Diabetes and Pregnancy

Report
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J. David Spencer, D.O., F.A.C.O.O.G.
 Diabetes
: a group of diseases due to high
levels of blood glucose
 Defects
in insulin production and / or the
action of insulin
 Affects
25.8 million people, 8.3 % of the
population of the United States
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18.8 million people diagnosed with Diabetes
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7 million people undiagnosed
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1.9 million people over age 20 dxed in 2010
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12.6 million, or 10.8 % of U.S. women over age 20 have
diabetes
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Higher than normal blood glucose or glycosylated
Hemoglobin A1C levels, but not high enough to be classified
as diabetes.
American Diabetes Association values placing
person at risk for DM:
Fasting blood sugar: 100 – 125 mg/dl.
2 hours after 75 gram glucose load:140-190
Hemoglobin A1C value: 5.7 – 6.4 % (or <6%)
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Developing type 2 diabetes
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Heart disease
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Stroke
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Gestational diabetes
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Pregestational or Overt Diabetes : a woman diagnosed with
diabetes prior to becoming pregnant
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Gestational Diabetes : a woman with glucose intolerance
first diagnosed while pregnant
Casual (random) blood glucose value over 200 mg/dl,
with classic symptoms: polydipsia, polyuria, unexplained
weight loss, ketoacidosis
OR Fasting (no caloric intake for 8 to 14 hours) plasma
glucose over 125 mg/dl
OR After 75 gram glucose load, 2 hour plasma glucose over
200 mg/dl
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Type 1 : formerly insulin dependent, or juvenile onset
diabetes
Type 2 : Formerly non-insulin dependent, or adult onset
diabetes
Other types of DM : genetic, drug related, chemical diabetes
Gestational diabetes
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Type 1 diabetic women : approx. 2 % of pregnancies that
have diabetes
Type 2 diabetic women : approx. 8 % of pregnancies with
diabetic mother
Gestational Diabetes Mellitus : Women who develop
diabetes in pregnancy account for about 90 % of
pregnancies with diabetes
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Incidence of DM in the U.S. is increasing
Incidence of Obesity in the U. S. is an epidemic
Strong relationship of obese patients developing diabetes.
This correlation has been called Diabesity
In 2008, about 60 % of reproductive age women in the U. S.
were overweight or obese
(What percent now?)
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Diabetic women planning to become pregnant should
optimize their health prior to conception with:
Nutritional management
Weight management
Glycemic control
BUT about 50% of all pregnancies are unplanned, therefore
unprepared
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Euglycemia at the time of conception reduces the risks of
: spontaneous abortion
: congenital anomalies
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Very strong positive correlation between hyperglycemia
during embryonic organogenesis and congenital (not
chromosomal) anomalies
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Birth defects affect about 1 in 33 pregnancies and are a
leading cause of pregnancy loss and neonatal deaths in the
U. S.
Not totally understood is how hyperglycemia causes
congenital anomalies
Diabetic women with good glycemic control have no
increase incidence of birth defects compared to general
population
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Unrecognized / undiagnosed or poorly controlled diabetes
increases maternal as well as fetal risks in pregnancy
Many reproductive age women are in this category, and
coupled with unplanned pregnancies, many women and
their babies are at risk
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Goals - achieve and maintain excellent control of diabetes
without hypoglycemia
- evaluate any other medical conditions
that may complicate a pregnancy
Glycosylated Hemoglobin A1C measurements reflect blood
sugar levels of preceeding 8 to 12 weeks can be useful in
assessing blood sugar control before becoming pregnant
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Obesity – even if not (yet) diabetic, overweight and obese
women have more complications in pregnancy, and a higher
than usual rate of Gestational Diabetes Mellitus.
Weight loss will decrease some of the complications of
pregnancy in obese women
Most weight loss medications should not be used in
pregnancy – so stop before conceiving
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Diabetics may have hyperlipidemia, and Statin drugs are
Category X and should not be used especially early in
gestation
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Dietary changes may help some, if statins have been used
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In women who have had diabetes for over 10 years, over 30
% have hypertension.
