Clinical Expert Series

Diabetic Ketoacidosis in Pregnancy

Baha M. Sibai, MD, and Oscar A. Viteri, MD

Pregnancies complicated by diabetic ketoacidosis are associated with increased rates of

perinatal morbidity and mortality. A high index of suspicion is required, because diabetic
ketoacidosis onset in pregnancy can be insidious, usually at lower glucose levels, and often
progresses more rapidly as compared with nonpregnancy. Morbidity and mortality can be
reduced with early detection of precipitating factors (ie, infection, intractable vomiting,
inadequate insulin management or inappropriate insulin cessation, b-sympathomimetic use,
steroid administration for fetal lung maturation), prompt hospitalization, and targeted therapy
with intensive monitoring. A multidisciplinary approach including a maternal-fetal medicine
physician, medical endocrinology specialists familiar with the physiologic changes in pregnancy,
an obstetric anesthesiologist, and skilled nursing is paramount. Management principles include
aggressive volume replacement, initiation of intravenous insulin therapy, correction of acidosis,
correction of electrolyte abnormalities and management of precipitating factors, as well as
monitoring of maternal-fetal response to treatment. When diabetic ketoacidosis occurs after
24 weeks of gestation, fetal status should be continuously monitored given associated fetal
hypoxemia and acidosis. The decision for delivery can be challenging and must be based on
gestational age as well as maternal-fetal responses to therapy. The natural inclination is to pro-
ceed with emergent delivery for nonreassuring fetal status that is frequently present during the
acute episode, but it is imperative to correct the maternal metabolic abnormalities first, because
both maternal and fetal conditions will likewise improve. Prevention strategies should include
education of diabetic pregnant women about the risks of diabetic ketoacidosis, precipitating
factors, and the importance of reporting signs and symptoms in a timely fashion.
(Obstet Gynecol 2014;123:167–78)
DOI: 10.1097/AOG.0000000000000060

D iabetic ketoacidosis is one of the most serious

acute complications of diabetes and is character-
ized by the triad of uncontrolled hyperglycemia, anion
gap metabolic acidosis, and ketosis.1,2 Diabetic ketoa-
cidosis is an infrequent complication of pregestational
or gestational diabetes mellitus (GDM) during preg-
nancy, but in the absence of prompt diagnosis and
treatment, it can be life-threatening to the mother
From the Division of Maternal-Fetal Medicine, Department of Obstetrics,
Gynecology and Reproductive Sciences, the University of Texas Health Science
Center at Houston, Houston, Texas.
Continuing medical education for this article is available at http://links.lww.
com/AOG/A457.
Corresponding author: Baha M. Sibai, MD, 6410 Fannin Street, Suite 210,
Houston, TX 77030; e-mail: Baha.M.Sibai@uth.tmc.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2013 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/14
and fetus. The worldwide prevalence of diabetes has
risen dramatically over the past two decades, corre-
sponding with increasing trends to higher-calorie diets
as well as decreased physical activity leading to obe-
sity. Furthermore, the increased rates of obese women
and the continued immigration to the United States
among populations with high prevalence of type 2
diabetes mellitus (DM) have all significantly contrib-
uted to the increasing incidence of gestational and
type 2 DM in pregnancy.3 During the past decade,
there has been considerable effort to improve preg-
nancy outcomes in women with type 1 and type 2 DM
as well as GDM with preconception and first-trimester
control of maternal hyperglycemia, early detection of
type 2 DM and GDM (universal screening), nutri-
tional counseling, frequent glucose monitoring,
proper oral hypoglycemic or insulin therapy, and
timely hospitalization and delivery.3,4 Nevertheless,
diabetic ketoacidosis continues to occur in a small
percentage of patients with diabetes in pregnancy.

