{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:35:27Z","timestamp":1790832927161,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["812660"],"award-info":[{"award-number":["812660"]}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/K017810\/1"],"award-info":[{"award-number":["BB\/K017810\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Homocysteine is a marker for derangements in one-carbon metabolism. Elevated homocysteine may represent a causal link between poor maternal nutrition and impaired embryonic and fetal development. We sought to investigate associations between reference range maternal homocysteine and embryonic and fetal growth. We enrolled 1060 singleton pregnancies (555 natural and 505 in vitro fertilization\/intracytoplasmic sperm injection (IVF\/ICSI) pregnancies) from November 2010 to December 2020. Embryonic and fetal body and head growth was assessed throughout pregnancy using three-dimensional ultrasound scans and virtual reality techniques. Homocysteine was negatively associated with first trimester embryonic growth in the included population (crown-rump length B \u22120.023 mm, 95% CI \u22120.038,\u22120.007, p = 0.004, embryonic volume B \u22120.011 cm3, 95% CI \u22120.018,\u22120.004, p = 0.003). After stratification for conception mode, this association remained in IVF\/ICSI pregnancies with frozen embryo transfer (crown-rump length B \u22120.051 mm, 95% CI \u22120.081,\u22120.023, p &lt; 0.001, embryonic volume B \u22120.024 cm3, 95% CI \u22120.039,\u22120.009, p = 0.001), but not in IVF\/ICSI pregnancies with fresh embryo transfer and natural pregnancies. Homocysteine was not associated with longitudinal measurements of head growth in first trimester, nor with second and third trimester fetal growth. Homocysteine in the highest quartile (7.3\u201314.9 \u00b5mol\/L) as opposed to the lowest (2.5\u20135.2 \u00b5mol\/L) was associated with reduced birth weight in natural pregnancies only (B \u221251.98 g, 95% CI \u221288.13,\u221215.84, p = 0.005). In conclusion, high maternal homocysteine within the reference range is negatively associated with first trimester embryonic growth and birth weight, and the effects of homocysteine are dependent on conception mode.<\/jats:p>","DOI":"10.3390\/nu14061129","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T01:53:54Z","timestamp":1646790834000},"page":"1129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["First Trimester Maternal Homocysteine and Embryonic and Fetal Growth: The Rotterdam Periconception Cohort"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3803-9851","authenticated-orcid":false,"given":"Eleonora","family":"Rubini","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2732-9688","authenticated-orcid":false,"given":"Katinka M.","family":"Snoek","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Schoenmakers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sten P.","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6375-215X","authenticated-orcid":false,"given":"Kevin D.","family":"Sinclair","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Nottingham, Leicestershire LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melek","family":"Rousian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4353-5756","authenticated-orcid":false,"given":"R\u00e9gine P. M.","family":"Steegers-Theunissen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.mce.2016.06.006","article-title":"One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health","volume":"435","author":"Kalhan","year":"2016","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/humupd\/dmt041","article-title":"The periconceptional period, reproduction and long-term health of offspring: The importance of one-carbon metabolism","volume":"19","author":"Twigt","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-animal-020518-115206","article-title":"One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development","volume":"7","author":"Clare","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1046\/j.1432-1327.2001.02278.x","article-title":"Roles of homocysteine in cell metabolism: Old and new functions","volume":"268","author":"Medina","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1071\/RD14377","article-title":"One-carbon metabolism and epigenetic regulation of embryo development","volume":"27","author":"Xu","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s00394-007-0667-6","article-title":"Relationship between dietary folate intakes, maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan","volume":"46","author":"Takimoto","year":"2007","journal-title":"Eur. J. Nutr."