{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:22:35Z","timestamp":1774354955976,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2017T013"],"award-info":[{"award-number":["2017T013"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003092","name":"Dutch Diabetes Research Foundation","doi-asserted-by":"publisher","award":["2017.81.002"],"award-info":[{"award-number":["2017.81.002"]}],"id":[{"id":"10.13039\/501100003092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"publisher","award":["543003109"],"award-info":[{"award-number":["543003109"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"publisher","award":["529051026"],"award-info":[{"award-number":["529051026"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC-2014-CoG-648916"],"award-info":[{"award-number":["ERC-2014-CoG-648916"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["727565"],"award-info":[{"award-number":["727565"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Women with obesity receive intensified antenatal care due to their increased risk of pregnancy complications, even though not all of these women develop complications. We developed a model based on maternal characteristics for prediction of healthy pregnancy outcomes in women with obesity or who are overweight. We assessed whether early-pregnancy metabolites improved prediction. In a population-based cohort study among a subsample of 1180 Dutch pregnant women with obesity or who are overweight, we developed a prediction model using 32 maternal socio-demographic, lifestyle, physical and pregnancy-related characteristics. We determined early-pregnancy amino acids, nonesterifed fatty acids, phospholipids and carnitines in blood serum using liquid chromatography-tandem mass spectrometry. A healthy pregnancy outcome was the absence of fetal death, gestational hypertension, preeclampsia, gestational diabetes, caesarian section, preterm birth, large-for-gestational-age at birth, macrosomia, postpartum weight retention and offspring overweight\/obesity at 5 years. Maternal age, relationship status, parity, early-pregnancy body mass index, mid-pregnancy gestational weight gain, systolic blood pressure and estimated fetal weight were selected into the model using backward selection (area under the receiver operating characteristic curve: 0.65 (95% confidence interval 0.61 to 0.68)). Early-pregnancy metabolites did not improve model performance. Thus, in women with obesity or who are overweight, maternal characteristics can moderately predict a healthy pregnancy outcome. Maternal early-pregnancy metabolites have no incremental value in the prediction of a healthy pregnancy outcome.<\/jats:p>","DOI":"10.3390\/metabo12010013","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:06:54Z","timestamp":1640567214000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prediction of Healthy Pregnancy Outcomes in Women with Overweight and Obesity: The Role of Maternal Early-Pregnancy Metabolites"],"prefix":"10.3390","volume":"12","author":[{"given":"Rama J.","family":"Wahab","sequence":"first","affiliation":[{"name":"The Generation R Study Group, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Pediatrics, Sophia\u2019s Children\u2019s Hospital, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent W. V.","family":"Jaddoe","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Pediatrics, Sophia\u2019s Children\u2019s Hospital, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romy","family":"Gaillard","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Pediatrics, Sophia\u2019s Children\u2019s Hospital, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/1471-0528.15661","article-title":"Impact of maternal body mass index and gestational weight gain on pregnancy complications: An individual participant data meta-analysis of european, north american and australian cohorts","volume":"126","author":"Santos","year":"2019","journal-title":"BJOG"},{"key":"ref_2","first-page":"1","article-title":"Births: Final data for 2017","volume":"67","author":"Martin","year":"2018","journal-title":"Natl. Vital Stat. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/S0140-6736(12)60820-4","article-title":"National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: A systematic analysis and implications","volume":"379","author":"Blencowe","year":"2012","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"j1","DOI":"10.1136\/bmj.j1","article-title":"Obesity and pregnancy: Mechanisms of short term and long term adverse consequences for mother and child","volume":"356","author":"Catalano","year":"2017","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/humupd\/dmp050","article-title":"Maternal metabolism and obesity: Modifiable determinants of pregnancy outcome","volume":"16","author":"Nelson","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1111\/1471-0528.15386","article-title":"Care of women with obesity in pregnancy: Green-top guideline no. 72","volume":"126","author":"Denison","year":"2019","journal-title":"BJOG"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.siny.2009.10.001","article-title":"Obstetric management of obesity in pregnancy","volume":"15","author":"Jarvie","year":"2010","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_8","unstructured":"Commissie Kwaliteit NVOG (2021, November 28). Nederlandse Vereniging voor Obstetrie en Gynaecologie; Zwangerschap bij Obesitas: 2009. Available online: https:\/\/www.nvog.nl\/wp-content\/uploads\/2017\/12\/Zwangerschap-bij-obesitas-1.0-12-06-2009.pdf."