ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Infants of mothers with diabetes (IMD)

Infants of mothers with diabetes (IMD)
Literature review current through: Jan 2024.
This topic last updated: May 04, 2023.

INTRODUCTION — Diabetes in pregnancy is associated with an increased risk of fetal, neonatal, and long-term complications in the offspring. Maternal diabetes may be pregestational (ie, type 1 or type 2 diabetes mellitus [DM] diagnosed before pregnancy) or gestational (ie, DM diagnosed during pregnancy). The outcome is generally related to the onset and duration of glucose intolerance during pregnancy and maternal glycemic control. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

This topic will review the complications seen in infants of mothers with diabetes (IMD). The prenatal management of pregestational and gestational diabetes mellitus is discussed in separate topic reviews:

(See "Gestational diabetes mellitus: Screening, diagnosis, and prevention".)

(See "Gestational diabetes mellitus: Obstetric issues and management".)

(See "Gestational diabetes mellitus: Glucose management and maternal prognosis".)

(See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

(See "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management".)

IMPACT OF MATERNAL DIABETES STATUS — The risk of complications in the offspring varies considerably depending upon whether the mother has pregestational or gestational diabetes mellitus (PGDM or GDM), whether the mother is insulin-dependent, and the degree of glycemic control achieved before and during pregnancy. Infants born to mothers with PGDM (ie, type 1 or type 2 DM diagnosed before pregnancy) have a higher risk of mortality and diabetes-related complications (eg, macrosomia, preterm birth, congenital abnormalities, and respiratory distress) compared with offspring of mothers with GDM [1-7]. The risk is particularly high in infants born to mothers with insulin-dependent DM and those with poor glycemic control before and during pregnancy. For infants born to mothers with GDM not requiring insulin, the risk of neonatal complications is modestly increased compared with the general population [2,6]. Strict glycemic control preconception and during pregnancy reduces the risk of perinatal mortality and morbidity. (See "Gestational diabetes mellitus: Screening, diagnosis, and prevention" and "Gestational diabetes mellitus: Glucose management and maternal prognosis", section on 'Rationale for treatment'.)

The impact of maternal diabetes status on neonatal outcomes was demonstrated in two population-based studies from France and Finland that included data on >160,000 infants born to mothers with diabetes (IMD) [2,6]. Among the 5291 infants born to mothers with type 1 DM, 36 percent were born preterm (<37 weeks gestation) and 41 percent were large for gestational age (LGA). By contrast, among the 5647 infants born to women with type 2 DM, 13 percent were preterm and 18 percent were LGA. Among the 151,056 infants born to women with GDM, 6 percent were preterm and 9 percent were LGA, rates that are only modestly higher than rates seen in the nondiabetic population (5 and 6 percent, respectively).

FETAL EFFECTS — Poor glycemic control in pregnant individuals with diabetes leads to adverse fetal effects throughout pregnancy, as follows [8]:

First trimester – In the first trimester and time of conception, maternal hyperglycemia can cause diabetic embryopathy, resulting in major birth defects and spontaneous abortions (table 1). This primarily occurs in pregnancies with pregestational diabetes mellitus (PGDM) [1,9,10]. The risk for congenital malformations associated with gestational diabetes mellitus (GDM) is only slightly increased compared with the general population. The risk of malformations increases as maternal fasting blood glucose levels and body mass index (BMI) increases when GDM is diagnosed early in pregnancy. These findings suggest that some of these mothers probably have undiagnosed type 2 DM [11,12]. (See 'Congenital abnormalities' below and "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

Second and third trimester – Diabetic fetopathy occurs in the second and third trimesters, resulting in fetal hyperglycemia, hyperinsulinemia, and macrosomia.

Effects of fetal hyperinsulinemia – Maternal hyperglycemia leads to fetal hyperglycemia resulting in fetal hyperinsulinemia and, after delivery, neonatal hypoglycemia. (See 'Hypoglycemia' below.)

Fetal hyperinsulinemia stimulates storage of glycogen in the liver, increased activity of hepatic enzymes involved in lipid synthesis, and accumulation of fat in adipose tissue. These metabolic effects might contribute to long-term metabolic complications in the offspring. (See 'Metabolic risks' below.)

Fetal hyperinsulinemia also increases the synthesis and deposition of fat and glycogen in the myocardial cells, which can lead to ventricular hypertrophy [13]. Fetal echocardiography may show evidence of hypertrophy starting at the end of the second and the beginning of the third trimester. Hypertrophy is characterized by marked thickening of the interventricular septum (IVS) [14]. In one study, prenatal echocardiographic measurements of IVS thickness performed at ≥35 weeks gestation correlated with risk of postnatal cardiac morbidity [15]. (See 'Ventricular hypertrophy' below.)

Fetal hyperinsulinemia is also thought to contribute to impaired or delayed lung maturation. (See 'Respiratory distress syndrome' below.)

Fetal hypoxemia – Animal studies have shown that chronic fetal hyperinsulinemia results in elevated metabolic rates that lead to increased oxygen consumption and fetal hypoxemia, as the placenta may be unable to meet the increased metabolic demands [16]. Fetal hypoxemia contributes metabolic acidosis, alterations in fetal iron distribution, increased erythropoiesis, and increased risk of fetal demise [17]. Stillbirth is more likely in pregnancies complicated by poorly controlled diabetes. (See "Gestational diabetes mellitus: Obstetric issues and management", section on 'Fetal surveillance' and "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management", section on 'Risk of stillbirth'.)

Increased erythropoiesis – Increased synthesis of erythropoietin leads to polycythemia and increased catecholamine production, which can result in hypertension and cardiac hypertrophy [18,19]. (See 'Polycythemia' below and 'Ventricular hypertrophy' below.)

As the fetal red cell mass increases, iron redistribution results in iron deficiency in developing organs, which may contribute to altered cardiac and neurologic development [17]. (See 'Congenital abnormalities' below and 'Ventricular hypertrophy' below.)

