MANAGEMENT OF DIABETES IN PREGNANCY: STANDARDSOFMEDICAL CAREINDIABETESD2021
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S200 Diabetes Care Volume 44, Supplement 1, January 2021
14. Management of Diabetes in American Diabetes Association
Pregnancy: Standards of Medical
Care in Diabetesd2021
Diabetes Care 2021;44(Suppl. 1):S200–S210 | https://doi.org/10.2337/dc21-S014
14. MANAGEMENT OF DIABETES IN PREGNANCY
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
includes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guidelines,
and tools to evaluate quality of care. Members of the ADA Professional Practice
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc21-
SPPC), are responsible for updating the Standards of Care annually, or more
frequently as warranted. For a detailed description of ADA standards, statements,
and reports, as well as the evidence-grading system for ADA’s clinical practice
recommendations, please refer to the Standards of Care Introduction (https://doi
.org/10.2337/dc21-SINT). Readers who wish to comment on the Standards of Care
are invited to do so at professional.diabetes.org/SOC.
DIABETES IN PREGNANCY
The prevalence of diabetes in pregnancy has been increasing in the U.S. in parallel with the
worldwide epidemic of obesity. Not only is the prevalence of type 1 diabetes and type 2
diabetes increasingin womenofreproductiveage, butthereisalso a dramaticincreaseinthe
reported rates of gestational diabetes mellitus. Diabetes confers significantly greater
maternal and fetal risk largely related to the degree of hyperglycemia but also related to
chronic complications and comorbidities of diabetes. In general, specific risks of diabetes in
pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise,
macrosomia, neonatal hypoglycemia, hyperbilirubinemia, and neonatal respiratory distress
syndrome, among others. In addition, diabetes in pregnancy may increase the risk ofobesity,
hypertension, and type 2 diabetes in offspring later in life (1,2).
PRECONCEPTION COUNSELING
Recommendations
14.1 Starting at puberty and continuing in all women with diabetes and re-
productive potential, preconception counseling should be incorporated into
routine diabetes care. A
14.2 Family planning should be discussed, and effective contraception (with Suggested citation: American Diabetes Associa-
consideration of long-acting, reversible contraception) should be prescribed tion. 14. Management of diabetes in pregnancy:
Standards of Medical Care in Diabetesd2021.
and used until a woman’s treatment regimen and A1C are optimized for Diabetes Care 2021;44(Suppl. 1):S200–S210
pregnancy. A
© 2020 by the American Diabetes Association.
14.3 Preconception counseling should address the importance of achieving glucose Readers may use this article as long as the work is
levels as close to normal as is safely possible, ideally A1C ,6.5% (48 mmol/ properly cited, the use is educational and not for
mol), to reduce the risk of congenital anomalies, preeclampsia, macrosomia, profit, and the work is not altered. More infor-
preterm birth, and other complications. B mation is available at https://www.diabetesjournals
.org/content/license.care.diabetesjournals.org Management of Diabetes in Pregnancy S201
All women of childbearing age with di- Table 14.1 for additional details on ele-
should ideally be managed be-
abetes should be informed about the ments of preconception care (16,18). Coun-
ginning in preconception in a
importance of achieving and maintaining seling on the specific risks of obesity in
multidisciplinary clinic including
as near euglycemia as safely possible pregnancy and lifestyle interventions to
an endocrinologist, maternal-
prior to conception and throughout preg- prevent and treat obesity, including referral
fetal medicine specialist, reg-
nancy. Observational studies show an to a registered dietitian nutritionist (RD/
istered dietitian nutritionist, and
increased risk of diabetic embryopathy, RDN), is recommended when indicated.
diabetes care and education
especially anencephaly, microcephaly, Diabetes-specific counseling should in-
specialist, when available. B
congenital heart disease, renal anoma- clude an explanation of the risks to mother
14.5 In addition to focused attention
lies, and caudal regression, directly pro- and fetus related to pregnancy and the ways
on achieving glycemic targets
portional to elevations in A1C during the to reduce risk including glycemic goal
A, standard preconception care
first 10 weeks of pregnancy (3). Although setting, lifestyle management, and med-
should be augmented with extra
observational studies are confounded by the ical nutrition therapy. The most important
focus on nutrition, diabetes edu-
association between elevated periconcep- diabetes-specific component of precon-
cation, and screening for diabetes
tional A1C and other poor self-care behavior, ception care is the attainment of glycemic
comorbidities and complications. E
the quantity and consistency of data are goals prior to conception. Diabetes-
14.6 Women with preexisting type 1
convincing and support the recommenda- specific testing should include A1C, creat-
or type 2 diabetes who are plan-
tion to optimize glycemia prior to conception, inine, and urinary albumin-to-creatinine
ning pregnancy or who have
given that organogenesis occurs primarily at ratio. Special attention should be paid to
become pregnant should be
5–8 weeks of gestation, with an A1C ,6.5% the review of the medication list for
counseled on the risk of develop-
(48 mmol/mol) being associated with the potentially harmful drugs (i.e., ACE in-
ment and/or progression of di-
lowest risk of congenital anomalies, pre- hibitors [19,20], angiotensin receptor
abetic retinopathy. Dilated eye
eclampsia, and preterm birth (3–7). blockers [19], and statins [21,22]). A
examinations should occur ideally
There are opportunities to educate all referral for a comprehensive eye exam
before pregnancy or in the first
women and adolescents of reproductive is recommended. Women with preexist-
trimester, and then patients should
age with diabetes about the risks of ing diabetic retinopathy will need close
be monitored every trimester and
unplanned pregnancies and about im- monitoring during pregnancy to assess
for 1 year postpartum as indicated
proved maternal and fetal outcomes for progression of retinopathy and pro-
bythedegreeofretinopathy andas
with pregnancy planning (8). Effective vide treatment if indicated (23).
