Corresponding Author: Eduard Gratacós, MD, PhD, BCNatal (Hospital Sant Joan de Déu and Hospital Clínic), Universitat de Barcelona, Sabino de Arana 1, 08036 Barcelona, Spain (egratacos@ub.edu).
Accepted for Publication: October 22, 2021.
Author Contributions: Drs Crovetto and Gratacós had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Crovetto and Crispi contributed equally.
Concept and design: Crovetto, Crispi, Martín-Asuero, Vieta, Estruch, Gratacós.
Acquisition, analysis, or interpretation of data: Crovetto, Crispi, Casas, Martín-Asuero, Borràs, Estruch, Gratacós.
Drafting of the manuscript: Crovetto, Crispi, Vieta, Gratacós.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Crovetto, Borràs, Estruch.
Obtained funding: Gratacós.
Administrative, technical, or material support: Crovetto, Martín-Asuero, Estruch.
Supervision: Crovetto, Crispi, Borràs, Vieta, Estruch, Gratacós.
Other - responsible for the Mediterranean diet program: Casas.
Other - responsible for the mindfulness-based stress reduction program: Martín-Asuero.
Conflict of Interest Disclosures: Dr Crovetto reported receiving personal fees from Centro de Investigaciones Biomédicas en Red sobre Enfermedades Raras for support for investigation (until July 2019) during the conduct of the study. Dr Crispi reported receiving grants from Hospital Clinic/Institut d'Investigacions Biomèdiques August Pi i Sunyer La Caixa foundation, Cerebra foundation, and Agència de Gestió d'Ajudes Universitaries i de Investigació (AGAUR) during the conduct of the study. Dr Martín-Asuero reported receiving grants from La Caixa during the conduct of the study and book royalties from Editorial Planeta and Méderic Ediciones, nonfinancial support from Soc Andorrana Ciencias, and personal fees from Instituto Guttmann and Technology Centre of Catalonia outside the submitted work and being the founder and owner of Instituto esMindfulness SL. Dr Borràs reported receiving personal fees from Fundació Privada per a la Recerca i la Docència Sant Joan de Déu during the conduct of the study. Dr Vieta reported receiving personal fees from Abbott, Allergan, Angelini, Sage, and Sanofi; and grants from Dainippon Sumitomo, Ferrer (money paid to his institution but no payment made as yet), and Janssen (money paid to his institution for trials on esketamine, JNJ-42165279, and MIJ821); and serving on advisory boards for and receiving personal fees from Lundbeck outside the submitted work. Dr Estruch reported receiving personal fees from Cerveza y salud, Fundación Dieta Mediterranea, Pernaud-Ricard, Instituto Cervantes, and nonfinancial support from Fundación de Investigación Sobre el Vino y Nutrición and Brewers of Europe; and grants from Grand Fountain Laboratories, Uriach Laboratories, Instituto de Salud Carlos III, EIT Digital, and JPI outside the submitted work. Dr Gratacós reported receiving grants from CaixaResearch (LCF/PR/GN18/10310003), Cerebra Foundation for the Brain Injured Child, and AGAUR Catalonia government (2017 SGR No. 1531) during the conduct of the study and book royalties from Columna Edicions and Editorial Medica Panamericana and grants from Roche Diagnostics International (paid to his institution) outside the submitted work. No other disclosures were reported.
Funding/Support: The project was partially funded by a grant from “La Caixa” Foundation (LCF/PR/GN18/10310003); Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); AGAUR under grant 2017 SGR No. 1531. Dr Crovetto has received support from Centro de Investigaciones Biomédicas en Red sobre Enfermedades Raras (CIBERER). Dr Nakaki has received support from a fellowship from “La Caixa” Foundation, Doctoral INPhINIT Retaining fellowship (LCF/BQ/DR19/11740018).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Information: The IMPACT BCN Trial Investigators appear in Supplement 4.
Data Sharing Statement: See Supplement 5.
