Dear readers of ADxS.org, please forgive the disruption.

ADxS.org needs about $53200 in 2024. In 2023 we received donations from third parties of about $ 32200. Unfortunately, 99.8% of our readers do not donate. If everyone who reads this request makes a small contribution, our fundraising campaign for 2024 would be over after a few days. This donation request is displayed 19,000 times a week, but only 40 people donate. If you find ADxS.org useful, please take a minute and support ADxS.org with your donation. Thank you!

Since 01.06.2021 ADxS.org is supported by the non-profit ADxS e.V..

$3391 of $53200 - as of 2024-02-01
6%
Header Image
2. Birth circumstances as the cause of ADHD

Sitemap

2. Birth circumstances as the cause of ADHD

Extensive evidence shows that harmful influences during birth are a significant risk factor for the development of neurodevelopmental disorders such as ADHD that occur long after the causative event1

The earlier the premature birth, the greater the risk of ADHD. A low birth weight also appears to increase the risk of ADHD, while a high birth weight reduces the risk.
Furthermore, oxygen deprivation at birth, low APGAR values after 1 minute, emergency caesarean sections, need for intensive medical care, neonatal jaundice, high serotonin metabolite levels in the umbilical cord blood and postnatal administration of antibiotics are associated with an increased risk of ADHD.

A long-term study found that of 318 children with birth problems, those who had developed ADHD as children only had 21% ADHD at age 40, but had poorer educational attainment, more ADHD symptoms and executive problems. Those who had attention problems as a child but no full-blown ADHD had 6.6% ADHD at age 40, while those who had no attention problems as a child had 6% ADHD. Controls without birth problems had 1.6% ADHD at the age of 40.2

The % values indicate the possible ADHD risk increase due to the respective cause.

2.1. Premature birth

Premature delivery significantly increases the risk of ADHD, and the earlier the premature birth, the greater the risk.3 The effect of premature birth on inattention (but not hyperactivity) ADHD appears to be mediated by reduced lung function and therefore oxygen deprivation4

Pregnancy week / increased risk of ADHD5

  • 23. to 28th / 2.1-fold (plus 110 %)
  • 29. to 32 / 1.6-fold (plus 60 %)
  • 33. to 34th / 1.4-fold (plus 40 %)
  • 35. to 36th / 1.3-fold (plus 30 %)
  • 37. to 38th / 1.15-fold (plus 15 %).

A Scottish cohort study found6

24. to 27th / 5-fold (plus 400 %)
28. to 32nd / 2-fold (plus 100 %)
33. to 36th / 1.59-fold (plus 59 %)
37. / 1.31-fold (plus 31 %)
38. / 1.14-fold (plus 14 %
39. / 0.98-fold (minus 2 %)
40. / 0.89-fold (minus 11 %) (usual duration of pregnancy)
41. / 0.87-fold (minus 13 %)
42. / 0.89-fold (minus 11 %)
43. / unchanged
44. and higher / unchanged

A Swedish cohort study found that the duration of the treatment was 37 weeks or longer:7

22. to 27th / 2.79-fold
28. to 31 / 1.61-fold
32. to 36th / 1.18-fold
SGA / 1.62-fold (SGA: small for gestational age, birth weight below the 10th percentile)
Preclampsia was associated with ADHD
Placental abruption was not associated with ADHD

Meta-analyses of 16 studies8 and 12 studies9 as well as further studies1011 12 confirm this, one study tends to confirm this.13
A single study found no correlation.14. A cohort study found a 3-fold increase in the risk of ADHD for births in the 28th week of pregnancy or earlier.15 The increased risk of ADHD results from the duration of pregnancy itself, i.e. not from the typical premature birth risks such as oxygen deficiency, cerebral haemorrhage or intrauterine growth retardation. This is also shown by the comparison with non-preterm twin siblings.16

Girls appear to have an increased risk of ADHD due to premature birth.16

A study of premature babies born between the 32nd and 36th week found that 65% of 7- to 10-year-olds had elevated levels in at least one of the ADHD symptom areas.17

One study found that the risk of ADHD was higher in spontaneous preterm births than in external medically induced preterm births. In addition, the risk of ADHD caused by a premature birth increased further if chorioamnionitis was added (ADHD risk increased by 175%):18 Another study found that spontaneous as well as medically induced preterm births increased the risk of ADHD,19

It is assumed that premature birth causes the supply of important substances to end too early, which impairs brain development. Repeated hypoxic-ischemic events are particularly common in premature infants, which could explain the high incidence of ADHD.20 It is hypothesized that an additional supply of allopregnanolone could be helpful, in addition to the already established administration of corticosteroids (once) and magnesium sulphate.2122 However, the fact that only spontaneous premature births, but not medically induced premature births, increase the risk of ADHD speaks against this - at least with regard to ADHD.
The association between preterm birth and inattention problems seems to be reinforced by lung problems.23 We hypothesize a connection with hypoxia.

