CC BY-NC-ND 4.0 · Ann Natl Acad Med Sci 2023; 59(03): 129-138
DOI: 10.1055/s-0043-1770157
Review Article

Effect of Sleep Restriction during Pregnancy on Fetal Brain Programming and Neurocognitive Development of Offspring: A Review

1   Division of Sleep Research, Department of Applied Biology, Biomedical Technology Wing, Satelmond Palace, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India
› Author Affiliations
Funding These studies were supported by research grants from the Cognitive Science Research Initiation Program of Department of Science and Technology, India (SR/CSI/110/2012 and SR/CSRI/102/2014).


We spend one-third of our lives in sleep, yet the core function of it still remains an enigma due to underlying complex neural processing in this altered state of consciousness. Sleep requirement varies with phase of development. Neonates spent about 85% of their time in sleep, which is polyphasic in nature. Gradually, this pattern takes the shape of a monophasic sleep in adolescents and adults, with changing micro- and macroarchitecture in every phase. Deprivation of sleep in adults impairs learning and memory, and reduces theta coherence among hippocampus and amygdale during sleep. However, sleep loss during pregnancy can affect the ontogenetic development of networks for sleep–wakefulness and the cognitive development of offspring. Even in normal pregnancy, poor sleep quality, reduced rapid eye movement (REM) sleep, and sleep fragmentation are common observation during the last trimester of pregnancy. Delta power, a marker for the homeostatic drive for sleep, in the NREM sleep during the last trimester of pregnancy and postpartum is increased. However, further sleep loss during late pregnancy is a growing concern. Neonates that are born to the total sleep-restricted dams present significant alterations in their emotional development (symptoms of hyperactivity, increased risk-taking behavior during periadolescence) and immature sleep–wakefulness patterns. The REM sleep restriction during late pregnancy elicits depressionlike traits in neonates, which persist until middle age. For a healthy development of brain and body, thorough understanding of the dynamic nature of sleep in relation to age and state (pregnancy) is instrumental in preventing the above-mentioned conditions of prenatal origin. Although sleep is essential for an active brain (for work during day), it remains an underestimated phenomenon. This review highlights the importance of sleep during pregnancy for a healthy brain network programming in offspring.

Publication History

Article published online:
08 August 2023

© 2023. National Academy of Medical Sciences (India). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

