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Infants of women with diabetes

Authors: Arieh Riskin, MD, MHA, PhD, Joseph A Garcia-Prats, MD
Section Editor: Joseph I Wolfsdorf, MD, BCh
Deputy Editor: Laurie Wilkie, MD, MS

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2023. | This topic last updated: Feb 10, 2020.

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 diagnosed before pregnancy with a prevalence rate of approximately 1.8 percent) or
gestational (ie, diabetes diagnosed during pregnancy with a prevalence rate of approximately
7.5 percent). The outcome is generally related to the onset and duration of glucose intolerance
during pregnancy and severity of the mother's diabetes. (See "Pregestational (preexisting)
diabetes: Preconception counseling, evaluation, and management".)

This topic will review the complications seen in the offspring of women with diabetes and the
management of affected neonates. The prenatal management of pregestational and
gestational diabetes mellitus is discussed in separate topic reviews. (See "Gestational diabetes
mellitus: Screening, diagnosis, and prevention" and "Pregestational (preexisting) diabetes
mellitus: Obstetric issues and management" and "Gestational diabetes mellitus: Obstetric
issues and management" and "Gestational diabetes mellitus: Glucose management and
maternal prognosis" and "Pregestational (preexisting) diabetes: Preconception counseling,
evaluation, and management".)

FETAL EFFECTS

Poor glycemic control in pregnant diabetic women leads to deleterious fetal effects throughout
pregnancy, as follows [1]:
● 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 [2]. The risk for congenital
malformations is only slightly increased with gestational diabetes mellitus (GDM)
compared with the general population (odds ratio [OR] 1.1-1.3). 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 are probably undiagnosed women with type 2 diabetes [3,4]. (See 'Congenital
anomalies' below and "Pregestational (preexisting) diabetes: Preconception counseling,
evaluation, and management".)

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

• 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 [5]. Fetal
hypoxemia contributes to increased mortality, metabolic acidosis, alterations in fetal
iron distribution, and increased erythropoiesis [6]. Increased synthesis of
erythropoietin leads to polycythemia [7,8]; promotes catecholamine production, which
can result in hypertension and cardiac hypertrophy; and may contribute to the 20 to 30
percent rate of stillbirth seen in poorly controlled diabetic pregnancies [9]. As the fetal
red cell mass increases, iron redistribution results in iron deficiency in developing
organs, which may contribute to cardiomyopathy and altered neurodevelopment [6].
Fetal hyperinsulinemia is also thought to contribute to impaired or delayed lung
maturation. (See 'Polycythemia and hyperviscosity syndrome' below and
'Cardiomyopathy' below and 'Respiratory distress' below and "Pregestational
(preexisting) diabetes mellitus: Obstetric issues and management" and "Gestational
diabetes mellitus: Obstetric issues and management", section on 'Fetal surveillance'
and "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management",
section on 'Initiation and frequency of fetal surveillance'.)

• Oxidative stress may play a role in maternal and fetal complications of diabetic
pregnancies [10,11]. For example, increased generation of reactive oxygen species with
inadequate antioxidant defenses in the fetal heart might lead to abnormal cardiac
remodeling and hypertrophic cardiomyopathy [4,12]. In addition, increased
erythropoietin production with resultant polycythemia in the newborn infant of a
mother with diabetes was related to the degree of oxidative stress [12,13].
 • Excessive nutrients delivered from the poorly controlled mother with diabetes cause
increased fetal growth, particularly of insulin-sensitive tissues (ie, liver, muscle, cardiac
muscle, and subcutaneous fat), resulting in macrosomia, defined as a birth weight (BW)
≥4000 g or greater than the 90th percentile for gestational age (GA) ( picture 1). (See
'Macrosomia' below and "Pregestational (preexisting) diabetes: Preconception
counseling, evaluation, and management".)

• Maternal hyperglycemia leads to fetal hyperglycemia resulting in fetal

hyperinsulinemia and neonatal hypoglycemia. Fetal hyperinsulinemia also 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 'Hypoglycemia'
below and 'Metabolic risks' below.)

