Prenatal diagnosis of congenital heart defects - a population based study

Aim: The aim of this study was to describe the efficiency of routine prenatal ultrasound screening for the detection of cardiac defects in a Swedish region and to study the effect of prenatal diagnosis on the survival and outcome of the child.
Methods: We identified all fetuses and infants with a diagnosed major cardiac defect born in 1999–2003 in a region of Sweden using a register of the regional paediatric cardiac clinic, various health-care registers and registers of prenatally detected malformations. The outcome of newborns with and without a prenatal diagnosis of a cardiac defect was compared.
Results: During the study period, 77 241 infants were born in the area. Among 145 major cardiac defects, 21% were detected prenatally. For the two university departments the detection rate was 38%. Of the major cardiac defects diagnosed <23 gestational weeks, 30% were terminated. No significant difference in the outcome was found between children with and without a prenatal diagnosis of a major cardiac defect.
Conclusions: It could not be shown that survival and outcome for children with major cardiac defects was better when the defect was known prenatally than if it was detected postnatally. The size of the study prohibits conclusions on moderate differences.     

Fetal Diagnosis of an “Extra Cardiac Chamber”

Congenital right ventricular aneurysms and diverticula are rare congenital anomalies and prenatal detection is uncommon. Distinguishing between these two anomalies by imaging alone is difficult. Recently, we were asked to review a 21-week ultrasound that detected an “extra cardiac chamber.” This represents the first report of an isolated out-pouching of the right ventricular free wall to be detected by prenatal screening ultrasound. Based on preoperative imaging, this out-pouching was diagnosed as a ventricular aneurysm, but intraoperative findings suggested it was a diverticulum. This case will review the differences between ventricular aneurysms and diverticula and illustrate the use and limitations of various imaging modalities used in their evaluation, both prenatally and postnatally. A plan of management is suggested.     

产前诊断脐膨出胎儿80例结局分析

目的了解80例产前诊断为脐膨出胎儿的结局。方法回顾性分析2004年12月到2010年1月广东省妇幼保健院产前超声检查诊断为“先天性脐膨出”的患儿临床资料,通过医院信息系统和电话随访相结合,记录孕妇和新生儿的诊疗资料。结果80例中,36例脐膨出胎儿伴发结构畸形,其中4例失访,3例行脐带血染色体检查,1例为47XXY,31例终止妊娠,1例死胎;44例单发脐膨出,5例失访,11例行脐带血染色体检查,均正常,28例终止妊娠,11例活产,其中1例出生时未见脐膨出,1例巨大脐膨出患儿一期手术后死亡,1例巨型脐膨出患儿予非手术治疗,8例小型脐膨出患儿均经一期手术治疗,无一例死亡,术后发育良好。结论运用产前超声和染色体检查等仔细甄别胎儿脐膨出,通过宫内转运或新生儿转运开展早期诊治,获产前诊断的单发小型脐膨出可以继续妊娠。     

Prenatal assessment of foot deformity

Congenital talipes equinovarus (CTEV) and other skeletal abnormalities can be diagnosed prenatally by ultrasound scan. If diagnosed, clinicians should be cautiously optimistic with the parents, particularly if the talipes diagnosed is isolated and not associated with other foetal abnormalities. There is no correlation between the prenatal appearance of the foot and the state of the foot at birth, nor with the necessity for surgical intervention.     

First trimester ultrasound screening for fetal aneuploidy and middle cerebral artery Doppler assessment for fetal alloimmunization

PURPOSE OF REVIEW: Traditional methods of fetal evaluation require invasive procedures (e.g. amniocentesis) with an inherent, albeit low, risk of complications and pregnancy loss. As medical knowledge and ultrasound technology have advanced, noninvasive modes of fetal evaluation have become increasingly used. Two disorders in which this has been most applied are fetal aneuploidy and alloimmunization to red blood cell antigens. RECENT FINDINGS: First-trimester screening protocols for fetal aneuploidy combine ultrasound measurement of the fetal nuchal translucency with the measurement of two maternal serum hormones, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. This combination detects approximately 85% of women pregnant with fetuses with trisomy 21. An increase in the velocity of fetal middle cerebral artery blood flow occurs in the setting of moderate to severe fetal anemia and can be measured with Doppler ultrasound. Middle cerebral artery evaluation is equally sensitive in the prediction of anemia as amniocentesis for bilirubin breakdown products and has less associated risk. It has an additional benefit because it can also be applied to causes of anemia other than hemolysis. SUMMARY: Noninvasive methods of fetal assessment are becoming increasingly commonplace. There has been a dramatic decrease in the use of prenatal diagnostic services as screening strategies have become available. Doppler assessment of the velocity of blood flow through the fetal middle cerebral artery will allow for more judicious application of invasive procedures to pregnancies at significant risk for anemia.     

