Fetal heart block: Vaginal delivery an option.

BACKGROUND: Fetal heart block (FHB) occurs in approximately 1:20 000 births and is associated with significant morbidity and mortality. Vaginal delivery with intrapartum fetal scalp lactate monitoring is offered as an option at our centre for selected cases, in contrast with the published literature advocating caesarean birth. AIMS: To review perinatal outcomes at delivery for FHB at a tertiary referral hospital. MATERIALS AND METHODS: Ours was a retrospective cohort study from 1 January, 2007 to 30 June, 2020. The infant outcomes are summarised in three delivery groups: vaginal delivery, planned caesarean section (CS) and unplanned CS. RESULTS: There were 23 newborns in the study period, with a median gestation at birth of 37.2 weeks and there was one antepartum fetal death in this cohort. Vaginal delivery was planned in 12 women: eight had normal births, three of these women progressed to an intrapartum (unplanned) CS and one woman had a planned CS. All live babies in the vaginal delivery cohort had an Apgar score greater than seven at five minutes. Of the 22 newborns, six required intubation, of which five had been delivered by a planned CS. CONCLUSION: Our data suggest that planned vaginal delivery is a safe option for selected women carrying a fetus with FHB. Managing labour with serial fetal scalp lactates, and the involvement of senior clinicians are important factors in achieving a successful outcome.

Clinical consequences of the extremely rare anti-PP1Pk isoantibodies in pregnancy: a case series and review of the literature.

BACKGROUND: The absence of the red cell antigens P, P1 and Pk , known as 'p', represents an extremely rare red cell phenotype. Individuals with this phenotype spontaneously form anti-PP1Pk isoantibodies, associated with severe haemolytic transfusion reactions, recurrent spontaneous abortion and haemolytic disease of the fetus and newborn (HDFN). METHODS: We report a series of four successful pregnancies in three women with anti-PP1Pk isoantibodies, one complicated by HDFN, another by intrauterine growth restriction, all managed supportively. We also review the literature regarding the management of pregnancy involving anti-PP1Pk isoimmunization. RESULTS: The literature surrounding anti-PP1Pk in pregnancy is limited to a very small number of case reports. The majority report management with therapeutic plasma exchange (TPE) with or without intravenous immunoglobulin. The relationship between titre and risk of pregnancy loss remains unclear, though a history of recurrent pregnancy loss appears important. Although a positive cord blood direct antiglobulin test is frequently noted, clinically significant HDFN appears uncommon, though possible. CONCLUSION: Early initiation of TPE in high risk patients should be strongly considered. If possible, pregnancies should be managed in a high-risk obstetric or maternal fetal medicine service. The fetus should be monitored closely with interval fetal ultrasound and middle cerebral artery peak systolic volume Doppler to screen for fetal anaemia. Timely sourcing of compatible blood products is likely to be highly challenging, and both directed and autologous donation should be contemplated where appropriate. The International Red Cell Donor Panel may also provide access to compatible products.

The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.

LARS2 variants are associated with Perrault syndrome, characterized by premature ovarian failure and hearing loss, and with an infantile lethal multisystem disorder: Hydrops, lactic acidosis, sideroblastic anemia (HLASA) in one individual. Recently we reported LARS2 deafness with (ovario) leukodystrophy. Here we describe five patients with a range of phenotypes, in whom we identified biallelic LARS2 variants: three patients with a HLASA-like phenotype, an individual with Perrault syndrome whose affected siblings also had leukodystrophy, and an individual with a reversible mitochondrial myopathy, lactic acidosis, and developmental delay. Three HLASA cases from two unrelated families were identified. All were males with genital anomalies. Two survived multisystem disease in the neonatal period; both have developmental delay and hearing loss. A 55-year old male with deafness has not displayed neurological symptoms while his female siblings with Perrault syndrome developed leukodystrophy and died in their 30s. Analysis of muscle from a child with a reversible myopathy showed reduced LARS2 and mitochondrial complex I levels, and an unusual form of degeneration. Analysis of recombinant LARS2 variant proteins showed they had reduced aminoacylation efficiency, with HLASA-associated variants having the most severe effect. A broad phenotypic spectrum should be considered in association with LARS2 variants.

Antenatal diagnosis of isolated infracardiac infradiaphragmatic total anomalous venous connection - Pictorial essay and discussion.

INTRODUCTION: Antenatal diagnosis of isolated infracardiac total anomalous pulmonary venous connection (TAPVC) is rare. Making the diagnosis antenatally is critical as delayed management could result in neonatal deterioration and poor outcome after surgery. METHOD: A multipara at 29 weeks of gestation was referred to our tertiary unit for ultrasound review. The fetal growth and biophysical profile were normal. A fetal echocardiogram revealed normal cardiac position with atrioventricular and ventriculoarterial concordance. There was a mild discrepancy in size of the right and left chambers of the heart. A connection between the pulmonary veins and the left atrium could not be established. A pulmonary venous confluence was noted posterior to the left atrium, from which a descending vertical vein emerged traversing the diaphragm and draining into the left portal vein into the liver. RESULTS: A diagnosis of infracardiac infradiaphragmatic total anomalous pulmonary venous connection was made. The pregnancy was delivered at 39 weeks by lower segment caesarean section. The antenatal findings were confirmed by postnatal echocardiogram. Successful sutureless repair of the pulmonary veins was performed. CONCLUSION: Isolated infracardiac total anomalous pulmonary venous connection can be diagnosed antenatally. This ensures early postnatal evaluation and successful repair.

