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Effect of atypical antipsychotics on fetal growth: is the placenta involved?

Raha S, Taylor VH, Holloway AC - J Pregnancy (2012)

Bottom Line: These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function.However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development.The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, McMaster University, 1200 Main Street West, Room 3N11, Hamilton, ON, Canada L8N 3Z5. rahas@mcmaster.ca

ABSTRACT
There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both increased and decreased, with maternal atypical antipsychotic use. These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function. However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development. The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive. This paper focuses on some possible pathways which may link atypical antipsychotics to placental dysfunction.

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Related in: MedlinePlus

Atypical antipsychotics may impact fetal growth, by altering placental function. Atypical antipsychotics (AA) such as Clozapine are known to effect liver and pancreas function. Such effects can result in altered systemic glucose levels. During pregnancy, this can result in gestational diabetes or contribute to increased nutrient transport across the placenta. In addition, AA can be directly transported across the maternal-fetal interface and potentially impact fetal metabolic balance. However, AAs in the maternal system could impact placental development or function and alter the release of endocrine factors which would impact on fetal growth and development. *Adapted from [72].
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fig1: Atypical antipsychotics may impact fetal growth, by altering placental function. Atypical antipsychotics (AA) such as Clozapine are known to effect liver and pancreas function. Such effects can result in altered systemic glucose levels. During pregnancy, this can result in gestational diabetes or contribute to increased nutrient transport across the placenta. In addition, AA can be directly transported across the maternal-fetal interface and potentially impact fetal metabolic balance. However, AAs in the maternal system could impact placental development or function and alter the release of endocrine factors which would impact on fetal growth and development. *Adapted from [72].

Mentions: There is compelling evidence that obesity in women, whether as a result of prepregnancy obesity, excessive gestational weight gain, and/or postpartum weight retention, is associated with an increased risk for many pregnancy-related health complications such as gestational diabetes and hypertensive disorders of pregnancy [60, 61]. In addition, maternal obesity also considerably increases the risk of fetal complications such as spontaneous abortion, stillbirth, congenital anomalies, neonatal death, and altered fetal growth. Indeed, in humans, obesity during pregnancy is associated with a significantly increased risk of macrosomia (commonly defined as birth weight ≥4500 g (8 lb 13 oz to 9 lb 15 oz)) as well as an increased risk of delivering a low birth weight baby [43, 60, 62–66]. Similarly, animal studies have also shown that maternal overweight and obesity results in altered fetal growth with reports of both increased and decreased birth weight [30, 67–69]. Therefore, based on the well-documented relationships between maternal obesity/diabetes and altered fetal growth, it is plausible that the altered fetal growth in women taking atypical antipsychotics may be a reflection of antipsychotic-induced changes in maternal metabolic or nutritional status [70]. In addition to the impact of maternal metabolic status on the pregnancy, atypical antipsychotics may also be transferred across the placenta and directly impact fetal growth. While there is limited evidence quantifying the extent to which these drugs are transferred across the placenta, the work of Schenker et al. [71] suggests that somewhere in the range of 5–14% of a labeled olanzapine can be transferred from maternal to fetal system in 4 h. However, the effects of atypical antipsychotics on fetal growth may be also mediated via altered placental development and/or function (Figure 1).


Effect of atypical antipsychotics on fetal growth: is the placenta involved?

Raha S, Taylor VH, Holloway AC - J Pregnancy (2012)

Atypical antipsychotics may impact fetal growth, by altering placental function. Atypical antipsychotics (AA) such as Clozapine are known to effect liver and pancreas function. Such effects can result in altered systemic glucose levels. During pregnancy, this can result in gestational diabetes or contribute to increased nutrient transport across the placenta. In addition, AA can be directly transported across the maternal-fetal interface and potentially impact fetal metabolic balance. However, AAs in the maternal system could impact placental development or function and alter the release of endocrine factors which would impact on fetal growth and development. *Adapted from [72].
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig1: Atypical antipsychotics may impact fetal growth, by altering placental function. Atypical antipsychotics (AA) such as Clozapine are known to effect liver and pancreas function. Such effects can result in altered systemic glucose levels. During pregnancy, this can result in gestational diabetes or contribute to increased nutrient transport across the placenta. In addition, AA can be directly transported across the maternal-fetal interface and potentially impact fetal metabolic balance. However, AAs in the maternal system could impact placental development or function and alter the release of endocrine factors which would impact on fetal growth and development. *Adapted from [72].
Mentions: There is compelling evidence that obesity in women, whether as a result of prepregnancy obesity, excessive gestational weight gain, and/or postpartum weight retention, is associated with an increased risk for many pregnancy-related health complications such as gestational diabetes and hypertensive disorders of pregnancy [60, 61]. In addition, maternal obesity also considerably increases the risk of fetal complications such as spontaneous abortion, stillbirth, congenital anomalies, neonatal death, and altered fetal growth. Indeed, in humans, obesity during pregnancy is associated with a significantly increased risk of macrosomia (commonly defined as birth weight ≥4500 g (8 lb 13 oz to 9 lb 15 oz)) as well as an increased risk of delivering a low birth weight baby [43, 60, 62–66]. Similarly, animal studies have also shown that maternal overweight and obesity results in altered fetal growth with reports of both increased and decreased birth weight [30, 67–69]. Therefore, based on the well-documented relationships between maternal obesity/diabetes and altered fetal growth, it is plausible that the altered fetal growth in women taking atypical antipsychotics may be a reflection of antipsychotic-induced changes in maternal metabolic or nutritional status [70]. In addition to the impact of maternal metabolic status on the pregnancy, atypical antipsychotics may also be transferred across the placenta and directly impact fetal growth. While there is limited evidence quantifying the extent to which these drugs are transferred across the placenta, the work of Schenker et al. [71] suggests that somewhere in the range of 5–14% of a labeled olanzapine can be transferred from maternal to fetal system in 4 h. However, the effects of atypical antipsychotics on fetal growth may be also mediated via altered placental development and/or function (Figure 1).

Bottom Line: These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function.However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development.The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, McMaster University, 1200 Main Street West, Room 3N11, Hamilton, ON, Canada L8N 3Z5. rahas@mcmaster.ca

ABSTRACT
There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both increased and decreased, with maternal atypical antipsychotic use. These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function. However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development. The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive. This paper focuses on some possible pathways which may link atypical antipsychotics to placental dysfunction.

Show MeSH
Related in: MedlinePlus