},{"key":"ref_8","first-page":"1055","article-title":"Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses","volume":"84","author":"Lindblad","year":"2005","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1471-0528.2012.03321.x","article-title":"Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: The Generation R Study","volume":"119","author":"Bergen","year":"2012","journal-title":"BJOG"},{"key":"ref_10","first-page":"523","article-title":"Periconceptional maternal one-carbon biomarkers are associated with embryonic development according to the Carnegie stages","volume":"32","author":"Parisi","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.fertnstert.2016.11.030","article-title":"Periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth trajectories: The Rotterdam Periconceptional Cohort (Predict Study)","volume":"107","author":"Parisi","year":"2017","journal-title":"Fertil Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1017\/S0007114515002081","article-title":"Prenatal folate, homocysteine and vitamin B12 levels and child brain volumes, cognitive development and psychological functioning: The Generation R Study","volume":"122","author":"Ars","year":"2019","journal-title":"Br. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1017\/S0007114521000581","article-title":"Maternal vitamin B12 status in early pregnancy and its association with birth outcomes in Canadian mother-newborn Dyads","volume":"126","author":"Tan","year":"2021","journal-title":"Br. J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/0002-9378(95)90474-3","article-title":"Neural tube defects and elevated homocysteine levels in amniotic fluid","volume":"172","author":"Boers","year":"1995","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1056\/NEJM199101173240315","article-title":"Neural-tube defects and derangement of homocysteine metabolism","volume":"324","author":"Boers","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/1471-0528.12592","article-title":"An optimal periconception maternal folate status for embryonic size: The Rotterdam Predict study","volume":"121","author":"Willemsen","year":"2014","journal-title":"BJOG"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6294444","DOI":"10.1093\/ije\/dyab030","article-title":"Cohort Profile Update: The Rotterdam Periconceptional Cohort and embryonic and fetal measurements using 3D ultrasound and virtual reality techniques","volume":"50","author":"Rousian","year":"2021","journal-title":"Int. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.nu.12.070192.001431","article-title":"Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease","volume":"12","author":"Kang","year":"1992","journal-title":"Annu. Rev. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fnut.2019.00049","article-title":"Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies","volume":"6","author":"Tinelli","year":"2019","journal-title":"Front. Nutr."},{"key":"ref_20","unstructured":"CBS (2021, December 20). Opleidingsniveau. Available online: https:\/\/www.cbs.nl\/nl-nl\/nieuws\/2019\/33\/verschil-levensverwachting-hoog-en-laagopgeleid-groeit\/opleidingsniveau."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/j.placenta.2018.01.001","article-title":"Virtual reality imaging techniques in the study of embryonic and early placental health","volume":"64","author":"Rousian","year":"2018","journal-title":"Placenta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.fertnstert.2010.12.032","article-title":"Virtual reality for embryonic measurements requiring depth perception","volume":"95","author":"Rousian","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/jcu.22207","article-title":"Design and validation of a 3D virtual reality desktop system for sonographic length and volume measurements in early pregnancy evaluation","volume":"43","author":"Baken","year":"2015","journal-title":"J. Clin. Ultrasound"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Husen, S.C., Koning, I.V., Go, A., van Graafeiland, A.W., Willemsen, S.P., Groenenberg, I.A.L., and Steegers-Theunissen, R.P.M. (2019). Three-dimensional ultrasound imaging of fetal brain fissures in the growth restricted fetus. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217538"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105224","DOI":"10.1016\/j.earlhumdev.2020.105224","article-title":"Growth trajectories of the human fetal brain in healthy and complicated pregnancies and associations with neurodevelopmental outcome in the early life course","volume":"151","author":"Welling","year":"2020","journal-title":"Early Hum. Dev."