Diabetes Mellitus in Pregnancy

Desmond M. Sutton, MD,* Christina S. Han, MD,† Erika F. Werner, MD, MS*
*Department of Obstetrics and Gynecology, Women and Infants Hospital of Brown University, Providence, RI
†
Center for Fetal Medicine and Women’s Ultrasound, and University of California at Los Angeles, Los Angeles, CA

Education Gaps
1. Suboptimal control of blood sugars in diabetes during pregnancy has the
potential for serious maternal and neonatal adverse effects.
2. Pediatric providers must be sensitive to the association between a
newborn’s risk and the mother’s level of glycemic control during pregnancy.

Abstract
Gestational and pregestational diabetes make up the most common maternal
metabolic disorder of pregnancy. Suboptimal control of blood glucose has the
potential for serious maternal and neonatal adverse effects. Neonates of
diabetic mothers are at risk for congenital malformations, perinatal mortality,
preeclampsia, preterm birth, increased birthweight, neonatal hypoglycemia
and respiratory distress. The nature and severity of risks depend on the timing
and duration of hyperglycemia. Through glycemic control and proper prenatal
care, many of these risks can be mitigated. Pediatric providers must be
sensitive to the association between a newborn’s risk and the mother’s level of
glycemic control, often linked to her adherence to prenatal care.

Objectives After completing this article, readers should be able to:

1. Understand the impact of maternal gestational and preexisting diabetes

AUTHOR DISCLOSURE Drs Sutton, Han, mellitus on the neonate.
and Werner have disclosed no financial
relationships relevant to this article. This 2. Distinguish between the fetal risks associated with gestational diabetes
commentary does not contain a discussion
of an unapproved/investigative use of a
and those associated with preexisting diabetes mellitus.
commercial product/device.
3. Become aware about the method of diagnosing gestational diabetes.
ABBREVIATIONS 4. Review typical maternal care for women with diabetes in pregnancy.
ACOG American College of Obstetricians
and Gynecologists
BMI body mass index
DKA diabetic ketoacidosis
DM diabetes mellitus INTRODUCTION
FGR fetal growth restriction
Diabetes is the most common metabolic disorder to affect pregnancy and is
GDM gestational diabetes mellitus
IUFD intrauterine fetal demise associated with increased maternal and neonatal morbidity. (1) Three types of
T1DM type 1 diabetes mellitus diabetes affect pregnancy: gestational diabetes mellitus (DM), type 2 DM (T2DM),
T2DM type 2 diabetes mellitus and type 1 DM (T1DM). The latter 2 are referred to as pregestational diabetes

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 because the onset predates the current pregnancy. Depend- has been estimated to affect 4% to 6% of pregnancies in
ing on the timing of onset, inappropriate glucose homeo- the United States. (13) GDM is most prevalent in women
stasis has been associated with congenital malformations, of Hispanic, African, Native American, Asian, and Pacific
miscarriage, perinatal mortality, preeclampsia, preterm birth, Island descent. (12)(14) Women with GDM are at higher
increased birthweight, neonatal hypoglycemia, and respira- risk for maternal, fetal, and neonatal complications (Fig 1).
tory distress. (1)(2)(3) In addition, increased insulin resis- (15)(16) Up to 50% of women with GDM will go on to
tance has been associated with recurrent miscarriage even in develop T2DM over their life course. (16)(17)
women with no known history of diabetes. (4)(5) Fetal expo- GDM represents the maternal system failing to adapt to
sure to maternal hyperglycemia can lead to hyperinsulinemia, normal pregnancy physiology. Early gestation is associated
resulting in short- and long-term complications, including with increases in maternal fat stores and decreases in free
childhood obesity and insulin resistance. (6)(7) fatty acid concentration. As gestation advances, insulin
sensitivity decreases in both the liver and peripheral tissue.
EPIDEMIOLOGY These changes are the physiologic consequence of placental
and maternal hormones, specifically human placental lac-
The prevalence of diabetes in pregnancy has increased
togen, progesterone, estrogen, cortisol, prolactin, and tumor
substantially over the last 20 years because of the obesity
necrosis factor alpha. This metabolic change is intended to
epidemic and improved DM screening. (8) In particular, the
increase glucose levels and allow for the increased energy
incidence of T2DM is anticipated to continue to rise, with
needs required for fetal growth. (18) Normally, the decreased
an expected increase of another 165% by 2050. (9) This
insulin sensitivity is associated with increased insulin se-
increase is anticipated because of the association between
cretion. However, in GDM, the increased secretion is not
obesity, sedentary lifestyles, and T2DM. From 1988 to 2010,
adequate and manifests as hyperglycemia during preg-
the mean body mass index (BMI) in the US adult population
nancy. Because of this pathophysiology, GDM develops over
with DM increased from 30.2 to 32.8 kg/m2. (8) In addition,
the course of pregnancy. Most commonly, women with
gestational diabetes mellitus (GDM) is associated with a
GDM are diagnosed at 24 to 28 weeks of gestation, the
high BMI; a woman’s risk of developing GDM increases
time of routine screening.
from as low as 4% if she is underweight to greater than 15%
if she is morbidly obese. (10) Overall, it is estimated that DM
complicates 6% to 7% of pregnancies in the United States. Pregestational Diabetes (Type 1 and Type 2
(11) GDM accounts for approximately 90% of these cases, Diabetes Mellitus)
with T2DM accounting for most of the remaining 10%. (12) The International Diabetes Federation estimated that 382
million people worldwide had DM in 2013. The Federation
predicts that by 2035, this number will rise to 592 million
CLASSIFICATION AND PATHOPHYSIOLOGY OF
people. These estimates include individuals with both
DIABETES IN PREGNANCY
T1DM and T2DM. In developed countries, it is estimated
Gestational Diabetes Mellitus that T2DM makes up 85% to 95% of all cases of DM. (19)
GDM is defined as carbohydrate intolerance of variable Although T1DM is less common, the onset is typically in
severity that starts or is first recognized in pregnancy. It childhood due to autoimmune destruction of the pancreatic

