European Journal of Cardiovascular Medicine

Diabetes during pregnancy can either be gestational diabetes mellitus (GDM) or pregestational diabetes mellitus. Gestational diabetes arises during pregnancy, typically resolving or persisting after delivery, while pregestational diabetes exists prior to conception. The prevalence of impaired glucose tolerance during pregnancy ranges between 3% and 10%, with the rate varying depending on the overall prevalence of diabetes in the population. The risk of complications associated with diabetes during pregnancy is significant, particularly regarding congenital malformations and the health of the foetus.1,2

Cardiovascular malformations are among the most common congenital defects observed in infants of diabetic mothers. These defects occur in 3% to 9% of diabetic pregnancies, with the incidence being 2.5 to 10 times higher compared to normal pregnancies. If the mother develops gestational diabetes and insulin resistance during the third trimester, the risk for major cardiovascular defects increases significantly. This heightened risk can have long-term implications for the health of the newborn and necessitates careful management of the mother's condition throughout pregnancy. 3,4

The foetal heart is particularly vulnerable to the effects of maternal diabetes, whether pregestational or gestational, through a complex, multifactorial pathogenesis. This pathogenesis can negatively affect both the structure and function of the foetal heart, as well as the feto-placental circulation. Factors such as the type of diabetes the mother has, her HbA1c level early in pregnancy, the degree and duration of hyperglycaemia, and the presence of hyperketonaemia all play a crucial role in determining the severity of foetal cardiac damage. The timing and control of maternal glucose levels during pregnancy are therefore essential in mitigating the risks to the developing foetus. 5-7

Even with strict maternal glycaemic control, hyperglycaemia remains teratogenic during critical periods of organogenesis, the phase when the foetus is undergoing crucial developmental processes. The effects of maternal hyperglycaemia during this time can lead to diabetic fetopathy, a condition that can cause glucose-mediated disturbances. These disturbances include abnormal left-right patterning of the developing heart, congenital cardiac malformations, foetal cardiomyopathy, foetal venous thrombosis, and alterations in placental villi vascularization. Additionally, maternal diabetes can lead to pathological foetal heart rates, further complicating the pregnancy. 8,9

The teratogenic effects of hyperglycaemia on the foetal heart highlight the importance of early and effective management of diabetes during pregnancy. It is crucial for expectant mothers with diabetes to maintain optimal blood glucose levels, particularly during the first trimester when organogenesis occurs. Even slight deviations from the target glucose levels can significantly increase the risk of foetal abnormalities, including congenital heart disease. As a result, routine monitoring and interventions aimed at controlling blood sugar are essential for minimizing the risks of foetal cardiac malformations and other complications associated with maternal diabetes.10,11

Maternal diabetes, whether gestational or pregestational, poses a significant risk to the foetus, particularly regarding the development of cardiovascular malformations. The pathophysiology behind these risks is complex, involving a combination of maternal glucose levels, the timing of hyperglycaemia, and the overall health of the mother. While strict glycaemic control can mitigate some of these risks, the potential for teratogenic effects during critical periods of foetal development underscores the need for vigilant management of diabetes during pregnancy. This management should include close monitoring of blood glucose levels, early screening for congenital heart defects in infants of diabetic mothers, and appropriate interventions to reduce the risk of adverse outcomes for both mother and child.12-14

In this context, this study was conducted with objective to study neonates born to mothers with diabetes mellitus to detect the spectrum of congenital heart disease (CHD).

This retrospective observational study was conducted in Kempegowda Institute of Medical Sciences Hospital and Research Centre. Participant details were obtained from the hospital records, and 56 infants born to diabetic mothers (pre gestational and gestational diabetic mother) were included in the study.

Study Population

The study population was categorized based on several factors: maternal age (<20, 20-30, >30 years), type of diabetes (gestational Diabetes Mellitus or pregestational diabetes), treatment (oral hypoglycaemic agents or insulin), mode of delivery (natural labour or caesarean section), baby's sex (male or female), birth weight, and echocardiogram results.