Oxidative stress – Oxidative stress may play a role in maternal and fetal complications of pregnancies complicated by diabetes [20,21]. For example, increased generation of reactive oxygen species with inadequate antioxidant defenses in the fetal heart might lead to abnormal cardiac remodeling and ventricular hypertrophy [12,22]. (See 'Congenital abnormalities' below and 'Ventricular hypertrophy' below.)

Oxidative stress also contributes to increased erythropoietin production with resultant polycythemia [22,23]. (See 'Polycythemia' below.)

Excess nutrients – Excessive nutrients delivered from the mother with poorly controlled diabetes cause increased fetal growth, particularly of insulin-sensitive tissues (ie, liver, muscle, cardiac muscle, and subcutaneous fat), resulting in macrosomia (picture 1). (See 'Macrosomia' below and "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

NEONATAL COMPLICATIONS — Infants of mothers with diabetes (IMD) are at increased risk for congenital anomalies, mortality, and morbidity compared with infants born to mothers without diabetes (table 2). Neonatal complications of IMD include (table 2) [24]:

Congenital abnormalities (see 'Congenital abnormalities' below)

Prematurity (see 'Prematurity' below)

Perinatal asphyxia (see 'Perinatal asphyxia' below)

Macrosomia (see 'Macrosomia' below)

Birth injury (largely due to macrosomia) (see 'Birth injury' below)

Respiratory distress (see 'Respiratory distress' below)

Metabolic complications (eg, hypoglycemia and hypocalcemia) (see 'Metabolic complications' below)

Polycythemia (see 'Polycythemia' below)

Low iron stores (see 'Low iron stores' below)

Hyperbilirubinemia (see 'Hyperbilirubinemia' below)

Ventricular hypertrophy (see 'Ventricular hypertrophy' below)

Although there have been advances in treatment of pregestational diabetes mellitus (PGDM) and screening and treatment of gestational diabetes mellitus (GDM), neonatal complications and congenital abnormalities continued to be observed in pregnancies complicated by diabetes and these complications contribute to a reported perinatal mortality rate that ranges from 0.5 to 2.5 percent in this population [2].

Congenital abnormalities — IMD are at increased risk for major congenital abnormalities (table 1) [17]. The overall risk for major congenital malformations among IMD is approximately 5 to 6 percent, with a higher prevalence (10 to 12 percent) among IMD whose mothers require insulin therapy [1,4,24,25]. These rates are substantially higher than in the general population, for whom the prevalence of major congenital abnormalities is approximately 2 to 4 percent among all livebirths. (See "Congenital anomalies: Epidemiology, types, and patterns", section on 'Epidemiology'.)

The risk of congenital abnormalities is related to maternal hyperglycemia at the time of conception and during early gestation. The risk is highest among IMD whose mothers had pregestational diabetes (approximately three-fold higher than the general newborn population) [26].

Congenital malformations account for approximately 50 percent of perinatal deaths in IMD [27]. This risk can be reduced by strict glycemic control during the pre- and periconceptual (first eight weeks of pregnancy) periods. (See "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management", section on 'Glycemic management'.)

Two-thirds of congenital anomalies in IMD involve either the cardiovascular system or central nervous system (CNS).

Cardiac – Cardiovascular malformations occur in 3 to 9 percent of diabetic pregnancies [2,28]. Reported cardiac defects in this population include (table 1) [24,25,28,29]:

Atrial septal defects (see "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis")

Ventricular septal defect (VSD) (see "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis")

Patent ductus arteriosus (PDA) (see "Clinical manifestations and diagnosis of patent ductus arteriosus (PDA) in term infants, children, and adults")

Transposition of the great arteries (TGA) (see "D-transposition of the great arteries (D-TGA): Anatomy, clinical features, and diagnosis")

Coarctation of the aorta

Hypoplastic left heart syndrome and other single ventricle defects (see "Hypoplastic left heart syndrome: Anatomy, clinical features, and diagnosis")

Double outlet right ventricle (DORV)

Truncus arteriosus (see "Truncus arteriosus")

Tricuspid atresia (see "Tricuspid valve atresia")

Pulmonic stenosis (see "Pulmonic stenosis in infants and children: Clinical manifestations and diagnosis")

CNS – Various types of CNS malformations have been reported in IMD, including (table 1) [25,26,30,31]:

Myelomeningocele (spina bifida) (see "Myelomeningocele (spina bifida): Anatomy, clinical manifestations, and complications")

Other neural tube defects, including closed spinal dysraphism (see "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management" and "Closed spinal dysraphism: Pathogenesis and types")

Anencephaly (see "Anencephaly")

Encephalocele (see "Primary (congenital) encephalocele")

Holoprosencephaly (see "Overview of craniofacial clefts and holoprosencephaly", section on 'Holoprosencephaly')

Caudal regression syndrome, which consists of a spectrum of structural defects of the caudal region, including incomplete development of the sacrum and, to a lesser degree, the lumbar vertebrae (picture 2); most cases occur in IMD [32] (see "Closed spinal dysraphism: Pathogenesis and types", section on 'Caudal regression or sacral agenesis')

Microcephaly (see "Microcephaly in infants and children: Etiology and evaluation")

Other – Other anomalies include (table 1) [24,25]:

Flexion contracture of the limbs.

Vertebral anomalies.

Cleft palate.

Intestinal anomalies including small left colon syndrome, which occurs primarily in infants of mothers with diabetes [33]. Small colon syndrome is a rare condition that presents as a transient inability to pass meconium, which resolves spontaneously.

Genitourinary abnormalities (eg, hydronephrosis, ureteral duplication, renal agenesis).

Prematurity — Spontaneous and medically indicated preterm delivery occur more frequently in diabetic than nondiabetic pregnancies [1,2]. Preterm labor and timing of delivery in diabetic pregnancies are discussed separately. (See "Gestational diabetes mellitus: Obstetric issues and management", section on 'Timing of birth' and "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management" and "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management", section on 'Preterm birth'.)

