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2. Birth circumstances as ADHD cause

2. Birth circumstances as ADHD cause

Extensive evidence shows that harmful influences during birth are a significant risk factor for the development of neurodevelopmental disorders that occur long after the causative event.1 This includes ADHD. One long-term study found that of 318 children with birth problems, those who had developed ADHD as children were only 21% ADHD at age 40, but had poorer educational attainment, more ADHD symptoms, and executive problems. Those who had attention problems as children but not full-blown ADHD had 6.6% ADHD at age 40; those who did not show attention problems as children had 6% ADHD. Controls without birth problems had ADHD at 40 years at 1.6%.2

2.1. Premature birth

Preterm delivery significantly increases the risk of ADHD, and the earlier the preterm delivery, the greater the risk:

Pregnancy week / risk increase for ADHD3

    1. to 28th / 2.1-fold (plus 110 %)
    1. up to 32. / 1.6-fold (plus 60 %)
    1. to 34th / 1.4 times (plus 40 %)
    1. up to 36th / 1.3 times (plus 30 %)
    1. to 38th / 1.15 times (plus 15%).

Meta-analyses of 16 studies4 and 12 studies5 as well as further studies67 8 confirm this, one study tends to confirm this,9 another single study does not,10. A cohort study comes to an increase of the ADHD risk by a factor of three with births in the 28th week of pregnancy or earlier.11 The increased ADHD(H)S risk results from the duration of pregnancy itself, i.e. not from the typical preterm birth risks such as oxygen deficiency, cerebral hemorrhage or intrauterine growth retardation.

A study of preterm infants born between 32 and 36 weeks found elevated scores in at least one of the ADHD symptom domains in 65% of 7- to 10-year-olds.12

Another study found that ADHD risk was increased more in spontaneous preterm births than in externally medically induced preterm births. Moreover, the risk of ADHD caused by preterm birth increased further when chorioamnionitis was added (ADHD risk increased by 175%):13

It is suspected that prematurity causes the supply of important substances to end too early, which impairs brain development. It is hypothesized that an additional supply of allopregnanolone could be helpful, in addition to the already established administration of corticosteroids (once) and magnesium sulfate.1415 However, this is contradicted - at least with regard to ADHD - by the finding that only spontaneous preterm births, but not medically induced preterm births, increase the ADHD risk.

Extreme preterm infants showed impairments in attentional guidance as preschoolers, but not in alerting efficiency or in executive aspects of attention.16

In the case of premature birth, the psychological risks to the child seem to result in part more from the premature birth itself, viz17

  • IQ
  • Preparation-Watchfulness
  • Error processing

and partly to be caused more by social or other family circumstances, viz

  • Inhibition
  • Verbal working memory

The usual number of weeks of pregnancy is 40.
Transmitted children born after the calculated date therefore have no increased risk of ADHD from this.

2.2. Low or high birth weight

Low birth weight is likely to increase ADHD risk.181920 Two other studies did not confirm this result.2122

One study found a 77% increased risk of ADHD at birth weight over 4000 grams.23

2.3. Oxygen deficiency at birth

Lack of oxygen at birth increases ADHD risk.24

Oxygen delivery to the newborn during birth correlates with a nearly tripled risk of ADHD.22
Hypoxy-ischemic conditions around birth (e.g., asphyxia) cause an inadequate supply of oxygen to the brain. This can lead to cognitive impairment. Their onset is influenced by dopamine transporter gene polymorphisms.25 Lack of oxygen during birth can cause long-term changes in the dopamine system, and dopamine is important for brain development.2627 Dysfunction of the dopamine system can cause brain developmental disorders such as those associated with ADHD.
One study found evidence that attentional problems following oxygen deprivation during birth are moderated by gevnariants of the dopamine transporter in the PFC.28
Key to this, one study describes a reduction in ischemic sequelae by methylphenidate via activation of the AMPK signaling pathway.29 Since AMPK affects dopamine balance, this may suggest that dopamine deficiency increases the damage of ischemic conditions.

It is well known that hypoxia (lack of oxygen) leads to excess adenosine. Adenosine is closely associated with the dopaminergic system. Adenosine antagonists are able to prevent and correct hypoxia damage. For more information see Adenosine The chapter Neurological Aspects.

