Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome in pregnancy.

The syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a rare mitochondrial disease with few documented cases in pregnancy. In this case report, we discuss the presentation and management of a 39-year-old grand multiparous lady with MELAS syndrome, which was diagnosed prior to her eighth pregnancy, discuss potential implications of the condition in pregnancy and summarise the current guidelines for the management of this rare condition.

Intraperitoneal transfusion for severe, early-onset rhesus disease requiring treatment before 20 weeks of gestation: A consecutive case series.

OBJECTIVE: To describe the management and perinatal outcomes of pregnancies affected by severe, early onset Rhesus isoimmunization treated with fetal intraperitoneal transfusions (IPTs). STUDY DESIGN: A ten-year consecutive case series of fetuses undergoing IPTs before 20 weeks gestation at Wessex Fetal Medicine Unit, Southampton, UK. Women with fetuses at risk of early onset fetal anaemia (before 20 weeks gestation) were identified from their obstetric history and maternal antibody levels at the time of booking. They were referred to our tertiary referral center. The decision to initiate transfusion was aided by middle cerebral artery peak systolic velocity as an indicator of fetal anaemia. No fetus was hydropic at the first transfusion. IPTs were commenced from as early as 15 weeks gestation in fetuses with difficult vascular access and performed regularly using this method until the cord could be successfully entered for intravascular transfusions. The main outcome measures were procedure and non procedure-related perinatal losses. RESULTS: 11 fetuses underwent 45 IPTs. 10/11 (91%) were delivered after 33 weeks gestation. There was one perinatal loss 1/11 (9%: 95% C.I 1.6-38%) from a cord accident during intravascular transfusion at 26 weeks gestation. There were no procedure related fetal losses or complications at the time of early IPTs. CONCLUSIONS: Previous studies report a perinatal loss rate with early intrauterine transfusion of 24% in gestations below 20 weeks using the intravascular route. This series suggests that intraperitoneal transfusion can be a safe and effective treatment for severe fetal anaemia at early gestations where vascular access is difficult.

Diagnosis and outcome in nonhydropic fetal pleural effusions.

OBJECTIVE: To determine the outcome of all pregnancies with nonhydropic fetal pleural effusions in the Wessex region. METHOD: Data were extracted from the Wessex congenital anomaly database for the years 1994-2015 inclusive. RESULTS: Sixty-two fetuses and babies were identified giving a total prevalence of 1:9500. Eight fetuses had bilateral effusions with additional, nonhydrops anomalies, and 54 had isolated effusions. Of the isolated cases, 36 presented before 24-week gestation: 12 were unilateral and 24 bilateral. All of the unilateral effusions resolved before or soon after birth with no other diagnosis but of the bilateral cases, four (17%) had a trisomy and three (13%) a genetic or syndrome diagnosis. Eighteen isolated cases presented after 24-week gestation, six were unilateral of which one had trisomy 21 (17%), and three (50%) Noonan's or another lymphoedema syndrome. Twelve were bilateral: One had trisomy 21, one an unbalanced translocation (17%), three had Noonan's or another lymphoedema syndrome, and two an unspecified syndrome (42%) at birth. CONCLUSION: These data suggest that a chromosomal microarray should be offered to all fetuses presenting with a pleural effusion in the absence of hydrops, and Noonan's syndrome testing should be considered for those that develop after 24 weeks. AIM: To determine the outcome of all pregnancies with nonhydropic fetal pleural effusions in the Wessex region from 1994-2015.

Intrauterine death rate in gastroschisis following the introduction of an antenatal surveillance program: Retrospective observational study.

AIM: To investigate whether an antenatal surveillance protocol including ultrasound and cardiotocograph monitoring reduces intrauterine death (IUD) in cases of gastroschisis. Secondary outcomes included neonatal death rate, mode of delivery and rate of intervention before planned time of delivery. METHODS: This was a retrospective observational study of all women with antenatally diagnosed gastroschisis who were managed according to the surveillance program between 2002 and 2015 in a tertiary fetal medicine and pediatric surgical center covering the Wessex region of England. We reviewed and analyzed data from the Wessex Antenatally Detected Anomalies (WANDA) database as well as prospectively managed maternity, ultrasound and neonatal databases over the given time period. Case notes were reviewed when delivery was expedited. RESULTS: The IUD rate was 2.2%, a 58% reduction since the introduction of the surveillance protocol. Delivery was expedited in 35.4% of cases, and in 86% of these, delivery was by cesarean section. In women being induced as planned at 38 weeks, the vaginal delivery rate was 88%, and for those in spontaneous labor before 38 weeks it was 75%. CONCLUSIONS: An antenatal surveillance program appears to reduce the IUD in gastroschisis. In one-third of cases, delivery was indicated before the planned date of delivery. When expedited delivery was indicated, the chance of cesarean section was high.

Relationship between neonatal gastroschisis and maternal body mass index in a United Kingdom population.