recommended by the eye care
preconception counseling could avert sub- Several studies have shown improved
provider. B
stantial health and associated cost bur- diabetes and pregnancy outcomes when
dens in offspring (9). Family planning care has been delivered from preconcep-
should be discussed, including the benefits The importance of preconception care tion through pregnancy by a multidisci-
of long-acting, reversable contraception, for all women is highlighted by the plinary group focused on improved glycemic
and effective contraception should be pre- American College of Obstetricians and control (24–27). One study showed that
scribed and used until a woman is prepared Gynecologists (ACOG) Committee Opin- care of preexisting diabetes in clinics that
and ready to become pregnant (10–14). ion 762, Prepregnancy Counseling (16). A included diabetes and obstetric specialists
To minimize the occurrence of com- key point is the need to incorporate a improved care (27). However, there is no
plications, beginning at the onset of question about a woman’s plans for consensus on the structure of multidisci-
puberty or at diagnosis, all girls and pregnancy into routine primary and gy- plinary team care for diabetes and preg-
women with diabetes of childbearing necologic care. The preconception care nancy, and there is a lack of evidence on the
potential should receive education about of women with diabetes should include impact on outcomes of various methods of
1) the risks of malformations associated the standard screenings and care recom- health care delivery (28).
with unplanned pregnancies and even mended for all women planning preg-
mild hyperglycemia and 2) the use of nancy (16). Prescription of prenatal
effective contraception at all times when vitamins (with at least 400 mg of folic GLYCEMIC TARGETS IN
preventing a pregnancy. Preconception acid and 150 mg of potassium iodide [17]) PREGNANCY
counseling using developmentally appro- is recommended prior to conception.
Recommendations
priate educational tools enables adoles- Review and counseling on the use of
14.7 Fasting and postprandial self-
cent girls to make well-informed decisions nicotine products, alcohol, and recrea-
monitoring of blood glucose
(8). Preconception counseling resources tional drugs, including marijuana, is im-
are recommended in both ges-
tailored for adolescents are available at no portant. Standard care includes screening
tational diabetes mellitus and
cost through the American Diabetes As- for sexually transmitted diseases and thy-
preexisting diabetes in preg-
sociation (ADA) (15). roid disease, recommended vaccinations,
nancy to achieve optimal glucose
routine genetic screening, a careful review
levels. Glucose targets are fasting
Preconception Care of all prescription and nonprescription
plasma glucose ,95 mg/dL
medications and supplements used, and
Recommendations (5.3 mmol/L) and either 1-h post-
a review of travel history and plans with
14.4 Women with preexisting diabe- prandial glucose ,140 mg/dL
special attention to areas known to have
tes who are planning a pregnancy (7.8 mmol/L) or 2-h postprandial
Zika virus, as outlined by ACOG. SeeS202 Management of Diabetes in Pregnancy Diabetes Care Volume 44, Supplement 1, January 2021
glucose ,120 mg/dL (6.7 mmol/ Table 14.1—Checklist for preconception care for women with diabetes (16,18)
Preconception education should include:
L).Somewomen with preexisting
, Comprehensive nutrition assessment and recommendations for:
diabetes should also test blood c Overweight/obesity or underweight
glucose preprandially. B c Meal planning
14.8 Due to increased red blood cell c Correction of dietary nutritional deficiencies
turnover, A1C is slightly lower in c Caffeine intake
c Safe food preparation technique
normalpregnancythaninnormal
, Lifestyle recommendations for:
nonpregnant women. Ideally, the c Regular moderate exercise
A1C target in pregnancy is ,6% c Avoidance of hyperthermia (hot tubs)
(42 mmol/mol) if this can be c Adequate sleep
achieved without significant hy- , Comprehensive diabetes self-management education
, Counseling on diabetes in pregnancy per current standards, including: natural history of insulin
poglycemia, but the target may resistance in pregnancy and postpartum; preconception glycemic targets; avoidance of DKA/
be relaxed to ,7% (53 mmol/ severe hyperglycemia; avoidance of severe hypoglycemia; progression of retinopathy; PCOS (if
mol) if necessary to prevent hy- applicable); fertility in patients with diabetes; genetics of diabetes; risks to pregnancy including
poglycemia. B miscarriage, still birth, congenital malformations, macrosomia, preterm labor and delivery,
