Hypertensive Disorders of Pregnancy Increase Neonatal Cerebral Regional Tissue Oxygen Saturation in the Early Postnatal Period: Partial Mediation by Preterm Birth

Yao Zhang^1,2Tong Yang^1,2Dengjun Liu^1,2Jiaxi Wu^1,2Yanxia Mao^1,2Dapeng Chen^1,2Jun Tang^1,2Yi Yang^1,2,3*Tao Xiong^1,2,4*

• ¹Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
• ²Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education, Chengdu, China
• ³Department of Pediatric Otolaryngology Head and Neck Surgery, West China Second University Hospital, Sichuan University, Chengdu, China
• ⁴Children's Medicine Key Laboratory of Sichuan Province, Chengdu, China

Objective: Hypertensive disorders of pregnancy (HDP) are closely related to placental disfunction and may association neonatal cerebral oxygenation. This study aimed to assess the correlation of maternal HDP on neonatal cerebral regional tissue oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE), and to determine whether preterm birth mediates these associations. Methods: An observational case-control study enrolled 16799 newborns as the basis for subsequent screening. Finally, 464 infants born to mothers exposed to HDP were selected as the case group, and 464 normal mothers were selected as the control group. Cerebral oxygenation was monitored weekly using near-infrared spectroscopy from birth until 28 days postnatally or discharge. crSO₂ values were recorded, and cFTOE was calculated at each time point. Generalized linear mixed models were employed to evaluate the association of HDP (and the subset of preeclampsia) with serial crSO₂ and cFTOE measurements. The mediation role of preterm birth was assessed using Model 4 of the SPSS PROCESS macro. Results: Neonates exposed to maternal HDP/preeclampsia showed significantly higher crSO2 (β=0.472, 95% CI: 0.122–0.823, p=0.008; β=0.625, 95% CI: 0.234–1.017, p=0.002, respectively) and lower cFTOE (β=-0.004, 95% CI: -0.008 to -0.001, p=0.027; β=-0.006, 95% CI: -0.010 to -0.002, p=0.006, respectively) during the first postnatal week compared to controls. Mediation analysis indicated that preterm birth accounted for 20.34% of the association between HDP and crSO2, and 17.85% of the association between preeclampsia and crSO2. This is a provisional file, not the final typeset article Conclusion: Maternal HDP is associated with elevated neonatal cerebral oxygenation and reduced cerebral oxygen extraction in the early postnatal period. These associations are partially mediated by preterm birth, which may be linked to impaired placental function in pregnancies complicated by HDP.