Do nutritional interventions before or during pregnancy affect placental phenotype? Findings from a systematic review of human clinical trials.

BackgroundMaternal nutritional interventions aim to address nutrient deficiencies in pregnancy, a leading cause of maternal and neonatal morbidity and mortality worldwide. How these interventions influence the placenta, which plays a vital role in fetal growth and nutrient supply, is not well understood. This is a major gap in understanding how such interventions could influence pregnancy outcomes and fetal health. We hypothesised that nutritional interventions influence placental phenotype, and that these placental changes relate to how successful, or not, the intervention is in improving pregnancy outcomes. MethodsWe conducted a systematic review and followed PRISMA-2020 reporting guidelines. Articles were retrieved from PubMed, Clinicaltrials.gov, and ICTRP-WHO using pre-defined search terms and screened by two reviewers using a 3-level process. Inclusion criteria considered articles published from January 2001-September 2021 that reported on clinical trials in humans, which administered a maternal nutritional intervention during the periconceptional or pregnancy period and reported on placental phenotype (shape and form, function or placental disorders). FindingsFifty-three eligible articles reported on (multiple) micronutrient- (n=33 studies), lipid- (n=11), protein- (n=2), and diet-/lifestyle-based (n=8) interventions. Of the micronutrient-based interventions, 16 (48%) associated with altered placental function, namely altered nutrient transport/metabolism (n=9). Nine (82%) of the lipid-based interventions associated with altered placental phenotype, including elevated placental fatty acid levels (n=5), altered nutrient transport/metabolism gene expression (n=4), and decreased inflammatory biomarkers (n=2). Of the protein-based interventions, two (66%) associated with altered placental phenotype, including increased placental efficiency (n=1) or decreased preeclampsia risk (n=1). Three (38%) of diet and lifestyle-based interventions associated with placental changes, namely placental gene expression (n=1) and disease (n=2). In studies with data on maternal (n=30) or offspring (n=20) outcomes, interventions that influenced placental phenotype were more likely to have also associated with improved maternal outcomes (11/15 [73%]) and offspring birth outcomes (6/11 [54%]), compared to interventions that did not associate with placental changes (2/15 [13%] and 1/9 [11%], respectively). ConclusionsPericonceptional and prenatal nutritional interventions to improve maternal/pregnancy health associate with altered placental development and function. These placental adaptations likely benefit the pregnancy and improve offspring outcomes. Understanding the placentas role in the success of interventions to combat nutrient deficiencies is critical for improving interventions and reducing maternal and neonatal morbidity and mortality globally.