Prenatal hypoxia caused massive changes in the dopaminergic system in mice:30

  • a reduction of dopaminergic progenitor cells
  • a delayed early lateral migration of DA neurons
  • a delayed expression of the receptors that control this process
  • a reduced expression of tyrosine hydroxylase in the postnatal striatum
  • an increased density of dopamine release sites with high probability within TH varicosities.

2.4. APGAR values below 7 after 1 minute

The lower the APGAR values, the higher the ADHD risk:

  • Below 5: 7-fold ADHD risk22 (The authors erroneously calculate 9% in controls instead of 0.9% in the text)
  • Between 5 and 7: more than tripled ADHD risk22
  • Below 7 after 1 minute: significantly increased ADHD risk21
  • From 8 no increased ADHD risk22

2.5. Cesarean section

A large meta-study of over 20 million births found that cesarean section increased ADHD(H)S risk by 17%.31 The risk of autism spectrum disorders was increased by 33%.

In contrast, other sources cite a risk increase of 6%32 or 3% to 9%33 or 5% to 15%.34 One small study found no increased ADHD risk from cesarean section.22

One study found that among siblings, only emergency cesarean section resulted in a statistically significant increase in risk for ADHD,34 another found that only cesarean section at birth (intrapartum) increased risk.33

2.6. Newborns with intensive care needs

Newborns who required intensive medical care showed a 60% increased risk of ADHD between the ages of 4 and 11 years.35

Newborns who required treatment in an incubator had a 4.5-fold risk of ADHD.22

2.7. Neonatal jaundice

Newborns with jaundice had a 33% increased ADHD risk. If the jaundice required treatment, the ADHD risk was 2.5 times greater than in unaffected individuals. The ADHD risk was particularly elevated when the jaundice was so severe that all of the newborn’s blood had to be replaced.22
Neonatal jaundice is associated with decreased urinary homovanillic acid in the first few days, suggesting decreased dopamine turnover.36

2.8. Serotonin metabolites in umbilical cord blood

Elevated umbilical cord blood levels of serotonin metabolites correlated with increased later ADHD risk:37

  • Tryptophan: 25 %
  • 5-HTP: 32 %
  • N-acetyltryptophan: 27 %

The risk of ASD or other mental disorders remained unchanged.

Elevated umbilical cord blood levels of the serotonin metabolite

  • 5-methoxytryptophol

correlated with a 21% reduced risk of ADHD and a 44% reduced risk of ASD)

2.9. Antibiotics after birth

One metastudy found a 12% increased ADHD risk from postnatal antibiotic administration.38

2.10. Characteristics without increased ADHD risk

The following factors do not appear to influence ADHD risk:

  • Mother age21
  • Number of pregnancies of the mother21
  • Mother’s educational level21
    • However, a lower level of maternal education is reported to correlate with increased screen use by children, which in turn correlates with behavioral problems.39
  • Mother size21
  • Umbilical artery blood values21
  • Apgar Score between 5 and 10 min21
    • Different: AGAP score between 5 and 7: ADHD risk more than tripled, only equal from 8 onwards22
  • Breastfeeding21
  • Elevated CRP (C-reactive protein) levels during pregnancy40
  • Artificial Insemination,41 whereas these mothers had slightly higher education than those in the comparison group.
  • Single/multiple birth22
  • Date of delivery22
  • Use of induction drugs22
  • Position of the child during delivery22
  • Changes in the amniotic fluid22
  • Problems with the placenta22
  • Bleeding during delivery22
  • Umbilical cord wrapped around the neck of the child22

  1. Shaw, Crombie, Zakar, Palliser, Hirst (2019): Perinatal compromise contributes to programming of GABAergic and glutamatergic systems leading to long-term effects on offspring behaviour. J Neuroendocrinol. 2019 Nov 23:e12814. doi: 10.1111/jne.12814.

  2. Schiavone, Virta, Leppämäki, Launes, Vanninen, Tuulio-Henriksson, Immonen, Järvinen, Lehto, Michelsson, Hokkanen (2019): ADHD and subthreshold symptoms in childhood and life outcomes at 40 years in a prospective birth-risk cohort. Psychiatry Res. 2019 Sep 25;281:112574. doi: 10.1016/j.psychres.2019.112574.

