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Preterm Birth Risk from Smoking Higher Than Previous Estimates

The risk of premature birth from smoking while pregnant may be more than twice as high as previous estimates, according to a new study from the University of Cambridge. 

Rather than relying on self-reported smoking status, as most previous studies have done, the researchers measured detectable serum cotinine levels during pregnancy, and correlated these with adverse foetal outcomes. They also measured paraxanthine levels to assess caffeine intake. 

They reported that although they found an increased risk of foetal growth restriction (FGR) associated with caffeine, this was attenuated when adjusting for maternal characteristics and cotinine-determined smoking status.

Pregnant women are recommended to stop smoking and limit caffeine intake because of the risk of complications. Smoking has been associated with an increased risk of FGR, premature birth, and low birthweight, though it has also been linked to a reduced risk of preeclampsia. 

As recently as 2021, a study of more than 130,000 women led by King's College London and UK pregnancy charity Tommy's found that one in five women planning a pregnancy smoked cigarettes, rising to 31% among those under 25 or with a BMI below 18.5.

High caffeine intake has also been associated with lower birthweights and possibly FGR. The team pointed out that caffeine is more difficult to avoid as is found in coffee, tea, chocolate, energy drinks, soft drinks, and some medications.

Self-reported Smoking Status May Be Inaccurate

However, most studies reporting adverse pregnancy outcomes with smoking or caffeine intake have used self-reported subjective data to estimate exposure. This is prone to both recall bias and under-reporting, so "may not reflect accurately the quantity that enters the maternal circulation", the researchers said.

Directly quantifying primary metabolites in maternal body fluids would provide a more objective measure, they reasoned. 

Their case cohort study, published in the International Journal of Epidemiology, assessed a subset of women from a larger study at the Rosie Hospital, Cambridge, recruited between 2008 and 2012 and followed from the time of dating ultrasound scans until delivery. 

Blood samples were taken at 12, 20, 28, and 36 weeks of gestational age, and analysed for metabolic products of both nicotine and caffeine. They compared results from 638 women who had at least one measured adverse pregnancy outcome — pre-eclampsia, spontaneous pre-term birth (PTB), FGR, gestational diabetes mellitus, or low birthweight — with those of 277 women who had not had such outcomes.

Serum Analysis a More Accurate Measure

Of the 89 patients assessed on serum measurements as having had consistent exposure to smoking throughout pregnancy, only 61 (68.5%) had self-reported as currently smoking. This confirmed that the measure was "a more objective way of assessing smoking behaviour", the researchers said.

Compared with no exposure, objectively assessed smoking exposure was associated with a more than doubled increased risk of PTB (adjusted odds ratio [OR] 2.58 (95% CI: 1.14 to 5.85) – more than twice the previous estimate of 1.27 from meta-analyses.

Consistently elevated cotinine levels were also associated with a four-fold risk of FGR (OR 4.07 (95% CI: 2.14 to 7.74), and with lower mean birthweight (–387g, 95% CI: –622 g to –153 g) – more than 10% lower than average neonatal weight. 

Unlike previous studies, however, there was no evidence that smoking reduced the risk of pre-eclampsia.

Although in univariate analysis there was an association between paraxanthine and FGR at most time points, all associations were attenuated after adjustment for maternal characteristics and objective (but not self-reported) smoking status. The researchers concluded that they "found no evidence that caffeine intake was linked to adverse outcomes".

Risk "Much Worse Than Previously Thought"

Corresponding author Professor Gordon Smith, head of the Department of Obstetrics and Gynaecology at the University of Cambridge, said: "We've known for a long time that smoking during pregnancy is not good for the baby, but our study shows that it's potentially much worse than previously thought."

Asked to comment by Medscape News UK, Dr Virginia Beckett, consultant obstetrician and spokesperson for the Royal College of Obstetricians and Gynaecologists, said: "This study adds to the existing evidence that smoking can lead to preterm birth and low birth weight."

She said it was "vital" that women were well informed about the risks and supported to stop smoking, and that midwives, obstetricians, and GPs could all signpost to resources to help.

Also commenting to Medscape News UK, Andrew Shennan, professor of obstetrics at King's College London and head of the Tommy's Preterm Surveillance Clinic at St Thomas' Hospital, said: "This is a good study as it used measures of smoking exposure and caffeine intake to confirm how much women were exposed to in pregnancy – just asking women is often inaccurate as those smoking a lot may not admit to it. 

"They confirmed the association of smoking with preterm birth, which is even stronger than previously thought. Women put their baby at significant risk if they smoke, and the more they reduce the better."

However, he added, it was "reassuring" for women that caffeine did not cause significant problems, and so dietary caffeine did not need to be avoided.

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