Abstract
Background
We aimed to quantify the risk of developmental difficulties at school entry among children with congenital heart defects (CHD), considering CHD severity. Elevated risks are established for children with complex CHD, but little is known about other CHD categories.
Methods
In this South Australian whole‐of‐population data linkage study, standardized assessments from the Australian Early Development Census were linked with perinatal records (2002–2014) and birth defects. Among singleton children, we compared the prevalence of developmental difficulties (special needs or developmental vulnerability) for subgroups with CHD (severe surgical, severe nonsurgical, non‐severe), and for unaffected peers, and calculated adjusted relative risks. Children with diagnosed syndromes or chromosomal disorders were excluded.
Results
Of 67 990 singleton children, 656 had a CHD diagnosis (9.6 per 1000 live births). Children with CHD had higher levels of special needs (13% [95% CI, 11–16]) or at least 1 developmental vulnerability (26% [95% CI, 23–29]) compared with children with no CHD (5.5% [95% CI, 5.3–5.7]; 21.6% [95% CI, 21.3–21.9]). The risk of developmental difficulties was elevated among children with complex CHD (ie, severe surgical, adjusted relative risk, 1.42 [95% CI, 1.20–1.68]) but also among severe nonsurgical CHD (adjusted relative risk, 1.52 [95% CI, 0.82–2.83]) and non‐severe CHD (adjusted relative risk, 1.35 [95% CI, 1.18–1.55]), although for severe nonsurgical CHD the CI includes the null.
Conclusions
Developmental difficulties were prevalent among children with CHD irrespective of the need for early surgical intervention. The basis for this broad effect requires further study. Monitoring of development is warranted among all children with CHD.
Keywords: birth defects, congenital heart defect, developmental vulnerability, early development, special needs
Subject Categories: Epidemiology, Pediatrics
Nonstandard Abbreviations and Acronyms
- AEDC
Australian Early Development Census
Clinical Perspective.
What Is New?
Developmental difficulties at school entry were prevalent among children with noncomplex forms of congenital heart defects, as well as those who likely required surgery in the first year of life.
What Are the Clinical Implications?
Early screening and follow‐up for developmental delay should be considered for all children with congenital heart defects, irrespective of the severity, so that children and families can access and benefit from early intervention. The pathogenesis of this broad association warrants further study.
Congenital heart defects (CHD) are the most common type of birth defect worldwide with a prevalence of 9.4 per 1000 live births (2010–2017), 1 with similar estimates in Australia (9.5 to 11.9 per 1000 births). 2 CHD comprises structural abnormalities of the heart or the great vessels present at or before birth. A quarter to a third of children with CHD require surgery or catheterization within the first year of life to survive. 2 , 3 Improvements in detection, intervention and pediatric health care have led to a substantial increase in the survival of children with CHD in recent decades. 3 , 4 For example, in some high‐income countries such as Sweden, 97% of children with CHD born after 2000 are expected to reach adulthood. 4 Despite the increase in survival rates, there is still a large disparity in the health and developmental outcomes of children with and without CHD. 3
Poor developmental outcomes have been studied extensively in the subgroup of children with CHD that requires surgery for survival in the first year of life. 5 , 6 This is frequently referred to as “complex” or “critical” CHD. These children are now established to be at risk of poor developmental outcomes, with follow‐up screening and early intervention recommended. 3 , 7 Less is known about the developmental outcomes of children with noncomplex CHD, although a recent study has suggested that these children are also at risk of poor developmental outcomes. 8
Poor developmental outcomes in children with CHD may be due to a range of factors, not limited to complex CHD, although surgery and postoperative factors can bring specific risks to those with complex CHD. 3 , 9 More generally, altered heart physiology can result in hypoxia or decreased oxygen and nutrient supply to the developing fetal and neonatal brain. 3 , 10 Lower cerebral tissue oxygenation has been observed in fetuses with complex CHD, 11 , 12 linked to alterations in brain development. 13 Structural brain abnormalities have also been found in studies of fetuses with noncomplex CHD. 14 Families where children have CHD may also experience substantial psychosocial and economic demands that could exacerbate the risk of poor developmental outcomes. 15
In this study, we use whole‐of‐population linked administrative data from South Australia to assess the prevalence of developmental difficulties at school entry among children with CHD. We use the classification system of Botto et al. to identify “severe” and “non‐severe” CHD based on the type of defects. 1 , 16 , 17 , 18 We further separate the severe group by the likelihood of requiring surgical intervention in the first year of life to approximate the category of complex CHD. We compare outcomes for these subgroups as well as for those children without CHD.