14.9 When used in addition to pre- hypertensive disorders in pregnancy, etc.
, Supplementation
and postprandial self-monitoring c Folic acid supplement (400 mg routine)
of blood glucose, continuous c Appropriate use of over-the-counter medications and supplements
glucose monitoring can help Medical assessment and plan should include:
to achieve A1C targets in di- , General evaluation of overall health
abetes and pregnancy. B , Evaluation of diabetes and its comorbidities and complications, including: DKA/severe
hyperglycemia; severe hypoglycemia/hypoglycemia unawareness; barriers to care;
14.10 When used in addition to self-
comorbidities such as hyperlipidemia, hypertension, NAFLD, PCOS, and thyroid dysfunction;
monitoring of blood glucose complications such as macrovascular disease, nephropathy, neuropathy (including autonomic
targeting traditional pre- and bowel and bladder dysfunction), and retinopathy
postprandial targets, continuous , Evaluation of obstetric/gynecologic history, including history of: cesarean section, congenital
glucose monitoring can reduce malformations or fetal loss, current methods of contraception, hypertensive disorders of
pregnancy, postpartum hemorrhage, preterm delivery, previous macrosomia, Rh
macrosomia and neonatal hypo-
incompatibility, and thrombotic events (DVT/PE)
glycemia in pregnancy compli- , Review of current medications and appropriateness during pregnancy
cated by type 1 diabetes. B Screening should include:
14.11 Continuous glucose monitoring , Diabetes complications and comorbidities, including: comprehensive foot exam;
metrics may be used as an ad- comprehensive ophthalmologic exam; ECG in women starting at age 35 years who have cardiac
junct but should not be used as a signs/symptoms or risk factors, and if abnormal, further evaluation; lipid panel; serum
creatinine; TSH; and urine protein-to-creatinine ratio
substitute for self-monitoring of , Anemia
blood glucose to achieve optimal , Genetic carrier status (based on history):
pre- and postprandial glycemic c Cystic fibrosis
targets. E c Sickle cell anemia
c Tay-Sachs disease
14.12 Commonly used estimated A1C
c Thalassemia
and glucose management indi- c Others if indicated
cator calculations should not be , Infectious disease
used in pregnancy as estimates c Neisseria gonorrhea/Chlamydia trachomatis
of A1C. C c Hepatitis C
c HIV
c Pap smear
Pregnancy in women with normal glu- c Syphilis
cose metabolism is characterized by fast- Immunizations should include:
ing levels of blood glucose that are lower , Rubella
than in the nonpregnant state due to , Varicella
insulin-independent glucose uptake by , Hepatitis B
, Influenza
the fetus and placenta and by mild , Others if indicated
postprandial hyperglycemia and carbo- Preconception plan should include:
hydrate intolerance as a result of diabe- , Nutrition and medication plan to achieve glycemic targets prior to conception, including
togenic placental hormones. In patients appropriate implementation of monitoring, continuous glucose monitoring, and pump technology
with preexisting diabetes, glycemic tar- , Contraceptive plan to prevent pregnancy until glycemic targets are achieved
, Management plan for general health, gynecologic concerns, comorbid conditions, or
gets are usually achieved through a com-
complications, if present, including: hypertension, nephropathy, retinopathy; Rh
bination of insulin administration and incompatibility; and thyroid dysfunction
medical nutrition therapy. Because glyce-
DKA, diabetic ketoacidosis; DVT/PE, deep vein thrombosis/pulmonary embolism; ECG,
mic targets in pregnancy are stricter than electrocardiogram; NAFLD, nonalcoholic fatty liver disease; PCOS, polycystic ovary syndrome;
in nonpregnant individuals, it is important TSH, thyroid-stimulating hormone.
that women with diabetes eat consistentcare.diabetesjournals.org Management of Diabetes in Pregnancy S203
amounts of carbohydrates to match with Lower limits are based on the mean of patient should be achieved without hy-
insulin dosage and to avoid hyperglycemia normal blood glucoses in pregnancy (35). poglycemia, which, in addition to the
or hypoglycemia. Referral to an RD/RDN Lower limits do not apply to diet-con- usual adverse sequelae, may increase
is important in order to establish a food trolled type 2 diabetes. Hypoglycemia in the risk of low birth weight (45). Given
plan and insulin-to-carbohydrate ratio and pregnancy is as defined and treated in the alteration in red blood cell kinetics
to determine weight gain goals. Recommendations 6.9–6.14 (Section during pregnancy and physiological
6 “Glycemic Targets,” https://doi changes in glycemic parameters, A1C levels
Insulin Physiology .org/10.2337/dc21-S006). These val- may need to be monitored more frequently
Given that early pregnancy is a time of ues represent optimal control if they can than usual (e.g., monthly).
