MOLINA HEALTHCARE OF

CALIFORNIA

GESTATIONAL DIABETES GUIDELINE

Molina Healthcare of California has adopted the American Diabetes Association: Clinical

Practice Recommendations. The guideline was reviewed and adopted by the Molina

Healthcare of California Clinical Quality Management Committee (CQMC) on

December 12, 2001, August 14, 2002, August 6, 2003, August 4, 2004, April 6, 2005,

April 5, 2006, April 4, 2007, March 12, 2008, March 10, 2010, March 16, 2011, and

March 21, 2012.

Molina Healthcare of California has adopted the American Diabetes Association: Clinical

Practice Recommendations. The guideline was reviewed and adopted by the Molina

Healthcare of California Clinical Quality Improvement Committee (CQIC) on March 13,

2013, February 12, 2014, March 11, 2015, March 16, 2016, and February 16, 2017.

The Clinical Practice Guideline may be accessed from:

http://care.diabetesjournals.org/content/diacare/suppl/2016/12/15/40.Supplement_1.DC1/

DC_40_S1_final.pdf

Guidelines for Screening and Treatment for Gestational Diabetes Mellitus (GDM)

Test results YES meet GDM criteria (#3)

High No No Risk Level? Average Test results meet (#1) GDM criteria (#3) Yes

No Meet criteria for insulin therapy (#4) Yes

Assess risk at initial visit

Screen for undiagnosed Diabetes type 2 at first prenatal visit

Usual care per routine guidelines

Glucose testing between 24 to 28 weeks of gestation (#2)

Consider insulin therapy

1. Refer for Nutritional counseling 2. Encourage daily self-monitoring of blood glucose 3. See CPG for additional recommendations

#1 – Definition of High Risk: Overweight (BMI ≥25 kg/m

2) and has additional risk factors:

Physical inactivity First-degree relative with diabetes High-risk race/ethnicity (e.g., African American, Latino,

Native American, Asian American, Pacific Islander) Women who delivered a baby weighing > 9lb or were

diagnosed with GDM Hypertension (≥140/90 mmHg or on therapy for

hypertension) HDL cholesterol level <35/dl (0.90 mmol/l) and/or a

triglyceride level > 250mg/dl (2.82 mmol/l) Women with polycystic ovarian syndrome (PCOS) A1C ≥5.7%, IGT, or IFG on previous testing Other clinical conditions associated with insulin resistance

(e.g., severe obesity, acanthosis, nigricans) History of CVD

#2 Glucose Testing for GDM Perform at 24-28 weeks gestation for women not previously diagnosed with overt diabetes using either of the two strategies:

“One-Step” 75g OGTT performed in the morning or after an overnight fast of at least 8 hours.

“Two-Step” 50g (non-fasting) OGTT screen following by a 100g OGTT for those who screen positive.

#3 Definition of GDM: Diabetes diagnosed in the 2nd

or 3rd trimester

of pregnancy that is not clearly overt diabetes. Criteria for diagnosis of GDM:

One- Step Two – Step

Fasting ≥ 92 mg/dL 1hr ≥ 180 mg/dL 2hr ≥ 153 mg/dL

Step 1: 50g GLT If ≥ 140 mg/dL after 1hr, proceed to step two. Step 2: 100 g OGTT (Diagnosis of GDM made if 2 or more of the following criteria are met or exceeded) Fasting ≥ 95 mg/dL 1hr ≥ 180 2hr ≥ 155 3hr ≥140

#4 Criteria to consider using insulin therapy – if the following are not maintained by medical nutrition therapy (MNT):

Fasting plasma glucose < 105mg/dl 1 hour post – prandial plasma glucose <155 mg/dl or 2 hour post-prandial < 130 mg/dl

Adopted by: Molina Healthcare Clinical Quality Management Committee: 3/16/11, 3/21/12 Molina Healthcare Clinical Quality Improvement Committee: 3/13/13, 2/12/14, 3/11/2015, 3/16/2016, 2/16/17

13. Management of Diabetesin PregnancyDiabetes Care 2017;40(Suppl. 1):S114–S119 | DOI: 10.2337/dc17-S016

For guidelines related to the diagnosis of gestational diabetes mellitus, please referto Section 2 “Classification and Diagnosis of Diabetes.”

