Prenatal diagnosis of parasitic conjoined twins with three‐dimensional ultrasound

Asymmetric and parasitic conjoined twins are extremely rare anomalies of monochorionic monoamniotic twins, consisting of an incomplete twin attached to the fully developed body of the co‐twin. Sonographic examination is essential for prenatal diagnosis as early detection of fetal anomalies with poor prognosis provides a chance to deliver the infant vaginally for the mother. We herein describe a case with a prenatal diagnosis of a parasitic twin using three‐dimensional (3‐D) ultrasound. The clear images obtained with 3‐D ultrasound helped in counseling the parents. Making an early prenatal diagnosis of severe fetal anomalies with careful and sophisticated sonographic examinations should be warranted.     

Prenatal diagnosis of urinary tract abnormalities by ultrasound

The capacity of a general ultrasound screening program to detect fetal malformations affecting the urinary tract was evaluated in an epidemiologic study. A total of 11,986 pregnant women, representing 97% of the pregnant population in Malm?, Sweden, from April 1978 through August 1983 were examined. On routine examinations performed by midwives in the 17th and 33rd gestational weeks, the fetal anatomy was carefully surveyed. The overall frequency of fetal malformations was 0.5%, with urinary tract abnormalities representing approximately 50% of the total number. In 20 of 33 cases, the ultrasound findings were those of hydronephrosis or hydroureter. In ten cases, a cystic renal malformation was found, and the remaining three cases represented double renal pelvis, Potter syndrome, and posterior urethral valve. A total of 28 abnormalities were unilateral and five bilateral. No case of unilateral absence of renal tissue was noted prenatally. Prenatal diagnosis of urinary tract abnormalities known to precipitate neonatal urosepsis and subsequent renal scarring and other complications makes it possible to start an early antibiotic prophylaxis regimen. A complete workup of the infants can be started early and before life-threatening complications occur.     

Spontaneous Intrauterine Repairment of Cleft Palate Induced by Amniocentesis in Rats

On day 15 of gestation, 180 fetal sacs in 43 pregnant Charles Foster rats were subjected to amniocentesis producing a series of total or partial clefts in the hard and soft palate regions. Fetuses recovered on days 19, 20 or 21 showed a gradual decline in the incidence of total clefts with increasing gestational age, i.e. 34% on day 19, 29% on day 20 and 13% on day 21, suggesting spontaneous ‘repairment’ of the clefts induced by amniotic sac puncture. Prenatal ‘repairment’ at times leaving residual partial clefts in the hard palate, suggested delayed rotation of the palatine shelves following reaccumulation of lost quantity of amniotic fluid and withdrawal of tongue obstruction. The experiment suggested that the palatine shelves retain intrinsic ‘shelf force’ for a much longer period than thought earlier. However, a gradual increase in the incidence of residual partial cleft with increasing gestational age, i.e. 45% on day 19; 50% on day 20 and 67% on day 21, respectively, suggests only incomplete (partial) repair in most of the cases probably due to paucity of time.     

Higher risk of orofacial clefts in children born to mothers with angina pectoris: A population‐based case‐control study

Previously an unexpected association of maternal angina pectoris (MAP) during pregnancy with a higher risk of orofacial clefts in their children was found. There were three objectives of this study: (i) to evaluate the validity of MAP‐diagnoses in the previous study and the recent history of mothers with MAP in a follow‐up study; (ii) to estimate the prevalence of other congenital abnormalities in the offspring of mothers with MAP; and (iii) to analyze the possible effect of confounders for the risk of orofacial clefts. The large dataset of population‐based Hungarian Case‐Control Surveillance System of Congenital Abnormalities, 1980–1996 was evaluated including 22 843 cases with congenital abnormalities and 38 151 controls without any defect. Twenty‐two cases (0.10%) and 12 controls (0.03%) were born to mothers with medically recorded MAP (odds ratio [OR] with 95% confidence interval [CI]: 3.7, 1.8–7.3). Of 22 cases, six had isolated cleft lip ± palate (OR with 95% CI: 13.3, 4.9–35.9) and two were affected with isolated cleft palate (OR with 95% CI: 10.5, 2.3–47.6). The diagnosis of MAP was confirmed in seven women visited at home in 2009–2010, two had recent myocardial infarction and five were smokers. There was no higher risk for other congenital abnormalities. In conclusion the higher risk of orofacial clefts was confirmed in the children of mothers with MAP and smoking may trigger the genetic predisposition of both MAP and orofacial clefts. However, the number of cases was limited and therefore further studies are needed to confirm or reject this theoretically and practically important observation.     

