Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring

Journal article


Panagiotopoulou, O., Syngelaki, A., Georgiopoulos, G., Simpson, J., Akolekar, R., Shehata, H., Nicolaides, K. H. and Charakida, M. 2020. Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring. American Journal of Obstetrics and Gynecology. https://doi.org/10.1016/j.ajog.2020.01.054
AuthorsPanagiotopoulou, O., Syngelaki, A., Georgiopoulos, G., Simpson, J., Akolekar, R., Shehata, H., Nicolaides, K. H. and Charakida, M.
Abstract

BACKGROUND: Maternal obesity increases the risk for pregnancy complications and adverse neonatal outcome and it has also been associated with long lasting adverse effects in the offspring, including increased body fat mass, insulin resistance and increased risk for premature cardiovascular disease. Lifestyle interventions in pregnancy have produced none or modest effects in reducing adverse pregnancy outcomes in obese mothers. Metformin use in Obese Pregnant women trial was associated with reduced adverse pregnancy outcomes and had no effect on birthweight. However, the long-term implications of metformin on the health of offspring remain unknown.

OBJECTIVE: The purpose of this study was to assess whether prenatal exposure to metformin can improve the cardiovascular profile and body composition in the offspring of obese mothers.

STUDY DESIGN: In 151 children from the Metformin use in Obese-Pregnant women trial we measured body composition, peripheral blood pressure and arterial pulse wave velocity. Central hemodynamics (central blood pressure and augmentation index) were estimated using the Vicorder device. Left ventricular cardiac function and structure were assessed by echocardiography.

RESULTS: Children were 3.9±1.0 years of age and 77 were exposed to metformin prenatally. There was no significant difference in peripheral blood pressure, arterial stiffness and body composition apart from gluteal and tricep circumferences which were lower in the metformin group (p<0.05). The metformin, compared to the placebo group, had lower central hemodynamics (mean adjusted decrease - 0.707mmHg for aortic systolic blood pressure, -1.65mmHg for aortic pulse pressure and -2.68% for augmentation index, p<0.05 for all) and lower left ventricular diastolic function (adjusted difference in left atrial area -0.525cm2, in isovolumic relaxation time -0.324msec and in pulmonary venous systolic wave 2.97cm/s, p<0.05 for all). There were no significant differences in metabolic profile between the groups.

CONCLUSION: Children of obese mothers who were prenatally exposed to metformin, compared to those exposed to placebo, have lower central hemodynamic and cardiac diastolic indices. These results suggest that administration of metformin in obese pregnant women may potentially have a beneficial cardiovascular effect for their offspring.

KeywordsObesity; Pregnancy; Children; Prenatal exposure; Offspring outcome; Placebo; Follow up
Year2020
JournalAmerican Journal of Obstetrics and Gynecology
PublisherElsevier
ISSN0002-9378
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ajog.2020.01.054
Official URLhttps://doi.org/10.1016/j.ajog.2020.01.054
Publication dates
Online01 Feb 2020
Publication process dates
Accepted27 Jan 2020
Deposited11 May 2020
Accepted author manuscript
License
Output statusPublished
Permalink -

https://repository.canterbury.ac.uk/item/8v3q6/metformin-use-in-obese-mothers-is-associated-with-improved-cardiovascular-profile-in-the-offspring

  • 36
    total views
  • 14
    total downloads
  • 4
    views this month
  • 1
    downloads this month

