Alteration in anxiety‐related behaviors and reduction of serotonergic neurons in raphe nuclei in adult rats prenatally exposed to ethanol

It is known that the developing serotonergic system is one of the targets of ethanol teratogenicity. Because serotonin has multiple functions in both mature and immature brains, disturbance of the serotonergic system by ethanol exposure in utero can be cause of a wide range of psychiatric problems in adulthood. In the present study, we observed serotonergic neurons in the midbrain raphe nuclei and anxiety‐like behaviors which would be affected by an altered serotonergic system in adult rats prenatally exposed to ethanol. Pregnant rats were fed a liquid diet containing 2.5–5.0% (w/v) ethanol on gestational days 10–21. Their offspring were examined at 60–70 days of age. A significant decrease in the number of serotonergic cells in the midbrain raphe nuclei was shown in prenatally ethanol‐exposed offspring. In an open field test, they spent more time in a central area compared to controls. Also in an elevated plus maze test, prenatally ethanol‐exposed offspring spent more time on the open arms than controls. These behavioral results suggested that prenatally ethanol‐exposed rats were less sensitive to anxiety. However, 44% of prenatally ethanol‐exposed offspring exhibited freezing behavior on the open arms of the elevated plus maze, causing strong anxiety, compared with 0% in intact control and 12.5% in isocaloric sucrose‐fed control groups. These findings suggest that prenatal ethanol exposure decreases both susceptibility and resistance of anxiety. Insufficient serotonergic actions caused by reduced serotonergic neurons in the raphe nuclei might contribute to the alterations in anxiety‐related behaviors observed in our prenatally ethanol‐exposed rats.     

Commentary: ‘Unhealthy diet,’ nutrient status,and ADHD symptoms: a confounding role for environmental nitrous oxide exposure – reflections on Rijlaarsdam et al. (2016)

Rijlaarsdam et al. (2016) recently published their findings utilizing a longitudinal design showing that prenatal ‘unhealthy diet’ was positively associated with IGF2 DNA methylation at birth across both youth cohorts. However, only in the EOP youth was prenatal ‘unhealthy diet’ positively associated with ADHD symptoms presumably through IGF2 DNA hypermethylation. Rijlaarsdam et al.'s ( 2016 ) choice to assess high fat and sugar diet with the Food Frequency Questionnaire (FFQ) may offer some indication as to prenatal nutrient status, as the foods identified by the FFQ in their study are relatively low in free choline. It has been shown that gestational choline deficiency in rats leads to hypermethylation of IGF2. Consistent with the literature describing an association between air pollution and cognitive neurodevelopmental impairment, the author of this commentary has previously proposed through empirical investigation that chronic environmental exposure to the trace levels of the pervasive air pollutant, nitrous oxide (N₂O), may facilitate core features of neurodevelopmental disorders, like ADHD. Impaired acetylcholine synthesis in rats exposed to N₂O has been shown, with a 53% reduction in [1‐2H2,2‐2H2] choline. Low‐dose N₂O exposure is also thought to stimulate central release of opioid peptides, like dynorphin, which play a role in significantly increasing food intake behavior and/or modulating sucrose intake. Taken altogether, these studies present a strong confounder to the interpretation made by Rijlaarsdam et al. ( 2016 ) that prenatal ‘unhealthy diet’ may play a role in the onset of ADHD symptoms in youth with EOP conduct problems through induction of IGF2 DNA hypermethylation. While the ‘unhealthy diet’ may represent possible maternal nutrient deficiencies during gestation, it is also possible that exposure to air pollutants, particularly N₂O, may not only directly reduce fetal cholinergic status thereby enhancing IGF2 DNA hypermethylation but may also significantly modulate maternal food intake behaviors (i.e. sucrose).     

