Cited by 448Birth, Development, and HealthStress Responses and CortisolMaternal Mental Health During Pregnancy and Postpartum

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The stress of being born

Lagercrantz, Hugo, Slotkin, Theodore A.·1986·Scientific American

DOI 10.1038/scientificamerican0486-100

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Gatti, M. G., Becucci, E., Fargnoli, F., et al. (2012) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2012.664351 · Cited by 22
“The catecholamine surge, triggered by vaginal delivery, may also be critical for the arousal at birth [21,22].”
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Maternal Perinatal Undernutrition Alters Neuronal and Neuroendocrine Differentiation in the Rat Adrenal Medulla at Weaning
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β-Adrenoceptor-mediated cell signaling in the neonatal heart and liver: responses to terbutaline
Auman, J. T., Seidler, F. J., Tate, C. A., et al. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.6.r1895 · Cited by 22
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Are developing β-adrenoceptors able to desensitize? Acute and chronic effects of β-agonists in neonatal heart and liver
Auman, J. T., Seidler, F. J., Tate, C. A., & Slotkin, T. A. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00122.2002 · Cited by 21
“These unique neonatal adaptations are thus likely to provide for maintenance of receptor-mediated signaling in the face of the high catecholamine levels in the period surrounding birth (23).”
BackgroundSelf-citation
Agonist-Induced Sensitization of β-Adrenoceptor Signaling in Neonatal Rat Heart: Expression and Catalytic Activity of Adenylyl Cyclase
Zeiders, J. L., Seidler, F. J., & Slotkin, T. A. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35131-6 · Cited by 22
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The Newborn's Reaction to Light as the Determinant of the Brain's Activation at Human Birth
Polese, D., Riccio, M. L., Fagioli, M., Mazzetta, A., Fagioli, F., Parisi, P., & Fagioli, M. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.933426 · Cited by 22
“As mentioned before, due to the strain of the childbirth process, the fetus releases an extraordinary amount of stress hormones, at even higher levels than mothers during labor or adults suffering from myocardial infarction (Lagercrantz and Bistoletti, 1977; Bistoletti et al., 1983; Lagercrantz and Slotkin, 1986; Gree…”
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Regulation of Oxygen Sensitivity in Adrenal Chromaffin Cells
Nurse, C. A., Buttigieg, J. A., Brown, S., et al. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05031.x · Cited by 21
Behavioral and cortisol responses to stress in newborn infants: Effects of mode of delivery
Chiş, A., Vulturar, R., Andreica, S., et al. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.09.024 · Cited by 21
Beta‐adrenoceptor agonist stimulation of pulmonary nitric oxide production in the rabbit
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“A common feature during the two latter conditions is an increased sympathetic activity with high concentrations of adrenaline in the blood (Lagercrantz & Slotkin, 1986).”
Background
CCK and development of mother preference in sheep: a neonatal time course study
Nowak, R., Breton, G., & Mellot, E. (2001) · Peptides · doi:10.1016/s0196-9781(01)00457-0 · Cited by 21
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Altered stress responses in adults born by Caesarean section
Dinan, T. G., Kennedy, P. J., Morais, L. H., Murphy, A., Long-Smith, C. M., Moloney, G. M., Bastiaanssen, T. F. S., Allen, A. P., Collery, A., Mullins, D., et al. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100425 · Cited by 24
“Perturbations in early life by C-section birth or antibiotic use have been linked to increased risk for developing childhood obesity (Cho and Norman, 2013; Li et al., 2013; Mueller et al., 2015; Yuan et al., 2016) and childhood asthma (Darabi et al., 2019; Metsala et al., 2015).”
Background
Chronic exposure of neonatal rat adrenomedullary chromaffin cells to opioidsin vitroblunts both hypoxia and hypercapnia chemosensitivity
Salman, S., Buttigieg, J. A., Zhang, M., et al. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.243477 · Cited by 20
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Salman, S., Buttigieg, J. A., & Nurse, C. A. (2014) · Journal of Experimental Biology · doi:10.1242/jeb.086165 · Cited by 20
“This CAT secretion is critical for the proper transition to extra-uterine life Th e Jo ur na l o f E xp er im en ta l B io lo gy (Lagercrantz and Slotkin, 1986).”
