diabetes & pregnancy by: carolyn connors. diabetics and pregnancy euglycemia is very important!...

Diabetes & PregnancyBy: Carolyn Connors

Diabetics and Pregnancy

Euglycemia is very important!Decreases likelihood of:

Miscarriage

Congenital anomalies

Macrosomia

Fetal death

Neonatal morbidity

Diabetic Embryopathy

Occurs in 6-7th weeks GA

Maternal Hyperglycemia leads to vascular disruption and yolk sac failure

Increased spontaneous abortions

Major malformations

Fetal Effects

Pathophysiology – Maternal hyperglycemia

Fetal hyperglycemia

Premature maturation of pancreatic islets

Hypertrophy of beta cells

Hyperinsulinemia

Hypertrophy of Beta Cells

Fetal Hypoxemia

Chronic fetal hyperinsulinemiaIncreased activity hepatic enzymes

Increased glycogen and lipid storage

Increased metabolic rates

Oxygen consumption increased

Fetal Hypoxemia

Stimulates erythropoietin polycythemia

Promotes catecholamine productionHTN

Cardiac hypertrophy

Contributes 20-30% stillbirth rate in poorly controlled diabetics

Neonatal Effects

Congenital anomalies –

Accounts for 50% of perinatal deaths of infants of diabetic mothers (IDM)

Relative risk increased 7% with IDM over general population

Congenital Anomalies

Two-thirds involve CVS or CNSAnencephaly and Spina bifida 20x more common in IDM

GU, GI, MSK defects increased

Congenital Anomalies

Left Colon Syndrome - Transient inability to pass meconium

Resolves spontaneously

Condition unique to IDM’s

Congential Anomalies

Caudal Regression Syndrome –

200x more common in IDM

Incomplete development of sacrum/lumbar region

Distal spinal cord disruptedNeurologic impairment varied

Leg deformities

Premature Delivery

Increased Iatrogenic premature delivery

Maternal preeclampsia

Increased spontaneous premature labour

Associated with poor glycemic control

High rates of UTI’s

Perinatal Asphyxia

Defined to include:Fetal heart rate abnormalities during labor

Low Apgar scores

Intrauterine death

Perinatal Asphyxia

Correlated with:

Maternal vascular diseaseEg: nephropathy

Hyperglycemia during labor

Prematurity

Increased Fetal Growth

Mostly during 3rd trimester

Disproportionate growthInsulin sensitive tissue eg. Liver, muscle, cardiac muscle, subcutaneous fat

Head circumference normal

Increased risk of hyperbilirubemia, hypoglycemia, acidosis

Macrosomia

Macrosomia

Birth weight > 90th percentile or > 4000g

Predisposes to birth injury Eg: Shoulder Dystocia

Brachial plexus injury

Clavicular/Humeral Fractures

Perinatal asphyxia

Shoulder Dystocia

Shoulder Dystocia

Occurs in 1/3 IDM > 4000g

Disproportionate growth contributes

C-Section often recommended if fetal weight > 4300g

Intrauterine Growth Restriction

Maternal Vasculopathy

Preclampsia

Congenital Anomalies

Very strict BG control

Respiratory Distress Syndrome

Causes amoung IDM:

Delayed maturation of surfactant synthesis

Hypertrophic cardiomyopathy

Retained lung fluid (TTN)

Increased rates of c-section

Hypertrophic Cardiomyopathy

Fetal hyperinsulinemia increases fat/glycogen deposit in cardiac muscle

Thickening interventricular septum30-50% IDM with hypertrophy on Echo

Obstructed left ventricular outflow5-10% symptomatic

Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy

Transient condition

Echo normalizes 6-12 months

Symptomatic infants recover after 2-3 weeks supportive care

Hypoglycemia

BG levels < 2.2

Occurs within hours of birth

Increased risk with both LGA and SGA infants

Polycythemia

13-33% IDM’s

Hct should be measured 12hrs after birth

Can lead to Hyperviscosity SyndromeRenal vein thrombosis

Vascular sludging, ischemia, infarction of vital organs

Polycythemia

Hyperbilirubinemia

Associated with:Poor maternal glycemic control

Polycythemia

Macrosomic infants

prematurity

Neurodevelopmental Outcome

Few studies available which adequately control confounders

Maternal ketones Poorer psychomotor development

Elevated HbA1c levels during pregnancy

Poorer intellectual performance

Neurodevelopmental Outcomes

Developmental Delay IUGR

Congenital malformations

Risk of Developing Diabetes

Type 1 DM:

Some genetic component:Offspring – 6%

Siblings – 5%

Identical twins – 30%

(general population – 0.4%)

Risk of Developing Diabetes

Type 2 DM:

Much larger genetic component

Abnormal intrauterine metabolic environment

IDM – 45%

Prediabetic – 8.6%

Nondiabetic – 1.4%

ObesityIncreased BMI noted in offspring of diabetic mothers (ages 5-19 yrs)

Birth weight not indicative

Impaired Glucose Tolerance

Prepregnancy Counselling

Required to decrease complications in known diabetics:

Macrosomia: 63% (10%)

C-Section: 56% (20%)

Preterm delivery: 42% (12%)

Preeclampsia: 18% (6%)

Congenital Malformations: 5% (3%)

Perinatal Mortality: 3% (<1%)

Complete History/Physical Exam

Duration/Type of DM

Acute complications

Chronic complications

Glucose management

Physical activity

Medication

Obs/Gyne History

Laboratory Investigations

UrinalysisTreat asymptomatic bacteriuria

Baseline renal functionTotal protein, serum Cr, CrCl

Thyroid FunctionTSH, Free T4

Comprehensive eye examWithin 12 months prior to pregnancy

Within 1st trimester

Followed closely up to 1 year postpartum

Assessing Glycemic Control

HgbA1C: mean blood glucose concentration over preceding 6 - 8 weeks

HgbA1A – In Pregnancy: Mean BG concentration over 4 – 6 weeksLife span of RBC shortened due to increased production

Hemoglobin A1C

Measured every 4-6 weeks

Goal < 6.1 prior to d/c contraceptionAssociated with lowest rate of adverse pregnancy outcome

Spontaneous abortion

Congenital malformation

Perinatal death

Assessing Glycemic Control

Glucose monitoring:Pregnancy associated with exaggerated rebound from hypoglycemia

Urine Ketones:Type 1 DM with illness or BG > 11.1

DKA associated with high fetal mortality rate

Ketonemia may have adverse developmental effects.

Target Blood Glucose Values

Fasting glucose < 5.2

1 hr postprandial glucose < 7.7

2 hr postprandial glucose < 6.6

Qhs < 5.9

Strict glycemic control decreases adverse fetal outcomes

Hazards of Strict Glycemic Control

1. Hypoglycemia – does not appear to be teratogenic in humans

Extremely strict control (BG < 4.8) can cause small-for-gestational age infants

Hazards of Strict Glycemic Control

2. Diabetic Retinopathy – Related to degree of baseline retinopathy

Magnitude of reduction of chronic hyperglycemia

Mediated by closure of small retinal blood vessels that were narrowed but patent

Frequent retinal evaluation recommended in high risk women

Retinopathy

Comprehensive eye examWithin 12 months prior to pregnancy

Within 1st trimester

Followed closely up to 1 year postpartum

Nutritional Therapy

Achieve euglycemia

Prevent ketosis

Provide adequate weight gain

Contribute to fetal well-being

Caloric Requirements

Increase 300 kcal/day in pregnancy

Based on BMI:30-40 kcal/kg/day – BMI < 22

30-35 kcal/kg/day – BMI 22-27

24 kcal/kg/day – BMI 27-29

12-15 kcal/kg/day – BMI > 30

Maternal obesity can cause:Excessive fetal growth

Increase glucose tolerance

Caloric restriction may be useful treatment

Oral Anti-hyperglycemic Agents

Sulfonylureas –

can cross the placenta causing fetal hyperinsulinemia:

Macrosomia

Neonatal hypoglycemia

Oral Anti-hyperglycemic Agents

Glyburide –

High protein binding so placental passage low

Several studies have not shown harmful effects

Oral Anti-Hyperglycemic Agents

Metformin and Thiazolindiones –Minimal information available

Recommendations

Oral anti-hyperglycemics not recommended in pregnancy

Some question as to usage in non-compliant patients on individualized basis

Insulin - patients unable to obtain euglycemia through diet alone

Insulin Therapy

Type 2 DM:Insulin during preconception period

Obtain adequate HgbA1C

Avoid excessive weight gain

Moderate low-impact exercise

Insulin Therapy

Rapid Acting Insulin (Lispro/Aspart)

Acceptable safety profiles

Minimal transfer across the placenta

No evidence teratogenesis

Note: Compared to Regular Insulin

Improves postprandial BG

Decreases risk hypoglycemia

Insulin Therapy

Longer Acting Insulin:

NPH recommended

Glargine:high affinity for IGF-1 receptor

Risk of macrosmia

Intrapartum Management

Latent phase – insulin to maintain BG 3.9-5.0

Active Phase – insulin resistance rapidly decreases

BG check hourly

Avoid boluses of glucoseIncreases risk of neonatal hypoglycemia

Fetal hypoxia

Fetal/neonatal acidosis

Postpartum Management

Postpartum - insulin requirements drop sharply

Short ½ lives of placental growth hormone and placental lactogen

Insulin doses readjusted 24-72 hrs

Note: Breast-feeding patients should remain on insulin

The End!