Recommendations

Preexisting Diabetesc Starting at puberty, preconception counseling should be incorporated into

routine diabetes care for all girls of childbearing potential. Ac Family planning should be discussed and effective contraception should be

prescribed and used until a woman is prepared and ready to become preg-nant. A

c Preconception counseling should address the importance of glycemic controlas close to normal as is safely possible, ideally A1C ,6.5% (48 mmol/mol), toreduce the risk of congenital anomalies. B

c Women with preexisting type 1 or type 2 diabetes who are planning preg-nancy or who have become pregnant should be counseled on the risk ofdevelopment and/or progression of diabetic retinopathy. Dilated eye exam-inations should occur before pregnancy or in the first trimester, and thenpatients should be monitored every trimester and for 1 year postpartum asindicated by degree of retinopathy and as recommended by the eye careprovider. B

Gestational Diabetes Mellitusc Lifestyle change is an essential component of management of gestational

diabetes mellitus and may suffice for the treatment for many women. Med-ications should be added if needed to achieve glycemic targets. A

c Insulin is the preferred medication for treating hyperglycemia in gestationaldiabetes mellitus, as it does not cross the placenta to a measurable extent.Metformin and glyburide may be used, but both cross the placenta to thefetus, withmetformin likely crossing to a greater extent than glyburide. All oralagents lack long-term safety data. A

c Metformin, when used to treat polycystic ovary syndrome and induce ovula-tion, need not be continued once pregnancy has been confirmed. A

General Principles for Management of Diabetes in Pregnancyc Potentially teratogenic medications (ACE inhibitors, statins, etc.) should be

avoided in sexually active women of childbearing age who are not using reli-able contraception. B

c Fasting and postprandial self-monitoring of blood glucose are recommendedin both gestational diabetes mellitus and preexisting diabetes in pregnancy toachieve glycemic control. Some women with preexisting diabetes should alsotest blood glucose preprandially. B

c Due to increased red blood cell turnover, A1C is lower in normal pregnancythan in normal nonpregnant women. The A1C target in pregnancy is 6–6.5%(42–48 mmol/mol); ,6% (42 mmol/mol) may be optimal if this can beachieved without significant hypoglycemia, but the target may be relaxedto ,7% (53 mmol/mol) if necessary to prevent hypoglycemia. B

c In pregnant patients with diabetes and chronic hypertension, blood pressuretargets of 120–160/80–105 mmHg are suggested in the interest of optimizinglong-term maternal health and minimizing impaired fetal growth. E

Suggested citation: American Diabetes Asso-ciation. Management of diabetes in preg-nancy. Sec. 13. In Standards of Medical Carein Diabetesd2017. Diabetes Care 2017;40(Suppl. 1):S114–S119

© 2017 by the American Diabetes Association.Readers may use this article as long as the workis properly cited, the use is educational and notfor profit, and the work is not altered. More infor-mation is available at http://www.diabetesjournals.org/content/license.

American Diabetes Association

S114 Diabetes Care Volume 40, Supplement 1, January 2017

13.MANAGEM

ENTOFDIABETES

INPREG

NANCY

DIABETES IN PREGNANCY

The prevalence of diabetes in pregnancyhas been increasing in the U.S. The ma-jority is gestational diabetes mellitus(GDM) with the remainder primarilypreexisting type 1 diabetes and type 2diabetes. The rise in GDM and type 2diabetes in parallel with obesity bothin the U.S. and worldwide is of particu-lar concern. Both type 1 diabetes andtype 2 diabetes confer significantlygreater maternal and fetal risk thanGDM, with some differences accordingto type of diabetes as outlined below. Ingeneral, specific risks of uncontrolled di-abetes in pregnancy include spontaneousabortion, fetal anomalies, preeclampsia,fetal demise, macrosomia, neonatal hy-poglycemia, and neonatal hyperbilirubine-mia, among others. In addition, diabetes inpregnancymay increase the risk of obesityand type 2 diabetes in offspring later in life(1,2).

PRECONCEPTION COUNSELING

All women of childbearing age with di-abetes should be counseled about theimportance of tight glycemic control priorto conception. Observational studies showan increased risk of diabetic embryopathy,especially anencephaly, microcephaly, con-genital heart disease, and caudal regressiondirectly proportional to elevations in A1Cduring the first 10 weeks of pregnancy. Al-though observational studies are confoundedby the association between elevatedpericonceptional A1C and other poor self-carebehaviors, thequantity andconsistencyof data are convincing and support the rec-ommendation to optimize glycemic con-trol prior to conception, with A1C,6.5%(48 mmol/mol) associated with the low-est risk of congenital anomalies (3,4).There are opportunities to educate all

women and adolescents of reproductiveage with diabetes about the risks of un-planned pregnancies and the opportuni-ties for improved maternal and fetaloutcomes with pregnancy planning (5).Effective preconception counselingcould avert substantial health and asso-ciated cost burden in offspring (6). Fam-ily planning should be discussed, andeffective contraception should be pre-scribed and used, until a woman is pre-pared and ready to become pregnant.To minimize the occurrence of com-

plications, beginning at the onset of pu-berty or at diagnosis, all women with

diabetes of childbearing potentialshould receive education about 1) therisks of malformations associated withunplanned pregnancies and poor meta-bolic control and 2) the use of effectivecontraception at all times when prevent-ing a pregnancy. Preconception counselingusing developmentally appropriate edu-cational tools enables adolescent girls tomake well-informed decisions (5). Pre-conception counseling resources tailoredfor adolescents are available at no costthrough the American Diabetes Associa-tion (ADA) (7).

