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Diabetes in Pregnancy: Antepartum Considerations and New Perspectives

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Diabetes in Pregnancy: Antepartum Considerations and New Perspectives Amy Rouse, MD Maternal-Fetal Medicine Saddleback Memorial Medical Center 31 January 2009 – PowerPoint PPT presentation

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Title: Diabetes in Pregnancy: Antepartum Considerations and New Perspectives


1
Diabetes in Pregnancy Antepartum Considerations
and New Perspectives
  • Amy Rouse, MD
  • Maternal-Fetal Medicine
  • Saddleback Memorial Medical Center
  • 31 January 2009

2
Objectives
  • After completing this session, the learner should
    be able
  • 1)  To identify key considerations in women with
    diabetes/ insulin resistance who may become
    pregnant
  • 2)  To recognize updated guidelines for
    identifying women at risk for gestational
    diabetes
  • 3)  To understand the impact of hyperglycemia
    below the threshold of a diagnosis of gestational
    diabetes

3
Part I Preconception
4
Preconception Issues
  • Any woman of reproductive age who is not actively
    using reliable contraception may become pregnant
  • Periconception glycemic control is the single
    most influential factor in embryonic development

5
Pregnancy Happens . . .
2009, The National Campaign to Prevent Teen and
Unplanned Pregnancy
6
Even to Women with Diabetes
  • St. James PJ et al
  • Prospective cohort study of 66 women with
    diabetes
  • 1/3 became pregnant within 5 years (n23)
  • Only 26 percent of pregnancies were planned
  • Conclusion Addressing pregnancy planning in
    women with diabetes must improve

Diabetes Care Vol 16, Issue 12 1572-1578 1993
7
Whites Classification in Pregnancy
Courtesy of Gabbe Obstetrics Normal and Problem
Pregnancies
8
Diabetes and Early Pregnancy Loss
  • Poor glycemic control is associated with
    increased spontaneous abortion
  • Higher loss rates with long standing disease or
    with vasculopathy
  • Class C, D, and F SAB rates of 25, 44, and
    22, respectively
  • Jovanovic Loss rate similar to general
    population with excellent glycemic control

9
Diabetes and Birth Defects
  • Background rate of major congenital malformations
    2
  • Infants of diabetic mothers 6-10, accounting
    for 40 of perinatal deaths in these babies
    (Reece EA 1996)

10
Diabetes and Birth Defects
  • UK data BMJ 2006 4.6 major congenital
    malformation rate in all pregestational diabetic
    pregnancies
  • Neural tube defects increased 4.2 fold
  • Congenital heart disease increased 3.4 fold

Only 65 of neonatal anomalies were identified
antenatally
11
Diabetes and Birth Defects
  • Miller et al 1981
  • 3.4 malformation rate if periconception HbA1c
    lt8.5
  • 22.4 malformation rate if periconception HbA1c
    gt8.5
  • End-organ damage not modifiable at time of
    pregnancy, but control is!

12
Diabetes and Birth Defects
  • Lucas et al 1989, n105
  • Overall malformation rate 13.3

13
Why do Birth Defects Happen?
  • Multifactorial
  • Clear direct association with hyperglycemia 3-6
    weeks after conception
  • Teratogenic potential of
  • Inositol
  • Prostaglandins
  • Reactive oxygen species

14
Why do Birth Defects Happen?
  • Hyperglycemia in embryo increases oxygen radical
    production -gt inhibits prostacyclin -gt increased
    thromboxanes/ prostaglandins -gt abnormal
    vascularization of developing tissue
  • Mouse model demonstrates decreased defects if
    prostaglandin inhibitors or antioxidants given
    (vitamins C and E)

15
Preventing Birth Defects
  • Planned pregnancy/ recognize potential for
    pregnancy
  • Preconception consultation
  • Achieve glycemic control (more to follow)
  • Multivitamins or prenatal vitamins
  • Folic acid supplementation

16
I dont have diabetes.
  • Increasing concerns in group of women with
  • Prediabetes, Impaired Glucose Tolerance
  • Polycystic Ovarian Syndrome (PCOS)
  • Obesity
  • We need your help! Screen and treat!