Background
Chronic hypoxia upregulates adenosine 2a receptor expression in chromaffin cells via hypoxia inducible factor-2α: Role in modulating secretion
Brown, S. T., Reyes, E. P., & Nurse, C. A. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.07.122 · Cited by 20
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“Further, the fetal environment is hypoxic relative to that of the neonate or adult [17,32], thus fostering the conditions for oxidative stress.”
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Lactate measurements in scalp and cord arterial blood
Nordström, L. (2001) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/00001703-200104000-00008 · Cited by 20
Cutaneous induction of breathing in perinatal rats
Ronca, A. E., & Alberts, J. R. (1995) · Psychobiology · doi:10.3758/bf03333072 · Cited by 20
Effects of norepinephrine on lung liquid production by in vitro lungs from fetal guinea pigs
Doe, S., Woods, B., & Perks, A. M. (1998) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-76-10-11-967 · Cited by 20
“large amounts of epinephrine and norepinephrine from the adrenals, but also substantial release from other postganglionic sympathetic sources (Lagercrantz and Bistoletti 1973; Lagercrantz and Slotkin 1986; Padbury and Martinez 1988).”
Background
Long-Term Impairment in the Neurochemical Activity of the Sympathoadrenal System after Neonatal Hypoxia in the Rat
Soulier, V., Peyronnet, J., Péquignot, J.-M., et al. (1997) · Pediatric Research · doi:10.1203/00006450-199707000-00006 · Cited by 20
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Zeiders, J. L., Seidler, F. J., & Slotkin, T. A. (2000) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00188-1 · Cited by 19
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Fetal and Birth Experiences: Proximate Effects, Developmental Consequences, Epigenetic Legacies
Ronca, A. E., & Alberts, J. R. (2016) · Springer eBooks · doi:10.1007/978-3-319-22023-9_2 · Cited by 19
Influence of the delivery modus on subpopulations and replication of lymphocytes in mothers and newborns
Almanzar, G., Schönlaub, J., Hammerer‐Lercher, A., Koppelstaetter, C., Bernhard, D., & Prelog, M. (2015) · Early Human Development · doi:10.1016/j.earlhumdev.2015.09.010 · Cited by 18
“Contractions of the uterus and fetal hypoxia during vaginal delivery normally stimulate a significant stress response with high catecholamine and cortisol concentrations in neonates [1,3,18,31–36].”
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Does Birth Trigger Cell Death in the Developing Brain?
Castillo‐Ruiz, A., Hite, T. A., Yakout, D. W., Rosen, T. J., & Forger, N. G. (2020) · eNeuro · doi:10.1523/eneuro.0517-19.2020 · Cited by 17
“In addition to the obligatory drop in progesterone, a vaginal birth triggers an “adaptive stress response” which leads to marked increases in vasopressin, glucocorticoids, and catecholamines in the offspring (for review, see Lagercrantz and Slotkin, 1986; Evers and Wellmann, 2016).”
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Counseling Women About Elective Cesarean Section
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Animal models for assessing impact of C-section delivery on biological systems
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Yli, B. M., Kro, G. B., Rasmussen, S., Khoury, J., Norén, H., Amer‐Wåhlin, I., Saugstad, O. D., & Stray‐Pedersen, B. (2011) · Journal of Perinatal Medicine · doi:10.1515/jpm.2011.126 · Cited by 16
Teratogenic effects of nitrofen on cellular and functional maturation of the rat lung
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Ontogeny of β-adrenoceptor/adenylyl cyclase desensitization mechanisms: the role of neonatal innervation
Slotkin, T. A., Saleh, J. L., Zhang, J., et al. (1996) · Brain Research · doi:10.1016/s0006-8993(96)00978-x · Cited by 17
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Nowak, R., Lévy, F., Chaillou, É., Cornilleau, F., Cognié, J., Marnet, P., Williams, P. D., & Keller, M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.612651 · Cited by 17
“More than 30 years ago, Lagercrantz and Slotkin (66) hypothesized that the catecholamine surge due to vaginal birth was responsible for infant arousal and could facilitate attachment between mother and child.”
