Motor Development Problems in Infancy Predict Mental Disorders in Childhood: Longitudinal Child Cohort Study


 The aim was to examine whether motor development problems in infancy predicted mental disorders later in childhood, taking a wide array of potential confounder variables into consideration. This longitudinal study included an unselected study population of 33,238 newborn children from the Copenhagen area in Denmark. Data on the predictor variable motor development problems at age 8-10 months was obtained from the community health nurses’ systematic evaluation of the child’s motor development problems during a home visit stored in the Child Health Database. Data on outcome, diagnosed mental disorders before age 8 years, was obtained from the Danish National Patient Register. The study included potential confounders obtained from the Child Health Database, the National Birth Register, and the Civil Registration System. The prevalence of motor development problems at age 8-10 months was 19.3% and the incidence of any diagnosed mental disorder from age 11 months to the 8th birthday was 4.0%. Motor development problems were associated with an overall increased risk of being diagnosed with a mental disorder before the 8th birthday, adjusted odds ratio (AOR) 1.47 (1.29-1.67), in particular diagnosed neuro-developmental disorders, AOR 1.77 (1.52-2.06), such as autism-spectrum disorders, AOR 1.63 (1.31-2.03), hyperactivity/ attention deficit disorders, AOR 1.29 (1.03-1.61) and disorders of intellectual disability, AOR 3.28 (2.39-4.49). Conclusion: Motor development problems as early at age 9-10 months are predictive of neurodevelopmental disorders at age 1-8 years. The findings call for clinical attention and more research in the preventive potentials in the community child health care.


Introduction
Available research suggest that motor development problems in infancy may be predictive of childhood neuro-developmental disorders, such as autism spectrum disorder (ASD) [1][2][3][4][5][6], disorders of hyperactivity and inattention (ADHD) [2,7,8], and disorders of intellectual disability (ID) [4]. None of the studies published so far have explored the predictiveness of systematically assessed motor development regarding the range of mental disorders seen in childhood, considering unmeasured confounding due to child and family variables [1,[3][4][5][6][7]. Moreover, there is a need to examine whether the municipal child health system can be used to identify children who are at a developmental risk regarding severe mental disorders. Therefore, the aim of this study was to use a large community based cohort to examine whether motor development problems in infancy predicted mental disorders later in childhood, taking a wide array of potential confounder variables into consideration.

Setting
In Denmark, the municipal health care system offers all families with newborn children a series of home visits delivered free of charge by a community health nurse (CHN) [9]. CHNs are registered nurses with a 1½ year further education comprising training in assessment of health and development in children. Approximately 97% of all families participate in these home visits. Most municipalities comply with recommendations from the National Health Authority and offer at least ve home visits (a) a few days after delivery, (b) 1-2 weeks, (c) 2-3 months, (d) 4-6 months and (e) 8.10 months after delivery. CHNs in a range of municipalities have organized a clinical database -the Child Health Database -with standardized data from their records. The health visitors apply a manual of de nitions to ensure comparability and stimulate validity of data in their records. The records include the child's unique person identi cation number which make it possible to link data with data from national health and sociodemographic registers which cover the total population in Denmark.
Study design and study population: Longitudinal study of children from birth to their 8th birthday using clinical data from the Child Health Database and register data from the National Birth Register, the Danish National Patient Register, and the Civil Registration System. Inclusion criteria: 1) All children from 16 municipalities in the Copenhagen region in Denmark born between 1st January 2002 and 31st December 2010 and having their 8th birthday before 1st January 2019 (n=47,167) and 2) included in the Child Health Database. Exclusion criteria: 1) Mental disorder diagnosed at hospital within the rst 10 months of the child's life (n=946); 2) missing data on motor development problems (n=8,634) or any applied control variable (n=4,349), leaving a nal sample of 33,238 children.
Measures: The predictor variable was problems of motor development problems assessed by the CHN at the scheduled home visit at child age 8-10 months. According to the guidelines and the manual for assessments at ages 8-10 months, the health visitor expressed a concern in the record if the child did not meet all these speci c developmental milestones: Unable to roll over from back to stomach and reverse, unable to sit independently, unable to move things from hand to hand, do not put things into the mouth, unable to crawl forwards and/or backwards, unable to pull to a standing position. We summarized the assessment into a dichotomous variable, +-motor development problems.
The outcome variable was any mental disorder diagnosed in hospital settings from child age 11 months to the 8th birthday, obtained from the Danish National Patient Register which includes all in-and outpatient and emergency hospital contacts with a 100% coverage [10]. In these settings, medical doctors conclude on the clinical and paraclinical data to diagnose mental disorders in accordance with the de ning criteria of the International Classi cation of Mental and Behavioral Disorders 10 (ICD-10) [10].
The analyses included the following potential confounders: From the National Birth Register: Sex, parity, gestational age (born 37th week or later vs. before); birth weight (<2500 g, 2500-3999 g, >3999 g); congenital malformation (yes, no); mother's and father's age at childbirth (<25 vs. ≥25); pregnancy complications (yes, no); cesarian section (yes, no); and Apgar score (9-10 vs. less). From the Civil Registration System: parents' education at childbirth ( ve levels); parents' employment (2, 1 or 0 employed parents), family composition (child lives with both parents, yes vs. no), and parents' origin (2, 1 or 0 parents of Danish origin). From the Child Health Database: Concern about mother's mental health in the rst six months after delivery (concern at 0 vs. at least one home visit); and concerns about the parent-child-relationship in the rst six months after delivery (concern at 0 vs. at least one home visit).

