- Email: [email protected]
Perception of pregnant Japanese women regarding the teratogenic risk of medication exposure during pregnancy and the effect of counseling through the Japan drug information institute in pregnancy
Reproductive Toxicology 79 (2018) 66–71
Contents lists available at ScienceDirect
Reproductive Toxicology journal homepage: www.elsevier.com/locate/reprotox
Perception of pregnant Japanese women regarding the teratogenic risk of medication exposure during pregnancy and the effect of counseling through the Japan drug information institute in pregnancy
T
⁎
Naho Yakuwaa,b, , Ken Nakajimaa,b, Sachi Koinumaa, Mikako Gotoa, Tomo Suzukia,c, Naoki Itoa,d, Omi Watanabea, Atsuko Murashimaa,c a
Japan Drug Information Institute in Pregnancy, National Center for Child Health and Development Tokyo, Japan Department of Pharmaceuticals, National Center for Child Health and Development, Tokyo, Japan Center for Maternal-Fetal, Neonatal and Reproductive Medicine, Department of Perinatology, National Center for Child Health and Development, Tokyo, Japan d Department of Pediatrics, Teikyo University, Tokyo, Japan b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Pregnancy Medication Teratogenic risk perception Visual analog scale Teratology information service Japan Counseling
Objective: To confirm the current state of Japanese women’s perception of the teratogenic risk of medication exposure during pregnancy, and to assess the effect of counseling by Japan Drug Information Institute in Pregnancy. Methods: We used VAS to monitor the sentiments of pregnant women, before and after face-to-face counseling, about their own teratogenic risk perception, and their intention to continue pregnancy. Pregnancy outcomes were investigated by mailed questionnaires. Results: Among 681 pregnant women, the median estimation of the risk of having a baby with a birth defect was 33.0% (interquartile range 16.0–50.0%) prior to counseling and 5.0% after counseling (2.0–11.0%). The median intention to continue pregnancy increased from 86.0% to 100.0% after counseling. The actual outcome survey revealed that almost all participants (97.1%) continued their pregnancies. Conclusions: Pregnant women tend to overestimate the fetal risks of medication exposure during pregnancy. Counseling would prevent unnecessary termination.
1. Introduction Medication exposure during pregnancy can affect both mother and fetus. In general, pregnant women tend to be very worried about medication use during pregnancy. Overestimation of the risks is problematic because it can lead to discontinuation of necessary treatment or termination of pregnancy. Teratology Information Services (TIS) have been established in various countries to provide pregnant women with evidence-based information on the safety of medication use during pregnancy. The Motherisk Program in Canada [1] consults with about 30,000 patients every year. Other well-established TIS networks are Mother to Baby (Organization of Teratology Information Specialists, OTIS [2]), and The European Network of Teratology Information Services (ENTIS) [3]. The largest TIS in Japan is Japan Drug Information Institute in Pregnancy [4]. Japan Drug Information Institute in Pregnancy was
established in October 2005 by the Ministry of Health, Labour and Welfare. Japan Drug Information Institute in Pregnancy cooperates and shares information with Motherisk. Like TIS in other countries, Japan Drug Information Institute in Pregnancy provides evidence-based counseling. We used visual analogue scale (VAS) to assess the sentiments of pregnant women, before and after face-to-face counseling, about 1) their own teratogenic risk perception, and 2) their intention to continue pregnancy. Pregnancy outcomes were investigated by mailed questionnaires. In other countries, several kinds of surveys have been conducted on fetal risk perception related to medication exposure during pregnancy. A large-scale study of 18 countries, including those in Europe, North America, and Australia, reported that pregnant women overestimate the actual risk of antibiotics, antidepressants, and over-the-counter drugs for nausea taken during pregnancy [5]. Other studies showed that pregnant women in Spain [6] and Norway [7] also overestimate the
Abbreviations: VAS, visual analog scale; TIS, Teratology Information Services ⁎ Corresponding author at: Pharmaceutical Department, National Center for Child Health and Development, Japan Drug Information Institute in Pregnancy, Okura 2-10-1, Setagaya-ku, Tokyo 157-8535, Japan. E-mail address: [email protected] (N. Yakuwa). https://doi.org/10.1016/j.reprotox.2018.05.009 Received 12 March 2018; Received in revised form 8 May 2018; Accepted 30 May 2018 Available online 06 June 2018 0890-6238/ © 2018 Elsevier Inc. All rights reserved.
