Association of premature birth and maternal education level on attention deficit hyperactivity disorder in children: A meta-analysis

Abstract

BACKGROUND

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in childhood. There is growing evidence that both preterm birth and maternal education levels substantially affect the likelihood of ADHD in children. However, there are limited systematic reviews and meta-analyses examining these associations.

AIM

To systematically review and conduct a meta-analysis on the association of preterm birth and maternal education level on the risk of ADHD in children.

METHODS

We conducted a comprehensive literature search across MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library, including studies published up to June 17, 2024. Data synthesis was performed using random-effect models, and the quality of studies was assessed using the Newcastle-Ottawa Scale.

RESULTS

This study included twelve studies, which revealed a significant association between premature delivery and an increased risk of ADHD in children [odds ratio (OR) = 2.76, 95% confidence interval (CI): 2.52-3.04, P < 0.001, I² = 1.9%). Conversely, higher maternal education levels were significantly associated with a reduced risk of ADHD in children (OR = 0.59, 95%CI: 0.48-0.73, P < 0.001, I² = 47.1%). Subgroup analysis further indicated that maternal education levels significantly influenced ADHD risk, particularly in studies conducted in China (OR = 0.59, 95%CI: 0.46-0.75, P < 0.001, I² = 81.2%), while no significant association was observed in studies from other regions (OR = 1.25, 95%CI: 0.66-2.40, P = 0.495, I² = 92.3%). The sensitivity analysis confirmed the robustness of our findings, showing no significant publication bias.

CONCLUSION

This study found that preterm birth significantly increases the risk of ADHD in children, while a higher maternal education level serves as a protective factor against ADHD. To reduce the incidence of ADHD in children, public health policies should focus on early intervention for preterm infants and improving maternal education levels.

Key Words: Attention deficit hyperactivity disorder; Maternal education level; Meta-analysis; Preterm birth; Systematic review

Core Tip: Preterm birth significantly increases the risk of attention deficit hyperactivity disorder (ADHD) in children, with those born prematurely before 32 weeks facing even higher vulnerability due to neurodevelopmental challenges. Conversely, higher maternal education levels correlate with reduced ADHD risk, particularly noted in studies from China where maternal education of more than 12 years lowered the risk significantly. The intersection of these factors compounds ADHD risk, emphasizing the need for early identification and targeted interventions. Healthcare strategies should include enhanced prenatal care and parent education programs, while policy efforts should focus on improving maternal education to mitigate ADHD risks effectively. Future research should focus on longitudinal studies and underlying mechanisms to refine preventive strategies.

INTRODUCTION

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsive behavior[1,2]. In recent years, a growing number of studies have focused on the role of environmental and social factors in the etiology of ADHD. Maternal education level and preterm birth (defined as gestation under 37 weeks) are two significant potential risk factors that have garnered considerable attention and research[3-9].

Social factors are considered to play a significant role in the etiology of ADHD[10,11]. Low family socioeconomic status may expose children to adverse environments - such as malnutrition, inadequate medical resources, and insufficient educational support - thereby increasing the risk of ADHD[12]. Parental educational levels, especially those of mothers, are regarded as important socioeconomic indicators influencing children’s health and development[13,14]. Lower maternal education is associated with insufficient cognitive stimulation for children and higher family stress, which may negatively impact children’s neural development[15]. A cohort study showed that the lower the mother’s level of education, the higher the probability that her child will develop ADHD. Specifically, children whose mothers have a middle school education, compared to those whose mothers hold a bachelor’s degree, have a significantly higher risk of ADHD [odds ratio (OR) = 9.21, 95% confidence interval (CI): 1.25-67.62][16]. This correlation may be related to factors such as limited parenting resources, poor nurturing environments, unfavorable family economic conditions, high stress, and lack of parenting knowledge. Additionally, issues of emotional support and resource allocation within family structures - such as single-parent households or families with multiple children - as well as environmental factors like pollution, noise, and overcrowding in living environments, may also affect children’s behavioral regulation abilities, thereby increasing the incidence of ADHD.