The psychological risks to the child in the event of a premature birth appear to result more from the premature birth itself, namely24

  • IQ
  • Preparation vigilance
  • Error processing

and partly caused more by social or other family circumstances, namely

  • Inhibition
  • Verbal working memory

The usual number is 40 weeks of pregnancy.
Transferred children who were born after the due date do not have an increased risk of ADHD.

In the case of extremely premature birth, obesity and diabetes in the mother also increased the risk of ADHD by 55 to 65% in each case25

Extremely preterm infants showed impairments in attentional guidance as preschoolers, but not in alerting efficiency or executive aspects of attention.26 Extreme prematurity appears to be associated with inattention rather than hyperactivity,1627 as well as anxiety and social difficulties.27

If, in addition to the premature birth, the mother also had an autoimmune disease, which alone also appears to increase the risk of ADHD, these risks did not add up.28

2.2. Low or high birth weight

A low birth weight is likely to increase the risk of ADHD.293031 Two other studies did not confirm this result.3233

A Scottish cohort study found an influence of birth weight on the risk of ADHD (determined on a gender-specific basis according to centiles)6
1 to 3: 134.1% (the 3% with the lowest birth weight had a 34% increased risk of ADHD)
4 to 10: 117.8 %
11 to 20: 109.2 %
21 to 80: 95.7 %
81 to 90: 86 %
91 to 97: 92.6 %
98 to 100: 95.5 % (the 3 % with the highest birth weight had a 4.5 % lower risk of ADHD)

Studies have found the risk of ADHD in

  • extremely low birth weight (< 1,000 g) of 13.8 %34
  • very low birth weight (< 1,500 g) increased by 51 %35
  • low birth weight (1,500-2,500 g) increased by 32 %35 to approx. 125 % (OR = 2.25)34
  • normal birth weight (from 2,500 g) unchanged35

One study found a 77% increased risk of ADHD with a birth weight over 4000 grams.36

2.3. Oxygen deficiency at birth

Lack of oxygen at birth increases the risk of ADHD.37

An oxygen supply for the newborn during birth (which became necessary due to a lack of oxygen) correlates with an almost tripled risk of ADHD.33
Hypoxy-ischemic conditions around birth (e.g. asphyxia) cause an inadequate supply of oxygen to the brain. This can lead to cognitive impairment. Their occurrence is influenced by dopamine transporter gene polymorphisms.38 Oxygen deprivation during birth can cause long-term changes in the dopamine system, where dopamine is important for brain development.3940 Oxygen deprivation at birth correlated with unoccupied (an excess of) D2/D3 dopamine receptors in a very small number of subjects.41
Disorders of the dopamine system can trigger brain development disorders such as those associated with ADHD.
One study found evidence that attention problems following oxygen deprivation during birth are moderated by gene variants of the dopamine transporter in the PFC.42
A study conclusively describes a reduction in the consequences of ischemia by methylphenidate through activation of the AMPK signaling pathway.43 As AMPK influences the dopamine balance, this could indicate that a dopamine deficiency increases the damage caused by ischemic conditions.

It is known that hypoxia (lack of oxygen) leads to an excess of adenosine. Adenosine is closely linked to the dopaminergic system. Adenosine antagonists are able to prevent and correct hypoxia damage. More on this under Adenosine In the chapter Neurological aspects.

Prenatal hypoxia caused massive changes in the dopaminergic system in mice:44

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

2.4. APGAR values below 7 after 1 minute

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

  • Under 5 after 1 minute: 7-fold ADHD risk33 (the authors incorrectly calculate 9% for controls instead of 0.9% in the text)
  • Between 5 and 7 after 1 minute: more than tripled risk of ADHD33
  • Under 7 after 1 minute: significantly increased risk of ADHD32
  • From 8 after 1 minute no increased risk of ADHD33

A Scottish cohort study found an influence of the 5-minute APGAR score on the risk of ADHD6
1 to 3: 9-fold ADHD risk
4 to 6: 1.5 times the risk of ADHD
7 to 10: 0.99 times the risk of ADHD

A meta-study found a significantly increased risk of ADHD (OR = 1.3 = approx. + 30%) in under 7s after 5 minutes.34

One study found no increase in ADHD risk with an APGAR score after 5 and 10 minutes32

2.5. Caesarean section

A comprehensive meta-study of over 20 million births found that a caesarean section increases the risk of ADHD by 17%.45 The risk of autism spectrum disorder was increased by 33%.

