Introduction

Diabetes mellitus is one of the most common medical problems worldwide. The World Health Organization has predicted that the prevalence of diabetes will increase by 35% by 2025.1 2 Women of Asian origin have more risk of developing diabetes. Now, gestational diabetes mellitus (GDM) is increasing and amounts to 17% in Asian women but only in 4% of American and European women.3 4 In southern India, the prevalence of GDM was 17% in urban women, 13.8% in semiurban, and 9.8% in rural.5

In the infants born to diabetic mother (IDM) the incidence of cardiac anomalies is 3 to 6% which is five times higher than nondiabetic pregnancy and most of the time it includes complex congenital heart disease.6 7 More frequently reported anomalies were conotruncal anomalies such as truncus arteriosus, tricuspid artesia (TA), and transposition of great arteries (TGA). The incidence of TGA in an overt diabetes mother is 17 times more than that of nondiabetic women.8 The closure of ductus and decrease in pulmonary pressure were delayed in infants of diabetic mothers compared with a normal neonate.9 10

Asymmetrical septal hypertrophy (ASH) seen in IDM is self-limiting with no clinical consequence and is a transient phenomenon which usually regresses within the first few months of life. Septal hypertrophy occurred even in a mother with good glycemic control, without relation to the type of diabetes.11 Lisowks et al reported an increased congenital heart disease (CHD) even with slightly elevated HbA1c in their study. Among the factors that may affect the prevalence and severity of cardiac malformation in fetuses of diabetic mothers, poorly controlled diabetic pregnancy has been associated with poorer cardiac function.7 8 17 18 As preconceptional maternal glycated hemoglobin is increased cardiac function is reduced.19

Materials and Methods

This cross-sectional study was conducted in the Department of Cardiology, Tirunelveli Medical College Hospital, over a period of one year (April 2017–March 2018) after obtaining ethical committee approval. Infants of diabetic mothers were screened for this study.

Inclusion criteria: All babies born to diabetic mother (both pregestational and gestational diabetic mother) were included. Pregestational—pregnant women who had diabetes before their pregnancy (known diabetic before pregnancy); gestational—pregnant women who had diabetes during their pregnancy (GDM) (nondiabetic before pregnancy).

Exclusion criteria: Babies born with features suggestive of chromosomal abnormality. Babies born to diabetic mothers as still birth and with other comorbidities like hypothyroidism, hypertension, anemia complicating pregnancy, and seizure disorder on antiepileptic drugs were excluded.

All babies satisfying the inclusion criteria were enrolled for study after obtaining informed consent. At first, a data sheet was completed for each newborn with the following information: maternal type of diabetes, treatment regimen, maternal glycemic control status, antenatal ultrasonogram, baby’s sex, birth weight, gestational age, and clinical features. Parameters used for glycemic control assessment was Hba1C. Values less than 6.5 were considered as good glycemic control and values more than 6.5 were considered as poor glycemic control.

All infants underwent a thorough physical examination with special attention to the cardiovascular system and the following investigations were done: oxygen saturation—by pulse oximetry, electrocardiogram, chest X-ray, and echocardiogram (ECG). Data were collected and recorded in the pro forma during the whole study period and entered in Microsoft Excel sheet and analyzed to identify the relation between maternal diabetes and cardiovascular abnormality among the IDM. The software used in this study for statistical analysis was SPSS software version 21.0 (IBM). Tests used for comparing mean were t-test and ANOVA (Analysis Of Variance). For comparing the relation between groups, Chi-square and Kruskal–Wallis tests were used.

Results

In the present study 100 diabetic mothers were included and their babies were screened for cardiac abnormalities. Among them, 17 mothers had pregestational diabetes and 83 mothers had gestational diabetes. Out of the 17 mothers with pregestational diabetes, 16 babies had cardiac abnormalities and 12 babies of the 83 mothers with gestational diabetes had echocardiography studies suggesting cardiac abnormalities. The ECHO abnormality was significantly more in the pregestational diabetes group (P value = 0.001) (Table 1).

