Prenatal MRI in Growth-Restricted Fetuses: Early Brain Changes Beyond Doppler Findings: A Retrospective Cohort Study

Prenatal MRI in Growth-Restricted Fetuses: Early Brain Changes Beyond Doppler Findings: A Retrospective Cohort Study | 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 Prenatal MRI in Growth-Restricted Fetuses: Early Brain Changes Beyond Doppler Findings: A Retrospective Cohort Study Bircan Yildirim Baydemir, Sahin Kaan Baydemir, Suat Fitoz, Acar Koc This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8462652/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Apr, 2026 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted 12 You are reading this latest preprint version Abstract Background To evaluate fetal brain changes in growth-restricted (FGR) and small-for-gestational-age (SGA) fetuses using diffusion-weighted magnetic resonance imaging (DW-MRI), and to correlate findings with Doppler ultrasound parameters. Methods In this retrospective study, we included singleton pregnancies diagnosed with FGR or SGA who underwent fetal brain MRI after 30 weeks of gestation. FGR was defined based on estimated fetal weight or abdominal circumference < 10th percentile with abnormal Doppler indices, while SGA fetuses had similar biometric criteria but normal Dopplers. Apparent diffusion coefficient (ADC) values were measured in multiple brain regions and compared between groups. Doppler indices and perinatal outcomes were also analyzed. Results A total of 44 patients (30 FGR, 14 SGA) were included. FGR fetuses had significantly higher umbilical artery pulsatility index, smaller biparietal and transverse cerebellar diameters, and lower ADC values in frontal white matter compared to SGA fetuses. ADC values in other brain regions were not significantly different. Lower frontal ADC values (< 1.7 × 10⁻³ mm²/s) were associated with lower 1-minute Apgar scores, lower cord pH, and higher NICU admissions. Conclusion DW-MRI may identify early brain alterations in FGR fetuses before overt clinical signs. Combined with Doppler findings, MRI can enhance risk stratification and guide timing of delivery. Fetal growth restriction Small for gestational age Diffusion-weighted MRI a-Apparent diffusion coefficient Fetal brain imaging Cerebroplacental ratio Background Fetal growth restriction (FGR) and small for gestational age (SGA) are both defined as an estimated fetal weight (EFW) below the 10th percentile for gestational age ( 1 , 2 ). While SGA fetuses typically carry a lower risk of complications, FGR represents a more severe condition and is a leading cause of perinatal morbidity and mortality ( 3 ). Newborns with FGR are more likely to experience birth acidosis, low Apgar scores, and require neonatal intensive care unit (NICU) ( 4 ). FGR is classified as early-onset (before 32 weeks) or late-onset (≥ 32 weeks) based on gestational age at diagnosis ( 5 ). An EFW below the 3rd percentile combined with abnormal umbilical artery (UA) Doppler findings indicates a more severe form, associated with increased neonatal morbidity and mortality ( 6 , 7 ). Intrauterine hypoxia in FGR can lead to fetal brain injury due to limited compensatory capacity. Brain-sparing responses, including peripheral vasoconstriction and cerebral vasodilation mediated by adenosine and nitric oxide, aim to improve cerebral oxygenation. With ongoing hypoxia, perfusion is redirected to vital areas such as the basal ganglia and pons ( 8 , 9 ). Absent or reversed UA end-diastolic flow indicates high placental resistance, while increased cerebral diastolic flow suggests compensatory vasodilation ( 8 , 10 ). This redistribution is assessed via middle cerebral artery ( 11 ) Doppler and the cerebroplacental ratio (CPR) ( 12 ) a key delivery timing criterion per ISUOG. CPR is calculated as MCA PI divided by UA PI and predicts adverse outcomes with 66% sensitivity and 85% specificity ( 9 , 13 , 14 ). However, the threshold for irreversible brain injury remains uncertain. Diffusion-weighted MRI (DW-MRI), increasingly applied in obstetric imaging, enables assessment of microstructural brain changes by measuring water diffusion, quantified as the apparent diffusion coefficient (ADC). Hypoxia-related extracellular edema alters ADC values, particularly in susceptible brain regions. Previous studies, though limited, have reported lower ADC values in FGR fetuses compared to normally grown fetuses, indicating early hypoxic injury ( 8 , 15 ). In this study, we compared FGR fetuses with abnormal UA Doppler findings to SGA fetuses with normal Doppler results. Our aim was to evaluate the utility of fetal brain MRI in detecting early hypoxic brain changes and to explore its potential role in guiding delivery timing. Methods This retrospective study included patients who were referred to the perinatology clinic of a university hospital between June 2017 and June 2018.cEthical approval was obtained from the University Ethics Committee's Institutional Review Board (approval no: 11-743-18). Singleton pregnancies diagnosed with either FGR or SGA and evaluated by fetal MRI were eligible for inclusion. Additional inclusion criteria were gestational age beyond 30 weeks and delivery at our institution. Exclusion criteria were: multiple pregnancies, known chromosomal abnormalities, congenital anomalies, confirmed or suspected intrauterine infection, and refusal to undergo MRI. Gestational age was determined by first-trimester crown–rump length measurement.. Patients were divided into two groups based on ISUOG criteria ( 16 ): the FGR group included fetuses with an abdominal circumference (AC) or estimated fetal weight (EFW) below the 3rd percentile, or absent end-diastolic flow in the UA, or AC/EFW below the 10th percentile combined with uterine artery pulsatility index (PI) > 95th percentile and/or UA-PI > 95th percentile. The SGA group included fetuses with AC/EFW < 10th percentile but with normal Doppler findings. MRI was performed following diagnosis. All conventional MRI sequences showed normal fetal brain morphology without structural anomalies. Patients in both groups were followed until delivery in accordance with current clinical guidelines ( 17 , 18 ). Antenatal and perinatal data were collected for all cases, except for two patients who delivered at another facility. MRI Protocol All fetal brain MRIs were performed using a standardized protocol on a 1.5 Tesla MR scanner (Philips, Insignia) with a conventional phased-array body coil. The following conventional sequences were used: a T2-weighted single-shot turbo spin-echo (T2-TSE) sequence and a steady state acquisition sequence (B-FFE) with a 4 mm slice thickness without gap, which were obtained in three orthogonal planes. T1-weighted spin-echo (T1-SE) with a 4 mm slice thickness was also obtained in the axial plane. DWI was performed using single-shot spin-echo-planar imaging ( 19 ) in the axial plane with the following parameters: 24 images in six non-collinear axis directions; EPI factor, 109; FOV, 240 mm; matrix, 240 × 165; slice thickness, 4 mm with a 1-mm gap. Diffusion-gradient values were b = 0 and b = 1000 s/mm 2 . ADC maps were generated automatically on the main MRI console. The ADC value of each area was measured by placing an ROI on eleven different regions. Neuroanatomical landmarks were used to standardize measurements. ADC measurements were obtained from regions, including the