VOL. 123, NO. 1, JANUARY 2014 OBSTETRICS & GYNECOLOGY 167

The purpose of this report is to review the English
literature regarding the incidence, pathophysiology,
risk factors, diagnosis, management, outcome, and
prevention of diabetic ketoacidosis in pregnancy.
INCIDENCE
The true incidence of diabetic ketoacidosis in preg-
nancy is difficult to ascertain and epidemiologic data
are based mainly on case reports, retrospective studies
with small numbers, and review articles.5–11 Histori-
cally, the reported incidence of diabetes in pregnancy
ranges from 6% to 7% with 90% of these cases repre-
senting women with GDM.12,13 The two populations
with the highest risk of diabetes in pregnancy are
obese African Americans and those of Hispanic or
Latino descent with an overall prevalence as high as
30%.12,14–16 Diabetic ketoacidosis occurrence during
pregnancy is exceedingly rare with a reported inci-
dence between 0.5% and 3% of all diabetic gesta-
tions.6,11 Formerly considered a hallmark of type 1
DM, diabetic ketoacidosis is now increasingly being
reported in individuals with poorly controlled type 2
DM or GDM.17,18 The incidence of diabetic ketoaci-
dosis in pregnancy is expected to increase because of
the increased frequency of type 2 DM and gestational
diabetes during pregnancy as a result of the change in
demographics of women who are pregnant. Pregnan-
cies in women 35 years or older are much more com-
mon than a decade ago. Advanced maternal age is
associated with increased rates of obesity and both
type 2 DM and GDM. Some of these women will also
conceive by assisted reproductive technology, resulting
in multifetal pregnancies. Indeed, higher order gesta-
tions are associated with increased rates of GDM; how-
ever, the magnitude of this risk is unclear.19,20 In
addition, multifetal gestations are associated with
increased rates of preterm labor or premature rupture
of membranes,19 resulting in the need for corticoste-
roids for fetal lung maturation, which, if complicated
by diabetes, may increase the maternal risk of diabetic
ketoacidosis.
PATHOPHYSIOLOGY
The metabolic profile of diabetic ketoacidosis is the
result of an exaggerated counterregulatory response
to a perceived lack of glucose supply at the cellular
level. In the absence of adequate insulin availability,
cells enter a state of starvation, which in turn activates
alternative energy-producing pathways. Levels of
glucagon and epinephrine are markedly elevated
during starvation. Glycogen storages are rapidly
depleted, and gluconeogenesis becomes the primary
metabolic pathway. There are abundant sources of
168 Sibai and Viteri Diabetic Ketoacidosis in Pregnancy
glucose precursors: lipolysis results in excess amounts
of glycerol released to the circulation and muscle
breakdown results in the release of amino acids, both
of which are readily available as sources of energy.
Furthermore, as a result of the state of insulin
resistance, there is increased lipolysis, which in turn
decreases adipocyte storage of free fatty acids.10
The metabolic derangements during an episode of
diabetic ketoacidosis result in a chain of events that self-
perpetuate the process in a vicious cycle. The elevated
glucose levels in the intravascular space create an
osmotic gradient, resulting in marked diuresis that in
turn leads to a profound state of dehydration and
hypovolemia. This further exacerbates the hyperglyce-
mia and acidosis because it promotes the activation of
other counterregulatory stress hormones (ie, growth
hormone, cortisol). Furthermore, measured sodium
levels can become abnormally low as a result of the
osmotic diuresis. Additionally, electrolyte salts contain-
ing sodium, potassium, and phosphorus become bound
to anions from ketoacids in the bloodstream and are
excreted in the urine.9 Protein breakdown (as a conse-
quence of the perceived state of starvation) and
decreased potassium cellular uptake resulting from
the lack of insulin result in normal or elevated serum
potassium levels in the presence of diminished total
body potassium.
During diabetic ketoacidosis, increased b-oxidation
of fatty acids resulting from insulin deficiency and con-
comitant elevations of counterregulatory hormones
increase production of acetyl CoA, which in turn is
converted by the liver to ketone bodies (3b-hydroxy-
butyrate and acetoacetate).21 Acetoacetate can undergo
decarboxylation and conversion to acetone (which
presents as a fruity odor in the patient’s breath). Increas-
ing amounts of ketone bodies in the bloodstream along
with lactic acid (which also serves as a gluconeogenesis
precursor) are the principal contributors to the meta-
bolic acidosis seen in patients with diabetic ketoacidosis
(Fig. 1).22
METABOLIC CONSIDERATIONS UNIQUE
TO PREGNANCY
Pregnancy is a state of insulin resistance, accelerated
starvation, and respiratory alkalosis, especially in the
late second and throughout the third trimester. Insulin
sensitivity has been demonstrated to decrease by as
much as 56% by 36 weeks of gestation.23 Several hor-
mones unique to pregnancy such as human placental
lactogen and prolactin antagonize the effects of insulin
at the cellular level. Other hormones unique to preg-
nancy also play a role in predisposing a diabetic preg-
nant woman to develop diabetic ketoacidosis. Early in
OBSTETRICS & GYNECOLOGY
 • Inadequate circulating insulin
• Increased insulin resistance

• Reduced glucose utilization • Increased counterregulatory

or storage hormones
◦ Muscles ◦ Glucagon
◦ Liver ◦ Cortisol
◦ Adipose tissue ◦ Catecholamines
◦ Growth hormone

