Tracing neurodevelopment and growth pattern in six-year-old children with idiopathic clubfoot: A national cohort study

doi:10.21203/rs.3.rs-4721120/v1

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Tracing neurodevelopment and growth pattern in six-year-old children with idiopathic clubfoot: A national cohort study

https://doi.org/10.21203/rs.3.rs-4721120/v1

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Study design:

Population-based retrospective cohort study

Objectives

Timely recognition and intervention are crucial for idiopathic clubfoot management, yet its developmental impact on children is underexplored. This study investigates neurodevelopment and physical growth in children with idiopathic clubfoot up to age six.

Methods

This population-based retrospective cohort study was conducted in South Korea (2009–2019) using linked data from National Health Insurance Service. The cohort included children diagnosed with idiopathic clubfoot and 1:10 exact match of unexposed children. Neurodevelopmental assessments were conducted using the validated Korean Developmental Screening Test, which covers six domains: gross motor skills, fine motor skills, cognition, language, social skills, and self-regulation, for children aged 42–71 months. Secondary outcomes measured were height and body mass index (BMI) Z-score during the same period.

Results

The cohort comprised 484 children with idiopathic clubfoot and 4,840 matched unexposed children. Children with clubfoot had a higher rate of premature birth (7.44% vs. 3.66%, p < 0.0001), lower birth weight (3.08 ± 0.59 kg vs. 3.20 ± 0.46 kg, p < 0.0001), and higher frequency of breastfeeding (42.9% vs. 33.7%, p < 0.001), compared to the unexposed children. In-depth evaluation of all six neurodevelopmental domains showed significant differences in children with clubfoot (overall aOR, 3.671; 95% CI, 2.463–5.471). Children with clubfoot showed a significant height delay (Z score, -1.63 below), but no BMI difference was noted.

Conclusions

Children with clubfoot exhibited differences in neurodevelopment and height. Early parental concern and proactive therapeutic interventions are crucial during the initial stages of developmental delay in children with clubfoot.

Idiopathic clubfoot

neurodevelopment

physical growth

developmental delay

cohort study

Clubfoot, a congenital deformity characterized by inward and downward twisting of the foot, is prevalent worldwide. (1) Although various types have been identified, including idiopathic and non-idiopathic forms, the etiology of the disorder remains complex and multifaceted. (1) Recent research has indicated a potential link between clubfoot and neurodevelopmental disorders, suggesting an underlying neurogenic origin or shared genetic pathways. (2) However, comprehensive studies in this domain remain scarce. (3, 4) Despite advancements in treatment techniques, such as the Ponseti method, the long-term neurodevelopmental outcomes in children with clubfoot are not well-documented, leading to a significant gap in understanding the full spectrum of the impact of the disorder. (5, 6)

The relationship among clubfoot, stature, and obesity is another understudied aspect of this condition. Taking into consideration the physical constraints and altered biomechanics imposed by clubfoot, it is plausible that these children exhibit differences in growth patterns and body composition compared to their peers. (7, 8) Furthermore, the potential interplay between clubfoot and comorbid conditions could indirectly influence growth and weight management. Despite these plausible associations, there is a lack of substantial research exploring how clubfoot affects height and propensity for obesity, leaving unanswered questions regarding the full physical ramifications of the condition.

This study aimed to bridge these gaps by investigating the neurodevelopmental trajectories and correlation between height and body mass index (BMI) in children born with clubfoot. Specifically, we examined whether clubfoot is an independent predictor of neurobehavioral disorders and altered growth patterns. Addressing these questions will not only deepen our understanding of the long-term outcomes of clubfoot, but also inform clinical practices and parental guidance. By elucidating these associations, this study aimed to contribute significantly to pediatric orthopedics and neurodevelopmental research, potentially leading to more holistic approaches in the management and follow-up of children with clubfoot.

