An Unusual Case of Transient Cardiac Calcification Identified on Antenatal Echocardiography: A Generalized Arterial Calcification of Infancy (GACI) Like Presentation.

Generalised arterial calcification of infancy (GACI) is an ultra-rare life-threatening genetic disorder. Arterial calcification is identified during foetal ultrasound scan (USS) as increased cardiac and/or vascular echogenicity. Inorganic pyrophosphate (PPi) is the main inhibitor of arterial calcification. Pathogenic variants in ENPP1, ABCC6 and NT5E causing low PPi lead to ectopic calcifications. Rheumatoid arthritis (RA) is an acquired condition that can also lead to arterial calcification in adults. We present an extremely rare case of a transient GACI-like condition identified during foetal echocardiogram of an infant born to a mother diagnosed with RA, which spontaneously resolved postnatally. This case highlights that foetal ultrasound scans of pregnant women with RA should be carefully evaluated for cardiovascular calcifications.

Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care.

Prospective risk of stillbirth according to fetal size at term.

OBJECTIVES: Fetal growth and size are associated with stillbirth risk. We wanted to investigate the week by week predictive value of fetal size at term on the prospective risk of stillbirth. METHODS: Anonymised database from the UK GAP program, with 2,094,702 term (≥37 weeks) deliveries including 4,670 stillbirths. Prospective stillbirth risk was defined as fetal death in the current week divided by total undelivered pregnancies. The data were analysed in five centile bands for stillbirth risk and risk ratios (RR) for 38, 39, 40 and 41+ weeks, using appropriate for gestational age (AGA) at 37 weeks as reference. RESULTS: Baseline stillbirth risk at 37 weeks was 0.29 per 1,000 and rose to 1.39 at 41+ weeks, with RR increasing to 4.8. In the 3<10 centile band risk rose from 0.72 to 2.43 over the same period, with RR increasing from 2.5 to 8.4. In the <3 centile group, the stillbirth risk rose from 1.62 to 6.16 (RR (5.6 to 21.2). In the 97>90 centile band, risk increased from 0.40 to 1.50 (RR 1.4 to 5.2) and for >97 centiles, it rose from 0.80 to 2.13 (RR 2.8-7.3). CONCLUSIONS: Prospective risk of fetal death at term is related to fetal size. The information provided, together with other considerations and results of investigations where available, will help clinicians to determine the advice to give to mothers about the best timing for delivery, balancing the baby's risk of compromise with iatrogenic sequelae of early delivery.

Robert's uterus (asymmetric septate uterus): a rare congenital Müllerian duct anomaly.

Müllerian anomalies such as Robert's uterus, which was first described by the French gynaecologist Dr Helene Robert in 1969, are rare clinical entities and have been reported in <3% of the female population. Robert's uterus is a rare phenomenon with a relative dearth of reported cases. Affected individuals may present with pelvic pain and dysmenorrhoea that intensifies near menses or acutely, with severe abdominal pain to the emergency department. They are also associated with adverse pregnancy outcomes, abnormal fetal presentation, preterm labour, recurrent pregnancy loss and infertility. Although ultrasound has a role in its initial assessment, MRI is the best modality to further delineate its anatomy. It is typically managed via laparotomy and total horn resection, endometrectomy of the blind cavity or abdominal metroplasty. The authors present the case of a 40-year-old woman at 19+3 weeks gestation with acute onset of left-sided abdominal pain. A transvaginal ultrasound and MRI of the pelvis confirmed a Robert's uterus with a viable pregnancy in the upper left horn. She developed a ruptured horn with significant haemoperitoneum. An emergency laparotomy was performed and a non-viable fetus was evident. Only a few cases of pregnancy in the blind hemicavity have been reported so far. This case also highlights the importance of considering this diagnosis in young females presenting with dysmenorrhoea and normal menstrual flow. It is imperative to render a prompt diagnosis, as minimally invasive procedures may be more effective if detected before the formation of adnexal endometriomas.

Timing of delivery in antenatal fetal hydronephrosis: a snap shot social media survery of obstetric and fetal medicine practice.

OBJECTIVES: To identify when obstetricians would deliver a fetus with antenatal hydronephrosis and normal liquor. Designed as snap-shot survey. Setting: Survey Monkey link. Population/sample were obstetrics and fetal medicine consultants who received the survey link via closed professional forums on the North West Coast Maternity Clinical Network, Facebook, and publicly on Twitter. METHODS: Survey link publicised as above, obstetric consultants were asked at what gestation would they deliver a fetus with antenatal hydronephrosis and normal liquor; and what criteria would they use to make that decision. Main outcome measures were number of years in practice, gestation at delivery, anteroposterior diameter (APD) of renal pelvis. RESULTS: A total of 44/102 respondents (43%) would deliver prior to 40 weeks (median no. of years as consultant 10 years [IQR 5-17]) vs. those who would not (median years as consultant 5.5 [IQR 3-12]). Re APD threshold of delivery: 17 indicated delivery if the APD were 20 mm, 10 if it were 21-30 mm and 16 if it were >30 mm. Re gestation at which they would deliver: 13 indicated 37-38 weeks, 13 indicated 38-39 weeks and 17 indicated 39-40 weeks. Reasons selected for delivery before term were obstetric anxiety n=2, maternal request n=2, maternal anxiety n=2 and concern about fatal renal damage/renal damage n=34. CONCLUSIONS: A surprising number of respondents would consider early delivery of a fetus with hydronephrosis and normal liquor despite the lack of evidence of benefit. The evidence supporting term delivery means that early term delivery is only indicated for obstetric reasons in this scenario.

