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November 6, 2023
Threatened spontaneous abortion is defined as vaginal bleeding without cervix dilation within 20 weeks of the onset of pregnancy.
Risk factors include advanced age, obesity, lifestyle (e.g., caffeine intake, lack of physical exercise, stress, cigarette smoking, and alcohol intake), socioeconomic variables, and low serum progesterone. Progesterone is a female hormone that plays a key role in the implantation of the fertilized egg, formation of the placenta, and sustaining a pregnancy.
Threatened spontaneous abortion affects roughly a fifth of pregnancies in the first trimester (first three months). Up to 11 weeks into pregnancy, it seldom leads to spontaneous abortion, but after 11 weeks the likelihood shoots up to as high as half of the affected pregnancies.
Denmark has universal single-payer health insurance. A team of researchers at Aarhus University used their country's comprehensive administrative and healthcare registries to explore any possible association between threatened spontaneous abortion and subsequent ADHD.
That enabled them to analyze a nationwide population of 1,864,221 singletons (as opposed to multiple births such as twins or triplets) live-born from 1979 to 2010. Of these children,59,134 (3.2%) experienced threatened spontaneous abortion within 20 weeks of gestation.
The team adjusted for a series of covariants that could confound outcomes: characteristics of mothers [age at childbirth, pre-pregnancy co-morbidities (somatic, neurologic, psychiatric), healthcare use, medication use, income, education, and employment]; fathers (age on the date of the child's birth, psychiatric co-morbidities a history of epilepsy, cerebral palsy, and ADHD); and children (birth year, birth order).
With these adjustments, they found that children who had experienced threatened spontaneous abortion were a fifth (21%) more likely to have ADHD. But it's exceedingly difficult to account for all confounding variables.
Because of the enormous size of the sample, however, the team was also able to compare 15,875 individuals who experienced threatened spontaneous abortions with an equal number of their paired full siblings who did not, to examine the effect of residual confounding variables. This time, they found no significant differences in the likelihood of ADHD between full siblings.
The authors observed that "controlling for family-shared factors, including genetic makeup and other factors remaining constant between pregnancies and in children's early environments, removed family-shared confounding." They concluded, "After removal, by the sibling design, of time-invariant family-shared confounding, there was no evidence of an increased risk of epilepsy or ADHD among TAB [Threatened Abortion]-affected children."
Elena Dudukina, Erzsébet Horváth-Puhó, HenrikToft Sørensen, and Vera Ehrenstein, “Long-term risk of epilepsy, cerebral palsy and attention-deficit/hyperactivity disorder in children affected by threatened abortion in utero,” International Journal of Epidemiology (2021)dyab069, published online, https://doi.org/10.1093/ije/dyab069.
The Background:
Stimulant medications (like methylphenidate and amphetamines) and non-stimulants (like atomoxetine and guanfacine) remain the first-line treatments for ADHD, but their long-term use is often constrained by parental concerns, side effects (reduced appetite, sleep disruption, cardiovascular effects), and the fact that roughly 30% of children respond only partially or not at all. These medications tend to help with attention and behavior, but they do less to address emotional regulation or broader physical health, leaving some parents to seek other safe, complementary treatments.
Nutritional approaches, including omega-3 fatty acids, are one such avenue. Oily fish is the natural source, but clinical trials typically rely on supplements instead, since they allow for precise dosing, avoid the heavy-metal exposure that can come with high fish intake, and sidestep the problem of inconsistent dietary habits. Two omega-3s stand out as particularly relevant: DHA, which supports brain structure and cell-to-cell communication, and EPA, which helps reduce brain inflammation and improve blood flow. Both influence the dopamine and serotonin systems implicated in ADHD.
The Study:
Previous meta-analyses have generally found only modest overall benefits with mixed results. This mixed-results pattern may reflect the fact that children who had low omega-3 levels to begin with stand to benefit more than those whose levels are already adequate. This meta-analysis set out to test that idea directly, asking whether a child's baseline omega-3 status predicts how well they respond to supplementation.
To be included, studies had to be randomized controlled trials (RCTs) involving children diagnosed with ADHD who did not have major coexisting medical conditions. Trials that used broad multinutrient interventions, where the effect of omega-3s specifically couldn't be isolated, were excluded.
The resulting analysis of seven RCTs covering 654 children found small overall improvements in ADHD symptoms with omega-3 supplementation, consistent with earlier meta-analyses. There was little variation across studies, but a clear signal of publication bias, which the authors did not attempt to statistically correct for.
