key: cord-0882362-6ozg7qkz
authors: Zaitsu, M.; Hosokawa, Y.; Okawa, S.; Hori, A.; Kobashi, G.; Tabuchi, T.
title: Use of heated tobacco products may be associated with hypertensive disorders of pregnancy and low birth weight in Japan: An analysis of the JACSIS study
date: 2021-04-17
journal: nan
DOI: 10.1101/2021.04.12.21255292
sha: bb634476678eea7c97078cb69974807eb5ec3bff
doc_id: 882362
cord_uid: 6ozg7qkz

Background: Little is known about heated tobacco product (HTP) use in pregnant women and associated maternal and neonatal risks for hypertensive disorders of pregnancy (HDP) and low birth weight (LBW). Thus, this study aimed to assess the status of HTP use among pregnant women in Japan and explore the risk of HDP and LBW associated with HTP use. Methods: Using data from the Japan "COVID-19 and Society" Internet Survey (JACSIS) study, a web-based nationwide survey, we investigated 558 post-delivery and 365 currently pregnant women in October 2020. We assessed the prevalence of ever HTP smokers (defined as ever experiencing HTP use) in post-delivery and currently pregnant women. Among post-delivery women, we collected the information regarding HDP and LBW based on their Maternal and Child Health Handbooks (maternal and newborn records). In the multivariable regression analysis, we estimated the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of ever HTP smokers for HDP and LBW compared with those of never HTP smokers using logistic regression. A stratified analysis with respect to combustible cigarette smoking (never/ever) was also performed. Results: The prevalence of ever HTP use were 11.7% and 12.6% in post-delivery and currently pregnant women, respectively. Among post-delivery women, ever HTP smokers had higher HDP incidence (13.8% vs. 6.5%, P=0.03), with an OR of 2.78 (95% CI 0.84--9.15) and higher LBW incidence (18.5% versus 8.9%, P=0.02), with an elevated OR of 2.08 (95% CI 0.80--5.39). A similar tendency was observed among never and ever combustible cigarette smokers. Conclusion: In Japan, the incidence of HTP use has exceeded 10% among pregnant women, and HTP smoking may be associated with increased maternal and neonatal risks. School-based tobacco prevention and cessation programs should be conducted regardless of product types to prevent life-threatening perinatal complications and deaths.

What this paper adds: 24 • Little is known about heated tobacco product (HTP) use and associated 25 perinatal risks among pregnant women. 26 • In Japan, the prevalence of ever HTP use exceeded 10% among pregnant 27 women. 28 • HTP use approximately doubled perinatal risk of hypertensive disorders of 29 pregnancy and low birth weight. 30 • When stratified by cigarette smoking status, a similar tendency was observed 31 among never and ever cigarette smokers. 32 33 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 17, 2021. ; https://doi.org/10.1101/2021.04.12.21255292 doi: medRxiv preprint smoking (never/ever) was also performed. 48 Results: The prevalence of ever HTP use were 11.7% and 12.6% in post-delivery and 49 currently pregnant women, respectively. Among post-delivery women, ever HTP smokers 50 had higher HDP incidence (13.8% vs. 6.5%, P=0.03), with an OR of 2.78 (95% CI 0.84-51 9.15) and higher LBW incidence (18.5% versus 8.9%, P=0.02), with an elevated OR of 2.08 52 (95% CI 0.80-5.39). A similar tendency was observed among never and ever combustible 53 cigarette smokers. 54 Conclusion: In Japan, the incidence of HTP use has exceeded 10% among pregnant women, 55 and HTP smoking may be associated with increased maternal and neonatal risks. School-56 based tobacco prevention and cessation programs should be conducted regardless of product 57 types to prevent life-threatening perinatal complications and deaths. 58 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 17, 2021. ; https://doi.org/10.1101/2021.04.12.21255292 doi: medRxiv preprint 4 Keywords: heated tobacco products, hypertensive disorders of pregnancy, 59 smoking, preconception 60 61 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This study aimed to assess the status of HTP use among pregnant women in Japan and 78 explore the risk of HDP and LBW associated with the use of HTP by analyzing data from a 79 nationwide web-based survey in Japan that contained pregnancy-related information and data 80 related to behavioral factors (e.g., HTP use and combustible cigarette smoking), and social 81 background. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

Data on HDP and LBW were extracted from the web-based self-reported questionnaires. We 109 defined the incidence of HDP based on whether the study participants had been diagnosed as 110 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. week of gestation).