Methods
Data Availability Statement
The researchers do not have permission to share the data as they were provided specifically for the scope of the research and approved by the ethics committees. Requests to access the data sets should be directed to the data custodians.
Data Sources and Study Population
In this population‐based cohort study, we used de‐identified, administrative, linked data for the state of South Australia. Individual‐level data from the South Australian Birth Defects Register, South Australian Perinatal Statistics Collection, and the Australian Early Development Census (AEDC) were linked by SA NT DataLink, the independent agency for South Australia and the Northern Territory, and de‐identified data were provided to researchers. 19 A low false linkage rate of 0.4% has been reported in the South Australia and the Northern Territory data linkage systems. 20
The South Australian government maintains a registry concerning all births occurring from 20 weeks' gestation (or >400 g). 21 Almost all births in the state occur in hospital, where staff complete a standard form recording sociodemographic details about the mother, her antenatal care, details of previous pregnancies, any pregnancy complications, and birth. Separately, all birth defects detected from birth up to the child's fifth birthday are notified to the South Australian Birth Defects Register. 22
Exposure (Congenital Heart Defects)
Information on CHD was extracted from the birth defects register using the International Classification of Diseases, Ninth Revision (ICD‐9) and British Paediatric Association codes 74500 to 74799. 22 Children with syndromes or chromosomal abnormality are established to have a high risk of developmental vulnerability, and we wished to make it clear that such cases are not driving our findings. Therefore, children with diagnosed syndromes or chromosomal abnormality (eg, Down syndrome/Trisomy 21, Turner syndrome, 22q11.2 deletion syndrome etc) were excluded. However, CHD accompanied by other defects (such as urogenital, musculoskeletal, gastrointestinal defects etc) was included.
We classified CHD into severe and non‐severe CHD based on the hierarchical classification of CHD phenotypes developed by Botto et al. (Table S5). 1 , 16 , 17 , 18 We used this classification system because it has been developed for epidemiological research and is based on the nature of the defect (whereas we do not know whether or not the newborn was cyanotic or whether or not surgery was undertaken). We further categorized the severe cases as severe surgical CHD and severe nonsurgical CHD. The severe surgical CHD were those likely to require surgery in the first year of life (also referred to as complex or critical CHD in other studies). 3 , 23 , 24 We have provided a figure showing the classification of subgroups of CHD used in our analyses (Figure S1).
Our focus is singleton children. For completeness, findings for multiple births are provided in Tables S1 and S3. All children with diagnosed syndromes and chromosomal disorders were excluded from analyses (ie, from numerator and denominator). (Information for these children is provided in Table S4).
Outcome (Special Needs and Developmental Vulnerability at School Entry)
Information on children's development at school entry was sourced from the AEDC, which commenced in 2009 and is undertaken every 3 years (2009/10, 2012, 2015, 2018; see Figure 1). The AEDC is based on standardized reporting by teachers of children's development in their first year of full‐time schooling (mean age 5 years and 7 months) across government, private, and Catholic schools in Australia. 25
Figure 1. Flowchart of the study population.
*AEDC data are collected from all children in their first year of full‐time schooling in Australia, but only every 3 years. AEDC indicates Australian Early Development Census; and CHD, congenital heart defects.
