Background

Congenital scoliosis is a spinal deformity present at birth and characterized by formation, segmentation, or mixed defects [1]. The spine is formed between four and six weeks—the crucial stage when associated anomalies could develop [2, 3]. Of these associated anomalies, intraspinal ones are characterized best, with no relationship with the type of spinal deformity, the level of hemivertebra, or gender [4].

Few studies have reported on the incidence of congenital heart disease associated with congenital scoliosis and whether there are risk factors that increase its incidence or whether it actually presents a risk in surgery. In addition, the studies include different populations. The knowledge of these data could lead to an “appropriate conversation with patients and families” and the establishment of a diagnostic algorithm showing the necessary imaging tests [5].

The diagnosis of cardiac anomalies could affect their prognosis. On the other hand, it has been observed that the diagnosis of intraspinal anomalies does not affect scoliosis correction, and there might not be an association between multiple intraspinal anomalies and previous correction surgery [6, 7].

In contrast, studies analyzing the risk of cardiac anomalies in spinal surgery tend to be case series and case reports showing high risk in patients undergoing Fontan or single ventricle surgery. Complications include pleural effusion, blood loss, and fluid management issues. There is a correlation between the high surgical risk and the magnitude of the curve, fused levels, surgery time, and cyanosis [8, 9]. This is why a diagnosis is crucial to optimize the patient’s condition before spinal correction surgery. Nowadays, there are more accurate diagnostic methods, such as echocardiography and magnetic resonance imaging (MRI), included in some cases as a diagnostic algorithm for patients with congenital scoliosis.

There is no meta-analysis describing the true incidence of cardiac anomalies in individuals with congenital scoliosis. Also, no meta-analysis indicates the most evidence-based risk factors. The present study aimed to investigate the incidence of cardiac anomalies in patients with congenital scoliosis and to assess which factors increase the occurrence of these abnormalities.

Material and methods

Eligibility criteria

This meta-analysis followed the PRISMA guidelines (Fig. 1) [10]. The study selection was done by two reviewers, who reached an agreement by discussion. We followed the PICOS strategy: (P) Patients with congenital scoliosis were studied. (I) This meta-analysis analyzed incidences with no intervention. (C) This meta-analysis analyzed incidences without comparison. (O) The outcomes were incidence of cardiac anomalies. (S) The studies were cohort studies. The exclusion criteria were: prenatal ultrasound diagnosis, noncongenital scoliosis, and duplicate data.

Fig. 1
figure 1

Study selection flow diagram (preferred reporting items for systematic reviews and meta-analysis)

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Information sources and search strategy

The databases PubMed (National Library of Medicine) and the Cochrane Collaboration Library were searched from 2000 to 2020. The selected articles were about cardiac anomalies associated with congenital scoliosis. The search terms were “congenital scoliosis” or “congenital vertebral deformit*” and “heart anomalies” or “heart abnormalities” or “cardiac anomalies” or “cardiac abnormalities.” The references of the first studies included were reviewed.

Data extraction and data items

Data extraction was performed by two reviewers using an Excel spreadsheet. If an agreement was not achieved, a third reviewer was asked to complete the data extraction form. For each study that met the criteria, the following information was extracted: The primary pooled outcome measure was the incidence of cardiac anomalies in individuals with congenital scoliosis. Demographic variables were also collected: author, years of publication, region, age, gender of the overall population, number of patients, and diagnosis. Information on the gender of those who experienced cardiac anomalies, the type of malformation (formation, segmentation, or mixed), and other associated anomalies were gathered as well.

Risk of bias assessment

The quality of the included studies was assessed independently by two authors using the Methodological Index for Non-Randomized Studies (MINORS) criteria [11]. The maximum score is 24 for comparative studies and 16 for noncomparative studies. For noncomparative studies, scores of 0–4 corresponded to very low quality, 5–7 corresponded to low quality, 8–12 corresponded to fair quality, and ≥ 13 corresponded to high quality. For comparative studies, scores of 0–6 corresponded to very low quality, 7–10 corresponded to low quality, 11–15 corresponded to fair quality, and ≥ 16 corresponded to high quality.

