Placental lesions and neonatal outcomes in pregnancies complicated by chronic fetal hypoxia: a retrospective cohort study

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However, the relationship between fetal heart rate patterns suggestive of chronic hypoxia, placental histopathological lesions, and neonatal outcomes remains poorly documented. This study aimed to evaluate the association between placental lesions and early neonatal outcomes in pregnancies complicated by chronic fetal hypoxia and to identify maternal factors associated with maternal vascular malperfusion. Methods We conducted a retrospective single-center cohort study at the University Hospital of Reims, France. Patients who underwent cesarean delivery for fetal heart rate abnormalities suggestive of chronic fetal hypoxia at 24 weeks of gestation or later between May 2023 and November 2025 were included if placental histopathological examination had been performed. Patients were divided into 2 groups according to the presence or absence of placental lesions. Placental examination was classified according to the Amsterdam consensus. The primary outcome was a composite adverse neonatal outcome defined by at least one of the following: arterial pH below 7.10, Apgar score at 5 minutes below 7, admission to neonatal care, respiratory distress syndrome, or early neonatal death. Quantitative variables were compared using the Mann-Whitney test and categorical variables using the Pearson chi-square or Fisher exact test. Results Thirty-four patients were included. No significant association was observed between placental lesions and the composite adverse neonatal outcome. The median gestational age at delivery was 30 weeks. Placental lesions were identified in 13 cases (38.2%). Histopathological abnormalities were predominantly represented by maternal vascular malperfusion lesions, including placental infarctions (64.7%) and decidual arteriopathy (61.8%). Newborns in the placental lesion group had a lower median birth weight than those without placental lesions (1,010 g vs 1,700 g; p = 0.06) and a higher proportion of birth weight at or below the 3rd percentile (38.5% vs 9.5%; p = 0.08). No significant differences were found for Apgar score, umbilical cord blood parameters, admission to neonatal care, respiratory distress syndrome, early neonatal death, or maternal factors associated with maternal vascular malperfusion. Conclusions Maternal vascular malperfusion lesions were the predominant placental abnormalities in pregnancies complicated by chronic fetal hypoxia. Although they were not associated with worse immediate neonatal outcomes, they appeared to be associated with impaired fetal growth. Larger multicenter studies are needed to clarify the prognostic significance of placental lesions. Fetal hypoxia Placental insufficiency Pregnancy outcome Cesarean delivery Fetal growth restriction Figures Figure 1 Background According to the recommendations of the French National College of Gynecologists and Obstetricians (CNGOF), fetal heart rate abnormalities can be classified into four categories, mainly related to mechanisms of intrapartum hypoxia: acute hypoxia, resulting from a sudden interruption of fetal oxygenation; subacute hypoxia, characterized by deep and repetitive decelerations with insufficient recovery time; gradually evolving hypoxia, secondary to a progressive deterioration of the tracing under the effect of uterine contractions; and chronic hypoxia, which precedes the onset of labor and most often reflects preexisting placental insufficiency (1). Chronic fetal hypoxia therefore reflects a prolonged impairment of placental perfusion. In response to this suboptimal intrauterine environment, the fetus activates adaptive mechanisms aimed at maintaining perfusion of vital organs (2,3). When these mechanisms become insufficient, metabolic and hemodynamic alterations may occur, exposing the fetus to sometimes severe neonatal complications, such as hypoxic-ischemic brain injury (4). Although several maternal risk factors have been described in the literature (5–9), the relationship between fetal heart rate patterns suggestive of chronic hypoxia and the corresponding placental abnormalities remains poorly documented. Histopathological examination of the placenta nevertheless represents a key tool for assessing maternal–fetal perfusion conditions and identifying lesions that may be involved in chronic fetal hypoxia, as well as their potential impact on neonatal outcomes. These considerations highlight the importance of analyzing the maternal, obstetric, and neonatal characteristics of patients presenting with fetal heart rate patterns suggestive of chronic fetal hypoxia, as well as their possible association with placental lesions. A better understanding of these relationships could contribute to refining the diagnosis of placental insufficiency and improving obstetric management in similar situations. The primary objective of this study was to describe neonatal outcomes among newborns from pregnancies complicated by chronic fetal hypoxia according to the presence or absence of placental lesions. The secondary objective was to identify maternal factors associated with maternal vascular malperfusion lesions in patients who underwent cesarean delivery for chronic fetal hypoxia. Methods Study design and population This was a retrospective single-center cohort study conducted at the University Hospital of Reims, France. Patients were eligible if the fetus presented a fetal heart rate pattern suggestive of chronic hypoxia at a gestational age of at least 24 weeks, and if the placenta had been sent for histopathological examination between May 1, 2023 and November 30, 2025. Patients were divided into two groups according to the placental histopathological findings: a group with placental lesions and a group without placental lesions. Neonatal outcomes were compared between these two groups. Exclusion criteria were minor patients or those under legal guardianship, multiple pregnancies, deliveries before 24 weeks of gestation, cases in which the placenta was not sent for pathological examination, and patients who refused or were unable to consent to the use of their medical data. Inclusion protocol Patients presenting to the obstetric emergency department or in early labor were monitored using continuous fetal heart rate monitoring. Chronic fetal hypoxia was defined by the combination of four criteria, as described in the literature (10): persistent tachycardia, absence of accelerations, repeated shallow decelerations and persistence of these abnormalities for more than 40 minutes. When a fetal heart rate pattern suggestive of chronic fetal hypoxia was identified, cesarean delivery could be decided by the attending obstetrician, in accordance with current recommendations (11). Immediately after delivery, the placenta was fixed in formalin and sent for histopathological analysis. A macroscopic and microscopic examination was performed by a fetopathologist or pathologist according to a standardized local protocol, following the International Amsterdam Placental Workshop Group Consensus, which classifies placental lesions into four categories : maternal vascular malperfusion (MVM) fetal vascular malperfusion (FVM) inflammatory lesions other miscellaneous lesions (12) Placental configuration abnormalities, umbilical cord insertion anomalies, and the presence of a single umbilical artery were also recorded because of their potential impact on maternal–fetal perfusion (13–16). At birth, neonatal anthropometric measurements were recorded. The Apgar score at 1, 3, 5, and 10 minutes was documented, and arterial and venous umbilical cord blood samples were collected. Data collection Data were retrospectively collected from electronic medical records and recorded in an anonymized database. The primary objective of this study was to describe neonatal outcomes among newborns from pregnancies complicated by chronic fetal hypoxia according to the presence or absence of placental lesions. The primary outcome was a composite adverse neonatal outcome, defined by the occurrence of at least one of the following events: arterial pH < 7.10, Apgar score at 5 minutes < 7, admission to a neonatal care unit, respiratory distress syndrome and early neonatal death. Placental lesions were defined by the presence of at least three maternal vascular malperfusion lesions or by the combination of maternal and fetal vascular malperfusion lesions (MVM and FVM). The secondary objective was to identify maternal factors associated with maternal vascular malperfusion lesions in patients who underwent cesarean delivery for chronic fetal hypoxia. Maternal vascular malperfusion was defined by the presence of at least three of the following lesions: placental infarction, basal decidual hematoma, thrombosis, accelerated villous maturation and decidual arteriopathy. Variables collected The collected variables included : maternal characteristics : maternal age, body mass index at the beginning of pregnancy, parity, smoking status, self-reported substance use (alcohol, cocaine, cannabis), obstetric history including recurrent miscarriage, intrauterine fetal death, fetal growth restriction below the 3rd percentile, preeclampsia, retroplacental hematoma diagnosed on placental examination, or emergency cesarean delivery, medical history including sickle cell disease, chronic anemia, severe asthma, chronic obstructive pulmonary disease, cardiac disease, preexisting diabetes, and chronic hypertension, pregnancy-related conditions including gestational diabetes, gestational hypertension, preeclampsia, or fetal growth restriction below the 3rd percentile ; delivery characteristics : mode of delivery and gestational age at delivery ; neonatal characteristics : live birth or stillbirth, sex, birth weight and percentile, Apgar score at 5 minutes < 7, arterial pH < 7.10, delta pH < 0.10, lactate level, base excess, arterial pO₂, arterial pCO₂, admission to neonatal intensive care unit, respiratory distress syndrome, necrotizing enterocolitis, acute kidney injury, hypoxic–ischemic brain injury and early neonatal death ; placental characteristics were assessed according to the Amsterdam consensus (12). Macroscopic features included : placental weight, cord insertion type, number of umbilical vessels, placental configuration and marginal decidual hematoma Histological features included : maternal vascular malperfusion lesions (placental infarction, basal decidual hematoma, accelerated villous maturation, and decidual arteriopathy including fibrinoid necrosis, spiral artery atherosis, and arterial thrombosis), fetal vascular malperfusion lesions (fetal circulation thrombosis and avascular villi), inflammatory lesions (chronic villitis, chronic intervillositis, acute chorioamnionitis, or fetal inflammatory response) and other lesions (chorangiosis, erythroblastosis, and massive perivillous fibrin deposition). Body mass index was calculated as weight in kilograms divided by height in meters squared (kg/m²). Gestational age was estimated using crown–rump length before 14 weeks of gestation (17) and head circumference after 14 weeks, according to national recommendations. Substance use was self-reported by the patients. Maternal chronic anemia was defined according to World Health Organization criteria, with moderate to severe anemia corresponding to hemoglobin levels below 10 g/dL (18). Fetal biometric percentiles were calculated using World Health Organization growth standards (19), and birth weight percentiles were determined using AUDIPOG growth charts (20). Preeclampsia was defined according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) as blood pressure ≥140/90 mmHg after 20 weeks of gestation associated with maternal and/or fetal complications, even in the absence of proteinuria ≥0.30 g/L. Gestational hypertension was defined as blood pressure ≥140/90 mmHg during pregnancy (21). According to CNGOF guidelines, gestational diabetes was defined by fasting plasma glucose ≥0.92 g/L in the first trimester, or abnormal values during a 75-g oral glucose tolerance test performed between 24 and 28 weeks of gestation (22). Respiratory distress syndrome was diagnosed based on clinical and radiographic signs of surfactant deficiency (23). Hypoxic–ischemic brain injury was diagnosed based on brain magnetic resonance imaging (24). Necrotizing enterocolitis was diagnosed based on a combination of clinical, biological, and radiological findings (25). According to the World Health Organization, early neonatal death was defined as death occurring within the first 7 days of life. Statistical analysis Quantitative variables were described using median and interquartile range [Q1–Q3] and compared between groups using the Mann–Whitney test. Categorical variables were presented as frequencies and percentages. Comparisons between groups were performed using the Pearson Chi-square test or the Fisher exact test when expected cell counts were less than five. A p-value < 0.05 was considered statistically significant. Ethics approval and consent to participate This study received ethical approval from the Ethics Committee for Research in Obstetrics and Gynecology (IRB CEROG 2025-OBS-0204), which exempts it from the requirement to obtain informed consent (26). Patients were informed about the use of their data and had the option to object. The study was conducted in accordance with the principles of the Declaration of Helsinki. Results Between May 1, 2023, and November 30, 2025, a total of 1,389 cesarean deliveries were performed at the University Hospital of Reims. Among these, 36 were performed for fetal heart rate abnormalities suggestive of chronic fetal hypoxia, representing 2.6% of all cesarean deliveries. Two patients were excluded because the placenta had not been sent for histopathological examination. A total of 34 patients were therefore included and divided into two groups according to the presence or absence of placental lesions. The flow diagram is presented in Figure 1. The general characteristics of the study population are presented in Table 1. The median maternal age was 28 years [26–36]. Obesity at the beginning of pregnancy was observed in 29.4% (n = 10) of patients, and active smoking in 32.3% (n = 11). During pregnancy, 38.2% (n = 13) developed preeclampsia, 17.6% (n = 6) had gestational diabetes, and 47.1% (n = 16) of fetuses had an estimated fetal weight at or below the 3rd percentile. Nearly all patients (97.1%, n = 33) delivered by cesarean section at a median gestational age of 30 weeks [28–36]. Placental lesions are summarized in Table 2. Among macroscopic abnormalities, the most frequent finding was placental hypotrophy, observed in 38.2% (n = 13) of cases, followed by marginal cord insertion (20.5%, n = 7) and velamentous cord insertion (5.9%, n = 2). On histological examination, maternal vascular malperfusion lesions were predominant. Placental infarctions were observed in 64.7% (n = 22) of patients, decidual