Hyperglycemia

• Maternal effects
◦ Osmotic diuresis • Increased hepatic glucose
◦ Hypovolemia production
◦ Hypokalemia ◦ Gluconeogenesis, glycogenolysis
• Fetal effects • Increased ketogenesis (liver)
◦ Hypokalemia leading to • Increased lipolysis
Fig. 1. Pathophysiology of diabetic
ketoacidosis in pregnancy. Modified arrythmias
from Sibai BM. Management of acute ◦ Hyperglycemia
obstetrics emergencies: female pelvic ◦ Hyperinsulinemia
surgery video, atlas series. 1st ed. • Release of free fatty acids and
Philadelphia (PA): Saunders, Elsevier; conversion to ketone bodies
2011. p. 140. ◦ 3β–hydroxybutirate
Maternal and fetal acidosis ◦ Acetoacetate
Sibai. Diabetic Ketoacidosis in Pregnancy.
Obstet Gynecol 2014. ◦ Acetone

pregnancy, high levels of human chorionic gonadotro-
pin are associated with increased nausea and vomiting,24
which may trigger a cascade of starvation, dehydration,
and acidosis as well as activation of stress-related hor-
mones (Fig. 1). Progesterone also decreases the gastro-
intestinal motility and enhances the carbohydrate
absorption, thus promoting hyperglycemia. Diabetic
pregnant women at more than 20 weeks of gestation
are more prone to develop more severe and rapidly
progressive episodes of diabetic ketoacidosis (usually
over hours) and at lower glycemic levels (less than
300 mg/dL).22 Furthermore, diabetic pregnant women
are more sensitive to starvation, infection, and extrinsic
ketogenic factors such as excessive alcohol intake.25 The
maternal metabolic rate increases by approximately 300
kcal/d in the third trimester.26,27 Maternal ketone body
levels during fasting are elevated by 33% during the
third trimester as compared with the postpartum
state.21,28 Ketone bodies can be detected in the urine
of pregnant women who are fasting in approximately
30% of the first morning specimens.21,29 Starvation re-
sulting from poor nutritional status or persistent vomit-
ing leads to reduced carbohydrate intake and both have
been associated with the development of diabetic ketoa-
cidosis in euglycemic diabetic pregnant women.25,30,31
Furthermore, it has been suggested that the develop-
ment of diabetic ketoacidosis and starvation in the preg-
nant type 1 diabetic with eating disorders may not be
rare.32 In addition, the increased minute alveolar venti-
lation places the pregnant woman in a state of respira-
tory alkalosis and is counterregulated by increased renal
excretion of bicarbonate. This results in a lowered buff-
ering capacity, which further contributes to the develop-
ment of diabetic ketoacidosis at lower glycemic levels
than those seen in nonpregnant patients.33
Euglycemic Ketoacidosis
Euglycemic ketoacidosis was first described by Munro
et al in 1973 and is defined as severe ketoacidosis with
a serum bicarbonate of 10 mEq/L or less in the
absence of pronounced hyperglycemia.34,35 All partic-
ipants had type 1 DM, and blood glucose levels were
less than 300 mg/dL. However, during pregnancy,
euglycemic ketoacidosis has also been reported to
occur in pregestational type 2 DM and GDM.18,36–38
True euglycemic ketoacidosis is exceedingly rare,
occurring in 0.8–1.1% of all episodes (depending on
the defining plasma bicarbonate concentration).7

VOL. 123, NO. 1, JANUARY 2014 Sibai and Viteri Diabetic Ketoacidosis in Pregnancy 169
Metabolic Considerations in the
Fetoplacental Compartment
The mechanism of fetal loss during episodes of
diabetic ketoacidosis still remains elusive. Both ketoa-
cids and glucose readily cross the placenta. Fetopla-
cental demands for glucose are considerable and
approach the equivalent of 150 g/d in the third
trimester.39 Glucose transport to the fetus is aug-
mented by a fivefold increase in the placental glucose
transporter (GLUT-1), which increases transplacental
glucose efflux even in the absence of maternal hyper-
glycemia.26,27 The effects of maternal acidosis, hyper-
glycemia, dehydration, or electrolyte imbalance on
fetal status is unclear, because data are based on lim-
ited case reports of fetal heart tracings or animal mod-
els.40,41 The massive osmotic diuresis and consequent
dehydration leads to volume depletion resulting in
reduced uteroplacental perfusion. In addition, maternal
acidemia can decrease the placental blood flow with
resultant fetal hypoxia. Fetal hypoxemia can also be
caused as a consequence of maternal hypophosphate-
mia, which causes a decrease in 2,3-diphosphoglycerate
resulting in a decreased oxygen release from the red
blood cells.42 Fetal hyperinsulinemia resulting from
maternal hyperglycemia also increases fetal oxygen
requirements by stimulating the oxidative metabolic
pathway.43 Maternal hypokalemia and fetal hyperinsu-
linemia could potentially cause fetal hypokalemia lead-
ing to fatal arrhythmias.9,22,44
Precipitating Factors for Diabetic Ketoacidosis
in Pregnancy
Factors precipitating episodes of diabetic ketoacidosis
in pregnant patients have been well established22,45,46
and are listed in Box 1. Vomiting and the use of beta-
mimetic drugs accounted for 57% of the episodes of
diabetic ketoacidosis in one case series.46 Schneider
et al16 evaluated 888 pregnant women with diabetes
using insulin over 10 years and found that 11 women
(1.2%) presented with diabetic ketoacidosis. The most
common causes of diabetic ketoacidosis in these pa-
tients were infections (27%) and a history of insulin
therapy omission (18%). Chen et al47 compared mul-
tiple daily insulin injections with continuous subcuta-
neous insulin infusions in the management of type 1
DM. Patients treated with continuous subcutaneous
insulin injections had a significantly higher rate of
diabetic ketoacidosis episodes (13% compared with
1.6%, P5.04).
Diabetic pregnant women on chronic corticoste-
roid therapy are at increased risk for diabetic ketoa-
cidosis because of the effects of steroids on serum
glucose values as well as increased risk for infection.48
170 Sibai and Viteri Diabetic Ketoacidosis in Pregnancy
Box 1. Precipitating Factors for Diabetic
Ketoacidosis in Pregnancy

