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302
WOMEN’S IMAGING

Imaging Review of Obstetric Sequelae

of Maternal Diabetes Mellitus

Hassan Aboughalia, MBBCh

Priya Pathak, MD
Deepashri Basavalingu, MD
Teresa Chapman, MD, MA
Margarita V. Revzin, MD, MS
Laura E. Sienas, MD
Gail H. Deutsch, MD
Douglas S. Katz, MD
Mariam Moshiri, MD
Abbreviations: ACOG = American College of
Obstetricians and Gynecologists, DM = diabe-
tes mellitus, EFW = estimated fetal body weight,
FGR = fetal growth restriction, GA = gestational
age, GDM = gestational DM, HbA1c = hemo-
globin A1c, HELLP = hemolysis, elevated liver
function, and low platelets, MFM = maternal
fetal medicine, SUA = single umbilical artery,
UTD = urinary tract dilatation
RadioGraphics 2022; 42:302–319
https://doi.org/10.1148/rg.210164
Content Codes:
From the Departments of Radiology (H.A.,
P.P., D.B., T.C.) and Laboratory Medicine and
Pathology (G.H.D.), University of Washington,
1959 NE Pacific St, Seattle, WA 98195; De-
partments of Radiology (T.C.) and Laboratory
Medicine and Pathology (G.H.D.), Seattle Chil-
dren’s Hospital, Seattle, Wash; Department of
Radiology and Biomedical Imaging, Yale School
of Medicine, New Haven, Conn (M.V.R.);
Departments of Obstetrics and Gynecology
(L.E.S.) and Radiology (M.M.), University of
Washington Medical Center, Seattle, Wash; and
Department of Radiology, NYU Langone Hos-
pital–Long Island and NYU Long Island School
of Medicine, Mineola, NY (D.S.K.). Presented
as an education exhibit at the 2020 RSNA An-
nual Meeting. Received May 3, 2021; revision
requested June 25 and received July 11; ac-
cepted July 15. For this journal-based SA-CME
activity, the authors M.V.R., G.H.D., D.S.K.,
and M.M. have provided disclosures (see end of
article); all other authors, the editor, and the re-
viewers have disclosed no relevant relationships.
Address correspondence to H.A. (e-mail:
ghalia@uw.edu; ha_aboughalia@yahoo.com).
©
RSNA, 2021
„
„
„
cord that may be associated with maternal DM.
Diabetes mellitus, whether preexisting or gestational, poses signifi-
cant risk to both the mother and the developing fetus. A myriad
of potential fetal complications in the setting of diabetic pregnan-
cies include, among others, congenital anomalies, delayed fetal
lung maturity, macrosomia, and increased perinatal morbidity and
mortality. Congenital anomalies most commonly involve the ner-
vous, cardiovascular, genitourinary, and musculoskeletal systems.
Delayed fetal lung maturity, probably secondary to hyperglycemia
suppressing surfactant secretion, is a major determinant of peri-
natal morbidity and mortality. Besides the potential complications
encountered during cesarean delivery in macrosomic fetuses,
vaginal delivery is also associated with increased risks of shoulder
dystocia, clavicular and humeral fractures, and brachial plexus
palsy. Maternal complications are related to the increased risk of
hypertensive diseases of pregnancy and associated preeclampsia
and hemolysis, elevated liver function, and low platelets (HELLP)
syndrome, as well as complications encountered at the time of
delivery secondary to fetal macrosomia and cesarean delivery.
Additional conditions encountered in the setting of maternal dia-
betes include polyhydramnios, placental thickening, and two-ves-
sel umbilical cord, each of which is associated with adverse fetal
and maternal outcomes including fetal growth restriction, preterm
labor, placental abruption, and premature rupture of membranes.
Imaging plays a vital role in the evaluation of the mother and the
fetus and can provide invaluable information that can be used
by maternal fetal medicine to manage this patient population ef-
fectively. The authors review the pathophysiologic alterations in-
duced by diabetes in pregnancy, discuss the imaging spectrum of
diabetic embryopathy, and provide a detailed review of potential
associated maternal complications.
Online supplemental material is available for this article.
©
RSNA, 2021 • radiographics.rsna.org
SA-CME LEARNING OBJECTIVES
After completing this journal-based SA-CME activity, participants will be able to:
List those fetal organ systems most impacted in mothers with DM.
Describe the diabetes-specific maternal disease processes that occur during pregnancy.
Recognize specific US features of the placenta, amniotic fluid volume, and umbilical
See rsna.org/learning-center-rg.

Introduction
Diabetes mellitus (DM) is due to impaired carbohydrate metabo-
lism secondary to defective insulin secretion or function and is one
of the most prevalent endocrine disorders worldwide. DM is classi-
cally categorized into type 1 and type 2 on the basis of epidemiology,
RG  •  Volume 42  Number 1 Aboughalia et al  303
TEACHING POINTS
„ The underlying pathophysiologic alteration in the majority of
patients with GDM is similar to that observed in patients with
type 2 DM and involves pancreatic β-cell dysfunction, lead-
ing to poor insulin production, and this is superimposed on a
background of insulin resistance in the muscles, liver, and fat.
Although GDM usually resolves following pregnancy, both
the affected mother and child are at increased risk of develop-
ing diabetes and cardiovascular diseases in the future.
„ Routine inclusion of fetal echocardiography is recommended
only in patients with preexisting DM, according to the most
recent AIUM guidelines.
„ Infants of women with pregestational DM have a two to five
times increased risk of congenital heart disease, the most
common of which is atrioventricular septal defects according
to a systematic review by Simeone et al. This risk is highest in
women who receive insulin therapy at the time of conception
and lower in women who develop gestational diabetes later
in pregnancy.
„ DM is associated with increased risk for preeclampsia, most
commonly in patients with type 1 DM, with a reported inci-
dence of 18% and a lesser incidence in pregnancies with type
2 DM and GDM.
„ A thick placenta is independently associated with adverse
perinatal outcome including FGR and need for emergency
cesarean delivery. DM is among the most common causes of
placental thickening, in addition to toxoplasmosis, other infec-
tions, rubella, cytomegalovirus, and herpes simplex (TORCH)
infection; triploidy; and fetal hydrops.
clinical presentation, and underlying metabolic
aberration. Type 2 DM accounts for more than
85% of the overall cases, with type 1 diabetes
accounting for 5%–10% (1). Other less com-
mon subtypes of DM exist, including gestational
diabetes, a distinct entity that requires special
attention as it carries significant maternal, fetal,
and neonatal health risks. During pregnancy, the
mother can either present with preexisting DM
(type 1 or 2) or can develop pregnancy-related
gestational diabetes. Recognized during the sec-
ond or third trimester of pregnancy, gestational
DM (GDM) is known to affect approximately
14% of pregnant patients worldwide. The under-
lying pathophysiologic alteration in the majority
of patients with GDM is similar to that observed
in patients with type 2 DM and involves pancre-
atic β-cell dysfunction, leading to poor insulin
production, and this is superimposed on a back-
ground of insulin resistance in the muscles, liver,
and fat. Although GDM usually resolves fol-
lowing pregnancy, both the affected mother and
child are at increased risk of developing diabetes
and cardiovascular diseases in the future (1,2).
Recognized risk factors for developing GDM
include obesity, advanced maternal age, eth-
nic group, micronutrient deficiencies, positive
family history of insulin resistance, and other
diseases of insulin resistance including polycys-
tic ovarian syndrome (1).
Screening for and Diagnosis of GDM
The U.S. Preventive Services Task Force rec-
ommends laboratory screening for GDM in
all women at or beyond 24 weeks of gestation
given that medical history alone is inadequate
in identifying women with GDM (3). According
to the American College of Obstetricians and
Gynecologists (ACOG), the most commonly
used method of screening for GDM is the 50-g,
1-hour oral glucose tolerance test (OGTT).
Abnormal screening test results are further con-
firmed by using the 100-g, 3-hour OGTT (Fig
1) (4). In certain situations, screening for GDM
can be done during the initiation of prenatal care,
particularly in patients with high risk for GDM
including those with obesity, history of GDM in
a prior pregnancy, family history of type 2 DM,
and prior history of poor obstetric outcomes (4).
Pathogenesis of Diabetic
Embryopathy
Diabetic embryopathy refers to the spectrum
of fetal malformations linked to DM during
pregnancy. Both type 1 and 2 DM demonstrate
overlapping rates of fetal malformations that
correlate with diabetic control, with an occur-
rence risk of 5% in patients with a hemoglobin
A1c (HbA1c) level less than 8%. This risk rises
to 25% in patients with HbA1c levels higher
than 10% (5). The etiopathogenesis of diabetes-
induced teratogenesis is complex and is still
incompletely understood. Maternal hyperglyce-
mia is a major factor implicated in teratogenesis
based on elevated HbA1c and glucose levels
directly correlating with increased risks of fetal
congenital malformations. Hyperglycemia results
in increased formation of oxygen free radicals
through various metabolic pathways, including
glycolysis, the citric acid cycle, and the hexose
monophosphate shunt pathway. In addition, there
is increased expression of nitric oxide synthase,
which produces reactive nitrogen species, alter-
ing signaling pathways of arachidonic acid (an
ω-6 fatty acid), inositol, and prostaglandins, and
increased intracellular concentration of advanced
glycosylation end products.
These metabolic derangements result in gene
dysregulation and apoptosis. Ketone bodies,
which are synthesized in higher amounts in ma-
ternal diabetes, are additional potential terato-
gens, acting in synergy with hyperglycemia. Gene
expression and epigenetic processes are affected
in diabetes as well, although no single gene that
correlates to increased risk of subsequent embry-
opathy has been identified to our knowledge (6,7).
Higher placental growth factors produced by the
diabetic environment lead to endothelial prolifera-
tion, neovascularization, villous malformations,
304  January-February 2022 radiographics.rsna.org