Preterm birth has been widely explored as a significant risk factor for ADHD[12,17]. Premature infants are predisposed to heightened physiological and neurodevelopmental risks, especially those born before 37 weeks of gestation[12]. Due to inadequate intrauterine development time, their nervous systems may remain incompletely matured, elevating the probability of neurodevelopmental disorders. The increased susceptibility to ADHD in preterm individuals may stem from disruptions in neurobiological brain development, including delayed or aberrant maturation of key regions such as the prefrontal cortex, basal ganglia, and cerebellum - structures crucial for attention regulation and impulse control[18]. Furthermore, preterm children may exhibit functional irregularities in neurotransmitter systems like dopamine and norepinephrine, which are essential for modulating attention, behavioral control, and cognitive functions[18]. Consequently, preterm birth may amplify the risk of ADHD through these neurobiological mechanisms.

Recent studies have revealed a significant increase in the risk of ADHD among preterm infants born to mothers with low educational levels, as compared to full-term infants born to mothers with higher educational levels[3,15]. Additionally, other research has indicated that low maternal education is not only associated with preterm birth but also with adverse birth outcomes such as low birth weight and small for gestational age infants[15]. These findings underscore the dual association of maternal education and preterm birth on the incidence of ADHD in children.

MATERIALS AND METHODS

Ethical approval

As this meta-analysis uses previously published data without involving individual-level data collection or analysis, ethical approval was not necessary. This research adheres to the ethical guidelines and best practices for meta-analyses, ensuring a rigorous and objective synthesis of existing evidence. The study has been registered with PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), registration number (CRD42024569277).

Search strategy

We conducted a comprehensive literature search in MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library, covering the period from each database’s inception to June 17, 2024. The search was limited to MeSH terms without additional restrictions. Our search strategy included combinations of keywords and medical subject headings related to “Preterm Births”, “Birth, Premature”, “Mother”, “Mother’s Clubs”, “Educational Achievement”, “Education Level”, “Educational Status”, “Paternal Education Levels”, “Maternal Education Levels”, “ADHD”, “ADDH”, “Attention Deficit Disorders with Hyperactivity”, “Attention Deficit-Hyperactivity Disorders”, “Hyperkinetic Syndrome”, and “Minimal Brain Dysfunction”, among others (Supplementary Table 1 for specific search steps). We also manually reviewed the reference lists of all identified studies and relevant reviews to ensure comprehensive coverage. Figure 1 illustrates the flowchart summarizing the identification and evaluation process of studies included in this review.

Figure 1  Flow diagram of study selection.

Study selection

After removing duplicate articles using EndNote, the author Yin-Kai Zhao reviewed the titles and abstracts of the studies. Studies that did not meet the inclusion and exclusion criteria were excluded. Subsequently, two authors (Yin-Kai Zhao and Miao-Miao Feng) independently screened the full texts of the papers based on the inclusion and exclusion criteria, conducting the reviews in a blinded manner. Upon completing this step, any decisions to include or exclude a study were re-evaluated. In cases of disagreement, a third researcher (Lu-Lu Hu) re-assessed the study. If the full text of a study was unavailable, an email or interlibrary loan request was sent to the primary author; studies that remained inaccessible were excluded.

In this study, the Newcastle-Ottawa Scale[19] was used as a tool to assess the methodological quality of observational studies. Based on the various criteria of this checklist, case-control or cohort studies were rated on a scale of 0 to 9, evaluating titles, abstracts, introductions, methods, and results (4 points for selection, 2 points for comparability, and 3 points for exposure or outcome). A Newcastle-Ottawa Scale score of ≥ 7 was considered indicative of high-quality research (low risk of bias), a score of 5-6 indicated moderate quality (moderate risk of bias), and a score below 5 indicated low quality (high risk of bias). However, no study was excluded due to low quality or high risk of bias; all studies were included in the analysis[20].

Data extraction

Data collection was conducted by two authors (Yin-Kai Zhao and Miao-Miao Feng) using the methods and results from preliminary studies. A table was created to extract information such as the first author’s name, publication year, country, preterm birth details, maternal education level, diagnostic criteria, and the age of included children. Data were extracted by Meng Li and reviewed by Ting-Ting Shi.

Risk of bias assessment

We utilized Stata 18 to assess the risk of bias through funnel plots and Egger’s quantitative analysis (P > 0.05 indicates no publication bias).

Statistical analysis

We employed meta-analysis techniques, utilizing the Mantel-Haenzel random effects model[21] to calculate the pooled estimates for each case. The resulting pooled estimates were expressed as the pooled OR along with the corresponding 95%CI. Heterogeneity among specific study estimates was assessed using the I² statistic[22], with values < 30%, 30%-60%, 61%-75%, and > 75% indicating low, moderate, substantial, and considerable heterogeneity, respectively. The quality of studies was evaluated using the Newcastle-Ottawa scale.