enhanced insulin sensitivity and lower be achieved safely. In practice, it may be
glucose levels, many women with type 1 challenging for women with type 1 di- Continuous Glucose Monitoring in
diabetes will have lower insulin require- abetes to achieve these targets without Pregnancy
ments and increased risk for hypoglyce- hypoglycemia, particularly women with CONCEPTT (Continuous Glucose Moni-
mia (29). Around 16 weeks, insulin a history of recurrent hypoglycemia or toring in Pregnant Women With Type 1
resistance begins to increase, and total hypoglycemia unawareness. If women Diabetes Trial) was a randomized con-
daily insulin doses increase linearly ;5% cannot achieve these targets without trolled trial of continuous glucose mon-
per week through week 36. This usually significant hypoglycemia, the ADA sug- itoring (CGM) in addition to standard
results in a doubling of daily insulin dose gests less stringent targets based on care, including optimization of pre-
compared with the prepregnancy re- clinical experience and individualization and postprandial glucose targets versus
quirement. The insulin requirement lev- of care. standard care for pregnant women with
els off toward the end of the third type 1 diabetes. It demonstrated the
trimester with placental aging. A rapid A1C in Pregnancy value of CGM in pregnancy complicated
reduction in insulin requirements can indi- In studies of women without preexisting by type 1 diabetes by showing a mild
cate the development of placental insuf- diabetes, increasing A1C levels within the improvement in A1C without an increase
ficiency (30). In women with normal normal range are associated with ad- in hypoglycemia and reductions in large-
pancreatic function, insulin production is verse outcomes (36). In the Hyperglyce- for-gestational-age births, length of stay,
sufficient to meet the challenge of this mia and Adverse Pregnancy Outcome and neonatal hypoglycemia (46). An ob-
physiological insulin resistance and to main- (HAPO) study, increasing levels of glyce- servational cohort study that evaluated
tain normal glucose levels. However, in mia were also associated with worsening the glycemic variables reported using
women with diabetes, hyperglycemia occurs outcomes (37). Observational studies in CGM found that lower mean glucose,
if treatment is not adjusted appropriately. preexisting diabetes and pregnancy show lower standard deviation, and a higher
the lowest rates of adverse fetal out- percentage of time in target range were
Glucose Monitoring comes in association with A1C ,6–6.5% associated with lower risk of large-for-
Reflecting this physiology, fasting and (42–48 mmol/mol) early in gestation gestational-age births and other adverse
postprandial monitoring of blood glucose (4–6,38). Clinical trials have not evalu- neonatal outcomes (47). Use of the CGM-
is recommended to achieve metabolic ated the risks and benefits of achieving reported mean glucose is superior to the
control in pregnant women with diabe- these targets, and treatment goals use of estimated A1C, glucose manage-
tes. Preprandial testing is also recommen- should account for the risk of maternal ment indicator, and other calculations to
ded when using insulin pumps or basal- hypoglycemia in setting an individualized estimate A1C given the changes to A1C
bolus therapy so that premeal rapid-acting target of ,6% (42 mmol/mol) to ,7% that occur in pregnancy (48). CGM time in
insulin dosage can be adjusted. Postprandial (53 mmol/mol). Due to physiological range (TIR) can be used for assessment of
monitoring is associated with better glyce- increases in red blood cell turnover, glycemic control in patients with type 1
mic control and lower risk of preeclampsia A1C levels fall during normal pregnancy diabetes, but it does not provide action-
(31–33). There are no adequately powered (39,40). Additionally, as A1C represents able data to address fasting and post-
randomized trials comparing different fast- an integrated measure of glucose, it may prandial hypoglycemia or hyperglycemia.
ing and postmeal glycemic targets in di- not fully capture postprandial hypergly- There are no data to support the use of
abetes in pregnancy. cemia, which drives macrosomia. Thus, TIR in women with type 2 diabetes or
Similar to the targets recommended although A1C may be useful, it should be GDM.
by ACOG (upper limits are the same as for used as a secondary measure of glycemic The international consensus on time
gestational diabetes mellitus [GDM], de- control in pregnancy, after self-monitor- in range (49) endorses pregnancy target
scribed below) (34), the ADA-recommen- ing of blood glucose. ranges and goals for TIR for patients with
ded targets for women with type 1 or In the second and third trimesters, type 1 diabetes using CGM as reported on
type 2 diabetes are as follows: A1C ,6% (42 mmol/mol) has the lowest the ambulatory glucose profile.
