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August 1, 2024
Lead’s neurotoxicity is well established, and organophosphate pesticides were deliberately developed first as nerve agents in warfare and then as insecticides.
Noting that “Epidemiologic research on chemical exposures associated with the development of ADHD is numerous; however, studies have employed various methods, and, in some cases, have resulted in seemingly conflicting results,” a U.S. study team has performed an updated meta-analysis applying “identical meta-analytic techniques to the literature on the associations between earlier chemical exposures and later ADHD.”
Lead
Meta-analysis of eleven studies reporting dichotomous outcomes with a combined 7,566 participants found children exposed to lead were almost twice as likely to subsequently be diagnosed with ADHD as their unexposed peers.
A second meta-analysis, of thirteen studies reporting continuous outcomes with a total of 1,775 participants, found a small effect size increase in ADHD diagnosis from exposure to lead.
Interestingly, meta-analysis of four studies with a combined 4,360 participants found no association between prenatal lead exposure and subsequent ADHD diagnosis.
On the other hand, meta-analysis of seven studies combining almost five thousand participants reported that cumulative lead exposure more than doubled the likelihood of subsequent ADHD.
In other words, it’s not so much prenatal exposure as exposure after birth that is associated with increased risk.
Organophosphates
Meta-analysis of four studies reporting continuous outcomes with a combined total of 692 persons likewise found a small effect size increase in ADHD diagnosis from exposure to organophosphates.
Mercury
Meta-analysis of six studies reporting continuous outcomes with a combined total of over 17 thousand participants found a tiny effect size increase in ADHD diagnosis from exposure to mercury.
On the other hand, meta-analysis of ten studies reporting dichotomous outcomes with a combined total of over 650,000 persons found no association whatsoever between mercury exposure and subsequent diagnosis of ADHD.
Other exposures
Meta-analysis of five studies involving more than 34,000 participants found no evidence of an association between exposure to anesthesia and ADHD.
Meta-analysis of three studies encompassing 1,739 individuals found no evidence of an association between exposure to cadmium and ADHD.
Meta-analysis of four studies combining more than 2,400 persons found no evidence of an association between exposure to hexachlorobenzene and ADHD.
A pair of meta-analyses, one of three studies reporting dichotomous outcomes including 2,050 participants, the other of nine studies reporting continuous outcomes involving almost three thousand participants, both found no evidence of an association between exposure to polychlorinated biphenyls (PCBs) and ADHD.
There was little variability (heterogeneity) among results reported by individual studies within these meta-analyses, but a serious limitation was the failure to check for publication bias.
The authors concluded, “given our findings related to exposure to mercury, organophosphates, and PCBs, further research may be helpful to better characterize these relationships. Many of our effect sizes were small, which is consistent with the literature indicating that many genetic and environmental factors contribute to ADHD. … Furthermore, our findings support existing regulations of certain chemicals,” and “may inform future regulatory decisions”
Lina V. Dimitrov, Jennifer W. Kaminski, Joseph R. Holbrook, Rebecca H. Bitsko, Michael Yeh, Joseph G. Courtney, Brenna O’Masta, Brion Maher, Audrey Cerles, Katherine McGowan, and Margaret Rush, “A Systematic Review and Meta-analysis of Chemical Exposures and Attention-Deficit/Hyperactivity Disorder in Children,” Prevention Science (2024), 25 (Suppl 2):S225–S248, https://doi.org/10.1007/s11121-023-01601-6.
Counting umbilical cord vessels is standard in prenatal ultrasounds and confirmed at birth. Single umbilical artery (SUA) occurs in about 1 in 200 cases, with roughly 10% associated with anomalies, including central nervous system defects. Isolated SUA (iSUA) means one artery is missing without other structural issues.
Research on SUA, especially isolated iSUA, and childhood neurodevelopmental disorders (NDD) is limited and inconclusive. iSUA is linked to preterm birth and small-for-gestational age (SGA), both of which are NDD risk factors.
This Norwegian nationwide population study aimed to assess NDD risk in children with iSUA at birth, the influence of sex, and how preterm birth and SGA mediate this relationship.
The nation’s universal single-payer health insurance and comprehensive population registries made it possible to analyze all 858,397 single births occurring from 1999 to 2013, with follow-up continuing through 2019. Among these cases, 3,532 involved iSUA.