Figure 1. Complications associated with

gestational diabetes.

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 islet cells. (20) T1DM usually presents abruptly at a young with an increased risk for anomalies because the condition does
age with insulinopenia and necessitates lifelong insulin not occur until later in pregnancy after organogenesis. (25) Most
replacement. common defects for women with T1DM and T2DM include
The pathophysiology of T2DM is less clearly understood cardiac followed by central nervous system and skeletal mal-
and involves metabolic, genetic, and environmental fac- formations (Fig 2). Ventricular septal defects and transposition
tors, which lead to a combination of insulin resistance of the great vessels are increased fivefold in insulin-dependent
and deficiency. Up to 17 genetic sequences that affect insulin diabetes. Sacral agenesis or caudal dysplasia, although not
secretion, function, and receptor production have been pathognomonic, should always prompt evaluation of the mother
associated with an increased risk for T2DM. (21) Adipose for DM, because it is one of the classic diabetic embryopathies.
tissue has also been shown to secrete cytokines and proteins (1)(22)
that contribute toward an increased risk for T2DM. (2) The risk for congenital malformations varies with ma-
ternal glycosylated hemoglobin level. Women with optimal
glucose control and a hemoglobin A1c of 5% to 6% have fetal
IMPACT OF DIABETES IN PREGNANCY ON
malformation rates similar to those of the general popula-
THE NEONATE
tion (2%–3%). In contrast, women with poor glucose control
The risk of developing neonatal complications due to dia- and hemoglobin A1c levels in excess of 10% have a 10% to
betes in pregnancy likely varies with: 25% risk of having a fetus with congenital malformations.
1. Time of onset of DM (22)(24)(26) For women with T1DM or T2DM, the focus
2. Degree of maternal hyperglycemia/hyperinsulinemia should be on achieving a hemoglobin A1c level less than 7%
3. Length of fetal exposure to hyperglycemia (GDM re- to reduce the risk of congenital anomalies. (24)(27) Daily
sulting in a shorter exposure than pregestational DM) prenatal vitamin supplementation that provides at least
4. Severity of maternal disease, because comorbidities (car- 1 mg of folic acid should also be prescribed for a minimum
diac and renal) have significant neonatal and obstetric of 3 months to reduce congenital neural tube defects. The
effects (1)(12)(22)(23) mechanism by which DM leads to fetal anomalies is mul-
We now describe the neonatal complications most often tifactorial (Fig 3). (25)
associated with T1DM, T2DM, and/or GDM.
Macrosomia and Birth Injury
Congenital Anomalies The American College of Obstetricians and Gynecolo-
Major congenital malformations occur in up to 6% to 12% gists (ACOG) defines macrosomia as birthweight exceeding
of the fetuses of women with T1DM or T2DM and are the 4,500 g for neonates of women with DM or GDM. It has
leading cause of perinatal mortality among women with been associated with birth trauma and need for cesarean
DM. (24) The initial injury that leads to malformations tends delivery. (1)(16) Studies have shown that insulin is the
to occur by the seventh week of gestation. GDM is not associated primary driving force in fetal growth, with growth restriction

Figure 2. Malformations associated with

pregestational diabetes mellitus.
CV¼cardiovascular; DM¼diabetes mellitus;
GI¼gastrointestinal; GU¼genitourinary;
Msk¼musculoskeletal; Neuro¼neurologic.