17
PCOS and Pregnancy Outcome
  • Thatcher SS 2006
  • Retrospective analysis in suburban REI practice,
    n237 pregnancies
  • Pts used metformin /- clomid, gonadotropins, or
    ART
  • Increased GDM and prematurity
  • Did not observe change in rate of malformation

18
Part II Early Identification of Gestational
Diabetes
19
Gestational Diabetes
  • Maternal Risks
  • Excessive weight gain
  • Preeclampsia
  • Cesarean section
  • Future gestational diabetes
  • Subsequent type 2 diabetes and heart disease
  • Risks to Offspring
  • Macrosomia
  • Birth trauma
  • Hypoglycemia
  • Delayed lung maturation
  • Hypocalcemia
  • Polycythemia
  • Stillbirth
  • Childhood disease

20
Neonatal Morbidity - Delayed Lung Maturation
  • Moore TM et al AJOG 2003

21
Neonatal Morbidity - Shoulder Dystocia
  • Nesbitt TS et al AJOG 1998

22
Neonatal Morbidity - Birth Trauma
  • Brachial plexus injury
  • Facial nerve injury
  • Fractures of humerus or clavicle
  • Cephalohematoma
  • Brain injury
  • Death

23
Neonatal Morbidity - Birth Trauma
  • Athukorala et al positive relationship between
    maternal fasting hyperglycemia and incidence of
    shoulder dystocia
  • Risk doubled with each 1 mmol increase in fasting
    glucose value on OGTT

24
Screening for GDM
  • First step Early identification of risk factors
  • Second step One hour 50 g glucose screen
  • Third step Three hour 100 g OGTT for diagnosis

25
Risk Factors for GDM Assess at First Prenatal
Visit
  • PCOS
  • Age gt 25 yrs
  • Members of certain ethnic groups
  • Multiparous women (13)
  • Left column are HIGH RISK factors
  • Overweight before pregnancy (BMI gt 25)
  • 1st degree relative with diabetes
  • Previous glucose intolerance/ GDM
  • Previous macrosomia or large for gestational age
    baby

26
Universal Screening v. Selective Screening for GDM
  • Cosson et al compared universal to selective
    screening
  • Universal group had more favorable fetal outcomes
  • Williams et al studied following ADA guidelines
    (not screening low risk)
  • 10 to 11 would not have been screened
  • Missed 4 who would have been diagnosed with GDM

27
Screening for GDM
  • High risk patient requires screening earlier in
    pregnancy, before 24-28 weeks, ideally at first
    prenatal visit
  • First trimester glucose intolerance triggers
    suspicious pre-existing overt diabetes (type 1 or
    type 2) or insulin resistance

28
ADA Position Statement 50G oral glucose
tolerance screen for GDM
  • 140mg cutoff -- 80 sensitivity
  • 130mg cutoff -- 90 sensitivity
  • Alternatively, patients with high risk factors
    can go directly to diagnostic testing instead of
    initial screening

29
Screening for GDM 50-g oral glucose challenge
30
Diagnosis of GDM Using 3-hour 100 g OGTT
  • KEEP IN MIND PATIENT MAY BE
  • undiagnosed type 2
  • mild abnormal glucose tolerance prior to
    pregnancy that worsens with gestation
  • normal glucose tolerance before pregnancy that
    becomes abnormal with advancing gestation
  • undiagnosed type 1 (symptoms but no diagnosis)

31
ADA and WHO Criteria for the Diagnosis of
Gestational Diabetes Mellitus
32
Part III Hyperglycemia, Not Diabetes, in
Pregnancy
Whattoexpect.com
33
HAPO Study Purpose
  • NEJM May 8, 2008
  • Hyperglycemia and Adverse Pregnancy Outcomes
  • To clarify risks of adverse outcomes associated
    with degrees of maternal glucose intolerance not
    meeting criteria for gestational diabetes mellitus

34
Background Pedersen Hypothesis
  • 1952 Maternal hyperglycemia causes fetal
    hyperglycemia, which leads to exaggerated fetal
    response to insulin