Skeletal abnormalities secondary to antenatal etidronate treatment for suspected generalised arterial calcification of infancy.

BACKGROUND: Generalised arterial calcification of infancy (GACI) is a rare disorder characterised by the deposition of hydroxyapatite crystals within the vessel walls. It is associated with a high mortality rate. Bisphosphonates have been used with some success in the treatment of GACI. However, there is a paucity of data on the antenatal use of bisphosphonates for GACI. In this paper, we report development of the skeletal changes suggestive of hypophosphatasia (HPP) in an infant with GACI, whose mother was treated with etidronate during pregnancy. CASE REPORT: A Caucasian infant boy had a suspected antenatal diagnosis of GACI based on the findings suggestive of calcification of the annulus of the tricuspid valve and wall of the right ventricular (RV) outflow tract and main pulmonary artery on foetal echocardiography and the genetic analysis which showed a pathogenic heterozygous mutation in ABCC6. Based on these findings, mother was started on etidronate treatment from 26 weeks of gestation. A healthy male baby was delivered at 38 weeks of gestation. Initial postnatal echocardiogram on day 1 of life was normal with good biventricular function; subtle changes suggestive of microcalcifications were detected on the CT angiography. Serum calcium, phosphate, alkaline phosphatase and renal profile were normal. Further, the serum inorganic pyrophosphate (PPi) level was significantly low. Skeletal changes suggestive of HPP were seen on the radiographs. The baby developed cardiac dysfunction on day 4 of life with evidence of ischaemic changes on electrocardiogram (ECG).Treatment with etidronate was started in view of probable evolving coronary calcifications. Despite treatment with cardiac supportive measures and bisphosphonate, he succumbed to death in the third week of life. DISCUSSION: We believe, this is the first report of skeletal changes suggestive of HPP, arising secondary to antenatal etidronate (first generation bisphosphonate) used for the treatment of suspected GACI due to a heterozygous ABCC6 mutation.

Antenatal diagnosis of total anomalous pulmonary venous connection in functional single ventricle hearts: Outcomes over 13-year period.

INTRODUCTION: A functionally single cardiac ventricle seen on foetal ultrasound scan carries a guarded prognosis. The antenatal diagnosis of anomalous pulmonary venous connection (APVC) remains challenging, if there is no associated structural cardiac abnormality. Antenatally, a combination of complex cardiac anomaly with suspected isomerism should raise the possibility of associated total anomalous pulmonary venous connection (TAPVC). There needs to be a high index of suspicion for TAPVC, in functional single ventricle and suspected isomerism, as this carries a very grim outcome postnatally. We illustrate foetal echocardiographic findings of suspected TAPVC and review outcomes of antenatal versus postnatal diagnosis of TAPVC with functional single ventricle. METHODS: We retrospectively reviewed our database over 13 years, focusing on foetal cardiac diagnosis, pregnancy outcomes, management and outcomes of livebirths with diagnosis of TAPVC with functional single ventricle. RESULTS: Thirteen patients were included in the review. For the nine antenatal patients, three pregnancies were terminated and six babies were born alive (four babies had compassionate care, two babies had cardiac surgery). One baby is alive at 8.5 years, after Fontan surgery. For the four postnatal patients, three babies had compassionate care (one alive at age 8.1 years) and one baby had cardiac surgery (died age nine weeks). Ten of the 13 patients have right atrial isomerism. Of these 10 patients, only two are alive. For the three non-isomeric babies, only one baby is still alive. There is heterogeneity of the type of TAPVC diagnosed with no particular group that offered better survival. CONCLUSION: Antenatal diagnosis of TAPVC, even in the context of functional single ventricle remains challenging. If isomerism is suspected, targeted evaluation of pulmonary venous connection should be done. This combination of cardiac lesion carries a very grim outcome. The ability to make this diagnosis antenatally will add to the information and counselling given to these parents.

Does serial 3rd trimester ultrasound improve detection of small for gestational age babies: Comparison of screening policies in 2 European maternity units.