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 noted in instances of beta cell dysfunction. (28) Typically, to fetal/neonatal hyperinsulinemia. Chronic maternal hyper-
fetuses of women with GDM or DM have normal growth of glycemia can cause fetal beta cell hyperplasia and exaggerated
lean body mass, but higher deposits of fat in the subcutane- insulin responses. Thus, the severity of the hypoglycemia
ous tissues of the abdomen and shoulder. The difference is thought to vary with maternal glucose control in the
between the chest-to-head and shoulder-to-head ratios, both latter half of pregnancy and during labor. Therefore, all
difficult to quantify antenatally, likely contributes to rates of neonates born to women with GDM or DM should have
shoulder dystocia and birth trauma observed in infants of postnatal glucose monitoring until metabolic stability is
diabetic mothers. (1)(25)(28)(29) achieved. (1)(27)(31)
Shoulder dystocia represents an obstetric emergency
because of the risk of hypoxia, hypoperfusion, and birth
Hyperbilirubinemia/Polycythemia
injury. The risk is proportional to fetal weight, with a risk of
As many as 25% of infants born to women with insulin-
5% to 7% if the neonate weighs more than 4,000 g. Maternal
dependent GDM or DM will be diagnosed with hyperbilir-
diabetes and use of operative delivery compounds this risk.
ubinemia and up to 5% will develop polycythemia. (33) Some
(29)(30) The vast majority of shoulder dystocias do not
of the increased risk for hyperbilirubinemia in DM-exposed
result in birth injury, but when they do, brachial plexus
neonates can be attributed to preterm birth, which is more
injury is the most common, followed by clavicle or humerus
common in GDM and DM. However, even among term
fracture and cephalhematoma. (31)
pregnancies, the risk is increased. One possible explanation
is fetal exposure to oxidative stress and excess insulin and
Fetal Growth Restriction insulin growth factors. Increased red cell mass due to poly-
Women with T1DM or long-standing T2DM complicated by cythemia contributes to hyperbilirubinemia, but increased
vascular disease or renal disease are at high risk for fetal bilirubin production as measured by carbon monoxide pro-
growth restriction (FGR), especially asymmetrical FGR, duction has been documented independent of polycythemia.
thought to be secondary to uteroplacental vasculopathy.
Diabetic ketoacidosis (DKA), maternal hypertension, pre-
Hypocalcemia
eclampsia, and structural anomalies, all of which are more
Hypocalcemia is one of the most common metabolic abnor-
common in women with T1DM and T2DM, are also known
malities in neonates of diabetic mothers. The pathophysi-
risk factors for FGR. (1)(27)
ology has not been fully delineated, but a breakdown in
magnesium-calcium economy, hypoxia, and preterm birth
Hypoglycemia are all thought to contribute to the increased risk. The risk of
Neonatal hypoglycemia is more common in neonates born developing hypocalcemia is thought to vary directly with
to women with GDM or DM. It is particularly frequent glucose control. One randomized, controlled trial demonstrated
among macrosomic newborns of diabetic mothers, affect- that suboptimal glucose control correlated with a higher
ing 15% to 25% of neonates. (32) The neonatal hypoglycemia incidence of hypocalcemia compared with tighter glycemic
seen in infants born to women with GDM and DM is due control (18).

Figure 3. Pathogenesis of malformations

associated with diabetes in pregnancy. One
hypothesis was that arachidonic acid release
from plasma membranes by phospholipase
A2 is reduced. Formation of several
embryonic structures, such as the palate, the
neural tube, the heart, and external genitalia,
involve folding and fusion of opposing layers
and require phosphatidylinositol turnover
and arachidonic acid signaling.

