Abstract
Objective:
To assess the impact of maternal smoking during pregnancy (MSDP) on the neonatal hypothalamic–pituitary–adrenal axis.
Study Design:
In a prospective observational study, salivary cortisol and cortisone levels were measured at the fourth day of life during resting conditions and in response to a pain-induced stress event in healthy neonates whose mothers smoked cigarettes during each stage of pregnancy and compared with controls.
Results:
Neonates in the control group (n=70) exhibited a physiologic stress response with a significant increase in cortisol (1.3 to 2.1 ng ml−1; P<0.05) and cortisone (11.8 to 17.8 ng ml−1; P<0.05) from baseline levels, whereas in neonates from mothers who smoked (n=33), cortisol (0.9 to 0.8 ng ml−1; P=0.77) and cortisone (11.5 to 13.0; P=0.19) stress response was not significantly different from baseline levels. A two-way analysis of variance confirmed these findings in both groups.
Conclusions:
Healthy neonates whose mothers smoked during pregnancy show a blunted stress response on the fourth day of life. Thus, MSDP leads to a dysregulation of the HPA axis with continued effects in neonatal life. This might explain long-term consequences of MSDP such as overweight, diabetes mellitus and modification of blood pressure control mechanisms in adult life.
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References
Heffner LJ, Sherman CB, Speizer FE, Weiss ST . Clinical and environmental predictors of preterm labor. Obstet Gynecol 1993; 81 (5)Pt 1)):750–757.
Curtin SC, Matthews TJ . Smoking prevalence and cessation before and during pregnancy: data from the birth certificate, 2014. Natl Vital Stat Rep 2016; 65 (1): 1–14.
Kmietowicz Z . Smoking rates among pregnant women fall to all time low of 11%. BMJ 2015; 350: h3335.
Pineles BL, Hsu S, Park E, Samet JM . Systematic review and meta-analyses of perinatal death and maternal exposure to tobacco smoke during pregnancy. Am J Epidemiol 2016; 184 (2): 87–97.
Harger JH, Hsing AW, Tuomala RE, Gibbs RS, Mead PB, Eschenbach DA et al. Risk factors for preterm premature rupture of fetal membranes: a multicenter case-control study. Am J Obstet Gynecol 1990; 163 (1 Pt 1): 130–137.
Bernstein IM, Mongeon JA, Badger GJ, Solomon L, Heil SH, Higgins ST . Maternal smoking and its association with birth weight. Obstet Gynecol 2005; 106 (5 Pt 1): 986–991.
Ananth CV, Savitz DA, Luther ER . Maternal cigarette smoking as a risk factor for placental abruption, placenta previa, and uterine bleeding in pregnancy. Am J Epidemiol 1996; 144 (9): 881–889.
Moore E, Blatt K, Chen A, Van Hook J, DeFranco EA . Relationship of trimester-specific smoking patterns and risk of preterm birth. Am J Obstet Gynecol 2016; 215 (1): 109.e1–6.
MacDorman MF, Cnattingius S, Hoffman HJ, Kramer MS, Haglund B . Sudden infant death syndrome and smoking in the United States and Sweden. Am J Epidemiol 1997; 146 (3): 249–257.
Mitchell EA, Milerad J . Smoking and the sudden infant death syndrome. Rev Environ Health 2006; 21 (2): 81–103.
Rayfield S, Plugge E . Systematic review and meta-analysis of the association between maternal smoking in pregnancy and childhood overweight and obesity. J Epidemiol Community Health 2017; 71 (2): 162–173.
Montgomery SM, Ekbom A . Smoking during pregnancy and diabetes mellitus in a British longitudinal birth cohort. BMJ 2002; 324 (7328): 26–27.
Cohen G, Jeffery H, Lagercrantz H, Katz-Salamon M . Long-term reprogramming of cardiovascular function in infants of active smokers. Hypertension 2010; 55 (3): 722–728.
Barker DJ, Osmond C . Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986; 1 (8489): 1077–1081.
Barker DJP, Eriksson JG, Forsén T, Osmond C . Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol 2002; 31 (6): 1235–1239.
McMillen IC, Robinson JS . Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 2005; 85 (2): 571–633.
Ward AMV, Syddall HE, Wood PJ, Chrousos GP . Phillips DIW. Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis: low birth weight and central HPA regulation. J Clin Endocrinol Metab 2004; 89 (3): 1227–1233.
