the liver and draining to one of a variety of sites, including to the heart directly. Prenatally, there is a recognized association of anomalous umbilical venous drainage with aneuploidy and other structural malformations. The fetus may also develop right heart failure because of unregulated volume loading. We report the postnatal development of diaphragmatic hernia in three fetuses with absent DV and umbilical venous drainage to the right atrium directly in two cases and to the coronary sinus in the third. In all fetuses, the abnormality was well-tolerated in pregnancy, with only a modest degree of right heart dilatation. All three neonates underwent repair of the diaphragmatic hernia and made a good recovery.

Radiofrequency ablation for selective reduction in complex monochorionic pregnancies.

Monochorionic pregnancies present unique challenges for selective fetal reduction, as vaso-occlusive procedures are required to ablate blood flow, usually in the umbilical cord, to achieve asystole in the selected fetus. We describe a case series of 35 monochorionic pregnancies (27 twins and eight triplets) undergoing selective fetal reduction using radiofrequency ablation. All procedures were performed under local anaesthesia. The procedure was technically successful in all cases. The live born rate was 88.6%. One (2.9%) woman miscarried within 2 weeks of the procedure, and two (5.7%) babies were stillborn. The median gestation at delivery was 36 weeks of gestation (range 24-41 weeks). There were no maternal complications. The median gestational age at procedure was 17 + 3 weeks (range from 12 + 5 to 27 + 4 weeks). All women had antenatal magnetic resonance imaging (MRI) post procedure. There were two (5.7%) cases of abnormal brain imaging. Our experience suggests that radiofrequency ablation is a safe and effective procedure for fetal reduction in complicated monochorionic pregnancies.