Table 3.

Effects of prenatal or early life exposure to valproate in children and laboratory animals.

Valproate	Effects on offspring of maternal AED use		Effects on offspring of early postnatal use
	Human	Rodent	Human	Rodent
Somatic
General body size	Decreased	Mixed results, high mortality	Short stature, high BMI	Decreased weight gain
Facial features	Dysmorphic
Limbs, skeleton	Dysmorphic	Dysmorphic
Developmental milestones	Decreased Apgar scores, motor delays	Delayed eye opening, righting reflexes		Delayed eye opening, righting reflexes
CNS
General brain size	Decreased	Decreased		Decreased brain weight
Specific brain areas	Decreased gray matter
Cerebellum		Decreased		High doses lead to apoptosis
Hippocampus				High doses lead to apoptosis
Sensory systems		Impaired olfaction, decreased pain	Impaired visuospatial function
Motor systems	Hypertonia	Hyperactivity, impaired on rotarod	Impaired motor performance	Impaired fine motor performance
Cognitive functions
IQ, BMDI score	Low IQ
Learning and memory	Delayed	General impairments	Improvements (*)	General impairments
Behavior
Mood (depression)	Increased depression
Attention deficits	Poor attention
Autistic-like behavior	6–8-fold increased risk	Decreased play, increased stereotypies		Decreased play
Schizophrenia-like		Pre-pulse inhibition deficits		Pre-pulse inhibition deficits
Anxiety	Perinatal distress/low adaptability	Increased anxiety-like behaviors

Somatic, cognitive and behavioral effects are shown for prenatal exposure (left) and early postnatal exposure (right). The table indicates common findings, and where variability is noted, it may be due to differences in the study parameters/methods, doses, or times of exposure.

^*indicates conflicting reports in the literature. References are provided in the text.

Abbreviation: BMDI, Bayley Mental Developmental Index.