Detection of fetal structural abnormalities at the 11–14 week ultrasound scan

The aim of this study was to evaluate the detection of fetal structural abnormalities by the 11–14 week scan. 2853 pregnant women were submitted to a routine ultrasound scan between the 11th and 14th week and the fetal skull, brain, spine, abdominal wall, limbs, stomach and bladder were examined. Following the scans the patientes were examined in the second or third trimester of pregnancy. An isolated increased nuchal translucency was not considered an abnormality. However, these patients had an early echocardiography assessment. Fetal structural abnormalities were classified as major or minor and of early or late onset. A total of 130 (4.6%) defects were identified and 29 (22.3%) of these were diagnosed at the 11–14 week scan, including nine cardiac defects associated with increased nuchal translucency. The antenatal ultrasound detection rate was 71.5%, and 31.2% were detected in the first-trimester assessment. 78.8% of the major defects were diagnosed by the prenatal scan and 37.8% by the 11–14 week scan. Fetal structural abnormalities at the 11–14 week scan were detected in approximately 22.3% of the cases, therefore, a second-trimester anomaly scan is important in routine antenatal care to increase the prenatal detection of fetal defects. Copyright © 2002 John Wiley & Sons, Ltd.     

Fetal bradycardia in the first trimester: an unusual presentation of atrial extrasystoles

We report a fetus with fetal bradycardia at 13 weeks of gestation secondary to atrial extrasystoles. The fetus subsequently developed paroxysmal supraventricular tachycardia and hydrops fetalis. The cardiac arrhythmia recovered spontaneously without any medical intervention. This case illustrates that atrial ectopic beats can present in the first trimester with fetal bradycardia. Rapidly evolving hydrops fetalis secondary to supraventricular tachycardia can develop, warranting close monitoring with weekly heart rate assessment. Fetal bradycardia secondary to atrial extrasystole should be differentiated from first trimester sinus bradycardia and those associated with major structural cardiac abnormality, which have a high fetal loss rate. Copyright © 2002 John Wiley & Sons, Ltd.     

Early detection of fetal cardiac abnormalities: how effective is it and how should we manage these patients?

Congenital heart defects (CHDs), the most commonly occurring congenital malformations, cause significant mortality and morbidity. With the recognition of early markers for CHD and the development of better ultrasound resolution, interest has turned toward performing a screening anomaly scan, including the heart, together with the nuchal scan. It is also possible, with adequate skill and training, to competently perform an echocardiogram <16 weeks' gestation. This article reviews the detection of major CHD in the first trimester and early second trimester including specific markers that help to identify high-risk groups for early fetal echocardiography (EFEC). CHD detection during first-trimester screening is low (2.3–56%) depending on the center's experience and the population studied. An increased nuchal translucency, abnormal ductus venosus flow, and tricuspid regurgitation in the first trimester are associated with an increased CHD risk and can be used together to identify high-risk fetuses for EFEC. EFEC requires skilled scanning and the expertise of a fetal echocardiographer. In high-risk populations, it is 78.5% sensitive with a 74.5% concordance between the EFEC and the mid-gestational echocardiogram. The availability of qualified personnel and diagnostic accuracy are prerequisites before EFEC can be introduced into management protocols. The limitations of EFEC should be recognized, and a later confirmatory echocardiogram is recommended. © 2014 John Wiley & Sons, Ltd.     

Ultrasound diagnosis of structural abnormalities in the first trimester

The advances in ultrasound technology have made it possible to identify fetal structural abnormalities and genetic syndromes in the first trimester. First trimester prenatal diagnosis of fetal central nervous system, renal, gastrointestinal, cardiac, and skeletal abnormalities is reviewed. Copyright © 2002 John Wiley & Sons, Ltd.     