Children may be classified as having special needs, based on an existing medical diagnosis, defined as “a child requiring special assistance because of chronic medical, physical or intellectually disabling conditions (eg, autism, cerebral palsy, Down syndrome), based on a medical diagnosis or medical diagnoses” (p. 82). 25 We do not have further developmental measures for the children who were classified as having special needs. That is because after the first round of AEDC assessments in 2009, the development of children with special needs has not been assessed in detail, with initial research (2009 data) showing almost all of these children were vulnerable in ≥1 developmental domains. 26
Under the AEDC program, all children are assessed in their first year of full‐time schooling using a standardized tool called the Australian version of the Early Development Instrument, 27 , 28 developed in Canada by Janus and Offord. 29 The instrument has ~100 questions covering the 5 key developmental domains of childhood: physical health and well‐being, social competence, emotional maturity, language and cognitive skills (school‐based), communication skills, and general knowledge. Children who score in the lowest 10% of the national population (ie, in the lowest decile) are classified as developmentally vulnerable for a specific domain. We combined the 2 outcomes of special needs and developmental vulnerability to highlight the extent of overall developmental difficulties for children with and without CHD.
Confounders
A confounding factor, by definition, must be associated with the occurrence of CHD, independently influence child development, and not be on the causal pathway connecting CHD with developmental outcomes. Maternal age and socioeconomic disadvantage meet these criteria; hence we adjusted for them in multivariable analyses. 25 , 30
In singleton children, a number of pregnancy‐related factors that are associated with poor developmental outcomes cannot be considered independent of CHD and thus do not meet the definition of a confounding variable. This is because it is likely that factors underlying poor placental and fetal development (eg, genetic factors or maternal diabetes) contribute to CHD and also to prematurity or low birth weight, thereby to poor developmental outcomes.
It is not our intention to try to partition such factors, but for completeness we present aspects of prevalence stratified by prematurity.
Information on confounders was sourced from the South Australian Perinatal Statistics Collection. Maternal age was grouped into 4 bands (<25, 25–29, 30–34, ≥35 years), as this grouping is widely used in perinatal epidemiology to reflect the risk profiles of women in different age groups. 21 The Index of Relative Socioeconomic Advantage and Disadvantage (quintile 1, most disadvantaged, to quintile 5, most advantaged) is an area‐level socioeconomic measure, developed by the Australian Bureau of Statistics using a wide range of information including education, income, employment, language, housing etc. 31 The Index of Relative Socioeconomic Advantage and Disadvantage is attributed to an individual based on postcode of residence.
Missing Data
As shown in the AEDC report for 2021, 25 there were 75 119 children from South Australia with AEDC assessments across 2009, 2012, 2015, and 2018. We received AEDC data only for children born in South Australia (n=70 658) and thus we estimate that 6% of the school entrants in each round were born elsewhere. 25 After removing duplicate records (n=82) and all children with diagnosed syndromes and chromosomal disorders (n=315), we had 70 260 children (singleton n=67 990) with linked perinatal and AEDC data (Figure 1).
About 1% of children in our data set lacked data on developmental outcomes for reasons such as the child has been in the class for <1 month, the child is <4 years old, and <75% of the items/questions were completed by the teacher for the given domain. 25 There were 7 children with CHD who were not classified as having special needs but AEDC scoring was incomplete so the extent of any developmental vulnerability was unclear; these were excluded.
Statistical Analysis
We calculated the prevalence of CHD among singleton children born in South Australia between 2002 and 2014.
In descriptive analyses, we compared the proportions of children with and without CHD who had special needs, developmental vulnerability in 1 domain or in ≥2 domains. We also compared these proportions among children with severe surgical, severe nonsurgical, non‐severe CHD, and no CHD. We further stratified prevalence estimates by presence of accompanying defect and by prematurity.
We fitted a log‐binomial model to estimate the risk of developmental difficulties among children with CHD and subgroups, compared with children without CHD. We used a log‐binomial model to directly estimate relative risk because developmental difficulties is not a rare outcome. We used a link test to assess the specification of the log‐binomial regression models, and the prediction squared term was consistent with a correctly specified model.
For the categorical outcome (special needs, developmental vulnerability in ≥2 domains, developmental vulnerability in 1 domain), we fit multinomial logistic regression models to estimate the relative risks. The goodness of fit test for the multinomial logistic regression model also showed no marked lack of fit of the model.
