==== Front PLoS One PLoS One plos PLOS ONE 1932-6203 Public Library of Science San Francisco, CA USA 10.1371/journal.pone.0286976 PONE-D-23-00885 Research Article Medicine and Health Sciences Surgical and Invasive Medical Procedures Medicine and Health Sciences Surgical and Invasive Medical Procedures Plastic Surgery and Reconstructive Techniques Cleft Lip and Palate Surgery Medicine and Health Sciences Surgical and Invasive Medical Procedures Obstetric Procedures Medicine and Health Sciences Women's Health Maternal Health Pregnancy Medicine and Health Sciences Women's Health Obstetrics and Gynecology Pregnancy Medicine and Health Sciences Medical Conditions Congenital Disorders Birth Defects Cleft Lip and Palate Biology and Life Sciences Developmental Biology Morphogenesis Birth Defects Cleft Lip and Palate Medicine and Health Sciences Otorhinolaryngology Cleft Lip and Palate Research and Analysis Methods Mathematical and Statistical Techniques Statistical Methods Forecasting Physical Sciences Mathematics Statistics Statistical Methods Forecasting Medicine and Health Sciences Surgical and Invasive Medical Procedures Plastic Surgery and Reconstructive Techniques Cleft Lip Surgery Biology and Life Sciences Nutrition Medicine and Health Sciences Nutrition Constructing of predictive model for the surgical effect of patients with cleft lip and palate Constructing of Predictive Model for the Surgical Effect of Patients with Cleft Lip and Palate Liu Na Conceptualization Methodology Writing – original draft Writing – review & editing 1 2 https://orcid.org/0000-0001-9808-4801 Yang Jingyuan Conceptualization Writing – review & editing 1 * Tan Fang Data curation Investigation 3 Zhu Haijian Data curation 2 1 Department of Epidemiology and Health Statistics, School of Public Health and Health, Guizhou Medical University, Guiyang, Guizhou Province, China 2 Department of Administrative Management, Guiyang Stomatological Hospital, Guiyang, Guizhou Province, China 3 Department of Oral and Maxillofacial Surgery, Guiyang Stomatological Hospital, Guiyang, Guizhou Province, China Ashaat Engy Asem Editor Human Genetics and Genome Research Institute, National Research Centre, EGYPT Competing Interests: The authors have declared that no competing interests exist. * E-mail: yangjingyuan@gmc.edu.cn 30 6 2023 2023 18 6 e028697628 1 2023 27 5 2023 © 2023 Liu et al 2023 Liu et al https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective To explore effective factors of surgical effect for patients with cleft lip and palate, and to construct the predictive model of surgical effect, which provide reference for improving the effect of cleft lip and palate surgery. Methods This study has been ethically reviewed and approved by the Medical Ethics Committee of Guiyang Stomatological Hospital before the study began.A total of 997 cases of cleft lip and palate surgical treatment in Guiyang Stomatological Hospital from 2015 to 2020 were collected. Logistic regression analysis was used to analyze the factors influencing the surgical outcome, and a score system was established by assigning values to the influencing factors using the nomogram. Data of 110 patients were verified, and decision curve analysis was used to evaluate the predicted results. Results Logistic regression analysis showed that the number of surgeries, surgical methods, breast milk, prenatal examination, nutrition during pregnancy and labor intensity during pregnancy were independent risk factors for poor surgical results (all P<0.05). The predictive model was built by including the number of surgeries, surgical methods, breast milk, prenatal examination, nutrition and labor intensity during pregnancy into the predictive scoring system. The critical value was 273, the area under ROC curve (AUC) was 0.733(95%CI:0.704~0.76), the sensitivity was 89.57%, and the specificity was 48.14%.When the external validation data of 110 patients were brought into the score, the AUC of poor diagnostic value reached 74.5%, P<0.05, which was close to the modeling accuracy of 73.3%. Conclusion This study constructed a predictive model of surgical effect for patients with cleft lip and palate, which can be used for the clinical prediction of cleft lip and palate patients in Guizhou Province. The authors received no specific funding for this work. Data AvailabilityAll relevant data are within the paper and its Supporting Information files. Data Availability All relevant data are within the paper and its Supporting Information files. ==== Body pmcIntroduction Cleft lip and palate is one of the most common congenital malformations of the oral and maxillofacial region, which is caused by the failure to achieve normal facial fusion due to pathogenic factors that affect the facial fusion during its embryonic development [1], and different degrees of malformation can cause different degrees of functional impairment, such as chewing, sucking, swallowing, speech, expression and appearance defects, which seriously affect the quality of life of the affected children. Cleft lip and palate are divided into cleft lip and palate, cleft lip, and cleft palate according to the site of the cleft [2]. China is a country with a high prevalence of cleft lip and palate, with an overall prevalence of about 1.67‰ [3], and Guizhou Province is one of the regions with a high prevalence of cleft lip and palate, with an incidence of about 1.92‰ [4]. Currently, treatment is mainly performed through surgical procedures, but there are still more problems of secondary deformities after surgery, such as obvious scarring and nasal collapse [5]. Regarding surgical outcomes, the main focus is on the observation of clinical postoperative outcomes, while the prediction of preoperative outcomes lacks corresponding tools, and the establishment of surgery-related predictive indexes would provide an important reference for patients’ families and surgeons. To this end, this study collected data related to the outcome of patients who had completed cleft lip and palate surgery in Guiyang Stomatological Hospital. It analyzed the factors influencing the surgical outcome and established a predictive assessment method for surgical outcome using column line diagrams, and constructed a predictive index system to play a role in improving the outcome of cleft lip and palate surgery, to improve the satisfaction of cleft lip and palate patients and their families with the surgical outcome and promoting the communication and cooperation between doctors and patients. Materials and methods Study subjects Cases of cleft lip and palate treated surgically by oral and maxillofacial surgery in an oral hospital in Guiyang.The purpose of information collection should be explained in detail to all subjects before