Study design and setting

This retrospective population-based cohort study conducted in South Korea utilized administrative claims data from the National Health Insurance Service (NHIS) and National Health Screening Program for Infants and Children (NHSPIC). Our study focused on individuals who were born between 2002–2005 and tracked until they reached the age of six years, as identified by the NHIS database, which covers more than 98% of the South Korean population. (9) The NHIS database includes comprehensive data on demographic characteristics, healthcare utilization, medical treatment, prescriptions, and procedures. (10) In this study, the exposure of interest was clubfoot, which was identified using the International Classification of Diseases, 10th revision (ICD-10) codes, and casting procedures. The NHIS data allowed accurate identification of individuals diagnosed with clubfoot during the study period. The outcomes of interest were neurodevelopmental and physical development assessed up to approximately six years of age. The NHIS database, along with linked data from the NHSPIC, provided the necessary information to evaluate these outcomes. Overall, this study leveraged the comprehensive and detailed NHIS and NHSPIC databases to investigate the association of clubfoot with subsequent neural and physical development in a large population-based cohort in South Korea.

Participants

This study initially included 1,919,162 children born in South Korea between 2009–2012. From this initial group, we identified children who underwent the Korean Developmental Screening Test for Infants and Children (K-DST) at ages 4, 5, and 6, totaling 1,325,317 individuals. Additionally, children with recorded birth weights were included, amounting to 1,809,566 participants. A total of 4,570 children with chromosomal anomalies (Q90–Q99) were excluded from the study because we only wanted to include idiopathic clubfoot cases. After applying the inclusion and exclusion criteria, the final cohort comprised 1,319,431 children. Within this cohort, children diagnosed with clubfoot using the ICD codes amounted to 2,904 individuals in total. Among them, 484 children who underwent casting procedures were classified as exposed individuals because the ICD code can sometimes be inaccurate. In the context of unexposed children, they were matched with others from the cohort at a 1:10 ratio based on birth year and sex. This resulted in a control group of 4,840 children. Consequently, the total number of study participants, combining exposed and unexposed children, was 5, 324.(Fig. 1)

Exposure

Patients with idiopathic clubfoot were diagnosed as per the ICD codes Q660X or Q668X, and also included those who underwent casting procedures (Electronic Data Interchange [EDI] codes: N0802, T6140, T6137, T6051, and T6052) within the one year after birth without fracture. Additionally, for children who underwent surgical treatment, surgeries were classified into non-extensive surgical procedures, such as heel cord lengthening (EDI code: N0921), subcutaneous tenotomy (N0911, N0912), and simple tendon lengthening (N0931), and extensive surgery, such as tendon and ligament reconstruction (N0932) or osteotomy (N0304, N0307).(11) Furthermore, the study participants were divided into groups based on whether the casting was performed on one or both sides. If a participant received two casting prescriptions on the same day, it was classified as bilateral casting.

Primary outcome: Neurodevelopment

The primary outcome of this study was neurodevelopmental status of children, which was assessed using the validated K-DST. (12) Assessments were conducted in the 5th (42–48 months), 6th (54–60 months), and 7th (66–71 months) phases. The K-DST consists of 48 items, covering six specific developmental domains: gross motor skills, fine motor skills, cognition, language, social skills, and self-regulation. In addition, an overall development assessment was conducted by integrating the six areas. Responses to the assessment items were provided by reliable informants, typically parents or guardians, who had observed the developmental progress of the child. In K-DST, scores falling one standard deviation (SD) or more above the mean within the age group are categorized as ‘Advanced Level’, within ± 1 SD as ‘Peer Level’, below − 1 SD but above − 2 SD as ‘Reassessment Recommended Level’, and below − 2 SD as ‘In-depth Evaluation Recommended Level’. (12, 13) In our study, the ‘In-depth Evaluation Recommended Level’ category was selected as the primary outcome.

Secondary outcome: Physical growth

The secondary outcome was anthropometric measurements, including height and BMI, which were evaluated at the same time as screening. BMI was defined as overweight with a BMI Z-score ranging between 1.04–1.63, and obesity with a BMI Z-score > 1.63.(14) For height, the degree of developmental delay was assessed based on the Z-score criteria derived from BMI. The results were analyzed for differences based on sex.

Covariate

We analyzed variables including sex and birth year, which were used for matching, along with additional variables such as premature birth, birth weight, birthplace, parental income level, and breastfeeding status at four months. Babies born before 37 weeks of gestation were categorized as premature. (15) The birthplace was categorized into Seoul, metropolitan areas, cities, and rural areas. Parental income level was analyzed by dividing it into four quartiles based on health insurance data. The analysis also considered breastfeeding status in children aged 4–6 months, with the following possible answers: ‘absolute breastfeeding’, ‘formula feeding’, or ‘mixed feeding’.