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 Cardiomyopathy care involves assessing and attempting to reverse their risk
Cardiomyopathy has been observed commonly, especially for future GDM. Women with a significant family history
in macrosomic infants of women with poorly controlled of DM or a history of GDM in a prior pregnancy should
DM and GDM. Fetal hyperinsulinemia causes asymmetric be tested for DM and prediabetes before conception. For
septal hypertrophy and potentially left ventricular outflow women with T1DM and T2DM, as discussed previously, the
obstruction, ultimately leading to congestive heart failure in risk for congenital anomalies varies directly with glu-
severe cases. The prevalence of clinical and subclinical cose control. Thus, women should work closely with their
forms of septal hypertrophy has been estimated to be as physician to optimize their glucose control and achieve a
high as 30% in poorly controlled pregestational DM. How- glycosylated hemoglobin concentration less than 7%. All
ever, this form of cardiomyopathy is usually transient and re- women should started taking folic acid (prenatal vitamins
solves by 6 months to 1 year of age. (14)(34) contain 400 mg of additional folic acid), which has been
shown to reduce the risk for neural tube defects in devel-
oping fetuses.
Respiratory Distress Syndrome
Once pregnant, women with risk factors for GDM (ie,
A retrospective cohort study of more than 800 infants born
previous pregnancy complicated by GDM, known impaired
to women with T1DM and T2DM found that they were 20
glucose metabolism, or obesity with BMI >30) should
times more likely to develop respiratory distress syndrome.
undergo early glucose screening around 16 weeks’ gestation
Among infants of diabetic mothers with poor glycemic
(Fig 4). (16)(36) All other women undergo universal GDM
control, lung maturation may be delayed by 10 days on
screening at 24 to 28 weeks of gestation. The commonly
average. (35) Because of maternal complications associated
used approach to screening in the United States is a mater-
with GDM and DM, such as preeclampsia, women with
nal serum glucose level drawn 1 hour after a 50-g oral
GDM and DM often deliver before 39 weeks’ gestation. The
glucose load. The screening cutoff varies center to center
delay in lung maturation common in DM further compli-
but is typically between 130 and 140 mg/dL (between 7.2 and
cates these iatrogenically early deliveries.
7.7 mmol/L). Those exceeding the screening threshold
undergo a 100-g 3-hour diagnostic oral glucose tolerance
Stillbirth test. (16) Currently, ACOG recommends the use of this
Before the use of insulin became common, intrauterine 2-step approach because it has proven clinical benefit.
fetal demise (IUFD) or stillbirth occurred in up to 30% of For women with pregestational DM, glucose control in
pregnancies complicated by T1DM. Although much less early pregnancy is vital to a normal organogenesis, neces-
frequent since the advent of insulin and reliable glucose sitating early prenatal care; thereafter patients should see
monitoring methods, women with all types of diabetes and a clinician approximately every 2 weeks to optimize their
poor glucose control still have stillbirths. The greatest risk is glucose control (Fig 5). Low-dose aspirin should also be
among women with vascular disease, hypoglycemia, DKA, discussed with all women with T1DM or T2DM as a means
macrosomia, polyhydramnios, and preeclampsia. The main of decreasing their risk of preeclampsia. (37) Given the risk
cause of stillbirth is hypothesized to be chronic intrauterine of fetal macrosomia, preterm delivery, and FGR for these
hypoxia. One proposed mechanism involves fetal hyper- women, early ultrasonography is also important to deter-
insulinemia, which causes an increase in oxygen con- mine the most accurate due date for a pregnancy. At ap-
sumption and decrease in arterial oxygen content. Maternal proximately 18 weeks, all women with T1DM or T2DM
uterine blood flow does not increase enough to allow for should undergo a level II, detailed anatomy ultrasonogra-
enhanced oxygen delivery to the increased metabolic de- phy. Most major congenital anomalies can be detected with
mands of the fetus. This hypoxic hypothesis is supported such specialized ultrasonography. Between 18 and 22 weeks
by both pathologic findings of extramedullary hematopoiesis of gestation, the fetal heart increases from approximately a
and cord blood of newborns of women with T1DM showing dime-sized structure to a quarter-sized structure. Given the
lactic acidosis and fetal erythema. (1) risk of cardiac defects for fetuses of women with T1DM or
T2DM, all women with DM should undergo fetal echocar-
diography at approximately 22 weeks of pregnancy. There-
MATERNAL MONITORING TO LIMIT NEONATAL EFFECTS
after, fetal growth is evaluated every 4 weeks on average,
Antenatal Care using ultrasonography, to aid in delivery planning.
Prenatal care should begin months before attempting preg- Women with any type of DM who need medications to
nancy. For women without T1DM or T2DM, preconception control their blood glucose levels are at particularly high risk

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 Figure 4. Screening for and management of gestational diabetes mellitus. AFI¼amniotic fluid index; DS¼diabetes screening; gDM¼gestational
diabetes mellitus; NSTs¼nonstress tests; PCOS¼polycystic ovary syndrome.

for placental insufficiency, preeclampsia, and stillbirth. Thus, of stillbirth is still increased within 1 week of a reactive
antepartum testing is recommended for these women in nonstress test for patients with DM. Therefore, most patients
the third trimester. The exact timing to initiate such screen- with DM and GDM requiring medication will require
ing varies considerably by practice, but is most com- twice-weekly testing. (1)(22)
monly conducted at 28 to 34 weeks of gestation. Antepartum
fetal monitoring may involve nonstress testing, amniotic Glucose Monitoring
fluid index assessment, biophysical profiles, and/or contrac- Unlike nonpregnant women, pregnant women are encour-
tion stress testing. Historical reports have shown that the risk aged to check their blood glucose 4 times daily: fasting in the

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 Figure 5. Management of pregestational diabetes mellitus. AFI¼amniotic fluid index; Hgb¼hemoglobin; NSTs¼nonstress tests; US¼ultrasonography;
USPSTF¼US Preventive Services Task Force.

