Abstract

Introduction:

A recent shift in mortality trends in children with congenital heart disease (CHD) has led to more patients reaching adulthood. Attention-deficit hyperactivity disorder (ADHD) is a prevalent and often underdiagnosed condition, with increased risk observed in children with CHD due to disease- and surgery-related factors. This study aimed to determine the incidence of ADHD one year after cardiac surgery in children and to identify associated clinical and operative risk factors.

Methods:

Children aged 3-5 years and 6-18 years who were to undergo cardiac surgery for CHD between December 2022 to June 2023, were evaluated pre-operatively and post-operatively ≥1 year after the surgery, after informed written consent.

Results:

Our study comprised of 98 children. The incidence of ADHD in children 1 year post cardiac surgery was 32.6%. We also found a statistically significant association between post- operative complications, longer CPB time, aortic cross-clamp time, duration of mechanical ventilation, ICU stay, and hospital stay and ADHD. No significant association was found with prior cardiac surgery, cyanosis, intraoperative complications, reintervention, or inotrope duration. CPB time >58 minutes, aortic cross-clamp time >46 minutes, hospital stay >8 days, and ICU stay ≥3 days demonstrated moderate to good predictive accuracy for ADHD.

Conclusion:

ADHD is a common outcome following pediatric cardiac surgery and is associated with perioperative factors, particularly markers of surgical complexity and postoperative recovery. Early identification using these predictors may help reduce long-term morbidity, though larger studies are needed to validate these findings.

Introduction

Congenital heart disease (CHD) is among the most prevalent congenital anomalies, afflicting 8–12 per 1,000 live births worldwide (1). Considering a rate of 9/1,000, about 1.35 million babies are born with CHD each year globally (2). For India, this translates to approximately 240,000 affected children per year (3). Owing to advancements made in medical technology and surgical techniques, there has been a shift in mortality trends in patients with CHDs (4). More than 90% of children born with CHD reach adulthood (5) and mortality rates have decreased by 31% over the last 20 years (4). As a result, the research focus has progressively shifted from improving survival to minimizing long-term morbidities associated with CHD and its treatment.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood behavioral disorder. According to Salari et al. (6), the incidence of ADHD is 7.6% in children aged 3 to 12 years and 5.6% in teenagers aged 12 to 18. Systematic reviews indicate that the community prevalence globally is between 2% and 7%, with an average of around 5% (5–10). However, ADHD remains under-recognized and underdiagnosed in many populations. Children with ADHD have poorer long-term outcomes with respect to academic achievement and attainment, occupational rank and job performance, risky sexual practices and early unwanted pregnancies, substance use, relationship difficulties, marital problems, traffic violations, and car accidents (11). Given these substantial consequences, early diagnosis and intervention are critical.

One of the most pressing parental concerns is the neurodevelopmental outcome of their child.

Children with CHD are at a 30% higher risk for inattention and hyperactivity compared to healthy individuals (5). The abnormal cerebral blood flow, which is altered antenatally and perinatally, potentially causes delays in brain development. Abnormal sulcal folding patterns have also been noted in adults with simple CHDs (ASD/VSD) (12).

Despite medical advancements, CHD and its’ management is not completely foolproof. Pediatric cardiologists and cardiac surgeons are hesitant with early repair, whether definitive or palliative, due to the multi-organ effect of cardiac surgery. Additional hypoxaemia, due to postponed correction of cardiac defects, seems to increase the risk for attentional dysfunction, hyperactivity and is considered responsible for further damage to the highly oxygen-sensitive regions of the prefrontal cortex (13). Unfortunately, there are no consensus guidelines on the neuroprotective strategies to be followed during surgeries. Studies have shown that the risk of developing ADHD in adolescence is significantly higher in cardiac surgery patients compared to healthy individuals. The symptoms may worsen by repeated exposure to anaesthetics and surgery-induced stress and inflammatory responses. Single, or repeated anaesthesia could be a risk factor for development of ADHD symptoms, independent of the surgery performed (14–16).

