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. 2023 Dec 25;52(6):1756-1765.
doi: 10.1093/ije/dyad123.

Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcomes

Roshan J Selvaratnam  1 , Ulla Sovio  2   3 , Emma Cook  2 , Francesca Gaccioli  2   3 , D Stephen Charnock-Jones  2   3 , Gordon C S Smith  2   3
Affiliations

Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcomes

Roshan J Selvaratnam et al. Int J Epidemiol. .

Abstract

Background: In pregnancy, women are encouraged to cease smoking and limit caffeine intake. We employed objective definitions of smoking and caffeine exposure to assess their association with adverse outcomes.

Methods: We conducted a case cohort study within the Pregnancy Outcome Prediction study to analyse maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age. Objective smoking status was defined based on detectable cotinine levels at each time point and objective caffeine exposure was based on tertiles of paraxanthine levels at each time point. We used logistic and linear regression to examine the association between cotinine, paraxanthine and the risk of pre-eclampsia, spontaneous pre-term birth (sPTB), fetal growth restriction (FGR), gestational diabetes mellitus and birthweight.

Results: There were 914 and 915 women in the smoking and caffeine analyses, respectively. Compared with no exposure to smoking, consistent exposure to smoking was associated with an increased risk of sPTB [adjusted odds ratio (aOR) = 2.58, 95% CI: 1.14 to 5.85)] and FGR (aOR = 4.07, 95% CI: 2.14 to 7.74) and lower birthweight (β = -387 g, 95% CI: -622 g to -153 g). On univariate analysis, consistently high levels of paraxanthine were associated with an increased risk of FGR but that association attenuated when adjusting for maternal characteristics and objective-but not self-reported-smoking status.

Conclusions: Based on objective data, consistent exposure to smoking throughout pregnancy was strongly associated with sPTB and FGR. High levels of paraxanthine were not independently associated with any of the studied outcomes and were confounded by smoking.

Keywords: Smoking; birthweight; caffeine; cotinine; fetal growth restriction; gestational diabetes; paraxanthine; pre-eclampsia; pre-term birth.

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Conflict of interest statement

G.C.S.S. and D.S.C.-J. have received research support from Roche Diagnostics Ltd, Illumina and Sera Prognostics (FGR, PE and pre-term birth). G.C.S.S.’s department has received payment from Roche for a talk given by G.S. (FGR). G.C.S.S. has been a paid consultant to GSK (pre-term birth) and is a member of a Data Monitoring Committee for GSK trials of RSV vaccination in pregnancy. Current or recent government or charity grant support: MRC, BBSRC, NIHR, Wellcome Trust & Wellcome Leap.

Figures

Figure 1.
Figure 1.
Adjusted difference (with 95% CI) in maternal sFlt-1 (A) and PlGF (B) values by objective smoking status at 12, 20, 28 and 36 wkGA, referent to no exposure to smoking throughout pregnancy. sFlt-1, soluble fms-like tyrosine kinase; PlGF, placental growth factor; wkGA, weeks of gestational age; MoM, multiples of the median. Maternal sFlt-1 and PlGF levels have been expressed as MoM, adjusted for gestational age, maternal weight and storage time at measurement and then log-transformed and converted into Z-scores, referent to the whole Pregnancy Outcome Prediction study cohort. Multivariable linear regression analyses were performed on the random sub-cohort. The reference group is women with no exposure to smoking throughout pregnancy. β coefficients were given per 1-SD increase in sFlt-1 or PlGF. The multivariable analyses were adjusted for maternal height, maternal age, maternal body mass index, marital status, maternal age at stopping full-time education and deprivation
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References

    1. Yang L, Feng L, Huang L. et al. Maternal factors for intrauterine growth retardation: systematic review and meta-analysis of observational studies. Reprod Sci 2023;30:1737–45. - PubMed
    1. Shah NR, Bracken MB.. A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery. Am J Obstet Gynecol 2000;182:465–72. - PMC - PubMed
    1. Di H-K, Gan Y, Lu K. et al. Maternal smoking status during pregnancy and low birth weight in offspring: systematic review and meta-analysis of 55 cohort studies published from 1986 to 2020. World J Pediatr 2022;18:176–85. - PubMed
    1. Rhee J, Kim R, Kim Y. et al. Maternal caffeine consumption during pregnancy and risk of low birth weight: a dose-response meta-analysis of observational studies. PLoS One 2015;10:e0132334. - PMC - PubMed
    1. Wei J, Liu C-X, Gong T-T, Wu Q-J, Wu L.. Cigarette smoking during pregnancy and preeclampsia risk: a systematic review and meta-analysis of prospective studies. Oncotarget 2015;6:43667–78. - PMC - PubMed

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