Fetoscopic Laser Ablation for Twin-to-Twin Transfusion Syndrome: A 15-year Review of Perinatal Survival.

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 4 5.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p<0.05). Dual survival decreased with increasing Quintero Stage (p<0.05). 80.6% (125/155) of pregnancies delivered prior to 34+6 weeks gestation. Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.

Sonographic markers of fetal adiposity and risk of Cesarean delivery.

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 < 0.0001) and rate of induction of labor (47% (108/232) vs 40% (834/2098); P = 0.048) than did those with an adiposity composite ≤ 90th centile. Fetuses with adiposity composite > 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P < 0.0001). After adjusting for birth weight, maternal BMI and need for induction of labor, fetal adiposity > 90th centile remained a risk factor for Cesarean delivery (P < 0.0001). A fetal adiposity composite > 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 < 0.001) vs 1.74 (95% CI, 1.29-2.35; P < 0.001). Having an adiposity composite > 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.

MRI in adult patients with aortic coarctation: diagnosis and follow-up.

Aortic coarctation is a disease that usually presents in infancy; however, a proportion of patients present for the first time in adulthood. These lesions generally require repair with either surgery or interventional techniques. The success of these techniques means that increasing numbers of patients are presenting for follow-up imaging in adulthood, whether their coarctation was initially repaired in infancy or as adults. Thus, the adult presenting to the radiologist for assessment of possible coarctation or follow-up of coarctation repair is not an uncommon scenario. In this review, we present details of the MRI protocols and MRI findings in these patients so that a confident and accurate assessment can be made.

Reassessing critical maternal antibody threshold in RhD alloimmunization: a 16-year retrospective cohort study.

OBJECTIVE: To determine the critical maternal antibody threshold for specialist referral in cases of RhD alloimmunization. METHODS: This was a retrospective cohort study, covering a 16-year period at the national tertiary fetal medicine center for management of alloimmunization. Data concerning RhD alloimmunized pregnant women were extracted from an institutional database and maternal anti-D antibody levels were cross-checked with the national reference laboratory. Fetal hemoglobin (Hb) levels were determined only at the first intrauterine transfusion (IUT) and were compared with the pretransfusion maternal anti-D antibody level (IU/mL). Sensitivity, specificity and positive and negative predictive values of maternal antibody thresholds for detecting moderate to severe (Hb ≤ 0.64MoM) fetal anemia were calculated. RESULTS: Between 1996 and 2011, 66 women underwent a first IUT for RhD alloimmunization at our institution. The highest serum anti-D antibody level was extracted for 208 RhD alloimmunized women who did not require IUT during the last 10 years of the study period. The traditional maternal antibody threshold of > 15 IU/mL failed to detect 20% of cases of moderate to severe fetal anemia. The ≥ 4 IU/mL threshold had 100% sensitivity but a 45% false-positive rate. The optimal anti-D antibody threshold for specialist referral in our population was ≥ 6 IU/mL; at this level, no case of moderate to severe anemia was missed and specificity was 61%. Use of this threshold would have eliminated 10% of referrals to our fetal medicine unit without compromising fetal outcomes. CONCLUSIONS: Setting the critical maternal RhD antibody level at >15 IU/mL does not provide sufficient sensitivity. The lower threshold of ≥ 4 IU/mL, though sensitive, is associated with a 45% false-positive rate. In our population, a threshold of ≥ 6 IU/mL minimizes false-positive referrals while maintaining 100% sensitivity for moderate to severe fetal anemia.

Red cell alloimmunisation following intrauterine transfusion and the feasibility of providing extended phenotype-matched red cell units.

