A prospective cohort study on the association of maternal perinatal cigarette smoking, alcohol consumption and their interactions with risk of neonatal low birth weight
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摘要:
目的 探究母亲围孕期吸烟和饮酒及其交互作用对新生儿低出生体重(low birth weight, LBW)的影响。 方法 在湖南省内招募首次参与孕早期产检的孕妇以构建孕早期队列，通过问卷和病历系统收集信息，通过电话随访孕妇以监测LBW等妊娠结局。采用logistic回归分析模型分析母亲围孕期吸烟和饮酒及其交互作用与LBW的关联。采用分层分析评估关联的稳定性。 结果 共纳入34 104对单胎孕妇及新生儿进行分析。新生儿中有3 020例被诊断为LBW，发生率为8.9%(95% CI: 8.6%~9.2%)。多因素logistic回归分析模型分析结果显示，母亲围孕期主动吸烟(OR=1.428, 95% CI: 1.147~1.777)、被动吸烟(OR=1.128, 95% CI: 1.031~1.235)和饮酒(OR=2.297, 95% CI: 1.949~2.706)均是新生儿LBW的危险因素(均P＜0.05)。交互作用分析结果显示，主动吸烟与饮酒存在拮抗效应的交互作用(OR=0.117, 95% CI: 0.049~0.278)。 结论 母亲围孕期主动吸烟、被动吸烟和饮酒及其交互作用与新生儿LBW的发生风险有关，提示母亲围孕期应保持健康行为方式，以预防LBW。 Abstract:Objective To assess the effects of maternal cigarette smoking and alcohol consumption and their interactions during periconceptional pregnancy on the risk of low birth weight (LBW) in newborns. Methods Pregnant women attending their initial early prenatal care in Hunan Province were recruited to establish a cohort. Information was collected through questionnaires and medical records, with telephone follow-ups to monitor pregnancy outcomes including LBW. The logistic regression analysis was applied to assess the associations of maternal periconceptional cigarette smoking, alcohol consumption, and their interactions with the risk of LBW. Meanwhile, stratified analysis was conducted to evaluate the stability of the associations. Results A total of 34 104 singleton pregnancies and newborns were included in this study. Among these newborns, 3 020 cases were diagnosed with LBW, with an incidence of 8.9% (95% CI: 8.6%-9.2%). The multivariate logistic regression analysis showed that maternal active smoking (OR=1.428, 95% CI: 1.147-1.777), passive smoking (OR=1.128, 95% CI: 1.031-1.235), and alcohol consumption (OR=2.297, 95% CI: 1.949-2.706) during periconceptional pregnancy were significantly associated with risk of LBW (all P < 0.05). Additionally, the interaction analysis revealed an antagonistic effect between active smoking and alcohol consumption (OR=0.117, 95% CI: 0.049-0.278). Conclusions Maternal periconceptional active smoking, passive smoking, alcohol consumption and their interactions are significantly associated with neonatal LBW, highlighting the importance of maintaining healthy behaviors during pregnancy to prevent LBW. -
Key words:
- Low birth weight /
- Cigarette smoking /
- Alcohol consumption /
- Interaction /
- Prospective cohort study
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表 1 不同暴露组基线特征比较
Table 1. Comparison of baseline characteristics among different exposure groups
基线特征 Baseline characteristics 围孕期主动吸烟