Glucose replacement to euglycemia causes hypoxia, acidosis, and decreased insulin secretion in fetal sheep with intrauterine growth restriction

Nutritional interventions for intrauterine growth restriction (IUGR) have raised concerns for fetal toxicity, the mechanisms of which are unknown. Most of these attempts did not aim to normalize fetal metabolic conditions. Therefore, we used a model of IUGR to determine whether normalization of fetal hypoglycemia for 2 wks would be tolerated and increase insulin concentrations and pancreatic beta-cell mass. IUGR fetuses received either a direct saline infusion (Sal, the control group) or a 30% dextrose infusion (Glu) to normalize glucose concentrations. Neither insulin concentrations (0.11 +/- 0.01 Glu vs. 0.10 +/- 0.01 ng/mL Sal) nor beta-cell mass (65.2 +/- 10.3 Glu vs. 74.7 +/- 18.4 mg Sal) changed. Glucose stimulated insulin secretion (GSIS) was lower in the Glu group. Glu fetuses became progressively more hypoxic: O2 content 1.4 +/- 0.5 Glu vs. 2.7 +/- 0.4 mM Sal, p < 0.05. Partial pressure of carbon dioxide (Paco2) (53.6 +/- 0.8 Glu vs. 51.6 +/- 0.8 Sal, p < 0.05) and lactate (7.74 +/- 3.82 Glu vs. 2.47 +/- 0.55 mM Sal, p < 0.0001) were greater and pH lower (7.275 +/- 0.071 Glu vs. 7.354 +/- 0.003 Sal, p < 0.01) in the Glu group. We conclude that correction of fetal hypoglycemia is not well tolerated and fails to increase insulin concentrations or beta-cell mass in IUGR fetuses.     

Urinary β2‐microglobulin and bronchopulmonary dysplasia: Trends in preterm infants

Background

The developmental process of bronchopulmonary dysplasia (BPD) is not identical between very preterm infants born small for gestational age (SGA) and those born appropriate for gestational age (AGA). In this study, we compared the pattern of the inflammatory response in infants of each group, by measuring urinary β2‐microglobulin (Uβ2M) as an alternative, concise, and less‐invasive biomarker.

Methods

Uβ2M and clinical details were examined at birth and at 4 weeks of age in 146 very preterm infants.

Results

Of the 57 infants diagnosed with BPD, 18 were SGA, and 39 were AGA. Uβ2M at birth was significantly lower in SGA BPD infants than in AGA BPD infants, but it increased with time. The prevalence of chorioamnionitis (CAM) was significantly lower in SGA BPD infants than in AGA BPD infants, while that of pregnancy‐induced hypertension was the opposite.

Conclusions

Exposure to prenatal factors other than CAM may sensitize fetal lungs to become vulnerable to postnatal inflammation in very preterm SGA infants with BPD.     

Prenatal diagnosis of Gaucher disease using next‐generation sequencing

In the prenatal diagnosis of Gaucher disease (GD), glucocerebrosidase (GBA) activity is measured with fetal cells, and gene analysis is performed when pathogenic mutations in GBA are identified in advance. Herein is described prenatal diagnosis in a family in which two children had GD. Although prior genetic information for this GD family was not obtained, next‐generation sequencing (NGS) was carried out for this family because immediate prenatal diagnosis was necessary. Three mutations were identified in this GD family. The father had one mutation in intron 3 (IVS2 + 1), the mother had two mutations in exons 3 (I[‐20]V) and 5 (M85T), and child 1 had all three of these mutations; child 3 had none of these mutations. On NGS the present fetus (child 3) was not a carrier of GD‐related mutations. NGS may facilitate early detection and treatment before disease onset.     

Morphological features and length measurements of fetal lateral ventricles at 16–25 weeks of gestation by magnetic resonance imaging

Normal growth of the lateral ventricles (LVs) was characterized three‐dimensionally using magnetic resonance imaging (MRI) data from 16 human fetuses at 16–25 weeks of gestation. The LV was differentiated into four primary regions, the anterior horn, central parts, posterior horn, and inferior horn, at 16 weeks of gestation. The LV changed shape mainly by elongation and narrowing, which corresponded to the external and internal growth of the surrounding cerebrum. Six length parameters measured in the LV correlated with biparietal diameter by simple regression analysis (R² range, 0.56–0.93), which may be valuable for establishing a standardized prenatal protocol to assess fetal well‐being and development across intrauterine periods. No correlation was found between biparietal diameter and LV volume (R² = 0.13).     