What's new in fetal medicine?]

One of the major progress in fetal medicine in recent years is the increased sensitivity of sonographic screening for foetal malformations, due to technical improvement but also to a better training of professionals. Screening for chromosomal abnormalities is no longer based on maternal age alone. Second trimester maternal serum screening (MSS) is increasingly used: thus in 1997, 376,798 MSS tests were performed in France, yielding to the prenatal diagnosis of 391 cases of Down's syndrome. First trimester sonographic nuchal translucency measurement (NTM) is an effective screening method when performed under stringent conditions. Quality control however, is more difficult to implement on a large scale for NTM than for MSS. Performing screening tests sequentially carries a danger of generating an unnecessarily high number of amniocentesis, which may be obviated by a rational calculation of an individual's risk to carry an aneuploid baby. First trimester MSS is expected to become standard practice in the next years, probably in combination with NTM. Cytogenetics underwent substantial innovations recently, due to the ever-increasing use of molecular cytogenetics. FISH techniques allow: 1) precise analysis of unexpected structural chromosomal abnormalities diagnosed by routine amniocentesis, 2) rapid screening of the most common aneuploidies by amniocentesis when a fetal structural anomaly is detected by 3rd trimester ultrasound, 3) diagnosis of micro-deletions suspected by fetal ultrasound or post-mortem. Prenatal diagnosis by maternal blood sampling and fetal cells or DNA analysis is now part of routine clinical practice in selected cases, such as fetal sexing in families affected by an X linked disease. Thus one can select those pregnancies eligible to invasive prenatal diagnosis. Pre implantation diagnosis, which has not been legal in France until 1999 is now increasingly used as an alternative to first trimester diagnosis. As for fetal therapy, a major recent breakthrough is the prenatal management of twin to twin transfusion syndrome by either amnioreduction or laser coagulation of inter-twin vascular shunts. In addition, new pathophysiologic concepts involving the renin angiotestin system could lead to further therapeutic innovations. A European randomised trial is now being completed to establish the respective indications of drainage and Laser. All this underscores that fetal medicine is no longer solely a succession of dramatic technical breakthroughs, but is entered an era of large-scale diffusion that requires evidence based evaluation.     

Dysmorphic choroid plexuses and hydrocephalus associated with increased nuchal translucency: Early ultrasound markers of de novo thanatophoric dysplasia type II with cloverleaf skull (Kleeblattschaedel)

Prenatal diagnosis of thanatophoric dysplasia (TD) type II presenting in the first trimester with increased nuchal translucency (NT) and cloverleaf skull (Kleeblattschaedel) have been scantly reported in the medical record. Abnormal choroid plexus has been seen in association with fetal anomalies. Here we described a case of increased NT associated with indented choroid plexuses, early onset hydrocephalus and cloverleaf skull in a fetus subsequently diagnosed at early second trimester to carry a de novo mutation encoding for TD type II. The findings of dysmorphic choroid plexus, early onset hydrocephalus and cloverleaf skull at first trimester scan may be early, useful ultrasound markers of TD type II. Molecular analysis to control for possible overlapping syndromes were performed and resulted negative. Postmortem X‐ray and 3D‐CT scan confirmed the cloverleaf skull, narrow thorax, straight femur with rhizomelic shortening of the limbs and the presence of a communicating hydrocephalus.     

Severe fetal anemia as a consequence of extra‐abdominal umbilical vein varix: A case report and review of the literature

Umbilical vein varix is associated with a high incidence of fetal anomalies and perinatal complications. There are two types of umbilical vein varix: fetal intra‐abdominal and extra‐abdominal. Herein, a case is reported of severe fetal anemia with extra‐abdominal umbilical vein varix. A 33‐year‐old primigravida was referred to our hospital for fetal growth restriction, fetal cardiomegaly, and decreased fetal movements at 26 weeks' gestation. A Doppler assessment showed an elevated middle cerebral artery peak systolic velocity at 2.2 MoM, suggesting fetal anemia. Umbilical vein varix had caused intermittent turbulent flow, provoking hemolytic anemia. Intrauterine transfusion improved fetal circulatory failure and anemia and prolonged gestational period. At 33 weeks' gestation, the patient underwent cesarean delivery due to nonreassuring fetal status. Pathological analysis revealed focal loss of vascular smooth muscle of the umbilical vein. Extra‐abdominal umbilical vein varix has been reported in 14 cases including this case. The antenatal diagnosis rate is reported to be 79%; fetal heartbeat abnormalities and fetal deaths were reported as 50% and 14%, respectively. Eighty‐six percent of patients had intra‐umbilical cord thrombosis, but currently this is the only case of hemolytic anemia. Furthermore, extra‐abdominal umbilical vein varix may present as fetal hydrops with anemia. During ultrasound examination of fetal anemia, umbilical cord screening should be performed with caution.     