arteriopathy in 61.8% (n = 21), and accelerated villous maturation in 41.2% (n = 14). Fetal vascular malperfusion lesions were also identified, including fetal vascular thrombosis (11.8%, n = 4) and avascular villi (17.6%, n = 6). Among inflammatory lesions, acute chorioamnionitis was the most frequent, observed in 20.6% (n = 7) of cases. Neonatal outcome analysis was performed on 32 patients due to two fetal deaths (one intrauterine fetal death in the placental lesion group and one stillbirth in the group without placental lesions). Among the 34 fetuses, 32 were born alive (Table 3). The median gestational age at birth was lower in the placental lesion group (28 weeks [26.5–37] vs 32 weeks [30–36]), although this difference was not statistically significant (p = 0.17). The median birth weight was lower in the placental lesion group (1,010 g [570–2,150]) compared with the group without placental lesions (1,700 g [1,185–2,498]), with a trend toward statistical significance (p = 0.06). Similarly, a higher proportion of newborns with birth weight at or below the 3rd percentile was observed in the placental lesion group (38.5% [5/13] vs 9.5% [2/21], p = 0.08). The composite adverse neonatal outcome occurred in 81.8% (27/33) of newborns, with no significant difference between groups (91.6% [11/12] in the placental lesion group vs 76.2% [16/21] in the group without placental lesions, p = 0.37): An Apgar score <7 at 5 minutes was observed in 31.2% (10/32) of cases and was more frequent in the group without placental lesions, without statistical significance (25% [3/12] vs 35% [7/20], p = 0.70). Arterial pH <7.10 was observed in 25% (8/32) of liveborn infants and was more frequent in the placental lesion group, without statistical significance (33.3% [4/12] vs 20% [4/20], p = 0.43). Admission to neonatal care occurred in 78.1% (25/32) of liveborn infants and was slightly more frequent in the placental lesion group, without statistical significance (83.3% [10/12] vs 75% [15/20], p = 0.68). Respiratory distress syndrome was observed in 56.2% (18/32) of cases and did not differ between groups (58.3% [7/12] vs 55% [11/20], p > 0.99). Early neonatal death occurred in 12.1% (4/33) of cases and was more frequent in the placental lesion group, without statistical significance (16.6% [2/12] vs 9.5% [2/21], p = 0.61). No statistically significant differences were observed for umbilical cord arterial and venous blood parameters, including delta pH ≥7.10 (p = 0.62), median lactate level (p = 0.42), lactate ≥6 mmol/L (p = 0.28), median base excess (p = 0.58), base excess ≤ −8 mmol/L (p > 0.99), median arterial pO₂ (p = 0.74), arterial pO₂ ≤15 mmHg (p = 0.68), median arterial pCO₂ (p = 0.78), and arterial pCO₂ ≥65 mmHg (p = 0.64). Regarding neonatal complications, necrotizing enterocolitis occurred in one newborn (3.1%, 1/32), in the placental lesion group (8.3% [1/12] vs 0%, p = 0.37). No cases of acute kidney injury were observed. Brain lesions were identified in 12.5% (4/33) of cases, with no significant difference between groups (p > 0.99). Maternal characteristics were compared according to the presence or absence of maternal vascular malperfusion lesions (Table 4). No statistically significant association was found between maternal vascular malperfusion and the maternal characteristics studied, including maternal age >40 years (p > 0.99), body mass index at the beginning of pregnancy (p > 0.99), nulliparity (p = 0.18), multiparity (p = 0.37), smoking (p = 0.63), preexisting diabetes (p > 0.99) or gestational diabetes (p = 0.56), chronic hypertension (p > 0.99) or gestational hypertension (p = 0.17), preeclampsia (p = 0.65), estimated fetal weight ≤3rd percentile (p = 0.32), or obstetric history such as recurrent miscarriage (p > 0.99), fetal growth restriction ≤3rd percentile (p = 0.32), and emergency cesarean delivery (p > 0.99). Discussion The various analyses performed in our study showed a population characterized by a high rate of prematurity and a high prevalence of maternal vascular risk factors. Placental lesions were largely dominated by maternal vascular malperfusion (MVM) lesions, particularly placental infarctions and decidual arteriopathy. Despite this high prevalence of histologic lesions, no statistically significant association was found between the presence of placental lesions and immediate neonatal outcome, assessed using a composite endpoint including both biological and clinical parameters. However, a trend toward lower birth weight and a higher proportion of newborns with birth weight below the 3rd percentile was observed in the presence of placental lesions. Several studies have described factors associated with placental insufficiency, including maternal age over 35 years, smoking, obesity, preeclampsia, and gestational diabetes (27). In our population, although the median maternal age was 28 years, the high frequency of several vascular risk factors, particularly preeclampsia (38.2%), smoking (32.3%), and obesity (29.4%), appears consistent with the pathophysiologic mechanisms described in the literature. The marked prematurity observed in our study, with a median gestational age of 30 weeks, may be explained by the context of chronic fetal hypoxia secondary to placental insufficiency, which has been described as a progressive condition that may lead to a decision for preterm delivery (28). In addition, nearly half of the fetuses had an estimated fetal weight below the 3rd percentile during pregnancy (47%), suggesting that suspicion of fetal growth restriction was common in this population. Regarding the placental lesions observed in our study, they were predominantly represented by maternal vascular malperfusion lesions, including placental infarctions (64.7%), decidual arteriopathy (61.8%), and accelerated villous maturation (41.2%). Fetal vascular malperfusion lesions were less frequent and do not appear to represent the main mechanism of chronic placental insufficiency in our population. Indeed, Redline et al. described maternal vascular malperfusion lesions as the typical histopathologic correlate of chronic placental insufficiency, in contrast to fetal vascular malperfusion lesions, which are more often associated with acute mechanisms, and this appears consistent with our findings (15). Inflammatory lesions were less commonly observed in our study. This low frequency is consistent with the Amsterdam Placental Workshop Group consensus, which considers inflammatory lesions as distinct entities and not the usual mechanism underlying chronic placental insufficiency (12). Some placental structural abnormalities, such as marginal cord insertion (20.5%) and velamentous cord insertion (5.9%), were observed in our population. These abnormalities have been described in the literature as potentially contributing to impaired maternal–fetal exchange, without being sufficient on their own to account for chronic fetal hypoxia (14). Our data did not show any association between the presence of placental lesions and adverse neonatal outcome as assessed by the composite endpoint, although a relationship cannot be formally excluded given the limited sample size. However, interpretation of this endpoint is limited by its heterogeneity and by the high frequency of some variables, such as admission to neonatal care and respiratory distress syndrome, both of which are closely related to prematurity. It may therefore be more relevant to interpret the results on a variable-by-variable basis. The rate of arterial pH < 7.10 did not differ significantly between the two groups. The same was true for all acid–base balance parameters, including ΔpH, lactate levels, base excess, and arterial pO₂ and pCO₂. Interpretation of umbilical cord blood samples relies on the distinction between respiratory acidosis and metabolic acidosis. Respiratory acidosis results from acute CO₂ accumulation, most often related to a sudden intrapartum event, and is associated with elevated pCO₂ and generally preserved base excess. In contrast, metabolic acidosis reflects prolonged tissue hypoxia leading to increased lactate production and negative base excess. A trend toward higher lactate levels was observed in the presence of placental lesions, although this did not reach statistical significance (6.0 [2.8–8.1] vs 4.3 [2.5–7.3], p = 0.42). Lactate is a sensitive marker of anaerobic metabolism and may increase in situations of prolonged hypoxia even in the absence of severe metabolic acidosis (29). Given the small sample size of our population, these findings may suggest that in cases of chronic hypoxia, fetal adaptive mechanisms and obstetric management allowed delivery to occur before major metabolic deterioration developed. Umbilical cord blood gas results should be interpreted with caution, as pH alone is not a specific marker of hypoxia or neurological severity (30). Moreover, in chronic hypoxia, adaptive mechanisms may allow relative preservation of acid–base balance until birth (29). These mechanisms include redistribution of blood flow to vital organs (brain-sparing effect), reduced oxygen consumption due to decreased fetal movements and slowed growth, increased oxygen-carrying capacity, and hemodynamic adaptations. The rate of Apgar score < 7 at 5 minutes did not differ significantly according to the presence or absence of placental lesions. The 5-minute Apgar score mainly reflects immediate cardiorespiratory adaptation of the newborn and is not a specific marker of the type of intrapartum hypoxia (31); it may also be influenced by other maternal or fetal factors. No difference in fetal sex distribution was observed between groups. Although sex-related differences in neonatal morbidity and mortality have been described, particularly in settings of acute hypoxia and extreme prematurity, these findings do not appear to be directly applicable to our population with chronic hypoxia (32). In addition, the limited size of our cohort reduced the statistical power of this analysis and does not allow a sex-related difference to be formally excluded. The rate of admission to neonatal care was high in both groups and was slightly higher in the placental lesion group, without a statistically significant difference (83.3% vs 75%, p = 0.68). Prematurity is the main indication for neonatal unit admission, with a marked increase in the need for specialized care among newborns delivered before 32 weeks of gestation (33,34). In our cohort, the median gestational age below 32 weeks may therefore explain the high admission rate observed, independently of placental abnormalities. The high frequency of respiratory distress syndrome observed in our cohort, with no significant difference between groups, is also consistent with the degree of prematurity of the newborns, since surfactant deficiency due to pulmonary immaturity is the major determinant of this complication (35). Finally, the rate of early neonatal death also did not differ between groups. The Amsterdam Placental Workshop Group consensus emphasizes the association of MVM lesions with hypertensive disorders of pregnancy and stillbirth, but also states that lesion severity, extent, and multifocality are more prognostically relevant than their mere presence (12). However, these characteristics were not assessed in our study. The lack of statistical significance for these variables may be explained by the limited sample size, as well as by the selection of our population, which consisted of patients who underwent cesarean delivery for fetal heart rate abnormalities suggestive of chronic hypoxia, likely before severe metabolic decompensation occurred. In our center, however, obstetric management is not standardized and also depends on human and organizational factors. Interpretation of neonatal outcome must also take into account antenatal therapies that may have modified immediate prognosis. Antenatal corticosteroid administration is known to significantly reduce respiratory morbidity in preterm infants, particularly respiratory distress syndrome, as well as neonatal mortality (36). Similarly, antenatal magnesium sulfate administered in the setting of threatened preterm birth is associated with a neuroprotective effect, especially in very preterm infants (37). The absence of systematic data on these therapies in our cohort does not allow evaluation of their potential impact. However, it is likely that they contributed to limiting the immediate clinical expression of chronic hypoxia. Thus, although the presence of placental lesions does not appear to significantly influence immediate neonatal status, their impact may be expressed differently, particularly through fetal growth parameters. Indeed, our data suggest a lower birth weight and a higher proportion of newborns with birth weight below the 3rd percentile in the group with placental lesions. These findings are consistent with the predominance of maternal vascular malperfusion lesions observed in our study, mainly represented by placental infarctions, decidual arteriopathy, and accelerated villous maturation. These lesions reflect chronic impairment of spiral artery remodeling and a progressive reduction in uteroplacental perfusion, resulting in decreased oxygen and nutrient delivery to the fetus. This progressive mechanism is associated with chronic placental insufficiency and fetal growth restriction (12,38,39). Interpretation of these findings must nevertheless take gestational age into account, as the median gestational age was lower in the placental lesion group (28 vs 32 weeks, p = 0.17). However, the high proportion of newborns with birth weight below the 3rd percentile in the placental lesion group suggests a specific effect beyond gestational age alone. This finding is pathophysiologically consistent and suggests that the main clinical expression of these placental lesions lies in progressive fetal growth impairment rather than in acute hypoxic decompensation at birth. The secondary objective of this study was to identify maternal factors associated with maternal vascular malperfusion lesions. No variable showed a statistically significant association with the presence of these lesions. This lack of significance must be interpreted in light of the very small size of the relevant subgroup (n = 6), which greatly limited the power of the analysis. Nevertheless, several trends appear consistent with the pathophysiology described in the literature (40), particularly for preeclampsia, which was more frequently observed in cases of maternal vascular malperfusion (50% vs 35.7%, p = 0.65). Similarly, a history of fetal growth restriction appeared more frequent in the lesion group (16.6% vs 3.6%, p = 0.32), which may reflect an underlying persistent maternal vascular predisposition. In contrast, some variables such as smoking, advanced maternal age, obesity, diabetes, or hypertension did not show concordant trends, which may be explained by the small sample size and clinical heterogeneity of the study population. Thus, although our study does not demonstrate