Congenital abnormalities in the offspring of pregnant women with type 1, type 2 and gestational diabetes mellitus: A population‐based case‐control study

To estimate the risk of structural birth defects (i.e. congenital abnormalities [CA]) in the offspring of pregnant women with type 1 (DM‐1), type 2 (DM‐2) and gestational diabetes mellitus (GDM) and to check the efficacy of recent specific care of diabetic pregnant women in the reduction of DM‐related CA. Comparison was made of the occurrence of medically recorded types of diabetes mellitus in pregnant women who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population‐based Hungarian Case‐Control Surveillance System of Congenital Abnormalities, 1980–1996. In the case group, which included 22 843 offspring, there were 79 (0.35%) pregnant women with DM‐1, 77 (0.34%) pregnant women with DM‐2 and 120 (0.53%) pregnant women with GDM. The control group comprised 38 151 newborns, and 88 (0.23%), 141 (0.37%) and 229 (0.60%) pregnant women with DM‐1, DM‐2 and GDM, respectively. The total rate of cases with CA was higher only in the DM‐1 group (adjusted OR with 95% CI: 1.5, 1.1–2.0) and within four specific types/groups: isolated renal a/dysgenesis, obstructive CA of the urinary tract, cardiovascular CA and multiple CA; namely, caudal dysplasia sequence. The risk of total CA was lower in the present study compared to the risk in previous studies and the DM‐1‐related spectrum of CA was also different. There was no higher risk of total CA in the offspring of pregnant women with DM‐2 and GDM. The certain part of maternal teratogenic effect of DM‐1 is preventable with appropriate periconceptional and prenatal care of diabetic women.     

Elastase, α1‐proteinase inhibitor,and interleukin‐8 in pre‐dialyzed and hemodialyzed patients with chronic kidney disease

Background: Neutrophil elastase in complex with α₁‐proteinase inhibitor (NE‐α₁PI) and interleukin (IL)‐8 may serve as indicators of neutrophil activation and inflammatory stage. The aim of the study was to evaluate NE‐α₁PI, α₁‐PI, and IL‐8 levels in the blood of patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) or conservatively treated (CT). The influence of a single HD session on the investigated parameters was also assessed. Methods: Blood samples were obtained from two groups of hemodialyzed patients (children/young adults [group HD1, n= 8] and adults [group HD2, n= 13]), as well as 13 CT patients and a group of healthy subjects. The proteins were measured using enzyme‐linked immunosorbent assay or radial immunodiffusion. Results: There were no significant differences in NE‐α₁PI, α₁‐PI, and IL‐8 concentrations between the HD1 and HD2 patients. The levels of NE‐α₁PI were considerably higher than normal in both groups of HD patients (before and after the HD session) and in the CT patients. Higher titers of NE‐α₁PI (P < 0.05) and α₁‐PI (P < 0.01) were obtained in the adults during the course of HD. Increased NE‐α₁PI was positively correlated with α₁‐PI. The serum concentration of IL‐8 was significantly higher in the HD2 patients before and after dialysis than in the controls. Conclusions: The data indicate that in CKD patients, neutrophils are highly activated both in the pre‐dialyzed period and on regular HD. Contact with the dialysis membrane during HD causes a significant increase in blood NE‐α₁PI and α₁‐PI in adults, but not in children/young adults. NE‐α₁PI seems to be a much better indicator of an inflammatory state in CKD patients than free α₁‐PI or IL‐8.     