Prenatal sonographic findings and prognosis of craniosynostosis diagnosed during the fetal and neonatal periods

The aim of the study was to explore the sonographic findings of fetuses with craniosynostosis and investigate their prognosis. We conducted a 5‐year, multicenter retrospective study and collected data on patients with craniosynostosis diagnosed in the perinatal period. Of 41 cases, 30 cases (73%) were syndromic craniosynostosis, eight cases (20%) were non‐syndromic craniosynostosis and the other three cases (7%) were secondary craniosynostosis of chromosomal deletion syndromes. The prenatal ultrasound detection rate was 61%. Half of the cases of syndromic craniosynostosis detected during the perinatal period were Pfeiffer syndrome; there were also six cases of Apert syndrome, three cases of Crouzon syndrome and other rare form of syndromic craniosynostosis (Beare‐Stevenson syndrome, Saethre‐Chotzen syndrome, cranioectodermal dysplasia, and thanatophoric dysplasia). Abnormal shape of the skull was the most common finding leading to prenatal diagnosis of craniosynostosis. Abnormal head biometry, which was the second most frequent finding, was closely correlated with deformation of the cranial shape. Three cases presented with ventriculomegaly and exophthalmos but normal cranial shape and size. The overall survival rate of infants with syndromic craniosynostosis was 79%, while all of the infants with non‐syndromic craniosynostosis survived. In conclusion, prenatal diagnosis of craniosynostosis is difficult, especially when dysmorphic change of the fetal cranium is not evident. Abnormal head biometry and ventriculomegaly could potentially be additional markers of fetal craniosynostosis and consequently increase the prenatal detection rate.     

The Weissenbacher-Zweymuller syndrome A case report with review of the world literature

This report describes a patient with a form of chondrodysplasia characterised by a rhizomelic shortening of the limbs, metaphyseal widening, vertebral coronal clefts and retrognathia. This syndrome was first described by Weissenbacher and Zweymuller in 1964. All the relevant literature available has been reviewed and it has been concluded there are mild and severe forms of this syndrome.     

Antenatal Ultrasound for Fetal Anomalies: Importance of Perinatal Autopsy

Sixty-one instances of congenital anomalies identified prenatally by ultrasound were reviewed to determine whether autopsy provided important additional information. An important finding was defined as one which would affect: 1) genetic counseling; 2) diagnosis of a syndrome; 3) determination of etiology or pathogenetic mechanism of the anomaly; or 4) interpretation of severity of the anomalies. In 28 cases (46%), post-mortem examination provided such information. All of these infants had multiple anomalies; correlations with oligohydramnios and poor fetal outcome were noted. Autopsy provided no additional meaningful information in 30 cases (49%), the majority (77%) of whom had isolated anomalies. In 3 cases (5%), due to tissue autolysis, autopsy provided less information than the previous ultrasound. Although most fetal anomalies are readily diagnosed by ultrasound, we found that postmortem examination is still necessary: 1) to confirm a prenatal diagnosis; 2) to delineate multiple anomalies; 3) when the ultrasound examination is limited by oligohydramnios; and 4) to obtain tissue for microscopic examination, cytogenetic and biochemical analysis, if these studies have not been performed prenatally.     