Figure 1.  Chart shows the diagnostic algorithm for GDM.

Figure 2.  Chart shows that complex pathogenic mechanisms initiated by diabetes induce hyperglycemia
in pregnancy and are involved in causing diabetic embryopathy, fetopathy, and pregnancy complications.
AGE = advanced glycosylation end product, IUGR = intrauterine growth restriction.

and thickening of the basal trophoblast mem-
brane, which cumulatively result in fetal hypoxia
(Fig 2).
The timing during which the previously de-
scribed sequences are initiated is highly correlated
with different maternal and fetal complications.
Metabolic derangements in early pregnancy,
typically before the 7th week of gestation, lead to
blastogenic malformations, spontaneous abor-
tions, and multiorgan and syndromic malforma-
tions. On the other hand, the development of
such metabolic alterations later in pregnancy is
associated with increased risk of macrosomia and
isolated fetal anomalies (8). In addition, abnor-
malities of organogenesis and placentation play a
major role in second-trimester pregnancy loss (9).
Role of US
The role of US in the management of diabetic
pregnancies is well established. US is routinely
used for assessment of fetal biometry and estima-
tion of the fetal weight, diagnosis of congenital
malformations, and monitoring of pregnancy in
general. Since maternal diabetes is considered
a high-risk condition, the American Institute of
Ultrasound in Medicine (AIUM) recommends
performing detailed diagnostic obstetric second-
trimester anatomy US in a referral center where
personnel have expertise in obstetric US. Fetal
structures evaluated during a detailed second-
trimester US examination in high-risk pregnancy
compared with those in a standard examination
are detailed in Table 1 (10). Fetal evaluation
should also be tailored further on the basis of any
findings on the anatomic image. For example,
fetal echocardiography may be warranted if a
cardiac defect is suspected. Routine inclusion of
fetal echocardiography is recommended only in
patients with preexisting DM, according to the
most recent AIUM guidelines (11). Some authors
advocate for serial US follow-up for assessment of
fetal growth and amniotic fluid volume, especially
RG  •  Volume 42  Number 1 Aboughalia et al  305

Table 1: Fetal Structures Evaluated at Standard and Detailed Second-Trimester US Examinations

Structures at Standard Additional Structures at Detailed

Region Second-Trimester US Second-Trimester US
Head and neck Lateral ventricles and choroid plexus, mid- Third and fourth ventricles, lateral ven-
line falx, cavum septum pellucidi, cerebel- tricular wall and integrity; cerebellar
lum, and cisterna magna lobes, vermis, and cisterna magna; cor-
pus callosum; brain parenchyma, cranial
vault, and neck
Face Upper lip Profile and nasal bones, coronal face
(nose, lips, and lens), mandible and
maxilla, orbits and ear position
Heart Cardiac activity, four-chamber view, right Situs; aortic arch, superior and inferior
and left ventricular outflow tracts vena cava view; three-vessel view, three-
vessel and trachea view; interventricular
septum
Lungs Not mandatory Lung, ribs, and diaphragm
Abdomen Stomach, kidneys and urinary bladder, Abdominal wall integrity, bowel, solid
umbilical cord insertion and vessel organs
number
Spine Cervical, thoracic, lumbar, and sacral spine Shape, curvature, and conus medullaris;
integrity of the spine and overlying soft
tissue; integrity of the spine and overly-
ing skin
Extremities and Legs and arms, hands and feet Number and position of the extremities
external genitalia and digits
Placenta Location and relationship to internal os, Implantation site for adherent placenta,
appearance placental thickness and any masses,
accessory placenta

during the third trimester when macrosomia can Congenital Anomalies

dictate the route of delivery (12).
A major potential limitation of US is obscura-
tion of fetal structures and associated congenital
anomalies secondary to maternal obesity related
to diabetes. In this setting, there should be a low
threshold to perform follow-up US for a more
favorable fetal position or pursue fetal MRI if
suspicion for an abnormality is high. US with
a transvaginal approach may also be preferable
in this patient population. Although maternal
diabetes does not increase the risk of chromo-
somal aneuploidy, maternal obesity related to
diabetes can impact aneuploidy screening. For
example, the nuchal translucency US examina-
tion in pregnant women with diabetes tends to
be longer in duration, and there is a reported
increased frequency of nonvisualization of the
fetal nasal bone resulting in an increased need
for transvaginal US examination (13).
Fetal Abnormalities
The spectrum of fetal abnormalities observed
in diabetic pregnancies includes fetal congenital
anomalies, delayed lung maturity, and altered
fetal weight, as well as perinatal morbidity and
mortality (Table 2).
Central Nervous System Anomalies.—Caudal
dysgenesis is 200 times more common in infants
of mothers with diabetes and is considered one
of the hallmarks of diabetic pregnancy (14). Ac-
cording to the Torotori classification for spinal
dysraphism, caudal dysgenesis is described as a
closed spinal dysraphism of a complex nature
without an associated subcutaneous mass (15).
Frequent other associated anomalies include
anorectal, genitourinary, and gastrointestinal
malformations (16). Mutations in the MNX1
(HLXB9) homeobox gene are implicated in
Currarino syndrome, characterized by sacral de-
fect, anal atresia, and anterior meningocele (17).
Caudal dysgenesis is classified into two types.
Type 1 describes spinal column termination at
the level of the S1 vertebral body or above. In
this type, there is abrupt and blunted termina-
tion of the spinal cord, with the conus medul-
laris level higher than normal. In type 2, the
osseous termination ends at the level of the
S2 vertebral body or below and is frequently
associated with cord tethering by a tight filum,
lipoma, lipomeningocele, and/or a terminal
myelocystocele (18).
306  January-February 2022 radiographics.rsna.org