OBJECTIVE: It has been reported that gastroschisis is associated with low maternal body mass index (BMI). We tested this hypothesis in the UK. STUDY DESIGN: We studied cases of gastroschisis ascertained from the regional fetal congenital anomaly register. We compared each affected mother with two controls from the birth register and maternity database. The first control was the next mother to deliver in the hospital, representing the normal population of mothers. The second control was the next mother to deliver an unaffected child whose age was within one year of that of the index case controlling for maternal age. RESULTS: There was a strong inverse association between maternal age and gastroschisis. An inverse association between gastroschisis and birth order was eliminated by adjustment for maternal age. The average age of mothers of affected children was 22.1 years; of the next delivery control was 28.8 years, and of the age matched control was 22.2 years. A weak non-statistically significant negative association between BMI and gastroschisis was further weakened by adjustment for maternal age. CONCLUSION: Our results confirm the previously reported association between low maternal age and gastroschisis but suggest that within our UK population the link between low BMI and gastroschisis reported elsewhere is explained by younger mothers being thinner.

The increasing incidence of foetal echogenic congenital lung malformations: an observational study.

OBJECTIVES: The aim of this study was to investigate the incidence of congenital lung malformations over the past 19 years. Congenital lung malformations (CLM) are a heterogeneous group of lung abnormalities. The antenatal diagnosis is important for foetal and neonatal management but there have been no studies examining whether the reported incidence of this abnormality is constant. METHODS: A retrospective cross-sectional study of cases identified from the Wessex Antenatally Detected Anomalies (WANDA) register 1994-2012. RESULTS: One hundred and thirty-three cases of CLM in 524 372 live and stillbirths were identified. All but seven were identified on antenatal ultrasound. During the early registry (1994-1998) the average incidence of CLM was 1.27 per 10,000 births. By the last 4 years (2008-2012) this had risen to 4.15 per 10,000 births, with a progressive increase during the intervening years. CONCLUSION: There was over a three-fold increase in the antenatally detected CLM in the Wessex region 1994-2012. Comparison with the antenatal detection of diaphragmatic hernia suggests that this is a true rise in incidence rather than an artefactual increase due to increased antenatal recognition secondary to improved ultrasound resolution and operator experience. These results have clinical and cost implications for practitioners of foetal medicine, neonatology and paediatric surgery services.

In utero magnetic resonance imaging for diagnosis of dural venous sinus ectasia with thrombosis in the fetus.

BACKGROUND: Dural venous sinus ectasia with thrombosis (DVSET) in the fetus is a rare condition that can be diagnosed prenatally with the use of fetal MR imaging, yet with limited indication of long-term clinical significance. OBJECTIVE: To describe and evaluate the diagnostic value of fetal MR imaging in the prenatal diagnosis of dural venous sinus ectasia with thrombosis and its clinical significance. MATERIALS AND METHODS: We report a series of nine fetuses with dural venous sinus ectasia with thrombosis. The mothers, located in four feto-maternal centres, were referred for fetal MR imaging due to space occupying lesions identified on second-trimester antenatal ultrasound. RESULTS: In all but one case the dural venous sinus ectasia with thrombosis was in the vicinity of the venous confluence (VC) with various extension in the posterior dural sinuses. Antenatal follow-up imaging was performed in seven cases and showed progression in one, stable appearances in one and regression in five cases. Three pregnancies were terminated. In the remaining six cases there was no reported neurological deficit at up to 44 months of clinical follow-up. CONCLUSION: This is among the largest series of postnatal clinical follow-up in cases of prenatal diagnosis of dural venous sinus ectasia with thrombosis in the literature. Clinical follow-up suggests a good prognosis when antenatal follow-up shows partial or complete thrombus resolution.

Gestation-specific reference intervals for right and left ventricular ejection force from 12 to 40 weeks of gestation.

AIM: Ejection force of the fetal cardiac ventricles has previously been described from 18weeks of gestation. We aimed to establish gestation-specific reference intervals for ventricular ejection force (VEF) from 12 to 40weeks of pregnancy. MATERIAL AND METHODS: In a cross-sectional observational study of singleton pregnancies, examinations were performed in 236 women evenly distributed across each week of pregnancy from 12 to 40weeks. Each mother was scanned once. For the aortic and pulmonary valves, the time to peak velocity (TPV) and the average (TAV) and peak flow velocity in systole (PSV) was measured. For each we averaged values from three consecutive complexes. The outlet valve diameters were measured and the VEF on both the right and left sides were calculated using the formula VEF=(1.055×valve area×time to peak velocity×TAV)×(PSV/TPV) where 1.055 represents the density of blood. Measurements were repeated in 40 women to assess intraobserver reproducibility and in 19 women for interobserver variability. RESULTS: We present reference intervals for right and left VEF. We demonstrated that the ventricular force on both right and left sides increases with advancing gestational age. CONCLUSION: Fetal cardiac physiology can be studied and Doppler indices reliably measured as early as the late first trimester of pregnancy. Ventricular ejection force and its relationship with fetal growth could be explored in future studies and this may eventually provide better understanding of changes which may predispose to adult cardiac disease.