Protracted vomiting, starvation

Infections (pyelonephritis, respiratory, chorioamnio-
nitis, ear infection, cellulitis, tooth abscess)

Undiagnosed diabetes

Poor control of blood sugars or poor compliance
with treatment

Insulin pump failure

Use of b-sympathomimetic agents for tocolysis

Steroid use for fetal lung maturation or for chronic
medical disorders

Diabetic gastroparesis
In addition, the administration of corticosteroids for
fetal lung maturation will result in acute elevations in
serum glucose values within 6 hours after the first
dose and can last up to 3 days after the last dose.49
Therefore, these women should be hospitalized for
frequent serum glucose values, and the dose of insulin
should be increased as needed. The effects of cortico-
steroids will be more pronounced when used in asso-
ciation with b-agonists that may be used to treat
uterine contractions and preterm labor.50
Gastroparesis usually occurs in patients with long-
standing diabetes in association with other microvascu-
lar complications such as nephropathy and retinopathy.
It is associated with delayed gastric emptying resulting
in protracted nausea, vomiting and dehydration, and
persistent postprandial hyperglycemia. These metabolic
abnormalities combined increase the risk of diabetic
ketoacidosis.45,51
MATERNAL AND
PERINATAL COMPLICATIONS
Although diabetic ketoacidosis is infrequent during
pregnancy, its development may result in serious
maternal morbidities (acute renal failure, adult respi-
ratory distress syndrome, myocardial ischemia, cere-
bral edema) and even death.9,10 The frequency of
these complications depends on the severity of the
maternal condition at the time of presentation and
adequacy of management used (stabilization of the
maternal condition before induction of labor or emer-
gency cesarean delivery). In recent years, the reported
maternal mortality in diabetic ketoacidosis has been
less than 1% with a reported fetal mortality rate of
9–36%.8,16,45 However, perinatal morbidities such as
OBSTETRICS & GYNECOLOGY
preterm delivery, hypoxia, and acidosis still remain
high.
An association has been reported between elevated
ketoacids during pregnancy and lower IQ scores as
well as decreased mental developmental score during
the second year of life.52 Furthermore, an association
has also been reported between ketonuria detected dur-
ing prenatal visits and adverse neurobehavioral out-
comes even in nondiabetic pregnancies.53 The fetal
brain is particularly susceptible to increased levels of
b-hydroxybutyrate and lactate concentrations, which
decrease glucose uptake by the fetal brain.54 Also, these
substances are known to accumulate in the basal gan-
glia of children during episodes of diabetic ketoacido-
sis.55,56 The acidotic environment that develops has
been associated with poor myelination and poor corti-
cal connectivity as well as aberrations in the hypocam-
pal neurons. These findings have been linked with
greater deficits in expressive language among children
diagnosed with autism spectrum disorder.48 Future
research is thus needed to further elucidate the effect
of maternal ketoacids on fetal brain injury.57,58
DIAGNOSIS OF DIABETIC KETOACIDOSIS
IN PREGNANCY
Clinical Presentation
The signs and symptoms of diabetic ketoacidosis during
pregnancy are not pathognomonic and tend to develop
faster during pregnancy than in the nonpregnant state
(Box 2). A high level of suspicion is required for prompt
recognition and management of the disease. An episode
of diabetic ketoacidosis may be the initial presentation
that leads to a diagnosis of type 1 diabetes. Intractable
nausea and vomiting in a known diabetic patient war-
rant laboratory evaluation for diabetic ketoacidosis.
Abdominal pain may be severe, and the gravid patient
might experience uterine contractions (Fig. 2A). Hyper-
glycemia leads to glucosuria, intravascular volume
depletion, increased diuresis, and dehydration. Kuss-
maul respirations and a fruity odor in the patient’s
breath might be present in advanced disease. Lethargy
and central nervous system manifestations are also an
effect of the buildup of ketoacids that could lead to
a state of disorientation, obtundation, and even coma
resulting from cerebral edema.59
Standard Laboratory Assessment
Common laboratory findings in diabetic ketoacidosis
are listed in Box 2. Initial laboratory testing in the symp-
tomatic hyperglycemic patient should include a com-
plete blood cell count with differential, liver function
tests, glucose, electrolytes, blood urea nitrogen, creati-
nine, arterial blood gases if bicarbonate is low, and
VOL. 123, NO. 1, JANUARY 2014
Box 2. Diagnosis of Diabetic Ketoacidosis
Signs and Symptoms