collection, and oral informed consent should be obtained from all subjects. The study was examined and approved by the Ethics Committee of Guiyang Stomatological. Hospital.Ethics approval number:GYSKLL-KY-20220107-01. Inclusion criteria: patients with non-syndromic cleft lip and palate; no other acute or chronic somatic diseases; no congenital malformations with other systems. Exclusion criteria: patients with incomplete information. Study methods Data collection The medical records of patients with cleft lip and palate surgery in a Stomatological Hospital in Guiyang City between 2015 and 2020 were retrospectively collected, and information collection forms were established, including gender, age, ethnicity, birth weight, history of cleft lip, health status, medical history status, fetal status, mode of delivery, breastfeeding status, obstetric examination status, pregnancy status, duration of surgery, number of operations, and mode of surgery, etc. Evaluation criteria of surgical effect The postoperative outcome evaluation used now mainly referred to the practice of West China College of Stomatology at Sichuan University was referred to the Asher-McDade scale [6] and Mortier PB scale [7], respectively. The Asher-McDade scale mainly included the evaluation of nasal morphology, nasal symmetry, upper lip contour, lip peak, etc. The evaluation of the Mortier PB scale mainly includes the evaluation of excessive mucosal tissue, insufficient mucosal height, incision marks, thin red lip on the affected side, narrow human middle, too long white lip, too short white lip, muscle break, obvious scar, etc. Structure of the surgical outcome evaluation team and tracking time The evaluation team was mainly composed of a physician with a senior title, a physician with an intermediate or junior title, and a nursing staff, and the tracking lasted for one year through outpatient follow-up, remote video, or photo follow-up. Measurements were taken through preoperative and postoperative photos to determine whether the symmetry and aesthetics of the nasolabial shape were restored after cleft lip surgery; the surgical status of cleft palate patients is judged by the degree of velopharyngeal closure, the function of an oropharyngeal area and the verbal ability. At the same time, the satisfaction of patients and their families with the surgery is also an evaluation indicator. The evaluation team scored based on the above indicators and finally made a comprehensive determination of the evaluation results of the three. 1 is very good, 2 is good, 3 is common, 4 is bad, and 5 is very bad. Development of predictive scoring tools The influencing factors of the surgical effect were analyzed according to the case-control study. The variables that were significant in the univariate analysis were included in the multivariate analysis. The results of the multivariate analysis were scored by using the column chart, and the prediction model was built. Verification truncation values were established to evaluate the predicted outcomes compared with actual surgical outcomes. And validate with external data. Statistical methods All data were statistically analyzed using SPSS17.0 statistical software and R software, and the chi-square test was used to compare the difference in the rate of poor surgical outcome in different subgroups, and logistic regression analysis was applied to analyze the influence of relevant factors on surgical outcome, and Fisher’s exact test was used for one-way analysis with sample size n < 40 or theoretical frequency T < 1, to compare good and poor surgical The difference of relevant factors in patients, the prediction score system was constructed by using nomogram column line plot, the value of its prediction was evaluated by using ROC curve, the sensitivity and specificity of prediction effect of prediction score were calculated, and the prediction results were evaluated by using decision curve analysis (DCA) and clinical impact curve analysis (DCA), and the test level α was taken as 0.05. Results General information about the subjects Among the 997 cleft lip and palate patients collected, 613 were males and 384 were females, with an age range of 2 to 40 years. 318 cases (32%) were cleft lip alone (CL); 169 cases (17%) were cleft palate alone (CP); 510 cases (51%) were cleft lip combined with cleft palate (CL+P), of which 882 cases (88.5%) were evaluated as good after surgery; 115 cases (11.5%) were evaluated as poor. 115 cases, accounting for 11.5% (as Tables 1 and 2). 10.1371/journal.pone.0286976.t001 Table 1 Type and composition ratio of cleft lip and palate. Type Number of cases Composition ratio (%) Cleft lip alone(CL) 318 32 Cleft lip combined with cleft palate(CL+P) 510 51 Cleft palate alone(CP) 169 17 Total 997 100 10.1371/journal.pone.0286976.t002 Table 2 Composition ratio of cleft lip and palate surgical outcomes. Postoperative outcome Number of cases Composition ratio (%) Good 882 88.5 Unsatisfactory 115 11.5 Total 997 100 Analysis of factors influencing surgical outcomes Single-factor analysis Single-factor analysis was used to compare the differences in factors associated with good and poor surgical patients (as Table 3), and the results showed that there were statistical differences (P<0.05) between poor and good surgeries in terms of the number of surgeries, surgical methods, breast milk, obstetric examinations, pregnancy nutrition, and labor intensity during pregnancy, so these factors needed to be screened out for subsequent multifactor analysis and the establishment of an index system. 10.1371/journal.pone.0286976.t003 Table 3 Single-factor analysis affecting surgical outcome. Category Good Poor T/c2 P Duration of surgery 72.33±29.29 75.77±32.34 -1.17 0.242 Number of surgeries 1.39±0.68 1.29±0.49 2.026 0.044 Birth weight 3.2±0.56 3.16±0.52 0.795 0.427 Surgical method Modified Lang method 325(85.3%) 56(14.7%) 26.637 <0.001 Inferior triangular flap method 229(83.6%) 45(16.4%) Rotational propulsion method 239(94.8%) 13(5.2%) Other 69(98.6%) 1(1.4%) History of cleft lip None 787(88.7%) 100(11.3%) 2.288 0.13 Yes 75(83.3%) 15(16.7%) Health status Good 855(88.1%) 115(11.9%) - 1△ Adverse 7(100%) 0(0%) Blood transfusion history None 856(88.2%) 114(11.8%) - 0.585△ Yes 6(85.7%) 1(14.3%) History of infectious disease None 860(88.4%) 113(11.6%) - 0.07△ Yes 2(50%) 2(50%) History of vaccination None 15(100%) 0(0%) - 0.24△ Yes 847(88%) 115(12%) History of allergy None 836(88.3%) 111(11.7%) - 0.772△ Yes 26(86.7%) 4(13.3%) Clinical manifestations None 837(88.3%) 111(11.7%) - 0.767△ Yes 25(86.2%) 4(13.8%) History of trauma None 848(88.4%) 111(11.6%) - 0.152△ Yes 14(77.8%) 4(22.2%) Other surgical histories None 840(88.2%) 112(11.8%) - 1△ Yes 22(88%) 3(12%) Number of births First birth 335(88.4%) 