Assessment of the results

The incidence of cardiac anomalies was calculated as the total number of patients with congenital cardiac anomalies divided by the total number of patients with congenital scoliosis. In studies in which the standard error (SE) was not reported, we calculated it from the prevalence using the following formula: SE = √p(1–p)/n and 95% CI = p ± 1.96xSE, where p = prevalence [12]. Pooled incidences with 95% confidence intervals (CIs) were calculated using a random-effects model. A fixed-effects model was used if heterogeneity was low (I2 < 50%). Otherwise, a random-effects model was used. All analyses were performed using the Review Manager 5.4 software package provided by the Cochrane Collaboration.

Additional analysis

Subgroup analyses were performed using the following variables: mean age and region of the studies. Funnel plots were used to examine the possibility of publication bias.

Results

Study selection

The initial search identified 48 results. After eliminating case reports and reviews, 13 articles were excluded. The titles and abstracts of the remaining 35 articles were then examined. Six studies met the inclusion criteria. After an in-depth analysis of these articles, three more were included based on the references cited in the six studies (Fig. 1).

Study characteristics

The main characteristics of the included articles are shown in Table 1 [5, 13,14,15,16,17,18,19,20]. A total of nine studies involving 2910 patients were included. The articles were published between 2002 and 2020. The age of the patients ranged from 3.5 to 14.9 years. The methodological index for nonrandomized studies (MINORS) assessment ranged between 10 and 12 points. According to the MINORS criteria, the studies were of fair quality.

Table 1 Main characteristics of the included studies
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Outcomes

The incidence rate of cardiac anomalies associated with congenital scoliosis was 21.05%, with 95% CI of 16.85–25.25% (Fig. 2). The incidence rates of these anomalies according to region were as follows: Europe, 28.93% (95% CI of 9.22–48.64%); USA, 27.21% (95% CI of 19.97–34.45%); and China, 15.33% (95% CI of 13.28–17.37%) (Fig. 3). Cardiac anomalies were diagnosed more frequently in patients over 10 years (24.29%, 95% CI of 19.02–29.57%) than in patients under 10 years (14.57%, 95% CI of 5.80–23.34%) (Fig. 4).

Fig. 2
figure 2

Meta-analysis of the pool incidence of cardiac anomalies in patients with congenital scoliosis

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Fig. 3
figure 3

Subgroup analysis dividing the global incidence of cardiac anomalies in patients with congenital scoliosis by regions (North America, Europe and China). Europe showed the highest incidence of cardiac anomalies followed by North America and China

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Fig. 4
figure 4

Subgroup analysis showing how the cardiac anomalies incidence according to diagnosis age

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Table 2 shows the cardiac abnormalities. Mitral valve prolapse was the most frequent cardiac anomaly, occurring in 48.45% of patients. The second most frequent anomaly was nonspecific valvular anomalies, representing 29.98% of the patients. The third most frequent abnormality was atrial septal defect (ASD), found in 29.98% of the patients. The other anomalies found were atrial septal aneurysm (24.42%), ventricular septal defect (VSD) (21.08%), patent foramen ovale (13.95%), Fallot tetralogy (10.87%), PDA (10.63%), dilation coronary sinus (8.47%), and dextrocardia (3.77%).

Table 2 Main cardiac anomalies associated with congenital scoliosis
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With respect to gender, cardiac anomalies occurred more frequently in females than in males (57.37%, 95% CI of 50.48–64.27% vs. 42.65%, 95% CI of 36.05–49.25%) (Fig. 5). There were significant differences, with cardiac anomalies being more frequent in females. Regarding the type of malformation, the incidence rates of cardiac anomalies related to formation, segmentation, and mixed defects were 40.76% (95% CI of 28.63–52.89%), 20.20% (95% CI of 12.75–27.65%), and 24.33% (95% CI of 10.53–38.14%), respectively (Fig. 6). Patients with formation defects showed a significantly higher incidence of cardiac anomalies than those with segmentation defects. Finally, the incidence of intraspinal anomalies with cardiac anomalies was 27.11%, (95% CI of 3.24–50.98%) (Fig. 7).

Fig. 5
figure 5

Forest plots showing the incidence among genders. Females showed a significant higher incidence of cardiac anomalies

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Fig. 6
figure 6

Forest plots showing the incidence among type of deformities. Formation defects showed the highest incidence followed by segmentation defects and mixed defects

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Fig. 7
figure 7

Forest plot showing the incidence of intraspinal anomalies associated with cardiac anomalies

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Discussion

This meta-analysis showed that the overall incidence of cardiac anomalies in patients with congenital scoliosis was 21.05%. It was also observed that females presented a higher incidence of cardiac anomalies. Regarding the type of malformation, those with formation defects showed a higher incidence of cardiac abnormalities. The regions with the highest incidence were Europe and USA, followed by China. Intramedullary anomalies were present in almost one-third of the patients with cardiac anomalies. The quality of the studies was consistent.

