Prenatal detection and outcome of major heart defects in a country with universal screening

ABSTRACT

Objective

To evaluate the Danish prenatal screening program for major fetal congenital heart defects (mCHD), focusing on incidence, detection rates (DRs), pregnancy outcomes and postnatal mortality.

Methods

This was a 5‐year nationwide cohort study conducted from January 2018 to December 2022 in Denmark. We included pregnancies suspected of and/or with a confirmed mCHD and children with a confirmed mCHD, and excluded those who were not screened, false‐positive cases and those who emigrated before delivery. The main outcome was the prenatal DR of mCHD. Secondary outcomes were rate of termination of pregnancy, liveborn incidence of mCHD, gestational age at delivery, neonatal surgery rate and postnatal mortality.

Results

Data from a total of 645 pregnancies and children with mCHD were retrieved from local databases and 602 were included in the final analysis. The prenatal DR of mCHD was 82.6% (497/602), with one of the highest DRs observed for univentricular heart (99.4% (159/160)) and the lowest DR for total anomalous pulmonary venous return (7.7% (1/13)). Termination of pregnancy occurred in 43.4% (261/602) of cases, with 52.5% (261/497) of prenatally detected cases opting for termination. The liveborn incidence of mCHD was 0.11% (1.1 per 1000 births), and the median gestational age at delivery was 39 + 2 weeks. Surgery was performed in 92.0% (300/326) of liveborn children, primarily within the first month after birth. The postnatal follow‐up time was between 8 months and 5 years, with a mortality rate of 9.8% (32/326), of which 50.0% occurred neonatally without surgery.

Conclusions

This study highlights increased prenatal DRs and a declining liveborn incidence of mCHD in Denmark, underscoring the efficacy of the national screening program and centralized care. Furthermore, the vast majority of patients were treated surgically, and the mortality rate was low. The declining liveborn incidence of mCHD should be monitored and potential causes explored further. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

INTRODUCTION

Major congenital heart defects (mCHD) are some of the most common serious malformations and affect approximately 0.2% of all pregnancies ¹ , ² . mCHD is usually defined as a serious congenital heart defect (CHD) requiring surgery or catheter intervention within the first year after birth. Children with mCHD are at increased risk of both morbidity and mortality. Previous studies have shown that prenatal detection may reduce these risks by enabling clinicians to plan and provide the best possible care when affected babies are born, and hence improve the overall outcome for these children ³ , ⁴ , ⁵ , ⁶ , ⁷ . Moreover, prenatal detection provides the possibility of thorough evaluation of the fetus, including genetic testing, which gives the parents extensive information regarding possible outcomes. This is important not only for those who continue the pregnancy, but also for those who eventually opt for termination of pregnancy (TOP).

The prenatal detection rate (DR) of mCHD has improved over the past decades, probably owing to training, better equipment and a systematic approach. The highest DRs are seen in tertiary centers, but only a few studies have investigated the performance of a national screening program, with results ranging from 42% to 83% ⁸ , ⁹ , ¹⁰ , ¹¹ . In Denmark, nationwide public tax‐funded prenatal ultrasound screening for all pregnant residents was implemented in 2004 by the Danish Health Authority. Lytzen et al. ² showed an increase in the prenatal DR of CHD in Denmark, from 4.5% in 1996 to 71% in 2013, with the implementation of national prenatal screening being the most significant contributing factor. In 2016, the Danish Health Authority centralized pediatric cardiothoracic surgery and catheter intervention at Rigshospitalet, Copenhagen, and at the same time a nationwide interdisciplinary collaboration on fetal mCHD was established between the three highly specialized centers in Denmark.

In this study, we aimed to evaluate the Danish screening program for mCHD, including the prenatal DR, liveborn incidence, pregnancy outcome and postnatal mortality, following the centralization of pediatric cardiothoracic surgery and the establishment of a nationwide interdisciplinary collaboration on fetal mCHD.