44(11.6%) 1.921 0.383 Second child 362(89.4%) 43(10.6%) Third child and above 165(85.5%) 28(14.5%) Full-term or not Full term 720(88.8%) 91(11.2%) 1.39 0.238 Not full term 142(85.5%) 24(14.5%) Delivery Normal birth 158(98.1%) 3(1.9%) - 1△ Cesarean section 11(100%) 0(0%) Breastfeeding No 504(90.5%) 53(9.5%) 6.347 0.012 Yes 358(85.2%) 62(14.8%) Maternal examination Done 838(88.7%) 107(11.3%) - 0.044△ Not done 24(75%) 8(25%) Nutrition during pregnancy Good 740(89.2%) 90(10.8%) 8.652 0.013 Medium 105(85.4%) 18(14.6%) Poor 17(70.8%) 7(29.2%) Spirituality during pregnancy Good 19(79.2%) 5(20.8%) 1.999 0.368 Medium 643(88.3%) 85(11.7%) Poor 200(88.9%) 25(11.1%) Labor intensity during pregnancy Light 629(90.6%) 65(9.4%) 13.775 0.001 Medium 89(84%) 17(16%) Heavy 144(81.4%) 33(18.6%) Trauma during pregnancy None 857(88.3%) 114(11.7%) - 0.529△ Yes 5(83.3%) 1(16.7%) Pregnancy illness None 802(88.3%) 106(11.7%) 0.116 0.734 Yes 60(87%) 9(13%) Pregnancy vomiting Light 310(86.1%) 50(13.9%) 3.171 0.205 Medium 334(88.6%) 43(11.4%) Heavy 218(90.8%) 22(9.2%) Parental drinking None 28(100%) 0(0%) - 0.586△ Yes 92(94.8%) 5(5.2%) Folic acid Not Taken 55(93.2%) 4(6.8%) - 0.188△ Have taken 65(98.5%) 1(1.5%) Note: △ indicates Fisher’s exact test; T/c2, indicates the statistic of T-test, and c2 indicates the statistic of chi-square test. Multi-factor analysis All the variables screened out in the univariate analysis of the rate of unsatisfactory surgical outcome, P<0.2 or 0.1 continued to select binary logistic regression for multifactor analysis, and the results showed (as Table 4) that the number of surgeries could significantly affect the surgical outcome, P<0.05, OR was 0.563, indicating that the more the number of surgeries, the lower the probability of unsatisfactory surgical outcomes, the surgical method could significantly affect the surgical The OR was 16.597 and 15.649, respectively, meaning that the probability of unsatisfactory surgical outcomes were 16.597 and 15.649 times higher for the modified Lan method and the lower triangular flap method than for the other surgical methods; breast milk could significantly affect the surgical outcome, P<0.05, indicating that The probability of having a unsatisfactory surgery was significantly higher for breast-fed than for non-breast-fed, with an OR of 1.935, implying that the rate of unsatisfactory surgical outcome for breast milk was 1.935 times higher than that for non-breast milk; maternal examination could significantly affect the surgical outcome, with P<0.05 and an OR of 2.619, implying that the rate of unsatisfactory surgical outcome was 2.619 times higher for non-maternal examination; pregnancy nutrition could significantly affect the surgical outcome, with P<0.05 and an OR 1.609 and 3.56, respectively, implying that those with moderate or poor nutrition during pregnancy were 1.609 and 3.56 times more likely to have poor surgical outcomes than those with good nutrition during pregnancy; labor intensity during pregnancy significantly affected surgical outcomes, P<0.05, OR 1.851 and 2.152, respectively, implying that those with moderate or heavy labor intensity during pregnancy were 1.851 and 2.512 times more likely to have poor surgical outcomes than those with light labor intensity during pregnancy. 1.851, 2.512 times. 10.1371/journal.pone.0286976.t004 Table 4 Multiple logistic regression analysis of surgical outcomes. Standard Error OR 95% confidence interval for OR P Lower limit Upper limit Number of surgeries 0.191 0.563 0.387 0.819 0.003 Mode of surgery <0.001 Modified Lang method 1.025 16.597 2.228 123.647 0.006 Inferior triangular flap method 1.026 15.649 2.093 116.981 0.007 Rotational propulsion method 1.051 3.862 0.492 30.309 0.199 Other 1 Breast milk Yes 0.218 1.935 1.261 2.968 0.003 No Maternal examination Done 0.459 2.619 1.064 6.442 0.036 Not done 1 Nutrition during pregnancy 0.017 Medium 0.295 1.609 0.902 2.87 0.107 Poor 0.5 3.56 1.337 9.479 0.011 Good 1 Labor intensity during pregnancy 0.003 Medium 0.305 1.851 1.017 3.368 0.044 Heavy 0.245 2.152 1.331 3.481 0.002 Light 1 Predictive scoring of surgical outcomes After exploring the influencing factors of surgical outcome, the nomogram statistical method was used to analyze and establish the predictive scoring system of surgical outcome, and the results were as follows (as Fig 1,Tables 5 and 6). 10.1371/journal.pone.0286976.g001 Fig 1 Surgical outcome prediction score. 10.1371/journal.pone.0286976.t005 Table 5 Surgical outcome prediction score table. Factor Category Score Number of surgeries 1 100 2 80 3 60 4 40 5 20 6 0 Surgical approach Modified Lang method 98 Inferior triangular flap method 96 Rotational advancement method 47 Other 0 Breastfeeding No 0 Yes 23 Antenatal examination Not Done 34 Done 0 Nutrition during pregnancy Good 0 Medium 17 Poor 44 Labor intensity during pregnancy Light 0 Medium 21 Heavy 27 10.1371/journal.pone.0286976.t006 Table 6 Predicted probability of poor surgical outcome. Overall score Probability of poor surgical outcome % 113 1.00% 170 5.00% 196 10.00% 212 15.00% 224 20.00% 234 25.00% 243 30.00% 251 35.00% 259 40.00% 266 45.00% 273 50.00% 280 55.00% 287 60.00% 294 65.00% 302 70.00% Diagnostic surgical outcome ROC curve According to the probability of poor surgical outcome corresponding to the scoring system, a cut point of 50%, i.e, a patient’s score greater than 273, means that the patient will have a poor surgical outcome. Verifying the prediction accuracy of the scoring system with c-index = 73.36%, the scores were brought into the patient data to obtain the diagnostic ROC curve of the nomo score on the surgical outcome as follows.(as Fig 2). 10.1371/journal.pone.0286976.g002 Fig 2 Diagnostic ROC curve of surgical outcome. Calibration plot of the scoring system To verify the accuracy of the above scoring system, the following calibration plot (calibration plot) is drawn as follows. (as Fig 3). 10.1371/journal.pone.0286976.g003 Fig 3 Scoring system calibration diagram. The intercept = 0.2846, slope = 0.8357, and it can be seen from the following plot that the prediction results and the diagonal line fit together, which means the prediction results are more accurate. Decision curve analysis (DCA) The predictive scoring system established by nomogram contains six indicators, namely, the number of surgeries, surgical method, breast milk, delivery examination, nutrition during pregnancy, and labor intensity during pregnancy, i.e, the predictive scoring system established by nomogram is based on the joint prediction of the six indicators, and on this basis, the net patient benefit (net The net benefit of the nomogram predictive scoring system is higher than the net benefit of any one indicator alone. As can be seen in the figure (as Fig 4) below, the net benefit of patients when predicting the surgical outcome of patients based on the nomogram score is shown in red, and it can be seen that the net benefit of patients with the nomogram score is the highest; the net benefit of patients who choose the nomogram score to predict whether or not they will experience a surgical outcome is higher. 