Table 2: Spectrum of Complications Encountered in Diabetic Pregnancies

Complications Description
Fetal complications
Congenital anomalies Nervous system: NTDs, holoprosencephaly-caudal dysgenesis
Heart and great vessels: VSD, conotruncal abnormalities
Genitourinary system: renal agenesis, UTD, MCDK, duplex kidney
Skeletal system: preaxial polydactyly, syndactyly, and radial ray
anomalies
Fetal lung maturity Maternal hyperglycemia interferes with corticosteroid therapy,
delaying lung maturation
Fetal growth Accelerated growth is usually apparent by the late second trimes-
ter, with a disproportionate increase in abdominal and head
circumferences; in addition, there is subcutaneous fat deposition
Miscellaneous Spontaneous abortion increases with poor glycemic control
Stillbirth is four times more common
Metabolic derangements and respiratory distress syndrome are
more frequent in infants of diabetic mothers
Maternal complications
Preeclampsia Diabetes increases the risk of preeclampsia, which correlates with
the extent of glycemic control (up to 18%); this in turn might
be associated with severe obstetric complications, including
HELLP syndrome
Placental abruption: placental detachment before delivery of the fetus
Cesarean delivery The main indication for cesarean delivery is macrosomia to avoid
shoulder dystocia
Long-term sequelae of cesarean delivery include increased risk of
abnormal placentation, as well as uterine dehiscence and rup-
ture in subsequent pregnancies
Other complications
Placental thickening Thick placenta independently associated with adverse pregnancy
and early maturation outcomes
Amniotic fluid volume Second most common cause of polyhydramnios
Oligohydramnios might be seen if there is long-standing diabetes
or associated maternal hypertension
  Umbilical cord SUA affects up to 6% of infants of diabetic mothers
Associated with increased frequency of growth retardation and
preterm delivery
Note.— MCDK = multicyclic dysplastic kidney, NTD = neural tube defect, SUA = single
umbilical artery, TA = truncus arteriosus, TGA = transposition of the great vessels, UTD =
urinary tract dilatation, VSD = ventricular septal defect.

At first-trimester US, caudal dysgenesis is sug-
gested when small crown-rump length, increased
nuchal translucency, and lower spine protuber-
ance are detected (19). The definitive diagnosis is
made at second-trimester US with demonstration
of abrupt termination of the spine. The fetal lower
extremities may show characteristic positioning
with hip abduction and knee flexion, called the
cross-leg tailor position or Buddha pose. The iliac
wings may be fused, yielding a shieldlike appear-
ance of the pelvic bones (Fig 3, Movie 1) (20).
MRI can better delineate the level of caudal dys-
genesis, associated spinal cord abnormalities, and
other accompanying anomalies. US follow-up is
recommend for evaluation of interval fetal growth
and amniotic fluid volume. Predelivery US is rec-
ommended to assess fetal presentation, as malpre-
sentations are common in caudal dysgenesis (21).
Infants of diabetic mothers are at increased risk
for other central nervous system (CNS) anoma-
lies. In 2008, Correa et al (22) published a large
U.S.-based multicenter study with 13 030 patients
that focused on analysis of the frequency of birth
defects in diabetes (22). The authors highlighted
the increased risk for congenital CNS anomalies
in diabetic pregnancies, particularly anencephaly,
encephalocele, and holoprosencephaly. The odds
ratio was higher in mothers with pregestational
DM in comparison with those with GDM. For
example, the odds ratio for the presence of anen-
RG  •  Volume 42  Number 1 Aboughalia et al  307

Figure 3.  Caudal dysgenesis. (A) Longitudinal gray-scale US image (sagittal orientation) shows a fetus at 23 weeks gestational age
(GA) with absence of caudal spinal elements in the lumbosacral region (arrow). (B) Transverse gray-scale US image of the same fetus
as in A shows associated abnormal approximation of the iliac bones (arrows). (C) Frontal radiograph of a different aborted fetus
shows premature truncation of the vertebral column at the L3 level (*). Note the shieldlike appearance of the pelvic bones (arrow).
(D) Sagittal T2-weighted MR image of the lumbosacral region in a different 1-day-old neonate shows premature truncation of the
spinal column with agenesis of the distal sacral elements (arrow). (E) Photograph of an aborted fetus with caudal dysgenesis shows
a foreshortened left leg with contracture of the ankle joint (arrow), highlighting the frequent association of caudal dysgenesis with
developmental abnormalities of the lower extremities. (F) Clinical photograph of a different aborted fetus with caudal dysgenesis
shows absence of an external anal opening in an imperforate anus (arrow).

cephaly in pregestational DM versus GDM was
3.39 versus 1.33, and for encephalocele was 2.09
versus 1.82, respectively (22). Another large-popu-
lation European study by Garne et al (23) in 2012
confirmed the increased risk of CNS anomalies
in the context of pregestational diabetes, with an
overall odds ratio of 1.23 for any CNS anomaly,
particularly for encephalocele (odds ratio, 3.22)
and anencephaly (odds ratio, 1.9).
Anencephaly is a lethal anomaly describing ab-
sent major portions of the brain, skull, and scalp
above the orbits (Fig 4). Exencephaly describes
abnormally formed brain tissue without the pres-
ence of a calvarium and can be diagnosed with
100% confidence at the time of nuchal trans-
lucency screening. This is considered an earlier
stage of anencephaly, with further destruction of
the brain tissue due to absence of the protective
calvarium, eventually leading to anencephaly (Fig
5, Movie 2) (24).
Encephalocele refers to protrusion of intracra-
nial structures through a defect in the skull, most
commonly occurring in the occipital or frontal
regions (Fig 6, Movie 3). On the basis of the con-
tents, a protrusion containing only meninges and
cerebrospinal fluid is called a meningocele, while
the presence of brain tissue in the sac content is
known as an encephalomeningocele. Encephalo-
cele outcome depends on its content and loca-
tion, and cesarean delivery is often pursued to
avoid injury of the intracranial structure at the
time of delivery (24,25).
Holoprosencephaly refers to a spectrum of
brain malformations that affect the developing
prosencephalon (forebrain), characterized by
varying degrees of failed cleavage of the cerebral
hemispheres and deep gray matter nuclei. Three
classic subtypes are described: alobar, semilobar,
and lobar holoprosencephaly (Fig 7, Table 3). No
fetal intervention is indicated, and termination
can be offered given the grave sequelae of the
disease and the high mortality observed in severe
cases of holoprosencephaly (26).
Cardiac Anomalies.—Infants of women with pre-
gestational DM have a two to five times increased
308  January-February 2022 radiographics.rsna.org

Figure 4.  Anencephaly. (A) Longitudinal gray-scale US image (sagittal orientation) of a fetus at 11 weeks 6 days GA shows lack
of brain development, with only a small amount of tissue above the orbits (arrow). (B) Coronal gray-scale US image of the face
of another fetus shows the characteristic “frog eye” appearance of the fetal head due to lack of brain matter development above
the orbits (arrows). (C) Clinical photograph of an aborted fetus shows total absence of the calvarium superior to the orbits with a
diminutive misshaped skull.

Figure 5.  Exencephaly. (A) Lon-

gitudinal transabdominal gray-scale
US image (sagittal orientation) of a
fetus at 12 weeks 5 days GA shows
disorganized fetal brain tissue with-
out a calvarium (arrow). (B) Sagit-
tal T2-weighted image of another
fetus at 21 weeks 4 days GA shows
absence of supratentorial brain with
abnormal exophytic neuronal tissue
in the posterior fossa and region of
the brainstem along the inferior cal-
varium (arrow).

risk of congenital heart disease, the most com-
mon of which is atrioventricular septal defects
according to a systematic review by Simeone et
al (27). This risk is highest in women who receive
insulin therapy at the time of conception and
lower in women who develop gestational diabetes
later in pregnancy (27). The risk for conotruncal
cardiac anomalies, including truncus arteriosus,
double-outlet right ventricle, transposition of the
great vessels, and tetralogy of Fallot, is statisti-
cally significantly higher when compared with
that for other cardiac anomalies. The proposed
theory for this difference is hyperglycemia-
induced neural crest cell death affecting the
morphogenesis of the developing heart (28).
Understanding the sonographic relationship
among the pulmonary and aortic arteries at fetal
US assessment is key to diagnose conotruncal
anomalies. Normally, the main pulmonary artery
lies to the left of the ascending aorta, and the
right pulmonary artery courses posterior to the
ascending aorta and below the aortic arch. This
relationship is best evaluated by using the outflow
tract projections, highlighting the origin and
orientation of the great vessels. Thus, they are of
great value in the assessment of the conotruncal
anomalies (29).
The essential underlying abnormality in
patients with tetralogy of Fallot is underdevel-
opment of the pulmonary infundibulum with a
resultant constellation of abnormalities includ-
ing right ventricular outflow stenosis, ventricu-
lar septal defect with an overriding aorta, and
later development of secondary right ventricular
hypertrophy. In truncus arteriosus, there is a
common arterial trunk instead of a separate
aorta and pulmonary artery (Fig 8). On the other
hand, transposition of the great vessels describes
reversed relationship between the pulmonary ar-
tery and aorta with secondary ventriculo-arterial
discordance (Fig 9). Double-outlet right ventricle
is another anomaly in which a major portion of
the aorta arises from the right ventricle, in addi-
tion to the pulmonary artery (29).
RG  •  Volume 42  Number 1 Aboughalia et al  309

