Is the apparently protective effect of maternal nicotine replacement therapy (NRT) used in pregnancy on infant development explained by smoking cessation?: secondary analyses of a randomised controlled trial

Abstract

ObjectiveTo investigate relationships between maternal smoking status in pregnancy and infant development. The largest randomised controlled trial of nicotine replacement therapy (NRT) for smoking cessation in pregnancy, the smoking, nicotine and pregnancy (SNAP) trial, found that at 1 month after randomisation, smoking cessation rates were doubled in the NRT group compared with the placebo group. At delivery, there was no significant difference in cessation rates between groups. Surprisingly, infants born to women randomised to NRT were more likely to have unimpaired development at 2 years. We hypothesised that this apparently protective effect was due to smoking cessation caused by NRT and so, investigate this relationship using the same cohort.DesignSecondary analysis of a randomised controlled trial.SettingSeven antenatal hospitals in the Midlands and North-West England.ParticipantsEight hundred and eighty-four pregnant smokers randomised to receive either NRT patches or visually-identical placebo in the SNAP trial. Participants’ smoking behaviour were recorded at randomisation, 1 month after their target quit date and at delivery.MethodsUsing logistic regression models, we investigated associations between participants’ smoking measures and infant development (assessed using the Ages and Stages questionnaire) at 2 years.Main outcome measures2 year infant development.ResultsDevelopmental impairment was reported for 12.7% of study 2 year olds. Maternal heaviness of smoking at randomisation (OR: 1.26, 95% CI: 0.82 to 1.96, p=0.091), validated smoking abstinence recorded at 1 month after a quit date (OR: 1.02, 95% CI: 0.60 to 1.74, p=0.914) and validated smoking abstinence recorded at both 1 month after a quit date and at the end of pregnancy (OR: 1.52, 95% CI: 0.81 to 2.85, p=0.795) were not independently associated with infant developmental impairment at 2 years.ConclusionWe found no evidence that NRT treatment improved infants' developmental outcomes through smoking cessation.Trial registration numberCTA03057/0002/001-0001; Post-results

Nicotine Replacement Therapy during Pregnancy and Child Health Outcomes: A Systematic Review

“…These papers reported different outcomes. One study investigated infantile colic [ 24 ], two studies infant development impairment and reported respiratory problems [ 25 , 26 ], one major congenital anomalies [ 27 ], and one attention-deficit/hyperactivity disorder [ 28 ].…”

“…In 2019, another secondary analysis of the SNAP trial was designed to investigate whether the absence of infants’ developmental impairments at 2 years was associated with maternal smoking status measured at different point in the trial [ 26 ]. After adjusting for some potential confounding factors which are known to be associated with infant development, this study did not report a significant association between measures of maternal tobacco smoke exposure and infant development impairment at age 2.…”

“…An association is also reported between exposition to NRT during pregnancy and attention-deficit/hyperactivity disorder in children after 5 years old in comparison with nonsmoking (in mothers and fathers). NRT exposure does not seem to be associated with infant behavioral impairment (based on responses to selected questionnaires sent to participants, with items including the ASQ-3); in comparison with placebo even a somewhat better outcome has been reported [ 25 , 26 , 30 ]. According to one report, NRT exposure during pregnancy was not associated with major congenital anomalies in comparison with a control group (no NRT and no smoking during pregnancy) [ 27 ].…”

“…The SNAP RCT provided the highest level of evidence about infant outcomes at the age of 2 years old [ 25 , 26 ]. The major limitation of this study is the very low compliance rates of both the nicotine (7.2%) and the placebo patches group (2.8%) which makes difficult to attribute any direct association between the study outcomes and exposure.…”

Neonatal nicotine exposure changes insulin status in fat depots: sex-related differences

“…5 Studies have shown that nicotine exposure during the fetal (via the placenta) or the postnatal (PN; via breast milk) periods negatively affects the development of the cardiovascular and nervous system of the offspring. [6][7][8] For years, our research group has been investigating a metabolic programming model of maternal nicotine-only exposure during the breastfeeding period and its impacts on the offspring's metabolism. 9 In this experimental model, adult male rats showed increased body mass, increased total adiposity, and adipocyte hypertrophy, both in the visceral and subcutaneous compartments.…”