Other sources, however, cite a risk increase of 6%46 or 3 to 9%47 or 5 to 15%.48 One small study found no increased risk of ADHD due to caesarean section.33

Several studies showed that only an emergency caesarean section resulted in a statistically significant increase in the risk of ADHD,48 or that children with ADHD were 5% more likely to have an emergency caesarean birth and 12% less likely to have a planned caesarean birth6
Another study confirmed that only a caesarean section at birth (intrapartum) increased the risk of ADHD.47

A meta-study found that a caesarean section increased the risk of ASD in girls by 66% and in boys by 17%.49 The risk of ADHD was also increased.

2.6. Newborns requiring intensive care

Newborns who required intensive medical care showed a 60% increased risk of ADHD at the age of 4 to 11 years.50

Newborns who had to be treated in an incubator had a 4.5-fold risk of ADHD.33

2.7. Neonatal jaundice

Jaundice is a yellowing of the skin and whites of the eyes caused by excess bilirubin. Bilirubin is a yellow breakdown product in the blood.

Newborns with jaundice show an increased risk of ADHD and ASD. The ADHD risk was increased by 14 to 31%51 and 33% respectively. If the jaundice required treatment, the risk of ADHD was 2.5 times higher than in those not affected. The risk of ADHD was particularly increased if the jaundice was so severe that all of the newborn’s blood had to be replaced.33
Neonatal jaundice is associated with reduced urinary homovanillic acid in the first few days, indicating reduced dopamine turnover.52

(Neonatal) hyperbilirubinemia, a (neonatal) bilirubin excess is associated with ADHD, a severe bilirubin excess with ASD.53
Hyperbilirubinemia in early childhood can cause a similar impairment of the frontostriatal network and similar symptoms to ADHD.5455 A registry study of n = 157,366 children found no correlation.56

Bilirubin dose-dependently inhibited the uptake of tyrosine (a precursor of dopamine) in the striatum in vitro.57 Bilirubin inhibits cAMP-stimulated dopamine synthesis58 and reduces the vesicular storage of dopamine and glutamate59.
Bilirubin (20-80 microM) did not directly affect dopamine release from striatal synaptosomes. It inhibited the initial rate of synaptosomal dopamine uptake and dopamine levels in the synaptosome after 10 minutes. Bilirubin appears to primarily inhibit neurotransmitter reuptake and the response to depolarizing stimuli.60

2.8. Serotonin metabolites in umbilical cord blood

Elevated umbilical cord blood levels of serotonin metabolites correlated with an increased risk of ADHD later in life:61

  • 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 the birth

A meta-study found a 12% increased risk of ADHD due to postnatal administration of antibiotics.62

2.10. Month of birth influences ADHD risk

Several studies found consistent data on how the month of birth influences the risk of ADHD and other mental disorders.63 This follows a general pattern of neurological disorders having the lowest risk at birth in spring, while cardiovascular disorders have the highest risk at birth in spring. Relevant factors could be vitamin D3 production during pregnancy and in the first months of life or, as most studies suggest, the relative age at school entry (in relation to the other children in the class).64656667
A Taiwanese study found a clear correlation with age at school enrollment.68

Interestingly, the asthma risk depending on the month of birth has an opposite pattern, although ADHD and asthma often occur comorbidly.69

2.11. Congenital heart defects (+ 200 %)

Congenital heart disease is a general term for a number of birth defects that affect the normal functioning of the heart.
A meta-study found a significantly increased risk of ADHD with congenital heart defects (OR = 3.04, approx. + 200 %).34

2.12. Characteristics without an increased risk of ADHD

The following factors do not appear to have any influence on the risk of ADHD:

  • Number of pregnancies of the mother32
  • Mother’s level of education32
    • However, a lower level of education of the mother is said to correlate with an increased screen consumption of the children, which in turn correlates with behavioral problems.70
  • Size of the mother32
  • Blood values of the umbilical artery32
  • Elevated CRP values (C-reactive protein) during pregnancy71
  • Artificial insemination,72 whereby these mothers had a slightly higher level of education than those in the comparison group.
  • Single/multiple birth33
  • Date of delivery33
  • Position of the child during delivery33
  • Changes in the amniotic fluid33
  • Problems with the placenta33
  • Bleeding during childbirth33
  • Umbilical cord wrapped around the baby’s neck33
  • Epidural analgesia during childbirth
    • Of 4,498,462 people (48.7 % female), 1,091,846 (24.3 %) were exposed to epidural analgesia during childbirth. Of these, 1.2% had ASD and 4.0% had ADHD. At the population level, epidural analgesia at birth showed an increased risk in offspring for ASD (1.20% vs. 1.07%) and ADHD (3.95% vs. 3.32%). However, when comparing full siblings exposed to epidural analgesia at birth in different ways, the associations were completely attenuated for both conditions (ASD: risk reduced by 2%; ADHD: risk reduced by 1%).73
  • Induction of labor
    • Use of induction drugs33
    • Through exogenous oxytocin74

  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. Fraiman YS, Guyol G, Acevedo-Garcia D, Beck AF, Burris H, Coker TR, Tiemeier H (2023): A Narrative Review of the Association between Prematurity and Attention-Deficit/Hyperactivity Disorder and Accompanying Inequities across the Life-Course. Children (Basel). 2023 Sep 30;10(10):1637. doi: 10.3390/children10101637. PMID: 37892300; PMCID: PMC10605109. REVIEW

  4. Litt JS, Johnson S, Marlow N, Tiemeier H (2023): Impaired pulmonary function mediates inattention in young adults born extremely preterm. Acta Paediatr. 2023 Feb;112(2):254-260. doi: 10.1111/apa.16586. PMID: 36330674.

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

  6. Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP (2017): Educational and Health Outcomes of Children Treated for Attention-Deficit/Hyperactivity Disorder. JAMA Pediatr. 2017 Jul 3;171(7):e170691. doi: 10.1001/jamapediatrics.2017.0691. PMID: 28459927; PMCID: PMC6583483. n = 766.244

  7. Beer RJ, Cnattingius S, Susser ES, Villamor E (2022): Associations of preterm birth, small-for-gestational age, preeclampsia and placental abruption with attention-deficit/hyperactivity disorder in the offspring: Nationwide cohort and sibling-controlled studies. Acta Paediatr. 2022 Aug;111(8):1546-1555. doi: 10.1111/apa.16375. Epub 2022 May 3. PMID: 35485179; PMCID: PMC9544732. n = 1.212.201

  8. 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

  9. 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

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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Ask H, Gustavson K, Ystrom E, Havdahl KA, Tesli M, Askeland RB, Reichborn-Kjennerud T (2018): Association of Gestational Age at Birth With Symptoms of Attention-Deficit/Hyperactivity Disorder in Children. JAMA Pediatr. 2018 Aug 1;172(8):749-756. doi: 10.1001/jamapediatrics.2018.1315. PMID: 29946656; PMCID: PMC6142916.

  17. 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

  18. 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.

  19. Beer RJ, Cnattingius S, Susser ES, Villamor E (2022): Associations of preterm birth, small-for-gestational age, preeclampsia and placental abruption with attention-deficit/hyperactivity disorder in the offspring: Nationwide cohort and sibling-controlled studies. Acta Paediatr. 2022 Aug;111(8):1546-1555. doi: 10.1111/apa.16375. PMID: 35485179; PMCID: PMC9544732. n = 1.212.201

  20. Lou HC (1996): Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta Paediatr. 1996 Nov;85(11):1266-71. doi: 10.1111/j.1651-2227.1996.tb13909.x. PMID: 8955450. REVIEW

  21. 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.

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

  23. Litt JS, Johnson S, Marlow N, Tiemeier H (2022): Impaired pulmonary function mediates inattention in young adults born extremely preterm. Acta Paediatr. 2023 Feb;112(2):254-260. doi: 10.1111/apa.16586. PMID: 36330674.

  24. 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.

  25. Cochran DM, Jensen ET, Frazier JA, Jalnapurkar I, Kim S, Roell KR, Joseph RM, Hooper SR, Santos HP Jr, Kuban KCK, Fry RC, O’Shea TM (2022): Association of prenatal modifiable risk factors with attention-deficit hyperactivity disorder outcomes at age 10 and 15 in an extremely low gestational age cohort. Front Hum Neurosci. 2022 Oct 20;16:911098. doi: 10.3389/fnhum.2022.911098. PMID: 36337853; PMCID: PMC9630552.