Perinatal asphyxia — IMD are at increased risk for perinatal asphyxia due to the effects of intrauterine hypoxemia, macrosomia (failure to progress and shoulder dystocia), and associated cardiac and neurologic conditions. In population-based study of >55,000 IDM patients, perinatal asphyxia occurred in 1.1 percent of deliveries [2]. (See "Perinatal asphyxia in term and late preterm infants".)

Macrosomia — Macrosomia or LGA (defined as birth weight [BW] >4000 g or >90th percentile for gestational age), is a common complication of diabetic pregnancies. The incidence is greatest in infants born to mothers with PGDM [1,2,6,34,35].

Macrosomia in IMD newborns is associated with disproportionate growth, resulting in an increased ponderal index (ie, higher body fat), higher chest-to-head and shoulder-to-head ratio, and thicker upper extremity skinfolds compared with non-IMD newborns of similar weight and length [34-37]. Macrosomic IMD newborns typically appear large and plethoric at birth, with excessive fat accumulation in the abdominal and scapular regions (picture 1).

Infants with macrosomia are more likely than those who are not macrosomic to have hyperbilirubinemia, hypoglycemia, acidosis, respiratory distress, shoulder dystocia, and brachial plexus injury [35,38]. Additional details about fetal macrosomia and LGA infants are provided separately. (See "Fetal macrosomia" and "Large for gestational age (LGA) newborn".)

Birth injury — Macrosomia predisposes to birth injury, especially shoulder dystocia. Shoulder dystocia occurs in nearly one-third of infants of mothers with diabetes with macrosomia [39] and is associated with increased risk of brachial plexus injury, clavicular or humeral fractures, perinatal asphyxia, and, less often, cephalohematoma, subdural hemorrhage, or facial palsy [3,24,40]. The risk of shoulder dystocia is also increased by the disproportionate growth that occurs in macrosomic infants, resulting in a higher chest-to-head and shoulder-to-head ratio than infants of mothers without diabetes [41]. (See "Neonatal birth injuries".)

The timing and route of delivery of infants of mothers with diabetes who are at risk for shoulder dystocia are discussed separately. (See "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management", section on 'Route' and "Gestational diabetes mellitus: Obstetric issues and management", section on 'Route of birth'.)

Respiratory distress

Respiratory distress syndrome — RDS due to surfactant deficiency occurs more frequently in infants of mothers with diabetes for the following two reasons [1,3,24,25,42]:

IMD are more likely to be delivered prematurely than infants born to mothers without diabetes. (See 'Prematurity' above.)

At a given gestational age, IMD are more likely to develop RDS because maternal hyperglycemia appears to impair or delay surfactant synthesis. The proposed underlying mechanism is neonatal hyperinsulinemia, which interferes with the induction of lung maturation by glucocorticoids [43-45].

However, in preterm infants born to mothers with well-controlled DM, the risk of RDS approaches that of infants born to mothers without diabetes at a similar gestational age [46-48].

The clinical manifestations, diagnosis, prevention, and management of RDS are discussed separately. (See "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis" and "Respiratory distress syndrome (RDS) in preterm infants: Management".)

Other causes of respiratory distress — In addition to RDS, other causes of respiratory distress in infants of mothers with diabetes include:

Transient tachypnea of the newborn (TTN) – TTN occurs two to three times more commonly in IMD than in infants born to mothers without diabetes [24,49]. The mechanism may be related to reduced fluid clearance in the diabetic fetal lung. Cesarean delivery, which is more frequently performed in diabetic versus nondiabetic pregnancies, may be a contributing factor [1,50]. The risk of developing respiratory distress after delivery is particularly high for infants with BW >4000 g [11,38,51]. TTN is discussed in greater detail separately. (See "Transient tachypnea of the newborn".)

Critical congenital heart disease. (See 'Congenital abnormalities' above and "Identifying newborns with critical congenital heart disease".)

Heart failure due to ventricular hypertrophy. (See 'Ventricular hypertrophy' below.)

Metabolic complications — Infants of mothers with diabetes are at increased risk for metabolic complications in the newborn period. The most common are hypoglycemia, hypocalcemia, and hypomagnesemia.

Hypoglycemia — Neonatal hypoglycemia (defined as blood glucose levels below 40 mg/dL [2.2 mmol/L] in the first 24 hours after birth) occurs frequently in IMD. Strict glycemic control during pregnancy decreases but does not eliminate the risk of neonatal hypoglycemia [52-55]. LGA infants are particularly likely to develop hypoglycemia [1,56,57]. Small for gestational age (SGA) infants are also at increased risk for persistent hypoglycemia because glycogen stores are reduced, and hyperinsulinemia impairs the ability to mobilize hepatic glycogen [58].

The onset of hypoglycemia typically occurs within the first few hours after birth. Thus, these infants require close blood glucose monitoring after delivery and frequently need enteral or parenteral glucose supplementation. In SGA infants, hypoglycemia may last longer than two to four days and may require more prolonged and higher rates of glucose infusion. The clinical manifestations, evaluation, and management of neonatal hypoglycemia are discussed in detail separately. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia" and "Management and outcome of neonatal hypoglycemia".)

Hypoglycemia is caused by persistent hyperinsulinemia in the newborn after interruption of the intrauterine glucose supply from the mother. Although there are no data on the caloric needs of IMD once glycemic control is established, it appears that the caloric needs of these infants are similar to those of infants of mothers without diabetes, and that subsequent weight loss and gain is self-regulated by the infant. However, offspring of diabetic pregnancies appear to be at risk for excess weight gain during childhood. (See 'Altered glucose metabolism and obesity' below.)

Hypocalcemia — Hypocalcemia occurs in approximately 5 percent of IMD, though some studies have reported rates as high as 30 percent [24,59]. The highest risk is in infants born to mothers with poorly controlled diabetes [59].

