Periconceptional smoking delays embryonic development, affects birth outcomes

Smoking during the periconceptional period was associated with delays in embryonic development, which cannot be offset later in pregnancy, according to findings published in Human Reproduction.

“It is known that maternal smoking causes adverse pregnancy outcomes such as smaller fetal growth measurements and lower birth weight,” Melek Rousian, PhD, principal investigator in the department of OB/GYN at Erasmus MC, University Medical Center in Rotterdam, The Netherlands, told Healio. “We were interested in a more comprehensive examination of the human embryo rather than just embryonic growth parameters such as crown-rump length.”

Rousian and colleagues enrolled 689 women — 96 of whom smoked — with an ongoing singleton pregnancy less than 8 weeks’ gestation between 2010 and 2018 and followed up until 1 year after delivery.

Participants underwent serial transvaginal 3D ultrasounds between 6 and 12 weeks’ gestation. Researchers used measurements taken during ultrasounds — which were performed weekly from 2010 to 2013 and bi-weekly after 2013 — to assess morphological development. They assigned Carnegie stages 12 to 23 based on internal and external development.

Rousian and colleagues determined second trimester development using head, abdominal and femur measurements available through medical records. They used birth weight to evaluate continued development.

Participants reported sociodemographic information, medical history and lifestyle behaviors through questionnaires; researchers asked about specific smoking habits, such as number of cigarettes smoked daily and cessation if applicable.

Periconceptional smoking, measured as cigarettes per day, had a nonsignificant association with delayed Carnegie stage. Smoking at least 10 cigarettes per day was most strongly associated with developmental delays, as it delayed final Carnegie stage by 0.9 days.

The number of cigarettes smoked in a day showed a significant association with delays in morphological development in women who conceived by in vitro fertilization or intracytoplasmic sperm injection, or ICSI, but did not show a significant association in women who conceived naturally.

Among women who conceived by IVF/ICSI, those who smoked at least 10 cigarettes a day reached final Carnegie stage 1.6 days later than those who did not.

“The compelling effect in the IVF/ICSI population may be due to very strict dating of the pregnancy,” Rousian said. “On the other hand, it is also said that due to the technique itself, IVF/ICSI pregnancies are more susceptible to external exposures. Furthermore, the effect of tobacco smoke might also be amplified in women achieving a pregnancy after IVF/ICSI since these women were exposed to a combination of both the risks related to the assisted reproduction procedure and the compounds of tobacco smoke causing further impaired development.”

In the second trimester, the number of cigarettes smoked per day was significantly associated with smaller femur length , as well as lower birth weight with a dose-response effect. Smoking one to nine cigarettes a day in the second trimester was significantly associated with larger head circumference.

In unadjusted modeling, delayed morphological development explained up to 61.1% of the association between smoking and fetal growth and 6.3% of the association between smoking and birth weight, Rousian and colleagues wrote.

“We were surprised to see that the delay in morphological development in early embryonic stage of the pregnancy had an effect on growth parameters later in pregnancy and even on birth weight,” Rousian said. “The impact of maternal smoking in the periconceptional period can thus not be recuperated later in pregnancy. This may imply we should advise women trying to conceive to quit smoking before pregnancy, as there is already a lasting adverse effect on the baby/fetus in the very early stages of pregnancy.”

The study population was recruited from a tertiary referral center, so findings may be limited in generalizability, the researchers said. Self-reported smoking habits and inability to examine morphological development more than 60 days after conception also limited the study.

“We were unable to look at the impact of smoking cessation or a reduction in the number of cigarettes. It would be very interesting to research the association between smoking cessation and embryonic development,” Rousian said. “In the future, we might be able to inform expectant parents using embryonic morphological development as a more reliable measure for health and development.”