NEONATAL EFFECTS

Infants of mothers with diabetes are at increased risk for congenital anomalies, mortality and
morbidity compared with neonates born to a mother without diabetes ( table 2). Neonatal
complications in offspring of mothers with diabetes include [14]:

● Congenital anomalies
● Prematurity
● Perinatal asphyxia
● Macrosomia, which increases the risk of birth injury (eg, brachial plexus injury)
● Respiratory distress
● Metabolic complications including hypoglycemia and hypocalcemia
● Hematologic complications including polycythemia and hyperviscosity
● Low iron stores
● Hyperbilirubinemia
● Cardiomyopathy

Although insulin treatment and intensive prenatal and neonatal care have improved, neonatal
complications and congenital anomalies observed in diabetic pregnancies contribute to a
reported perinatal mortality rate that ranges from 0.6 to 4.8 percent.

Pregestational versus gestational diabetes — Infants born to mothers with pregestational

diabetes have a higher risk of mortality and morbidity compared with offspring from mothers
with gestational DM; these infants are more likely to be macrosomic, preterm, and have
congenital anomalies and respiratory distress [2,15-19]. For infants born to mothers with
gestational DM, the risk of adverse neonatal effects modestly increases when mothers require
insulin treatment during pregnancy compared with infants whose mothers are managed by
diet alone [20]. Strict glycemic control preconception and during pregnancy is associated with
lower 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'.)

Infants of mothers who have insulin-treated DM are more likely to be preterm and macrosomic
than infants born to mothers with type 2 DM not treated with insulin as well as infants of
mothers with gestational diabetes. This was illustrated in a population study of all live births in
Finland between 2004 and 2014. Infants of women with any type of DM who received insulin
therapy were at highest risk for large for gestational age and preterm birth (40 and 37 percent,
odds ratio [adjusted OR] 43.8, 95% CI 40.88-46.93 and 11.17, 95% CI 10.46-11.93, respectively),
infants of women with type 2 DM not receiving insulin were at mild to moderately increased risk
(12.8 and 10.1 percent, aOR 9.57, 95% CI 8.65-10.58 and 2.12, 95% CI 1.9-2.36, respectively), and
infants of women with gestational DM not receiving insulin were mildly or no increased risk (5
and 5 percent, aOR 3.8, 95% CI 3.66-3.96 and 1, respectively) compared with women with no
diabetes (2 and 5 percent) [18]. These data can be useful for counseling women with diabetes
about risks for LGA and PTB in offspring. (See "Pregestational (preexisting) diabetes:
Preconception counseling, evaluation, and management", section on 'Fetal and neonatal risks'
and "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management".)

Congenital anomalies — Infants of mothers with diabetes are at significant risk for major
congenital anomalies due to maternal hyperglycemia at the time of conception and during
early gestation ( table 1) [6]. The overall reported risk for major malformations is
approximately 5 to 6 percent, with a higher prevalence rate of 10 to 12 percent when mothers
require insulin therapy [2,14,16,21]. In a study of 13,030 infants with congenital anomalies and
4895 without birth defects, when compared with a reference group of nondiabetic control
mothers, the risk of isolated and multiple congenital anomalies was highest in infants of
mothers with pregestational diabetes (adjusted odd ratios [OR] 3.17, 95% CI 2.2-4.99 and
adjusted OR 8.62, 95% CI 5.27-14.1, respectively) followed by infants born to mothers with
gestational diabetes (adjusted OR 1.42, 95% CI 1.17-1.73 and adjusted OR 1.5, 95% CI 1.13-2.0)
[22].

Congenital malformations account for approximately 50 percent of the perinatal deaths in

infants of mothers with diabetes [23]. This risk can be reduced by strict glycemic control during
the pre- and periconceptual (first eight weeks of pregnancy) periods. Two-thirds of the
anomalies in infants of mothers with diabetes involve either the cardiovascular system (8.5 per
100 live births) or central nervous system (CNS; 5.3 per 100 live births) [21].

● Cardiac – Cardiovascular malformations occur in 3 to 9 percent of diabetic pregnancies

[21,24]. Cardiac defects that present more frequently in Infants of mothers with diabetes
than in the normal newborn population include transposition of the great arteries (TGA),
double outlet right ventricle (DORV), ventricular septal defect (VSD), truncus arteriosus,
tricuspid atresia, and patent ductus arteriosus (PDA) [14,21,24].