We had prespecified adjustment for maternal age and area‐level disadvantage (Index of Relative Socioeconomic Advantage and Disadvantage). Given they were categorical variables, the functional form of their relationship with the outcome was not considered. Therefore, we did not consider nonlinearity of the effects of age or disadvantage in the statistical models. Maternal age and area‐level disadvantage were not highly correlated.
All analyses were conducted using Stata MP version 18. We have followed the Reporting of Studies Conducted Using Observational Routinely Collected Health Data checklist for reporting in this article. 32
Ethics Approval
This study was approved by Human Research Ethics Committee, South Australian Department for Health and Wellbeing (HREC 00371). We used a deidentified administrative data set; therefore obtaining individual consent was not possible or expected and was waived by the ethics committee. 33
Results
Of the 67 990 singleton children with linked perinatal AEDC data, 656 had a diagnosis of CHD, corresponding to a prevalence of 9.6 per 1000 live births (Table 1). The most common CHD was ventricular septal defect, which affected 4.7 per 1000 children, followed by patent ductus arteriosus (1.7 per 1000 children) and atrial septal defect (1.2 per 1000 children). When we grouped CHD based on severity, 35% of the total CHD cases were severe. About 27% of total CHD were severe surgical cases (equivalent to 2.6 per 1000 births) and 7.6% were severe nonsurgical cases.
Table 1.
Characteristics of Congenital Heart Defects Among Singleton Children
| N=67 990 | Per 1000 live births | % of total CHD | |
|---|---|---|---|
| No CHD | 67 334 | ||
| Any CHD | 656 | 9.6 | |
| CHD severity | |||
| Severe surgical CHD | 178 | 2.6 | 27.1 |
| Severe nonsurgical CHD | 50 | 0.7 | 7.6 |
| Non‐severe CHD | 428 | 6.3 | 65.2 |
| CHD with and without other defect | |||
| CHD without other defects | 553 | 8.1 | 84.3 |
| CHD with other defects | 103 | 1.5 | 15.7 |
| CHD and accompanying defects | |||
| CHD and urogenital defects | 41 | 0.6 | 6.3 |
| CHD and musculoskeletal defects | 41 | 0.6 | 6.3 |
| CHD and gastrointestinal defects | 33 | 0.5 | 5.0 |
| CHD and respiratory defects | 13 | 0.2 | 2.0 |
| CHD and nervous system defects | 6 | 0.1 | 0.9 |
| Some common CHD types | |||
| Ventricular septal defect | 317 | 4.7 | 48.3 |
| Patent ductus arteriosus | 117 | 1.7 | 17.8 |
| Atrial septal defect | 83 | 1.2 | 12.7 |
| Coarctation of aorta | 39 | 0.6 | 5.9 |
| Transposition of great vessels | 24 | 0.4 | 3.7 |
| Tetralogy of Fallot | 15 | 0.2 | 2.3 |
A child with CHD could have >1 accompanying defect. Children could also have >1 type of CHD. Children with syndromes or chromosomal disorders were excluded. CHD indicates congenital heart defects.
Table 2 presents maternal and gestational characteristics of singleton children with and without CHD. The occurrence of CHD was slightly elevated among children whose mothers were >35 years of age. There was no clear socioeconomic patterning of CHD, based on the area‐level measure (Index of Relative Socioeconomic Advantage and Disadvantage).
Table 2.
