Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study.
<h4>Background</h4>Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0262987 |
| _version_ | 1819319880415969280 |
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| author | Sindre Grindheim Cathrine Ebbing Henriette Odland Karlsen Svein Magne Skulstad Francisco Gómez Real Marianne Lønnebotn Tone Løvvik Eszter Vanky Jørg Kessler |
| author_facet | Sindre Grindheim Cathrine Ebbing Henriette Odland Karlsen Svein Magne Skulstad Francisco Gómez Real Marianne Lønnebotn Tone Løvvik Eszter Vanky Jørg Kessler |
| author_sort | Sindre Grindheim |
| collection | DOAJ |
| description | <h4>Background</h4>Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life.<h4>Material and methods</h4>This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics.<h4>Results</h4>There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44-0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population.<h4>Conclusion</h4>Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life. |
| first_indexed | 2024-12-24T11:10:43Z |
| format | Article |
| id | doaj.art-34c040da4b4a4bacbbab41fef3171867 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T11:10:43Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-34c040da4b4a4bacbbab41fef31718672022-12-21T16:58:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01171e026298710.1371/journal.pone.0262987Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study.Sindre GrindheimCathrine EbbingHenriette Odland KarlsenSvein Magne SkulstadFrancisco Gómez RealMarianne LønnebotnTone LøvvikEszter VankyJørg Kessler<h4>Background</h4>Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life.<h4>Material and methods</h4>This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics.<h4>Results</h4>There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44-0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population.<h4>Conclusion</h4>Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.https://doi.org/10.1371/journal.pone.0262987 |
| spellingShingle | Sindre Grindheim Cathrine Ebbing Henriette Odland Karlsen Svein Magne Skulstad Francisco Gómez Real Marianne Lønnebotn Tone Løvvik Eszter Vanky Jørg Kessler Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study. PLoS ONE |
| title | Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study. |
| title_full | Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study. |
| title_fullStr | Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study. |
| title_full_unstemmed | Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study. |
| title_short | Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study. |
| title_sort | metformin exposure maternal pcos status and fetal venous liver circulation a randomized placebo controlled study |
| url | https://doi.org/10.1371/journal.pone.0262987 |
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