The comprehensive analysis revealed that most studies categorized preterm and term births into extremely preterm (< 28 weeks), very preterm (28-31 completed weeks), moderate-late preterm (32-36 completed weeks), and term (37-41 completed weeks). To standardize criteria and mitigate the association of subtle differences in preterm definitions across articles, we defined preterm status using very preterm (gestational age < 31 + 6 weeks), mid-late premature (gestational age 32-36 completed weeks), preterm (gestational age < 36 + 6 weeks), and term (gestational age 37-41 completed weeks)[23,24]. Maternal education levels were categorized as follows: Completion of primary education as 6 years, junior high school as 9 years, high school as 12 years, and college or university and above as > 12 years.

Statistical heterogeneity was assessed using the Cochrane χ² test (Q test), with P < 0.05 indicating significant statistical heterogeneity. Study-specific risk estimates were combined through random effects meta-analysis. Forest plots were used to detail the associations between preterm birth, maternal education, and ADHD outcomes in children. Additionally, subgroup analyses and meta-regression were conducted based on child age stratification (above 10 years, below 10 years), study type (retrospective, other), geographic region (China, others), study design (single-center, multicenter), and different study periods to identify potential sources of heterogeneity. Sensitivity analyses were performed using the backward elimination method (removing one item at a time) to test the robustness of the results against the influence of specific studies. Potential publication bias was captured and its association on the validity of estimates was examined using funnel plots. Statistical analyses were conducted using SPSS 28.0 (IBM, Chicago, IL, United States) and Stata 18 software. P < 0.05 was considered statistically significant unless otherwise specified in the article.

RESULTS

Study characteristics

This article summarizes a meta-analysis aimed at evaluating the association of preterm birth and maternal education level on the prevalence of ADHD in children. A comprehensive literature search identified 697 articles from PubMed, 5443 from Web of Science, 1502 from Embase, and 543 from the Cochrane Library. Endnote software was used to remove 3427 duplicates. After screening and evaluation by reviewers, 12 studies were included in the meta-analysis. These studies were conducted in various regions, including 4 studies from China and 8 from other areas such as South Africa, the United States, and Finland. A total of 101612 samples were included, with most studies providing detailed follow-up data on preterm birth, maternal education, and ADHD prevalence in children. Detailed characteristics of the included studies are presented in Table 1. A summary of the meta-analysis results is presented in Table 2.

Table 1 Characteristics of the included studies.

Ref.	Area	Sort	Intervention	Period	Age	Sample size	Sample source	NOS score	Language	Diagnostic basis
Kong et al[25], 2024	Finland	Prospective cohort study	Premature	1996-2018	4-22	57236	N/A	7	English	ICD-10 codes
Perapoch et al[27], 2021	Spain	Retrospective cohort study	Premature	1995-2007	7-19	7488	N/A	9	English	ICD-10
Bora et al[28], 2014	New Zealand	Retrospective cohort study	Premature	1998-2000	9	217	N/A	8	English	SDQ
Cherkes-Julkowski[26], 1998	N/A	Prospective cohort study	Premature	N/A	11	48	N/A	8	English	Stanford-Binet, 4th
Huang et al[16], 2018	China	Retrospective cohort study	Education level of mother	2013-2014	6-12	270	Multicenter	9	Chinese	DSM-5
St Sauver et al[33], 2004	United States	Case control study	Education level of mother	1976-1982	14-20	5701	Multicenter	7	English	DSM-4
Rydell[32], 2010	Sweden	Prospective cohort study	Education level of mother	None	10	1206	Single center	9	English	DSM-4
Chen et al[29], 2024	China	Retrospective cohort study	Education level of mother	2022-2023	6-12	11190	Multicenter	7	English	Parent Symptom Questionnaire
Hsu et al[31], 2022	Taiwan, China	Retrospective cohort study	Education level of mother	2000-2011	6-11	1855	Multicenter	5	English	DSM-IV-TR
Yan et al[35], 2018	China	Cross-sectional	Education level of mother	2014	3-6	15291	Single center	7	Chinese	Conners concise questionnaire
Cochran et al[30], 2022	United States	Prospective	Education level of mother	2002-2004	10-15	1010	Multicenter	9	English	Child Symptom Inventory-4
van Dyk et al[34], 2015	South Africa	Case control	Education level of mother	N/A	5-13	100	Single center	6	English	DSM-4

NOS: Newcastle-Ottawa Scale; N/A: Not applicable; ICD: International Classification of Diseases; SDQ: Strengths and Difficulties Questionnaire; DSM-4: Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition.