risk of large-for-gestational-age infants
c Fasting glucose 70–95 mg/dL (3.9–5.3 (38,41,42), preterm delivery (43), and c Target range 63–140 mg/dL (3.5–
mmol/L) and either preeclampsia (1,44). Taking all of this 7.8 mmol/L): TIR, goal .70%
c One-hour postprandial glucose 110– into account, a target of ,6% (42 c Time below range (,63 mg/dL [3.5
140 mg/dL (6.1–7.8 mmol/L) or mmol/mol) is optimal during pregnancy mmol/L]), goal ,4%
c Two-hour postprandial glucose 100– if it can be achieved without significant c Time below range (,54 mg/dL [3.0
120 mg/dL (5.6–6.7 mmol/L) hypoglycemia. The A1C target in a given mmol/L]), goal ,1%S204 Management of Diabetes in Pregnancy Diabetes Care Volume 44, Supplement 1, January 2021
c Time above range (.140 mg/dL [7.8 Lifestyle Management Pharmacologic Therapy
mmol/L]), goal ,25%. After diagnosis, treatment starts with Treatment of GDM with lifestyle and
medical nutrition therapy, physical ac- insulin has been demonstrated to im-
tivity, and weight management, depend- prove perinatal outcomes in two large
MANAGEMENT OF GESTATIONAL ing on pregestational weight, as outlined randomized studies as summarized in a
DIABETES MELLITUS in the section below on preexisting type 2 U.S. Preventive Services Task Force re-
Recommendations diabetes, as well as glucose monitoring view (59). Insulin is the first-line agent
14.13 Lifestyle behavior change is an aiming for the targets recommended by recommended for treatment of GDM in
essential component of man- the Fifth International Workshop-Confer- the U.S. While individual RCTs support
agement of gestational diabe- ence on Gestational Diabetes Mellitus (54): limited efficacy of metformin (60,61) and
tes mellitus and may suffice for glyburide (62) in reducing glucose levels
the treatment of many women. c Fasting glucose ,95 mg/dL (5.3 mmol/L) for the treatment of GDM, these agents
Insulinshouldbeaddedifneeded and either are not recommended as first-line treat-
to achieve glycemic targets. A c One-hour postprandial glucose ,140 ment for GDM because they are known to
14.14 Insulin is the preferred medica- mg/dL (7.8 mmol/L) or cross the placenta and data on long-term
tion for treating hyperglycemia c Two-hour postprandial glucose ,120 safety for offspring is of some concern
in gestational diabetes mellitus. mg/dL (6.7 mmol/L) (34). Furthermore, glyburide and met-
Metformin and glyburide should formin failed to provide adequate glyce-
not be used as first-line agents, Glycemic target lower limits defined mic control in separate RCTs in 23% and
as both cross the placenta to the above for preexisting diabetes apply for 25–28% of women with GDM, respec-
fetus. A Other oral and nonin- GDM that is treated with insulin. Depend- tively (63,64).
sulin injectable glucose-lowering ing on the population, studies suggest
Sulfonylureas
medications lack long-term safety that 70–85% of women diagnosed with
Sulfonylureas are known to cross the
data. GDM under Carpenter-Coustan can
placenta and have been associated
14.15 Metformin, when used to treat control GDM with lifestyle modification
with increased neonatal hypoglycemia.
polycystic ovary syndrome and alone; it is anticipated that this pro-
Concentrations of glyburide in umbilical
induce ovulation, should be dis- portion will be even higher if the lower
cord plasma are approximately 50–70%
continued by the end of the first International Association of the Diabe-
of maternal levels (63,64). Glyburide was
trimester. A tes and Pregnancy Study Groups (55)
associated with a higher rate of neonatal
diagnostic thresholds are used.
hypoglycemia and macrosomia than in-
GDM is characterized by increased risk sulin or metformin in a 2015 meta-analysis
of large-for-gestational-age birth weight Medical Nutrition Therapy and systematic review (65).
and neonatal and pregnancy complica- Medical nutrition therapy for GDM is an More recently, glyburide failed to be
tions and an increased risk of long-term individualized nutrition plan developed found noninferior to insulin based on a
maternal type 2 diabetes and offspring between the woman and an RD/RDN composite outcome of neonatal hypo-
abnormal glucose metabolism in child- familiar with the management of GDM glycemia, macrosomia, and hyperbiliru-
hood. These associations with maternal (56,57). The food plan should provide binemia (66). Long-term safety data for
oral glucose tolerance test (OGTT) re- adequate calorie intake to promote fetal/ offspring exposed to glyburide are not
sults are continuous with no clear in- neonatal and maternal health, achieve available (66).