Statistical procedures
The rst step was contingency tables for inspection of data and use of chi 2 -test for heterogeneity (not shown in table). The second step was logistic regression analysis of the association between motor development problems at age 8-10 months and diagnosed mental disorder from age 11 months to the 8th birthday, adjusted for all potential confounder variables.

Results
Within the study population of 33,238 children, 19.3% had motor development problems at age 8-10 months. The number of children diagnosed with at least one mental disorder from age 11 months to the 8th birthday was 1,331 (4.0%); 878 (2.6%) were diagnosed with a neuro-developmental disorder, and 671 (2.0%) with a behavioural or emotional disorder. Children who had motor development problems at ages 8-10 months had increased risk of being diagnosed with a mental disorder before the 8th birthday, adjusted OR (95% CI) 1.47 (1.29-1.67 (Table 1). The association between motor development problems in infancy and behavioural or emotional disorders was signi cant in the crude analysis, whereas adjusted analysis showed AOR 1.13 (0.94-1.36). Children with motor development problems in infancy had increased risk of any neuro-developmental disorder (AOR=1.77 (1.52-2.06)) and more speci cally increased risk of ASD (AOR=1.63 (1.31-2.03)), disorders of hyperactivity and inattention (AOR=1.29 (1.03-1.61)) and mental retardation (AOR=3.28 (2.39-4.49)). These estimated attenuated only slightly when adjusted for child and family adversities, such as prematurity, pregnancy and birth complications, low parental education, and maternal and relational problems in infancy.

Discussion
This longitudinal study showed that motor development problems in infancy was associated with diagnosed neuro-developmental disorders in childhood but not behavioural or emotional disorders. Our ndings correspond with the current conceptualization of neuro-developmental disorders [11] as characterized by onset in infancy or early childhood; impairment or delay in the development of functions that are strongly related to the biological maturation of the central nervous system; and a steady course that do not involve remissions and relapses that characterizes many other mental disorders [12]. Due to comprehensive data from national registries, it was possible to adjust for an array of potential confounder of suggested importance in the developmental trajectories of neuro-developmental disorders, including markers of pre-and perinatal adversities. Notably, the associations between motor development problems at ages 8-10 months attenuated only slightly when adjusted for a large number potential confounders.
Overall, our ndings of elevated risk for neuro-developmental disorders corresponds with recent studies of ASD and ADHD [1][2][3][5][6][7][8]. There are several hypotheses that link between motor development problems in early childhood and later neuro-developmental disorders [7,12]. converging on the genetic/epigenetic, and environmental in uences on pre-and postnatal brain maturation and development [12]. However, the present study was not suited to further explore the possible neuro-developmental trajectories.
The strength of the study is the large and unselected study population, the use of standardized data on child development from the CHNs' manualized examinations, the use of validated data on child mental disorders and comprehensive data on child and family variables from population registers, allowing for the extensive control for potential confounders. One limitation is that the validity of the motor skills examination is unknown, although if follows speci c guidelines. From a research point of view, there is a need for insight into the neuro-developmental mechanisms which connect motor development problems and neuro-developmental disorders. Further, we need more information on how to help parents and professionals to deal with motor development problems, methods which are sensitive to the course of developmental change in skills over time [1]. The practical and public health perspectives imply that early identi cation of motor development problems may be an important element to provide a timely diagnosis of neuro-developmental disorders and an early preventive effort to help children at risk [7,12]. Availability of data and material: The data underlying this article will be shared on reasonable request to the Principal Investigator, Dr. Trine Pagh Pedersen (tppe@sdu.dk).
Code availability: Not applicable.
Authors' contributions: All authors contributed substantially to the conception and design of the paper, and to the interpretation of data. TPP and SWP acquired the data. SWP and TPP performed the analyses. SWP and BEH wrote the rst draft of the manuscript. All authors contributed to the writing of the manuscript and a critical revision of the intellectual content. All authors have approved the nal version of the manuscript and are accountable for all aspects of the work.
Ethical approval:The study was approved by the Danish Data Protection Agency (registration number 10.366, University of Southern Denmark) and complied with national regulations of data protection and consent. Linkage with register data was administered by Statistics Denmark and the involved researchers did not have access to personal identi cation. According to the Danish legislation, informed consent is not required for register-based studies.