McBain Rosemary D, Crowther Caroline A, Middleton Philippa
ARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, Australia, 5000.
Cochrane Database Syst Rev. 2015 Sep 3;2015(9):CD000020. doi: 10.1002/14651858.CD000020.pub3.
During pregnancy, a Rhesus negative (Rh-negative) woman may develop antibodies when her fetus is Rhesus positive (Rh-positive). These antibodies may harm Rh-positive babies.
To assess the effects of antenatal anti-D immunoglobulin on the incidence of Rhesus D alloimmunisation when given to Rh-negative women without anti-D antibodies.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies.
Randomised trials in Rh-negative women without anti-D antibodies given anti-D after 28 weeks of pregnancy, compared with no treatment, placebo or a different regimen of anti-D.
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
We included two trials involving over 4500 women, comparing anti-D prophylaxis with no anti-D during pregnancy in this review. Overall, the trials were judged to be at moderate to high risk of bias. The quality of the evidence for pre-specified outcomes was also assessed using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.In regards to primary review outcomes, there did not appear to be a clear difference in the risks of immunisation when women who received anti-D at 28 and 34 weeks' gestation were compared with women who were not given antenatal anti-D: risk ratio (RR) for incidence of Rhesus D alloimmunisation during pregnancy was 0.42 (95% confidence interval (CI) 0.15 to 1.17, two trials, 3902 women; GRADE: low quality evidence); at birth of a Rh-positive infant the RR was 0.42 (95% CI 0.15 to 1.17, two trials, 2297 women); and within 12 months after birth of a Rh-positive infant the average RR was 0.39 (95% CI 0.10 to 1.62, two trials, 2048 women; Tau²: 0.47; I²: 39%; GRADE: low quality evidence). Neither of the trials reported on incidence of Rhesus D alloimmunisation in subsequent pregnancies.Considering secondary outcomes, in one trial, women receiving anti-D during pregnancy were shown to be less likely to register a positive Kleihauer test (which detects fetal cells in maternal blood) in pregnancy (at 32 to 25 weeks) (RR 0.60, 95% CI 0.41 to 0.88; 1884 women; GRADE: low quality evidence) and at the birth of a Rh-positive infant (RR 0.60, 95% CI 0.46 to 0.79; 1189 women; GRADE: low quality evidence). No clear differences were seen for neonatal jaundice (RR 0.26, 95% CI 0.03 to 2.30; 1882 infants; GRADE: very low quality evidence). Neither of the trials reported on adverse effects associated with anti-D treatment.
AUTHORS' CONCLUSIONS: Existing studies do not provide conclusive evidence that the use of anti-D during pregnancy benefits either mother or baby in terms of incidence of Rhesus D alloimmunisation during the pregnancy or postpartum, or the incidence of neonatal morbidity (jaundice) (low to very low quality evidence). However women receiving anti-D may be less likely to register a positive Kleihauer test in pregnancy and at the birth of a Rh-positive infant (low quality evidence). Fewer women who receive anti-D during pregnancy may have Rhesus D antibodies in a subsequent pregnancy, with benefits for the baby, however this needs to be tested in studies of robust design.
孕期中，当恒河猴阴性（Rh阴性）女性的胎儿为恒河猴阳性（Rh阳性）时，她可能会产生抗体。这些抗体可能会伤害Rh阳性的婴儿。
评估产前抗D免疫球蛋白用于未产生抗D抗体的Rh阴性女性时，对Rh D同种免疫发生率的影响。
我们检索了Cochrane妊娠与分娩组试验注册库（2015年5月31日）以及检索到的研究的参考文献列表。
对妊娠28周后给予抗D的未产生抗D抗体的Rh阴性女性进行的随机试验，与未治疗、安慰剂或不同方案的抗D进行比较。
两位综述作者独立评估试验是否纳入及偏倚风险，提取数据并检查其准确性。
本综述纳入了两项涉及4500多名女性的试验，比较了孕期抗D预防与不进行抗D治疗的情况。总体而言，试验被判定为存在中度至高偏倚风险。还使用GRADE（推荐分级、评估、制定和评价）方法评估了预先设定结局的证据质量。关于主要综述结局，当比较妊娠28周和34周接受抗D的女性与未接受产前抗D的女性时，免疫风险似乎没有明显差异：孕期Rh D同种免疫发生率的风险比（RR）为0.42（95%置信区间（CI）0.15至1.17，两项试验，3902名女性；GRADE：低质量证据）；Rh阳性婴儿出生时RR为0.42（95%CI 0.15至1.17，两项试验，2297名女性）；Rh阳性婴儿出生后12个月内平均RR为0.39（95%CI 0.10至1.62，两项试验，2048名女性；Tau²：0.47；I²：39%；GRADE：低质量证据）。两项试验均未报告后续妊娠中Rh D同种免疫的发生率。考虑次要结局，在一项试验中，孕期接受抗D的女性在孕期（32至25周）（RR 0.60，95%CI 0.41至0.88；1884名女性；GRADE：低质量证据）和Rh阳性婴儿出生时（RR 0.60，95%CI 0.46至0.79；1189名女性；GRADE：低质量证据）进行Kleihauer试验（检测母血中胎儿细胞）呈阳性的可能性较小。新生儿黄疸方面未见明显差异（RR 0.26，95%CI 0.03至2.30；1882名婴儿；GRADE：极低质量证据）。两项试验均未报告与抗D治疗相关的不良反应。
现有研究未提供确凿证据表明孕期使用抗D在妊娠期间或产后的Rh D同种免疫发生率或新生儿发病率（黄疸）方面对母亲或婴儿有益（低至极低质量证据）。然而，接受抗D的女性在孕期和Rh阳性婴儿出生时进行Kleihauer试验呈阳性的可能性可能较小（低质量证据）。孕期接受抗D的女性在后续妊娠中产生Rh D抗体的可能较少，对婴儿有益，不过这需要在设计严谨的研究中进行验证。