Reproductive Toxicology 79 (2018) 66–71
N. Yakuwa et al.
pregnancy (intention to continue pregnancy). We conducted the VAS survey before and after counseling.
fetal risk of medication during pregnancy. Similar results have been obtained by TIS in Canada (Motherisk) [8–13] and Turkey [14]. In addition, TIS have investigated the effects of counseling on the perception of the teratogenic risk of medications and intention to continue pregnancy [15]. In Japan, one study [16] have investigated teratogenic risk perception associated with medication exposure during pregnancy and intention to continue pregnancy, and no study to date has connected intention to continue pregnancy with actual pregnancy outcomes. Therefore, in this study, we assessed the current status of teratogenic risk perception associated with medication exposure during pregnancy in Japan, and evaluated the effect of counseling on pregnant women.
2.3. Collection of data on pregnancy outcomes To collect pregnancy outcomes, we sent postcards stamped and personal information protection stickers in the envelope to women who received counseling. The cards were mailed in the month following the expected date of delivery. If we did not receive a response from the pregnant women, we sent another postcard 2 months later (3 months from the expected date of delivery). Women sent personal information protection stickers on the card to us. Based on the responses, we collected data on pregnancy outcomes, including pregnancy continuation (live birth, stillbirth, miscarriage), and pregnancy termination (induced abortion).
2. Materials and methods 2.1. Collection of information on the characteristics of pregnant women
2.4. Study population
We collected information on the characteristics of pregnant women and their medications using interview sheets by questionnaires completed by the women at the time they applied for counseling. This information included age, gestational age (weeks), height, weight, pregnancy history, alcohol use, smoking, planned or unplanned pregnancy, and medications.
We included pregnant women who underwent face-to-face counseling at the National Center for Child Health and Development, with expected dates of delivery between October 2005 and December 2016. Pregnant women who received counseling after 22 weeks and pregnant women who went to counseling several times were excluded.
2.2. Collection of data on pregnant women’s own teratogenic risk perception and intention to continue pregnancy
2.5. Current status of pregnant women’s own teratogenic risk perception and evaluation of the importance of counseling
At the time of counseling, we used the visual analogue scale (VAS) that a tool developed and published by Koren et al in [8] to ask pregnant women (Fig. 1) about 1) their assessment of the likelihood of congenital anomaly in the fetus (pregnant woman’s own teratogenic risk perception), and 2) the extent to which they wanted to continue the
Based on the VAS results, we compared pregnant women’s own teratogenic risk perception and Intention to continue pregnancy before and after counseling, used this information to evaluate the usefulness of counseling. In addition, we investigated the real pregnancy continuation rate based on information obtained from the postcard. Fig. 1. Visual analogue scale (VAS). At the time of counseling, we used the VAS to ask pregnant women about 1) their assessment of the likelihood of congenital anomaly in the fetus (pregnant woman’s own teratogenic risk perception), and 2) the extent to which they wanted to continue the pregnancy (intention to continue pregnancy).
67
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Fig. 2. Pregnant women participating in this study.
2.6. Statistical analysis
Table 1 Characteristics of pregnant women participating in this study (n = 681).
Data were analyzed using IBM SPSS Statistics version 20. The Wilcoxon signed-rank test was used to detect changes in VAS, with the significance level set at 5% (α = 0.05).
