Time Of Prenatal Diagnosis Research Articles

Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland

Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, β2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, β2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and β2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. The combination of thrombocytes, β2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

Optimizing prenatal diagnosis and referral of classic bladder exstrophy: Lessons from a single-institution experience

Classic bladder exstrophy (CBE) is a malformation of the genitourinary system that occurs due to failure of abdominal wall closure. Unlike other malformations of similar incidence, prenatal diagnosis of CBE relies on suggested, rather than formal, diagnostic criteria. This report describes prenatal diagnosis of CBE in the largest single-institutional cohort to date and delineates key sonographic findings and protocols for specialist referral. A single-institutional database was reviewed for CBE patients born since 2000. Data on screening ultrasound use, gestational age at ultrasound, and abnormal findings were extracted. Where possible, time of prenatal diagnosis (pre- or postnatal and gestational age), ultrasound findings and other imaging data, specialist referral, institution of birth and closure, and outcome of primary closure attempt were compared. Of 557 patients born with CBE between 2000 and 2022, 284 met inclusion criteria and complete data were available for 280 (229 born domestically and 51 born internationally) who were included for analysis. Abnormal sonography suggestive of CBE was present for 48% (n=134) of patients, for whom absent bladder was the most common abnormal finding (76% [102/134]). Of domestic patients, 46% (n=106) were diagnosed prenatally at a median gestational age of 22 weeks (inter-quartile range [IQR]: 20-24), and 14% (n=32) underwent confirmatory fetal magnetic resonance imaging. Of domestic patients with abnormal prenatal findings, 75% (n=80/106) consulted with maternal-fetal medicine and 58% (n=62/106) consulted with pediatric urology. On univariate analysis, prenatal diagnosis was positively associated with primary repair at Association for the Bladder Exstrophy Community-recognized centers of excellence (54% vs. 38%, p=0.02) and negatively associated with osteotomy at primary closure (41% vs 59%, p=0.003) but not success of primary closure (74% vs. 82%, p=0.07). Rates of prenatal diagnosis in this cohort were similar to previous reports of smaller cohorts. Diagnosis allows for comprehensive pre- and postnatal follow-up with a pediatric urologist, with implications on birth planning and decisions on termination of pregnancy. Because of the previously-reported association between exstrophy and invitro fertilization, these pregnancies should undergo detailed sonography. Any nonvisualization of the fetal bladder should prompt a detailed exam, and any finding characteristic of bladder exstrophy warrants referral to pediatric urology. Although CBE is a rare disorder, it is underdiagnosed during pregnancy. Sonographers and obstetricians should be aware of characteristic findings and best practices following diagnosis. Early referral to pediatric urology and maternal-fetal medicine is important for counseling and postnatal planning.

Challenges faced in management of a neonate with ambiguous genitalia

A neonate born with atypical sex development presents with challenges to the clinician as well as parents. There are challenges in diagnosis, gender assignment, initiating and adherence to treatment, follow up, counseling and prenatal diagnosis and counselling. There are uncertainties in the time of prenatal diagnosis as well. The objective of this case report is to highlight the challenges faced by a parent of a neonate with ambiguous genitalia.

Risk factors analysis for clinical symptoms of prenatally diagnosed choledochal cysts: a retrospective study

BackgroundThis study aimed to screen the impact factors for clinical symptoms of prenatally diagnosed choledochal cysts (CDCs), to warn about the occurrence of clinical symptoms and the timing of surgery.MethodsMedical records of patients with prenatally diagnosed CDCs admitted to our hospital from April 2013 to April 2018 were retrospectively reviewed. Fetal hilar or abdominal cysts were found by prenatal ultrasonogram. All patients underwent laparoscopic cyst excision and hepaticojejunostomy in our center. Univariate analysis and multivariate logistic regression analysis were performed to screen the factors related to clinical symptoms intimately.ResultsTwo hundred eighteen cases were included. One hundred thirty-four patients (134/218, 61.5%) presented clinical symptoms before surgery. The results of univariate analysis showed that patients with clinical symptoms had earlier time of prenatal diagnosis (P = 0.002), higher values of GGT, TBIL, DBIL (P < 0.001, P < 0.001, P < 0.001, respectively) and larger maximum diameter of cyst before surgery (P = 0.012). Multivariate logistic regression analysis suggested that the time of prenatal diagnosis (P = 0.001, OR = 0.898, 95% CI: 0.845 ~ 0.955) and the GGT value within one week of life (P = 0.028, OR = 1.002, 95% CI: 1.000 ~ 1.003) were independent influencing factors for symptoms.ConclusionsFor children with prenatally diagnosed CDCs, approximately 2/3 patients presented noticeable clinical symptoms before surgery. The time of prenatal diagnosis and the GGT value within 1 week of life were independent impact factors for the occurrence of clinical symptoms.

