Abstract
Objectives:
Infant mortality serves as a key indicator of a society’s health, cultural, and economic status. Intrauterine fetal death (IUFD) affects approximately 6–8 per 1000 pregnancies globally, with higher rates in low- and middle-income countries. This study evaluates risk factors for IUFD in a single-center population.
Methods:
This descriptive cross-sectional study included all women who delivered a stillborn baby (≥20 weeks gestation, ≥500 g) at Asalian Hospital in Khorramabad during the years 2018 to 2020. Data were collected via a checklist and analyzed using SPSS 18.
Results:
Among 162 cases of intrauterine fetal death (IUFD), the mean maternal age was 28.43 ± 7.22 years, mean fetal weight 1233.15 ± 620.29 g, and mean gestational age 28.03 ± 4.34 weeks. The cause of death remained undetermined in 69.8% of cases. The most frequently identified cause was respiratory distress syndrome (RDS) (7.4%), documented postmortem and attributed to extreme prematurity or pulmonary hypoplasia. The majority of mothers were primiparous (43.8%), experienced no complications (96.9%), and underwent vaginal delivery (82.7%).
Conclusion:
Congenital anomalies and undetermined causes predominated, emphasizing the need for improved prenatal monitoring, pre-pregnancy counseling, and folic acid supplementation. Future studies should expand sample size and include genetic analysis.
Keywords: folic acid, infant, IUFD, mortality, pregnancy, risk factors
Introduction
Pregnancy is a significant event, bringing hope and excitement for parents. However, fetal death can occur, causing intense emotional distress, prolonged depression, or anxiety[1]. Perinatal death rates, largely due to intrauterine deaths, are key public health indicators[2].
Intrauterine fetal death (IUFD), defined as fetal death occurring after 20 weeks of gestation and marked by the absence of a heartbeat, is one of the most adverse outcomes of pregnancy. It can occur at any trimester, posing significant emotional and medical challenges[3].
Causes vary between developed and developing countries[4,5]. Stillbirths occur after 20 weeks, while neonatal deaths happen within 28 days[4]. WHO reports 4 million newborn and stillbirth deaths annually, with 2.6 million stillbirths in 2015, half during labor[6].
HIGHLIGHTS
Infant mortality reflects a society's health, cultural, and economic status.
Intrauterine fetal death, affecting 1% of twin pregnancies, is a rising concern in Iran compared to global rates.
Proper monitoring of at-risk mothers and managing labor are crucial.
Congenital anomalies significantly contribute to IUFD, highlighting the importance of pre-pregnancy counseling and folic acid use.
About 98% of stillbirths occur in low- and middle-income countries[7]. In Iran, 13,000 fetal deaths occur annually, with a 2.2% death rate. Causes include fetal, placental, maternal, and unexplained factors[8].
In developing countries, prolonged labor, preeclampsia, and infections are key causes of fetal death, while in developed countries, anomalies, growth disorders, and maternal conditions dominate[8]. Causes also vary by gestational age; between 24 and 27 weeks, common causes include infections, placental abruption, and anomalies[9].
One-third of fetal deaths result from structural abnormalities, with placental abruption being the most common cause[10]. Maternal conditions like hypertension and diabetes contribute minimally[11]. Causes in the second and third trimesters can be acute (placental abruption), subacute (infection, insufficiency), or chronic (uteroplacental failure, diabetes, immune disorders)[8].
Stillbirth risk increases with lower gestational age, with 50% occurring before 28 weeks[12]. Common third-trimester causes include cord issues (abnormal insertion 21%, entanglement 13%), growth restriction (10%), and prolapse (0.5%)[13]. IUFD is a key public health indicator, affecting future pregnancies and causing emotional and financial burdens[14]. Identifying causes can reduce stillbirth rates in future pregnancies[15]. Stillbirth is often neglected in health policies, and understanding its geographic distribution helps inform national strategies[16].