Reasons for trisomy 13 or 18 births despite the availability of prenatal diagnosis and pregnancy termination

BACKGROUND: Few studies have evaluated the reasons why lethal chromosomal anomalies continue to occur despite the importance of this question for maximizing perinatal care. AIMS: To determine why trisomy 13 or 18 births continue to occur in Alaska. STUDY DESIGN: Case series involving review of maternal and infant medical records. SUBJECTS: All 28 known infants and fetuses that died with trisomy 13 or 18 during 1992-2001 and their mothers. OUTCOME MEASURES: The proportion of mothers that declined or received a variety of routine prenatal tests, the results of prenatal testing, and the impact of testing on decisions related to pregnancy. RESULTS: Seventeen women declined pregnancy termination or amniocentesis, 10 had no prenatal risk factors and were not offered these procedures, and one woman had an amniocentesis but was not offered pregnancy termination. Twenty-six women had >/=1 prenatal ultrasounds; for 17 women, these were interpreted as normal throughout pregnancy (n=11) or until after 30 weeks gestation (n=6) despite substantial fetal malformations. Fourteen of 15 women with an abnormal ultrasound had an amniocentesis compared to one of eight women whose only risk factor was advanced maternal age. CONCLUSIONS: Most trisomy 13 or 18 deliveries occurred to women who declined amniocentesis or pregnancy termination. Failure to identify abnormalities on prenatal ultrasound may have contributed to the decision not to have these procedures.     

Parental experiences after prenatal diagnosis of fetal abnormality

For many pregnant women, prenatal testing is a routine component of contemporary pregnancy care. Receiving a prenatal diagnosis is frequently associated with intense feelings of shock and grief; the extent of which may be unrelated to the pregnancy gestation or the condition diagnosed. During this time of crisis, parents are often faced with important choices about their pregnancy. Levels of understanding and experiences of professional support throughout this time likely impact decisions that are made and how they are subsequently perceived. Despite considerable advances in prenatal testing technologies over the last 20 years there is a paucity of research examining parental experiences in-depth. Future advances such as prenatal exome sequencing will further increase the scope of prenatal testing and numbers of parents who receive a prenatal diagnosis. It is imperative that large-scale studies are performed to ensure that protocols are in place to adequately support couples at this time.     

Community-wide screening for cystic fibrosis carriers could replace newborn screening for the diagnosis of cystic fibrosis

Most babies with cystic fibrosis (CF) are born to parents who did not know they were carriers until their baby was diagnosed with CF, usually by newborn screening. It is only after the birth of their first child with CF that couples are offered genetic counselling and reproductive choices. Most use this information for prenatal testing of subsequent pregnancies. With the high uptake of first trimester screening for Down syndrome (80% in Victoria) most couples have had screening during the CF affected pregnancy. Yet screening for CF carrier status is available, costs are similar to that for Down syndrome screening and CF carrier screening only ever needs to be done once. Waiting for couples to have a baby with CF before they are identified as carriers denies them choice. A national policy on CF carrier screening in Australia, and determination to equitably fund such a programme, is required.     

First and second trimester screening for fetal structural anomalies

Fetal structural anomalies are found in up to 3% of all pregnancies and ultrasound-based screening has been an integral part of routine prenatal care for decades. The prenatal detection of fetal anomalies allows for optimal perinatal management, providing expectant parents with opportunities for additional imaging, genetic testing, and the provision of information regarding prognosis and management options. Approximately one-half of all major structural anomalies can now be detected in the first trimester, including acrania/anencephaly, abdominal wall defects, holoprosencephaly and cystic hygromata. Due to the ongoing development of some organ systems however, some anomalies will not be evident until later in the pregnancy. To this extent, the second trimester anatomy is recommended by professional societies as the standard investigation for the detection of fetal structural anomalies. The reported detection rates of structural anomalies vary according to the organ system being examined, and are also dependent upon factors such as the equipment settings and sonographer experience. Technological advances over the past two decades continue to support the role of ultrasound as the primary imaging modality in pregnancy, and the safety of ultrasound for the developing fetus is well established. With increasing capabilities and experience, detailed examination of the central nervous system and cardiovascular system is possible, with dedicated examinations such as the fetal neurosonogram and the fetal echocardiogram now widely performed in tertiary centers. Magnetic resonance imaging (MRI) is well recognized for its role in the assessment of fetal brain anomalies; other potential indications for fetal MRI include lung volume measurement (in cases of congenital diaphragmatic hernia), and pre-surgical planning prior to fetal spina bifida repair. When a major structural abnormality is detected prenatally, genetic testing with chromosomal microarray is recommended over routine karyotype due to its higher genomic resolution.     