Serum calcium levels typically reach a nadir between 24 and 72 hours after birth. Hypocalcemia usually is asymptomatic and resolves without treatment [24]. As a result, routine screening is not necessary. However, calcium levels should be measured in infants with signs of hypocalcemia (jitteriness, lethargy, apnea, tachypnea, or seizures, and in those with prematurity, asphyxia, respiratory distress).

The clinical manifestations, evaluation, and management of neonatal hypocalcemia are discussed separately. (See "Neonatal hypocalcemia".)

Hypomagnesemia — Hypomagnesemia occurs in up to 40 percent of IMD within the first three days after birth [60,61]. It has been proposed that low neonatal levels reflect maternal hypomagnesemia caused by increased urinary loss secondary to diabetes. Prematurity can also be a contributing factor.

Hypomagnesemia usually is transient and asymptomatic and, thus, usually does not require treatment. However, hypomagnesemia can reduce both parathyroid hormone (PTH) secretion and PTH responsiveness [13,62]. As a result, in some neonates with both hypocalcemia and hypomagnesemia, the hypocalcemia may not respond to treatment until the hypomagnesemia is corrected [63].

Polycythemia — Polycythemia, defined as a central venous hematocrit of >65 percent, is more likely in IMD compared with infants whose mothers are not diabetic [1]. In a case series of 276 IMD newborns, 5 percent had documented polycythemia [24]. The underlying pathogenesis is due to increased erythropoietin concentrations caused by chronic fetal hypoxemia [18,19]. Delayed cord clamping may contribute to the high hematocrit [64].

To detect polycythemia, the hematocrit should be measured within 12 hours of birth.

Polycythemia may lead to hyperviscosity syndrome, including vascular sludging, ischemia, and infarction of vital organs. Hyperviscosity is thought to contribute to the increased risk of renal vein thrombosis seen in IMD [65].

The clinical manifestations, management, and outcome of polycythemia are discussed separately. (See "Neonatal polycythemia".)

Low iron stores — The combined erythrocyte and storage iron pools are lower in infants of mothers with diabetes. The degree of low iron stores at birth is inversely related to the degree of polycythemia, suggesting a shunting of fetal iron into the red cell mass [66]. It is thought that the excess iron in the polycythemic red blood cell (RBC) mass is recirculated as the excess RBCs break down. Thus, iron supplementation is generally not necessary.

Hyperbilirubinemia — Hyperbilirubinemia occurs in 10 to 30 percent of infants of mothers with diabetes [24]. The risk is particularly high in preterm neonates. In addition to prematurity, other factors associated with neonatal jaundice include poor maternal glycemic control, macrosomia, and polycythemia [60,67]. (See "Unconjugated hyperbilirubinemia in term and late preterm newborns: Screening" and "Unconjugated hyperbilirubinemia in term and late preterm newborns: Initial management".)

Ventricular hypertrophy — IMD are at increased risk for transient left ventricular hypertrophy (LVH) [1,68,69]. It is usually a benign finding that does not cause clinical symptoms and resolves spontaneously over the first year of life [70]. However, a small minority of affected infants may develop respiratory distress or signs of heart failure. The chest radiograph may show cardiomegaly; but LVH is best detected by echocardiography. The characteristic echocardiographic finding is marked thickening of the interventricular septum, whereas the free wall of the left ventricle is relatively spared. Given the benign natural history, screening echocardiograms are generally not necessary if the infant is otherwise well and has no clinical signs of heart disease (including normal pulse oximetry screen).

LVH resolves as plasma insulin concentrations normalize. Symptomatic infants typically recover after two to three weeks of supportive care, and echocardiographic findings resolve within 6 to 12 months [71].

Like most neonatal complications in IMD, ventricular hypertrophy is most likely to occur if the mother had poor glycemic control during pregnancy [72-74].

OVERVIEW OF NEONATAL MANAGEMENT — The management of infants of mothers with diabetes (IMD) focuses on anticipating and treating complications associated with maternal hyperglycemia. The risk of complications varies depending on the gestational age (GA), birth weight (BW), and the degree and severity of maternal hyperglycemia as discussed above. (See 'Impact of maternal diabetes status' above and 'Neonatal complications' above.)

Delivery room care – Immediately after delivery, routine neonatal care is provided that includes drying, clearing the airway of secretions, maintaining warmth, and a rapid assessment of the infant's clinical status based on heart rate, respiratory effort, tone, and an examination to identify any major congenital anomaly. The need for further intervention is based on this initial evaluation. If the infant does not require additional resuscitation, the infant should be given to the mother for skin-to-skin care and initiation of breastfeeding in the delivery room. (See "Neonatal resuscitation in the delivery room", section on 'Resuscitation' and "Overview of the routine management of the healthy newborn infant", section on 'Delivery room care'.)

Screening for common complications Routine newborn screening should be performed for all IMD as in the general newborn population. This includes the "blood spot" screening panel for genetic and metabolic conditions, pulse oximetry screening to detect critical congenital heart disease, routine screening for hyperbilirubinemia, and screening for hearing loss. These screening tests are discussed in greater detail separately. (See "Overview of newborn screening" and "Overview of the routine management of the healthy newborn infant", section on 'Routine newborn screening'.)

Additional screening for IMD newborns includes:

Screening for hypoglycemia, as discussed separately. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Screening'.)

Screening for polycythemia by measuring the venous hematocrit within 12 hours after delivery. (See "Neonatal polycythemia", section on 'Diagnosis'.)

Routine measurement of calcium and magnesium levels is generally not necessary; however, levels should be checked if the newborn has concerning clinical signs of hypocalcemia or hypomagnesemia (eg, seizure or jitteriness). (See 'Hypocalcemia' above and 'Hypomagnesemia' above and "Neonatal hypocalcemia".)

If there are no significant complications that require further intervention, routine newborn care should be provided. (See "Overview of the routine management of the healthy newborn infant".)

