Placental inflammatory response and association with the severity of neonatal hypoxic ischemic encephalopathy

Placental lesions are associated with worse neonatal outcomes, but their association with neonatal hypoxic-ischemic encephalopathy (HIE), including the full range of severity from mild to severe HIE, has not been well described.

To determine the association of acute and chronic placental lesions with mild versus moderate to severe HIE; secondarily, to assess the impact of multiple placental lesions on severity of HIE.

This retrospective study of prospectively collected data included neonates born at ≥36 weeks, with a birth weight of >1800 g, diagnosed with HIE between January 2012 and November 2022. The cohort was divided into those with mild versus moderate to severe HIE, based on the modified Sarnat staging. Placental histologic diagnoses were made according to the Amsterdam Placental Workshop Group Consensus Statement. Placental pathologic lesions were classified into acute inflammation with attention to stages and grades of maternal and fetal inflammatory responses (MIR and FIR, respectively), maternal vascular malperfusion, fetal vascular malperfusion, villitis of unknown etiology, and other lesions. Chi-square and Fisher's exact test were used to compare rates of placental pathologies between mild and moderate to severe HIE groups.

Of 394 neonates ≥36 weeks' gestation diagnosed with HIE, 172 had mild HIE and received supportive care, while 180 had moderate to severe HIE and underwent therapeutic hypothermia. 42 patients were excluded due to lack of placental pathology reports. FIR was significantly associated with moderate to severe HIE vs. mild HIE (53 % vs. 38 %, P < 0.01). Higher grade and stage of FIR was also associated with worse severity of HIE (moderate to severe HIE showed FIR stage ≥2 in 81 % and grade 2 in 15 % vs. 34 % and 3 % in those with mild HIE, respectively). MIR was diagnosed in more placentas from the moderate to severe HIE group (58 % vs. 47 %, P = 0.04) with higher stage and grade MIR in patients with moderate to severe HIE (86 % with MIR stage ≥2 and 19 % with MIR grade 2). High-grade (patchy/diffuse) chronic villitis was more prevalent in the moderate to severe HIE group vs. mild HIE group (18 % vs. 8 %, P < 0.01).

There is a higher prevalence of placental inflammatory lesions in neonates with moderate to severe HIE compared to those with mild HIE.