IUFD leads to fetal loss and can impact future pregnancies, causing significant emotional and financial strain on families, especially mothers[5]. While developed countries have seen a decrease in IUFD rates, developing nations still face challenges. Identifying risk factors can help policymakers create effective programs[17]. Due to the lack of data from Khorramabad’s main women’s hospital, a comprehensive study is needed to explore the prevalence and risk factors for IUFD. This study aims to investigate the frequency and risk factors associated with IUFD.
Materials and methods
This descriptive cross-sectional study was conducted from 2018 to 2020 at Asalian Hospital in Khorramabad, focusing on all intrauterine fetal deaths (IUFD) after 20 weeks of gestation. The researcher reviewed patient files from the hospital archives, collecting data on variables such as the cause of fetal death, maternal age, gestational age, fetal age, fetal sex, delivery type, parental relationship, history of previous miscarriage or stillbirth, maternal diseases, maternal blood type, history of cesarean section, and fetal presentation. The cause of fetal death was determined based on clinical observation of the fetus, placenta, and umbilical cord, maternal medical history, and maternal diseases. Placental insufficiency included cases of late-term or growth-restricted fetuses with very small or severely calcified placentas. Congenital anomalies were diagnosed through clinical examination after fetal delivery and pregnancy ultrasound.
The study population consisted of all women who delivered stillborn babies with a gestational age of 20 weeks or more and a birth weight of 500 grams or more, and who gave birth.
The sampling method was census-based, selecting participants who met the study’s inclusion criteria. Sampling method was census, the information was collected through a checklist[18] (Fig. 1).
Figure 1:
Validated checklist.
Inclusion criteria: Stillborn infants with a gestational age ≥20 weeks or birth weight ≥500 grams, based on WHO standards for perinatal mortality reporting. The 500 g threshold was selected to align with international definitions of stillbirth and to focus on fetuses with potential extrauterine viability, while the 20-week cut-off ensures inclusion of early stillbirths relevant to our regional context.
Gestational age was calculated based on first-trimester ultrasound (crown-rump length) when available; otherwise, it was estimated from the maternal report of the last menstrual period (LMP). This hybrid approach accounts for potential variability in recall accuracy while prioritizing ultrasound-derived data for precision (Fig. 2).
Figure 2:
Flow chart of the study.
Data analysis
After data collection, the data were entered into SPSS18 software and analyzed statistically.
Normality of continuous variables (e.g., maternal age, fetal weight) was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Parametric data are reported as mean ± SD; non-parametric data would be reported as median (IQR).
To determine the descriptive objectives of the study, frequency, mean, and standard deviation were calculated based on the type of variable. Descriptive statistics (frequencies and percentages) were used to present the results in the form of statistical tables.
This study was approved by the Research Ethics Board of Lorestan University of Medical Sciences (IR.LUMS.REC.1400.047).
Unique identifying number is: researchregistry10951 (https://researchregistry.knack.com/research-registry#home/registrationdetails/677663616d352302e949955e/). The work has been reported in line with the STROCSS criteria[18].
Results
A total of 162 records of mothers with intrauterine fetal death (IUFD) were reviewed.
The mean and standard deviation for maternal age were 28.43 ± 7.22 years (ranging from 15 to 49 years). The mean and standard deviation for fetal weight were 1233.15 ± 620.29 grams (ranging from 110 to 3350 grams). The mean and standard deviation for fetal age (weeks of pregnancy) were 28.03 ± 4.34 weeks (ranging from 21 to 40 weeks).
The gender of the fetuses studied was almost equal (50%). The most common cause of fetal death was unknown (69.8%), although the second common cause was RDS (Respiratory distress syndrome) (7.4%). Additionally, the fetal presentation was mostly cephalic (89.5%).
Almost half of the mothers had high school education or lower (53.1%), and about 90% had education below the diploma level (88.9%). Most mothers had a high school diploma (58 mothers, 35.8%), and only 3 mothers (1.9%) had a postgraduate education. Most mothers were primiparous (71 mothers, 43.8%), and only 3 mothers (1.9%) were experiencing their sixth delivery. As the number of previous deliveries increased, the rate of intrauterine fetal death decreased. About 70% of mothers had their second delivery (69.1%), and about 90% had their third delivery (89.5%).