morning and 1 to 2 hours after every meal. (16) Postprandial of neonatal complications due to prematurity. Patients with
blood glucose values are particularly important because fasting blood glucose levels less than 95 mg/dL (5.2 mmol/L)
normal values are associated with a lower incidence of and postprandial blood glucose levels less than 140 mg/dL
large-for-gestational age infants and lower rates of cesarean (7.7 mmol/L) 1 hour after meals or less than 120 mg/dL
delivery due to cephalopelvic disproportion. (38) Both the (6.6 mmol/L) 2 hours after meals are usually considered
American Diabetes Association and ACOG recommend a “well controlled.” These cases can be managed expectantly
threshold of 140 mg/dL (7.7 mmol/L) at 1 hour or 120 mg/dL until at least 39 weeks of gestation. (22)(39) Women with
at 2 hours after meals. (39) “poorly controlled” glycemic levels can be offered delivery in
the late preterm or early term period. (22)(40) New data
Pharmacotherapy suggest that women with GDM who will deliver before 37
For all women with T1DM and nearly all with T2DM, insulin weeks of gestation should receive antenatal corticosteroids
is necessary throughout pregnancy. Dosages need to be to reduce the risk of respiratory distress and prolonged
monitored closely and adjusted every week because insulin neonatal hospitalization. (41) Unfortunately, for women
requirements often increase dramatically during preg- with pregestational DM, the data available thus far support
nancy. For women with GDM, initial treatment involves antenatal corticosteroids only if the delivery is to occur
diet therapy. When goal glucose levels cannot be achieved before 34 weeks. This is because the risks and benefits of
consistently via nutrition and exercise, pharmacologic ther- corticosteroids in this population between 34 and 37 weeks’
apy is recommended. Current evidence does not favor gestation have not been investigated. Induction of labor to
the use of either insulin or oral antidiabetic agents for avoid macrosomia has not been shown to prevent birth
treatment of GDM with regard to short-term outcomes. trauma. (22)(42)(43) Furthermore, cesarean delivery should
However, the literature is still lacking in data on long-term be reserved for cases in which the estimated fetal weight is
outcomes in diabetic pregnant women treated with oral greater than 4,500 g. (16)(44)
medications.
CONCLUSIONS

Delivery Planning Diabetes in pregnancy (GDM, T2DM, and T1DM) affects the
The timing of delivery for patients with GDM and DM is care of the mother but also has major implications for her
guided by the risk of IUFD and macrosomia versus the risk offspring. During pregnancy, the fetus is at increased risk

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 for congenital anomalies, growth abnormalities, prematu- 8. Selvin E, Parrinello CM, Sacks DB, Coresh J. Trends in prevalence
and control of diabetes in the United States, 1988-1994 and 1999-
rity, and stillbirth. At birth, injury, respiratory complications,
2010. Ann Intern Med. 2014;160(8):517–525 [PubMed: 24733192]
and metabolic derangements occur with regularity in sub-
9. Gale EA. Is there really an epidemic of type 2 diabetes? Lancet.
optimal glucose control. Furthermore, long after birth, chil- 2003;362(9383):503–504 [PubMed: 12932378]
dren born to women with GDM or DM are at increased risk 10. Kim SY, Saraiva C, Curtis M, Wilson HG, Troyan J, Sharma AJ.
for childhood obesity and metabolic syndrome. (45) To com- Fraction of gestational diabetes mellitus attributable to overweight
pletely assess a newborn’s risk, pediatric providers must be and obesity by race/ethnicity, California, 2007-2009. Am J Public
Health. 2013;103(10):e65–e72 [PubMed: 23947320]
aware of the mother’s level of glycemic control as well as the
11. Albrecht SS, Kuklina EV, Bansil P, et al. Diabetes trends among
severity of her disease. Only with a complete maternal history
delivery hospitalizations in the U.S., 1994-2004. Diabetes Care.
can they completely identify infants at highest risk of mor- 2010;33(4):768–773 [PubMed: 20067968]
bidity and mortality related to diabetes in pregnancy. 12. Moyer VA; U.S. Preventive Services Task Force. Screening for
gestational diabetes mellitus: U.S. Preventive Services Task Force
recommendation statement. Ann Intern Med. 2014;160(6):414–420
[PubMed: 24424622]
American Board of Pediatrics 13. American Diabetes Association. Clinical practice recommenda-
tions 2007: diagnosis and classification of diabetes. Diabetes Care.
Neonatal—Perinatal Content 1997;30(suppl 1):S42–S47 [PubMed: 17192378]
Specifications 14. Cunningham FG, Whitridge J. Diabetes. In: Corton MM, Leveno K,
• Know how maternal obesity may influence pregnancy and Bloom S, Hauth J, Rouse D, Spong C, eds. Williams Obstetrics. New
pregnancy outcome. York, NY: McGraw-Hill; 2010;chap 52:1104–1125

