CEREBELLAR HYPOPLASIA POSSIBLY DUE TO CARBAMAZEPINE


This was a 20 year old primi gravida on treatment for long standing seizure disorder ; she was on tab carbamazepine 200  mgm twice daily for a long time . The scan was done around 26 weeks of gestation.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2970517/ – this link discusses teratogenic effects of anti epileptic drugs.

Carbamazepine (CBZ) is an iminostilbene derivative used primarily in the management of epilepsy and trigeminal neuralgia.

Observational studies have shown that the use of CBZ in pregnancy is associated with a higher risk of MCMs ( Major Congenital Malformations ) in the exposed offspring.

Other investigations using different methodologies have failed to find an increased statistical risk of MCMs due to CBZ exposure .

Morrow et al. reported 20 MCMs among 900 CBZ-exposed pregnancies, which is a prevalence rate of 2.2% with 95% CI: 1.4–3.4 . This is the lowest risk for MCMs amongst all AED monotherapy exposures reported in the literature . When dosage was compared between healthy and malformed infants, there was no statistical significance (p = 0.56), suggesting that genetic factors are interacting with the CBZ exposure contributing disproportionately to the risk for MCMs.

Association between CBZ exposure and specific MCMs :

increased risk of orofacial clefts

cardiac malformations

 increased risk for NTDs 

The images are given below.

bpd corresponds to 25 w ga

bpd corresponds to 25 w ga

Cerebellum appears relatively smaller and corresponds to a GA of 22 to 23 weeks. Usually the cerebellum corresponds very closely to the GA  and would be very useful to follow in cases of IUGR.

 CARBAMAZEPINE CEREBELLAR HYPO_2

CARBAMAZEPINE CEREBELLAR HYPO_12

CARBAMAZEPINE CEREBELLAR HYPO_11

The following are 3 D  reconstructed sagittal and coronal images .

CARBAMAZEPINE CEREBELLAR HYPO_14 CARBAMAZEPINE CEREBELLAR HYPO_13

The following images show the face and the palate. 

CARBAMAZEPINE CEREBELLAR HYPO_3 CARBAMAZEPINE CEREBELLAR HYPO_4 CARBAMAZEPINE CEREBELLAR HYPO_5 CARBAMAZEPINE CEREBELLAR HYPO_6 CARBAMAZEPINE CEREBELLAR HYPO_7 CARBAMAZEPINE CEREBELLAR HYPO_8 CARBAMAZEPINE CEREBELLAR HYPO_9 CARBAMAZEPINE CEREBELLAR HYPO_10

The following images show the sections of the heart.

CARBAMAZEPINE CEREBELLAR HYPO_22 CARBAMAZEPINE CEREBELLAR HYPO_23 CARBAMAZEPINE CEREBELLAR HYPO_24 CARBAMAZEPINE CEREBELLAR HYPO_25

The following images show the spine.

CARBAMAZEPINE CEREBELLAR HYPO_20 CARBAMAZEPINE CEREBELLAR HYPO_21

The abdominal images are given below.

CARBAMAZEPINE CEREBELLAR HYPO_17 CARBAMAZEPINE CEREBELLAR HYPO_18 CARBAMAZEPINE CEREBELLAR HYPO_19

The limbs are shown below.

CARBAMAZEPINE CEREBELLAR HYPO_27 CARBAMAZEPINE CEREBELLAR HYPO_28 CARBAMAZEPINE CEREBELLAR HYPO_29

This fetus did not show any oro-facial clefts ; heart and spine appeared normal. 

Cerebellum was < 2.3 %tile , suggestive of possible cerebellar hypoplasia. Unfortunately this patient was lost for follow up . 

The following link gives more information about use of carbamazwpine in pregnancy.

http://www.drugs.com/pro/carbamazepine.html#_E434F86B-5F32-6E00-818D-B05080BAA2A6

Usage in Pregnancy

Carbamazepine can cause fetal harm when administered to a pregnant woman.

Epidemiological data suggest that there may be an association between the use of Carbamazepine during pregnancy and congenital malformations, including spina bifida. There have also been reports that associate Carbamazepine with developmental disorders and congenital anomalies (e.g., craniofacial defects, cardiovascular malformations, hypospadias and anomalies involving various body systems). Developmental delays based on neurobehavioral assessments have been reported. In treating or counseling women of childbearing potential, the prescribing physician will wish to weigh the benefits of therapy against the risks. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Retrospective case reviews suggest that, compared with monotherapy, there may be a higher prevalence of teratogenic effects associated with the use of anticonvulsants in combination therapy. Therefore, if therapy is to be continued, monotherapy may be preferable for pregnant women.

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