10.1371/journal.pone.0286976.g004 Fig 4 Decision Curve Analysis (DCA). Clinical impact curve analysis (DCA) In the clinical impact curve(as Fig 5), the red curve indicates the number of people classified as positive (high-risk population) by the SIMPLE model at each threshold probability, and the blue curve shows the number of true positives at each threshold probability, when the threshold probability is low, the difference between the predicted high-risk number and the actual number of positives is large (red and blue distance is large), and as the threshold probability increases, the difference between the predicted high-risk number and the actual number of positives gradually decreases (As the threshold probability increases, the difference between the predicted number of high-risk and the actual number of positives gradually decreases (red-blue distance gradually decreases), and the predicted number of positives and the actual number of positives match when the threshold probability > 40%. The threshold probability used in this study was 40% (i.e., when the probability of a poor surgical outcome was higher than 40%, the patient was predicted to have a poor surgical outcome), meaning that the number of predicted positives and the number of actual positives matched, i.e., using the current nomogram-based predicted poor surgical outcome scoring system, as long as the predicted positives (appearing to have a poor surgical outcome), then the person actually had a greater probability of having a poor surgical outcome. 10.1371/journal.pone.0286976.g005 Fig 5 Clinical impact curve. Creating a test set to validate accuracy The data from 110 patients with external validation data were brought into the score and the diagnostic ROC curve of the nomo score on the surgical outcome was obtained and is shown in Fig 6. 10.1371/journal.pone.0286976.g006 Fig 6 Test curve. The unsatisfactory and diagnostic value of the nomo score obtained by external validation reached an AUC of 74.5%, p<0.05. This is close to the modeling accuracy of 73.3%, indicating a good validation effect. The predictive accuracy of the predicted versus real surgery was 93.6%.(as Table 7). 10.1371/journal.pone.0286976.t007 Table 7 Comparison of predicted surgical outcome and real surgical outcome. Predicted surgical outcome Total Good Unsatisfactory Real surgical outcome Good 101 3 104 Unsatisfactory 4 2 6 Total 105 5 110 Discussion Cleft lip and palate is one of the most common congenital defects, which brings a heavy economic burden to patients’ families and society. Surgery is the most effective way to treat cleft lip and palate, and as new methods of cleft lip revision are constantly being introduced, accurate preoperative outcome assessment is of great significance to facilitating preoperative doctor-patient communication, medical strategy development, resource allocation optimization, prognosis judgment, and medical quality improvement. The present study showed that the number of surgeries, surgical method, breast milk, obstetric examination, pregnancy nutrition, and labor intensity during pregnancy were independent risk factors for the poor surgical outcome (all P < 0.05), and based on this analysis using columnar plots and establishing a risk score, the area under the ROC curve (AUC) was 0.733 (95% CI: 0.704 to 0.76) sensitivity. 89.57% Specificity 48.14%. Data from 110 patients with external validation data were brought into the score to establish a predictive scoring system incorporating a total of 5 indicators such as several operations, mode of surgery, breast milk, labor and delivery, nutrition during pregnancy, and labor intensity during pregnancy (all P < 0.05) The critical value was 273 points. The diagnostic value of the under-optimal AUC reached 74.5%, P<0.05, which is close to the modeling accuracy of 73.3%, indicating a good validation effect. In this study, by screening 26 indicators of cleft lip and palate case data surgically treated in Guiyang Stomatological Hospital, we finally found that the number of surgeries, surgical methods, breast milk, maternal examination, nutrition during pregnancy, and labor intensity during pregnancy were important predictive indicators, and through these important predictive indicators, a predictive evaluation system of cleft lip and palate surgical outcomes was constructed, which can be used for the clinical prediction of surgical outcome of cleft lip and palate patients initially. These predictors reflect the factors affecting surgical outcomes mainly include maternal pregnancy and external reasons for surgery, and this study tried to explore these two factors to improve outcomes of cleft lip and palate surgery and patients’ satisfaction. Several indicators from the mother’s pregnancy period reflect some extent that the knowledge of the mother of a cleft lip and palate family about eugenics during pregnancy is related to the healthy birth of the child [8], From the perspective of pregnancy nutrition, whether a pregnant woman takes multivitamin supplements and folic acid antagonists in early pregnancy is the main indicator of nutrition during pregnancy. Studies have shown that folic acid not only protects the fetus from external stimuli during the sensitive period of embryonic development but also plays a significant role in the prevention of neural tube deficiency and CLP in the fetus [9]. From the perspective of labor intensity during pregnancy, most of the subjects in this study come from families in rural areas of Guizhou, and they were engaged in farm work or physical labor during pregnancy until delivery, so we used the labor intensity during pregnancy as an indicator of high-intensity delivery. From the perspective of breast milk, in the early stages of infant feeding, children with cleft lip and palate have difficulties in breastfeeding compared to normal children because their mouths cannot form a completely closed structure to generate the negative pressure required for effective sucking [10]. The poor feeding situation eventually leads to lower-than-average weight gain, and a high incidence of coughing, vomiting, and respiratory infections, which is related to their nutritional and health status before undergoing surgery and has a strong correlation with the success of the surgery and the prognosis [11]. Therefore, it is more important to remind relevant medical staff to start feeding instruction and