. 2018 Dec 11;114(3):406–424. doi: 10.1111/add.14473

Table 1.

Characteristics of included studies.

Study	Participants potentially providing longitudinal data (n)	Characteristics of participants		Setting, design & exposures	Body fluid used and assay timings	Assay results
Cohort studies
Gennser, Maršál & Brantmark 1975 33	12	Values are ranges Maternal age 20–31 years^a Gestational age 33–39 weeks^a Daily cigarette consumption 7–20^a		Sweden Laboratory‐based longitudinal cohort study; not a smoking cessation intervention study One of each below exposure was used on consecutive days: • 1 ‘standard’ cigarette: talking not permitted and deep inhalation encouraged; average smoking time was 5 minutes • 2 mg gum chewed for 30 minutes • 4 mg gum chewed for 30 minutes	Blood nicotine 5 and 30 minutes after starting to smoke a cigarette 30 and 60 minutes after starting to chew 1 piece of gum	Mean ± SEM (ng/ml) Smoking (n = 12) 5 minutes 41.3 ± 3.5 30 minutes 19.6 ± 1.4 2 mg gum (n = 6) 30 minutes 10.4 ± 0.6 60 minutes 10.0 ± 0.7 4 mg gum (n = 6) 30 minutes 17.5 ± 1.3 60 minutes 14.7 ± 1.3
Oncken et al. 1996 34	15	Values are means ± SD Maternal age 28 ± 6^b Weight (lb) 169 ± 29^b Gestational age 28.1 ± 3.2^b Daily cigarette consumption 19 ± 6^b Fagerström value 5.7 ± 2^b		United States Longitudinal cohort study; not a smoking cessation intervention study Women allocated to receive a 5‐day course of 2 mg NRT gum and advised to use ≥ 6 pieces/day but < 30 pieces/day and ≤ 2 pieces/hour Observed chewing to ensure proper technique on first use Reported daily adherence (mean ± SD) Day 1, 6 ± 3 pieces, day 2, 9 ± 5, day 3, 8 ± 3, day 4, 8 ± 3, day 5, 5 ± 2 (last day was only a half‐day)	Blood cotinine 30 minutes after last cigarette After 5 days using nicotine gum while remaining abstinent Also presented trough and peak nicotine levels after smoking one cigarette and chewing 1 piece 2 mg gum	Mean ± SD (ng/ml) Smoking (n = 15) 153 ± 18 5 days gum (n = 15) 33 ± 8 1 cigarette Trough 6.7 ± 0.8 Peak 19.7 ± 1.5 1 piece 2‐mg gum Trough 3.3 ± 0.5 Peak 5.7 ± 0.7
Oncken et al. 1997 35	15	Values are means ± SD Maternal age 28 ± 5.4 Gestational age 28 weeks, 3 days ±20 days Height 161 ± 5.9 cm Weight 63.3 ± 9.2 kg Daily cigarette consumption 20.2 ± 5.2 Values are ns Ethnicity data White 10 Black 2 Hispanic 3		United stated Laboratory‐based longitudinal cross‐over study; not a smoking cessation intervention study Two groups of women used Both groups: Smoked ad libitum for 8 hours Abstinent for 13 hours before placement of a 21‐mg transdermal nicotine patch for 8 hours They were randomized to either smoking or patch use in session 1 and then a week later crossed over to the other experimental condition	Blood nicotine Hourly assays when smoking Assays at 2 3, 4, 6 & 8 hours after placement of nicotine patch Maximum mean nicotine concentration, time to reach max. and the mean area plasma nicotine concentration‐time curve were reported in the text of this paper	Mean ± SD (ng/ml) Maximal plasma level smoking 19.7 ± 8.09 Patch 16.0 ± 3.5 Time to reach max Smoking 5 hours ± 2.4 Patch 3.2 hours ± 1.7 Area under the plasma Nicotine concentration time curve Smoking 89 ng hour/ml Patch 93 ng hour/ml Mean difference ± SEM 4.8 ± 10.3 ng hour/ml
