Koelewijn J M, Vrijkotte T G M, van der Schoot C E, Bonsel G J, de Haas M
Sanquin Research, Amsterdam, The Netherlands.
Transfusion. 2008 May;48(5):941-52. doi: 10.1111/j.1537-2995.2007.01625.x. Epub 2008 Feb 1.
Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated.
Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified.
The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1.
First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.
胎儿及新生儿溶血病(HDFN)是一种严重疾病,由母体针对胎儿红细胞(RBC)的同种异体抗体引起。评估了孕早期抗体筛查程序对及时检测由抗-D以外抗体导致的HDFN的效果。
在全国范围内,所有通过孕早期抗体筛查检测出抗-D以外同种异体抗体的女性(在18个月内连续305,000例妊娠中有1,002例)被纳入一项前瞻性指数队列研究。在一项平行覆盖验证研究中,回顾性确定了筛查程序漏检的由抗-D以外抗体导致HDFN的患者。
孕早期筛查时抗体筛查阳性的患病率为每100,000例中有1,232例;抗-D以外同种异体抗体的患病率为每100,000例中有328例,其中每100,000例中有191例因父亲携带该抗原而提示有发生HDFN的风险。总体而言,有风险的胎儿中3.7%发生了需要宫内或产后(换血)输血的严重HDFN:抗-K导致的为11.6%;抗-c导致的为8.5%;抗-E导致的为1.1%;抗-c、抗-D或抗-E以外的Rh抗体导致的为3.8%;抗-Rh抗体或抗-K以外的抗体导致的,有风险的胎儿中无一例发生。所有检测出抗体的患病儿童均得到及时治疗,1岁时健康。覆盖验证研究显示筛查程序的敏感性为75%。8例漏检病例中有5例由抗-c导致,至少1例因延误造成永久性损伤。
孕早期筛查能够及时治疗由抗-D以外抗体导致的HDFN,然而,敏感性仅为75%。对c抗体阴性的女性在孕30周进行二次筛查将加强筛查程序。由抗-D以外抗体导致的严重HDFN与抗-K、抗-c以及程度较轻的其他Rh同种异体抗体有关。