● CNS – Anencephaly and spina bifida are 13 and 20 times more frequent, respectively,
among Infants of mothers with diabetes compared with infants of mothers without
diabetes [21]. The majority of cases of caudal regression syndrome occur in Infants of
mothers with diabetes [25]. This syndrome 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), and occurs approximately 200 times more
frequently in Infants of mothers with diabetes than in other infants [26]. (See "Closed
spinal dysraphism: Pathogenesis and types", section on 'Risk factors'.)

● Other anomalies include [14,21]:

• 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 [27]. Small colon syndrome is a rare condition that
presents as a transient inability to pass meconium, which resolves spontaneously.

Preterm delivery — Spontaneous and medically indicated preterm delivery occur more

frequently in diabetic than nondiabetic pregnancies [2] ( table 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 — Infants of mothers with diabetes are at increased risk for intrauterine or
perinatal asphyxia due to macrosomia (failure to progress and shoulder dystocia) and
cardiomyopathy (fetal heart rate abnormalities), which often is defined broadly in the literature
to include fetal heart rate abnormalities during labor, low Apgar scores (calculator 1), and
intrauterine death ( table 2).
In one study of 162 infants of mothers with diabetes, 27 percent had perinatal asphyxia [28].
Perinatal asphyxia correlated with hyperglycemia in labor, prematurity, and nephropathy.
Maternal vascular disease, manifested by nephropathy, may contribute to the development of
fetal hypoxia and subsequent perinatal asphyxia.

Macrosomia — Macrosomia, defined as birth weight (BW) greater than the 90th percentile on a
population-appropriate growth chart or above 4000 g, is a common complication and can occur
in all diabetic pregnancies. However, the incidence appears to be greater in infants born to
mothers with pregestational diabetes [2,29,30].

Macrosomia is associated with disproportionate growth, resulting in an increased ponderal

index that results in higher chest-to-head and shoulder-to-head ratio, higher body fat, and
thicker upper extremity skinfolds compared with nondiabetic control infants of similar weight
and length [29-32]. As a result, at birth, infants of mothers with diabetes typically appear large
and plethoric, with excessive fat accumulation in the abdominal and scapular regions, and have
visceromegaly ( 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 [30,33]. Fetal macrosomia including risk factors and complications for delivery and
neonate are discussed separately. (See "Fetal macrosomia" and "Large for gestational age
newborn", section on 'Neonatal morbidity' and "Shoulder dystocia: Risk factors and planning
birth of high-risk pregnancies".)

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 [34]
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
[14,15,35]. 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 [36].

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 — It has been commonly assumed that respiratory distress is a frequent
complication in infants of mothers with diabetes due to the increased risk of neonatal
respiratory distress syndrome (RDS) secondary to surfactant deficiency. However, a secondary
analysis of the Antenatal Late Preterm Delivery Steroids (ALPS) trial reported that after
adjusting for confounding variables (eg, age of the mother and gestational age [GA] at delivery)
neonates born to mothers with gestational diabetes had similar rates of respiratory distress as
those born to mothers without diabetes [37]. This report included only late preterm births (GA
between 34 0/7 and 36 5/7 weeks) and did not provide information about each participant's
glucose control and diabetes treatment. Therefore, good glycemic control may have reduced
the risk of respiratory problems in the infants of women with GDM. (See "Gestational diabetes
mellitus: Obstetric issues and management", section on 'Consequences of GDM'.)

Respiratory distress syndrome — RDS due to surfactant deficiency occurs more frequently in

infants of mothers with diabetes for the following two reasons [2,14,15,21,38]:

● Infants of mothers with diabetes are more likely to be delivered prematurely than infants
born to mothers without diabetes. (See 'Preterm delivery' above.)

