Maternal Risk and Protective Factors for Spontaneous Abortion: A Prospective Cohort Study in Mashhad, Iran

Maternal Risk and Protective Factors for Spontaneous Abortion: A Prospective Cohort Study in Mashhad, Iran | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Maternal Risk and Protective Factors for Spontaneous Abortion: A Prospective Cohort Study in Mashhad, Iran Veda Vakili, Navid Eshaghi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8351871/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Spontaneous abortion is a common pregnancy complication with multifactorial etiology. Identifying maternal risk and protective factors is essential for prevention and improved prenatal care . Methods We conducted a prospective cohort study of 72,500 pregnancies registered in 2024 at health centers affiliated with Mashhad University of Medical Sciences, Iran. Pregnancies were followed to determine outcomes. Maternal characteristics, BMI, medical history, blood type, supplementation, and lifestyle factors were recorded at baseline. Multivariable logistic regression was used to identify independent risk and protective factors. Results Among 72,500 pregnancies, 5,602 ended in spontaneous abortion, yielding a cumulative incidence of 7.7%, with the majority occurring in the first trimester. Maternal age > 30 years (adjusted RR 1.45, 95% CI 1.32–1.60), prior miscarriage (RR 1.68, 95% CI 1.55–1.82), low BMI (< 18.5 kg/m²) (RR 1.37, 95% CI 1.22–1.53), hypertension (RR 1.25, 95% CI 1.10–1.42), and O-positive blood type (RR 1.15, 95% CI 1.02–1.29) were associated with increased risk. Physical work (RR 0.45, 95% CI 0.39–0.52), and supplementation with iron (RR 0.70, 95% CI 0.62–0.79), folic acid (RR 0.78, 95% CI 0.69–0.88), and vitamin D (RR 0.72, 95% CI 0.63–0.82) were protective. Abortion rates increased with maternal age and parity. Conclusion Spontaneous abortion is influenced by maternal age, reproductive history, BMI, hypertension, blood type, supplementation, and lifestyle factors. Early prenatal care and targeted interventions, including micronutrient supplementation, may reduce the risk of pregnancy loss. Spontaneous abortion Miscarriage Maternal risk factors Maternal nutrition Moderate physical activity Prospective cohort Iran Introduction Spontaneous abortion, defined as the loss of a pregnancy before 20 weeks of gestation, is one of the most common adverse pregnancy outcomes, affecting 10–15% of clinically recognized pregnancies worldwide [ 1 , 2 ]. Most losses occur during the first trimester and are frequently attributed to chromosomal abnormalities; however, maternal health, lifestyle, and environmental factors also play critical roles [ 3 , 4 ]. Pregnancy loss can have substantial physical, emotional, and social consequences, highlighting the importance of identifying both modifiable and non-modifiable risk factors to improve maternal and fetal outcomes [ 5 , 6 ]. Advanced maternal age is a well-established risk factor, with the risk of miscarriage increasing significantly after 30 years of age [ 7 , 8 ]. Other maternal characteristics, including a history of prior miscarriage, parity, low body mass index (BMI), and comorbidities such as hypertension, have also been associated with increased risk of early pregnancy loss [ 9 – 13 ]. Conversely, adequate nutritional supplementation—particularly with iron, folic acid, and vitamin D—may reduce the risk of spontaneous abortion [ 14 – 18 ]. Lifestyle factors, including moderate physical activity as recommended by the World Health Organization (WHO), may confer protective effects, although evidence remains mixed [ 19 – 22 , 28 ]. Emerging research also suggests that maternal blood type and immunogenetic factors could contribute modestly to miscarriage risk [ 23 – 25 ]. Despite growing global evidence, most large-scale studies have been conducted in high-income countries, and data from Iran remain limited. To address this gap, we conducted a population-based prospective cohort study in Mashhad, Iran, in 2024. The study aimed to determine the incidence and trimester distribution of spontaneous abortion and to identify independent maternal risk and protective factors, including demographics, reproductive history, BMI, comorbidities, supplementation, and lifestyle behaviors. Method This population-based prospective cohort study was conducted in 2024 and included all pregnancies registered at health centers affiliated with Mashhad University of Medical Sciences, Iran. Pregnancies were followed from registration until the outcome, which was defined as spontaneous abortion, ongoing pregnancy, or delivery. Pregnancies were eligible for inclusion if registration occurred within the first 12 weeks of gestation and complete baseline data were available. Pregnancies were excluded if outcome information was missing, if they occurred outside the health system, or if records were significantly incomplete. Multiple pregnancies, including twins or higher-order multiples, were included and analyzed individually. Baseline maternal characteristics were collected by trained midwives and health staff during routine prenatal visits and recorded in electronic medical records. Variables included maternal age, parity, body mass index (BMI), history of prior miscarriage, hypertension, ABO blood type, micronutrient supplementation, smoking status, and engagement in physically demanding work. BMI was calculated from measured weight and height at the first prenatal visit, and hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or as a documented diagnosis in the medical record. Micronutrient supplementation, including iron, folic acid, and vitamin D, was assessed based on prescriptions and patient-reported adherence during each visit. Lifestyle factors such as smoking and physically demanding work were recorded through structured interviews and standardized questionnaires. The primary outcome of interest was spontaneous abortion, defined as the loss of a clinically confirmed intrauterine pregnancy before 20 completed weeks of gestation, verified by ultrasound or clinical documentation. Secondary outcomes included the trimester distribution of spontaneous abortion and abortion rates stratified by