Antenatal ultrasound for fetal anomalies: importance of perinatal autopsy

Sixty-one instances of congenital anomalies identified prenatally by ultrasound were reviewed to determine whether autopsy provided important additional information. An important finding was defined as one which would affect: 1) genetic counseling; 2) diagnosis of a syndrome; 3) determination of etiology or pathogenetic mechanism of the anomaly; or 4) interpretation of severity of the anomalies. In 28 cases (46%), post-mortem examination provided such information. All of these infants had multiple anomalies; correlations with oligohydramnios and poor fetal outcome were noted. Autopsy provided no additional meaningful information in 30 cases (49%), the majority (77%) of whom had isolated anomalies. In 3 cases (5%), due to tissue autolysis, autopsy provided less information than the previous ultrasound. Although most fetal anomalies are readily diagnosed by ultrasound, we found that post-mortem examination is still necessary: 1) to confirm a prenatal diagnosis; 2) to delineate multiple anomalies; 3) when the ultrasound examination is limited by oligohydramnios; and 4) to obtain tissue for microscopic examination, cytogenetic and biochemical analysis, if these studies have not been performed prenatally.     

Acrania/encephalocele sequence (exencephaly) associated with 92,XXXX karyotype: Early prenatal diagnosis at 9+5 weeks by 3D transvaginal ultrasound and coelocentesis

A 27-year-old pregnant woman was diagnosed by 3D transvaginal ultrasound as carrying a fetus of 9⁺⁵ weeks gestation affected by acrania/encephalocele (exencephaly) sequence. A 2D transvaginal ultrasound-guided aspiration of 5 mL of extra-coelomic fluid was performed under cervical block before uterine suction. Conventional cytogenetic analysis demonstrated a 92,XXXX karyotype. Transvaginal 2D ultrasound-guided coelocentesis for rapid karyotyping can be proposed to women who are near to miscarriage or in cases where a prenatal ultrasound diagnosis of congenital anomaly is performed at an early stage of development. Genetic analysis can be performed using traditional cytogenetic analysis or can be aided by fluorescence in situ hybridization (FISH). Coelocentesis may become an integral part of first trimester armamentarium and may be clinically useful in the understanding of the pathogenesis of early prenatally diagnosed congenital anomalies.     

A tetralogy of fallot associated with a stenotic pulmonary valve and agenesis of the ductus arteriosus in a 13-week-old fetus: the role of postmortem examination

Prenatal diagnosis at very early gestational age may disclose fetal anomalies, although this diagnosis is limited by lack of details on ultrasound (US) examination; hence, the importance of postmortem (PM) examination. We present a case of a 13-week-old fetus terminated as a result of significantly raised nuchal translucency, which additionally presented a tetralogy of Fallot with a stenotic pulmonary valve and agenesis of ductus arteriosus. These cardiac defects are not detected by US at this gestational age. On the other hand, PM examinations are being performed more frequently in these cases with the aid of a dissecting microscope and using delicate instruments. This case illustrates the need for a closer collaboration between fetal medicine and fetal pathology in order to reach a more accurate diagnosis, which provides the basis for adequate reproductive counseling.     

Advances in maternal fetal medicine practice

Maternal fetal medicine (MFM) is a subspecialty of obstetrics that focuses on identified risk pregnancies. The role includes obstetric ultrasound for fetal assessment and diagnosis of anomalies, invasive prenatal diagnosis and management of pregnancies complicated by maternal medical disorders, multiple fetuses and the antenatal management of extreme prematurity. Skill specialisation within MFM includes fetal interventions such as fetal shunting procedures, intrauterine transfusion, fetoscopic laser photocoagulation of anastomotic vessels for twin to twin transfusion syndrome and ex utero intrapartum treatment. MFM specialists are actively involved in clinical and basic science research to improve maternal and neonatal outcomes. Most Australian MFM specialists are associated with metropolitan teaching hospitals. MFM sub‐specialisation has reduced the impact of disability associated with aneuploidy, structural anomalies, multiple pregnancy and extreme prematurity. Management aims are to give families timely counselling, appropriate intervention, and optimisation of the time and location of delivery. The aim of this paper is to update the reader regarding current advances in MFM practices.     

Chorioretinal lacuna in the amniotic band syndrome

The malformations in the amniotic band syndrome (ABS) are due to entrapment of fetal parts by fibrous band in the amniotic sac. Limbs are most commonly affected followed by craniofacial defects in one third of patients. Ocular defects include corneal leukomas and lid colobomas often contiguous with facial clefts, strabismus, hypertelorism, and microphthalmos. Unilateral chorioretinal defects or lacunae are rare findings in the ABS. We report a female infant with such a lacunar defect along with central nervous abnormalities, and discuss the differential diagnosis and the embryopathic implications.     

