In utero and lactational exposure to the Selective Serotonin Reuptake Inhibitor fluoxetine compromises pup bones at weaning

Abstract

Selective Serotonin Reuptake Inhibitors (SSRIs) such as fluoxetine are widely prescribed to pregnant and breastfeeding women, yet the effects of peripartum SSRI exposure on neonatal bone are not known. In adult populations, SSRI use is associated with compromised bone health, and infants exposed to in utero SSRIs have a smaller head circumference and are shorter, suggesting possible effects on longitudinal growth. Yet no study to date has examined the effects of peripartum SSRIs on long bone growth or mass. We used microCT to determine the outcomes of in utero and lactational SSRI exposure on C57BL6 pup bone microarchitecture. We found that peripartum exposure to 20 mg/kg fluoxetine reduced femoral bone mineral density and bone volume fraction, negatively impacted trabecular and cortical parameters, and resulted in shorter femurs on postnatal day 21. Although SSRIs are considered the first-choice antidepressant for pregnant and lactating women due to a low side effect profile, SSRI exposure may compromise fetal and neonatal bone development.

Peripartal treatment with low‐dose sertraline accelerates mammary gland involution and has minimal effects on maternal and offspring bone

“…Offspring serum calcium concentrations were unchanged throughout lactation and were unaffected by sertraline treatment, suggesting that although milk calcium content was mildly decreased, the offspring still received adequate calcium from the diet. Offspring exposed to fluoxetine during pregnancy and lactation had shorter long bones and a decreased head circumference (Weaver et al, 2019 ), but we did not observe a change in long bone length with sertraline treatment. This suggests in utero and lactational exposure to sertraline does not impact offspring bone formation.…”

“…In utero and lactational exposure to fluoxetine impaired offspring trabecular and cortical bone, resulting in decreased trabecular BV/TV and increased cortical porosity (Weaver et al, 2019 ). We therefore examined if in utero and lactation exposure to sertraline similarly decreased offspring bone.…”

“…Previously, we demonstrated that peripartum fluoxetine treatment results in a sustained reduction of maternal BMD compared to pregnancy and lactation alone (Weaver et al, 2018 ). Additionally, in utero and lactational exposure to fluoxetine reduced offspring long bone length and reduced offspring head circumference (Weaver et al, 2019 ). Together, this raises concerns about long‐term bone health among women who are prescribed an SSRI during pregnancy and lactation and how exposure to an SSRI impacts the developing offspring.…”

“…Different SSRIs, and different pharmacological doses of SSRIs, have been shown to have differential effects on bone microarchitecture in non-lactation models and have disparate effects on the developing offspring when taken throughout pregnancy (Koren & Nordeng, 2012;Kumar et al, 2018). Given our previous study with fluoxetine demonstrating reduced maternal bone mass as well as reduced offspring bone formation (Weaver et al, 2018(Weaver et al, , 2019, it raised the question whether these effects are fluoxetine-specific or consistent across the class of SSRIs. Therefore, we investigated the most prescribed peripartum SSRI, sertraline (Zoloft ™ ), on maternal calcium trafficking and BMD to determine if maternal bone mass effects vary among SSRIs.…”

Influence of Serotonin on the Metabolism of Bone Tissue

“…[76] Вважають, що флуоксетин впливає безпосередньо на кістки, гальмуючи розвиток скелета. Зроблено висновок про важливість вивчення впливу різних класів та доз СІЗЗС під час вагітності та лактації на здоров'я скелета потомства [78].…”