Thursday, 24 December 2009

Congenital adrenal hyperplasia in Pregnancy

Information on Congenital adrenal hyperplasia for Public

Congenital adrenal hyperplasia occurs as a result of gene mutation.

This results in defective glucocorticoid & mineralocorticoid synthesis.

Excellent Power point explaining congenital adrenal hyperplasia is here

Diagram explaining adrenal hormone synthesis

Mode of inheritance is autosomal recessive.

Clinical features

3 catergories of diseasse - depending on the type of mutation

(I)Salt Wasting(SW)

(II) Simple Virilising(SV)

(III) Non-Classic(NC)

The condition is usually diagnosed in infancy

(A) Female infant-ambigious genetalia

(B)Acute illness due to hyponatraemia (salt losing crisis due to mineralocorticoid defeciency)

90% due to 21 hydroxylase enzyme deficiency.These patients have both glucocorticoid & mineralocorticoid defeciency.

5-8% due to 11 hydroxylase deficiency.These patients have excess deoxycortisol, that shows mineralocorticoid activity,leading to hypertension.

How the disease affect pregnancy?
(A)Reduction in fertility , especially in patients with salt wasting type disease.

Reasons: (i) inadequate control of hyperandrogenism
(ii)Inadequate introitus due to poor surgical repair

(B) Disease inheritance by fetus

(C) Risk of Miscarriage,pre-eclampsia & IUGR increased

(D) Masculinization can lead to android type pelvis that may lead to failure to progress in labour.



2 Types of Clical problems

(I) Pregnant women with Congenital adrenal hyperplasia

(II)Women who is carrier for Congenital adrenal hyperplasia with previously affected child( or with a heterozygous partner)

Genetic counselling

(I) This is a autosomal recessive disorder.

(II)Prenatal diagnosis is possible with a battery of gene probes through chorionic villus sampling at 10 weeks

(III) In the past diagnosis made by estimation of 17 hydroxy progestrone & androgen levels in amniotic fluid.

(IV)Zygosity of partner for Congenital adrenal hyperplasia gene can be done.In case gene deletion ,30% of heterozygous , diagnosis can be made accurately.The other 70 % has gene mutation which can be mimicked by pseudo genes of normal individuals. So negative gene testing in the partner reduces the probability of heterozygosity from 1:50 to 1:70.

Differentiation of female genitalia occurs between 9-10 weeks,so even a diagnosis at 10weeks would be late in preventing masculinization of a female fetus with congenital adrenal hyperplasia.

Dexamethasone,the steroid which is capable of crossing the placenta, can be used to suppress the fetal adrenal gland to avoid masculinization. The therapy should be started at least by the fifth week.It may even be started preconceptually. This treatment regime isn't always successful in preventing masculinisation.

Maternal compliance is shown by reduced urinary cortisol or oestriol level.

If the chorionic villus sampling shows a female fetus with congenital adrenal hyperplasia(CAH), the treatment should be continued till delivery.In case of female fetus with congenital adrenal hyperplasia ,termination is also an option.

In a pregnancy with CAH in a male fetus or unaffected fetus the treatment should be discontinued.

Fetal sex determination by ultra sound scan is helpful as maternal androgen excess has minimal effects on male fetus.

Pregnant women with congenital adrenal hyperplasia
On the other hand some steroids can cause masculinization but patients need steroid to suppress their disease activity.However the placental aromatase activity is sufficient to prevent masculinization of fetus.

Hydrocortisone, cortisone acetate, prednisone, methylprednisolone are inactivated in the placenta but dexamethasone crosses the placenta and causes neonatal adrenal suppression.

Regular assessment of clinical status,serum electrolytes and serum androgen levels to adjust the glucocorticoid and mineralocorticoid therapy.

Generally the patients with 21-hydroxylase deficiency doesn't require alteration in dosage during pregancy.

Serum testosterone & free testosterone levels should me measured every 6 weeks in first trimester & every 8 weeks thereafter.Aim is to maintain free testosterone levels at high to normal levels for pregnancy.

Labour & delivery

Elective caesarean is indicated in patients who had genital reconstructive surgery.

Caesaren section rate among these patients is increased and this could be attributed to android type pelvis resulting from masculinization.

Stress dose glucocorticoid therapy ( Hydrocortisone 100 mg IM ) is indicated for patients undergoing labour.

Newborn should be examined for ambiguous genitalia.Female pseudohermaphroditism is either due to maternal hyperandrogenism or fetal 21 hydroxylase deficiency(if father is a carrier).