Early Detection of Isolated Severe Congenital Heart Defects Is Associated with a Lower Threshold to Terminate the Pregnancy

Introduction: Early detection of isolated severe congenital heart defects (CHDs) allows extra time for chromosomal analysis and informed decision making, resulting in improved perinatal management and patient satisfaction. Therefore, the aim of this study was to assess the value of an additional first-trimester screening scan compared to only a second-trimester scan in fetuses diagnosed with isolated severe CHDs. Prenatal detection rate, time of prenatal diagnosis, and pregnancy outcome were evaluated in the Netherlands after implementation of a national screening program. Materials and Methods: We performed a retrospective geographical cohort study and included 264 pre- and postnatally diagnosed isolated severe CHD cases between January 1, 2007, and December 31, 2015, in the Amsterdam region. Severe CHD was defined as potentially life threatening if intervention within the first year of life was required. Two groups were defined: those with a first- and second-trimester anomaly scan (group 1) and those with a second-trimester anomaly scan only (group 2). A first-trimester scan was defined as a scan between 11 + 0 and 13 + 6 weeks of gestation. Results: Overall, the prenatal detection rate for isolated severe CHDs was 65%; 63% were detected before 24 weeks of gestation (97% of all prenatally detected CHDs). Prenatal detection rate was 70.2% in the group with a first- and second-trimester scan (group 1) and 58% in the group with a second-trimester scan only (group 2) (p < 0.05). Median gestational age at detection was 19 + 6 (interquartile range [IQR] 15 + 4 – 20 + 5) in group 1 versus 20 + 3 (IQR: 20 + 0 – 21 + 1) in group 2 (p < 0.001). In group 1, 22% were diagnosed before 18 weeks of gestation. Termination of pregnancy rate in group 1 and group 2 were 48% and 27%, respectively (p < 0.01). Median gestational age at termination did not differ between the two groups. Conclusion: Prenatal detection rate of isolated severe CHDs and termination of pregnancy rate was higher in the group with both a first- and second-trimester scan. We found no differences between timing of terminations. The additional time after diagnosis allows for additional genetic testing and optimal counseling of expectant parents regarding prognosis and perinatal management, so that well-informed decisions can be made.

“It becomes your whole life”—Exploring experiences of reciprocal translocation carriers and their partners

AbstractReciprocal translocation carriers are often diagnosed when they are experiencing difficulties conceiving or after a pregnancy affected by an unbalanced set of chromosomes inherited from the balanced carrier parent. Having a reciprocal translocation is not uncommon; carriers can benefit from reproductive options to achieve a healthy, chromosomally balanced, pregnancy. The aim of this study was to explore the lived experience of carriers and their partners. We conducted 13 semi‐structured telephone interviews. Participants were recruited through Victorian Clinical Genetics Services and interviews took place between May and September 2020. Interview transcripts were analyzed using thematic analysis. Reciprocal translocation carriers and their partners described long term emotional and reproductive impacts, with carrier status identified at the time of prenatal diagnosis having marked emotional consequences. Couples facing reproductive challenges found the diagnosis created uncertainty for their future. When considering a pregnancy, couples worried about experiencing a miscarriage; during pregnancy, there was a reluctance to have an invasive diagnostic procedure due to fearing the risk of losing an unaffected pregnancy. Adaptation to their new reality involved having access to accurate information, peer support and maintaining hope. Couples valued having the option to know the carrier status of their children. The complex impacts of carrying a reciprocal translocation highlight the importance of access to specialist genetic counseling services to ensure couples are supported in understanding the implications of their translocation

Prenatal diagnosis at different gestational times and clinical features of choledochal cysts: a single tertiary center report.