health education for children with cleft lip and palate as early as possible after birth, focus on instructing parents of children on feeding skills, such as bottle placement and angle, feeding position, and handling of coughing, and start feeding instruction and intervention for children with cleft lip and palate and their parents as early as possible [12] to promote the healthy growth of children with cleft lip and palate. Some studies have shown that the high incidence of their relatives is related to the proximity of blood relations [13] with significant family aggregation [14],a child with cleft lip and palate is already a heavy burden for these families, and to avoid further cleft lip and palate in the family fetus, the impact of predictive indicators on the surgical outcome can also be more directly enhanced by reminding families of cleft lip and palate patients, especially the mothers, of health education during pregnancy. cleft lip and palate is a congenital malformation of maxillofacial development. It has unique pathological and anatomical characteristics and surgical revision methods, involving the skin, mucosa, muscle, cartilage, and bone of the lip, and most of them need one or several more revisions after the first-stage repair to make their nasolabial close to or reach the normal shape [15]. The degree of deformity of the child, the operating skill of the physician, the cooperation of the anesthesiologist, and the nursing support are necessary for a successful surgery. Therefore, we believe that the clinician should scientifically screen the patient before the surgery and provide the best treatment plan for different patients that are targeted and suitable for individual conditions. Individualized treatment is not a random combination of techniques based on subjective empirical preferences, but follows a standardized design concept, which requires the physician to fully understand the scope of use, advantages, and disadvantages of different technical options. In addition, preoperative communication with the child’s family is essential, and the principles of standardized design and the family’s opinions must be taken into account in the selection of surgical methods. In this way, during preoperative doctor-patient communication, the assessment of the preoperative prediction system can be used to help parents establish a good mentality, to improve the quality of doctor-patient communication, to rationalizing the surgical outcomes and helping parents establish a good mindset is beneficial to the recovery and psychological growth of cleft lip and palate patients. This study shows a preliminary exploration of factors related to the influence of surgical outcome, and there are still some limitations, and the specificity of the included indicators for prediction is still not enough, but this study provides a certain basis for future surgical prediction, and more appropriate indicators can be selected in future studies to establish an accurate, reliable, and convenient surgical outcome prediction system to be applied in clinical practice and provide a reference basis for clinicians to carry out cleft lip surgery In the future, we can establish an accurate, reliable and convenient prediction system for clinical practice to provide a reference basis for clinicians to perform cleft lip surgery.Cleft lip revision is a complex systemic project, and continuous. "Evaluate-improve-reevaluate-improve again" is the only way to continuously improve its revision effect, so that patients can return to society physically and mentally healthy and socially accepted [16], and the surgical prediction index model established in this preliminary study can provide a basis for evaluation and improvement. Supporting information S1 Data The dataset used for analyses. (XLSX) Click here for additional data file. We would like to thank all participants in this study. 10.1371/journal.pone.0286976.r001 Decision Letter 0 Vall-llosera Camps Miquel Staff Editor © 2023 Miquel Vall-llosera Camps 2023 Miquel Vall-llosera Camps https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ********** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No Reviewer #2: Yes ********** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: No ********** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear authors. I like to provide you some observations regarding your interesting study. An important limitation are the groups conformation and follow up time. Outcomes have been considered as good or poor however these were estimated using subjective scales like Asher Mc Dade. In addition, there is not a correlation between the categories of used scales and your categories (good and poor). It is not clear how are you considering the outcomes as good and poor in this study. In addition, the follow up time used in this study is not adequate to evaluate a surgical outcome, this should be at least one year. Finally, the most important predictive factor is probably the surgeon performance and this was not included. In addition, should be important to analyze the clinical relevance of the statistical significant factors like nutritional ones. Reviewer #2: Thank you for providing me with the opportunity to review the manuscript entitled “Constructing of Predictive Model for the Surgical Effect of Patients with Cleft Lip and Palate” for consideration for publication in PLOS One. Here, the authors have created a predictive model to evaluate post-operative surgical aesthetic outcomes in cleft lip and nasal deformity repair in a rather large cohort of patients between 2015 – 2020. The number of patients and data incorporated into the model is impressive and the predictive nature of it impressive as well; however, it does raise many questions and comments. 1. The article would benefit from significant revision to enhance readability. 