Statistical analysis

Data were expressed as mean ± standard deviation (SD) or 95% confidence interval (CI). Generalized estimating equations were used in this study to analyze neurodevelopmental and physical growth outcomes during the 5th, 6th, and 7th phases. Continuous variables in each group were compared using independent sample t-tests, whereas nominal variables were analyzed using Chi-square test. For neurodevelopmental assessment items and physical growth measures including height and BMI, adjustments were made for several covariates. These included sex and birth year, which were used as matching variables, as well as premature birth (yes or no), birth weight (continuous value), birthplace (Seoul, metropolitan, city, or rural), parental income level (quartile level), and breastfeeding status (yes or no). All statistical analyses were performed using the SAS statistical analysis software, version 9.4 (SAS Institute Inc., Cary, NC, USA). Level of significance was set at two-tailed p-value of < 0.05.

The study population included 484 patients with clubfoot, of which 303 (62.6%) were boys. Among these children, 36 (7.4%) were born prematurely, which was significantly higher than the 177 (3.7%) matched unexposed children. The average birth weight of infants with clubfoot was 3.08 kg (SD, 0.59), which was significantly lower than the 3.2 kg (SD, 0.46) of unexposed children. However, birthplace, parental income level, and birth year did not show any significant correlation with the incidence of clubfoot. Infants with clubfoot received their first cast at an average age of eight months. More than half of these infants (264/484, 54.6%) required four or more casts, and more than half (285/484, 58.9%) underwent surgery at an average age of 12.8 months after birth. Among them, 155 underwent less extensive surgery, while 130 underwent more extensive procedures. A total of 135 (27.9%) patients had bilateral clubfoot (Table 1).

Table 1

Patient characteristics
	Matched unexposed individuals (N = 4840)	Patients with idiopathic clubfoot (N = 484)	P value
Sex (Male/Female)	3,030/1,810	303/181	1.000
Premature birth	177 (3.7)	36 (7.4)	< 0.0001^*
Breast feeding status
Exclusive breast feeding	1,376 (42.9)	102 (33.7)	0.0017^*
Others	1,833 (57.1)	201 (66.4)	0.0017^*
Calendar birth year
2009	720 (14.9)	72 (14.9)	1.000
2010	1250 (25.8)	125 (25.8)
2011	1340 (27.7)	134 (27.7)
2012	1530 (31.6)	153 (31.6)
Birthplace
Seoul	896 (18.7)	105 (21.8)	0.2475
Metropolitan	1,155 (24.1)	102 (21.2)
City	2,379 (49.7)	235 (48.9)
Rural	355 (7.4)	39 (8.1)
Missing	55 (1.4)	3 (0.8)
Income
Quartile 1	521 (10.8)	54 (11.2)	0.5218
Quartile 2	1,036 (21.4)	98 (20.3)
Quartile 3	1,826 (37.8)	194 (40.1)
Quartile 4	1,275 (26.3)	114 (23.6)
Missing	182 (3.8)	24 (5.0)
Birth weight, kg	3.20 ± 0.46	3.08 ± 0.59	< 0.0001^*
Bilateral clubfoot		135 (27.9)	-
Age at first cast application (in months)		7.9 ± 2.3	-
Cast frequency			-
Once		88 (18.2)	-
Twice		81 (16.7)	-
Thrice		51 (10.5)	-
Four or more times		264 (54.6)	-
Surgery (n)		285 (58.9)	-
Non-extensive surgery		155 (54.4)	-
Extensive surgery		130 (45.6)	-
Values are expressed as number (%) or mean ± standard deviation, unless otherwise indicated.
Student’s t-test was used to analyze birth weight; Chi-square test was used to analyze sex, premature birth, birth year, birthplace, and income.
^*P < 0.05

Main outcome

For the main outcomes, we evaluated the overall neurodevelopmental outcomes in children with clubfoot. Compared to unexposed children, children with clubfoot showed a significantly increased odds ratio (OR) of 3.67 (95% CI, 2.46–5.47) for neurodevelopmental issues, even after controlling for confounding variables. No significant interaction with time was observed for these outcomes (p = 0.198). This increase was consistent across all six domains. The domains where elevated risk was observed included gross motor skills (adjusted OR[aOR], 10.1; 95% CI, 5.78–17.6), fine motor skills (aOR, 4.2; 95% CI, 2.35–7.36), cognition (aOR, 3.44; 95% CI, 2.05–6.23), language (aOR, 3.57; 95% CI, 1.43–5.27), social skills (aOR, 2.74; 95% CI, 1.43–5.27), and self-regulation (aOR, 5.12; 95% CI, 2.69–9.77), all showing significant differences (Table 2).

