Study suggests yes, but more research is needed before recommendations are made

Treating pregnant women with either a structured Mediterranean diet or mindfulness-based stress reduction may reduce the risk of their child being born small for gestational age (SGA), according to findings from the Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN); however, those findings will require replication before either intervention can be recommended, the investigators added.

Babies who are born SGA, or with a birth weight below the 10th percentile, face substantial perinatal morbidity and mortality, and SGA is associated with long-term adverse neurologic and cardiometabolic outcomes. Currently, there is no effective therapy or prevention strategy recommended for the prevention of SGA in newborns. However, a pair of interventions aimed at improving diet and stress in expectant mothers—a Mediterranean diet and structured mindfulness-based stress reduction—may offer some protective effect, Eduard Gratacós, MD, PhD, of the Universitat de Barcelona in Barcelona, Spain, and colleagues from IMPACT BCN explained in JAMA.

The IMPACT BCN investigators assessed whether structured lifestyle interventions based on either the Mediterranean diet or stress reduction led to reduced rates of birth weight below the 10th percentile compared to usual care in a cohort of 1,221 pregnant individuals at high risk for SGA.

They found that both interventions were associated with reductions in the incidence of babies born SGA compared to infants born to mothers in the control group, as well as substantial reductions in the incidence of adverse perinatal outcomes.

However, while these findings may point the way towards future pregnancy interventions to reduce SGA incidence, given a number of limitations—including the speculative nature of the study hypotheses, limitations in generalizability, and low proportions of patients with obesity or metabolic conditions—the study authors concluded that these findings “should be considered preliminary unless and until they are replicated, including in more diverse populations.”

The parallel, unblinded, randomized IMPACT BCN trial was conducted at BCNatal (Hospital Clínic and Hospital Sant Joan de Déu) in Barcelona, Spain, among 1,221 individuals with singleton pregnancies at high risk for SGA from Feb. 1, 2017 to Oct. 10, 2019, with follow-up until delivery.

Patients were randomized 1:1:1 to one of three study groups: the Mediterranean diet intervention, the stress reduction program, or usual care. The non-pharmacological interventions were carried out as follows.

The Mediterranean diet intervention was adapted from the PREDIMED trial. Patients were given 2 L of olive oil and 450 g of walnuts a month at no cost. Dietitians conducted face-to-face interviews once a month from enrollment through the end of the intervention, and participants received dietary training and advice to increase diet adherence, “including recipes, a quantitative 1-week shopping list of food items according to the season of the year, and a weekly plan of meals with detailed menus that were also available on the trial website,” the study authors explained. “Participants were encouraged to increase the intake of whole grain cereals (≥5 servings/d); vegetables and dairy products (≥3 servings/d); fresh fruit (≥2 servings/d); and legumes, nuts, fish, and white meat (≥3 servings/week), as well as olive oil use for cooking and dressings.”

The stress reduction program was based on the program described by Kabat-Zinn and adapted for the pregnancy status of the participants. “Stress reduction instructors all self-identified as women, shared several meditations focused on the participant’s relationship with the fetus, encouraged informal ’being with the baby’ practices, and taught prenatal yoga positions,” they explained. “The 8-week program-structured intervention included weekly 2.5-hour sessions, 1 full-day session, and daily home practice. The stress reduction program included formal and informal techniques, with the goal of enhancing nonjudgmental present-focused awareness and reducing rumination (dysregulated focus on the past) and anxiety. The sessions included didactic presentations, formal 45-minute meditation practices with various mindfulness meditations, mindful yoga, body awareness, and group discussion. Home practice was strongly encouraged and was recommended to consist of 45-minute daily formal practice (e.g., sitting and walking meditation, body scanning, yoga stretching) and informal practice (e.g., mindfulness of daily activities, the 3-minute breathing space).”

The study’s primary endpoint was the percentage of newborns who were SGA at delivery; the secondary endpoint was the percentage of newborns with adverse perinatal outcomes, defined as a composite of either preterm birth less than 37 weeks’ gestation, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, Apgar score below 7 at five minutes, or the presence of any major neonatal morbidity (intraventricular hemorrhage grade III/IV, necrotizing enterocolitis, periventricular leukomalacia, sepsis, bronchopulmonary dysplasia, or hypoxic-ischemic encephalopathy).

Of the 1,221 pregnant individuals randomized, 1,184 completed the trial; of these, 392 were assigned to the Mediterranean diet group, 391 to the stress reduction group, and 401 to the usual care group. The majority of participants were White (80.1% in the diet group, 77% in the stress reduction group, 78.8% in usual care) and had high socioeconomic status (59.7%, 54.7%, and 57.1%, respectively).

“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=0.004), 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=0.02),” the study authors reported. “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=0.01), 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=0.02).”

These findings from IMPACT BCN “are novel in demonstrating that nutritional and psychological interventions may have a clinically important effect on fetal growth beyond usual prenatal care,” Margaret Bublitz, PhD, and Methodius G. Tuuli, MD, MPH, MBA, both of The Warren Alpert School of Medicine of Brown University in Providence, Rhode Island, wrote in an accompanying editorial. “These results are biologically plausible… [and] represent important novel findings, given that there is no proven intervention for prevention of SGA.”

The study authors pointed out several study limitations that they argued preclude recommending these interventions to pregnant women at this stage:

  • The biological basis of the study hypotheses and results is speculative.
  • The effect size in the control group was smaller than predicted.
  • There were imbalances in prognostic characteristics between groups at baseline.
  • The excess number of early births in the control group were primarily early in the intervention period, “raising a question of whether the observed differences were due to the intervention or represent a chance outcome.”
  • A healthier diet may have reduced stress levels, and vice versa.
  • There was not enough attention paid to ensuring control participants had the same number of study visits and personal interactions as the intervention groups.
  • The interventions were started mid-pregnancy and only in high-risk patients, which may limit generalizability.
  • The study was conducted in a high-resource setting and primarily among White patients.
  • There was a low proportion of patients with obesity, gestational diabetes, and large-for-gestational-age newborns, and the interventions may not be effective in these patients.

“With only short-term outcomes reported, it is unknown if these interventions have lasting effects for mother or child,” Bublitz and Tuuli added in their editorial. “The composite adverse perinatal outcome included a heterogeneous group of outcome measures, some of which are not causally related to SGA. Moreover, even though the study showed benefit, it is notable that adherence to the interventions was relatively low (60% for Mediterranean diet and 50% for mindfulness-based stress reduction). In addition, the investigators did not test the effect of a combination of the two interventions to assess for a possible additive or synergistic effect.”

Bublitz and Tuuli ultimately agreed that the findings by Gratacós et al should not be integrated into clinical practice until the results are replicated and until the IMPACT BCN study authors can ascertain neurodevelopmental outcomes among these offspring at 2 years of age.

  1. Treating pregnant women with either a structured Mediterranean diet or mindfulness-based stress reduction may reduce the risk of their child being born small for gestational age.

  2. Be aware that due to a large number of study limitations, the IMPACT BCN results will require further replication before these interventions can be integrated into clinical practice.

John McKenna, Associate Editor, BreakingMED™

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.

The editorialists had no relevant relationships to disclose.

Cat ID: 41

Topic ID: 83,41,730,41,138,94,925