Long-term health outcomes of children born to mothers with hyperemesis gravidarum: a systematic review and meta-analysis.

OBJECTIVE: Hyperemesis gravidarum (HG) is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficit. Maternal undernutrition is associated with adverse offspring health outcomes. Whether HG permanently affects offspring health remains unclear. This review aimed to evaluate effects of maternal HG on offspring health. DATA SOURCES: Medline and Embase were searched from inception to September 6th, 2021. STUDY ELIGIBILITY: Studies reporting on health at any age beyond the perinatal period of children born to mothers with HG were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis, where possible. In meta-analyses with high heterogeneity (I2>75%), we did not provide a pooled odds ratio (OR). RESULTS: Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that HG was associated with anxiety disorder (OR 1.74, 95% CI: 1.04;2.91, I2: 0%) and sleep problems in offspring (OR 2.94, 95% CI: 1.25;6.93, I2: 0%). HG was associated with testicular cancer in male offspring aged up to 40 years upon meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed based on a wide 95% prediction interval (PI) (OR 1.60, 95% CI: 1.07;2.39, I2: 0%, 95% PI: 0.83-3.08). All six studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with HG in comparison to children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled OR. The majority of studies reporting on cognitive and motor problems found an increase among HG-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from HG affected pregnancies in comparison to unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of HG-exposed children had inconsistent findings. CONCLUSION: Our systematic review showed that maternal HG is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders and possibly testicular cancer, although evidence is based on few studies of low quality.