MEDICAL DISORDERS COMPLICATING PREGNANCY

ENDOCRINE DISORDERS IN PREGNANCY

Prof.S.SUNDAR’s unitDr.N. ARUN KUMAR,PG

Gestational Diabetes Mellitus

What is GDM?

• Corbohydrate intolerance of variable severity with onset or first recognition during pregnancy

Pre-Gestational Diabetes

• a known diabetic becomes pregnant• hyperglycemia presents throughout

pregnancy and not just in the 2nd half as occurs in GDM

• more prone for certain complications

Pathophysiology of GDMFetoplacental hormones

(GH, cortisol, prolactin, HPL)

Increased insulin resistance

Compensatory increase in insulin secretion

if not so Normal pregnancy

GDM

Insulin resistance & stress due to

placental hormones

Compensatory increase in

insulin secretion

Epidemiology

• Prevalence of GDM vary worldwide because of different criteria and screening regimen used for diagnosing GDM in various countries

• India – 6% - 18%

Risk factors for GDM • Strong family h/o DM• Age >25 years• Women who delivered large infants (>4Kg)• h/o recurrent fetal loss• Part h/o glucose intolerance / diabetes in previous pregnancies• Obese/ over weight women (>15% of non-pregnant ideal body weight)• h/o still-birth, unexplained neonatal death, congenital malformations,

prematurity• h/o pre-eclampsia• h/o polyhydramnios• h/o traumatic delivery• Chronic hypertension• Recurrent severe moniliasis/UTI

Whom to screen?Low risk Universal

Universal screening is good in Indian setting because of the very high prevalence of both GDM & background T2DM

When to screen?

1st trimester

2nd trimester

3rd trimester

How to screen?

If normal glucose tolerance in 1st trimester

Repeat at 24-28 weeks

Repeat at 32-34 weeks

Repeat at later weeks (if increased Maternal weight gain & suspected

Fetal macrosomia)

ADA Procedure

50 gm of GCT (Without regard to the

time of last meal or time of the day)

If 1 hr GCT value

>140mg% <140mg%

100 gm of OGTT NORMAL at fasting

• 100 gm of OGTT is positive if there is any of the following 2 values:

• Plasma glucose at 0 hr ≥95 mg%• Plasma glucose at 1 hr ≥180 mg%• Plasma glucose at 2 hr ≥155 mg%• Plasma glucose at 3 hr ≥140 mg%

WHO Procedure• 75 gm of OGTT• If 2 hr value ≥140 mg% positive for GDM• This is parallel to impaired glucose tolerance

in non-pregnant women

• ADVANTAGES:• Need not be fasting• Least disturbances in pregnant women’s

routine activities• Serves as both screening & diagnostic

procedures

Glycemic criteria for diagnosis of different categories of glucose intolerance by 75 gm, 2 hr OGTT

Criteria Fasting plasma glucose

2 hr plasma glucose

Normal glucose tolerance <100 mg% <140 mg%

Impaired fasting glucose 100-125 mg% -

Impaired glucose tolerance

- 140-199 mg%

Diabetes mellitus ≥126 mg% ≥200 mg%

Plasma glucose In pregnancy Outside pregnancy

2 hr ≥200 mg% DM DM

2 hr 140-199 mg% GDM IGT

2 hr 120-139 mg% GGI Normal

2 hr <120 mg% Normal Normal

Maternal complicationsEffects of diabetes on mother Effects of pregnancy on

diabetes1st trimester – risk of recurrent abortions More insulin is necessary to achieve

metabolic control

Infection – chorioamnionitis & postpartum endometritis

Progression to diabetic retinopathy

Pre eclampsia – 10-25 % Worsening of diabetic nephropathy

Postpartum bleeding Increased risk of death for patients with diabetic cardiomyopathy & MI

Caesarian section – due to fetal macrosomia & CPD

Fetal complications

• Congenital abnormalities – due to metabolic derangements present at the time of conception, during blastogenesis & organogenesis

• Hyperglycmia macrosomia traumatic delivery• Hypocalcemia• Intermittent hypoglycemia IUGR• Hyperviscosity syndrome• Hyaline membrane disease• Apnoea & bradycardia• Unexplained fetal demise (last 4-8 weeks of gestation)

Effect on fetal growth

Maternal hyperglycemia priming (16 weeks)

fetal pancreas

increased beta cell mass

Increased insulin secretion

Persistent fetal hyperinsulinemia

Over growth of insulin-sensitive tissue(mainly adipose tissue)

Accelerated fetal growth(fetal macrosomia)

Macrosomic baby !

Neonatal complications

• Respiratory distress• Hypoglycemia• Hypocalcemia• Hyperbilirubinemia• Cardiac hypertrophy• Long term effects on cognitive development

Inter-generational effect !!!

GDM

DM in offspring

GDM

DM in offspring GDM……………………….....

