Diabetes mellitus (DM) in pregnancy or gestational diabetes can cause various complications to the mother and the fetus. The risk of congenital abnormalities increases in infants with DM mothers.

Diabetes is one of the most common problems in pregnancy. In 2017, about 1 in 3 women of reproductive age developed diabetes mellitus, and about 1 in 7 pregnancies were pregnancies with gestational diabetes.

Pregnancy with gestational diabetes often has various complications, both for the mother and the fetus. Gestational diabetes increases the risk of the mother experiencing DM 7 times more often than normoglycemic pregnancy. Babies with DM mothers can also experience various complications, including congenital abnormalities, such as heart malformations, anencephaly, cleft lip, and so on. However, doctors and pregnant women's awareness about diabetes and its consequences are still minimal, especially in developing countries.



Diabetes Complications for Pregnancy and Infants

Diabetes can cause various complications that complicate pregnancy, such as preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), delivery by cesarean section, abortion, stillbirth. Diabetes can also cause problems in babies. Complications that are often found in infants with DM mothers include:
  • Neonatal hypoglycemia
  • Macrosomia
  • Prematurity
  • Polycythemia
  • Respiratory distress syndrome
  • Neonatal hyperbilirubinemia
  • Cardiomyopathy
  • Congenital malformations. It can occur in pregestational diabetes, both diabetes mellitus types 1 and 2, or gestational diabetes.



Relations Between Hyperglycemia and Congenital Malformations

Hyperglycemia is the main condition in diabetes, which is considered to be teratogenic. Studies show that hyperglycemia can expose the fetus to a variety of mechanisms that interfere with organogenesis.

Hyperglycemia is thought to increase osmotic stress and suppress the glucose transporter GLUT-1 and the cell cycle. These effects are thought to cause a slowdown in the embryonic development stage due to increased apoptosis of embryonic cells, decreased endothelial cell proliferation in embryos, and impaired embryonic blood flow.

Hyperglycemia particularly causes several mechanisms, namely: the decreased proliferation of endocardial and myocardial cells, hemodynamic disturbances, depression, and apoptosis of neural crest cells, and disruption of cell migration in the embryo.

These mechanisms cause DM mothers' babies to have a higher risk of congenital malformations of the cardiovascular, central nervous, and skeletal systems. Congenital abnormalities that are often found in infants with DM mothers are:
  • Neural tube defects: anencephaly, spina bifida aperta, meningocele, encephalocele
  • Cardiac septal abnormalities and blood vessel transposition
  • Femoral shortening and lower limb abnormalities
The infants' defect size also depends on the mother's blood sugar level based on HbA1c. However, to date, there are no definite guidelines for the limit of HbA1c for mothers during pregestation and pregnancy.



Clinical Evidence on the Association of Diabetes Mellitus and Congenital Malformations

A recent cohort study in Sweden showed that the risk of major and minor heart malformations was higher in infants with type 1 DM mothers (33 cases / 1000 births and 22 cases / 1000 births) than infants of non-DM mothers (15 cases / 1000 births and 18 cases / 1000 births).

These rates also increase with the increase in maternal HbA1c, with the number of major heart malformation cases as much as 49 per 1000 births (HbA1c 6.5% -7.8%) compared to 101 per 1000 births (HbA1c ≥ 9.1%). A similar increase in rates was observed for minor heart defects with maternal HbA1c 6.5% -7.8% versus ≥9.1% (19/1000 births vs. 32/1000 births).

The cohort study in Italy also shows the same thing. A total of 62 out of 2269 infants with DM mothers had congenital malformations, while 162 out of 10,648 infants with non-DM mothers had congenital malformations. This study concluded that the malformations prevalency is more influenced by type 2 DM—these malformations, especially for cardiovascular, genitourinary, and musculoskeletal disorders.
Other studies have shown that infants' congenital abnormalities are more common in women with diabetes, either pregestational diabetes or gestational diabetes. The risk was 1.5-2x higher in pregestational type 1 diabetes and gestational diabetes than in nonDM women.

Several other studies have also shown an increased risk of type 2 pregestational diabetes mellitus. The risk of malformations increases with the delayed or insufficient antenatal examination, poor glycemic control, inadequate folate supplementation, and maternal obesity.

A meta-analysis of 17 studies showed that the risk of congenital malformations is higher in infants of DM mothers, either pregestational or gestational. The risk of congenital malformations was 16% higher in gestational DM than in non-DM mothers. However, this risk is much lower than in mothers with pregestational DM.



Screening of Babies from Diabetes Mothers

The high risk of abnormalities due to DM makes screening in babies with DM mothers and gestational diabetes necessary. However, until now, there are no definite clinical guidelines on this matter. Screening in infants can be done intrauterine with ultrasound. Some other examinations that need special attention to babies with DM mothers include:

a. Cardiorespiratory examination

The cardiorespiratory examination is performed when there is cyanosis, either based on clinical conditions or oxygen saturation. Examinations can be done in the form of echocardiography to screen for heart malformations, especially ventricular septal defect (VSD) and arterial transposition (transposition of great arteries / TGA), as well as chest x-rays if there are signs of respiratory distress.

b. Barium Enema

A barium enema may be used to screen for Hirschprung's Morbus, colonic atresia, or other congenital disorders of the gastrointestinal system. Perform a barium enema if the baby has feeding intolerance, abdominal distension, nonbilose emesis, and meconium passage.

c. Laboratory examination

Laboratory tests that can be performed for screening are:
  • Check blood sugar within 1-2 hours after birth and monitor serum glucose for 24 hours if hypoglycemia is present.
  • Hematocrit examination within 1 hour of delivery for polycythemia and hyperviscosity syndrome
  • Calcium and magnesium tests if there are symptoms of hypocalcemia or hypomagnesia
  • Serum bilirubin measurement



Management of Detected Abnormalities

Management of babies of DM mothers must be well prepared, especially for abnormalities that have been detected prenatally. The possibility of requiring treatment in a neonatal intensive care unit (NICU) should also be prepared.

Babies of DM mothers should also be consulted with a pediatrician or subspecialty pediatrician if necessary. If there are no signs of complications, infants of DM mothers can receive routine neonatal care.


Conclusion
Congenital malformations were found to occur more frequently in infants of mothers with diabetes, both pregestational and gestational diabetes.

The most common congenital malformations are heart, neural tube, genitourinary and musculoskeletal defects. The risk of this malformation was found to be much higher in pregestational diabetes mellitus, especially in type 1 diabetes mellitus.

The risk also becomes higher if maternal glycemic control is not good based on the HbA1c value. This suggests that glycemic control is very important for women and needs special attention from doctors or other medical personnel. Still, there are no definite guidelines for pregestational HbA1c targets in women with diabetes mellitus.

Screening DM in infants is also recommended, especially for babies whose mothers with diabetes. Post-delivery management of infants of diabetes mellitus mothers should be better prepared and should receive care from a pediatrician.


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