Recurrent fetal hydrops with maternal M alloimmunisation: not a benign condition.

Haemolytic disease of the fetus and newborn (HDFN) is associated with red cell antibodies. Anti-M usually results in a mild haemolysis and is rarely clinically significant. There is no established consensus on management of pregnancies with anti-M. A case of recurrent HDFN with maternal M alloimmunisation was identified at a tertiary hospital in Australia. We collected the patient and neonate's clinical and pathological data and interpreted the case with available literature. This is the first case in literature of recurrent fetal hydrops in the setting of M alloimmunisation. Neonate was delivered in a poor condition, intubated and admitted to the neonatal intensive care unit for ionotropic support, red cell transfusion and plasma transfusion for coagulopathy. Direct Coombs test was positive, confirming HDFN. Although anti-M rarely causes HDFN, accurate history, fetal surveillance and monitoring is essential for identification of fetal anaemia. Concurrent placental disease may increase fetal risk from anti-M antibodies.

Maternal Flt-1 and endoglin expression by circulating monocyte subtype and polarization in preeclampsia and fetal growth restriction.

OBJECTIVE: Circulating levels of the anti-angiogenic factors sFlt-1 and sEndoglin are elevated in preeclampsia (PE) and fetal growth restriction (FGR), mainly secreted from placental trophoblast. This study aims to identify the contributory role of monocyte Flt-1 and endoglin expression in PE and FGR. STUDY DESIGN: A prospective cross-sectional study was conducted and patients recruited from four clinical groups including normal pregnancy, PE, FGR and PE + FGR. Peripheral blood samples and cord blood were collected from 54 pregnant women between 24-40 weeks of gestation. Monocyte subset distribution was assessed using CD14 and CD16 expression and the surface expression of Flt-1, endoglin, CD86 and CD163 assessed by flow cytometry. We compared these factors between (1) clinical groups. (2) monocyte subset (3) monocyte polarization and (4) gestational age. RESULTS: Across all clinical groups, Flt-1 was mainly expressed by classical and intermediate monocytes, but no differences between clinical groups were observed. Surface expression of endoglin was higher on intermediate and non-classical monocytes and decreased in PE + FGR total monocytes. Flt-1 and endoglin expression correlated with increasing gestational age as well as higher CD86/CD163 ratio favouring M1 polarisation. The fetal monocyte endoglin expression was increased in FGR. CONCLUSION: We conclude that monocyte Flt-1 and endoglin expression increase with gestational age and with M1 polarization suggesting their upregulation with inflammatory changes in monocytes. Endoglin expression by M1 monocytes may play a part in increased cardiovascular risk associated with preeclampsia. Endoglin expression on fetal monocytes is increased in FGR as a likely response to placental injury.

Value of single and paired serum human chorionic gonadotropin measurements in predicting outcome of in vitro fertilisation pregnancy.

OBJECTIVES: To assess whether paired human chorionic gonadotropin (hCG) measurements in early pregnancy are more effective than a single measurement, in predicting the outcome for an in vitro fertilisation pregnancy. DESIGN: Retrospective analysis. SETTING: Westmead Fertility Centre, Westmead Hospital, Sydney, Australia. MATERIALS AND METHODS: Serial hCG measurements in 143 patients at Westmead Fertility Centre, from August 1997 to April 2000, were studied retrospectively. The predictive value of single hCG measurements relative to the published assay reference ranges were evaluated. The predictive value of serial hCG levels in predicting pregnancy outcome was assessed separately. Normal daily rate of rise (ROR) of hCG was defined as the mean ROR for ongoing pregnancies +/- 1 SD. Abnormal daily ROR was defined as a daily increase in hCG less than the mean ROR for ongoing pregnancies--1 SD. MAIN OUTCOME MEASURES: Viability of the pregnancy at 20 weeks' gestation. RESULTS: An initial hCG measurement below the 5th centile reference limit for gestation has 85% (confidence interval (CI) 75-92%) positive predictive value for non-viability, with a sensitivity of 40% (CI 33-48). Serial testing of borderline samples for ROR did not improve positive predictive value (70%: CI 50-86%) or sensitivity (30%: CI 20-43%) in identifying non-ongoing pregnancies. CONCLUSIONS: In assisted reproductive technologies pregnancies, comparison of a single hCG value with appropriate reference ranges enables approximately 40% of non-viable pregnancies to be identified with a high positive predictive value. Repeated measurements did not contribute further to the predictive value.