Mean ± SD (range) Mean weeks of pregnancy at the time of counseling (weeks) Mean age at the time of counseling (years) Planning for pregnancy expected pregnancy unexpected pregnancy no answer Main medication that led subject to seek counseling psychiatric disorder cold symptoms infectious disease digestive disease allergy epilepsy other Cases of consultation on teratogenic drugs n = 65 / 681 isotretinoin vitamin A (more than 50,000 units) methotrexate warfarin antiepileptic drugs (valproic acid、carbamazepine、 phenytoin、phenobarbital)
2.7. Ethics This study was approved by the ethics committee of the National Center for Child Health and Development (accession No. 1322). 3. Results 3.1. Characteristics of pregnant women We included 681 pregnant women in this study (Fig. 2). The characteristics of the pregnant women are provided in Table 1. More than 70% of the subjects had unexpected pregnancies. Counseling regarding psychiatric medications accounted for more than 40% of cases. 3.2. Status prior to counseling (Fig. 3) Status prior to counseling of pregnant women’s own teratogenic risk perception and Intention to continue pregnancy were shown in Fig. 3.
10.0 ± 3.8 32.0 ± 4.7 192 487 2 302 63 49 43 32 22 170 65 (9.5%) 2 2 7 3 51
Similarly, the median Intention to continue pregnancy value increased from 86.5% (interquartile range 50.0 - 100.0) to 100.0% (96.0 - 100.0). This change was also statistically significant (p < 0.01).
3.3. Changes after counseling (Fig. 4) 3.4. Survey of pregnancy outcomes (Table 2)
After counseling, the median pregnant women’s own teratogenic risk perception value decreased from 33.0% (interquartile range 16.0 50.0) to 5.0% (2.0 - 11.0). This change was statistically significant (p < 0.01). Similarly, the median Intention to continue pregnancy value increased from 86.0% (interquartile range 50.0 - 100.0) to 100.0% (95.0 - 100.0). This change was also statistically significant (p < 0.01). When excluding cases of consultation on teratogenic drugs (Table 1), the median pregnant women’s own teratogenic risk perception value decreased from 33.0% (interquartile range 15.0 - 50.0) to 4.0% (1.0 - 10.0). This change was statistically significant (p < 0.01).
Assessment of pregnancy outcomes, performed by postcard survey, revealed that 97.1% (661/681) of subjects continued their pregnancy, resulting in 617 live births, 2 stillbirths, and 42 miscarriages. The remainder (2.9%, 20/681) discontinued pregnancy (induced abortion).
68
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Fig. 3. Status prior to counseling.
4. Discussion
possibility that pregnant women’s own teratogenic risk perception was overestimated.
4.1. Current status of pregnant women 4.2. Effect of counseling
In our study, pregnant woman’s own teratogenic risk perception prior to counseling was high at 33.0%. Even after excluding cases of consultation on teratogenic drugs (Table 1), the pregnant women’s own teratogenic risk perception before the counseling was no change. In TIS in other countries, pregnant women’s own teratogenic risk perception prior to counseling has been reported as 24.0% in pregnant women exposed to drugs, chemicals, or radiation [8]; 37.5% in pregnant women exposed to cocaine [9]; 22.3% in pregnant women with depression [13]; and 45.0% in pregnant women who were counseled about non-teratogenic drugs [14]. As in other countries, pregnant women in Japan overestimate the risk of medication exposure during pregnancy. Differences are probably due to different populations in different countries with different risk perceptions. Pregnant women who responded with a pregnant women’s own teratogenic risk perception of 50.0% accounted for approximately 20.0% of all subjects. Because many pregnant women may report a 50% risk if they cannot judge the risk to the fetus, we considered the
4.2.1. Decrease in pregnant women’s own teratogenic risk perception, increase in intention to continue pregnancy Pregnant woman’s own teratogenic risk perception decreased from 33.0% to 5.0% (p < 0.01) and Intention to continue pregnancy increased from 86.0% to 100.0% (p < 0.01) after counseling (Fig. 2). This is consistent with the results of TIS studies in other countries [8,9,13,14]. In addition, this finding indicates that Japan Drug Information Institute in Pregnancy counseling effectively decreased pregnant woman’s own teratogenic risk perception and increased Intention to continue pregnancy. 4.2.2. Convergence of variability There was large variability in pregnant woman’s own teratogenic risk perception and Intention to continue pregnancy before counseling, but both variabilities decreased after counseling. This finding suggests that pregnant woman’s own teratogenic risk perception initially varied 69