Figure 6.  Meningoencephalocele. (A) Transabdominal transverse gray-scale US image shows an ex-
tracranial complex cystic structure consisting of herniating meninges and cerebrospinal fluid commu-
nicating with the skull cavity through a calvarial defect (arrow). The complex nature of the cystic lesion
suggests the presence of brain parenchyma within the hernia sac. (B) Clinical photograph of a different
neonate shows a large skin-covered circumscribed bulge in the occipital region, compatible with an
encephalocele.

Figure 7.  Alobar holoprosencephaly in a fetus at 23 weeks 3 days GA. (A) Transabdominal transverse gray-scale US image shows
fused thalami (arrow) and an enlarged posterior midline fluid space (*). (B) Axial T2-weighted MR image shows the enlarged pos-
terior midline fluid space (*). (C) Axial T2-weighted MR image at the level of the orbits shows thalamic fusion (arrow). Fetal hypo-
telorism is additionally noted (*).

Table 3: Subtypes of Holoprosencephaly

Structure

Subtype/Region Interhemispheric Fissure Deep Gray Matter Nuclei Ventricular System

Lobar Present anteriorly and posteriorly Almost completely separated Attempt at third ventricle
and temporal horn for-
mation
Frontal horns present
Semilobar Absent anteriorly but present Varying degrees of separation Attempt at third ventricle
posteriorly Fused thalami and temporal horn for-
mation
Frontal horns absent
Alobar Absent anteriorly and posteriorly Fused Large monoventricle
Absent third ventricle
310  January-February 2022 radiographics.rsna.org

Figure 8.  Truncus arteriosus in a

fetus at 26 weeks GA. (A) Transab-
dominal transverse gray-scale US
image shows cardiomegaly with
a common outflow tract (arrow)
on the three-vessel view. (B) Color
Doppler US image shows the com-
mon outflow tract (arrow).

Figure 9. Transposition of the

great arteries in a fetus at 34 weeks
GA. (A) Transabdominal transverse
gray-scale US image shows an ante-
riorly located left ventricular outflow
tract (arrow) arising from the right
ventricle (RV). (B) Note the abnor-
mal parallel configuration of the
aortic outflow tract (AO) and pulmo-
nary outflow tract (PA) on the aortic
arch view.

Finally, it is also important to highlight that
these infants are prone to develop hypertrophic
cardiomyopathy, which is noted in up to 30% of
infants of diabetic mothers at echocardiography.
This condition manifests postnatally with respi-
ratory distress, and in up to 12% of cases it can
manifest as heart failure, requiring supportive
therapy (30).
Renal Anomalies.—Congenital abnormalities of
the kidney and urinary tract (CAKUT) account
for up to 20% of all prenatally detected birth
defects and 50% of pediatric chronic kidney
disease cases (31,32). CAKUT are commonly
subdivided into three categories according to
their embryologic origin: renal parenchymal
malformations, anomalies of renal embryonic
migration, and outflow abnormalities (33). The
risk of CAKUT increases by 50% in diabetic
pregnancies regardless of diabetes subtype, with
a higher risk in pregestational DM (34). It is
suggested that the teratogenic effect of hypergly-
cemia on renal development mainly affects the
ureteric branching during morphogenesis and
nephrogenesis (35).
The most commonly encountered CAKUT
in infants of diabetic mothers include renal
agenesis (Fig 10), urinary tract dilatation
(UTD) (Fig 11), multicystic dysplastic kidneys
(Fig 12), and duplicated collecting system (Fig
13) (36). Prenatal US plays an important role
in the assessment of fetal kidneys and collect-
ing system dilatation. The Society for Pedi-
atric Urology, in consensus with the AIUM
and ACOG, published guidelines for a UTD
classification system, which aims to unify the
sonographic nomenclature and classification for
UTD while standardizing imaging evaluation
and postnatal follow-up. Factors governing this
classification include anterior-posterior renal
pelvic diameter, calyceal dilatation, renal paren-
chymal abnormalities, ureteral dilatation, and
bladder abnormalities (37). Based on the UTD
classification, fetuses with a dilated ureter in the
context of collecting system dilatation are at in-
creased risk for developing postnatal uropathies,
and hence the anomaly is classified as UTD
A2–3. These patients require follow-up prenatal
imaging as well as postnatal US and consulta-
tion by a pediatric urologist. A full discussion
of the UTD classifications and guidelines are
beyond the scope of this article, and we refer the
reader to the review article by Nguyen et al (37).
Musculoskeletal Anomalies.—Polydactyly
(supernumerary digits) is an uncommon find-
ing during fetal evaluation. It can be isolated
or syndromic, such as with Ellis-van Crev-
RG  •  Volume 42  Number 1 Aboughalia et al  311

Figures 10–13.  (10) Unilateral renal agenesis in a fetus at 20 weeks 4 days GA. (10A) Transabdominal transverse gray-scale US im-
age at the level of the renal fossa shows absence of the left kidney (*). (10B) Longitudinal gray-scale US image (coronal orientation)
shows again an empty renal fossa with an elongated adrenal gland (arrow). (10C) Coronal color Doppler US image shows absence
of the left renal artery (*), the expected location of the origin of the renal artery from the aorta. (11) UTD in a fetus at 33 weeks 3
days GA. Longitudinal gray-scale US image (coronal orientation) shows dilatation of the right renal pelvis (measuring up to 16 mm)
and of the central and peripheral calyces (arrow), corresponding to UTD A2–3. (12) Multicystic dysplastic kidney. (12A) Transverse
gray-scale US image of a fetus at 32 weeks 1 day GA shows bilateral enlarged cystic kidneys with an echogenic cortex, multiple small
cysts (arrows), and a dilated renal pelvis (P). (12B) Gross pathology photograph of the kidney from a different 22-week-old aborted
fetus shows a multicystic appearance with lack of corticomedullary differentiation. (13) Duplicated renal collecting system in a
fetus at 29 weeks 6 days GA. (13A) Longitudinal gray-scale US image (coronal orientation) shows left renal duplication with renal
pelvis dilatation, parenchymal thinning, and ureteral dilatation (calipers) of the upper moiety (UM), as well as dilatation of the lower
moiety (LM). (13B) Longitudinal gray-scale US image (coronal orientation) of the bladder shows an associated ureterocele (arrow).