frontal and occipital white matter, thalami, centrum semiovale, pons, and cerebellar hemispheres. ADC values of frontal and occipital white matter were measured at the level of the frontal horn and the atria on the same axial slice, with an average ROI surface of 30–60 mm2 for each hemisphere. On the first axial slice located above the ventricles, ROI with an average surface of 30–60 mm2 was placed in the center of the white matter of the centrum semiovale for each hemisphere, and at the level of the basal ganglia, ADC values of the bilateral thalamus with an average ROI surface of 30–60 mm2 were calculated. With an avarege ROI surface of 5–15 mm2, at the level of the middle cerebellar peduncles, ADC values of both cerebellar white matter and one measurement for the pons at the level of the central pons were made. For each ROI, a mean ± SD ADC value (×10 − 3 mm 2 /s) was obtained. Brain biometry measurements were also obtained. Supratentorial measurements, including biparietal diameter (BPD) and fronto–occipital diameter (FOD), and infratentorial measurements, including transverse cerebellar diameter (TCD), were calculated. Statistical Analysis Statistical analysis was performed using the software IBM SPSS 11.5 (SPSS Inc., Chicago, IL, USA). Kolmogorov-Smirnov/Shapiro-Wilk tests were used to determine distribution of variables. Descriptive analyses were presented as means and standard deviations for normally distributed variables or medians and range for non-normally distributed variables. Statistical analyses were performed using independent-samples Student’s t-test for normally distributed continuous data and Mann–Whitney U test for non-normally distributed continuous data. The Chi-square test or Fisher’s exact test, where appropriate, were used to compare the proportions in different groups. A p-value < 0.05 was considered statistically significant. Results A total of 70 patients diagnosed with FGR or SGA were followed at our perinatology clinic. Of these, 30 patients with FGR and 14 with SGA met the inclusion criteria and were enrolled in the study.Maternal demographic characteristics are presented in Table 1 . There were no statistically significant differences between the groups in terms of maternal age, gravida, parity, systemic diseases, adverse obstetric history, or gestational age at the time of MRI. The mean gestational age at the time of MRI was 33.3 ± 3.1 weeks in the FGR group and 34.0 ± 2.3 weeks in the SGA group. Table 1 Maternal Demographic and Clinical Characteristics of the Study Population FGR (n = 30) SGA (n = 14) p value Maternal Characteristics Age, years, mean ± SD 26.8 ± 5.1 24.2 ± 3.7 0.128 Gravida, mean ± SD 1.8 ± 1.5 1.5 ± 0.6 0.059 Parity, mean ± SD 0.5 ± 0.6 0.5 ± 0.7 0.064 Systemic diseases, n (%) 17 (56.7) 6 (42.9) 0.393 History of Adverse Perinatal Outcome n (%) 7 (23.3) 2 (14.3) 0.695 Gestational age at MRI, weeks, mean ± SD 33.3 ± 3.1 34.0 ± 2.3 0.062 *T test or Chi-square test SD: Standard deviation Doppler ultrasound and MRI findings are summarized in Table 2 . The FGR group had significantly higher UA pulsatility index (PI) compared to the SGA group (1.23 ± 0.47 vs. 0.98 ± 0.11; p = .002). No significant differences were observed between the groups in terms of MCA PI or CPR. Both biparietal and transcerebellar diameters were significantly smaller in the FGR group compared to the SGA group (80.3 ± 9.4 vs. 85.8 ± 2.9, p = .002; and 41.0 ± 7.2 vs. 44.7 ± 4.0, p = .002, respectively). Additionally, ADC values of the frontal white matter were significantly lower in the FGR group than in the SGA group (p = .003 for the right frontal lobe and p = .026 for the left frontal lobe). No significant differences were observed in the ADC values of other brain regions, including the occipital white matter, centrum semiovale, thalami, cerebellum, and pons. Table 2 Fetal Doppler and MRI Findings in FGR and SGA Groups FGR (n = 30) SGA (n = 14) p value Fetal Findings at Doppler Umblical Artery Doppler PI, mean ± SD 1.23 ± 0.47 0.98 ± 0.11 0.002 Middle Cerebral Artery Doppler PI, mean ± SD 1.51 ± 0.47 1.56 ± 0.34 0.531 Cerebro-Plasental Ratio (CPR), mean ± SD 1.37 ± 0.62 1.53 ± 0.32 0.054 Fetal Findings at MRI – Diameters Biparietal Diameter (BPD), mean ± SD 80.3 ± 9.4 85.8 ± 2.9 0.002 Fronto-Occipital Diameter (FOD), mean ± SD 97.6 ± 10.4 101.3 ± 5.5 0.298 Trans Cerebellar Diameter (TCD), mean ± SD 41.0 ± 7.2 44.7 ± 4.0 0.002 Fetal Findings at MRI – ADC measurements (10 -3 mm 2 /s ) Frontal WM – right, mean ± SD 1.63 ± 0.25 1.71 ± 0.19 0.003 Frontal WM – left, mean ± SD 1.66 ± 0.22 1.70 ± 0.20 0.026 Occipital WM – right, mean ± SD 1.54 ± 0.23 1.61 ± 0.14 0.292 Occipital WM – left, mean ± SD 1.60 ± 0.23 1.56 ± 0.16 0.641 Centrum Semiovale – right, mean ± SD 1.55 ± 0.17 1.57 ± 0.21 0.722 Centrum Semiovale – left, mean ± SD 1.51 ± 0.17 1.55 ± 0.17 0.585 Thalami – right, mean ± SD 0.88 ± 0.40 0.97 ± 0.29 0.460 Thalami – left, mean ± SD 1.05 ± 0.17 1.06 ± 0.10 0.566 Cerebellum – right, mean ± SD 1.30 ± 0.15 1.26 ± 0.10 0.373 Cerebellum – left, mean ± SD 1.27 ± 0.20 1.22 ± 0.10 0.256 Pons, mean ± SD 0.85 ± 0.34 0.84 ± 0.27 0.658 *T test or Chi-square test SD: Standard deviation WM: White Matter Perinatal outcomes are shown in Table 3 . The rate of cesarean delivery was 68.9% in the FGR group and 38.4% in the SGA group. The mean gestational age at birth was 36.14 ± 2.94 weeks in the FGR group and 37.85 ± 0.98 weeks in the SGA group. However, there were no statistically significant differences between the groups in terms of gestational age at delivery or mode of delivery. The time interval between MRI and birth was significantly shorter in the FGR group (p = .01). The 1-minute Apgar scores were lower in the FGR group (6.69 ± 1.60 vs. 7.23 ± 0.83; p = .004), while 5-minute Apgar scores were comparable between the groups (8.59 ± 1.78 vs. 9.08 ± 0.49; p = .069). UA pH levels were significantly lower in the FGR group than in the SGA group (7.09 ± 0.01 vs. 7.29 ± 0.09; p = .001). Two neonates born at external centers were lost to follow-up. Among the remaining newborns, 16 (38%) required admission to the NICU. NICU admission was significantly more common in the FGR group than in the SGA group (48.2% vs. 15.3%; p = .042). Table 3 Perinatal Outcomes of the Study Groups FGR (n = 29) SGA (n = 13) P value Caesarean Section, n (%) 20 (68.9) 5 (38.4) 0.063 Gestational age at birth, weeks, mean ± SD 36.14 ± 2.94 37.85 ± 0.98 0.067 Birth weight, grams, mean ± SD 2003.5 ± 508.2 2566.4 ± 316.9 0.066 1-minute APGAR scores, mean ± SD 6.69 ± 1.60 7.23 ± 0.83 0.004 5-minute APGAR scores, mean ± SD 8.59 ± 1.78 9.08 ± 0.49 0.069 Cord blood arterial pH, mean ± SD 7.09 ± 0.01 7.29 ± 0.09 0.001 Hospitalization at NICU, n (%) 14 (48.2) 2 (15.3) 0.042 *T test or Chi-square test SD: Standard deviation NICU: Neonatal Intensive Care Unit Discussion This study evaluated MRI and Doppler findings in fetuses with FGR and SGA. FGR fetuses had smaller biparietal and transverse cerebellar diameters and lower ADC values in the frontal white matter. UA Doppler PI was significantly higher in the FGR group, while MCA PI and CPR were comparable between groups, suggesting that hypoxic brain injury may precede the compensatory brain-sparing effect. Since brain sparing initially preserves frontal regions before redirecting flow to deeper structures like the basal ganglia and pons, early changes in frontal ADC values may indicate evolving