Study objectives

In this study, we aimed to assess the incidence of ADHD one year following cardiac surgery in children aged 3–5 years (using the ADHD Rating Scale-IV, Preschool Version) and 6–18 years (using the Conners 3 Short Form—Parent version). Additionally, we sought to identify clinical and operative predictors associated with the development of ADHD symptoms in this population.

Methodology

Following approval from the institutional ethics committee, this prospective observational study was conducted at Medanta Hospital, Gurugram, Haryana, India, over a period of 18 months (December 2022—June 2024). The study included pediatric patients aged 3–5 years and 6–18 years who were scheduled to undergo cardiac surgery for congenital heart disease (CHD) between December 2022 and June 2023.

Exclusion criteria

The exclusion criteria were children with known case of neuropsychiatric illness or receiving treatment for the same, genetic syndromes associated with cognitive deficits (eg: Downs syndrome), multiple congenital anomalies, severe neurological impairment, lack of perioperative data and lack of parental or primary care giver's consent.

Preoperative assessment

Eligible participants were assessed both preoperatively and at least one year postoperatively, following informed written consent from parents or primary caregivers. Baseline demographic and clinical data were collected, including age, sex, vital signs, cardiac examination findings, echocardiographic diagnosis, and history of previous cardiac surgeries.

ADHD screening was conducted preoperatively. Children who screened negative were enrolled in the study. For children aged 3–5 years, the ADHD Rating Scale IV—Preschool Version was completed by the parent or primary caregiver. For those aged 6–18 years, the Conners' Parent Rating Scale–Short Form was used. Self-report was not included due to developmental variability in insight and reliability across the 6–18-year age range, and to ensure feasibility and consistency in the hospital setting.

Intraoperative data collection

Intraoperative variables documented included the type of surgical procedure performed, durations of cardiopulmonary bypass (CPB), aortic cross-clamp (ACC), and deep hypothermic circulatory arrest (DHCA), the lowest temperature during CPB, and any intraoperative complications along with their management.

Postoperative data collection

Postoperative outcomes assessed were duration of ICU stay, total hospital stay, duration of mechanical ventilation, inotropic support, need for extracorporeal membrane oxygenation (ECMO), requirement for reintervention, and the occurrence and management of postoperative complications such as hypoglycemia, seizures, or cardiac arrest.

Follow-up and ADHD assessment

At least one year following surgery, all participants underwent reassessment using age-appropriate, validated ADHD screening questionnaires during their routine follow-up outpatient visits. These assessments were conducted by trained pediatricians. Children with scores indicative of ADHD were referred to a child psychiatrist for confirmatory diagnosis and further management. However, psychiatric diagnostic outcomes were not systematically captured within the study database, as the study was designed to evaluate screening results rather than establish formal psychiatric diagnoses.

Sample size calculation

The primary objective of the study was to determine the incidence, i.e., the development of ADHD after 1 year of cardiac surgery. The likely value of incidence (i) is not known for the Indian subcontinent. In such situations, a sample size of 96 was recommended for estimating the incidence within 10% margin of error and with 95% confidence level.

Data management and statistical analysis

The analysis involved profiling patients based on demographic characteristics, clinical parameters (both preoperative and postoperative), and surgical findings. Descriptive statistics for quantitative variables were reported as means with standard deviations, while categorical variables were presented as absolute numbers and percentages. Comparative analyses were conducted between patients who developed ADHD and those who did not, examining various preoperative, postoperative, and background parameters. Independent samples t-tests were used to compare means between groups. Cross-tabulations were created for categorical variables, and associations were tested using the Chi-square test. Univariate logistic regression analysis was performed to assess the relationship between demographic, clinical, and surgical variables and the risk of developing ADHD. Variables found to be statistically significant in the univariate analysis were further included in a multivariate logistic regression model to identify independent predictors. A p value of <0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY).