2D echocardiography reports of 56 babies were studied, out of which 9 babies had a normal ECHO and heart defects were seen in 47 cases. Among these, atrial septal defect (ASD) alone was the most observed anomaly, present in 33 cases (58.9%). Patent ductus arteriosus (PDA) was noted in 9 cases (16.0%). Ventricular septal defect (VSD) alone was seen in 2 cases (3.6%), while a combination of PDA and ASD was also found in 2 cases (3.6%). Additionally, one case (1.8%) exhibited both VSD and ASD.

Table 1: Descriptive data of mother:

Most mothers were aged 20–30 years (78.6%) and had gestational diabetes (83.9%), with metformin being the most common treatment (71.4%). LSCS was the predominant mode of delivery (82.1%), female babies were slightly more common (55.4%), and majority of newborns had a birth weight between 2.5–3.99 kg (71.4%).

Table 2: Association of Parity, Mode of Delivery, Type of Diabetes Mellitus, and Treatment with 2D ECHO Findings:

                    P-values are calculated using Fisher’s Exact Test

Table 3: Mother age vs. Heart defect:

                             Chi-Square Tests

Among 56 cases, heart defects were more common in mothers aged 20–30 years (47 cases) than those over 30 (9 cases), with ASD being the most frequent defect. Statistical analysis showed no significant association between maternal age and type of heart defect (Fisher’s Exact Test, p = 0.314).

Table 4: GA vs Heart defeat:

Out of 56 cases, majority of heart defects were observed in neonates born at 29–36 weeks of gestation (43 cases) compared to 13 cases at 37–40 weeks, with ASD being the most common anomaly in both groups. Statistical analysis showed no significant association between gestational age and type of heart defect (Fisher’s Exact Test, p = 0.719).

Table 5: Type of DM vs Heart defeat:

Among the 56 cases, heart defects were seen in 33 out of 47 cases of mothers with GDM, opposed to those with pregestational diabetes showing 8 cases with heart defects out of 9, with ASD being the most common defect in both groups. However, the association between type of diabetes and heart defects was not statistically significant (Fisher’s Exact Test, p = 0.418).

In our study of 56 infants born to diabetic mothers, 16% had normal 2D echocardiography findings, while atrial septal defect (ASD) was the most common heart defect (58.9%), followed by patent ductus arteriosus (PDA) in 16%, ventricular septal defect (VSD) in 3.6%, and combined lesions of PDA with ASD and VSD with ASD in 3.6% and 1.8%, respectively. Most mothers were aged 20–30 years (78.6%) and diagnosed with gestational diabetes mellitus (83.9%), treated predominantly with metformin (71.5%) or insulin (28.5%). Caesarean section was the most common delivery mode (82.1%), and 55.4% of infants were female. Birth weights ranged from 2.5 to 3.99 kg in 71.4% of cases. These findings are comparable to a prospective study by Eisa RA & Babiker MS, 2019 involving 356 children in Saudi Arabia, which reported PDA (47.5%) and ASD (41.9%) as the most frequent congenital heart defects. Although ASD was more prevalent in our study, both the studies emphasize the clinical relevance of these anomalies in diabetic pregnancies.15 This also correlates with a study done by Shankar P et al, 2019 where they found that the most common cardiac anomaly in infants of diabetic mothers was PDA.16  Also, Dawid G et al, 2006 in a Polish study found that 38.1 % of infants born to diabetic mothers showed the presence of an ostium secundum ASD.17 Dominic B et al studied the spectrum of congenital heart diseases in infants of diabetic mothers, and their findings were that out of those infants with heart defects, 50% were ASD and the rest were VSD.18 Both these studies correspond with our findings of high incidence of ASD in infants born to diabetic mothers. On the contrary, Algosaddi MA et al, 2023 did a retrospective study in which 2079 mothers and their infants were enrolled. They found that PDA was the most common echocardiography finding (38.3%) followed by hypertrophic cardiomyopathy and ventricular septal defect. While our study did find PDA to be among the common findings, VSD was rare, and we did not record any case of hypertrophic cardiomyopathy.19