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Relph, S., Guo, Y., Harvey, A.L.J., Vieira, M.C., Corsi, D.J., Gaudet, L.M., and Pasupathy, D. (2021). Characteristics associated with uncomplicated pregnancies in women with obesity: A population-based cohort study. BMC Pregnancy Childbirth, 21.","DOI":"10.1186\/s12884-021-03663-2"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vieira, M.C., White, S.L., Patel, N., Seed, P.T., Briley, A.L., Sandall, J., Welsh, P., Sattar, N., Nelson, S.M., and Lawlor, D.A. (2017). Prediction of uncomplicated pregnancies in obese women: A prospective multicentre study. BMC Med., 15.","DOI":"10.1186\/s12916-017-0956-8"},{"key":"ref_11","unstructured":"Achterberg, P.W., Harbers, M.M., Post, N.A.M., and Visscher, K. (2020). Beter weten: Een beter begin: Samen sneller naar een betere zorg rond de zwangerschap, Knowing More: A Better Start: Better and Faster Collaboration to Improve Maternity Care."},{"key":"ref_12","unstructured":"NHS England (2016). Better Births: Improving Outcomes of Maternity Services in England: A Five Year Forward View for Maternity Care."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"f6470","DOI":"10.1136\/bmj.f6470","article-title":"Sharper focus on uncomplicated pregnancy","volume":"347","author":"Knight","year":"2013","journal-title":"BMJ"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.metabol.2018.11.009","article-title":"Metabolically healthy versus metabolically unhealthy obesity","volume":"92","author":"Iacobini","year":"2018","journal-title":"Metabolism"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1111\/aogs.13929","article-title":"Pregnancy in metabolic healthy and unhealthy obese women","volume":"99","author":"Larsson","year":"2020","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e315","DOI":"10.1210\/clinem\/dgab596","article-title":"Maternal body mass index, early-pregnancy metabolite profile and birthweight","volume":"107","author":"Wahab","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"McBride, N., Yousefi, P., White, S.L., Poston, L., Farrar, D., Sattar, N., Nelson, S.M., Wright, J., Mason, D., and Suderman, M. (2020). Do nuclear magnetic resonance (nmr)-based metabolomics improve the prediction of pregnancy-related disorders? Findings from a uk birth cohort with independent validation. BMC Med., 18.","DOI":"10.1186\/s12916-020-01819-z"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"(2015). Practice bulletin no 156: Obesity in pregnancy. Obstet. Gynecol., 126, e112\u2013e126.","DOI":"10.1097\/AOG.0000000000001211"},{"key":"ref_19","unstructured":"National Institute of Health and Care Excellence (2021, November 28). Weight Management before, during and after Pregnancy, Available online: https:\/\/www.nhs.uk\/Planners\/pregnancycareplanner\/Documents\/NICE_reference_weight_management_pregnancy.pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S2213-8587(16)30107-3","article-title":"Influence of maternal obesity on the long-term health of offspring","volume":"5","author":"Godfrey","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00592-019-01291-z","article-title":"Impact of maternal bmi and gestational diabetes mellitus on maternal and cord blood metabolome: Results from the preobe cohort study","volume":"56","author":"Shokry","year":"2019","journal-title":"Acta Diabetol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11306-019-1553-y","article-title":"Are we close to defining a metabolomic signature of human obesity? A systematic review of metabolomics studies","volume":"15","author":"Gil","year":"2019","journal-title":"Metabolomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/ijo.2016.153","article-title":"Association of maternal prepregnancy bmi with metabolomic profile across gestation","volume":"41","author":"Hellmuth","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ijo.2015.15","article-title":"Maternal obesity and metabolic risk to the offspring: Why lifestyle interventions may have not achieved the desired outcomes","volume":"39","author":"Catalano","year":"2015","journal-title":"Int. J. Obes."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rodrigues-Krause, J., Krause, M., Rocha, I., Umpierre, D., and Fayh, A.P.T. (2018). Association of l-arginine supplementation with markers of endothelial function in patients with cardiovascular or metabolic disorders: A systematic review and meta-analysis. Nutrients, 11.","DOI":"10.3390\/nu11010015"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00726-010-0598-z","article-title":"Beneficial effects of l-arginine on reducing obesity: Potential mechanisms and important implications for human health","volume":"39","author":"McKnight","year":"2010","journal-title":"Amino Acids"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2174\/1389203717666160627074017","article-title":"L-arginine modulates glucose and lipid metabolism in obesity and diabetes","volume":"18","author":"Hu","year":"2017","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00726-008-0210-y","article-title":"Arginine metabolism and nutrition in growth, health and disease","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., and Tain, Y.L. (2019). Impact of arginine nutrition and metabolism during pregnancy on offspring outcomes. Nutrients, 11.","DOI":"10.3390\/nu11071452"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Terstappen, F., Tol, A.J.C., Gremmels, H., Wever, K.E., Paauw, N.D., Joles, J.A., Beek, E.M.V., and Lely, A.T. (2020). Prenatal amino acid supplementation to improve fetal growth: A systematic review and meta-analysis. Nutrients, 12.","DOI":"10.3390\/nu12092535"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s10654-016-0224-9","article-title":"The generation r study: Design and cohort update 2017","volume":"31","author":"Kooijman","year":"2016","journal-title":"Eur. J. Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s10654-008-9309-4","article-title":"The generation r study: Design and cohort update until the age of 4 years","volume":"23","author":"Jaddoe","year":"2008","journal-title":"Eur. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Voortman, T., Steegers-Theunissen, R.P.M., Bergen, N.E., Jaddoe, V.W.V., Looman, C.W.N., Kiefte-de Jong, J.C., and Schalekamp-Timmermans, S. (2020). Validation of a semi-quantitative food-frequency questionnaire for dutch pregnant women from the general population using the method or triads. Nutrients, 12.","DOI":"10.3390\/nu12051341"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1093\/eurheartj\/ehr275","article-title":"Blood pressure tracking during pregnancy and the risk of gestational hypertensive disorders: The generation r study","volume":"32","author":"Gaillard","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s10654-014-9980-6","article-title":"The generation r study: Biobank update 2015","volume":"29","author":"Kruithof","year":"2014","journal-title":"Eur. J. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Verlohren, S., Galindo, A., Schlembach, D., Zeisler, H., Herraiz, I., Moertl, M.G., Pape, J., Dudenhausen, J.W., Denk, B., and Stepan, H. (2010). An automated method for the determination of the sflt-1\/pigf ratio in the assessment of preeclampsia. Am. J. Obstet. Gynecol., 202.","DOI":"10.1016\/j.ajog.2009.09.016"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e113","DOI":"10.1016\/j.ajog.2019.03.025","article-title":"Is maternal lipid profile in early pregnancy associated with pregnancy complications and blood pressure in pregnancy and long term postpartum?","volume":"221","author":"Adank","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.2337\/dc19-2580","article-title":"Associations of maternal glycemia in the first half of pregnancy with alterations in cardiac structure and function in childhood","volume":"43","author":"Wahab","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ernst, G.D., de Jonge, L.L., Hofman, A., Lindemans, J., Russcher, H., Steegers, E.A., and Jaddoe, V.W. (2011). C-reactive protein levels in early pregnancy, fetal growth patterns, and the risk for neonatal complications: The generation r study. Am. J. Obstet. Gynecol., 205.","DOI":"10.1016\/j.ajog.2011.03.049"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0002-9378(85)90298-4","article-title":"Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study","volume":"151","author":"Hadlock","year":"1985","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1093\/ije\/dyu036","article-title":"Tracking of fetal growth characteristics during different trimesters and the risks of adverse birth outcomes","volume":"43","author":"Gaillard","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1161\/CIRCULATIONAHA.113.003881","article-title":"Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: The generation r study","volume":"128","author":"Gaillard","year":"2013","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11306-020-01667-1","article-title":"A population-based resource for intergenerational metabolomics analyses in pregnant women and their children: The generation r study","volume":"16","author":"Voerman","year":"2020","journal-title":"Metabolomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1016\/j.jacc.2016.09.972","article-title":"The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease","volume":"68","author":"Ussher","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cmet.2016.09.018","article-title":"Metabolomics and metabolic diseases: Where do we stand?","volume":"25","author":"Newgard","year":"2017","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.jchromb.2011.01.010","article-title":"Quantification of 22 plasma amino acids combining derivatization and ion-pair lc-ms\/ms","volume":"879","author":"Harder","year":"2011","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN) (1984). Nomenclature and symbolism for amino acids and peptides. Recommendations 1983. Eur. J. Biochem., 138, 9\u201337.","DOI":"10.1111\/j.1399-3011.1984.tb00922.x"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1021\/ac202602u","article-title":"Nonesterified fatty acid determination for functional lipidomics: Comprehensive ultrahigh performance liquid chromatography-tandem mass spectrometry quantitation, qualification, and parameter prediction","volume":"84","author":"Hellmuth","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Uhl, O., Fleddermann, M., Hellmuth, C., Demmelmair, H., and Koletzko, B. (2016). Phospholipid species in newborn and 4 month old infants after consumption of different formulas or breast milk. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162040"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1111\/j.1651-2227.1991.tb11945.x","article-title":"An update of the swedish reference standards for weight, length and head circumference at birth for given gestational age (1977\u20131981)","volume":"80","author":"Niklasson","year":"1991","journal-title":"Acta Paediatr. Scand."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/1\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:53:12Z","timestamp":1760169192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/1\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,24]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["metabo12010013"],"URL":"https:\/\/doi.org\/10.3390\/metabo12010013","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,24]]}}}