Abstract
Smoking in pregnancy causes substantial avoidable harm to mothers and offspring; nicotine replacement therapy (NRT) may prevent this, and is used to help women to quit. A recently updated Cochrane Review of randomized controlled trials (RCTs) investigating impacts of NRT in pregnancy focuses primarily on efficacy data, but also reports adverse impacts from NRT. Here we identify and summarize NRT impacts on adverse pregnancy outcomes reported in non-randomized controlled trials (non-RCTs). Systematic reviews and meta-analyses of RCTs and non-RCT studies of NRT in pregnancy, with design-specific risk of bias assessment and grading of recommendations, assessment, development and evaluations (GRADE) criteria applied to selected outcomes. Relevant Cochrane Review findings are reported alongside those from this new review. Seven RCTs were included; n=2340. Nine meta-analyses were performed; non-statistically significant estimates indicated potentially reduced risk from NRT compared with smoking for mean birth weight, low birth weight, preterm birth, intensive care admissions, neonatal death, congenital anomalies and caesarean section and potentially increased risks for miscarriage and stillbirth. GRADE assessment for mean birth weight and miscarriage outcomes indicated 'low' confidence in findings. Twenty-three non-RCTs were included; n=931 163. Eleven large studies from five routine health-care cohorts reported clinical outcomes; 12 small studies investigated mainly physiological outcomes within in-patient women given NRT. Findings from meta-analyses for congenital anomalies, stillbirth and preterm birth were underpowered and not in a consistent direction; GRADE assessment of confidence in findings was 'very low'. Routine health-care studies were of higher quality, but implications of reported findings were unclear as there was inadequate measurement and reporting of women's smoking. Available evidence from randomized controlled trials and non-randomized comparative studies does not currently provide clear evidence as to whether maternal use of nicotine replacement therapy during pregnancy is harmful to the fetus.
Highlights
Smoking in pregnancy has adverse effects on the health of pregnant women and their offspring in the pre‐ and perinatal periods and in later life [1,2,3]
Full results, including the PRISMA diagram, are found in the published Cochrane Review (CR) [13], but of nine randomized controlled trials (RCTs) which investigated nicotine replacement therapy (NRT) use in pregnancy, seven reported infant and fetal safety outcomes [23,24,25,26,27,28,29] and all were conducted in high‐ income countries (n = 2340)
All RCTs recruited pregnant women who smoked and, as with non‐RCTs, pregnancies would have been exposed to tobacco smoke before women joined trials
Summary
Smoking in pregnancy has adverse effects on the health of pregnant women and their offspring in the pre‐ and perinatal periods and in later life [1,2,3]. Stopping smoking in pregnancy improves birth outcomes [7] and reduces the burden of health‐care costs to the National Health Service (NHS) [8]. For very long [10] and adherence to NRT by pregnant women tends to be lower than in non‐pregnant smokers [10,11,12] This poor adherence may at least partially explain why NRT has been found to be less effective when used in pregnancy [13]. A recently updated Cochrane Review of randomized controlled trials (RCTs) investigating impacts of NRT in pregnancy focuses primarily on efficacy data, and reports adverse impacts from NRT. We identify and summarize NRT impacts on adverse pregnancy outcomes reported in non‐randomized controlled trials (non‐RCTs). Routine health‐care studies were of higher quality, but implications of reported findings were unclear as there was inadequate measurement and reporting of women’s smoking
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