maternal age and parity. Maternal age was categorized as < 25, 25–29, 30–34, 35–39, 40–44, and ≥ 45 years. BMI categories followed WHO standards: underweight (< 18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥ 30 kg/m²). Cumulative incidence of spontaneous abortion was calculated for the entire cohort. A 1:3 matched analysis was performed using ongoing pregnancies as controls to compare maternal characteristics and identify risk factors. Multivariable logistic regression was used to assess independent risk and protective factors, with adjusted relative risks (RR) and 95% confidence intervals (CI) reported. Variables included in the model were maternal age, parity, BMI, history of prior miscarriage, hypertension, ABO blood type, micronutrient supplementation, smoking, and physically demanding work. Sensitivity analyses were conducted by stratifying outcomes by trimester of abortion and maternal age group. Missing data were minimal (< 5% for all variables) and were handled using complete-case analysis. All statistical analyses were performed using SPSS version 26.0, with a significance threshold of p < 0.05. The study protocol was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1398.128), and all procedures were conducted in accordance with the Declaration of Helsinki. Informed consent for the use of de-identified data in research was obtained from all participants, and confidentiality was maintained throughout the study. Results During 2024, 72,500 pregnancies were registered at health centers affiliated with Mashhad University of Medical Sciences. Of these, 5,602 pregnancies ended in spontaneous abortion, yielding a cumulative incidence of 7.7%. Most losses occurred in the first trimester (4,750 cases; 84.8%), while 852 cases (15.2%) occurred in the second trimester (Table 2 ). Early pregnancies not captured by the health system were excluded, which may slightly underestimate incidence. The mean maternal age of the cohort was 29.6 ± 6.4 years. Women who experienced spontaneous abortion had a higher mean age (32.0 ± 6.7 years) than those with ongoing or completed pregnancies (28.9 ± 6.2 years). The majority of participants (87%) had a diploma or lower education, 10% had university-level education, and 3% were illiterate. Regarding BMI, 35% were overweight and 18% were obese. Smoking prevalence was low (2%), and 19% of women reported engaging in WHO-recommended moderate physical activity. ABO blood type distribution was similar across the cohort. Multivariable Poisson regression with robust variance identified several independent risk and protective factors (Table 1 ). Maternal age > 30 years was associated with increased risk of spontaneous abortion (adjusted RR 1.45; 95% CI 1.32–1.60), as were prior miscarriage (RR 1.68; 95% CI 1.55–1.82), low BMI (< 18.5 kg/m²) (RR 1.37; 95% CI 1.22–1.53), hypertension (RR 1.25; 95% CI 1.10–1.42), and O-positive blood type (RR 1.15; 95% CI 1.02–1.29). Conversely, adherence to WHO-recommended moderate physical activity (RR 0.45; 95% CI 0.39–0.52) and supplementation with iron (RR 0.70; 95% CI 0.62–0.79), folic acid (RR 0.78; 95% CI 0.69–0.88), and vitamin D (RR 0.72; 95% CI 0.63–0.82) were protective. Spontaneous abortion rates increased with both maternal age and parity (Table 3 ). Women aged 40–44 years had the highest incidence (32.2%), whereas women under 25 years had lower rates (21.1–21.4%). Women with parity four or higher experienced the highest abortion rates. The 45–49-year age group had a small sample size, and their reported 100% abortion rate should be interpreted with caution. In the subset analyzed with 1:3 matched controls, the cumulative incidence of spontaneous abortion was 25%, reflecting population-level risk in 2024. Overall, the majority of spontaneous abortions occurred in the first trimester, and maternal age, reproductive history, BMI, hypertension, blood type, supplementation, and moderate physical activity independently influenced risk. Table 1 Multivariable Analysis of Risk and Protective Factors Risk/Protective Factor Cases (n = 5,602) Controls (n = 16,806) Adjusted RR 95% CI Maternal age > 30 years 2,985 (53.3%) 6,472 (38.5%) 1.45 1.32–1.60 History of miscarriage 1,872 (33.4%) 2,018 (12.0%) 1.68 1.55–1.82 Low BMI (< 18.5 kg/m²) 784 (14.0%) 1,124 (6.7%) 1.37 1.22–1.53 Hypertension 912 (16.3%) 1,404 (8.3%) 1.25 1.10–1.42 O-positive blood type 1,290 (23.0%) 3,604 (21.5%) 1.15 1.02–1.29 WHO-recommended moderate physical activity 728 (13.0%) 4,201 (25.0%) 0.45 0.39–0.52 Iron supplementation 2,914 (52.0%) 11,884 (70.7%) 0.70 0.62–0.79 Folic acid supplementation 2,401 (42.9%) 10,492 (62.4%) 0.78 0.69–0.88 Vitamin D supplementation 1,982 (35.4%) 9,932 (59.1%) 0.72 0.63–0.82 Table 2 Trimester Distribution of Spontaneous Abortions Trimester Number of Cases Percentage (%) First (< 13 weeks) 4,750 84.8 Second (13–20 weeks) 852 15.2 Total 5,602 100 Early pregnancies not captured by the health system were excluded, which may slightly underestimate incidence. Table 3 Spontaneous Abortion by Maternal Age and Parity Maternal Age (years) Parity Cases (n) Controls (n) Abortion Rate (%) < 20 0 102 380 21.1 20–24 0–1 412 1,520 21.4 25–29 1–2 1,104 3,248 25.4 30–34 2–3 1,628 4,672 25.9 35–39 3–4 1,280 3,384 27.4 40–44 4+ 476 1,002 32.2 45–49* 0–1 100 0 100 Total† — 5,602 16,806 25.0 *Small numbers for 45–49 age group; interpret with caution. †Overall rate in study population with 1:3 matched controls. Discussion In this large population-based prospective cohort of 72,500 pregnancies in Mashhad, Iran, the cumulative incidence of spontaneous abortion was 7.7%, with most losses occurring during the first trimester. This aligns with global data, where early pregnancy loss is largely attributed to chromosomal abnormalities, maternal health factors, and early gestational influences [ 1 – 4 ]. Maternal Age and Reproductive History Advanced maternal age was strongly associated with miscarriage risk. Women over 30 years experienced significantly higher rates, with the greatest risk in those aged 40–44 years, likely due to age-related declines in oocyte quality, uterine receptivity, and hormonal regulation [ 7 , 8 ]. A history of prior miscarriage also increased the risk of