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

  27. Johnson S, Marlow N (2011): Preterm birth and childhood psychiatric disorders. Pediatr Res. 2011 May;69(5 Pt 2):11R-8R. doi: 10.1203/PDR.0b013e318212faa0. PMID: 21289534.

  28. Ellul P, Wallez S, Acquaviva E, Rosenzwajg M, Klatzmann D, Delorme R, Melchior M (2023): Children with a history of both maternal immune activation and prematurity are not at increased risk of ADHD symptoms. Eur Child Adolesc Psychiatry. 2023 Aug 3. doi: 10.1007/s00787-023-02276-8. PMID: 37535256.

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

  30. 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.

  31. 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.

  32. 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.

  33. 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

  34. Jenabi E, Ayubi E, Farashi S, Bashirian S, Mehri F (2023): The neonatal risk factors associated with attention-deficit/ hyperactivity disorder: an umbrella review. Clin Exp Pediatr. 2023 Jul 14. doi: 10.3345/cep.2022.01396. PMID: 37448127. METASTUDY

  35. Ni M, Li L, Li W, Zhang Q, Zhao J, Shen Q, Yao D, Wang T, Li B, Ding X, Qi S, Huang X, Liu Z (2023): Examining the relationship between birth weight and attention-deficit hyperactivity disorder diagnosis. Front Psychiatry. 2023 May 24;14:1074783. doi: 10.3389/fpsyt.2023.1074783. PMID: 37293403; PMCID: PMC10244743. N = 60.358

  36. 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

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

  38. 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.

  39. 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

  40. 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

  41. Lou, Rosa, Pryds, Karrebaek, Lunding, Cumming, Gjedde (2004): ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow. Dev Med Child Neurol. 2004 Mar;46(3):179-83. doi: 10.1017/s0012162204000313. PMID: 14995087. n = 6

  42. 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

  43. 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.

  44. 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.

  45. 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

  46. 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

  47. 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

  48. 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

  49. Chen M, Lin Y, Yu C, Fu R, Shentu H, Yao J, Huang J, He Y, Yu M. Effect of cesarean section on the risk of autism spectrum disorders/attention deficit hyperactivity disorder in offspring: a meta-analysis. Arch Gynecol Obstet. 2023 May 23. doi: 10.1007/s00404-023-07059-9. PMID: 37219611.

  50. 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.

  51. Chou HC, Lin HC, Huang KH, Chang YC (2023): Associations between neonatal jaundice and autism spectrum disorder or attention deficit hyperactivity disorder: Nationwide population based cohort study. J Formos Med Assoc. 2023 May 22:S0929-6646(23)00179-1. doi: 10.1016/j.jfma.2023.05.010. PMID: 37225632.

  52. 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.

  53. Jayanti S, Dalla Verde C, Tiribelli C, Gazzin S (2023): Inflammation, Dopaminergic Brain and Bilirubin. Int J Mol Sci. 2023 Jul 14;24(14):11478. doi: 10.3390/ijms241411478. PMID: 37511235; PMCID: PMC10380707.

  54. Hokkanen L, Launes J, Michelsson K (2014): Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates-a 30 year prospective follow-up study. PeerJ. 2014 Mar 4;2:e294. doi: 10.7717/peerj.294. PMID: 24688870; PMCID: PMC3961148.

  55. Jangaard KA, Fell DB, Dodds L, Allen AC (2008):Outcomes in a population of healthy term and near-term infants with serum bilirubin levels of >or=325 micromol/L (>or=19 mg/dL) who were born in Nova Scotia, Canada, between 1994 and 2000. Pediatrics. 2008 Jul;122(1):119-24. doi: 10.1542/peds.2007-0967. PMID: 18595994.

  56. Kuzniewicz M, Escobar GJ, Newman TB (2009): No association between hyperbilirubinemia and attention-deficit disorder. Pediatrics. 2009 Feb;123(2):e367-8. doi: 10.1542/peds.2008-2803. PMID: 19171601.

  57. Amato MM, Kilguss NV, Gelardi NL, Cashore WJ (1994): Dose-effect relationship of bilirubin on striatal synaptosomes in rats. Biol Neonate. 1994;66(5):288-93. doi: 10.1159/000244119. PMID: 7873694.

  58. Brann, B. S., Cashore, W. J., Patrick, R., Oh, W. (1985): In vitro effect of bilirubin on dopamine synthesis in adult rat brain synaptosomes. Pediatric Research, 19(4), 335-335.