This study aimed to evaluate the effect of prenatal diagnosis at different gestational times on the clinical features of patients with choledochal cysts (CDCs). Medical records of patients with prenatally diagnosed CDCs admitted to our hospital (April 2013-April 2018) were retrospectively reviewed. The clinical characteristics and pathological CDC features were analyzed. Two hundred eighteen cases were included. Patients were divided into two groups. Group 1 and group 2 had a prenatal diagnosis at ≤ 27weeks of gestation (second trimester of gestation, n = 157) and > 27weeks (third trimester of gestation, n = 61), respectively. The incidence of jaundice and the TBIL, IBIL and GGT levels were higher in Group 1 (P = 0.021, P = 0.029, P = 0.042, P = 0.007, respectively). The maximum cyst diameter at the time of surgery was larger in Group 1 (P = 0.015). An association study showed that the time of prenatal diagnosis was negatively correlated with the maximum cyst diameter both postnatally (r = -0.223, P = 0.001) and at the time of surgery (r = -0.268, P < 0.001). Unlike patients diagnosed at a late prenatal age, patients diagnosed at an early prenatal age tend to present clinical symptoms (jaundice, manifested as high indirect bilirubin), hepatic function damage, and large cysts at the time of surgery.

Utilization of a Prenatal Palliative Care Consultation Pathway for Congenital Heart Disease.

Over 4 decades, short- and long-term survival for children with congenital heart disease (CHD) has significantly increased. Those with complex CHD have a 1-year mortality rate of approximately 25%. Prenatal access to palliative care ensures a comprehensive approach to the infant's physical, emotional, spiritual, and psychosocial well-being and offers enhanced support for parents and families while providing an interprofessional approach to care. Pediatric cardiac provider attitudes, knowledge, patterns of prenatal palliative care, and consultation for fetuses with complex heart disease to guide increased and appropriate prenatal consultation were explored for a quality improvement project completed at a single institution. A retrospective cardiac database review identified that 21.5% of maternal patients seen prenatally and carrying a fetus with complex CHD would have qualified for prenatal palliative care consultation. To increase prenatal palliative care consultation, a pathway for referral was developed. A pre-evaluation of pediatric cardiac provider attitudes regarding palliative care was measured. Survey data informed the intervention phase of prenatal palliative care educational material development, which was presented to pediatric cardiac providers. The number of prenatal palliative care consults was tracked. A postintervention survey completed by pediatric cardiac providers showed increased understanding and utilization of palliative care for comfort and support and not just reserved for death preparation. Greater than 93% agreed or strongly agreed that they gained a better understanding of appropriate use of palliative/supportive care. As pediatric cardiac providers become more knowledgeable about early integration of palliative care, parents and infants will benefit greatly from referrals and initiation of palliative care at the time of prenatal diagnosis.

Prenatal sonographic findings in a cohort of foetuses with a confirmed 22q11.2 microdeletion at a single Chinese Tertiary Centre

The aim of this study was to present prenatal ultrasound findings, molecular testing results and pregnancy outcomes of cases with 22q11.2 deletion (del22q11.2) diagnosed prenatally. A total of 76 foetuses were included. All cases were diagnosed by using chromosomal microarray analysis. Data on prenatal diagnosis, ultrasound findings, pregnancy outcomes and inheritance of del22q11.2 were reviewed. Congenital heart defects (CHDs) were the most common indications (47/76, 61.8%) for prenatal testing and were isolated in 52.6% (40/76). The constitution of CHDs comprised predominantly of conotruncal defects (61.7%; 29/47). Other cardiac anomalies were encountered in 38.3% (18/47) of cases. Extracardiac findings, including unilateral multicystic dysplastic kidney, clubfoot, increased nuchal translucency, intrauterine growth retardation and polyhydramnios, were found in 31.6% (24/76) of cases, and were combined with CHDs in 7 cases. Twelve cases had normal sonographic scans at the time of prenatal diagnosis. Foetal CHDs, especially conotruncal defects, are the most predictive association with del22q11.2. The information about del22q11.2 should also be part of the contents in comprehensive pre-test counselling even for those who are referred for diagnostic testing with foetal extracardiac findings. Impact statement What is already known on this subject? 22q11.2 deletion (del22q11.2) is the most common microdeletion syndrome in humans. At present, the main indications for prenatal testing for del22q11.2 are pregnancies of abnormal sonographic findings, especially foetal congenital heart defects. What do the results of this study add? Many extracardiac malformations, including some lethal or mildly non-specific ones, could be associated with foetal del22q11.2. There were also del22q11.2 foetuses had normal sonographic scans at the time of prenatal diagnosis. What are the implications of these findings for clinical practice and/or further research? The information about del22q11.2 should also be part of the contents in comprehensive pre-test counselling even for those who are referred for diagnostic testing with indications other than foetal cardiac anomalies.