a statistically significant association, the observed trends are in keeping with the known pathophysiology linking vascular disorders and placental lesions. The main limitation of our study was the small sample size, with only 34 patients included, which may be explained by the rarity of chronic fetal hypoxia (2.9% of cesarean deliveries in our center). The single-center design is also a limitation. However, this methodological choice ensured homogeneity of obstetric practices and standardization of histopathologic analyses, which would be difficult to reproduce in a multicenter setting. In addition, our population was potentially selected, since it included only patients who underwent cesarean delivery for fetal heart rate abnormalities suggestive of chronic hypoxia. Patients with unrecognized chronic hypoxia or chronic hypoxia not leading to cesarean delivery were not represented, which may have introduced selection bias. However, although management of chronic fetal hypoxia is not protocolized in our center, practices are highly homogeneous, making major selection bias less likely. Furthermore, regular training in fetal heart rate interpretation is provided in the department, including teaching sessions and e-learning modules, which likely contributes to harmonization of clinical practice. Finally, the use of a composite adverse neonatal outcome may be debated. Combining biological and clinical parameters of different natures makes this endpoint heterogeneous, and some components may strongly influence its frequency, thereby limiting the specificity of the analysis. The literature specifically addressing chronic fetal hypoxia remains limited, as most studies group fetal heart rate abnormalities together without distinguishing between acute and chronic mechanisms. Our focused work on this topic therefore represents an original contribution. Systematic histopathologic examination of the placentas is a major methodological strength. Examination was performed by a fetopathologist according to the criteria of the international Amsterdam consensus, ensuring a standardized and reproducible analysis. Among the 36 patients initially identified, two were excluded because no histopathologic examination had been performed, thereby ensuring homogeneity of the histologic data analyzed. This study allowed a better characterization of the placental lesion profile associated with chronic fetal hypoxia. It highlights the predominance of maternal vascular malperfusion lesions, consistent with the presence of an underlying maternal vascular predisposition. In addition, our results suggest that the main clinical expression of these histologic lesions is fetal growth restriction. This observation contributes to a better understanding of fetal adaptive mechanisms in the setting of chronic hypoxia. The predominance of maternal vascular malperfusion lesions observed in our cohort suggests the presence of an underlying maternal vascular background that may recur in a subsequent pregnancy. Christians et al. suggest that obstetric complications such as preeclampsia, fetal growth restriction, or prematurity tend to recur from one pregnancy to another, independently of placental histologic lesions (41). These data suggest that placental malperfusion may be the expression of an overall maternal predisposition. McBride et al. showed that maternal vascular malperfusion lesions are associated with preexisting or early-pregnancy maternal cardiovascular and thrombogenic profiles, further supporting the hypothesis of an underlying maternal vascular background (42). Although no current recommendation supports aspirin therapy based solely on placental histologic findings, identification of malperfusion lesions may help refine risk stratification in a future pregnancy, in addition to recognized clinical risk factors. Current international recommendations support administration of low-dose aspirin (100–150 mg/day), started early between 11 and 14 weeks of gestation and continued until 34–36 weeks, in patients at high risk of preeclampsia (43,44). In addition, placental examination could be incorporated into a secondary prevention strategy, by optimizing modifiable cardiovascular risk factors before conception. Smoking cessation is a major target, as tobacco exposure is associated with impaired uteroplacental perfusion and an increased risk of fetal growth restriction (45). Likewise, management of obesity, optimization of blood pressure in patients with chronic hypertension, and glycemic control in patients with diabetes may help reduce the risk of vascular complications during pregnancy. The findings of this study are limited to evaluation of early neonatal outcomes. The absence of a significant association between placental lesions and immediate neonatal status does not preclude a potential impact of chronic hypoxia on later development. Indeed, fetal growth restriction related to placental insufficiency, birth weight, and gestational age are major determinants of long-term outcome (46). Several studies have shown that chronic placental insufficiency is part of the developmental origins of adult disease framework, including hypertension, coronary artery disease, kidney disease, type 2 diabetes, metabolic syndrome, and pulmonary disease (46–51). Beyond metabolic and cardiovascular consequences, data also suggest that chronic hypoxia associated with fetal growth restriction may impair brain maturation, even in the absence of severe acute asphyxia at birth. Miller et al. showed that chronic placental insufficiency is associated with white matter alterations, abnormal myelination, and changes in neuronal connectivity. These abnormalities appear to be related to disrupted organization of brain networks rather than massive neuronal loss (52). Brain imaging studies in newborns with fetal growth restriction have demonstrated reduced brain volumes and abnormalities of white matter microstructure, which may later be associated with cognitive impairment (53). Therefore, the absence of immediate neonatal complications in our cohort does not rule out delayed neurodevelopmental consequences. Longitudinal studies including extended neurodevelopmental follow-up would be necessary to assess the long-term consequences of chronic fetal hypoxia associated with placental malperfusion lesions in our population. The limited sample size of our cohort does not allow formal exclusion of a moderate association. Larger multicenter studies, with multivariable analyses adjusted for gestational age, birth weight, and maternal comorbidities, are needed to better define the prognostic role of placental lesions. Conclusion This study highlighted the predominance of maternal vascular malperfusion lesions and their consequences, particularly with respect to birth weight. Our findings suggest that the clinical expression of chronic fetal hypoxia is not necessarily immediate. However, the absence of an immediate neonatal impact does not rule out potential longer-term consequences, particularly on neurodevelopment. Placental examination may therefore contribute to a better understanding of the underlying mechanisms and help refine management in subsequent pregnancies, in addition to established clinical risk factors. The limited sample size of our cohort does not allow a moderate association to be formally excluded. Larger multicenter studies, with multivariable analyses adjusted for gestational age, birth weight, and maternal comorbidities, are needed to better define the prognostic role of placental lesions. Abbreviations CNGOF: French National College of Gynecologists and Obstetricians WHO: World Health Organization BMI: Body Mass Index FHR abnormality: Fetal Heart Rate Abnormality MVM: Maternal Vascular Malperfusion FVM: Fetal Vascular Malperfusion FGR: Fetal Growth Restriction EFW: Estimated Fetal Weight ISSHP: International Society for the Study of Hypertension in Pregnancy Declarations Ethics approval and consent to participate : This study received approval from the Ethics Committee for Research in Gynecology and Obstetrics under reference IRB CEROG 2025-OBS-0204. Patient data were anonymized prior to statistical analysis. Patients were informed of the use of their data for research purposes and were given the opportunity to oppose the use of their data. Consent for publication : Patients were informed of the use of their data for research purposes and were given the opportunity to oppose the use of their data. Availability of data and materials : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests : The authors declare that they have no competing interests. Funding : not applicable Authors contributions - M.V : Conceptualization (supporting), Formal Analysis, Investigation (lead), Methodology (supporting), Project Administration (lead), Writing – Original Draft Preparation (lead), Writing – Review ; Editing - C.J : Investigation (supporting), Writing – Review - R.G : Conceptualization (supporting), Writing – Review (equal) - G.L :Writing – Review (equal) - O.G : Writing – Review (equal) - M.S : Conceptualization (lead), Methodology (supporting), Writing – Review (equal) - B.B : Conceptualization (supporting), Methodology (lead), Writing – Review (equal) Acknowledgements : not applicable References Descourvières L, Mentele J, Guittet L, Vardon D, Marret S, Riethmuller D, et al. Types of intrapartum hypoxia in the newborn at term with metabolic acidemia: a retrospective study. Acta Obstet Gynecol Scand. 2022;101(10):1276-81. Allison BJ, Brain KL, Niu Y, Cross CM, Itani N, Kane AD, et al. Fetal in vivo continuous cardiovascular function during chronic hypoxia. J Physiol. 2016;594(5):1247-64. Richardson BS, Bocking AD. Metabolic and circulatory adaptations to chronic hypoxia in the fetus. Comp Biochem Physiol A Mol Integr Physiol. 1998;119(3):717-23. Salihagić-Kadić A, Medić M, Jugović D, Kos M, Latin V, Kušan Jukić M, et al. Fetal cerebrovascular response to chronic hypoxia-implications for the prevention of brain damage. J Matern Fetal Neonatal Med. 2006;19(7):387-96. Maberry MC, Ramin SM, Gilstrap LC 3rd, Leveno KJ, Dax JS. Intrapartum asphyxia in pregnancies complicated by intra-amniotic infection. Obstet Gynecol. 1990;76(3):351-4. Escobar J, Teramo K, Stefanovic V, Andersson S, Asensi MA, Arduini A, et al. Amniotic fluid oxidative and nitrosative stress biomarkers correlate with fetal chronic hypoxia in diabetic pregnancies. Neonatology. 2013;103(3):193-8. Hayes EK, Lechowicz A, Petrik JJ, Storozhuk Y, Paquette M, Yockell-Lelièvre J, et al. Adverse fetal and neonatal outcomes associated with a life-long high fat diet: role of altered development of the placental vasculature. PLoS One. 2012;7(3):e33370. Davis L, Thornburg KL, Giraud GD. The effects of anaemia as a programming agent in the fetal heart. J Physiol. 2005;565(Pt 1):35-41. Makowski EL, Battaglia FC, Meschia G. Effect of maternal exposure to high altitude upon fetal oxygenation. Am J Obstet Gynecol. 1968;100(6):852-61. Pereira S, Chandraharan E. Recognition of chronic hypoxia and pre-existing foetal injury on the cardiotocograph (CTG): urgent need to think beyond the guidelines. Porto Biomed J. 2017;2(4):124-9. Pulgar VM, Zhang J, Massmann GA, Figueroa JP. Prolonged mild hypoxia alters fetal sheep electrocorticogram activity. J Soc Gynecol Investig. 2006;13(6):404-11. Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler MA, et al. Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group consensus statement. Arch Pathol Lab Med. 2016;140(7):698-713. Stanek J. Hypoxic patterns of placental injury: a review. Arch Pathol Lab Med. 2013;137(5):706-12. Ebbing C, Kiserud T, Johnsen SL, Albrechtsen S, Rasmussen S. Prevalence, risk factors and outcomes of velamentous and marginal cord insertions: a population-based study of 634,741 pregnancies. PLoS One. 2013;8(7):e70380. Redline RW. Placental pathology: a systematic approach with clinical correlations. Placenta. 2021;104:31-9. Hua M, Odibo AO, Longman RE, Macones GA, Roehl KA, Cahill AG. Single umbilical artery and its associated findings. Obstet Gynecol. 2010;115(5):930-4. Robinson HP. Sonar measurement of fetal crown-rump length as means of assessing maturity in first trimester of pregnancy. Br Med J. 1973;4(5893):28-31. World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. https://www.who.int/vmnis/indicators/haemoglobin. Accessed 4 Mar 2026. Kiserud T, Piaggio G, Carroli G, Widmer M, Carvalho J, Neerup Jensen L, et al. The World Health Organization fetal growth charts: a multinational longitudinal study of ultrasound biometric measurements and estimated fetal weight. Lancet. 2017;389(10099):1447-58. Mamelle N, Munoz F. An international standard for fetal growth. Fetal Diagn Ther. 1997;12(2):122-8. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis and management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. Collège National des Gynécologues et Obstétriciens Français. Diabète gestationnel: recommandations pour la pratique clinique. Paris: CNGOF; 2018. https://www.cngof.fr/pratiques-cliniques/recommandations-pour-la-pratique-clinique. Accessed 6 Mar 2026. Rubarth LB, Quinn J. Respiratory development and respiratory distress syndrome. Neonatal Netw. 2015;34(4):231-8. Volpe JJ. Hypoxic-ischemic encephalopathy: clinical aspects. N Engl J Med. 2001;344(14):1065-71. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis: therapeutic decisions based upon clinical staging. Ann Surg. 1978;187(1):1-7. Dabi Y, Thubert T, Fuchs F, Barjat T, Belaisch-Allart J, Ceccaldi PF, et al. How is functioning the Ethical Review Comité d’Ethique pour la Recherche en Obstétrique et Gynécologie (CEROG)? J Gynecol Obstet Hum Reprod. 2022;51(3):102352. Wardinger JE, Vadakekut ES. Placental insufficiency. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Gagnon R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol. 2003;110 Suppl 1:S99-107. Westgate J, Garibaldi JM, Greene KR. Umbilical cord blood gas analysis at delivery: a time for quality data. Br J Obstet Gynaecol. 1994;101(12):1054-63. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee Opinion No. 348: Umbilical cord blood gas and acid-base analysis. Obstet Gynecol. 2006;108(5):1319-22. American Academy of Pediatrics Committee on Fetus and Newborn; American College of Obstetricians and Gynecologists Committee on Obstetric Practice. The Apgar score. Pediatrics. 2015;136(4):819-22. Clifton VL. Sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta. 2010;31 Suppl:S33-9. Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics. 2000;106(4):659-71. Euro-Peristat Project. European Perinatal Health Report: core indicators of the health and care of pregnant women and babies in Europe in 2018. Luxembourg: Publications Office of the European Union; 2022. https://www.europeristat.com. Accessed 6 Mar 2026. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, et al. European consensus guidelines on the management of respiratory distress syndrome - 2019 update. Neonatology. 2019;115(4):432-50. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2017;3(3):CD004454. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulfate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;(1):CD004661. Agarwal R, Tiwari A, Wadhwa N, Radhakrishnan G. Placental histopathological findings in preterm/term and early/late onset small for gestational age: are they significant? Indian J Pathol Microbiol. 2017;60(2):232-5. Baschat AA, Hecher K. Fetal growth restriction due to placental disease. Semin Perinatol. 2004;28(1):67-80. Ogge G, Chaiworapongsa T, Romero R, Hussein Y, Kusanovic JP, Yeo L, et al. Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia. J Perinat Med. 2011;39(6):641-52. Christians JK, Huicochea Munoz MF. Pregnancy complications recur independently of maternal vascular malperfusion lesions. PLoS One. 2020;15(2):e0228664. McBride CA, Bernstein IM, Sybenga AB, McLean KC, Orfeo T, Bravo MC. Placental maternal vascular malperfusion is associated with prepregnancy and early pregnancy maternal cardiovascular and thrombotic profiles. Reprod Med (Basel). 2022;3(1):50-61. Rolnik DL, Wright D, Poon LCY, Syngelaki A, O’Gorman N, de Paco Matallana C, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377(7):613-22. Poon LC, Shennan A, Hyett JA, Kapur A, Hadar E, Divakar H, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145 Suppl 1:1-33. England LJ, Levine RJ, Mills JL, Klebanoff MA, Yu KF, Cnattingius S. Adverse pregnancy outcomes in snuff users. Am J Obstet Gynecol. 2003;189(4):939-43. Baschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol. 2011;37(5):501-14. Barker DJ. The developmental origins of adult disease. J Am Coll Nutr. 2004;23(6 Suppl):588S-95S. Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, Le Noble F, et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010;121(22):2427-36. Luyckx VA, Brenner BM. Birth weight, malnutrition and kidney-associated outcomes-a global concern. Nat Rev Nephrol. 2015;11(3):135-49. Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001;60:5-20. Stocks J, Sonnappa S. Early life influences on the development of chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2013;7(3):161-73. Tolcos M, Rees S. Chronic placental insufficiency in the fetal guinea pig affects neurochemical and neuroglial development but not neuronal numbers in the brainstem: a new method for combined stereology and immunohistochemistry. J Comp Neurol. 1997;379(1):99-113. Borradori Tolsa C, Zimine S, Warfield SK, Freschi M, Sancho Rossignol A, Lazeyras F, et al. Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction. Pediatr Res. 2004;56(1):132-8. Tables Table 1 - Maternal characteristics Variables Total (N = 34) Age (years) – median [Q1–Q3] 28 [26-36] Age ≥ 40 years 1 (2.9) BMI (kg/m²) at the beginning of pregnancy – n (%)* 40 (kg/m2) 4 (11.8) BMI* ≥ 30 kg/m² at the beginning of pregnancy – n (%) 10 (29.4) Parity Nulliparous – n (%) 19 (55.9) Multiparous – n (%) 15 (44.1) Smoking during pregnancy – n (%) 11 (32.3) Other substance use – n (%) 0 (0) Medical history – n (%) Sickle cell disease 1 (2.9) Chronic anemia 1 (2.9) Severe respiratory disease 1 (2.9) Maternal cardiac disease 1 (2.9) Preexisting diabetes 2 (5.8) Chronic hypertension‡ 1 (2.9) Obstetric history – n (%) ≥3 early miscarriages 2 (5.8) Intrauterine fetal death 0 (0) Placental abruption 0 (0) Preeclampsia 0 (0) FGR§ ≤ 3rd percentile 2 (5.8) Previous cesarean delivery 2 (5.8) Current pregnancy – n (%) Gestational diabetes 6 (17.6) Isolated gestational hypertension‡ 1 (2.9) Preeclampsia 13 (38.2) Estimated fetal weight ≤ 3rd percentile 16 (47.1) Mode of delivery – n (%) Cesarean delivery 33 (97.1) Vaginal delivery 1 (2.9) Gestational age at delivery (weeks) – median [Q1–Q3]* 30 [28-36] *BMI: body mass index; § FGR: fetal growth restriction. Table 2 – Placental lesions identified in pregnancies complicated by chronic fetal hypoxia Variables Total (N = 34) Macroscopic findings Placental hypotrophy – n (%) 13 (38.2) Marginal decidual hematoma – n (%) 1 (2.9) Umbilical cord abnormalities – n (%) Marginal cord insertion 7 (20.5) Velamentous cord insertion 2 (5.9) Single umbilical artery 1 (2.9) Placental configuration abnormalities – n (%) Bilobed placenta 0 (0) Circumvallate placenta 1 (2.9) Histological findings Maternal vascular malperfusion lesions – n (%) Placental infarction 22 (64.7) Basal decidual hematoma 3 (8.8) Accelerated villous maturation 14 (41.2) Decidual arteriopathy 21 (61.8) Fetal vascular malperfusion lesions – n (%) Fetal vascular thrombosis 4 (11.8) Avascular villi 6 (17.6) Chronic inflammatory lesions – n (%) Chronic villitis 1 (2.9) Chronic intervillositis 0 (0) Acute inflammatory lesions – n (%) Acute chorioamnionitis 7 (20.5) Fetal inflammatory response 3 (8.8) Other unclassified lesions – n (%) Chorangiosis 3 (8.8) Erythroblastosis 3 (8.8) Massive perivillous fibrin deposition 5 (14.7) Table 3 – Neonatal characteristics according to the presence or absence of placental lesions Variables Total Placental lesion group No placental lesion group p (N = 34) (N = 13) (N = 21) Live birth – n (%) 32 (94.1) 12 (92.3) 20 (95.2) > 0.99 Gestational age at birth (weeks) – median [Q1–Q3] 30 [28-36] 28 [26.5-37] 32 [30-36] 0,17 Fetal sex – n (%) > 0.99 Female 15 (44.1) 6 (46.1) 9 (42.8) Male 19 (55.8) 7 (53.9) 12 (57.1) Birth weight (g) – median [Q1–Q3] 1360 [700-2275] 1010 [570-2150] 1700 [1185–2498] 0.06 Birth weight ≤3rd percentile – n (%) 7 (20.6) 5 (38.5) 2 (9.5) 0.08 Birth weight ≥97th percentile – n (%) 0 (0) 0 (0) 0 (0) NA Apgar score <7 at 5 minutes – n/N (%) 10/32 (31.2) 3/12 (25) 7/20 (35) 0.7 Arterial pH ≤7.10 – n/N (%) 8/32 (25) 4/12 (33.3) 4/20 (20) 0.43 ΔpH ≥0.10 – n/N (%) 4/32 (12.5) 2/12 (16.6) 2/20 (10) 0.62 Umbilical cord lactate level (mmol/L) – median [Q1–Q3] 4.6 [2.5-8.6] 6.0 [2.8–8.1] 4.3 [2.5–7.3] 0.42 Lactate ≥6 mmol/L – n/N (%) 12/32 (37.5) 6/12 (50) 6/20 (30) 0.28 Umbilical cord base excess (mmol/L) – median [Q1–Q3] -5.1 [-9.7 ; -2.2] −6.5 [−8.2 ; −2.6] −5.1 [−9.6 ; −3.0] 0.58 Base excess ≤−8 mmol/L – n/N (%) 16/32 (50) 6/12 (50) 10/20 (50) > 0.99 Umbilical cord arterial pO₂ (mmHg) – median [Q1–Q3] 15 [10-62] 14.5 [9.0–41.5] 16.5 [12.5–65.5] 0.74 Arterial pO₂ ≤15 mmHg – n/N (%) 7/32 (21.8) 2/12 (16.6) 5/20 (25) 0.68 Umbilical cord arterial pCO₂ (mmHg) – median [Q1–Q3] 53 [46-63] 55 [51.5–61.5] 52.5 [45.5–62.5] 0.78 Arterial pCO₂ ≥65 mmHg – n/N (%) 6/32 (18.7) 3/12 (25) 3/20 (15) 0.64 Admission to neonatal care – n/N (%) 25/32 (78.1) 10/12 (83.3) 15/20 (75) 0.68 Respiratory distress syndrome – n/N (%) 18/32 (56.2) 7/12 (58.3) 11/20 (55) > 0.99 Necrotizing enterocolitis – n/N (%) 1/32 (3.1) 1/12 (8.3) 0 (0) 0.37 Acute kidney injury – n/N (%) 0/32 (0) 0/12 (0) 0/20 (0) NA Hypoxic–ischemic brain injury – n/N (%) 4/32 (12.5) 1/12 (8.3) 3/20 (15) > 0.99 Early neonatal death – n/N (%) 4/33 (12.1) 2/12 (16.6) 2/21 (9.5) 0.61 Composite adverse neonatal outcome – n/N (%) 27/33 (81.8) 11/12 (91.6) 16/21 (76.2) 0.37 Table 4 – Maternal characteristics according to the presence or absence of maternal vascular malperfusion lesions Variables Total MVM∗ present No MVM∗ p (N = 34) (N = 6) (N =28) Maternal age ≥40 years – n (%) 1 (2.9) 0 (0) 1 (3.6) > 0.99 BMI† ≥30 kg/m² at the beginning of pregnancy – n (%) 11 (32.4) 2 (33.3) 9 (32.1) > 0.99 Nulliparity – n (%) 19 (55.9) 2 (33.3) 17 (60.7) 0.18 Multiparity – n (%) 15 (44.1) 4 (66.7) 11 (39.3) 0.37 Smoking during pregnancy – n (%) 11 (32.3) 1 (7.7) 10 (35.7) 0.63 Preexisting diabetes – n (%) 2 (5.8) 0 (0) 2 (7.1) > 0.99 Gestational diabetes – n (%) 6 (17.6) 0 (0) 6 (21.4) 0.56 Chronic hypertension‡ – n (%) 1 (2.9) 0 (0) 1 (3.6) > 0.99 Isolated gestational hypertension‡ – n (%) 1 (2.9) 1 (16.6) 0 (0) 0.17 Preeclampsia – n (%) 13 (38.2) 3 (50) 10 (35.7) 0.65 Estimated fetal weight ≤3rd percentile – n (%) 16 (47.1) 3 (50) 13 (46.4) > 0.99 History of ≥3 early miscarriages – n (%) 2 (5.8) 0 (0) 2 (7.1) > 0.99 History of fetal growth restriction ≤3rd percentile – n (%) 2 (5.8) 1 (16.6) 1 (3.6) 0.32 History of cesarean delivery – n (%) 2 (5.8) 0 (0) 2 (7.1) > 0.99 BMI: body mass index; ∗ MVM: maternal vascular malperfusion. 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subacute hypoxia, characterized by deep and repetitive decelerations with insufficient recovery time; gradually evolving hypoxia, secondary to a progressive deterioration of the tracing under the effect of uterine contractions; and chronic hypoxia, which precedes the onset of labor and most often reflects preexisting placental insufficiency (1).\u003c/p\u003e\n\u003cp\u003eChronic fetal hypoxia therefore reflects a prolonged impairment of placental perfusion. In response to this suboptimal intrauterine environment, the fetus activates adaptive mechanisms aimed at maintaining perfusion of vital organs (2,3). When these mechanisms become insufficient, metabolic and hemodynamic alterations may occur, exposing the fetus to sometimes severe neonatal complications, such as hypoxic-ischemic brain injury (4). Although several maternal risk factors have been described in the literature (5\u0026ndash;9), the relationship between fetal heart rate patterns suggestive of chronic hypoxia and the corresponding placental abnormalities remains poorly documented.\u003c/p\u003e\n\u003cp\u003eHistopathological examination of the placenta nevertheless represents a key tool for assessing maternal\u0026ndash;fetal perfusion conditions and identifying lesions that may be involved in chronic fetal hypoxia, as well as their potential impact on neonatal outcomes.\u003c/p\u003e\n\u003cp\u003eThese considerations highlight the importance of analyzing the maternal, obstetric, and neonatal characteristics of patients presenting with fetal heart rate patterns suggestive of chronic fetal hypoxia, as well as their possible association with placental lesions. A better understanding of these relationships could contribute to refining the diagnosis of placental insufficiency and improving obstetric management in similar situations.\u003c/p\u003e\n\u003cp\u003eThe primary objective of this study was to describe neonatal outcomes among newborns from pregnancies complicated by chronic fetal hypoxia according to the presence or absence of placental lesions. The secondary objective was to identify maternal factors associated with maternal vascular malperfusion lesions in patients who underwent cesarean delivery for chronic fetal hypoxia.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy design and population\u003c/h2\u003e\n\u003cp\u003eThis was a retrospective single-center cohort study conducted at the University Hospital of Reims, France. Patients were eligible if the fetus presented a fetal heart rate pattern suggestive of chronic hypoxia at a gestational age of at least 24 weeks, and if the placenta had been sent for histopathological examination between May 1, 2023 and November 30, 2025.\u003c/p\u003e\n\u003cp\u003ePatients were divided into two groups according to the placental histopathological findings: a group with placental lesions and a group without placental lesions. Neonatal outcomes were compared between these two groups.\u003c/p\u003e\n\u003cp\u003eExclusion criteria were minor patients or those under legal guardianship, multiple pregnancies, deliveries before 24 weeks of gestation, cases in which the placenta was not sent for pathological examination, and patients who refused or were unable to consent to the use of their medical data.\u003c/p\u003e\n\u003ch2\u003eInclusion protocol\u003c/h2\u003e\n\u003cp\u003ePatients presenting to the obstetric emergency department or in early labor were monitored using continuous fetal heart rate monitoring.\u003c/p\u003e\n\u003cp\u003eChronic fetal hypoxia was defined by the combination of four criteria, as described in the literature (10): persistent tachycardia, absence of accelerations, repeated shallow decelerations and persistence of these abnormalities for more than 40 minutes.\u003c/p\u003e\n\u003cp\u003eWhen a fetal heart rate pattern suggestive of chronic fetal hypoxia was identified, cesarean delivery could be decided by the attending obstetrician, in accordance with current recommendations (11).\u003c/p\u003e\n\u003cp\u003eImmediately after delivery, the placenta was fixed in formalin and sent for histopathological analysis. A macroscopic and microscopic examination was performed by a fetopathologist or pathologist according to a standardized local protocol, following the International Amsterdam Placental Workshop Group Consensus, which classifies placental lesions into four categories :\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ematernal vascular malperfusion (MVM)\u003c/li\u003e\n \u003cli\u003efetal vascular malperfusion (FVM)\u003c/li\u003e\n \u003cli\u003einflammatory lesions\u003c/li\u003e\n \u003cli\u003eother miscellaneous lesions (12)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003ePlacental configuration abnormalities, umbilical cord insertion anomalies, and the presence of a single umbilical artery were also recorded because of their potential impact on maternal\u0026ndash;fetal perfusion (13\u0026ndash;16).\u003c/p\u003e\n\u003cp\u003eAt birth, neonatal anthropometric measurements were recorded. The Apgar score at 1, 3, 5, and 10 minutes was documented, and arterial and venous umbilical cord blood samples were collected.\u003c/p\u003e\n\u003ch2\u003eData collection\u003c/h2\u003e\n\u003cp\u003eData were retrospectively collected from electronic medical records and recorded in an anonymized database.\u003c/p\u003e\n\u003cp\u003eThe primary objective of this study was to describe neonatal outcomes among newborns from pregnancies complicated by chronic fetal hypoxia according to the presence or absence of placental lesions.\u003c/p\u003e\n\u003cp\u003eThe primary outcome was a composite adverse neonatal outcome, defined by the occurrence of at least one of the following events: arterial pH \u0026lt; 7.10, Apgar score at 5 minutes \u0026lt; 7, admission to a neonatal care unit, respiratory distress syndrome and early neonatal death.\u003c/p\u003e\n\u003cp\u003ePlacental lesions were defined by the presence of at least three maternal vascular malperfusion lesions or by the combination of maternal and fetal vascular malperfusion lesions (MVM and FVM).\u003c/p\u003e\n\u003cp\u003eThe secondary objective was to identify maternal factors associated with maternal vascular malperfusion lesions in patients who underwent cesarean delivery for chronic fetal hypoxia.\u003c/p\u003e\n\u003cp\u003eMaternal vascular malperfusion was defined by the presence of at least three of the following lesions: placental infarction, basal decidual hematoma, thrombosis, accelerated villous maturation and decidual arteriopathy.