First trimester three-dimensional transvaginal imaging of alobar holoprosencephaly associated with proboscis and hypotelorism (ethmocephaly) in a 46,XX fetus

A 19-year-old woman was scanned at 10(+6) weeks gestation by 2D-3D ultrasound. The fetus had a crown-rump length of 40.9 mm, with the cephalic pole occupied by a single cystic cavity measuring 10.6 x 7.7 x 6.8 mm and severe hypotelorism associated with mid-facial hypoplasia. 3D ultrasound confirmed the malformations seen on the 2D scan and enabled the visualization of a proboscis and a low-set right ear. Fetal karyotyping was performed by chorionic villus sampling. Due to major fetal malformations of the fetus, the patient opted for termination of pregnancy. First trimester sonographic diagnosis of holoprosencephaly relies on bilateral visualization of choroid plexuses in what has been called the 'butterfly' sign. Differential diagnosis between holoprosencephaly and hydranencephaly may be difficult in the first trimester of pregnancy. However, midline structures such as falx cerebri, interhemispheric fissure and third ventricle are present in hydranencephaly and are absent in alobar holoprosencephaly, and thalami are never fused in hydranencephaly. 3D ultrasound has demonstrated an increased definition of anatomical abnormalities of malformations, compared with 2D ultrasound, and has proven to be crucial in the decision-making process of parents and in later prenatal counseling, especially in this case where necroscopy examination was refused by the parents. Images obtained by 3D ultrasound gave detailed insight into this ventral midline anomaly, depicting much of the disordered prosencephalic development.     

Double-outlet single ventricle and an abdominal vascular mass: In utero diagnosis with pathological confirmation

Summary A fetal echocardiographic scan was performed when routine prenatal ultrasound screening failed to identify four cardiac chambers. The scan showed a single ventricle with an associated circoid varicosity. Because of these anomalies, amniocentesis was suggested and trisomy 18 confirmed. The presence of major cardiac structural anomaly should prompt careful and specific review of all fetal anatomy to screen for syndrome identification and consideration of amniocentesis.     

Multiplex PCR in noninvasive prenatal diagnosis for FGFR3‐related disorders

Thanatophoric dysplasia and achondroplasia are allelic disorders caused by a constitutively active mutation in the FGFR3 gene. Because thanatophoric dysplasia is a lethal disorder and achondroplasia is non‐lethal, they need to be distinguished after ultrasound identification of fetal growth retardation with short limbs. Accordingly, we have developed a noninvasive prenatal test using cell‐free fetal DNA in the maternal circulation to distinguish thanatophoric dysplasia and achondroplasia. A multiplex PCR system encompassing five mutation hotspots in the FGFR3 gene allowed us to efficiently identify the responsible mutation in cell‐free DNA in all examined pregnancies with a suspected thanatophoric dysplasia or achondroplasia fetus. This system will be helpful in the differential diagnosis of thanatophoric dysplasia and achondroplasia in early gestation and in couples concerned about the recurrence of thanatophoric dysplasia due to germinal mosaicism.     

Three-dimensional first trimester fetal volumetry: comparison with crown rump length

BACKGROUND: Ultrasonographic volumetry measurements of human fetus have become possible using three-dimensional ultrasound systems. OBJECTIVE: To evaluate the weekly increase of fetal volume during the first trimester of normal pregnancies compared to the crown rump length and creating a first trimester fetal volume nomogram. METHODS: Crown rump length and three-dimensional ultrasonographic volumetry measurements performed on 72 first trimester fetuses using virtual organ computer aided analysis (VOCAL). RESULTS: A significant direct correlation (r = 0.939) was found between the calculated fetal volumes and crown rump lengths. A 6-12 weeks gestation fetal volume nomogram was proposed. CONCLUSION: Fetal volume database in the first trimester may serve as a reference table for diagnosis of early pregnancy failure.     

Prenatal diagnosis of Pena-Shokeir syndrome phenotype by ultrasonography and MR imaging

Pena-Shokeir syndrome phenotype is characterized by neurogenic arthrogryposis, facial anomalies, polyhydramnios and lung hypoplasia. Prenatal US is crucial in showing Pena-Shokeir syndrome phenotype in addition to demonstrating reduced fetal movements or akinesia as an underlying aetiological factor as early as the 14th week of gestation. Several reports of prenatal diagnosis of Pena-Shokeir syndrome phenotype by US have been published. In this report, MRI findings providing prenatal diagnosis are presented.