Background
Different impacts on brain function depending on the mode of delivery
Ikeda, K., Onimaru, H., Matsuura, T., & Kawakami, K. (2019) · Brain Research · doi:10.1016/j.brainres.2019.06.008 · Cited by 16
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High vagal tone is associated with more efficient regulation of homeostasis in low-risk human fetuses
Groome, L. J., Loizou, P. C., Holland, S. B., Smith, L. A., & Hoff, C. J. (1999) · Developmental Psychobiology · doi:10.1002/(sici)1098-2302(199907)35:1 · Cited by 46
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“In 1986, Lagercrantz [12] reported that the mode of delivery affected neonatal catecholamine concentrations.”
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C-fos gene expression in rat brain around birth: effect of asphyxia and catecholamines
Tang, L., Ringstedt, T., Pequignot, J., et al. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02199-x · Cited by 16
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Anesthesia for Cardiovascular Surgery
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Lactate, lactate/pyruvate ratio and catecholamine interrelations in cord blood at delivery in complicated pregnancies
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“Such catecholamines are essential for survival of the fetus during birth and normal initiation of breathing (21, 22).”
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Differences in the quantal release of catecholamines in chromaffin cells of rat embryos and their mothers
Fernández‐Morales, J., Cortés-Gil, L., de Diego, A. M. G., & de Diego, A. M. G. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00086.2009 · Cited by 15
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Resuscitation in the Delivery Room
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Perinatal exposure to methadone: how do early biochemical alterations cause neurofunctional disturbances?
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Goldstein, D. S., & Eisenhofer, G. (2001) · Comprehensive physiology · doi:10.1002/cphy.cp070402 · Cited by 15
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Opinions of the Midwives about Enabling Factors of Skin-To-Skin Contact Immediately after Birth: A Descriptive Study.
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Effects of fetal dexamethasone exposure on postnatal control of cardiac adenylate cyclase: β‐adrenergic receptor coupling to GS regulatory protein
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CONTINUOUS INTRAPARTUM FETAL SCALP TISSUE pH AND ECG MONITORING BY A FIBEROPTIC PROBE
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cAMP and Ca2+Involvement in the Mitochondrial Response of Cultured Fetal Rat Hepatocytes to Adrenaline
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β-Adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization
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“These are triggered by intense catecholaminergic stimulation (17) so that maintenance of -AR signaling is critical to perinatal survival and indeed to trophic effects on general somatic growth (16, 38).”
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The Effect of Fetal Gender on the Delivery Outcome in Primigravidae Women with Induced Labours for all Indications
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“During the progression of labor, as uterine contractions intensify [up to .2 min every 2 min (4)], so do the episodes of hypoxia (10, 12, 34, 35 ); commonly encountered mild moderate placental abruption can also further compromise fetal oxygenation (4).”
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“Consequently, healthy newborns attain normoxia within 3 to 5 minutes after birth (97).”
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Infants' response to the audible and visible properties of the human face: II. Discrimination of differences between singing and adult-directed speech
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Lactate in cord blood and its relation to fetal gluconeogenesis in at term deliveries
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“Catecholamines are crucially involved in adaptive mechanisms at birth [9–11].”
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A Critical Period for the Role of Thyroid Hormone in Development of Renalα-Adrenergic Receptors
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“…responses to birth, with plasma catecholamine concentrations in the newborn during normal delivery greatly exceeding concentrations encountered in the mother during labour, or in other adults during grossly pharmacological situations (Jones, 1980; Hagnevik et al. 1984; Lagercrantz & Slotkin, 1986).”
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β-Adrenoceptor modulation of transiently overexpressed α2-adrenoceptors in brain and peripheral tissues: cellular mechanisms underlying the developmental toxicity of terbutaline
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Maternal and Infant Outcomes After Different Methods of Umbilical Cord Management
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Trace conditioning in 1‐day‐old rats
Bordner, K. A., & Spear, N. E. (2005) · Developmental Psychobiology · doi:10.1002/dev.20108 · Cited by 9
Mechano- and chemoreceptor modulation of renal sympathetic nerve activity at birth in fetal sheep
Segar, J. L., Smith, O. J., & Holley, A. T. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1295 · Cited by 9
Toxic effects of hypoxia on neonatal cardiac function in the rat: α-adrenergic mechanisms
Seidler, F. J., Brown, K. K., Smith, P. G., et al. (1987) · Toxicology Letters · doi:10.1016/0378-4274(87)90170-6 · Cited by 9
Self-citation
Long-term outcomes after neonatal acidemia
Zaigham, M., Källén, K., Sundberg, T.-M., & Olofsson, P. (2025) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2025.02.028 · Cited by 12
Low glucose sensitivity and polymodal chemosensing in neonatal rat adrenomedullary chromaffin cells
Livermore, S., Piskuric, N. A., Buttigieg, J. A., Zhang, M., & Nurse, C. A. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00170.2011 · Cited by 8
“Indeed, other metabolic factors including low O2 (hypoxia) and high CO2/H (acid hypercapnia), associated with fetal asphyxia during birth and neonatal apnoeic episodes, have been shown to stimulate catecholamine secretion from neonatal AMCs via direct, nonneurogenic mechanisms (4, 31, 40, 41, 48, 56, 58).”