Non-mosaic trisomy 22: a report of 2 cases

Non-mosaic trisomy 22 is a common cause of first trimester miscarriage and has a livebirth incidence of 1 in 30 000–50 000. Consequently there is a paucity of information for counselling parents. Detection in the second trimester is rare. It is commonly associated with severe growth retardation and multiple structural abnormalities. Oligohydramnios is frequently seen and can make detection of other abnormalities difficult. The outlook is uniformly poor and survival beyond the first trimester may present management dilemmas. A thorough fetal assessment including high-resolution cytogenetics with or without FISH is required for counselling. Careful plans for intrapartum and neonatal management may be necessary. The recurrence risk is thought to be low but information is very limited as there have been no reported cases of recurrence. We present two case of non-mosaic trisomy 22 including the first to be diagnosed subsequent to investigation for a high serum screening Down's risk. Copyright © 2006 John Wiley & Sons, Ltd.     

First-trimester fetal heart block and increased nuchal translucency: an indication for early fetal echocardiography

Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-trimester fetal bradycardia may result from heart block associated with complex congenital heart disease. We report two cases detected in the first trimester of pregnancy, in which both fetuses showed an increased nuchal translucency and bradycardia. Fetal karyotype was normal in both fetuses. First-trimester fetal echocardiography was performed and, in both cases, complex congenital heart disease was diagnosed. We discuss the added role of fetal heart rate in first-trimester ultrasound screening, in fetuses with increased nuchal translucency and normal karyotype. We stress, as well, the importance of echocardiography performed in the first trimester as a potential tool for early diagnosis in selected cases. Copyright © 2005 John Wiley & Sons, Ltd.     

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Objectives

To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities.

Methods

This is a national study including 1901 pregnancies with NT≥95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Results of detailed ultrasound examinations, karyotyping, genotyping, pregnancy and neonatal outcomes, investigation by a clinical geneticist and post-mortem investigations were collected.

Results

In total, 821 (43%) pregnancies had at least one abnormality. The rate of abnormalities was 21% for fetuses with NT between 95^th and 99^th percentile and 62% for fetuses with NT≥99^th percentile. Prevalence of single-gene disorders, submicroscopic, chromosomal and structural abnormalities was 2%, 2%, 30% and 9%, respectively.

Conclusion

Although cfDNA is superior to the combined test, especially for the detection of trisomy 21, 34% of the congenital abnormalities occurring in fetuses with increased NT may remain undetected in the first trimester of pregnancy, unless cfDNA is used in combination with fetal sonographic assessment, including NT measurement.     

Nuchal translucency thickness and outcome in chromosome translocation diagnosed in the first trimester

In order to determine the significance of nuchal translucency thickness on the subsequent natural history of first-trimester fetuses with a chromosome translocation, seven consecutive cases diagnosed between 11 and 13 weeks of gestation were reviewed. Nuchal translucency measurements were successfully obtained before chorionic villus sampling (CVS) in all cases. Three fetuses had an unbalanced translocation and all were associated with increased nuchal translucency and multiple anomalies at the detailed second-trimester scan. There were no survivors in this group. The remaining four fetuses had a balanced translocation; all had normal nuchal translucency thickness and no structural anomalies were detected in the second trimester. Three of these fetuses were born at ≥35 weeks of gestation and were phenotypically normal. However, an unexpected single fetal demise occurred in a dichorionic twin pregnancy at 28 weeks of gestation. It is concluded that nuchal translucency measurements provide important prognostic information on pregnancy outcome in first-trimester fetuses with a chromosome translocation. In parents with a known balanced translocation, the detection of increased nuchal translucency at 11–14 weeks of gestation is associated with unbalanced translocations, structural anomalies and poor pregnancy outcome. Copyright © 2001 John Wiley & Sons, Ltd.     