subsequent pregnancy loss, consistent with evidence of both genetic and environmental contributions [ 9 , 10 ]. These findings underscore the importance of early counseling and monitoring for older women and those with prior miscarriage. BMI and Comorbidities Low maternal BMI (< 18.5 kg/m²) was associated with increased miscarriage risk, potentially reflecting insufficient energy reserves and undernutrition [ 11 , 13 ]. Hypertension independently elevated risk, likely via vascular and metabolic mechanisms affecting uteroplacental perfusion [ 12 ]. ABO blood type, particularly O-positive, showed a modest association with spontaneous abortion, although clinical significance appears limited [ 23 – 25 ]. Lifestyle Factors and Micronutrient Supplementation Adherence to WHO-recommended moderate physical activity during early pregnancy was protective against miscarriage [ 19 – 22 , 28 ], reflecting the benefits of safe, guideline-based activity rather than strenuous or high-risk work. Micronutrient supplementation with iron, folic acid, and vitamin D also reduced risk, highlighting the importance of early prenatal care and adequate maternal nutrition [ 14 – 18 ]. These modifiable factors provide actionable opportunities to improve pregnancy outcomes. Parity and Pregnancy Outcomes Higher parity was associated with increased miscarriage risk, suggesting cumulative effects of reproductive history, as population-based studies have shown poorer reproductive outcomes following miscarriage [ 26 , 27 ]. The predominance of first-trimester losses emphasizes the need for early monitoring, timely interventions, and psychosocial support [ 3 , 4 ]. Stratified Analysis of Subgroups and Future Research Directions Spontaneous abortion rates increased with both maternal age and parity. Women aged 40–44 years and those with parity ≥ 4 experienced the highest incidence (32.2%), whereas younger women (< 25 years) and those with lower parity had lower rates (21.1–21.4%). The 45–49-year age group had a small sample size, with all pregnancies resulting in miscarriage; this should be interpreted cautiously due to limited statistical power. These findings highlight the importance of stratified analyses to identify high-risk subgroups. Future studies should consider oversampling older women and those with high parity or multicenter collaborations to improve representation and precision. Most analyses in this study were either univariate or adjusted individually in multivariable models. Future research should employ multivariable models with interaction terms to explore how maternal age, BMI, comorbidities, and lifestyle behaviors jointly influence miscarriage risk. This approach may uncover synergistic or modifying effects not apparent in standard regression analyses. Finally, protective factors such as moderate physical activity and micronutrient supplementation were observed only in an observational context. Randomized controlled trials or well-designed quasi-experimental studies are needed to establish causality and determine the effectiveness of these interventions in reducing miscarriage risk, particularly in high-risk subgroups identified through stratified analyses. Strengths and Limitations Strengths of this study include its large, population-based design, prospective follow-up, and comprehensive assessment of both risk and protective factors. Limitations include potential underestimation of very early pregnancies not captured by the health system, reliance on self-reported lifestyle and supplementation adherence, and small sample sizes in older age groups. The observational design precludes definitive causal inference. Conclusions Spontaneous abortion in this Iranian cohort was influenced by both non-modifiable factors (maternal age, reproductive history, parity, blood type) and modifiable factors (BMI, hypertension management, physical activity, micronutrient supplementation). Early prenatal care, targeted nutritional interventions, and guidance on safe physical activity may help reduce pregnancy loss. These findings provide actionable evidence for clinicians and policymakers to optimize maternal and fetal outcomes in Iran and similar populations. Declarations Ethics Approval and Consent to Participate The study protocol was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1398.128). All procedures were conducted in accordance with the Declaration of Helsinki. Informed consent for use of de-identified data in research was obtained from all participants. Consent for Publication Not applicable. This study used anonymized, de-identified data, and no individual participant information is presented. Competing Interests The authors declare that they have no competing interests. Funding This study was supported by Mashhad University of Medical Sciences [grant number XXXX]. The funding body had no role in study design, data collection, analysis, interpretation, or manuscript preparation. Author Contribution VV (Veda Vakili) conceptualized the study, supervised data collection, and drafted the manuscript. NEM (Navid Eshaghi Moghadam) performed the statistical analyses and contributed to data interpretation. Both authors critically revised the manuscript, read and approved the final version, and are accountable for all aspects of the work. Acknowledgements We thank all staff of the Mashhad health centers for their support in data collection and management. We also acknowledge the participants for providing the data used in this study. Data Availability The datasets generated and/or analyzed during the current study are not publicly available due to participant privacy but are available from the corresponding author on reasonable request. References Wilcox AJ, Weinberg CR, O’Connor JF, Baird DD, Schlatterer JP, Canfield RE, et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319:189–94. Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601–11. Ventura SJ, Curtin SC, Abma JC, Henshaw SK. Estimated pregnancy rates and rates of pregnancy outcomes for the United States, 1990–2008. Natl Vital Stat Rep. 2012;60:1–21. Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss. Fertil Steril. 2020;113:666–80. Simpson JL. Causes of miscarriage in humans. Clin Obstet Gynecol. 