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Original Investigation
April 1, 2020

Association of Preeclampsia in Term Births With Neurodevelopmental Disorders in Offspring

Author Affiliations
  • 1Department of Pediatrics, University of Washington, Seattle
  • 2Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
  • 3Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  • 4Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, North Carolina
  • 5Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
JAMA Psychiatry. Published online April 1, 2020. doi:10.1001/jamapsychiatry.2020.0306
Key Points

Question  Is preeclampsia linked to the neurodevelopment of offspring beyond its established association with cerebral palsy?

Findings  In this population-based birth cohort of 980 560 participants based on the Norwegian Medical Birth Registry, preeclampsia in term pregnancies was associated with an increased risk of cerebral palsy, autism, attention-deficit/hyperactivity disorder, epilepsy, and intellectual disability in offspring.

Meaning  After excluding the possible role of preterm delivery, preeclampsia in term pregnancies was associated with an increased risk of neurodevelopmental disorders among offspring.

Abstract

Importance  Preeclampsia during pregnancy has been linked to an increased risk of cerebral palsy in offspring. Less is known about the role of preeclampsia in other neurodevelopmental disorders.

Objective  To determine the association between preeclampsia and a range of adverse neurodevelopmental outcomes in offspring after excluding preterm births.

Design, Setting, and Participants  This prospective, population-based cohort study included singleton children born at term from January 1, 1991, through December 31, 2009, and followed up through December 31, 2014 (to 5 years of age), using Norway’s Medical Birth Registry and linked to other demographic, social, and health information by Statistics Norway. Data were analyzed from May 30, 2018, to November 17, 2019.

Exposures  Maternal preeclampsia.

Main Outcomes and Measures  Associations between preeclampsia in term pregnancies and cerebral palsy, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), epilepsy, intellectual disability, and vision or hearing loss using multivariable logistic regression.

Results  The cohort consisted of 980 560 children born at term (48.8% female and 51.2% male; mean [SD] gestational age, 39.8 [1.4] weeks) with a mean (SD) follow-up of 14.0 (5.6) years. Among these children, 28 068 (2.9%) were exposed to preeclampsia. Exposed children were at increased risk of ADHD (adjusted odds ratio [OR], 1.18; 95% CI, 1.05-1.33), ASD (adjusted OR, 1.29; 95% CI, 1.08-1.54), epilepsy (adjusted OR, 1.50; 95% CI, 1.16-1.93), and intellectual disability (adjusted OR, 1.50; 95% CI, 1.13-1.97); there was also an apparent association between preeclampsia exposure and cerebral palsy (adjusted OR, 1.30; 95% CI, 0.94-1.80).

Conclusions and Relevance  Preeclampsia is a well-established threat to the mother. Other than the hazards associated with preterm delivery, the risks to offspring from preeclampsia are usually regarded as less important. This study’s findings suggest that preeclampsia at term may have lasting effects on neurodevelopment of the child.

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    1 Comment for this article
    EXPAND ALL
    The forgotten variables in the association between preeclampsia and neurodevelopmental disorders
    Carlos Escudero, MD, PhD | Vascular Physiology Laboratory, Basic Sciences Department, Universidad del Bio-Bio. Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillán, Chile
    The association between preeclampsia and high risk of developing neurodevelopmental disorders was recently studied by Sun et al1. We agree with the authors that there are many other variables that may affect the association demonstrated, including some that could not be studied, such as the characteristics of breastfeeding, or early stimulation, which are important factors in neurodevelopment.
    This study indicates the association of preeclampsia with severe neurocognitive disorders in offspring. However, there are other types of equally important disorders that can also occur in those children, such as alterations in verbal reasoning and reduction in verbal skills2. Spoken language is
    a component of superior cognitive functions, for which development is a complex process of continuous evolution that is naturally learned by a series of interactions with the environment. Recently, we found that preschool children of mothers who had preeclampsia presented a decreased capacity to understand and to express a narrative discourse3, which may negatively impact their subsequent schooling.
    The referred study was carried out in a Swedish population, where the preeclampsia rate was 2.9% (28,068 individuals). Of this population, ~3% of the children had clinical records of neurological disorders. Therefore, a large proportion of the “exposed” population (~27,444; 97%) might be at increased risk for other neurodevelopmental alterations, including linguistic or communicative disorders. Therefore, language disorders receiving less clinical attention, but with a profound effects on cognitive, academic, and social performance, should be explored in future population studies. Furthermore, the language analysis should consider the evolution of communicative skills (expressive and comprehensive) framed at the levels of phonetic-phonological (sound production), lexical-semantic (meaning of words and relationships between them), morphosyntactic (structure of words and sentences), pragmatic (use of language), and narrative discourse.
    Another aspect is the lack of population studies in Latin America where preeclampsia complicates 5-17% of pregnancies4. Additionally, other characteristics of pregnancies in Latin America—such as the socio-cultural context; the lower maternal age of pregnancy, which is associated with higher parity; the lower schooling of the parents—to list a few adjustment variables from the Swedish study, are confounder variables that might differentially affect the relationship between pregnancy complications and future wellbeing in the offspring. We want to emphasize, the increased vulnerability of the children of mothers with preeclampsia in Latin American countries that unfortunately are not receiving adequate attention in governmental policies or as a target for research.

    Yesenia Torres
    Jesenia Acurio
    Carlos Escudero

    References

    1. Sun BZ, Moster D, Harmon QE, Wilcox AJ. Association of Preeclampsia in Term Births With Neurodevelopmental Disorders in Offspring. JAMA Psychiatry 2020.
    2. Whitehouse AJ, Robinson M, Newnham JP, Pennell CE. Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring? Paediatr Perinat Epidemiol 2012; 26(2): 101-8.
    3. Acurio J, Torres Y, Manriquez G, et al. [Alteration in the narrative discourse in children born to mother who had preeclampsia]. Rev Logop Fon Audiol 2020; In press.
    4. Giachini FR, Galaviz-Hernandez C, Damiano AE, et al. Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries. Curr Hypertens Rep 2017; 19(10): 83.
    CONFLICT OF INTEREST: None Reported
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