eld syndrome or trisomy 13. Adam et al (38)
evaluated 18 fetuses with diabetic embryopathy
and polydactyly in an attempt to establish any
association between polydactyly and diabetic
embryopathy and found that proximally placed
preaxial hallucal polydactyly (an additional digit
along the radial side of the hand) is linked to
diabetic embryopathy. This relationship is stron-
ger if there are associated spine segmentation
anomalies and tibial hemimelia (partial or com-
plete absence of the tibia) (38). In the literature,
a radial ray spectrum of anomalies involving
the radius, radial carpal bones, or thumb is also
described in the context of diabetic pregnancies
(Fig 14, Movie 4) (39). The oculoauriculoverte-
bral sequence, previously known as Goldenhar
syndrome, defined as defects in anatomic struc-
tures arising from the first and second branchial
312  January-February 2022 radiographics.rsna.org
Figure 14.  Radial ray
anomaly. Longitudinal
gray-scale US images
of a fetus at 19 weeks
GA show absence of
the right radius and ab-
sence of the thumb, with
a fixed severely flexed
wrist position.
arches, with variable abnormalities of the eyes,
ears, and vertebral column, is also known to be
associated with radial ray anomalies and diabetic
embryopathy (40).
Delayed Lung Maturity
Lung immaturity is a major determinant of
perinatal morbidity and mortality. In diabetic
pregnancies, lung maturity is delayed, thought
to be linked to inhibition of surfactant secretion
by type 2 pneumocytes secondary to hypergly-
cemia (41). Lung maturity is primarily assessed
by measurement of the concentration of vari-
ous surfactant by-products, including lecithin,
sphingomyelin, and phosphatidylglycerol within
the amniotic fluid. However, amniocentesis also
carries the risk of membrane rupture, direct
fetal injury, infection, and fetal loss (42). The
use of MRI has been investigated as a means
for lung maturity assessment. Fetal lung sig-
nal intensity gradually changes over gestation
and is a potential marker for lung maturity.
Several groups have reported on the validity of
the lung-to-liver signal intensity ratio (LLSIR),
which has a linear relationship to GA in normal
fetuses. However, the exact LLSIRs at different
gestational ages are still to be validated in large
normative studies (42,43).
Fetal Growth Disorders
Macrosomic and large for GA fetuses are
frequently encountered in diabetic pregnan-
cies. Fetal macrosomia is diagnosed when the
estimated fetal body weight (EFW) is more
than 4000 g (Fig 15). On the other hand, large
for GA generally implies a birth weight greater
than or equal to the 90th percentile for a given
GA according to the ACOG practice bulletin on
macrosomia (44). Uncontrolled diabetes during
pregnancy resulting in maternal hyperglycemia
causes fetal hyperglycemia and stimulates fetal
insulin release and increases fetal fat deposi-
tion. This effect can be noted as early as in the
second trimester of pregnancy, with a dispropor-
tionate increase in the fetal abdominal and head
circumferences, and associated subcutaneous fat
deposition.
Both maternal and fetal morbidity increase
with increasing EFW (45). According to the
ACOG practice bulletin summary, the risk
of developing a large for GA fetus is 29% in
women with diet-controlled GDM, 30% in
women with medication-controlled GDM, and
38% in women with preexisting diabetes (44).
Disproportionate deposition of fat around the
fetal shoulders is responsible for the higher inci-
dence of shoulder dystocia in infants of diabetic
mothers (46). Thus, the ACOG guidelines sug-
gest offering cesarean delivery to mothers with
diabetes when the estimated fetal weight is more
than 4500 g, in comparison with mothers with-
out diabetes where cesarean delivery is offered
when the estimated fetal weight is greater than
5000 g. In addition to shoulder dystocia, fetuses
of diabetic women are also at increased risk for
clavicular and humeral fractures and brachial
plexus palsy regardless of fetal weight at birth
(Fig 16) (47).
Several studies have investigated the accuracy
of various imaging modalities in fetal weight
assessment. A systematic review by Cooma-
rasamy et al (48) showed that the fetal biometric
measurements such as abdominal circumference
and EFW obtained at two-dimensional US are
not adequate predictors for increased postna-
tal weight. Other literature suggests a relatively
higher sensitivity of MRI for predicting large
fetal weight at birth compared with that of US
(49), although the ACOG recommends further
research to justify performing MRI in this set-
ting (44).
Diabetic pregnancy can be also associated
with fetal growth restriction (FGR), where EFW
is lower than the 10th percentile for GA, and is
RG  •  Volume 42  Number 1 Aboughalia et al  313

Figure 15.  Large for GA fetus at 31 weeks GA. (A) Transverse gray-scale US image shows increased
abdominal circumference and EFW, with an EFW of 2413 g. (B) Graphs show that both abdominal cir-
cumference (left) and EFW (right) are greater than the 99th percentile for GA.

an established risk factor for perinatal morbid-
ity and mortality (50). FGR is primarily seen in
mothers with long-standing pregestational dia-
betes and is attributed to vasculopathy resulting
in placental dysfunction and impairment of fetal
growth (51). FGR can also be noted as a conse-
quence of diabetes-associated congenital mal-
formation and/or maternal hypertensive disease
(52). Thus, it is recommended to pursue US
surveillance every 3–4 weeks once a diagnosis of
FGR is established. Serial EFW measurements
over time can provide an overall picture of
growth trajectory, allowing appropriate follow-
up and intervention. Furthermore, Doppler
US of the umbilical artery can be performed
to distinguish high-risk FGR and to assess for
deterioration over time. A full discussion of fetal
Doppler US evaluation is beyond the scope of
this article. However, lack or reversal of diastolic
flow in the umbilical artery is associated with
adverse prenatal outcomes (53).
Perinatal Morbidity and Mortality
Diabetic pregnancies are associated with in-
creased perinatal morbidity and mortality.
Patients with pregestational DM are at increased
risk for spontaneous abortion, especially in the
context of poor glycemic control evidenced by
elevated HbA1c levels, which can also manifest
as associated fetal congenital anomalies (Figs
17, 18) (54). Infants of diabetic mothers are at
increased risk of preterm delivery (either spon-
taneous or medically indicated), as well as still-
birth (relative risk [RR] = 1.34) (55,56). Given
the increased risk of stillbirth in this population,
antenatal testing with nonstress test or biophysi-
cal profile is recommended in the third trimes-
ter. This, together with hyperglycemia-induced
delayed lung maturation, contributes to surfac-
tant deficiency disease, manifesting at neonatal
imaging as low lung volumes and diffuse granu-
lar opacities (Fig 19) (57). Other factors that
contribute to perinatal asphyxia include neo-
natal cardiomyopathy and nephropathy. These
infants are also prone to metabolic disturbances
including hypoglycemia, hypocalcemia, and
hypomagnesemia (57). Given these increased
risks of complication, neonates of women with
diabetes have increased risk of neonatal inten-
sive care unit admissions.
314  January-February 2022 radiographics.rsna.org

Figure 18.  Spontaneous abortion. Longitudinal transvagi-

nal gray-scale US image (sagittal orientation) in a 31-year-
old woman with vaginal bleeding and severe cramps at 8
weeks gestation shows the presence of a gestational sac
containing a fetal pole within the cervix. The fetus and ges-
tational sac were subsequently expelled.
Figure 16.  Shoulder dystocia. Frontal radiograph
in a 3-day-old neonate shows a displaced angulated
fracture of the proximal left humerus (arrow) follow-
ing delivery.

Figure 19.  Respiratory distress syndrome. Frontal chest

radiograph of a neonate a few hours after delivery shows
low lung volumes and diffuse granular ground-glass opac-
ities bilaterally. The endotracheal tube and enteric tubes
are in situ.

Figure 17.  Early failure of intrauterine pregnancy.