Out of the 100 mothers, 93 had good glycemic control and 7 had poor glycemic control. In this study 21 babies born to mothers with good glycemic control and 7 babies born to mothers with poor glycemic control had cardiac abnormality (Table 2).

There was significant influence of maternal diabetes treatment regimen in the outcome of cardiac abnormality among IDM. Out of 100 diabetic mothers, 66 were on meal plan, 21 were on oral hypoglycemic agent (OHA) metformin, and 13 were on insulin therapy. Among 66 babies whose mothers were on the meal plan, 8 had cardiac abnormality. Of the 21 mothers on OHA, 7 babies had cardiac abnormality and 13 insulin taking mothers, 13 babies had cardiac abnormality (Table 3).

Out of the 100 IDM, 28 babies had cardiac disease, 5 babies had cyanotic heart disease, and 23 babies had acyanotic heart disease. Out of the 66 mothers on meal plan, 8 babies had cardiac abnormality and all the 8 babies had acyanotic heart disease—atrial septal defect (ASD) in 4, patent foramen ovale (PFO) in 3, patent ductus arteriosus (PDA) in 1. Among the 21 mothers on OHA metformin, 7 babies had cardiac abnormality and all the 7 babies had acyanotic heart disease—ASD in 1, ventricular septal defect (VSD) in 2, PFO in 1, PDA in 1, asymmetrical septal hypertrophy (ASH) in 2. But among the 13 mothers on insulin there were babies with acyanotic as well as cyanotic heart diseases, 5 babies had cyanotic congenital heart disease (CCHD—transposition of great arteries (TGA) in 2, hypoplastic left heart syndrome (HLHS) in 1, TA (1), truncus arteriosus (1) and 8 babies had acyanotic congenital heart disease (ACHD)—ASD in 1,VSD in 1,PDA in 1,ASH in 4, and PFO in 1 (Table 4).

Among the 100 IDM, 4 were small for gestational age (SGA), 80 were appropriate for gestational age (AGA), 16 were large for gestational age (LGA). ECHO abnormality was present in all groups. Out of the 100 babies admitted in the Neonatal Intensive Care Unit (NICU), 15 were with symptoms and 85 were asymptomatic. Among 15 symptomatic babies, 13 had cardiac abnormality and among the 85 asymptomatic babies, 15 had cardiac abnormality (Table 5).

Out of the 100 newborns taken in the study, 14 newborns had murmur and 86 newborns had no murmur. Out of the 14 newborn babies with murmur, 11 had ECHO abnormality. Out of the 86 newborn babies without a murmur, 17 had ECHO abnormality. All newborns with abnormal SpO₂ had cardiac abnormality, signifying the importance of SpO₂ monitoring (Table 6).

Discussion

GDM complicates 1 to 3% of all pregnancies. Different studies showed that congenital anomalies occur three to five times more commonly in the IDM than in the general population.12

In the present study, 100 IDM were subjected to ECG; of this, 28 (28%) babies had cardiac abnormality. Among them 5 babies had CCHD and 23 babies had ACHD. A similar study done on cardiovascular malformations in IDM by Meyer et al showed a lower incidence of 3.2 to 6.9 and a study by Tabib et al showed an incidence of 8.8%.13 14

Of the 100 IDM babies studied 17% of the mothers were found to have pregestational diabetes and 83% were found to have gestational diabetes. In this study 94% of babies born to mothers with pregestational diabetes had cardiac abnormality when compared with 14% babies born to mothers with gestational diabetes, which was a significant finding. Out of the 28 babies who showed cardiac abnormality, 16 babies (57%) were born to mothers with pregestational diabetes and 12 babies (43%) were born to mothers with gestational diabetes. Of the 16 babies born to mothers with pregestational diabetes, 11 babies (68.7%) had ACHD and 5 babies (31.3%) had CCHD. All the 12 babies born to mothers with gestational diabetes had acyanotic disease.