Among four RCTs involving 369 children with low baseline omega-3 levels, supplementation produced a moderate improvement in ADHD symptoms, with consistent results across studies. By contrast, the six RCTs covering 559 children with normal or high baseline omega-3 levels showed no improvement at all, again with consistent results across studies.
The Results:
The authors concluded: this systematic review and meta-analysis offers preliminary evidence that children’s response to long-chain omega-3 supplementation for ADHD may depend on their starting omega-3 nutritional status. Larger effects emerged in the subgroups defined by individual studies as having low baseline levels, while normal, high, or unstratified groups showed little evidence of benefit. In other words, there may be a benefit to children with ADHD taking omega-3 supplements, but only if they are already deficient.
Even still, a sensitivity analysis limited to ADHD symptom-rating scales found only a numerically higher effect in the low-baseline group. This means that these results, though positive, are not considered statistically significant.
The Take-Away:
Given that the evidence rests on just seven trials, that “low baseline” was defined differently across studies (using different biological markers and thresholds), and that several subgroup comparisons were not planned in advance, the authors caution that these findings should be treated as hypothesis-generating rather than conclusive.
The Background:
Previous research has suggested that people with ADHD have higher rates of death than those without the condition. Until now, many of those studies lacked the detail needed to untangle why this might be the case. A recent meta-analysis of eight separate studies reported that ADHD roughly doubled the risk of death, and it hinted that factors like socioeconomic status and other mental illnesses might help explain the link.
The Study:
To explore this in more detail, researchers used the US National Health Interview Survey, a nationally representative prospective cohort of just over 52,000 adults. Survey records were linked with the National Death Index, and participants were followed from the date of interview until death or December 31, 2019, whichever came first. The main outcome was death from any cause. With a median follow-up of just under eight years, there were 6,024 deaths recorded.
When the team adjusted their analysis for age, sex, ethnicity, and the year of the survey, having ADHD was associated with a 58% higher risk of death. Controlling further for family income and educational level reduced that increased risk slightly, to 50%.
Controlling for health conditions (like high blood pressure, diabetes, stroke, heart disease, and cancer) and lifestyle factors (smoking, alcohol use, physical activity, and body weight) also reduced the association to about 46%.
By contrast, when the researchers adjusted for two psychiatric conditions (anxiety and depression) commonly found alongside ADHD, the link between ADHD and higher mortality disappeared statistically. In other words, once anxiety and depression were taken into account, ADHD itself was no longer associated with a clearly measurable increase in the risk of death.
What Does This Mean?
The authors conclude that the apparent effect of ADHD on mortality seems to operate largely through accompanying mental illness, and to a lesser extent through lifestyle and physical health problems. They suggest that treating and managing these co-occurring issues (through medications, therapy, and behavioral interventions) might help reduce the risk of premature death in people with ADHD, although they note that further evidence is needed.
The Background:
Dementia is a rapidly growing public health problem affecting more than 50 million people worldwide. Nearly 10 million new cases are diagnosed each year, and that number is expected to almost triple by 2050. The most common form is Alzheimer’s disease, accounting for roughly 60–70% of cases, followed by vascular dementia at around 20%. Other types include dementia with Lewy bodies, Parkinson’s disease dementia, and frontotemporal dementia. While no cure exists, managing modifiable risk factors (such as high blood pressure, smoking, physical inactivity, and poorly controlled diabetes) can delay or slow both the onset and progression of the condition.
Several studies have reported an elevated dementia risk among people with ADHD, and a number of mechanisms may explain this association. These include shared genetic or neurobiological vulnerabilities, reduced cognitive reserve (leaving the brain less resilient to age-related damage), and greater lifetime exposure to other established dementia risk factors.
Earlier reviews explored the possible link between ADHD and dementia, but tended toward a broader scope (incorporating other neurodegenerative disorders or mixing study designs), which introduced substantial variability and precluded quantitative synthesis. The relevant research literature has also expanded considerably since those reviews appeared.
The Study:
This meta-analysis restricted inclusion to case-control and cohort studies, yielding five that met the criteria. One was a case-control study with 400 participants; the other four were cohort studies collectively covering 3.7 million individuals, two retrospective and two prospective.
The Results:
Pooling the four cohort studies, individuals with ADHD showed approximately two-and-a-half times the dementia risk of those without the diagnosis. There was no indication of publication bias.
The Take-Away:
The authors concluded that ADHD is associated with a significantly increased risk of all-cause dementia in later life, while noting that its relationship to specific dementia subtypes remains less clear and warrants attention in future research.
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