Transverse M-mode transvaginal US image centered
over the fetal pole obtained at 7 weeks and 3 days
GA (crown-rump length, 12 mm) shows absence of
fetal heart activity.
Maternal Abnormalities
Hypertensive Diseases
Based on the ACOG guidelines, hyperten-
sive disorders of pregnancy are classified into
four subtypes: preeclampsia and/or eclampsia,
chronic hypertension, chronic hypertension
with superimposed preeclampsia, and gesta-
tional hypertension. Preeclampsia is defined as
elevated blood pressure during the second half
of pregnancy in association with other physi-
ologic disturbances including proteinuria, new
thrombocytopenia, disturbed kidney function,
abnormal liver enzymes, or cerebral or visual
symptoms (58,59). DM is associated with in-
creased risk for preeclampsia, most commonly
in patients with type 1 DM, with a reported
incidence of 18% and a lesser incidence in
pregnancies with type 2 DM and GDM (60,61).
Preeclampsia is a spectrum of a disease com-
prising abnormal blood pressure and laboratory
values and can progress to eclampsia (seizures)
or hemolysis, elevated liver enzymes, and low
platelets (HELLP) syndrome (62). HELLP
syndrome has a grave prognosis with a myriad
of consequences including rupture of a hepatic
subcapsular hematoma and hepatic necrosis (Fig
20), disseminated intravascular coagulation, and
maternal mortality (62). HELLP syndrome is
diagnosed on the basis of clinical symptoms and
laboratory markers. Imaging is reserved to help
evaluate complications, particularity hepatic
subcapsular hematoma and capsular rupture
(63). Also, preeclampsia is a strong predispos-
ing factor for placental abruption and premature
placenta separation, which are associated with
high maternal and fetal morbidity and mortality
RG  •  Volume 42  Number 1 Aboughalia et al  315
Figure 21.  Marginal placental abruption. Trans-
verse gray-scale US image of the uterus in a 26-week
pregnancy shows a large heterogeneous retropla-
cental hemorrhage at the uterine fundus (calipers).
FH = fetal head.
(Fig 21). Reported maternal complications of
placental abruption include hemorrhage, dis-
seminated intravascular coagulation, and renal
failure, while fetal complications include FGR
and preterm delivery (64).
Complications Related to Delivery
DM is independently associated with an in-
creased need for cesarean delivery. In a study by
Ehrenberg et al (65), the odds ratio of cesarean
delivery is 1.8 in women with diet-controlled
GDM, 3.2 in women with medication-con-
trolled GDM, and 4.5 in women with preges-
tational DM (65). Although cesarean delivery
is considered a relatively safe procedure, there
is increased risk for the development of subse-
quent complications, adding to the burden to
any future pregnancy (Table 4, Figs 22–24). On
the other hand, attempted vaginal delivery, when
appropriate by institutional guidelines, might be
complicated with cephalopelvic disproportion,
resulting in need for cesarean delivery; maternal
vaginal and perineal lacerations; and fetal shoul-
der dystocia (66).
Figure 20.  HELLP syndrome in a
31-year-old woman who presented
with severe abdominal pain at 37
weeks of gestation. (A) Transverse
gray-scale US image of the right
upper abdomen shows a hetero-
geneous subcapsular collection or
hematoma along the right hepatic
lobe (arrow). (B) Axial intravenous
contrast-enhanced CT image of
the abdomen obtained 4 days later
shows an evolving subcapsular he-
patic hematoma (arrow).
Other Abnormalities
Placental Thickening
A thick placenta is independently associated
with adverse perinatal outcome including FGR
and need for emergency cesarean delivery (67).
DM is among the most common causes of pla-
cental thickening, in addition to toxoplasmosis,
other infections, rubella, cytomegalovirus, and
herpes simplex (TORCH) infection; triploidy;
and fetal hydrops. At US, placental thickness is
obtained through a perpendicular measurement
at the mid placenta, excluding the myometrium,
from the subplacental veins to the amniotic fluid
surface of the placenta (Fig 25). It is important
to recognize that myometrial contraction and
placental abruption are important pitfalls to be
avoided during placental thickness assessment.
The reported thresholds for a thickened pla-
centa, measured as a perpendicular line extend-
ing from the subplacental veins to the amniotic
fluid at the midportion of the placenta while
excluding the myometrium, are 33 mm for an
anterior placenta and 40 mm for a posterior
placenta (68).
Polyhydramnios
DM accounts for up to 20%–25% of pregnan-
cies diagnosed with polyhydramnios, defined as
amniotic fluid index greater than 25 or a maxi-
mum vertical pocket greater than 8 cm (Fig 26)
(69). Polyhydramnios is independently associ-
ated with an increased risk of adverse pregnancy
outcomes, including preterm labor, placental
abruption, and premature rupture of mem-
branes (70). In selected patients, amnioreduc-
tion might be pursued in light of amniotic fluid
index and clinical status, the details of which
are beyond the scope of this article. Prenatal
normalization of hyperglycemia and symptom-
atic management decrease the incidence of
polyhydramnios and can be used as a marker for
glycemic control during pregnancy. Research by
Dashe et al (71) has suggested that the amniotic
fluid index parallels the amniotic fluid glucose
316  January-February 2022 radiographics.rsna.org

Table 4: Short- and Long-term Complications of Cesarean Delivery

Duration Type Complications

Short-term Maternal Infection, bleeding, thromboembolism, visceral injury, anesthesia
complications, maternal mortality
Neonatal Infection, psychologic, maldevelopment, allergies
Long-term Nongravid uterus Cesarean scar complications (eg, dysmenorrhea, endometriosis, fistula)
Gravid uterus Placental adhesion disorder, cesarean ectopic pregnancy, uterine
dehiscence and rupture, repeat cesarean delivery

Figures 22–24.  (22) Isthmocele. Longitudinal transvaginal gray-scale US image

(sagittal orientation) in a 37-year-old woman with a history of cesarean delivery
and vaginal bleeding shows a focal deficiency containing fluid in the lower ante-
rior uterine wall at the site of the cesarean scar (arrow). (23) Cesarean scar–associ-
ated ectopic pregnancy. Longitudinal transvaginal gray-scale US image (sagittal
orientation) in a 37-year-old woman with a history of prior cesarean delivery at 8
weeks and 5 days gestation shows the presence of a gestational sac containing a
fetal pole embedded in the cesarean delivery scar. (24) Placenta accreta spectrum
in a patient with a history of multiple cesarean deliveries. (24A) Longitudinal
gray-scale US image of the placenta shows an anterior placenta (P) in the lower
uterine segment. Note the progressive thinning of the overlying myometrium
(calipers) toward the lower uterine segment, with no perceptible retroplacental
clear space just posterior to the bladder wall (arrow). (24B) Color Doppler US
image shows multiple prominent myometrial vessels (arrow) extending into the
posterior bladder wall, indicating bladder invasion. Placenta percreta was con-
firmed at pathologic analysis.

level. Less commonly, oligohydramnios in dia-
betic pregnancies is multifactorial and reflects
long-standing DM, fetal renal abnormality, or
presence of maternal hypertension.
Abnormalities of the Umbilical Cord
GDM is a known risk factor for the develop-
ment of a single umbilical artery (SUA). Other
implicated risk factors include advanced mater-
nal age, smoking, pregestational diabetes, hyper-
tension, preeclampsia, and epilepsy (72). The
risk for congenital anomalies (the most common
of which are genitourinary and cardiovascular)
and chromosomal abnormalities is eight and
16 times higher in fetuses with an SUA, respec-
tively. In addition, an SUA is associated with an
increased risk for prematurity, growth restric-
tion, and adverse neonatal outcomes (73). A
suggested cause for SUA is decreased amount
of Wharton jelly, a gelatinous substance within
the umbilical cord that surrounds the vessels
(74). SUA can be identified at both fetal US
and MRI. A transverse US image near the fetal
insertion of the cord can better demonstrate an
SUA since the umbilical arteries commonly fuse
near the placental insertion site. In addition, a
longitudinal image at the level of the urinary
bladder shows an SUA lateral to the urinary
bladder (Fig 27). Doppler US can further con-
firm this finding (72). In such cases, detailed
fetal anatomy evaluation is recommended. Fetal
echocardiography and karyotype analysis can be
pursued in cases that display associated congeni-
tal anomalies. Increased risk of growth retarda-
RG  •  Volume 42  Number 1 Aboughalia et al  317

Figure 25.  Thickened

placenta. (A) Transverse
gray-scale US image of a
gravid uterus at 28 weeks
GA shows placental thick-
ness measuring up to 5.4
cm (calipers). (B) Axial
T2-weighted MR image
in a different patient at 19
weeks GA shows a thick-
ened anterior placenta
measuring up to 5.1 cm
(calipers).