OBJECTIVES: To analyse the incidence of additional alloantibody formation following intrauterine red cell transfusion and to evaluate the feasibility of providing extended phenotype-matched red cells in future intrauterine transfusion (IUT). BACKGROUND: IUT is performed in severe, life-threatening fetal anaemia, usually in alloimmunised pregnancies. Its complications include the formation of additional alloantibodies to other red cell antigens. MATERIALS AND METHODS: This was an 11-year retrospective, observational study of additional alloantibody formation in patients receiving IUT in the National Maternity Hospital, Dublin. The study included evaluation of the donor population in the Republic of Ireland (RoI) with regards to the feasibility of providing extended phenotype-matched units in future IUT. RESULTS: Following IUT, 22% of mothers formed additional red cell alloantibodies. In 67% of cases, the transfused donor red cells expressed the cognate antigen. Suitable donors are available for most combinations of Fy, Jk and Ss antigens. CONCLUSIONS: In our population, it is feasible to provide more extensively phenotype-matched red cells for future IUT. These can be supplied from the current donor pool with no significant extra phenotyping required. We consider their provision to be a reasonable proactive step in a known at-risk group.

A correlation between severe haemolytic disease of the fetus and newborn and maternal ABO blood group.

OBJECTIVE: To analyse anti-D quantification levels and frequency of intrauterine transfusion (IUT), per maternal ABO blood group. BACKGROUND: Maternally derived red cell allo-antibodies can target fetal red cell antigens in utero leading to haemolytic disease and fetal anaemia. When a clinically significant allo-antibody is formed the priority is ascertaining the risk to the fetus and maternal ABO blood groups are not considered relevant. MATERIALS AND METHODS: This was a 10-year retrospective, observational study carried out on women referred for anti-D quantification (n = 1106), and women whose fetuses required an IUT to treat fetal anaemia (n = 62) due to anti-D, in the Republic of Ireland. RESULTS: Relative to the overall incidence of RhD allo-immunisation by blood group, women of blood group A were more likely to require IUT compared with those who were blood group O (P = 0.002). CONCLUSION: It is known that ABO feto-maternal compatibility can influence the incidence and level of red cell allo-antibodies in pregnancy; however, it does not account for the significantly high rate of severe haemolytic disease requiring IUT seen in blood group A women.

Routine obstetric ultrasound services.

Antenatal ultrasonography is widely used in pregnancy to assess fetal growth, wellbeing and anatomy. Although ultrasound screening is now an integral part of routine antenatal care, recommendations for the delivery of obstetric ultrasound vary from country to country. A recent survey of English maternity units reported that 100% of women are offered routine mid-trimester fetal anomaly scanning, in line with expert recommendations. Currently in Ireland, no national guidance exists to inform practitioners on the minimum standards for obstetric ultrasound practice. In 2012, we conducted a structured telephone survey of all 20 maternity units in Ireland (n = 74,377 births). Routine mid-trimester anomaly scanning was offered universally to all women in 7/20 (35%) units, offered selectively to some women in 9/20 (45%) units and not offered to any women in 4/20 (20%) of units. The time allotted for a complete fetal anatomical survey was 10-15 minutes in 4/16 (25%) units, 20 minutes in 7/16 (44%) units and 25-30 minutes in 5/16 (31%) units. Written guidelines on the appropriate management of "soft markers" for fetal aneuploidy were routinely used in 11/16 (69%) of units. In no Irish unit currently, are images from fetal anomaly scanning routinely reviewed by an Obstetrician with an interest in fetal medicine. 19/20 (95%) of respondents believed that a minimum of 2 scans should be offered in routine uncomplicated pregnancies. Improvements in the availability of obstetric ultrasound to pregnant women in Ireland will require increased staffing numbers at both the ultrasonographer and fetal specialist levels. There is a clear need for national guidelines on the provision of routine obstetric ultrasound in Ireland.

Successful fetoscopic laser coagulation for twin-to-twin transfusion syndrome under local anaesthesia.