After adjusting for confounders such as parental age, education, and maternal health factors, no overall link was found between iSUA and later ADHD diagnosis. However, females with iSUA had about a 40% higher risk of subsequent ADHD compared to those without iSUA, even after adjustment.
The authors concluded, “The present study indicates that iSUA is weakly associated with ID [intellectual disability] and ADHD, and these associations are influenced by sex. This association is mediated negligibly through preterm birth and SGA. The associations were not clinically significant, and the absence of associations of iSUA with other NDD is reassuring. This finding can be useful in the counseling of expectant parents of fetuses diagnosed with iSUA.”
Refractive errors, such as myopia (nearsightedness), hyperopia (farsightedness), and astigmatism (distorted vision due to irregular curvature of the eye or lens), are common worldwide. These conditions affect 12%, 5%, and 15% of children, and rise significantly in adults to 26.5%, 31%, and 40%. Additionally, strabismus (misalignment of the eyes) and amblyopia (reduced vision in one eye from uneven image formation, often linked to strabismus) occur globally at rates of 2% and 1.4%, respectively.
Visual impairment can affect children’s concentration in school, and studies suggest a link between eye disorders and ADHD.
To investigate this relationship, two researchers – one based in the US and the other in Israel –carried out a nationwide retrospective cohort study using electronic medical records of all insured individuals aged 5 to 30 who were part of Maccabi Health Services, Israel’s second largest health maintenance organization, between 2010 and 2022.
Of over 1.6 million insured members (2010–2020), inclusion/exclusion criteria and propensity score matching for age and sex were applied, along with a one-year wash-out period between the first eye diagnosis and ADHD diagnosis. In total, 221,707 cases were matched with controls without eye disorders at a 1:2 ratio, resulting in a cohort of 665,121 participants.
Overall, those with any previous eye diagnosis were 40% more likely to have a subsequent ADHD diagnosis. This was slightly higher for females (45%) than for males (35%). It was also slightly higher for children and adolescents (42%) than for adults (37%).
More specifically:
The authors concluded that eye disorders are associated with ADHD. They noted these associations were more marked in females and children and adolescents, although, as noted above, those differences were small. They recommended that primary care providers and neurologists consider risk stratification for early screening, and that ophthalmologists refer high-risk patients for ADHD evaluation.
Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, are often prescribed during pregnancy to treat heartburn and gastroesophageal reflux disease.
Research shows changes in the gut microbiome can negatively affect neurodevelopment. Since acid-suppressive medications alter gut microbiota, maternal use during pregnancy may impact offspring’s neurodevelopment. Because PPIs and H2 receptor antagonists readily cross the placental barrier, they could potentially influence fetal neurodevelopment.
The link between prenatal exposure to acid-suppressive medications and major neuropsychiatric disorders is not well understood. With the use of these medications during pregnancy rising, it is important to assess their impact on children's long-term neurodevelopment. This study examined whether maternal use of acid-suppressive drugs is associated with increased risk of neuropsychiatric disorders in children, using a large, nationwide birth cohort from South Korea.
South Korea operates a single-payer health insurance system, providing coverage for over 97% of its citizens. The National Health Insurance Service (NHIS) maintains a comprehensive database with sociodemographic details, medical diagnoses, procedures, prescriptions, health examinations, and vital statistics for all insured individuals.
A Korean research team analyzed data from over three million mother-child pairs (2010–2017) to assess the risks of prenatal exposure to acid-suppressing medications. They applied propensity scoring to adjust for maternal age, number of children, medical history, and outpatient visits before pregnancy, to minimize confounding factors. That narrowed the cohort to just over 800,000 pairs, with half in the exposed group.
With these adjustments, prenatal exposure to acid-suppressing medications was associated with 14% greater likelihood of being subsequently diagnosed with ADHD.
Yet, when 151,737 exposed births were compared to the same number of sibling controls, no association was found between prenatal exposure and subsequent ADHD, which suggests unaccounted familial and genetic factors influenced the preceding results.
The Take-Away:
Evidence of these medications negatively affecting pregnancies is mixed, mostly observational, and generally reassuring when these medications are used appropriately. Untreated GERD and gastritis, however, have known risks and associations with the development of various cancers. With no evidence of an association with ADHD (or for that matter any other neuropsychiatric disorder), there is no current evidence-based reason for expectant mothers to discontinue use of acid-suppressing medications.
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