Citation: Hernández-Martínez, C.; Canals, J.; Voltas, N.; Martín-Luján, F.; Arija, V. Circulating Levels of Short-Chain Fatty Acids during Pregnancy and Infant Neurodevelopment. Nutrients 2022, 14, 3946. https://doi.org/10.3390/ nu14193946 Academic Editor: Gary David Lopaschuk Received: 10 August 2022 Accepted: 21 September 2022 Published: 23 September 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Article Circulating Levels of Short-Chain Fatty Acids during Pregnancy and Infant Neurodevelopment Carmen Hernández-Martínez 1,2,3 , Josefa Canals 1,2,3 ,Núria Voltas 1,2,3,4 , Francisco Martín-Luján 5 and Victoria Arija 1,3, * 1 Research Group in Nutrition and Mental Health (NUTRISAM), Universitat Rovira i Virgili, 43204 Reus, Spain 2 Research Center for Behavioral Assessment (CRAMC), Universitat Rovira i Virgili, 43003 Tarragona, Spain 3 Pere Virgili Institute for Health Research (IISPV), Universitat Rovira i Virgili, 43201 Reus, Spain 4 Serra Húnter Fellow, Department of Psychology, Faculty of Education Sciences and Psychology, Universitat Rovira i Virgili, 43007 Tarragona, Spain 5 Research Support Unit Tarragona, Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP JGol), 43202 Reus, Spain * Correspondence: victoria.arija@urv.cat Abstract: Background: Short-chain fatty acids (SCFA) play a key role in the gut microbiota–brain crosstalk regulating the main neurodevelopmental processes during pregnancy. The aim of this study is to investigate the longitudinal relationship between prenatal levels of the main SCFAs in maternal serum and infant cognitive development and temperament on day 40 postpartum after adjusting for several pre-, peri- and post-natal confounders. Methods: A sample of 357 healthy mother–infant pairs were followed from the beginning of pregnancy to 40 days after birth. Serum SCFA concentrations were assessed in the first and third trimester of pregnancy by LC-MS/MS; and socio-demographic, nutritional, and psychological variables were collected. At 40 days, the Bayley Scales of Infant Development-III and the Early Infancy Temperament Questionnaire were administered. Results: Lower serum levels of acetic, butyric and isobutyric acid, mainly during the first trimester, were related to better language and psychomotor development and, in the case of butyric acid, better intensity behavior in infants. Medium levels of propionic acid were related to better scores for development, mood and temperament. Conclusions: These findings suggest that in a community sample of healthy pregnant women from a Mediterranean region of northern Spain, lower serum levels of SCFAs, especially in the first trimester of pregnancy, seem to be related to better infant neurodevelopment Keywords: short chain fatty acids; acetic acid; propionic acid; butyric acid; isobutyric acid; pregnancy; neurodevelopment; cognitive development; infant 1. Introduction The gut microbiota is the ecological community of symbiotic and pathogenic microor- ganisms present in the gut, some of which are critically involved in gut–brain communi- cation [1]. Short-chain fatty acids (SCFAs) are the main metabolites produced by the gut microbiota when it assimilates dietary fiber and protein. Early childhood is a dynamic time for gut colonization and brain development, but little is known about the relationship between these two processes [2]. Both the gut and the brain undergo rapid changes during pregnancy and the early postnatal period, and disruption during these early colonization processes can precipitate a cascade of repercussions that may lead to behavioral and cogni- tive impairments in infants [3]. The relationship between the mother’s microbiota during gestation and the infant’s brain, behavior and cognitive development has been studied very little and most evidence comes from animal models. These models suggest that gut colo- nization by microbiota has become integrated into the programming of brain development and interacts in key developmental periods that affect infants’ synaptic activity, cognitive Nutrients 2022, 14, 3946. https://doi.org/10.3390/nu14193946 https://www.mdpi.com/journal/nutrients