Prenatal diagnosis of osteogenesis imperfecta type II by three‐dimensional computed tomography: The current state of fetal computed tomography

We report a case of osteogenesis imperfecta (OI) (OMIM166210) type II, in which a prenatal diagnosis was made by three‐dimensional computed tomography (3D‐CT). Subsequent molecular analysis revealed a recurrent, heterozygous mutation in COL1A2. Fetal CT is a powerful tool for visualizing the fetal skeleton and can provide a definitive diagnosis of fetal skeletal dysplasias; however, whether or not its employment for prenatal diagnosis is warranted in terms of fetal radiation risks remains controversial, both medically and ethically. Based on our experience, we review the current state of fetal CT for the diagnosis of skeletal dysplasias, with a discussion of the relevant literature.     

Dose‐related cerebellar abnormality in rats with prenatal exposure to X‐irradiation by magnetic resonance imaging volumetric analysis

Cerebellar abnormalities in 4‐week‐old rats with a single whole body X‐irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 were examined by magnetic resonance imaging (MRI) volumetry. A 3D T₂W‐MRI anatomical sequence with high‐spatial resolution at 11.7‐tesla was acquired from the fixed rat heads. By MRI volumetry, whole cerebellar volumes decreased dose‐dependently. Multiple linear regression analysis revealed that the cortical volume (standardized β = 0.901; P < 0.001) was a major explanatory variable for the whole cerebellar volume, whereas both volumes of the white matter and deep cerebellar nuclei also decreased depending on the X‐irradiation dose. The present MRI volumetric analysis revealed a dose‐related cerebellar cortical hypoplasia by prenatal exposure to X‐irradiation on E15.     

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.     

Re‐evaluation of lung to thorax transverse area ratio immediately before birth in predicting postnatal short‐term outcomes of fetuses with isolated left‐sided congenital diaphragmatic hernia: A single center analysis

We aimed to investigate whether the lung‐to‐thorax transverse area ratio (LTR) immediately before birth is of diagnostic value for the prediction of postnatal short‐term outcomes in cases of isolated left‐sided congenital diaphragmatic hernia (CDH). We retrospectively reviewed the cases of fetal isolated left‐sided CDH managed at our institution between April 2008 and July 2016. We divided the patients into two groups based on LTR immediately before birth, using a cut‐off value of 0.08. We compared the proportions of subjects within the two groups who survived until discharge using Fisher's exact test. Further, using Spearman's rank correlation, we assessed whether LTR was correlated with length of stay, duration of mechanical ventilation, and supplemental oxygen. Twenty‐nine subjects were included (five with LTR < 0.08, and 24 with LTR ≥ 0.08). The proportion of subjects surviving until discharge was 40% (2/5) for patients with LTR < 0.08, as compared with 96% (23/24) for those with LTR ≥ 0.08. LTR measured immediately before birth was negatively correlated with the postnatal length of stay (Spearman's rank correlation coefficient, rs = ?0.486), and the duration of supplemental oxygen (rs = ?0.537). Further, the duration of mechanical ventilation was longer in patients with a lower LTR value. LTR immediately before birth is useful for the prediction of postnatal short‐term outcomes in fetuses with isolated left‐sided CDH. In particular, patients with prenatal LTR value less than 0.08 are at increased risk of postnatal death.     

Long‐term cardiovascular reprogramming by short‐term perinatal exposure to nicotine's main metabolite cotinine

Aim

Gather ‘proof‐of‐concept’ evidence of the adverse developmental potential of cotinine (a seemingly benign biomarker of recent nicotine/tobacco smoke exposure).

Methods

Pregnant C57 mice drank nicotine‐ or cotinine‐laced water for 6 wks from conception (N_PRE = 2% saccharin + 100 μg nicotine/mL; C_PRE = 2% saccharin + 10 μg cotinine/mL) or 3 wks after birth (C_POST = 2% saccharin + 30 μg cotinine/mL). Controls drank 2% saccharin (CTRL). At 17 ± 1 weeks (male pups; CTRL n = 6; C_POST n = 6; C_PRE n = 8; N_PRE n = 9), we assessed (i) cardiovascular control during sleep; (ii) arterial reactivity ex vivo; and (iii) expression of genes involved in arterial constriction/dilation.