Some commonly used anti-hypertensive medications are
not teratogenic, and may be continued in pregnancy
- Methyldopa
- Calcium channel blockers
- Beta blockers
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Diuretics : may affect fetal renal development, amniotic
fluid levels
Angiotensin Converting Enzyme inhibitors and Angiotensin
Receptor Blockers
-probably safe in first trimester, but later in pregnancy
reduce fetal renal blood flow, decrease fetal urine output
and result in oligohydramnios
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If nutritional management and exercise do not result in
normal blood sugar levels, medication is indicated.
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Insulin
Oral hypoglycemic agents
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Insulin most like human insulin is preferred for use in
pregnancy - fewer antibodies
limited transplacental crossing
- no teratogenicity
 Most clinical experience with Lispro (Humulin)
Aspart (Novolog), Regular and NPH insulin
 Type 1 diabetics should remain on insulin in pregnancy
-
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First generation sulfonylureas should not be used in
pregnancy – placental transfer results in fetal
hyperinsulinemia, prolonged newborn post-partum
hypoglycemia
Glyburide, second generation – low placental transfer.
Stimulates maternal pancreas to produce more insulin
May be continued in pregnancy
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Metformin – frequently used in women with insulin
resistance, metabolic syndrome, infertility, polycystic ovary
syndrome
Does cross placenta, no teratogenicity, minimal fetal
affects.
Decreases maternal peripheral resistance to insulin,
inhibits gluconeogenesis
May be continued in pregnancy
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The control of blood sugar levels, and evaluation of medical
conditions and pre-pregnancy medications, will allow the
woman to have a healthier and safer start to her pregnancy
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Occur to assure adequate supply of metabolic fuels to the
growing fetus and accommodate energy needs of the
mother
Some of these changes can be affected by pre-gestational
diabetes.
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Glucose homeostasis is a balance of insulin secretion and
insulin resistance
Both effects occur at increased rates in pregnancy
Insulin receptor sites are decreased by Human Chorionic
Somatomammotropin, Prolactin, and Placental Human
Growth Hormone.
Endogenous glucose production is increased
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Pregnancy hormones cause hyperplasia of pancreatic islet
beta cells, increasing insulin
After eating, increases in insulin release cause increases in
glucose uptake in muscle, fat
In fasting state in pregnancy, increased insulin levels
magnify the hypoglycemic state, but gluconeogenesis and
transfer of glucose through placenta maintain fetal glucose
levels
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In the third trimester of pregnancy :
o Fetal growth accelerates
o Maternal and fetal metabolic demands increase
o Insulin resistance increases
Pregestational, or gestational impairments of glucose
metabolism adversely affect control of blood sugar levels,
resulting in hyperglycemia
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Gestational diabetes mellitus is impaired glucose tolerance
with onset or first recognition during pregnancy
5 to 10 % of U. S. pregnancies are complicated by diabetes
Women with Type 1 diabetes - about 1-2 %
Women with Type 2 diabetes - about 10 %
Women developing DM in pregnancy – 90%
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Because of serious complications of unrecognized diabetes
in pregnancy, screening for GDM has been done for many
decades
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Initial screening looks at maternal factors
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Blood tests make the diagnosis
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Low risk (the woman must meet all criteria)
o Age less than 25
o Weight normal before pregnancy (BMI 19-25)
o No history of abnormal glucose tolerance
o No history of adverse pregnancy outcome
o No known first degree relatives with diabetes
o Ethnicity with low prevalence of diabetes
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High risk
o Over age 25 (some use 30)
o Obese (BMI over 30 kg/m2, or weigh over 90 kg)
o Polycystic ovary syndrome
o History of gestational diabetes
o Previous Macrosomic / Large for Gestational age infant
o Previous unexplained pregnancy loss
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High risk
-Strong immediate family history of diabetes
-Previous child with congenital anomaly
-Elevated blood sugar (FBS >140; RBS >200)
-“Prediabetes” – mildly elevated glucose or
Glycosylated Hemoglobin A1C
-Member of ethnic group with increased incidence of
diabetes
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Low risk patients – oral glucose load 24 to 28 weeks
gestation
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High risk patients – screen with blood test as soon as
possible in the pregnancy.
