Additionally, the mother was of African origin, which further increases her risk of gestational diabetes. Therefore, olanzapine seems a plausible cause of this baby’s hypoglycaemia, either through direct action on the infant’s basal insulin levels, or via undiagnosed maternal gestational diabetes. Olanzapine has an in vivo placental passage ratio of 72.2% [Newport et al. 2007], and several case reports on its use have described uneventful pregnancies and healthy Inhibitors,research,lifescience,medical infants. The

largest study to date found that olanzapine did not increase the risk of major congenital malformations, but was associated with a higher maternal BMI, maternal gestational diabetes and low birth weight [Reis and Kallen, 2008]. Another prospective study also reported a Inhibitors,research,lifescience,medical tendency towards low birth weight and neonatal intensive care admission [McKenna et al. 2005]. In contrast, others have linked maternal olanzapine with a higher incidence of large for gestational age (LGA) infants and higher mean birth weight [Babu et al. 2010; Inhibitors,research,lifescience,medical MacRitchie et al. 2006; Newham et al. 2008]. Predisposing factors for LGA infants include maternal obesity, type 1 diabetes mellitus, gestational diabetes mellitus and maternal weight gain, all conditions that

have been shown to be exacerbated or precipitated by some antipsychotics, including olanzapine. However, a large recent linkage study has found that women taking antipsychotic medication during pregnancy have an increased risk of gestational diabetes and a higher incidence of SGA infants [Boden et al. 2012]; olanzapine and clozapine therapy

were not associated with a higher incidence Inhibitors,research,lifescience,medical of gestational diabetes compared with other antipsychotics. Also of note was that the high incidence of SGA infants born Inhibitors,research,lifescience,medical to women on antipsychotics was explained by confounders such as smoking, which is a possible cause in this case. The mechanism for an olanzapine-induced metabolic syndrome is not well understood. However, the insulin below resistance induced by olanzapine treatment is rapid, Vemurafenib solubility dmso occurring within days, separately from weight gain [Ebenbichler et al. 2003]. Potential causative mechanisms may involve free fatty acids, leptin and tumour necrosis factor α [Kahn and Flier, 2000]. Studies have also shown that weight gain is due to the accumulation of white adipose tissue, and that low-grade adipose inflammation may play a role in this [Victoriano et al. 2010]. Conclusion Olanzapine exposure during pregnancy was associated with neonatal hyperinsulinaemia in the absence of proven gestational diabetes. Given the mechanisms discussed above, olanzapine is a potential causative agent either acting directly on the infant’s own glucose metabolism or indirectly via the mother.