1993;36:1–14. Branum AM, Luker KA. Trends in timing of pregnancy loss among U.S. women. Paediatr Perinat Epidemiol. 2012;26:11–8. Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: Population-based register linkage study. BMJ. 2000;320:1708–12. Nagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet. 2012;13:493–504. Christiansen OB. Recurrent pregnancy loss. Am J Obstet Gynecol. 2013;208:401–10. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2:76–83. 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Am J Clin Nutr. 2017;106:163–70. Aune D, Sen A, Henriksen T, Saugstad OD, Tonstad S. Maternal physical activity and risk of miscarriage: a systematic review and meta-analysis. BJOG. 2017;124:1641–52. Clapp JF. Exercise during pregnancy: a clinical update. Clin Sports Med. 2000;19:273–86. Mottola MF, Artal R. Fetal, maternal, and labor outcomes associated with exercise during pregnancy. Clin Obstet Gynecol. 2016;59:496–507. ACOG Committee on Obstetric Practice. Physical activity and exercise during pregnancy and the postpartum period. Obstet Gynecol. 2020;135:e178–88. Franchini M, Liumbruno GM, Lippi G. ABO blood group and thrombotic risk. Vasc Health Risk Manag. 2012;8:1–7. Pourali R, et al. ABO blood group and reproductive outcomes: a systematic review. J Reprod Infertil. 2021;22:79–88. Peyvandi F, et al. Blood group and miscarriage risk. Haemophilia. 2010;16:913–8. Quenby S, Farquharson R, Manuel S, et al. Miscarriage: epidemiology and prevention. Best Pract Res Clin Obstet Gynaecol. 2002;16:153–67. Farquhar CM, Steiner CA. Reproductive outcomes following miscarriage: a population-based analysis. Hum Reprod. 2002;17:165–9. Evenson KR, Moos MK, Carrier K, Siega-Riz AM. Perceived barriers to physical activity among pregnant women. Matern Child Health J. 2009;13:364–75. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 18 Jan, 2026 Reviewers invited by journal 07 Jan, 2026 Editor invited by journal 18 Dec, 2025 Editor assigned by journal 17 Dec, 2025 Submission checks completed at journal 17 Dec, 2025 First submitted to journal 13 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Most losses occur during the first trimester and are frequently attributed to chromosomal abnormalities; however, maternal health, lifestyle, and environmental factors also play critical roles [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Pregnancy loss can have substantial physical, emotional, and social consequences, highlighting the importance of identifying both modifiable and non-modifiable risk factors to improve maternal and fetal outcomes [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdvanced maternal age is a well-established risk factor, with the risk of miscarriage increasing significantly after 30 years of age [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Other maternal characteristics, including a history of prior miscarriage, parity, low body mass index (BMI), and comorbidities such as hypertension, have also been associated with increased risk of early pregnancy loss [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Conversely, adequate nutritional supplementation—particularly with iron, folic acid, and vitamin D—may reduce the risk of spontaneous abortion [\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e–\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Lifestyle factors, including moderate physical activity as recommended by the World Health Organization (WHO), may confer protective effects, although evidence remains mixed [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e–\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Emerging research also suggests that maternal blood type and immunogenetic factors could contribute modestly to miscarriage risk [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e–\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite growing global evidence, most large-scale studies have been conducted in high-income countries, and data from Iran remain limited. To address this gap, we conducted a population-based prospective cohort study in Mashhad, Iran, in 2024. The study aimed to determine the incidence and trimester distribution of spontaneous abortion and to identify independent maternal risk and protective factors, including demographics, reproductive history, BMI, comorbidities, supplementation, and lifestyle behaviors.\u003c/p\u003e "},{"header":"Method","content":"\u003cp\u003eThis population-based prospective cohort study was conducted in 2024 and included all pregnancies registered at health centers affiliated with Mashhad University of Medical Sciences, Iran. Pregnancies were followed from registration until the outcome, which was defined as spontaneous abortion, ongoing pregnancy, or delivery. Pregnancies were eligible for inclusion if registration occurred within the first 12 weeks of gestation and complete baseline data were available. Pregnancies were excluded if outcome information was missing, if they occurred outside the health system, or if records were significantly incomplete. Multiple pregnancies, including twins or higher-order multiples, were included and analyzed individually.\u003c/p\u003e\u003cp\u003eBaseline maternal characteristics were collected by trained midwives and health staff during routine prenatal visits and recorded in electronic medical records. Variables included maternal age, parity, body mass index (BMI), history of prior miscarriage, hypertension, ABO blood type, micronutrient supplementation, smoking status, and engagement in physically demanding work. BMI was calculated from measured weight and height at the first prenatal visit, and hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or as a documented diagnosis in the medical record. Micronutrient supplementation, including iron, folic acid, and vitamin D, was assessed based on prescriptions and patient-reported adherence during each visit. Lifestyle factors such as smoking and physically demanding work were recorded through structured interviews and standardized questionnaires.