In our study of 56 cases, 47 exhibited acyanotic congenital heart defects (ACHD) on 2D ECHO, while 9 were normal. Among the cases, 31 mothers were primigravida and 25 were multigravida, with no significant association between parity and heart defects (p=1.000). Mode of delivery showed 34 ACHD cases born via caesarean section and 7 via vaginal delivery, also without significant difference (p=1.000). Regarding diabetes type, 33 ACHD cases were born to mothers with gestational diabetes mellitus (GDM) and 8 to mothers with Pregestational DM diabetes, showing no significant association (p=0.235). Treatment patterns included 32 mothers treated with metformin, 9 with insulin, with no statistically significant relationship to heart defects (p=0.108). These findings partially align with the study by Sikarwar R & Hatkar PA 2019, who evaluated 80 diabetic and gestational diabetic pregnant women with foetal 2D echocardiography and reported a low incidence of congenital heart disease, identifying three foetal cases with defects including TAPVC, VSD, and right atrial enlargement, with postnatal confirmation for two of these anomalies.20 Although their sample was larger, they also found that foetal echocardiography is essential for antenatal detection of CHD in diabetic pregnancies but highlighted limited association between maternal diabetes type and CHD incidence.

In our study, out of 56 cases involved, 47 mothers were aged 20–30 years and 9 were over 30, with no statistically significant association found between maternal age and the type of congenital heart defect (CHD) (Pearson Chi-Square p=0.345; Fisher’s Exact Test p=0.314). Among younger mothers, normal 2D ECHO was observed in 8 babies, while ASD was the most frequent defect (26 cases), followed by PDA (9), VSD (1), PDA with ASD (2), and VSD with ASD (1). In mothers over 30, 1 baby had normal findings, 7 had ASD, and 1 had VSD. These results differ from a study by Thomas W. Rowland et al, which analysed 470 infants of diabetic mothers, revealed a 4 percent incidence, with most common findings being transposition of great arteries, ventricular septal defects and coarctation of aorta.21

Our study involved 56 infants, out of which 43 were born between 29–36 weeks of gestation and 13 between 37–40 weeks. Among the preterm group (29–36 weeks), 7 had normal echocardiographic findings, while 26 had atrial septal defect (ASD), 7 had patent ductus arteriosus (PDA), 1 had ventricular septal defect (VSD), 1 had PDA with ASD, and 1 had VSD with ASD. In the term group (37–40 weeks), 2 infants had normal findings, 7 had ASD, 2 had PDA, 1 had VSD, and 1 had PDA with ASD. Statistical analysis showed no significant association between gestational age and the type of heart defect observed (Pearson Chi-Square p=0.631; Fisher’s Exact Test p=0.719). This is comparable to a study by Chu PY, et. al; 2016, which highlights that ASD and VSD are among the most common congenital cardiac lesions in preterm. 22 Our study supports the frequency of these defects in early gestational ages but does not establish a gestational-age-based predisposition in infants of diabetic mothers.

A systematic review done by Chen L, et. al; 2019 revealed that infants born to mothers with diabetes had a significantly higher risk of congenital heart disease. They also found that this risk was significantly higher among mothers who had pregestational diabetes mellitus than those who had gestational diabetes. The most common phenotypes of heart disease found by them was double outlet right ventricle and tricuspid atresia, which we did not see in our study, but the other common presentation of atrial septal defect correlates with our findings.23

