Preclinical data suggest that gestational exposure to selective serotonin reuptake inhibitors (SSRI) alter gut innervation, and delays colonic motility. In this study we investigated associations between gestational SSRI exposure and offspring disorders of gut-brain interaction (DGBI). Using population-based registries, we included all single-birth Danish children born 1997–2015 with follow-up until outcome occurrence, age 15 years, death, emigration, or December 2018. Children to mothers who continued SSRIs during pregnancy and children to mothers who discontinued SSRI use before pregnancy were compared using Cox regression. Main outcomes were the first diagnosis of a childhood DGBI (functional nausea and vomiting, functional abdominal pain disorders, functional diarrhea, and functional constipation), or a physician-prescribed laxative. Among 1,158,560 children, 21,969 children (1.9%) were exposed to SSRIs prenatally and 30,174 children (2.6%) were born to mothers who discontinued SSRIs before pregnancy. Overall, the estimated 15-year cumulative incidence of any DGBI was 15.5% (95% CI, 14.9–16.2) in the SSRI-exposed group and 14.7% (14.0–15.3) in the unexposed group. SSRI-exposed children had an overall increased risk of DGBIs (HR 1.08, [1.02–1.14]), which was driven by functional constipation (HR 1.19, [1.10–1.28]) rather than functional nausea and vomiting (HR 0.97, [0.83–1.13]) or functional abdominal pain disorders (HR 0.90, [0.81–1.00]). These data suggest that prenatal SSRI exposure is associated with an increased risk of developing functional constipation. These findings are also consistent with extensive preclinical data supporting key roles for serotonin in gut development and function. Together findings support the need for further investigation of the long-term impact of maternal depression and SSRI exposure on development of common gastrointestinal disorders.

临床前数据表明，妊娠期暴露于选择性 5-羟色胺再摄取抑制剂 （SSRI） 会改变肠道神经支配，并延迟结肠运动。在这项研究中，我们调查了妊娠 SSRI 暴露与后代肠脑相互作用障碍 （DGBI） 之间的关联。使用基于人群的登记库，我们纳入了 1997-2015 年出生的所有单胎丹麦儿童，并进行了随访直至结局发生、年龄 15 岁、死亡、移民或 2018 年 12 月。使用 Cox 回归比较在怀孕期间继续使用 SSRI 的母亲与母亲的孩子以及怀孕前停止使用 SSRI 的母亲的孩子。主要结局是首次诊断为儿童 DGBI （功能性恶心和呕吐、功能性腹痛障碍、功能性腹泻和功能性便秘），或医生开具的泻药。在 1,158,560 名儿童中，21,969 名儿童 （1.9%） 产前暴露于 SSRIs，30,174 名儿童 （2.6%） 是怀孕前停用 SSRIs 的母亲所生。总体而言，SSRI 暴露组任何 DGBI 的估计 15 年累积发生率为 15.5% （95% CI，14.9-16.2），未暴露组为 14.7% （14.0-15.3）。暴露于 SSRI 的儿童患 DGBI 的风险总体增加 （HR 1.08， [1.02–1.14]），这是由功能性便秘 （HR 1.19， [1.10–1.28]）驱动的，而不是功能性恶心和呕吐 （HR 0.97， [0.83–1.13]） 或功能性腹痛疾病 （HR 0.90， [0.81–1.00]）。这些数据表明，产前 SSRI 暴露与发生功能性便秘的风险增加有关。这些发现也与支持 5-羟色胺在肠道发育和功能中的关键作用的大量临床前数据一致。 总之，研究结果支持进一步调查孕产妇抑郁症和 SSRI 暴露对常见胃肠道疾病发展的长期影响的必要性。