Factors related to the occurrence of fetal birth defects and the construction of a Nomogram model

Introduction

Birth defects (BD), also known as congenital anomalies, are abnormal phenomena that occur in embryos or fetuses during development, including physical, physiological, and metabolic aspects. Specifically, they manifest as various congenital disabilities such as congenital malformations and metabolic defects. However, BD can lead to early miscarriage and fetal malformation.^1,2 The etiology of BD in newborns is not yet clear, and the causes are complex. Most scholars believe that it may be related to genetics and the environment, or possibly a combination of multiple factors.^3,4 The study found that over 7.9 million newborns worldwide are born with BD each year. The likelihood of BD occurrence is 6.42% in low-income countries, 5.57% in middle-income countries, and 4.72% in high-income countries, accounting for nearly 3% of all newborns. In China, there are 900,000 new cases of BD each year.⁵ The occurrence of BD not only affects the health of newborns but also severely impacts their quality of life due to treatment and brings economic burdens to families. Therefore, identifying factors influencing neonatal BD in clinical settings, and implementing prevention and treatment can effectively reduce the risk of its occurrence. The nomogram, as a risk assessment model, can integrate various influencing factors and intuitively present the risk values of assessment results.⁶ Currently, there are few reports on the risk research of BD in newborns. Therefore, this study aims to explore the construction of a nomogram model and the factors influencing the occurrence of fetal BD.

Data and Methods

General Data

From September 2021 to September 2023, 341 newborns treated in Meizhou people’s hospital were selected and randomly divided into a modeling group (239 cases) and a validation group (102 cases) in a 7:3 ratio (using a random number table method). The case collection flow chart is shown in Figure 1. Based on fetal outcomes, the modeling group was divided into a BD group and a non-BD group. Inclusion criteria: (1) Meeting the diagnostic criteria for fetal BD;⁷ (2) Complete data; (3) Consent form signed by family members. Exclusion criteria: (1) Parents with birth defects; (2) Pregnant women with cognitive impairments; (3) Patients with malignant tumors; (4) Pregnant women unwilling to participate in this study. See Figure 1.This study was approved by the ethics committee of our hospital.

Figure 1 Flow chart of case collection.

Clinical Data Collection

Prenatal examination and delivery data of pregnant women in the modeling group and validation group were collected, mainly including maternal age, fetal gender, gestational age, history of adverse pregnancy outcomes, gestational hypertension, alcohol consumption, smoking, history of colds, educational level, place of residence, whether it was the first pregnancy, history of antibiotic use during pregnancy, adverse emotions during pregnancy, timing of folic acid intake, whether it was a multiple pregnancy, and eugenic screening.

Data Collection Method

Data collectors with over five years of work experience and strong research capabilities were responsible for verifying and entering the data to ensure its validity and authenticity.

Observational Indicators

Clinical data was collected to: (1) Analyze the distribution of types of neonatal BD (Birth Defects); (2) Compare the clinical data between the modeling group and the validation group; (3) Compare the clinical data between the BD group and the non-BD group; (4) Develop a nomogram model for fetal BD, and draw an ROC curve to evaluate the discrimination and consistency of the BD nomogram model in assessing fetuses.

Statistical Processing

Data was analyzed using SPSS 25.0. Count data were tested with X² test and expressed as cases (%). Multifactorial logistic regression analysis was used to analyze the risk factors for BD in fetuses; R3.6.3 software was used to construct the Nomogram model for assessing BD in fetuses. ROC curves were drawn to evaluate the discrimination of the Nomogram model for BD in fetuses; calibration curves were drawn to assess consistency. A P-value of <0.05 was considered statistically significant.

Results

Distribution of Neonatal BD Types

As shown in Table 1, the top five BDs were congenital heart disease, polydactyly and syndactyly, cleft lip and palate, ear deformities, and foot deformities, with incidence rates of 23.81%, 20.63%, 12.70%, 11.11%, and 7.94%, respectively.

Table 1 Distribution of Neonatal Defects

Comparison of Clinical Data Between Modeling and Validation Groups

Table 2 shows that there was no significant difference in clinical data between the modeling and validation groups (P > 0.05).

Table 2 Comparison of Clinical Data Between the Modeling Group and the Validation Group

Comparison of Clinical Data Between BD and Non-BD Groups

In this study, 63 out of 239 newborns had BD, with an incidence rate of 26.36%. There were significant differences between the BD and non-BD groups in terms of maternal age, gestational weeks, history of adverse pregnancy outcomes, gestational hypertension, adverse emotions during pregnancy, and timing of folic acid intake (P < 0.05). There were no significant differences in other clinical data between the two groups (P > 0.05). See Table 3.

Table 3 Comparison of Clinical Data Between BD Group and BD Group

Multifactorial Logistic Regression Analysis of Neonatal BD Occurrence

Taking whether neonates had BD as the dependent variable (yes=1, no=0), and maternal age, gestational weeks, history of adverse pregnancy outcomes, gestational hypertension, adverse emotions during pregnancy, and timing of folic acid intake as independent variables, with variable assignment methods shown in Table 4. The results of the multifactorial logistic regression analysis indicated that maternal age (OR: 4.125, 95% CI: 1.475–11.537), gestational weeks (OR: 3.066, 95% CI: 1.143–8.224), history of adverse pregnancy outcomes (OR: 10.628, 95% CI: 3.725–30.318), gestational hypertension (OR: 5.658, 95% CI: 1.878–17.043), adverse emotions during pregnancy (OR: 5.467, 95% CI: 2.032–14.705), and timing of folic acid intake (OR: 4.586, 95% CI: 1.603–13.120) were risk factors for neonatal BD (P < 0.05). See Table 5.