Preconception TestingPreconception counseling visits should in-clude rubella, syphilis, hepatitis B virus,and HIV testing, as well as Pap smear, cer-vical cultures, blood typing, prescriptionofprenatal vitamins (with at least 400 mg offolic acid), and smoking cessation counsel-ing if indicated. Diabetes-specific testingshould include A1C, thyroid-stimulatinghormone, creatinine, and urinary albumin–to–creatinine ratio; review of the medi-cation list for potentially teratogenicdrugs, i.e., ACE inhibitors (8), angiotensinreceptor blockers (8), and statins (9,10);and referral for a comprehensive eyeexam. Women with preexisting diabeticretinopathy will need close monitoringduring pregnancy to ensure that retinop-athy does not progress.

GLYCEMIC TARGETS INPREGNANCY

Pregnancy in women with normal glu-cose metabolism is characterized byfasting levels of blood glucose that arelower than in the nonpregnant state dueto insulin-independent glucose uptakeby the fetus and placenta and by post-prandial hyperglycemia and carbohydrateintolerance as a result of diabetogenicplacental hormones.

Insulin PhysiologyEarly pregnancy is a time of insulin sen-sitivity, lower glucose levels, and lowerinsulin requirements in women withtype 1 diabetes. The situation rapidlyreverses as insulin resistance increasesexponentially during the second andearly third trimesters and levels off to-ward the end of the third trimester. Inwomen with normal pancreatic func-tion, insulin production is sufficient tomeet the challenge of this physiologicalinsulin resistance and to maintain

normal glucose levels. However, inwomen with GDM and preexisting dia-betes, hyperglycemia occurs if treat-ment is not adjusted appropriately.

Glucose MonitoringReflecting this physiology, fasting andpostprandial monitoring of blood glucoseis recommended to achieve metaboliccontrol in pregnant women with diabe-tes. Preprandial testing is also recom-mended for women with preexistingdiabetes using insulin pumps or basal-bolus therapy, so that premeal rapid-acting insulin dosage can be adjusted.Postprandial monitoring is associatedwith better glycemic control and lowerrisk of preeclampsia (11–13). There areno adequately powered randomized trialscomparing different fasting and postmealglycemic targets in diabetes in pregnancy.

Similar to the targets recommended bythe American College of Obstetricians andGynecologists (14), theADA-recommendedtargets for women with type 1 or type 2diabetes (the same as for GDM; describedbelow) are as follows:

○ Fasting#95 mg/dL (5.3 mmol/L) andeither

○ One-hour postprandial #140 mg/dL(7.8 mmol/L) or

○ Two-hour postprandial #120 mg/dL(6.7 mmol/L)

These values represent optimal control ifthey can be achieved safely. In practice, itmay be challenging for womenwith type 1diabetes to achieve these targets withouthypoglycemia, particularly women with ahistory of recurrent hypoglycemia or hypo-glycemia unawareness.

If women cannot achieve these tar-gets without significant hypoglycemia,the ADA suggests less stringent targetsbased on clinical experience and individ-ualization of care.

A1C in PregnancyObservational studies show the lowestrates of adverse fetal outcomes in associa-tionwith A1C,6–6.5% (42–48mmol/mol)early in gestation (4,15–17). Clinical tri-als have not evaluated the risks and ben-efits of achieving these targets, andtreatment goals should account for therisk of maternal hypoglycemia in set-ting an individualized target of ,6%(42 mmol/mol) to ,7% (53 mmol/mol).Due to physiological increases in red

care.diabetesjournals.org Management of Diabetes in Pregnancy S115

blood cell turnover, A1C levels fall duringnormal pregnancy (18,19). Additionally, asA1C represents an integrated measure ofglucose, it may not fully capture postpran-dial hyperglycemia, which drives macro-somia. Thus, although A1C may be useful,it should be used as a secondary measureof glycemic control, after self-monitoringof blood glucose.In the second and third trimesters,

A1C,6% (42 mmol/mol) has the lowestrisk of large-for-gestational-age infants,whereas other adverse outcomes increasewithA1C$6.5% (48mmol/mol). Takingallof this into account, a target of 6–6.5%(42–48 mmol/mol) is recommended but,6% (42 mmol/mol) may be optimal aspregnancy progresses. These levels shouldbe achieved without hypoglycemia, which,in addition to the usual adverse sequelae,may increase the risk of low birth weight.Given the alteration in red blood cell kinet-ics during pregnancy and physiologicalchanges in glycemic parameters, A1C levelsmayneed tobemonitoredmore frequentlythan usual (e.g., monthly).

