A vast study on nicotinic substitutes, Varénicline and Bupropion suggest that no increased risk of congenital malformation is associated with these treatments in relation to maternal smoking, although digestive and renal abnormalities have been observed.
The nicotine substitutes (NRT), the Varénicline (partial agonist of the nicotinic acetylcholine receiver), and the bupropion, antagonist of this same receiver, are effective pharmacotherapy in smoking cessation. However, their effects on the fetus remain poorly known. A Cochrane review about the potential teratogenicity of NRT transdermal patches has proven to be not conclusive, as well as two vast cohort studies. At the same time, evidence of the safety of Varénicline during pregnancy remain limited, based only on some observational studies. As for the data concerning bupropion, it is of low quality. Faced with these uncertainties, current recommendations recommend that they are cautious to NRT during pregnancy and decide against the use of Varénicline and Bupropion.
A vast international cohort
In this context, T. Tran et al. conducted a vast international cohort study (Australia, new Zealand, Norway, Sweden) in order to specify the risk of major congenital malformations (MCM) in the event of exposure to this type of pharmacotherapy. The overall cohort included 5.2 million births (3 million women) between 2002 and 2018. In total, 391,474 newborns had been exposed to a smoking cessation treatment during the period extending from 90e day before design at the end of 1is Trimes of pregnancy, either to maternal smoking during the first trimester of pregnancy. The exclusion criteria were: multiple pregnancies, mortinagers, pregnancies started within 6 months after childbirth or with congenital malformation of viral cause, by chromosomal anomalies or genetic syndrome, and the use of two distinct anti -Bacle treatments during 1is quarter.
Depending on the country, the NRTs were available either over -the -counter or prescription; Varénicline and bupropion were delivered only on prescription. MCMs were listed according to the Eurocat classification, 1-4. The main evaluation criterion was the overall number of MCM and the organ reached (heart, members, oro-facial system …), by comparing the pregnancies exposed to a pharmacological treatment of smoking withdrawal to those during which the mother had continued to smoke without anti-tabac. Several covariables were analyzed. The prevalence of MCMs in exposed children and in those not exposed has been calculated for 1000 living births.
No more major malformations than in the event of continuation of smoking
After various exclusions, a pairing with a view to establishing the propensity score included 135,284 Dyades Mère-Enfant, including 9,325 new born exhibited at NRT, 3034 at La Varénicline and 1042 in Bupropion.
The overall prevalence of MCMs has not been significantly different, establishing itself at 37.6/ 1000 emerging living in the group exposed to anti-tabac drugs of the NRT type versus 34.4/1000 in the Control group, a rep of 1.10 (95 % CI: 0.98-1.22). Nor was there any difference according to the organs affected, apart from a slightly stronger prevalence of malformations of the digestive system in children exposed to NRTs, of the order of 3.8 vs 2.5/ 1000, or a repair to 1.53 (CI: 1.05- 2.23).
The overall risk of MCM was not higher for the Varénicline compared to the control group, establishing itself at 32.7 vs 36.6/1000 emerging living (arr 0.90 [IC : 0,73-1,10]). However, it should be noted that, under Varénicline, the prevalence of MCMs of the kidneys and urinary tracts, including congenital hydronephrosis, was higher (11.5 vs 4.2/1000), these data, however, based only on a very low number of children. The same observations were made for the bupropion, the overall prevalence of the MCMs establishing 35.5 vs 38.8 / 1000 (arr to 0.93 [IC : 0,67-1,29]) With, even, a tendency to prevalence of lower cardiac MCM.
Reassuring results
Thus, this cohort study, a priori the largest ever carried out, suggests that there is no increased risk of MCM after exposure to NRT, Varénicline and Bupropion before the design and during the first trimester of pregnancy, compared to that observed in pregnant women who have continued their smoking. These results are reassuring, especially since the NRTs are, in clinical practice, offered to pregnant women when behavioral therapies are failing.
Nevertheless, more malformations of the digestive system under NRT, including Hirschsprung’s disease, was observed, but it could be there, after multiple adjustments, a fortuitous discovery. Likewise, observations concerning Varénicline overlap, overall the previous studies, the prevalence observed higher of renal MCMs and urinary tracts to be analyzed with great caution. As for the bupropion, the data is recent but its use, with a view to stopping smoking during a pregnancy remains very marginal.
The main strength of this work lies in the magnitude of the cohort, with taking into account several major co-variables. On the contraryfunctional neurological deficits have not been studied, such as infantile development disorders. There was also a lack of information on the nature and intensity of smoking in pregnant women. Classification errors were able to arise and future mothers were able to stop tobacco when they were announced. Finally, stillborn children were excluded from the study.
In conclusion, neither the NRT, nor the Varénicline, nor the bupropion taken during the 1is Quarter of a pregnancy do not seem associated with an increased risk of MCM, compared to that in women who have continued their smoking poisoning. Although we note, under NRT, a higher prevalence of digestive anomalies and in varecicline of renovations, their number has remained very limited and could have been by chance. These notions are therefore reassuring, having regard to the major deleterious effects of smoking during pregnancy, both for maternal health and for that of the child. However, additional studies remain necessary …
