Part 17 (2/2)

SYNDROMES AND ISOLATED CONGENITAL ANOMALIES.

a.s.sOCIATED WITH ANTICONVULSANTS.

The range of dysmorphic features that have been a.s.sociated with exposure to anticonvulsants during embryogenesis is wide (Table 9.3). Syndromologists who are 'splitters'

a.s.sign a new syndrome name to each drug's collection of defects. Those who are 'lumpers' use the 'fetal anticonvulsant syndrome' as an umbrella for all the defects that occur with all anticonvulsants. On balance, each drug seems to have a signature constellation of anomalies, ranging from minor craniofacial dysmorphia to spina bifida (Table 9.3). Dysmorphic features a.s.sociated with older anticonvulsants have been studied extensively, but newer ones have not been studied as thoroughly.

The overall frequency of congenital anomalies was 4.2 percent among 3607 cases of anticonvulsant exposure during pregnancy in the UK Epilepsy and Pregnancy Register, a prospective, observational, registration, and follow-up study. Decomposing the rates among the congenital anomalies, 6.0 percent of infants exposed to polytherapy had congenital anomalies compared to 3.7 percent among those exposed only to monotherapy during gestation. Valproic acid was a.s.sociated with a higher frequency of congenital anomalies (6.3 percent) than other anticonvulsants in the study. Notably, high doses (>200 mg) of lamotrigene were a.s.sociated with an increased frequency of congenital anomalies (5.4 percent). Similarly, high doses of valproic acid (>800 mg) were a.s.sociated with a 9.1 percent congenital anomaly rate. When valproic acid was a component of Table 9.3 Table 9.3 Syndromic features a.s.sociated with exposure to antiepileptic drugs (AEDs) during embryogenesis Syndromic features a.s.sociated with exposure to antiepileptic drugs (AEDs) during embryogenesis Syndromes and isolated congenital anomalies a.s.sociated with anticonvulsants Syndromes and isolated congenital anomalies a.s.sociated with anticonvulsants Drug Drug Distinctive Facial Cleft lip/ Growth Microcephaly NTDs Hypoplastic distal CHD.

UGD.

facies clefting palate delay phalanges Carbemazepine +.

Clorazepam +.

Dionesa +.

Phen.o.barbital +.

Phenytoin +.

Primidone +.

Valproic acid +.

New generation AEDs Felbamate ?.

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