Table 1.
Summary of study characteristics and results. CI: confidence interval.
| Author | Year | No. of Multiply Exposed Children | No. of Unexposed Children | Age at Exposure | Outcome | Results | p-Value |
|---|---|---|---|---|---|---|---|
| Wilder | 2009 | 100 children had 2 GAs | 4764 | Before 4 y.o. | Learning disability, measured with the Minnesota regression formula, issued by the Minnesota Department of Education | HR = 1.59, 95% CI: 1.06–2.37 | p < 0.001 |
| 44 children had at least 3 GAs | HR = 2.60, 95% CI: 1.60–4.24 | ||||||
| DiMaggio | 2011 | 71 children had 2 GAs | 10,146 | Before 3 y.o. | Diagnosis of developmental and behavioral disorders according to ICD-9-CM codes | HR = 2.8, 95% CI: 2.5–3.1 | p < 0.05 |
| 23 children had at least 3 GAs | HR = 4.0, 95% CI: 3.5–4.5 | p < 0.05 | |||||
| Ing | 2012 | 52 | 1523 | Before 3 y.o. | CELF, Raven’s CPM, MAND and CBCL tests | Statistically significant impairment of total language (HR = 2.68, 95% CI: 1.07–6.72) and receptive language (HR = 3.52, 95% CI: 1.38–9.00), while cognition and abstract reasoning abilities were impaired but did not reach statistically significance. | Statistically significant (p < 0.05) for total language and receptive language |
| Sprung | 2012 | 64 | 5007 | Before 2 y.o. | ADHD prevalence | Children exposed to at least 2 GA had a higher risk of developing ADHD (HR = 1.95, 95% CI: 1.03–3.71). | p < 0.05 |
| Graham | 2016 | 620 | 13,586 | Before 4 y.o. | EDI questionnaire | Overall EDI score in mGA-exposed children was lower by 1.2 points compared to unexposed children (95% CI: −1.83–0.61). A subanalysis by age showed a statistically significant result when the age at exposure was 2–4 y.o. (overall result and the subdomains regarding common knowledge, language/cognitive and physical well-being). |
p < 0.001 |
| Glatz | 2017 | 2897 children had 2 GAs | 159,619 | Before 4 y.o. | Academic performances, measured evaluating school grades at age 16 and IQ test at age 18 | OR = 1.26, 95% CI: 0.94–1.70 | Not statistically significant |
| 820 children had at least 3 GAs | OR = 1.95, 95% CI: 1.22–3.11 | p < 0.05 | |||||
| MASK study | 2018 | 206 | 411 | Before 3 y.o. | FSIQ standard score and individual domains of neuropsychological assessments. Parental reports, such as the CLDQ, the CBCL and the Behavior Rating Inventory of Executive Function |
Children exposed to mGA did not differ in intelligence quotient from unexposed children. Nevertheless, a statistically significant decrease in processing speed (3.51 lower) and motor abilities (5.53 lower) was noted. Moreover, multiply exposed children’s parents reported a significant increase in behavioral and reading disorders. |
Statistically significant for processing speed and motor abilities scores (p < 0.05 and p < 0.001, respectively), as well as for parental reports |
| Tsai | 2018 | 342 | 34,678 | Before 3 y.o. | ADHD prevalence | HR = 1.71, 95% CI: 1.01–2.90 | p < 0.05 |
| AVON study | 2020 | 212 | 12,111 | Before 4 y.o. | Motor, cognitive, linguistic, educational, social and behavioral neurodevelopmental outcomes | Children exposed to at least 2 GA had a statistically significant higher risk of developing motor and socio-behavioral developmental outcomes, such as dynamic balance, manual dexterity and social communication scores. | p < 0.01 |
| Feng | 2020 | 2873 children had 2 GAs | 22,914 | Before 2 y.o. | Diagnosis of developmental delay according to ICD-9-CM codes | HR =1.476, 95% CI: 1.155–1.887 | p < 0.05 |
| 2703 children had at least 3 GAs | HR 2.222, 95% CI: 1.810–2.621 | p < 0.001 |