● At a given gestational age, infants of mothers with diabetes are more likely to develop RDS
because maternal hyperglycemia appears to delay surfactant synthesis. The proposed
underlying mechanism is neonatal hyperinsulinemia, which interferes with the induction
of lung maturation by glucocorticoids [39-41]. The risk of RDS in preterm infants of
mothers whose diabetes is well-controlled approaches that of infants born to mothers
without diabetes at a similar gestational age [37,42,43].

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)
and cardiomyopathy. (See 'Cardiomyopathy' below.)

TTN occurs two to three times more commonly in infants of mothers with diabetes than in
normal infants [14,44]. 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 [2,45]. (See "Transient tachypnea of the newborn".)

In infants born to mothers with gestational diabetes mellitus (GDM), the risk for respiratory
distress increases for those with BW >4000 g [3,33,46].

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 — Hypoglycemia, defined as blood glucose levels below 40 mg/dL (2.2 mmol/L)

in the first 24 hours of life, occurs frequently in infants of mothers with diabetes [2], even in
mothers who receive intensive prenatal care [14,47]. 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 glucose supplementation, including parenteral glucose
infusion. In our experience, the hyperinsulinemic state typically lasts two to four days. In
neonates requiring glucose supplementation, the maintenance of normal plasma glucose levels
while supplemental glucose is being weaned is evidence of resolving hyperinsulinism. Further
testing should be undertaken to define the cause of persistent hypoglycemia in infants who
continue to require glucose infusions at rates exceeding 8 to 10 mg/kg per minute to maintain
normal plasma glucose levels beyond the first week of life. (See "Management and outcome of
neonatal hypoglycemia", section on 'Evaluation of infants with persistent hypoglycemia'.)

Hypoglycemia is likely caused by persistent hyperinsulinemia in the newborn after interruption

of the intrauterine glucose supply from the mother. In particular, macrosomic infants with
increased BW (>90th percentile or >4000 g) are more likely to develop hyperinsulinemia and
hypoglycemia [2,48,49]. Strict glycemic control during pregnancy decreases, but does not
abolish, the risk of neonatal hypoglycemia [50,51]. (See "Gestational diabetes mellitus: Glucose
management and maternal prognosis" and "Pregestational (preexisting) diabetes mellitus:
Antenatal glycemic control" and "Pregestational (preexisting) and gestational diabetes:
Intrapartum and postpartum glucose management" and "Gestational diabetes mellitus:
Obstetric issues and management".)

Infants of mothers with diabetes who are preterm or small for gestational age (SGA) are at
increased risk for persistent hypoglycemia because glycogen stores are reduced, and
hyperinsulinemia impairs the ability to mobilize hepatic glycogen [52]. In these infants,
hypoglycemia may last longer than two to four days and may require more prolonged and
higher rates of glucose infusion.

Although there are no data on the caloric needs of infants of mothers with diabetes 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 'Obesity and glucose metabolism' below.)

The clinical manifestations, evaluation, and management of neonatal hypoglycemia are

discussed separately. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia"
and "Management and outcome of neonatal hypoglycemia".)

Hypocalcemia — The reported prevalence of hypocalcemia, defined as a total serum calcium

concentration less than 7 mg/dL (1.8 mmol/L) or an ionized calcium value less than 4 mg/dL (1
mmol/L), or in infants with BW less than 1500 g, an ionized calcium less than 3.2 mg/dL (0.8
mmol/L), ranges from at least 5 percent and up to 30 percent in infants of mothers with
diabetes ( table 2) [14,53]. Good glycemic control during pregnancy reduces the risk of
neonatal hypocalcemia [53].

The lowest serum calcium concentration typically occurs between 24 and 72 hours after birth.
Hypocalcemia usually is asymptomatic and resolves without treatment [14]. As a result, routine
screening is not recommended. However, the serum calcium concentration should be
measured in infants with jitteriness, lethargy, apnea, tachypnea, or seizures, and in those with
prematurity, asphyxia, respiratory distress, or suspected infection.

The clinical manifestations, evaluation, and management of neonatal hypocalcemia are

discussed separately. (See "Neonatal hypocalcemia".)

Hypomagnesemia — Hypomagnesemia, defined as serum magnesium concentration less

than 1.5 mg/dL (0.75 mmol/L), occurs in up to 40 percent of infants of mothers with diabetes
within the first three days after birth [54,55]. It has been proposed that low neonatal levels are
due to maternal hypomagnesemia caused by increased urinary loss secondary to diabetes.
Prematurity may be a contributing factor.

