Discussion
hypoxia, apnea/hypopnea, heterogeneous disorder, OSA, mild/moderate OSA, preeclampsia
PREECLAMPSIA, HIGH-RISK PREGNANCIES, HYPOXIA, PREECLAMPSIA, HYPERTENSIVE DISORDER, HIGH-RISK PREGNANCY
We conducted an RCT of high-risk pregnant women with mild/moderate OSA (RDI IQR 5–29.8 and AHI IQR 4–13) to assess the efficacy of CPAP in reducing BP and gestational hypertensive disorders. Our findings indicate that CPAP significantly reduced BP, with larger effects on DBP and MAP than SBP. Results were robust for all approaches including modified-intention-to-treat, per-protocol, and counterfactual approaches. In addition, CPAP treatment also significantly reduced preeclampsia and hypertensive disorders in pregnancy by 9% and 11%, respectively.Although modified-intention-to-treat analysis is claimed as the least biased because it preserves random allocations, it may underestimate the causal-treatment effect because of dilution of noncompliers [DBP significantly affects uteroplacental hemodynamics and is more strongly associated with the risk of preeclampsia than SBP [Moreover, the true clinical effect may be larger with higher adherence to CPAP during pregnancy. Of note, this BP-lowering effect of CPAP was seen in both subgroups of participants, i.e. those who did and did not take anti-hypertensive medications. Fewer anti-hypertensive medications were required among those taking anti-hypertensive medications in the CPAP group (Table BP changes in our participants demonstrated the well-described pattern of mid-pregnancy fall, regardless of intervention groups [Preeclampsia is a heterogeneous disorder involving multiple placental mechanisms ranging from poor implantation to placental stress and hypoxia caused by “abnormal placentation” as in early-onset preeclampsia or “maternal stress factors” as in late-onset preeclampsia [Our findings replicated Guilleminault’s studies which similarly showed that the BP-lowering effect of CPAP was markedly apparent after 6 months of gestation, with more anti-hypertensive medication requirement in controls, and more favorable pregnancy outcomes in the CPAP-group [Recent data indicated that airflow limitation or RERA could cause an increase in BP similar to apnea/hypopnea in pregnant population [One strength of our trial was that full-night polysomnography was performed on all participants to detect both early-pregnancy and new-onset OSA. Due to different exposure time, early-pregnancy OSA (or probably chronic longstanding OSA) and new-onset OSA may be clinically different [The high OSA detection rate in our study may not reflect the true OSA prevalence of this population because only 385 (35.1%) of the total 1098 high-risk pregnant women agreed to participate for polysomnography. There might be a selection bias in that those who had more symptoms might have been more motivated to participate. Furthermore, the highly sensitive diagnosis with polysomnography and RDI criteria was used in a high-risk pregnancy population. Based on the home-sleep-apnea test (AHI ≥ 5 criteria), previous studies found OSA prevalence in high-risk pregnancy during 1st and 3rd trimesters of approximately 28–60.3% and 24–50%, respectively [The main limitation of our trial was CPAP nonadherence, which occurred in a large percentage of participants, comparable to other RCTs [Our results may not be generalizable to pregnant women without pre-defined high-risk factors or those with severe OSA. Despite successful treatment case reports, the magnitude of CPAP treatment effect on severe cases is unknown [In conclusion, evidence from a multicenter RCT of high-risk pregnancies with mild/moderate OSA indicates that early CPAP treatment significantly lowers DBP, MAP, and reduces the incidence of preeclampsia and hypertensive disorders in pregnancy. This raises the need for early diagnosis and treatment of OSA in high-risk pregnancies.