Figures 26–27.  (26) Polyhydramnios. (26A) Transverse transabdominal US image shows a maximum vertical pocket of the amni-
otic fluid measuring up to 10.1 cm (calipers). The amniotic fluid index measured 27.1 cm (not shown). (26B) Sagittal T2-weighted
MR image in a different patient at 34 weeks gestation shows polyhydramnios as a large amount of fluid surrounding the fetus.
(27) Two-vessel umbilical cord. Transverse color Doppler US image of a fetus at 20 weeks GA at the level of the urinary bladder
shows a two-vessel umbilical cord with an SUA (arrow) in the left perivesical region.

tion in this population necessitates regular fetal References

growth monitoring (75).
Conclusion
A pregnancy complicated by preexisting DM or
GDM is associated with significant health risk
to the mother and developing fetus. The fetus
is at risk for congenital anomalies, delayed lung
maturity, macrosomia, and perinatal morbidity
and mortality. The mother is at risk for develop-
ing hypertensive diseases of pregnancy, as well
as a spectrum of complications in relation to
delivery. Understanding the role of imaging in
diabetic pregnancies serves to improve commu-
nications between the provider and the radiolo-
gist and allows appropriate imaging follow-up,
pregnancy management, and delivery planning.
Disclosures of conflicts of interest.—M.V.R. Editorial board
member of RadioGraphics (not involved in the handling of
this article); royalties from Elsevier for Diagnostic Radiology.
G.H.D. Consultant to Boehringer Ingelheim to determine
patient eligibility for a drug study; money to institution from
NIH-NHLBI for LungMAP grant. D.S.K. Editorial board
member of RadioGraphics (not involved in the handling of this
article). M.M. Editor of RSNA Case Collection.
1. Forouhi NG, Wareham NJ. Epidemiology of diabetes.
Medicine (Abingdon) 2014;42(12):698–702.
2. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers
MH. The pathophysiology of gestational diabetes mellitus.
Int J Mol Sci 2018;19(11):3342.
3. U.S. Preventive Services Task Force. Gestational Diabetes:
Screening. https://www.uspreventiveservicestaskforce.org/
uspstf/recommendation/gestational-diabetes-screening.
4. ACOG Practice Bulletin No. 190: Gestational Diabetes
Mellitus. Obstet Gynecol 2018;131(2):e49–e64.
5. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner
RE. Pre-conception care of diabetes, congenital mal-
formations, and spontaneous abortions. Diabetes Care
1996;19(5):514–541.
6. Ornoy A. Embryonic oxidative stress as a mechanism of
teratogenesis with special emphasis on diabetic embryopa-
thy. Reprod Toxicol 2007;24(1):31–41.
7. Eriksson UJ, Wentzel P. The status of diabetic embryopathy.
Ups J Med Sci 2016;121(2):96–112.
8. Castori M. Diabetic embryopathy: a developmental per-
spective from fertilization to adulthood. Mol Syndromol
2013;4(1-2):74–86.
9. Bhandari J, Thada PK, Khattar D. Diabetic Embryopa-
thy. Treasure Island, FL: StatPearls Publishing, 2020.
10. AIUM practice parameter for the performance of
detailed second- and third-trimester diagnostic ob-
stetric ultrasound examinations. J Ultrasound Med
2019;38(12):3093–3100.
11. AIUM practice parameter for the performance of fetal
echocardiography. J Ultrasound Med 2020;39(1): E5–E16.
318  January-February 2022 radiographics.rsna.org
12. Ahmed B, Abushama M, Khraisheh M, Duden-
hausen J. Role of ultrasound in the management of
diabetes in pregnancy. J Matern Fetal Neonatal Med
2015;28(15):1856–1863.
13. Hopkins MK, Dugoff L. Screening for aneuploidy in the
patient with diabesity: Pearls and pitfalls. Clin Obstet
Gynecol 2021;64(1):136–143.
14. Kucera J. Rate and type of congenital anomalies among off-
spring of diabetic women. J Reprod Med 1971;7(2):73–82.
15. Tortori-Donati P, Rossi A, Cama A. Spinal dysraphism:
a review of neuroradiological features with embryological
correlations and proposal for a new classification. Neu-
roradiology 2000;42(7):471–491.
16. Warner T, Scullen TA, Iwanaga J, et al. Caudal regression
syndrome—A review focusing on genetic associations.
World Neurosurg 2020;138:461–467.
17. Hagan DM, Ross AJ, Strachan T, et al. Mutation analysis
and embryonic expression of the HLXB9 Currarino syn-
drome gene. Am J Hum Genet 2000;66(5):1504–1515.
18. Pang D. Sacral agenesis and caudal spinal cord malformations.
Neurosurgery 1993;32(5):755–778; discussion 778–779.
19. González-Quintero VH, Tolaymat L, Martin D, Roma-
guera RL, Rodríguez MM, Izquierdo LA. Sonographic
diagnosis of caudal regression in the first trimester of
pregnancy. J Ultrasound Med 2002;21(10):1175–1178.
20. Heuser CC, Hulinsky RS, Jackson GM. Caudal regression
syndrome. In: Copel JA, D’Alton ME, Feltovich H, et al,
eds. Obstetric Imaging: Fetal Diagnosis and Care. 2nd
ed. Philadelphia, Pa: Elsevier, 2017; 291–294.
21. Negrete LM, Chung M, Carr SR, Tung GA. In utero
diagnosis of caudal regression syndrome. Radiol Case
Rep 2015;10(1):1049.
22. Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus
and birth defects. Am J Obstet Gynecol 2008;199(3):237.
e1–237.e9.
23. Garne E, Loane M, Dolk H, et al. Spectrum of congenital
anomalies in pregnancies with pregestational diabetes. Birth
Defects Res A Clin Mol Teratol 2012;94(3):134–140.
24. Bromley B. Diagnostic imaging of fetal anomalies. J
Ultrasound Med 2003;22(8):850.
25. Aboughalia H, Bastawrous S, Revzin MVMV, Delaney
SS, Katz DS, Moshiri M. Imaging findings in associa-
tion with altered maternal alpha-fetoprotein levels during
pregnancy. Abdom Radiol (NY) 2020;45(10):3239–3257.
26. Griffiths PD, Jarvis D. In utero MR imaging of fetal
holoprosencephaly: A structured approach to diag-
nosis and classification. AJNR Am J Neuroradiol
2016;37(3):536–543.
27. Simeone RM, Devine OJ, Marcinkevage JA, et al. Dia-
betes and congenital heart defects: a systematic review,
meta-analysis, and modeling project. Am J Prev Med
2015;48(2):195–204.
28. Øyen N, Diaz LJ, Leirgul E, et al. Prepregnancy diabetes
and offspring risk of congenital heart disease: A nationwide
cohort study. Circulation 2016;133(23):2243–2253.
29. Revels JW, Wang SS, Itani M, et al. Radiologist’s guide to
diagnosis of fetal cardiac anomalies on prenatal ultrasound
imaging. Ultrasound Q 2019;35(1):3–15.
30. Narchi H, Kulaylat N. Heart disease in infants of diabetic
mothers. Images Paediatr Cardiol 2000;2(2):17–23.
31. Dias T, Sairam S, Kumarasiri S. Ultrasound diagnosis
of fetal renal abnormalities. Best Pract Res Clin Obstet
Gynaecol 2014;28(3):403–415.
32. Saran R, Robinson B, Abbott KC, et al. US renal data
system 2016 annual data report: epidemiology of kidney
disease in the United States. Am J Kidney Dis 2017;69(3
Suppl 1):A7–A8 [Published correction appears in Am J
Kidney Dis 2017;69(5):712.].
33. Ramanathan S, Kumar D, Khanna M, et al. Multi-
modality imaging review of congenital abnormalities
of kidney and upper urinary tract. World J Radiol
2016;8(2):132–141.
34. Parimi M, Nitsch D. A systematic review and meta-analysis
of diabetes during pregnancy and congenital genitouri-
nary abnormalities. Kidney Int Rep 2020;5(5):678–693.
35. Hokke SN, Armitage JA, Puelles VG, et al. Altered ure-
