Table 1_Global, regional and national trends in the burden of persistent pulmonary hypertension of the newborn and essentials of its management from 1993 to 2023: a scoping review.docx

BackgroundPersistent pulmonary hypertension of the newborn (PPHN) is a frequent neonatal emergency in the neonatal intensive care unit (NICU), representing a challenging condition that has not been extensively studied. PPHNremains associated with a high mortality and morbidity.
ObjectiveThis scoping review was undertaken to provide a global overview of several key aspects: (1) the prevalence/incidence and etiologies of PPHN, (2) the mortality rate linked to PPHN during hospitalization and the primary causes of such mortality, (3) the risk factors related to PPHN, and (4) the approaches to managing PPHN. The aim of this scoping review was not to assess the methodological soundness of the identified studies, but instead to deliver a broad, comprehensive perspective on PPHN, identify gaps within the current literature, and outline potential avenues for future research. The results are anticipated to assist in developing public health strategies aimed at reducing the morbidity and mortality tied to PPHN globally.
MethodsWe conducted a digital search in MEDLINE and the Cochrane Library, from January 1, 1993 to December 31, 2023.We incorporated observational studies, interventional studies, and reviews that provided adequate data on the incidence/prevalence, mortality rates, predictors, etiological factors, diagnosis, and management of PPHN among the general neonatal population (age 0–28 days old). This procedure followed the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extensions for Scoping Reviews (PRISMA-ScR). Additionally, we utilized the methodological framework for scoping reviews as outlined by Arksey and O'Malley, which consists of formulating the research question, conducting a search for pertinent studies, selecting the studies, organizing the data, and compiling, summarizing and reporting the findings.
ResultsA total of 128 research articles were collected from 27 countries categorized as either high-income or low- and middle-income countries (LMICs). The prevalence of PPHN ranges from 0.1%–8.1% in the different study populations. The highest global prevalence rates are observed in Europe and Asia, while lower prevalence rates are reported in the Americas and Africa. Neonatal infections are the leading cause of PPHN in Asia and the Americas, whereas meconium aspiration syndrome predominates in Europe. Several independent risk factors for PPHN include premature birth, male sex, ethnicity, extremes of birth weight, advanced maternal age, maternal obesity, multiple births, maternal smoking, pregestational/gestational diabetes mellitus, infectious history, caesarean delivery, antenatal drug exposure, fetal distress, APGAR score and meconium-stained amniotic fluid. The PPHN-related in-hospital mortality rate associated with PPHN ranges from 3.0%–57.9%, with the highest rates reported in Asia and the lowest in the United States of America (USA) and the United Kingdom (UK). It is advised that clinical evaluation incorporates the oxygenation index (OI) to assist in guiding medical practice.
ConclusionPPHN has a high global burden, driven by neonatal infections and meconium aspiration syndrome, particularly pronounced in LIMCs where there is a pressing need for more intensive treatments and innovative solutions, ideally supported by region-specific subsidies, to address this concerning burden.

背景 新生儿持续性肺动脉高压（Persistent pulmonary hypertension of the newborn, PPHN）是新生儿重症监护病房（neonatal intensive care unit, NICU）中常见的新生儿急症，属于诊疗难度较高的病症，目前尚未得到充分研究。PPHN仍与较高的病死率及致残率相关。
目的 本范围综述（scoping review）旨在从全球视角概述PPHN的若干核心议题：(1) PPHN的患病率/发病率与病因；(2) 住院期间与PPHN相关的病死率及主要死亡原因；(3) PPHN的相关危险因素；(4) PPHN的管理策略。本次范围综述的目的并非评估纳入研究的方法学严谨性，而是为PPHN提供全面且广泛的认知，明确当前文献中的研究空白，并梳理未来研究的潜在方向。预期研究结果将助力制定全球范围内降低PPHN相关病死率与致残率的公共卫生策略。
方法 本研究于1993年1月1日至2023年12月31日期间，在MEDLINE及考克兰图书馆（Cochrane Library）中开展电子检索。纳入针对普通新生儿人群（年龄0~28日龄）的PPHN发病率/患病率、病死率、预测因素、病因、诊断及管理提供充分数据的观察性研究、干预性研究及综述类文献。本研究遵循《系统综述与Meta分析扩展指南-范围综述》（Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extensions for Scoping Reviews, PRISMA-ScR）的规范流程，并采用Arksey与O'Malley提出的范围综述方法学框架，该框架包括确定研究问题、检索相关文献、筛选研究、整理数据、汇总总结并报告研究结果五个环节。
结果 本研究共纳入来自27个国家的128篇研究论文，这些国家分为高收入国家及中低收入国家（low- and middle-income countries, LMICs）。PPHN的患病率在不同研究队列中为0.1%~8.1%。全球患病率最高的地区为欧洲与亚洲，美洲与非洲的患病率相对较低。亚洲与美洲地区PPHN的首要病因为新生儿感染，而欧洲则以胎粪吸入综合征为主。PPHN的多项独立危险因素包括早产、男性性别、种族、出生体重异常、产妇高龄、产妇肥胖、多胎妊娠、产妇吸烟、孕前/妊娠期糖尿病、感染史、剖宫产分娩、产前药物暴露、胎儿窘迫、APGAR评分及羊水胎粪污染。PPHN相关的住院病死率为3.0%~57.9%，其中亚洲地区病死率最高，美国（United States of America, USA）与英国（United Kingdom, UK）最低。临床评估建议纳入氧合指数（oxygenation index, OI）以指导临床实践。
结论 PPHN具有沉重的全球疾病负担，其主要驱动因素为新生儿感染与胎粪吸入综合征，在中低收入国家（LMICs）这一负担尤为突出。这些地区亟需更强化的治疗手段与创新解决方案，最好能结合区域专属的支持政策，以应对这一令人担忧的疾病负担。