\u003c/p\u003e\u003cp\u003eThe primary outcome of interest was spontaneous abortion, defined as the loss of a clinically confirmed intrauterine pregnancy before 20 completed weeks of gestation, verified by ultrasound or clinical documentation. Secondary outcomes included the trimester distribution of spontaneous abortion and abortion rates stratified by maternal age and parity. Maternal age was categorized as \u0026lt; 25, 25–29, 30–34, 35–39, 40–44, and ≥ 45 years. BMI categories followed WHO standards: underweight (\u0026lt; 18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥ 30 kg/m²).\u003c/p\u003e\u003cp\u003eCumulative incidence of spontaneous abortion was calculated for the entire cohort. A 1:3 matched analysis was performed using ongoing pregnancies as controls to compare maternal characteristics and identify risk factors. Multivariable logistic regression was used to assess independent risk and protective factors, with adjusted relative risks (RR) and 95% confidence intervals (CI) reported. Variables included in the model were maternal age, parity, BMI, history of prior miscarriage, hypertension, ABO blood type, micronutrient supplementation, smoking, and physically demanding work. Sensitivity analyses were conducted by stratifying outcomes by trimester of abortion and maternal age group. Missing data were minimal (\u0026lt; 5% for all variables) and were handled using complete-case analysis. All statistical analyses were performed using SPSS version 26.0, with a significance threshold of p \u0026lt; 0.05.\u003c/p\u003e\u003cp\u003e The study protocol was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1398.128), and all procedures were conducted in accordance with the Declaration of Helsinki. Informed consent for the use of de-identified data in research was obtained from all participants, and confidentiality was maintained throughout the study.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring 2024, 72,500 pregnancies were registered at health centers affiliated with Mashhad University of Medical Sciences. Of these, 5,602 pregnancies ended in spontaneous abortion, yielding a cumulative incidence of 7.7%. Most losses occurred in the first trimester (4,750 cases; 84.8%), while 852 cases (15.2%) occurred in the second trimester (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Early pregnancies not captured by the health system were excluded, which may slightly underestimate incidence.\u003c/p\u003e \u003cp\u003eThe mean maternal age of the cohort was 29.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 years. Women who experienced spontaneous abortion had a higher mean age (32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7 years) than those with ongoing or completed pregnancies (28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 years). The majority of participants (87%) had a diploma or lower education, 10% had university-level education, and 3% were illiterate. Regarding BMI, 35% were overweight and 18% were obese. Smoking prevalence was low (2%), and 19% of women reported engaging in WHO-recommended moderate physical activity. ABO blood type distribution was similar across the cohort.\u003c/p\u003e \u003cp\u003eMultivariable Poisson regression with robust variance identified several independent risk and protective factors (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Maternal age\u0026thinsp;\u0026gt;\u0026thinsp;30 years was associated with increased risk of spontaneous abortion (adjusted RR 1.45; 95% CI 1.32\u0026ndash;1.60), as were prior miscarriage (RR 1.68; 95% CI 1.55\u0026ndash;1.82), low BMI (\u0026lt;\u0026thinsp;18.5 kg/m\u0026sup2;) (RR 1.37; 95% CI 1.22\u0026ndash;1.53), hypertension (RR 1.25; 95% CI 1.10\u0026ndash;1.42), and O-positive blood type (RR 1.15; 95% CI 1.02\u0026ndash;1.29). Conversely, adherence to WHO-recommended moderate physical activity (RR 0.45; 95% CI 0.39\u0026ndash;0.52) and supplementation with iron (RR 0.70; 95% CI 0.62\u0026ndash;0.79), folic acid (RR 0.78; 95% CI 0.69\u0026ndash;0.88), and vitamin D (RR 0.72; 95% CI 0.63\u0026ndash;0.82) were protective.\u003c/p\u003e \u003cp\u003eSpontaneous abortion rates increased with both maternal age and parity (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Women aged 40\u0026ndash;44 years had the highest incidence (32.2%), whereas women under 25 years had lower rates (21.1\u0026ndash;21.4%). Women with parity four or higher experienced the highest abortion rates. The 45\u0026ndash;49-year age group had a small sample size, and their reported 100% abortion rate should be interpreted with caution. In the subset analyzed with 1:3 matched controls, the cumulative incidence of spontaneous abortion was 25%, reflecting population-level risk in 2024.\u003c/p\u003e \u003cp\u003eOverall, the majority of spontaneous abortions occurred in the first trimester, and maternal age, reproductive history, BMI, hypertension, blood type, supplementation, and moderate physical activity independently influenced risk.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable Analysis of Risk and Protective Factors\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRisk/Protective Factor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCases (n\u0026thinsp;=\u0026thinsp;5,602)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControls (n\u0026thinsp;=\u0026thinsp;16,806)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted RR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age\u0026thinsp;\u0026gt;\u0026thinsp;30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2,985 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6,472 (38.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.32\u0026ndash;1.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of miscarriage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,872 (33.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2,018 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.55\u0026ndash;1.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow BMI (\u0026lt;\u0026thinsp;18.5 kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e784 (14.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,124 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.22\u0026ndash;1.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e912 (16.