Normal fetal cardiac anatomy–a basis for the echocardiographic detection of abnormalities

Real-time examination of the fetal heart in 350 pregnancies has allowed a composite picture of normal fetal cardiac anatomy to be established and echocardiographic interpretation has been confirmed by anatomical studies. Two echocardiographic sections are readily obtainable and are suggested as applicable to routine scanning but the specialist nature of interpreting abnormalities is stressed. Six abnormalities have been suspected during the study and five confirmed anatomically or at cardiac catheterization. In view of the low incidence of congenital heart disease in a normal obstetric population, high risk groups should perhaps be selected for cardiac scanning at the present time. These include mothers of previously affected babies, diabetic mothers and certain abnormalities of pregnancy. Fetal ascites is particularly important, being present in three of the four proven cases of cardiac abnormality.     

The history of the second-trimester sonographic markers for detecting fetal Down syndrome,and their current role in obstetric practice

This review summarizes the development, history and use of second-trimester sonographic markers for the detection of fetal Down syndrome over three decades. Starting with the nuchal fold thickening in 1985 and culminating in the genetic sonogram in the 1990s. The combination of second-trimester serum screening with the ultrasound markers improved the detection rate of affected fetuses but also allowed patients to decrease their risk of carrying a fetus with Down syndrome if the genetic sonogram was normal. More recently the role of the genetic sonogram and its markers have changed with the wide spread use of first-trimester screening. This prior screening ultimately decreases the prevalence of fetal Down syndrome in the second trimester to less than 85% of what it was in the first-trimester as most fetuses with Down syndrome are now identified early. Current interpretation of the second-trimester Down syndrome markers must be based on the result of the first trimester and combined screening to achieve the most accurate risk estimate of an affected fetus. Copyright © 2010 John Wiley & Sons, Ltd.     

Trisomy 18 in chorionic villus sampling: Problems and consequences

Among 1547 patients undergoing first-trimester prenatal diagnosis, 100 fetal chromosome aberrations were detected. Thirteen of these involved chromosome 18. In two structural abnormalities of chromosome 18, the aberration could be excluded in amniotic fluid cells and two healthy infants were born. Trisomy 18 was not confirmed in amniotic fluid cells in three trisomy 18 mosaics. In eight non-mosaic trisomy 18 first-trimester diagnoses, the diagnosis was excluded by amniotic fluid cells or fetal cultures in four, and confirmed in the remaining four. Diagnosis of chromosome 18 aberrations in the direct preparation should be confirmed in the long-term culture of the chorionic villus sample or by amniotic fluid cultures.     

Sonographic detection of central nervous system defects in the first trimester of pregnancy

The fetal central nervous system can already be examined in the first trimester of pregnancy. Acrania, alobar holoprosencephaly, cephaloceles, and spina bifida can confidently be diagnosed at that stage and should actively be looked for in every fetus undergoing first-trimester ultrasound. For some other conditions, such as vermian anomalies and agenesis of the corpus callosum, markers have been identified, but the diagnosis can only be confirmed in the second trimester of gestation. For these conditions, data on sensitivity and more importantly specificity and false positives are lacking, and one should therefore be aware not to falsely reassure or scare expecting parents based on first-trimester findings. This review summarizes the current knowledge of first-trimester neurosonography in the normal and abnormal fetus and gives an overview of which diseases can be diagnosed. © 2016 John Wiley & Sons, Ltd.     

First trimester screening cannot predict adverse outcomes yet

The use of first trimester screening to detect aneuploidy has become an integral part of prenatal care. The application of similar screening algorithms to identify women at the highest risk for other adverse pregnancy outcomes in the first trimester could potentially have a major clinical impact. There has been much investigation into the ability to identify patients early in pregnancy at high risk for adverse pregnancy outcomes who may benefit from further surveillance and/or intervention. For this to be the case, however, as is true of any useful screening test, effective interventions need to be available. Unfortunately, for fetal growth restriction and stillbirth, no such interventions exist short of delivery. For preeclampsia, low dose aspirin has been demonstrated to be of benefit in specific subgroups. For preterm birth, although there are efficacious treatments, first trimester serum markers or cervical length measurements do not add significantly beyond historical or demographic factors, in prediction of preterm birth. Given the current evidence, first trimester screening, via serum or ultrasound markers, does not have sufficiently high enough positive predictive values for the development of preeclampsia, fetal growth restriction, preterm birth or stillbirth. In order to develop effective screening algorithms for adverse pregnancy outcomes in the first trimester, understanding the heterogeneous phenotype of these complications and the underlying pathophysiology is needed. © 2014 John Wiley & Sons, Ltd.     