MANAGEMENT OF GESTATIONALDIABETES MELLITUS

GDM is characterized by increased riskof macrosomia and birth complicationsand an increased risk of maternal type 2diabetes after pregnancy. The associa-tion of macrosomia and birth complica-tions with oral glucose tolerance test(OGTT) results is continuous, with noclear inflection points (20). In otherwords, risks increase with progressive hy-perglycemia. Therefore, all womenshouldbe tested as outlined in Section 2 “Clas-sification and Diagnosis of Diabetes.”Although there is some heterogeneity,many randomized controlled trialssuggest that the risk of GDM may bereduced by diet, exercise, and lifestylecounseling (21,22).

Lifestyle ManagementAfter diagnosis, treatment starts withmedical nutrition therapy, physical activ-ity, and weight management dependingon pregestational weight, as outlined inthe section below on preexisting type 2diabetes, and glucose monitoring aimingfor the targets recommended by the FifthInternational Workshop-Conference onGestational Diabetes Mellitus (23):

○ Fasting#95 mg/dL (5.3 mmol/L) andeither

○ One-hour postprandial #140 mg/dL(7.8 mmol/L) or

○ Two-hour postprandial #120 mg/dL(6.7 mmol/L)

Depending on the population, studiessuggest that 70–85%ofwomendiagnosedwith GDM under Carpenter-Coustan orNational Diabetes Data Group (NDDG)criteria can control GDM with lifestylemodificationalone; it is anticipated that thisproportion will be even higher if the lowerInternational Association of the Diabetesand Pregnancy Study Groups (IADPSG)(24) diagnostic thresholds are used.

Pharmacologic TherapyWomen with greater initial degrees of hy-perglycemia may require early initiation ofpharmacologic therapy. Treatment hasbeen demonstrated to improve perinataloutcomes in two large randomized studiesas summarized in a U.S. Preventive Ser-vices Task Force review (25). Insulin is thefirst-line agent recommended for treat-ment of GDM in the U.S. While individualrandomized controlled trials support theefficacy and short-term safety of metfor-min (26,27) and glyburide (28) for thetreatment of GDM, both agents cross theplacenta. Long-term safety data are notavailable for any oral agent (29).

Sulfonylureas

Concentrations of glyburide in umbilicalcord plasma are approximately 70% ofmaternal levels (30). Glyburide may beassociated with a higher rate of neona-tal hypoglycemia and macrosomia thaninsulin or metformin (31).

Metformin

Metformin may be associated with alower risk of neonatal hypoglycemiaand less maternal weight gain than in-sulin (31–33); however, metformin mayslightly increase the risk of prematurity.Furthermore, nearly half of patientswith GDM who were initially treatedwith metformin in a randomized trialneeded insulin in order to achieve ac-ceptable glucose control (26). Umbilicalcord blood levels of metformin arehigher than simultaneous maternal lev-els (34,35). None of these studies ormeta-analyses evaluated long-term out-comes in the offspring. Patients treatedwith oral agents should be informed thatthey cross the placenta, and although noadverse effects on the fetus have beendemonstrated, long-term studies arelacking.

Randomized, double-blind, controlledtrials comparing metformin with othertherapies for ovulation induction inwomen with polycystic ovary syndromehave not demonstrated benefit in pre-venting spontaneous abortion or GDM(36), and there is no evidence-basedneed to continue metformin in such pa-tients once pregnancy has been con-firmed (37–39).

Insulin

Insulin may be required to treat hyper-glycemia, and its use should follow theguidelines below.

MANAGEMENT OF PREEXISTINGTYPE 1 DIABETES AND TYPE 2DIABETES IN PREGNANCY

Insulin UseInsulin is the preferred agent for manage-ment of both type 1 diabetes and type 2diabetes in pregnancy.

The physiology of pregnancy necessi-tates frequent titration of insulin tomatch changing requirements and un-derscores the importance of daily andfrequent self-monitoring of blood glu-cose. In the first trimester, there isoften a decrease in total daily insulinrequirements, and women, particularlythose with type 1 diabetes, may experi-ence increased hypoglycemia. In thesecond trimester, rapidly increasing in-sulin resistance requires weekly or bi-weekly increases in insulin dose toachieve glycemic targets. In general, asmaller proportion of the total daily doseshould be given as basal insulin (,50%)and a greater proportion (.50%) as pran-dial insulin. In the late third trimester,there is often a leveling off or small de-crease in insulin requirements. Due tothe complexity of insulin management inpregnancy, referral to a specialized centeroffering team-based care (with teammembers including high-risk obstetrician,endocrinologist or other provider experi-enced in managing pregnancy in womenwith preexisting diabetes, dietitian, nurse,and social worker, as needed) is recom-mended if this resource is available.

None of the currently available insulinpreparations have been demonstratedto cross the placenta.

