RESEARCH ARTICLE Language regression is associated with faster early motor development in children with autism spectrum disorder Liora Manelis, Gal Meiri, Michal Ilan, Hagit Flusser, Analya Michaelovski, Michal Faroy, Orly Kerub, Ilan Dinstein , and Idan Menashe Language regression (LR) is a consistent and reproducible phenomenon that is reported by ~25% of parents who have children with autism spectrum disorder (ASD). However, there is controversy regarding the etiological and clinical signifi- cance of this phenomenon. Here, we examined data from a cohort of 218 children with ASD from the Negev Autism Cen- ter in Israel. We identified 36 children with ASD who were reported to exhibit clear LR by their parent on three independent occasions and compared them to 104 children whose parents did not report any concern of regression (NR). We compared a variety of key developmental characteristics across these two groups. We found that the age at which children with ASD in the LR group achieve key developmental milestones of crawling, walking, and use of first words is significantly younger than the age of children in the NR group, and comparable to the age of typically developing chil- dren. In contrast, no differences were observed in physical growth characteristics such as head circumference, weight, or height between the groups. Furthermore, almost all children with LR were born close to full term (>35 weeks) and none had a history of hypotonia. Notably, despite their apparently typical early development, children with LR were diagnosed with more severe symptoms of ASD than children with NR. These results strengthen the motivation to continue and study LR among children with ASD and suggest that early detection and intervention studies of ASD may benefit from stratifying children into LR and NR groups. Autism Res 2020, 13: 145–156. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: The presence of language regression (LR) among children with autism is still a matter of scientific debate. Here, we show that children with autism and reported LR start to crawl, talk, and walk at the same age as other typically developing children and significantly earlier than other children with autism. These findings, along with other medical differences between these groups, suggest that children who experienced LR comprise a distinct subgroup within the autism spectrum. Keywords: autism spectrum disorder; language regression; early development; motor development Introduction A major goal of contemporary research of autism spectrum disorder (ASD) is to characterize the large behavioral, bio- logical, and clinical heterogeneity apparent across children with ASD. This is critical for developing new early detec- tion measures and therapies for specific subtypes of ASD (i.e., personalized medicine) [Loth et al., 2016; State et al., 2012]. One well-known developmental characteristic that may hold relevant potential is regression [Hansen et al., 2008]. Regression (i.e., loss of previously acquired skills) is reported by parents of approximately one-third of children with ASD [Barger, Campbell, & McDonough, 2013]. The clinical significance and utility of this phenomenon have been debated for many years [Pearson, Charman, Happé, Bolton, & McEwen, 2018] with some suggesting that regression may characterize unique subgroups of children with ASD with distinct etiologies [Stefanatos, 2008; Tuchman & Rapin, 1997] and others suggesting that regression, to one degree or another, is a common finding in most children with ASD [Ozonoff et al., 2010; Thurm, Powell, Neul, Wagner, & Zwaigenbaum, 2018]. An important aspect of the debate about regression is its precise definition. Some studies have defined regres- sion broadly as the loss of any skill including motor and cognitive skills, while others have focused on the social communication and language skills that are specific to ASD [Barger et al., 2013; Hansen et al., 2008; Ozonoff From the Psychology Department, Ben Gurion University, Beer Sheva, Israel (L.M., M.I., I.D.); Zlotowski Center for Neuroscience, Ben Gurion University, Beer Sheva, Israel (L.M., I.D., I.M.); Pre-School Psychiatry Unit, Soroka University Medical Center, Beer Sheva, Israel (G.M., M.I., M.F.); Zusman Child Development Center, Soroka University Medical Center, Beer Sheva, Israel (H.F., A.M.); Ministry of Health, Jerusalem, Israel (O.K.); Cognitive and Brain Sciences Department, Ben Gurion University, Beer Sheva, Israel (I.D.); Public Health Department, Ben Gurion University, Beer Sheva, Israel (I.M.) Liora Manelis and Gal Meiri contributed equally to this work. Received May 19, 2019; accepted for publication July 26, 2019 Address for correspondence and reprints: Idan Menashe, Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. E-mail: idanmen@bgu.ac.il Published online 30 August 2019 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/aur.2197 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. INSAR Autism Research 13: 145–156, 2020 145