  • References

  • 1 Aserinsky E, Kleitman N. Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. Science 1953; 118 (3062): 273-274
  • 2 Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron 2010; 68 (06) 1023-1042
  • 3 Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev 2012; 92 (03) 1087-1187
  • 4 Okun ML, Roberts JM, Marsland AL, Hall M. How disturbed sleep may be a risk factor for adverse pregnancy outcomes. Obstet Gynecol Surv 2009; 64 (04) 273-280
  • 5 Chang JJ, Pien GW, Duntley SP, Macones GA. Sleep deprivation during pregnancy and maternal and fetal outcomes: is there a relationship?. Sleep Med Rev 2010; 14 (02) 107-114
  • 6 Pires GN, Andersen ML, Giovenardi M, Tufik S. Sleep impairment during pregnancy: possible implications on mother-infant relationship. Med Hypotheses 2010; 75 (06) 578-582
  • 7
  • 8 Gulia KK, Patel N, Radhakrishnan A, Kumar VM. Reduction in ultrasonic vocalizations in pups born to rapid eye movement sleep restricted mothers in rat model. PLoS One 2014; 9 (01) e84948
  • 9 Gulia KK, Patel N, Kumar VM. Increased ultrasonic vocalizations and risk-taking in rat pups of sleep-deprived dams. Physiol Behav 2015; 139: 59-66
  • 10 Radhakrishnan A, Aswathy BS, Kumar VM, Gulia KK. Sleep deprivation during late pregnancy produces hyperactivity and increased risk-taking behavior in offspring. Brain Res 2015; 1596: 88-98
  • 11 Sivadas N, Radhakrishnan A, Aswathy BS, Kumar VM, Gulia KK. Dynamic changes in sleep pattern during post-partum in normal pregnancy in rat model. Behav Brain Res 2017; 320: 264-274
  • 12 Gulia KK, Kumar VM. Ultrasonic vocalizations and behavior of rat pups born from sleep-deprived dams. In: Brudzynski SM. ed. Handbook of Behavioral Neuroscience Series. Handbook of Ultrasonic Vocalizations: A Window into the Emotional Brain. Vol. 25. Philadelphia, PA: Elsevier; 2018: 467-478
  • 13 Aswathy BS, Kumar VM, Gulia KK. The effects of rapid eye movement sleep deprivation during late pregnancy on newborns' sleep. J Sleep Res 2018; 27 (02) 197-205
  • 14 Aswathy BS, Kumar VM, Gulia KK. Immature sleep pattern in newborn rats when dams encountered sleep restriction during pregnancy. Int J Dev Neurosci 2018; 69: 60-67
  • 15 Gulia KK, Aswathy BS, Kumar VM. Developmental aspects of sleep. In: Gozal D, Kheirandish-Gozal L. eds. Pediatric Sleep Medicine. Cham: Springer; 2021: 115-122
  • 16 Gulia KK, Sivadas N, Kumar VM. Reduced theta coherence and P wave ratio linked to memory deficits after sleep deprivation in rat model. Sleep Vigil 2017; 1: 21-29
  • 17 Gulia KK, Kumar VM. Proper sleep during pregnancy for mental health of new-born: an evidence based appeal to policy makers. Sleep Vigil 2018; 2: 97-98
  • 18 Pires GN, Benedetto L, Cortese R. et al. Effects of sleep modulation during pregnancy in the mother and offspring: evidence from preclinical research. J Sleep Res 2021; 30 (03) e13135
  • 19 Golub HL, Corwin MJ. Infant cry: a clue to diagnosis. Pediatrics 1982; 69 (02) 197-201
  • 20 Zeskind PS, McMurray MS, Garber KA. et al. Development of translational methods in spectral analysis of human infant crying and rat pup ultrasonic vocalizations for early neurobehavioral assessment. Front Psychiatry 2011; 2: 56
  • 21 O'Donnell K, O'Connor TG, Glover V. Prenatal stress and neurodevelopment of the child: focus on the HPA axis and role of the placenta. Dev Neurosci 2009; 31 (04) 285-292
  • 22 Lester BM. Developmental outcome prediction from acoustic cry analysis in term and preterm infants. Pediatrics 1987; 80 (04) 529-534
  • 23 LaGasse LL, Neal AR, Lester BM. Assessment of infant cry: acoustic cry analysis and parental perception. Ment Retard Dev Disabil Res Rev 2005; 11 (01) 83-93
  • 24 Corwin MJ, Lester BM, Sepkoski C, Peucker M, Kayne H, Golub HL. Newborn acoustic cry characteristics of infants subsequently dying of sudden infant death syndrome. Pediatrics 1995; 96 (1, Pt 1): 73-77
  • 25 Juntunen K, Sirviö P, Michelsson K. Cry analysis in infants with severe malnutrition. Eur J Pediatr 1978; 128 (04) 241-246
  • 26 Zeskind PS, McMurray MS, Cox Lippard ET, Grewen KM, Garber KA, Johns JM. Translational analysis of effects of prenatal cocaine exposure on human infant cries and rat pup ultrasonic vocalizations. PLoS One 2014; 9 (10) e110349
  • 27 Chittora A, Patil HA. Data collection of infant cries for research and analysis. J Voice 2017; 31 (02) 252.e15-252.e26
  • 28 Orlandi S, Reyes Garcia CA, Bandini A, Donzelli G, Manfredi C. Application of pattern recognition techniques to the classification of full-term and preterm infant cry. J Voice 2016; 30 (06) 656-663