Management of common complications – Details of the management of specific complications seen in IMD are provided in separate topic reviews:

Critical congenital heart disease (see "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Initial management')

Respiratory distress syndrome (see "Respiratory distress syndrome (RDS) in preterm infants: Management")

Transient tachypnea of the newborn (TTN) (see "Transient tachypnea of the newborn", section on 'Management')

Hyperbilirubinemia (see "Unconjugated hyperbilirubinemia in term and late preterm newborns: Initial management")

Hypoglycemia (see "Management and outcome of neonatal hypoglycemia")

Hypocalcemia (see "Neonatal hypocalcemia", section on 'Management')

Polycythemia (see "Neonatal polycythemia", section on 'Management')

Heart failure due to ventricular hypertrophy (see "Heart failure in children: Management")

LONG-TERM OUTCOME

Metabolic risks

Diabetes — Infants of mothers with diabetes (IMD) have an increased risk of developing diabetes mellitus later in life. This risk is partly due to genetically determined factors [75].

Risk of type 1 diabetes mellitus (T1DM) – The lifetime risk of T1DM is 2 percent in offspring of a mother with T1DM, 6 percent in siblings, and 65 percent by age 60 years in identical twins (versus 0.3 to 0.4 percent in individuals with no family history of T1DM) [76]. (See "Pathogenesis of type 1 diabetes mellitus".)

Risk of type 2 diabetes mellitus (T2DM) – The lifetime risk for a first-degree relative of a patient with T2DM is 5 to 10 times higher than that of age- and weight-matched individuals without a family history of T2DM. (See "Pathogenesis of type 2 diabetes mellitus".)

The development of T2DM also may be affected by the abnormal intrauterine metabolic environment of a diabetic pregnancy. Data from studies performed in Pima Indians, who have the highest rates of gestational diabetes, demonstrate that 45 percent of offspring of mothers with gestational diabetes develop T2DM between 20 and 24 years of age compared with offspring of prediabetic (9 percent) or women without diabetes (1 percent) [77,78]. This increased risk persists despite accounting for paternal history of diabetes, age of onset of diabetes in parents, and the child's body mass index (BMI), suggesting that the intrauterine environment contributed to the development of diabetes, in addition to genetic factors. In a follow-up study, more than two-thirds of offspring of mothers with gestational diabetes developed T2DM by 34 years of age [79].

Altered glucose metabolism and obesity — Intrauterine exposure to hyperglycemia resulting in fetal hyperinsulinemia may affect the development of adipose tissue and pancreatic beta cells leading impaired glucose metabolism and increased risk for obesity in later childhood and/or adulthood. This can occur both in offspring of mother with pregestational and gestational diabetes [80-90].

Neurodevelopmental outcome — Most of the available observational studies suggest that maternal diabetes negatively impacts cognitive development in the offspring [91-95], though some studies have found little to no effect [96]. However, the studies have important limitations, most notably the inability to completely control for confounding factors (eg, parental education, socioeconomic status, comorbidities).

A 2016 systematic review identified 14 observational studies examining the association between maternal diabetes (pregestational or gestational) and offspring's cognitive development [92]. Eight studies found at least one negative association. The different studies used different tools to evaluate cognitive outcomes and therefore pooling of the results was not feasible. In a representative study, mean scores on standardized intelligence tests at age 8 years of age were 3 to 7 points lower in children born to mothers with diabetes compared with the reference healthy population [95]. However, after controlling for important confounders, the difference was no longer statistically significant.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Care during pregnancy for people with type 1 or type 2 diabetes (The Basics)")

Beyond the Basics topics (see "Patient education: Care during pregnancy for patients with type 1 or 2 diabetes (Beyond the Basics)" and "Patient education: Gestational diabetes (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Impact of maternal diabetes status – Diabetes in pregnancy is associated with an increased risk of fetal, neonatal, and long-term complications in offspring. The risk of complications varies considerably depending upon whether the mother has pregestational or gestational diabetes mellitus (PGDM or GDM), whether the mother is insulin-dependent, and the degree of glycemic control achieved before and during pregnancy. (See 'Impact of maternal diabetes status' above.)

Neonatal complications of maternal diabetes – Infants of mothers with diabetes (IMD) are at increased risk for the following adverse effects (table 2):

Congenital anomalies, especially cardiovascular and central nervous system (CNS) defects (table 1) (see 'Congenital abnormalities' above)

Prematurity (see 'Prematurity' above and "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management", section on 'Preterm birth')

Perinatal asphyxia (see 'Perinatal asphyxia' above and "Perinatal asphyxia in term and late preterm infants")

Macrosomia or large for gestational age (defined as a birth weight [BW] >4000 g or >90th percentile for gestational age) (picture 1) (see 'Macrosomia' above and "Large for gestational age (LGA) newborn")

Respiratory distress (see 'Respiratory distress' above)

Hypoglycemia that generally occurs within the first few hours after birth (see 'Hypoglycemia' above and "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia")

Hypocalcemia that is generally asymptomatic (see 'Hypocalcemia' above and "Neonatal hypocalcemia")

Polycythemia (see 'Polycythemia' above and "Neonatal polycythemia")

Low iron stores (see 'Low iron stores' above)

Hyperbilirubinemia (see 'Hyperbilirubinemia' above and "Unconjugated hyperbilirubinemia in neonates: Risk factors, clinical manifestations, and neurologic complications")

Transient ventricular hypertrophy that is usually asymptomatic (see 'Ventricular hypertrophy' above)

Overview of management – The management of IMD focuses on anticipating and treating complications associated with maternal hyperglycemia. The clinical assessment focuses on the respiratory and cardiac status of the infant and identifying any major congenital abnormalities (table 1). (See 'Overview of neonatal management' above.)

In addition to routine newborn care and screening procedures, IMD newborns should undergo screening for hypoglycemia and polycythemia, as discussed separately. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Screening' and "Neonatal polycythemia", section on 'Diagnosis'.)