Type 1 DiabetesWomen with type 1 diabetes have an in-creased risk of hypoglycemia in the firsttrimester and, like all women, have al-tered counterregulatory response in

S116 Management of Diabetes in Pregnancy Diabetes Care Volume 40, Supplement 1, January 2017

pregnancy that may decrease hypoglycemiaawareness. Education for patients andfamily members about the prevention,recognition, and treatment of hypogly-cemia is important before, during, andafter pregnancy to help to prevent andmanage the risks of hypoglycemia. In-sulin resistance drops rapidly with de-livery of the placenta. Women becomevery insulin sensitive immediately fol-lowing delivery and may initially re-quire much less insulin than in theprepartum period.Pregnancy is a ketogenic state, and

women with type 1 diabetes, and to alesser extent those with type 2 diabe-tes, are at risk for diabetic ketoacidosisat lower blood glucose levels than in thenonpregnant state. Women with preex-isting diabetes, especially type 1 diabe-tes, need ketone strips at home andeducation on diabetic ketoacidosis pre-vention and detection. In addition, rapidimplementation of tight glycemic con-trol in the setting of retinopathy is asso-ciated with worsening of retinopathy(40).

Type 2 DiabetesType 2 diabetes is often associated withobesity. Recommended weight gainduring pregnancy for overweightwomen is 15–25 lb and for obesewomen is 10–20 lb (41). Glycemic con-trol is often easier to achieve in womenwith type 2 diabetes than in those withtype 1 diabetes but can require muchhigher doses of insulin, sometimes ne-cessitating concentrated insulin formu-lations. As in type 1 diabetes, insulinrequirements drop dramatically afterdelivery. The risk for associated hyper-tension and other comorbidities may beas high or higher with type 2 diabetes aswith type 1 diabetes, even if diabetes isbetter controlled and of shorter appar-ent duration, with pregnancy loss ap-pearing to be more prevalent in thethird trimester in women with type 2 di-abetes compared with the first trimesterin women with type 1 diabetes (42,43).

POSTPARTUM CARE

Postpartum care should include psychoso-cial assessment and support for self-care.

LactationIn light of the immediate nutritional andimmunological benefits of breastfeed-ing for the baby, all women including

those with diabetes should be supportedin attempts to breastfeed. Breastfeedingmay also confer longer-term metabolicbenefits to both mother (44) and off-spring (45).

Gestational Diabetes Mellitus

Initial Testing

Because GDM may represent preexistingundiagnosed type 2 or even type 1 diabe-tes, women with GDM should be testedfor persistent diabetes or prediabetesat 4–12 weeks’ postpartum with a 75-gOGTT using nonpregnancy criteria asoutlined in Section 2 “Classification andDiagnosis of Diabetes.”

Postpartum Follow-up

The OGTT is recommended over A1C atthe time of the 4- to 12-week postpar-tum visit because A1C may be persis-tently impacted (lowered) by theincreased red blood cell turnover re-lated to pregnancy or blood loss at de-livery and because the OGTT is moresensitive at detecting glucose intoler-ance, including both prediabetes anddiabetes. Reproductive-aged womenwith prediabetes may develop type 2 di-abetes by the time of their next preg-nancy and will need preconceptionevaluation. Because GDM is associatedwith increased maternal risk for diabe-tes, women should also be tested every1–3 years thereafter if the 4- to 12-week75-g OGTT is normal, with frequency oftesting depending on other risk factorsincluding family history, prepregnancyBMI, and need for insulin or oral glucose-lowering medication during pregnancy.Ongoing evaluation may be performedwith any recommended glycemic test(e.g., hemoglobin A1C, fasting plasmaglucose, or 75-g OGTT using nonpreg-nant thresholds).

Gestational Diabetes Mellitus and Type 2

Diabetes

Women with a history of GDM have agreatly increased risk of conversion totype 2 diabetes over time and not solelywithin the 4- to 12-week postpartumtime frame (46). In the prospectiveNurses’ Health Study II, subsequent di-abetes risk after a history of GDM wassignificantly lower in women who fol-lowed healthy eating patterns (47). Ad-justing for BMI moderately, but notcompletely, attenuated this associa-tion. Interpregnancy or postpartumweight gain is associated with increased

risk of adverse pregnancy outcomes insubsequent pregnancies (48) and ear-lier progression to type 2 diabetes.

Both metformin and intensive life-style intervention prevent or delay pro-gression to diabetes in women withprediabetes and a history of GDM. Ofwomen with a history of GDM and pre-diabetes, only 5–6 women need to betreated with either intervention to pre-vent one case of diabetes over 3 years(49). In these women, lifestyle interven-tion and metformin reduced progres-sion to diabetes by 35% and 40%,respectively, over 10 years comparedwith placebo (50). If the pregnancy hasmotivated the adoption of a healthierdiet, building on these gains to supportweight loss is recommended in the post-partum period.

Preexisting Type 1 and Type 2DiabetesInsulin sensitivity increases with deliv-ery of the placenta and then returns toprepregnancy levels over the following1–2weeks. In women taking insulin, par-ticular attention should be directed tohypoglycemia prevention in the settingof breastfeeding and erratic sleep andeating schedules.