  • 29 Farsaie Alaie H, Abou-Abbas L, Tadj C. Cry-based infant pathology classification using GMMs. Speech Commun 2016; 77: 28-52
  • 30 Sharma S, Asthana S, Mittal VK. A database of infant cry sounds to study the likely causes of cry. Paper presented at: Proceedings of the 12th International Conference on Natural Language Processing; December 11–14,. 2015 ; Trivandrum, India.
  • 31 Kheddache Y, Tadj C. Identification of diseases in newborns using advanced acoustic features of cry signals. Biomed Signal Process Control 2019; 50: 35-44
  • 32 Meghasree, Nataraja NP. Acoustic features of cry of infants with high risk factors. Int J Health Sci Res 2019; 9 (12) 62-67
  • 33 Parga JJ, Lewin S, Lewis J. et al. Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?. Pediatr Res 2020; 87 (03) 576-580
  • 34 Pisanski K, Raine J, Reby D. Individual differences in human voice pitch are preserved from speech to screams, roars and pain cries. R Soc Open Sci 2020; 7 (02) 191642
  • 35 Tonkiss J, Bonnie KE, Hudson JL, Shultz PL, Duran P, Galler JR. Ultrasonic call characteristics of rat pups are altered following prenatal malnutrition. Dev Psychobiol 2003; 43 (02) 90-101
  • 36 D'Amato FR, Scalera E, Sarli C, Moles A. Pups call, mothers rush: does maternal responsiveness affect the amount of ultrasonic vocalizations in mouse pups?. Behav Genet 2005; 35 (01) 103-112
  • 37 Gale CR, Martyn CN. Birth weight and later risk of depression in a national birth cohort. Br J Psychiatry 2004; 184: 28-33
  • 38 Gale CR, O'Callaghan FJ, Godfrey KM, Law CM, Martyn CN. Critical periods of brain growth and cognitive function in children. Brain 2004; 127 (Pt 2): 321-329
  • 39 Gulia KK, Kumar VM. Sleep disorders in the elderly: a growing challenge. Psychogeriatrics 2018; 18 (03) 155-165
  • 40 Karlsson KAE, Blumberg MS. The union of the state: myoclonic twitching is coupled with nuchal muscle atonia in infant rats. Behav Neurosci 2002; 116 (05) 912-917
  • 41 Losito E, Eisermann M, Vignolo P, Hovhannisyan S, Magny JF, Kaminska A. Benign neonatal sleep myoclonus evokes somatosensory responses. J Clin Neurophysiol 2017; 34 (06) 484-491
  • 42 Olischar M, Klebermass K, Waldhoer T, Pollak A, Weninger M. Background patterns and sleep-wake cycles on amplitude-integrated electroencephalography in preterms younger than 30 weeks gestational age with peri-/intraventricular haemorrhage. Acta Paediatr 2007; 96 (12) 1743-1750
  • 43 Korte J, Wulff K, Oppe C, Siegmund R. Ultradian and circadian activity-rest rhythms of preterm neonates compared to full-term neonates using actigraphic monitoring. Chronobiol Int 2001; 18 (04) 697-708
  • 44 Ardura J, Andrés J, Aldana J, Revilla MA. Development of sleep-wakefulness rhythm in premature babies. Acta Paediatr 1995; 84 (05) 484-489
  • 45 Holditch-Davis D. The development of sleeping and waking states in high-risk preterm infants. Infant Behav Dev 1990; 13: 513-531
  • 46 Foreman SW, Thomas KA, Blackburn ST. Preterm infant state development. J Obstet Gynecol Neonatal Nurs 2008; 37: 657-665 PubMed
  • 47 Mennella JA, Garcia-Gomez PL. Sleep disturbances after acute exposure to alcohol in mothers' milk. Alcohol Fayettev N 2001; 25: 153-158 PubMed
  • 48 Hilakivi L. Effects of prenatal alcohol exposure on neonatal sleep-wake behaviour and adult alcohol consumption in rats. Acta Pharmacol Toxicol (Copenh) 1986; 59 (01) 36-42
  • 49 Garcia-Rill E, Buchanan R, McKeon K, Skinner RD, Wallace T. Smoking during pregnancy: postnatal effects on arousal and attentional brain systems. Neurotoxicology 2007; 28 (05) 915-923
  • 50 Richardson HL, Walker AM, Horne RSC. Maternal smoking impairs arousal patterns in sleeping infants. Sleep 2009; 32 (04) 515-521
  • 51 Cohen E, Wong FY, Wallace EM. et al. EEG power spectrum maturation in preterm fetal growth restricted infants. Brain Res 2018; 1678: 180-186
  • 52 Borbély AA. The S-deficiency hypothesis of depression and the two-process model of sleep regulation. Pharmacopsychiatry 1987; 20 (01) 23-29
  • 53 Samson-Dollfus D, Nogues B, Menard JF, Bertoldi-Lefever I, Geffroy D. Delta, theta, alpha and beta power spectrum of sleep electroencephalogram in infants aged two to eleven months. Sleep 1983; 6 (04) 376-383
  • 54 Lo CC, Chou T, Penzel T. et al. Common scale-invariant patterns of sleep-wake transitions across mammalian species. Proc Natl Acad Sci U S A 2004; 101 (50) 17545-17548