Results

Blood cotinine levels recapitulated those of passive smoker mothers’ infants. Pups exposed to cotinine exhibited (i) mild bradycardia – hypotension at rest (p < 0.001); (ii) attenuated (C_PRE, p < 0.0001) or reverse (C_POST; p < 0.0001) BP stress reactivity; (iii) adrenergic hypocontractility (p < 0.0003), low protein kinase C (p < 0.001) and elevated adrenergic receptor mRNA (p < 0.05; all drug‐treated arteries); and (iv) endothelial dysfunction (N_PRE only).

Conclusion

Cotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion into cotinine. Low‐level exposure to this metabolite may pose unrecognised perinatal risks. Adults must avoid inadvertently exposing a foetus or infant to cotinine as well as nicotine.     

Congenital heart disease in a Chinese hospital: pre‐ and postnatal detection,incidence, clinical characteristics and outcomes

Background: The pre‐ and postnatal detection rate, incidence, clinical characteristics and outcomes of congenital heart disease (CHD) have been studied in developed countries for many years, but rarely have large‐scale studies been reported in Chinese populations. The aim of the present study was to investigate the pre‐ and postnatal detection rates, incidence, clinical characteristics and outcomes of CHD in a Chinese hospital in order to improve the future screening and treatment of CHD. Methods: Fetuses without risk factors for CHD were screened using basic cardiac ultrasound examination (BCUE). Fetuses with suspected cardiac malformation revealed by BCUE and fetuses with risk factors were screened using extended cardiac ultrasound examination. Outcomes recorded from fetal, neonatal and postmortem records over 4 years (2006–2009) included: therapeutic termination of pregnancy, spontaneous abortions or stillbirths, deaths at birth or in the neonatal period (before 28 days of age), and rate of birth and clinical characteristics of newborns. Results: A total of 34 071 fetuses were screened for CHD during a period of 4 years, of which 173 fetuses were screened for CHD using BCUE and 301 fetuses were screened using extended cardiac ultrasound examination. The incidence of fetal CHD increased from 1.1% in 2006 to 2.4% in 2009 (P < 0.05), yielding an overall incidence of 1.5% (523/34 071). Of the fetuses with CHD, 48.2% (252/523) died before 28 days of age (including intra‐uterine death and termination of pregnancy), 51.8% (271/523) lived more than 28 days and the incidence of live newborns with CHD was 0.80% (271/34071). Conclusions: The prevalence of CHD was quite common in this Chinese hospital. Detailed profiles of CHD suggest that, while training programs in obstetric screening at this hospital were beneficial, prenatal intervention, treatment and care of fetal CHD were inefficient and should be strengthened in China.     

Effortful control mediates associations of fetal growth with hyperactivity and behavioural problems in 7‐ to 9‐year‐old children

Background: Inverse associations of fetal growth with behavioural problems in childhood have been repeatedly reported, suggesting long‐term effects of the prenatal developmental environment on behaviour later in life. However, no study so far has examined effects on temperament and potential developmental pathways. Temperamental traits may be particularly susceptible to neurodevelopmental alterations, and they are linked to behavioural problems. Therefore, we tested for associations of fetal growth with behavioural problems in children and tested if temperament mediated such effects. Methods: One hundred and thirty‐nine mother–child pairs were recruited in early pregnancy. Weight, head circumference and gestational age were measured at birth, and the mother reported on their child’s behavioural problems and temperament at age 7 to 9 years. Results: Birth weight and head circumference at birth adjusted for gestational age (i.e., fetal growth) were inversely associated with hyperactivity and total behavioural problems, and positively associated with the temperamental trait Effortful Control. Path analyses showed that Effortful Control mediated the effects of fetal growth on hyperactivity and total behavioural problems. Conclusions: Our results suggest that an adverse fetal environment is associated with behavioural problems in childhood, in particular in those children that show a low capacity for attentional and behavioural regulation. An adverse fetal environment might induce vulnerability for behavioural problems, or it might induce changes in temperament and behavioural problems independently, representing a common cause. Pathways are likely to be based on long‐lasting neurodevelopmental alterations due to prenatal adversity.     