Screening for fetal aneuploidies at 11 to 13 weeks

Effective screening for major aneuploidies can be provided in the first trimester of pregnancy. Screening by a combination of fetal nuchal translucency and maternal serum free-β-human chorionic gonadotrophin and pregnancy-associated plasma protein-A can identify about 90% of fetuses with trisomy 21 and other major aneuploidies for a false-positive rate of 5%. Improvement in the performance of first-trimester screening can be achieved by firstly, inclusion in the ultrasound examination assessment of the nasal bone and flow in the ductus venosus, hepatic artery and across the tricuspid valve, and secondly, carrying out the biochemical test at 9 to 10 weeks and the ultrasound scan at 12 weeks. Copyright © 2011 John Wiley & Sons, Ltd.     

First-trimester prenatal diagnosis in haemophilia A and B families—10 years experience from a centre in India

During the last 10 years (1995–2005) we have offered diagnosis in 438 families out of 502 families referred, by chorionic villus sampling procedure between 10 and 12 weeks of pregnancy in severe haemophilia A and B families. Sixty four families could not be offered a diagnosis in the first trimester either due to non-informativeness with the available techniques or due to the absence of affected members in the family and were subsequently offered diagnosis in the second trimester by direct analysis of factor VIII/IX clotting activity and antigen in the fetal blood samples. For first-trimester diagnosis in the chorionic villus samples, we have used both direct and indirect methods, that is, intron 22 and 1 inversions in the factor VIII gene, a multiplex PCR for the detection of gross deletions in the factor IX gene and RFLP analysis using a battery of markers within and outside the factor VIII/IX gene. The informativeness of all these techniques was found to be 92.21% in case of haemophilia A and 83.91% in case of haemophilia B. We followed up 122 children out of 326 (diagnosed unaffected prenatally) after birth and the diagnosis was adequately reconfirmed by both factor assays and by DNA analysis. Only one case of misdiagnosis was detected so far (0.22%), where the diagnosis was based only on the extragenic marker of the factor VIII gene. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management

Cases where initial prenatal diagnosis was made of isolated unilateral multicystic kidney (UMCK) were reviewed to determine appropriate counselling and management strategies. For the 73 cases, chromosome abnormalities, pregnancy complications and family histories were reviewed. In addition, subsequently diagnosed birth defects, and pediatric medical and surgical outcomes were available for 54 cases. Of those with outcome information available renal/genital–urinary tract abnormalities were diagnosed subsequently in 33% and non-renal abnormalities in 16% of cases. Of the non-renal abnormalities, congenital heart defects were most frequent (7%). One chromosome abnormality, a trisomy 21, was present among 32 cases where karyotypes were known (3%). Amniotic fluid volume abnormalities were present in 11 cases but not predictive of associated anomalies, with the exception of one case where polyhydramnios accompanied multiple malformations consistent with VATER association. A family history of structural renal anomalies was reported in 11 cases (20%). There were 14 cases of partial or complete involution (25%), including two cases of complete prenatal involution of the cystic kidneys. No long-term associated morbidity such as hypertension or malignancy was present in our cohort. Based on our study and corroborating literature, amniocentesis should be offered to women when a seemingly isolated UMCK is detected on routine prenatal ultrasound. Furthermore, a detailed ultrasound with careful assessment of the fetal heart and contralateral kidney is indicated at diagnosis and during the third trimester to assess for further evidence of structural abnormalities, as well as amniotic fluid volume abnormalities. Careful assessment of the newborn is indicated with appropriate speciality referral as required. Copyright © 2002 John Wiley & Sons, Ltd.     