Hyperventilation–tachypnea

Sinus tachycardia

Hypotension or dehydration

Change in sensorium, disorientation, or coma

Kussmaul respirations or fruity breath

Nonreassuring fetal tracing

Polyuria or polydipsia

Nausea or vomiting

Abdominal pain or contractions

Blurred vision

Muscle weakness
Laboratory Findings

Plasma glucose level (usually greater than 250 mg/dL)*†

Arterial pH less than 7.30*

Anion gap greater than 12 mEq/L*

Elevated base deficit*

Positive serum/urine ketones, especially 3b-hydrox-
ybutyrate (most abundant)‡

Falsely normal potassium level might be present

Low serum bicarbonate (often less than 15 mEq/L)

Elevated serum blood urea nitrogen and creatinine
resulting from dehydration and possible renal failure
* These values are variable.
† Diabetic ketoacidosis in pregnancy can present with
much lower glucose levels.
‡ Siemens Multistix 10SG only detect acetoacetate.
anion gap or serum ketones. Acidosis is the hallmark
of diabetic ketoacidosis with a serum bicarbonate con-
centration that is usually less than 15 mEq/L.11 Hyper-
glycemia (plasma glucose level greater than 300), anion
gap metabolic acidosis, and ketosis (positive serum and
urine ketones) are seen in virtually all cases of diabetic
ketoacidosis. An anion gap is present because the aci-
dosis is caused by unmeasured anions (ie, ketoacids
and lactate). In acute diabetic ketoacidosis, the ketone
body ratio (3-b-hydroxybutyrate:acetoacetate) rises
from normal (1:1) to as high as 10:1. As mentioned,
the plasma glucose level is usually higher than 300 mg/
dL but lower levels are not uncommon during
Sibai and Viteri Diabetic Ketoacidosis in Pregnancy 171
pregnancy. Falsely normal or elevated potassium levels
might be present; however, it is likely that the total
body potassium is decreased and the patient is dehy-
drated and hypokalemic. Blood urea nitrogen and cre-
atinine levels may be elevated as a result of renal
dysfunction.21
MANAGEMENT OF DIABETIC
KETOACIDOSIS IN PREGNANCY
Diabetic ketoacidosis in pregnancy is an obstetric and
medical emergency and therefore requires prompt and
aggressive treatment in a specialized care unit (Fig. 3).
Management should be provided by physicians with
172 Sibai and Viteri Diabetic Ketoacidosis in Pregnancy
special expertise in the area, ideally including maternal-
fetal medicine and medical endocrinology specialists, an
obstetric anesthesiologist, and skilled nursing support.
The principles of management of diabetic ketoacidosis
during pregnancy are the same as that in the nonpreg-
nant state. They consist of aggressive volume replace-
ment, intravenous (IV) insulin therapy, correction of
acidosis and abnormal electrolytes, correction of the
underlying pathology, and intensive monitoring of
maternal and fetal response to the treatment.
Fluid Replacement
Initial fluid replacement is first accomplished with
normal saline. It is imperative to establish early IV
Fig. 2. A. Fetal heart rate monitoring
of a patient during an acute episode
of diabetic ketoacidosis demonstrat-
ing uterine contractions, minimal
variability, and late decelerations
(solid arrows) after each contraction
(dashed arrows). B. After correction of
maternal hyperglycemia and acidosis,
uterine contractions and late decel-
erations were resolved. In addition,
there is now moderate variability. C.
Fetal tracing in a patient who pre-
sented with acute diabetic ketoaci-
dosis at 34 weeks of gestation
demonstrates repetitive late deceler-
ations (solid arrows) and minimal
variability. She was rushed for an
emergency cesarean delivery result-
ing in the delivery of a premature
newborn with Apgar scores of 2, 3,
and 5 at 1, 5, and 10 minutes,
respectively. The arterial cord pH was
6.85.
Sibai. Diabetic Ketoacidosis in Pregnancy.
Obstet Gynecol 2014.
OBSTETRICS & GYNECOLOGY
 • Confirm diagnosis (See Box 2)
• Secure airway and oxygenation
• Admit for intensive monitoring
• Obtain adequate intravenous
access* and insert indwelling
catheter

