Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, St. Mary's Hospital, 5th Floor (Research), Oxford Road, Manchester, M13 9WL, UK.
Centre for Biostatistics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
BMC Pregnancy Childbirth. 2021 Oct 20;21(1):706. doi: 10.1186/s12884-021-04178-6.
Advanced maternal age (≥35 years) is associated with increased rates of adverse pregnancy outcome. Better understanding of underlying pathophysiological processes may improve identification of older mothers who are at greatest risk. This study aimed to investigate changes in oxidative stress and inflammation in older women and identify clinical and biochemical predictors of adverse pregnancy outcome in older women.
The Manchester Advanced Maternal Age Study (MAMAS) was a multicentre, observational, prospective cohort study of 528 mothers. Participants were divided into three age groups for comparison 20-30 years (n = 154), 35-39 years (n = 222) and ≥ 40 years (n = 152). Demographic and medical data were collected along with maternal blood samples at 28 and 36 weeks' gestation. Multivariable analysis was conducted to identify variables associated with adverse outcome, defined as one or more of: small for gestational age (< 10th centile), FGR (<5th centile), stillbirth, NICU admission, preterm birth < 37 weeks' gestation or Apgar score < 7 at 5 min. Biomarkers of inflammation, oxidative stress and placental dysfunction were quantified in maternal serum. Univariate and multivariable logistic regression was used to identify associations with adverse fetal outcome.
Maternal smoking was associated with adverse outcome irrespective of maternal age (Adjusted Odds Ratio (AOR) 4.22, 95% Confidence Interval (95%CI) 1.83, 9.75), whereas multiparity reduced the odds (AOR 0.54, 95% CI 0.33, 0.89). In uncomplicated pregnancies in older women, lower circulating anti-inflammatory IL-10, IL-RA and increased antioxidant capacity (TAC) were seen. In older mothers with adverse outcome, TAC and oxidative stress markers were increased and levels of maternal circulating placental hormones (hPL, PlGF and sFlt-1) were reduced (p < 0.05). However, these biomarkers only had modest predictive accuracy, with the largest area under the receiver operator characteristic (AUROC) of 0.74 for placental growth factor followed by TAC (AUROC = 0.69).
This study identified alterations in circulating inflammatory and oxidative stress markers in older women with adverse outcome providing preliminary evidence of mechanistic links. Further, larger studies are required to determine if these markers can be developed into a predictive model of an individual older woman's risk of adverse pregnancy outcome, enabling a reduction in stillbirth rates whilst minimising unnecessary intervention.
高龄产妇（≥35 岁）与不良妊娠结局的发生率增加有关。更好地了解潜在的病理生理过程可能有助于识别风险最大的高龄产妇。本研究旨在探讨高龄妇女氧化应激和炎症的变化，并确定高龄妇女不良妊娠结局的临床和生化预测指标。
曼彻斯特高龄产妇研究（MAMAS）是一项针对 528 名母亲的多中心、观察性、前瞻性队列研究。参与者按年龄分为三组进行比较：20-30 岁（n=154）、35-39 岁（n=222）和≥40 岁（n=152）。在 28 周和 36 周妊娠时收集人口统计学和医疗数据以及产妇血液样本。进行多变量分析以确定与不良结局相关的变量，不良结局定义为以下一种或多种情况：小于胎龄儿（<第 10 百分位）、胎儿生长受限（<第 5 百分位）、死胎、新生儿重症监护病房（NICU）入院、早产<37 周或 5 分钟时 Apgar 评分<7。在母体血清中定量测定炎症、氧化应激和胎盘功能障碍的生物标志物。采用单变量和多变量逻辑回归分析与不良胎儿结局的关联。
无论产妇年龄如何，吸烟与不良结局相关（调整后的优势比（AOR）4.22，95%置信区间（95%CI）1.83，9.75），而多胎妊娠则降低了这种风险（AOR 0.54，95%CI 0.33，0.89）。在高龄妇女的无并发症妊娠中，循环中抗炎性白细胞介素 10（IL-10）、白细胞介素受体拮抗剂（IL-RA）水平降低，抗氧化能力（TAC）增加。在有不良结局的高龄产妇中，TAC 和氧化应激标志物增加，母体循环胎盘激素（hPL、PlGF 和 sFlt-1）水平降低（p<0.05）。然而，这些生物标志物的预测准确性仅为中等，其中胎盘生长因子的接收者操作特征（ROC）曲线下面积（AUROC）最大，为 0.74，其次是 TAC（AUROC=0.69）。
本研究在不良妊娠结局的高龄妇女中发现了循环中炎症和氧化应激标志物的改变，为机制联系提供了初步证据。进一步的大型研究需要确定这些标志物是否可以发展成为个体高龄妇女不良妊娠结局风险的预测模型，从而降低死产率，同时尽量减少不必要的干预。