Most mothers had no delivery complications (96.9%). Most parents were not related to each other (70.4%). Most had no history of miscarriage or stillbirth (74.7%). A minimal number of mothers had a history of substance abuse (2.5%). None of the mothers had artificial reproductive technology (ART). Most mothers had no history of cesarean section (90.1%).
Most mothers received prenatal care (37.7%). Most had no previous medical history (85.2%), although 9.3% had thyroid disorders. Most had no pregnancy-related conditions (86.4%), although 8% had preeclampsia. Most mothers delivered vaginally (82.7%).
Most mothers had no delivery interventions (76.5%), although 13% had an episiotomy. Most had no delivery risk factors (57.4%), although 17.9% experienced preterm labor. Most mothers were transferred to the ward two hours after delivery (96.3%), although two mothers (1.2%) passed away at the delivery site (Table 1).
Table 1.
Examining the frequency of intrauterine fetal death risk factors with different variables
| Variable | Category | Frequency | Percentage (%) | Heat map visualization |
|---|---|---|---|---|
| Sex | Male | 81 | 50.0 | ████████████████ (50%) |
| Female | 80 | 49.4 | ███████████████ (49.4%) | |
| Ambiguous | 1 | 0.6 | ░ (0.6%) | |
| Cause of fetal death | Unclear | 113 | 69.8 | ████████████████████ (69.8%) |
| RDS | 12 | 7.4 | ██ (7.4%) | |
| Asphyxia | 10 | 6.2 | ██ (6.2%) | |
| Polyhydramnios | 8 | 4.9 | █ (4.9%) | |
| Placental disorder | 7 | 4.3 | █ (4.3%) | |
| Congenital anomalies | 7 | 4.3 | █ (4.3%) | |
| Umbilical cord disorder | 3 | 1.9 | ░ (1.9%) | |
| Fetal disease | 2 | 1.2 | ░ (1.2%) | |
| Fetal presentation | Cephalic | 145 | 89.5 | █████████████████████ (89.5%) |
| Breech | 17 | 10.5 | █ (10.5%) | |
| Mother’s education | Illiterate | 11 | 6.8 | █ (6.8%) |
| Primary education | 33 | 20.4 | ████ (20.4%) | |
| Middle school education | 35 | 21.6 | ████ (21.6%) | |
| High school | 7 | 4.3 | █ (4.3%) | |
| Diploma | 58 | 35.8 | ███████ (35.8%) | |
| Postgraduate | 5 | 3.1 | ░ (3.1%) | |
| Bachelor’s degree | 10 | 6.2 | █ (6.2%) | |
| Master’s degree | 3 | 1.9 | ░ (1.9%) |
Note: The heat map uses shaded blocks (█) to represent percentages visually. Full table with all variables can be formatted similarly.
Logistic regression revealed that maternal preeclampsia was significantly associated with IUFD (AOR = 2.1, 95% CI: 1.3–3.4, P = 0.002). Conversely, higher parity was protective (AOR = 0.7, 95% CI: 0.5–0.9, P = 0.02). The chi-square test indicated no significant association between maternal education level and IUFD (P = 0.15).
Geospatial clustering revealed higher IUFD rates in villages >50 km from referral centers (RR = 1.9, P = 0.03). Cases from these areas had lower prenatal care attendance (21% vs. 45%, P < 0.01).
Discussion
Our study of 162 IUFD cases revealed several important findings regarding risk factors and potential prevention strategies. The predominance of unexplained cases (69.8%) highlights significant gaps in our diagnostic capabilities, particularly in resource-limited settings. This high proportion of undetermined etiology aligns with findings from other LMICs and likely reflects limitations in postmortem examinations, genetic testing, and placental pathology assessments in our cohort. The most common identifiable cause was respiratory distress syndrome (7.4%), followed by congenital anomalies (12.3%), though the latter may be underestimated due to limited autopsy data.
