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Maternal spontaneous abortion and the risk of attention-deficit/hyperactivity disorder in offspring: a
Hui Wang1, Fei Li1, Maohua Miao2
1MOE-Shanghai Key Laboratory of Children's Environmental Health, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
Maternal history of spontaneous abortion (SA) is linked to a higher risk of attention-deficit/hyperactivity disorder (ADHD) in children. This risk increases with the number of SAs and is highest in firstborns following recurrent SAs.
Area of Science:
- Reproductive health and child neurodevelopmental disorders.
- Epidemiology of pregnancy outcomes and child psychiatric conditions.
Background:
- Maternal spontaneous abortion (SA) is associated with pregnancy complications and adverse birth outcomes, known risk factors for ADHD.
- Previous research has not established a direct link between maternal SA history and offspring ADHD risk.
Purpose of the Study:
- To investigate the association between a maternal history of spontaneous abortion (SA) and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring.
- To quantify the risk increase based on the number of SAs and birth order.
Main Methods:
- A population-based cohort study in Denmark involving over 1 million live-born children.
- Children were followed from age 3 until ADHD diagnosis, death, emigration, or end of 2016.
- Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Main Results:
- Children of mothers with a history of SA had a 11% increased rate of ADHD (HR, 1.11; 95% CI, 1.07-1.15).
- The risk of ADHD increased with the number of maternal SAs: HR of 1.09 for one SA and 1.22 for at least two SAs.
- Findings remained consistent after adjusting for confounders like socioeconomic status, birth order, and parental psychiatric history.
Conclusions:
- A maternal history of spontaneous abortion is associated with an increased risk of ADHD in offspring.
- The risk is dose-dependent on the number of SAs and is highest in firstborns of mothers with recurrent SAs.
- Given the frequency of SA, even a small increase in neurodevelopmental risks has significant public health implications.
Study Question:
Is a maternal history of spontaneous abortion (SA) associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring?
Summary Answer:
Our results suggest an association between maternal history of SA and ADHD in offspring, with the risk increasing with the number of maternal SA and highest in the firstborn children whose mothers had had recurrent SAs after adjusting for a number of potential confounders.
What Is Known Already:
A history of SA has been associated with more complications in next pregnancies and adverse childbirth outcomes, which are risk factors for ADHD in the offspring. However, no previous study has investigated whether maternal SA increases risk of ADHD in the offspring.
Study Design, Size, Duration:
This population-based study included all live-born children in Denmark from 1 January 1995 to 31 December 2012 (n = 1 062 667). All children were followed from 3 years of age until the day of ADHD diagnosis, death, emigration or 31 December 2016, whichever came first.
Participants/Materials, Setting, Methods:
There were 130 206 (12.2%) children born to mothers who had at least one SA. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Main Results And The Role Of Chance:
During a median follow-up of 9.4 years (interquartile range, 5.4-14.3), 25 747 children were diagnosed with ADHD. Overall, children of mothers with a history of SA had an increased rate of ADHD (HR, 1.11; 95% CI, 1.07 to 1.15). The HRs increased with the number of maternal SA, 1.09 (95% CI, 1.05 to 1.13) for one SA and 1.22 (95% CI, 1.12 to 1.33) for at least two SAs, respectively. These findings were consistent when we took into consideration a number of factors, such as maternal socioeconomic status, type of SA, birth order, parental history of psychiatric disorders, pregnancy characteristics and adverse birth outcomes.
Limitations, Reasons For Caution:
Misclassification of SA was possible as we used population-based register data to capture maternal history of SA. However, any misclassification of maternal history of SA would be non-differential with regard to the diagnosis of ADHD in offspring, which generally leads to underestimation of the associations. Furthermore, probabilistic sensitivity analysis suggested that only 1% of change in the estimate may have been due to misclassification of SA.
Wider Implications Of The Findings:
SA is quite frequent (varying from 15 to 20%), and a small increase of neurodevelopmental problems in offspring could have major public health implications.
Study Funding/Competing Interest(S):
This work was supported by grants from the National Natural Science Foundation of China (No. 81703237, No. 81530086 and No. 81761128035), National Key Research and Development Program (2018YFC1002801, 2016YFC1000505), Shanghai Municipal Commission of Health and Family Planning (No. 2017ZZ02026, No. 2017EKHWYX-02), the Novo Nordisk Foundation (NNF18OC0052029), the Danish Council for Independent Research (DFF-6110-00019), the Nordic Cancer Union (176673, 186200 and R217-A13234-18-S65), Karen Elise Jensens Fond (2016) and Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (2018YJRC03). All authors report no conflict of interest.
Trial Registration Number:
NA.
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