The placenta plays a central role in regulating the exchange of oxygen and nutrients between the maternal and fetal circulations and is therefore critical for fetal growth, development, and neonatal outcomes (Carbillon et al., 2022; Burton et al., 2016; Zur et al., 2024; Kulkarni et al., 2021). When placental function is impaired, the fetus may be exposed to chronic hypoxia, which contributes to stillbirth, fetal growth restriction (FGR), and adverse neonatal conditions (Silver, 2018). A key pathological mechanism underlying placental dysfunction is maternal vascular malperfusion (MVM), characterized by impaired maternal blood flow to the intervillous space. MVM reflects defective spiral artery remodeling and abnormal placental vascular development, and is a hallmark lesion in pregnancies complicated by hypertensive disorders, FGR, and placental insufficiency (Zur et al., 2020).

Chronic intrauterine hypoxia has profound consequences for fetal brain development. To preserve oxygen delivery to vital organs, the fetus initiates a compensatory “brain-sparing effect,” redistributing blood flow toward the cerebral circulation (Miller et al., 2016). Although initially protective, prolonged hypoxia may exceed compensatory capacity and lead to structural and functional alterations of the developing brain, including reduced brain volume and white matter injury (Su et al., 2015; Nijman et al., 2024; Alves de Alencar Rocha et al., 2017). These disturbances are closely associated with long-term neurodevelopmental disorders in offspring, such as cognitive deficits and motor dysfunction (Sadhwani et al., 2022; Spinillo et al., 2021; Ibrahim et al., 2025). Prior studies have demonstrated that the degree of placental pathology correlates with the risk of neonatal brain injury and later neurodevelopmental abnormalities, suggesting that placental lesions may serve as early markers of neurological vulnerability (Spinillo et al., 2023).

Notably, the severity of placental injury may exhibit a cumulative effect—specifically, a greater number of pathological subtypes of MVM correlates with a more pronounced impact on adverse neonatal outcomes.

Near-infrared spectroscopy (NIRS) permits continuous, non-invasive assessment of cerebral regional oxygen saturation (crSO₂) and cerebral fractional tissue oxygen extraction (cFTOE), thereby reflecting the balance between cerebral oxygen supply and consumption. These parameters have been associated with the prediction of neonatal brain injury and long-term outcomes (Chock et al., 2020; Ćaleta et al., 2024). However, few studies have examined how placental pathology influences postnatal cerebral oxygenation. Moreover, to our knowledge, no study has evaluated whether the cumulative burden of MVM lesions—reflected by the number of distinct pathological subtypes—affects cerebral oxygenation patterns in neonates.

Prior study indicates that multiple placental lesions can exert additive or synergistic effects on pregnancy outcomes, and evaluating the cumulative burden of MVM may provide a more accurate representation of placental dysfunction than assessing individual lesions alone (Arts et al., 2022). Whether such cumulative pathological load translates into measurable differences in early cerebral oxygen delivery and utilization in neonates remains unknown.

Therefore, the present study aimed to investigate the association between the cumulative burden of placental MVM and early cerebral oxygenation in neonates. By comparing longitudinal crSO₂ and cFTOE patterns across infants with varying degrees of MVM burden, we sought to determine whether increasing placental vascular pathology is associated with altered cerebral oxygen metabolism during the critical early postnatal period. Such findings may help clarify mechanisms linking placental dysfunction to neonatal brain vulnerability and support the use of placental pathology as an early indicator for targeted cerebral monitoring and neurodevelopmental risk stratification.

A total of 508 neonates were included in the final analysis. Based on the number of MVM lesion subtypes, 161 infants (31.7%) were classified into the no MVM group, 319 (62.8%) into the 1–2 MVM subtypes group, and 28 (5.5%) into the 3–5 MVM subtypes group.

MVM can disrupt fetal oxygen supply and contribute to severe neurological complications, such as reduced fetal brain volume (Oh et al., 2021). By monitoring cerebral tissue oxygenation status in neonates during the neonatal period, this study systematically investigated the dynamic association between the severity of maternal placental MVM pathology (quantified by the number of MVM lesion types) and neonatal cerebral oxygen metabolism. Key findings revealed that neonates with 3–5 types of MVM lesions in the maternal placenta exhibited significantly higher crSO₂ and lower cFTOE within the first postnatal week, compared to those with fewer or no MVM lesions. These results suggest that severe MVM exerts a distinct impact on cerebral oxygen saturation in early neonates.

