Supplementary Material for: Prenatal Methamphetamine Exposure and Adverse Neonatal Outcomes: A Nationwide Cohort Study

<b><i>Background:</i></b> There is limited knowledge on the adverse outcomes in newborns after maternal methamphetamine (MA) use during pregnancy. <b><i>Objectives:</i></b> To compare neonatal outcomes in newborns exposed to MA with the newborns of opioid-exposed mothers and of mothers from the general population (GP). <b><i>Method:</i></b> A cohort study using nationwide registries in Czechia (2000–2014). Women hospitalized with a main diagnosis of MA use disorder during pregnancy (<i>n</i> = 258) and their newborns were defined as MA-exposed. The comparison groups consisted of women (<i>n</i> = 199) diagnosed with opioid use disorder during pregnancy, defined as opioid-exposed, and women (<i>n</i> = 1,511,310) with no substance use disorder diagnosis (GP). The neonatal outcomes studied were growth parameters, gestational age, preterm birth, and Apgar score. To explore the associations between MA exposure and neonatal outcomes, regression coefficients (<i>b</i>) and odds ratios from multivariable linear and binary logistic regression were estimated. <b><i>Results:</i></b> MA-exposed women had similar socio-economic characteristics to opioid-exposed, both of which were worse than in the GP. After adjustment, MA exposure was associated with a more favourable birthweight when compared to the opioid-exposed (adjusted mean differences [aMD] <i>b</i> = 122.3 g, 95% CI: 26.0–218.5) and length (aMD <i>b</i> = 0.6 cm, 0.0–1.1). Unadjusted results from the comparison with the GP showed that the MA group had poorer neonatal outcomes, especially in the growth parameters. Adjustment for background characteristics had a profound effect on the comparison with the GP. After adjustment, MA exposure was associated only with a slightly reduced birthweight (aMD <i>b</i> = −63.0 g, −123.0 to −3.1) and birth length (aMD <i>b</i> = −0.3 cm, −0.6 to 0.0). <b><i>Conclusions:</i></b> Although the observed negative outcomes were large in the MA-exposed newborns, the adjustment had a profound effect on the comparison with the GP, indicating the large influence of lifestyle and socio-economic factors in these high-risk pregnancies. MA-exposed newborns had better neonatal outcomes compared to opioids-exposed.

**背景：** 目前关于孕产妇孕期使用甲基苯丙胺（methamphetamine, MA）后新生儿不良结局的研究认知仍较为匮乏。
**研究目的：** 对比孕期暴露于MA的新生儿、孕期阿片类药物暴露产妇所诞新生儿，以及普通人群（general population, GP）产妇所诞新生儿的围产期结局。
**研究方法：** 本研究为一项基于捷克2000-2014年全国登记数据库的队列研究。将孕期以甲基苯丙胺使用障碍为主要诊断住院的产妇（n=258）及其新生儿纳入MA暴露组。对照组分为两类：一是孕期确诊阿片类药物使用障碍的产妇（n=199）及其新生儿，定义为阿片暴露组；二是无物质使用障碍诊断的普通人群产妇（n=1,511,310），即普通人群组（GP）。本研究关注的新生儿结局包括生长参数、胎龄、早产发生情况及Apgar评分（Apgar score）。为探究MA暴露与新生儿结局的关联，本研究通过多变量线性回归与二元logistic回归分析，估算了回归系数（b）与比值比。
**研究结果：** MA暴露组产妇的社会经济特征与阿片暴露组相近，且二者均差于普通人群组。经混杂因素校正后，相较于阿片暴露组，MA暴露组新生儿的出生体重更高（校正均数差[aMD] b=122.3 g，95%置信区间：26.0–218.5），身长也更长（校正均数差[aMD] b=0.6 cm，0.0–1.1）。未校正分析结果显示，与普通人群组相比，MA暴露组新生儿的围产期结局更差，尤其体现在生长参数方面。对混杂因素进行校正后，该差异出现显著变化：经校正后，相较于普通人群组，MA暴露组新生儿仅表现为出生体重轻度降低（校正均数差[aMD] b=−63.0 g，−123.0 至 −3.1）和出生身长轻度缩短（校正均数差[aMD] b=−0.3 cm，−0.6 至 0.0）。
**研究结论：** 尽管MA暴露组新生儿曾被观察到存在较为显著的不良结局，但经混杂因素校正后，与普通人群组的对比结果出现了显著变化，提示生活方式与社会经济因素在这类高风险妊娠中发挥了重要影响。相较于阿片暴露组新生儿，MA暴露组新生儿的围产期结局更优。