flection points (37,50). Offspring with glycemic goals, and promote weight gain
exposure to untreated GDM have re- according to 2009 Institute of Medicine Metformin
duced insulin sensitivity and b-cell com- recommendations (58). There is no de- Metformin was associated with a lower
pensation and are more likely to have finitive research that identifies a specific risk of neonatal hypoglycemia and less
impaired glucose tolerance in childhood optimal calorie intake for women with maternal weight gain than insulin in
(51). In other words, short-term and GDM or suggests that their calorie needs systematic reviews (65,67–69). However,
long-term risks increase with progres- aredifferentfromthoseofpregnantwomen metformin readily crosses the placenta,
sive maternal hyperglycemia. There- without GDM. The food plan should be resulting in umbilical cord blood levels of
fore, all women should be tested as based on a nutrition assessment with guid- metformin as high or higher than simul-
outlined in Section 2 “Classification ance from the Dietary Reference Intakes taneous maternal levels (70,71). In the
and Diagnosis of Diabetes” (https:// (DRI). The DRI for all pregnant women Metformin in Gestational Diabetes: The
doi.org/10.2334/dc21-S002). Although recommends a minimum of 175 g of Offspring Follow-Up (MiG TOFU) study’s
there is some heterogeneity, many ran- carbohydrate, a minimum of 71 g of protein, analyses of 7- to 9-year-old offspring, the
domized controlled trials (RCTs) suggest and 28 g of fiber. The diet should emphasize 9-year-old offspring exposed to metfor-
that the risk of GDM may be reduced by monounsaturated and polyunsaturated min in the Auckland cohort for the treat-
diet, exercise, and lifestyle counseling, fats while limiting saturated fats and ment of GDM were heavier and had a
particularly when interventions are avoiding trans fats. As is true for all nutrition higher waist-to-height ratio and waist
started during the first or early in the therapy in patients with diabetes, the circumference than those exposed to
second trimester (52–54). There are no amount and type of carbohydrate will im- insulin (72). This was not found in the
intervention trials in offspring of moth- pact glucose levels. Simple carbohydrates Adelaide cohort. In two RCTs of metformin
ers with GDM. will result in higher postmeal excursions. use in pregnancy for polycystic ovarycare.diabetesjournals.org Management of Diabetes in Pregnancy S205
syndrome, follow-up of 4-year-old offspring lesser extent those with type 2 diabetes,
pregnancy. A Insulin is the pre-
demonstrated higher BMI and increased are at risk for diabetic ketoacidosis
ferred agent for the manage-
obesity in the offspring exposed to metfor- (DKA) at lower blood glucose levels
ment of type 2 diabetes in
min (73,74). A follow-up study at 5–10 years than in the nonpregnant state. Women
pregnancy. E
showed that the offspring had higher BMI, with type 1 diabetes should be pre-
14.17 Either multiple daily injections
weight-to-height ratios, waist circumferen- scribed ketone strips and receive edu-
or insulin pump technology can
ces, and a borderline increase in fat mass cation on DKA prevention and detection.
be used in pregnancy compli-
(74,75). Metformin is being studied in two DKA carries a high risk of stillbirth. Women
cated by type 1 diabetes. C
ongoing trials in type 2 diabetes (Metformin in DKA who are unable to eat often require
in Women with Type 2 Diabetes in Preg- 10% dextrose with an insulin drip to
The physiology of pregnancy necessi-
nancy Trial [MiTY] [76] and Medical Optimi- adequately meet the higher carbohydrate
tates frequent titration of insulin to
zation of Management of Type 2 Diabetes demands of the placenta and fetus in the
match changing requirements and under-
Complicating Pregnancy [MOMPOD] [77]), third trimester in order to resolve their
scores the importance of daily and fre-
but long-term offspring data will not be ketosis.
quent self-monitoring of blood glucose.
available for some time. A recent meta- Retinopathy is a special concern in
Due to the complexity of insulin manage-
analysis concluded that metformin expo- pregnancy. The necessary rapid imple-
ment in pregnancy, referral to a special-
sure resulted in smaller neonates with mentation of euglycemia in the setting of
ized center offering team-based care
acceleration of postnatal growth resulting retinopathy is associated with worsening
(with team members including maternal-
in higher BMI in childhood (74). of retinopathy (23).
fetal medicine specialist, endocrinologist
Randomized, double-blind, controlled
or other provider experienced in managing
trials comparing metformin with other Type 2 Diabetes
pregnancy in women with preexisting di-
therapies for ovulation induction in Type 2 diabetes is often associated with
abetes, dietitian, nurse, and social worker,
women with polycystic ovary syndrome obesity. Recommended weight gain during
as needed) is recommended if this resource
have not demonstrated benefit in pre- pregnancy for women with overweight is
is available.
venting spontaneous abortion or GDM 15–25 lb and for women with obesity is 10–
None of the currently available human
(78), and there is no evidence-based 20 lb (58). There are no adequate data on
insulin preparations have been demon-
need to continue metformin in such optimal weight gain versus weight main-
strated to cross the placenta (84–89). A
patients (79–81). tenance in women with BMI .35 kg/m2.
recent Cochrane systematic review was
There are some women with GDM Glycemic control is often easier to
not able to recommend any specific in-
requiring medical therapy who, due to achieve in women with type 2 diabetes
sulin regimen over another for the treat-
cost, language barriers, comprehension, than in those with type 1 diabetes but can
ment of diabetes in pregnancy (90).
or cultural influences, may not be able to require much higher doses of insulin,
While many providers prefer insulin
use insulin safely or effectively in preg- sometimes necessitating concentrated
pumps in pregnancy, it is not clear that
nancy. Oral agents may be an alternative insulin formulations. As in type 1 diabe-
they are superior to multiple daily in-
in these women after a discussion of the tes, insulin requirements drop dramati-
jections (91,92). Hybrid closed-loop in-
known risks and the need for more long- cally after delivery.