Table 2 Summary of meta-analysis results of the influence of premature delivery and mother’s education level on attention deficit hyperactivity disorder.

Intervention measure	Item	Z	OR	95%CI	P value	I2
Premature	Premature vs term	21.13	2.76	2.52-3.04	< 0.001	1.9%
	Very premature vs mild-late premature	3.66	1.95	1.37-2.79	< 0.001	87.3%
Education level of mother	≥ 12 years vs < 12 years	1.56	0.78	0.57-1.07	0.119	91.7%
	≥ 12 years vs < 9 years	2.19	0.61	0.39-0.95	0.029	84.5%
	≥ 12 years vs < 9 years1	4.98	0.59	0.48-0.73	< 0.001	47.1%
	≥ 12 years vs 9-12 years	2.40	0.74	0.58-0.95	0.016	77.6%
	9-12 years vs < 9 years	1.44	0.74	0.49-1.11	0.150	59.2%

¹Eliminate the literature with great heterogeneity.

OR: Odds ratio; CI: Confidence interval.

Qualitative assessment

The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of each study, with scores ranging from 5 to 9 (mean score: 7.583), indicating a generally accepted methodological approach. Table 1 lists the scores for each study, while Table 3 provides a detailed breakdown of the scoring criteria.

Table 3 Assessment of quality of studies by the Newcastle-Ottawa scale.

Ref.	Selection			Comparability			Outcome			Score
	1	2	3	4	5a	5b	6	7	8
Kong et al[25], 2024	1	1		1	1		1	1	1	7
Perapoch et al[27], 2021	1	1	1	1	1	1	1	1	1	9
Bora et al[28], 2014	1	1	1	1	1	1	1		1	8
Cherkes-Julkowski[26], 1998	1	1	1	1	1	1		1	1	8
Huang et al[16], 2018	1	1	1	1	1	1	1	1	1	9
St Sauver et al[33], 2004	1	1	1		1	1	1		1	7
Rydell[32], 2010	1	1	1	1	1	1	1	1	1	9
Chen et al[29], 2024		1	1	1	1	1	1		1	7
Hsu et al[31], 2022	1		1		1	1			1	5
Yan et al[35], 2018	1		1	1	1	1		1	1	7
Cochran et al[30], 2022	1	1	1	1	1	1	1	1	1	9
van Dyk et al[34], 2015		1	1	1	1	1			1	6

1: The exposed cohort is representative; 2: Study cohort with unexposed; 3: Exposure factor identified; 4: No positive results at the start of the study; 5: Cohort comparability based on design or analysis (a: Study age controls; b: Study controls for any additional factors); 6: Outcome assessment is reliable; 7: Follow-up time is long enough; 8: Adequacy of cohort follow-up.

Preterm birth and childhood ADHD

Twelve articles were included in the analysis, with only four considered for examining the association between preterm birth and ADHD in children[25-28], as shown in Figure 2A. The meta-analysis revealed a significant association between preterm birth and an increased risk of ADHD compared to full-term birth (OR = 2.76, 95%CI: 2.52-3.04, P < 0.001, Figure 2A). No significant heterogeneity was observed among the included studies (I² = 1.9%, Q = 3.06, heterogeneity P = 0.383). Additionally, only two studies[25,27] compared very preterm and mid-late preterm births, indicating that earlier preterm birth is associated with a higher risk of ADHD (OR = 1.95, 95%CI: 1.37-2.79, P < 0.001, Figure 2B). However, significant heterogeneity was found in this comparison (I² = 87.3%, Q = 7.85, P = 0.005), which may limit the conclusiveness of this finding (I² = 87.3%, Q = 7.85, heterogeneity P = 0.005).

Figure 2 Meta-analysis of premature delivery and attention deficit hyperactivity disorder in children. A: Premature vs term; B: Very preterm vs mid-late premature. OR: Odds ratio; CI: Confidence interval.