Additional details of the management of specific complications seen in IMD are provided in separate topic reviews:

Critical congenital heart disease (see "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Initial management')

Respiratory distress syndrome (see "Respiratory distress syndrome (RDS) in preterm infants: Management")

Transient tachypnea of the newborn (TTN) (see "Transient tachypnea of the newborn", section on 'Management')

Hyperbilirubinemia (see "Unconjugated hyperbilirubinemia in term and late preterm newborns: Initial management")

Hypoglycemia (see "Management and outcome of neonatal hypoglycemia")

Hypocalcemia (see "Neonatal hypocalcemia", section on 'Management')

Polycythemia (see "Neonatal polycythemia", section on 'Management')

Heart failure due to ventricular hypertrophy (see "Heart failure in children: Management")

Long-term outcome – Long-term data on offspring of diabetic mothers suggest that prenatal exposure to hyperglycemia increases the risk of metabolic complications later in life (eg, impaired glucose metabolism, obesity, type 2 diabetes mellitus). Most of the available observational studies suggest that maternal diabetes negatively impacts cognitive development in the offspring, although some studies have found little to no effect. (See 'Long-term outcome' above.)

  1. Riskin A, Itzchaki O, Bader D, et al. Perinatal Outcomes in Infants of Mothers with Diabetes in Pregnancy. Isr Med Assoc J 2020; 22:569.
  2. Billionnet C, Mitanchez D, Weill A, et al. Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012. Diabetologia 2017; 60:636.
  3. Michael Weindling A. Offspring of diabetic pregnancy: short-term outcomes. Semin Fetal Neonatal Med 2009; 14:111.
  4. Yang J, Cummings EA, O'connell C, Jangaard K. Fetal and neonatal outcomes of diabetic pregnancies. Obstet Gynecol 2006; 108:644.
  5. Kapoor N, Sankaran S, Hyer S, Shehata H. Diabetes in pregnancy: a review of current evidence. Curr Opin Obstet Gynecol 2007; 19:586.
  6. Kong L, Nilsson IAK, Gissler M, Lavebratt C. Associations of Maternal Diabetes and Body Mass Index With Offspring Birth Weight and Prematurity. JAMA Pediatr 2019; 173:371.
  7. Battarbee AN, Venkatesh KK, Aliaga S, Boggess KA. The association of pregestational and gestational diabetes with severe neonatal morbidity and mortality. J Perinatol 2020; 40:232.
  8. Buchanan TA, Kitzmiller JL. Metabolic interactions of diabetes and pregnancy. Annu Rev Med 1994; 45:245.
  9. Lemaitre M, Bourdon G, Bruandet A, et al. Pre-gestational diabetes and the risk of congenital heart defects in the offspring: A French nationwide study. Diabetes Metab 2023; 49:101446.
  10. Chen LJ, Chiu CH, Huang JY, et al. Maternal diabetes mellitus and birth defects in Taiwan: A 5-year nationwide population-based cohort study. J Chin Med Assoc 2023; 86:589.
  11. Mitanchez D, Burguet A, Simeoni U. Infants born to mothers with gestational diabetes mellitus: mild neonatal effects, a long-term threat to global health. J Pediatr 2014; 164:445.
  12. Mitanchez D, Yzydorczyk C, Siddeek B, et al. The offspring of the diabetic mother--short- and long-term implications. Best Pract Res Clin Obstet Gynaecol 2015; 29:256.
  13. Tyrala EE. The infant of the diabetic mother. Obstet Gynecol Clin North Am 1996; 23:221.
  14. Hornberger LK. Maternal diabetes and the fetal heart. Heart 2006; 92:1019.
  15. Elmekkawi SF, Mansour GM, Elsafty MS, et al. Prediction of Fetal Hypertrophic Cardiomyopathy in Diabetic Pregnancies Compared with Postnatal Outcome. Clin Med Insights Womens Health 2015; 8:39.
  16. Philips AF, Dubin JW, Matty PJ, Raye JR. Arterial hypoxemia and hyperinsulinemia in the chronically hyperglycemic fetal lamb. Pediatr Res 1982; 16:653.
  17. Nold JL, Georgieff MK. Infants of diabetic mothers. Pediatr Clin North Am 2004; 51:619.
  18. Widness JA, Teramo KA, Clemons GK, et al. Temporal response of immunoreactive erythropoietin to acute hypoxemia in fetal sheep. Pediatr Res 1986; 20:15.
  19. Widness JA, Teramo KA, Clemons GK, et al. Direct relationship of antepartum glucose control and fetal erythropoietin in human type 1 (insulin-dependent) diabetic pregnancy. Diabetologia 1990; 33:378.
  20. Sarikabadayi YU, Aydemir O, Aydemir C, et al. Umbilical cord oxidative stress in infants of diabetic mothers and its relation to maternal hyperglycemia. J Pediatr Endocrinol Metab 2011; 24:671.
  21. Lappas M, Hiden U, Desoye G, et al. The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. Antioxid Redox Signal 2011; 15:3061.
  22. Topcuoglu S, Karatekin G, Yavuz T, et al. The relationship between the oxidative stress and the cardiac hypertrophy in infants of diabetic mothers. Diabetes Res Clin Pract 2015; 109:104.
  23. Escobar J, Teramo K, Stefanovic V, et al. Amniotic fluid oxidative and nitrosative stress biomarkers correlate with fetal chronic hypoxia in diabetic pregnancies. Neonatology 2013; 103:193.
  24. Cordero L, Treuer SH, Landon MB, Gabbe SG. Management of infants of diabetic mothers. Arch Pediatr Adolesc Med 1998; 152:249.
  25. Becerra JE, Khoury MJ, Cordero JF, Erickson JD. Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics 1990; 85:1.
  26. Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol 2008; 199:237.e1.
  27. Weintrob N, Karp M, Hod M. Short- and long-range complications in offspring of diabetic mothers. J Diabetes Complications 1996; 10:294.
