4.2. Comparison with Existing LiteratureIn line with our meta-analysis, other studies have shown a similar increase in CP [38,62]. After adjusting for confounding factors, Spinillo et al. [45] found that infants from pregnancies complicated by placental abruption were 3.9 times more likely than controls to have neonatal death or cerebral palsy. This finding was echoed in the long-term follow-up study conducted by Pariente et al. [24]. Infants born to mothers with placental abruption showed higher rates of cerebral palsy (0.73 vs. 0.10 per 1000 person-years) than the control group without abruption. Of all the selected studies, only Furukawa et al. [30] showed no significant difference in the incidence of cerebral palsy between the abruption and control groups.Several studies in the literature have shown a direct relationship between placental abruption and cerebral palsy [7,21]. The precipitating and pathologic factor contributing to the development of cerebral palsy is fetal acidemia, resulting from impaired gas exchange and endothelial dysfunction, as reflected by abnormal umbilical pH/cord gases. Placental abruption is associated with acidosis, impaired gas exchange and endothelial dysfunction [63]. Since neuronal tissue is sensitive to metabolic disturbances [64], placental abruption could lead to hypoxia, hypercapnia, and in turn, CP. Moreover, studies have shown lower umbilical cord blood pH after placental abruption in the CP group than in the non-CP group [22]. In cases with umbilical pH 65,66]. Acidemia (pH ≤ 7.0) [67] occurred in 114 of 168 (69.2%) cases of severe CP, and a majority of these were also pregnancies complicated by placental abruption [68]. Another report documented that more than half of all CP cases showed umbilical cord blood pH 69].Risk factors for abruption include maternal habits such as alcohol consumption and smoking during pregnancy, as well as multiparity and hypertensive disorders in pregnancy [70,71,72]. In particular, alcohol consumption (OR 3.38, 95% CI (2.01–5.68)), smoking during pregnancy (OR 3.50, 95% CI (1.32–9.25)), number of deliveries (OR 1.28, 95% CI (1.05–1.56)), and hypertensive disorders in pregnancy (OR 2.25, 95% CI (1.27–4.07) are significant risk factors for CP following placental abruption [22]. Moreover, heavy alcohol consumption may cause neurodevelopmental abnormalities, such as fetal alcohol syndrome and CP [73]. Smoking and hypertensive disorders also contribute to endothelial dysfunction [74,75] and uteroplacental insufficiency [76], potentially leading to higher rates of maternal, fetal, and infant mortality, and severe morbidity [77].Our meta-analysis did not show a difference in the odds of IVH. It is possible that this meta-analysis did not have sufficient power to detect statistical differences. Spinillo et al. [45] showed significantly higher risk of grades III and IV intraventricular hemorrhage in comparison with control subjects (OR 3.5; 95% CI, 1.01 to 12.2), and even after adjusting for confounding factors, the difference remained statistically significant (OR 4.8; 95% CI 1.2 to 19.3). However, two additional studies [30,50] that assessed severe IVH did not show a significant difference between the abruption and absence of abruption groups.Despite these findings, a previous study demonstrated a simultaneously high prevalence of low Apgar scores, prematurity, acidosis, and perinatal asphyxia, among IVH infants [45]. Moreover, among preterm infants born to mothers with placental abruption, there could have been differences in prenatal care received, differences in gestational age at birth, or complex vascular placental diseases, which could heighten the risk of IVH [78]. IVH can result from the interruption of maternal–fetal exchange, which impairs blood flow [79,80]. The presence of coagulation abnormalities associated with fetal asphyxia could also elevate the risk of IVH [79].We did not note any statistical difference in the odds of PVL between women with placental abruption. Two of our included studies reported no significant difference in PVL rates between the cases and controls [45,50]. However, histopathological lesions show disturbance of uteroplacental circulation, including placental abruption, and are more common in infants with PVL [81]. Only one study [46] documented HIE and showed that the development quotient of children in the study in their Gesell Developmental Scale was significantly lower in the placental abruption group than in the no-abruption group, indicative of greater neurological impairment.In contrast, a previous study reported higher occurrence of severe asphyxia in infants with PVL born to mothers with placental abruption, explaining how episodes of prolonged hypoxia result in severe metabolic acidosis, followed by higher rates of motor and cognitive deficits in surviving infants [82]. Gonen et al. found that severe neonatal morbidity (≥ 1 severe neonatal complications: seizures, IVH, HIE, PVL, blood transfusion, NEC, or death) was independently associated with early abruption (aOR = 5.3, 95% CI = 3.9–7.6), placental maternal vascular malperfusion (MVM) (aOR = 1.5, 95% CI = 1.2–1.9), and placental maternal inflammatory response (MIR) lesions (aOR = 1.9, 95% CI = 1.4–2.3) [83]. Early occurrence of abruption leads to higher rates of MVM, MIR and placental hemorrhage. In a setting of preeclampsia, other studies have suggested that MVM and MIR lesions are independently associated with lower gestational age at delivery and adverse neonatal outcomes, such as small-for-gestational age, cerebral morbidity or death [84,85]. Moreover, Sehgal et al. found that maternal vascular malperfusion, accelerated villous maturation, and fetal vascular malperfusion were features that were significantly more common in preterm fetal growth restriction (FGR) placentae than in preterm appropriately grown infants [86]. Preterm births have in turn been associated with long-term adverse neonatal outcomes, such as autism, HIE, and other neurodevelopmental disabilities [87,88,89,90]. 4.3. LimitationsAll studies in the meta-analysis were retrospective in nature and primarily relied on clinical diagnosis of placental abruption. Hence, exploration of additional variables or potential confounders, is not possible. In addition, there is no true gold standard for diagnosing placental abruption. As such, abruption was diagnosed differently across the studies, including referencing clinical diagnoses, ultrasonography, and histopathology findings. Hence, variation in the field makes it challenging to compare findings across studies and to make definitive clinical recommendations. In general, the prevalence of placental abruption is low [91], and the incidence of CP and neurological complication appears even lower. The attributable fraction for the abruption–neurological outcome association is likely very small with minimal population impact, given that abruption is unpreventable, and no existing interventions can treat it [38].There were more preterm births in women with placental abruption than without abruption; therefore, adjusting for lower gestational age (and thus prematurity) would have been ideal to accurately examine the impact of placental abruption on cerebral palsy. Only two of the eight studies had any follow-up on infants from pregnancies complicated by placental abruption. Therefore, these studies had a poor score on the Newcastle–Ottawa scale. The absence of follow-up is also a limitation since there is evidence of increased risk of neurodevelopmental abnormalities in childhood due to prenatal hypoxia during pregnancy [92]. Hence, it is likely that these studies may have underreported cerebral palsy or other neurodevelopmental outcomes. There was overlap of data (double counting) in two articles authored by the same research group [44,45]; however, we did not include both studies in the meta-analysis, as that would have skewed numbers and led to biased results. Instead, we only included one article [45], which had a robust number of controls, and whose cases of abruption were not divided according to clinical grade of IVH. Since our sample size was small, we were unable to perform subgroup analysis to examine confounders of interest such as maternal alcohol consumption, smoking, prematurity, and other parameters. Most of the data reported in our included studies were too variable, as indicated by high I2 in the meta-analysis. Therefore, more consistent measures to comprehensively analyze neurodevelopmental outcomes will be needed in future placental abruption studies.