Maternal education level and childhood ADHD

Twelve articles were included in the analysis, with only eight considered for examining the association between maternal education level and ADHD in children[16,29-35], as shown in Figure 3. The meta-analysis indicated that maternal education of ≥ 12 years was associated with a reduced risk of ADHD in children compared to < 12 years of education, with an OR of 0.78 (95%CI: 0.57-1.07, P = 0.119, Figure 3A), although significant heterogeneity was observed (I² = 91.7%, Q = 84.55, heterogeneity P < 0.001). Compared to maternal education of < 9 years, ≥ 12 years of education was significantly associated with a reduced risk of ADHD in children, with an OR of 0.61 (95%CI: 0.19-0.95, P = 0.029, Figure 3B), but significant heterogeneity was again observed (I² = 84.5%, Q = 32.25, heterogeneity P < 0.001). After manually excluding three studies with high heterogeneity[16,32,34], the meta-analysis showed more statistically significant results, with an OR of 0.59 (95%CI: 0.48-0.73, P < 0.001, Figure 3C) and no significant heterogeneity (I² = 47.1%, Q = 3.78, heterogeneity P = 0.151).

Figure 3 Meta-analysis forest map of mothers with different years of education. A: ≥ 12 years vs 12 years; B: ≥ 12 years vs 9 years; C: ≥ 12 years vs 9 years; D: ≥ 12 years vs 9-12 years; E: 9-12 years vs < 9 years. After the adjustment of meta-analysis, the studies with large heterogeneity were manually excluded. OR: Odds ratio; CI: Confidence interval.

Additionally, we compared maternal education levels of ≥ 12 years with 9-12 years. The results were consistent with previous analyses, showing that higher maternal education was associated with a lower risk of ADHD in children (OR = 0.74, 95%CI: 0.58-0.95, P = 0.016, Figure 3D), despite significant heterogeneity (I² = 77.6%, Q = 22.29, heterogeneity P < 0.001). Finally, we analyzed the differences between maternal education levels of 9-12 years and < 9 years, revealing an OR of 0.73 (95%CI: 0.49-1.11, P = 0.150, Figure 3E), with significant heterogeneity observed (I² = 59.2%, Q = 7.36, heterogeneity P = 0.061).

Subgroup and sensitivity analyses

We also conducted a subgroup analysis (Figure 4 and Table 4) to explore the relationship between maternal education levels and the risk of ADHD in children under different influencing factors. Our subgroup analysis used 12 years of maternal education as the grouping variable, comparing studies from China and other regions (United States, Finland, South Africa, Spain, New Zealand, and Sweden). In China, maternal education significantly influenced ADHD risk, with an OR of 0.59 (95%CI: 0.46-0.75, P < 0.001, Figure 4A), though significant heterogeneity was observed (I² = 81.2%, Q = 15.95, heterogeneity P = 0.001). In other regions, maternal education levels showed no statistically significant association on the risk of ADHD (OR = 1.25, 95%CI: 0.66-2.40, P = 0.495, Figure 4A), with significant heterogeneity observed (I² = 92.3%, Q = 39.06, heterogeneity P < 0.001). We also compared single-center and multi-center studies, finding no statistically significant difference in the association of maternal education on the risk of ADHD. For multi-center studies, the OR was 0.67 (95%CI: 0.41-1.12, P = 0.128, Figure 4B), with significant heterogeneity observed (I² = 94.2%, Q = 69.11, heterogeneity P < 0.001). For single-center studies, the OR was 0.97 (95%CI: 0.59-1.61, P = 0.912, Figure 4B), with significant heterogeneity observed (I² = 81.2%, Q = 14.48, heterogeneity P < 0.001).

Figure 4 Subgroup analysis of the influence of mother's education level on attention deficit hyperactivity disorder in children forest map. A: China vs other country; B: Multicenter vs single center. OR: Odds ratio; CI: Confidence interval.

Table 4 Subgroup analysis summary table of mothers’ education years ≥ 12 years vs < 12 years.

Analysis specification	Z	OR	95%CI	P value	I2
All	1.56	0.78	0.57-1.07	0.119	91.7%
China	4.21	0.59	0.46-0.75	< 0.001	81.2%
Other	0.68	1.25	0.66-2.40	0.495	92.3%
Multicenter	1.52	0.67	0.41-1.12	0.128	94.2%
Single	0.11	0.97	0.59-1.61	0.912	86.2%

OR: Odds ratio; CI: Confidence interval.

