2. Preconception Counseling and Management of Diabetic Patients During Pregnancy
Ghorbani H.MD
Fellow of Endocrinology
Research Institute for Endocrine Sciences
2007 Oct-18

3. Preconception Counseling
Prepregnancy evaluation and counseling of women DM → minimize the risk to the F&M
Poor glycemic control during organogenesis→ spontaneous abortion & congenital anomalies
Thus, the importance of evaluating glycemic control before conception cannot be overstated.
Uptodate 2007

4. Preconception Care of Women With Diabetes
Congenital malformations 6-9% vs. general population risk of 2- 3%.
Congenital defects account for 50% of perinatal mortality
Diabetes associated malformations are more often lethal or significantly disabling and generally involve 1 or more organ systems.
Spontaneous abortion in poorly controoled diabetes twice the rate in women without diabetes.
J Perinat Neonat Nurs Vol. 18, No. 1, pp. 14–25 c 2004

5. CONGENITAL MALFORMATIONS AND SPONTANEOUS ABORTIONS
The malformations most commonly associated with diabetes occur before the 7th week after conception
The finding of multiple associated anomalies suggests a"hit"during blastogenesis that occurs during the first 4 weeks of fetal development
Anomalies during blastogenesis tend to be more severe than those that occur during organogenesis (weeks 4 to 5 after conception)
And may increase the risk of spontaneous abortions
joslins textbook 2005

6. Thus, interventions to control glycemia and reduce the risk of malformations must begin before conception and continue through the first 7 weeks after conception.
joslins textbook 2005

7. Preconception Care of Women With Diabetes
The institution of strict glycemic control, as
soon as the woman with diabetes determines
that she is pregnant, very often is too late
to prevent structural damage to fetal organs
which have already formed.
J Perinat Neonat Nurs Vol. 18, No. 1, pp. 14–25 c 2004

8. Management of women with diabetes before conception
Information and counselling should be provided to all women of reproductive age with diabetes
A meta-analysis has demonstrated a significantly lower prevalence of major congenital anomalies in offspring of women who attended for prepregnancy counselling (relative risk, 0.36; 95% CI, 0.22–0.59; absolute risk, 2.1% v 6.5%).
MJA • Volume 183 Number 7 • 3 October 2005

10. PERICONCEPTIONAL CARE OF WOMEN WITH DIABETES
Because most pregnancies of diabetic women are either unplanned or
without prenatal care until organogenesis has occurred, the efficacy of the intervention has been limited.
Education combined with accessibility to preconception care is the cornerstone of care
Obstet Gynecol Clin N Am 34 (2007) 225–239

11. A complete history and physical examination should be performed at the preconception visit.
This evaluation should include:
Information on the duration and type of diabetes
History of acute and chronic complications
Current and past glucose management
Physical activity, comorbid medical conditions
Gynecologic and obstetric history
Family issues.
Uptodate 2007

12. Diabetes complications review
Retinopathy:
The eye examination should be conducted through dilated pupils by a person experienced in retinal examination.
Preexisting retinopathy may progress more rapidly in pregnancy.
Retinopathy that requires laser therapy should be treated before pregnancy.
MJA • Volume 183 Number 7 • 3 October 2005

13. Nephropathy:
Overnight or 24 hour urine sample to quantify the albumin excretion rate.
Patients with pre-existing microalbuminuria are more likely to develop preeclampsia
If renal function is significantly impaired (cr> 0.2mmol/L), there is an increased risk of progression to dialysis during pregnancy
MJA • Volume 183 Number 7 • 3 October 2005

14. Nephropathy:
In patients with diabetic nephropathy and mild to moderate renal dysfunction ( cr 1.4 mg/dL and GFR over 90 mL/min), pregnancy per se does not worsen long-term outcom
Pregnancy seems to accelerate renal function
deterioration in women with moderate to severe renal dysfunction at the beginning of pregnancy.
Obstet Gynecol Clin N Am 34 (2007) 225–239