Fetal gastrointestinal malformations

In an audit to evaluate fetal gastrointestinal (GIT) malformations, case sheets of all mothers who gave birth to newborns with GIT malformations were analysed regarding the maternal history, prenatal ultrasound and the postnatal structural malformations and perinatal management. In 1999, eleven babies were born with gastrointestinal malformations, one was a still birth. Nine had associated malformations of other systems, two had trisomy 21. Eight babies were operated in the immediate newborn period, 5 survived. Ultrasound was not very accurate in the diagnosis of GIT anomaly in this series. In view of associated chromosomal and structural anomaly a fetal ECHO and genetic amniocentesis is warranted. Most of these babies require immediate surgery after birth, so they need to be delivered in a centre which is equipped with good neonatal and pediatric surgery care.     

Familial severe congenital diaphragmatic hernia: Left herniation in one sibling and bilateral herniation in another

Familial congenital diaphragmatic hernia (CDH) is extremely rare; it comprises about 2% of all CDH cases. The empirical risk is about 2%, increasing to 10% in a family with two affected children. This report describes severe CDH in two siblings who had been diagnosed prenatally. The female newborn diagnosed with left CDH prenatally was born at 38 weeks of gestation. Despite surgical repair and intensive treatment, she died 10 days after birth. Her younger brother was born at 39 weeks of gestation after being diagnosed with bilateral CDH prenatally, and died 75 min after birth. Both infants had neither other congenital anomaly nor chromosomal abnormalities. Their parents are healthy without consanguinity. Their first daughter and the fourth child have no congenital anomalies.     

Prenatal diagnosis

With the leaping advances in knowledge of genetics, its applications in patient management are also increasing. Prenatal diagnosis is the most useful application as it offers prospective parents the assurance of having an unaffected child in situations of high recurrence risks. Pretest and post test counseling is an integral part of prenatal diagnosis. All Pediatricians and Obstetricians should be familiar with the basic prerequisites of prenatal screening/testing. Timely referral, preferably prepregnancy is important. There is more or less a consensus regarding offering prenatal diagnosis for lethal/chronic disabling or difficult/expensive to treat conditions. Ethical issues are already around regarding prenatal testing for disabilities like deafness and late onset disorders. The present communication is an effort to present the clinician’s perspective of prenatal diagnosis     

The role of the pediatric surgeon in the perinatal multidisciplinary team

BACKGROUND AND AIM: The pediatric surgeons' understanding of the etiology of many prenatally diagnosed surgical conditions has grown significantly in recent years. The impact of prenatal pediatric surgical consultation on the perinatal course has not been explored extensively. The aim of this study was to explore the pediatric surgeon's role as a team member on the management and outcome of prenatally diagnosed surgical congenital anomalies. MATERIAL AND METHODS: A retrospective study was performed of all pregnant women diagnosed at our institution by antenatal ultrasound as having a fetus with congenital anomalies. The pediatric surgeon's role in decisions on the termination of pregnancy, IN UTERO intervention, or an altered mode or timing of delivery was studied. Patients were divided according to prenatal decisions into 5 groups; group one included those who had nonaggressive obstetric management, groups two and three included pregnancies where the mode or time of delivery was changed, group four consisted of patients who underwent amniocentesis for karyotype analysis and group five had a termination of pregnancy. RESULTS: There were 406 fetuses diagnosed with congenital anomalies out 20 995 pregnancies. The incidence of congenital anomalies was 1.93 %. The total number of surgical anomaly cases was 234/400 (58.5 %). The pediatric surgeon was the team leader for the management and counseling of parents in 184 out of 227 cases (82.4 %) in group one, two (0.85 %) and 10 (4.3 %) patients in groups 2 and 3, respectively. The pediatric surgeon was the main team member who took the decision in groups 4 and 5. Eighty-three out of 400 cases (35.5 %) had amniocentesis. Although termination of pregnancy in 26/83 (31.3 %) or an altered mode or time of delivery was the outcome for group four; this was not related to the results of the test. Twenty-six pregnancies (11 %) were terminated in group five. The pregnancy terminations included fetuses with Potter's and VATER syndrome, multiple congenital anomalies and conjoined twins. CONCLUSION: The pediatric surgeon should be a member of the perinatal multidisciplinary team. Prenatal pediatric surgical consultations have a significant impact on the perinatal management of a fetus with congenital anomalies by providing obstetric colleagues and families with valuable information into the surgical management of anomalies.     