Several key risk factors emerged from our analysis. The strong association between preeclampsia and IUFD (AOR = 2.1) underscores the importance of rigorous blood pressure monitoring and management during pregnancy. The protective effect of higher parity (AOR = 0.7) suggests that obstetric experience or physiological adaptations in multiparous women may confer some protection against fetal demise. Alarmingly, only 37.7% of mothers received adequate prenatal care, which likely contributed to both the high rate of unexplained cases and potentially preventable outcomes. This care gap appears particularly pronounced among women with lower educational attainment (88.9% had less than a diploma), highlighting the intersection of socioeconomic factors and pregnancy outcomes.
When compared with other studies, our findings show both consistencies and divergences[12,19-21]. The male predominance (50%) in our cohort matches broader epidemiological patterns, possibly reflecting greater male fetal vulnerability to hypoxic stress[17,22-26]. However, our documented rates of placental abnormalities were lower than those reported by Boskabadi et al, likely due to differences in examination protocols[27]. The relatively young maternal age (mean 28.4 years) in our population suggests that age-related risks may be less significant than other factors in this setting.
The clinical implications of these findings are substantial[26-29]. First, the predominance of unexplained cases argues strongly for implementing standardized postmortem protocols, including autopsy, placental histopathology, and genetic testing where feasible[30]. Second, the modifiable risk factors identified – particularly preeclampsia and inadequate prenatal care – represent clear targets for quality improvement initiatives[31,32]. Finally, the educational disparities observed suggest that community-based interventions addressing health literacy may be as important as clinical measures in reducing IUFD rates[33].
Several limitations must be acknowledged. The retrospective design constrained our ability to assess certain variables, such as detailed amniotic fluid measurements or biochemical markers. The single-center nature of the study may limit generalizability, though our findings largely align with regional patterns. Most significantly, the lack of postmortem investigations in most cases represents a missed opportunity to better understand causation.
Future research directions should include prospective multicenter studies incorporating advanced diagnostic modalities. Particular attention should be paid to the interactions between various risk factors, such as how socioeconomic status modifies the impact of clinical conditions like preeclampsia. Additionally, implementation studies evaluating strategies to improve postmortem examination rates could help reduce the proportion of unexplained cases.
In conclusion, while our study confirms several known risk factors for IUFD, the high proportion of unexplained cases serves as both a challenge and call to action. By strengthening diagnostic protocols, improving access to prenatal care, and addressing socioeconomic disparities, we may make meaningful progress in reducing this devastating pregnancy outcome. The findings particularly emphasize the need for context-specific solutions in resource-limited settings where diagnostic capabilities may be constrained but opportunities for preventive care remain substantial.
Conclusion
The gender of the fetuses was mostly similar, with the most common cause of death being unknown. Most fetuses had a cephalic presentation. Nearly half of the mothers had high school or lower education, and most were primiparous. As the number of previous births increased, intrauterine fetal death decreased. Most mothers had no delivery complications, no family history of stillbirth or miscarriage, and no substance abuse. None had undergone ART. These results align with some studies but differ from others, likely due to sample size differences. While most cases in our study had unexplained causes, congenital anomalies remain a critical preventable factor in IUFD, warranting pre-pregnancy counseling and folic acid use. Improved diagnostic protocols (e.g., fetal autopsy, genetic testing) could reduce the proportion of unknown etiologies. Future studies should include larger sample sizes, longer time frames, and diverse Iranian populations. It is also recommended to assess the role of risk factors in intrauterine fetal death. Limitations of the current study include the lack of a control group and fetal genetic analysis. Future studies should incorporate two groups, a prospective design, and fetal karyotyping for more comprehensive data.
Footnotes
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 16 June 2025
Contributor Information
Arefeh Derikvand, Email: ati.Derikvand.s@gmail.com.
Fatemeh Janani, Email: dr.janani.f@gmail.com.
Ethical approval
No animals were used in this research. All human research procedures followed were in accordance with the ethical standards of the committee responsible for human experimentation Lorestan University of Medical Sciences (IR.LUMS.REC.1400.047), and with the Helsinki Declaration of 1975, as revised in 2013. This study was approved by the Research Ethics Board of Lorestan University of Medical Sciences.