Characteristics of Singleton Children With and Without Congenital Heart Defects
| Factor | No CHD | CHD | Severe surgical | Severe nonsurgical | Other CHD |
|---|---|---|---|---|---|
| N=67 990 | 67 334 | 656 | 178 | 50 | 428 |
| Maternal age, y | |||||
| <25 | 13 592 (20.2) | 144 (22.0) | 48 (27.0) | 13 (26.0) | 83 (19.4) |
| 25–29 | 19 394 (28.8) | 159 (24.2) | 40 (22.5) | 11 (22.0) | 108 (25.2) |
| 30–34 | 21 149 (31.4) | 212 (32.3) | 48 (27.0) | 16 (32.0) | 148 (34.6) |
| ≥35 | 13 199 (19.6) | 141 (21.5) | 42 (23.6) | 10 (20.0) | 89 (20.8) |
| Socioeconomic status | |||||
| Quintile 1 most disadvantaged | 16 400 (24.4) | 169 (25.8) | 50 (28.1) | 7 (14.0) | 112 (26.2) |
| Quintile 2 | 13 619 (20.2) | 135 (20.6) | 34 (19.1) | 7 (14.0) | 94 (22.0) |
| Quintile 3 | 12 263 (18.2) | 127 (19.4) | 36 (20.2) | 16 (32.0) | 75 (17.5) |
| Quintile 4 | 13 871 (20.6) | 129 (19.7) | 36 (20.2) | 10 (20.0) | 83 (19.4) |
| Quintile 5 most advantaged | 11 181 (16.6) | 96 (14.6) | 22 (12.4) | 10 (20.0) | 64 (15.0) |
| Preexisting diabetes | 408 (0.6) | 18 (2.7) | — | — | 14 (3.3) |
| Gestational diabetes | 3724 (5.5) | 43 (6.6) | 16 (9.0) | — | 24 (5.6) |
| Preexisting hypertension | 761 (1.1) | 11 (1.7) | 5 (2.8) | — | 6 (1.4) |
| Gestational hypertension | 4880 (7.2) | 72 (11.0) | 22 (12.4) | — | 46 (10.7) |
| Biological sex of the baby | |||||
| Female | 32 479 (48.2) | 335 (51.1) | 78 (43.8) | 19 (38.0) | 238 (55.6) |
| Male | 34 855 (51.8) | 321 (48.9) | 100 (56.2) | 31 (62.0) | 190 (44.4) |
| Preterm | |||||
| Premature, <37 wk | 4309 (6.4) | 103 (15.7) | 23 (12.9) | — | 77 (18.0) |
Children with syndromes and chromosomal disorders were excluded. Small numbers have been suppressed due to ethical consideration. CHD indicates congenital heart defect.
Overall 13% (95% CI, 10.8%–16.1%) of children with CHD had special needs compared with 5.5% (95% CI, 5.3%–5.7%) of children without CHD (Figure 2). A high proportion of children had special needs among both the severe surgical CHD (15% [95% CI, 10.2–20.8]) and non‐severe CHD (13% [95% CI, 10.5–17.0]) groups, with lower numbers in the severe nonsurgical group making that estimate imprecise.
Figure 2. Developmental difficulties at school entry among singleton children with and without congenital heart defect (CHD) and by CHD severity.
A, With and without CHD; B, by CHD severity. Children with syndromes and chromosomal disorders were excluded. CHD indicates congenital heart defect; and DV, developmentally vulnerable.
We examined combinations of the 5 different developmental vulnerabilities but could not see a distinct pattern in children with CHD (Figure 3). However, there were multiple combinations where there were apparent increases in developmental vulnerabilities among children with CHD compared with those without CHD, such as the combination of domain 1 (physical health and well‐being), and domain 3 (emotional maturity), 4.8% versus 1.9%. Among children with CHD and at least 1 developmental vulnerability, 55% had a combination of ≥2 domains affected. The most common single domain affected was physical health and well‐being.
Figure 3. Among singleton children with and without CHD who do not have special needs but are developmentally vulnerable in at least one domain, patterns of single and multiple domains affected.
A, Children without CHD (N=14 407). B, Children with CHD (N=167). Domain: 1 (
) Physical health and well‐being, 2 (
) Social competence, 3 (
) Emotional maturity, 4 (
) Language and cognitive skills (school‐based), 5+ Communication skills and general knowledge. Vertical line connecting symbols shows co‐occurring domains of vulnerability. CHD indicates congenital heart defect.
Developmental vulnerability in at least 1 domain was 26% (95% CI, 22.5–29.2) among children with CHD, compared with 21.6% (95% CI, 21.3–21.9) among children without CHD. A similar proportion of children with severe surgical CHD (28% [95% CI, 21.7–34.9]) or severe nonsurgical CHD (32% [95% CI, 21.0–46.8]) were developmentally vulnerable in at least 1 domain.