Table 2

Proportion of the study population requiring reassessment and in-depth evaluation based on K-DST results (overall and six specific domains)
	Matched unexposed individuals (n = 4840)	Patients with clubfoot (n = 484)	Odd ratio
	Matched unexposed individuals (n = 4840)	Patients with clubfoot (n = 484)	Estimate	Wald 95% CI	P value
Overall	144 (3.0)	59 (12.2)	3.671	2.463–5.471	< 0.0001^*
Gross motor	57 (1.2)	44 (9.4)	10.077	5.771–17.594	< 0.0001^*
Fine motor	71 (1.5)	32 (6.8)	4.162	2.354–7.361	< 0.0001^*
Cognition	79 (1.7)	32 (6.8)	3.439	1.914–6.176	< 0.0001^*
Language	79 (1.7)	33 (7.0)	3.573	2.049–6.233	< 0.0001^*
Social skills	69 (1.5)	28 (6.0)	2.741	1.426–5.266	0.0025^*
Self-help	57 (1.2)	31 (6.6)	5.122	2.685–9.770	< 0.0001^*
Values are expressed as number (%)
K-DST, Korean Developmental Screening Test for Infants and Children
^*P < 0.05

These results indicate that the subgroup analysis, which evaluated the overall developmental assessment of both unilateral and bilateral clubfeet, did not reveal significant difference in the proportion of patients requiring in-depth evaluation (p = 0.3394). Furthermore, there was no significant difference in the need for in-depth evaluation between patients with clubfoot who underwent surgical treatment and those who did not (p = 0.1967) (Table 3).

Secondary outcome

When assessing physical development, including height and obesity, in children aged 4–6 years, those with clubfoot did not show an increased risk of obesity compared to the matched unexposed children. This was consistent for both boys (aOR, 1.166; 95% CI, 0.885–1.535) and girls (aOR, 1.297; 95% CI, 0.728–2.311). Moreover, no significant differences were observed between the two groups. Interestingly, the risk was higher in children with clubfoot compared to the matched unexposed children when the height Z-score value was less than − 1.63. This difference was consistent in both boys (aOR, 2.725; 95% CI, 1.884–3.941, p < 0.0001) and girls (aOR, 3.947; 95% CI, 2.550–6.108, p < 0.0001). This trend remained consistent for height Z-score values below − 1.03 as well. (Table 4)

Similar to neurodevelopment assessment, subgroup analyses were conducted for height and BMI based on presence of surgery and whether clubfoot was unilateral or bilateral. In all subgroups, no significant difference was observed in terms of BMI. However, for height, both the unilateral and bilateral groups, regardless of sex, showed an increased risk of having a height Z-score below − 1.63 compared to the matched unexposed children, with no difference in interaction between the two groups. This trend was also observed when comparing the surgical and non-surgical groups.

Until now, research on idiopathic clubfoot has predominantly focused on the conditions that may accompany it at birth. There has been little exploration of the developmental process of individuals with clubfoot in comparison to typically developing children during subsequent growth stages. This study used extensive national datasets to examine the developmental milestones achieved between 42–71 months post birth in South Korean children diagnosed with idiopathic clubfoot. The study findings showed that patients with idiopathic clubfoot exhibited overall neurodevelopmental delay, particularly in terms of all six detailed items of K-DST (gross motor skills, fine motor skills, cognition, language, social skills, and self-regulation), indicating the necessity for careful observation due to functional impairment compared to normal children. Additionally, in anthropometric measurements, patients with clubfoot showed a distinct decrease in height. Based on these findings, clinicians should closely monitor and proactively intervene in the developmental delays and growth issues observed in patients with idiopathic clubfoot.