ContraceptionA major barrier to effective preconcep-tion care is the fact that the majority ofpregnancies are unplanned. Planningpregnancy is critical in women with pre-existing diabetes due to the need forpreconception glycemic control andpreventive health services. Therefore,all women with diabetes of childbearingpotential should have family planningoptions reviewed at regular intervals.This applies to women in the immediatepostpartum period. Women with diabe-tes have the same contraception optionsand recommendations as those withoutdiabetes. The risk of an unplanned preg-nancy outweighs the risk of any givencontraception option.

PREGNANCY AND DRUGCONSIDERATIONS

In normal pregnancy, blood pressure islower than in the nonpregnant state.In a pregnancy complicated by diabe-tes and chronic hypertension, targetgoals for systolic blood pressure 120–160 mmHg and diastolic blood pres-sure 80–105 mmHg are reasonable(51). Lower blood pressure levels may

care.diabetesjournals.org Management of Diabetes in Pregnancy S117

be associated with impaired fetal growth.In a 2015 study targeting diastolic bloodpressure of 100mmHg versus 85mmHg inpregnant women, only 6% of whom hadGDMat enrollment, there was no differ-ence in pregnancy loss, neonatal care,or other neonatal outcomes, althoughwomen in the less intensive treatmentgroup had a higher rate of uncontrolledhypertension (52).During pregnancy, treatment with

ACE inhibitors and angiotensin receptorblockers is contraindicated becausethey may cause fetal renal dysplasia, oli-gohydramnios, and intrauterine growthrestriction (8). Antihypertensive drugsknown to be effective and safe in preg-nancy include methyldopa, labetalol, dil-tiazem, clonidine, and prazosin. Chronicdiuretic use during pregnancy is not rec-ommended as it has been associatedwith restricted maternal plasma volume,which may reduce uteroplacental perfu-sion (53). On the basis of available evi-dence, statins should also be avoided inpregnancy (54).

References1. Holmes VA, Young IS, Patterson CC, et al.;Diabetes and Pre-eclampsia Intervention TrialStudy Group. Optimal glycemic control, pre-eclampsia, and gestational hypertension inwomen with type 1 diabetes in the diabetesand pre-eclampsia intervention trial. DiabetesCare 2011;34:1683–16882. Dabelea D, Hanson RL, Lindsay RS, et al. In-trauterine exposure to diabetes conveys risksfor type 2 diabetes and obesity: a study of dis-cordant sibships. Diabetes 2000;49:2208–22113. Guerin A, Nisenbaum R, Ray JG. Use of ma-ternal GHb concentration to estimate the risk ofcongenital anomalies in the offspring of womenwith prepregnancy diabetes. Diabetes Care2007;30:1920–19254. Jensen DM, Korsholm L, Ovesen P, et al. Peri-conceptional A1C and risk of serious adversepregnancy outcome in 933 women with type 1diabetes. Diabetes Care 2009;32:1046–10485. Charron-Prochownik D, Sereika SM, BeckerD, et al. Long-term effects of the booster-enhanced READY-Girls preconception counsel-ing program on intentions and behaviors forfamily planning in teens with diabetes. DiabetesCare 2013;36:3870–38746. Peterson C, Grosse SD, Li R, et al. Preventablehealth and cost burden of adverse birth out-comes associated with pregestational diabetesin the United States. Am J Obstet Gynecol 2015;212:74.e1–74.e97. Charron-Prochownik D, Downs J. Diabetesand Reproductive Health for Girls. Alexandria,VA, American Diabetes Association, 20168. Bullo M, Tschumi S, Bucher BS, BianchettiMG, Simonetti GD. Pregnancy outcome follow-ing exposure to angiotensin-converting enzymeinhibitors or angiotensin receptor antagonists: a