• Know the effects on the fetus and/or newborn infant of maternal 15. Yogev Y, Xenakis EM, Langer O. The association between preeclampsia
and the severity of gestational diabetes: the impact of glycemic control.
diabetes mellitus (including gestational diabetes) and their
Am J Obstet Gynecol. 2004;191(5):1655–1660 [PubMed: 15547538]
management.
16. Committee on Practice Bulletins–Obstetrics. Practice bulletin
• Know the neonatal complications of abnormal presentations
no. 137: gestational diabetes mellitus. Obstet Gynecol. 2013;122
(breech, shoulder dystocia, etc). (2 pt 1):406–416 [PubMed: 23969827]
17. England LJ, Dietz PM, Njoroge T, et al. Preventing type 2 diabetes:
public health implications for women with a history of gestational
diabetes mellitus. Am J Obstet Gynecol. 2009;200(4):365.e1–365.e8
[PubMed: 18691691]
References 18. Hytten FE. Weight gain in pregnancy. In: Hytten F, Chamberlain G,
eds. Clinical Physiology in Obstetrics. Oxford, UK: Blackwell
1. Landon MB, Catalano PM, Gabbe SG. Diabetes mellitus Scientific; 1991:173–203
complicating pregnancy. In: Gabbe SG, Niebyl JR, Simpson JL, et al,
19. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U,
eds. Obstetrics: Normal and Problem Pregnancies. Philadelphia, PA:
Shaw JE. Global estimates of diabetes prevalence for 2013 and
Churchill Livingstone/Elsevier; 2007;chap 39:887–921
projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137–149
2. Schaefer-Graf UM, Buchanan TA, Xiang A, Songster G, Montoro M, [PubMed: 24630390]
Kjos SL. Patterns of congenital anomalies and relationship to initial
20. Leslie RD, Williams R, Pozzilli P. Clinical review: type 1 diabetes and
maternal fasting glucose levels in pregnancies complicated by type 2
latent autoimmune diabetes in adults: one end of the rainbow. J Clin
and gestational diabetes. Am J Obstet Gynecol. 2000;182(2):313–320
Endocrinol Metab. 2006;91(5):1654–1659 [PubMed: 16478821]
[PubMed: 10694330]
21. Florez JC. Clinical review: the genetics of type 2 diabetes: a realistic
3. Sibai BM, Caritis S, Hauth J, et al; National Institute of Child Health
appraisal in 2008. J Clin Endocrinol Metab. 2008;93(12):4633–4642
and Human Development Network of Maternal-Fetal Medicine
[PubMed: 18782870]
Units. Risks of preeclampsia and adverse neonatal outcomes among
women with pregestational diabetes mellitus. Am J Obstet Gynecol. 22. American College of Obstetrics & Gynecology. ACOG practice
2000;182(2):364–369 [PubMed: 10694338] bulletin no. 60: pre-gestational diabetes mellitus. Obstet Gynecol.
4. Craig LB, Ke RW, Kutteh WH. Increased prevalence of insulin 2005;105(3):675–685. [PubMed: 15738045]
resistance in women with a history of recurrent pregnancy loss. 23. White P. Pregnancy complicating diabetes. Am J Med. 1949;7
Fertil Steril. 2002;78(3):487–490 (5):609–616 [PubMed: 15396063]
5. García-Patterson A, Gich I, Amini SB, Catalano PM, de Leiva A, 24. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-
Corcoy R. Insulin requirements throughout pregnancy in women conception care of diabetes, congenital malformations, and
with type 1 diabetes mellitus: three changes of direction. spontaneous abortions. Diabetes Care. 1996;19(5):514–541
Diabetologia. 2010;53(3):446–451 [PubMed: 20013109] [PubMed: 8732721]
6. Feig DS, Palda VA. Type 2 diabetes in pregnancy: a growing concern. 25. Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR.
Lancet. 2002;359(9318):1690–1692 [PubMed: 12020549] Creasy & Resnik’s Maternal-Fetal Medicine Principles and Practice.
7. Silverman BL, Metzger BI, Cho NH, et al. Impaired glucose intolerance Philadelphia: Saunders; 2009
in adolescent offspring of diabetic mothers: relationship to fetal 26. Greene MF, Hare JW, Cloherty JP, Benacerraf BR, Soeldner JS.
hyperinsulinism. Diabetes Care. 1995;18:611 – 617 [PubMed: 8585997] First-trimester hemoglobin A1 and risk for major malformation and

e40 NeoReviews

Downloaded from http://publications.aap.org/neoreviews/article-pdf/18/1/e33/882353/neoreviews_01werner.pdf

by guest
 spontaneous abortion in diabetic pregnancy. Teratology. 1989;39 37. Henderson JT, Whitlock EP, O’Connor E, Senger CA, Thompson
(3):225–231 [PubMed: 2727930] JH, Rowland MG. Low-dose aspirin for prevention of morbidity and
27. Jovanovic L, Nakai Y. Successful pregnancy in women with type 1 mortality from preeclampsia: a systematic evidence review for the
diabetes: from preconception through postpartum care. Endocrinol U.S. Preventive Services Task Force. Ann Intern Med. 2014;160
Metab Clin North Am. 2006;35(1):79–97, vi [vi.] (10):695–703 [PubMed: 25329211]