Many studies presented diagnoses of new cardiac anomalies through the protocol [5]. Therefore, the incidence could be underestimated in retrospective studies. Some of the patients diagnosed during the study were treated for the anomalies [5]. This highlights the importance of the diagnosis of cardiac anomalies. In addition, all studies used echocardiography, so training in this procedure is crucial. Furdock et al. [5] proposed to perform echocardiography in patients with mixed defects and congenital kyphosis [5]. Intraspinal defects were also associated with congenital kyphosis [13]. In our study, the formation defects presented a higher risk for cardiac anomalies. On the other hand, Reckles et al. [21] performed echocardiography on patients who were going to undergo surgery and found cardiac anomalies in 10% of these patients [21]. In our analysis, only three studies discussed whether patients with congenital scoliosis underwent surgery [5, 15, 16]. Bozcali et al. [16] also strongly recommended routine echocardiography for patients with idiopathic and congenital scoliosis [16]. Regarding whether cardiac anomalies represent a risk, the literature supports intraoperative and postoperative risks. Severe correction has been associated with cardiopulmonary decompensation. Renal anomalies have also been associated with metabolic disturbances [22].

In our study, it was observed that the females presented a higher incidence of cardiac anomalies, and formation defects were the most frequent associated defect. In a meta-analysis of the incidence and characteristics of intraspinal anomalies, no differences were observed in terms of gender or type of malformation [4]. The location could not be analyzed because it was not reported in the articles. Bollini et al. [15] observed that the incidence of cardiac anomalies were greater when the location of the deformity was the thoracic region [15]. In addition, the relationship between cardiac and intraspinal anomalies was well established. Bollini et al. [15] also established the relationship between cardiac abnormalities and urogenital, gastrointestinal, and ocular anomalies [15]. Sevencan et al. [19] observed that up to 57.9% of patients had associated intraspinal anomalies [19]. On the other hand, cardiopulmonary mortality increased due to the progression of untreated curves [23]. These cardiopulmonary changes caused by deformity, such as right ventricular alteration and cor pulmonale, negatively affect patients with cardiac anomalies, especially those affecting the right heart [23]. Some articles specified the type of risk for each anomaly. Patients with Fontan circulation showed altered coagulation, and patients with single ventricle defects showed increased bleeding due to higher venous pressures [8, 24, 25].

A prenatal diagnosis of anomalies could also be done. The mean incidence found in these articles was 25.97% (95% CI of 7.36–44.58%) [26,27,28,29]. Further, the most frequent anomalies were an abnormal cardiac axis, double-outlet right ventricle, tetralogy of Fallot, ASD, and VSD [26,27,28,29]. The incidence of valvular anomalies was lower in the diagnosis of prenatal cardiac anomalies than in the postnatal diagnosis included in our study. Therefore, efforts in postnatal ultrasound could be made to find or focus on this type of anomalies, especially mitral valve prolapse.

This study had several limitations. Maternal or familial risk factors could not be analyzed because they were not collected in the individual studies. In addition, there was high heterogeneity. On the other hand, the incidence data is determined by the practitioner’s ultrasound experience. Also, it is to be expected that children with a severe heart disease may die earlier and the incidence may be underestimated. Moreover, not all studies presented diagnostic algorithms. Some performed ultrasound on all children, some on those who were going to undergo surgery, and some on those who fulfilled certain characteristics; other studies did not specify.

Conclusion

The incidence rate of cardiac anomalies in patients with congenital scoliosis was 21.05%, with mitral valve prolapse being the most frequent. The incidence was higher in Europe. Cardiac anomalies increased in females and in those with formation defects. Future studies should focus on whether cardiac abnormalities actually increase the risk of spinal surgery. Further studies are also needed to stratify by type of deformity, identify which factors lead to an increased risk, and study maternal risk factors by region or according to different biomarkers linked directly to risk factors. This study could provide guidance to ultrasound practitioners in identifying the most frequent cardiac anomalies, facilitating their detection and diagnosis with greater accuracy.