Periconceptional active smoking②围孕期被动吸烟
Periconceptional passive smoking②围孕期饮酒
Periconceptional alcohol consumption②否 No 是 Yes P值
value否 No 是 Yes P值
value否 No 是 Yes P值
value社会人口学特征 Social demographics 年龄(＜35岁) Age(< 35 years) 27 624(82.9) 655(84.2) 0.341 22 561(83.0) 5 718(82.6) 0.473 27 427(82.9) 852(82.1) 0.466 民族(汉族) Ethnic group (Han) 32 890(98.7) 766(98.5) 0.571 26 820(98.7) 6 836(98.8) 0.414 32 633(98.7) 1 023(98.6) 0.706 居住地(城镇地区) Residence (urban area) 20 630(61.9) 444(57.1) 0.006 16 746(61.6) 4 328(62.5) 0.150 20 508(62.0) 566(54.5) 0.001 受教育水平(大专以下) Education level (below college) 11 960(35.9) 282(36.2) 0.837 9 744(35.8) 2 498(36.1) 0.695 11 865(35.9) 377(36.3) 0.773 既往妊娠史 Previous pregnancy history 初潮年龄(＜15岁) Menarche age(< 15 years) 29 356(88.1) 686(88.2) 0.941 23 972(88.2) 3 212(11.8) 0.284 29 154(88.2) 888(85.5) 0.010 孕次(＝1次) Parity (=1 time) 10 255(30.8) 238(30.6) 0.914 8 325(30.6) 10 493(30.8) 0.257 10 164(30.7) 329(31.7) 0.511 不良妊娠史(有) Adverse pregnancy history (yes) 1 801(54.1) 43(55.7) 0.376 14 729(54.2) 3 718(53.7) 0.498 17 856(54.0) 591(56.9) 0.062 妊娠并发症(有) Pregnancy complications (yes) 7 636(22.9) 184(23.7) 0.629 6 236(22.9) 1 584(22.9) 0.930 7 396(22.4) 424(40.8) 0.001 孕早期健康状况 Early pregnancy health status 感冒(有) Cold (yes) 3 054(9.2) 82(10.5) 0.189 2 497(9.2) 639(9.2) 0.901 3 032(9.2) 104(10.0) 0.351 发热(有) Fever (yes) 1 177(3.5) 26(3.3) 0.777 958(3.5) 245(3.5) 0.948 1 162(3.5) 41(3.9) 0.454 全身感染(有) Systemic infection (yes) 50(0.2) 1(0.1) 0.878 36(0.1) 15(0.2) 0.105 49(0.1) 2(0.2) 0.715 呼吸道感染(有) Respiratory tract infection (yes) 377(1.1) 9(1.2) 0.947 308(1.1) 78(1.1) 0.967 371(1.1) 15(1.4) 0.333 泌尿道感染(有) Urinary tract infection (yes) 96(0.3) 3(0.4) 0.617 83(0.3) 16(0.2) 0.306 95(0.3) 4(0.4) 0.563 生殖道感染(有) Genital tract infection (yes) 743(2.2) 14(1.8) 0.421 596(2.2) 161(2.3) 0.499 732(2.2) 25(2.4) 0.675 围孕期用药情况 Periconceptional medication use 围孕期服用叶酸(是) Periconceptional folic acid use (yes) 31 826(95.5) 730(93.8) 0.027 1 190(4.4) 358(5.2) 0.005 1 324(4.0) 224(21.6) < 0.001 孕前3个月口服避孕药(是)
Oral contraceptive use 3 months before pregnancy (yes)614(1.8) 16(2.1) 0.661 500(1.8) 130(1.9) 0.828 618(1.9) 12(1.2) 0.093 围孕期营养状况 Periconceptional nutritional status 孕前BMI Pre-pregnancy BMI/(kg·m-2) 0.228 0.201 0.955 正常 Normal 23 364(70.1) 561(72.1) 19 027(70.0) 4 898(70.8) 23 196(70.2) 729(70.2) 异常 Abnormal 9 962(29.9) 217(27.9) 8 157(30.0) 2 022(29.2) 9 870(29.8) 309(29.8) 孕期体重增加 Gestational weight gain/kg① 0.695 0.397 0.837 正常 Normal 24 114(72.4) 558(71.7) 19 694(72.4) 4 978(71.9) 23 924(72.4) 9 142(27.6) 异常 Abnormal 9 212(27.6) 220(28.3) 7 490(27.6) 1 942(28.1) 748(72.1) 290(27.9) 营养不良(有) Malnutrition (yes) 470(1.4) 8(1.0) 0.370 378(1.4) 100(1.4) 0.730 478(1.4) 0(0) < 0.001 饮食不平衡(有) Unbalanced diet (yes) 3 820(11.5) 