[14] We defined the incidence of LBW on the basis of the diagnosis of 114 LBW (birth weight <2500 g). 115 All participants were asked to provide information from their Maternal and Child In the questionnaire, study participants were asked to indicate their smoking status (never, 126 once or a few times but not habitually, former, sometimes, or every day) for each HTP 127 available in the study period (Ploom Tech, Ploom Tech plus, Ploom S, IQOS, glo, glo sens, 128 and PULZE). If they answered "never" for all HTPs, we defined them as never HTP smokers; 129 the remaining participants were considered ever HTP smokers. 130 We also classified the status of combustible cigarette smoking (never/ever 135 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. women. Additionally, we described detailed HTP smoking status cross-classified according 140 to the combustible cigarette smoking status of currently pregnant and post-delivery women. 141 To assess the potential association between HTP smoking and perinatal risk of HDP 142 and LBW, we restricted the sample to 558 post-delivery women who could complete all the 143 assessments during their pregnancy (Table 1 ). In the multivariable logistic regression 144 analyses, the odds ratio (OR) and 95% confidence interval (CI) of ever HTP smokers for 145 HDP risk were estimated with adjustment for age (model 1, the main model in the present 146 study). The reference group comprised never HTP smokers. In model 2, we fully adjusted for 

Among 558 post-delivery women, the incidences of HDP and LBW were 7.3% (n=41) and 157 10.0% (n=56), respectively, and the prevalence of ever HTP smokers was 11.7% (n=65, 158 Table 1 ). Furthermore, among 365 currently pregnant women, the prevalence of ever HTP 159 smokers was 12.6% (n=46), which did not differ from that of HTP smokers among post-160 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Among post-delivery women, the HDP incidence was higher in ever HTP smokers than 164 in never HTP smokers (13.8% vs. 6.5%; Table 1 ). Similarly, the incidence of LBW was 165 higher among ever HTP smokers than among never HTP smokers (18.5% vs. 8.9%, Table 1 ). 166 When stratified by combustible cigarette smoking, a similar tendency was observed among 167 never and ever combustible cigarette smokers (Table 1) . 168 In the regression analysis, the age-adjusted ORs for HDP and LBW were elevated in 169 ever HTP smokers (model 1, Figure 1 ); the ORs for HDP and LBW were 2.48 (95% CI, During the COVID-19 pandemic in Japan, the incidence of HTP use among pregnant women 182 is likely to exceed 10%, and we found that HTP use may be associated with perinatal risk of 183 HDP and LBW. Although the impact was attenuated after controlling for other potential 184 explanatory factors and the significance disappeared due to weak statistical power, the 185 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 192 We also found that LBW, a well-known smoking-related neonatal risk,[18] was 193 associated with HTP use. In fact, the incidence of HTP use doubled the risk of LBW, and the 194 association was stronger among never combustible cigarette smokers. These results seem to 195 be reliable because the incidence estimate of approximately 10% LBW found in our study 196 (using Maternal and Child Health Handbooks) is consistent with the general statistics 197 reported for Japanese pregnant women. [19] This also implies that aerosols of HTPs 198 containing nicotine and other inhalable substances can cause acute adverse health events on 199 the development of infants. 200 To the best of our knowledge, this is the first report of a potential association between 201 HTP use and perinatal risks. Although smoking plays a controversial role,[9] recent evidence 202 suggests that combustible cigarette smoking is associated with increased HDP risk. [10, 11] 203 Another study also reported the risk of snuff use for preeclampsia, a severe phenotype of (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. In conclusion, the incidence of HTP use seems to exceed 10% among pregnant women, 247 and HTP smoking may be associated with increased maternal and neonatal risks in Japan. 248 With no doubt, smoking in reproductive age can cause unfavorable perinatal outcomes. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The data that support the findings of this study are available on reasonable request. However, 263 restrictions apply to the availability of these data due to personal identification; research data 264 are not shared. If any person wishes to verify our data, they are most welcome to contact the 265 corresponding author. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 17, 2021. ; https://doi.org/10.1101/2021.04.12.21255292 doi: medRxiv preprint

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Heat-not-burn tobacco products: a 292 systematic literature review

The global impact of pre-eclampsia and eclampsia

Current status of pregnancy-related maternal 296 mortality in Japan: a report from the Maternal Death Exploratory Committee in Japan

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No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity

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Study profile: The Japan

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Organization for Economic Cooperation and Development. OECD Family Database 325

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No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted