2. 复旦大学附属妇产科医院产科, 上海 200011
2. Department of Obstetrics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China
近年来,睡眠与妊娠结局之间关系的研究成为热点[1-5]。出生体质量是胎儿生长的重要指标,影响出生后健康状况、器官功能和疾病的发生发展[6-7]。低出生体质量的新生儿心血管疾病、肥胖、Ⅱ型糖尿病和高血压风险增加之间存在相关性[8-10]。目前关于睡眠与子代出生体质量之间关系的研究结论并不一致。本文主要从母亲孕期睡眠呼吸障碍(sleep-disordered breathing,SDB)、睡眠持续时间、睡眠质量及睡眠姿势4个方面对睡眠与子代出生体质量之间的关系作一综述。
1 SDBSDB是指一系列夜间呼吸障碍,包括原发性打鼾、上呼吸道阻力增加和阻塞性睡眠呼吸暂停(obstructive sleep apnea, OSA),其特征是在睡眠中反复出现完全或部分上气道塌陷,反复出现通气异常和觉醒[11]。SDB是最常见的睡眠障碍之一,影响高达32%的孕妇[12]。
目前大多数研究[5]未发现子代出生体质量与打鼾的相关性。但是,一项纳入1 000余名孕妇的前瞻性研究[13]显示,频繁或几乎总是打鼾的妇女子代低出生体质量的风险增加;校正是否为早产儿因素后,打鼾不再与子代低出生体质量相关。另有研究[14-17]认为,打鼾妇女子代出生体质量较不打鼾妇女高,可能与母亲肥胖有关。Olivarez等[17]通过体质指数(body mass index, BMI)分层分析发现,仅BMI>30 kg/m2的妇女打鼾与子代高出生体质量有关。Ge等[14]则发现,在中国人群中,孕期打鼾者分娩巨大儿的风险增加。其中,与BMI<24 kg/m2的不打鼾者相比,BMI<24 kg/m2的打鼾者和超重/肥胖(BMI≥24 kg/m2)的打鼾者分娩巨大儿的相对风险都增加[14]。此外,Tauman等[18]在122例孕妇中进行的横断面研究发现,打鼾妇女所生婴儿的脐带血中核红细胞含量较高,提示胎儿存在低氧血症。
柏林问卷(Berlin questionnaire,BQ)包含打鼾、白天嗜睡、高血压和BMI等内容,阳性提示OSA高风险[19]。Higgins等[15]报告,与BQ阴性妇女相比,BQ阳性妇女的子代出生体质量显著升高。而Ugur等[20]的前瞻性研究显示,与BQ阴性妇女相比,BQ阳性妇女的子代存在低出生体质量趋势;Chen等[21]也认为,母亲诊断OSA与子代低出生体质量风险增加有关;Louis等[22]则发现,与单纯肥胖的妇女相比,伴OSA的肥胖妇女婴儿体质量显著降低。此外,Sharma等[23]对273名妇女进行的一项前瞻性研究未发现子代出生体质量与BQ阳性的关系,但发现打鼾妇女的子代存在出生体质量降低的趋势;Guilleminault等[24]的研究结果相似。
3个荟萃分析[1-2, 25]结果显示,孕妇SDB与子代低出生体质量之间存在相关性。而Li等[26]的一项纳入8 749名妇女(15项研究)的荟萃分析则显示,孕妇SDB和子代低出生体质量无关。另外3项大型研究[13, 15, 27](1 000名以上参与者)发现SDB与出生体质量不相关。导致这些研究结果不一致的原因可能如下:(1)SDB测量的时期不一致,严重程度也未得到一致评估;(2)低出生体质量与胎儿宫内生长受限不同,无须进行胎龄校正,故未排除早产等混杂因素的影响。总之,研究总体结果支持孕妇SDB导致子代低出生体质量[28]。但是大多数研究中潜在的混杂变量未得到控制,这可能是导致这种关联不明确的原因[28]。
2 睡眠持续时间美国国家睡眠基金会建议成年人每晚睡眠时间为7~9 h,认为每晚睡眠时间不足6 h为睡眠不足[29]。然而,怀孕期间睡眠不足尚无定论。而且,怀孕期间所需的最佳夜间睡眠时间也不确定,同时不同年龄、种族和胎次的妇女的最佳夜间睡眠时间也可能不同。
一项前瞻性研究[30]中,孕30周时卧床时间<7 h抑郁妇女的子代出生体质量较卧床时间>9 h的抑郁妇女的子代低。一项纳入739名孕妇的前瞻性研究[31]发现,母亲孕期睡眠时间不足8 h与子代低出生体质量的风险增加有关。一项对176名孕妇进行的前瞻性队列研究[32]发现,初产妇怀孕期间睡眠时间减少,子代出生体质量降低。另一项对3 567名孕妇的前瞻性研究[33]发现,与睡眠8~9 h/d相比,孕早期睡眠7 h/d的孕妇子代出生体质约减少42.70 g,睡眠不足7 h/d的孕妇子代低出生体质量的风险增加83%。Rabkin等[34]发现,怀孕中期和晚期每晚睡眠超过9 h的妇女,其子代平均出生体质量略有增加,且从怀孕中期开始子代出生体质量与母亲睡眠时间正相关。
然而,一项横断面研究[35]表明母亲短睡眠与子代低出生体质量之间无相关性。一项横断面研究[36]则发现,母亲睡眠不足8 h与子代出生体质量大于3 500 g相关。一项前瞻性研究[37]发现,与睡眠6.0~7.9 h/d的孕妇相比,睡眠9.0~9.9 h/d的子代低出生体质量与小于胎龄儿的发生率降低。另一项前瞻性研究[38]发现,孕妇孕前及孕期睡眠时间与新生儿出生体质量呈倒U形关系。该研究显示,在孕前睡眠时间不足7 h/d的妇女中,每天多睡1 h,子代出生体质量平均增加44.7 g,但在排除其他潜在混杂因素后差异无统计学意义;然而,对于每天睡眠超过9 h的孕妇,每增加1 h睡眠时间会使子代出生体质量平均减少39.2 g,调整混杂因素和母亲抑郁焦虑等因素后,结果相似[38]。
总之,大部分研究认为母亲睡眠不足与子代出生体质量降低相关,少量研究认为母亲睡眠不足导致子代出生体质量增加或与子代出生体质量无关。大多数研究未用一致的短睡眠时间定义,而采用主观的、自我报告的睡眠时间,且为相对短的时间。因此,需要基于客观测量数据进一步研究孕期睡眠时间和子代出生体质量之间的关联模式。
3 睡眠质量睡眠质量差在妊娠妇女中很常见,其中胎次和胎龄等因素可能影响睡眠质量。Wilson等[39]报告,孕晚期睡眠效率下降,表现为觉醒增加、深度睡眠减少。Signal等[40]证明,初产妇通常睡眠效率较低,在床时间更长,从孕中期起睡眠期间醒来的时间较经产妇长。睡眠质量差可能会对母体妊娠结局产生负面影响[4],进而影响胎儿结局。然而,很少有研究探讨孕期睡眠质量差对子代出生体质量的影响。
最常采用匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)[41]评估睡眠质量。Rajendiran等[42]发现,睡眠良好和睡眠不良者子代出生体质量之间没有差异;但是,亚组分析显示,孕妇睡眠越差(PSQI得分>18分),子代出生体质量越低。一项涉及1 466对母婴的前瞻性研究[43]发现,分娩女性子代的孕妇孕期PSQI评分与子代出生体质量负相关,但分娩男性子代母亲的睡眠质量与子代体质量之间无相关性。此外,妊娠晚期睡眠质量差是子代低出生体质量的危险因素[43]。Dolatian等[44]发现,睡眠质量在不同子代出生体质量(<2 500 g、2 600~3 000 g、3 001~4 000 g和>4 000 g)的孕妇间差异无统计学意义,虽然指出睡眠障碍组子代出生体质量较低,但未提供具体数据。一项研究[36]通过孕妇主观描述睡眠是“清爽的”“相对清爽的”“不清爽的”来评估其睡眠质量,发现与睡眠“不清爽的”或“相对清爽的”的孕妇相比,睡眠“清爽的”孕妇女性子代出生体质量>2 500 g的概率更高,同时发现孕晚期睡眠障碍可能导致子代出生体质量下降[36]。
上述研究表明,母亲睡眠质量差可能导致子代出生体质量降低。但是睡眠质量评估受主观因素影响,因此需要进行大规模的纵向研究来验证这一关系。
4 睡眠姿势妊娠晚期产妇仰卧位与下腔静脉压迫有关[45],因此为防止心脏输出量下降和促进母体血液流向胎盘,应避免这种体位[46]。发生急性胎儿窘迫时,孕妇左侧卧位有助于胎儿复苏[47]。产科手术或操作(如超声波和腹部触诊)时,通常会将妇女置于左侧倾斜位置。有研究[48]建议仰卧低血压综合征孕妇或体位依赖性SDB孕妇避免仰卧位。但是,孕妇睡眠体位常被忽略。有研究[49]表明,大多数孕妇存在仰卧位睡眠。这表明胎儿可能会重复地暴露在氧气和营养物减少的环境中,导致胎儿生长受限甚至死亡。
目前关于孕妇睡眠姿势与子代出生体质量的研究较少,有2项研究[35, 50]发现孕妇仰卧位睡眠与子代低出生体质量相关。一项纳入1 804名孕妇的荟萃分析[50]发现,与其他入睡姿势相比,孕晚期以仰卧位姿势入睡的女性子代出生体质量平均降低144 g,子代出生体质量降低与已知出生体质量相关的变量无关,以非仰卧位姿势(左侧卧位、右侧卧位以及其他姿势)入睡的孕妇平均子代出生体质量相似。一项横断面研究[35]发现,怀孕期间仰卧位睡眠妇女发生子代低出生体质量和死产的风险增加,且低出生体质量可能是仰卧位睡眠导致死产的因素。
母体仰卧位睡眠导致胎儿不良结局的潜在机制可能包括母体氧饱和度降低、胎盘血流灌注减少和间歇性胎儿低氧血症[5]。临床医生应加强孕妇睡眠姿势与子代低出生体质量之间关系的研究。
5 小结与展望健康和疾病的发展起源(developmental origins of health and disease,DOHaD)理论认为胎儿能根据子宫内环境信号作出适应性调整,从而提高在不利的出生后环境下的即时存活率。如果子宫内适应不正确或出生后环境发生重大变化,导致产前宫内适应和产后生活环境不匹配,就可能使成年期患病风险增加[51]。怀孕期间发生的生理变化与睡眠结构变化有关。这些变化会在心理层面、代谢和表观遗传学层面影响母亲及其后代的健康[52]。此外,睡眠时间和质量可能对饮食模式有影响,而饮食模式直接影响后代的健康[53]。
低出生体质量与新生儿发病率和死亡率相关,并与成年期慢性疾病的发展有关[54]。多数研究认为母亲睡眠障碍与子代出生体质量降低相关。需要进一步的纵向研究来证实母亲睡眠障碍和子代出生体质量之间的关联模式。通过不同的人群样本,纳入激素和心理健康生物标志物等指标,并采用客观的睡眠时间和睡眠质量评估方法(如目前许多智能穿戴设备上提供的方法)有利于明确该关联模式。
利益冲突:所有作者声明不存在利益冲突。
[1] |
PAMIDI S, PINTO L M, MARC I, et al. Maternal sleep-disordered breathing and adverse pregnancy outcomes: a systematic review and metaanalysis[J]. Am J Obstet Gynecol, 2014, 210(1): 52. e1-52. e14.
[DOI]
|
[2] |
DING X X, WU Y L, XU S J, et al. A systematic review and quantitative assessment of sleep-disordered breathing during pregnancy and perinatal outcomes[J]. Sleep Breath, 2014, 18(4): 703-713.
[DOI]
|
[3] |
PALAGINI L, GEMIGNANI A, BANTI S, et al. Chronic sleep loss during pregnancy as a determinant of stress: impact on pregnancy outcome[J]. Sleep Med, 2014, 15(8): 853-859.
[DOI]
|
[4] |
AUGUST E M, SALIHU H M, BIROSCAK B J, et al. Systematic review on sleep disorders and obstetric outcomes: scope of current knowledge[J]. Am J Perinatol, 2013, 30(4): 323-334.
|
[5] |
WARLAND J, DORRIAN J, MORRISON J L, et al. Maternal sleep during pregnancy and poor fetal outcomes: a scoping review of the literature with meta-analysis[J]. Sleep Med Rev, 2018, 41: 197-219.
[DOI]
|
[6] |
RISNES K R, VATTEN L J, BAKER J L, et al. Birthweight and mortality in adulthood: a systematic review and meta-analysis[J]. Int J Epidemiol, 2011, 40(3): 647-661.
[DOI]
|
[7] |
SMITH C J, RYCKMAN K K, BARNABEI V M, et al. The impact of birth weight on cardiovascular disease risk in the Women's Health Initiative[J]. Nutr Metab Cardiovasc Dis, 2016, 26(3): 239-245.
[DOI]
|
[8] |
TARRY-ADKINS J L, OZANNE S E. Mechanisms of early life programming: current knowledge and future directions[J]. Am J Clin Nutr, 2011, 94(6 Suppl): 1765S-1771S.
|
[9] |
LILLYCROP K A, BURDGE G C. Epigenetic mechanisms linking early nutrition to long term health[J]. Best Pract Res Clin Endocrinol Metab, 2012, 26(5): 667-676.
[DOI]
|
[10] |
WANG G, WALKER S O, HONG X, et al. Epigenetics and early life origins of chronic noncommunicable diseases[J]. J Adolesc Health, 2013, 52(2 Suppl 2): S14-S21.
|
[11] |
DEMPSEY J A, VEASEY S C, MORGAN B J, et al. Pathophysiology of sleep apnea[J]. Physiol Rev, 2010, 90(1): 47-112.
[DOI]
|
[12] |
LOUIS J M, KOCH M A, REDDY U M, et al. Predictors of sleep-disordered breathing in pregnancy[J]. Am J Obstet Gynecol, 2018, 218(5): 521 e1-521 e12.
[DOI]
|
[13] |
MICHELI K, KOMNINOS I, BAGKERIS E, et al. Sleep patterns in late pregnancy and risk of preterm birth and fetal growth restriction[J]. Epidemiology, 2011, 22(5): 738-744.
[DOI]
|
[14] |
GE X, TAO F B, HUANG K, et al. Maternal snoring may predict adverse pregnancy outcomes: a cohort study in China[J]. PLoS One, 2016, 11(2): e0148732.
[DOI]
|
[15] |
HIGGINS N, LEONG E, PARK C S, et al. The Berlin Questionnaire for assessment of sleep disordered breathing risk in parturients and non-pregnant women[J]. Int J Obstet Anesth, 2011, 20(1): 22-25.
[DOI]
|
[16] |
KO H S, KIM M Y, KIM Y H, et al. Obstructive sleep apnea screening and perinatal outcomes in Korean pregnant women[J]. Arch Gynecol Obstet, 2013, 287(3): 429-433.
[DOI]
|
[17] |
OLIVAREZ S A, FERRES M, ANTONY K, et al. Obstructive sleep apnea screening in pregnancy, perinatal outcomes, and impact of maternal obesity[J]. Am J Perinatol, 2011, 28(8): 651-658.
[DOI]
|
[18] |
TAUMAN R, MANY A, DEUTSCH V, et al. Maternal snoring during pregnancy is associated with enhanced fetal erythropoiesis--a preliminary study[J]. Sleep Med, 2011, 12(5): 518-522.
[DOI]
|
[19] |
NETZER N C, STOOHS R A, NETZER C M, et al. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome[J]. Ann Intern Med, 1999, 131(7): 485-491.
|
[20] |
UGUR M G, BOYNUKALIN K, ATAK Z, et al. Sleep disturbances in pregnant patients and the relation to obstetric outcome[J]. Clin Exp Obstet Gynecol, 2012, 39(2): 214-217.
|
[21] |
CHEN Y H, KANG J H, LIN C C, et al. Obstructive sleep apnea and the risk of adverse pregnancy outcomes[J]. Am J Obstet Gynecol, 2012, 206(2): 136. e1-e5.
|
[22] |
LOUIS J M, AUCKLEY D, SOKOL R J, et al. Maternal and neonatal morbidities associated with obstructive sleep apnea complicating pregnancy[J]. Am J Obstet Gynecol, 2010, 202(3): 261. e1-e5.
|
[23] |
SHARMA S K, NEHRA A, SINHA S, et al. Sleep disorders in pregnancy and their association with pregnancy outcomes: a prospective observational study[J]. Sleep Breath, 2016, 20(1): 87-93.
[DOI]
|
[24] |
GUILLEMINAULT C, QUERRA-SALVA M, CHOWDHURI S, et al. Normal pregnancy, daytime sleeping, snoring and blood pressure[J]. Sleep Med, 2000, 1(4): 289-297.
[DOI]
|
[25] |
BROWN N T, TURNER J M, KUMAR S. The intrapartum and perinatal risks of sleep-disordered breathing in pregnancy: a systematic review and metaanalysis[J]. Am J Obstet Gynecol, 2018, 219(2): 147-161. e1.
[DOI]
|
[26] |
LI L W, ZHAO K, HUA J, et al. Association between sleep-disordered breathing during pregnancy and maternal and fetal outcomes: an updated systematic review and meta-analysis[J]. Front Neurol, 2018, 9: 91.
[DOI]
|
[27] |
O'BRIEN L M, BULLOUGH A S, OWUSU J T, et al. Snoring during pregnancy and delivery outcomes: a cohort study[J]. Sleep, 2013, 36(11): 1625-1632.
[DOI]
|
[28] |
FARABI S S, BARBOUR L A, HERNANDEZ T L. Sleep-disordered breathing in pregnancy: a developmental origin of offspring obesity?[J]. J Dev Orig Health Dis, 2021, 12(2): 237-249.
[DOI]
|
[29] |
HIRSHKOWITZ M, WHITON K, ALBERT S M, et al. National Sleep Foundation's sleep time duration recommendations: methodology and results summary[J]. Sleep Health, 2015, 1(1): 40-43.
[DOI]
|
[30] |
OKUN M L, LUTHER J F, WISNIEWSKI S R, et al. Disturbed sleep and inflammatory cytokines in depressed and nondepressed pregnant women: an exploratory analysis of pregnancy outcomes[J]. Psychosom Med, 2013, 75(7): 670-681.
[DOI]
|
[31] |
ABEYSENA C, JAVAWARDANA P, SENEVIRATNE RDE A. Effect of psychosocial stress and physical activity on low birthweight: a cohort study[J]. J Obstet Gynaecol Res, 2010, 36(2): 296-303.
[DOI]
|
[32] |
FRANCO-SENA A B, KAHN L G, FARIAS D R, et al. Sleep duration of 24 h is associated with birth weight in nulli- but not multiparous women[J]. Nutrition, 2018, 55-56: 91-98.
[DOI]
|
[33] |
WANG W Y, ZHONG C R, ZHANG Y, et al. Shorter sleep duration in early pregnancy is associated with birth length: a prospective cohort study in Wuhan, China[J]. Sleep Med, 2017, 34: 99-104.
[DOI]
|
[34] |
RABKIN C S, ANDERSON H R, BLAND J M, et al. Maternal activity and birth weight: a prospective, population-based study[J]. Am J Epidemiol, 1990, 131(3): 522-531.
[DOI]
|
[35] |
OWUSU J T, ANDERSON F J, COLEMAN J, et al. Association of maternal sleep practices with pre-eclampsia, low birth weight, and stillbirth among Ghanaian women[J]. Int J Gynaecol Obstet, 2013, 121(3): 261-265.
[DOI]
|
[36] |
ZAFARGHANDI N, HADAVAND S, DAVATI A, et al. The effects of sleep quality and duration in late pregnancy on labor and fetal outcome[J]. J Matern Fetal Neonatal Med, 2012, 25(5): 535-537.
[DOI]
|
[37] |
MURATA T, KYOZUKA H, FUKUDA T, et al. Maternal sleep duration and neonatal birth weight: the Japan Environment and Children's Study[J]. BMC Pregnancy Childbirth, 2021, 21(1): 295.
[DOI]
|
[38] |
MARINELLI M, CARSIN A E, TURNER M C, et al. Maternal sleep duration and neonate birth weight: a population-based cohort study[J]. Int J Gynaecol Obstet, 2021.
|
[39] |
WILSON D L, BARNES M, ELLETT L, et al. Decreased sleep efficiency, increased wake after sleep onset and increased cortical arousals in late pregnancy[J]. Aust N Z J Obstet Gynaecol, 2011, 51(1): 38-46.
[DOI]
|
[40] |
SIGNAL T L, GANDER P H, SANGALLI M R, et al. Sleep duration and quality in healthy nulliparous and multiparous women across pregnancy and post-partum[J]. Aust N Z J Obstet Gynaecol, 2007, 47(1): 16-22.
[DOI]
|
[41] |
BUYSSE D J, REYNOLDS C F, MONK T H 3RD, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research[J]. Psychiatry Res, 1989, 28(2): 193-213.
[DOI]
|
[42] |
RAJENDIRAN S, SWETHA KUMARI A, NIMESH A, et al. Markers of oxidative stress in pregnant women with sleep disturbances[J]. Oman Med J, 2015, 30(4): 264-269.
[DOI]
|
[43] |
LIU H, LI H, LI C, et al. Associations between maternal sleep quality throughout pregnancy and newborn birth weight[J]. Behav Sleep Med, 2021, 19(1): 57-69.
[DOI]
|
[44] |
DOLATIAN M, MEHRABAN Z, SADEGHNIAT K. The effect of impaired sleep on preterm labour[J]. West Indian Med J, 2014, 63(1): 62-67.
|
[45] |
KERR M G, SCOTT D B, SAMUEL E. Studies of the inferior vena cava in late pregnancy[J]. Br Med J, 1964, 1(5382): 532-533.
|
[46] |
JEFFREYS R M, STEPANCHAK W, LOPEZ B, et al. Uterine blood flow during supine rest and exercise after 28 weeks of gestation[J]. BJOG, 2006, 113(11): 1239-1247.
[DOI]
|
[47] |
THURLOW J A, KINSELLA S M. Intrauterine resuscitation: active management of fetal distress[J]. Int J Obstet Anesth, 2002, 11(2): 105-116.
[DOI]
|
[48] |
MORONG S, HERMSEN B, VRIES DE N. Sleep-disordered breathing in pregnancy: a review of the physiology and potential role for positional therapy[J]. Sleep Breath, 2014, 18(1): 31-37.
[DOI]
|
[49] |
O'BRIEN L M, WARLAND J. Typical sleep positions in pregnant women[J]. Early Hum Dev, 2014, 90(6): 315-317.
[DOI]
|
[50] |
ANDERSON N H, GORDON A, LI M, et al. Association of supine going-to-sleep position in late pregnancy with reduced birth weight: a secondary analysis of an individual participant data meta-analysis[J]. JAMA Netw Open, 2019, 2(10): e1912614.
[DOI]
|
[51] |
VICKERS M H. Early life nutrition, epigenetics and programming of later life disease[J]. Nutrients, 2014, 6(6): 2165-2178.
[DOI]
|
[52] |
PIRES G N, BENEDETTO L, CORTESE R, et al. Effects of sleep modulation during pregnancy in the mother and offspring: evidences from preclinical research[J]. J Sleep Res, 2021, 30(3): e13135.
|
[53] |
POT G K. Sleep and dietary habits in the urban environment: the role of chrono-nutrition[J]. Proc Nutr Soc, 2018, 77(3): 189-198.
[DOI]
|
[54] |
YADAV D K, SHUKLA G S, GUPTA N, et al. Maternal and obstetric factors associated with low birth weight[J]. J Nepal Health Res Counc, 2020, 17(4): 443-450.
[DOI]
|