A review of the efficacy and outcome of fifteen fetoscopic laser ablations under local anaesthesia for twin to twin transfusion syndrome (TTTS) in the National Maternity Hospital Dublin was undertaken. The mean gestation at laser was 19.7 weeks (range 16-25 weeks) with a mean gestation at delivery of 29.1 weeks (range 20-35 weeks). The overall liveborn birth rate was 79% (22 infants) and one pregnancy was still ongoing. There were four neonatal deaths secondary to complications of prematurity. The surviving eighteen infants (64%) undergo regular paediatric review. The procedure was performed successfully in all cases with local anaesthesia. In no case was there maternal discomfort that warranted the procedure to be abandoned and good visual access of the vascular anastamoses was obtained in all cases. Local anaesthesia therefore offers a safe effective anaesthetic option for fetoscopic laser coagulation in monochorionic pregnancies complicated by TTTS.

Thoraco-amniotic shunting for fetal pleural effusion--a case series.

Fetal pleural effusion is a rare occurrence, with an incidence of 1 per 10-15,000 pregnancies. The prognosis is related to the underlying cause and is often poor. There is increasing evidence that in utero therapy with thoraco-amniotic shunting improves prognosis by allowing lung expansion thereby preventing hydrops and pulmonary hypoplasia. This is a review of all cases of fetal pleural effusion managed over an eight year period the National Maternity Hospital Dublin. Over the nine year period there were 21 cases of fetal pleural effusion giving an overall incidence of 1 per 9281 deliveries. Of these, 15 underwent thoraco-amniotic shunting. There were associated anomalies diagnosed in 5 (33%) of cases. The overall survival in our cohort was 53%. The presence of hydrops was a poor prognostic factor, with survival in cases with hydrops of 33% (3/9) compared to 83% (5/6) in those cases without associated hydrops.

Cardiac drugs used in cross-sectional cardiac imaging: what the radiologist needs to know.

The demand for cross-sectional imaging of the heart is increasing dramatically and in many centres these imaging techniques are being performed by radiologists. Although radiologists are familiar with the computed tomography (CT) and magnetic resonance imaging (MRI) techniques to generate high-quality images and with using contrast agents, many are less familiar with administering the drugs necessary to perform CT coronary angiography and cardiac MR reliably. The aim of this article is to give an overview of the indications for and the contraindications to administering cardiac drugs in cross-sectional imaging departments. We also outline the complications that may be encountered and provide advice on how to treat these complications when they occur.

Natural history of apparently isolated severe fetal ventriculomegaly: perinatal survival and neurodevelopmental outcome.

OBJECTIVE: To review the prenatal diagnosis of apparently isolated severe ventriculomegaly (SVM) in a tertiary referral fetal medicine unit and report on perinatal and neurodevelopmental outcomes. METHODS: All cases of isolated SVM referred to Fetal Medicine at the NMH between 2000 and 2008 were identified. Outcome information was obtained from detailed telephone interviews with parents and paediatric records and histopathology in cases of stillborn fetuses. RESULTS: Thirty-six cases of SVM were referred, out of which 19 were diagnosed with 'apparently' isolated SVM. Macrocrania was present in 88% at 36 weeks (mean HC 439 mm). Cephalocentesis was performed in six cases with poor prognosis. All resulted in perinatal loss. The neurodevelopmental outcome of survivors with isolated SVM (ten live-born survivors) showed major neurological morbidity in 50% (5/10) of the cases, mild morbidity in 40% (4/10) and a normal outcome in only one case. CONCLUSION: Isolated SVM had a very poor perinatal outcome with neurological and physical disability in the overwhelming majority. Only one case of the 17 (6%) diagnosed initially with 'apparently' isolated SVM was born alive without handicap. Information from our series may aid couples in decision making about pregnancy interruption and the difficult decision of prenatal or intrapartum cephalocentesis.

Update on the management of non-anti D antibodies.

With the development of the Rh D immunoglobulin and utilisation in clinical practice, severe rhesus iso-immunisation is rarely seen today. Antibodies against other blood groups are now more common than anti-D and while the majority do not cause significant haemolysis, there are reports of serious morbidity with antibodies other than anti-D. We reviewed retrospectively all cases (excluding anti-D and anti kell antibodies) where antibodies were detected at routine booking visit between 1997-2001 and correlated the type of antibody to clinical outcome as assessed by coombs test, postnatal phototherapy and transfusion. Our approach to these cases does not involve invasive test as amniocentesis and relies on the ultrasound monitoring, level of antibodies and timely delivery with appropriate paediatric follow up. Over five years period 150 women were identified with antibodies other than anti-D or anti-kell. There were no directly related deaths. Many authorities suggest amniocentesis for specific antibodies to assess fetal haemolysis and plan management. This study support a non-invasive approach with mortality and minimal morbidity.