Additional Contributions: We thank the study participants for their personal time and commitment to this trial. We also thank all the medical staff, residents, midwives, and nurses of BCNatal, especially Laura Segales, BsC; Marta Dacal, MsC; Maria Laura Boutet, MD; Annachiara Basso, MD; Marta Larroya, MD; Marta Camacho, MD; Marta Garcia, MsC; Mireia Pascual, APRN; and Alba Camacho, APRN (BCNatal Fetal Medicine Research Center, Barcelona, Spain), for their support in the recruitment, interventions, and data collection of the trial; Carlos Galante, MsC (Department of Internal Medicine, Hospital Clinic, Barcelona, Spain, Barcelona, Spain), for his support in the Mediterranean diet intervention; Georgina Badosa, MsC; Amaia Helguera, BsC; and Sylvia Comas, MsC (Instituto esMindfulness, Barcelona, Spain), for their support in the stress reduction intervention; and Julian Lozano-Castellón, MsC; Anallely López-Yerena, MsC; Inés Domínguez-López, BsC; and Maria Marhuenda-Muñoz, MsC (School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain), for their support in the biomarkers analysis of Mediterranean diet compliance. We thank the Clinic-IDIBAPS Biobank for valuable management of samples. Laura Segales, Marta Dacal, Marta Garcia, Mireia Pascual, Alba Camacho, Carlos Galante, Georgina Badosa, Amaia Helguera, Sylvia Comas, Julian Lozano-Castellón, Anallely López-Yerena, Inés Domínguez-López, and Maria Marhuenda-Muñoz received economic compensation for their role in the study. Additionally, the members of the IMPACT BCN Trial Investigators group made the following contributions: C. Paules, A. Nakaki, K. Vellvé, and G. Casu were directly involved in participant recruitment and data collection; S. Castro-Barquero and T. Freita were dietitians involved in the Mediterranean diet program; A. M. Ruiz-León and R. M. Lamuela-Raventós were responsible for the analysis of fatty acids and hydroxytyrosol metabolites; M. T. Oller-Guzmán was a mindfulness-based stress reduction instructor who led several groups; A. Martínez-Aràn and I. Morilla were psychologists involved in the stress reduction program; A. Gomez-Gomez and O. J. Pozo were responsible for the analysis of the 24-hour urinary cortisone/cortisol ratio; M. C. Collado and M. Selma-Royo contributed to the analysis and interpretation of the biological effects of the interventions; M. Domenech helped to implement the Mediterranean diet program; A. Arranz was responsible for the postnatal follow-up; F. Figueras contributed to the study design and manuscript writing, and supervised the statistical analysis.
2.Sacchi
C , Marino
C , Nosarti
C , Vieno
A , Visentin
S , Simonelli
A . Association of intrauterine growth restriction and small for gestational age status with childhood cognitive outcomes: a systematic review and meta-analysis.
JAMA Pediatr. 2020;174(8):772-781. doi:
10.1001/jamapediatrics.2020.1097PubMedGoogle ScholarCrossref 3.Raghavan
R , Dreibelbis
C , Kingshipp
BL ,
et al. Dietary patterns before and during pregnancy and birth outcomes: a systematic review.
Am J Clin Nutr. 2019;109(suppl_7):s729-s756. doi:
10.1093/ajcn/nqy353PubMedGoogle Scholar 4.Traylor
CS , Johnson
JD , Kimmel
MC , Manuck
TA . Effects of psychological stress on adverse pregnancy outcomes and nonpharmacologic approaches for reduction: an expert review.
Am J Obstet Gynecol MFM. 2020;2(4):100229. doi:
10.1016/j.ajogmf.2020.100229PubMedGoogle Scholar 6.Estruch
R , Ros
E , Salas-Salvadó
J ,
et al; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts.
N Engl J Med. 2018;378(25):e34. doi:
10.1056/NEJMoa1800389PubMedGoogle Scholar 8.H Al Wattar
B , Dodds
J , Placzek
A ,
et al; ESTEEM study group. Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): a pragmatic multicentre randomised trial.
PLoS Med. 2019;16(7):e1002857. doi:
10.1371/journal.pmed.1002857PubMedGoogle Scholar 9.Assaf-Balut
C , García de la Torre
N , Durán
A ,
et al. A Mediterranean diet with additional extra virgin olive oil and pistachios reduces the incidence of gestational diabetes mellitus (GDM): a randomized controlled trial: the St. Carlos GDM Prevention Study.
PLoS One. 2017;12(10):e0185873. doi:
10.1371/journal.pone.0185873PubMedGoogle Scholar 10.Assaf-Balut
C , García de la Torre
N , Duran
A ,
et al. A Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios improves pregnancy outcomes in women without gestational diabetes mellitus: a sub-analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study.