35
HAPO Study Cooperative Research Group
  • Cohort study
  • Fifteen centers in nine countries
  • 25,505 pregnant women underwent 75 g oral GTT at
    24-32 weeks gestation
  • Patients and providers blinded to results unless
    unsafe
  • Fasting gt105 mg/ dL
  • 2 hour glucose gt 200 mg/ dL
  • Any glucose lt 45 mg/ dL or gt 160 mg/ dL

36
HAPO Study Exclusions
  • lt 18 y/o
  • Delivering outside of study facility
  • Unknown dating/ poor dating
  • Multiple gestation
  • Conception by IVF or gonadotropin use
  • Prior dx of GDM or DM
  • Prior glucose testing this pregnancy
  • Infection with HIV, Hep B, Hep C

37
HAPO Study Primary Outcomes
  • Birth weight gt 90th percentile for gestational
    age
  • Primary cesarean delivery
  • Clinical neonatal hypoglycemia
  • Cord-blood serum C-peptide level above 90th
    percentile

38
HAPO Study Secondary Outcomes
  • Delivery lt 37 weeks gestation
  • Shoulder dystocia or birth injury
  • Need for admission to NICU
  • Hyperbilirubinemia
  • Preeclampsia

39
HAPO Statistics
  • Continuous variables mean and standard
    deviation
  • Categorial data number and percentage
  • Glucose measurements evaluated as both continuous
    and categorical for primary outcomes
  • For secondary outcomes, only continuous

40
HAPO Data Analysis, Categorical
  • Glycemic values categorized into seven levels for
    fasting, 1- and 2-hour values
  • Ex fasting subsets included
  • 100-104 (105 unblinded) 99th percentile
  • 95-99 97th percentile
  • 90-94
  • 85-89
  • 80-84
  • 75-79
  • lt75

41
HAPO Data Analysis, Continuous
  • Odds ratios calculated for a 1 standard deviation
    increase
  • Fasting
  • 1-hour
  • 2-hour
  • Logistic regression models
  • Adjusted for confounders
  • BMI
  • Age
  • Smoking
  • Hypertension
  • Family history of DM, etc.

42
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Mean values were recorded as fasting 81, 1 hr
134, 2 hr 111
48
Summary of HAPO Findings
  • Associations between increasing fasting, 1-hour,
    and 2-hour glucose values and
  • Birthweight gt 90th percentile
  • Cord blood serum C-peptide
  • Primary cesarean (weaker)
  • Neonatal hypoglycemia (weaker)
  • Premature delivery
  • Shoulder dystocia/ birth injury
  • NICU admission
  • Hyperbilirubinemia
  • Preeclampsia
  • All in patients who are below criteria for GDM

49
Future Study
  • Instead of screening for glucose intolerance,
    screening for hypoglycemia? (Everyone at risk
    goes on the diet)
  • Screening and treating for macrosomia? For
    diabetogenic pregnancies?
  • Establishment of new thresholds for diagnosing
    gestational diabetes or gestational glucose
    intolerance? (Ex One abnormal value on 3 hr GTT?
    One SD above the mean?)
  • Stronger evidence that treatment improves
    (clinically relevant) outcomes?

50
Will More Treatment Mean Better Outcomes?
  • ACHOIS Trial Evaluated neonatal outcomes in
    women with gestational diabetes
  • NNT to avoid one adverse outcome 43
  • HAPO demonstrated fewer IUGR/ SGA babies
  • Problems if aggressively treat mild
    hyperglycemia?
  • Associations not tested, may not be causally
    mediated

51
What to do Today Dont Forget Postpartum Testing
  • All women with diagnosis of gestational diabetes
    should be offered screening in the nonpregnant
    state
  • Fasting glucose
  • 2-hour 75 g OGTT
  • Cohort study demonstrated 58 risk of overt DM
    within 8 years (previously quoted 15 yrs)
  • Weight loss and lifestyle changes can reduce risk
    by 50

52
Summary
  • The optimal time to positively influence
    pregnancy outcome is before the patient gets
    pregnant
  • Role of primary care physicians and educators is
    critical (this means you!)
  • Gestational diabetes can be identified in the
    first trimester in a cohort of high risk patients
  • Small differences in blood glucose translate to
    significant differences in pregnancy outcomes
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