Myofibroblast differentiation in the connective tissues of the amnion and chorion of term human fetal membranes-implications for fetal membrane rupture and labour.

An area of the fetal membranes, within the rupture tear after spontaneous delivery at term, exhibits altered morphology compared to more distal sites. It is characterized by marked swelling of the amniotic and chorionic connective tissue layers, consistent with structural weakness, and a marked reduction of the thickness of both the cytotrophoblast and decidual layers. These features, albeit less extreme, have been identified in fetal membranes in the lower uterine pole in patients prior to labour. In this study of pre-labour, labour-affected and post-labour term fetal membranes, we report that these regions are associated with an alteration in the phenotype of the vimentin positive mesenchymal cell population of the chorionic connective tissue reticular layer, and are consistent with myofibroblastic differentiation, i.e. alpha-smooth muscle actin (alpha-sma) expression. In the reticular layer of the lower uterine pole biopsies in the labour-affected group the numbers and densities of alpha-sma immunoreactive positive cells were 17-fold (P=0.04) and 8.5-fold (P=0.02) higher than in mid-zone biopsies. After delivery, in rupture line biopsies the numbers and densities were 50-fold (P=0. 002) and 36-fold (P=0.003) higher compared to mid zone biopsies. The percentage of the vimentin positive population positive for alpha-sma was 2-5 per cent in mid-zone biopsies compared to 49 per cent (P=0.03) in the labour-affected 'cervical' biopsies and 69 per cent (P=0.05) in the rupture line biopsies. Within the tear sites, alpha-sma positive cells were also detected within the fibroblastic layer of the amniotic connective tissue. Although there was no significant difference between the numbers and density of alpha-sma cells in the reticular layers between mid and lower uterine pole biopsies in the pre-labour group, in a proportion of patients the biopsies were similar to labour-affected biopsies indicating that this alteration occurs prior to clinically apparent labour in these patients. The incidence of alpha-sma positive cells in the reticular layer correlated with morphological changes within the fetal membranes, for example thickness of reticular (r(2)=0.349, P=0.0006) and amniotic connective tissue layers (r(2)=0.389, P=0.0002). This suggests that cellular activities associated with myofibroblastic differentiation in the reticular layer of the chorion may be associated with the observed connective tissue changes, fetal membrane rupture and labour.

Neonatal alloimmune thrombocytopenia in the Irish population: a discrepancy between observed and expected cases.

AIMS: To estimate the rate of detection of neonatal alloimmune thrombocytopenia (NAITP) in the Irish population, to investigate clinical presentation and outcome in affected infants, and to determine the extent, if any, to which this condition is underdiagnosed at present. METHODS: Cases were collected in a retrospective fashion from a review of platelet serology laboratory records from January 1992 to December 2000. Clinical data were obtained from hospital records. Testing for maternal antiplatelet antibody was by one or more of the following: the platelet suspension immunofluorescence test, a commercial antigen capture enzyme linked immunosorbent assay (GTI-PakPlus), and the monoclonal antibody immobilisation of platelet antigens assay. Platelet antigen typing was by the polymerase chain reaction technique with sequence specific primers. RESULTS: Twenty seven serologically verified cases of NAITP were identified in 18 families. Maternal antibody to human platelet antigen 1a accounted for 25 of the 27 confirmed cases. Twenty one of 26 infants were born with severe thrombocytopenia. Nineteen of 27 infants had bleeding manifestations at birth. Petechiae and bruising were most commonly observed (n = 17). There were no documented cases of intracranial haemorrhage in this group but systematic cranial ultrasound was not performed. CONCLUSIONS: Screening studies in predominantly white populations have estimated the incidence of NAITP to be between 1 in 1000 and 1 in 2000 live births. With 50 000 births each year in Ireland, these results give a clinical detection rate for NAITP of just 1 case in 16 500 live births, strongly suggesting that NAITP is currently underdiagnosed. Antenatal screening to detect women at risk of having babies with NAITP is now scientifically feasible and should be considered.

