Evidence map›Paper›PMID 41549243›Full record

SynthesisBMC oral health2026

Growth factor analysis in children with non-syndromic orofacial clefts: a systematic review.

Mohamed Zahoor Ul Huqh, Hashim Bin Yaacob, Suresh Kandagal Veerabhadrappa, Johari Yap Abdullah, Samiullah Dowlath Saheb, Syed Altafuddin Quadri, Anand Marya, Siddharthan Selvaraj

Abstract readSystematic Review
In one paragraph

Synthesis in BMC oral health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Mohamed Zahoor Ul HuqhFaculty of Dentistry, SEGi University, Kota Damansara, Petaling Jaya, Selangor, 47810, Malaysia. dr.mdzahoor@gmail.com.
Hashim Bin YaacobFaculty of Dentistry, SEGi University, Kota Damansara, Petaling Jaya, Selangor, 47810, Malaysia.
Suresh Kandagal VeerabhadrappaFaculty of Dentistry, SEGi University, Kota Damansara, Petaling Jaya, Selangor, 47810, Malaysia.
Johari Yap AbdullahCraniofacial Imaging Lab, School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu, 16150, Malaysia.
Samiullah Dowlath SahebDepartment of Anatomy, Kulliah of Dentistry, International Islamic University, Kuantan, 25200, Malaysia.
Syed Altafuddin QuadriDepartment of Allied Dental Health Science, College of Applied Medical Science, King Khalid University, Abha, 62521, Kingdom of Saudi Arabia. aasayed@kku.edu.sa.
Anand MaryaFaculty of Dentistry, University of Puthisastra, Phnom Penh, 12211, Cambodia.
Siddharthan SelvarajFaculty of Dentistry, University of Puthisastra, Phnom Penh, 12211, Cambodia.

Funding

The authors extend their appreciation to the Deanship of Research and Graduate Studies at King Khalid University for funding this work through Large Research Project. RGP2/542/46.
6 · The paper itself

Abstract

backgroundOrofacial clefts (OFCs) are one of the most prevalent congenital abnormalities that affect the lip and/or palate and can cause significant growth retardation in newborns. Several studies have revealed that children with congenital defects or genetic syndromes have their own growth pattern, which may differ from that of normal children. However, during infancy and until around age two, these babies usually show a period of catch-up growth in length, weight, and head circumference for both boys and girls. It was noted out that both genders had smaller physical dimensions than normal children. In order to partially elucidate the biological mechanism affecting children with non-syndromic OFCs, this systematic review aims to assess the relative expression and localization of growth factors and their receptors in craniofacial tissues.

methodA comprehensive literature search was carried out on May 1, 2025, using three important databases: Web of Science Core collection, PubMed, and Scopus. The search was limited to only English-language studies involving human subjects, but it was not limited by publication date. To find potentially relevant publications, specific keywords and database-specific search techniques were used.

resultsBased on predefined inclusion criteria, 20 studies were selected from a total of 191 articles following a thorough screening process. Growth factors and susceptibility to OFCs were found to be significantly correlated in the analysis of the reports of the chosen studies. Particularly, OFCs and their risk were consistently associated with fibroblast growth factor receptor (FGFR1) and transforming growth factor (TGFβ3). More angiogenesis in compromised tissues is suggested by the elevated levels of two angiogenesis-related proteins, vascular endothelial growth factor (VEGF) and Cluster of differentiation (CD34). Similarly, the studies that used unilateral samples showed relatively high levels of TGFβ3, FGFR1, and bone morphogenetic protein (BMP2/4), which were also higher in bone cells, connective tissues, and epithelia.

conclusionThe reviewed studies indicate a role of growth-related proteins in the pathophysiology of non-syndromic OFCs. This is demonstrated by the fact that FGFR1 is higher in all studies, TGFβ3 is upregulated in all the studies, and angiogenesis markers (VEGF and CD34) are consistently higher in cases. Additional investigation is needed to determine whether FGFR1 and TGFβ3 can serve as biomarkers or targets for intervention in OFC-related abnormalities.

Indexed as

Cleft LipCleft PalateIntercellular Signaling Peptides and ProteinsAntigens, CD34Bone Morphogenetic ProteinsBrainChild, PreschoolFemaleHumansInfantInfant, NewbornMaleReceptor, Fibroblast Growth Factor, Type 1Transforming Growth Factor beta3Vascular Endothelial Growth Factor AAntigens, CD34Bone Morphogenetic ProteinsFGFR1 protein, humanIntercellular Signaling Peptides and ProteinsReceptor, Fibroblast Growth Factor, Type 1TGFB3 protein, humanTransforming Growth Factor beta3Vascular Endothelial Growth Factor AVEGFA protein, humanBone morphogenic proteinFibroblasts growth factorMatrix metalloproteinasesNon-syndromic clefsTransforming growth factor

Identifiers

PMID41549243
PMCPMC12903246

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.