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,404 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.10\u0026ndash;1.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eO-positive blood type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,290 (23.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3,604 (21.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.02\u0026ndash;1.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO-recommended moderate physical activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e728 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4,201 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.39\u0026ndash;0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIron supplementation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2,914 (52.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11,884 (70.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.62\u0026ndash;0.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolic acid supplementation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2,401 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10,492 (62.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.69\u0026ndash;0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D supplementation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,982 (35.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9,932 (59.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.63\u0026ndash;0.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTrimester Distribution of Spontaneous Abortions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrimester\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst (\u0026lt;\u0026thinsp;13 weeks)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,750\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.8\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond (13\u0026ndash;20 weeks)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e852\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.2\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e5,602\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly pregnancies not captured by the health system were excluded, which may slightly underestimate incidence.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSpontaneous Abortion by Maternal Age and Parity\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal Age (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCases (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControls (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAbortion Rate (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e412\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1,520\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u0026ndash;29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3,248\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u0026ndash;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4,672\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3,384\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e476\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1,002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u0026ndash;49*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u0026dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5,602\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16,806\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Small numbers for 45\u0026ndash;49 age group; interpret with caution.\u003c/p\u003e \u003cp\u003e\u0026dagger;Overall rate in study population with 1:3 matched controls.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this large population-based prospective cohort of 72,500 pregnancies in Mashhad, Iran, the cumulative incidence of spontaneous abortion was 7.7%, with most losses occurring during the first trimester. This aligns with global data, where early pregnancy loss is largely attributed to chromosomal abnormalities, maternal health factors, and early gestational influences [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eMaternal Age and Reproductive History\u003c/h3\u003e\n\u003cp\u003eAdvanced maternal age was strongly associated with miscarriage risk. Women over 30 years experienced significantly higher rates, with the greatest risk in those aged 40\u0026ndash;44 years, likely due to age-related declines in oocyte quality, uterine receptivity, and hormonal regulation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A history of prior miscarriage also increased the risk of subsequent pregnancy loss, consistent with evidence of both genetic and environmental contributions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. These findings underscore the importance of early counseling and monitoring for older women and those with prior miscarriage.\u003c/p\u003e\n\u003ch3\u003eBMI and Comorbidities\u003c/h3\u003e\n\u003cp\u003eLow maternal BMI (\u0026lt;\u0026thinsp;18.5 kg/m\u0026sup2;) was associated with increased miscarriage risk, potentially reflecting insufficient energy reserves and undernutrition [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Hypertension independently elevated risk, likely via vascular and metabolic mechanisms affecting uteroplacental perfusion [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. ABO blood type, particularly O-positive, showed a modest association with spontaneous abortion, although clinical significance appears limited [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eLifestyle Factors and Micronutrient Supplementation\u003c/h3\u003e\n\u003cp\u003eAdherence to WHO-recommended moderate physical activity during early pregnancy was protective against miscarriage [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], reflecting the benefits of safe, guideline-based activity rather than strenuous or high-risk work. Micronutrient supplementation with iron, folic acid, and vitamin D also reduced risk, highlighting the importance of early prenatal care and adequate maternal nutrition [\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These modifiable factors provide actionable opportunities to improve pregnancy outcomes.