Outcome of fetal echocardiography: A 17 year single‐institution experience in Japan

Background: The aim of this retrospective study was to evaluate the influence of prenatal diagnosis on perinatal outcomes of congenital heart disease (CHD) over a 17 year period at a single center. Methods: The perinatal outcome of CHD in 146 patients diagnosed on fetal echocardiography between 1994 and 2010 were reviewed. The characteristics of 193 neonatal inpatients with CHD treated at the authors’ department between 2001 and 2010 were also analyzed; among the inpatients, 61 were diagnosed before birth (prenatal group) and 132 were diagnosed after birth (postnatal group). Results: Among the 146 patients prenatally diagnosed with CHD, the prenatal mortality, including abortion and stillbirth, decreased from 1994 to 2010. Among the 193 neonatal inpatients, the prenatal group had lower gestational age and bodyweight than the postnatal group. Further, the prenatal group had lower blood pH at admission, but no patient in that group experienced ductal shock, although six patients in the postnatal group did. The average dose of prostaglandin E1 used in duct‐dependent CHD was significantly lower in the prenatal group than in the postnatal group (3.4 vs. 4.6 ng/kg per min; P = 0.015). Conclusions: Prenatal diagnosis of CHD enables planned labor, prevents ductal shock, and reduces prostaglandin E1 side‐effects and medical expenditure.     

Potentially effective method for fetal gender determination by noninvasive prenatal testing for X‐linked disease

Examination of maternal plasma cell‐free DNA (cfDNA) for noninvasive prenatal testing for fetal trisomy is a highly effective method for pregnant women at high risk. This can be also applied to fetal gender determination in female carriers of severe X‐linked disease. Polymerase chain reaction (PCR) analysis is a relatively simpler and less expensive method of detecting Y chromosome‐specific repeats (Y‐specific PCR; YSP), but is limited by the risk of false‐negative results. To address this, we have developed a combined strategy incorporating YSP and an estimation of the fetal DNA fraction. Multiplex PCR for 30 single nucleotide polymorphism (SNP) loci selected by high heterozygosity enables the robust detection of the fetal DNA fraction in cfDNA. The cfDNA sample is first subjected to YSP. When the YSP result is positive, the fetus is male and invasive testing for an X‐linked mutation is then required. When the YSP result is negative, the cfDNA sample is analyzed using multiplex PCR. If fetal DNA is then found in the cfDNA, invasive testing is not then required. If the multiplex PCR analysis of cfDNA is negative for fetal DNA, the fetal gender cannot be determined and invasive testing is still required. Our technique provides a potentially effective procedure that can help to avoid unnecessary invasive prenatal testing in some female carriers of severe X‐linked disease.     

Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study

The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth.     

Truncus Arteriosus: Diagnostic Accuracy,Outcomes, and Impact of Prenatal Diagnosis

Limited data exist on the impact of prenatal diagnosis and outcomes of fetal truncus arteriosus (TA). We sought to assess prenatal diagnostic accuracy and prenatal outcomes in fetuses with TA and compare postnatal outcomes in neonates with prenatally and postnatally diagnosed TA. Records were reviewed for patients diagnosed with TA in utero or at ≤60 days of life from 1992 to 2007. Forty-three (32%) of 136 TA patients had prenatal diagnosis. Five patients with TA were prenatally misdiagnosed, and 5 with other congenital heart diseases were misdiagnosed with TA prenatally. Of 28 fetuses diagnosed at <24 weeks gestation, 19 (68%) did not survive to birth because of spontaneous fetal death (n = 2) or because of elective termination (n = 17). Pregnancy termination was not more likely for fetuses with extracardiac anomalies. Of 19 live-born patients with correct prenatal diagnosis of TA, 2 (11%) died before surgery, and 4 (24%) died in the early postoperative period. All patients who died presurgically had been diagnosed prenatally. Overall, early postoperative mortality was 10%. Prenatal diagnosis of TA remains challenging and is associated with a high rate of elective termination. Fetal diagnosis was associated with younger age at repair but was not associated with improved neonatal survival.