One step – first option
2 hour glucose tolerance test
75 gram oral glucose load, draw blood sugar 2 hours
later
some modify and do Fasting : <95 mg/dl
1 hour : <180 mg/dl
2 hour : <155 mg/dl
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One step – second option
3 hour glucose tolerance test
Fasting (for 8 – 14 hours) : <95 mg/dl
100 gram oral load of glucose
1 hour post-prandial : <180 mg/dl
2 hour post-prandial : <155 mg/dl
3 hour post-prandial : < 140 mg/dl
A diagnosis of GDM is made with 2 abnormal values
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Two step option
First done is 50 gram oral glucose load, without regard to time
of day or last meal
blood sugar one hour later : <140 (or <130)
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If elevated, the previously described 3 hour glucose
tolerance test, with 100 gram load, same values, is
performed
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Abnormal glucose screening tests, or elevated glycosylated
hemoglobin A1C prior to 20 weeks gestation is strongly
suspicious for unrecognized, undiagnosed pregestational
DM
Uncommonly, type 1 DM may be discovered as presenting
with ketoacidosis in pregnancy, especially if in first trimester
Both, by definition, are still GDM
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Gestational diabetes dxed early in pregnancy with high risk
patient may very well be pregestational diabetes
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Possible DM related underlying medical conditions need to
be investigated, such as diabetic vasculopathy
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Proposed in the 1970’s, as a reflection of duration and
multi-organ medical impact of women with diabetes who
became pregnant
TYPE
AGE AT ONSET
(YRS)
DURATION OF
DM (YRS)
COMPLICATIONS
A1
ANY AGE
ANY LENGTH
None; diet controlled
A2
ANY AGE
ANY LENGTH
None; requires RX
B
<20
OR <10
No vascular disease
C
10-19
OR 10-19
No vascular disease
D1-5
<10
OR >20
Retinopathy or HTN
E(NOW CLASS
D3)
Arterial calcification
F
Proteinuria; nephropathy
G
Pregnancy failures
H
Arterisclerotic heart disease
R
Proliferative retinopathy
T
After renal transplant
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Glycosylated Hemoglobin A1C – in pregnancy mean red
blood cell production increases, RBC life is shortened
Gly Hgb A1C in pregnancy is a reflection of mean RBC blood
glucose levels over 4 to 6 weeks, not 8 – 12 weeks
More frequent monitoring of this test will give better
reflection of long term glycemic state
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Caloric demands are increased in pregnancy
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Carbohydrate type and amount should be decreased in
diabetics in pregnancy
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Weight gain recommendation in pregnancy has changed
PRE-PREGNANCY BMI
BMI (KG/M2 )
TOTAL WT GAIN RATE OF WT
(LBS)
GAIN 2nd-3rd
TRIMESTERS
(PER WK)
UNDERWEIGHT
<18.5
28-40
1-1.3
NORMAL WT
18.5-24.9
25-35
0.8-1
OVERWEIGHT
25-29.9
15-25
0.5-0.7
OBESE
>30
11-20
0.4-0.6
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Weight gain beyond IOM guidelines in pregnancy is
associated with increased adverse maternal and neonatal
outcomes
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Home glucose monitoring determines if diet or medication
maintains tight glycemic control
Fasting blood sugar value should be < 95 mg/dl
1 hour postprandial value should be <140
2 hour postprandial value should be <120
Peak postprandial glucose concentration is 60 to 90
minutes after eating
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Hyperglycemia and Adverse Pregnancy Outcomes study
(HAPO) – even small elevations in blood glucose levels in
pregnancy are associated with increased maternal and fetal
complications in pregnancy
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Type 1 diabetics are maintained on insulin, although type
and dose will change in pregnancy
Type 2 and GDM mothers may try oral hypoglycemic drugs,
but may need insulin to give appropriate control
Nutritional management is maintained
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Frequent home glucose monitoring is required to avoid
prolonged hyperglycemic or hypoglycemia in the pregnant
diabetic patient
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Perinatal mortality decreased due to improved diabetic
metabolic control, fetal surveillance, and neonatal care
- 1960’s > 20 %
- now < 5%
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Risk and severity of complications are related to severity
and duration of hyperglycemia
Poorly controlled gestational diabetics may have serious
complications
Women with pregestational diabetes are at increased risk if
poorly controlled prior to and during pregnancy
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Retinopathy – esp in pregestational DM
Neuropathy
Nephropathy - proteinuria
Cardiovascular – HTN, PIH, preeclampsia
Diabetic ketoacidosis
Infections
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Spontaneous abortion
Congenital anomalies
o Cardiovascular
o Musculoskeletal
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- Central Nervous System
- Genitourinary
Fetal Growth Restriction
Macrosomia – birth injuries
Abnormalities of amniotic fluid
Unexplained fetal demise
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First Trimester
- viability, gestational age
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Second Trimester - fetal structure (ultrasound)
- biochemical markers
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Third Trimester
- fetal well being: NST,CST,BPP
- ? Estimated fetal weight?