  3. Lindström, Lindblad, Hjern (2011): Preterm birth and attention-deficit/hyperactivity disorder in schoolchildren. Pediatrics. 2011 May;127(5):858-65. n = 1.180.616

  4. Kelly, Griffith (2019): The Influence of preterm birth beyond infancy: Umbrella review of outcomes of adolescents and adults born preterm. J Am Assoc Nurse Pract. 2019 Oct 18. doi: 10.1097/JXX.0000000000000248. REVIEW

  5. Franz, Bolat, Bolat, Matijasevich, Santos, Silveira, Procianoy, Rohde, Moreira-Maia (2018): Attention-Deficit/Hyperactivity Disorder and Very Preterm/Very Low Birth Weight: A Meta-analysis. Pediatrics. 2018 Jan;141(1). pii: e20171645. doi: 10.1542/peds.2017-1645. n = 1787

  6. Srinivas Jois (2019): Neurodevelopmental outcome of late-preterm infants: A pragmatic review. Aust J Gen Pract. 2018 Nov;47(11):776-781.

  7. Soncini, Belotto, Diaz (2019): Association Between Prematurity and Diagnosis of Neurodevelopment Disorder: A Case-Control Study. J Autism Dev Disord. 2019 Sep 24. doi: 10.1007/s10803-019-04235-2. REVIEW

  8. Hee Chung, Chou, Brown (2020): Neurodevelopmental outcomes of preterm infants: a recent literature review. Transl Pediatr. 2020 Feb;9(Suppl 1):S3-S8. doi: 10.21037/tp.2019.09.10. PMID: 32206579; PMCID: PMC7082240. REVIEW

  9. Montagna, Karolis, Batalle, Counsell, Rutherford, Arulkumaran, Happe, Edwards, Nosarti (2020): ADHD symptoms and their neurodevelopmental correlates in children born very preterm. PLoS One. 2020 Mar 3;15(3):e0224343. doi: 10.1371/journal.pone.0224343. PMID: 32126073; PMCID: PMC7053718. n = 119

  10. Schwenke, Fasching, Faschingbauer, Pretscher, Kehl, Peretz, Keller, Häberle, Eichler, Irlbauer-Müller, Dammer, Beckmann, Schneider (2018): Predicting attention deficit hyperactivity disorder using pregnancy and birth characteristics. Arch Gynecol Obstet. 2018 Sep 8. doi: 10.1007/s00404-018-4888-0. n = 573

  11. Perapoch, Vidal, Gómez-Lumbreras, Hermosilla, Riera, Cortés, Céspedes, Ramos-Quiroga, Morros (2019): Prematurity and ADHD in Childhood: An Observational Register-Based Study in Catalonia. J Atten Disord. 2019 Aug 14:1087054719864631. doi: 10.1177/1087054719864631.

  12. Jin, Yoon, Song, Kim, Chung (2020): Long-term Cognitive, Executive and Behavioral Outcomes of Moderate and Late Preterm at School Age. Clin Exp Pediatr. 2020 Feb 6:10.3345/kjp.2019.00647. doi: 10.3345/kjp.2019.00647. PMID: 32024339. n = 37

  13. Raghavan, Helfrich, Cerda, Ji, Burd, Wang, Hong, Fu, Pearson, Fallin, Zuckerman, Wang (2019): Preterm birth subtypes, placental pathology findings, and risk of neurodevelopmental disabilities during childhood. Placenta. 2019 Aug;83:17-25. doi: 10.1016/j.placenta.2019.06.374.

  14. Shaw, Berry, Dyson, Crombie, Hirst, Palliser (2019): Reduced Neurosteroid Exposure Following Preterm Birth and Its’ Contribution to Neurological Impairment: A Novel Avenue for Preventative Therapies. Front Physiol. 2019 May 15;10:599. doi: 10.3389/fphys.2019.00599. eCollection 2019.