Export as

Related outputs

Second trimester contingent screening for small for gestational age neonates.
Nowacka, U, Papastefanou, I., Bouariu, A, Syngelaki, A., Akolekar, R. and Nicolaides, K H 2021. Second trimester contingent screening for small for gestational age neonates. Ultrasound in Obstetrics & Gynecology. https://doi.org/10.1002/uog.23730
Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and updated meta‐analysis
Judah, H., Gil, M., Syngelaki, A., Galeva, S., Jani, J., Akolekar, R. and Nicolaides, K. H. 2021. Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and updated meta‐analysis. Ultrasound in Obstetrics & Gynecology. 58 (4), pp. 178-189. https://doi.org/10.1002/uog.23648
Fetal loss after chorionic villus sampling in twin pregnancies
Elger, T., Akolekar, R., Syngelaki, A., De Paco Matallana, C., Molina, F. S., Gallardo Arozena, M., Chaveeva, P., Persico, N., Accurti, V., Kagan, O., Prodan, N., Cruz, J. and Nicolaides, K. H. 2021. Fetal loss after chorionic villus sampling in twin pregnancies. Ultrasound in Obstetrics & Gynecology. 58 (1), pp. 48-55. https://doi.org/10.1002/uog.23694
Evaluation of the RCOG guideline in the prediction of small for gestational age neonates and comparison with the competing risks model.
Papastefanou, I., Nowacka, Urszula, Buerger, Olga, Akolekar, Ranjit, Wright, David and Nicolaides, Kypros H 2021. Evaluation of the RCOG guideline in the prediction of small for gestational age neonates and comparison with the competing risks model. BJOG: An International Journal of Obstetrics & Gynaecology. https://doi.org/10.1111/1471-0528.16815
Kielland’s rotational forceps delivery: comparison of maternal and neonatal outcomes with pregnancies delivering by non-rotational forceps
Giacchino, Tara, Karkia, Rebecca, Zhang, W., Ahmed, Hasib and Akolekar, Ranjit 2021. Kielland’s rotational forceps delivery: comparison of maternal and neonatal outcomes with pregnancies delivering by non-rotational forceps. Journal of Obstetrics and Gynaecology. https://doi.org/10.1080/01443615.2021.1907557
Reference ranges for the pulsed wave doppler of the fetal cardiac inflow and outflow tracts from 13 to 36 weeks gestation: Short title: Zidere, Fetal inflow and outflow tract, Pulsed wave Doppler, z scores.
Zidere, V., Vigneswaran, T. V., Syngelaki, A., Charakida, M., Allan, L. D., Nicolaides, K. H., Simpson, J. M and Akolekar, R. 2021. Reference ranges for the pulsed wave doppler of the fetal cardiac inflow and outflow tracts from 13 to 36 weeks gestation: Short title: Zidere, Fetal inflow and outflow tract, Pulsed wave Doppler, z scores. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography. https://doi.org/S0894-7317(21)00467-3
Perinatal outcome of pregnancies with prenatal diagnosis of vasa previa: systematic review and meta‐analysis
Zhang, W., Geris, S., Al‐Emara, N., Ramadan, G., Sotiriadis, A. and Akolekar, R. 2021. Perinatal outcome of pregnancies with prenatal diagnosis of vasa previa: systematic review and meta‐analysis. Ultrasound in Obstetrics & Gynecology. 57 (5), pp. 710-719. https://doi.org/10.1002/uog.22166
Value of routine ultrasound examination at 35-37 weeks' gestation in diagnosis of fetal abnormalities
Ficara, A., Syngelaki, A., Hammami, A., Akolekar, R. and Nicolaides, K. H. 2020. Value of routine ultrasound examination at 35-37 weeks' gestation in diagnosis of fetal abnormalities. Ultrasound in Obstetrics and Gynecology. 55 (1), pp. 75-80. https://doi.org/10.1002/uog.20857
Diagnosis of fetal defects in twin pregnancies at routine 11-13-week ultrasound examination
Syngelaki, A., Cimpoca, B., Litwinska, E., Akolekar, R. and Nicolaides, K. H. 2020. Diagnosis of fetal defects in twin pregnancies at routine 11-13-week ultrasound examination. Ultrasound in Obstetrics and Gynecology. 55 (4), pp. 474-481. https://doi.org/10.1002/uog.21938
ISUOG Consensus Statement on organization of routine and specialist obstetric ultrasound services in the context of COVID-19
Abu-Rustum, R. S., Akolekar, R., Sotiriadis, A., Salomon, L. J., Da Silva Costa, F., Wu, Q., Frusca, T., Bilardo, C. M., Prefumo, F. and Poon, L. C. 2020. ISUOG Consensus Statement on organization of routine and specialist obstetric ultrasound services in the context of COVID-19. Ultrasound in Obstetrics and Gynecology. https://doi.org/10.1002/uog.22029
Comparison of different methods of measuring angle of progression in prediction of labor outcome