In our study of 56 infants born to diabetic mothers, 47 were from pregnancies complicated by gestational diabetes mellitus (GDM) and 9 from Pregestational diabetes. Among them, 9 infants—all from the GDM group—had normal echocardiographic findings. Atrial septal defect (ASD) was observed in 26 infants of GDM mothers and 7 of Pregestational DM diabetes mothers, while patent ductus arteriosus (PDA) was seen in 8 infants of GDM mothers and 1 infant of an Pregestational DM diabetes mother. Ventricular septal defect (VSD) occurred in 1 infant from each group. Combined defects of PDA with ASD were identified in 2 infants from the GDM group, and a combination of VSD with ASD was found in 1 infant from the same group. Statistical analysis showed no significant association between the type of maternal diabetes and the specific type of congenital heart defect observed (Pearson Chi-Square p=0.834; Fisher’s Exact Test p=0.709). When compared with the findings of Hromadnikova I, et. al; 2020, who demonstrated that children exposed to GDM during pregnancy exhibited a significantly altered microRNA expression profile—associated with diabetes, cardiovascular, and cerebrovascular disease pathways—and were more likely to develop valve and structural heart abnormalities, our study similarly supports the link between GDM and congenital heart defects, although without showing statistically significant variation between GDM and pregestational diabetes groups. While Hromadnikova et al. emphasized molecular and long-term cardiovascular risk based on gene expression patterns and the presence of heart anomalies in exposed children, our research provides direct clinical evidence of specific congenital heart defects in neonates but does not extend into molecular profiling or long-term follow-up. Together, these findings underscore the cardiovascular implications of maternal diabetes and reinforce the need for early screening and long-term monitoring of exposed offspring.24

Our study substantiates the prevalence of congenital heart disease (CHD) among infants of diabetic mothers, with Atrial Septal Defects seen in most of the studied subjects. To prevent CHD in newborns, we strongly recommend that pregnant women with diabetes should be supported to achieve and maintain optimal glycaemic control and ensure treatment compliance. Additionally, we advocate for routine echocardiogram (ECHO) screening for all infants born to diabetic mothers, regardless of clinical presentation, in order to offer early intervention and prevent further morbidity and mortality.

1.       Reitzle L, Heidemann C, Baumert J, Kaltheuner M, Adamczewski H, Icks A, Scheidt-Nave C. Pregnancy complications in women with pregestational and gestational diabetes mellitus. Deutsches Ärzteblatt International. 2023 Feb 10;120(6):81.

2.       Karcaaltincaba D, Kandemir O, Yalvac S, Güvendag-Guven S, Haberal A. Prevalence of gestational diabetes mellitus and gestational impaired glucose tolerance in pregnant women evaluated by National Diabetes Data Group and Carpenter and Coustan criteria. International Journal of Gynecology & Obstetrics. 2009 Sep 1;106(3):246-9.

3.       Loffredo CA. Epidemiology of cardiovascular malformations: prevalence and risk factors. American journal of medical genetics. 2000 Dec;97(4):319-25.

4.       Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cifkova R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang IM. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy: the task force for the management of cardiovascular diseases during pregnancy of the European Society of Cardiology (ESC). European heart journal. 2018 Sep 7;39(34):3165-241.

5.       Ornoy A, Becker M, Weinstein-Fudim L, Ergaz Z. Diabetes during pregnancy: a maternal disease complicating the course of pregnancy with long-term deleterious effects on the offspring. a clinical review. International Journal of Molecular Sciences. 2021 Mar 15;22(6):2965.

6.       Ornoy A, Reece EA, Pavlinkova G, Kappen C, Miller RK. Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Research Part C: Embryo Today: Reviews. 2015 Mar;105(1):53-72.

7.       Basu M, Garg V. Maternal hyperglycemia and fetal cardiac development: Clinical impact and underlying mechanisms. Birth defects research. 2018 Dec 1;110(20):1504-16.

8.       Negrato CA, Marques PR, Leite HB, Torigoe CN, Silva BF, Costa K, Kamei JM, Zampa CL, Toni AC, Pereira IC, Heinzelmann GL. Glycemic and nonglycemic mechanisms of congenital malformations in hyperglycemic pregnancies: a narrative review. Archives of Endocrinology and Metabolism. 2022 Oct 10;66(6):908-18.

9.       Pierpont ME, Brueckner M, Chung WK, Garg V, Lacro RV, McGuire AL, Mital S, Priest JR, Pu WT, Roberts A, Ware SM. Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association. Circulation. 2018 Nov 20;138(21):e653-711.