Table 4 Methods for Assigning Values to Independent Variables

Table 5 Results of Multivariate Logistic Regression Analysis of Fetal BD

Construction of the Nomogram Model for Neonatal BD Occurrence

The identified risk factors were introduced into R software to construct the Nomogram model for assessing the risk of neonatal BD occurrence. By summing the scores of each variable, a total score is calculated to assess the risk of neonatal BD occurrence. It can be seen that in this model, the most important factor affecting the score was the history of adverse pregnancy outcomes, followed by gestational hypertension, adverse emotions during pregnancy, timing of folic acid intake, maternal age, and gestational weeks. See Figure 2.

Figure 2 Nomogram model of BD in the fetus.

Internal Validation of the Nomogram Model for Neonatal BD

The area under the ROC curve (AUC) of the modeling group was 0.938 (95% CI: 0.892–0.984) (see Figure 3A), and the slope of the calibration curve was close to 1 (see Figure 3B), with an H-L test result of X² = 8.342, P = 0.692, indicating good consistency.

Figure 3 Internal validation of a Nomogram model of neonatal BD. (A) ROC curves of the modeling group; (B) Calibration curves of the modeling group.

External Validation of the Nomogram Model for Neonatal BD

The AUC of the external validation was 0.961 (95% CI: 0.938–0.984) (Figure 4A); the slope of the calibration curve was close to 1 (Figure 4B), with an H-L test result of X² = 7.634, P = 0.635, indicating good consistency.

Figure 4 External validation of a Nomogram model of neonatal BD. (A):Verify the group ROC curves; (B)Calibration curve of the verification group.

Discussion

BD is a global public health issue, with high disability and mortality rates in newborns. Furthermore, the pathogenesis of BD is complex, likely caused by a combination of various factors.^8,9 Studies report that the incidence of BD in newborns in China is about 5%, with nearly one-third of pediatric hospitalizations due to BD. Additionally, BD accounts for approximately 20% of total deaths (infants and young children), significantly impacting families and society.¹⁰ This study shows that out of 239 newborns, 63 had BD, with an incidence rate of 26.36%, indicating a higher incidence and underscoring the need to strengthen the prevention and control of BD. Therefore, constructing a Nomogram model for the occurrence of BD in newborns is particularly important.

This study, after analyzing neonatal BD types, found that congenital heart disease, polydactyly and syndactyly, etc., had higher incidence rates, severely affecting the health of newborns, although some conditions can be corrected with treatment.¹¹ Multifactor logistic regression analysis in this study showed that maternal age, gestational weeks, history of adverse pregnancy outcomes, gestational hypertension, adverse emotions during pregnancy, and timing of folic acid intake are risk factors for neonatal BD. Among these, (1) maternal age >35 years increases the risk of BD due to reduced vitality of body functions, endocrine disorders, declining fertility, decreased ovarian function, insufficient nutrient supply to the fetus, placental disorders, and increased risk of chromosomal abnormalities in the fetus. With the implementation of the two-child policy, the number of older mothers is increasing, thus raising the risk of BD. Therefore, it is necessary to intensify publicity, encourage childbirth at the optimal age, and conduct thorough examinations.^12,13 (2) Neonates born before 37 weeks of gestation have a higher risk of BD, possibly related to various maternal diseases and potentially influencing BD. Pregnant women should focus on nutritional intake to ensure sufficient nutrition for fetal development and reduce the occurrence of BD.^14,15 (3) Couples with a history of adverse pregnancy outcomes have a higher likelihood of chromosomal abnormalities, which may also be associated with chromosomal abnormalities in the mother.^16,17 (4) Hypertension during pregnancy can lead to various diseases in the fetus, including cardiovascular diseases, increasing the risk of BD.¹⁸ (5) Adverse emotions during pregnancy can increase the secretion of thyroid hormones and adrenocortical hormones, which are transmitted to the embryo through the placenta and other pathways, hindering fetal development and affecting the formation of fetal organs, thereby leading to BD. Hence, pregnant women should regulate their emotions, participate in psychological counseling, ensure emotional stability, and avoid adverse emotions.^19,20 (6) Folic acid is essential in embryonic development and can prevent congenital heart diseases and other BDs. Taking folic acid for less than three months increases the risk of BD.^21,22 In light of these risk factors, it is important to emphasize the popularization of eugenics knowledge, strengthen propaganda and education, ensure proper prenatal care, timely supplement folic acid, maintain a balanced diet, exercise regularly, ease the tension of pregnant women, and advise them to avoid harmful substances to possibly prevent the occurrence of BD.

In this study, a Nomogram model for the occurrence of BD in newborns was constructed based on the above-mentioned influencing factors. The Nomogram can effectively assess risks, thereby enabling effective prevention in clinical practice. In our study, the AUCs for the modeling and validation groups were 0.938 and 0.961, respectively, indicating high discrimination. Furthermore, the slope of the calibration curve was close to 1, suggesting that the model’s assessment of the risk of BD in newborns is consistent with the actual risk. Clinical medical staff can use the risk factors to assess the risk of BD in newborns and intervene early. This study has limitations, such as a small sample size. Future work will aim to validate the findings with a larger sample size.

Conclusion

In summary, maternal age, gestational weeks, history of adverse pregnancy outcomes, gestational hypertension, adverse emotions during pregnancy, and timing of folic acid intake are risk factors for the occurrence of BD in newborns. The Nomogram model constructed based on these factors demonstrates good discrimination and consistency and can assess the risk of BD in newborns.