PRENATAL DIAGNOSIS OF β-THALASSEMIA IN EGYPT: Implementing Accurate High-Tech Methods Did not Reflect Much on the Outcome

The clinical severity of thalassemia major makes it a priority genetic disease for prevention programs through prenatal diagnosis for carrier couples. Incorporation of automated DNA sequencing that enables the characterization of mutations not detected by other mutation specific detection procedures was a prime goal of this work. Automated DNA sequencing was offered on fetal tissues in 30 pregnancies during the year 2005. The pregnancies were at high risk for homozygosity or compound heterozygosity for β-thalassemia based on mutation analysis of both parents before prenatal diagnosis. Both parents have β-thalassemia trait. Fetal samples were collected by chorionic villus sampling (CVS) in the first trimester and by amniocentesis in the second trimester. The point mutations were characterized by PCR (ARMS). The absence of the expected fragment with all the mutant ARMS primers insinuated an uncharacterized DNA segment that was further subjected to direct automated fluorescent DNA sequencing in an attempt to know if the fetus was affected by parents’ mutations. If no mutation was detected using the PCR ARMS, the sample was further analyzed using direct automated fluorescent DNA sequencing. The mean gestation when carrying out the invasive procedure was 14 (10 –18) weeks. All mothers had a previous affected pregnancy, and 13 had two or more previous affected pregnancies. Pregnancies were: 8 carrier fetuses (trait) and 22 affected fetuses in which 2 were homozygous and 20 double heterozygous. Fourteen parents of affected fetuses preferred to continue pregnancy and the babies were born as diagnosed. The other 8 parents decided on termination and DNA of the abortuses proved to be as previously diagnosed by DNA sequencing. The use of PCR amplification and direct sequencing have permitted the accurate characterization of unidentified alleles and successfully solved 100% of the examined samples. However, it has resulted in minor changes of the outcome as the majority of couples preferred continuation of pregnancy.     

Applications and limits of prenatal diagnosis (author's transl)

By means of antenatal diagnosis mainly chromosome aberrations, malformations and inborn errors of metabolism may be recorded. At present there exist four ways for gaining information on the fetus in a pregnant woman: analysis of the amniotic fluid after amniocentesis, fetoscopy, ultrasound diagnosis and analysis of the maternal serum. Prenatal diagnosis becomes necessary in pregnancies where a child suffering from a severe illness or malformation is to be expected. Only if the disorder can be diagnosed by antenatal diagnosis and its severity justifies abortion prenatal diagnosis is to be carried out. Most cases transferred to antenatal diagnosis are pregnancies of women in advanced age because of the increasing risk of carrying a child with Down's syndrome. Another important group is formed by pregnant women with a previous child with Down's syndrome or another chromosomal disorder.     