OBJECTIVE: Methods for the antenatal detection of small for gestational age babies (SGA) differ between countries. The aim of this study was to compare the diagnostic accuracy of routine versus selective small for gestational age babies screening policy using data from two European Maternity Units. STUDY DESIGN: This was a retrospective cohort study from Liverpool Women's Hospital, UK, that uses selective third trimester sonography and from the University Hospital Centre Zagreb, Croatia, that uses routine third trimester sonography for SGA detection. Screen positive cases were defined as pregnancies with estimated fetal weight (EFW) <10th centile at the last 3rd trimester scan. True positives had both EFW and birth weight <10th centile. Pregnancy management data and perinatal outcomes were retrieved from hospital electronic data and special care baby unit (SCBU) reports. RESULTS: The proportion of small for gestational age babies was higher in Liverpool (7.8%) compared with Zagreb (4%); P<0.001. Sensitivity for detection of SGA babies in Zagreb was 27% (95%CI 15%-44%) and 33% (95%CI 23%-45%) in Liverpool. The specificity was high in both centres (Zagreb 100% (95%CI); Liverpool 98% (95%CI)). The induction of labour for antenatally diagnosed SGA babies was more common in Liverpool (38.5%) than in Zagreb (9.1%). In both centres, all antenatally diagnosed SGA babies admitted to SCBU were preterm babies. Their indications for admission to SCBU were complications related to prematurity. CONCLUSION: The effectiveness of selective SGA screening policy is comparable to universal third trimester ultrasound screening. Further prospective evaluations of SGA screening policies are warranted and they should include full cost-effectiveness analysis and assessment of possible harm from increased interventions leading to more preterm births.

Quantifying the impact of deprivation on preterm births: a retrospective cohort study.

BACKGROUND: Social deprivation is associated with higher rates of preterm birth and subsequent infant mortality. Our objective was to identify risk factors for preterm birth in the UK's largest maternity unit, with a particular focus on social deprivation, and related factors. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective cohort study of 39,873 women in Liverpool, UK, from 2002-2008. Singleton pregnancies were stratified into uncomplicated low risk pregnancies and a high risk group complicated by medical problems. Multiple logistic regression, and generalized additive models were used to explore the effect of covariates including area deprivation, smoking status, BMI, parity and ethnicity on the risk of preterm birth (34⁺° weeks). In the low risk group, preterm birth rates increased with deprivation, reaching 1.6% (CI95 1.4 to 1.8) in the most deprived quintile; the unadjusted odds ratio comparing an individual in the most deprived quintile, to one in the least deprived quintile was 1.5 (CI95 1.2 to 1.9). Being underweight and smoking were both independently associated with preterm birth in the low risk group, and adjusting for these factors explained the association between deprivation and preterm birth. Preterm birth was five times more likely in the high risk group (RR 4.8 CI95 4.3 to 5.4), and there was no significant relationship with deprivation. CONCLUSIONS: Deprivation has significant impact on preterm birth rates in low risk women. The relationship between low socio-economic status and preterm births appears to be related to low maternal weight and smoking in more deprived groups.

Von Willebrand factor expression in endometrial endothelial cells in women with menorrhagia.

This prospective study assessed von Willebrand factor (VWF) expression in the endometrium using immunohistochemical staining in women with menorrhagia with or without von Willebrand disease (VWD) compared with a control group of women with normal menstrual loss. Endometrial VWF expression is significantly lower in women with VWD, which may play a local underlying role in pathogenesis of menorrhagia in these women.

Antenatal diagnosis of twin-reversed arterial perfusion sequence (acardiac amorphous) in a triplet pregnancy: case report.

Acardiac twinning is the most extreme form of twin-twin transfusion syndrome occurring in monzygotic twin pregnancies with monochorionic placentation. A case of acardiac amorphous foetus, occurring in association with spontaneously conceived triplet pregnancy, diagnosed on ultrasound in early second trimester is described and its antenatal management and brief review of literature discussed.

Recent onset neurofibromatosis complicating eclampsia with maternal death: a case report.

Neurofibromatosis in pregnancy has been associated with poor perinatal outcome. A 30-year-old multigravida developed peripheral lesions of neurofibromatosis during the third month of pregnancy. She had eclampsia complicated with fatal left-sided massive intracerebral haemorrhage detected on computed tomography at 8.5 months gestation. Investigations were suggestive of HELLP syndrome. A still-born male baby was delivered. In spite of all supportive measures the patient died on the third postpartum day. We conclude that recent onset neurofibromatosis in current pregnancy should be considered as a predictor of potentially adverse maternal and fetal outcome and such pregnancies be managed in tertiary level referral centre.

Leiomyosarcoma of the broad ligament mimicking as ovarian carcinoma--a case report.

A 55-year-old postmenopausal lady presented with signs and symptoms of ovarian malignancy. Laparotomy revealed a 8 x 8-cm degenerated, cystic and haemorrhagic mass arising from left broad ligament which on histopathology proved to be leiomyosarcoma.

Vaginal birth of conjoined thoracopagus--a rare event.

An extremely rare case of vaginal birth of preterm conjoined thoracopagus twins diagnosed after delivery is being described and brief review of literature discussed.

Long retained intravaginal foreign body: a case report.

Recurrent vaginal discharge in children may be due to variety of causes. Intravaginal foreign body retained for long duration can be a diagnostic dilemma. This report presents the case of a girl who had an intravaginal foreign body for over four years duration. Recurrent, unremitting, foul-smelling, bloody vaginal discharge in a child should alert the clinician to the possibility of a retained vaginal foreign body.