  28. Wren C, Birrell G, Hawthorne G. Cardiovascular malformations in infants of diabetic mothers. Heart 2003; 89:1217.
  29. Aloqab FW, Almajed MR, Binsanad NA, et al. Maternal diabetes as a teratogenic factor for congenital heart defects in infants of diabetic mothers. Birth Defects Res 2023; 115:764.
  30. Khoury MJ, Becerra JE, Cordero JF, Erickson JD. Clinical-epidemiologic assessment of pattern of birth defects associated with human teratogens: application to diabetic embryopathy. Pediatrics 1989; 84:658.
  31. Kokhanov A. Congenital Abnormalities in the Infant of a Diabetic Mother. Neoreviews 2022; 23:e319.
  32. Mills JL. Malformations in infants of diabetic mothers. Teratology 1982; 25:385.
  33. Ellis H, Kumar R, Kostyrka B. Neonatal small left colon syndrome in the offspring of diabetic mothers-an analysis of 105 children. J Pediatr Surg 2009; 44:2343.
  34. Persson M, Pasupathy D, Hanson U, Norman M. Birth size distribution in 3,705 infants born to mothers with type 1 diabetes: a population-based study. Diabetes Care 2011; 34:1145.
  35. Persson M, Fadl H, Hanson U, Pasupathy D. Disproportionate body composition and neonatal outcome in offspring of mothers with and without gestational diabetes mellitus. Diabetes Care 2013; 36:3543.
  36. Ballard JL, Rosenn B, Khoury JC, Miodovnik M. Diabetic fetal macrosomia: significance of disproportionate growth. J Pediatr 1993; 122:115.
  37. McFarland MB, Trylovich CG, Langer O. Anthropometric differences in macrosomic infants of diabetic and nondiabetic mothers. J Matern Fetal Med 1998; 7:292.
  38. Esakoff TF, Cheng YW, Sparks TN, Caughey AB. The association between birthweight 4000 g or greater and perinatal outcomes in patients with and without gestational diabetes mellitus. Am J Obstet Gynecol 2009; 200:672.e1.
  39. Acker DB, Sachs BP, Friedman EA. Risk factors for shoulder dystocia in the average-weight infant. Obstet Gynecol 1986; 67:614.
  40. Gregory KD, Henry OA, Ramicone E, et al. Maternal and infant complications in high and normal weight infants by method of delivery. Obstet Gynecol 1998; 92:507.
  41. Nesbitt TS, Gilbert WM, Herrchen B. Shoulder dystocia and associated risk factors with macrosomic infants born in California. Am J Obstet Gynecol 1998; 179:476.
  42. Robert MF, Neff RK, Hubbell JP, et al. Association between maternal diabetes and the respiratory-distress syndrome in the newborn. N Engl J Med 1976; 294:357.
  43. Bourbon JR, Farrell PM. Fetal lung development in the diabetic pregnancy. Pediatr Res 1985; 19:253.
  44. Gewolb IH, O'Brien J. Surfactant secretion by type II pneumocytes is inhibited by high glucose concentrations. Exp Lung Res 1997; 23:245.
  45. Gewolb IH. Effect of high glucose on fetal lung maturation at different times in gestation. Exp Lung Res 1996; 22:201.
  46. Werner EF, Romano ME, Rouse DJ, et al. Association of Gestational Diabetes Mellitus With Neonatal Respiratory Morbidity. Obstet Gynecol 2019; 133:349.
  47. Bental Y, Reichman B, Shiff Y, et al. Impact of maternal diabetes mellitus on mortality and morbidity of preterm infants (24-33 weeks' gestation). Pediatrics 2011; 128:e848.
  48. Piper JM. Lung maturation in diabetes in pregnancy: if and when to test. Semin Perinatol 2002; 26:206.
  49. Persson B, Hanson U. Neonatal morbidities in gestational diabetes mellitus. Diabetes Care 1998; 21 Suppl 2:B79.
  50. Pinter E, Peyman JA, Snow K, et al. Effects of maternal diabetes on fetal rat lung ion transport. Contribution of alveolar and bronchiolar epithelial cells to Na+,K(+)-ATPase expression. J Clin Invest 1991; 87:821.
  51. Das S, Irigoyen M, Patterson MB, et al. Neonatal outcomes of macrosomic births in diabetic and non-diabetic women. Arch Dis Child Fetal Neonatal Ed 2009; 94:F419.
  52. Yamamoto JM, Corcoy R, Donovan LE, et al. Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial. Diabet Med 2019; 36:1046.
  53. Cowett RM, Susa JB, Giletti B, et al. Glucose kinetics in infants of diabetic mothers. Am J Obstet Gynecol 1983; 146:781.
  54. Aucott SW, Williams TG, Hertz RH, Kalhan SC. Rigorous management of insulin-dependent diabetes mellitus during pregnancy. Acta Diabetol 1994; 31:126.
  55. Arimitsu T, Kasuga Y, Ikenoue S, et al. Risk factors of neonatal hypoglycemia in neonates born to mothers with gestational diabetes. Endocr J 2023; 70:511.
  56. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358:1991.
  57. Metzger BE, Persson B, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia. Pediatrics 2010; 126:e1545.
  58. Kalhan SC, Savin SM, Adam PA. Attenuated glucose production rate in newborn infants of insulin-dependent diabetic mothers. N Engl J Med 1977; 296:375.
  59. Demarini S, Mimouni F, Tsang RC, et al. Impact of metabolic control of diabetes during pregnancy on neonatal hypocalcemia: a randomized study. Obstet Gynecol 1994; 83:918.
  60. Rosenn B, Miodovnik M, Tsang R. Common clinical manifestations of maternal diabetes in newborn infants: implications for the practicing pediatrician. Pediatr Ann 1996; 25:215.
  61. Tsang RC, Strub R, Brown DR, et al. Hypomagnesemia in infants of diabetic mothers: perinatal studies. J Pediatr 1976; 89:115.