78(10.0) 0.213 3 112(11.4) 786(11.4) 0.834 3 654(11.1) 244(23.5) < 0.001 体力活动程度 Physical activity level 0.521 0.012 < 0.001 轻 Light 26 938(80.8) 636(81.7) 22 052(81.1) 5 522(79.8) 26 654(80.6) 920(88.6) 一般或重 Moderate or vigorous 6 388(19.2) 142(18.3) 5 132(18.9) 1 398(20.2) 6 412(19.4) 118(11.4) 本次妊娠并发症 Current pregnancy complications 妊娠期贫血(有) Pregnancy anemia (yes) 2 394(7.2) 42(5.4) 0.056 1 946(7.2) 490(7.1) 0.823 2 398(7.3) 38(3.7) < 0.001 子痫前期(有) Preeclampsia (yes) 762(2.3) 26(3.3) 0.053 622(2.3) 166(2.4) 0.584 737(2.2) 51(4.9) < 0.001 妊娠糖尿病(有) Gestational diabetes mellitus (yes) 5 310(15.9) 120(15.4) 0.701 4 330(15.9) 1 100(15.9) 0.947 5 254(15.9) 176(17.0) 0.355 高脂血症(有) Hyperlipidemia (yes) 367(1.1) 8(1.0) 0.847 311(1.1) 64(0.9) 0.118 363(1.1) 12(1.2) 0.859 甲状腺功能亢进(有) Hyperthyroidism (yes) 619(1.9) 17(2.2) 0.504 521(1.9) 115(1.7) 0.162 620(1.9) 16(1.5) 0.434 甲状腺功能减退(有) Hypothyroidism (yes) 4 684(14.1) 10(13.2) 0.517 3 782(13.9) 1 005(14.5) 0.192 4 642(14.0) 145(14.0) 0.949 注：①孕期体重增加正常指孕期体重增加范围为10~19.9 kg，异常指孕期体重增加＜10 kg或者≥20 kg；②以人数(占比%)表示。
Note: ① Gestational weight gain is considered normal when it ranges between 10 to 19.9 kg, whereas an abnormal gestational weight gain is defined as less than 10 kg or greater than or equal to 20 kg; ② Number of people (proportion/%).
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表 2 母亲围孕期吸烟及饮酒与低出生体重的关联分析
Table 2. Analysis of the associations between maternal periconceptional cigarette smoking, alcohol consumption and low birth weight
暴露因素
Exposure factor模型1 Model 1① 模型2 Model 2 ② 模型3 Model 3 ③ OR值value (95% CI) P值value OR值value (95% CI) P值value OR值value (95% CI) P值value 主动吸烟 Active smoking 1.428(1.147~1.777) ＜0.001 1.538(1.226~1.929) ＜0.001 1.371(1.089~1.725) 0.007 被动吸烟 Passive smoking 1.128(1.031~1.235) 0.009 1.127(1.027~1.237) 0.012 1.132(1.031~1.242) 0.009 饮酒 Alcohol consumption 2.297(1.949~2.706) ＜0.001 2.032(1.707~2.419) ＜0.001 1.975(1.656~2.356) ＜0.001 注：①模型1，未校正模型；②模型2，在模型1的基础上，进一步校正年龄、教育水平、人均月收入、不良妊娠史、妊娠期贫血、孕前BMI、本次孕期体重增加、孕前糖尿病、孕前泌尿道感染、孕前生殖道感染、围孕期服用叶酸、妊娠期糖尿病、妊娠期高脂血症、妊娠期甲状腺功能亢进、妊娠期甲状腺功能减退等可能的混杂因素；③模型3，在模型2基础上对主动吸烟、被动吸烟和饮酒进行校正。
Note: ① Model 1，unadjusted model；② Model 2，based on model 1, further adjusted for potential confounding factors, including age, education level, per capita monthly income, history of adverse pregnancy, pregnancy anemia, pre-pregnancy BMI, gestational weight gain, pre-gestational diabetes mellitus, pre-gestational urinary tract infection, pre-gestational genital tract infection, periconceptional folic acid use, gestational diabetes mellitus, gestational hyperlipidemia, gestational hyperthyroidism, and gestational hypothyroidism；③ Model 3, in addition to model 2, adjusted for active smoking, passive smoking, and alcohol consumption.