teric branching morphogenesis and nephron endowment
in offspring of diabetic and insulin-treated pregnancy.
PLoS One 2013;8(3):e58243.
36. Dunn V, Nixon GW, Jaffe RB, Condon VR. Infants of
diabetic mothers: radiographic manifestations. AJR Am
J Roentgenol 1981;137(1):123–128.
37. Nguyen HT, Benson CB, Bromley B, et al. Multidisci-
plinary consensus on the classification of prenatal and
postnatal urinary tract dilation (UTD classification
system). J Pediatr Urol 2014;10(6):982–998.
38. Adam MP, Hudgins L, Carey JC, et al. Preaxial hallucal
polydactyly as a marker for diabetic embryopathy. Birth
Defects Res A Clin Mol Teratol 2009;85(1):13–19.
39. Society for Maternal-Fetal Medicine (SMFM); Gandhi
M, Rac MWF, McKinney J. Radial ray malformation.
Am J Obstet Gynecol 2019;221(6):B16–B18.
40. Wang R, Martínez-Frías ML, Graham JM Jr. Infants of
diabetic mothers are at increased risk for the oculo-auri-
culo-vertebral sequence: A case-based and case-control
approach. J Pediatr 2002;141(5):611–617.
41. Gewolb IH, O’Brien J. Surfactant secretion by type II
pneumocytes is inhibited by high glucose concentrations.
Exp Lung Res 1997;23(3):245–255.
42. Moshiri M, Mannelli L, Richardson ML, et al. Fetal
lung maturity assessment with MRI fetal lung-to-liver
signal-intensity ratio. AJR Am J Roentgenol 2013;201(6):
1386–1390.
43. Brewerton LJ, Chari RS, Liang Y, Bhargava R. Fetal lung-
to-liver signal intensity ratio at MR imaging: development
of a normal scale and possible role in predicting pulmonary
hypoplasia in utero. Radiology 2005;235(3):1005–1010.
44. Macrosomia: ACOG Practice Bulletin Summary, Number
216. Obstet Gynecol 2020;135(1):246–248.
45. Boulet SL, Alexander GR, Salihu HM, Pass M. Macro-
somic births in the united states: determinants, outcomes,
and proposed grades of risk. Am J Obstet Gynecol
2003;188(5):1372–1378.
46. McFarland MB, Trylovich CG, Langer O. Anthropomet-
ric differences in macrosomic infants of diabetic and non-
diabetic mothers. J Matern Fetal Med 1998;7(6):292–295.
47. Bahar AM. Risk factors and fetal outcome in cases of shoul-
der dystocia compared with normal deliveries of a similar
birthweight. Br J Obstet Gynaecol 1996;103(9):868–872.
48. Coomarasamy A, Connock M, Thornton J, Khan KS.
Accuracy of ultrasound biometry in the prediction of
macrosomia: a systematic quantitative review. BJOG
2005;112(11):1461–1466.
49. Malin GL, Bugg GJ, Takwoingi Y, Thornton JG, Jones
NW. Antenatal magnetic resonance imaging versus ultra-
sound for predicting neonatal macrosomia: a systematic
review and meta-analysis. BJOG 2016;123(1):77–88.
50. American College of Obstetricians and Gynecologists’
Committee on Practice Bulletins—Obstetrics and the
Society for Maternal-Fetal Medicine. ACOG Practice
Bulletin No. 204: Fetal growth restriction. Obstet Gynecol
2019;133(2):e97–e109.
51. Gutaj P, Wender-Ozegowska E. Diagnosis and manage-
ment of IUGR in pregnancy complicated by type 1 diabetes
mellitus. Curr Diab Rep 2016;16(5):39.
52. Suhag A, Berghella V. Intrauterine growth restriction
(IUGR): Etiology and diagnosis. Curr Obstet Gynecol
Rep 2013;2(2):102–111.
53. Debbink MP, Son SL, Woodward PJ, Kennedy AM.
Sonographic assessment of fetal growth abnormalities.
RadioGraphics 2021;41(1):268–288.
54. Greene MF, Hare JW, Cloherty JP, Benacerraf BR,
Soeldner JS. First-trimester hemoglobin A1 and risk for
major malformation and spontaneous abortion in diabetic
pregnancy. Teratology 1989;39(3):225–231.
55. Rosenstein MG, Cheng YW, Snowden JM, Nicholson JM,
Doss AE, Caughey AB. The risk of stillbirth and infant
death stratified by gestational age in women with gesta-
tional diabetes. Am J Obstet Gynecol 2012;206(4):309.
e1–309.e7.
56. Melamed N, Chen R, Soiberman U, Ben-Haroush A,
Hod M, Yogev Y. Spontaneous and indicated preterm
delivery in pregestational diabetes mellitus: etiology and
risk factors. Arch Gynecol Obstet 2008;278(2):129–134
RG  •  Volume 42  Number 1 Aboughalia et al  319
57. Michael Weindling A. Offspring of diabetic pregnancy:
short-term outcomes. Semin Fetal Neonatal Med
2009;14(2):111–118.
58. Hypertension in Pregnancy: Executive Summary. Obstet
Gynecol 2013;122(5):1122–1131.
59. Duley L. The global impact of pre-eclampsia and eclampsia.
Semin Perinatol 2009;33(3):130–137.
60. Schneider S, Freerksen N, Röhrig S, Hoeft B, Maul H.
Gestational diabetes and preeclampsia: similar risk factor
profiles? Early Hum Dev 2012;88(3):179–184.
61. Weissgerber TL, Mudd LM. Preeclampsia and diabetes.
Curr Diab Rep 2015;15(3):9.
62. 62 Nunes JO, Turner MA, Fulcher AS. Abdominal imag-
ing features of HELLP syndrome: a 10-year retrospective
review. 2005;185:1205-1210.
63. Chan AD, Gerscovich EO. Imaging of subcapsular hepatic
and renal hematomas in pregnancy complicated by pre-
eclampsia and the HELLP syndrome. J Clin Ultrasound
1999;27(1):35–40.
64. Tikkanen M. Placental abruption: epidemiology, risk
factors and consequences. Acta Obstet Gynecol Scand
2011;90(2):140–149.
65. Ehrenberg HM, Durnwald CP, Catalano P, Mercer BM.
The influence of obesity and diabetes on the risk of cesarean
delivery. Am J Obstet Gynecol 2004;191(3):969–974.
66. Ramos SZ, Waring ME, Leung K, Amir NS, Bannon AL,
Moore Simas TA. Attempted and successful vacuum-
assisted vaginal delivery by prepregnancy body mass index.
Obstet Gynecol 2017;129(2):311–320.
67. Miwa I, Sase M, Torii M, Sanai H, Nakamura Y, Ueda
K. A thick placenta: a predictor of adverse pregnancy
outcomes. Springerplus 2014;3(1):353.
This journal-based SA-CME activity has been approved for AMA PRA Category 1 Credit . See rsna.org/learning-center-rg.
68. Fadl S, Moshiri M, Fligner CL, Katz DS, Dighe M.
Placental imaging: normal appearance with review of
pathologic findings. RadioGraphics 2017;37(3):979–998.
69. Moore LE. Amount of polyhydramnios attributable to
diabetes may be less than previously reported. World J
Diabetes 2017;8(1):7–10.
70. Ross MG, Brace RA; National Institute of Child Health
and Development Workshop Participants. National
Institute of Child Health and Development Conference
summary: amniotic fluid biology—basic and clinical
aspects. J Matern Fetal Med 2001;10(1):2–19.
71. Dashe JS, Nathan L, McIntire DD, Leveno KJ. Cor-
relation between amniotic fluid glucose concentration
and amniotic fluid volume in pregnancy complicated by
diabetes. Am J Obstet Gynecol 2000;182(4):901–904.
72. Moshiri M, Zaidi SF, Robinson TJ, et al. Comprehensive
imaging review of abnormalities of the Umbilical Cord.
RadioGraphics 2014;34(1):179–196.
73. Murphy-Kaulbeck L, Dodds L, Joseph KS, Van den Hof
M. Single umbilical artery risk factors and pregnancy
outcomes. Obstet Gynecol 2010;116(4):843–850.
74. Raio L, Ghezzi F, Di Naro E, Franchi M, Brühwiler H,
Lüscher KP. Prenatal assessment of Wharton’s jelly in
umbilical cords with single artery. Ultrasound Obstet
Gynecol 1999;14(1):42–46.
75. Lubusky M, Dhaifalah I, Prochazka M, et al. Single
umbilical artery and its siding in the second trimester
of pregnancy: relation to chromosomal defects. Prenat
Diagn 2007;27(4):327–331.
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