Ультразвуковые признаки пренатально диагностированных кист яичников: что важно для прогноза

Aim: to assess the outcomes of prenatally diagnosed ovarian cysts and to identify ultrasound features associated with the prognosis of surgical treatment Patients and Methods: this retrospective study evaluated 59 fetal ovarian cysts diagnosed during ultrasound screening in the prenatal ultrasound center. The following parameters were reviewed: parity, maternal age, time of prenatal diagnosis, ultrasound cystic features and structure, and the outcomes of fetal ovarian cysts. Results: fetal ovarian cysts were detected during pregnancy in women with a median age of 30.6 years (17–42 years), 40.7% of them were primipara. A median gestational age at the date of prenatal cyst diagnosis was 33.5 (21.2–38) weeks of pregnancy. In 25.4% of cases the ovarian cysts had complex echotexture, and in 33.2% of cases a cyst diameter was ≥40 mm. In 32.2% of cases, the cysts were located at some distance from the bladder; 39% of the cysts were fully or partially visualized in the abdomen. The spontaneous cyst resolution by the time of delivery was reported in 37.3% of cases, including 40% of complex cysts. After birth, 35.6% of ovarian cysts disappeared and 20% of complex cysts demonstrated regression. Also, the regression occurred in 26.3% of cysts ≥ 40 mm. Overall, spontaneous resolution was reported for 60% of complex cysts, 42.1% of cysts ≥40 mm, 52.6% of cysts distinct from the bladder and 56.5% of cysts located in the abdomen. Postnatal surgery was performed in 27.1% of the newborn girls. The likelihood of surgical treatment was higher in the newborns with prenatal cysts ≥ 40 mm comparing to cysts &lt; 40 mm (odds ratio (OR), 7.78 (95% confidence interval (CI), 2.12–28.53)) and cysts located in the abdomen comparing to cysts located in the fetal pelvis (OR, 16.25 (95% CI, 3.84–68.82)). No correlation was found between ultrasound features of ovarian cysts and torsion Conclusion: the ultrasound features of prenatally diagnosed ovarian cysts which are important for predicting a higher risk of postnatal surgical procedures include the cyst diameter (≥ 40 mm) and the location (especially in the abdomen). These factors should be taken into consideration for choosing a maternity hospital and prenatal consulting of parents. KEYWORDS: fetal ovarian cyst, prenatal diagnosis, ultrasound features, outcome, prognosis. FOR CITATION: Tihonenko I.V. Ultrasound features of prenatally diagnosed ovarian cysts: what is important for the prognosis. Russian Journal of Woman and Child Health. 2022;5(4):287–291 (in Russ.). DOI: 10.32364/2618-8430-2022-5-4-287-291.

Redefining the Relationship: Palliative Care in Critical Perinatal and Neonatal Cardiac Patients.

Patients with perinatal and neonatal congenital heart disease (CHD) represent a unique population with higher morbidity and mortality compared to other neonatal patient groups. Despite an overall improvement in long-term survival, they often require chronic care of complex medical illnesses after hospital discharge, placing a high burden of responsibility on their families. Emerging literature reflects high levels of depression and anxiety which plague parents, starting as early as the time of prenatal diagnosis. In the current era of the global COVID-19 pandemic, the additive nature of significant stressors for both medical providers and families can have catastrophic consequences on communication and coping. Due to the high prognostic uncertainty of CHD, data suggests that early pediatric palliative care (PC) consultation may improve shared decision-making, communication, and coping, while minimizing unnecessary medical interventions. However, barriers to pediatric PC persist largely due to the perception that PC consultation is indicative of “giving up.” This review serves to highlight the evolving landscape of perinatal and neonatal CHD and the need for earlier and longitudinal integration of pediatric PC in order to provide high-quality, interdisciplinary care to patients and families.