Yes
Mechanical ventilation required?
Consider intensive care
unit admission
No No

Fluid replacement Insulin therapy

Fluid deficit (approximately Short–acting intravenous
100 mL/kg) insulin (10 units bolus)

0.9% sodium chloride

1–2 L/h x 2 h Continue basal infusion
rate of 1–2 units/hour†

Evaluate corrected
serum sodium level

Corrected serum (Na+) Corrected serum (Na+)

140 mEq/L or greater less than 140 mEq/L

0.45% sodium chloride 0.9% sodium chloride

250–500 mL/hour 250–500 mL/hour

Serum glucose
250 mg/dL or less

Add dextrose 5% in 0.45%

sodium chloride or dextrose
5% in 0.9% sodium chloride

Serum K+ less than 5 mEq/L
and urine output more than
0.5 mL/Kg/hour
Replace K+ as per
protocol (Table 1)
• Close monitoring first 4 hours Continous fetal monitoring
◦ Hourly urine output if 24 weeks of
◦ Vital signs every 15 minutes gestation or more§
◦ Measure arterial blood gas,
capillary serum ketones,
electrolytes, glucose and anion
gap‡ every 1–3 hours
◦ Aggressive investigation and
management of precipitating
factors

Serum bicarbonate
and anion gap normalize|| • Discontinue insulin infusion 2
hours after subcutaneous long-
acting insulin
No Yes • Initiate subcutaneous weight-
Insulin drip until oral intake Patient tolerating oral intake based insulin
is tolerated • Check capillary glucose fasting
and 2 hours post-prandial
• Consultation to nutrition, diabetes
and insulin education services

Fig. 3. An algorithm for the management of diabetic ketoacidosis in pregnancy. *Intravenous access should be obtained with two
large-bore catheters or central venous catheter placement. †If serum glucose level does not fall by 50‒70 mg/dL within an hour,
double the insulin infusion dose until this goal is achieved. ‡Anion gap: [Na+]–[Cl– + HCO3–], corrected serum sodium: Serum
Na+ (mEq/L)+(1.6 mEq/L for each 100 mg/dL glucose level greater than 100 mg/dL). §No interventions on fetal behalf should be
performed until stabilization of acute maternal condition has been achieved. kUse of bicarbonate in severe acidosis is debatable
(see text). Some authors recommend administering 50 mEq of intravenous bicarbonate only if pH less than 7.
Sibai. Diabetic Ketoacidosis in Pregnancy. Obstet Gynecol 2014.