Significance of septations in isolated fetal cystic hygroma detected in the first trimester

Recent reports have indicated an increased risk for fetal chromosome abnormalities, especially autosomal trisomy, in fetuses with isolated cystic hygroma, or prominent nuchal membranes, detected by ultrasonography during the first trimester. However, these reports present contradictory information regarding the prognostic significance of septations within the cystic hygroma. We evaluated, in blind fashion, 55 consecutive cases of isolatd fetal cystic hygroma detected at or before 13·9 weeks' gestation to determine the association between septations and fetal chromosome complement. Septations were associated (P<0·05) with an increased risk for fetal chromosome abnormalities. However, the incidence of chromosome abnormalities was also increased (12·5 per cent) among cases not characterized by septations. Thus, we believe it prudent to offer invasive prenatal testing to all women found to be carrying fetuses with cystic hygroma, irrespective of the presence or absence of septations.     

The influence of prenatal diagnosis on postnatal outcome in patients with structural congenital heart disease

Examination of the fetal heart has become an established part of mid-trimester anomaly scanning. Along side this has emerged the ability to diagnose congenital heart disease in the fetus with accuracy. Despite this, the development of screening programmes to look for fetal cardiac disease has only been partially successful. Furthermore, when detected, there seems to be little survival advantage associated with prenatal diagnosis. Demonstrating such an advantage is complicated by the nature of fetal cardiac disease, which tends to be severe and is often associated with extra-cardiac abnormalities. More selective studies, mostly involving small numbers of cases, are now beginning to demonstrate both improved survival and reduced morbidity in prenatally diagnosed infants presenting to cardiac intensive care units compared to those with a postnatal diagnosis. Copyright © 2004 John Wiley & Sons, Ltd.     

Prenatal diagnosis of giant cystic hygroma: Prognosis,counselling, and management; case presentation and review of the recent literature

Cystic hygromas have historically been associated with a grim prognosis when discovered during prenatal sonographic study of the fetus. This same grim prognosis is not observed by the paediatric surgeon who evaluates the neonate or paediatric patient. We present a fetal patient with a massive anterior cystic hygroma discovered in the third trimester prior to 30 weeks. This case and a review of the literature suggest tailoring the prognosis by category when counselling patients: (1) first trimester, normal karyotype-good; (2) first trimester, abnormal karyotype-poor; (3) second trimester and early third-poor to guarded; and (4) mid to late third trimester-good.     

Fetal arthrogryposis multiplex congenita/fetal akinesia deformation sequence (FADS)—Aetiology,diagnosis, and management

Arthrogryposis multiplex congenita (AMC) refers to an aetiologically heterogenous condition, which consists of joint contractures affecting two or more joints starting prenatally. The incidence is approximately one in 3000 live births; however, the prenatal incidence is higher, indicating a high intrauterine mortality. Over 320 genes have been implicated showing the genetic heterogeneity of the condition. AMC can be of extrinsic aetiology resulting from intrauterine crowding secondary to congenital structural uterine abnormalities (eg, bicornuate or septate uterus), uterine tumors (eg, fibroid), or multifetal pregnancy or intrinsic/primary/fetal aetiology, due to functional abnormalities in the brain, spinal cord, peripheral nerves, neuromuscular junction, muscles, bones, restrictive dermopathies, tendons and joints. Unlike many of the intrinsic/primary/fetal causes which are difficult to treat, secondary AMC can be treated by physiotherapy with good response. Primary cases may present prenatally with fetal akinesia associated with joint contractures and occasionally brain abnormalities, decreased muscle bulk, polyhydramnios, and nonvertex presentation while the secondary cases usually present with isolated contractures. Complete prenatal and postnatal investigations are needed to identify an underlying aetiology and provide information regarding its prognosis and inheritance, which is critical for the obstetrical care providers and families to optimize the pregnancy management and address future reproductive plans.