Hypomagnesemia usually is transient and asymptomatic and, thus, usually is not treated.
However, hypomagnesemia can reduce both parathyroid hormone (PTH) secretion and PTH
responsiveness [56,57]. As a result, in some neonates with hypocalcemia and hypomagnesemia,
the hypocalcemia may not respond to treatment until the hypomagnesemia is corrected [58].

Polycythemia and hyperviscosity syndrome — Elevated hematocrits including polycythemia,

defined as a central venous hematocrit of more than 65 percent, are more likely in infants of
mothers with diabetes than in infants whose mothers are not diabetic [2]. In a large case series,
of the 276 infants with measured hematocrits, 17 percent of infants of mothers with diabetes
had hematocrits above 60 percent, including 5 percent of infants with polycythemia [14]. The
underlying pathogenesis is due to increased erythropoietin concentrations caused by chronic
fetal hypoxemia [7,8]. Transfusion of placental blood to the fetus associated with maternal or
fetal distress also may contribute to a high hematocrit [59]. Higher hemoglobin and hematocrit
values in the newborn are associated with fetal exposure to oxidative stress [12].
Polycythemia may lead to hyperviscosity syndrome, including vascular sludging, ischemia, and
infarction of vital organs. Hyperviscosity is thought to contribute to the increased incidence of
renal vein thrombosis seen in infants of mothers with diabetes [60]. To detect polycythemia, the
hematocrit should be measured within 12 hours of birth.

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 [61]. However, there
are no data on iron supplementation therapy and it is not currently recommended. It is thought
that the excess iron in the polycythemic red cell mass will be recirculated as the excess red
blood cells break down.

Hyperbilirubinemia — Hyperbilirubinemia occurs in 11 to 29 percent of infants of mothers

with diabetes, especially in preterm infants [14]. In addition to prematurity, other factors
associated with neonatal jaundice include poor maternal glycemic control, macrosomia, and
polycythemia [54,62]. (See "Screening for hyperbilirubinemia in term and late preterm
newborns" and "Initial management of unconjugated hyperbilirubinemia in term and late
preterm newborns".)

Cardiomyopathy — Infants of mothers with diabetes are at increased risk for transient

hypertrophic cardiomyopathy [2,63,64]. In this condition, the most prominent change is
thickening of the interventricular septum (IVS) with reduction in the size of the ventricular
chambers, resulting in potential obstruction of left ventricular outflow. Outflow obstruction
occasionally is aggravated by anterior systolic motion of the mitral valve.

Infants often are asymptomatic, but 5 to 10 percent have respiratory distress or signs of poor
cardiac output or heart failure. The chest radiograph may show cardiomegaly; but hypertrophy
is best detected by echocardiography. Cardiomyopathy is transient and 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 [65].
Supportive care for symptomatic infants includes increased intravenous (IV) fluid administration
and propranolol. Inotropic agents are contraindicated because they may decrease ventricular
size and further obstruct cardiac outflow [66].

Cardiac hypertrophy is thought to be caused by fetal hyperinsulinemia, which increases the

synthesis and deposition of fat and glycogen in the myocardial cells [56]. It is most likely to
occur in mothers with poor glycemic control during pregnancy [67,68]. However, increased
cardiac muscle mass also occurs in fetuses of mothers with diabetes with good metabolic
control (mean glycated hemoglobin [HbA1c] 7.5 percent) [69]. One study suggests that there is
a correlation between high degrees of oxidative stress and the abnormal cardiac remodeling
resulting in selective morphologic hypertrophy [12].

Fetal echocardiography shows 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
IVS, and less of the left ventricular (LV) free walls [70]. Another study suggested that a prenatal
echocardiographic measurements (at 35 weeks or more) of IVS thickness ≥4.5 mm and/or
IVS/left myocardial wall thickness (LMWT) ratio ≤1.18 were not only predictive of hypertrophic
cardiomyopathy, but were also associated with increased risk for intrauterine and perinatal
mortality [71].