Mothers with pregestational diabetes who closely monitor and keep their blood sugar in the normal range at the time of conception and early in pregnancy have a much lower risk of having a baby with CHD. Currently the American Heart Association recommends that all pregestational diabetic women undergo a fetal ECG between 18 and 22 weeks of gestation to thoroughly assess the developing baby for the possibility of CHD.

In this study, among the 100 IDM babies, 93% of mothers had well-controlled glycemic status and 7% had poorly controlled glycemic status. ECHO abnormality was found to be more significant in babies born to mothers with poorly controlled diabetes with a preponderance of cyanotic heart disease. It showed that the mother’s glycemic status had a significant influence on cardiovascular anomalies, which is compatible with the studies done by Khan et al and Mekwana et al.15 16 Babies of mothers with poorly controlled glycemic status had poorer cardiac function.17 18

Increase in blood sugar levels in the mother leads to high blood sugar in the developing fetus, thus creating an abnormal biochemical environment which will have negative impact on genes responsible for normal development. The types of congenital heart defects associated with maternal diabetes are known to form very early in pregnancy.

In this study with 100 IDM babies, 14 babies presented with a murmur, 5 babies with low SpO₂, and 3 babies with external congenital anomalies like polydactyl and cleft palate. Of the 14 babies with murmur, 11 babies (78%) had ECHO abnormality and all babies with low SpO₂ and external congenital anomalies had ECHO abnormality. IDM babies whose X-rays showed cardiomegaly (9%) had ECHO abnormality more of septal hypertrophy. Abnormal ECG was found in 8 babies out of the 100 examined and all had ECHO abnormality more of septal hypertrophy, ASD, and TGA.

In acyanotic heart diseases, ASH was detected more than other cardiac abnormalities. On studying the relation between the type of heart lesion and maternal diabetes, septal hypertrophy was more in pregestational diabetic mother (7 out of 17) followed by ASD (3), VSD (2), and PDA (1). This was in concordance with the previous studies done by Tabib et al and Zielinsky et al.14 19

Babies born to pregestational diabetic mothers showed more cyanotic heart disease, TGA (2), TA (1), truncus arteriosus (1), and HLHS (1), and babies born to GDM mothers had more acyanotic heart disease. On studying the relationship between maternal diabetes and treatment plan, babies whose mothers were on insulin had several ECHO abnormality. Of which, 5 babies had cyanotic heart disease—TGA (2), HLHS (1), tricuspid atresia (1), and truncus arteriosus (1). Babies whose mothers were on meal plan also had cardiac abnormality but of acyanotic heart disease—ASD (4), PFO (3), and PDA (1). Mothers with OHA treatment had ECHO abnormality of ASD (1), VSD (2), PFO (1), PDA (1), and ASH (2).

Based on diabetic control, babies born to mothers with poor glycemic control, had significant ECHO abnormality with more incidence of cyanotic heart disease—TGA (2), TA (1), HLHS (1), truncus arteriosus (1), and acyanotic heart disease—ASH (1) and ASD (1). Most of the babies born to well-controlled mothers had more of acyanotic heart disease, with increased ASH (6), PFO (4), VSD (4), PDA (3), and ASD (4).

Conclusion

CHD is more common among IDM. Among CHD, acyanotic heart disease was more common than cyanotic heart disease. Among acyanotic heart disease ASH was more common than ASD, VSD, PDA, and PFO. Among the cyanotic heart disease, transposition of great arteries, HLHS, tricuspid atresia, and truncus arteriosus were more common.

A better understanding of the clinical impact of the maternal hyperglycemic status on offspring’s health early in life is needed to form strategies for the prevention of cardiovascular disease in IDM. A long-term follow-up of children is mandatory for further assessment of their cardiovascular health.