28. Catalano PM, Thomas A, Huston-Presley L, Amini SB. Increased 38. de Veciana M, Major CA, Morgan MA, et al. Postprandial versus
fetal adiposity: a very sensitive marker of abnormal in utero preprandial blood glucose monitoring in women with gestational
development. Am J Obstet Gynecol. 2003;189(6):1698–1704 diabetes mellitus requiring insulin therapy. N Engl J Med. 1995;333
[PubMed: 14710101] (19):1237–1241 [PubMed: 7565999]
29. Bernstein IM, Goran MI, Amini SB, Catalano PM. Differential 39. Lydon K, Dunne FP, Owens L, et al. Psychological stress associated
growth of fetal tissues during the second half of pregnancy. with diabetes during pregnancy: a pilot study. Ir Med J. 2012;105(5
Am J Obstet Gynecol. 1997;176(1 pt 1):28–32 [PubMed: 9024084] suppl):26–28 [PubMed: 22838106]
30. Langer O, Berkus MD, Huff RW, Samueloff A. Shoulder dystocia: 40. Kjos SL, Henry OA, Montoro M, Buchanan TA, Mestman JH.
should the fetus weighing greater than or equal to 4000 grams be Insulin-requiring diabetes in pregnancy: a randomized trial of active
delivered by cesarean section? Am J Obstet Gynecol. 1991;165 induction of labor and expectant management. Am J Obstet Gynecol.
(4 Pt 1):831–837 [PubMed: 1951539] 1993;169(3):611–615 [PubMed: 8372870]
31. Nesbitt TS, Gilbert WM, Herrchen B. Shoulder dystocia and 41. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; NICHD
associated risk factors with macrosomic infants born in California. Maternal–Fetal Medicine Units Network. Antenatal betamethasone
Am J Obstet Gynecol. 1998;179(2):476–480 [PubMed: 9731856] for women at risk for late preterm delivery. N Engl J Med. 2016;374
32. Alam M, Raza SJ, Sherali AR, Akhtar AS. Neonatal complications in (14):1311–1320 [PubMed ID: 26842679]
infants born to diabetic mothers. J Coll Physicians Surg Pak. 2006;16 42. Sanchez-Ramos L, Bernstein S, Kaunitz AM. Expectant
(3):212–215 [PubMed: 16542603] management versus labor induction for suspected fetal
33. Cordero L, Treuer SH, Landon MB, Gabbe SG. Management of macrosomia: a systematic review. Obstet Gynecol. 2002;100(5 pt
infants of diabetic mothers. Arch Pediatr Adolesc Med. 1998;152 1):997–1002 [PubMed: 12423867]
(3):249–254 [PubMed: 9529462] 43. Chauhan SP, Hendrix NW, Magann EF, Morrison JC, Kenney SP,
34. Mace S, Hirschfield SS, Riggs T, Fanaroff AA, Merkatz IR. Devoe LD. Limitations of clinical and sonographic estimates of birth
Echocardiographic abnormalities in infants of diabetic mothers. weight: experience with 1034 parturients. Obstet Gynecol. 1998;91
J Pediatr. 1979;95(6):1013–1019 [PubMed: 159351] (1):72–77 [PubMed: 9464724]
35. Robert MF, Neff RK, Hubbell JP, Taeusch HW, Avery ME. 44. Garabedian C, Deruelle P. Delivery (timing, route, peripartum
Association between maternal diabetes and the respiratory-distress glycemic control) in women with gestational diabetes mellitus.
syndrome in the newborn. N Engl J Med. 1976;294(7):357–360 Diabetes Metab. 2010;36(6 pt 2):515–521 [PubMed: 21163417]
[PubMed: 1246288] 45. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in
36. Metzger BE, Lowe LP, Dyer AR, et al; HAPO Study Cooperative childhood: association with birth weight, maternal obesity, and
Research Group. Hyperglycemia and adverse pregnancy outcomes. gestational diabetes mellitus. Pediatrics. 2005;115(3):e290–e296
N Engl J Med. 2008;358(19):1991–2002 [PubMed: 18463375] [PubMed: 15741354]

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 NeoReviews Quiz
There are two ways to access the journal CME quizzes:
1. Individual CME quizzes are available via a handy blue CME link in the Table of Contents of any issue.
2. To access all CME articles, click “Journal CME” from Gateway’s orange main menu or go directly to: http://www.
aappublications.org/content/journal-cme.

