Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China (Fudan University), China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Environ Int. 2019 Feb;123:70-78. doi: 10.1016/j.envint.2018.11.053. Epub 2018 Nov 28.
The association between antibiotic use during pregnancy and neonatal birth outcomes has received considerable attention. Most of the previous assessment of antibiotic exposure during pregnancy relied on questionnaires and clinical prescriptions, and very few studies examined pregnancy exposure to antibiotics using human biomonitoring data.
To explore the association between the cumulative exposure of antibiotics during the whole pregnancy and neonatal birth measurements using biomonitoring data of antibiotics in meconium.
Three hundred and sixty nine pregnant women within the Maternal Psychological and Environmental Assessments of Kids Cohort Study were randomly selected into this study. Eighteen common antibiotics of six categories (six β‑lactams, three tetracyclines, four sulfonamides, one phenicols, one lincosamides and three fluoroquinolones) were selected as the target antibiotics in meconium. The measurement was conducted by ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry platform. Neonatal birth measurements were obtained from the medical records. Multiple linear regression models were used to examine the associations of antibiotic exposure with neonatal birth outcome (birth weight, birth length) and placental growth indicators (placental surface area, placental weight). Logistic regressions were used to evaluate associations with small for gestational age (SGA) and large for gestational age (LGA).
Twelve of the eighteen antibiotics were found in 62.1% of the meconium, with detection rates ranging from 0.3% to 43.9%. The three antibiotics with the highest detection rates were chlortetracycline (43.9%), penicillin (16.5%) and chloramphenicol (10.8%), respectively. The highest antibiotic concentration among detected antibiotics was penicillin (24,243.15 μg/kg). The concentration of penicillin was positively associated with the birth weight (β: 0.025; 95% CIs: 0.003-0.047). A significant positive association was also observed between the concentration of chlortetracycline and the placental surface area (β: 2.559; 95% CIs: 0.296-4.822). These associations were sex related and mainly observed in female newborns. Exposure to penicillin was also found to be associated with increased risk of LGA, which was consistent with changes in birth weight.
Pregnancy exposure to certain antibiotics was associated with altered fetal growth and development, which may affect the normal growth trajectory of infants and children in later life.
抗生素在孕期的使用与新生儿出生结局之间的关系已受到广泛关注。之前对孕期抗生素暴露的评估大多依赖于问卷调查和临床处方,很少有研究使用人体生物监测数据来评估孕期抗生素暴露。
使用胎粪中抗生素的生物监测数据,探究整个孕期抗生素累积暴露与新生儿出生测量值之间的关系。
从母婴心理与环境评估儿童队列研究中随机抽取 369 名孕妇参与本研究。选择 18 种六类常见抗生素(6 种β-内酰胺类、3 种四环素类、4 种磺胺类、1 种酚类、1 种林可酰胺类和 3 种氟喹诺酮类)作为胎粪中的目标抗生素。通过超高效液相色谱-四极杆飞行时间质谱联用平台进行检测。从病历中获取新生儿出生测量值。采用多元线性回归模型来检验抗生素暴露与新生儿出生结局(出生体重、出生体长)和胎盘生长指标(胎盘面积、胎盘重量)之间的关联。采用 logistic 回归来评估与小于胎龄儿(SGA)和大于胎龄儿(LGA)相关的关联。
在 62.1%的胎粪中发现了 18 种抗生素中的 12 种,检测率为 0.3%至 43.9%。检测率最高的三种抗生素分别为金霉素(43.9%)、青霉素(16.5%)和氯霉素(10.8%)。检测到的抗生素中浓度最高的是青霉素(24243.15μg/kg)。青霉素浓度与出生体重呈正相关(β:0.025;95%置信区间:0.003-0.047)。金霉素浓度与胎盘面积也呈显著正相关(β:2.559;95%置信区间:0.296-4.822)。这些关联具有性别相关性,主要见于女婴。青霉素暴露还与 LGA 风险增加有关,这与出生体重的变化一致。
孕期接触某些抗生素与胎儿生长和发育的改变有关,这可能会影响婴儿和儿童在以后生活中的正常生长轨迹。