Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Department of Biostatistics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Hum Reprod. 2022 Apr 1;37(4):696-707. doi: 10.1093/humrep/deac018.
Is periconceptional maternal smoking associated with embryonic morphological development in ongoing pregnancies?
Smoking during the periconceptional period is associated with a delayed embryonic morphological development which is not fully recuperated beyond the first trimester of pregnancy.
Smoking during pregnancy decreases prenatal growth, increasing the risk of preterm birth, small for gestational age (GA) and childhood obesity.
STUDY DESIGN, SIZE, DURATION: Between 2010 and 2018, 689 women with ongoing singleton pregnancies were periconceptionally enrolled in a prospective cohort study with follow-up until 1 year after delivery.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Between 7 + 0 and 10 + 3 weeks, GA serial three-dimensional transvaginal ultrasound scans were performed. Embryonic morphological development as assessed by the Carnegie developmental stages was evaluated using Virtual Reality techniques. In the absence of fetal morphology classification methods beyond the embryonic period, fetal ultrasound measurements at around 20 weeks' GA, and birth weight were used to assess fetal growth. Linear mixed models were used to evaluate the association between smoking and the Carnegie stages. Regarding first-trimester morphological development, we additionally stratified our findings for mode of conception. Multiple linear regression models were used to study the association between smoking, fetal growth and birth weight. To investigate to which extent delayed embryonic morphological development mediated the effect of smoking, contemporary mediation analysis was used. Adjustments were made for potential confounders and other covariates.
A total of 689 singleton ongoing pregnancies were included and 1210 Carnegie stages were determined. Maternal periconceptional smoking represented by the number of cigarettes/day was associated with a slight non-significant delay of the Carnegie stages (βcigarettes/day = -0.058, 95% CI -0.122; 0.007, P = 0.080). Smoking of ≥10 cigarettes/day showed the strongest association (β≥10 cigarettes/day = -0.352, 95% CI -0.648; -0.057, P = 0.019), as reflected by a 0.9-day delay in reaching the final Carnegie stage. Stratification for mode of conception showed a stronger negative association between the number of cigarettes/day in the IVF/ICSI group (βcigarettes/day = -0.126, 95% CI -0.200; -0.051, P = 0.001) compared to naturally conceived pregnancies (βcigarettes/day = 0.009, 95% CI -0.093; 0.111, P = 0.867). In the IVF/ICSI group, periconceptional smoking of ≥10 cigarettes/day was associated with in a 1.6 day delay in reaching the final Carnegie stage (β≥10 cigarettes/day = -0.510, 95% CI -0.834; -0.186, P = 0.002). In the second trimester, periconceptional smoking was associated with a smaller femur length (βcigarettes/day = -0.077, 95% CI -0.147; -0.008, P = 0.029) and a larger head circumference (β1-9 cigarettes/day = 0.290, 95% CI 0.065; 0.514, P = 0.012). Smoking was associated with a lower birth weight, with a dose-response effect (βcigarettes/day = -0.150, 95% CI -0.233; -0.068, P < 0.001). Furthermore, using the unadjusted model, 40-60% of the association between smoking and fetal ultrasound parameters and 6.3% of the association between smoking and birth weight can be explained by a delayed embryonic morphology.
LIMITATIONS, REASONS FOR CAUTION: The study population was recruited from a tertiary referral center. Smoking habits were explored using self-reported questionnaires and checked for consistency by trained researchers.
This study shows that the association of periconceptional maternal smoking and human morphological development can already be detected early in the first trimester of pregnancy using embryonic morphology as outcome. One of the key messages of this study is that the delay, or dysregulation, in embryonic morphology is associated with allometric growth reflected by smaller fetal measurements at 20 weeks gestation and lower weight at birth. The delay in embryonic morphology, measured in early pregnancy, cannot be recuperated during the pregnancy. The results of this study emphasize the importance of smoking intervention programs prior to conception. More research is warranted to assess the association between periconceptional smoking cessation and embryonic development.