Reproductive Toxicology 79 (2018) 66–71
N. Yakuwa et al.
%
%
100
100
90
90
80
80
70
70
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60 50
50
40
40
30
30
20
20
10
10
0
p<0.01
60
0
before
before
after
after
Fig. 4. Pregnant women’s own teratogenic Risk Perception and Intention to Continue Pregnancy median values and interquartile ranges before vs. after counseling. The median pregnant women’s own teratogenic risk perception value decreased from 33.0% (interquartile range 16.0–50.0) to 5.0% (2.0–11.0) (p < 0.01) The median Intention to continue pregnancy value increased from 86.0% (50.0–100.0) to 100.0% (95.0–100.0) (p < 0.01)
Funding
Table 2 Postcard survey of pregnancy outcomes.
Japan Drug Information Institute in Pregnancy is managed by the Ministry of Health, Labor and Welfare project expenses. This study was conducted based on the operating expenses of Japan Drug Information Institute in Pregnancy.
N sending of the postcard questionnaire no answer to the postcard questionnaire ineligible due to gestational age at counseling women who could survey of outcome Outcome: continued pregnancy livebirth stillbirth miscarriage discontinued pregnancy
823 111 31 681
Conflict of interest declaration
661 617 2 42 20
All authors declare no conflict of interest. Acknowledgements We thank all the women who participated in the study.
among participants, but that a certain level of understanding was obtained after counseling. Intention to continue pregnancy also varied among participants before counseling, but became less variable after counseling. The reduction in the variability of pregnant woman’s own teratogenic risk perception was associated with a smaller variability in Intention to continue pregnancy after the counseling. Taken together, these findings suggest that pregnant woman’s own teratogenic risk perception affects Intention to continue pregnancy.
References [1] Motherisk http://www.motherisk.org/, 2018 (accessed 5 January 2018). [2] Organization of Teratology Information Specialists (OTIS), https://mothertobaby. org/, (Accessed 5 January 2018). [3] European Network of Teratology Information Service (ENTIS), https://www.entisorg.eu/, (Accessed 5 January 2018). [4] Japan Drug Information Institute in Pregnancy, https://www.ncchd.go.jp/kusuri/, (Accessed 5 January 2018). [5] I. Petersen, R.L. McCrea, A. Lupattelli, H. Nordeng, Women’s perception of risks of adverse fetal pregnancy outcomes: a largescale multinational survey, BMJ Open 5 (2015) e007390. [6] E. Sanz, R. Gomez-Lopez, M.J. Martinez-Quintas, Perception of teratogenic risk of common medicines, Eur. J. Obstet. Gynecol. Reprod. Biol. 95 (2001) 27–31. [7] H. Nordeng, E. Ystrøm, A. Einarson, Perception of risk regarding the use of medications and other exposures during pregnancy, Eur. J. Clin. Pharmacol. 66 (2010) 207–214. [8] G. Koren, M. Bologa, D. Long, Y. Feldman, N.H. Shear, Perception of teratogenic risk by pregnant women exposed to drugs and chemicals during the first trimester, Am. J. Obstet. Gynecol. 160 (1989) 1190–1194. [9] G. Koren, D. Gladstone, C. Robeson, I. Robieux, The perception of teratogenic risk of cocaine, Birth Defect. Res. A. 46 (1992) 567–571. [10] P. Mazzotta, L.A. Magee, C. Maltepe, A. Lifshitz, Y. Navioz, G. Koren, The perception of teratogenic risk by women with nausea and vomiting of pregnancy, Reprod. Toxicol. 13 (1999) 313–319. [11] A. Einarson, P. Selby, G. Koren, Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counseling, J. Psychiatry Neurosci. 26 (2001) 44–48. [12] L. Bonari, G. Koren, T.R. Einarson, J.D. Jasper, A. Taddio, A. Einarson, Use of antidepressants by pregnant women: evaluation of perception of risk, efficacy of evidence-based counseling, and determinants of decision making, Arch. Women Ment. Health. 8 (2005) 214–220. [13] A. Walfisch, C. Sermer, I. Matok, A. Einarson, G. Koren, Perception of teratogenic
