Early-onset fetal growth restriction treated with the long-acting phosphodiesterase-5 inhibitor tadalafil: a case report

Sakamoto, Mito; Osato, Kazuhiro; Kubo, Michiko; Nii, Masafumi; Tanaka, Hiroaki; Murabayashi, Nao; Umekawa, Takashi; Kamimoto, Yuki; Ikeda, Tomoaki

doi:10.1186/s13256-016-1098-x

Cited by 16 publications

(11 citation statements)

References 9 publications

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“…Tadalafil, a selective PDE5 inhibitor, has been used to treat pulmonary hypertension in pregnant women. We have recently shown a potential therapeutic effect for tadalafil on PE and FGR in small clinical trials 9–12 . In addition, our animal experiments have demonstrated that tadalafil treatment elevates maternal urinary excretion of cGMP and dilates the maternal blood sinuses in the placenta, which facilitates fetal growth 13 .…”

Section: Introductionmentioning

confidence: 99%

Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions

Tachibana

Umekawa

Yoshikawa

et al. 2019

Sci Rep

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We have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.

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Section: Introductionmentioning

confidence: 99%

Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions

Tachibana

Umekawa

Yoshikawa

et al. 2019

Sci Rep

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“…Recently, PDE5 inhibitors, which act by dilating arteries and increasing blood flow and are used to treat erectile dysfunction and pulmonary hypertension 6 , were suggested as a potential remedy for FGR 7 . Concurrently, our study showed that tadalafil, a selective PDE5 inhibitor, could be used in this manner [8][9][10][11][12] . However, the effect of L-NAME on the metabolic status of the offspring, as well as tadalafil's potential to modulate such outcomes, has not been investigated.…”

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confidence: 58%

Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring

Kawamura

Tanaka

Tachibana

et al. 2021

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We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.

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“…It is hypothesized that sildenafil citrate may improve the uteroplacental blood flow of EO-FGR-affected pregnancies. [3][4][5]…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase type 5 inhibitor use among pregnant and reproductive‐age women in the United States

Liu

Menzin

Woods

et al. 2020

Pharmacoepidemiology and Drug

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PurposeTo assess the prevalence and potential indications of PDE5 inhibitor use among pregnant and reproductive‐age women in the United States.MethodsWe identified women 15 to 50 years with a livebirth from January 2001 through March 2018 in Sentinel Database. We assessed the prevalence of PDE5 inhibitor use prior to and during pregnancy by trimester, identified potential on‐ and off‐label indications using predefined diagnosis codes recorded within 90 days before the estimated last menstrual period through delivery. Separately, we used data from IQVIA's National Prescription Audit and Total Patient Tracker to estimate the dispensed prescriptions for PDE5 inhibitors and the number of patients with PDE5 inhibitor prescriptions.ResultsWe identified approximately 3.3 million pregnancies during 2001 to 2018, 96 of which had PDE5 inhibitor use during pregnancy. Prevalence of PDE5 inhibitor use was 2.61, 0.62, and 0.62 per 100, 000 live‐born pregnancies during the first, second, or third trimesters, respectively. Among women exposed to a PDE5 inhibitor from 90 days before conception to the end of pregnancy, 25.0%, 31.1%, and 15.5% had a diagnosis code for fetal growth restriction, preeclampsia, and pulmonary arterial hypertension. In IQVIA data, an estimated 223, 000 prescriptions from July 2015 through June 2018 and 58, 000 women received prescriptions for PDE5 inhibitors in 2017, of whom approximately 15, 000 (26%) were aged 15 to 50 years.ConclusionWe found a low prevalence of PDE5 inhibitor use in pregnant and reproductive‐age women. Given the very low prevalence of use and the inconsistency of neonatal mortality data across STRIDER centers, the risk to public health is low at present.

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Early-onset fetal growth restriction treated with the long-acting phosphodiesterase-5 inhibitor tadalafil: a case report

Cited by 16 publications

References 9 publications

Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions

Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions

Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring

Phosphodiesterase type 5 inhibitor use among pregnant and reproductive‐age women in the United States

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