  59. Roseth S, Hansen TW, Fonnum F, Walaas SI (1998): Bilirubin inhibits transport of neurotransmitters in synaptic vesicles. Pediatr Res. 1998 Sep;44(3):312-6. doi: 10.1203/00006450-199809000-00008. PMID: 9727706.

  60. Ochoa EL, Wennberg RP, An Y, Tandon T, Takashima T, Nguyen T, Chui A (1993): Interactions of bilirubin with isolated presynaptic nerve terminals: functional effects on the uptake and release of neurotransmitters. Cell Mol Neurobiol. 1993 Feb;13(1):69-86. doi: 10.1007/BF00712990. PMID: 8096165.

  61. 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

  62. 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.

  63. Boland MR, Shahn Z, Madigan D, Hripcsak G, Tatonetti NP (2015): Birth month affects lifetime disease risk: a phenome-wide method. J Am Med Inform Assoc. 2015 Sep;22(5):1042-53. doi: 10.1093/jamia/ocv046. PMID: 26041386; PMCID: PMC4986668.

  64. Halldner L, Tillander A, Lundholm C, Boman M, Långström N, Larsson H, Lichtenstein P (2014): Relative immaturity and ADHD: findings from nationwide register oder, parent- and self-reports. J Child Psychol Psychiatry. 2014 Aug;55(8):897-904. doi: 10.1111/jcpp.12229. PMID: 24673585.

  65. Karlstad Ø, Furu K, Stoltenberg C, Håberg SE, Bakken IJ (2017):ADHD treatment and diagnosis in relation to children’s birth month: Nationwide cohort study from Norway. Scand J Public Health. 2017 Jun;45(4):343-349. doi: 10.1177/1403494817708080. PMID: 28482754.

  66. Vuori M, Martikainen JE, Koski-Pirilä A, Sourander A, Puustjärvi A, Aronen ET, Chudal R, Saastamoinen LK (2020): Children’s Relative Age and ADHD Medication Use: A Finnish Population-Based Study. Pediatrics. 2020 Oct;146(4):e20194046. doi: 10.1542/peds.2019-4046. PMID: 32958613.

  67. Sayal K, Chudal R, Hinkka-Yli-Salomäki S, Joelsson P, Sourander A (2017): Relative age within the school year and diagnosis of attention-deficit hyperactivity disorder: a nationwide population-based study. Lancet Psychiatry. 2017 Nov;4(11):868-875. doi: 10.1016/S2215-0366(17)30394-2. PMID: 29033006.

  68. Hsu CW, Tseng PT, Tu YK, Lin PY, Hung CF, Liang CS, Hsieh YY, Yang YH, Wang LJ, Kao HY (2021): Month of birth and mental disorders: A population-based study and validation using global meta-analysis. Acta Psychiatr Scand. 2021 Aug;144(2):153-167. doi: 10.1111/acps.13313. PMID: 33930177; PMCID: PMC8360113.

  69. Koskinen A, Lemmetyinen R, Luukkainen A, Kankaanranta H, Ilmarinen P, Karjalainen J, Pekkanen J, Huhtala H, Haukka J, But A, Toppila-Salmi S (2023): Season of birth affects the risk of adult-onset asthma in Finland. Allergy. 2023 Feb;78(2):555-558. doi: 10.1111/all.15504. PMID: 36067009; PMCID: PMC10087432.

  70. 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

  71. 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.

  72. 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.

  73. Hegvik, Klungsøyr, Kuja-Halkola, Remes, Haavik, D’onofrio, Metsä-Simola, Engeland, Fazel, Lichtenstein, Martikainen, Larsson, Sariaslan (2022): Labor epidural analgesia and subsequent risk of offspring autism spectrum disorder and attention-deficit/hyperactivity disorder: A cross-national cohort study of 4.5 million individuals and their siblings. Am J Obstet Gynecol. 2022 Aug 13:S0002-9378(22)00650-0. doi: 10.1016/j.ajog.2022.08.016. PMID: 35973476. n = 4.498.462

  74. Shinohara S, Horiuchi S, Shinohara R, Otawa S, Kushima M, Miyake K, Yui H, Kojima R, Ooka T, Akiyama Y, Yokomichi H, Yamagata Z (2023): Japan Environment and Children’s Study Group. A nationwide, prospective, cohort study on exogenous oxytocin and delays in early child development: the Japan environment and children’s study. Eur J Pediatr. 2023 Jul 3. doi: 10.1007/s00431-023-05079-w. PMID: 37395828.