1. A woman undergoing antenatal screening is found to have gestational diabetes mellitus. NOTE: Learners can take
Which of the following statements concerning the current risk of gestational diabetes and NeoReviews quizzes and
pathophysiology during pregnancy is correct? claim credit online only
A. Gestational diabetes complicates approximately 15% of pregnancies in the United at: http://Neoreviews.org.
States.
B. The prevalence of gestational diabetes has been declining over the past 20 years. To successfully complete
C. In gestational diabetes, there is increased insulin sensitivity in the liver and 2017 NeoReviews articles
peripheral tissues, but decreased insulin secretion due to pancreatic insufficiency, for AMA PRA Category 1
with resultant hyperglycemia. CreditTM, learners must
D. Up to 50% of women with gestational diabetes mellitus will go on to develop type 2 demonstrate a minimum
diabetes mellitus over their life course. performance level of 60%
E. The most common timing of diagnosis of gestational diabetes is at the first or higher on this
antenatal visit between 4 and 8 weeks’ gestational age. assessment, which
2. A woman with type 1 diabetes mellitus is pregnant and receiving antenatal care and measures achievement of
counseling. Which of the following correctly characterizes the risk of adverse outcomes for the educational purpose
the fetus/infant? and/or objectives of this
A. Major congenital malformations occur in 6% to 12% of such pregnancies, with activity. If you score less
initial injury leading to malformation by the seventh week of gestation. than 60% on the
B. The most common congenital defect is renal agenesis. assessment, you will be
C. Ventricular septal defects are less likely to be seen in insulin-dependent diabetes given additional
compared with non–insulin-dependent diabetes. opportunities to answer
D. The most common cardiac defect seen in all types of diabetes during pregnancy is questions until an overall
an Ebstein anomaly. 60% or greater score is
E. Congenital anomalies in the skeletal system are more common in gestational achieved.
diabetes than in type 1 diabetes mellitus.
3. A woman with gestational diabetes mellitus is at 37 weeks’ gestation. The estimated fetal This journal-based CME
weight is 3,900 g. Which of the following statements correctly describes the risk of activity is available
macrosomia and related morbidities? through Dec. 31, 2019,
A. The risk of shoulder dystocia is not increased until the birthweight exceeds 4,500 g. however, credit will be
B. Typically, fetuses of women with gestational diabetes have increased growth of recorded in the year in
lean body mass, with normal deposits of fat within subcutaneous tissues of which the learner
abdomen and shoulder. completes the quiz.
C. If there is shoulder dystocia resulting in birth injury, brachial plexus is the most
common injury.
D. Operative delivery reduces the risk of shoulder dystocia.
E. The risk of shoulder dystocia is relatively easy to predict antenatally, because the
chest-to-head and shoulder-to-head ratios are standard accurate measurements
with ultrasonography.
4. A pregnant woman with type 2 diabetes mellitus is being monitored regularly. Which of
the following strategies in monitoring and treatment for this mother and fetus is most
appropriate?
A. Fetal echocardiography is unnecessary unless there is a family history of congenital
heart disease.
B. Unless there are periods of glucose instability, blood glucose level does not need to
be checked on a daily basis.
C. For nearly all women with type 2 diabetes mellitus, insulin is necessary in preg-
nancy, often with increased dosage requirements.

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 D. In case the mother has feelings of guilt, she should be counseled that the risk for
congenital anomalies or other neonatal morbidities is not related to glucose
control.
E. Unlike other pregnancies, folic acid should be avoided during pregnancy because
of the possibility of toxicity in combination with hyperglycemia.
5. A pregnant woman with gestational diabetes consistently has had fasting blood glucose
higher than 100 mg/dL (5.5 mmol/L) and postprandial blood glucose higher than 140 mg/
dL (7.7 mmol/L) 1 hour after meals during her pregnancy. She is considered to have poorly
controlled glycemic levels. She is at 31 weeks’ gestation. Which of the following strategies
in timing of delivery is appropriate for this patient?
A. There should be expectant management with close monitoring, but no plans for
induction or planned delivery until 40 weeks or later.
B. To prevent additional hyperglycemia, antenatal corticosteroids should be avoided,
because guidelines suggest no corticosteroid administration unless delivery will
occur before 28 weeks of gestation.
C. Induced delivery before 32 weeks of gestation is recommended, because ongoing
hyperglycemia in the fetus is likely to lead to a major congenital anomaly.
D. Induction of labor to avoid macrosomia is advised to prevent birth trauma.
E. Cesarean delivery should be reserved for cases in which the estimated fetal weight
is greater than 4,500 g.

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