Management of GDM

obstetricianDiabetologist

/physician

pediatrician dietician

Components of GDM management

Medical Nutrition Therapy (MNT)1

2 Physical activity

3 Pharmacological therapy

Medical Nutrition Therapy (MNT)

• Adequate calories & nutrients• Expected weight gain: 300-400gm/week• Total weight gain: 10-12 kg• Obese pregnant women: 5-6 kg• Meal plan: to provide sufficient calories to

sustain adequate nutrition for mother & fetus to avoid excess weight gain & PP

hyperglycemia

Medical Nutrition Therapycontd…

• Calorie requirement depends on age, pre-pregnancy weight, activity & gestational week of pregnancy

• Increase of 300kcal/day above basal requirement is needed in 2nd & 3rd trimester

Calorie counting

• Distributing calorie consumption especially break fast

• Splitting the usual break fast into 2 equal halves with a gap of 2 hr in between

• Undue peak in plasma glucose levels after ingestion of the total quantity of break fast at one time is avoided

• >90% of GDM can be managed by MNT

Physical Activity

Exercises that use upper body muscles or those exercises which place little mechanical stress

Brisk walking or arm exercise while seated in a chair for at least 10 mins after each meal

Planned physical activity – those who are capable of participating

Glycemic targets

Effects of 2 hr PG on offspring

Acute Chronic If 2 hr PG >140mg%

Increase in birth weight, neonatal adiposity, cord c peptide level >90th percentile

If 2 hr PG in 3rd trimester 120-139mg%

Risk of having T2DM at 24 years -19%

If 2 hr PG in 3rd trimester 140-199mg%

Risk of having T2DM at 24 years -30%

Diagnosis of GDM

In 1st & 2nd trimester in 3rd trimester

MNT for 2 weeks MNT for 1 week

if fails if fails Insulin therapy insulin therapy

Insulin therapy

Pre-mix insulin 30/70 4 U – 0 – 0 If target glycemic levels not achieved increase 2 units every 4th day (max 10 U)

If FPG >90mg% 6 U – 0 – 4 U

If 2 hr PG is >200mg% 8 U – 0 – 0

General concepts in insulin therapy• Start with possible lowest effective dose• Of the total insulin dose 2/3 in morning, 1/3 in evening• Of the total insulin dose 1/3 is regular insulin, 2/3 is basal

insulin• Increase gradually every 4th day according to FBS/PPBS values• If PPBS is high, increase the dose of regular insulin in the morning• If FBS is high, add basal insulin at night• Insulin requirements increased by 50% from 20-24 weeks to 30-32

weeks• GDM women don’t require >20 units/day• Pre-GDM women during pregnancy may require higher doses• Insulin dosages is always individualized & adjusted on follow up

OADs

• Tolbutamide, chlorpropamide, glipizide diffuse across placenta freely – fetal hyperinsulinemia & prolonged neonatal hypoglycemia

• Glyburide crosses the placenta the least• Fetal concentration of glibenclamide reaches not

more than 1-2% of maternal levels – not associated with excess anomalies or hypoglycemia

• Glybenclamide – safe & equally effective as insulin

Metformin

• Safe for use in GDM• Alone or in combination with insulin – not

associated with increased perinatal complications as compared to insulin

• Combined treatment with both insulin & metformin – req lower dose of insulin, lesser weight gain than those on insulin alone

USG fetal measurements

• Done in every trimester• Fetal echo –must at 24 weeks to R/O cardiac

defects• Fetal biophysical profile in late trimester• Doppler umbilical blood flow measurement or

CTG at 36 weeks in GDM with other pregnancy complications PE, HTN, APH, IUGR

Timing of delivery

• Delivery before full term avoided, unless there is e/o macrosomia, polyhydramnios, poor metabolic control & other obstetric indications

• Increased obstetric interventions (induction, caesarian section)

Delivery

• Maintain good glycemic control during labour• Avoid hypoglycemia• Lower insulin requirements are common

(often no insulin is necessary)• Blood sugar monitoring after delivery, 24 hrs

postpartum if found to be high, follow up• Presence of neonatologist –must.

Plasma glucose & Insulin/ iv fluids during labour

Blood sugar at the onset of labour

Insulin /iv fluids

< 70 mg% 5% GNS @ 100ml/hr

90-120mg% NS @ 100ml/hr

120-140mg% 4 units HA in 1 pint NS @ 100ml/hr

140-180mg% 6 units HA in 1 pint NS @ 100ml/hr

>180mg% 8 units HA in 1 pint NS @ 100 ml/hr

Neonatal management

• Normal birth weight: 2.5-3.5 kg• Monitoring for respiratory distress• Capillary blood glucose at 1, 2, 4 hrs after

delivery & before feeding (cut off 44mg%)• Early breast feeding• In nursing PreGDM mothers good glycemic

control during lactation, by insulin.