Ethical issuesConsent, scientific and ethical review

This study was initiated after clearance from the institutional ethical committee. Each subject has been enrolled with informed written consent.

Confidentiality

Patient records have been kept confidential and anonymous. Patients who opted to withdraw consent during the study period have continued to receive standard care as per the hospital practice.

Results

Our study population comprised of 98 children, whose pre-operative parameters and complications are described in Table 1.

VariableNumber of patients (n = 98)Percentage (%)GenderFemale3838.8%Male6061.2%History of Cardiac SurgeryYes3333.7%CPB (+)2678.8%CPB (−)721.2%No6566.3%Type of CHDAcyanotic4040.8%Cyanotic5859.2%Intra-operative complicationsYes66.1%No9293.9%ReinterventionYes44.1%No9495.9%Post operative complicationsYes4647.0%No5253.0%If yes (n = 46)Rhythm Abnormalities2043.5%Hypertension817.4%Hemoptysis- Coiling24.3%Acute kidney injury12.2%Prolonged Pleural Drain (>3 days)613%Post-periocardiotomy Syndrome36.5%Low cardiac output state24.3%Prolonged oxygen support (8 days)24.3%Thrombectomy24.3%

Distribution of all pre-operative parameters and complications in study group.

The mean age at surgery was 7.9 ± 4.1 years. 10 patients underwent closed heart surgery. 18 patients went on CPB but did not undergo aortic cross clamping. Intra- operatively, the mean bypass time was 63.6 ± 21.3 min and aortic cross-clamp time was 46.9 ± 16.9 min. All patients were cooled to 34.4 ± 1.5°Celsius and only one patient was cooled to 25 degrees. None of the patients in the study group underwent DHCA. Post operatively, the mean duration on the mechanical ventilator was 16.7 ± 9.8 h. Mean duration of inotrope requirement was 2.5 ± 1.1 days. The mean duration of hospital stay was 8.7 ± 2.1 days, which included ICU stay, the mean duration of which was 2.8 ± 1.1 days.

Incidence of ADHD post cardiac surgery

The ADHD questionnaire was performed 13.5 ± 1.2 months from surgery. The incidence of ADHD post cardiac surgery in our study was 32.6% (Table 2).

ADHD QuestionnaireNumber of patientsPercentage (%)ADHD Rating scale IV—Preschool1818.4%Connors8081.6%InterpretationInattentive2222.4%Hyperactive + Impulsive1010.2%Nil6667.3%Preoperative clinical parameters and ADHD test result

There was no statistically significant association between preoperative clinical parameters (gender, history of cardiac surgery, and type of CHD) with positive ADHD test result (p value >0.05) (Table 3). The mean age group of patients who tested positive for ADHD was 8.6 ± 4.2 years, while those who tested negative had a mean age group of 7.6 ± 4 years. The difference in age group was not statistically significant; hence the groups were demographically similar in age.

ParameterPositiveNegativeTotalChi square Valuep—valuen%n%n%GenderFemale1026.3%2873.7%38100.0%1.1330.287Male2236.7%3863.3%60100.0%H/O cardiac surgeryNo1827.7%4772.3%65100.0%2.1600.142Yes1442.4%1957.6%33100.0%Type of CHDAcyanotic922.5%3177.5%40100.0%3.1680.075Cyanotic2339.7%3560.3%58100.0%

Association of pre-operative clinical parameters with ADHD test result.

Figure 1 shows the age wise distribution of children who tested positive for ADHD.

Age wise distribution of children who tested ADHD Positive.

Complications and ADHD test result

We did not find a statistically significant difference between intra-operative complications or need of re-interventon with ADHD test result (p value >0.05 in both) (Table 4). However, 68.1% of those who did not require reintervention tested negative for ADHD. We also found a statistically significant association (p value 0.045) between presence of post- operative complications and positive test result of ADHD questionnaire.