  15. Interventionen während Schwangerschaft und Geburt zur Vorbeugung von Zerebralparese: Eine Übersicht über systematische Reviews von Cochrane, 2017 REVIEW

  16. Walczak-Kozłowska, Mańkowska, Chrzan-Dętkoś, Harciarek (2019): Attentional system of very prematurely born preschoolers. Dev Psychol. 2019 Nov 25. doi: 10.1037/dev0000865.

  17. James, Rommel, Rijsdijk, Michelini, McLoughlin, Brandeis, Banaschewski, Asherson, Kuntsi (2019): Is association of preterm birth with cognitive-neurophysiological impairments and ADHD symptoms consistent with a causal inference or due to familial confounds? Psychol Med. 2019 Jun 3:1-7. doi: 10.1017/S0033291719001211.

  18. http://www.tanjakassuba.com/wp-content/uploads/2015/03/BIOPSY Disorders HPA_SS2007.pdf, Seite 33

  19. Rangan, Banting, Favotto, Schmidt, Saigal, Van Lieshout (2019):: Maternal mental health and internalizing and externalizing psychopathology in extremely low birth weight adults. J Dev Orig Health Dis. 2019 Nov 22:1-8. doi: 10.1017/S2040174419000771.

  20. Zavadenko, Davydova. Nevrologicheskie narusheniia i rasstroĭstva psikhicheskogo razvitiia u deteĭ, rozhdennykh nedonoshennymi (s ékstremal’no nizkoĭ, ochen’ nizkoĭ i nizkoĭ massoĭ tela) [Neurological and neurodevelopmental disorders in preterm-born children (with extremely low, very low or low body weight)]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(12):12-19. Russian. doi: 10.17116/jnevro201911912112. PMID: 31994509.

  21. Schwenke, Fasching, Faschingbauer, Pretscher, Kehl, Peretz, Keller, Häberle, Eichler, Irlbauer-Müller, Dammer, Beckmann, Schneider (2018): Predicting attention deficit hyperactivity disorder using pregnancy and birth characteristics. Arch Gynecol Obstet. 2018 Sep 8. doi: 10.1007/s00404-018-4888-0.

  22. Lipińska, Słopień, Pytlińska, Słopień, Wolańczyk, Bryńska (2021): The role of factors associated with the course of pregnancy and childbirth in attention deficit hyperactivity disorder (ADHD). Psychiatr Pol. 2021 Jun 30;55(3):659-673. English, Polish. doi: 10.12740/PP/OnlineFirst/110686. PMID: 34460889. n = 311

  23. Van Lieshout, Savoy, Ferro, Krzeczkowski, Colman (2019): Macrosomia and psychiatric risk in adolescence. Eur Child Adolesc Psychiatry. 2020 Jan 1. doi: 10.1007/s00787-019-01466-7. n = 1.817

  24. Banaschewski, Ursachen von ADHS, Neurologen und Psychiater im Netz

  25. Miguel, Pereira, Barth, de Mendonça Filho, Pokhvisneva, Nguyen, Garg, Razzolini, Koh, Gallant, Sassi, Hall, O’Donnell, Meaney, Silveira (2019): Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children. Biol Psychiatry. 2019 Apr 3. pii: S0006-3223(19)31154-0. doi: 10.1016/j.biopsych.2019.03.983.

  26. Giannopoulou, Pagida, Briana, Panayotacopoulou (2018): Perinatal hypoxia as a risk factor for psychopathology later in life: the role of dopamine and neurotrophins. Hormones (Athens). 2018 Mar;17(1):25-32. doi: 10.1007/s42000-018-0007-7. PMID: 29858855. REVIEW

  27. Decker, Rye (2002): Neonatal intermittent hypoxia impairs dopamine signaling and executive functioning. Sleep Breath. 2002 Dec;6(4):205-10. doi: 10.1007/s11325-002-0205-y. PMID: 12524574. REVIEW

  28. Miguel, Pereira, Barth, de Mendonça Filho, Pokhvisneva, Nguyen, Garg, Razzolini, Koh, Gallant, Sassi, Hall, O’Donnell, Meaney, Silveira (2019): Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children. Biol Psychiatry. 2019 Oct 15;86(8):621-630. doi: 10.1016/j.biopsych.2019.03.983. PMID: 31142432. n = 431

  29. Li, Huang, Yang, Huang (2021): Methylphenidate exerts neuroprotective effects through the AMPK signaling pathway. Hum Exp Toxicol. 2021 Sep;40(9):1422-1433. doi: 10.1177/0960327121996021. PMID: 33660552.

