背景:长效杀虫网(LLINs)是孕妇的主要媒介控制工具,但是它们的功效可能会受损,在某种程度上,由于拟除虫菊酯抗性。2017年,乌干达卫生部将一项集群随机对照试验纳入了全国LLIN运动,其中健康分区(HSD)的随机子集接受了胡椒基丁醚(PBO)治疗的LLINs,一种已知能部分恢复拟除虫菊酯敏感性的化学增效剂。使用来自小型的数据,非随机选择的HSD子集,本次要分析使用准实验方法量化LLIN运动对妊娠结局的总体影响.在探索性分析中,评估了PBO和常规(非PBO)LLINs在妊娠结局方面的差异.
方法:从12个HSD的21个医疗机构回顾性收集了出生登记数据(n=39,085),LLIN活动之前29个月和之后9个月(从2015年到2018年)。在12个HSD中,六个收到的常规LLINs,五个收到的PBOLLINs,其中一人收到了传统和PBOLLINs的混合。中断时间序列分析(ITSA)用于估计活动前后死产和低出生体重(LBW;<2500g)的每月发生率变化。具有稳健标准误差的泊松回归建模活动效果,根据卫生设施水平的差异进行调整,季节性变化,和随时间变化的母亲特征。PBO和常规LLINs之间的比较是使用差异估计器进行估计的。
结果:ITSAs估计,在9个月期间,该活动与死产发生率降低26%[95%CI:7-41](发生率比率(IRR)=0.74[0.59-0.93])和LBW发生率降低15%[-7,33](IRR=0.85[0.67-1.07])相关。运动后7-9个月分娩的妇女对死产发生率的影响最大(IRR=0.60[0.41-0.87]),而LLINs将覆盖其大部分妊娠。通过比较PBO与常规LLINs的差异分析,估算的IRR对于死胎发生率为0.78[95%CI:0.52,1.16],对于LBW发生率为1.15[95%CI:0.87,1.52]。
结论:在乌干达这个地区,在拟除虫菊酯抗性高的地方,这项研究发现,大规模的LLIN运动与降低死产发生率有关。这项运动的效果对于那些在怀孕早期就接受LLINs的女性来说是最大的,建议在怀孕早期预防疟疾可能具有重要的益处,而这些益处不一定通过产前疟疾服务实现。比较PBO和常规LLINs对妊娠结局的探索性分析结果尚无定论,很大程度上是由于越过null的置信区间很宽。因此,未来的研究需要更大的样本量。
BACKGROUND: Long-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance. In 2017, the Ugandan Ministry of Health embedded a cluster randomized controlled
trial into the national LLIN campaign, where a random subset of health subdistricts (HSDs) received LLINs treated with piperonyl butoxide (PBO), a chemical synergist known to partially restore pyrethroid sensitivity. Using data from a small, non-randomly selected subset of HSDs, this secondary analysis used quasi-experimental methods to quantify the overall impact of the LLIN campaign on pregnancy outcomes. In an exploratory analysis, differences between PBO and conventional (non-PBO) LLINs on pregnancy outcomes were assessed.
METHODS: Birth registry data (n = 39,085) were retrospectively collected from 21 health facilities across 12 HSDs, 29 months before and 9 months after the LLIN campaign (from 2015 to 2018). Of the 12 HSDs, six received conventional LLINs, five received PBO LLINs, and one received a mix of conventional and PBO LLINs. Interrupted time-series analyses (ITSAs) were used to estimate changes in monthly incidence of stillbirth and low birthweight (LBW; <2500 g) before-and-after the campaign. Poisson regression with robust standard errors modeled campaign effects, adjusting for health facility-level differences, seasonal variation, and time-varying maternal characteristics. Comparisons between PBO and conventional LLINs were estimated using difference-in-differences estimators.
RESULTS: ITSAs estimated the campaign was associated with a 26% [95% CI: 7-41] reduction in stillbirth incidence (incidence rate ratio (IRR) = 0.74 [0.59-0.93]) and a 15% [-7, 33] reduction in LBW incidence (IRR=0.85 [0.67-1.07]) over a 9-month period. The effect on stillbirth incidence was greatest for women delivering 7-9 months after the campaign (IRR=0.60 [0.41-0.87]) for whom the LLINs would have covered most of their pregnancy. The IRRs estimated from difference-in-differences analyses comparing PBO to conventional LLINs was 0.78 [95% CI: 0.52, 1.16] for stillbirth incidence and 1.15 [95% CI: 0.87, 1.52] for LBW incidence.
CONCLUSIONS: In this region of Uganda, where pyrethroid resistance is high, this
study found that a mass LLIN campaign was associated with reduced stillbirth incidence. Effects of the campaign were greatest for women who would have received LLINs early in pregnancy, suggesting malaria protection early in pregnancy can have important benefits that are not necessarily realized through antenatal malaria services. Results from the exploratory analyses comparing PBO and conventional LLINs on pregnancy outcomes were inconclusive, largely due to the wide confidence intervals that crossed the null. Thus, future studies with larger sample sizes are needed.