METHODS

This was a nationwide Danish cohort study, which included all children with a confirmed mCHD born between 1 January 2018 and 31 December 2022, as well as all fetuses, whether terminated or liveborn, with suspected and/or confirmed mCHD and a due date also between 1 January 2018 and 31 December 2022. Exclusion criteria were as follows: (1) not screened in Denmark; (2) cases with coarctation of the aorta (CoA) that did not require surgery postnatally; and (3) emigration before delivery (missing outcome). The study was registered in The Capital Region, Denmark (P 2023‐19) and permission to access patient files was granted by The Center of Health, The Capital Region, Denmark (R‐23002300).

In Denmark, all pregnant women are offered two prenatal ultrasound examinations, one in the first trimester and one in the second trimester, which was introduced in 2004 by the Danish Health Authority. The first‐trimester ultrasound scan determines the viability of the pregnancy, number of fetuses and gestational age of the pregnancy, and provides the possibility of screening for aneuploidies. Second‐trimester ultrasound is performed at approximately 20 weeks' gestation to screen for malformations and assess fetal growth. All ultrasound screenings are performed by trained and certified sonographers and take place in one of the 17 obstetric departments that perform prenatal screening. The images from screening are evaluated by a doctor only if there is suspicion of an anomaly. The second‐trimester screening for CHD includes a mandatory evaluation of the four‐chamber view, the outflow tract views and the three‐vessel‐and‐trachea view ¹² . More than 95% of the pregnant residents in Denmark participate in the screening program ¹³ . When mCHD is detected prenatally, the parents are offered chromosomal microarray (CMA) testing and in recent years sometimes whole‐exome sequencing and whole‐genome sequencing, to check for underlying genetic disease in the fetus. In 2016, all pediatric cardiothoracic surgery was centralized to Rigshospitalet, Copenhagen, Denmark, and a national collaboration on fetal mCHD was established. The collaboration consists of specialists in fetal medicine, pediatric cardiologists and cardiologists from the three highly specialized centers in Denmark (Odense University Hospital, Odense; Aarhus University Hospital, Aarhus; and Copenhagen University Hospital Rigshospitalet, Copenhagen), which represents three of the five regions in Denmark, as well as fetal medicine specialists from the two remaining regions. All cases of suspected mCHD are referred to one of the highly specialized centers for evaluation and counseling by experts. Once every other week, national video conferences are held to discuss diagnosis, prognosis and plans for individual cases. All continuing pregnancies with an expected need for surgery within 4 weeks after delivery or complex cases are referred for delivery at Rigshospitalet, to where the women are transferred prior to their due date.

The mCHD diagnoses that required or were expected to require intervention prior to 1 year of age included: aortic stenosis (AS) and pulmonary stenosis (PS) requiring surgery including balloon dilation, atrioventricular septal defect (AVSD), CoA and/or hypoplastic aortic arch requiring surgery within the first year after birth, congenitally corrected transposition of the great arteries (ccTGA), double‐outlet right ventricle (DORV), Ebstein's anomaly, hypoplastic right heart syndrome, hypoplastic left heart syndrome, interrupted aortic arch (IAA), pulmonary atresia (PA), tetralogy of Fallot (ToF), total anomalous pulmonary venous return (TAPVR), transposition of the great arteries (TGA) and truncus arteriosus. We included each patient once, hence, only the most serious diagnosis is listed in cases in which more than one diagnosis was present. In this study, hypoplastic left heart syndrome and hypoplastic right heart syndrome were combined and defined as a univentricular heart (UVH). In Denmark, routine screening for TAPVR is not performed; however, in this study we chose to include it owing to its severity. Cases with minor CHD, such as ventricular septal defects, were not included even if surgery was performed within the first year after birth.