\u003c/p\u003e\n\u003ch2\u003eVariables collected\u003c/h2\u003e\n\u003cp\u003eThe collected variables included :\u0026nbsp;\u003c/p\u003e\n\u003cul class=\"decimal_type\"\u003e\n \u003cli\u003ematernal characteristics :\u0026nbsp;maternal age, body mass index at the beginning of pregnancy, parity, smoking status, self-reported substance use (alcohol, cocaine, cannabis), obstetric history including recurrent miscarriage, intrauterine fetal death, fetal growth restriction below the 3rd percentile, preeclampsia, retroplacental hematoma diagnosed on placental examination, or emergency cesarean delivery, medical history including sickle cell disease, chronic anemia, severe asthma, chronic obstructive pulmonary disease, cardiac disease, preexisting diabetes, and chronic hypertension, pregnancy-related conditions including gestational diabetes, gestational hypertension, preeclampsia, or fetal growth restriction below the 3rd percentile ;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003edelivery characteristics : mode of delivery and gestational age at delivery ;\u003c/li\u003e\n \u003cli\u003eneonatal characteristics : live birth or stillbirth, sex, birth weight and percentile, Apgar score at 5 minutes \u0026lt; 7, arterial pH \u0026lt; 7.10, delta pH \u0026lt; 0.10, lactate level, base excess, arterial pO₂, arterial pCO₂, admission to neonatal intensive care unit, respiratory distress syndrome, necrotizing enterocolitis, acute kidney injury, hypoxic\u0026ndash;ischemic brain injury and early neonatal death ;\u003c/li\u003e\n \u003cli\u003eplacental characteristics were assessed according to the Amsterdam consensus (12).\u003cul\u003e\n \u003cli\u003eMacroscopic features included : placental weight, cord insertion type, number of umbilical vessels, placental configuration and marginal decidual hematoma\u003c/li\u003e\n \u003cli\u003eHistological features included : maternal vascular malperfusion lesions (placental infarction, basal decidual hematoma, accelerated villous maturation, and decidual arteriopathy including fibrinoid necrosis, spiral artery atherosis, and arterial thrombosis), fetal vascular malperfusion lesions (fetal circulation thrombosis and avascular villi), inflammatory lesions (chronic villitis, chronic intervillositis, acute chorioamnionitis, or fetal inflammatory response) and other lesions (chorangiosis, erythroblastosis, and massive perivillous fibrin deposition).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eBody mass index was calculated as weight in kilograms divided by height in meters squared (kg/m\u0026sup2;).\u003c/p\u003e\n\u003cp\u003eGestational age was estimated using crown\u0026ndash;rump length before 14 weeks of gestation (17) and head circumference after 14 weeks, according to national recommendations.\u003c/p\u003e\n\u003cp\u003eSubstance use was self-reported by the patients.\u003c/p\u003e\n\u003cp\u003eMaternal chronic anemia was defined according to World Health Organization criteria, with moderate to severe anemia corresponding to hemoglobin levels below 10 g/dL (18).\u003c/p\u003e\n\u003cp\u003eFetal biometric percentiles were calculated using World Health Organization growth standards (19), and birth weight percentiles were determined using AUDIPOG growth charts (20).\u003c/p\u003e\n\u003cp\u003ePreeclampsia was defined according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) as blood pressure \u0026ge;140/90 mmHg after 20 weeks of gestation associated with maternal and/or fetal complications, even in the absence of proteinuria \u0026ge;0.30 g/L.\u003c/p\u003e\n\u003cp\u003eGestational hypertension was defined as blood pressure \u0026ge;140/90 mmHg during pregnancy (21).\u003c/p\u003e\n\u003cp\u003eAccording to CNGOF guidelines, gestational diabetes was defined by fasting plasma glucose \u0026ge;0.92 g/L in the first trimester, or abnormal values during a 75-g oral glucose tolerance test performed between 24 and 28 weeks of gestation (22).\u003c/p\u003e\n\u003cp\u003eRespiratory distress syndrome was diagnosed based on clinical and radiographic signs of surfactant deficiency (23).\u003c/p\u003e\n\u003cp\u003eHypoxic\u0026ndash;ischemic brain injury was diagnosed based on brain magnetic resonance imaging (24).\u003c/p\u003e\n\u003cp\u003eNecrotizing enterocolitis was diagnosed based on a combination of clinical, biological, and radiological findings (25).\u003c/p\u003e\n\u003cp\u003eAccording to the World Health Organization, early neonatal death was defined as death occurring within the first 7 days of life.\u003c/p\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eQuantitative variables were described using median and interquartile range [Q1\u0026ndash;Q3] and compared between groups using the Mann\u0026ndash;Whitney test. Categorical variables were presented as frequencies and percentages. Comparisons between groups were performed using the Pearson Chi-square test or the Fisher exact test when expected cell counts were less than five. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThis study received ethical approval from the Ethics Committee for Research in Obstetrics and Gynecology (IRB CEROG 2025-OBS-0204), which exempts it from the requirement to obtain informed consent (26). Patients were informed about the use of their data and had the option to object. The study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween May 1, 2023, and November 30, 2025, a total of 1,389 cesarean deliveries were performed at the University Hospital of Reims. Among these, 36 were performed for fetal heart rate abnormalities suggestive of chronic fetal hypoxia, representing 2.6% of all cesarean deliveries.\u003c/p\u003e\n\u003cp\u003eTwo patients were excluded because the placenta had not been sent for histopathological examination. A total of 34 patients were therefore included and divided into two groups according to the presence or absence of placental lesions. The flow diagram is presented in Figure 1.\u003c/p\u003e\n\u003cp\u003eThe general characteristics of the study population are presented in Table 1. The median maternal age was 28 years [26\u0026ndash;36]. Obesity at the beginning of pregnancy was observed in 29.4% (n = 10) of patients, and active smoking in 32.3% (n = 11). During pregnancy, 38.2% (n = 13) developed preeclampsia, 17.6% (n = 6) had gestational diabetes, and 47.1% (n = 16) of fetuses had an estimated fetal weight at or below the 3rd percentile. Nearly all patients (97.1%, n = 33) delivered by cesarean section at a median gestational age of 30 weeks [28\u0026ndash;36].\u003c/p\u003e\n\u003cp\u003ePlacental lesions are summarized in Table 2. Among macroscopic abnormalities, the most frequent finding was placental hypotrophy, observed in 38.2% (n = 13) of cases, followed by marginal cord insertion (20.5%, n = 7) and velamentous cord insertion (5.9%, n = 2).\u003c/p\u003e\n\u003cp\u003eOn histological examination, maternal vascular malperfusion lesions were predominant. Placental infarctions were observed in 64.7% (n = 22) of patients, decidual arteriopathy in 61.8% (n = 21), and accelerated villous maturation in 41.2% (n = 14). Fetal vascular malperfusion lesions were also identified, including fetal vascular thrombosis (11.8%, n = 4) and avascular villi (17.6%, n = 6). Among inflammatory lesions, acute chorioamnionitis was the most frequent, observed in 20.6% (n = 7) of cases.\u003c/p\u003e\n\u003cp\u003eNeonatal outcome analysis was performed on 32 patients due to two fetal deaths (one intrauterine fetal death in the placental lesion group and one stillbirth in the group without placental lesions).\u003c/p\u003e\n\u003cp\u003eAmong the 34 fetuses, 32 were born alive (Table 3). The median gestational age at birth was lower in the placental lesion group (28 weeks [26.5\u0026ndash;37] vs 32 weeks [30\u0026ndash;36]), although this difference was not statistically significant (p = 0.17). The median birth weight was lower in the placental lesion group (1,010 g [570\u0026ndash;2,150]) compared with the group without placental lesions (1,700 g [1,185\u0026ndash;2,498]), with a trend toward statistical significance (p = 0.06). Similarly, a higher proportion of newborns with birth weight at or below the 3rd percentile was observed in the placental lesion group (38.5% [5/13] vs 9.5% [2/21], p = 0.08).\u003c/p\u003e\n\u003cp\u003eThe composite adverse neonatal outcome occurred in 81.8% (27/33) of newborns, with no significant difference between groups (91.6% [11/12] in the placental lesion group vs 76.2% [16/21] in the group without placental lesions, p = 0.37):\u003c/p\u003e\n\u003cul class=\"decimal_type\"\u003e\n \u003cli\u003eAn Apgar score \u0026lt;7 at 5 minutes was observed in 31.2% (10/32) of cases and was more frequent in the group without placental lesions, without statistical significance (25% [3/12] vs 35% [7/20], p = 0.70).\u003c/li\u003e\n \u003cli\u003eArterial pH \u0026lt;7.10 was observed in 25% (8/32) of liveborn infants and was more frequent in the placental lesion group, without statistical significance (33.3% [4/12] vs 20% [4/20], p = 0.43).\u003c/li\u003e\n \u003cli\u003eAdmission to neonatal care occurred in 78.1% (25/32) of liveborn infants and was slightly more frequent in the placental lesion group, without statistical significance (83.3% [10/12] vs 75% [15/20], p = 0.68).\u003c/li\u003e\n \u003cli\u003eRespiratory distress syndrome was observed in 56.2% (18/32) of cases and did not differ between groups (58.3% [7/12] vs 55% [11/20], p \u0026gt; 0.99).\u003c/li\u003e\n \u003cli\u003eEarly neonatal death occurred in 12.1% (4/33) of cases and was more frequent in the placental lesion group, without statistical significance (16.6% [2/12] vs 9.5% [2/21], p = 0.61).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNo statistically significant differences were observed for umbilical cord arterial and venous blood parameters, including delta pH \u0026ge;7.10 (p = 0.62), median lactate level (p = 0.42), lactate \u0026ge;6 mmol/L (p = 0.28), median base excess (p = 0.58), base excess \u0026le; \u0026minus;8 mmol/L (p \u0026gt; 0.99), median arterial pO₂ (p = 0.74), arterial pO₂ \u0026le;15 mmHg (p = 0.68), median arterial pCO₂ (p = 0.78), and arterial pCO₂ \u0026ge;65 mmHg (p = 0.64).\u003c/p\u003e\n\u003cp\u003eRegarding neonatal complications, necrotizing enterocolitis occurred in one newborn (3.1%, 1/32), in the placental lesion group (8.3% [1/12] vs 0%, p = 0.37). No cases of acute kidney injury were observed. Brain lesions were identified in 12.5% (4/33) of cases, with no significant difference between groups (p \u0026gt; 0.99).\u003c/p\u003e\n\u003cp\u003eMaternal characteristics were compared according to the presence or absence of maternal vascular malperfusion lesions (Table 4). No statistically significant association was found between maternal vascular malperfusion and the maternal characteristics studied, including maternal age \u0026gt;40 years (p \u0026gt; 0.99), body mass index at the beginning of pregnancy (p \u0026gt; 0.99), nulliparity (p = 0.18), multiparity (p = 0.37), smoking (p = 0.63), preexisting diabetes (p \u0026gt; 0.99) or gestational diabetes (p = 0.56), chronic hypertension (p \u0026gt; 0.99) or gestational hypertension (p = 0.17), preeclampsia (p = 0.65), estimated fetal weight \u0026le;3rd percentile (p = 0.32), or obstetric history such as recurrent miscarriage (p \u0026gt; 0.99), fetal growth restriction \u0026le;3rd percentile (p = 0.32), and emergency cesarean delivery (p \u0026gt; 0.99).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe various analyses performed in our study showed a population characterized by a high rate of prematurity and a high prevalence of maternal vascular risk factors. Placental lesions were largely dominated by maternal vascular malperfusion (MVM) lesions, particularly placental infarctions and decidual arteriopathy. Despite this high prevalence of histologic lesions, no statistically significant association was found between the presence of placental lesions and immediate neonatal outcome, assessed using a composite endpoint including both biological and clinical parameters. However, a trend toward lower birth weight and a higher proportion of newborns with birth weight below the 3rd percentile was observed in the presence of placental lesions.\u003c/p\u003e\n\u003cp\u003eSeveral studies have described factors associated with placental insufficiency, including maternal age over 35 years, smoking, obesity, preeclampsia, and gestational diabetes (27). In our population, although the median maternal age was 28 years, the high frequency of several vascular risk factors, particularly preeclampsia (38.2%), smoking (32.3%), and obesity (29.4%), appears consistent with the pathophysiologic mechanisms described in the literature.\u003c/p\u003e\n\u003cp\u003eThe marked prematurity observed in our study, with a median gestational age of 30 weeks, may be explained by the context of chronic fetal hypoxia secondary to placental insufficiency, which has been described as a progressive condition that may lead to a decision for preterm delivery (28). In addition, nearly half of the fetuses had an estimated fetal weight below the 3rd percentile during pregnancy (47%), suggesting that suspicion of fetal growth restriction was common in this population.\u003c/p\u003e\n\u003cp\u003eRegarding the placental lesions observed in our study, they were predominantly represented by maternal vascular malperfusion lesions, including placental infarctions (64.7%), decidual arteriopathy (61.8%), and accelerated villous maturation (41.2%). Fetal vascular malperfusion lesions were less frequent and do not appear to represent the main mechanism of chronic placental insufficiency in our population. Indeed, Redline et al. described maternal vascular malperfusion lesions as the typical histopathologic correlate of chronic placental insufficiency, in contrast to fetal vascular malperfusion lesions, which are more often associated with acute mechanisms, and this appears consistent with our findings (15).\u003c/p\u003e\n\u003cp\u003eInflammatory lesions were less commonly observed in our study. This low frequency is consistent with the Amsterdam Placental Workshop Group consensus, which considers inflammatory lesions as distinct entities and not the usual mechanism underlying chronic placental insufficiency (12).\u003c/p\u003e\n\u003cp\u003eSome placental structural abnormalities, such as marginal cord insertion (20.5%) and velamentous cord insertion (5.9%), were observed in our population. These abnormalities have been described in the literature as potentially contributing to impaired maternal\u0026ndash;fetal exchange, without being sufficient on their own to account for chronic fetal hypoxia (14).\u003c/p\u003e\n\u003cp\u003eOur data did not show any association between the presence of placental lesions and adverse neonatal outcome as assessed by the composite endpoint, although a relationship cannot be formally excluded given the limited sample size. However, interpretation of this endpoint is limited by its heterogeneity and by the high frequency of some variables, such as admission to neonatal care and respiratory distress syndrome, both of which are closely related to prematurity.\u003c/p\u003e\n\u003cp\u003eIt may therefore be more relevant to interpret the results on a variable-by-variable basis.