Wright et al. 1997 23	6	Values are means & ranges Maternal age 25.7 (21–31) Weight 82.05 kg (66.1–87.5 kg) Gestational age 34.2 (28.1–37) All white participants Daily cigarette consumption ½–2 packs		United States Laboratory‐based cohort study; not a smoking cessation intervention study Smoking as normal prior to starting study Abstinent for 11 hours prior to patch placement. Transdermal patch 21 mg worn for 8 hours	Saliva nicotine and cotinine Minimum 1 hour after last cigarette 8 hours after of started patch	Mean, range (μg/l)^c Cotinine values (n = 6) Smoking 100 (40–155) Patch 55 (20–100) Nicotine values (n = 6) smoking 19 (7–48) Patch 19 (6–41)
Ogburn et al. 1999 36	21	Values are means ± SD Maternal age 26.5 ± 5.7 Gestation at enrolment 27.4 ± 2.7 Daily cigarette consumption 20.5 ± 8.7		United States Laboratory‐based cohort study; not a smoking cessation intervention study Smoking as usual prior to day of admission Abstinence started on admission and continued for in‐patient period Transdermal patch 22 mg/24 hours worn each day of in‐patient stay	Blood nicotine and cotinine At 2 p.m. after a normal morning's smoking and at least 10 minutes after last cigarette On all of days 1–4, 8 hours after patch placement on each day	Mean ± SD (ng/ml) Cotinine values Smoking 116 ± 54 (n = 21) Day 1 patch 142 ± 47 (n = 21) Day 2 patch 128 ± 38 (n = 20) Day 3 patch 123 ± 42 (n = 20) Day 4 patch 117 ± 38 (n = 20) Nicotine values Smoking 14.4 ± 9.7 (n = 20) Day 1 patch 12.7 ± 4.2 (n = 21) Day 2 patch 12.8 ± 4.5 (n = 20) Day 3 patch 13.7 ± 6.0 (n = 20) Day 4 patch11.8 ± 3.9 (n = 20)
Hegaard, Kjærgaard, Møller, Wachmann & Ottesen 2004 29	75	Values are means ± SD Gestation at enrolment 21.5 ± 8.4^b Daily cigarette consumption 12.5 ± 5.2^b Values are ns		Denmark Longitudinal cohort study; smoking cessation intervention study Smoking as normal prior to study Fagerström score used to allocate NRT; higher score, higher dose used and women followed up in 3 parallel groups Women with Fagerström score of 2–4 used up to 12 pieces of 2 mg gum daily For scores of 4–7, 15 mg/16‐hour nicotine patches were used For scores of 7–10, 15 mg/16‐hour nicotine patches plus up to 8 daily pieces of 2 mg gum were used	Saliva cotinine Baseline measurement taken before starting NRT, while still smoking but no time from last cigarette given 1–2 weeks after smoking cessation while using NRT and abstinent; no time from last gum or from patch placement given	Mean ± SD (ng/ml) 2 mg gum (n = 6) Smoking 132 ± 95 NRT 35 ± 28 Mean difference, 95% CI = –97 (−6–200) Smoking 173 ± 41 NRT 70 ± 33 Mean difference, 95% CI = –103 (60–146) Patch 15 mg/16 hours, 2 mg gum (n = 5) Smoking 246 ± 91 NRT 105 ± 51 Mean difference, 95% CI = –141 (47–236)
		Fagerström value	n
		2–4	6
		4–7	7
		7–10	5
Oncken, Campbell, Chan, Hatsukami & Kranzler 2009 30	14	Values are means ± SD Maternal age Patch 29.86 ± 6.52 Spray 30.29 ± 5.09 Gestation at enrolment Patch 32.06 ± 2.64 Spray 31.70 ± 3.2 Daily consumption of cigarettes Patch 19.64 ± 3.66 Spray 16.71 ± 5.90 Fagerström value Patch 6.71 ± 1.60 Spray 6.29 ± 1.11 Ethnicity data Caucasian patch 85.7%; spray 71.4%		United States Longitudinal cohort study; smoking cessation intervention study Women smoked 7 cigarettes over 7 hours (1 per hour) in a monitoring session Then they were allocated to one of two types of NRT for 4 days, or the placebo equivalent. They were not monitored during the 4 days and then returned for a 2nd monitoring session NRT used: Transdermal patch 15 mg/16 hours (1 patch per day). During monitoring session patch was placed at 10 a.m. Nasal spray (1 mg/dose) dose = 1spray to each nostril; instructed to use up to 24 daily doses. During monitoring session nasal spray was used twice at the equivalent times to cigarette 1, 4 