In Denmark, all residents are assigned a unique social security number at birth or upon immigration, allowing the follow‐up of patients from birth until death. All children who had undergone cardiac surgery (including catheter‐based interventions) were identified by surgical lists at Rigshospitalet. Cases diagnosed prenatally were retrieved from regional Astraia databases (Astraia GmbH, Munich, Germany), which, besides the ultrasound images from all prenatal exams, also contain results from other prenatal exams, treatment plans and fetal diagnoses. The Astraia software is used nationwide for all prenatal ultrasound screening and exams in the public healthcare system in Denmark. All patient files for both mothers and children were reviewed, and information retrieved (Sundhedsplatformen (Epic Systems Corp., Madison, WI, USA) and EPJ (Systematic A/S, Aarhus, Denmark)). In all cases, we retrieved data on due date and prenatal detection. For cases with a prenatal diagnosis, we also collected information on gestational age at time of diagnosis, detailed prenatal echocardiographic findings and extracardiac anomalies. Associated anomalies included all other extracardiac malformations and pathogenic genetic aberrations. In cases without prenatal detection, age at postnatal mCHD detection was recorded, as well as the mode of detection. For all cases, information on all genetic testing performed (prenatally, postnatally or postmortem) was retrieved as well as outcome. For children who underwent surgery, age at the time of surgery was noted. When relevant, autopsy reports were assessed. All cases were followed up until at least 1 year after birth. All data were collected in five identical, regional Research Electronic Data Capture (REDCap) software databases (https://projectredcap.org/) that were then combined into one.

The main outcome was the prenatal DR of mCHD. Secondary outcomes were the rate of TOP, liveborn incidence of mCHD, gestational age at delivery, neonatal surgery rate and postnatal mortality.

Statistical analysis

Statistical analysis was performed using Stata version 18 (Stata Corp., College Station, TX, USA). Results for prenatal mCHD DR and TOP rates are given as percentages. The DR was calculated both including TAPVR and without TAPVR. Gestational age at the time of diagnosis, delivery or surgery is given as median (interquartile range (IQR)). Comparison across years was performed using the chi‐square test and comparison of the gestational age at delivery between pregnancies with prenatally detected mCHD and those which went undetected was performed using the Mann–Whitney U‐test; a significance level of 0.05 was chosen.

RESULTS

Prenatal detection

In total, 645 cases were retrieved from the databases, of which 43 were excluded. Thus, 602 mCHD cases were included in the final analysis. Among the excluded cases, 18 were observed prenatally for possible CoA, 13 cases were not screened prenatally or had emigrated prior to birth, 11 cases were from Greenland or the Faroe Islands, and one case was suspected to have a CHD but the pregnancy was terminated at gestational week 12 owing to a genetic disorder. The overall prenatal DR of mCHD was 82.6% (497/602), with a median gestational age at diagnosis of 20 + 3 weeks (143 (IQR, 136–146) days) (Table 1). When TAPVR was excluded, the prenatal DR of mCHD was 84.2% (496/589). There was no difference in DRs across the 5 years (P = 0.7). The distribution of diagnoses and type‐specific DRs are listed in Table 1. One of the highest DRs was observed in pregnancies with UVH, with only one case missed prenatally during the study period (99.4% (159/160)). Conversely, the lowest DR of 7.7% (1/13) was observed for TAPVR.

Table 1.

Types of major congenital heart defect (mCHD), prenatal detection rates and gestational age (GA) at diagnosis in 602 cases of mCHD

mCHD	Cases	Prenatal detection	GA at diagnosis (days)
Aortic stenosis	22 (3.7)	16/22 (72.7)	145 (142–154)
AVSD	51 (8.5)	37/51 (72.5)	142 (117–147)
CoA	82 (13.6)	48/82 (58.5)	145 (141–149)
ccTGA	11 (1.8)	10/11 (90.9)	144 (142–146)
DORV	35 (5.8)	33/35 (94.3)	144 (125–149)
Ebstein's anomaly	13 (2.2)	12/13 (92.3)	142 (138–209)
UVH	160 (26.6)	159/160 (99.4)	141 (115–145)
Interrupted aortic arch	6 (1.0)	6/6 (100.0)	141 (137–145)
Pulmonary atresia	14 (2.3)	13/14 (92.9)	143 (142–146)
Pulmonary stenosis	16 (2.7)	13/16 (81.3)	146 (144–152)
ToF	86 (14.3)	72/86 (83.7)	143 (139–147)
TAPVR	13 (2.2)	1/13 (7.7)	235
TGA	80 (13.3)	68/80 (85.0)	143 (141–146)
Truncus arteriosus	12 (2.0)	8/12 (66.7)	145 (137–150)
Complex first‐trimester mCHD	1 (0.2)	1/1 (100.0)	88
Total	602 (100.0)	497/602 (82.6)	143 (136–146)

