Background
Diabetes has long been associated with maternal and perinatal morbidity and mortality.

Approximately 6 % of pregnancies are complicated by maternal diabetes mellitus (80 % of which are gestational). Of mothers with preexisting diabetes, 35% had type1 DM and 65% had type2 DM.

Before the discovery of insulin in 1921, women with diabetes rarely reached reproductive age or survived pregnancy. In fact, pregnancy termination was routinely recommended for women with diabetes because of high mortality rates. Fetal and neonatal mortality rates were as high as 65% before the development of specialized maternal, fetal, and neonatal care. Since then, infants of diabetic mothers (IDMs) have experienced a nearly 30-fold decrease in morbidity and mortality rates.

The best prevention is preconceptional diabetic care. With excellent glycemic control throughout pregnancy, the overall mortality rate approaches that of the general population.

A past history of LGA infants, diabetes, stillbirth, hypertension, obesity, glycosuria, a current history of excessive weight gain in the present pregnancy or low socioeconomic class place the mother at an increased risk of poor glucose control during pregnancy and increase her risk of delivering an infant with subsequent complications.

Pathogenesis
Reduced insulin activity in pregnant diabetic women leads to a metabolically abnormal environment.
As a result, diabetic embryopathy occurs in the sixth to seventh weeks of gestation (birth defects and spontaneous abortions), and diabetic fetopathy (predominantly macrosomia and fetal hyperinsulinemia).

Maternal hyperglycemia -fetal hyperglycemia – fetal hyperinsulinemia
lipogenesis, protein synthesis, glycogen synthesis, glucose oxidation, glucose uptake by the liver.
During labor, the separation of placenta suddenly-Interruption of glucose infusion into the neonate without proportional effect on the hyperinsulinemia – Deceased lipolysis during the first hour after birth-  hypoglycemia

Clinical picture:
Infants are macrosomic. They may be normal or LBW if associated with maternal vascular disease. Plethoric facies.

They tend to be tremulous and hyperexcitable during the first three days of life. Hypotonia and lethergy with poor suckling may occur due to hypoglycemia. Early appearance of the last 2 signs is more likely related to hypoglycemia while their late appearance may be due to hypocalcemia.

The nadir of blood glucose is reached between 1- 3 hours after birth.

Specific Problems frequently observed in IDM

Respiratory Distress:

Causes of RD:

• RDS due to hyperinsulinemia which blocks cortisol induction of lung maturation(block surfactant synthesis).
• Cardiac or pulmonary anomalies.
• Transient tachypnea of newborn.
• Polycythemia
• Hypertrophic cardiomyopathy.
• Pneumonia , pneumothorax

Hypoglycemia : Blood glucose < 40 mg/dl.
* Asymptomatic
* Symptomatic : Jitteriness, seizures, lethargy, poor feeding, weak or high pitched cry, apnea, cyanosis hypothermia, tachypnea.

Polycythemia as a central hematocrit level higher than 65%.
Maternal-fetal hyperglycemia and fetal hypoxia due to increased glycosylated Hb in both maternal & fetal serum is a strong stimulus for fetal erythropoietin production and subsequent increase in fetal hemoglobin concentration

Jaundice
Prematurity , increased enterohepatic circulation , impairment of the hepatic conjugation of bilirubin , decreased RBCs life span due to less deformable red cell membrane related to glycosylation of the RBCs membrane leading to hemolysis.

Congenital anomalies
Most studies show a 6 to 9 % incidence of major anomalies in IDMs , compared with a usual major anomaly rate for the general population of 2 %

Vertebral & Skeletal : Spina bifida, caudal regression , sacral agenesis

GIT : Dudenal or anorectal atresia, small left colon syndrome.

CNS: anencephaly ,meningocele, macrocephaly

Cardiac: VSD, ASD, TGV, hypoplastic Lt. V, situs inversus

Renal: Absent kidney, polycystic , double ureter

Macrosomia
Infants with birth weight more than 4000 gm or above the 90th percentile or more than 2 SD above the mean for age. It is correlated with poor maternal glycemic control.

Infants of diabetic mothers experience higher levels of glucose during gestation, resulting in pancreatic beta-cell hyperplasia, with increased secretion of insulin and proinsulin factors (insulinlike growth factor-1, insulin like growth factor-binding protein-3). Amino acid availability is also increased.

All of these factors are involved in the excessive growth observed in the infants of diabetic mothers.

Myocardial dysfunction
Cardiomyopathy with ventricular hypertrophy and outflow tract obstruction may occur in as many as 30% of these infants.

The cardiomyopathy may present with heart failure, cardiomegaly and poor cardiac output.

• Renal vein thrombosis
• Feeding problems

Poor feeding is a major problem in IDM. It may be related to prematurity, RD,
or other problems. However, it is often present in the absence of other problems.

Laboratory Studies
Glucose concentration (serum or whole-blood), Serum calcium, magnesium, bilirubin level, CBC count, ABG

Imaging Studies

• Chest radiography
• Abdominal, pelvic, or lower extremity radiography
• Barium enema
• Echocardiography
• The cord blood C-peptide and C-peptide: glucose ratio was raised in nearly half of the babies of poorly controlled diabetic mothers and was frequently associated with neonatal hypoglycemia.
• Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome.
• Increased oxidative stress is detected.
• Complications caused by maternal hyperglycemia during pregnancy are reflected by elevated HbA1C levels, particularly during the first trimester of pregnancy as it is a direct measure of glucose control in the mother.

Higher levels are predictive of increased risks for congenital anomalies.
Thus, the incidence of complications has been reported as: 3.4% with HbA1C levels lower than 8.5% , 22.4% with levels higher than 8.5%.

Inheritence

• In type 1 diabetes:

If the mother has the disease the risk of the offspring developing the disease is 1-4%. If the father has the disease the risk to the offspring is 10%. If both have the disease the risk is 20%.

• In type 2 diabetes:

If one parent has the disease, the risk to the offspring is 30%. If both parents have it, the risk to the offspring is 50-60%.

Prognosis

• Is very good when appropriate care is provided during the perinatal period.
• Clinical and epidemiological data suggest that elevated insulin levels during perinatal life may program the infant to develop obesity and diabetes later in life.
• Infants of mothers with poor glucose control during pregnancy are at highest risk for neurodevelopmental deficits.

Dr. Maha Hassan Mohamed
Specialist -Paedatrics
GMC hospital,Ajman, UAE.