  • 55 Chu-Shore J, Westover MB, Bianchi MT. Power law versus exponential state transition dynamics: application to sleep-wake architecture. PLoS One 2010; 5 (12) e14204
  • 56 Blumberg MS, Seelke AMH, Lowen SB, Karlsson KÆ. Dynamics of sleep-wake cyclicity in developing rats. Proc Natl Acad Sci U S A 2005; 102 (41) 14860-14864
  • 57 Datta S, Hobson JA. Neuronal activity in the caudolateral peribrachial pons: relationship to PGO waves and rapid eye movements. J Neurophysiol 1994; 71 (01) 95-109
  • 58 Vertes RP, Kocsis B. Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 1997; 81 (04) 893-926
  • 59 Gulia KK. Dynamism in activity of the neural networks in brain is the basis of sleep-wakefulness oscillations. Front Neurol 2012; 3: 38
  • 60 Barker DJ. Fetal programming of coronary heart disease. Trends Endocrinol Metab 2002; 13 (09) 364-368
  • 61 Amgalan A, Andescavage N, Limperopoulos C. Prenatal origins of neuropsychiatric diseases. Acta Paediatr 2021; 110 (06) 1741-1749
  • 62 Calkins K, Devaskar SU. Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care 2011; 41 (06) 158-176
  • 63 Monk C, Lugo-Candelas C, Trumpff C. Prenatal developmental origins of future psychopathology: mechanisms and pathways. Annu Rev Clin Psychol 2019; 15: 317-344
  • 64 Su Y, D'Arcy C, Meng X. Research review: developmental origins of depression—a systematic review and meta-analysis. J Child Psychol Psychiatry 2021; 62 (09) 1050-1066
  • 65 Peng Y, Wang W, Tan T. et al. Maternal sleep deprivation at different stages of pregnancy impairs the emotional and cognitive functions, and suppresses hippocampal long-term potentiation in the offspring rats. Mol Brain 2016; 9: 17
  • 66 Jia P, Manuel AM, Fernandes BS, Dai Y, Zhao Z. Distinct effect of prenatal and postnatal brain expression across 20 brain disorders and anthropometric social traits: a systematic study of spatiotemporal modularity. Brief Bioinform 2021; 22 (06) bbab214
  • 67 Warland J, Dorrian J, Morrison JL, O'Brien LM. Maternal sleep during pregnancy and poor fetal outcomes: a scoping review of the literature with meta-analysis. Sleep Medicine Reviews 2018; 41: 197-219 PubMed
  • 68 Wang R, Xu M, Yang W. et al. Maternal sleep during pregnancy and adverse pregnancy outcomes: a systematic review and meta-analysis. J Diabetes Investig 2022; 13 (07) 1262-1276
  • 69 Yang Z, Zhu Z, Wang C, Zhang F, Zeng H. Association between adverse perinatal outcomes and sleep disturbances during pregnancy: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2022; 35 (01) 166-174
  • 70 Gulia KK, Mallick HN, Kumar VM. Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats. Neuroscience 2003; 116 (04) 921-923
  • 71 Gulia KK, Mallick HN, Kumar VM. Sleep-related penile erections do not occur in rats during carbachol-induced rapid eye movement sleep. Behav Brain Res 2004; 154 (02) 585-587
  • 72 Gulia KK, Kumar VM, Mallick HN. Role of the lateral septal noradrenergic system in the elaboration of male sexual behavior in rats. Pharmacol Biochem Behav 2002; 72 (04) 817-823
  • 73 Gulia KK, Jodo E, Kawauchi A. et al. The septal area, site for the central regulation of penile erection during waking and rapid eye movement sleep in rats: a stimulation study. Neuroscience 2008; 156 (04) 1064-1073
  • 74 Gulia KK, Kayama Y, Koyama Y. Assessment of the septal area neuronal activity during penile erections in rapid eye movement sleep and waking in the rats. J Physiol Sci 2018; 68 (05) 567-577
  • 75 Gulia KK, Mallick HN, Kumar VM. Ambient temperature related sleep changes in rats neonatally treated with capsaicin. Physiol Behav 2005; 85 (04) 414-418
  • 76 Felder JN, Baer RJ, Rand L, Jelliffe-Pawlowski LL, Prather AA. Sleep disorder diagnosis during pregnancy and risk of preterm birth. Obstet Gynecol 2017; 130 (03) 573-581
  • 77 O'Donnell KJ, Meaney MJ. Fetal origins of mental health: the developmental origins of health and disease hypothesis. Am J Psychiatry 2017; 174 (04) 319-328
  • 78 Abbott PW, Gumusoglu SB, Bittle J, Beversdorf DQ, Stevens HE. Prenatal stress and genetic risk: how prenatal stress interacts with genetics to alter risk for psychiatric illness. Psychoneuroendocrinology 2018; 90: 9-21
  • 79 Lavonius M, Railo H, Karlsson L. et al. Maternal sleep quality during pregnancy is associated with neonatal auditory ERPs. Sci Rep 2020; 10 (01) 7228
  • 80 Badran M, Yassin BA, Lin DTS, Kobor MS, Ayas N, Laher I. Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring. J Physiol 2019; 597 (22) 5349-5364