15. Macrovascular disease:
Pre-existing heart disease, requires cardiological review before conception
Significant CHD should be treated before pregnancy.
MJA • Volume 183 Number 7 • 3 October 2005

16. Management of hypertension
 Ideally, all antihypertensive drugs should be stopped before conception if the BP remains below 130/80 mmHg with dietary salt restriction.
Methyl dopa
Hydralazine
B-blocker
Ca canal blocker
ACEI and ARBs are contraindicated
Thiazid is relatively contraindicated
BP should be managed aggressively
Uptodate 2007

17. Autonomic neuropathy:
The presence of autonomic neuropathy resulting in gastroparesis, orthostatic hypotension or hypoglycaemic
unawareness may severely complicate the management of
diabetes in pregnancy.
Other related issues:
Thyroid function should be measured for women with T1D
MJA • Volume 183 Number 7 • 3 October 2005

18. Management of hyperlipidemia
Statins are contraindicated & should be discontinued before conception
Hypertriglyceridemia treat with diet , supplementation with medium chain TG and
use of intravenous heparin
Joslin text book 2005

19. Bacteriuria
 Women should be screened for asymptomatic bacteriuria and those with positive test results should be treated to prevent development of pyelonephritis
Uptodate 2007

20. Preconception Counseling
Clinically proven ischemic CAD →pregnancy is contraindicated.
women with diabetic Autonomic neuropathy involving the
CV system → fixed heart rate → pregnancy should be avoided.
Gastroenteropathy is a relative contraindication to pregnancy.
Women with active untreated PR should be counseled to delay pregnancy until after laser photocoagulation
J Perinat Neonat Nurs Vol. 18, No. 1, pp. 14–25 c 2004

21. Preconception Treatment Goals
Goal Plasma(mg/dl) Wholeblood(mg/dl)
Fasting and Premeal
glucose
2-hpp
HbA1c <7%;normal if possible
Avoid hypoglycemia
Joslin text book 2005

22. WHITE CLASSIFICATION OF DM DURING PREGNANCY
Gestational DM
Class A : diet alone ,any duration or age
Class B : age at onset > 20 y& duration < 10y
Class C : age at onset or duration 10 – 19 y
Class D : age < 10 y or duration > 20 y or background retinopathy or HTN ( not preeclampsia)
Class R : proliferative retinopathy or vitreous HE
Class F : nephropathy with p. uria > 500 mg
Class RF : R & F
Class H : heart dx
Class T : prior renal transplantation
Joslin textbook 2005
joslins textbook 2005

23. Postconception Ttreatment Goals
Goal Plasma whole blood
Fasting and premeal glocose
BS -1hpp
BS -2hpp
Urinary ketones Negative
Normalization of HbA1c
Avoidance of severe hypoglycemia
Joslin textbook 2005

24. Management during pregnancy
Routinely review women every 1–4 weeks during the first 30 weeks and then every 1–2 weeks until delivery, depending on diabetes control and the presence of diabetic and obstetric complications.
It is recommended that tests be performed fasting and 1–2 hours after meals.
The HbAlc level should be monitored every 4–8
weeks and kept within the normal range.
MJA • Volume 183 Number 7 • 3 October 2005

25. Management during pregnancy
Women should be monitored for signs or progression of diabetic complications, particularly:
Retinopathy
Proteinuria
Proteinuria should be assessed by dipstick at regular intervals, and quantitated where appropriate.
MJA • Volume 183 Number 7 • 3 October 2005

26. Complications of Diabetes during Pregnancy

27. NEPHROPATHY
pregnancy per se does not appear to hasten the natural progression to ESRD for most women
This depends upon the initial degree of renal impairment.
The risk is substantially increased in women with a cr above 2.0 mg/dL , many of whom have more than 2 g of proteinuria per day.
Uptodate 2007

28. NEPHROPATHY
These findings can be considered relative contraindications to pregnancy.
A GFR below 50 mL/min before pregnancy is associated with a high prevalence of HTN and fetal wastage
Uptodate 2007

29. The four major factors that have been associated with the development and progression of DN:
Microalbuminuria
Degree of glycemic control
Blood pressure
Pregnancy
Uptodate 2007

30. CCBs may have similar renal protective effects as ACEI
Lowering BP, reducing microalbuminuria, and improving glycemic control have a protective effect on the glomeruli and decrease the GFR
CCBs may have similar renal protective effects as ACEI
These agents are a reasonable option for the treatment
of HTN in pregnant women with DN,microalbuminuria,
or microvascular disease.
Uptodate 2007

31. EFFECT OF NEPHROPATHY ON PREGNANCY
Overt nephropathy is associated with a variety of pregnancy
complications:
Fetal growth restriction
Nonreassuring fetal status
Preeclampsia
As a consequence, preterm delivery and cesarean birth are often required for maternal or fetal indications.
Uptodate 2007

32. Hypertensive disorder
Patients with preexisting diabetes are at increased risk of hypertensive complications during pregnancy:
Chronic HTN
Preeclampsia—eclampsia
Preeclampsia--eclampsia superimposed on chronic HTN
Gestational HTN
joslins textbook 2005

33. Hypertensive disorder
Chronic HTN: before or up to 20th weeks of gestation & if HTN continue after 12 week after pregnancy
Preeclampsia-eclampsia : ≥ 140/90 mmhg ,usually after 20th weeks of gestation with proteinuria more than 300mg/24 hrs
Preeclampsia-eclampsia superimposed on chronic HTN
Gestational HTN
joslins textbook 2005

34. Hypertensive disorder
Start treatment from BP ≥ 130/ 80 mmHg especially if microalbuminuria or proteinuria is present
joslins textbook 2005

35. Ophthalmic assessmen
Comprehensive eye examinatin in pt with planing for pregnancy
who become pregnant should have a comprehensive eye examination in the first trimester and close f/u throughout pregnancy and for one year postpartum.
Frequent monitoring is helpful to look for early worsening of retinopathy as glycemic control improves
Laser photocoagulation should be considered for women with severe preproliferative diabetic retinopathy.
Uptodate 2007

36. Retinopathy Risk of progression of retinopathy increase in pregnancy
Risk is influenced with :
severity of baseline retinopathy
HbAlc more than 6 SD above normal
intensively treated pt has 1.6 fold increase risk of retinopathy
Conventionally treated pt has 2.4 fold increase in retinopathy
In DCCT study ,no difference in level of retinopathy in pt who became pregnant as compared with pt who never p.
joslins textbook 2005

39. Management during pregnancy
Formal eye review should be at least 3-monthly if:
baseline retinopathy is present
If there is a rapid improvement in glycaemic control
There has been a long duration of pre-existing diabetes.
MJA • Volume 183 Number 7 • 3 October 2005

40. Frequency of testing during pregnancy in women with pregestatonal diabetes
Test Frequency
Hemoglobin A1c Every 4-6 weeks
Blood glucose Home measurements 4-8 times daily
Urine ketones During period of illness; when any blood glucose value is > 200 mg/dl
Urine protein Diptstick , quantitate 24 hour excretion each trimester in women with nephropathy
Serum creatinine Each trimester in women with nephropathy
Thyroid function tests Baseline measurements of serum free T4 and TSH
Eye examination Baseline and then as necessary per retinal specialist
Uptodate 2007

41. Fetal Surveillance
The priciple is to verify fetal viability in the first trimester
Validate fetal structural integrity in the second trimester
Monitor fetal growth during most of the third trimester
And ensure fetal well-being in late third trimester
Maternal- Fetal Medicine Textbook 2004

42. Fetal surveillance
In the past, unexplained fetal death occurred in 10-30% of type 1 diabetic pregnancies associated with macrosomia, hydramnios, preeclampsia,and vascular disease. Fetal surveillance is of utmost importance in optimizing a good outcome for both mother and fetus
Endocrinol Metab Clin N Am 35 (2006) 79–97