2. My largest concern is related to the model. a. There is a significant amount of data included in the model with many confounders that have not been addressed. b. How did the authors decide on what was an intense labor? What about nutrition? Did the authors have data on intensity of labor in a 40 year old? Im assuming the data was incomplete for some of these patients. c. Were cleft lips (incomplete) compared against complete cleft lips? LAHSHAL nomenclature or some standardized nomenclature would be needed. One cannot compare an incomplete cleft lip with a spared alveolus to a complete cleft lip and palate. Was NAM available or some form of presurgical molding? Was syndromic status taken into consideration? d. The model seems to include revisions as well. This raises another question about homogeneity when it comes to the model. The model includes patients of all ages, cleft types, and revision status. This introduces a significant amount of variability as it ignores the importance of facial growth. Number of surgeries would certainly correlate with a poor result – the fact that one is operating more than once on a lip means the index procedure may not have been as ideal. Issues such as these do not seem to have been taken into considering in the statistical model. e. Cleft lip and palate outcomes assessment is complex. There are many rating scales and there is a lot of room for subjectivity. While the authors have used somewhat standardized scales, there is still room for significant subjectivity. f. The authors discuss using this in the preoperative consultation. What actions can a provider take to improve the outcome? Based on the data, surgical method and breast feeding are the only two “modifiable” factors that can be changed after a child is born. Do the authors recommend that they care giver abstain from breast-feeding (I would not recommend this based on the wealth of information supporting the significant benefits associated with breast feeding, especially in resource-constrained settings? How this is used in the clinic is not explored. I would be worried that, as constructed, this could become somewhat of a self-fulfilling prophecy. g. Surgical method was important. What method should be used? This is not really discussed. Tables and figures should be referenced in the manuscript in order. For example, Table 3 comes before Table 1. Thank you very much for this opportunity. ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Percy ROSSELL-PERRY Reviewer #2: No ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. 10.1371/journal.pone.0286976.r002 Author response to Decision Letter 0 Submission Version1 23 May 2023 RE: Constructing of Predictive Model for the Surgical Effect of Patients with Cleft Lip and Palate (PONE-D-23-00885) Dear Editors and Reviewers, Thanks a lot for giving us the opportunity to revise our manuscript. We express our sincere thanks to the reviewers for the constructive and thoughtful comments on previous draft. Those comments are all valuable and very helpful for revising and improving our paper. We have studied comments carefully and have made correction. The revised manuscript is highlighted with a yellow background in the revised manuscript. We hope the revision is acceptable and we look forward to hearing from you soon. Once again thank you very much for your comments and suggestions. With best wishes. Yours sincerely, Jingyuan Yang Reviewer #1 (Comments to the Authors) An important limitation are the groups conformation and follow up time. Response: Thanks to the referee for the good review and kind suggestion. The evaluation team was mainly composed of a physician with a senior title, a physician with an intermediate or junior title, and a nursing staff, and the tracking lasted for one year through outpatient follow-up, remote video, or photo follow-up. We did it mainly because most of the cleft lip and palate patients come from poor families in remote rural mountainous areas of Guizhou, and their surgical costs and travel expenses come from the national major disease program for cleft lip and palate patients. Therefore, the travel expenses for postoperative follow-up are an additional financial burden for the patient’s families. We followed up with patients to the maximum extent possible to save them from traveling. We finished one outpatient follow-up and two remote video and photo follow-ups within one year after surgery. Add the above changes to“Structure of the surgical outcome evaluation team and tracking time”on Page4，Lines 81-91. Reviewer #1 (Comments to the Authors) Outcomes have been considered as good or poor however these were estimated using subjective scales like Asher Mc Dade. In addition, there is not a correlation between the categories of used scales and your categories (good and poor). Response: Thanks to the referee for the good review and kind suggestion. As stated by the experts, our evaluation has a certain degree of subjectivity, which is an objective problem for us, and we will also incorporate more rigorous evaluation indicators in our later studies, but for this study, we mainly followed the following indicators for the reference of surgical outcomes: 1. Measurements were taken through preoperative and postoperative photos to determine whether the symmetry and aesthetics of the nasolabial shape were restored after cleft lip surgery; the degree of velopharyngeal closure, the function of an oropharyngeal area and the verbal ability of cleft palate patients; 2. The satisfaction of patients and their families with the surgery. The evaluation team scored based on the above indicators and finally made a comprehensive determination of the evaluation results of the three. Therefore, the judgment of this study still has a certain scientific basis. Reviewer #1 (Comments to the Authors) In addition, the follow up time used in this study is not adequate to evaluate a surgical outcome, this should be at least one year. Response: Thanks to the referee for the good review and kind suggestion. The tracking in this study lasted for one year through outpatient follow-up, remote video, or photo follow-up. We did it mainly because most of the cleft lip and palate patients come from poor families in remote rural mountainous areas of Guizhou, and their surgical costs and travel expenses come from the national major disease program for cleft lip and palate patients. Therefore, the travel expenses for postoperative follow-up are an additional financial burden for the patient’s families. We followed up with patients to the maximum extent possible to save them from traveling. We finished one outpatient follow-up and two remote video and photo follow-ups within one year after surgery. Reviewer #1 (Comments to the Authors) Finally, the most important predictive factor is probably the surgeon performance and this was not included. In addition, should be important to analyze the clinical relevance of the statistical significant factors like nutritional ones. Response: Thanks to the referee for the good review and kind suggestion. In this study, the surgeon's performance was attributed to the surgical method as a predictor. Due to data on surgeon performance intraoperatively could not be collected objectively, we believe that physicians' preoperative scientific provision of targeted, optimal treatment plans and surgical methods for different patients that are appropriate for individual conditions is an important factor in surgical outcomes, but it was generally finished according to existing norms and was not included in this analysis because differences involving individual protocols are not comparable. In the "Discussion" on Page19,Lines263-267, we revised according to your advice as follows: the degree of deformity of a child, the operating skill of the physician, the cooperation of the anesthesiologist, and the nursing support are necessary for a successful surgery. Therefore, we believe that the clinician should scientifically screen the patient before the surgery and provide the best treatment plan for different patients that are targeted and suitable for individual conditions. As for nutritional factors, we focused on statistical analysis from the correlation of nutrition during pregnancy and conducted a comprehensive evaluation of whether a pregnant woman takes multivitamin supplements and folic acid antagonists in early pregnancy as the main indicator. In the " Discussion" on Page18,Lines 234-238, we revised according to your advice as follows: From the perspective of pregnancy nutrition, whether a pregnant woman takes multivitamin supplements and folic acid antagonists in early pregnancy is the main indicator of nutrition during pregnancy. Studies have shown that folic acid not only protects the fetus from external stimuli during the sensitive period of embryonic development but also plays a significant role in the prevention of neural tube deficiency and CLP in the fetus. Reviewer #2 (Comments to the Authors) 1. The article would benefit from significant revision to enhance readability. Response: Thanks to the referee for the good review and kind suggestion. The article details have been revised according to this revised version. Reviewer #2 (Comments to the Authors) 2.a. There is a significant amount of data included in the model with many confounders that have not been addressed. Response: Thanks to the referee for the good review and kind suggestion. We also realized the problem you mentioned. This study conducted statistical analysis from a large sample perspective and used a multi-factor model analysis to control potential confounding factors to some extent, but the variables included in the model were still relatively limited. Because most of our cleft lip and palate patients come from poor families in remote rural mountainous areas of Guizhou, this construction model still provides a scientific basis to convince more children with cleft lip and palate to receive surgical treatment as early as possible. b. How did the authors decide on what was an intense labor? What about nutrition? Did the authors have data on intensity of labor in a 40 year old? Im assuming the data was incomplete for some of these patients. Response: Thanks to the referee for the good review and kind suggestion. Most of the subjects in this study (cleft lip and palate patients) were from families in rural areas of Guizhou, and they were engaged in farm work or physical labor during pregnancy until delivery, so we used the labor intensity during pregnancy as an indicator of high-intensity delivery, with mild being those who worked in a sitting position, moderate being those who bore load <20 kg each time and worked in a standing position, and severe being those who bore load >20 kg each time, and these data were obtained mainly through questionnaires (interviews) with the mothers. In the "Discussion" on Page18 Lines238-242, we modified it according to your advice as follows: From the perspective of labor intensity during pregnancy, most of the subjects in this study come from families in rural areas of Guizhou, and they were engaged in farm work or physical labor during pregnancy until delivery, so we used the labor intensity during pregnancy as an indicator of high-intensity delivery. As for nutritional factors, we focused on statistical analysis from the correlation of nutrition during pregnancy and conducted a comprehensive evaluation of whether a pregnant woman takes multivitamin supplements and folic acid antagonists in early pregnancy as the main indicator. In the "Discussion" Page18,Lines 234-238, we revised according to your advice as follows: From the perspective of pregnancy nutrition, whether a pregnant woman takes multivitamin supplements and folic acid antagonists in early pregnancy is the main indicator of nutrition during pregnancy. Studies have shown that folic acid not only protects the fetus from external stimuli during the sensitive period of embryonic development but also plays a significant role in the prevention of neural tube deficiency and CLP in the fetus. c. Were cleft lips (incomplete) compared against complete cleft lips? LAHSHAL nomenclature or some standardized nomenclature would be needed. One cannot compare an incomplete cleft lip with a spared alveolus to a complete cleft lip and palate. Was NAM available or some form of presurgical molding? Was syndromic status taken into consideration? Response: Thanks to the referee for the good review and kind suggestion. In this study, due to the large sample size and many variables, our comparison of patients' surgical outcomes was mainly on the overall situation after individual surgery. Measurements were taken through preoperative and postoperative photos to determine whether the symmetry and aesthetics of the nasolabial shape were restored after cleft lip surgery, the degree of velopharyngeal closure, the function of an oropharyngeal area, and the verbal ability of cleft palate patients, as well as the degree of satisfaction of patients and their families with the surgery. This study focused on several factors that may have an impact on the outcome of cleft lip and cleft palate surgery. Therefore, no specific comparison of surgical outcomes for the diagnosis of cleft lip or cleft palate was performed. We considered syndromic status, and all cases were non-syndromic cleft lip and palate patients, as mentioned in the "Materials and methods : non-syndromic cleft lip and palate patients".