  30. Brandon, Cui, Luan, Ali, Pertile, Alexander, Eyles (2022): Prenatal hypoxia alters the early ontogeny of dopamine neurons. Transl Psychiatry. 2022 Jun 7;12(1):238. doi: 10.1038/s41398-022-02005-w. PMID: 35672280; PMCID: PMC9174174.

  31. Zhang, Sidorchuk, Sevilla-Cermeño, Vilaplana-Pérez, Chang, Larsson, Mataix-Cols, Fernández de la Cruz (2019): Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019 Aug 2;2(8):e1910236. doi: 10.1001/jamanetworkopen.2019.10236. n = 20.607.935 Geburten, REVIEW

  32. Xu, Zhang, Zhou, Jiang, Jiang, Zhou (2019): Meta-analysis found that studies may have overestimated Caesarean section risks for attention deficit hyperactivity disorder by ignoring confounding factors. Acta Paediatr. 2019 Aug 31. doi: 10.1111/apa.14994. n = 2.500.000 Geburten

  33. Axelsson, Clausen, Petersen, Hageman, Pinborg, Kessing, Bergholt, Rasmussen, Keiding, Løkkegaard (2018): Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder. J Child Psychol Psychiatry. 2018 Aug 23. doi: 10.1111/jcpp.12961. n = 671.592 Geburten

  34. Curran, Khashan, Dalman, Kenny, Cryan, Dinan, Kearney (2016): Obstetric mode of delivery and attention-deficit/hyperactivity disorder: a sibling-matched study. Int J Epidemiol. 2016 Apr;45(2):532-42. doi: 10.1093/ije/dyw001. n = 1.722.548 Geburten

  35. Chiorean, Savoy, Beattie, El Helou, Silmi, Van Lieshout (2020): Childhood and adolescent mental health of NICU graduates: an observational study. Arch Dis Child. 2020 Jan 23;archdischild-2019-318284. doi: 10.1136/archdischild-2019-318284. PMID: 31974300.

  36. Karoum, Ruthven, Sandler (1975); Urinary phenolic acid and alcohol excretion in the newborn. Arch Dis Child. 1975 Aug;50(8):586-94. doi: 10.1136/adc.50.8.586. PMID: 1200675; PMCID: PMC1545531.

  37. Raghavan, Anand, Wang G, Hong X, Pearson, Zuckerman, Xie H, Wang X (2022): Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder. Transl Psychiatry. 2022 Jul 9;12(1):270. doi: 10.1038/s41398-022-01992-0. PMID: 35810183. n = 996

  38. Ai, Zhao, Shi, Zhu (2021): Antibiotic exposure and childhood attention-deficit/hyperactivity disorder: systematic review and meta-analysis. Psychopharmacology (Berl). 2021 Oct 23. doi: 10.1007/s00213-021-05989-3. PMID: 34687335.

  39. Xie, Deng, Cao, Chang (2020): Digital screen time and its effect on preschoolers’ behavior in China: results from a cross-sectional study. Ital J Pediatr. 2020 Jan 23;46(1):9. doi: 10.1186/s13052-020-0776-x. PMID: 31973770. n = 1.897

  40. Chudal, Brown, Gyllenberg, Hinkka-Yli-Salomäki, Sucksdorff, Surcel, Upadhyaya, Sourander (2019): Maternal serum C-reactive protein (CRP) and offspring attention deficit hyperactivity disorder (ADHD). Eur Child Adolesc Psychiatry. 2019 Jul 16. doi: 10.1007/s00787-019-01372-y.

  41. Al-Hathlol, Al-Obaid, Al-Gholaiqa, Al-Hathlol, Abdulaal, Al-Hajress, Al-Joufi, Al-Hassan, Al-Otaibi (2019): School performance and long-term outcomes of very preterm children conceived via in vitro fertilization. JBRA Assist Reprod. 2019 Sep 26. doi: 10.5935/1518-0557.20190063.