ParameterPositiveNegativeTotalChi Squa re Valuep—valuen%n%n%Intra-op. ComplicationsNo2931.5%6368.5%92100.0%0.8750.350Yes350.0%350.0%6100.0%ReinterventionNo3031.9%6468.1%94100.0%0.5710.450Yes250.0%250.0%4100.0%Post op. ComplicationsNo1223.5%3976.5%51100.0%4.0250.045Yes2042.6%2757.4%47100.0%

Association of complications with respect ADHD test result.

When further explored, we calculated that those with post-operative complication were more likely to test as inattentive and 76.4% of children without post-operative tested negative for the ADHD questionnaire (Table 5).

ParameterInattentiveHyperactive + ImpulsiveNilTotalN%N%N%N%Post operative complicationNo1121.5%11.96%3976.4%51100.0%Yes1123.4%919.2%2757.4%47100.0%

Post-operative complications and ADHD questionnaire score.

Operative and ICU parameters and ADHD test result

There was a statistically significant association between duration of cardiopulmonary bypass, aortic cross clamp time, MV duration, hospital stay (ICU + ward stay) with a positive outcome on the ADHD questionnaire (Table 6). On subset analysis of hospital stay, we found that the duration of ICU stay had a statistically significant association with positive ADHD test result (p value 0.002). Figure 2 shows box and whisker plot representation of CPB Time and ADHD Questionnaire.

ParameterPositive mean ± SDNegative mean ± SDMean ± Std err of the difference95% confidence interval of the differencet- valuep valueLowerUpperBypass Time (minutes)73.1 ± 2559.1 ± 17.714 ± 4.45.222.83.1640.002Aortic CC time60.6 ± 21.941.9 ± 11.418.6 ± 3.811.126.24.924<0.001MV (hours)20 ± 9.815.1 ± 9.44.8 ± 2.10.88.92.3500.021Inotropes (days)2.6 ± 1.12.4 ± 1.10.2 ± 0.2−0.30.60.7360.464Hospital Stay (days)9.9 ± 2.38 ± 1.61.9 ± 0.41.12.74.620<0.001ICU stay (days)3.3 ± 1.32.5 ± 0.90.7 ± 0.20.31.13.1990.002Time since surgery (months)13.3 ± 113.6 ± 1.3−0.3 ± 0.3−0.80.2−1.0710.287

Comparison of mean value of operative and ICU parameters with ADHD test result.

Box and whisker plot representation of CPB time and ADHD questionnaire.

Our data revealed that the children who had a longer CPB time, longer aortic cross-clamp time and longer hospital stay were more likely to test as inattentive (Table 7). Additionally, those who had a longer duration on MV and ICU stay were more likely to test as hyperactive + impulsive (Table 7). It is important to note that the mechanical ventilation duration corresponds to the duration in ICU, and not during cardiac surgery.

ParameterInattentiveHyperactive + ImpulsiveNilF—valuep—valueBypass Time (minutes)79.2 ± 27.560.4 ± 11.559.1 ± 17.78.327<0.001Aortic CC time64.7 ± 24.750.2 ± 5.341.9 ± 11.414.790<0.001MV (hours)18.2 ± 4.323.8 ± 16.315.1 ± 9.43.9880.022Hospital Stay (days)10 ± 2.69.7 ± 1.88 ± 1.610.670<0.001ICU stay3.1 ± 1.23.6 ± 1.52.5 ± 0.96.0130.003

Comparison of mean value of statistically significant parameters with ADHD test result.

Using ROC analysis, CPB time of >58 min showed a good accuracy to predict ADHD positive, with sensitivity of 83.9% and specificity of 56.9% (Figure 3, Tables 8, 9).

ROC curve: CPB time (min.) and ADHD Positive.

ParameterAUCStd. ErrorAsymptotic 95% confidence intervalp—valueLower boundUpper boundCPB Time (minutes)0.7010.0570.5890.8130.002

ROC analysis: CPB time and ADHD positive.