Service de Médecine Interne, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Inserm UMR-S970, Paris, France.
Centre de Formation et d'Appui Sanitaire Monkole, Kinshasa, Democratic Republic of the Congo.
Lancet Haematol. 2022 Mar;9(3):e208-e216. doi: 10.1016/S2352-3026(22)00004-7.
Many children with sickle cell disease living in sub-Saharan Africa die before reaching age 5 years. We estimate the child mortality associated with sickle cell anaemia using an indirect approach to overcome the absence of systematic screening at birth.
We did a retrospective, multicentre, case-control study in five countries in sub-Saharan Africa (Burkina Faso, Democratic Republic of the Congo, Côte d'Ivoire, Mali, and Senegal). Women with at least one child with a confirmed SS haemoglobin phenotype (sickle cell anaemia) and who had at least three (alive or deceased) children from the same father born more than 5 years ago were recruited at an outpatient consultation in a sickle cell disease care centre. Women who had children without sickle cell disease (control group) were recruited from the same area, with inclusion criteria of being a neighbour or relative of one of the mothers included in the study who had a child with sickle cell anaemia, having no child or other first-degree relative with major sickle cell syndrome, having at least three children (alive or deceased) born more than 5 years ago, and having a confirmed haemoglobin AA phenotype. During the mothers' interview, we collected data concerning the mortality of siblings from the same father of a child with sickle cell anaemia and characteristics of the family, such as age at the time of the survey and the level of education of both parents. Mortality rates were calculated for children younger than 1, 5, and 10 years using the Kaplan-Meier method after excluding the index children. We assumed, as per Mendel law, that in families who have a child with sickle cell anaemia and healthy heterozygous parents, 25% of children born on average have sickle cell anaemia. A multivariate Cox model was used to describe socioeconomic and geographical factors associated with mortality.
Between Sept 1, 2017, and Nov 30, 2020, 1563 women who had at least one child with sickle cell anaemia and 4972 women from the same neighbourhood who had children without sickle cell disease were assessed for eligibility. Of 1563 women, 248 were excluded because the genotype of the index child was SC or S β-thalassaemia. 1315 families with cases of sickle cell anaemia and 1243 control families were included in the study. The median age of children (alive) was 14 years (IQR 8-20) in control families and 13 years (8-19) in families with cases of sickle cell anaemia. 5532 [50·6%] of 10 924 children were male. Mortality rates were 15·3% (95% CI 13·3-17·3) for children with sickle cell anaemia younger than 1 year, 36·4% (33·4-39·4) for those younger than 5 years, and 43·3% (39·3-47·3) for those younger than 10 years. Multivariate Cox survival analysis showed that belonging to a family with sickle cell anaemia (hazard ratio [HR] 2·23, 95% CI 1·96-2·54), living in the Democratic Republic of the Congo (HR 1·64, 1·34-2·01), having an older parent (father or mother age had similar effect; HR 1·12, 1·05-1·19 per 10 years of age), or a significantly higher global Multidimensional Poverty Index (HR 1·09, 1·03-1·14), independently increased the risk of mortality. Whereas, living in Senegal (HR 0·70, 95% CI 0·57-0·86) or having a mother with higher education (high school HR 0·66, 0·55-0·80 or advanced HR 0·41, 0·28-0·61) independently decreased the risk of mortality.
Although higher than in high-income countries and affected by non-specific socioeconomic factors, the estimated mortality in children with sickle cell anaemia living in sub-Saharan African cities was substantially lower than previous estimates, suggesting an improvement of sickle cell anaemia care in this setting.
Fondation Pierre Fabre.
For the French translation of the abstract see Supplementary Materials section.
许多生活在撒哈拉以南非洲的镰状细胞病儿童在 5 岁之前死亡。我们使用间接方法估计镰状细胞性贫血相关的儿童死亡率，以克服出生时没有系统筛查的问题。
我们在撒哈拉以南非洲的五个国家（布基纳法索、刚果民主共和国、科特迪瓦、马里和塞内加尔）进行了一项回顾性、多中心、病例对照研究。在镰状细胞疾病护理中心的门诊咨询中招募了至少有一个 SS 血红蛋白表型（镰状细胞贫血）的孩子且至少有三个（存活或死亡）来自同一父亲且出生超过 5 年的孩子的女性。从同一地区招募了没有镰状细胞病的孩子（对照组）的女性，其纳入标准为是研究中患有镰状细胞贫血的孩子的母亲的邻居或亲属，没有孩子或其他第一级亲属患有主要镰状细胞综合征，至少有三个（存活或死亡）出生超过 5 年的孩子，并且具有确定的 AA 血红蛋白表型。在母亲访谈期间，我们收集了来自患有镰状细胞贫血的孩子的同一父亲的兄弟姐妹的死亡率数据以及家庭特征，例如调查时的年龄和父母双方的教育水平。排除索引儿童后，使用 Kaplan-Meier 法计算 1 岁以下、5 岁以下和 10 岁以下儿童的死亡率。根据孟德尔定律，我们假设在有镰状细胞贫血和健康杂合父母的家庭中，平均有 25%的孩子患有镰状细胞贫血。使用多变量 Cox 模型描述与死亡率相关的社会经济和地理因素。
2017 年 9 月 1 日至 2020 年 11 月 30 日，评估了 1563 名至少有一个患有镰状细胞贫血的孩子的女性和 4972 名来自同一社区且没有镰状细胞病的孩子的女性的入选资格。在 1563 名女性中，有 248 名因索引儿童的基因型为 SC 或 Sβ-地中海贫血而被排除在外。有 1315 个镰状细胞贫血病例家庭和 1243 个对照家庭纳入研究。对照组儿童（存活）的中位年龄为 14 岁（IQR 8-20），镰状细胞贫血病例家庭为 13 岁（8-19）。5532 名[50.6%]10924 名儿童为男性。1 岁以下儿童死亡率为 15.3%（95%CI 13.3-17.3），5 岁以下儿童为 36.4%（33.4-39.4），10 岁以下儿童为 43.3%（39.3-47.3）。多变量 Cox 生存分析表明，属于镰状细胞贫血家庭（风险比[HR]2.23，95%CI 1.96-2.54）、生活在刚果民主共和国（HR 1.64，1.34-2.01）、父母年龄较大（父亲或母亲年龄的影响相似；每增加 10 岁，HR 1.12，1.05-1.19）或全球多维贫困指数显著升高（HR 1.09，1.03-1.14），均增加了死亡率的风险。而生活在塞内加尔（HR 0.70，95%CI 0.57-0.86）或母亲受教育程度较高（高中 HR 0.66，0.55-0.80 或高级 HR 0.41，0.28-0.61）则独立降低了死亡率的风险。
尽管高于高收入国家且受非特异性社会经济因素影响，但估计撒哈拉以南非洲城市中镰状细胞性贫血儿童的死亡率显著低于之前的估计，表明在这种环境下镰状细胞性贫血的护理得到了改善。
Pierre Fabre 基金会。