956 Pregnancies complicated by any fetal anomaly are at increased risk for maternal morbidity and mortality

Limited information exists regarding the impact of any fetal anomaly on maternal outcomes. We sought to determine if expectant management of a pregnancy complicated by fetal anomalies was an independent risk factor for severe maternal morbidity or mortality. This was a retrospective cohort study of the NICHD Consortium for Safe Labor (CSL) database. The exposure of interest was pregnancies complicated by any fetal anomaly. The outcome analyzed was a composite outcome of death, intensive care admission, pulmonary embolism, severe pre-eclampsia, eclampsia, or hysterectomy. Cases with missing information were excluded. After an unadjusted analysis, propensity scoring was utilized. Covariates were demographic factors, prior obstetric outcomes, and pre-existing medical comorbidities which would be available to clinicians at the time of second trimester fetal anatomy ultrasound assessment. Cases and controls were matched with preference given to exact matches. Sampling was done without replacement, and greedy match tolerance was within a probability of 0.1. Multivariable analysis was performed to adjust for propensity score. Of the 228,562 deliveries in the CSL database, 179,452 met inclusion criteria. 12,797(7.1%) were complicated by fetal anomalies, and 4510 (2.5%) we're complicated by the composite outcome. Fetal anomalies increase the relative risk of severe morbidity or mortality (RR 2.1 p<0.0001, 95%CI 1.94-2.28, NNH 39) in unadjusted analysis. Propensity scoring led to 7623 matched cases and controls, and pregnancies complicated by fetal anomalies increased the odds of the composite outcome (aOR 1.73 p<0.0001, 95%CI 1.44-2.07). Pregnancies complicated by any fetal anomaly nearly double the patient's underlying risk of severe maternal morbidity or mortality. This information should be utilized in shared decision-making at the time of prenatal diagnosis. Future studies should attempt to stratify patient risk based on the type and severity of the complicating fetal anomaly.

The Trend in Timing of Prenatal Diagnosis for Thalassemia at a Chinese Tertiary Obstetric Center

Thalassemia is a great health burden in mainland China. Carrier screening and prenatal diagnosis (PND) are essential for its prevention. The aim of this study was to describe the trend in the timing of PND for thalassemia in at-risk families in mainland China. All women who were at-risk for thalassemia and received PND at a mainland Chinese tertiary obstetric center between 2011 and 2019 were included. Information required for the survey was obtained from the database of the institute. In total, 4045 women underwent PND for thalassemia, including 1720 for β-thalassemia (β-thal) and 2325 for α-thalassemia (α-thal). The median gestational age for the PND procedure was 13 weeks. The number of PNDs performed increased year by year over this period. For both β-thal and α-thal, the proportion of women undergoing early PND also increased along with the time span. A total of 428 cases was diagnosed prenatally to be affected with β-thal major (β-TM) and 769 were affected with Hb Bart’s disease. Most of the β-TM pregnancies and all of the Hb Bart’s disease pregnancies were terminated. With the implementation of effective screening measures, births of affected infants have been dramatically avoided, and early PND has become the main approach, thus allowing the possibility of obtaining results at an earlier stage of pregnancy.

Congenital Cardiothoracic Surgeons and Palliative Care: A National Survey Study.