Data are given as n (%), n/N (%) or median (interquartile range). AVSD, atrioventricular septal defect; ccTGA, congenitally corrected transposition of the great arteries; CoA, coarctation of the aorta; DORV, double‐outlet right ventricle; TAPVR, total anomalous pulmonary venous return; TGA, transposition of the great arteries; ToF, tetralogy of Fallot; UVH, univentricular heart.

Termination of pregnancy

The overall proportion of TOP was 43.4% (261/602) (Table 2). Genetic testing was performed in 490/602 (81.4%) fetuses/children, of which 94/490 (19.2%) had pathogenic genetic aberrations. Therefore, the conservative estimate of genetic aberrations was 15.6% (94/602) in our cohort. Among cases with prenatal mCHD detection, a total of 52.5% (261/497) chose to terminate the pregnancy, of which 36.0% (94/261) had associated anomalies. In cases of prenatal detection and genetic aberrations detected prenatally, 72.2% (57/79) chose TOP, similar to those with prenatal detection and extracardiac malformations detected prenatally (75.3% (64/85)). The highest proportion of termination in the prenatally detected cases was seen in pregnancies with fetal UVH (88.1%), IAA (100.0%) and truncus arteriosus (87.5%). Conversely, only 16.2% of pregnancies with fetal TGA were terminated, of which 36.4% had associated anomalies. A total of 75.5% (197/261) of all TOP cases had either UVH or another type of mCHD with associated anomalies. One pregnancy had a complex mCHD detected in the first trimester with multiple extracardiac anomalies and was terminated before a specific diagnosis was made. Among all cases of TOP, 50.6% (132/261) had an autopsy performed in which the mCHD diagnosis was confirmed. A total of 15 (2.5%) cases died in utero (three cases of AVSD and two cases each of CoA, DORV, Ebstein's anomaly, UVH, PA and ToF), of which eight (53.3%) fetuses had pathogenic genetic aberrations.

Table 2.

Termination of pregnancy (TOP) rates in 602 cases of major congenital heart defect (mCHD), according to whether defect was detected prenatally and whether there were associated anomalies

mCHD	Cases	Overall TOP	TOP with prenatal mCHD detection	TOP with mCHD and associated anomalies	TOP with isolated mCHD
Aortic stenosis	22	2/22 (9.1)	2/16 (12.5)	0/2 (0)	2/20 (10.0)
AVSD	51	20/51 (39.2)	20/37 (54.1)	14/26 (53.8)	6/25 (24.0)
CoA	82	14/82 (17.1)	14/48 (29.2)	4/12 (33.3)	10/70 (14.3)
ccTGA	11	6/11 (54.5)	6/10 (60.0)	1/1 (100.0)	5/10 (50.0)
DORV	35	13/35 (37.1)	13/33 (39.4)	8/11 (72.7)	5/24 (20.8)
Ebstein's anomaly	13	4/13 (30.8)	4/12 (33.3)	0/1 (0)	4/12 (33.3)
UVH	160	140/160 (87.5)	140/159 (88.1)	37/42 (88.1)	103/118 (87.3)
Interrupted aortic arch	6	6/6 (100.0)	6/6 (100.0)	4/4 (100.0)	2/2 (100.0)*
Pulmonary atresia	14	7/14 (50.0)	7/13 (53.8)	1/2 (50.0)	6/12 (50.0)
Pulmonary stenosis	16	4/16 (25.0)	4/13 (30.8)	2/4 (50.0)	2/12 (16.7)
ToF	86	26/86 (30.2)	26/72 (36.1)	14/25 (56.0)	12/61 (19.7)
TAPVR	13	0/13 (0)	0/1 (0)	0/3 (0)	0/10 (0)
TGA	80	11/80 (13.8)	11/68 (16.2)	4/4 (100.0)	7/76 (9.2)
Truncus arteriosus	12	7/12 (58.3)	7/8 (87.5)	4/6 (66.7)	3/6 (50.0)
Complex first‐trimester mCHD	1	1/1 (100.0)	1/1 (100.0)	1/1 (100.0)	—
Total	602	261/602 (43.4)	261/497 (52.5)	94/144 (65.3)	167/458 (36.5)

Data are given as n or n/N (%).