In the present study, neonates with 3-5 types of MVM had a slightly lower median gestational age (33.36 weeks) compared to those in the no MVM group (34 weeks) and the 1-2 types of MVM group (34 weeks). Placental dysfunction is strongly associated with preterm birth (Brink et al., 2022; Visser et al., 2021), a finding consistent with a prior study of 728 patients with gestational hypertension that reported a decreasing MVM incidence with advancing gestational age (95.4% at <34 weeks, 69.8% at 34–36 weeks, and 50% at ≥37 weeks) (Freedman et al., 2023). Collectively, these observations support the conclusion that severe MVM constitutes a critical pathological substrate for preterm birth.

In addition, neonates in the 3-5 types of MVM group had a lower median birth weight (1,695 g) compared to those in the no MVM group (1840 g) and the 1-2 types of MVM group (1880 g), suggesting a strong association between MVM and fetal intrauterine growth restriction (Zur et al., 2024). Notably, while no statistically significant difference was observed in the incidence of small for gestational age across the three groups (P = 0.123)—a finding potentially attributed to limited sample size—the numerical trend in birth weight still supports the presence of an underlying association between MVM severity and fetal growth impairment.

With respect to maternal complications, the incidence of HDP in the 3-5 types of MVM subtypes group was 71.43%, which was significantly higher than that in the 1-2 types of MVM subtypes group (44.2%) and the no MVM group (40.37%). This finding aligns with current pathophysiological understanding: the pathological basis of HDP lies in insufficient spiral artery remodeling caused by impaired trophoblast invasion, whose placental manifestation is MVM, with the incidence of MVM positively correlated with the severity of HDP (Weiner et al., 2018). Notably, a study by Richter et al. reported an association between preeclampsia and lower cFTOE in early neonates, which is consistent with the results of the present study (Richter et al., 2020).

In the present study, neonates with 3-5 types of MVM exhibited a cerebral oxygenation profile characterized by elevated crSO₂ and reduced cFTOE during the early neonatal period. This seemingly paradoxical observation—chronic intrauterine hypoxia associated with postnatal increases in cerebral oxygen saturation—could potentially be interpreted as reflecting persistence of fetal cerebral blood flow compensatory mechanisms into the neonatal period. To counteract chronic intrauterine hypoxia, the fetus activates a “brain-sparing effect” that prioritizes cerebral perfusion over other organ systems. Such hemodynamic adaptations may persist postnatally for a transient period. For instance, prior research has demonstrated that preterm infants maintain higher cerebral blood flow even at corrected gestational age compared to term infants (Bouyssi-K et al., 2018). In the current study, the 3-5 types of MVM group had a slightly lower median gestational age than other groups, and their elevated cerebral oxygen saturation may reflect a more robust cerebral blood flow regulatory state linked to their younger gestational age. In essence, the presence of 3-5 types of MVM may induce a fetal cerebral adaptive pattern of “hyperperfusion with reduced oxygen extraction,” which persists transiently in the early postnatal period.

In the present study, crSO₂ levels in all neonates exhibited a downward trend with increasing postnatal age, while cFTOE levels gradually increased—consistent with findings reported by Mohamed et al. (2021). Notably, neonates with placental findings of MVM (particularly those with 3-5 types) had higher crSO₂ than those in the no MVM group during the first two postnatal weeks, but lower crSO₂ in later weeks; the magnitude of this crSO₂ shift was positively correlated with MVM severity. This observation suggests that the early cerebral hyperperfusion induced by MVM may resolve as vascular regulatory capacity normalizes, potentially unmasking latent effects on cerebral oxygen metabolism over time. Differences in cFTOE across the three groups reached statistical significance only during the first postnatal week. Longitudinal analyses of the data revealed that neither the between-group main effect nor the time × group interaction effect reached statistical significance. These findings collectively indicate that intergroup differences in cerebral oxygenation were primarily restricted to the early neonatal period, rather than persisting longitudinally.