Background
Chronic opioids regulate KATP channel subunit Kir6.2 and carbonic anhydrase I and II expression in rat adrenal chromaffin cells via HIF-2α and protein kinase A
Salman, S., Holloway, A. C., & Nurse, C. A. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00135.2014 · Cited by 8
Elective caesarean delivery adversely affects preductal oxygen saturation during birth transition
Zanardo, V., Cengio, V. D., Parotto, M., et al. (2015) · Archives of Disease in Childhood Fetal & Neonatal · doi:10.1136/archdischild-2015-308304 · Cited by 8
Chronic Prenatal Nicotine Exposure Alters Enkephalin mRNA Regulation in the Perinatal Rat Adrenal Medulla
Wong, T., Wickström, R., & Holgert, H. (2003) · Pediatric Research · doi:10.1203/01.pdr.0000057985.43569.95 · Cited by 8
Left Ventricular Norepinephrine and Epinephrine Kinetics at Birth in Lambs
Smolich, J. J., Cox, H. S., Berger, P. J., WALKER, A. M., Eisenhofer, G., & Esler, M. (1997) · Circulation Research · doi:10.1161/01.res.81.3.438 · Cited by 8
Current Perspectives on Temperature Management and Hypothermia in Low Birth Weight Infants
Fastman, B. R., Howell, E. A., Holzman, I. R., et al. (2014) · Newborn and Infant Nursing Reviews · doi:10.1053/j.nainr.2014.03.005 · Cited by 7
Age-Related Modulation of Dopamine D1 Receptor mRNA Level by Hypoxia in Rabbit Adrenal Gland
Labaune, J.-M., Boutroy, M., & Bairam, A. (2003) · Neonatology · doi:10.1159/000068925 · Cited by 7
Influence of prenatal adrenaline infusion on arterial blood gases after Caesarean delivery in the lamb
Berger, P. J., Kyriakides, M. A., Smolich, J., et al. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00377.x · Cited by 7
“These actions led Lagercrantz & Slotkin (1986) to propose that antenatal administration of a â_agonist could be useful to compensate for the lack of an adrenaline surge in babies delivered by elective Caesarean section.”
BackgroundResultInfluential
Do catecholamines contribute to the effects of neonatal hypoxia on development of brain and heart? Influence of concurrent α‐adrenergic blockade on ornithine decarboxylase activity
Slotkin, T. A., Orband‐Miller, L. A., & Queen, K. L. (1987) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(87)90059-1 · Cited by 7
Self-citation

Authors: Lagercrantz, H., & Slotkin, T. A.
ORCID: Lagercrantz, Hugo
Slotkin, Theodore A.
Venue: Scientific American
Publisher: Springer Science and Business Media LLC
Published: 1986-04
Volume: 254
Issue: 4
Pages: 100-107
ISSN: 0036-8733 (ISSN-L)
DOI: 10.1038/scientificamerican0486-100
OpenAlex: W2012602762
Cited by: 448
References: 0
Citations by year: 2026: 8 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 7 · 2020: 15 · 2019: 15 · 2018: 12 · 2017: 6 · 2016: 15 · 2015: 15 · 2014: 25 · 2013: 11 · 2012: 18
FWCI: 11.23
Type: journal article
Language: en
Open access: closed
Locations: Scientific American (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Keywords: births, stress, childbirth, maternal stress
MeSH terms: Adrenal Medulla, Animals, Asphyxia Neonatorum, Catecholamines, Female, Fetal Hypoxia, Fetus, Gestational Age, Humans, Infant, Newborn, Labor, Obstetric, Pregnancy, Respiratory Physiological Phenomena, Sheep, Stress, Physiological, Rats

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