sulin pumps that allow for the achievement
term safety data in offspring. However, The risk for associated hypertension
of pregnancy fasting and postprandial gly-
due to the potential for growth restric- and other comorbidities may be as high
cemic targets may reduce hypoglycemia
tion or acidosis in the setting of placental or higher with type 2 diabetes as with
and allow for more aggressive prandial
insufficiency, metformin should not be type 1 diabetes, even if diabetes is better
dosing to achieve targets. Not all hybrid
used in women with hypertension or controlled and of shorter apparent du-
closed-loop pumps are able to achieve the
preeclampsia or at risk for intrauterine ration, with pregnancy loss appearing to
pregnancy targets.
growth restriction (82,83). be more prevalent in the third trimester
in women with type 2 diabetes compared
Insulin
Type 1 Diabetes with the first trimester in women with
Insulin use should follow the guidelines
Women with type 1 diabetes have an type 1 diabetes (93,94).
below. Both multiple daily insulin injec-
tions and continuous subcutaneous in- increased risk of hypoglycemia in the first
sulin infusion are reasonable delivery trimester and, like all women, have al- PREECLAMPSIA AND ASPIRIN
strategies, and neither has been shown tered counterregulatory response in
Recommendation
to be superior to the other during preg- pregnancy that may decrease hypogly-
14.18 Women with type 1 or type 2
nancy (84). cemia awareness. Education for patients
diabetes should be prescribed
and family members about the preven-
low-dose aspirin 100–150 mg/
MANAGEMENT OF PREEXISTING tion, recognition, and treatment of hy-
TYPE 1 DIABETES AND TYPE 2
day starting at 12 to 16 weeks
poglycemia is important before, during,
DIABETES IN PREGNANCY of gestation to lower the risk
and after pregnancy to help to prevent
of preeclampsia. E A dosage of
Insulin Use and manage the risks of hypoglycemia.
162 mg/day may be acceptable;
Insulin resistance drops rapidly with de-
Recommendations currently in the U.S., low-dose
livery of the placenta.
14.16 Insulin should be used for man- aspirin is available in 81-mg
Pregnancy is a ketogenic state, and
agement of type 1 diabetes in tablets. E
women with type 1 diabetes, and to aS206 Management of Diabetes in Pregnancy Diabetes Care Volume 44, Supplement 1, January 2021
Diabetes in pregnancy is associated with blockers is contraindicated because
14.25 Women with a history of gesta-
an increased risk of preeclampsia (95). they may cause fetal renal dysplasia,
tional diabetes mellitus should
The U.S. Preventive Services Task Force oligohydramnios, pulmonary hypoplasia,
have lifelong screening for the
recommends the use of low-dose aspirin and intrauterine growth restriction (19).
development of type 2 diabetes
(81 mg/day) as a preventive medication A large study found that after adjusting
or prediabetes every 1–3 years. B
at 12 weeks of gestation in women who for confounders, first trimester ACE in-
14.26 Women with a history of gesta-
are at high risk for preeclampsia (96). hibitor exposure does not appear to be
tional diabetes mellitus should
However, a meta-analysis and an addi- associated with congenital malforma-
seek preconception screening
tional trial demonstrate that low-dose tions (20). However, ACE inhibitors and
for diabetes and preconception
aspirin ,100 mg is not effective in re- angiotensin receptor blockers should be
care to identify and treat hyper-
ducing preeclampsia. Low-dose aspirin stopped as soon as possible in the first
glycemia and prevent congenital
.100 mg is required (97–99). A cost- trimester to avoid second and third tri-
malformations. E
benefit analysis has concluded that this mester fetopathy (20). Antihypertensive
14.27 Postpartum care should include
approach would reduce morbidity, save drugs known to be effective and safe in
psychosocial assessment and
lives, and lower health care costs (100). pregnancy include methyldopa, nifedipine,
support for self-care. E
However, there is insufficient data re- labetalol, diltiazem, clonidine, and prazo-
garding the benefits of aspirin in women sin. Atenolol is not recommended, but
with preexisting diabetes (98). More other b-blockers may be used, if necessary. Gestational Diabetes Mellitus
studies are needed to assess the long- Chronic diuretic use during pregnancy is Initial Testing
term effects of prenatal aspirin exposure not recommended as it has been associ- Because GDM often represents previ-
on offspring (101). ated with restricted maternal plasma vol- ously undiagnosed prediabetes, type 2
ume, which may reduce uteroplacental diabetes, maturity-onset diabetes of the
perfusion (105). On the basis of available young, or even developing type 1 di-
PREGNANCY AND DRUG abetes, women with GDM should be
evidence, statins should also be avoided in
CONSIDERATIONS
pregnancy (106). tested for persistent diabetes or predi-
Recommendations See PREGNANCY AND ANTIHYPERTENSIVE MEDI- abetes at 4–12 weeks postpartum with a
14.19 In pregnant patients with diabe- CATIONS in Section 10 “Cardiovascular Dis- 75-g OGTT using nonpregnancy criteria
tes and chronic hypertension, a ease and Risk Management” (https://doi as outlined in Section 2 “Classification
blood pressure target of 110– .org/10.2337/dc21-S010) for more infor- and Diagnosis of Diabetes” (https://doi
135/85 mmHg is suggested in mation on managing blood pressure in .org/10.2334/dc21-S002).