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表 3 母亲围孕期吸烟及饮酒与低出生体重关联的敏感性分析
Table 3. Sensitivity analysis of the associations between maternal periconceptional cigarette smoking, alcohol consumption and low birth weight
变量
VariableOR值 value(95% CI) 围孕期主动吸烟
Periconceptional active smoking围孕期被动吸烟
Periconceptional passive smoking围孕期饮酒
Periconceptional alcohol consumption年龄/岁 Age/years ＜35 1.427(1.116~1.824) 1.039(0.936~1.153) 2.257(1.873~2.719) ≥35 1.478(0.910~2.403) 1.471(1.225~1.767) 2.429(1.715~3.440) 民族 Ethnic group 汉族 Han 1.456(1.170~1.813) 1.123(1.026~1.230) 2.279(1.931~2.689) 少数民族 Minorities 0.970(0.954~0.987) 1.511(0.730~3.130) 3.573(1.087~11.740) 居住地 Residence 城镇地区 Urban area 1.268(0.898~1.791) 1.290(1.136~1.465) 0.682(0.458~1.015) 乡村地区 Rural area 1.474(1.105~1.966) 1.006(0.884~1.145) 3.755(3.078~4.580) 受教育水平 Education level 大专以下 Below college level 1.393(1.019~1.904) 1.098(0.967~1.247) 2.187(1.719~2.783) 大专及以上 College and above 1.471(1.078~2.009) 1.159(1.018~1.320) 2.455(1.956~3.081) 初潮年龄/岁 Menarche age/years ＜15 1.335(1.051~1.695) 1.111(1.009~1.224) 2.826(2.390~3.341) ≥15 2.164(1.248~3.751) 1.250(0.973~1.606) 0.959(0.953~0.966) 孕次/次 Parity/times 1 1.001(0.827~1.211) 1.701(1.116~2.593) 2.160(1.547~3.015) ＞1 1.175(1.060~1.302) 1.346(1.042~1.740) 2.367(1.959~2.860) 不良妊娠史 Adverse pregnancy history 无 No 1.487(1.033~2.140) 1.078(0.926~1.256) 2.893(2.236~3.744) 有 Yes 1.383(1.051~1.821) 1.162(1.038~1.300) 1.967(1.590~2.433) 妊娠并发症 Pregnancy complications 无 No 1.193(1.074~1.326) 1.624(1.268~2.080) 0.781(0.565~1.079) 有 Yes 0.973(0.816~1.160) 0.966(0.604~1.545) 4.682(3.776~5.805) 感冒 Cold 无 No 1.133(1.030~1.246) 1.437(1.140~1.812) 2.305(1.939~2.740) 有 Yes 1.082(0.808~1.447) 1.339(0.683~2.623) 2.214(1.326~3.697) 发热 Fever 无 No 1.111(1.013~1.218) 1.431(1.146~1.788) 2.319(1.963~2.740) 有 Yes 1.657(1.064~2.581) 1.332(0.393~4.509) 1.782(0.732~4.336) 全身感染 Systemic infection 无 No 1.126(1.029~1.233) 1.417(1.137~1.765) 2.310(1.961~2.721) 有 Yes 1.091(0.277~4.296) 1.083(0.926~1.267) 0.947(0.879~1.021) 呼吸道感染 Respiratory tract infection 无 No 1.128(1.030~1.236) 1.441(1.156~1.795) 2.277(1.929~2.688) 有 Yes 1.121(0.560~2.244) 0.748(0.092~6.098) 3.210(1.054~9.780) 泌尿道感染 Urinary tract infection 无 No 1.426(1.145~1.777) 1.132(1.034~1.239) 2.292(1.944~2.702) 有 Yes 1.346(0.117~5.480) 0.870(0.254~2.973) 2.800(0.374~20.949) 生殖道感染 Genital tract infection 无 No 1.434(1.149~1.789) 1.126(1.027~1.234) 2.339(1.983~2.760) 有 Yes 1.273(0.280~5.785) 1.184(0.701~2.001) 1.038(0.304~3.541) 围孕期服用叶酸 Periconceptional folic acid use 否 No 1.215(0.952~1.550) 1.106(1.006~1.215) 1.854(1.519~2.262) 是 Yes 4.112(2.277~7.427) 1.302(0.954~1.778) 2.725(1.962~3.783) 孕前3个月口服避孕药