hypoxic injury ( 8 , 20 ). These results support the potential of MRI for earlier detection of brain damage and more informed delivery planning. Previous studies have shown reduced brain volumes and dimensions in FGR fetuses. Peretz et al. and Polat et al. reported that overall brain structures were significantly smaller in FGR cases, likely due to brain sparing mechanisms ( 21 , 22 ). Similarly, a prospective cohort study using MRI found that FGR fetuses had reduced occipitofrontal and biparietal diameters compared to normally grown fetuses ( 23 ). Our findings are consistent, showing significantly smaller biparietal and transverse cerebellar diameters in FGR compared to SGA fetuses. Diffusion-weighted MRI studies have shown reduced ADC values in FGR fetuses, indicating early ischemic injury. Abdel Razek et al. found globally decreased ADC values in FGR brains ( 15 ). while Arthurs et al. demonstrated significantly lower ADC values in specific regions such as the frontal white matter, thalami, centrum semiovale, and pons in severe FGR( 8 ). Although our study observed similar ADC values in these regions, no significant differences were found between FGR and SGA groups, possibly due to the inclusion of SGA fetuses—who may also experience mild hypoxia—as controls. Kutuk et al. showed significantly reduced ADC values in periatrial and frontal white matter, thalami, and basal ganglia in FGR fetuses, particularly in those with reversed umbilical artery flow ( 24 ). Similarly, in our cohort, lower frontal white matter ADC values were associated with elevated UA PI, supporting a link between Doppler abnormalities and microstructural brain changes. A multicenter study reported that SGA fetuses with adverse outcomes had lower frontal white matter ADC values, and proposed a threshold of 1.7 × 10⁻³ mm²/s for risk prediction, though without statistical significance ( 25 ). In line with these findings, our study showed that ADC values below this threshold were linked to lower 1-minute Apgar scores, lower UA pH, and higher NICU admission rates. A previous study showed significantly lower ADC values in the cerebellar hemispheres, thalami, and caudate nucleus of FGR fetuses ( 26 ). Although severity-based subgroups were defined, no significant differences in ADC values were found between them. Head circumference was also lower in more severe cases. In our study, UA Doppler PI was significantly higher in FGR compared to SGA fetuses, whereas MCA PI remained similar. Moradi et al. reported no significant UA Doppler PI differences between FGR subgroups, possibly due to differences in study methodology or comparator groups. Our findings emphasize the potential of MRI, particularly ADC measurements, in distinguishing FGR from SGA and detecting early brain injury. FGR fetuses had higher UA Doppler PI, smaller brain diameters, and lower frontal white matter ADC values. When combined with Doppler studies, MRI may help determine optimal delivery timing and improve outcomes. Although promising, these results need to be validated in larger prospective studies, and standardized protocols are required to support wider clinical application in high-risk pregnancies. MRI, especially ADC measurement, shows promise in detecting early brain injury in FGR before brain-sparing occurs. Reduced frontal white matter ADC values may indicate early hypoxic effects. Future research should refine MRI protocols, assess long-term neurodevelopmental outcomes, and compare MRI with Doppler to define its added value. Development of standardized guidelines and protocols is essential to support its clinical use, particularly in resource-limited settings. MRI-guided intervention trials may further establish its role in managing high-risk pregnancies. Our study has some limitations. First, its retrospective design inherently limits causal inferences; a prospective approach would provide more robust evidence. Second, the sample size was relatively small, which may reduce the generalizability of the findings. Additionally, the absence of a control group consisting of normally growing fetuses limits the ability to compare findings across the full growth spectrum. Nevertheless, a notable strength of this study is the inclusion of SGA fetuses as a comparison group, enabling a focused assessment of MRI-detected brain alterations specifically attributable to FGR. Conclusions This study demonstrated that fetuses with FGR exhibit smaller biparietal and transverse cerebellar diameters and significantly lower ADC values in the frontal white matter compared to SGA fetuses. These findings suggest that MRI, particularly diffusion-weighted imaging, may play an important role in identifying early brain alterations associated with FGR before the onset of overt clinical signs or Doppler abnormalities. Incorporating MRI into the prenatal assessment of growth-restricted fetuses may aid in optimizing the timing of delivery and improving neonatal outcomes. Further prospective studies are warranted to validate these findings and to explore the long-term neurodevelopmental implications of early MRI-detected brain changes in FGR. Declarations Ethics approval and consent to participate Ethical approval was obtained from the University Ethics Committee's Institutional Review Board (approval no: 11-743-18). Written informed consent was obtained from all participants prior to inclusion in the study. Consent for publication Not applicable. No individual-level identifiable data are included in the manuscript. Availability of data and materials The data supporting the findings of this study were derived from retrospective clinical records and contain potentially identifiable patient information. Due to ethical restrictions imposed by local institutional review boards, national data protection regulations, and the risk of patient re-identification, these data cannot be made publicly available. Access to anonymized data may be considered upon reasonable request to the corresponding author, subject to approval by the relevant ethics committees and, where applicable, the establishment of a data sharing agreement. Competing interests The authors declare that they have no competing interests. Funding This study received no external funding. Authors' contributions BYB conceived and designed the study, collected and processed the data, and drafted the manuscript. SKB contributed to data collection and processing and performed the statistical analysis. SF was responsible for magnetic resonance imaging evaluation and data analysis. AK author contributed to the study design, performed critical revision of the manuscript for important intellectual content, and contributed to data analysis. All authors read and approved the final manuscript. Acknowledgements The authors have no acknowledgements to declare. References Lees CC, Stampalija T, Baschat A, da Silva Costa F, Ferrazzi E, Figueras F, et al. ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet Gynecol. 2020;56(2):298–312. Society for Maternal-Fetal Medicine. 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Cite Share Download PDF Status: Published Journal Publication published 25 Apr, 2026 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Revision requested 27 Jan, 2026 Reviews received at journal 23 Jan, 2026 Reviews received at journal 22 Jan, 2026 Reviewers agreed at journal 17 Jan, 2026 Reviews received at journal 14 Jan, 2026 Reviewers agreed at journal 11 Jan, 2026 Reviewers agreed at journal 08 Jan, 2026 Reviewers invited by journal 08 Jan, 2026 Editor invited by journal 30 Dec, 2025 Editor assigned by journal 29 Dec, 2025 Submission checks completed at journal 29 Dec, 2025 First submitted to journal 27 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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Baydemir","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYBACA2YILcNwgIHh8J+KA2DegQdEaOEBamF8wHPmAJAF1JKATwsDQguzAW8bRAsDPi3m7LwPP/zccZiH7/bpNAnJeXfk7MUOPwTaYien24Bdi2Uzu7Fk75nDPJLncrdJGG57ZswjnWYA1JJsbHYAh8MOs7Ex8LYd5jE4w7tNInHb4cQe6QSQlgOJ2/BoYfwL03JwDkhL+geCWpihtmw2bGwAacnBb4tlMxuztGxbOo/kGd6NjxmOHTbmuZ1TcCDBALdfzPmPMX5822Ytx3eGd8NhhprDcuyz0zd/+FBhJ4dLCxQ0YzgYr3IQqCOoYhSMglEwCkYwAAC6P2G7NT9LzgAAAABJRU5ErkJggg==","orcid":"","institution":"Ankara University","correspondingAuthor":true,"prefix":"","firstName":"Bircan","middleName":"Yildirim","lastName":"Baydemir","suffix":""},{"id":571601137,"identity":"95b20e1a-5138-492d-81a2-6dad08490f76","order_by":1,"name":"Sahin Kaan Baydemir","email":"","orcid":"","institution":"Ankara 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18:23:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8462652/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8462652/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12884-026-09164-4","type":"published","date":"2026-04-25T15:58:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":100034761,"identity":"80219899-454f-40ad-9a53-2ef6aef81fef","added_by":"auto","created_at":"2026-01-12 10:11:19","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":97342,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8462652/v1/520de5c4d31778776b10bafd.docx"},{"id":100034760,"identity":"a1c3dc79-1b67-4d15-9f39-eca4c82ced9b","added_by":"auto","created_at":"2026-01-12 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16:19:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":262755,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8462652/v1/d4ca5a47-82cd-4eea-bb20-b6fb9691ded0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePrenatal MRI in Growth-Restricted Fetuses: Early Brain Changes Beyond Doppler Findings: A Retrospective Cohort Study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eFetal growth restriction (FGR) and small for gestational age (SGA) are both defined as an estimated fetal weight (EFW) below the 10th percentile for gestational age (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). While SGA fetuses typically carry a lower risk of complications, FGR represents a more severe condition and is a leading cause of perinatal morbidity and mortality (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Newborns with FGR are more likely to experience birth acidosis, low Apgar scores, and require neonatal intensive care unit (NICU) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFGR is classified as early-onset (before 32 weeks) or late-onset (\u0026ge;\u0026thinsp;32 weeks) based on gestational age at diagnosis (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). An EFW below the 3rd percentile combined with abnormal umbilical artery (UA) Doppler findings indicates a more severe form, associated with increased neonatal morbidity and mortality (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIntrauterine hypoxia in FGR can lead to fetal brain injury due to limited compensatory capacity. Brain-sparing responses, including peripheral vasoconstriction and cerebral vasodilation mediated by adenosine and nitric oxide, aim to improve cerebral oxygenation. With ongoing hypoxia, perfusion is redirected to vital areas such as the basal ganglia and pons (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Absent or reversed UA end-diastolic flow indicates high placental resistance, while increased cerebral diastolic flow suggests compensatory vasodilation (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This redistribution is assessed via middle cerebral artery (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Doppler and the cerebroplacental ratio (CPR) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) a key delivery timing criterion per ISUOG. CPR is calculated as MCA PI divided by UA PI and predicts adverse outcomes with 66% sensitivity and 85% specificity (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). However, the threshold for irreversible brain injury remains uncertain.\u003c/p\u003e \u003cp\u003eDiffusion-weighted MRI (DW-MRI), increasingly applied in obstetric imaging, enables assessment of microstructural brain changes by measuring water diffusion, quantified as the apparent diffusion coefficient (ADC). Hypoxia-related extracellular edema alters ADC values, particularly in susceptible brain regions. Previous studies, though limited, have reported lower ADC values in FGR fetuses compared to normally grown fetuses, indicating early hypoxic injury (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, we compared FGR fetuses with abnormal UA Doppler findings to SGA fetuses with normal Doppler results. Our aim was to evaluate the utility of fetal brain MRI in detecting early hypoxic brain changes and to explore its potential role in guiding delivery timing.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This retrospective study included patients who were referred to the perinatology clinic of a university hospital between June 2017 and June 2018.cEthical approval was obtained from the University Ethics Committee's Institutional Review Board (approval no: 11-743-18). Singleton pregnancies diagnosed with either FGR or SGA and evaluated by fetal MRI were eligible for inclusion. Additional inclusion criteria were gestational age beyond 30 weeks and delivery at our institution. Exclusion criteria were: multiple pregnancies, known chromosomal abnormalities, congenital anomalies, confirmed or suspected intrauterine infection, and refusal to undergo MRI. Gestational age was determined by first-trimester crown\u0026ndash;rump length measurement..\u003c/p\u003e \u003cp\u003ePatients were divided into two groups based on ISUOG criteria (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e): the FGR group included fetuses with an abdominal circumference (AC) or estimated fetal weight (EFW) below the 3rd percentile, or absent end-diastolic flow in the UA, or AC/EFW below the 10th percentile combined with uterine artery pulsatility index (PI)\u0026thinsp;\u0026gt;\u0026thinsp;95th percentile and/or UA-PI\u0026thinsp;\u0026gt;\u0026thinsp;95th percentile. The SGA group included fetuses with AC/EFW\u0026thinsp;\u0026lt;\u0026thinsp;10th percentile but with normal Doppler findings. MRI was performed following diagnosis. All conventional MRI sequences showed normal fetal brain morphology without structural anomalies. Patients in both groups were followed until delivery in accordance with current clinical guidelines (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Antenatal and perinatal data were collected for all cases, except for two patients who delivered at another facility.