Recent studies, including those by Loof et al.(3, 16, 17), have established a link between idiopathic clubfoot in infants and various neurodevelopmental issues, such as motor deficits, hyperactivity, language difficulties, attention problems, and social skill challenges. The aforementioned studies reported that children with idiopathic clubfoot exhibited significant delays in motor skills, such as running, walking, and hopping, as well as in cognitive domains, such as language, perception, and self-regulation, compared with their typically developing peers.(3, 16, 17) Notably, our study also confirms these findings, indicating a consistent pattern across different research. Furthermore, a high incidence of attention deficit/hyperactivity disorder was also noted among patients with clubfoot. This body of research, which included a substantial number of patients with clubfoot and utilized nation-wide data, underscores the importance of early interventions for these developmental delays. (18–20) Such interventions are crucial for improving the overall developmental trajectory and quality of life of children with clubfoot, highlighting the need for increased awareness among parents along with regular assessments and interventions during pediatric health checkups. (17, 18, 21)

Interestingly, among the physical growth parameters, while there was no difference in BMI, a disadvantage in height was observed among children with clubfoot. Height, a trait influenced by genetic and environmental components, is often affected by factors like growth delays, puberty timing, and medical conditions such as Down and Turner syndromes. (22, 23) The XXXXY variant of Klinefelter syndrome has been identified as the only condition till date wherein clubfoot and short stature can coexist.(24) The 49,XXXXY variant of Klinefelter syndrome is an uncommon form characterized by distinctive skeletal abnormalities (such as clubfoot, cubitus varus, and flat foot) along with significant cognitive, behavioral, and intellectual disabilities. Unlike other Klinefelter syndrome variants, individuals with 49,XXXXY often exhibit a short stature.(24) Moreover, in cases of Larsen syndrome, there is a potential for the coexistence of clubfoot and short stature. The etiology of Larsen syndrome has been linked to mutations in the FLNB gene, which encodes the cytoskeletal protein filamin B, a pivotal contributor to skeletal development.(25) However, in this study, children with chromosomal abnormalities were excluded, and the findings suggested that growth discrepancies were not related to chromosomal anomalies. Although some studies suggest that genetic factors may simultaneously contribute to the development of clubfoot and short stature, detailed investigations focusing specifically on short stature traits in individuals with clubfoot remain scarce.(26, 27) However, it is important to note that differences in height may not be entirely due to genetic predisposition. It could also be associated with a range of factors implicated in the etiology of clubfoot, such as vascular and environmental influences, in utero positioning, and anatomical variations. (28–30). Our study adds a new dimension to this discussion by confirming an increased rate of preterm births among infants diagnosed with idiopathic clubfoot. Given that preterm birth is affected by a wide array of maternal and fetal characteristics, this correlation suggests that the underlying causes of clubfoot may extend beyond genetic factors. (31, 32) This finding underscores the importance of broadening research efforts to explore the diverse factors that influence the occurrence of clubfoot and its impact on growth patterns, with special emphasis on skeletal development.

Our study has made significant advancements by establishing a connection between clubfoot and short stature. Higher prevalence of short stature was noted among patients with idiopathic clubfoot of both sexes. This observation is particularly pertinent in children aged 42–71 months. This underscores the need for further research to explore the persistence and implications of this difference in stature as children grow.

This study had a few limitations that need consideration. First, the developmental assessment in this study was limited to children aged 42–71 months. Further research is required to investigate developmental disorders as children grow older. However, to address this limitation, GEE were conducted by controlling for the time variable during this specific period. Consequently, there was no observed tendency for developmental disorders to worsen as the children grew older. Second, although this study targeted all children in Korea during the specified period, the frequency of clubfoot was relatively low, making the sample size of 484 relatively small for being classified as "big data." Nevertheless, considering the absence of big data studies recruiting such patient population, this study holds significance.

Individuals with clubfoot demonstrated developmental delays across various domains, including gross motor skills, fine motor skills, cognition, language, social skills, and self-regulation, in contrast to their typically developing counterparts. Additionally, given the short stature of patients with clubfoot in comparison to their peers, it is imperative to actively monitor and observe not only the apparent structural deformities in the feet, but also the potential presence of various developmental disorders that might coexist.