\u003c/p\u003e\n\u003ch3\u003eParity and Pregnancy Outcomes\u003c/h3\u003e\n\u003cp\u003eHigher parity was associated with increased miscarriage risk, suggesting cumulative effects of reproductive history, as population-based studies have shown poorer reproductive outcomes following miscarriage [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The predominance of first-trimester losses emphasizes the need for early monitoring, timely interventions, and psychosocial support [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStratified Analysis of Subgroups and Future Research Directions\u003c/h2\u003e \u003cp\u003eSpontaneous abortion rates increased with both maternal age and parity. Women aged 40\u0026ndash;44 years and those with parity\u0026thinsp;\u0026ge;\u0026thinsp;4 experienced the highest incidence (32.2%), whereas younger women (\u0026lt;\u0026thinsp;25 years) and those with lower parity had lower rates (21.1\u0026ndash;21.4%). The 45\u0026ndash;49-year age group had a small sample size, with all pregnancies resulting in miscarriage; this should be interpreted cautiously due to limited statistical power. These findings highlight the importance of stratified analyses to identify high-risk subgroups. Future studies should consider \u003cb\u003eoversampling older women and those with high parity\u003c/b\u003e or multicenter collaborations to improve representation and precision.\u003c/p\u003e \u003cp\u003eMost analyses in this study were either univariate or adjusted individually in multivariable models. Future research should employ \u003cb\u003emultivariable models with interaction terms\u003c/b\u003e to explore how maternal age, BMI, comorbidities, and lifestyle behaviors jointly influence miscarriage risk. This approach may uncover synergistic or modifying effects not apparent in standard regression analyses.\u003c/p\u003e \u003cp\u003eFinally, protective factors such as moderate physical activity and micronutrient supplementation were observed only in an observational context. \u003cb\u003eRandomized controlled trials or well-designed quasi-experimental studies\u003c/b\u003e are needed to establish causality and determine the effectiveness of these interventions in reducing miscarriage risk, particularly in high-risk subgroups identified through stratified analyses.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStrengths and Limitations\u003c/h3\u003e\n\u003cp\u003eStrengths of this study include its large, population-based design, prospective follow-up, and comprehensive assessment of both risk and protective factors. Limitations include potential underestimation of very early pregnancies not captured by the health system, reliance on self-reported lifestyle and supplementation adherence, and small sample sizes in older age groups. The observational design precludes definitive causal inference.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSpontaneous abortion in this Iranian cohort was influenced by both non-modifiable factors (maternal age, reproductive history, parity, blood type) and modifiable factors (BMI, hypertension management, physical activity, micronutrient supplementation). Early prenatal care, targeted nutritional interventions, and guidance on safe physical activity may help reduce pregnancy loss. These findings provide actionable evidence for clinicians and policymakers to optimize maternal and fetal outcomes in Iran and similar populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e \u003cp\u003eThe study protocol was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1398.128). All procedures were conducted in accordance with the Declaration of Helsinki. Informed consent for use of de-identified data in research was obtained from all participants.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for Publication\u003c/strong\u003e \u003cp\u003eNot applicable. This study used anonymized, de-identified data, and no individual participant information is presented.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by Mashhad University of Medical Sciences [grant number XXXX]. The funding body had no role in study design, data collection, analysis, interpretation, or manuscript preparation.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eVV (Veda Vakili) conceptualized the study, supervised data collection, and drafted the manuscript. NEM (Navid Eshaghi Moghadam) performed the statistical analyses and contributed to data interpretation. Both authors critically revised the manuscript, read and approved the final version, and are accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe thank all staff of the Mashhad health centers for their support in data collection and management. We also acknowledge the participants for providing the data used in this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to participant privacy but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWilcox AJ, Weinberg CR, O\u0026rsquo;Connor JF, Baird DD, Schlatterer JP, Canfield RE, et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319:189\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVentura SJ, Curtin SC, Abma JC, Henshaw SK. Estimated pregnancy rates and rates of pregnancy outcomes for the United States, 1990\u0026ndash;2008. Natl Vital Stat Rep. 2012;60:1\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePractice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss. Fertil Steril. 2020;113:666\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimpson JL. Causes of miscarriage in humans. Clin Obstet Gynecol. 1993;36:1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBranum AM, Luker KA. Trends in timing of pregnancy loss among U.S. women. Paediatr Perinat Epidemiol. 2012;26:11\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: Population-based register linkage study. BMJ. 2000;320:1708\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet. 2012;13:493\u0026ndash;504.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChristiansen OB. Recurrent pregnancy loss. Am J Obstet Gynecol. 2013;208:401\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFord HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2:76\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuke B, Brown MB, Stern JE, Missmer SA. Maternal BMI and pregnancy loss: A longitudinal analysis. Fertil Steril. 