\u003c/p\u003e\n\u003cp\u003eThe rate of arterial pH \u0026lt; 7.10 did not differ significantly between the two groups. The same was true for all acid\u0026ndash;base balance parameters, including \u0026Delta;pH, lactate levels, base excess, and arterial pO₂ and pCO₂.\u003c/p\u003e\n\u003cp\u003eInterpretation of umbilical cord blood samples relies on the distinction between respiratory acidosis and metabolic acidosis. Respiratory acidosis results from acute CO₂ accumulation, most often related to a sudden intrapartum event, and is associated with elevated pCO₂ and generally preserved base excess. In contrast, metabolic acidosis reflects prolonged tissue hypoxia leading to increased lactate production and negative base excess. A trend toward higher lactate levels was observed in the presence of placental lesions, although this did not reach statistical significance (6.0 [2.8\u0026ndash;8.1] vs 4.3 [2.5\u0026ndash;7.3], p = 0.42). Lactate is a sensitive marker of anaerobic metabolism and may increase in situations of prolonged hypoxia even in the absence of severe metabolic acidosis (29).\u003c/p\u003e\n\u003cp\u003eGiven the small sample size of our population, these findings may suggest that in cases of chronic hypoxia, fetal adaptive mechanisms and obstetric management allowed delivery to occur before major metabolic deterioration developed.\u003c/p\u003e\n\u003cp\u003eUmbilical cord blood gas results should be interpreted with caution, as pH alone is not a specific marker of hypoxia or neurological severity (30). Moreover, in chronic hypoxia, adaptive mechanisms may allow relative preservation of acid\u0026ndash;base balance until birth (29). These mechanisms include redistribution of blood flow to vital organs (brain-sparing effect), reduced oxygen consumption due to decreased fetal movements and slowed growth, increased oxygen-carrying capacity, and hemodynamic adaptations.\u003c/p\u003e\n\u003cp\u003eThe rate of Apgar score \u0026lt; 7 at 5 minutes did not differ significantly according to the presence or absence of placental lesions. The 5-minute Apgar score mainly reflects immediate cardiorespiratory adaptation of the newborn and is not a specific marker of the type of intrapartum hypoxia (31); it may also be influenced by other maternal or fetal factors.\u003c/p\u003e\n\u003cp\u003eNo difference in fetal sex distribution was observed between groups. Although sex-related differences in neonatal morbidity and mortality have been described, particularly in settings of acute hypoxia and extreme prematurity, these findings do not appear to be directly applicable to our population with chronic hypoxia (32). In addition, the limited size of our cohort reduced the statistical power of this analysis and does not allow a sex-related difference to be formally excluded.\u003c/p\u003e\n\u003cp\u003eThe rate of admission to neonatal care was high in both groups and was slightly higher in the placental lesion group, without a statistically significant difference (83.3% vs 75%, p = 0.68). Prematurity is the main indication for neonatal unit admission, with a marked increase in the need for specialized care among newborns delivered before 32 weeks of gestation (33,34). In our cohort, the median gestational age below 32 weeks may therefore explain the high admission rate observed, independently of placental abnormalities.\u003c/p\u003e\n\u003cp\u003eThe high frequency of respiratory distress syndrome observed in our cohort, with no significant difference between groups, is also consistent with the degree of prematurity of the newborns, since surfactant deficiency due to pulmonary immaturity is the major determinant of this complication (35).\u003c/p\u003e\n\u003cp\u003eFinally, the rate of early neonatal death also did not differ between groups. The Amsterdam Placental Workshop Group consensus emphasizes the association of MVM lesions with hypertensive disorders of pregnancy and stillbirth, but also states that lesion severity, extent, and multifocality are more prognostically relevant than their mere presence (12). However, these characteristics were not assessed in our study.\u003c/p\u003e\n\u003cp\u003eThe lack of statistical significance for these variables may be explained by the limited sample size, as well as by the selection of our population, which consisted of patients who underwent cesarean delivery for fetal heart rate abnormalities suggestive of chronic hypoxia, likely before severe metabolic decompensation occurred. In our center, however, obstetric management is not standardized and also depends on human and organizational factors.\u003c/p\u003e\n\u003cp\u003eInterpretation of neonatal outcome must also take into account antenatal therapies that may have modified immediate prognosis. Antenatal corticosteroid administration is known to significantly reduce respiratory morbidity in preterm infants, particularly respiratory distress syndrome, as well as neonatal mortality (36). Similarly, antenatal magnesium sulfate administered in the setting of threatened preterm birth is associated with a neuroprotective effect, especially in very preterm infants (37). The absence of systematic data on these therapies in our cohort does not allow evaluation of their potential impact. However, it is likely that they contributed to limiting the immediate clinical expression of chronic hypoxia.\u003c/p\u003e\n\u003cp\u003eThus, although the presence of placental lesions does not appear to significantly influence immediate neonatal status, their impact may be expressed differently, particularly through fetal growth parameters. Indeed, our data suggest a lower birth weight and a higher proportion of newborns with birth weight below the 3rd percentile in the group with placental lesions.\u003c/p\u003e\n\u003cp\u003eThese findings are consistent with the predominance of maternal vascular malperfusion lesions observed in our study, mainly represented by placental infarctions, decidual arteriopathy, and accelerated villous maturation. These lesions reflect chronic impairment of spiral artery remodeling and a progressive reduction in uteroplacental perfusion, resulting in decreased oxygen and nutrient delivery to the fetus. This progressive mechanism is associated with chronic placental insufficiency and fetal growth restriction (12,38,39).\u003c/p\u003e\n\u003cp\u003eInterpretation of these findings must nevertheless take gestational age into account, as the median gestational age was lower in the placental lesion group (28 vs 32 weeks, p = 0.17). However, the high proportion of newborns with birth weight below the 3rd percentile in the placental lesion group suggests a specific effect beyond gestational age alone. This finding is pathophysiologically consistent and suggests that the main clinical expression of these placental lesions lies in progressive fetal growth impairment rather than in acute hypoxic decompensation at birth.\u003c/p\u003e\n\u003cp\u003eThe secondary objective of this study was to identify maternal factors associated with maternal vascular malperfusion lesions. No variable showed a statistically significant association with the presence of these lesions. This lack of significance must be interpreted in light of the very small size of the relevant subgroup (n = 6), which greatly limited the power of the analysis.\u003c/p\u003e\n\u003cp\u003eNevertheless, several trends appear consistent with the pathophysiology described in the literature (40), particularly for preeclampsia, which was more frequently observed in cases of maternal vascular malperfusion (50% vs 35.7%, p = 0.65). Similarly, a history of fetal growth restriction appeared more frequent in the lesion group (16.6% vs 3.6%, p = 0.32), which may reflect an underlying persistent maternal vascular predisposition. In contrast, some variables such as smoking, advanced maternal age, obesity, diabetes, or hypertension did not show concordant trends, which may be explained by the small sample size and clinical heterogeneity of the study population.\u003c/p\u003e\n\u003cp\u003eThus, although our study does not demonstrate a statistically significant association, the observed trends are in keeping with the known pathophysiology linking vascular disorders and placental lesions.\u003c/p\u003e\n\u003cp\u003eThe main limitation of our study was the small sample size, with only 34 patients included, which may be explained by the rarity of chronic fetal hypoxia (2.9% of cesarean deliveries in our center). The single-center design is also a limitation. However, this methodological choice ensured homogeneity of obstetric practices and standardization of histopathologic analyses, which would be difficult to reproduce in a multicenter setting.\u003c/p\u003e\n\u003cp\u003eIn addition, our population was potentially selected, since it included only patients who underwent cesarean delivery for fetal heart rate abnormalities suggestive of chronic hypoxia. Patients with unrecognized chronic hypoxia or chronic hypoxia not leading to cesarean delivery were not represented, which may have introduced selection bias. However, although management of chronic fetal hypoxia is not protocolized in our center, practices are highly homogeneous, making major selection bias less likely. Furthermore, regular training in fetal heart rate interpretation is provided in the department, including teaching sessions and e-learning modules, which likely contributes to harmonization of clinical practice.\u003c/p\u003e\n\u003cp\u003eFinally, the use of a composite adverse neonatal outcome may be debated. Combining biological and clinical parameters of different natures makes this endpoint heterogeneous, and some components may strongly influence its frequency, thereby limiting the specificity of the analysis.\u003c/p\u003e\n\u003cp\u003eThe literature specifically addressing chronic fetal hypoxia remains limited, as most studies group fetal heart rate abnormalities together without distinguishing between acute and chronic mechanisms. Our focused work on this topic therefore represents an original contribution.\u003c/p\u003e\n\u003cp\u003eSystematic histopathologic examination of the placentas is a major methodological strength. Examination was performed by a fetopathologist according to the criteria of the international Amsterdam consensus, ensuring a standardized and reproducible analysis. Among the 36 patients initially identified, two were excluded because no histopathologic examination had been performed, thereby ensuring homogeneity of the histologic data analyzed.\u003c/p\u003e\n\u003cp\u003eThis study allowed a better characterization of the placental lesion profile associated with chronic fetal hypoxia. It highlights the predominance of maternal vascular malperfusion lesions, consistent with the presence of an underlying maternal vascular predisposition.\u003c/p\u003e\n\u003cp\u003eIn addition, our results suggest that the main clinical expression of these histologic lesions is fetal growth restriction. This observation contributes to a better understanding of fetal adaptive mechanisms in the setting of chronic hypoxia.\u003c/p\u003e\n\u003cp\u003eThe predominance of maternal vascular malperfusion lesions observed in our cohort suggests the presence of an underlying maternal vascular background that may recur in a subsequent pregnancy. Christians et al. suggest that obstetric complications such as preeclampsia, fetal growth restriction, or prematurity tend to recur from one pregnancy to another, independently of placental histologic lesions (41). These data suggest that placental malperfusion may be the expression of an overall maternal predisposition. McBride et al. showed that maternal vascular malperfusion lesions are associated with preexisting or early-pregnancy maternal cardiovascular and thrombogenic profiles, further supporting the hypothesis of an underlying maternal vascular background (42).\u003c/p\u003e\n\u003cp\u003eAlthough no current recommendation supports aspirin therapy based solely on placental histologic findings, identification of malperfusion lesions may help refine risk stratification in a future pregnancy, in addition to recognized clinical risk factors. Current international recommendations support administration of low-dose aspirin (100\u0026ndash;150 mg/day), started early between 11 and 14 weeks of gestation and continued until 34\u0026ndash;36 weeks, in patients at high risk of preeclampsia (43,44).\u003c/p\u003e\n\u003cp\u003eIn addition, placental examination could be incorporated into a secondary prevention strategy, by optimizing modifiable cardiovascular risk factors before conception. Smoking cessation is a major target, as tobacco exposure is associated with impaired uteroplacental perfusion and an increased risk of fetal growth restriction (45). Likewise, management of obesity, optimization of blood pressure in patients with chronic hypertension, and glycemic control in patients with diabetes may help reduce the risk of vascular complications during pregnancy.\u003c/p\u003e\n\u003cp\u003eThe findings of this study are limited to evaluation of early neonatal outcomes. The absence of a significant association between placental lesions and immediate neonatal status does not preclude a potential impact of chronic hypoxia on later development.\u003c/p\u003e\n\u003cp\u003eIndeed, fetal growth restriction related to placental insufficiency, birth weight, and gestational age are major determinants of long-term outcome (46). Several studies have shown that chronic placental insufficiency is part of the developmental origins of adult disease framework, including hypertension, coronary artery disease, kidney disease, type 2 diabetes, metabolic syndrome, and pulmonary disease (46\u0026ndash;51).\u003c/p\u003e\n\u003cp\u003eBeyond metabolic and cardiovascular consequences, data also suggest that chronic hypoxia associated with fetal growth restriction may impair brain maturation, even in the absence of severe acute asphyxia at birth. Miller et al. showed that chronic placental insufficiency is associated with white matter alterations, abnormal myelination, and changes in neuronal connectivity. These abnormalities appear to be related to disrupted organization of brain networks rather than massive neuronal loss (52).\u003c/p\u003e\n\u003cp\u003eBrain imaging studies in newborns with fetal growth restriction have demonstrated reduced brain volumes and abnormalities of white matter microstructure, which may later be associated with cognitive impairment (53).\u003c/p\u003e\n\u003cp\u003eTherefore, the absence of immediate neonatal complications in our cohort does not rule out delayed neurodevelopmental consequences. Longitudinal studies including extended neurodevelopmental follow-up would be necessary to assess the long-term consequences of chronic fetal hypoxia associated with placental malperfusion lesions in our population.