Ethics approval and consent to participate: This study was approved by the Institutional Review Board (IRB) of CHA Bundang Medical Center (IRB number: 2023-10-204). Approval date: 2023-10-23. This study was performed in line with the principles of the Declaration of Helsinki

Due to the study's retrospective design and the use of anonymized clinical data for analysis, the requirement for informed consent was exempted. Additionally, the Institutional Review Board (IRB) of CHA Bundang Medical Center granted approval for this exemption (IRB number: 2023-10-204)

Consent for publication : Not applicable

Availability of data and materials : This study was based on the National Health Claims Database established by the National Health Insurance Service of the Republic of Korea. Applications for using the National Health Insurance Service data are reviewed by the Inquiry Committee of Research Support. If an application is approved, raw data are provided to the applicant for a fee. We cannot provide access to data, analytical methods, or research materials to other researchers due to the intellectual property rights of this database that is owned by the National Health Insurance Corporation. However, investigators who wish to reproduce our results or replicate the procedure can use the database, which is open for research purposes (https://nhiss.nhis.or.kr/ accessed on 7 July 2023).

Competing interests: The authors declare that they have no competing interests

Funding: This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HR22C1605-C) and a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C2005916).

Authors’ contributions

(I) Concept and design: S.T.C, M.Y.H, S.C.L; (II) Administrative support: S.T.C, M.Y.H, S.C.L; (III) Provision of study materials or patients: S.T.C, M.Y.H, S.C.L; (IV) Collection and assembly of data: M.Y.H, S.C.L; (V) Data analysis and interpretation: S.T.C, H.Y, S.J, J.H.K, E.K.H, B.E.H, W.L; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Acknowledgements : None