4.2.3. Survey on pregnancy outcomes We investigated actual pregnancy outcomes. In other countries, such investigations of actual pregnancy results have been limited. Koren et al [15] analyzed the association between the results of an attitude survey of the likelihood to continue pregnancy and actual pregnancy outcome, before and after counseling, in pregnant women who indicated that they were less than 50% likely to continue the pregnancy. In our study, almost all (97.1%) participants continued their pregnancies. We confirmed that our counseling not only was effective in increasing Intention to continue pregnancy, but also was associated with actual pregnancy continuation. 5. Study limitations Pregnant women who received consultation may have had greater anxiety than pregnant women in general. 70
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counselling women on drug, chemical, and radiation exposure during the first trimester, Teratology 41 (6) (1990) 657–661. [16] K. Nakajima, M. Ishii, K. Kushida, A. Murashima, K. Yamaguchi, N. Watanabe, N. Arata, N. Ito, O. Watanabe, S. Irie, M. Kitagawa, A comparison of the incidence of drug-associated congenital abnormalities during pregnancy expected by patient and the improvement of such after counseling with a pharmacist, J. Jpn. Soc. Hosp. Pharm. 45 (3) (2009) 377–380.
risk and the rated likelihood of pregnancy termination:association with maternal depression, Can. J. Psychiatry 56 (2011) 761–767. [14] Y.C. Kaplan, B.Karadas¸G. Kücuksolak, B. Ediz, Ö. Demir, K. Sozmen, H. Nordeng, Counselling pregnant women at the crossroads of Europe and Asia: effect of teratology information service in Turkey, Int. J. Clin. Pharm. 39 (2017) 783–790, http://dx.doi.org/10.1007/s11096-017-0496-5. [15] G. Koren, A. Pastuszak, Prevention of unnecessary pregnancy terminations by
71
Contents lists available at ScienceDirect
Reproductive Toxicology journal homepage: www.elsevier.com/locate/reprotox
Perception of pregnant Japanese women regarding the teratogenic risk of medication exposure during pregnancy and the effect of counseling through the Japan drug information institute in pregnancy
T
⁎
Naho Yakuwaa,b, , Ken Nakajimaa,b, Sachi Koinumaa, Mikako Gotoa, Tomo Suzukia,c, Naoki Itoa,d, Omi Watanabea, Atsuko Murashimaa,c a
Japan Drug Information Institute in Pregnancy, National Center for Child Health and Development Tokyo, Japan Department of Pharmaceuticals, National Center for Child Health and Development, Tokyo, Japan Center for Maternal-Fetal, Neonatal and Reproductive Medicine, Department of Perinatology, National Center for Child Health and Development, Tokyo, Japan d Department of Pediatrics, Teikyo University, Tokyo, Japan b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Pregnancy Medication Teratogenic risk perception Visual analog scale Teratology information service Japan Counseling
Objective: To confirm the current state of Japanese women’s perception of the teratogenic risk of medication exposure during pregnancy, and to assess the effect of counseling by Japan Drug Information Institute in Pregnancy. Methods: We used VAS to monitor the sentiments of pregnant women, before and after face-to-face counseling, about their own teratogenic risk perception, and their intention to continue pregnancy. Pregnancy outcomes were investigated by mailed questionnaires. Results: Among 681 pregnant women, the median estimation of the risk of having a baby with a birth defect was 33.0% (interquartile range 16.0–50.0%) prior to counseling and 5.0% after counseling (2.0–11.0%). The median intention to continue pregnancy increased from 86.0% to 100.0% after counseling. The actual outcome survey revealed that almost all participants (97.1%) continued their pregnancies. Conclusions: Pregnant women tend to overestimate the fetal risks of medication exposure during pregnancy. Counseling would prevent unnecessary termination.