Frick, A., Kostiv, V., Vojtassakova, D., Akolekar, R. and Nicolaides, K. H. 2020. Comparison of different methods of measuring angle of progression in prediction of labor outcome. Ultrasound in Obstetrics & Gynecology. 55 (3), pp. 391-400. https://doi.org/10.1002/uog.21913
Value of routine ultrasound examination at 35–37 weeks' gestation in diagnosis of non‐cephalic presentation
De Castro, H., Ciobanu, A., Formuso, C., Akolekar, R. and Nicolaides, K. H. 2020. Value of routine ultrasound examination at 35–37 weeks' gestation in diagnosis of non‐cephalic presentation. Ultrasound in Obstetrics & Gynecology. 55 (2), pp. 248-256. https://doi.org/10.1002/uog.21902
Impaired placental perfusion and major fetal cardiac defects
Fantasia, I., Andrade, W., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Impaired placental perfusion and major fetal cardiac defects. Ultrasound in Obstetrics and Gynecology. 53 (1), pp. 68-72. https://doi.org/10.1002/uog.20149
Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test
Galeva, S., Konstantinidou, L., Gil, M.M., Akolekar, R. and Nicolaides, K.H. 2019. Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test. Ultrasound in Obstetrics and Gynecology. 53 (2), pp. 208-213. https://doi.org/10.1002/uog.20160
ALEX Fetal Medicine Foundation reference ranges for umbilical artery and middle cerebral artery pulsatility index and cerebroplacental ratio
Ciobanu, A., Wright, A., Syngelaki, A., Wright, D., Akolekar, R. and Nicolaides, K.H. 2019. ALEX Fetal Medicine Foundation reference ranges for umbilical artery and middle cerebral artery pulsatility index and cerebroplacental ratio. Ultrasound in Obstetrics and Gynecology. 53 (4), pp. 465-472. https://doi.org/10.1002/uog.20157
Prediction of adverse perinatal outcome by cerebroplacental ratio in women undergoing induction of labor
Fiolna, M., Kostiv, V., Anthoulakis, C., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of adverse perinatal outcome by cerebroplacental ratio in women undergoing induction of labor. Ultrasound in Obstetrics and Gynecology. 53 (4), pp. 473-480. https://doi.org/10.1002/uog.20173
Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35-37 weeks' gestation
Ciobanu, A., Rouvali, A., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35-37 weeks' gestation. American Journal of Obstetrics & Gynecology. 220 (5), pp. 486.e1-486.e11. https://doi.org/10.1016/j.ajog.2019.01.227
Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 20 and 36 weeks
Ciobanu, A., Formuso, C., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 20 and 36 weeks. Ultrasound in Obstetrics and Gynecology. 53 (4), pp. 488-495. https://doi.org/10.1002/uog.20243
Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Akolekar, R., Ciobanu, A., Zingler, E., Syngelaki, A. and Nicolaides, K.H. 2019. Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. American Journal of Obstetrics & Gynecology. 221 (1), pp. 65.e1-65.e18. https://doi.org/10.1016/j.ajog.2019.03.002
Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates
Ciobanu, A., Khan, N., Syngelaki, A., Akolekar, R. and Nicolaides, K. H. 2019. Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates. Ultrasound in Obstetrics and Gynecology. 53 (6), pp. 761-768. https://doi.org/10.1002/uog.20258
Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks
Ciobanu, A., Anthoulakis, C., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks. Ultrasound in Obstetrics and Gynecology. 53 (5), pp. 630-637. https://doi.org/10.1002/uog.20267
Maternal and neonatal complications of fetal macrosomia: cohort study
Beta, J., Khan, N., Fiolna, M., Khalil, A., Ramadan, G. and Akolekar, R. 2019. Maternal and neonatal complications of fetal macrosomia: cohort study. Ultrasound in Obstetrics and Gynecology. 54 (3), pp. 319-325. https://doi.org/10.1002/uog.20279
Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis
Beta, J., Zhang, W., Geris, S., Kostiv, V. and Akolekar, R. 2019. Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 452-457. https://doi.org/10.1002/uog.20293
Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Ciobanou, A., Jabak, S., De Castro, H., Frei, L., Akolekar, R. and Nicolaides, K. H. 2019. Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 54 (1), pp. 79-86. https://doi.org/10.1002/uog.20346
Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis
Salomon, L. J., Sotiriadis, A., Wulff, C. B., Odibo, A. and Akolekar, R. 2019. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 442-451. https://doi.org/10.1002/uog.20353
Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound
Khan, N., Ciobanu, A., Karampitsakos, T., Akolekar, R. and Nicolaides, K. H. 2019. Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound. Ultrasound in Obstetrics and Gynecology. 54 (2), pp. 326-333. https://doi.org/10.1002/uog.20377
Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation
Akolekar, R., Panaitescu, A. M., Ciobanu, A., Syngelaki, A. and Nicolaides, K. H. 2019. Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 54, pp. 484-491. https://doi.org/10.1002/uog.20391
Prevention of stillbirths: impact of a two-stage screening for vasa previa
Zhang, W., Geris, S., Beta, J., Ramadan, G., Nicolaides, K. H. and Akolekar, R. 2019. Prevention of stillbirths: impact of a two-stage screening for vasa previa. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 605-612. https://doi.org/10.1002/uog.21953
Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta
Vigneswaran, T. V., Zidere, V., Chivers, S., Charakida, M., Akolekar, R. and Simpson, J. M. 2019. Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta. Ultrasound in Obstetrics and Gynecology. https://doi.org/10.1002/uog.21957
Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus
Minnella, G. P., Crupano, F. M., Syngelaki, A., Zidere, V., Akolekar, R. and Nicolaides, K. H. 2019. Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 637-644. https://doi.org/10.1002/uog.21956
Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation
Dragan, I., Georgiou, T., Prodan, N., Akolekar, R. and Nicolaides, K. H. 2017. Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 49 (1), pp. 73-77. https://doi.org/10.1002/uog.17301
Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (3), pp. 308-315. https://doi.org/10.1002/uog.14898
Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 194-202. https://doi.org/10.1002/uog.14928
Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result
Revello, R., Sarno, L., Ispas, A., Akolekar, R. and Nicolaides, K. H. 2016. Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 698-704. https://doi.org/10.1002/uog.15851
Metformin versus placebo in obese pregnant women without diabetes mellitus
Syngelaki, A., Nicolaides, K. H., Balani, J., Hyer, S., Akolekar, R., Kotecha, R., Pastides, A. and Shehata, H. 2016. Metformin versus placebo in obese pregnant women without diabetes mellitus. New England Journal of Medicine. 374, pp. 434-43. https://doi.org/10.1056/NEJMoa1509819
Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy
Sarno, L., Revello, R., Hanson, E., Akolekar, R. and Nicolaides, K. H. 2016. Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 705-11. https://doi.org/10.1002/uog.15913
Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks
Mastrodima, S., Akolekar, R., Yerlikaya, G., Tzelepis, T. and Nicolaides, K. H. 2016. Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 613-617. https://doi.org/10.1002/uog.17289
Prediction of stillbirth from maternal demographic and pregnancy characteristics
Yerlikaya, G., Akolekar, R., McPherson, K., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal demographic and pregnancy characteristics. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 607-612. https://doi.org/10.1002/uog.17290
Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies
Peeva, G., Chaveeva, P., Gil Guevara, E., Akolekar, R. and Nicolaides, K. H. 2016. Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies. Fetal Diagnosis and Therapy. 40 (3), pp. 174-180. https://doi.org/10.1159/000443792
Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks
Akolekar, R., Tokunaka, M., Ortega, N., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 624-630. https://doi.org/10.1002/uog.17295
Prediction of stillbirth from placental growth factor at 11-13 weeks
Akolekar, R., Machuca, M., Mendes, M., Paschos, V. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 618-623. https://doi.org/10.1002/uog.17288
Prediction of stillbirth from placental growth factor at 19-24 weeks
Aupont J. E., Akolekar, R., Illian, A., Neonakis, S. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 631-635. https://doi.org/10.1002/uog.17229
Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2015. Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 203-209. https://doi.org/10.1002/uog.15663