Affected fetuses would require steroid treatment but even the unaffted fetus would require short term steroid support when its adrenal activity is suppressed in utero as the result of treatment of mother.


1.Nelson-Piercy C. Handbook of obstetric medicine. Taylor & Francis; 2002.

2.Swiet MD. Medical disorders in obstetric practice. Wiley-Blackwell; 2002.


4.K. Hagenfeldt , P.O. Janson , G. Holmdahl , H. Falhammar , H. Filipsson , L. Frisén , M. Thorén , and A. Nordenskjöld
Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency Hum. Reprod. Advance Access published on July 1, 2008, DOI 10.1093/humrep/den118.Hum. Reprod. 23: 1607-1613.

Tuesday, 1 December 2009

Artificial heart valve in pregnancy

Preconceptual evaluation

cardiac function should be assessed-Clinical/Echo/Exercise testing
moderately or severely symptomatic (class III and IV) should be advised against pregnancy

(B)Fetal risks-abortion/prematurity/intrauterine growth restriction/congenital abnormalities-due to warfarin/inheritance in patient's with congenital heart disease

Inheritance of congenital heart disease

(C)Anticoagulation should be discussed-if anticoagulation is altered there is an increased risk thromboembolism. If thromboembolism occurs during pregnancy the risk to the fetus increased again.

(D) management planned by multi disciplinary team(Obstetrician/cardiologist/Cardiothoracic surgeon)

2 major types of valves

1.mechanical- Suggested INR is 3-4.Failure to anti coagulate could result in valve thrombosis and stroke.Subcutaneous heparin anti coagulation may inadequate in patients with artificial valves.
three categories : caged-ball tilting-disc bi leaflet valves prosthetic or homo graft-
three categories hetero grafts homo grafts auto grafts.

They don't require anti coagulation but shorter lives than mechanical valve.Patients may need anti coagulation if they develop Atrial fibrillation.

Opinion varies as to whether pregnancy accelerate homo graft valve deterioration.

Fetal risks of Warfarin
Chodrodysplasia punctata
Optic atropy

Factors determining the choice of anticoagulation
1.Site of valve replacement(mitral more thrombogenic aortic)

2.Type of valve ( ball & cage more thrombogenic than bi leaflet valves)

3.Past history of thromboembolic events

4.No of mechanical valves

5.patient choice

Anticoagulation regimens-3 broad possibilities

1.Warfarin throughout the pregnancy
2.Heparin & warfarin alternatively Heparin between 6-12 weeks & after 36 weeks
3.Heparin throughout the pregnancy

Aspirin is a useful adjunct when heparin is used.

If LMWH is used anti Xa levels should be monitored 4-6 hrs post injection.LMWH doesn't cross placenta

Advantages of LMWH

1.fewer bleeding complications
2.lower frequency of thrombocytopenia
3.lower incidence of osteoporosis
4.longer half life
5.more predictable dose response

The following is the commonly used regime

Conception is difficult to time & risk of congenital malformation is likely to be minimal in the first 4 weeks, so patient could conceive on warfarin.

Then patients are given intravenous heparin aiming to double APTT during 6-12 weeks.

Patient can be converted to warfarin from 12 weeks.

At 37 weeks patient us converted to continuous intravenous heparin.

If patients goes into labour while on warfarin vitamin K & FFP should be given & heparin should be commenced.
Heparin & LMWH can be reversed with protamine sulphate.

Postpartum patient continues on heparin for 3-7 days.Patient can breast feed while in heparin or warfarin.

Patients on dindevan shouldn't breast feed.

Antibiotic prophylaxis is indicated in patient with artificial valve.
Current recommendations amoxicillin 2g i.v & gentamicin 1.5 mg/kg i.v

Heart failure in pregnancy

medicine that can be used:digoxin, diuretics, nitrates, hydralazine, and
beta blockers.

medicine that should be avoided:angiotensin-converting enzyme
inhibitors and angiotensin receptor antagonist amiodarone sodium nirtotroprusside

Valve thrombosis in pregnancy

Thrombolysis is the first line approach
Surgery is reserved for patients in thrombolysis is contraindicated.

Patient information leaflet :Breast feeding while on anticoagulation


1.Nelson-Piercy C. Handbook of obstetric medicine. Taylor & Francis; 2002.

2.Swiet MD. Medical disorders in obstetric practice. Wiley-Blackwell; 2002.

3.Elkayam U, Bitar F. Valvular Heart Disease and Pregnancy: Part II: Prosthetic Valves. J Am Coll Cardiol. 2005 Aug 2;46(3):403-410.

4.The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

Evidence-Based Guidelines