产前诊断胆道闭锁影像学研究

目的：胆道闭锁早期诊断困难,而产前诊断更是极少发现。本文对产前诊断的胆道闭锁影像学特点进行探讨。方法回顾我院2010年至2012年收治的产前诊断9例产前诊断胆道畸形患儿,入院手术年龄24 d至2岁。全部患儿行腹腔镜胆道造影,4例诊断胆道闭锁,5例诊断先天性胆管扩张症,胆道闭锁患儿中2例接受腹腔镜下肝管空肠ROUX-Y吻合术,2例接受开腹肝门空肠吻合术。观察其临床表现,超声和实验室指标,术中情况,术后恢复情况等。结果4例患儿产前超声未见胆囊或胆囊显示不清。产前超声发现肝门部囊肿的3例患儿,囊肿小且均无明显增大,张力较高,呈规则圆形。产前诊断发现肝门囊肿的3例患儿术中证实为胆总管远端闭锁（Ⅰ型胆道闭锁）,未发现胆囊也未发现囊肿的1例患儿证实为Ⅲ型胆道闭锁。生后全部胆道闭锁患儿出现黄疸,最早出现在生后第2天,但都未出现陶土样便。全部胆道闭锁患儿囊肿大小形态无明显变化。全部患儿查ALT、AST、rGGT、直接胆红素和总胆红素进行性升高。2例接受腹腔镜下肝管空肠ROUX-Y吻合术,2例接受开腹肝门空肠吻合术。全部4例患儿术后恢复好。结论产前超声检查可以确定胆道闭锁,如果发现肝门部囊肿的胎儿,应定期接受超声检查,如果囊肿在孕期变化不明显,应怀疑囊肿型胆道闭锁。如产前超声未发现胆囊结构,则应怀疑为Ⅲ型胆道闭锁。生后应密切观察、超声、生化、黄疸情况。如果黄疸进行性加重可及早进行腹腔镜胆道造影及手术治疗。     

Ethical considerations in prenatal testing: Genomic testing and medical uncertainty

Prenatal diagnostic testing has recently progressed from karyotype to routinely available chromosomal microarray, and the potential for fetal whole exome sequencing, both through invasive diagnostic testing and, in some cases, non-invasive prenatal testing. These tests bring beneficence through providing a higher diagnostic yield, often with lower risks of miscarriage than previously available testing, but also raise the question of harms related to an increase in uncertain and unknown results. Some parents-to-be report a desire to learn as much information as possible prenatally, and there may be beneficence in providing them with this information. However, the potential uncertainty these tests may create may raise anxiety and may complicate pregnancy decision-making for both patients and providers. This article reviews current prenatal technologies and the growing research on the clinical and ethical aspects of uncertainty as it relates to expanding prenatal testing options.     

Issues in counseling for Down syndrome

We studied the background information, concerns and specific queries of thirty-four families of children with Down syndrome. Majority of the parents were aware that their child has Down syndrome and has or will have mental retardation. However, most of the families were ignorant about the lack of curative treatment, chromosomal nature of the disorder and prenatal screening and testing options.     

Fetal counselling for surgical conditions

Foetal counselling is best achieved by a multidisciplinary team that can favourably influence the perinatal management of prenatally diagnosed anomalies and provide this information to prospective parents. Prenatal diagnosis has remarkably improved our understanding of surgically correctable congenital malformations. It has allowed us to influence the delivery of the baby, offer prenatal surgical management and discuss the options of termination of pregnancy for seriously handicapping or lethal conditions. Antenatal diagnosis has also defined an in utero mortality for some lesions such as diaphragmatic hernia and sacrococcygeal teratoma so that true outcomes can be measured. The limitation of in-utero diagnosis cannot be ignored. The aim of prenatal counselling is to provide information to prospective parents on foetal outcomes, possible interventions, appropriate setting, time and route of delivery and expected postnatal outcomes, immediate and long term.     

未通过听力初筛新生儿家长知信行状况及相关因素分析

目的了解家长对新生儿听力筛查的知晓度、认可度、心理状态以及依从性,进一步分析其影响因素。方法 2010年9月至2011年6月,采用问卷调查的形式,在北京妇产医院(三级医院)及海淀区妇幼保健院(二级医院)对未通过新生儿听力筛查的家长进行相关问卷的调查。结果共发放问卷680份,全部收回。有效问卷653份,有效率(96%)。数据分析显示,384例(58.8%)家长表示在入院宣教时了解到新生儿听力筛查,仅90例(13.7%)家长表示在产前宣教时即了解到。647例(99.1%)家长认为筛查有必要,但仅479例(73.4%)家长认可普筛中使用诱发型耳声发射(OAE)和自动听觉脑干诱发电位(AABR)联合筛查。517例(79.2%)家长对初筛结果未通过表示担心。对于降低假阳性转诊的三阶段筛查模式,464例(71.0%)家长表示愿意接受。经多因素Logistic回归分析显示,母亲学历和分娩医院级别越高者,家长的担心情绪越低(P<0.05);母亲学历高者,更容易接受三阶段筛查模式(P<0.05)。结论大部分家长对新生儿听力筛查持认可态度,但对其认知程度和依从性有待提高。母亲学历及分娩医院级别越高,家长对初筛未通过的担心情绪越低。加强宣教力度才能更好的推进听力筛查工作的进一步发展。