systematic review. Hypertension 2012;60:444–4509. Taguchi N, Rubin ET, Hosokawa A, et al. Pre-natal exposure to HMG-CoA reductase inhibi-tors: effects on fetal and neonatal outcomes.Reprod Toxicol 2008;26:175–17710. Bateman BT, Hernandez-Diaz S, FischerMA,et al. Statins and congenital malformations: co-hort study. BMJ 2015;350:h103511. Manderson JG, Patterson CC, Hadden DR,Traub AI, Ennis C, McCance DR. Preprandial ver-sus postprandial blood glucose monitoring intype 1 diabetic pregnancy: a randomized con-trolled clinical trial. Am J Obstet Gynecol 2003;189:507–51212. de Veciana M, Major CA, Morgan MA, et al.Postprandial versus preprandial blood glucosemonitoring in women with gestational diabetesmellitus requiring insulin therapy. N Engl J Med1995;333:1237–124113. Jovanovic-Peterson L, Peterson CM, ReedGF, et al. Maternal postprandial glucose levelsand infant birth weight: the Diabetes in EarlyPregnancy Study. The National Institute of ChildHealth and Human DevelopmentdDiabetes inEarly Pregnancy Study. Am J Obstet Gynecol1991;164:103–11114. Committee on Practice BulletinsdObstetrics.Practice Bulletin No. 137: gestational diabetesmellitus. Obstet Gynecol 2013;122:406–41615. Nielsen GL, Møller M, Sørensen HT. HbA1cin early diabetic pregnancy and pregnancy out-comes: a Danish population-based cohort studyof 573 pregnancies in women with type 1 dia-betes. Diabetes Care 2006;29:2612–261616. Suhonen L, Hiilesmaa V, Teramo K. Glycaemiccontrol during early pregnancy and fetal malfor-mations in womenwith type 1 diabetesmellitus.Diabetologia 2000;43:79–8217. Maresh MJA, Holmes VA, Patterson CC,et al.; Diabetes and Pre-eclampsia InterventionTrial Study Group. Glycemic targets in the sec-ond and third trimester of pregnancy forwomen with type 1 diabetes. Diabetes Care2015;38:34–4218. Nielsen LR, Ekbom P, Damm P, et al. HbA1clevels are significantly lower in early and latepregnancy. Diabetes Care 2004;27:1200–120119. Mosca A, Paleari R, Dalfra MG, et al. Refer-ence intervals for hemoglobin A1c in pregnantwomen: data from an Italian multicenter study.Clin Chem 2006;52:1138–114320. Metzger BE, Lowe LP, Dyer AR, et al.; HAPOStudy Cooperative Research Group. Hyperglyce-mia and adverse pregnancy outcomes. N Engl JMed 2008;358:1991–200221. Bain E, CraneM, Tieu J, Han S, Crowther CA,Middleton P. Diet and exercise interventionsfor preventing gestational diabetes mellitus.Cochrane Database Syst Rev 2015;4:CD01044322. Koivusalo SB, Rono K, Klemetti MM, et al.Gestational diabetes mellitus can be preventedby lifestyle intervention: the Finnish GestationalDiabetes Prevention Study (RADIEL): a random-ized controlled trial. Diabetes Care 2016;39:24–3023. Metzger BE, Buchanan TA, Coustan DR,et al. Summary and recommendations of theFifth International Workshop-Conference onGestational Diabetes Mellitus. Diabetes Care2007;30(Suppl. 2):S251–S260

24. Mayo K, Melamed N, Vandenberghe H,Berger H. The impact of adoption of the Inter-national Association of Diabetes in PregnancyStudy Group criteria for the screening and di-agnosis of gestational diabetes. Am J ObstetGynecol 2015;212:224.e1–224.e925. Hartling L, Dryden DM, Guthrie A, Muise M,Vandermeer B, Donovan L. Benefits and harmsof treating gestational diabetes mellitus: a sys-tematic review and meta-analysis for the U.S.Preventive Services Task Force and the NationalInstitutes of Health Office of Medical Applica-tions of Research. Ann Intern Med 2013;159:123–12926. Rowan JA, Hague WM, Gao W, Battin MR,Moore MP; MiG Trial Investigators. Metforminversus insulin for the treatment of gestationaldiabetes. N Engl J Med 2008;358:2003–201527. Gui J, Liu Q, Feng L. Metformin vs insulin inthe management of gestational diabetes: ameta-analysis. PLoS One 2013;8:e6458528. Langer O, Conway DL, Berkus MD, XenakisEM, Gonzales O. A comparison of glyburide andinsulin in women with gestational diabetes mel-litus. N Engl J Med 2000;343:1134–113829. Coustan DR. Pharmacological managementof gestational diabetes: an overview. DiabetesCare 2007;30(Suppl. 2):S206–S20830. Hebert MF, Ma X, Naraharisetti SB, et al.;Obstetric-Fetal Pharmacology Research UnitNetwork. Are we optimizing gestational diabe-tes treatment with glyburide? The pharmaco-logic basis for better clinical practice. ClinPharmacol Ther 2009;85:607–61431. Balsells M, Garcıa-Patterson A, Sola I, RoqueM, Gich I, Corcoy R. Glibenclamide, metformin,and insulin for the treatment of gestational dia-betes: a systematic review and meta-analysis.BMJ 2015;350:h10232. Jiang Y-F, Chen X-Y, Ding T, Wang X-F, ZhuZ-N, Su S-W. Comparative efficacy and safety ofOADs in management of GDM: network meta-analysis of randomized controlled trials. J ClinEndocrinol Metab 2015;100:2071–208033. Camelo Castillo W, Boggess K, Sturmer T,Brookhart MA, Benjamin DK Jr, Jonsson FunkM. Association of adverse pregnancy outcomeswith glyburide vs insulin in women with ges-tational diabetes. JAMA Pediatr 2015;169:452–45834. Vanky E, Zahlsen K, Spigset O, Carlsen SM.Placental passage of metformin in women withpolycystic ovary syndrome. Fertil Steril 2005;83:1575–157835. Charles B, Norris R, Xiao X, Hague W. Pop-ulation pharmacokinetics of metformin in latepregnancy. Ther Drug Monit 2006;28:67–7236. Vanky E, Stridsklev S, Heimstad R, et al.Metformin versus placebo from first trimesterto delivery in polycystic ovary syndrome: a ran-domized, controlled multicenter study. J ClinEndocrinol Metab 2010;95:E448–E45537. Legro RS, Barnhart HX, Schlaff WD, et al.;Cooperative Multicenter Reproductive Medi-cine Network. Clomiphene, metformin, orboth for infertility in the polycystic ovary syn-drome. N Engl J Med 2007;356:551–56638. Palomba S, Orio F Jr, Falbo A, et al. Pro-spective parallel randomized, double-blind,double-dummy controlled clinical trial compar-ing clomiphene citrate and metformin as thefirst-line treatment for ovulation induction in