The present study advances understanding by elucidating the cumulative effect of placental MVM lesions. Herein, we quantified the “cumulative burden of placental dysfunction” using the number of distinct MVM lesion subtypes present in the mother, and for the first time, correlated this metric with neonatal cerebral oxygenation parameters (crSO₂, cFTOE). Our findings indicate that when MVM lesions accumulate to three or more subtypes, they exert a significant impact on the cerebral tissue oxygenation status of offspring. This work suggests that a simplified quantitative assessment of placental pathology reports—specifically, enumerating the number of MVM lesion subtypes—may provide useful postnatal contextual information for interpreting early cerebral oxygenation patterns in neonates. Recognition of a higher cumulative MVM burden on placental examination may help identify neonates who could benefit from closer cerebral oxygenation monitoring during the first postnatal week, a critical period of physiological transition.

The present study, while offering valuable insights, is not without its limitations. One of the primary constraints lies in the relatively small size of the sample. When we take a closer look at the data, the issue becomes even more pronounced, particularly in the 3 - 5 types of MVM group. The number of cases is notably scarce. In statistical analysis, a small sample size may lead to a lack of statistical power. With a limited number of cases in the 3 - 5 types of MVM group, there is a heightened risk of type II errors. Although we observed statistically significant associations in the multiple regression model, we must state that this finding is mainly based on a small sample subgroup. Therefore, this association conclusion should be regarded as preliminary, highlighting the possible important link between the cumulative load of MVM and early cerebral oxygenation patterns, but the effect strength and generalizability still need to be confirmed through prospective studies with expanded samples, especially by increasing the number of severe MVM cases.

Another limitation of this study is that other placental pathological categories, including fetal vascular malperfusion (FVM) and maternal or fetal inflammatory responses (MIR/FIR), were not included in adjusted or sensitivity analyses. We explored the feasibility of incorporating FVM and inflammatory lesions into sensitivity analyses; however, due to very low event numbers and non-standardized reporting, such analyses were considered statistically unreliable and were therefore not presented. In addition, data on these lesions were derived from routine pathology reports, were not systematically graded or quantified, and showed low prevalence with no significant differences across MVM burden groups (Supplementary Table S1). Under these conditions, further adjustment was unlikely to meaningfully alter effect estimates and could have compromised model stability, particularly given the small sample size in the highest MVM burden group. Nevertheless, residual confounding by other placental pathologies cannot be completely excluded, underscoring the need for future prospective studies with standardized placental phenotyping.

It is important to note this is a retrospective observational study. A potential selection bias exists in this study. The neonates born to the included mothers who underwent placental pathological testing limit the generalizability of the results to the entire neonatal population—particularly to healthy full-term infants without overt clinical risk factors. This skews our study cohort toward mother-infant dyads with underlying risks or comorbidities. Retrospective observational studies rely on existing data. While they can provide a wealth of information based on real-world scenarios, they also come with inherent limitations. The current monitoring interval time for brain tissue oxygen saturation in this study may not be optimal. By having a relatively long monitoring interval, we might be missing out on more subtle changes in brain tissue oxygen saturation during the neonatal period.

Furthermore, preterm birth is widely recognized as one of the primary clinical outcomes of severe MVM, with a well-established bidirectional association between the two. As such, gestational age was not forcedly adjusted as a confounder in our primary analytical model—this decision was made to avoid over-adjustment bias and prevent masking the changes in cerebral tissue oxygen saturation (ctSO₂) directly driven by MVM itself. However, we acknowledge that this approach introduces a critical analytical challenge: it hinders the complete disentanglement of MVM’s direct effects on ctSO₂ from its indirect effects mediated through preterm birth. To address this limitation, future prospective studies should employ more refined study designs (e.g., gestational age matching or stratification by preterm status) in larger cohorts to further dissect the causal pathways underlying this relationship.

An association was observed between the presence of 3-5 types of maternal vascular malperfusion (MVM) and altered cerebral oxygenation parameters during the early postnatal period. These findings indicate that the cumulative burden of MVM lesions identified on postpartum placental examination may provide useful contextual information for interpreting early neonatal cerebral oxygenation patterns and highlight the need for closer physiological observation during the first postnatal week.