September 5, 2024

Swedish Nationwide Population Study Finds No Association Between Acetaminophen Use During Pregnancy and Offspring ADHD

A 2021 consensus statement by an international group of scientists and clinicians (Bauer et al.) recommended that pregnant individuals “forego [acetaminophen] unless its use is medically indicated,” due to the potential risk of developmental disorders such as autism and attention-deficit/hyperactivity disorder (ADHD). 

A mostly Swedish research team, collaborating with a U.S. researcher, nevertheless noted that previous studies have been limited by: 

  • Confounding by indication, because acetaminophen is taken for infection, fever, and pain (including pain from autoimmune disease), which are themselves risk factors for neurodevelopmental disorders such as ADHD. 
  • Confounding by parental health and genetics, because neurodevelopmental disorders are highly heritable. 
  • Small sample sizes. 

Sweden has a single-payer health insurance system that includes virtually its entire population, and national registers that enable tracking the health history of mothers and their children, including their children’s siblings. 

The team used the Swedish registers to identify the roughly two-and-a-half million children born in Sweden from mid-1995 through 2019. They were also able to identify all siblings to be able to control for otherwise unmeasured familial and genetic confounding. 

Almost 186,000 of these children were exposed to acetaminophen during pregnancy.  

After adjusting for available known confounders, including (but not limited to) child sex and birthdate, mother’s age and medical history, use of any other painkillers, use of any psychoactive medications, country of birth, residential region, smoking status, highest household education, and disposable income, children exposed to acetaminophen during pregnancy were 7% more likely to be diagnosed with ADHD subsequently than those who were not exposed. 

However, roughly the same results were found for other painkillers, including aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and antimigraine medication.   High doses of acetaminophen did not produce any stronger association with subsequent ADHD than low dosage. 

Moreover, when confining results to siblings – 8,526 children who were exposed versus 87,679 who were unexposed – the association between acetaminophen use during pregnancy and subsequent offspring ADHD vanished altogether (and, again, at every dose level). The associations similarly vanished with every other painkiller medication.  

The Swedish team concluded, “Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in models without sibling control may have been attributable to confounding.” 

Viktor H. Ahlqvist, Hugo Sjöqvist, Christina Dalman, Håkan Karlsson, Olof Stephansson, Stefan Johansson, Cecilia Magnusson, Renee M. Gardner, and Brian K. Lee, “Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability,” JAMA (2024), 331(14):1205-1214, https://doi.org/10.1001/jama.2024.3172

Ann Z. Bauer, Shanna H. Swan, David Kriebel, Zeyan Liew, Hugh S. Taylor, Carl-Gustaf Bornehag, Anderson M. Andrade, Jørn Olsen, Rigmor H. Jensen, Rod T. Mitchell, Niels E. Skakkebaek, Bernard Jégou, and David M. Kristensen, “Consensus Statement: Paracetamol use during pregnancy — a call for precautionary action,” Nature Reviews Endocrinology (2021), 17, 757-766, https://doi.org/10.1038/s41574-021-00553-7

Brandlistuen, R. E., Ystrom, E., Nulman, I., Koren, G. & Nordeng, H. (2013). Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol 42, 1702-13.  

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Population Study Finds No ADHD- or ASD- Related Benefits From Eating Organic Food During Pregnancy

Norwegian Nationwide Population Study Finds No ADHD- or ASD- Related Benefits From Eating Organic Food During Pregnancy

Background:

Organic farming aims to protect biodiversity, promote animal welfare, and avoid using pesticides and fertilizers made from petrochemicals. Some pesticides are designed to target insects’ nervous systems but can also affect brain development and health in larger animals, including humans.

Many people believe organic food is healthier than conventionally produced food, which might be true for certain foods and health factors. But does eating organic food during pregnancy impact the chances of a child developing ADHD or autism spectrum disorder (ASD)?

In Norway, researchers can use detailed national health records to study these connections on a population-wide level, thanks to the country’s single-payer healthcare system and national registries.

Method:

The Norwegian Mother, Father, and Child Cohort Study (MoBa) invites parents to participate voluntarily and has a 41% participation rate. The study includes:

  • 114,500 children
  • 95,200 mothers
  • 75,200 fathers

For this research, a team tracked 40,707 mother-child pairs from children born between 2002 and 2009. They used questionnaires to measure how much organic food mothers consumed during pregnancy. ADHD and ASD symptoms in children were assessed using validated rating scales.

The final analysis included:

  • 40,586 pairs for ADHD symptoms
  • 40,117 pairs for ASD symptoms

The researchers adjusted for factors like maternal age, education, previous pregnancies, BMI before pregnancy, smoking and alcohol use during pregnancy, birth year and season, and the child’s sex.