^*Complicated cases of interrupted aortic arch with other cardiac anomalies and uncertainty whether biventricular repair would be possible. AVSD, atrioventricular septal defect; ccTGA, congenitally corrected transposition of the great arteries; CoA, coarctation of the aorta; DORV, double‐outlet right ventricle; TAPVR, total anomalous pulmonary venous return; TGA, transposition of the great arteries; ToF, tetralogy of Fallot; UVH, univentricular heart.

Liveborn incidence and postnatal outcomes

Postnatal outcomes are shown in Table 3. In total, 326 children were liveborn. In the same period, 305 483 children were born in Denmark; hence, the liveborn incidence of mCHD was 1.1 per 1000 births among included cases (which would be unchanged if the 13 children with mCHD excluded owing to lack of prenatal screening were included). The median gestational age at delivery was 39 + 2 weeks (275 (IQR, 267–278) days). Children with Ebstein's anomaly (n = 7) were born at a median gestational age of 251 (IQR, 241–269) days. The median gestational age at delivery differed between pregnancies with prenatally detected mCHD (273 (IQR, 265–277) days) and those undetected prenatally (277 (IQR, 270–284) days) (P < 0.001).

Table 3.

Postnatal outcomes of 326 liveborn children with major congenital heart defect (mCHD)

					Mortality (n/N (%))
mCHD	Liveborn children (n)	Incidence (per 10 000 live births)	GA at delivery (days)	Age at first surgery (days)	Overall*	Prior to surgery†
Aortic stenosis	20	0.65	270 (249–277)	24 (4–71)	6/20 (30.0)	3/6 (50.0)
AVSD	28	0.92	272 (266–279)	93 (68–143)	0/28 (0)	—
CoA	66	2.16	275 (266–283)	10 (6–31)	3/66 (4.5)	0/3 (0)
ccTGA	5	0.16	281 (274–282)	—	1/5 (20.0)	1/1 (100.0)
DORV	20	0.65	273 (265–276)	54 (7–162)	0/20 (0.0)	—
Ebstein's anomaly	7	0.23	251 (241–269)	9 (2–14)	3/7 (42.9)	2/3 (66.7)
UVH	18	0.59	275 (270–277)	7 (5–12)	7/18 (38.9)	3/7 (42.9)
Pulmonary atresia	5	0.16	271 (262–276)	7 (5–86)	2/5 (40.0)	1/2 (50.0)
Pulmonary stenosis	12	0.39	272 (263–274)	3 (2–114)	0/12 (0)	—
ToF	58	1.90	277 (267–279)	162 (64–184)	1/58 (1.7)	0/1 (0)
TAPVR	13	0.43	278 (272–283)	10 (4–51)	3/13 (23.1)	1/3 (33.3)
TGA	69	2.26	275 (269–277)	6 (4–8)	5/69 (7.2)	5/5 (100.0)‡
Truncus arteriosus	5	0.16	281 (262–288)	12 (11–24)	1/5 (20.0)	0/1 (0)
Total	326	10.66	275 (267–278)	12 (6–93)	32/326 (9.8)	16/32 (50.0)

Data are given as median (interquartile range), unless stated otherwise.

^*Percentage out of liveborn children.

^†Deaths prior to surgery/deaths overall.

^‡Three of five children were born prematurely (gestational age (GA) < 34 + 2 weeks) and one child born at term had prenatally undetected transposition of the great arteries (TGA). AVSD, atrioventricular septal defect; ccTGA, congenitally corrected transposition of the great arteries; CoA, coarctation of the aorta; DORV, double‐outlet right ventricle; TAPVR, total anomalous pulmonary venous return; ToF, tetralogy of Fallot; UVH, univentricular heart.