S118 Management of Diabetes in Pregnancy Diabetes Care Volume 40, Supplement 1, January 2017

nonobese anovulatory women with polycysticovary syndrome. J Clin Endocrinol Metab2005;90:4068–407439. Palomba S, Orio F Jr, Nardo LG, et al. Met-formin administration versus laparoscopicovarian diathermy in clomiphene citrate-resistantwomenwith polycystic ovary syndrome: a prospec-tive parallel randomized double-blind placebo-controlled trial. J Clin Endocrinol Metab 2004;89:4801–480940. Chew EY, Mills JL, Metzger BE, et al. Meta-bolic control and progression of retinopathy.The Diabetes in Early Pregnancy Study. NationalInstitute of Child Health and Human Develop-ment Diabetes in Early Pregnancy Study. Diabe-tes Care 1995;18:631–63741. National Research Council; Institute ofMedicine; Food and Nutrition Board; Board onChildren, Youth, and Families; Committee to Re-examine IOM Pregnancy Weight Guidelines.Weight Gain During Pregnancy: Reexaminingthe Guidelines. Washington, DC, The NationalAcademies Press, 2009. Available from http://www.nap.edu/catalog/12584. Accessed 5 Octo-ber 201642. Clausen TD, Mathiesen E, Ekbom P, HellmuthE, Mandrup-Poulsen T, Damm P. Poor pregnancyoutcome inwomenwith type2diabetes. DiabetesCare 2005;28:323–328

43. Cundy T, Gamble G, Neale L, et al. Differingcauses of pregnancy loss in type 1 and type 2diabetes. Diabetes Care 2007;30:2603–260744. Stuebe AM, Rich-Edwards JW, Willett WC,Manson JE, Michels KB. Duration of lactationand incidence of type 2 diabetes. JAMA 2005;294:2601–261045. Pereira PF, Alfenas R de C, Araujo RM. Doesbreastfeeding influence the risk of developingdiabetes mellitus in children? A review of cur-rent evidence. J Pediatr (Rio J) 2014;90:7–1546. Kim C, Newton KM, Knopp RH. Gestationaldiabetes and the incidence of type 2 diabetes: asystematic review. Diabetes Care 2002;25:1862–186847. Tobias DK, Hu FB, Chavarro J, Rosner B,Mozaffarian D, Zhang C. Healthful dietary pat-terns and type 2 diabetes mellitus risk amongwomen with a history of gestational diabetesmellitus. Arch Intern Med 2012;172:1566–157248. Villamor E, Cnattingius S. Interpregnancyweight change and risk of adverse pregnancyoutcomes: a population-based study. Lancet2006;368:1164–117049. Ratner RE, Christophi CA, Metzger BE, et al.;Diabetes Prevention Program Research Group.Prevention of diabetes in women with a historyof gestational diabetes: effects of metformin

and lifestyle interventions. J Clin Endocrinol

Metab 2008;93:4774–477950. Aroda VR, Christophi CA, Edelstein SL, et al.;

Diabetes Prevention Program Research Group.

The effect of lifestyle intervention andmetformin

on preventing or delaying diabetes among

women with and without gestational diabetes:

the Diabetes Prevention Program Outcomes

Study 10-year follow-up. J Clin Endocrinol Metab

2015;100:1646–165351. American College of Obstetricians and Gy-

necologists; Task Force on Hypertension in

Pregnancy. Hypertension in pregnancy. Report

of the American College of Obstetricians and

Gynecologists’ Task Force on Hypertension in

Pregnancy. Obstet Gynecol 2013;122:1122–

113152. Magee LA, von Dadelszen P, Rey E, et al.

Less-tight versus tight control of hypertension

in pregnancy. N Engl J Med 2015;372:407–41753. Sibai BM. Treatment of hypertension in

pregnant women. N Engl J Med 1996;335:257–

26554. Kazmin A, Garcia-Bournissen F, Koren G.

Risks of statin use during pregnancy: a system-

atic review. J Obstet Gynaecol Can 2007;29:

906–908

care.diabetesjournals.org Management of Diabetes in Pregnancy S119