The Frequency of Cardiac Complications in Infants of Diabetic Mothers in NICU; A Cross Sectional Prospective Study

Introduction

Infant of a diabetic mother (IDM) is defined as a neonate born to mother who had diabetes mellitus, but this term refers specifically to the neonate born to a woman who had persistently elevated blood sugar during pregnancy [1]. Women with diabetes in pregnancy (type 1, type 2 and gestational) are at increased risk for adverse pregnancy outcomes. Adequate glycemic control before and during pregnancy is crucial to improving outcome [2].

Congenital cardiovascular defects are one of the prevalent groups of birth anomalies; roughly affecting 6–8 babies per 1000 live births. The cause of cardiovascular defects is usually not known but some are genetic while few have an environmental etiology. About 1 out of 100 of these cases is due to some maternal disease. [3] In Europe, while estimating the causes of neonatal mortality 10.4% of these infants had a congenital heart disease. It was seen that neonatal mortality rate decreased due to increasing termination of pregnancy and survival after cardiac surgeries [4]

Infants of diabetic mother are more prone to develop congenital anomalies and defects. Overall risk of development of congenital malformations increases by 2-12% compared to normal neonates, most frequent being the congenital heart disease (CHD) and poly-malformation syndrome [5]. Frequency of CHD in IDM babies is about 5%, Most frequent ones are ventricular septal defect (VSD), transposition of great arteries (TGA), aortic stenosis, truncus arteriosus and double outlet right ventricle [6].The neonatal mortality rate is >5 times that of infants of non- diabetic mothers and is higher at all gestational ages and in every birth weight for gestational age category [7].

Aim of the work: To evaluate the frequency of cardiac complications in infants of diabetic mothers in our NICU unit as well as the effect of diabetes control on them.

Methods

This study was a cross sectional prospective study conducted at neonatal intensive care units (NICU) of pediatric department at Al-Azhar Assuit university hospital, Minia health insurance hospital and Minia university hospital between January 2021 and June 2021. The study included 60 neonates subdivided into two groups as follow: Group I (30 cases): Included infants of diabetic mothers with a diagnosis of congenital heart disease. Group II (30 controls): Included normal healthy infants of non-diabetic mothers.

Inclusion criteria: All newborn to diabetic mother admitted to NICU either preterm or full term & male or female.

Exclusion criteria: Any infant of non-diabetic mother.

All participants were subjected to the following: Thorough history taken included: Maternal dietetic history, occupation, and consanguinity. Neonatal history included gender, gestational age, presence of pre-gestational or gestational diabetes, ante-natal steroids, mode of delivery, and birth weight. Physical examination of infant included: Birth-weight, general condition, neonatal reflexes, vital signs, assessment of the degree and severity of respiratory distress if present, cardiovascular, abdominal and extremities examination.

Investigation: Complete blood count (CBC), C-reactive protein (CRP), and random blood glucose (RBS) and chest X ray (for the presence of cardiomegaly, RDS or any other abnormalities).

Echocardiography examination was performed by a pediatric cardiologist for all the study participants. The examination was consisted of M-mode, 2-D, pulsed, continuous wave and color Doppler blood flow velocity measurements of the heart valves. Echocardiographic assessment was to document presence of pulmonary hypertension as well as presence of patent foramen oval (PFO) and/or patent ductus arteriosus (PDA), to detect other congenital heart diseases, to evaluate chamber enlargement and pulmonary artery dilation and to evaluate ventricular function as well.

Ethical considerations

This study’s protocol was accepted by the Ethical Committee of the Faculty of Medicine, Al-Azhar, and corresponded with the provision of the Declaration of Helsinki in 1964 and its later amendments or comparable ethical standards. Informed signed consent was collected from the parents of each neonate before their inclusion in the study

Statistical analysis

Quantitative data were presented as mean+ standard deviation (SD), while qualitative data were demonstrated as frequency and percent (%). The significance of comparison between mean values of two groups was evaluated by Student’s t-test for continuous normally distributed variables. Categorical data were assessed by chi-square test and Independent-Samples Mann-Whitney U Test. The significance of comparison between more than two groups was performed by analysis of variance for parametric continuous variables. Significant differences were denoted by p < 0.05. Statistical analysis was performed using the Statistical Software Package SPSS 23 (SPSS, Inc., Chicago, IL).

Results

During the study period a total of 60 neonates were enrolled in the study who were subdivided into two groups as follow: Group I (30 cases): Included infants of diabetic mother with a diagnosis of congenital heart disease. Group II (30 controls): Included normal healthy infants of diabetic mother.

Table 1 showed   statistically significant increase in the neonatal weight in group I compared to the control group II (p<0.001). The assessment of studied patients revealed that the number of known diabetic women was significantly higher in group I compared to group II that show increase prevalence of women with gestational diabetes (p= 0.02).

Table 2 demonstrates the echocardiographic findings in infants in group I as follow: Patent ductus arteriosus (PDA) [46%], Patent foramen ovale (PFO) [40%], hypertrophic cardiomyopathy (HCMP) [30%], ventricular septal defect (VSD) [20%], and atrial septal defect (ASD) [20%].

Table 3 illustrates the relation between glycemic control and echocardiographic findings in group I. (Table 4) showed  the comparison between the studied groups regarding complications and mortality. Regarding birth injury, one case had shoulder dystocia, brachial plexus injury (Erb’s paralysis) and cephalohematoma respectively while 2 cases had fracture clavicle in group I.

There were 21 (70%) diabetic mothers in group I had babies with hypoglycemia compared to 15 (50%) diabetic mothers in group II with no statistically significant difference between them. In group I, 4 (13.3%) cases had polycythemia. One (3.3%) case died due to pulmonary hypertension in group I.