Chen C, Kaushal N, Scher DM, Doyle SM, Blanco JS, Dodwell ER. Clubfoot Etiology: A Meta-Analysis and Systematic Review of Observational and Randomized Trials. J Pediatr Orthop. 2018;38(8):e462-e9.
Pavone V, Chisari E, Vescio A, Lucenti L, Sessa G, Testa G. The etiology of idiopathic congenital talipes equinovarus: a systematic review. J Orthop Surg Res. 2018;13(1):206.
Loof E, Andriesse H, Brostrom EW, Andre M, Bolte S. Neurodevelopmental difficulties in children with idiopathic clubfoot. Dev Med Child Neurol. 2019;61(1):98-104.
Andriesse H, Westbom L, Hägglund G. Motor ability in children treated for idiopathic clubfoot. A controlled pilot study. BMC Pediatr. 2009;9:78.
Cady R, Hennessey TA, Schwend RM. Diagnosis and Treatment of Idiopathic Congenital Clubfoot. Pediatrics. 2022;149(2).
Scher DM. The Ponseti method for treatment of congenital club foot. Curr Opin Pediatr. 2006;18(1):22-5.
Ester AR, Weymouth KS, Burt A, Wise CA, Scott A, Gurnett CA, et al. Altered transmission of HOX and apoptotic SNPs identify a potential common pathway for clubfoot. American Journal of Medical Genetics Part A. 2009;149A(12):2745-52.
Basit S, Khoshhal KI. Genetics of clubfoot; recent progress and future perspectives. Eur J Med Genet. 2018;61(2):107-13.
Kim OH, Lee SW, Ha EK, Kim JH, Jo YH, Rhie S, et al. Neurodevelopmental outcomes and comorbidities of children with congenital muscular torticollis: evaluation using the National Health Screening Program for Infants and Children database. Clin Exp Pediatr. 2022;65(6):312-9.
Kim JH, Yi YY, Ha EK, Cha HR, Han MY, Baek HS. Neurodevelopment at 6 years of age in children with atopic dermatitis. Allergol Int. 2023;72(1):116-27.
Zionts LE, Zhao G, Hitchcock K, Maewal J, Ebramzadeh E. Has the rate of extensive surgery to treat idiopathic clubfoot declined in the United States? J Bone Joint Surg Am. 2010;92(4):882-9.
Kim D, Choe YJ, Durrani BAZ, Kim E, Byeon J, Eun BL. Korean Developmental Screening Test for Infants and Children (K-DST): development, applications, and implications for future early childhood development interventions. Clin Exp Pediatr. 2023;66(7):288-93.
Yi YY, Ha EK, Shin J, Baek HS, Cha HR, Kim JH, et al. Neurodevelopment in Term Infants with Normal Birthweight following Postnatal Systemic Steroid Exposure. Neuroepidemiology. 2024.
Kim JH, Ha EK, Lee SW, Cha HR, Baek HS, Han MY. Growth pattern during early infancy, body mass index during childhood and childhood asthma. Clin Exp Allergy. 2023;53(1):39-51.
Institute of Medicine Committee on Understanding Premature B, Assuring Healthy O. The National Academies Collection: Reports funded by National Institutes of Health. In: Behrman RE, Butler AS, editors. Preterm Birth: Causes, Consequences, and Prevention. Washington (DC): National Academies Press (US) Copyright © 2007, National Academy of Sciences.; 2007.
Lööf E, Andriesse H, André M, Böhm S, Iversen MD, Broström EW. Gross Motor Skills in Children With Idiopathic Clubfoot and the Association Between Gross Motor Skills, Foot Involvement, Gait, and Foot Motion. Journal of Pediatric Orthopaedics. 2019;39(7):359-65.
Lööf E. Additional challenges in children with idiopathic clubfoot: is it just the foot? J Child Orthop. 2019;13(3):245-51.
Roostaei M, Baharlouei H, Azadi H, Fragala-Pinkham MA. Effects of Aquatic Intervention on Gross Motor Skills in Children with Cerebral Palsy: A Systematic Review. Phys Occup Ther Pediatr. 2017;37(5):496-515.
Fricke S, Bowyer-Crane C, Haley AJ, Hulme C, Snowling MJ. Efficacy of language intervention in the early years. J Child Psychol Psychiatry. 2013;54(3):280-90.
Lucas BR, Elliott EJ, Coggan S, Pinto RZ, Jirikowic T, McCoy SW, et al. Interventions to improve gross motor performance in children with neurodevelopmental disorders: a meta-analysis. BMC Pediatr. 2016;16(1):193.
Corrado B, Sommella N, Ciardi G, Raiano E, Scala I, Strisciuglio P, et al. Can early physical therapy positively affect the onset of independent walking in infants with Down syndrome? A retrospective cohort study. Minerva Pediatr (Torino). 2022;74(1):31-9.
Cavarzere P, Pietrobelli A, Gandini A, Munari S, Baffico AM, Maffei M, et al. Role of genetic investigation in the diagnosis of short stature in a cohort of Italian children. J Endocrinol Invest. 2023.
Raja MR, Chatterjee S, Agrawal N, Chakraborty PP. Short stature, cubitus varus, foot deformity and intellectual disability with sexual infantilism: clinical clues to 49,XXXXY variant of Klinefelter syndrome. BMJ Case Rep. 2023;16(1).
Siafaka A, Angelis S, Piagkou M, Apostolopoulos A, Troupis T, Filippou D. Larsen Syndrome and Associated Spinal Deformities. Cureus. 2023;15(7):e41655.
Superti-Furga A, Unger S. CHST3-Related Skeletal Dysplasia. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews(®). Seattle (WA): University of Washington, Seattle Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.
Ferreira C. Saul-Wilson Syndrome. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews(®). Seattle (WA): University of Washington, Seattle Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.
Siapkara A, Duncan R. Congenital talipes equinovarus: a review of current management. J Bone Joint Surg Br. 2007;89(8):995-1000.
Gibbons PJ, Gray K. Update on clubfoot. J Paediatr Child Health. 2013;49(9):E434-7.
Balasankar G, Luximon A, Al-Jumaily A. Current conservative management and classification of club foot: A review. J Pediatr Rehabil Med. 2016;9(4):257-64.
Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75-84.
Goldenberg RL, Goepfert AR, Ramsey PS. Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol. 2005;192(5 Suppl):S36-46.

Table 3 and 4 are available in the Supplementary Files section.

No competing interests reported.

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Tracing neurodevelopment and growth pattern in six-year-old children with idiopathic clubfoot: A national cohort study

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Abstract

Study design:

Objectives

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Results

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INTRODUCTION

METHODS

Study design and setting

Participants

Exposure

Primary outcome: Neurodevelopment

Secondary outcome: Physical growth

Covariate

Statistical analysis

RESULTS

Main outcome

Secondary outcome

DISCUSSION

CONCLUSIONS

Declarations

References

Table 3 and 4

Additional Declarations

Supplementary Files

Status:

Version 1