We conducted a sensitivity analysis, through a step-by-step exclusion process, we found that the results did not show significant variation; all the outcomes after exclusion fell within the 95%CI of the pooled result (OR = 0.78, 0.57-1.07) in Figure 5. Results indicated that the significant association between preterm birth and the risk of ADHD in children is consistent and robust. Similarly, the significant association between maternal education level and the risk of ADHD in children is also consistent and robust. Therefore, despite observed heterogeneity, sensitivity analyses support the conclusion that both preterm birth and maternal education levels are associated with an increased risk of ADHD in children.

Figure 5 Sensitivity analysis chart of mother’s education level. CI: Confidence interval.

Publication bias assessment

Funnel plots were created and analyzed, along with Egger’s quantitative analysis (Figure 6, Tables 4 and 5). In addition, we conducted a meta-regression analysis and did not identify any significant sources of heterogeneity (Table 6). All analyses revealed no evidence of publication bias, thereby supporting the reliability of the aggregated results.

Figure 6  Funnel diagram of meta-analysis of mother’s education level.

Table 5 Summary of publication bias.

Intervention measure	Item	Incorporate literature	t	P value	95%CI
Premature	Premature vs term	4	0.67	0.570	-3.02 to 4.13
Education level of mother	≥ 12 years vs < 12 years	8	0.57	0.591	-4.91 to 7.88
	≥ 12 years vs < 9 years	6	-0.13	0.905	-4.90 to 4.49
	≥ 12 years vs < 9 years1	3	-3.29	0.188	-10.13 to 5.96
	≥ 12 years vs 9-12 years	6	-0.93	0.405	-10.85 to 5.41
	9-12 years vs < 9 years	4	-1.28	0.330	-9.43 to 5.11

¹Eliminate the literature with great heterogeneity

CI: Confidence interval.

Table 6 Summary of meta-regression.

Condition	t	P value	OR	95%CI
Merge	0.45	0.686	0.78	-4.81 to 6.38
Quality	0.21	0.894	0.04	-0.58 to 0.66
China	3.10	0.053	3.16	-6.40 to 0.09
Age1	2.33	0.102	2.60	-0.96 to 6.17
Multicenter	0.17	0.876	0.09	-1.56 to 1.74

¹The groups were divided by age: Children aged 10 were included in the control group, while the intervention group consisted of samples with ages above 10.

OR: Odds ratio; CI: Confidence interval.

DISCUSSION

This systematic review and meta-analysis identified a significant association between preterm birth and maternal education levels with the risk of developing ADHD in children. Our analysis, which included twelve studies, revealed that children born prematurely have a markedly increased risk of ADHD compared to full-term infants (OR = 2.76, 95%CI: 2.52-3.04, P < 0.001, I² = 1.9%). This risk was even more pronounced in those born before 32 weeks, indicating a gradient of vulnerability with the degree of prematurity. Additionally, our findings showed that higher maternal education serves as a protective factor against ADHD in children, with a notably reduced risk (OR = 0.59, 95%CI: 0.48-0.73, P < 0.001, I² = 47.1%). Subgroup analysis further suggested that this protective effect of maternal education was particularly significant in studies conducted in China (OR = 0.59, 95%CI: 0.46-0.75, P < 0.001, I² = 81.2%), while no significant association was observed in studies from other regions (OR = 1.25, 95%CI: 0.66-2.40, P = 0.495, I² = 92.3%). The sensitivity analysis confirmed the robustness of these findings and revealed no significant publication bias, underscoring the reliability of the results. This comprehensive evaluation highlights the importance of both biological and socioeconomic factors in the development of ADHD in children.

The study suggests that preterm birth and maternal education level may have a cumulative effect on the risk of ADHD in children, based on their independent and interactive influences on ADHD risk. Preterm children are more prone to neurodevelopmental issues[36,37], while lower maternal education is often associated with adverse environmental factors such as lower family socioeconomic status, insufficient cognitive stimulation, and a lack of parenting knowledge[38-40]. These factors can exacerbate the negative impact of preterm birth on a child’s neurodevelopment. Consequently, when both preterm birth and low maternal education are present, the risk of ADHD in children may not only add up but could even exhibit a multiplicative effect.

The decision to combine these two risk factors for stratified analysis stems from their independently significant roles in ADHD risk, as well as their potential interrelation. Moreover, maternal education level is not only a key indicator of socioeconomic status but also directly influences parenting practices and cognitive stimulation within the home[40], offering a more targeted perspective for understanding ADHD risk in children. While other risk factors, such as family socioeconomic status, parental mental health, and environmental pollution, also exist, they are somewhat related to maternal education and preterm birth. Analyzing these two independent yet crucial factors together can help to unravel the complexity of ADHD risk in children and provide scientific support for the development of effective public health policies and early intervention strategies.