and 7, and once in place of the 2nd, 3rd, 5th and 6th cigarette	Serum nicotine & cotinine (cotinine used in analysis) 1st laboratory‐based smoking session; after overnight (8 hours) abstinence. Assays taken before and after 1st and 7th cigarette and after 4th cigarette; average of these samples reported 2nd laboratory session: on the 5th treatment day, after overnight NRT abstinence. In both patch and spray groups samples were taken at equivalent times to the smoking session; average of these samples reported	Mean ± SD (ng/ml) Patch (n = 7) smoking 138 ± 55 Patch 75 Mean difference ± SD −63 ± 33 Spray (n = 7) Smoking 130 ± 57 NRT session spray 39 Mean difference ± SD −91 ± 38
Randomized controlled trial data
Wisborg, Henriksen, Jespersen & Secher 2000 37	124 randomized to nicotine	Values are means ± SD Maternal age 28.2 ± 4.9^b Daily cigarette consumption 13.4 ± 4.0^b		Denmark Randomized controlled trial study; smoking cessation intervention study; recruited from Aarhus Hospital Women randomized to NRT were issued with 8 week's 15 mg/16 hours nicotine patches, followed by a further 3 weeks of 10 mg/16 hours nicotine patches	Saliva cotinine While still smoking usual amount: no time from last cigarette reported At 8 & 11 weeks from starting nicotine patch Further assays at 4 weeks before expected delivery, but unclear whether NRT was still supplied	Mean ± SD (ng/ml) Smoking (baseline) (n = 124) 231 ± 125 8 weeks^d patch (n = 90) 153 11 weeks^d patch (n = 83) 121 4 weeks^d pre‐delivery patch (n = 75) 120
Oncken et al. 2008 38	100 randomized to nicotine	Values are means ± SD Maternal age 25.5 ± 6.8^b Gestation at enrolment 17.1 ± 5.6^b Daily consumption of cigarettes before pregnancy 17.5 ± 9.6^b last 7 days before enrolment 10.2 ± 6.6 Fagerström value 3.83 ± 1.91^b Values are ns Ethnicity data^b		United States Randomized controlled trial; smoking cessation intervention study; recruited from Hartford, New Britain, Springfield medical sites Women randomized to NRT arm were encouraged to stop smoking or to reduce the number of cigarettes smoked If quitting they were instructed to chew one piece of gum for every cigarette they usually smoked per day and to begin on their quit date. If not abstinent they were to chew one piece of gum for each cigarette eliminated; not exceeding 20 pieces/day They were given gum for 6 weeks to use as above and for a further 6 weeks to taper the amount used and stop	Urine cotinine While still smoking usual amount: no time from last cigarette reported 6 weeks after starting gum & 32–34 weeks gestation Further measurements taken at 3–7 days, 2 weeks & 3 weeks after quit date, and 6–12 weeks postpartum but values not reported	Mean ± SD (ng/ml) Smoking (baseline) (n = 93) 672 ± 438 6 weeks^d of 2 mg gum (n = 51) 542 ± 454 32–34 weeks^d gestation after NRT treatment finished (n = 54) 492.45 ± 443
		Hispanic	53
		Non‐Hispanic white	38
		Non‐Hispanic black	8
		Other	1
El‐Mohandes et al. 2013 22	26 randomized to nicotine	Values are means ± SD Maternal age 27.5 ± 5^b Gestation at enrolment 19.6 ± 5.1^b Ethnicity data^b All self‐report as a minority ethnicity BMI 28.1 ± 10.7^b Daily cigarette consumption 7 ± 7.4^b Values are ns Amount of cigarette		United States Randomized clinical trial; smoking cessation intervention study; recruited from prenatal care sites in the DC metropolitan area Women randomized to NRT used transdermal 14‐mg patch for approx. 2–4 weeks before first sampling, followed by transdermal 7 mg patch for approx. 