the interest of reducing the pregnancy. Postpartum Follow-up
risk for accelerated maternal hy- The OGTT is recommended over A1C at
pertension A and minimizing im- POSTPARTUM CARE 4–12 weeks postpartum because A1C
paired fetal growth. E may be persistently impacted (lowered)
Recommendations
14.20 Potentially harmful medications by the increased red blood cell turnover
14.21 Insulin resistance decreases dra-
in pregnancy (i.e., ACE inhibitors, related to pregnancy, by blood loss at
matically immediately postpar-
angiotensin receptor blockers, delivery, or by the preceding 3-month
tum, and insulin requirements
statins) should be stopped at glucose profile. The OGTT is more sen-
need to be evaluated and ad-
conception and avoided in sex- sitive at detecting glucose intolerance,
justed as they are often roughly
ually active women of childbear- including both prediabetes and diabetes.
half the prepregnancy require-
ing age who are not using reliable Women of reproductive age with pre-
ments for the initial few days
contraception. B diabetes may develop type 2 diabetes by
postpartum. C
14.22 A contraceptive plan should be the time of their next pregnancy and will
In normal pregnancy, blood pressure is need preconception evaluation. Because
discussed and implemented with
lower than in the nonpregnant state. In a GDM is associated with an increased
all women with diabetes of re-
pregnancy complicated by diabetes and lifetime maternal risk for diabetes esti-
productive potential. A
chronic hypertension, a target goal blood mated at 50–60% (107,108), women
14.23 Screen women with a recent
pressure of 110–135/85 mmHg is sug- should also be tested every 1–3 years
history of gestational diabetes
gested to reduce the risk of uncontrolled thereafter if the 4–12 weeks postpartum
mellitus at 4–12 weeks postpar-
maternal hypertension and minimize im- 75-g OGTT is normal. Ongoing evaluation
tum, using the 75-g oral glucose
paired fetal growth (102–104). The 2015 may be performed with any recommen-
tolerance test and clinically ap-
study (104) excluded pregnancies com- ded glycemic test (e.g., annual A1C,
propriate nonpregnancy diag-
plicated by preexisting diabetes and only annual fasting plasma glucose, or tri-
nostic criteria. B
6% had GDM at enrollment. There was no ennial 75-g OGTT using nonpregnant
14.24 Women with a history of gesta-
difference in pregnancy loss, neonatal thresholds).
tional diabetes mellitus found to
care, or other neonatal outcomes be-
have prediabetes should receive
tween the groups with tighter versus less Gestational Diabetes Mellitus and Type 2
intensive lifestyle interventions
tight control of hypertension (104). Diabetes
and/or metformin to prevent
During pregnancy, treatment with ACE Women with a history of GDM have a
diabetes. A
inhibitors and angiotensin receptor greatly increased risk of conversion tocare.diabetesjournals.org Management of Diabetes in Pregnancy S207
type 2 diabetes over time (108). Women increase the risk of overnight hypogly- on intentions and behaviors for family planning
with GDM have a 10-fold increased risk cemia, and insulin dosing may need to in teens with diabetes. Diabetes Care 2013;36:
3870–3874
of developing type 2 diabetes compared be adjusted. 9. Peterson C, Grosse SD, Li R, et al. Preventable
with women without GDM (107). Abso- health and cost burden of adverse birth out-
lute risk increases linearly through a Contraception comes associated with pregestational diabetes in
woman’s lifetime, being approximately A major barrier to effective preconcep- the United States. Am J Obstet Gynecol 2015;
20% at 10 years, 30% at 20 years, 40% at tion care is the fact that the majority of 212:74.e1–74.e9
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30 years, 50% at 40 years, and 60% at pregnancies are unplanned. Planning
Brooks JL, Bryant AG. Contraceptive use among
50 years (108). In the prospective pregnancy is critical in women with pre- women with prediabetes and diabetes in a US
Nurses’ Health Study II (NHS II), sub- existing diabetes due to the need for national sample. J Midwifery Womens Health
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vent congenital malformations and re- 11. Morris JR, Tepper NK. Description and com-
GDM was significantly lower in women
parison of postpartum use of effective contra-
who followed healthy eating patterns duce the risk of other complications.
ception among women with and without
(109). Adjusting for BMI attenuated Therefore, all women with diabetes of diabetes. Contraception 2019;100:474–479
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completely. Interpregnancy or post- planning options reviewed at regular device in women with diabetes mellitus type I
intervals to make sure that effective and II: a systematic review. ISRN Obstet Gynecol
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2013;2013:814062
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outcomes in subsequent pregnancies tained. This applies to women in the reversible contraceptiondhighly efficacious, safe,
(110) and earlier progression to type 2 immediate postpartum period. Women and underutilized. JAMA 2018;320:397–398
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