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMRI Protocol\u003c/h2\u003e \u003cp\u003eAll fetal brain MRIs were performed using a standardized protocol on a 1.5 Tesla MR scanner (Philips, Insignia) with a conventional phased-array body coil. The following conventional sequences were used: a T2-weighted single-shot turbo spin-echo (T2-TSE) sequence and a steady state acquisition sequence (B-FFE) with a 4 mm slice thickness without gap, which were obtained in three orthogonal planes. T1-weighted spin-echo (T1-SE) with a 4 mm slice thickness was also obtained in the axial plane.\u003c/p\u003e \u003cp\u003eDWI was performed using single-shot spin-echo-planar imaging (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) in the axial plane with the following parameters: 24 images in six non-collinear axis directions; EPI factor, 109; FOV, 240 mm; matrix, 240 \u0026times; 165; slice thickness, 4 mm with a 1-mm gap. Diffusion-gradient values were b\u0026thinsp;=\u0026thinsp;0 and b\u0026thinsp;=\u0026thinsp;1000 s/mm\u003csup\u003e2\u003c/sup\u003e. ADC maps were generated automatically on the main MRI console. The ADC value of each area was measured by placing an ROI on eleven different regions. Neuroanatomical landmarks were used to standardize measurements. ADC measurements were obtained from regions, including the frontal and occipital white matter, thalami, centrum semiovale, pons, and cerebellar hemispheres.\u003c/p\u003e \u003cp\u003eADC values of frontal and occipital white matter were measured at the level of the frontal horn and the atria on the same axial slice, with an average ROI surface of 30\u0026ndash;60 mm2 for each hemisphere. On the first axial slice located above the ventricles, ROI with an average surface of 30\u0026ndash;60 mm2 was placed in the center of the white matter of the centrum semiovale for each hemisphere, and at the level of the basal ganglia, ADC values of the bilateral thalamus with an average ROI surface of 30\u0026ndash;60 mm2 were calculated. With an avarege ROI surface of 5\u0026ndash;15 mm2, at the level of the middle cerebellar peduncles, ADC values of both cerebellar white matter and one measurement for the pons at the level of the central pons were made. For each ROI, a mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD ADC value (\u0026times;10\u0026thinsp;\u0026minus;\u0026thinsp;3 mm\u003csup\u003e2\u003c/sup\u003e/s) was obtained. Brain biometry measurements were also obtained. Supratentorial measurements, including biparietal diameter (BPD) and fronto\u0026ndash;occipital diameter (FOD), and infratentorial measurements, including transverse cerebellar diameter (TCD), were calculated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using the software IBM SPSS 11.5 (SPSS Inc., Chicago, IL, USA). Kolmogorov-Smirnov/Shapiro-Wilk tests were used to determine distribution of variables. Descriptive analyses were presented as means and standard deviations for normally distributed variables or medians and range for non-normally distributed variables. Statistical analyses were performed using independent-samples Student\u0026rsquo;s t-test for normally distributed continuous data and Mann\u0026ndash;Whitney U test for non-normally distributed continuous data. The Chi-square test or Fisher\u0026rsquo;s exact test, where appropriate, were used to compare the proportions in different groups. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 70 patients diagnosed with FGR or SGA were followed at our perinatology clinic. Of these, 30 patients with FGR and 14 with SGA met the inclusion criteria and were enrolled in the study.Maternal demographic characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were no statistically significant differences between the groups in terms of maternal age, gravida, parity, systemic diseases, adverse obstetric history, or gestational age at the time of MRI. The mean gestational age at the time of MRI was 33.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 weeks in the FGR group and 34.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 weeks in the SGA group.\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\u003eMaternal Demographic and Clinical Characteristics of the Study Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFGR (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSGA (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMaternal Characteristics\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, mean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravida, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic diseases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (56.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of Adverse Perinatal Outcome n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.695\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at MRI, weeks, mean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.3 \u0026plusmn; 3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.0 \u0026plusmn; 2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*T test or Chi-square test SD: Standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDoppler ultrasound and MRI findings are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The FGR group had significantly higher UA pulsatility index (PI) compared to the SGA group (1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47 vs. 0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11; p\u0026thinsp;=\u0026thinsp;.002). No significant differences were observed between the groups in terms of MCA PI or CPR. Both biparietal and transcerebellar diameters were significantly smaller in the FGR group compared to the SGA group (80.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4 vs. 85.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9, p\u0026thinsp;=\u0026thinsp;.002; and 41.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2 vs. 44.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0, p\u0026thinsp;=\u0026thinsp;.002, respectively). Additionally, ADC values of the frontal white matter were significantly lower in the FGR group than in the SGA group (p\u0026thinsp;=\u0026thinsp;.003 for the right frontal lobe and p\u0026thinsp;=\u0026thinsp;.026 for the left frontal lobe). No significant differences were observed in the ADC values of other brain regions, including the occipital white matter, centrum semiovale, thalami, cerebellum, and pons.\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\u003eFetal Doppler and MRI Findings in FGR and SGA Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFGR (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSGA (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFetal Findings at Doppler\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUmblical Artery Doppler PI, mean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle Cerebral Artery Doppler PI, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.531\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebro-Plasental Ratio (CPR), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFetal Findings at MRI \u0026ndash; Diameters\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiparietal Diameter (BPD), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFronto-Occipital Diameter (FOD), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.6 \u0026plusmn; 10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101.3 \u0026plusmn; 5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrans Cerebellar Diameter (TCD), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.0 \u0026plusmn; 7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.7 \u0026plusmn; 4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFetal Findings at MRI \u0026ndash; ADC measurements (10\u003c/b\u003e\u003csup\u003e\u003cb\u003e-3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003emm\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/s\u003c/b\u003e \u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrontal WM \u0026ndash; right, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.63 \u0026plusmn; 0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.71 \u0026plusmn; 0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrontal WM \u0026ndash; left, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.66 \u0026plusmn; 0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.70 \u0026plusmn; 0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.026\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOccipital WM \u0026ndash; right, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.54 \u0026plusmn; 0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.61 \u0026plusmn; 0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOccipital WM \u0026ndash; left, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.60 \u0026plusmn; 0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.56 \u0026plusmn; 0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.641\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentrum Semiovale \u0026ndash; right, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.55 \u0026plusmn; 0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.57 \u0026plusmn; 0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.722\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentrum Semiovale \u0026ndash; left, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.51 \u0026plusmn; 0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.55 \u0026plusmn; 0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.585\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThalami \u0026ndash; right, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.88 \u0026plusmn; 0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.97 \u0026plusmn; 0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.460\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThalami \u0026ndash; left, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.05 \u0026plusmn; 0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.06 \u0026plusmn; 0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellum \u0026ndash; right, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.30 \u0026plusmn; 0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26 \u0026plusmn; 0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.373\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellum \u0026ndash; left, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.27 \u0026plusmn; 0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.22 \u0026plusmn; 0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.256\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePons, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85 \u0026plusmn; 0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.84 \u0026plusmn; 0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*T test or Chi-square test SD: Standard deviation WM: White Matter\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePerinatal outcomes are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The rate of cesarean delivery was 68.9% in the FGR group and 38.4% in the SGA group. The mean gestational age at birth was 36.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.94 weeks in the FGR group and 37.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98 weeks in the SGA group. However, there were no statistically significant differences between the groups in terms of gestational age at delivery or mode of delivery. The time interval between MRI and birth was significantly shorter in the FGR group (p\u0026thinsp;=\u0026thinsp;.01). The 1-minute Apgar scores were lower in the FGR group (6.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.60 vs. 7.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83; p\u0026thinsp;=\u0026thinsp;.004), while 5-minute Apgar scores were comparable between the groups (8.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.78 vs. 9.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49; p\u0026thinsp;=\u0026thinsp;.069). UA pH levels were significantly lower in the FGR group than in the SGA group (7.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 vs. 7.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09; p\u0026thinsp;=\u0026thinsp;.001). Two neonates born at external centers were lost to follow-up. Among the remaining newborns, 16 (38%) required admission to the NICU. NICU admission was significantly more common in the FGR group than in the SGA group (48.2% vs. 15.3%; p\u0026thinsp;=\u0026thinsp;.042).\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\u003ePerinatal Outcomes of the Study Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFGR (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSGA (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean Section, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (68.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at birth, weeks, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight, grams, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2003.5\u0026thinsp;\u0026plusmn;\u0026thinsp;508.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2566.4\u0026thinsp;\u0026plusmn;\u0026thinsp;316.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-minute APGAR scores, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.69 \u0026plusmn; 1.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.23 \u0026plusmn; 0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5-minute APGAR scores, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.59 \u0026plusmn; 1.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.08 \u0026plusmn; 0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCord blood arterial pH, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.09 \u0026plusmn; 0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.29 \u0026plusmn; 0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization at NICU, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (48.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.042\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*T test or Chi-square test SD: Standard deviation NICU: Neonatal Intensive Care Unit\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated MRI and Doppler findings in fetuses with FGR and SGA. FGR fetuses had smaller biparietal and transverse cerebellar diameters and lower ADC values in the frontal white matter. UA Doppler PI was significantly higher in the FGR group, while MCA PI and CPR were comparable between groups, suggesting that hypoxic brain injury may precede the compensatory brain-sparing effect. Since brain sparing initially preserves frontal regions before redirecting flow to deeper structures like the basal ganglia and pons, early changes in frontal ADC values may indicate evolving hypoxic injury (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These results support the potential of MRI for earlier detection of brain damage and more informed delivery planning.