Some infants develop congestive cardiomyopathy, a more diffuse process of hypertrophy and
hyperplasia of the myocardial cells that frequently occurs in association with perinatal asphyxia,
hypoglycemia, or hypocalcemia [68]. Echocardiography shows a dilated and poorly contractile
heart. This condition usually is also reversible as the metabolic derangements are corrected.

NEONATAL MANAGEMENT

The management of infants of women with diabetes needs to anticipate and treat any
complication associated with maternal hyperglycemia as well as provide routine neonatal care.
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.

In our practice, we use the following approach:

● Prior to delivery, an assessment of the need for neonatal resuscitation is made based on
the GA, anticipated BW, presence of a congenital anomaly or labor complications, and the
mode of delivery (eg, cesarean delivery). (See "Neonatal resuscitation in the delivery
room", section on 'Anticipation of resuscitation need'.)

● 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'.)

● Further evaluation following transition from the delivery room includes a comprehensive
examination, and laboratory screening for hypoglycemia and polycythemia.

• If cyanosis is detected, the infant should be assessed for cardiac and respiratory
disease including measurement of oxygen saturation by pulse oximetry. (See
"Approach to cyanosis in the newborn".)

• Glucose monitoring is performed within one to two hours after birth or whenever
symptoms consistent with hypoglycemia occur. Samples should be obtained before
feedings. Surveillance is performed for the first 12 to 24 hours of life. Monitoring is
continued after 24 hours of life, in infants with low plasma glucose concentrations (less
than 45 mg/dL, 2.5 mmol/L) until feedings are well established and glucose values have
normalized [72]. In our centers, intervention for hypoglycemia is initiated at glucose
levels <40 mg/dL (2.2 mmol/L) during the first 24 hours of life, and <50 mg/dL (2.8
mmol/L) between 24 and 48 hours of life. (See 'Hypoglycemia' above and "Management
and outcome of neonatal hypoglycemia".)

• The hematocrit should be measured within the first few hours of delivery. (See
'Polycythemia and hyperviscosity syndrome' above and "Neonatal polycythemia".)

• Bilirubin levels should be measured if the infant appears to be jaundiced. (See

"Screening for hyperbilirubinemia in term and late preterm newborns" and
"Unconjugated hyperbilirubinemia in preterm infants <35 weeks gestation".)

• Calcium and magnesium levels should be obtained in any infant with symptoms
compatible with either 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".)

LONG-TERM OUTCOME

Long-term outcome data show that prenatal exposure to hyperglycemia increases the risk of
postnatal metabolic complications and impacts neurodevelopmental outcome [73-76].
Metabolic risks

Diabetes — Infants of mothers with diabetes have an increased risk of developing diabetes,

which is, in part, genetically determined [77]. The lifelong risk of type 1 diabetes is 2 percent in
offspring of a mother with type 1 diabetes, 6 percent in siblings, and 65 percent by age 60 years
in identical twins (versus 0.3 to 0.4 percent in subjects with no family history) [78]. (See
"Pathogenesis of type 1 diabetes mellitus".)

The development of type 2 diabetes also is influenced by genetic susceptibility. The lifetime risk
for a first-degree relative of a patient with type 2 diabetes is 5 to 10 times higher than that of
age- and weight-matched subjects without a family history. (See "Pathogenesis of type 2
diabetes mellitus".)

The development of type 2 diabetes 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 type 2 diabetes between 20 and 24 years of age
compared with offspring of prediabetic (9 percent) or women without diabetes (1 percent)
[79,80]. 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 type 2 diabetes by 34 years of age [81].

Obesity and glucose metabolism — Intrauterine exposure to hyperglycemia resulting in fetal

hyperinsulinemia may affect the development of adipose tissue and pancreatic beta cells
leading to increased BMI and impaired glucose metabolism, which may result in an increased
risk for obesity. This effect is seen in offspring as adults or older children for both
pregestational [82-84] and gestational diabetes [85-91].

Neurodevelopmental outcome — Data are limited regarding the effect of maternal

pregestational and gestational diabetes on the subsequent neurodevelopmental outcome of
offspring.