VOL. 123, NO. 1, JANUARY 2014 Sibai and Viteri Diabetic Ketoacidosis in Pregnancy 173
access with two large-bore catheters or central venous
catheter placement. In patients with diabetic ketoaci-
dosis, the fluid deficit is typically 100 mL/kg of body
weight,60 which is equivalent to 6–10 L based on
maternal weight. Immediate effects of this aggressive
hydration are hemodilution and an increase in tissue
perfusion resulting in a decrease of glucose and potas-
sium levels. It is important to replace 75% of the fluid
deficit during the first 24 hours of treatment and the
total volume should be completed within 48 hours.
Isotonic normal saline is administered at a rate of
1–2 L/h for 1–2 hours. Once this is completed,
normal saline is then administered at a rate of 250–
500 mL/h and continued until glucose values are less
than 250 mg/dL. Once this is achieved, administra-
tion of an IV solution with 5% dextrose is started. The
subsequent choice for fluid replacement depends on
the hydration state, serum electrolyte levels, and
hemodynamic stability, and it should be continued
until the calculated fluid deficit is corrected. If hyper-
natremia develops, switching to 0.45% saline until cor-
rection of hypernatremia is recommended (to replace
free water loss as a result of the glucose-induced
osmotic diuresis).10 Close hemodynamic monitoring
should be performed during the first 4 hours; this
includes hourly urine output through an indwelling
catheter and vital signs surveillance every 15 minutes.
Continuous oxygen saturation should be monitored
and supplemental oxygen is given as needed. The
patient’s response to treatment is evaluated with arte-
rial blood gas monitoring, serum ketones, electrolytes,
glucose, and anion gap every 1–3 hours. Investigation
and management of the precipitating factors should be
performed simultaneously and corrected promptly.22
Insulin Therapy
Correction of hyperglycemia is best achieved with IV
short-acting insulin. Regular insulin is administered as
an 8- to 10-unit bolus followed by 0.1 units/kg/h until
the serum bicarbonate and anion gap normalize and
serum ketones become absent. Because correction of
acidemia takes much longer than correction of hyper-
glycemia, insulin should be continued at a basal
infusion rate of 1–2 units/h after normoglycemia is
established and to be discontinued only after the first
subcutaneous dose of regular insulin is administered.10
Monitoring of Acidosis and Correction
of Electrolytes
Correction of electrolyte imbalances, particularly
hypokalemia, should start as soon as adequate renal
function is documented. As mentioned, serum levels
of potassium may appear deceivingly normal or
174 Sibai and Viteri Diabetic Ketoacidosis in Pregnancy
slightly elevated, but the total body potassium is
usually low. In diabetic ketoacidosis, the total potas-
sium deficit is typically 5–10 mEq/L. During the
administration of insulin, volume replacement, and
correction of acidosis, potassium shifts from the extra-
cellular to the intracellular space. To prevent fatal ar-
rhythmias, it is important to keep serum potassium
levels between 4 and 5 mEq/L. This is best accom-
plished by IV administration of potassium chloride
(Table 1 ).60 Adequate urine output must be main-
tained at all times (greater than 0.5 mL/kg/h). Phos-
phate replacement is not usually required unless levels
fall below 1 mg/dL, cardiac dysfunction ensues, or
signs of obtundation are noted. Phosphorus may be
replaced in conjunction with potassium by adminis-
tering 10–20 mEq/L of potassium phosphate for each
10–20 mEq/L of potassium chloride.11 The need for
replacement of other electrolytes including bicarbon-
ate, magnesium, and calcium is debatable. Administra-
tion of bicarbonate may be associated with profound
alkalosis or worsening acidemia secondary to increased
partial pressure of carbon dioxide, leading in turn to
impaired fetal oxygen transfer.10 Some authors recom-
mend bicarbonate administration during severe acid-
emia (pH less than 7) or in patients complicated by
cardiac dysfunction, sepsis, or shock61; however, fur-
ther research is required to assess the potential risks
and benefits of such therapy.
In the setting of diabetic ketoacidosis in patients
with type 1 DM, point-of-care b-hydroxybutyrate cap-
illary ketone testing is routinely used.62,63 This test
only measures 3-b-hydroxybutyrate, whereas the ni-
troprusside test for ketones in urine detects only ace-
toacetate.62 Point-of-care capillary testing assists in
prompt detection and subsequent management of dia-
betic ketoacidosis. Ketone levels can be checked seri-
ally and are more accurate than urine ketone testing,
because concentrations of 3-b-hydroxybutyrate are
typically 10-fold higher compared with acetoacetate.64
In response to insulin, 3-b-hydroxybutyrate levels
commonly decrease long before acetoacetate levels.21
Table 1. Suggested Protocol for Potassium
Repletion According to Serum Levels
Potassium Level Intervention
Greater than 5 mEq/L No treatment
4–5 mEq/L 20 mEq/L replacement
3–4 mEq/L 30–40 mEq/L replacement
3 mEq/L or less 40–60 mEq/L replacement
Data from Carroll MA, Yeomans ER. Diabetic ketoacidosis in
pregnancy. Crit Care Med 2005;33(suppl):S347–53.
OBSTETRICS & GYNECOLOGY
MANAGEMENT COMPLICATIONS
AND PROGNOSIS
The vast majority of patients with diabetic ketoacido-
sis in pregnancy recover with no sequelae. Delayed
recognition and inappropriate management carry
elevated maternal and fetal morbidity. Most compli-
cations result from inadequate fluid management and
premature discontinuation of insulin. In addition,
failure to promptly recognize and correct precipitating
factors (ie, infections) is associated with a worse
prognosis and higher recurrence rates (ie, inadequate
home insulin administration).
A rare but potentially fatal complication is cerebral
edema. In most reported series, no direct association
with the metabolic disturbances in diabetic ketoacidosis
has been reported, although aggressive hydration
(particularly with hypotonic solutions) is certainly
a contributing factor.59 Furthermore, the occurrence
of hyperchloremic acidosis has been reported in pa-
tients resuscitated with normal saline given its relative