10.    Armengaud JB, Simeoni U. Offspring of mothers with hyperglycemia in pregnancy: Short-term consequences for newborns and infants. Gestational diabetes. 2019 Dec 19;28:194-200.

11.    Wender-Ożegowska E, Wroblewska K, Zawiejska A, Pietryga M, Szczapa J, Biczysko R. Threshold values of maternal blood glucose in early diabetic pregnancy-prediction of fetal malformations. Acta obstetricia et gynecologica Scandinavica. 2005 Jan 1;84(1):17-25.

12.    Corrigan N, Brazil DP, McAuliffe F. Fetal cardiac effects of maternal hyperglycemia during pregnancy. Birth Defects Research Part A: Clinical and Molecular Teratology. 2009 Jun;85(6):523-30.

13.    Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. International journal of molecular sciences. 2018 Oct 26;19(11):3342.

14.    Apata T, Samuel D, Valle L, Crimmins SD. Type 1 Diabetes and Pregnancy: Challenges in Glycemic Control and Maternal–Fetal Outcomes. InSeminars in Reproductive Medicine 2024 Oct 8. Thieme Medical Publishers, Inc..

15.    Eisa RA, Babiker MS. Prevalence of VSD, PDA, and ASD in Saudi Arabia by echocardiography: a prospective study. Journal of Diagnostic Medical Sonography. 2019 Jul;35(4):282-8.

16.    Shankar P, Marol JS, Lysander SD, Manohar A. Cardiovascular malformations in infants of diabetic mothers: a retrospective study. International Journal of Contemporary Pediatrics. 2019 Aug 23;6(5):1998.

17.    Dawid G, Czeszynska MB, Horodnicka-Jozwa A, Wnuk W, Mojsiewicz M, Hnatyszyn G, et al. [Secundum atrial septal defect in newborns of diabetic mothers]. PubMed. 2006 Mar 21;9(3 Pt 1):355–64.

18.    Dominic B, Mithun HK. Spectrum of congenital heart diseases in infants of diabetic mothers. Karnataka Paediatr J. 2025;40:19-22. doi: 10.25259/KPJ_29_2024

19.    Mohammed Abdullah Algossadi, Walid Abdel Wahab Eid, Renad Mohammed Alshehri, Reema Mohammed Alshehri and Abdulaziz Mohammed Alshehri. Prevalence of congenital heart defects in infants of diabetic mothers in Aseer region, Southwestern, Saudi Arabia. Int. J. Pediatr. Neonatology 2023;5(1):10-14.

20.    Sikarwar R, Hatkar PA. Study of fetal 2D echo in pregnant women with diabetes and gestational diabetes mellitus. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2019 Nov 1;8(11):4214-8.

21.    Rowland TW, Hubbell JP, Nadas AS. Congenital heart disease in infants of diabetic mothers. The Journal of Pediatrics. 1973 Nov;83(5):815–20Backer CL, Eltayeb O, Mongé MC, Mazwi ML, Costello JM. Shunt lesions part I: patent ductus arteriosus, atrial septal defect, ventricular septal defect, and atrioventricular septal defect. Pediatric Critical Care Medicine. 2016 Aug 1;17(8):S302-9.

22.    Chu PY, Li JS, Kosinski AS, Hornik CP, Hill KD. Congenital Heart Disease in Premature Infants 25-32 Weeks’ Gestational Age. The Journal of Pediatrics. 2017 Feb;181:37-41.e1.

23.    Chen L, Yang T, Chen L, Wang L, Wang T, Zhao L, et al. Risk of congenital heart defects in offspring exposed to maternal diabetes mellitus: an updated systematic review and meta-analysis. Archives of Gynecology and Obstetrics. 2019 Nov 12;300(6):1491–506.

24.    Hromadnikova I, Kotlabova K, Dvorakova L, Krofta L, Sirc J. Substantially altered expression profile of diabetes/cardiovascular/cerebrovascular disease associated microRNAs in children descending from pregnancy complicated by gestational diabetes mellitus—one of several possible reasons for an increased cardiovascular risk. Cells. 2020 Jun 26;9(6):1557.