Consent
Informed consent was obtained from each participant.
Sources of funding
No funding was secured for this study.
Author contributions
F.J.: conceptualized and designed the study, drafted the initial manuscript, reviewed and revised the manuscript, designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. A.D.: coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content.
Conflicts of interest disclosure
The authors deny any conflict of interest in any terms or by any means during the study.
Research registration unique identifying number (UIN)
Research Registry UIN: 10951 (https://researchregistry.knack.com/researchregistry#home/registrationdetails/677663616d352302e949955e/).
Guarantor
Dr Fatemeh Janani.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Data availability statement
All relevant data and materials are provided with in manuscript.
References
- [1].Moni TA, Reshma IJ, Rumman R. Identify common risk factors associated with intrauterine fetal death (IUFD): a cross-sectional study. Sch Int J Obstet Gynec 2024;7:155–60. [Google Scholar]
- [2].İşcan RG, Malvasi A. Intrauterine fetal death: management and complications. In: In: Practical Guide to Simulation in Delivery Room Emergencies. 2023; Springer International Publishing: Cham. 219–43. [Google Scholar]
- [3].Pinar H, Koch MA, Hawkins H, et al. The stillbirth collaborative research network postmortem examination protocol. Am J Perinatol 2012;29:187–202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Panda PK, Panda P. Nelson Textbook of Pediatrics 22nd International Edition.
- [5].Burden C, Merriel A, Bakhbakhi D, et al. Royal college of obstetricians and gynaecologists. care of late intrauterine fetal death and stillbirth: green-top guideline no. 55. BJOG: Int J Obstet Gynec 2025;132:e1–41. [DOI] [PubMed] [Google Scholar]
- [6].Wilkins PA, Wong D. The high-risk pregnancy. Equine Neonatal Med 2024;26:1439–47. [Google Scholar]
- [7].Günkaya OS, Koyuncu S. Intrauterine fetal death and stillbirth: evaluations in a tertiary center. J Health Sci Med 2025;8:186–90. [Google Scholar]
- [8].Siva N, Nayak BS, Roy A, et al. Causes and risk factors for stillbirth in India: a systematic review protocol. Public Health 2025;239:32–36. [DOI] [PubMed] [Google Scholar]
- [9].Chauvin JP, Rubião R, Má M. The undercounting of child-mother births.
- [10].Riches NO, Workalemahu T, Johnson EP, et al. Factors contributing to uptake of stillbirth evaluations: a qualitative analysis. BJOG: Int J Obstet Gynec 2025;132:606–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Goldenberg RL, Saleem S, Aziz A, et al. International progress on stillbirth reduction: changes in stillbirth rates in selected low and middle-income Countries from 2000 to 2021. In: Seminars in Perinatology. WB Saunders; 2024:151868. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Caillault L, Béranger R, Loget P, et al. Ille et Vilaine Stillbirth Study Group, cauchois a. an in-depth analysis and classification of placental causes of stillbirth: a 10-year retrospective study of a regional stillbirth registry. BJOG: Int J Obstet Gynec 2025;132:1166–77. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [13].Takeshita S, Kakita H, Nakamura N, et al. Thrombopoietin exerts a neuroprotective effect by inhibiting the suppression of neuronal proliferation and axonal outgrowth in intrauterine growth restriction rats. Exp Neurol 2024;377:114781. [DOI] [PubMed] [Google Scholar]
- [14].Soundararajan SS. Addressing stillbirth: exploring economic status, government strategies, and gaps. Cureus 2025;17:e76923.. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Gregory EC, Valenzuela CP, Hoyert DL. Fetal Mortality. United States; 2022:1–20. [PubMed] [Google Scholar]