● A review of the literature reported that maternal gestational diabetes seems to be

negatively associated with offspring's childhood cognitive development, particularly
language development [92]. However, the quality of the evidence was poor, as most
studies did not adequately control for confounding factors such as pre-pregnancy obesity
or maternal socioeconomic status, and failed to provide or report adequate blinding.
 ● In a subsequent report from the National Institute of Child Health and Human
Development (NICHD) Neonatal Research Network of extremely preterm infants
(gestational age [GA] from 22 to 28 weeks) born from 2006 to 2011, there was no
difference in neurodevelopmental outcome amongst the initial three study groups (infants
born to mothers using insulin before pregnancy, infants born to those starting insulin
during pregnancy, and infants born to maternal controls) at 18 to 22 months corrected
age [93].

● In a Danish cohort study, adolescents born to mothers with pregestational type 1 diabetes
had lower scores on cognitive testing compared with controls after adjustment for
confounding factors [94]. Confounding factors based on parental reporting by
questionnaire included sex, age at follow-up, parity, parental educational achievement,
maternal age at delivery, presence of neonatal complications, maternal complications,
gestational age, and maternal socioeconomic status.

Other limited data suggest that poorly controlled maternal diabetes during pregnancy may
impact neurodevelopmental outcome [73,94,95]. However, evidence is circumstantial and of
poor quality.

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

Diabetes in pregnancy is associated with an increased risk of fetal, neonatal, and long-term
complications in offspring.

● Adverse effects of diabetes during pregnancy that affect the fetus include spontaneous
abortions, major malformations, and stillbirths. In addition, maternal hyperglycemia leads
to increased fetal growth resulting in macrosomia and fetal hyperinsulinemia, which
increase the risk of neonatal hypoglycemia. (See 'Fetal effects' above.)

● Infants of mothers with diabetes are at increased risk for mortality and morbidity
compared with infants born to mothers without diabetes. The risk of neonatal
complications generally increases with poor maternal glycemic control. Potential adverse
effects include:

• Congenital anomalies, especially cardiovascular and central nervous system (CNS)

defects. (See 'Congenital anomalies' above.)

• Preterm birth. (See 'Preterm delivery' above.)

• Perinatal asphyxia. (See 'Perinatal asphyxia' above.)

• Macrosomia, defined as a birth weight (BW) greater than the 90th percentile or greater
than 4000 g. In infants of mothers with diabetes, macrosomia is associated with
disproportionate growth that results in high chest-to-head and shoulder-to-head ratios
that predispose to birth injury, especially shoulder dystocia ( picture 1). (See
'Macrosomia' above.)

• Respiratory distress is a common complication primarily due to the increased risk of

respiratory distress syndrome (RDS). (See 'Respiratory distress' above.)

• Hypoglycemia that generally occurs within the first few hours after birth. (See
'Hypoglycemia' above.)

• Hypocalcemia is commonly observed but generally is asymptomatic. (See

'Hypocalcemia' above.)

• Polycythemia and hyperviscosity. (See 'Polycythemia and hyperviscosity syndrome'

above.)
 • Low iron stores.

• Hyperbilirubinemia. (See 'Hyperbilirubinemia' above.)

• Transient hypertrophic cardiomyopathy that is generally asymptomatic. However, a

subset of affected infants (5 to 10 percent) may present with respiratory distress, poor
cardiac output, or heart failure. (See 'Cardiomyopathy' above.)

● The management of infants of women with diabetes needs to anticipate and treat any
complication associated with maternal hyperglycemia and also provides routine neonatal
care. It includes a physical examination that focuses on the respiratory and cardiac status
of the infant and identifies any major congenital anomaly. One hour after delivery,
laboratory evaluation includes measurement of the infant's blood glucose and hematocrit
to screen for hypoglycemia and polycythemia. (See 'Neonatal management' above.)

● Long-term outcome data suggest that prenatal exposure to hyperglycemia increases the
risk of postnatal metabolic complications (eg, diabetes, increased body mass index [BMI],
and impaired glucose metabolism) and may also negatively impact neurodevelopmental
outcome. (See 'Long-term outcome' above.)

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