\u003c/p\u003e\n\u003cp\u003eThe limited sample size of our cohort does not allow formal exclusion of a moderate association. Larger multicenter studies, with multivariable analyses adjusted for gestational age, birth weight, and maternal comorbidities, are needed to better define the prognostic role of placental lesions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlighted the predominance of maternal vascular malperfusion lesions and their consequences, particularly with respect to birth weight. Our findings suggest that the clinical expression of chronic fetal hypoxia is not necessarily immediate. However, the absence of an immediate neonatal impact does not rule out potential longer-term consequences, particularly on neurodevelopment.\u003c/p\u003e\n\u003cp\u003ePlacental examination may therefore contribute to a better understanding of the underlying mechanisms and help refine management in subsequent pregnancies, in addition to established clinical risk factors.\u003c/p\u003e\n\u003cp\u003eThe limited sample size of our cohort does not allow a moderate association to be formally excluded. Larger multicenter studies, with multivariable analyses adjusted for gestational age, birth weight, and maternal comorbidities, are needed to better define the prognostic role of placental lesions.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCNGOF: French National College of Gynecologists and Obstetricians\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;WHO: World Health Organization\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;BMI: Body Mass Index\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;FHR abnormality: Fetal Heart Rate Abnormality\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;MVM: Maternal Vascular Malperfusion\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;FVM: Fetal Vascular Malperfusion\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;FGR: Fetal Growth Restriction\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;EFW: Estimated Fetal Weight\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;ISSHP: International Society for the Study of Hypertension in Pregnancy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate : This study received approval from the Ethics Committee for Research in Gynecology and Obstetrics under reference IRB CEROG 2025-OBS-0204. Patient data were anonymized prior to statistical analysis. Patients were informed of the use of their data for research purposes and were given the opportunity to oppose the use of their data.\u003c/p\u003e\n\u003cp\u003eConsent for publication : Patients were informed of the use of their data for research purposes and were given the opportunity to oppose the use of their data.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests : The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding : not applicable\u003c/p\u003e\n\u003cp\u003eAuthors contributions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- M.V : Conceptualization (supporting), Formal Analysis, Investigation (lead), Methodology (supporting), Project Administration (lead), Writing \u0026ndash; Original Draft Preparation (lead), Writing \u0026ndash; Review ; Editing\u003c/p\u003e\n\u003cp\u003e- C.J : Investigation (supporting), Writing \u0026ndash; Review\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- R.G : Conceptualization (supporting), Writing \u0026ndash; Review (equal)\u003c/p\u003e\n\u003cp\u003e- G.L :Writing \u0026ndash; Review (equal)\u003c/p\u003e\n\u003cp\u003e- O.G : Writing \u0026ndash; Review (equal)\u003c/p\u003e\n\u003cp\u003e- M.S : Conceptualization (lead), Methodology (supporting), Writing \u0026ndash; Review (equal)\u003c/p\u003e\n\u003cp\u003e- B.B : Conceptualization (supporting), Methodology (lead), Writing \u0026ndash; Review (equal)\u003c/p\u003e\n\u003cp\u003eAcknowledgements : not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eDescourvi\u0026egrave;res L, Mentele J, Guittet L, Vardon D, Marret S, Riethmuller D, et al. 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Am J Obstet Gynecol. 2003;189(4):939-43.\u003c/li\u003e\n \u003cli\u003eBaschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol. 2011;37(5):501-14.\u003c/li\u003e\n \u003cli\u003eBarker DJ. The developmental origins of adult disease. J Am Coll Nutr. 2004;23(6 Suppl):588S-95S.\u003c/li\u003e\n \u003cli\u003eCrispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, Le Noble F, et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010;121(22):2427-36.\u003c/li\u003e\n \u003cli\u003eLuyckx VA, Brenner BM. Birth weight, malnutrition and kidney-associated outcomes-a global concern. Nat Rev Nephrol. 2015;11(3):135-49.\u003c/li\u003e\n \u003cli\u003eHales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001;60:5-20.\u003c/li\u003e\n \u003cli\u003eStocks J, Sonnappa S. Early life influences on the development of chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2013;7(3):161-73.\u003c/li\u003e\n \u003cli\u003eTolcos M, Rees S. Chronic placental insufficiency in the fetal guinea pig affects neurochemical and neuroglial development but not neuronal numbers in the brainstem: a new method for combined stereology and immunohistochemistry. J Comp Neurol. 1997;379(1):99-113.\u003c/li\u003e\n \u003cli\u003eBorradori Tolsa C, Zimine S, Warfield SK, Freschi M, Sancho Rossignol A, Lazeyras F, et al. Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction. Pediatr Res. 2004;56(1):132-8.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"513\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99.8051%;\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003e- Maternal characteristics\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 388px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e(N = 34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eAge (years) \u0026ndash; median [Q1\u0026ndash;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e28 [26-36]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eAge \u0026ge; 40 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eBMI (kg/m\u0026sup2;) at the beginning of pregnancy \u0026ndash; n (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026lt; 18 (kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;18-24,9 (kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e16 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;25-29,9 (kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e7 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;30-34,9 (kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;35-39,9 (kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e4 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026gt; 40 (kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e4 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eBMI* \u0026ge; 30 kg/m\u0026sup2; at the beginning of pregnancy \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e10 (29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eParity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Nulliparous \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e19 (55.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Multiparous \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e15 (44.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eSmoking during pregnancy \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e11 (32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eOther substance use \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eMedical history \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Sickle cell disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Chronic anemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Severe respiratory disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Maternal cardiac disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Preexisting diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Chronic hypertension\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eObstetric history \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026ge;3 early miscarriages\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Intrauterine fetal death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Placental abruption\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Preeclampsia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;FGR\u0026sect; \u0026le; 3rd percentile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Previous cesarean delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eCurrent pregnancy \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Gestational diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e6 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Isolated gestational hypertension\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Preeclampsia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e13 (38.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Estimated fetal weight \u0026le; 3rd percentile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e16 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eMode of delivery \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Cesarean delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e33 (97.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Vaginal delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 388px;\"\u003e\n \u003cp\u003eGestational age at delivery (weeks) \u0026ndash; median [Q1\u0026ndash;Q3]*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 125px;\"\u003e\n \u003cp\u003e30 [28-36]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*BMI: body mass index; \u0026sect; FGR: fetal growth restriction.\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"587\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 587px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e \u0026ndash; Placental lesions identified in pregnancies complicated by chronic fetal hypoxia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 363px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 363px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e(N = 34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eMacroscopic findings\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003ePlacental hypotrophy \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e13 (38.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eMarginal decidual hematoma \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eUmbilical cord abnormalities \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eMarginal cord insertion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e7 (20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eVelamentous cord insertion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e2 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eSingle umbilical artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003ePlacental configuration abnormalities \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eBilobed placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eCircumvallate placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eHistological findings\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eMaternal vascular malperfusion lesions \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003ePlacental infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e22 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eBasal decidual hematoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e3 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eAccelerated villous maturation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e14 (41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eDecidual arteriopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e21 (61.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eFetal vascular malperfusion lesions \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eFetal vascular thrombosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e4 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eAvascular villi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e6 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eChronic inflammatory lesions \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eChronic villitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eChronic intervillositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eAcute inflammatory lesions \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eAcute chorioamnionitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e7 (20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eFetal inflammatory response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e3 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eOther unclassified lesions \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eChorangiosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e3 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eErythroblastosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e3 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 363px;\"\u003e\n \u003cp\u003eMassive perivillous fibrin deposition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 224px;\"\u003e\n \u003cp\u003e5 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"937\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 99.8933%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e \u0026ndash; Neonatal characteristics according to the presence or absence of placental lesions\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 416px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003ePlacental lesion group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003eNo placental lesion group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e(N = 34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e(N = 13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e(N = 21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eLive birth \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e32 (94.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e12 (92.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e20 (95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eGestational age at birth (weeks) \u0026ndash; median [Q1\u0026ndash;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e30 [28-36]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e28 [26.5-37]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e32 [30-36]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0,17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eFetal sex \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e15 (44.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e6 (46.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e9 (42.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e19 (55.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e7 (53.