43. US is the most useful tool for the assessment of the fetus.
Fetal surveillance
US is the most useful tool for the assessment of the fetus.
It can be used to : Estimate gestational age Screen for structural anomalies Evaluate growth Assess amniotic fluid volume Determine fetal status dynamically through Doppler and biophysical studies
Endocrinol Metab Clin N Am 35 (2006) 79–97

44. Fetal surveillance
Macrosomia is usually defined as fetal weight greater than 4.0 kg to 4.5 kg or birth weight above the 90th percentile for gestational age
Macrosomia occurs in approximately 88% of fetuses in whom the abdominal circumference and estimated fetal weight both exceed the 90th percentile
Endocrinol Metab Clin N Am 35 (2006) 79–97

45. Fetal surveillance
US is essential for the evaluation of congenital anomalies.
A structural ultrasonogram can detect both neural tube defects and major cardiac defects
US is performed in the third trimester for the assessment of
growth and development and the presence of macrosomia.
Endocrinol Metab Clin N Am 35 (2006) 79–97

46. Antepartum surveillance
In women who have diet-controlled gestational diabetes, fetal surveillance is not initiated usually until 40 weeks
Most centers defer testing until the 35th week if there is excellent glycemic control, but testing is started much earlier in women who have poor control, nephropathy,or hypertension
Endocrinol Metab Clin N Am 35 (2006) 79–97

47. Fetal surveillance in type I and type II diabetic pregnancies
Time Test
Preconception Maternal glycemic control
8-10 w sonographic crown –rump measurement
16 w Maternal serum alpha- fetoprotein level
20-22 w high–resolution sonography, fetal cardiac echography in women in suboptimal diabetic control at first prenatal visit
24w Baseline sonographic growth assessment of the fetus
28 w Daily fetal movement counting by the mother
32 w Repeat sonography for fetal growth
34 w Biophysical testing:
2X weekly NST or
weekly CST or
weekly biophysical profile
36w Estimation of fetal weight by sonography
w Amniocentesis and delivery for patients in poor control
38.5 – 40 w Delivery without amniocentesis for patients in good control who have excellent dating criteria
Maternal- Fetal Medicine Textbook 2004

48. TESTS OF FETAL WELL - BEING
comment
Reassuring result
frequency
test
Performed in all patients
Ten movement in <60 min
Every night from 28 w
Fetal movement counting
Being at w with insulin dependent diabetes
Two heart – rate acceleration in 20 minutes
Twice weekly
Non- stress test
Same as for non stress test
No heart rate decelerations in response to ≥ 3 contrations in 10 minutes
weekly
Contraction stress test
3 movement =2
1 flexion = 2
30 sec breathing = 2
2 cm amniotic fluid = 2
Score of 8 in 30 minutes
Ultrasound biophysical profile
Maternal- Fetal Medicine Textbook 2004

49. CONFIRMATION OF FETAL MATURITY BEFORE INDUCTION OR PLANNING CESAREAN
Phosphatidyl glycerol > 3% in amniotic fluid collected from vaginal pool or by amniocentesis
Completion of weeks gestation
Normal LMP
First pelvic examination before 12 weeks confirm dates.
Sonogram before 24 weeks confirm dates
Documentation of more than 18 weeks by fetoscope of FHT
Maternal- Fetal Medicine Textbook 2004

50. Medications used in management of premature labour
β-sympathomimetic agents given to suppress uterine contractions and corticosteroids given to enhance fetal lung maturity.
Following administration of salbutamol, there may be a rapid rise in blood glucose level
Alternative tocolytic agents such as nifedipine are recommended.
Following administration of corticosteroid, the rise in blood glucose level usually starts about 6–12 hours later, and may persist for up to 5 days
BS level monitored every 1–2 hours until glycaemic control has stabilised
MJA • Volume 183 Number 7 • 3 October 2005

51. Delivery
Delivery should be at term unless obstetric or medical factors dictate otherwise (eg, fetal macrosomia, polyhydramnios, poor metabolic control, preeclampsia,IUGR).
Vaginal delivery is preferable unless there is an obstetric or medical contraindication.
Birthweight exceeds 4250–4500g warrants consideration of elective caesarean section.
MJA • Volume 183 Number 7 • 3 October 2005

