Research paperSequential risk of depression in children born prematurely: A nationwide population- based analysis
Introduction
Live-born infants who are delivered before 37 weeks from the first day of the last menstrual period are termed premature. Due to advancements in assisted reproductive technology and obstetric and neonatal medical care, preterm birth rates have increased while preterm mortality rates have declined (Doyle, 2006). Several studies have shown that improved survival rates are accompanied by increased rates of complications related to preterm birth, such as medical and neurodevelopmental disabilities. A growing body of evidence suggests that the complications associated with preterm birth are likely the result of insufficient gestational age (Stephens et al., 2009).
Many studies have reported a relationship between either preterm birth or low birth weight (LBW) and later comorbidity in adulthood including cardiovascular disease, hypertension, and type II diabetes (Barker et al., 1989, 2006, Barker, 2004, Huxley et al., 2007, Whincup et al., 2008). Some studies on neurodevelopmental disabilities and cognitive deficits have revealed LBW children are at risk of mental disorders (Escobar et al., 1991, McCormick, 1997, Bhutta et al., 2002). The pathogenesis of brain injury in the premature brain is complex and is influenced by a myriad of antenatal, perinatal, and postnatal complications. The adverse effects of preterm birth on normal processes are comprehensive, such as neuronal migration, synaptogenesis, myelination, and cytological maturation.
The psychiatric problems associated with preterm birth and LBW are garnering increasing awareness (Botting et al., 1997, Mathewson et al., 2017). Increasing bodies of evidence suggest that either preterm birth or LBW is a risk factor for some psychiatric disorders including emotional disorders, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). One study suggested that depression is likely associated with preterm birth or LBW (Patton et al., 2004).
Data regarding the relationship between depression and preterm birth are scant, and this relationship warrants clarification. Therefore, we conducted a population-based national cohort study to determine the risk of depression in those born prematurely.
Section snippets
Data source and participants
Data of the participants of this study were extracted from the National Health Insurance Research Database, which contains medical records of patients who have joined the National Health Insurance (NHI) program in Taiwan. The NHI program was instituted in 1995 and currently covers over 99% of Taiwan's residents. The study population comprised people aged younger than 18 years.
In this study, we classified preterm infants (case cohort) and full-term infants (control cohort) according to the
Distribution of demographics
The study population comprised 21,478 preterm children and 85,903 full-term children (Table 1). The mean ages of the case and control cohorts were 9.72 and 9.88 years, respectively. A significant difference in mean age was observed between the two groups (p < 0.001). In the case cohort, the proportion of male patients was higher than that of female patients by 11%. Approximately 60% of preterm children lived in an area with level 1 or level 2 urbanization. In addition, 60% of preterm children
Discussion
The present study included a large study population and long observational period, and the findings reveal that preterm children had a 2.75-fold higher risk of depression than full-term children. Previous studies have reported that adolescents with a very LBW (VLBW) or extremely LBW (ELBW) had an increased prevalence of depression, which is consistent with our findings (Botting et al., 1997, Saigal et al., 2003).
Why preterm children are associated with a higher risk of depression during
Strengths and limitations
A key strength of this study is its population-based design and inclusion of all preterm infants born in Taiwan from 2000 to 2010. Therefore, this study had sufficient power to detect small effects. Depression is a dynamic illness that occasionally relapses and remits. Most studies have adopted questionnaires at one time point in childhood or adult life; this is likely to underestimate the rate of depression. By contrast, we selected participants who received a clinical diagnosis of depression
Conclusions
The findings of the present study suggest that preterm infants have a significantly higher risk of depression in adolescence, compared with full-term infants. Health care providers should maintain a high index of suspicion when encountering cases involving children who were born prematurely, and early psychiatric referral is warranted for them.
Conflict of interest
All authors declare that they have no conflict of interest.
Author contributions
Data collection and organization: All authors.
Data analysis and interpretation: All authors.
Manuscript writing: All authors.
Final approval of the manuscript: All authors.
Acknowledgements
This work was supported by grants from the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital (CMU107-ASIA-19, DMR-107-192), Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005-), Tseng-Lien Lin Foundation, Taichung, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. The funders had no role in the study design, data collection and analysis, publication decision,
References (35)
- et al.
Weight in infancy and death from ischaemic heart disease
Lancet
(1989) Evaluation of neonatal intensive care for extremely-low-birth-weight infants
Semin. Fetal Neonatal Med.
(2006)- et al.
A multilevel analysis of the relation of socioeconomic status to adolescent depressive symptoms: does school context matter?
J. Pediatr.
(2003) - et al.
Is birth weight a risk factor for ischemic heart disease in later life?
Am. J. Clin. Nutr.
(2007) - et al.
Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities
Pediatr. Neurol.
(2005) - et al.
Prematurity, maternal stress, and mother-child interactions
Early Hum Dev.
(2004) - et al.
What explains the relation between family poverty and childhood depressive symptoms?
J. Psychiatry Res.
(2008) Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances
Lancet Neurol
(2009)The developmental origins of adult disease
J. Am. Coll. Nutr.
(2004)- et al.
Mechanisms of disease: in utero programming in the pathogenesis of hypertension
Nat. Clin. Pract. Nephrol.
(2006)
Cognitive and behavioral outcomes of school-aged children who were born preterm
JAMA
Attention deficit hyperactivity disorders and other psychiatric outcomes in very low birth weight children at 12 years
J. Child Psychol. Psyc.
Emotional, behavioral, social, and academic outcomes in adolescents born with very low birth weight
Pediatrics
Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort
Arch Gen Psychiatry
Outcome among surviving very low birthweight infants: a meta-analysis
Arch Dis Child
Longitudinal study assessing the joint effects of socio-economic status and birth risks on adult emotional and nervous conditions
Br. J. Psychiatry Suppl.
Birth weight and later risk of depression in a national birth cohort
Br. J. Psychiatry
Cited by (4)
Polygenic scores for schizophrenia and major depression are associated with psychosocial risk factors in children: evidence of gene–environment correlation
2022, Journal of Child Psychology and Psychiatry and Allied DisciplinesResearch Review: Developmental origins of depression – a systematic review and meta-analysis
2021, Journal of Child Psychology and Psychiatry and Allied DisciplinesAnxiety and Depressive Disorders in Children Born Preterm: A Meta-Analysis
2021, Journal of Developmental and Behavioral Pediatrics
- 1
Both authors equally contributed.