A total of 300 (92.0%) of the children underwent surgery, with 179 (59.7%) operated on within the first 28 days after birth. The median age at first surgery was 12 (IQR, 6–93) days. Thirty‐two (9.8%) liveborn infants died postnatally at a median age of 14 (range, 2–122) days, including 19 (59.4%) who died within 28 days after birth. Follow‐up ranged from 8 months to 5 years. Half of the postnatal deaths occurred before surgery. The postsurgery mortality rate was 5.3% (16/300). Postnatal mortality varied according to diagnosis, with the highest rates (approximately 40.0%) observed in cases with UVH, PA or Ebstein's anomaly. Among children with TGA, five (7.2%) died postnatally before surgery. Of these, three were detected prenatally (4.4% of prenatally detected TGA cases (3/68)) and two were not (16.7% of prenatally undetected TGA cases (2/12)). Two of the prenatally diagnosed TGA cases who died were born prematurely.

DISCUSSION

This large, nationwide study presents comprehensive data on mCHD in Denmark across a 5‐year period following the centralization of pediatric cardiothoracic surgery and establishment of a nationwide multidisciplinary collaboration on fetal mCHD. The overall liveborn incidence of mCHD was 1.1/1000, with a prenatal DR of 82.6% and a postnatal mortality rate of 9.8%. This is the first nationwide study to report data on incidence, prenatal DR, pregnancy outcome and postnatal mortality in both fetuses and children with mCHD.

A large retrospective, register‐based study by Lytzen et al. ² reported data on incidence, DR and terminations of mCHD in Denmark between 1996 and 2013. The liveborn incidence of mCHD declined from 0.15% in 2013 to 0.11% between 2018 and 2022, while the prenatal DR increased from 71% to 82.6%. As only proportions were reported in the study by Lytzen et al. ² , direct comparisons are not possible. Lytzen et al. ² evaluated the Danish screening program from 1996, when no general screening was offered, until 2013. Universal screening was implemented by the National Board of Health in 2004 and includes first‐ and second‐trimester ultrasound screening. The initial guideline for the second‐trimester scan included the four‐chamber view of the heart. In 2013, the guideline was updated to also include the three‐vessel‐and‐trachea view and the outflow tract views. At the same time, the Danish Society for Fetal Medicine offered courses and training in cardiac screening. This improved not only the technical skills but also the awareness of sonographers. All children born with mCHD were scheduled to undergo surgery at either Copenhagen University Hospital Rigshospitalet or Aarhus University Hospital up until 2016, and fetuses with prenatally detected mCHD were referred to one of those hospitals for delivery. In 2016, pediatric cardiothoracic surgery was centralized to Rigshospitalet owing to a decline in the number of operations per year, with the aim of strengthening surgical expertise by concentrating procedures at a single center rather than maintaining two centers. There was, until 2016, no standardized prenatal collaboration on these cases, but, along with the centralization, a large, standardized collaboration, including fetal medicine specialists, fetal and pediatric cardiologists and patient coordinators was established. Besides biweekly conferences, a report from the previous year is presented at the yearly meeting for members of the Danish Society for Fetal Medicine that includes both doctors and sonographers. This has probably contributed to an increased focus on fetal CHD. Along with the DR of mCHD, the median gestational age at detection of 20 + 3 weeks (143 (IQR, 136–146) days) is important to mention, as it highlights the high quality of the screening program. The Danish DR is similar to that found by Tomek et al. ⁹ in their nationwide study of CHD in the Czech Republic, in which the DR plateaued at approximately 82% in the last years of the study period. There are discrepancies between the types of mCHD detected prenatally in the Czech Republic and in Denmark. For instance, Denmark reports higher DRs for TGA, CoA and IAA compared with the Czech Republic (85% vs 70%, 59% vs 50% and 100% vs 60%, respectively). Conversely, the Czech Republic reports higher prenatal DRs for truncus arteriosus and AVSD compared with Denmark (> 90% vs 67% and > 90% vs 73%, respectively). These differences may reflect variations in focus and training between the two countries. By identifying and addressing these differences, it may be possible to achieve higher DRs.