52. Indication for delivery diabetic pregnancy
Fetal Non reactive, Positive CST
mature fetus
Sonographic evidence of fetal growth arrest
Decline in fetal growth rate with decreased amnionic fluid
40 – 41 w gestation
Maternal Severe preeclampsia
Mild preeclampsia, mature fetus
Markedly falling renal function
Obstetric preterm labor with failure of tocolysis
Mature fetus , inducible cervix
Maternal- Fetal Medicine Textbook 2004

53. Thank you

54. Fetal Monitoring
Evaluations for neural tube defects and other congenital malformations begin with triple-screen testing at approximately 15 to 21 weeks of gestation.
A fetal anatomic survey is performed at 18 weeks of gestation.
Fetal echocardiography may be performed at 20 to 22 weeks of gestation

55. Cardiac evaluation Indications for screening for CAD:
women 35 years or older withe one or more:
Hypertension (blood pressure> 130/80mm Hg)
, Smoking
Positive family history
Hypercholesterolemia (LDL >100 mg/dL,HDL :<40 mg/dL)
Renal disease (microalbuminuria or nephropathy)

56. Fetal Monitoring
Ultrasound is used at 28 weeks of gestation to evaluate
fetal growth and the quantity of amniotic fluid.
Fetal surveillance,including nonstress test and biophysical profile as well as maternal monitoring of fetal activity is initiated in the third trimester to reduce the risk of stillbirth.

57. labor and Delivery
The method of delivery is based on the usual obstetric indications,as well as on fetal weight and the presence or absence of active retinal changes. Infants of diabetic mothers are more likely to be macrosomic.
Cesarean sections are recommended for fetuses of an estimated weight greater than 4,500 g.
It is important to maintain euglycemia during labor or prior
to a scheduled cesarean section.

58. Postpartum Management
Insulin dosing should be titrated daily toward the preconception dose as necessary.
Urine microalbumin, thyroid function, and HbAlc
should be reevaluated.
The American Academy of Pediatrics considers the ACEIs captopril and enalapril safe for use by the breastfeeding mother and are resumed in patients with nephropathy, microalbuminuria and hypertension .

59. First trimester Same as preconception counseling care
Evaluate risk factors

60. Second trimester
Visit the pt every 2 to 4 weeks or more if pt has complications or glycemic control is suboptimal .
Maternal analyte screening : screening for aneuploidy or neural tube defects ( α fetoprotein ,unconjucated estriol ,HCG,inhibin A )
Diabetes does not increase the risk of fetal aneuploidy.
Sonography : at 18 weeks of gestation

61. Third trimester
Visit for every 1 to 2 weeks untile 32 wks of gestation & then weekly
Glycemic control
Sonography
Estimation of fetal size
Surveillance for pregnancy complication
Fetal surveillance : weekly NST at 32 weeks with suboptimal HbA1C & from weeks with nl HbA1C & two times per week from 36 weeks until delivery
Assess for macrosomia ,premature labor , hydramnious

62. Fetal Surveillance
The goals of management of diabetic pregnancy are to prevent stillbirth and asphyxia while minimizing maternal morbidity associated with delivery. This involves monitoring fetal growth in order to select the proper timing and route of delivery. The first is testing fetal well- being at frequent intervals and fetal size.

63. Fetal Surveillance
The priciple is to verify fetal viability in the first trimester
Validate fetal structural integrity in the second trimester
Monitor fetal growth during most of the third timester
Ensure fetal well-bing in the late third trimester

64. Thank you

66. glycemic control plays an important role in reducing the frequency of fetal and neonatal complications.
(HbA1C values are useful in evaluating a woman's glycemic control early in pregnancy.
One goal of preconception care of women with diabetes is to evaluate glycemic control and recommend adjustments in diet, medications, and lifestyle, as needed, to achieve euglycemia.
Type 2 diabetics on oral anti-hyperglycemic agents should be switched to insulin therapy preconceptionally

67. Prepregnancy evaluation and counseling of women DM → minimize the risk to the F&M
Women who are in poor glycemic control during the period of fetal organogenesis, which is nearly complete by seven weeks postconception, have a high incidence of spontaneous abortion and fetuses with congenital anomalies
Thus, the importance of evaluating glycemic control in women with DM and achieving good glycemic control before conception cannot be overstated.