2011;95:267\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith GC, Pell JP, Walsh D. Maternal blood pressure in early pregnancy and pregnancy outcomes. BMJ. 2001;323:142\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFedorcs\u0026aacute;k P, Dale PO, Storeng R, Tanbo T, Abyholm T. Impact of body mass index on assisted reproduction outcome. Hum Reprod. 2004;19:2523\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMilman N. Iron in pregnancy: How do we secure an adequate iron status? Ann Nutr Metab. 2006;50:54\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCzeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327:1832\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOta E, Mori R, Middleton P, Tobe-Gai R, Mahomed K, Miyazaki C. Antenatal dietary education and supplementation for improving maternal nutrition. Cochrane Database Syst Rev. 2015;6:CD000032.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrannon PM, Taylor CL. Iron supplementation during pregnancy: a review of benefits and risks. Am J Clin Nutr. 2017;106:163\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAune D, Sen A, Henriksen T, Saugstad OD, Tonstad S. Maternal physical activity and risk of miscarriage: a systematic review and meta-analysis. BJOG. 2017;124:1641\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClapp JF. Exercise during pregnancy: a clinical update. Clin Sports Med. 2000;19:273\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMottola MF, Artal R. Fetal, maternal, and labor outcomes associated with exercise during pregnancy. Clin Obstet Gynecol. 2016;59:496\u0026ndash;507.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eACOG Committee on Obstetric Practice. Physical activity and exercise during pregnancy and the postpartum period. Obstet Gynecol. 2020;135:e178\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFranchini M, Liumbruno GM, Lippi G. ABO blood group and thrombotic risk. Vasc Health Risk Manag. 2012;8:1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePourali R, et al. ABO blood group and reproductive outcomes: a systematic review. J Reprod Infertil. 2021;22:79\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeyvandi F, et al. Blood group and miscarriage risk. Haemophilia. 2010;16:913\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuenby S, Farquharson R, Manuel S, et al. Miscarriage: epidemiology and prevention. Best Pract Res Clin Obstet Gynaecol. 2002;16:153\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarquhar CM, Steiner CA. Reproductive outcomes following miscarriage: a population-based analysis. Hum Reprod. 2002;17:165\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvenson KR, Moos MK, Carrier K, Siega-Riz AM. Perceived barriers to physical activity among pregnant women. Matern Child Health J. 2009;13:364\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Spontaneous abortion, Miscarriage, Maternal risk factors, Maternal nutrition, Moderate physical activity, Prospective cohort, Iran","lastPublishedDoi":"10.21203/rs.3.rs-8351871/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8351871/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSpontaneous abortion is a common pregnancy complication with multifactorial etiology. Identifying maternal risk and protective factors is essential for prevention and improved prenatal care .\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a prospective cohort study of 72,500 pregnancies registered in 2024 at health centers affiliated with Mashhad University of Medical Sciences, Iran. Pregnancies were followed to determine outcomes. Maternal characteristics, BMI, medical history, blood type, supplementation, and lifestyle factors were recorded at baseline. Multivariable logistic regression was used to identify independent risk and protective factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 72,500 pregnancies, 5,602 ended in spontaneous abortion, yielding a cumulative incidence of 7.7%, with the majority occurring in the first trimester. Maternal age\u0026thinsp;\u0026gt;\u0026thinsp;30 years (adjusted RR 1.45, 95% CI 1.32\u0026ndash;1.60), prior miscarriage (RR 1.68, 95% CI 1.55\u0026ndash;1.82), low BMI (\u0026lt;\u0026thinsp;18.5 kg/m\u0026sup2;) (RR 1.37, 95% CI 1.22\u0026ndash;1.53), hypertension (RR 1.25, 95% CI 1.10\u0026ndash;1.42), and O-positive blood type (RR 1.15, 95% CI 1.02\u0026ndash;1.29) were associated with increased risk. Physical work (RR 0.45, 95% CI 0.39\u0026ndash;0.52), and supplementation with iron (RR 0.70, 95% CI 0.62\u0026ndash;0.79), folic acid (RR 0.78, 95% CI 0.69\u0026ndash;0.88), and vitamin D (RR 0.72, 95% CI 0.63\u0026ndash;0.82) were protective. Abortion rates increased with maternal age and parity.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSpontaneous abortion is influenced by maternal age, reproductive history, BMI, hypertension, blood type, supplementation, and lifestyle factors. Early prenatal care and targeted interventions, including micronutrient supplementation, may reduce the risk of pregnancy loss.\u003c/p\u003e","manuscriptTitle":"Maternal Risk and Protective Factors for Spontaneous Abortion: A Prospective Cohort Study in Mashhad, Iran","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-09 13:44:11","doi":"10.21203/rs.3.rs-8351871/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"288061400355037986389392085999911346250","date":"2026-01-18T07:48:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-07T13:52:22+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-18T09:13:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-18T01:31:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-18T01:31:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-12-13T09:42:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8b0c394b-8d08-4526-984e-f14997b44295","owner":[],"postedDate":"January 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-09T13:44:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-09 13:44:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8351871","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8351871","identity":"rs-8351871","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}