The majority of children with advanced heart disease in the inpatient setting die in an intensive care unit under 1 year of age following multiple interventions. While pediatric cardiology and palliative care provider attitudes have been described, little is known about pediatric cardiothoracic surgeon attitudes toward palliative care in children with advanced heart disease. To describe perspectives of pediatric cardiothoracic surgeons regarding palliative care in pediatric heart disease. Cross-sectional web-based national survey. Of the 220 surgeons who were e-mailed the survey, 36 opened the survey and 5 did not meet inclusion criteria (n = 31). Median years of practice was 23.5 (range: 12-41 years), and 87.1% were male. Almost all (90%) reported that they had experience consulting palliative care. While 68% felt palliative care consultation was initiated at the appropriate time, 29% felt it occurred too late. When asked the appropriate timing for palliative care consultation in hypoplastic left heart syndrome, 45% selected "at time of prenatal diagnosis" and 30% selected "when surgical and transcatheter options have been exhausted." Common barriers to palliative care involvement included the perception of "giving up" (40%) and concern for undermining parental hope (36%). While a majority of pediatric cardiothoracic surgeons are familiar with palliative care, there is variation in perception of appropriate timing of consultation. Significant barriers to consultation still exist, including concern that parents will think they are "giving" up, undermining parental hope, and influence of palliative care on the medical care team's approach.

Pediatric Cardiothoracic Surgeons and Palliative Care: A National Survey Study (S851)

1.Outline pediatric cardiothoracic surgeons’ understanding and use of pediatric palliative care.2.Describe the barriers perceived by pediatric cardiothoracic surgeons to palliative care consultation. Among children with heart disease who die in the hospital, the majority occur within the first year of life in an intensive care setting. Discrepancies in understanding of prognosis and perceptions of suffering between parents and physicians caring for children with heart disease have been identified. While pediatric cardiology and palliative care (PC) provider attitudes towards PC have been described, no studies have assessed the perspectives of pediatric cardiothoracic surgeons (CTS). •Evaluate pediatric CTS understanding and use of PC.•Describe barriers perceived by pediatric CTS to PC consultation. A survey was distributed electronically to pediatric CTS in the United States. Subjects were excluded if they did not have a pediatric component to their practice. The survey consisted of 22 primarily closed-ended questions with multiple choice answers. Of the 220 CTS who were mailed the survey, 36 opened the survey and 5 did not meet inclusion criteria (n=31). Median years of practice was 23.5 and 87.1% were male. Almost all (90%) reported that they had experience consulting PC. While 68% felt PC consultation was initiated at the appropriate time, 29% felt it occurred too late. When asked the appropriate timing for PC consultation in patients with hypoplastic left heart syndrome, 45% selected “at time of prenatal diagnosis” and 30% selected “when surgical and transcatheter options have been exhausted.” Common barriers to PC involvement included the perception of “giving up” (40%) and concern for undermining parental hope (36%). While a majority of pediatric CTS are familiar with PC, there is variation in perception of appropriate timing of consultation and significant barriers to consultation still exist.

Fast-Track Strategy for the Prevention of Hb Bart’s Hydrops Fetalis Syndrome

We propose a fast-track strategy [direct blood DNA analysis using a quantitative real-time polymerase chain reaction (PCR) technique] for the early risk detection and prenatal diagnosis of α(0)-thalassemia (SEA and Thai deletion). Blood DNA samples were obtained from a volunteer group of 1235 ANC couples. They were assessed using quantitative real-time PCR to detect carriers of α(0)-thalassemia (SEA and Thai deletion). At-risk couples were identified, and further prenatal diagnosis by amniocentesis was implemented. Fetal DNA was isolated from the amniotic cells and characterized by quantitative real-time PCR to detect the α(0)-thalassemia mutation, which was reconfirmed using the droplet digital PCR method. Fifteen at-risk couples were identified. The timing of prenatal diagnosis was appropriate for all couples and four of the fetuses were diagnosed with Bart’s hydrops fetalis. The results were compatible with those calculated using the Hardy-Weinberg equation for a recessively inherited single gene disorder. The conclusion was that the fast-track strategy could shorten screening policy timelines, promoting early risk detection for couples and early prenatal diagnosis. The fast-track strategy might be beneficial for the prevention of hemoglobin Bart’s hydrops fetalis syndrome.