There was a small decline in the liveborn incidence of mCHD in Denmark, from 0.15% in 2013 to 0.11% between 2018 and 2022. Lytzen et al. ² did not include AS and PS as well as TAPVR in their study, hence, the incidence has probably declined even more. The underlying reasons for the decline have not been investigated in the current study, but could possibly be related to CMA as standard genetic testing in pregnancies with a high first‐trimester risk for trisomies or anomalies rather than karyotyping ¹⁴ . Moreover, the etiology of CHD is multifactorial and includes consideration of maternal health and teratogens. Consequently, possible explanations for the declining incidence could be healthier pregnant women with better blood glucose control in diabetics, less smoking and alcohol consumption and better micronutrient status because of supplementation ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ .

We found that 52.5% of cases with a mCHD detected prenatally opted for TOP, which is 5% points lower than has previously been reported in Denmark ² . This decline could be due to the shift to CMA as the primary genetic test, probably increasing parental reassurance that the mCHD is isolated, but possibly also because of better surgical outcomes. The overall TOP rate of 43.4% was remarkably similar to that found in the Czech study (43%) ⁹ . In this study, we found that 19.2% (94/490) of cases had pathogenic genetic aberrations. In a Danish study from 2008 to 2018, the prevalence of chromosomal aberrations was 13% ¹⁴ . The higher prevalence in the current study can be attributed to the increasing use of whole exome and whole genome sequencing analysis. However, it is still lower than the prevalence reported in other studies, which may be because of the universal first‐trimester screening with a very high uptake in Denmark ¹⁹ , ²⁰ . The proportion with associated anomalies was similar to that found in the Czech study ⁹ . We found that 14.3% of pregnancies with isolated CoA resulted in TOP. However, we excluded 18 cases in which CoA was only suspected prenatally. Diagnosing CoA prenatally can be challenging, as it often presents subtly, such as with mild ventricular imbalance. As a result, some cases are monitored during pregnancy despite having a low risk of postnatal CoA. These cases are frequently delivered at other highly specialized centers, not necessarily Rigshospitalet. Upon review, all cases of TOP involving isolated CoA were clearly severe, with significant left ventricular involvement or additional cardiac anomalies, except for one case that involved other obstetric complications.

The median gestational age at delivery was ≥ 39 weeks, not only in pregnancies with prenatally detected mCHD but also in those diagnosed postnatally. This is comparable to the findings of a Canadian study ²¹ , and is an improvement compared with previously reported Danish data ²² . Delivery at term has been shown to improve the outcome in children with CHD ²³ , ²⁴ . The postnatal mortality rate of < 10% in this study included presurgical patients who chose comfort care (50.0%) and is relatively low compared with other studies. A previous Danish study, conducted between 1996 and 2013, found a mortality rate of 20% within the first year after birth ²² . A national study from Sweden found a mortality rate of approximately 19% ²⁵ . However, this study included patients from 1980 to 2017, hence the data may not reflect the current situation. A more recent EUROCAT study found a mortality rate among children with mCHD of 12% ²⁶ , and a Norwegian study found a mortality rate of 10% ²⁷ .

This study has several notable strengths. It includes nationwide data in a country with universal healthcare. Detailed data were collected comprehensively in patient files that held information on all cases of mCHD. Owing to the centralization of pediatric cardiothoracic surgery and interventions to one hospital, identification of all children who had undergone cardiac surgery or catheter‐based interventions was simple. A limitation of this study is the relatively short study period of 5 years, which makes changes over time difficult to investigate. However, owing to a large nationwide Danish study performed on almost the same diagnoses from 1996 to 2013, comparisons were possible. Moreover, we may have missed some postnatal cases of undiagnosed mCHD that died prior to diagnosis.

In conclusion, this 5‐year nationwide Danish study highlights increased prenatal DRs, a declining liveborn incidence of mCHD and a low postnatal mortality rate, underscoring the efficacy of the national screening program and centralized pediatric cardiothoracic care. The declining incidence of mCHD should be monitored and potential causes explored further.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.