Ann Nutr Metab. 2019;74(1):69-79. doi:
10.1159/000495793PubMedGoogle ScholarCrossref 16.Crovetto
F , Crispi
F , Borras
R ,
et al. Mediterranean diet, mindfulness-based stress reduction and usual care during pregnancy for reducing fetal growth restriction and adverse perinatal outcomes: IMPACT BCN (improving mothers for a better prenatal care trial Barcelona): a study protocol for a randomized controlled trial.
Trials. 2021;22(1):362. doi:
10.1186/s13063-021-05309-2PubMedGoogle ScholarCrossref 17.Juton
C , Castro-Barquero
S , Casas
R ,
et al. Reliability and concurrent and construct validity of a food frequency questionnaire for pregnant women at high risk to develop fetal growth restriction.
Nutrients. 2021;13(5):1629. doi:
10.3390/nu13051629
PubMedGoogle ScholarCrossref 19.American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics and the Society forMaternal-FetalMedicin. ACOG practice bulletin No. 204: fetal growth restriction.
Obstet Gynecol. 2019;133(2):e97-e109. doi:
10.1097/AOG.0000000000003070PubMedGoogle ScholarCrossref 21.Ross
S , Milne
J , Dwinnell
S ,
et al. Is it possible to estimate the minimal clinically important treatment effect needed to change practice in preterm birth prevention? results of an obstetrician survey used to support the design of a trial.
BMC Med Res Methodol. 2012;12:31. doi:
10.1186/1471-2288-12-31PubMedGoogle ScholarCrossref 22.Bakalis
S , Akolekar
R , Gallo
DM , Poon
LC , Nicolaides
KH . Umbilical and fetal middle cerebral artery Doppler at 30-34 weeks’ gestation in the prediction of adverse perinatal outcome.
Ultrasound Obstet Gynecol. 2015;45(4):409-420. doi:
10.1002/uog.14822PubMedGoogle ScholarCrossref 23.Miranda
J , Triunfo
S , Rodriguez-Lopez
M ,
et al. Performance of third-trimester combined screening model for prediction of adverse perinatal outcome.
Ultrasound Obstet Gynecol. 2017;50(3):353-360. doi:
10.1002/uog.17317PubMedGoogle ScholarCrossref 25.Khoury
J , Henriksen
T , Christophersen
B , Tonstad
S . Effect of a cholesterol-lowering diet on maternal, cord, and neonatal lipids, and pregnancy outcome: a randomized clinical trial.
Am J Obstet Gynecol. 2005;193(4):1292-1301. doi:
10.1016/j.ajog.2005.05.016PubMedGoogle ScholarCrossref 28.Bussières
EL , Tarabulsy
GM , Pearson
J ,
et al. Maternal prenatal stress and infant birth weight and gestational age: a meta-analysis of prospective studies.
Dev Rev. 2015;23:179-199. doi:
10.1016/j.dr.2015.04.001Google Scholar 30.Guo
P , Zhang
X , Liu
N ,
et al. Mind-body interventions on stress management in pregnant women: a systematic review and meta-analysis of randomized controlled trials.
J Adv Nurs. 2021;77(1):125-146. doi:
10.1111/jan.14588PubMedGoogle ScholarCrossref 32.Galante
J , Friedrich
C , Dawson
AF ,
et al. Mindfulness-based programmes for mental health promotion in adults in nonclinical settings: a systematic review and meta-analysis of randomised controlled trials.
PLoS Med. 2021;18(1):e1003481. doi:
10.1371/journal.pmed.1003481PubMedGoogle Scholar 34.Crispi
F , Miranda
J , Gratacós
E . Long-term cardiovascular consequences of fetal growth restriction: biology, clinical implications, and opportunities for prevention of adult disease.
Am J Obstet Gynecol. 2018;218(2S):S869-S879. doi:
10.1016/j.ajog.2017.12.012PubMedGoogle Scholar 36.Katanoda
K , Noda
M , Goto
A , Mizunuma
H , Lee
JS , Hayashi
K . Impact of birth weight on adult-onset diabetes mellitus in relation to current body mass index: the Japan Nurses’ Health Study.
J Epidemiol. 2017;27(9):428-434. doi:
10.1016/j.je.2016.08.016PubMedGoogle ScholarCrossref 38.Poston
L , Bell
R , Croker
H ,
et al; UPBEAT Trial Consortium. Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.
Lancet Diabetes Endocrinol. 2015;3(10):767-777. doi:
10.1016/S2213-8587(15)00227-2PubMedGoogle ScholarCrossref