( Page3,Lines63-64) d. The model seems to include revisions as well. This raises another question about homogeneity when it comes to the model. The model includes patients of all ages, cleft types, and revision status. This introduces a significant amount of variability as it ignores the importance of facial growth. Number of surgeries would certainly correlate with a poor result – the fact that one is operating more than once on a lip means the index procedure may not have been as ideal. Issues such as these do not seem to have been taken into considering in the statistical model. Response: Thanks to the referee for the good review and kind suggestion. There are still problems in the data analysis as stated by the experts. There is variability in facial growth, and the number of surgeries introduces a corresponding bias. The proportion of subjects with multiple surgeries in this study was small and was excluded at the time of the study. The variability of facial growth may be a long-term process that is difficult to assess, and this follow-up was within 1 year, so the effect of facial growth can be considered minor, and the advice of experts has important reference value for future studies by our group. e. Cleft lip and palate outcomes assessment is complex. There are many rating scales and there is a lot of room for subjectivity. While the authors have used somewhat standardized scales, there is still room for significant subjectivity. Response: Thanks to the referee for the good review and kind suggestion. Finally, our evaluation has a certain degree of subjectivity, which is an objective problem for us, and we will also incorporate more rigorous evaluation indicators in our later studies, but for this study, we mainly followed the following indicators for the reference of surgical outcomes: 1. Measurements were taken through preoperative and postoperative photos to determine whether the symmetry and aesthetics of the nasolabial shape were restored after cleft lip surgery; the degree of velopharyngeal closure, the function of an oropharyngeal area and the verbal ability of cleft palate patients; 2. The satisfaction of patients and their families with the surgery. The evaluation team scored based on the above indicators and finally made a comprehensive determination of the evaluation results of the three. We have added the above changes to " Structure of the surgical outcome evaluation team and tracking time."(Page4,Lines81-91) f. The authors discuss using this in the preoperative consultation. What actions can a provider take to improve the outcome? Based on the data, surgical method and breast feeding are the only two “modifiable” factors that can be changed after a child is born. Do the authors recommend that they care giver abstain from breast-feeding (I would not recommend this based on the wealth of information supporting the significant benefits associated with breast feeding, especially in resource-constrained settings? How this is used in the clinic is not explored. I would be worried that, as constructed, this could become somewhat of a self-fulfilling prophecy. Response: Thanks to the referee for the good review and kind suggestion. First, we absolutely support breastfeeding and strongly advocate and agree with breastfeeding. However, the rate of poor surgical outcome of breastfed children with cleft lip and palate in the study was 1.935 times higher than that of non-breastfed, which is clearly contrary to a large number of objective studies, and our analysis suggests that it may be due to the following reasons: First, our data collection on breastfeeding was mainly before the surgery, in the early stages of infant feeding, children with cleft lip and palate have difficulties in breastfeeding compared to normal children because their mouths cannot form a completely closed structure to generate the negative pressure required for effective sucking. The poor feeding situation eventually leads to lower-than-average weight gain, and a high incidence of coughing, vomiting, and respiratory infections, which is related to their nutritional and health status before undergoing surgery and has a strong correlation with the success of the surgery and the prognosis. Second, we believe that the concluding data should not be generalized to breast milk and non-breast milk. Therefore, it is more important to remind relevant medical staff to start feeding instruction and health education for children with cleft lip and palate as early as possible after birth, focus on instructing parents of children on feeding skills, such as bottle placement and angle, feeding position, and handling of coughing, and start feeding instruction and intervention for children with cleft lip and palate and their parents as early as possible to promote the healthy growth of children with cleft lip and palate. We have added the above changes to “Discussion" on Page18,Lines243-254. g. Surgical method was important. What method should be used? This is not really discussed. Response: Thanks to the referee for the good review and kind suggestion. The degree of deformity of a child, the operating skill of the physician, the cooperation of the anesthesiologist, and the nursing support are necessary for a successful surgery. Therefore, we believe that the clinician should scientifically screen the patient before the surgery and provide the best treatment plan for different patients that are targeted and suitable for individual conditions. Individualized treatment is not a random combination of techniques based on subjective empirical preferences, but follows a standardized design concept, which requires the physician to fully understand the scope of use, advantages, and disadvantages of different technical options. In addition, preoperative communication with the child's family is essential, and the principles of standardized design and the family's opinions must be taken into account in the selection of surgical methods. We have added the above changes to "Discussion" on Page19,Lines263-272. Tables and figures should be referenced in the manuscript in order. For example, Table 3 comes before Table 1. Response: Thanks to the referee for the good review and kind suggestion. Adjustments have been made accordingly. Attachment Submitted filename: Response to Reviewers.docx Click here for additional data file. 10.1371/journal.pone.0286976.r003 Decision Letter 1 Ashaat Engy Asem Academic Editor © 2023 Engy Asem Ashaat 2023 Engy Asem Ashaat https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version1 29 May 2023 Constructing of Predictive Model for the Surgical Effect of Patients with Cleft Lip and Palate PONE-D-23-00885R1 Dear Dr. Yang, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Engy Asem Ashaat Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: 10.1371/journal.pone.0286976.r004 Acceptance letter Ashaat Engy Asem Academic Editor © 2023 Engy Asem Ashaat 2023 Engy Asem Ashaat https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 22 Jun 2023 PONE-D-23-00885R1 Constructing of Predictive Model for the Surgical Effect of Patients with Cleft Lip and Palate Dear Dr. Yang: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Engy Asem Ashaat Academic Editor PLOS ONE ==== Refs References 1 Yuxing Zhang , Xiaoxia Qiu , Ping Wei , et al . Analysis of the epidemiological status of cleft lip and palate in Guangxi[J]. Chinese Journal of Eugenics and Genetics, 2016, 24 (1 ):104–105. 2 Ma J , Hu C ,Zhai K ,et al . Characterization of 1428 cases of congenital cleft lip and palate in Ningxia[J]. Journal of Ningxia Medical University,2019,41 (10 ):1042–1043. 3 Fan D , Wu S , Liu L ,et al . 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