Fetal intracranial immature teratoma: presentation of a case and a systematic review of the literature

Objectives: To describe a case diagnosed with intracranial teratoma in week 32 of gestation, as well as review of the literature in order to discern the appropriate treatment method and general prognosis of this anomaly.Methods: A literature search was performed on the prenatal diagnosis of congenital intracranial teratomas in MEDLINE, EMBASE, Cochrane library data bases. Evaluated in this review are parameters such as time of prenatal diagnosis, associated pathology, size of tumors, method of terminating pregnancy, perinatal outcome and histological study of the tumor.Results: A total of 49 cases were found, of which 12 were finished gestation, 28 cesarean section was performed and only nine had vaginal delivery. All died in the neonatal period except in three cases with intrauterine death after diagnosis.Conclusion: As the incidence of intracranial immature teratomas is very low and the prognosis is poor, their prenatal diagnosis and obstetric management present a great challenge for the planning of a follow-up and treatment of the disease in accordance with the preferences of the parents.

Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis

Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy. We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection. We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination. In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm(3), and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, P= .001, and P= .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive valuefor symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively. Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling.

Donor catch-up growth after laser surgery for twin–twin transfusion syndrome

ObjectiveTo assess fetal growth after laser surgery for TTTS at the time of prenatal diagnosis, birth, and at 2years of age. Design/methodsGrowth data were collected from surviving children treated between 2007 and 2010 as part of a study to assess neurodevelopment at 24months (±6weeks) corrected age. Fetal weights were obtained via ultrasound using Hadlock's formula at the time of preoperative assessment for laser surgery. Birth weights were recorded by the staff at the delivering institutions. Weights at 2years corrected age were recorded at the time of neurodevelopmental testing. Weights were converted into percentiles according to standard growth curves. Growth restriction was defined as <10th percentile for given age. Multilevel latent growth curve models in Mplus (twins nested in families) examined weight change over time as a function of donor status, and repeated measures ANOVA was utilized to assess in donor–recipient weight discordance over time for twin pairs. Results99 of 206 children (56 of 130 families) were studied. There were no differences between enrolled and non-enrolled patients in donor/recipient status and survival rates, fetal demise, intrauterine growth restriction, Quintero stage, and gestational age of surgery or delivery. 48.5% were donors. The median fetal, birth, and 2-year weights for all twins were 288g, 1.9kg, and 11.8kg, respectively, and the overall prevalence of growth restriction was 28%, 22%, and 3%, respectively. Growth restriction rates at prenatal diagnosis were 56% in donors vs. 2% in recipients (OR=64.3, p<0.001); at birth, 35% vs. 10% (OR=5.0, p<0.01); and at 2years, 6% vs. 0%. Donors showed significant gains in weight percentile (B=13.1, p<0.001) and a significant decrease in growth restriction rates over time (B=−1.6, p<0.001). Weight discordance between donor and recipient pairs also significantly decreased over time (linear F(1,42)=54.34, p<0.001). ConclusionsAfter laser surgery for TTTS, donor twins exhibit significant catch-up growth by two years of age.

Trends in timing of prenatal diagnosis and abortion for fetal chromosomal abnormalities

Our objective was to evaluate changes in the timing of prenatal diagnosis and abortion for chromosomal abnormalities over the past 10 years. This retrospective review identified singleton pregnancies with fetal chromosomal abnormalities that were diagnosed from 2005-2014 and included Down syndrome, Trisomy 18, and Trisomy 13. The study period was divided into 3 intervals: 2005-2006; 2007-2011; and 2012-2014. Gestational ages at prenatal diagnosis and abortion were compared over these intervals. The 213 cases included 142 cases of Down syndrome (66.7%), 47 cases of Trisomy 18 (22.1%), and 24 cases of Trisomy 13 (11.3%). Two hundred one women (94.4%) chose to undergo abortion. The median gestational ages at prenatal diagnosis and abortion for Trisomy 18 or 13 were 12 weeks (interquartile range, 12-13 weeks) and 13 weeks (interquartile range, 12-15.5 weeks) and did not change over the study period. In contrast, in pregnancies with Down syndrome, the median gestational age at prenatal diagnosis (16, 13, and 12 weeks; P < .001) and abortion (17, 14, and 13 weeks; P < .001) both decreased significantly over the study intervals. In Down syndrome pregnancies, the proportion of women who underwent chorionic villus sampling significantly increased over the 3 study intervals (36%, 63%, and 86%; P < .001). Since 2005, the gestational ages at prenatal diagnosis and abortion for Down syndrome have declined significantly. These changes are likely attributable to improvements in early screening that leads to higher rates of chorionic villus sampling.