acidic pH of 5.5 and high chloride content. It has been
proposed that the use of more physiologic, balanced
crystalloid solutions such as PlasmaLyte during resus-
citation may reduce the incidence of this complication
given similar serum chloride concentrations and neu-
tral pH.65 Other complications with varying degrees of
severity have been described and include hypoglyce-
mia, acute respiratory distress syndrome, pulmonary
edema, and bronchial mucous plugging.66–68 Aggres-
sive potassium replacement during the acute episode
in the absence of adequate urine output may result in
fatal arrhythmias.
Investigation and Management of
Precipitating Factors
Once hemodynamic status and metabolic abnormal-
ities have been addressed, it is important to evaluate
for and treat potential precipitating factors such as
infection or use of b-sympathomimetic agents. Infec-
tions are major precipitating factors for diabetic ketoa-
cidosis, and thus evaluation for infection should be
done even in the absence of fever. The source of
infection can be the urinary tract, upper airway or
pneumonia, gallbladder, ear, tooth abscess, cellulitis,
or wound infections in case of surgery.69 Once iden-
tified, the source of infection should be treated with
appropriate antibiotics, surgery, or antibiotics and sur-
gery as indicated. In addition, if b-agonists are being
used, they should be discontinued.4
Fetal Monitoring and Timing of Delivery
The metabolic derangements that take place during
diabetic ketoacidosis result in fetal hypoxemia and
VOL. 123, NO. 1, JANUARY 2014
acidosis, which may influence all modes of fetal
testing. Fetal heart rate monitoring is recommended
in patients with gestational age of 24 or more weeks.33
Fetal heart rate monitoring during the acute episode
of diabetic ketoacidosis often reveals minimal or
absent variability, absent accelerations, repetitive vari-
able, and late decelerations (Fig. 2A). The fetal bio-
physical profile can also be abnormal, and Doppler
studies may show signs of blood flow redistribution
(ie, increased umbilical artery pulsatility index and
reduced middle cerebral artery pulsatility index).70
The frequency and severity of these abnormalities will
depend on severity and duration of diabetic ketoaci-
dosis. After correction of the metabolic derangements
in diabetic ketoacidosis and maternal stabilization,
these fetal abnormalities will usually improve; how-
ever, it may take 4–8 hours for the fetal heart rate
tracing to become normal.71
The decision to continue pregnancy or to proceed
with delivery in the setting of diabetic ketoacidosis can
be challenging, but it must be based on fetal gesta-
tional age, maternal status, fetal status, and the
response to treatment. The natural inclination is to
proceed with emergent cesarean delivery for concern-
ing fetal status before stabilizing the maternal condi-
tion. Diabetic ketoacidosis per se is not an indication
for emergent delivery because a premature decision to
proceed with cesarean delivery increases the risk of
maternal mortality and morbidity. In addition, it may
lead to unnecessary preterm delivery of a hypoxic and
acidotic neonate (Fig. 2C). It is imperative to stabilize
the maternal condition first because this will often
improve the fetal status and potentially avoid the pre-
viously mentioned complications. If fetal status does
not improve or if the maternal condition continues to
deteriorate despite aggressive therapy, delivery is war-
ranted. On the other hand, if maternal condition sta-
bilizes and the fetal abnormalities resolve, pregnancy
is continued and most often patients will be dis-
charged home safely.
PREVENTION
Women with pregestational DM planning pregnancy
should be educated about the risks of diabetic ketoaci-
dosis before conception as well as during pregnancy. In
addition, all pregnant women not known to be diabetic
should receive screening for GDM at 24–28 weeks of
gestation and earlier in pregnancy in those with certain
risk factors (obesity, strong family history of type 2 DM,
obesity, history of GDM, impaired glucose metabolism,
or glucosuria).12,72 Those with pregestational and GDM
should be instructed about the importance of compli-
ance with diet, exercise, compliance with prenatal visits,
Sibai and Viteri Diabetic Ketoacidosis in Pregnancy 175
measurements and recordings of glucose values, and
therapy (oral agents or insulin). All pregnant patients
should be vaccinated against influenza during the flu
season. In addition, they need to be educated about
precipitating factors, signs, and symptoms of diabetic
ketoacidosis including when to seek medical help.3 Pa-
tients with either persistent blood glucose values above
200 mg/dL despite therapy, persistent vomiting, diar-
rhea, polyuria, drowsiness, or who have evidence of
infections require prompt hospitalization.
Medical providers should have a low threshold for
hospitalization of patients who demonstrate repeated
episodes of noncompliance with instructions and
therapy, because such patients are at very high risk
for diabetic ketoacidosis. In case of threatened or true
preterm labor, medical providers should avoid using
subcutaneous or oral terbutaline. If true preterm labor
is present, the patient should be hospitalized and
treated with a different class of tocolytic. In addition,
if corticosteroids are used for fetal lung maturity, the
dose of insulin should be adjusted accordingly.4
CONCLUSION
Diabetic ketoacidosis is a rare but serious complica-
tion of diabetes in pregnancy with deleterious con-
sequences for both the mother and the fetus. Prompt
recognition of precipitating factors, aggressive correc-
tion of volume depletion and electrolyte imbalance,
and insulin administration are paramount in the
management of diabetic ketoacidosis. A multidisci-
plinary approach and continuous monitoring of the
maternal response to therapy are critical to decrease
the overall morbidity and mortality. After viability,
fetal monitoring also is indicated, and it is imperative
to correct the maternal metabolic abnormalities
before considering emergent delivery, because both
maternal and fetal conditions will likewise improve.73
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