Figure 1 showed   some clinical and echocardiographic findings in group I. 70% infants had hypoglycemia, 73.3% had respiratory distress, 36.7% had jaundice, 50% had plethora, 86.7% infants had murmur, 20 % had ASD, 46.7% had PDA, and 40 % had PFO.

Figure 2 demonstrated the significant difference between the study groups regarding neonatal blood glucose levels (P = 0.025). Our results showed that there was statistically significant increase in the hematocrit level in group I who had infant with congenital heart disease compared to the control group (group II) [47.9 ± 2.68 43.7 ± 2.20, respectively; p = 0.001] as shown in (Figure 3). Pulmonary artery systolic pressure was significantly higher in uncontrolled diabetic compared to controlled diabetic cases (P <0.001) as shown in (Figure 4).

Discussion

Cardiovascular abnormalities in infants of diabetic mothers occur either as congenital heart diseases (3–5%) or cardiomyopathy (10–20%) [8]. Our results showed no significant difference between the two studied groups regarding the treatment methods used in diabetes. None of the studied women in control group had hypertension or cardiac diseases while in group I there was one female had hypertension and cardiac diseases with no statistically significant difference between the two groups. Our results were supported by three meta-analyses conducted by Lisowski et al., [9], Simeone et al., [10] & Hoang et al. [11] as they demonstrated that there were associations between maternal DM and CHDs. As regard assessment of clinical and echocardiographic findings in group I. 70% infants had hypoglycemia, 73.3% infants had respiratory distress, 36.7% infants had jaundice, 50% had plethora, and 86.7% infants had murmur. 66.7% infants had ASD, 93.3% infants had PDA and 93.3% infants had PFO. On comparison of the hematocrit levels between group I and group II, there was statistically significant increase in the hematocrit level in group I compared to the control group (group II). These results were similar to the study done by Metzger et al., [12] who reported that IDMs have higher levels of hematocrit levels and this could be explained by the positive effect of fetal insulin on erythropoiesis.

In addition, there was statistically significant decrease in blood glucose level in infants in group I compared to those in the control group and this agrees with Mimouni et al., [13] who showed that the prevalence of hypoglycemic episodes in IDMs is as high as 40% when compared with the control group. This metabolic risk is believed to be due to the relative fetal hyperinsulinism, manifested as a feedback mechanism for the balance of the high glucose levels induced by the maternal diabetes [14].

The present study demonstrated that The frequency and patterns of different cardiac malformations in neonates in the two groups as follows: 14 cases of Patent ductus arteriosus (PDA), 12 cases of Patent foramen ovale (PFO), 9 cases of hypertrophic cardio-myopathy (HCMP), 6 cases of ventricular septal defect (VSD), 6 cases of atrial septal defect (ASD) was detected in a fetus of group I. There was statistically increase in pulmonary artery systolic pressure in group I who had infant with congenital heart disease compared to control group (group II). Our results were supported by study of Shankar et al., [15], as they reported that the most common cardiac anomalies in infants of diabetic mothers were PDA, PFO, and hypertrophic cardiomyopathy. The prevalence of cardiovascular anomalies for all types of malformations in infants born to diabetic mothers is 42.8% and the incidence of other diseases, such as ventricular septal defect, atrial septal defect, displacement of mediastinal great vessels and valve atresia, is estimated at 11.4%.

Abu-Sulaiman and Subaih, [16], demonstrated that he most common echocardiographic findings were patent ductus arteriosus (PDA; 70%), patent foramen ovale (68%), atrial septal defect (5%), small muscular ventricular septal defect (4%), mitral valve prolapses (2%), and pulmonary stenosis (1%). Hypertrophic cardiomyopathy (HCMP) was observed in 38% of cases, mainly hypertrophy of the interventricular septum. Severe forms of CHD encountered were D-transposition of great arteries, tetralogy of Fallot, and hypoplastic left heart syndrome (1% each). Isolated aortic stenosis and coarctation of aorta were not encountered in this series. Overall incidence of congenital heart disease was 15% after excluding PDA and HCMP.

As regard relation between the glycemic control and cardiac findings in group I. It was found that incidence of HCMP, VSD and pulmonary artery systolic pressure (PASP) was significantly higher in uncontrolled diabetic compared to the controlled diabetic cases. Also, severity of tricuspid regurge was significantly increased in uncontrolled diabetic cases compared to controlled diabetic cases (P= 0.003). On the contrary, incidence of PDA was significantly lower in uncontrolled diabetic cases compared to controlled diabetic cases (P= 0.011). There was no statistically significant difference between controlled and uncontrolled group regarding PFO, ASD and mitral regurge incidence. Our results were supported by study of Sobeih et al., [17].

The current study showed that regarding birth injury, one case had shoulder dystocia, brachial plexus injury (Erb’s paralysis) and cephalhematoma respectively while 2 cases had fracture clavicle in group I. There were 20 (66.7%) diabetic mothers in group I had babies with hypocalcemia compared to zero cases in diabetic mothers in group II with high statistically significant difference between them (p<0.001). There were 21 (70%) diabetic mothers in group I had babies with hypoglycemia compared to 15 (50%) diabetic mothers in group II with no statistically significant difference between them. In group I, 4 (13.3%) cases had polycythemia. One (3.3%) case died due to pulmonary hypertension in group I.

Conclusions

The incidence of cardiovascular anomalies in infants of diabetic mothers is significantly higher than in the infants of non-diabetic mothers also the incidence of cardiac complication is higher in infants of poor controlled diabetic mother than in those of controlled mothers, so early diagnostic procedures can lead to better supportive care for infants of diabetic mothers.