},{"key":"ref_26","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 measurement\u2014A prospective study","volume":"151","author":"Hadlock","year":"1985","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1093\/humrep\/det375","article-title":"Periconception maternal characteristics and embryonic growth trajectories: The Rotterdam Predict study","volume":"28","author":"Wilbers","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1093\/humrep\/dex079","article-title":"Prenatal cerebellar growth trajectories and the impact of periconceptional maternal and fetal factors","volume":"32","author":"Koning","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.rbmo.2018.12.016","article-title":"Effect of human embryonic morphological development on fetal growth parameters: The Rotterdam Periconceptional Cohort (Predict Study)","volume":"38","author":"Parisi","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1093\/humrep\/dew043","article-title":"Growth trajectories of the human embryonic head and periconceptional maternal conditions","volume":"31","author":"Koning","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/uog.20272","article-title":"ISUOG Practice Guidelines: Ultrasound assessment of fetal biometry and growth","volume":"53","author":"Salomon","year":"2019","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"383.e1","DOI":"10.1016\/j.ajog.2018.12.023","article-title":"From population reference to national standard: New and improved birthweight charts","volume":"220","author":"Hoftiezer","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, C., Luo, D., Wang, Q., Ma, Y., Ping, L., Wu, T., Tang, J., Peng, D., and Zhao, P. (2020). Serum homocysteine and folate concentrations in early pregnancy and subsequent events of adverse pregnancy outcome: The Sichuan Homocysteine study. BMC Pregnancy Childbirth, 20.","DOI":"10.1186\/s12884-020-02860-9"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.nutres.2017.10.008","article-title":"Total homocysteine is positively correlated with body mass index, waist-to-hip ratio, and fat mass among overweight reproductive women: A cross-sectional study","volume":"48","author":"Hamadneh","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e12675","DOI":"10.1111\/mcn.12675","article-title":"Folate, vitamin B12, and homocysteine in smoking-exposed pregnant women: A systematic review","volume":"15","author":"Tuenter","year":"2019","journal-title":"Matern. Child. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Drake, A.J., O\u2019Shaughnessy, P.J., Bhattacharya, S., Monteiro, A., Kerrigan, D., Goetz, S., Raab, A., Rhind, S.M., Sinclair, K.D., and Meharg, A.A. (2015). In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver. BMC Med., 13.","DOI":"10.1186\/s12916-014-0251-x"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.1007\/s12325-020-01474-z","article-title":"Folic Acid Supplementation in Patients with Elevated Homocysteine Levels","volume":"37","author":"Kaye","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1159\/000468935","article-title":"Fresh and Frozen-Thawed Embryo Transfer Compared to Natural Conception: Differences in Perinatal Outcome","volume":"82","author":"Spijkers","year":"2017","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s10815-016-0850-x","article-title":"Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles","volume":"34","author":"Luke","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.rbmo.2021.04.013","article-title":"Prenatal growth trajectories and birth outcomes after frozen-thawed extended culture embryo transfer and fresh embryo transfer: The Rotterdam Periconception Cohort","volume":"43","author":"Hoek","year":"2021","journal-title":"Reprod. Biomed. Online"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rubini, E., Baijens, I.M.M., Horanszky, A., Schoenmakers, S., Sinclair, K.D., Zana, M., Dinnyes, A., Steegers-Theunissen, R.P.M., and Rousian, M. (2021). Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review. Genes, 12.","DOI":"10.3390\/genes12101634"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"572","DOI":"10.3945\/jn.109.118158","article-title":"Infant birth size is not associated with maternal intake and status of folate during the second trimester in Norwegian pregnant women","volume":"140","author":"Nilsen","year":"2010","journal-title":"J. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3177\/jnsv.57.130","article-title":"Elevated maternal serum folate in the third trimester and reduced fetal growth: A longitudinal study","volume":"57","author":"Takimoto","year":"2011","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/ppe.12297","article-title":"Maternal and Neonatal Markers of the Homocysteine Pathway and Fetal Growth: The Generation R Study","volume":"30","author":"Bergen","year":"2016","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.placenta.2021.09.012","article-title":"Periconceptional maternal and paternal homocysteine levels and early utero-placental (vascular) growth trajectories: The Rotterdam periconception cohort","volume":"115","author":"Hoek","year":"2021","journal-title":"Placenta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0301-2115(00)00492-9","article-title":"Clotting disorders and placental abruption: Homocysteine\u2014A new