\u003c/p\u003e \u003cp\u003ePrevious studies have shown reduced brain volumes and dimensions in FGR fetuses. Peretz et al. and Polat et al. reported that overall brain structures were significantly smaller in FGR cases, likely due to brain sparing mechanisms (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Similarly, a prospective cohort study using MRI found that FGR fetuses had reduced occipitofrontal and biparietal diameters compared to normally grown fetuses (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Our findings are consistent, showing significantly smaller biparietal and transverse cerebellar diameters in FGR compared to SGA fetuses. Diffusion-weighted MRI studies have shown reduced ADC values in FGR fetuses, indicating early ischemic injury. Abdel Razek et al. found globally decreased ADC values in FGR brains (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). while Arthurs et al. demonstrated significantly lower ADC values in specific regions such as the frontal white matter, thalami, centrum semiovale, and pons in severe FGR(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Although our study observed similar ADC values in these regions, no significant differences were found between FGR and SGA groups, possibly due to the inclusion of SGA fetuses\u0026mdash;who may also experience mild hypoxia\u0026mdash;as controls. Kutuk et al. showed significantly reduced ADC values in periatrial and frontal white matter, thalami, and basal ganglia in FGR fetuses, particularly in those with reversed umbilical artery flow (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Similarly, in our cohort, lower frontal white matter ADC values were associated with elevated UA PI, supporting a link between Doppler abnormalities and microstructural brain changes.\u003c/p\u003e \u003cp\u003eA multicenter study reported that SGA fetuses with adverse outcomes had lower frontal white matter ADC values, and proposed a threshold of 1.7 \u0026times; 10⁻\u0026sup3; mm\u0026sup2;/s for risk prediction, though without statistical significance (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In line with these findings, our study showed that ADC values below this threshold were linked to lower 1-minute Apgar scores, lower UA pH, and higher NICU admission rates. A previous study showed significantly lower ADC values in the cerebellar hemispheres, thalami, and caudate nucleus of FGR fetuses (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Although severity-based subgroups were defined, no significant differences in ADC values were found between them. Head circumference was also lower in more severe cases. In our study, UA Doppler PI was significantly higher in FGR compared to SGA fetuses, whereas MCA PI remained similar. Moradi et al. reported no significant UA Doppler PI differences between FGR subgroups, possibly due to differences in study methodology or comparator groups.\u003c/p\u003e \u003cp\u003eOur findings emphasize the potential of MRI, particularly ADC measurements, in distinguishing FGR from SGA and detecting early brain injury. FGR fetuses had higher UA Doppler PI, smaller brain diameters, and lower frontal white matter ADC values. When combined with Doppler studies, MRI may help determine optimal delivery timing and improve outcomes. Although promising, these results need to be validated in larger prospective studies, and standardized protocols are required to support wider clinical application in high-risk pregnancies.\u003c/p\u003e \u003cp\u003eMRI, especially ADC measurement, shows promise in detecting early brain injury in FGR before brain-sparing occurs. Reduced frontal white matter ADC values may indicate early hypoxic effects. Future research should refine MRI protocols, assess long-term neurodevelopmental outcomes, and compare MRI with Doppler to define its added value. Development of standardized guidelines and protocols is essential to support its clinical use, particularly in resource-limited settings. MRI-guided intervention trials may further establish its role in managing high-risk pregnancies.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, its retrospective design inherently limits causal inferences; a prospective approach would provide more robust evidence. Second, the sample size was relatively small, which may reduce the generalizability of the findings. Additionally, the absence of a control group consisting of normally growing fetuses limits the ability to compare findings across the full growth spectrum. Nevertheless, a notable strength of this study is the inclusion of SGA fetuses as a comparison group, enabling a focused assessment of MRI-detected brain alterations specifically attributable to FGR.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study demonstrated that fetuses with FGR exhibit smaller biparietal and transverse cerebellar diameters and significantly lower ADC values in the frontal white matter compared to SGA fetuses. These findings suggest that MRI, particularly diffusion-weighted imaging, may play an important role in identifying early brain alterations associated with FGR before the onset of overt clinical signs or Doppler abnormalities. Incorporating MRI into the prenatal assessment of growth-restricted fetuses may aid in optimizing the timing of delivery and improving neonatal outcomes. Further prospective studies are warranted to validate these findings and to explore the long-term neurodevelopmental implications of early MRI-detected brain changes in FGR.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the University Ethics Committee\u0026apos;s Institutional Review Board (approval no: 11-743-18).\u0026nbsp;Written informed consent was obtained from all participants prior to inclusion in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. No individual-level identifiable data are included in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study were derived from retrospective clinical records and contain potentially identifiable patient information. Due to ethical restrictions imposed by local institutional review boards, national data protection regulations, and the risk of patient re-identification, these data cannot be made publicly available.\u003c/p\u003e\n\u003cp\u003eAccess to anonymized data may be considered upon reasonable request to the corresponding author, subject to approval by the relevant ethics committees and, where applicable, the establishment of a data sharing agreement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBYB conceived and designed the study, collected and processed the data, and drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eSKB contributed to data collection and processing and performed the statistical analysis.\u003c/p\u003e\n\u003cp\u003eSF was responsible for magnetic resonance imaging evaluation and data analysis.\u003c/p\u003e\n\u003cp\u003eAK author contributed to the study design, performed critical revision of the manuscript for important intellectual content, and contributed to data analysis.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no acknowledgements to declare.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLees CC, Stampalija T, Baschat A, da Silva Costa F, Ferrazzi E, Figueras F, et al. ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet Gynecol. 2020;56(2):298\u0026ndash;312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSociety for Maternal-Fetal Medicine. Electronic address pso, Martins JG, Biggio JR, Abuhamad A. Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012). Am J Obstet Gynecol. 2020;223(4):B2-B17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSwanson AM, David AL. Animal models of fetal growth restriction: Considerations for translational medicine. Placenta. 2015;36(6):623\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadden JV, Flatley CJ, Kumar S. Term small-for-gestational-age infants from low-risk women are at significantly greater risk of adverse neonatal outcomes. 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The role of brain sparing in the prediction of adverse outcomes in intrauterine growth restriction: results of the multicenter PORTO Study. Am J Obstet Gynecol. 2014;211(3):e2881\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdel Razek AAK, Thabet M, Salam EA. Apparent Diffusion Coefficient of the Placenta and Fetal Organs in Intrauterine Growth Restriction. J Comput Assist Tomogr. 2019;43(3):507\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016;48(3):333\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e(RCOG) RCoOG. Small-for-Gestational-Age Fetus, Investigation and Management (Green-top Guideline No. 31). 2013.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma D, Shastri S, Farahbakhsh N, Sharma P. Intrauterine growth restriction - part 1. J Matern Fetal Neonatal Med. 2016;29(24):3977\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDominguez-Valentin M, Haupt S, Seppala TT, Sampson JR, Sunde L, Bernstein I, et al. Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database. EClinicalMedicine. 2023;58:101909.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu MY, Milligan N, Keating S, Windrim R, Keunen J, Thakur V, et al. The hemodynamics of late-onset intrauterine growth restriction by MRI. Am J Obstet Gynecol. 2016;214(3):367. e1- e17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeretz R, Halevy T, Gafner M, Fried S, Revesz Y, Mayer A, et al. Volumetric Brain MRI Study in Fetuses with Intrauterine Growth Restriction Using a Semiautomated Method. AJNR Am J Neuroradiol. 2022;43(11):1674\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePolat A, Barlow S, Ber R, Achiron R, Katorza E. Volumetric MRI study of the intrauterine growth restriction fetal brain. Eur Radiol. 2017;27(5):2110\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Oliveira Junior RE, Teixeira SR, Santana EFM, Elias Junior J, Costa FDS, Araujo Junior E, et al. Magnetic resonance imaging of skull and brain parameters in fetuses with intrauterine growth restriction. Radiol Bras. 2021;54(3):141\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKutuk MS, Sahin M, Gorkem SB, Doganay S, Ozturk A. Relationship between Doppler findings and fetal brain apparent diffusion coefficient in early-onset intra-uterine growth restriction(). J Matern Fetal Neonatal Med. 2018;31(23):3201\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJouannic JM, Blondiaux E, Senat MV, Friszer S, Adamsbaum C, Rousseau J, et al. Prognostic value of diffusion-weighted magnetic resonance imaging of brain in fetal growth restriction: results of prospective multicenter study. Ultrasound Obstet Gynecol. 2020;56(6):893\u0026ndash;900.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoradi B, Nezhad ZA, Saadat NS, Shirazi M, Borhani A, Kazemi MA. Apparent diffusion coefficient of different areas of brain in foetuses with intrauterine growth restriction. Pol J Radiol. 2020;85:e301\u0026ndash;8.\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":true,"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":"Fetal growth restriction, Small for gestational age, Diffusion-weighted MRI, a-Apparent diffusion coefficient, Fetal brain imaging, Cerebroplacental ratio","lastPublishedDoi":"10.21203/rs.3.rs-8462652/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8462652/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo evaluate fetal brain changes in growth-restricted (FGR) and small-for-gestational-age (SGA) fetuses using diffusion-weighted magnetic resonance imaging (DW-MRI), and to correlate findings with Doppler ultrasound parameters.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this retrospective study, we included singleton pregnancies diagnosed with FGR or SGA who underwent fetal brain MRI after 30 weeks of gestation. FGR was defined based on estimated fetal weight or abdominal circumference\u0026thinsp;\u0026lt;\u0026thinsp;10th percentile with abnormal Doppler indices, while SGA fetuses had similar biometric criteria but normal Dopplers. Apparent diffusion coefficient (ADC) values were measured in multiple brain regions and compared between groups. Doppler indices and perinatal outcomes were also analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 44 patients (30 FGR, 14 SGA) were included. FGR fetuses had significantly higher umbilical artery pulsatility index, smaller biparietal and transverse cerebellar diameters, and lower ADC values in frontal white matter compared to SGA fetuses. ADC values in other brain regions were not significantly different. Lower frontal ADC values (\u0026lt;\u0026thinsp;1.7 \u0026times; 10⁻\u0026sup3; mm\u0026sup2;/s) were associated with lower 1-minute Apgar scores, lower cord pH, and higher NICU admissions.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDW-MRI may identify early brain alterations in FGR fetuses before overt clinical signs. Combined with Doppler findings, MRI can enhance risk stratification and guide timing of delivery.\u003c/p\u003e","manuscriptTitle":"Prenatal MRI in Growth-Restricted Fetuses: Early Brain Changes Beyond Doppler Findings: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 10:11:14","doi":"10.21203/rs.3.rs-8462652/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-27T10:38:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-23T21:13:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-22T18:50:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"225107366229647500629253895140701406128","date":"2026-01-17T21:46:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-14T19:35:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"94239858164259238879048497659268572715","date":"2026-01-12T01:14:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"110685397434530982648843906096204241839","date":"2026-01-08T12:00:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-08T11:37:59+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-30T11:06:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-30T01:45:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-30T01:45:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-12-27T18:08:37+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":"721c4c2a-6246-45f4-85de-f50772dd2fb0","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T16:19:24+00:00","versionOfRecord":{"articleIdentity":"rs-8462652","link":"https://doi.org/10.1186/s12884-026-09164-4","journal":{"identity":"bmc-pregnancy-and-childbirth","isVorOnly":false,"title":"BMC Pregnancy and Childbirth"},"publishedOn":"2026-04-25 15:58:52","publishedOnDateReadable":"April 25th, 2026"},"versionCreatedAt":"2026-01-12 10:11:14","video":"","vorDoi":"10.1186/s12884-026-09164-4","vorDoiUrl":"https://doi.org/10.1186/s12884-026-09164-4","workflowStages":[]},"version":"v1","identity":"rs-8462652","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8462652","identity":"rs-8462652","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}