Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction on Prevention of Small-for-Gestational Age Birth Weights in Newborns Born to At-Risk Pregnant Individuals: The IMPACT BCN Randomized Clinical Trial

Abstract

Importance: Being born small for gestational age (SGA) is a leading cause of perinatal morbidity and mortality with no effective prevention or therapy. Maternal suboptimal nutrition and high stress levels have been associated with poor fetal growth and adverse pregnancy outcomes.

Objective: To investigate whether structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (stress reduction) in high-risk pregnancies can reduce the percentage of newborns who were born SGA and other adverse pregnancy outcomes.

Design, setting, and participants: Parallel-group randomized clinical trial conducted at a university hospital in Barcelona, Spain, including 1221 individuals with singleton pregnancies (19-23 weeks' gestation) at high risk for SGA. Enrollment took place from February 1, 2017, to October 10, 2019, with follow-up until delivery (final follow-up on March 1, 2020).

Interventions: Participants in the Mediterranean diet group (n = 407) received 2 hours monthly of individual and group educational sessions and free provision of extra-virgin olive oil and walnuts. Individuals in the stress reduction group (n = 407) underwent an 8-week stress reduction program adapted for pregnancy, consisting of weekly 2.5-hour sessions and 1 full-day session. Individuals in the usual care group (n = 407) received pregnancy care per institutional protocols.

Main outcomes and measures: The primary end point was the percentage of newborns who were SGA at delivery, defined as birth weight below the 10th percentile. The secondary end point was a composite adverse perinatal outcome (at least 1 of the following: preterm birth, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, low Apgar score, or presence of any major neonatal morbidity).

Results: Among the 1221 randomized individuals (median [IQR] age, 37 [34-40] years), 1184 (97%) completed the trial (392 individuals assigned to the Mediterranean diet group, 391 to the stress reduction group, and 401 to the usual care group). SGA occurred in 88 newborns (21.9%) in the control group, 55 (14.0%) in the Mediterranean diet group (odds ratio [OR], 0.58 [95% CI, 0.40-0.84]; risk difference [RD], -7.9 [95% CI, -13.6 to -2.6]; P = .004), and 61 (15.6%) in the stress reduction group (OR, 0.66 [95% CI, 0.46-0.94]; RD, -6.3 [95% CI, -11.8 to -0.9]; P = .02). The composite adverse perinatal outcome occurred in 105 newborns (26.2%) in the control group, 73 (18.6%) in the Mediterranean diet group (OR, 0.64 [95% CI, 0.46-0.90]; RD, -7.6 [95% CI, -13.4 to -1.8]; P = .01), and 76 (19.5%) in the stress reduction group (OR, 0.68 [95% CI, 0.49-0.95]; RD, -6.8 [95% CI, -12.6 to -0.3]; P = .02).

Conclusions and relevance: In this randomized trial conducted at a single institution in Spain, treating pregnant individuals at high risk for SGA with a structured Mediterranean diet or with mindfulness-based stress reduction, compared with usual care, significantly reduced the percentage of newborns with birth weight below the 10th percentile. Due to important study limitations, these findings should be considered preliminary and require replication, as well as assessment in additional patient populations, before concluding that these treatments should be recommended to patients.

Trial registration: ClinicalTrials.gov Identifier: NCT03166332.

Conflict of interest statement

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.

Figures

Figure 1.. Flow of Participants in a Study of the Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction on Prevention of Small-for-Gestational Age Birth Weights

Participants who withdrew consent delivered at between 33 and 40 weeks’ gestation.

Figure 2.. Scatterplots of Birth Weight vs Gestational Age at Delivery in Each Study Group With Jitter Random Noise to Avoid Overlaps

Lines indicate the 10th birth weight percentile. For each study group, vertical box plot represents birth weight and horizontal box plot, gestational age at delivery. For each box plot, lines in the middle indicate the median; box ends, IQR; whiskers, values within 1.5× the IQR; and dots, values beyond the whiskers.