Overall, 39% (95% CI, 35.3–42.7) of singleton children with CHD had developmental difficulties compared with 27% (95% CI, 26.8–27.5) in the general population. Not only did children with severe surgical CHD have developmental difficulties at school entry (43% [95% CI, 35.5–50.0]), but also a large proportion of children with severe nonsurgical CHD (38% [95% CI, 26.2–52.9]) and non‐severe CHD (37% [95% CI, 33.0–42.2]) had developmental difficulties (Table 3).
Table 3.
Risk of Special Needs and Developmental Vulnerability at School Entry Among Singleton Children With CHD and by Types of CHD, Compared With Children Without CHD
| N | No developmental difficulties | Developmental difficulties | Special needs | DV in ≥2 domains | DV in 1 domain | Missing data | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| N (%) | N (%) | RRR (95% CI) | N (%) | RRR (95% CI) | N (%) | RRR (95% CI) | N (%) | RRR (95% CI) | N (%) | ||
| No CHD | 67 334 | 48 527 (72.1) | 18 118 (26.9) | Reference | 3711 (5.5) | Reference | 7453 (11.1) | Reference | 6954 (10.3) | Reference | 689 (1.0) |
| CHD | 656 | 396 (60.4) | 253 (38.6) | 1.38 (1.22–1.57) | 86 (13.1) | 2.83 (2.21–3.63) | 95 (14.5) | 1.56 (1.06–2.3) | 72 (11.0) | 1.26 (0.97–1.65) | 7 (1.1) |
| CHD severity | |||||||||||
| No CHD | Reference | Reference | Reference | Reference | |||||||
| Severe surgical CHD | 178 | 101 (56.7) | 75 (42.1) | 1.42 (1.2–1.68) | 26 (14.6) | 3.25 (2.26–4.67) | 31 (17.4) | 1.88 (1.47–2.41) | 18 (10.1) | 1.2 (0.72–1.98) | — |
| Severe nonsurgical CHD | 50 | 30 (60.0) | 19 (38.0) | 1.52 (0.82–2.83) | — | 1.43 (0.34–5.93) | 9 (18.0) | 2.15 (0.56–8.33) | — | 1.69 (0.38–7.46) | — |
| Non‐severe CHD | 428 | 265 (61.9) | 159 (37.1) | 1.35 (1.18–1.55) | 57 (13.3) | 2.82 (2.27–3.49) | 55 (12.9) | 1.37 (0.92–2.03) | 47 (11.0) | 1.24 (0.82–1.88) | 4 (0.9) |
| Accompanying defect | |||||||||||
| No CHD | Reference | Reference | Reference | Reference | |||||||
| CHD with other defects | 103 | 44 (42.7) | 57 (55.3) | 1.86 (1.65–2.1) | 31 (30.1) | 9.18 (5.64–14.96) | 12 (11.7) | 1.8 (0.82–3.96) | 14 (13.6) | 2.24 (1.13–4.44) | — |
| CHD without other defects | 553 | 352 (63.7) | 196 (35.4) | 1.28 (1.08–1.52) | 55 (9.9) | 2.04 (1.43–2.9) | 83 (15.0) | 1.53 (0.96–2.43) | 58 (10.5) | 1.14 (0.83–1.56) | 5 (0.9) |
| Preterm | |||||||||||
| No CHD | 4309 | 2702 (62.7) | 1555 (36.1) | Reference | 383 (8.9) | Reference | 612 (14.2) | Reference | 560 (13.0) | Reference | 52 (1.2) |
| CHD | 103 | 52 (50.5) | 50 (48.5) | 1.29 (1.16–1.43) | 21 (20.4) | 2.79 (1.97–3.95) | 18 (17.5) | 1.51 (0.72–3.17) | 11 (10.7) | 1.02 (0.82–1.26) | — |
| Full term | |||||||||||
| No CHD | 63 025 | 45 825 (72.7) | 16 563 (26.3) | Reference | 3328 (5.3) | Reference | 6841 (10.9) | Reference | 6394 (10.1) | Reference | 637 (1.0) |
| CHD | 553 | 344 (62.2) | 203 (36.7) | 1.38 (1.19–1.61) | 65 (11.8) | 2.63 (1.99–3.48) | 77 (13.9) | 1.53 (1.03–2.27) | 61 (11.0) | 1.28 (0.9–1.83) | 6 (1.1) |
Developmental difficulties: children who had special needs or were developmentally vulnerable in at least one domain. Children with syndromes and chromosomal disorders were excluded. RRR are adjusted for maternal age and area‐level socioeconomic advantage or disadvantage. CHD indicates congenital heart defect; DV, developmental vulnerability; and RRR, relative risk ratios.
