Infants of Diabetic MothersThe control of diabetes mellitus with insulin has led to the survival of increasing numbers of diabetic women who bear children.Their infants and the infants of women who later develop diabetes share certain distinctive morphologic characteristics, including large size, macrosomia, and high morbidity risks.Diabetic mothers have a high incidence of polyhydramnios, pre-eclampsia,pyelonephrits,preterm labor, and chronic hypertension; their fetal mortality rate, which is high at all gestational ages, especially so after 32 wk, is greater than that of nondiabetic mothers.Fetal wastage throughout pregnancy is associated with poorly controlled maternal diabetes, especially ketoacidosis and congenital anomalies. Diabetics mothers produce an excess of high-birth weight infants at all gestational ages and, if complicated with vascular disease, of low birth weight infants at 37- to 40-wk gestations.The neonatal mortality rate is over 5 times that of infants of non diabetics mothers and is higher at all gestational ional ages and in every birth weight for gestational age category.
The probable pathogenic sequence is that maternal hyperglycemia causes fetal hyperglycemia, and the fetal pancreatic response leads to fetal hyperinsulinemia; fetal hyperinsulinemia and hyperglycemia then cause increased hepatic glucose uptake and glycogen synthesis, accelerated lipogenesis, and augmented protein synthesis.Related pathologic findings are the hypertrophy and hyperplasia of the pancreatic islets with a disproportionate increase in the number of B cells; increased weights of the placenta and infants organs except for the brain; myocardial hypertrophy; increased amounts of cytoplasm in liver cells; and extramedullary hematopoiesis. Hyperinsulinism produces fetal acidoses, which may result in an increased rate of stillbirth. The separation of the placenta at birth suddenly interrupts glucose infusion into the neonate without a proportional effect on the hyperinsulinism, resulting in hypoglycemia and attenuated lipolysis during the first hours after birth.
Hyperinsulinemia has been documented in infants of gestational diabetic mothers and in those of insulin-dependent diabetic mothers without insulin antibodies.With good prenatal diabetic control, the incidence of macrosomia and hypoglycemia have decreased.
Although hyperinsulinism is probably the main cause of hypoglycemia, the diminished epinephrine and glucagon responses that occur may be contributing factors.Congenital anomalies correlate with poor metabolic control and may be due to hyperglycemia-induced teratogenesis.
The infants tend to be large and plump as a result of increased body fat and enlarged viscera, with puffy, plethoric facies resembling those of patients who have been receiving a corticosteroid. These infants may ,however , also be of normal birth weight, particularly if they are delivered before term or if there is associated maternal vascular disease.
The infants tend to be tremulous and hyperexcitable during the first 3 days of live, although hypotonia, lethargy,and poor sucking also may occur.They may have any of the diverse manifestations of hypoglycemia. Early appearance of these signs is more likely to be related to hypoglycemia and later appearance related to hypocalcemia; these abnormalities also may occur together. Perinatal asphyxia or hyperbilirubinemia may produce similar signs. Rarely, hypomagnesemia may be associated with the hypocalcemia. Many infants of diabetic mothers develop tachypnea during the first 5 days of live,which may be a transient manifestation of hypoglycemia, hyporthermia,polycythemia,cardiac failure, transient tachypnea,or cerebral edema from birth trauma or asphyxia.A greater incidence of respiratory distress syndrome appears in infants of diabetic mothers born at comparable gestational age; the greater incidence is possible related to an antagonistic effect between cortisol and insulin on surfactant synthesis.
Cardiomegaly is common, and heart failure occurs in 5-10% of infants of diabetic mothers. Birth trauma is also common due to fetal macrosomia.Neurological development and ossification centers tend to be immature and correlate with the brain size(which is not increased)and gestational age rather than with total body weight.There is also an increased incidence of hyperbilirubinemia,polycythemia,and renal vein thrombosis; the latter should be suspected in the presence of a flank mass, hematuria, and thrombocytopenia.
The incidence of congenital anomalies is increased 3-fold in infants of diabetic mothers; cardiac malformations and lumbosacral agenesis are most common. Additional anomalies include neural tube defects, hydronephrosis, renal agenesia, duodenal or anorectal atresia, holoprosencefaly. These infants may also develop abdominal distention caused by a transient delay in the development of the left side of the colon,the left colon syndrome.
Physical development is normal,but oversized infants may be predisposed to be obesity in childhood that may extend into adult live. Desagreement persists about whether or not a slightly increased risk of impaired intellectual development exists unrelated to hypoglycemia probably increases the risk.
Management of these infants should be initiated before birth by frequent prenatal evaluation of all pregnant women with overt or gestational diabetes,by evaluation of fetal maturity, by biophysical profile, by Doppler velocimetry,and by planning delivery of these infants in hospitals where expert obstetric and pediatric care is continuously available. Asymptomatic infants should have a blood sugar determination within 1 hr of birth and then every hour for the next 6-8 hr; if clinically well and normoglicemic,oral or gavage feedings initially with 5% glucose water, followed by breast milk or formula, should be started at 2-3 hr of age and continued at 3-hr intervals.If any question arises about infant’s ability to tolerate oral feeding, the feeding should be discontinued and glucose given by peripheral intravenous infusion at a rate of 4-8 mg/kg/min. Hypoglycemia should be treated, even in asymptomatic infants, with intravenous infusions of glucose sufficient to keep the blood levels well above this level. Bolus injections of hypertonic glucose should be avoided because they may cause further hyperinsulinemia and potentially produce rebound hypoglycemia.