1. Introduction Medication exposure during pregnancy can affect both mother and fetus. In general, pregnant women tend to be very worried about medication use during pregnancy. Overestimation of the risks is problematic because it can lead to discontinuation of necessary treatment or termination of pregnancy. Teratology Information Services (TIS) have been established in various countries to provide pregnant women with evidence-based information on the safety of medication use during pregnancy. The Motherisk Program in Canada [1] consults with about 30,000 patients every year. Other well-established TIS networks are Mother to Baby (Organization of Teratology Information Specialists, OTIS [2]), and The European Network of Teratology Information Services (ENTIS) [3]. The largest TIS in Japan is Japan Drug Information Institute in Pregnancy [4]. Japan Drug Information Institute in Pregnancy was
established in October 2005 by the Ministry of Health, Labour and Welfare. Japan Drug Information Institute in Pregnancy cooperates and shares information with Motherisk. Like TIS in other countries, Japan Drug Information Institute in Pregnancy provides evidence-based counseling. We used visual analogue scale (VAS) to assess the sentiments of pregnant women, before and after face-to-face counseling, about 1) their own teratogenic risk perception, and 2) their intention to continue pregnancy. Pregnancy outcomes were investigated by mailed questionnaires. In other countries, several kinds of surveys have been conducted on fetal risk perception related to medication exposure during pregnancy. A large-scale study of 18 countries, including those in Europe, North America, and Australia, reported that pregnant women overestimate the actual risk of antibiotics, antidepressants, and over-the-counter drugs for nausea taken during pregnancy [5]. Other studies showed that pregnant women in Spain [6] and Norway [7] also overestimate the
Abbreviations: VAS, visual analog scale; TIS, Teratology Information Services ⁎ Corresponding author at: Pharmaceutical Department, National Center for Child Health and Development, Japan Drug Information Institute in Pregnancy, Okura 2-10-1, Setagaya-ku, Tokyo 157-8535, Japan. E-mail address: [email protected] (N. Yakuwa). https://doi.org/10.1016/j.reprotox.2018.05.009 Received 12 March 2018; Received in revised form 8 May 2018; Accepted 30 May 2018 Available online 06 June 2018 0890-6238/ © 2018 Elsevier Inc. All rights reserved.
Reproductive Toxicology 79 (2018) 66–71
N. Yakuwa et al.
pregnancy (intention to continue pregnancy). We conducted the VAS survey before and after counseling.
fetal risk of medication during pregnancy. Similar results have been obtained by TIS in Canada (Motherisk) [8–13] and Turkey [14]. In addition, TIS have investigated the effects of counseling on the perception of the teratogenic risk of medications and intention to continue pregnancy [15]. In Japan, one study [16] have investigated teratogenic risk perception associated with medication exposure during pregnancy and intention to continue pregnancy, and no study to date has connected intention to continue pregnancy with actual pregnancy outcomes. Therefore, in this study, we assessed the current status of teratogenic risk perception associated with medication exposure during pregnancy in Japan, and evaluated the effect of counseling on pregnant women.
2.3. Collection of data on pregnancy outcomes To collect pregnancy outcomes, we sent postcards stamped and personal information protection stickers in the envelope to women who received counseling. The cards were mailed in the month following the expected date of delivery. If we did not receive a response from the pregnant women, we sent another postcard 2 months later (3 months from the expected date of delivery). Women sent personal information protection stickers on the card to us. Based on the responses, we collected data on pregnancy outcomes, including pregnancy continuation (live birth, stillbirth, miscarriage), and pregnancy termination (induced abortion).