Table 3 shows the adjusted risk of developmental difficulties, separated into special needs, developmental vulnerability in ≥2 domains or in only 1 domain at school entry among children with CHD and CHD subgroups, compared with those without CHD. All risks were elevated among children who had severe surgical, severe nonsurgical, and nonsevere CHD compared with children without CHD, although effect estimates were imprecise for some comparisons as the CIs were wide including the null, notably for the severe nonsurgical CHD, due to small numbers.
There was a substantially higher risk of special needs among children with CHD and accompanying defects, but these children account for 16% of all CHD. Preterm birth occurred in 16% of children with CHD, and almost half of these had developmental difficulties. Patent ductus arteriosus was more common in children born preterm (4.1 per 1000, Table S2), compared with term births (1.6 per 1000). Among all those born preterm the prevalence of developmental difficulties was 37%. For those born preterm with PDA only the prevalence of developmental difficulties was 56% (9/16), and 48% (41/86) for those with preterm and other type of CHD (including 2 with PDA and other CHD), and 37% for those preterm without CHD; small numbers limit comparison. Comparison between CHD subtypes for those born preterm was also limited due the small numbers (Figure S2, Table S2).
DISCUSSION
This study using population‐based linked data from South Australia showed that around 39% of singleton children with CHD (that is not part of a diagnosed syndromes or chromosomal disorders) have developmental difficulties at school entry: overall, 13% have special needs and a further 26% have at least 1 developmental vulnerability. Among children with non‐severe CHD the prevalence of developmental difficulties was similar to the group with severe surgical CHD (corresponding to “complex” or “critical”). Importantly children with non‐severe CHD comprised 65% of all CHD. The consequences for children and the burden carried by families, schools, and communities is of practical significance yet the extent of developmental problems in this group of children is poorly recognized.
The overall finding that developmental difficulties occurs in a substantial proportion of children with CHD is consistent with established literature. There are plausible biological mechanisms explaining why children with CHD are at an increased risk of developmental vulnerability. For example, altered heart physiology can result in reduced nutrients and oxygen supply to the developing fetal or neonatal brain, which could lead to delayed brain maturation or development. 3 , 10 , 13 However, most of this evidence is based on studies of complex CHD. 11 , 12 A few studies that were not limited to complex CHD have also reported that in utero structural abnormalities of the brain were observed in both simple and complex forms of CHD. 14 For example, a study of 338 women with fetuses that had CHD diagnosed by echocardiography, whose unborn children underwent second and third‐trimester magnetic resonance imaging, showed that structural brain abnormalities were detected among 23% of fetuses with CHD compared with 1.5% in fetuses without CHD, 14 these abnormalities were found in both simple and complex forms of CHD (separate percentages not provided). 14
Although relatively little is known about children with noncomplex CHD, 3 several other recent cohort studies 8 , 34 reported that not only children with complex CHD but also children who had not undergone any surgery for their CHD were developmentally vulnerable at preschool or school age, compared with children without CHD. For example, a recent large population‐based linked data study of children born in Florida between 2008 and 2016 (~2 million children, CHD n=35 786) demonstrated that preschool‐aged children with more severe CHD as well as less severe CHD had an increased risk of poor developmental outcomes including intellectual disability, developmental delay and language and speech impairment. 8 Similarly a population‐based linked data study from Denmark reported that special education during school was received by 18% children with simple CHD, 24% children with complex CHD, and 10% children without CHD. 35
In 2012 the American Heart Association released a scientific statement proposing routine neurodevelopmental surveillance and remedial programs for children with CHD undergoing surgery in infancy. 36 The 2024 scientific statement by the American Heart Association stratifies children with CHD into 3 risk categories for developmental delay or disorder, considering only those with complex CHD to be high risk; the statement acknowledges that less is known about the outcomes of children with milder forms of CHD, and these children should have surveillance and screening according to the guidelines of the American Academy of Pediatrics (based on risk factor such as prematurity, not CHD). 3 , 37 This is echoed in the recent Australian national standard of care for CHD. 7 The results presented here suggest these policies may deserve to be reviewed.