68. The three major potential fetal/pregnancy complications among women with pregestational diabetes are: congenital malformations, spontaneous abortion, and macrosomia.
Hyperglycemia is probably the most important determinant
of these risks.
This conclusion is supported by repeated observations that normalizing blood glucose concentrations before and early in pregnancy can reduce the risk of spontaneous abortion and congenital malformations to nearly that of normal women

69. Management of women with diabetes before conception
Information and counselling should be provided to all women of reproductive age with diabetes
A meta-analysis has demonstrated a significantly lower prevalence of major congenital anomalies in offspring of women who attended for prepregnancy counselling (relative risk, 0.36; 95% CI, 0.22–0.59; absolute risk, 2.1% v 6.5%).

70. Assessment of renal function
Spot urine for microalbumin /cr or time collection for 24 hrs
Serum cr
Cr> 2mg/dl & GFR < 50 ml/min. & proteinuria more than 2 gr /day can be considered relative contraindications to pregnancy

71. Initial prepregnancy assessment should document baseline renal function, include protein excretion, serum creatinine, and creatinine clearance
The risk of permanent decline in renal function is substantially increased in women with a urine creatinine concentration above 2.0 mg/dL many of whom have more than 2 g of proteinuria per day.
These findings can be considered relative contraindications to pregnancy.
A creatinine clearance below 50 mL/min before pregnancy is associated with a high prevalence of hypertension and fetal wastage

72. Preconception treatment goal
Plasma
FBS:
2hpp :
HbA1C : < 7% ; normal if possible
Avoid hypoglycemia
Joslin text book 2005

73. Cardiac evaluation Testing may include one or more of the following:
electrocardiogram, echocardiogram, and exercise
tolerance testing with the recognition that the resting
electrocardiogram is the least sensitive of these tests.

74. Thyroid disorders
 Prepregnancy evaluation should include measurement of serum TSH

75. Preconception counseling
Education
Maternal risk assessment
Fetal risk assessment
Metabolic goals should be established prior to conception
Self-management skills should be reviewed.
Nutrition counseling to establish an individualized meal plan should be provided.

76. Daily folic acid : 1 mg prior conception & continue after conception
Mental health professional should be available
A formal dilated funduscopic examination and clearance for pregnancy by an ophthalmologist

77. Treatment of Diabetes during Pregnancy
Home blood glucose monitoring is performed a minimum of four times daily,including before breakfast, 2 hours after meals, before driving,and with signs or symptoms of hypoglycemia.
Premeal and middle-of-the-night testing may be necessary in some patients.
First-void urine samples are tested for ketones.

78. Insulin requirements: what to expect
Hypoglycaemia, especially overnight, is more frequent from the 6th to 18th weeks of gestation
Insulin requirements can fall after 32 weeks
Any fall greater than 5%–10% should lead to an assessment of fetal wellbeing

79. First trimester ultrasound examination
First trimester US examination is often obtained to document viability
As the rate of spontaneous abortion is higher in diabetic women
and
To assist in estimation of gestational age
Uptodate 2007

80. Fetal assessment
Screening for fetal anomalies should be done with first and second trimester
ultrasound and a fetal echocardiogram between 20 and 22 weeks’ gestation. As
Obstet Gynecol Clin N Am 31 (2004) 907– 933

81. Fetal Risk

82. Obstetric management
US examination for fetal morphology should be offered at 18–20 weeks.
Further examinations to assess fetal growth should be performed at 28–30 weeks and repeated at 34–36 weeks.
The latter will help to determine the timing and route of delivery.
MJA • Volume 183 Number 7 • 3 October 2005