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e12 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eBirth weight (g) \u0026ndash; median [Q1\u0026ndash;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1360 [700-2275]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1010 [570-2150]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e1700 [1185\u0026ndash;2498]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eBirth weight \u0026le;3rd percentile \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e7 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e5 (38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e2 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eBirth weight \u0026ge;97th percentile \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eApgar score \u0026lt;7 at 5 minutes \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e10/32 (31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e3/12 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e7/20 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eArterial pH \u0026le;7.10 \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e8/32 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e4/12 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e4/20 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003e\u0026Delta;pH \u0026ge;0.10 \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4/32 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2/12 (16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e2/20 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eUmbilical cord lactate level (mmol/L) \u0026ndash; median [Q1\u0026ndash;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4.6 [2.5-8.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e6.0 [2.8\u0026ndash;8.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e4.3 [2.5\u0026ndash;7.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eLactate \u0026ge;6 mmol/L \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e12/32 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e6/12 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e6/20 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eUmbilical cord base excess (mmol/L) \u0026ndash; median [Q1\u0026ndash;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e-5.1 [-9.7 ; -2.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026minus;6.5 [\u0026minus;8.2 ; \u0026minus;2.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026minus;5.1 [\u0026minus;9.6 ; \u0026minus;3.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eBase excess \u0026le;\u0026minus;8 mmol/L \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e16/32 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e6/12 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e10/20 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eUmbilical cord arterial pO₂ (mmHg) \u0026ndash; median [Q1\u0026ndash;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e15 [10-62]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e14.5 [9.0\u0026ndash;41.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e16.5 [12.5\u0026ndash;65.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eArterial pO₂ \u0026le;15 mmHg \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e7/32 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2/12 (16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e5/20 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eUmbilical cord arterial pCO₂ (mmHg) \u0026ndash; median [Q1\u0026ndash;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e53 [46-63]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e55 [51.5\u0026ndash;61.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e52.5 [45.5\u0026ndash;62.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eArterial pCO₂ \u0026ge;65 mmHg \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e6/32 (18.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e3/12 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e3/20 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eAdmission to neonatal care \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e25/32 (78.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e10/12 (83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e15/20 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eRespiratory distress syndrome \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e18/32 (56.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e7/12 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e11/20 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eNecrotizing enterocolitis \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1/32 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1/12 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eAcute kidney injury \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0/32 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e0/12 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e0/20 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eHypoxic\u0026ndash;ischemic brain injury \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4/32 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1/12 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e3/20 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eEarly neonatal death \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4/33 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2/12 (16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e2/21 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 416px;\"\u003e\n \u003cp\u003eComposite adverse neonatal outcome \u0026ndash; n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e27/33 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e11/12 (91.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 162px;\"\u003e\n \u003cp\u003e16/21 (76.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"924\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 924px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e \u0026ndash; Maternal characteristics according to the presence or absence of maternal vascular malperfusion lesions\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 370px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003eMVM\u0026lowast; present\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003eNo MVM\u0026lowast;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 86px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e(N = 34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e(N = 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e(N =28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eMaternal age \u0026ge;40 years \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e1 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eBMI\u0026dagger; \u0026ge;30 kg/m\u0026sup2; at the beginning of pregnancy \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e11 (32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e9 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eNulliparity \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e19 (55.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e17 (60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eMultiparity \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e15 (44.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e4 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e11 (39.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eSmoking during pregnancy \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e11 (32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e10 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003ePreexisting diabetes \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e2 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eGestational diabetes \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e6 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e6 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eChronic hypertension\u0026Dagger; \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e1 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eIsolated gestational hypertension\u0026Dagger; \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003ePreeclampsia \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e13 (38.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e3 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e10 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eEstimated fetal weight \u0026le;3rd percentile \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e16 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e3 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e13 (46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eHistory of \u0026ge;3 early miscarriages \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e2 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eHistory of fetal growth restriction \u0026le;3rd percentile \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e1 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 370px;\"\u003e\n \u003cp\u003eHistory of cesarean delivery \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e2 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e2 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBMI: body mass index; \u0026lowast; MVM: maternal vascular malperfusion.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Fetal hypoxia, Placental insufficiency, Pregnancy outcome, Cesarean delivery, Fetal growth restriction","lastPublishedDoi":"10.21203/rs.3.rs-9096778/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9096778/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic fetal hypoxia is commonly associated with placental insufficiency and reflects prolonged impairment of uteroplacental perfusion. However, the relationship between fetal heart rate patterns suggestive of chronic hypoxia, placental histopathological lesions, and neonatal outcomes remains poorly documented. This study aimed to evaluate the association between placental lesions and early neonatal outcomes in pregnancies complicated by chronic fetal hypoxia and to identify maternal factors associated with maternal vascular malperfusion.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective single-center cohort study at the University Hospital of Reims, France. Patients who underwent cesarean delivery for fetal heart rate abnormalities suggestive of chronic fetal hypoxia at 24 weeks of gestation or later between May 2023 and November 2025 were included if placental histopathological examination had been performed. Patients were divided into 2 groups according to the presence or absence of placental lesions. Placental examination was classified according to the Amsterdam consensus. The primary outcome was a composite adverse neonatal outcome defined by at least one of the following: arterial pH below 7.10, Apgar score at 5 minutes below 7, admission to neonatal care, respiratory distress syndrome, or early neonatal death. Quantitative variables were compared using the Mann-Whitney test and categorical variables using the Pearson chi-square or Fisher exact test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThirty-four patients were included. No significant association was observed between placental lesions and the composite adverse neonatal outcome. The median gestational age at delivery was 30 weeks. Placental lesions were identified in 13 cases (38.2%). Histopathological abnormalities were predominantly represented by maternal vascular malperfusion lesions, including placental infarctions (64.7%) and decidual arteriopathy (61.8%). Newborns in the placental lesion group had a lower median birth weight than those without placental lesions (1,010 g vs 1,700 g; p\u0026thinsp;=\u0026thinsp;0.06) and a higher proportion of birth weight at or below the 3rd percentile (38.5% vs 9.5%; p\u0026thinsp;=\u0026thinsp;0.08). No significant differences were found for Apgar score, umbilical cord blood parameters, admission to neonatal care, respiratory distress syndrome, early neonatal death, or maternal factors associated with maternal vascular malperfusion.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eMaternal vascular malperfusion lesions were the predominant placental abnormalities in pregnancies complicated by chronic fetal hypoxia. Although they were not associated with worse immediate neonatal outcomes, they appeared to be associated with impaired fetal growth. Larger multicenter studies are needed to clarify the prognostic significance of placental lesions.\u003c/p\u003e","manuscriptTitle":"Placental lesions and neonatal outcomes in pregnancies complicated by chronic fetal hypoxia: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-04 09:47:54","doi":"10.21203/rs.3.rs-9096778/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-13T04:11:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T09:52:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"45308574015643699834139039616695101225","date":"2026-05-06T07:48:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-05T16:27:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-02T11:06:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6669848526913367318827164854613397813","date":"2026-05-02T10:29:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135763182704475960968369408354779864079","date":"2026-05-01T00:54:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"287499255996736447263487211847478696352","date":"2026-04-29T14:25:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"194363212639400728138582604048234802044","date":"2026-04-27T14:42:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"337157409605254554268708338021990789524","date":"2026-04-24T13:01:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-22T12:44:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-20T11:41:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-27T11:55:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-26T10:45:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2026-03-26T10:40:59+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":"91a5af07-c5de-4781-a3b1-8bd246b1e2ce","owner":[],"postedDate":"May 4th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-13T04:11:35+00:00","index":75,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T09:52:54+00:00","index":74,"fulltext":""},{"type":"reviewerAgreed","content":"45308574015643699834139039616695101225","date":"2026-05-06T07:48:33+00:00","index":73,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-05T16:27:54+00:00","index":72,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-02T11:06:57+00:00","index":69,"fulltext":""},{"type":"reviewerAgreed","content":"6669848526913367318827164854613397813","date":"2026-05-02T10:29:49+00:00","index":68,"fulltext":""},{"type":"reviewerAgreed","content":"135763182704475960968369408354779864079","date":"2026-05-01T00:54:07+00:00","index":67,"fulltext":""},{"type":"reviewerAgreed","content":"287499255996736447263487211847478696352","date":"2026-04-29T14:25:07+00:00","index":65,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T09:47:54+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-04 09:47:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9096778","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9096778","identity":"rs-9096778","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}