Follow up in GDM

OGTT with 75 gm oral glucose (WHO criteria) at 6-8 weeks postpartum if normal

twice yearly or yearly follow up

• Considerable proportion of GDM women continue to have glucose intolerance

• Counselling • Increased risk of T2DM, metabolic syndrome• Healthy eating & exercise pattern• Planning future pregnancy contraceptive

advice & counselling• Pre conception OGTT

Carry home messages……..• Universal screening at 1st trimester, possibly at 1st ante natal visit

• Use WHO criteria with single step procedure

• Start insulin with possible lowest effective dose & stick into the insulin protocol

• FBS maintained ≤90mg%; PPBS maintained ≤120mg%

• USG & other fetal mesurements should be done at every trimester

• Proper obstetric interventions (induction, C.S.) should be needed at proper time

• Good glycemic control should be achieved during labour by using proper insulin & IV fluids as per the protocol

• Post partum follow up is must

PREGNANCY & THYROID DISORDER

Changes in Thyroid gland

asialo hCG

increase in Sr.TG conc.

Thyroid gland

enlarges by an average of 18%

Thyrotropic effect of

hCG & asialo-hCG

Increased estrogen

Increased hepatic synthesis & decreased metabolic

clearance of TBG

Increased TBG

Increased total T4 & T3Free T4 & T3 conc. Normal

5 factors that alter Thyroid function in Pregnancy

1. Transient increase in hCG during 1st trimester stimulates TSH-R (transient gestational hyperthyroidism)

2. Estrogen induced increase in TBG3. Alterations in immune system onset, exacerbation

or amelioration of underlying autoimmune thyroid disease

4. Increase thyroid hormone metabolism by placenta5. Increase in urinary iodide excretion decreased

thyroid hormone production in areas of marginal iodine deficiency

Hypothyroidism in pregnancy

• Women with a h/o or high risk of hypothyroidism ensure euthyroid prior to conception & during early pregnancy

Whom to screen?

• if they have goiter/features of hypothyroidism

• family h/o autoimmune thyroid disease

When to evaluate?

• Prior to conception

• Immediately after pregnancy is confirmed

• At the beginning of 2nd & 3rd trimester

Maternal hypothyroidism

Adversely affect

Fetal neural developmen

t

Treatment of Hypothyroidism in pregnancy

• Levothyroxine is the drug of choice

• Usual dosage in non-pregnant state 1.6 mcg/kg/day (typically 100-150 mcg/day)

• Dose is increased by ≥50% during pregnancy

• Returned to previous levels after delivery

Diagnosis of thyrotoxicosis during pregnancy

• Decrease in Sr.TSH levels <0.1mU/L• In 8-14 weeks hCG causes stimulation of

thyroid gland only modest suppression of TSH (0.1-0.4 mU/L)

• Confirmation of thyrotoxicosis Sr.TSH <0.1mU/L; increase in free T4

TSH

Treatment of thyrotoxicosis in pregnancy

Anti Thyroid Drugs

• Propyl thio uracil (PTU) usual initial dose is 100-200 mg every 6-8 hr

• Carbimazole / Methimazole usual initial dose is 10-20 mg every 8-12 hr

• MOA: all drugs inhibit the function of TPO, reducing oxidation & organification of iodide

Anti thyroid drug of choice in pregnancy

PTU

Anti Thyroid Drugs

• No greater risk to mother & fetus• Medical treatment is the treatment of choice• Dosage of ATD required to control the disease

in later phases of pregnancy is decreased ( because of usual improvement in disease due to immunosuppression decrease in TRAb in pregnancy)

• PTU & methimazole crosses placenta concentrated in fetal thyroid goiterous hypothyroidism in fetus

• 150 mcg/day of PTU to mother decrease fetal free T4 & increase TSH

• PTU >200mcg/day especially in 3rd trimester fetal goiter & neonatal respiratory distress

• Sr. free T4 should be maintained in upper normal range; no attempt made to normalize Sr.TSH conc.

• Daily maintenance dose of PTU ≤200mcg/day in early pregnancy

• PTU is the drug of choice • Pregnant women with Grave’s disease –

monitoring fetus for intrauterine thyroid dysfunction (fetal heart rate, USG assessment of fetal growth rate, presence of goiter)

• If dosage requirement >200mcg/day: indication for subtotal thyroidectomy (in 2nd trimester)

• Beta blocker: IUGR, delayed lung development, neonatal hypoglycemia, (can be given in lower dose for short period)

• Post partum period is a time of major risk of relapse

• Breast feeding is safe with lower doses of anti thyroid drugs

A common clinical problem

• Parallels influence of maternal hypothyroidism on fetal brain development & decreased IQ

• Better to maintain in slightly hyperthyroid state rather than slightly hypothyroid state

Over-treatment of hyperthyroidism

Carry home message…….• Transient gestational hyperthyroidism is common in 1st

trimester (TSH level should be <0.1mU/L to diagnose thyrotoxicosis)

• Look at free T4 & T3; not total T4 & T3• PTU is the drug choice – dose in early pregnancy is <200

mcg/day; later phases <150 mcg/day• Radio iodine treatment is contraindicated• Subtotal thyroidectomy – indicated in 2nd trimester, if the

need of PTU >200 mcg/day• Over treatment of hyperthyroidism is a common clinical

problem• Keep Sr. free T4 in upper level of normal range