2 weeks before the second sampling Some women received 21 mg patch for first 2 weeks of NRT due to higher baseline cotinine levels but would have been on 14 mg patch at time of first sampling. Samples were also taken later when it is unclear if women were still given NRT	Saliva cotinine While still smoking usual amount: no time from last cigarette reported After using a 14 mg patch for approx. 2‐4 weeks (and having been using NRT for average 3.7 weeks) After using a 7 mg patch for approx. 2 weeks (and having been using NRT for average 7.8 weeks)	Mean ± SD (ng/ml) Smoking (baseline) (n = 26) 171 ± 143 14 mg patch^d (n = 26) 142^c 7 mg patch^d (n = 26) 129^c
		Smoke all of a cig.	7
		Smoke most of a cig.	3
		Smoke half a cig.	15
		Inhalation Inhale deeply	8
		Inhale moderately	10
		Inhale slightly	8
Berlin, Grangé, Jacob & Tanguy 2014 39	203 randomized to nicotine	Values are median & interquartile range Maternal age 29.1 (25–34)^b Gestation at randomization 17 (15–20)^b BMI pre‐pregnancy 23 (20–27)^b Daily cigarette consumption 11 (8–15)^b Fagerström value 5 (3–6)^b Values are ns Ethnicity data^b European 194 African 6 Asian 1 Other 2 Time to first cigarette^b > 60 minutes 31 31–60 minutes 36 6–30 minutes 74 ≤ 5 minutes 62		France Randomized controlled trial; smoking cessation intervention study; recruited from maternity wards Nicotine patch between 10–30 mg/day adjusted to participant cotinine level (mean ± SD = 18 ± 6.8 mg/day) used from quit date until delivery with brief smoking lapses permitted	Saliva cotinine While still smoking usual amount: no time from last cigarette reported 2 weeks after quit date while using nicotine patch 8 weeks after quit date while using nicotine patch	Mean ± SE (μg/l) Smoking (baseline) 119 ± 1.09 2 weeks patch^d 108 ± 1.1 8 weeks patch^d 80 ± 1.1 Unclear how many women sampled at each visit
Bowker, Lewis, Coleman, Vaz & Cooper 2014 40	33	Values are median & interquartile range Maternal age 26.12 (22.29–32.35) Gestation at baseline 14.4 (13.3–17.8) Ethnicity data All white except one Asian/other BMI 25.6 (22.7–29.3) Women with partners who smoke 23 (70%) Heaviness of smoking index 3 (2–3) Values are ns Number of cigarettes smoked 5–10 cigarettes (22) 11–15 (8) >20 (3)		United Kingdom Secondary analysis of data from intervention arm of randomized controlled trial of NRT; smoking cessation intervention study; recruited from antenatal clinics Transdermal patch 15 mg/16 hour used for up to 2 months after quit date while remaining abstinent; instructed to stop NRT if smoking re‐starts	Saliva cotinine While still smoking usual amount: no time from last cigarette reported 4 weeks from quit date while using 15 mg/16‐hour nicotine patch and abstinent Reported difference in cotinine from smoking to NRT use when starting Cotinine level > 150 ng/ml and when <150 ng/ml	Median & interquartile range (ng/ml) Smoking (n = 33) 98.5 (71.3–177.8) NRT (abstinent) (n = 33) 62.8 (33.3–82.7) Median cotinine difference with baseline cotinine: >150 ng/ml −134.8 < 150 ng/ml–27.9

Values only reported for all participants in the study, not solely women in the longitudinal analysis.

Values reported for all women enrolled, not only women analysed.

Data valued obtained using WebPlotDigitizer and SD not available 24.

Samples taken on all randomized to nicotine in RCT irrespective of smoking status; women could be smoking or abstinent. SEM = standard error of the mean; SD = standard deviation; CI = confidence interval; NRT = nicotine replacement therapy; BMI = body mass index.