Population included in the study
For this study, 77 patients with CHD not surgically or interventionally corrected were evaluated as can be seen in figure 1.
The patients included in the study came from different areas of the country, with a wide spread (counties highlighted in blue in figure 2), covering almost the entire surface of Romania.
The age of the children included in the study was between 3 weeks and 5 years, following a non-Gaussian distribution, with the predominance of infants, as can be seen in figure 3.
Patients were dichotomized into two groups based on peripheral blood oxygen saturation (SpO2): the cyanotic group (SpO2<95%) and the non-cyanotic group (SpO2>=95%), as shown in figure 4 and 5.
Children with different types of CHD were included in the study, the most common of which were ventricular septal defects in the non-cyanotic group and tetralogy of Fallot in the cyanotic group (figure 5).
From the point of view of the gender distribution of the patients in the studied group, the batch was balanced with a ratio of male:female=1:1 (52% males, 48% females).
From the point of view of the environment of origin, the rural environment (57%) slightly predominated over the urban environment (43%).
The patients included in the study were selected based on the inclusion criterion "understands the Romanian language". However, the study also included other ethnic groups besides the Romanian, namely Roma, Hungarian and others (e.g. Turkish), as can be seen in fig.6.
In 6 families (7.6%) there were congenital malformations such as congenital single kidney, anorectal malformation, limb malformations or history of pathologies such as muscular dystrophy and infantile paralysis. In another 6 families (7.6%) there were CHD in the familial antecedents (aortic pathology, septal defects, persistent arterial duct). In 36 cases (45.5%) CHD occurred in the first child in the family, and the rest were recorded in subsequent pregnancies. During the course of the pregnancy, in 10 cases (12.6%) there were complications such as intrauterine dead twin, intrauterine growth retardation, maternal thrombophilia, maternal infections (urinary tract infection, SARS COV 2 infection, vaginitis), hypertension and maternal cholestasis.
Anamnestic, neonatal, clinical and laboratory characteristics of the patients
The anamnestic, neonatal, clinical and laboratory characteristics of the patients included in the study are represented in the table 1. Based on the analyzed characteristics, we demonstrated that the two samples from the population included in the study (non-cyanotic CHD and cyanotic CHD) were uniform. Statistically significant differences were found only between the level of hemoglobin oxygen saturation and the level of hemoglobin, consistent with the diagnosis of cyanotic or non-cyanotic CHD. Hospitalization in neonatal intensive care was more frequent in the group with cyanotic CHD, basically only for monitoring and not for specific interventions.
Table 1. The anamnestic, clinical and laboratory characteristics of the patients
Characteristics
|
Non-cyanotic CHD (n=46)
|
Cyanotic CHD (n=31)
|
P value
|
Anamnestic characteristics
|
|
|
|
Congenital malformations in the family (no/yes)
|
43/3
|
28/3
|
0.61
|
Congenital cardiac malformations in the family (no/yes)
|
42/4
|
27/4
|
0.55
|
Maternal age at birth (years)
|
28.4 ± 5.7
|
28.7± 6.4
|
0.82
|
Paternal age at birth (years)
|
31.9 ± 5.2
|
33.2± 8.6
|
0.4
|
Children in the family (single/multiple)
|
24/22
|
12/19
|
0.24
|
In vitro fertilization (no/yes)
|
43/3
|
30/1
|
0.52
|
Prenatal CHD diagnosis (no/yes)
|
34/12
|
18/25
|
0.14
|
Pregnancy evolution (physiological/pathological)
|
38/8
|
23/8
|
0.37
|
Child rank (first/not first)
|
25/21
|
11/20
|
0.1
|
Environment of origin (Urban/Rural)
|
21/25
|
13/18
|
0.74
|
Neonatal characteristics
|
Gestational age (weeks)
|
38.2 ± 1.6
|
38.4 ± 1.9
|
0.4
|
Apgar score
|
9
|
9
|
0.23
|
Birth weight (g)
|
3049 ± 459
|
3123±706
|
0.58
|
Length at birth (cm)
|
50.1 ± 6
|
50.6 ± 5
|
0.74
|
Type of birth (vaginal/caesarean section)
|
18/28
|
15/16
|
0.42
|
Neonatal intensive care admission (no/yes)
|
40/6
|
21/10
|
0.04
|
Prostaglandin administration (no/yes)
|
45/1
|
27/4
|
0.06
|
Inotropic administration (no/yes)
|
46/0
|
29/0
|
|
Neonatal complications (no/yes)
|
39/7
|
26/4
|
0.82
|
Neonatal intubation (no/yes)
|
46/0
|
28/2
|
0.07
|
Feeding (breast milk/formula/mixed)
|
14/24/7
|
13/11/7
|
0.38
|
Clinical characteristics
|
Sex (M/F)
|
26/20
|
14/17
|
0.32
|
Age (months)
|
12.5 ± 15
|
10.9 ± 6
|
0.33
|
Weight (kg)
|
7.84 ± 3.6
|
8.06 ± 1.9
|
0.08
|
Height (cm)
|
70. ± 14.9
|
72.03 ± 6.9
|
0.26
|
Head circumference (cm)
|
43.6 ± 4.6
|
45.1 ± 5.1
|
0.13
|
Saturation (%)
|
97 ± 1
|
83 ± 7
|
<0.0001
|
Paraclinical characteristics
|
Hemoglobin (g/dl)
|
11.7 ± 1.4
|
14.1 ± 2.7
|
<0.0001
|
Albumin (g/dl)
|
4.4 ± 0.4
|
4.3 ± 0.4
|
0.39
|
pH
|
7.4 ± 0.05
|
7.4 ± 0.05
|
0.07
|
Data are represented as mean ± SD, median, percentage (%) or n (total number).