Phillips DIW, Bennett FI, Wilks R, Thame M, Boyne M, Osmond C et al. Maternal body composition, offspring blood pressure and the hypothalamic-pituitary-adrenal axis. Paediatr Perinat Epidemiol 2005; 19 (4): 294–302.
Matta SG, Fu Y, Valentine JD, Sharp BM . Response of the hypothalamo-pituitary-adrenal axis to nicotine. Psychoneuroendocrinology 1998; 23 (2): 103–113.
Rohleder N, Kirschbaum C . The hypothalamic-pituitary-adrenal (HPA) axis in habitual smokers. Int J Psychophysiol 2006; 59 (3): 236–243.
Mantagos S, Koulouris A, Vagenakis A . A simple stress test for the evaluation of hypothalamic-pituitary-adrenal axis during the first 6 months of life. J Clin Endocrinol Metab 1991; 72 (1): 214–216.
Woodside DB, Winter K, Fisman S . Salivary cortisol in children: correlations with serum values and effect of psychotropic drug administration. Can J Psychiatry 1991; 36 (10): 746–748.
Stahl F, Amendt P, Dörner G . Total and free cortisol plasma levels in pre- and postnatal life. Endokrinologie 1979; 74 (2): 243–246.
Santiago LB, Jorge SM, Moreira AC . Longitudinal evaluation of the development of salivary cortisol circadian rhythm in infancy. Clin Endocrinol (Oxf) 1996; 44 (2): 157–161.
Gunnar MR . Reactivity of the hypothalamic-pituitary-adrenocortical system to stressors in normal infants and children. Pediatrics 1992; 90 (3 Pt 2): 491–497.
Rauh M, Gröschl M, Rascher W, Dörr HG . Automated, fast and sensitive quantification of 17 alpha-hydroxy-progesterone, androstenedione and testosterone by tandem mass spectrometry with on-line extraction. Steroids 2006; 71 (6): 450–458.
Schäffer L, Luzi F, Burkhardt T, Rauh M, Beinder E . Antenatal betamethasone administration alters stress physiology in healthy neonates. Obstet Gynecol 2009; 113 (5): 1082–1088.
Stroud LR, Papandonatos GD, Rodriguez D, McCallum M, Salisbury AL, Phipps MG et al. Maternal smoking during pregnancy and infant stress response: test of a prenatal programming hypothesis. Psychoneuroendocrinology 2014; 48: 29–40.
McDonald SD, Walker M, Perkins SL, Beyene J, Murphy K, Gibb W et al. The effect of tobacco exposure on the fetal hypothalamic-pituitary-adrenal axis. BJOG 2006; 113 (11): 1289–1295.
Schäffer L, Müller-Vizentini D, Burkhardt T, Rauh M, Ehlert U, Beinder E . Blunted stress response in small for gestational age neonates. Pediatr Res 2009; 65 (2): 231–235.
Schuetze P, Lopez FA, Granger DA, Eiden RD . The association between prenatal exposure to cigarettes and cortisol reactivity and regulation in 7-month-old infants. Dev Psychobiol 2008; 50 (8): 819–834.
Ramsay DS, Lewis M . The effects of birth condition on infants’ cortisol response to stress. Pediatrics 1995; 95 (4): 546–549.
Liu L, Liu F, Kou H, Zhang BJ, Xu D, Chen B et al. Prenatal nicotine exposure induced a hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in intrauterine growth retardation offspring rats. Toxicol Lett 2012; 214 (3): 307–313.
Alves E, Azevedo A, Correia S, Barros H . Long-term maintenance of smoking cessation in pregnancy: an analysis of the birth cohort generation XXI. Nicotine Tob Res 2013; 15 (9): 1598–1607.
Falk L, Nordberg A, Seiger A, Kjaeldgaard A, Hellström-Lindahl E . Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum. Neuroscience 2005; 132 (2): 389–397.
Yang K, Julan L, Rubio F, Sharma A, Guan H . Cadmium reduces 11 beta-hydroxysteroid dehydrogenase type 2 activity and expression in human placental trophoblast cells. Am J Physiol Endocrinol Metab 2006; 290 (1): E135–E142.
Chen M, Wang T, Liao Z-X, Pan X-L, Feng Y-H, Wang H . Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat. Exp Toxicol Pathol 2007; 59 (3–4): 245–251.
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Haslinger, C., Bamert, H., Rauh, M. et al. Effect of maternal smoking on stress physiology in healthy neonates. J Perinatol 38, 132–136 (2018). https://doi.org/10.1038/jp.2017.172
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DOI: https://doi.org/10.1038/jp.2017.172