A comparison of Doppler flow velocity waveforms, amniotic fluid columns, and the nonstress test as a means of monitoring post-dates pregnancies.

Five hundred thirty-four pregnancies exceeding 294 days were monitored by weekly sonographic estimations of amniotic fluid columns, daily maternal recordings of fetal movements, and thrice-weekly nonstress tests. In addition, each woman received twice-weekly studies of the uteroplacental and umbilical circulations by means of Doppler ultrasound. There were no fetal deaths in the study. Of the individual methods of fetal surveillance, absence of end-diastolic frequencies in the umbilical artery was the most sensitive, predicting 91% of fetuses who developed fetal distress in the first stage. Combining the test with sonographic estimation of amniotic fluid columns improved the prediction to 100%, with only a minimal fall in the specificity. These results strongly suggest that a combination of umbilical artery Doppler waveforms and amniotic fluid determinations is an adequate method of monitoring the post-dates pregnancy.

Acute twin-twin transfusion: a possible mechanism for brain-damaged survivors after intrauterine death of a monochorionic twin.

Intrauterine death of one twin in monochorionic pregnancies is associated with increased mortality and morbidity for the survivor. This has been attributed to the consequences of intrauterine disseminated intravascular coagulation (DIC) initiated by the dead twin. We describe a case in which the fetal cerebral and renal lesions typically found in survivors occurred without any derangement in coagulation. Instead, acute twin-twin transfusion was suggested by the presence of severe anemia in the surviving fetus at delivery. We suggest that the lesions frequently found in the survivors are often due to acute hemodynamic and ischemic changes resulting from acute twin-twin transfusion at the time of intrauterine death, rather than to late-onset DIC. This hypothesis has an important implication for future management: Intervention must occur before intrauterine death if neurologic sequelae in the survivor are to be prevented.

Multiple and massive arteriovenous malformations in pregnancy.

Arteriovenous malformations (AVM) are rare in the reproductive years of life. There is a paucity of data regarding AVMs in pregnancy. Pregnancy can influence both the development and the progression of AVMs. The tendency to bleed is unpredictable. Many AVMs undergo spontaneous postpartum regression. We report on a 30-year old primipara with multiple generalised AVMs, both congenital and acquired, and a massive congenital AVM involving her entire right upper limb and shoulder girdle. Magnetic resonance imaging suggested there were AVMs in both the pelvis and the lower abdominal wall. The main management dilemma was mode of delivery. A trial of vaginal delivery was successful after spontaneous onset at term. The patient had a series of significant postpartum haemorrhages, warranting blood transfusion.

High delivery intervention rates in nulliparous women over age 35.

OBJECTIVE: To assess the effect of maternal age and parity on obstetric interventions and pregnancy outcome. STUDY DESIGN: A retrospective review of 35,140 deliveries including 4268 parturients aged 35 years or more (1985-1992). Obstetrical interventions and outcome were analyzed in relation to age and parity. RESULTS: Nulliparous women aged 35 years or more had a 2-fold increase in cesarean delivery rate over younger nulliparae, and 50% more cesarean deliveries than the multiparae aged 35 years or more. Similar trends were observed in preterm labor, labor induction, breech presentation, and instrumental delivery. Higher risk was encountered in neonatal 1 min Apgar scores < 3, and in admissions to the neonatal intensive care unit. There were no differences in all parameters between women over age 40 and women aged 35-40 years. The perinatal mortality was not increased and was similar in all groups. CONCLUSIONS: Nulliparae aged more than 35 years are at increased risk for interventions and cesarean sections. However, women aged 35-40 have a similar risk as women aged over 40 years.