STUDY FUNDING/COMPETING INTEREST(S): The work was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest.
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受孕前母亲吸烟是否与持续妊娠中的胚胎形态发育有关？
受孕前吸烟与胚胎形态发育延迟有关，这种延迟在妊娠第一季度后并未完全恢复。
怀孕期间吸烟会降低产前生长速度，增加早产、小于胎龄儿（GA）和儿童肥胖的风险。
研究设计、规模、持续时间：2010 年至 2018 年期间，689 名患有持续性单胎妊娠的女性在前瞻性队列研究中进行了受孕前登记，随访至分娩后 1 年。
参与者/材料、设置、方法：在 7+0 至 10+3 周之间，进行了 GA 连续三维经阴道超声扫描。胚胎形态发育通过使用虚拟现实技术评估的卡内基发育阶段进行评估。由于胚胎期之后没有胎儿形态分类方法，因此在大约 20 周 GA 时使用胎儿超声测量值和出生体重来评估胎儿生长。线性混合模型用于评估吸烟与卡内基阶段之间的关联。关于第一季度的形态发育，我们还对受孕方式进行了分层，以评估我们的发现。使用多元线性回归模型研究吸烟、胎儿生长和出生体重之间的关联。为了研究胚胎形态发育延迟在多大程度上介导了吸烟的影响，我们使用了当代中介分析。对潜在的混杂因素和其他协变量进行了调整。
共纳入 689 例单胎持续妊娠，确定了 1210 个卡内基阶段。以每天吸烟的支数表示的母亲受孕前吸烟与卡内基阶段的轻微非显著延迟有关（β支/天=-0.058，95%CI-0.122；0.007，P=0.080）。每天吸烟≥10 支的吸烟量与最强的关联有关（β≥10 支/天=-0.352，95%CI-0.648；-0.057，P=0.019），反映出达到最终卡内基阶段的时间延迟了 0.9 天。对于受孕方式的分层显示，在 IVF/ICSI 组中，每天吸烟的支数与每天吸烟的支数之间的负相关更强（β支/天=-0.126，95%CI-0.200；-0.051，P=0.001）与自然受孕妊娠相比（β支/天=0.009，95%CI-0.093；0.111，P=0.867）。在 IVF/ICSI 组中，受孕前每天吸烟≥10 支与达到最终卡内基阶段的时间延迟了 1.6 天有关（β≥10 支/天=-0.510，95%CI-0.834；-0.186，P=0.002）。在孕中期，受孕前吸烟与股骨长度较小（β支/天=-0.077，95%CI-0.147；-0.008，P=0.029）和头围较大（β1-9 支/天=0.290，95%CI 0.065；0.514，P=0.012）有关。吸烟与出生体重较低有关，存在剂量反应效应（β支/天=-0.150，95%CI-0.233；-0.068，P<0.001）。此外，使用未调整的模型，吸烟与胎儿超声参数之间的关联以及吸烟与出生体重之间的关联有 40-60%可以用胚胎形态发育的延迟来解释，而有 6.3%可以用胚胎形态发育的延迟来解释。
局限性、谨慎的原因：研究人群是从三级转诊中心招募的。吸烟习惯是通过经过培训的研究人员使用自我报告的问卷来探索的，并进行了一致性检查。
本研究表明，使用胚胎形态作为结果，早在妊娠第一季度就可以检测到受孕前母亲吸烟与人类形态发育的关联。本研究的一个关键信息是，胚胎形态的延迟或失调与 20 周妊娠时的胎儿测量值较小和出生体重较低等比例生长有关。妊娠早期测量的胚胎形态发育延迟在妊娠期间无法恢复。本研究的结果强调了在受孕前实施吸烟干预计划的重要性。需要进一步研究来评估受孕前戒烟与胚胎发育之间的关联。
研究资金/利益冲突：该工作由荷兰鹿特丹伊拉斯谟医学中心妇产科部门资助。作者没有利益冲突。
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