  62. Freitag JJ, Martin KJ, Conrades MB, et al. Evidence for skeletal resistance to parathyroid hormone in magnesium deficiency. Studies in isolated perfused bone. J Clin Invest 1979; 64:1238.
  63. Banerjee S, Mimouni FB, Mehta R, et al. Lower whole blood ionized magnesium concentrations in hypocalcemic infants of gestational diabetic mothers. Magnes Res 2003; 16:127.
  64. O W, Omori K, Emmanouilides GC, Phelps DL. Placenta to lamb fetus transfusion in utero during acute hypoxia. Am J Obstet Gynecol 1975; 122:316.
  65. Kuhle S, Massicotte P, Chan A, Mitchell L. A case series of 72 neonates with renal vein thrombosis. Data from the 1-800-NO-CLOTS Registry. Thromb Haemost 2004; 92:729.
  66. Georgieff MK, Landon MB, Mills MM, et al. Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 1990; 117:455.
  67. Peevy KJ, Landaw SA, Gross SJ. Hyperbilirubinemia in infants of diabetic mothers. Pediatrics 1980; 66:417.
  68. Ullmo S, Vial Y, Di Bernardo S, et al. Pathologic ventricular hypertrophy in the offspring of diabetic mothers: a retrospective study. Eur Heart J 2007; 28:1319.
  69. Veille JC, Sivakoff M, Hanson R, Fanaroff AA. Interventricular septal thickness in fetuses of diabetic mothers. Obstet Gynecol 1992; 79:51.
  70. Monda E, Verrillo F, Altobelli I, et al. Natural history of left ventricular hypertrophy in infants of diabetic mothers. Int J Cardiol 2022; 350:77.
  71. Way GL, Wolfe RR, Eshaghpour E, et al. The natural history of hypertrophic cardiomyopathy in infants of diabetic mothers. J Pediatr 1979; 95:1020.
  72. Mace S, Hirschfield SS, Riggs T, et al. Echocardiographic abnormalities in infants of diabetic mothers. J Pediatr 1979; 95:1013.
  73. Heart Disease: A Textbook of Cardiovascular Medicine, Braunwald E (Ed), Saunders, Philadelphia 1997.
  74. Chandra T, Tripathi S, Tiwari A, et al. Role of cord blood IGF-1 and maternal HbA1c levels to predict interventricular septal hypertrophy among infants of diabetic mothers: A case-control study. Early Hum Dev 2023; 179:105751.
  75. Reece EA, Homko CJ. Infant of the diabetic mother. Semin Perinatol 1994; 18:459.
  76. Redondo MJ, Jeffrey J, Fain PR, et al. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med 2008; 359:2849.
  77. Pettitt DJ, Aleck KA, Baird HR, et al. Congenital susceptibility to NIDDM. Role of intrauterine environment. Diabetes 1988; 37:622.
  78. Dabelea D, Hanson RL, Bennett PH, et al. Increasing prevalence of Type II diabetes in American Indian children. Diabetologia 1998; 41:904.
  79. Dabelea D, Knowler WC, Pettitt DJ. Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians. J Matern Fetal Med 2000; 9:83.
  80. Silverman BL, Rizzo TA, Cho NH, Metzger BE. Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care 1998; 21 Suppl 2:B142.
  81. Mughal MZ, Eelloo J, Roberts SA, et al. Body composition and bone status of children born to mothers with type 1 diabetes mellitus. Arch Dis Child 2010; 95:281.
  82. Sobngwi E, Boudou P, Mauvais-Jarvis F, et al. Effect of a diabetic environment in utero on predisposition to type 2 diabetes. Lancet 2003; 361:1861.
  83. Touger L, Looker HC, Krakoff J, et al. Early growth in offspring of diabetic mothers. Diabetes Care 2005; 28:585.
  84. Vääräsmäki M, Pouta A, Elliot P, et al. Adolescent manifestations of metabolic syndrome among children born to women with gestational diabetes in a general-population birth cohort. Am J Epidemiol 2009; 169:1209.
  85. Vohr BR, McGarvey ST, Tucker R. Effects of maternal gestational diabetes on offspring adiposity at 4-7 years of age. Diabetes Care 1999; 22:1284.
  86. Clausen TD, Mathiesen ER, Hansen T, et al. Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes. J Clin Endocrinol Metab 2009; 94:2464.
  87. Page KA, Romero A, Buchanan TA, Xiang AH. Gestational diabetes mellitus, maternal obesity, and adiposity in offspring. J Pediatr 2014; 164:807.
  88. Logan KM, Gale C, Hyde MJ, et al. Diabetes in pregnancy and infant adiposity: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2017; 102:F65.
  89. Lawlor DA, Lichtenstein P, Långström N. Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families. Circulation 2011; 123:258.
  90. Mantzorou M, Papandreou D, Pavlidou E, et al. Maternal Gestational Diabetes Is Associated with High Risk of Childhood Overweight and Obesity: A Cross-Sectional Study in Pre-School Children Aged 2-5 Years. Medicina (Kaunas) 2023; 59.
  91. Rizzo TA, Dooley SL, Metzger BE, et al. Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol 1995; 173:1753.
  92. Adane AA, Mishra GD, Tooth LR. Diabetes in Pregnancy and Childhood Cognitive Development: A Systematic Review. Pediatrics 2016; 137.
  93. Bytoft B, Knorr S, Vlachova Z, et al. Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study). Diabetes Care 2016; 39:1356.
  94. Sells CJ, Robinson NM, Brown Z, Knopp RH. Long-term developmental follow-up of infants of diabetic mothers. J Pediatr 1994; 125:S9.
  95. Fraser A, Nelson SM, Macdonald-Wallis C, Lawlor DA. Associations of existing diabetes, gestational diabetes, and glycosuria with offspring IQ and educational attainment: the Avon Longitudinal Study of Parents and Children. Exp Diabetes Res 2012; 2012:963735.
  96. Boghossian NS, Hansen NI, Bell EF, et al. Outcomes of Extremely Preterm Infants Born to Insulin-Dependent Diabetic Mothers. Pediatrics 2016; 137.
Topic 5058 Version 35.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