Parental attitude to participating in long-term follow-up studies of their children's health after in utero diagnosis of abnormalities.

OBJECTIVE: To determine whether parents might be distressed if approached to take part in long-term follow-up of their children's health and development. METHODS: A short, closed format anonymous questionnaire seeking parental opinion on being asked about their child's health was offered to attendees for obstetric ultrasound and parents of children attending paediatric cardiology clinics. RESULTS: In total, 70% of the 266 respondents were attending for ultrasound and approximately 30% paediatric cardiology clinics. In total, 66 respondents had children with long-term health problems, 28 with learning difficulties and 61 had previously had an abnormal obstetric ultrasound scan. Greater than 90% of parents were happy to be contacted and asked questions about their children's health and development, regardless of their child's health or their experiences during prenatal ultrasonography. CONCLUSIONS: Our results provide reassurance to future researchers and ethics committees that studies of children's later health after in utero diagnosis of anomalies are unlikely to prove unacceptable to many parents.

Phenotypic analysis of circulating dendritic cells during the second half of human gestation.

Dendritic cells (DCs) have been characterized as having an immature phenotype in infants when compared with adults; but it is unclear whether the phenotype or function of these populations changes during human intrauterine development. Three-colour flow cytometry was used to phenotype fetal/neonatal circulating DCs during the second half (>20-wk gestation) of pregnancy, (n = 34) and adults (n = 9). DCs were identified from peripheral blood mononuclear cells (PBMCs) or cord blood mononuclear cells (CBMCs) as staining brightly for HLA-DR but negative for T cell, B cell, monocyte, and NK cell lineage markers. The surface molecule of interest was detected in a third colour. During gestation CD34, a marker of immaturity was significantly higher, and CD4, a differentiation marker, was significantly lower than adult levels. The percentage of CD11c+ cells did not differ significantly at any age, although a trend to reduced intensity of expression at earlier stages of gestation was observed. Significantly fewer DCs expressed the IgG receptors CD32 and CD64 at all gestations. The percentage of HLA-DR+/lin- cells expressing CD40 was lowest at 20-23 wks and was always significantly lower on DCs from cord blood vs. adult blood. Similarly, the percentage of CD86+ and CD54+ DCs was significantly lower than adults throughout gestation. Thus, immaturity of cord blood DCs is likely to arise as a consequence of decreased ability to take up antigen (at least via IgG-mediated mechanisms) and reduced provision of co-stimulation.

Intraperitoneal transfusion in severe, early-onset Rh isoimmunization.

OBJECTIVE: To describe the management of five women with severe, early-onset Rh isoimmunization with a series of intraperitoneal transfusions. METHODS: Intraperitoneal transfusions were started at 15 to 16 weeks of pregnancy, with small volumes of blood given weekly until the umbilical cord could be successfully entered and further transfusions given intravascularly. RESULTS: The initial range of anti-D immune globulin levels was 24-244 international units, and all women had severe Rh isoimmunization complicating previous pregnancies. No fetus was severely anemic at the first intravascular transfusion (lowest hemoglobin 8.9 g/dL), and there were no fetal losses. Middle cerebral artery peak systolic velocity responded to treatment with intraperitoneal transfusions, suggesting that even at 15 to 16 weeks of gestation it correlates with fetal hemoglobin. CONCLUSION: This series shows that intraperitoneal transfusions can be used to successfully treat severe, early-onset Rhesus disease.

Retrospective audit of different antenatal screening policies for Down's syndrome in eight district general hospitals in one health region.

OBJECTIVE: To compare the effectiveness of different screening policies for the antenatal detection of Down's syndrome. DESIGN: Retrospective six year survey. SETTING: Maternity units of eight districts. PARTICIPANTS: Women who completed their pregnancies between 1 January 1994 and 31 December 1999 (155 501 deliveries). MAIN OUTCOME MEASURES: Cases of Down's syndrome identified before 24 weeks' gestation. RESULTS: 335 cases of Down's syndrome were identified, 323 in continuing pregnancies or liveborn children. Of these, 171 were identified antenatally. Seven different screening policies were used, in three principal groups: serum screening offered to all mothers, maternal age with serum screening or nuchal translucency available to limited groups, and maternal age combined with anomaly scans. The districts that used serum screening detected 57%, those using maternal age plus serum or nuchal translucency screening 52%, and those using a maternal age of > or =35 and anomaly scans detected 54%. The least successful district, which offered amniocentesis only to women aged over 37 years, detected only 31%. If amniocentesis had been offered from 35 years, as in all other districts, the detection rate would have risen to 54%. Across the region 15% (range 12-20%) of pregnant women were 35 years or more at delivery, and 58% (33-69%) of infants with Down's syndrome were born to women in this age range. CONCLUSIONS: Current additional serum or nuchal translucency screening techniques for antenatal detection of Down's syndrome are less advantageous than previously supposed. More pregnant women were aged over 35 than has been presumed in statistical models used in demonstration projects of serum screening and, as a result, the proportion of affected fetuses in this age group is much greater than predicted.