Key Findings:
  • There was a weak connection between higher organic food consumption and fewer ADHD symptoms in children. However, this link disappeared when maternal ADHD symptoms were considered (31,411 pairs) or when the analysis was limited to siblings (5,534 pairs).
  • Similarly, weak associations between organic food and fewer ASD symptoms disappeared when focusing on siblings (4,367 pairs).
Conclusion:

The researchers concluded that eating organic food during pregnancy has no meaningful effect on the likelihood of a child developing ADHD or ASD. They stated, “The results do not indicate any clinically significant protective or harmful effects of eating organic food during pregnancy on symptoms of ADHD and ASD in the offspring. Based on these findings, we do not recommend any specific advice regarding intake of organic food during pregnancy.”

January 27, 2025

Meta-analysis Finds Little or No Link Between Assisted Reproductive Technologies and ADHD

Background:

Infertility affects about one in six couples worldwide. To address this, medical experts have developed Assisted Reproductive Technologies (ART), including In Vitro Fertilization (IVF) with or without Intra-Cytoplasmic Sperm Injection (ICSI).

Some research suggests that children conceived through ART might have higher rates of intellectual disabilities, cerebral palsy, cancer, and neurological issues compared to children conceived naturally. However, studies looking at a possible link between ART and ADHD have produced mixed and conflicting results.

Until now, there hasn’t been a meta-analysis examining the connection between ART and ADHD. A South Korean research team has conducted the first systematic review and meta-analysis on this topic. Their final analysis included eight studies with a total of over ten million participants, comprising six cohort studies and two cross-sectional studies.

Method:

The research focused on two types of studies:

  1. Cohort Studies: These follow two groups (one exposed to ART and one not exposed) over time to see if a specific outcome, like ADHD, occurs.
  2. Cross-Sectional Studies: These compare the prevalence of ADHD at a single point in time between those exposed to ART and those who weren’t.

Both types of studies are observational, meaning they don’t involve controlled experiments and can be influenced by confounding factors.  So they can document interesting associations, not causality.  The studie were mostly large-scale national studies and used clinical ADHD diagnoses.

Key Findings:
  • Cohort Studies: Meta-analysis of six cohort studies, involving nearly 8 million participants, found no link between ART and ADHD. However, there was high variability (heterogeneity) in the results from individual studies.
  • Cross-Sectional Studies: Meta-analysis of two cross-sectional studies, covering over 2.3 million participants, also found no link between ART and ADHD. Heterogeneity was moderate.
  • Adjustment for Confounding: A separate analysis of three studies that adjusted for confounding factors (like socioeconomic status or parental health) involved more than 7.5 million participants. It found a very small association, with ART-conceived children being 8% more likely to develop ADHD. There was no variability among these studies.
Conclusion:

The researchers concluded that while there may be a small association between ART and ADHD, the effect is minimal, and the results are influenced by differences in study designs. They advised interpreting these findings with caution, noting, “The limited effect size and inherent heterogeneity underscore the need for cautious interpretation.”

January 24, 2025

Taiwan nationwide population study documents link between ADHD and periodontitis in adolescents

Background:

Periodontitis, commonly known as gum disease, is a condition where the gums become inflamed. If untreated, it can cause the gums to pull back from the teeth, exposing their base, which may eventually lead to loose teeth or tooth loss. While this condition mostly affects adults, it’s also common among teens who don’t floss or brush their teeth properly.

Until now, only a few small studies have looked at a possible link between ADHD and gum disease. A team in Taiwan recently conducted a nationwide study to explore this connection.

Taiwan has a universal health insurance program, introduced in 1995, that provides medical care to nearly all (99.7%) residents. The Taiwan National Health Research Database collects and oversees all insurance claims, making it an excellent resource for large-scale studies.

Methods:

The researchers used the database to identify teens aged 12 to 19 with ADHD (diagnosed by a psychiatrist) who had no history of gum disease between 2001 and 2011. These teens made up the ADHD group. They matched each ADHD participant with four teens who didn’t have ADHD or gum disease, creating a control group. The groups were matched by age, gender, enrollment date, family income, place of residence, and other health conditions (like obesity, diabetes, smoking, depression, and substance use).

All diagnoses of gum disease were confirmed by board-certified dentists.

The study included:

  • 16,211 teens with ADHD
  • 162,110 matched controls
Key Findings:
  • Teens with ADHD were 2.3 times more likely to develop gum disease than those in the control group without ADHD.
  • There were no significant differences between boys and girls or among teens from different income levels (low, medium, or high).
  • ADHD medications, mainly methylphenidate, didn’t affect the likelihood of developing gum disease. This was true for both short-term and long-term users compared to non-users.
Conclusion:

The researchers concluded that teens with ADHD have a higher risk of developing gum disease later on, even after accounting for other risk factors like smoking, diabetes, and depression. They stated, “ADHD is an independent risk factor for developing periodontitis.”

January 23, 2025