Oral contraceptives use 3 months before pregnancy否 No 1.454(1.168~1.811) 1.116(1.019~1.223) 2.285(1.938~2.695) 是 Yes 0.973(0.960~0.986) 2.200(1.114~4.346) 3.053(0.646~14.429) 孕前BMI Pre-pregnancy BMI/(kg·m-2) 正常 Normal 1.480(1.134~1.932) 1.139(1.018~1.275) 2.392(1.956~2.924) 异常 Abnormal 1.362(0.927~2.003) 1.118(0.960~1.301) 2.142(1.612~2.846) 孕期体重增加 Gestational weight gain/kg 正常 Normal 1.767(1.353~2.308) 1.171(1.040~1.318) 2.046(1.640~2.553) 异常 Abnormal 0.993(0.676~1.458) 1.064(0.923~1.225) 2.801(2.167~3.620) 营养不良 Malnutrition 无 No 1.463(1.173~1.826) 1.106(1.008~1.213) 2.389(2.027~2.815) 有 Yes 0.802(0.160~4.022) 1.853(1.169~2.938) - 饮食不平衡 Unbalanced diet 无 No 1.491(1.183~1.880) 1.139(1.033~1.256) 2.094(1.724~2.545) 有 Yes 1.090(0.557~2.133) 1.069(0.842~1.356) 2.495(1.825~3.409) 体力活动程度 Physical activity level 轻 Light 1.425(1.114~1.823) 1.230(1.112~1.360) 2.200(1.839~2.632) 一般或重 Moderate or vigorous 1.452(0.899~2.346) 0.803(0.654~0.987) 3.379(2.234~5.112) 妊娠期贫血 Pregnancy anemia 无 No 1.434(1.144~1.798) 1.139(1.037~1.251) 2.217(1.870~2.627) 有 Yes 1.429(0.596~3.426) 1.014(0.735~1.399) 5.197(2.653~10.180) 子痫前期 Preeclampsia 无 No 1.441(1.137~1.826) 1.122(1.017~1.237) 2.123(1.770~2.547) 有 Yes 0.833(0.378~1.839) 1.268(0.885~1.817) 2.660(1.312~5.393) 妊娠糖尿病 Gestational diabetes mellitus 无 No 1.426(1.123~1.811) 1.092(0.989~1.206) 2.354(1.968~2.814) 有 Yes 1.438(0.830~2.489) 1.323(1.066~1.643) 2.027(1.346~3.053) 高脂血症 Hyperlipidemia 无 No 1.410(1.130~1.758) 1.124(1.027~1.231) 2.299(1.950~2.711) 有 Yes 3.490(0.676~18.005) 1.566(0.674~3.637) 2.069(0.434~9.854) 甲状腺功能亢进 Hyperthyroidism 无 No 1.434(1.150~1.787) 1.135(1.036~1.242) 2.321(1.970~2.735) 有 Yes 1.185(0.152~9.230) 0.454(0.136~1.518) 0.974(0.961~0.986) 甲状腺功能减退 Hypothyroidism 无 No 1.368(1.081~1.732) 1.105(1.003~1.217) 2.247(1.884~2.679) 有 Yes 1.906(1.054~3.446) 1.327(1.031~1.709) 2.688(1.710~4.226)
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表 4 母亲围孕期吸烟及饮酒与低出生体重关联的交互作用分析
Table 4. Analysis of interactions between maternal periconceptional cigarette smoking, alcohol consumption and LBW
交互作用因子
Interaction factor模型1 Model 1① 模型2 Model 2② OR值value
(95% CI)P值
valueOR值value
(95% CI)P值
value主动吸烟×被动吸烟 Active smoking×passive smoking 1.014(0.612~1.680) 0.957 0.946(0.558~1.605) 0.838 主动吸烟×饮酒 Active smoking×alcohol consumption 0.117(0.049~0.278) ＜0.001 0.127(0.052~0.306) ＜0.001 被动吸烟×饮酒 Passive smoking×alcohol consumption 1.533(1.037~2.267) 0.032 1.496(0.985~2.271) 0.059 注：①模型1，未校正模型；②模型2，校正年龄、教育水平、人均月收入、不良妊娠史、妊娠期贫血、孕前BMI、本次孕期体重增加、孕前糖尿病、孕前泌尿道感染、孕前生殖道感染、围孕期服用叶酸、妊娠期糖尿病、妊娠期高脂血症、妊娠期甲状腺功能亢进、妊娠期甲状腺功能减退等可能的混杂因素。
Note: ① Model 1, unadjusted model；②Model 2, adjusted for potential confounding factors, including age, education level, per capita monthly income, history of adverse pregnancy, pregnancy anemia, pre-pregnancy BMI, gestational weight gain, pre-gestational diabetes mellitus, pre-gestational urinary tract infection, pregestational genital tract infection, periconceptional folic acid use, gestational diabetes mellitus, gestational hyperlipidemia, gestational hyperthyroidism, and gestational hypothyroidism.
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