Our findings and those of similar studies 8 , 34 , 35 highlight the importance of monitoring of all children with CHD, regardless of the severity, for neurodevelopmental deficits. Doing so would assist in facilitating the provision of early support and intervention to help these children reach their full developmental potential, as these early interventions are linked with improved outcomes such as school achievement, employment, mental well‐being, and quality of life. 38 Studies have shown that children who are monitored or screened are more likely to receive early interventions than children receiving no monitoring or screening. 39 Some research suggests that preliminary interventions among infants with CHD were linked with improved outcomes such as feeding, early cognitive development, and physiological regulations. 40 There are effective programs and early interventions available for children born preterm that have other medical conditions; however, their feasibility, applicability, and effectiveness for use in the population with CHD is largely understudied. 40
We reiterate that these findings are not due to the presence of children with diagnosed syndromes, or those who were multiple births, as these children were excluded. The total estimate of children at risk is therefore conservative. Children with CHD and other accompanying defects had a substantially higher risk of developmental difficulties than other children, but these represent a small fraction of all those with CHD. Developmental difficulties affected over a third of those born preterm (comprising 6% of all births); CHD occurred more frequently among these births than term births and may to some extent contribute to an excess of developmental difficulties in children born preterm.
Our study has multiple strengths. We used population‐based government administrative birth defect registry data, with defects reported to the child's fifth birthday, and a relatively large sample size, enhancing external validity. The AEDC program involves standardized assessment of developmental outcomes at school entry for all children with few exceptions. The data linkage system in Australia is considered high quality.
Our study also has some limitations. We did not have access to hospital procedure codes, consequently we cannot be sure if the children grouped as surgical CHD actually underwent surgery. Therefore, there might be some misclassification, however, our estimates are similar to those reported elsewhere. There might be some undetected syndromes or genetic abnormalities in children that could be contributing to developmental outcomes. The definition/classification of severe and non‐severe CHD varies in different classification systems, however our estimate of non‐severe CHD (6.3 per 1000 live births) is similar to that reported for Oceania in a recent meta‐analysis of over 260 studies. 1 We do not have data on children who were not born in Australia.
Conclusions
Our population‐based cohort study showed that developmental difficulties were prevalent among groups of children with noncomplex CHD who did not require surgery for survival in the first year of life, as well as those with complex CHD. The needs of these children and families for monitoring and developmental support should be recognized, so that they can access and benefit from early intervention services.
Disclosures
None.
Source of Funding
This work was supported by the Medical Research Future Fund (Grant ID ARGCHDG000041).
Supporting information
Tables S1–S5
Figures S1–S2
RECORD Checklist
Acknowledgments
We thank SA NT DataLink for facilitating and conducting the data linkage. We also thank the data custodians (South Australian Department of Education and the Department for Health and Wellbeing) for providing us deidentified data. This study uses data from the Australian Early Development Census, which is funded by the Australian Government Department of Education. The findings or views reported are those of the authors and should not be attributed to the Department or the Australian Government. Open access publishing facilitated by Adelaide University, as part of the Wiley ‐ Adelaide University agreement via the Council of Australasian University Librarians.
This article was sent to Daniel E. Clark, MD, MPH, Associate Editor, for review by expert referees, editorial decision, and final disposition.
Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.125.045529
For Sources of Funding and Disclosures, see page 11.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Tables S1–S5
Figures S1–S2
RECORD Checklist
Data Availability Statement
The researchers do not have permission to share the data as they were provided specifically for the scope of the research and approved by the ethics committees. Requests to access the data sets should be directed to the data custodians.