A LANDMARK umbrella review has brought unprecedented clarity to the wide range of non-genetic factors that may influence miscarriage risk, while simultaneously revealing how little high-quality evidence currently exists. Researchers analysed findings from 147 meta-analyses covering 227 non-genetic exposures.
The review examined risk factors across multiple domains, including hormone levels, nutrition, environmental toxins, medication use, reproductive history, and occupational exposures. Despite the breadth of data, no factor met the threshold for strong or high-certainty evidence, highlighting the persistent complexity of miscarriage research.
Miscarriage Risk Linked to Multiple Modifiable Factors
However, the authors identified 45 risk factors supported by “suggestive evidence”, meaning that the associations were statistically significant but still vulnerable to bias or confounding. Among these were several clinically relevant and potentially modifiable exposures, including hypothyroidism, vitamin B12 deficiency, elevated urinary phthalates, use of statins and certain anti-inflammatory medications.
Other identified factors included polycystic ovary syndrome and short interpregnancy intervals. Importantly, many commonly cited risks, such as caffeine intake, maternal stress, or occupation, showed weak or insufficient evidence.
The researchers emphasise that these findings should not currently guide screening or clinical decision-making. Instead, the review provides a roadmap to help prioritise high-quality research and inform public-health strategy.
They also argue that some exposures already warrant attention from a precautionary perspective, particularly chemical exposures found in plastics and consumer products, and nutritional deficiencies that can be corrected through routine care.
Urgent Need for Higher-Quality Miscarriage Research
Miscarriage affects up to one in five recognised pregnancies, yet remains under-researched and often poorly understood. This umbrella review underscores that reproductive loss is rarely attributable to a single factor and that more rigorous prospective studies are urgently needed. By identifying promising leads and methodological gaps, the study aims to accelerate progress toward meaningful prevention strategies.
Reference
Arshadi M et al. Non-genetic risk factors of miscarriage: a comprehensive umbrella review of systematic reviews and meta-analyses. Reprod Health. 2025;22(1):25–45.