Abbreviations: CHD=congenital heart defect;
Results of preoperative psychomotor development assessment
The evaluation of the psychomotor development revealed that children included in the study, considered normally developed following the clinical examination, presented a delay in the neurological development after being evaluated with the aid of the Denver test: 97% of those with cyanotic CHD and 54% of those with non-cyanotic CHD as can be seen in the figure 7.
For each patient, following the Denver test, 4 domains were evaluated (personal-social, fine motor, language, gross motor), specific levels of development were determined (basic level, passing level, high level, top level of development) and functional estimates were calculated (functionality score, development score) both in the group with non-cyanotic CHD and in the group with cyanotic CHD. A delay in psychomotor development was observed in a high percentage of cases, as shown in figure 8 and figure 9. Patients with non-cyanotic CHD registered developmental delay in a percentage varying between 16-73%. Patients with cyanotic CHD registered developmental delay in a percentage varying between 42-85%. Gross motor and personal-social domains were the most affected in both groups.
Regarding development scores represented in the table 2, they were lower in the cyanotic group but without statistically significantly difference.
Table 2: Development scores – comparison between the group with non-cyanotic CHD and the group with cyanotic CHD
Domain
|
Non-cyanotic CHD
|
Cyanotic CHD
|
P value
|
Personal-social DS
|
0.91 ± 0.4
|
0.92 ± 0.3
|
0.83
|
Fine-motor DS
|
1.25 ± 0.7
|
1.11 ± 0.3
|
0.81
|
Language DS
|
1.45 ± 1
|
0.94 ± 0.3
|
0.14
|
Gross-motor DS
|
0.8 ± 0.3
|
0.81 ± 0.2
|
0.93
|
Global DS
|
1.1 ± 0.6
|
0.94 ± 0.2
|
0.35
|
Abbreviations: CHD=congenital heart defect; DS=developmental score
General development and functionality scores were also calculated, which were lower in the group with cyanotic CHD, but the difference did not reach statistical significance (p=0.35), as can be seen in figure 10.
Factors that correlate with psychomotor development
It was checked which of the factors listed in the table 3 correlates with neurological development and a statistically significant correlation was obtained for the prenatal diagnosis (p=0.012) and for the type of diet (p=0.008).
Table 3: Correlation between psychomotor development and diverse factors
Characteristics
|
Correlation coefficient
|
Confidence interval
|
p value
|
Anamnestic characteristics
|
|
|
|
Congenital malformations in the family (no/yes)
|
0.07
|
-0.34-0.49
|
0.72
|
Congenital cardiac malformations in the family (no/yes)
|
0.17
|
-0.19-0.53
|
0.35
|
Maternal age at birth (years)
|
0.01
|
-0.003-0.03
|
0.1
|
Paternal age at birth (years)
|
0.01
|
-0.001-0.033
|
0.07
|
Children in the family (single/multiple)
|
0.02
|
-0.19-0.25
|
0.81
|
In vitro fertilization (no/yes)
|
0.16
|
-0.34-0.66
|
0.52
|
Prenatal CHD diagnosis (no/yes)
|
0.33
|
0.06-0.53
|
0.012
|
Pregnancy evolution (physiological/pathological)
|
0.19
|
-0.080.46
|
0.16
|
Child rank (first/not first)
|
-0.02
|
-0.25-0.2
|
0.82
|
Environment of origin (Urban/Rural)
|
0.03
|
-0.19-0.26
|
0.75
|
Neonatal characteristics
|
Gestational age (weeks)
|
-0.02
|
-0.08-0.04
|
0.45
|
Apgar score
|
0.002
|
-0.13-0.12
|
0.91
|
Birth weight (g)
|
0.0001
|
-0.0003-0.00005
|
0.14
|
Length at birth (cm)
|
0.04
|
-0.02-0.01
|
0.68
|
Type of birth (vaginal/caesarean section)
|
0.19
|
-0.02-0.42
|
0.08
|
Neonatal intensive care admission (no/yes)
|
0.16
|
-0.16-0.39
|
0.41
|
Prostaglandin administration (no/yes)
|
0.00003
|
-0.45-0.46
|
0.99
|
Inotropic administration (no/yes)
|
-
|
-
|
-
|
Neonatal complications (no/yes)
|
0.58
|
-0.06-0.56
|
0.12
|
Neonatal intubation (no/yes)
|
0.4
|
-0.29-1.1
|
0.25
|
Feeding (breast milk/formula/mixed)
|
0.19
|
0.05-0.34
|
0.008
|
Clinical characteristics
|
Sex (M/F)
|
-0.1
|
-0.33-0.11
|
0.33
|
Age (months)
|
-0.002
|
-0.01-0.006
|
0.57
|
Weight (kg)
|
-0.01
|
-0.05-0.02
|
0.4
|
Height (cm)
|
-0.003
|
-0.01-0.006
|
0.49
|
Head circumference (cm)
|
-0.01
|
-0.03-0.01
|
0.3
|
Cyanosis (no/yes)
|
0.13
|
-0.09-0.36
|
0.24
|
Saturation (%)
|
-0.009
|
-0.2-0.004
|
0.18
|
Paraclinical characteristics
|
Hemoglobin (g/dl)
|
0.03
|
-0.009-0.08
|
0.11
|
Albumin (g/dl)
|
0.02
|
-0.27-0.32
|
0.87
|
pH
|
-0.25
|
-2.24-1.73
|
0.79
|
The multivariate analysis of these variables in relation to neurological development did not reveal statistically significant results.