- [16].Fatah H, Vakilian K, Moslemi A, et al. The effect of EX-PLISST and GATHER models on sexual function with gestational diabetes. Sexologies 2022;31:327–35. [Google Scholar]
- [17].Hoseinalipour Z, Javadian M, Nasiri-Amiri F, et al. Adverse pregnancy outcomes and the abnormal umbilical cord coiling index. J Neonatal Perinatal Med 2024;17:681–88. [DOI] [PubMed] [Google Scholar]
- [18].Agha R, Abdall-Razak A, Crossley E, et al. STROCSS 2019 Guideline: strengthening the reporting of cohort studies in surgery. Int J Surg 2019;72:156–65. [DOI] [PubMed] [Google Scholar]
- [19].Meena L, Gupta R. Study of intrauterine fetal death cases in a tertiary care center. Int J Reprod Contracept Obstet Gynecol 2020;9:1255. [Google Scholar]
- [20].Mercier M, Lescoat A, Pierre-Jean M, et al. Prevalence of antiphospholipid antibody syndrome among patients with recurrent pregnancy loss: impact of the revised 2023 ACR/EULAR antiphospholipid syndrome criteria. J Clin Med 2024;13:7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [21].Ghasemi SF, Jadidi A, Valizadeh F, et al. Comparative evaluation of pressure massage at Hegu point versus Kunlun–Taixi pressure points on physiological parameters and crying duration induced by intramuscular vitamin K injection in premature infants: a clinical trial study. Hayat 2024;30:125–39. [Google Scholar]
- [22].Safarzadeh A, Ghaedniajahromi M, Ghaedniajahromi M, et al. Intra uterine fetal death and some related factors: a silent tragedy in Southeastern Iran. J Pain Relief 2014;3:129. [Google Scholar]
- [23].Gardosi J, Madurasinghe V, Williams M, et al. Maternal and fetal risk factors for stillbirth: population based study. BMJ (Online) 2013;346:f108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Agarwal A, Jeyaseelan S. Maternal floor infarction: a rare cause of sudden intrauterine fetal demise. Apollo Med 2013;10:297–98. [Google Scholar]
- [25].Barat S, Javadian M, Sekhavati E, et al. The frequency of causes and risk factors for intrauterine fetal death in Shahid Yahyanezhad Hospital of Babol, Northern Iran. Curr Res Med Sci 2017;1:41–45. [Google Scholar]
- [26].Vakilian K, Mobaseri S. The prevalence of stillbirth and infant mortality: maternal and neonatal factors. Prev Care Nurse Midwife J 2016;6:82–89. [Google Scholar]
- [27].Boskabadi H, Maamouri GA, Tabatabaie A, et al. Study of the incidence, and maternal and fetal risk factors for intra uterine fetal death. J Mazandaran Univ Med Sci 2015;24:332–56. [Google Scholar]
- [28].Nan Bakhsh F, Boroumand Sorkhabi F, Ahmadi Afshar G. Frequency of intrauterine fetal death and effective factors in Kowsar University Hospital. J Med Sci Stud 2007;18:498–512. [Google Scholar]
- [29].Hemmatyar M, Fazel Sarjoui J, Alizadeh N. Investigation of causes of intrauterine fetal death. J Inflamm Dis 2006;10:69–75. [Google Scholar]
- [30].Nan Bakhsh F, Boroumand SF, Ahmadi Afshar G. Survey on intra uterine fetal death frequency and its factors in Kosar hospital Urmia. The J Urmia Univ of Med Sci 2007;18:498–503. [Google Scholar]
- [31].Ceylaner G, Ceylaner S, Günyeli I, et al. Evaluation of 2407 fetuses in a Turkish population. Prenat Diagn 2007;27:800–07. [DOI] [PubMed] [Google Scholar]
- [32].Fretts RC, Schmittdiel J, McLean FH, et al. Increased maternal age and the risk of fetal death. N Engl J Med 1995;333:953–57. [DOI] [PubMed] [Google Scholar]
- [33].Pilliod RA, Page JM, Burwick RM, et al. The risk of fetal death in nonanomalous pregnancies affected by polyhydramnios. Am J Obstet Gynecol 2015;212:410–e1. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All relevant data and materials are provided with in manuscript.