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Polycythemia - Hyperviscosity
Neonatal hypoglycemia
Neonatal hypocalcemia
Neonatal hyperbilirubinemia
Respiratory distress syndrome
Neurologic or Developmental issues
Long term risks (obesity, diabetes)
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Whatever the type of diabetes
1 to 3 days after delivery, fasting or random glucose –
monitor levels and RX
Gestational diabetes
6 to 12 weeks after delivery, 75 gram oral
glucose load
Over 50% of GDM patients develop type 2 DM
30 to 50 % recurrence of GDM in other pregnancy
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Women with diabetes can have safe, successful
pregnancies with proper care prior to and during the
pregnancy.
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Thank you.
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? Questions ?
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1. Centers for Disease Control and Prevention. National diabetes fact sheet; national
estimates and general information on diabetes and prediabetes in the United States,
2011. Atlanta, GA U.S. Department of Health and Human Services, centers for Disease
Control and Prevention 2011.
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2. Landon MB, Gable SG. Gestational diabetes mellitus Obstet Gynecol 2011; 118(6):
1379-1393
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3. Correa A, Gilboa SM, Botto LD, et al. Lack of periconceptional vitamins or
supplements that contain folic acid and diabetes mellitus associated birth defects. Am J
Obstet Gynecol March 2012; 218: 218-221
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4. Dhulkotia JS, Ola B, Fraser R, et al. Oral hypoglycemic agents vs. insulin in
management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet
Gynecol Nov 2010; 203: 457-465
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5. Sulak JS. Know the normal numbers – and yours! The Female Patient 2012; 37: 1720.
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6. International Association of Diabetes and Pregnancy Study Group Consensus Panel.
Metzger BE, Gabbe SG, et al. International association of diabetes and pregnancy study
groups recommendations on the diagnosis and classification of hyperglycemia in
pregnancy. Diabetes Care 2010; 33 (3): 676-682.
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7. HAPO Study Cooperative Research Group. Metzger BE, Lowe LP, et al. Hyperglycemia
and Adverse Pregnancy Outcomes. N Engl J Med 2008; 358: 1991.
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8. U. S. Preventive Services Task Force. Screening for gestational diabetes mellitus: U. S.
Preventive Services Task Force recommendation statement. Ann Intern Med 2008; 148:
759.
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9. Correa A, Gilboa SA, Besser LM, et al. Diabetes mellitus and birth defects. Am J
Obstet Gynecol 2008; 199: 237.
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10. Yee LM, Cheng YW, Inturrisi M, et al. Effect of gestational weight gain on perinatal
outcomes in women with type 2 diabetes mellitus using the 2009 Institute of Medicine
guidelines. Am J Obstet Gynecol Sep. 2011; 205: 257.
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11. Moore, LE. Gestational diabetes: Should you use oral agents? Contemp Ob Gyn Feb
2012
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12. Metzger BE, Buchanan TA, Coustan DR, et al. Summary and recommendations of the
Fifth International Workshop-Conference on Gestational Diabetes. Diabetes Care 30
(Suppl 2): S251, 2007.
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13. Preconceptional counseling (Chapter 7); Diabetes (Chapter 52). In Cunningham FG,
Leveno KJ, et al (eds). Williams Obstetrics, 23rd ed. Saunders Elsevier, New York, 2010.

14. Endocrinology of Pregnancy (Chapter 8); Maternal Nutrition (Chapter 10); Diabetes in
Pregnancy (Chapter 46). In Creasy RK, Resnick R, Iams J. (eds). Creasy and Resnick’s
Maternal-Fetal Medicine: Principles and Practice, 6th ed. New York, McGraw Hill Medical,
2009.
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15. Jovanovic L. Glycemic control in women with type 1 and type 2 diabetes mellitus
during pregnancy. Up To Date, Feb 2012.
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16. D’Antona D. Maternal endocrine and metabolic adaptation to pregnancy. Up To
Date, Oct 2010.

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