Preterm birth, defined as delivery before 37 weeks of gestation, is consistently linked to an increased risk of neurodevelopmental disorders, including ADHD) This meta-analysis consolidates findings from multiple studies to elucidate the relationship between preterm birth and the prevalence of ADHD in children. Our analysis included 12 studies that investigated the association between preterm birth and ADHD. The results indicated that, compared to full-term children, those born preterm have a significantly increased risk of developing ADHD. This suggests that the earlier the birth, the higher the risk of ADHD, potentially due to the increased vulnerability of the developing brain to extrauterine environmental and biological stress factors[41-44].

The neurodevelopmental pathways linking preterm birth to ADHD are intricate[45,46]. One hypothesized mechanism involves the incomplete development of neural circuits responsible for attention and executive functions, which are critical for impulse control and sustained attention. Additionally, preterm infants often experience a range of medical complications, such as intraventricular hemorrhage and periventricular leukomalacia, which may further disrupt brain development and contribute to the emergence of ADHD[41,47].

Maternal education level is a key socioeconomic indicator influencing child health and development[48]. Our meta-analysis investigated the correlation between maternal education levels and the risk of ADHD in children, revealing that lower levels of maternal education are associated with an increased risk of ADHD. The studies included in this analysis indicate that children of mothers with lower educational attainment have an increased likelihood of developing ADHD. Specifically, in Chinese studies, the pooled OR for ADHD in children whose mothers have more than 12 years of education shows a significant difference compared to studies from other regions. This heterogeneity in findings suggests that the impact of maternal education on ADHD risk may vary depending on regional socioeconomic and cultural contexts.

The relationship between maternal education level and ADHD can be attributed to multiple factors. Lower maternal education levels are typically associated with reduced access to healthcare resources, insufficient knowledge about child development, and lower socioeconomic status[49]. These factors may create environments that are detrimental to neurodevelopment, thereby increasing the risk of ADHD. For instance, children from low socioeconomic families may experience higher levels of stress, reduced cognitive stimulation, and poorer nutrition, all of which can negatively association brain development and function[15,50,51]. Additionally, maternal education level influences parenting practices and the ability to provide a supportive learning environment[52]. Educated mothers are more likely to engage in activities that promote cognitive and behavioral development, such as reading to their children and providing structured daily routines[52-54]. These activities are crucial for developing attention and self-regulation skills, which are often lacking in children with ADHD.

The joint association of prematurity and maternal low education on ADHD risk presents a compounded challenge. Our analysis indicates that these factors independently increase ADHD risk, but when combined, they may exhibit additive or even multiplicative effects. This intersectionality suggests that children who are both premature and have mothers with low education levels are particularly susceptible to ADHD. The interplay between the biological vulnerabilities associated with prematurity and the environmental disadvantages linked to low maternal education exacerbates the risk. Premature infants already face neurological immaturity and potential medical complications, which are further compounded by suboptimal developmental environments typically provided by mothers with low education, thereby increasing the likelihood of ADHD. The findings from this meta-analysis underscore the importance of risk mitigation strategies for premature infants and children of mothers with low educational attainment. Healthcare providers should prioritize early identification and support for these high-risk groups. Interventions may include enhanced prenatal and postnatal care for mothers and infants, the implementation of parent education programs, and ensuring access to early childhood development services.

Public health strategies should also focus on improving educational opportunities for women, as maternal education profoundly association children’s health outcomes. Policies supporting maternal education can yield long-term benefits for both mothers and their children, reducing the incidence of ADHD and other developmental disorders. Furthermore, research should continue to explore the mechanisms linking prematurity, maternal education, and ADHD. Longitudinal studies tracking children from birth through adolescence can provide valuable insights, identifying critical periods for intervention.

CONCLUSION

In conclusion, this meta-analysis confirms that preterm birth and low maternal education levels are significant risk factors for ADHD in children. The evidence underscores the need for comprehensive strategies that address both medical and socioeconomic factors to effectively reduce the prevalence of ADHD. By understanding and addressing these risk factors, healthcare providers and policymakers can improve health outcomes for children and families affected by ADHD.