risk factor","volume":"95","author":"Eskes","year":"2001","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Chaudhry, S.H., Taljaard, M., MacFarlane, A.J., Gaudet, L.M., Smith, G.N., Rodger, M., Rennicks White, R., Walker, M.C., and Wen, S.W. (2019). The role of maternal homocysteine concentration in placenta-mediated complications: Findings from the Ottawa and Kingston birth cohort. BMC Pregnancy Childbirth, 19.","DOI":"10.1186\/s12884-019-2219-5"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3945\/ajcn.111.016212","article-title":"Maternal homocysteine and small-for-gestational-age offspring: Systematic review and meta-analysis","volume":"95","author":"Hogeveen","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/ije\/dyu132","article-title":"Maternal homocysteine in pregnancy and offspring birthweight: Epidemiological associations and Mendelian randomization analysis","volume":"43","author":"Yajnik","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1373\/clinchem.2004.032904","article-title":"Maternal homocysteine before conception and throughout pregnancy predicts fetal homocysteine and birth weight","volume":"50","author":"Murphy","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e2000734","DOI":"10.1002\/mnfr.202000734","article-title":"One Carbon Metabolism and Mammalian Pregnancy Outcomes","volume":"65","author":"Cai","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_52","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_53","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/j.1469-8749.2009.03513.x","article-title":"Fetal growth from mid- to late pregnancy is associated with infant development: The Generation R Study","volume":"52","author":"Henrichs","year":"2010","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Broere-Brown, Z.A., Schalekamp-Timmermans, S., Jaddoe, V.W.V., and Steegers, E.A.P. (2019). Deceleration of fetal growth rate as alternative predictor for childhood outcomes: A birth cohort study. BMC Pregnancy Childbirth, 19.","DOI":"10.1186\/s12884-019-2358-8"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/humupd\/dml063","article-title":"Impact of folate and homocysteine metabolism on human reproductive health","volume":"13","author":"Forges","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e13998","DOI":"10.1097\/MD.0000000000013998","article-title":"Hyperhomocysteinemia in men with a reproductive history of fetal neural tube defects: Three case reports and literature review","volume":"98","author":"Yu","year":"2019","journal-title":"Medicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e28600","DOI":"10.2196\/28600","article-title":"Optimizing the Periconception Lifestyle of Women With Overweight Using a Blended Personalized Care Intervention Combining eHealth and Face-to-face Counseling (eFUSE): Protocol for a Randomized Controlled Trial","volume":"10","author":"Schoenmakers","year":"2021","journal-title":"JMIR Res. Protoc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e19378","DOI":"10.2196\/19378","article-title":"Impact of a Blended Periconception Lifestyle Care Approach on Lifestyle Behaviors: Before-and-After Study","volume":"22","author":"Snoek","year":"2020","journal-title":"J. Med. Internet Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e15773","DOI":"10.2196\/15773","article-title":"A Mobile App Lifestyle Intervention to Improve Healthy Nutrition in Women Before and During Early Pregnancy: Single-Center Randomized Controlled Trial","volume":"22","author":"Koster","year":"2020","journal-title":"J. Med. Internet Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.rbmo.2017.06.014","article-title":"Healthy preconception nutrition and lifestyle using personalized mobile health coaching is associated with enhanced pregnancy chance","volume":"35","author":"Koster","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.fertnstert.2020.04.051","article-title":"First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: A single-blinded multicenter randomized controlled trial","volume":"114","author":"Oostingh","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e13935","DOI":"10.2196\/13935","article-title":"Mobile Health Coaching on Nutrition and Lifestyle Behaviors for Subfertile Couples Using the Smarter Pregnancy Program: Model-Based Cost-Effectiveness Analysis","volume":"7","author":"Oostingh","year":"2019","journal-title":"JMIR Mhealth Uhealth"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/6\/1129\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:33:44Z","timestamp":1760135624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/6\/1129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":62,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["nu14061129"],"URL":"https:\/\/doi.org\/10.3390\/nu14061129","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]}}}