2. Materials and methods 2.1. Collection of information on the characteristics of pregnant women
2.4. Study population
We collected information on the characteristics of pregnant women and their medications using interview sheets by questionnaires completed by the women at the time they applied for counseling. This information included age, gestational age (weeks), height, weight, pregnancy history, alcohol use, smoking, planned or unplanned pregnancy, and medications.
We included pregnant women who underwent face-to-face counseling at the National Center for Child Health and Development, with expected dates of delivery between October 2005 and December 2016. Pregnant women who received counseling after 22 weeks and pregnant women who went to counseling several times were excluded.
2.2. Collection of data on pregnant women’s own teratogenic risk perception and intention to continue pregnancy
2.5. Current status of pregnant women’s own teratogenic risk perception and evaluation of the importance of counseling
At the time of counseling, we used the visual analogue scale (VAS) that a tool developed and published by Koren et al in [8] to ask pregnant women (Fig. 1) about 1) their assessment of the likelihood of congenital anomaly in the fetus (pregnant woman’s own teratogenic risk perception), and 2) the extent to which they wanted to continue the
Based on the VAS results, we compared pregnant women’s own teratogenic risk perception and Intention to continue pregnancy before and after counseling, used this information to evaluate the usefulness of counseling. In addition, we investigated the real pregnancy continuation rate based on information obtained from the postcard. Fig. 1. Visual analogue scale (VAS). At the time of counseling, we used the VAS to ask pregnant women about 1) their assessment of the likelihood of congenital anomaly in the fetus (pregnant woman’s own teratogenic risk perception), and 2) the extent to which they wanted to continue the pregnancy (intention to continue pregnancy).
67
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N. Yakuwa et al.
Fig. 2. Pregnant women participating in this study.
2.6. Statistical analysis
Table 1 Characteristics of pregnant women participating in this study (n = 681).
Data were analyzed using IBM SPSS Statistics version 20. The Wilcoxon signed-rank test was used to detect changes in VAS, with the significance level set at 5% (α = 0.05).
Mean ± SD (range) Mean weeks of pregnancy at the time of counseling (weeks) Mean age at the time of counseling (years) Planning for pregnancy expected pregnancy unexpected pregnancy no answer Main medication that led subject to seek counseling psychiatric disorder cold symptoms infectious disease digestive disease allergy epilepsy other Cases of consultation on teratogenic drugs n = 65 / 681 isotretinoin vitamin A (more than 50,000 units) methotrexate warfarin antiepileptic drugs (valproic acid、carbamazepine、 phenytoin、phenobarbital)
2.7. Ethics This study was approved by the ethics committee of the National Center for Child Health and Development (accession No. 1322). 3. Results 3.1. Characteristics of pregnant women We included 681 pregnant women in this study (Fig. 2). The characteristics of the pregnant women are provided in Table 1. More than 70% of the subjects had unexpected pregnancies. Counseling regarding psychiatric medications accounted for more than 40% of cases. 3.2. Status prior to counseling (Fig. 3) Status prior to counseling of pregnant women’s own teratogenic risk perception and Intention to continue pregnancy were shown in Fig. 3.
10.0 ± 3.8 32.0 ± 4.7 192 487 2 302 63 49 43 32 22 170 65 (9.5%) 2 2 7 3 51
Similarly, the median Intention to continue pregnancy value increased from 86.5% (interquartile range 50.0 - 100.0) to 100.0% (96.0 - 100.0). This change was also statistically significant (p < 0.01).
3.3. Changes after counseling (Fig. 4) 3.4. Survey of pregnancy outcomes (Table 2)
After counseling, the median pregnant women’s own teratogenic risk perception value decreased from 33.0% (interquartile range 16.0 50.0) to 5.0% (2.0 - 11.0). This change was statistically significant (p < 0.01). Similarly, the median Intention to continue pregnancy value increased from 86.0% (interquartile range 50.0 - 100.0) to 100.0% (95.0 - 100.0). This change was also statistically significant (p < 0.01). When excluding cases of consultation on teratogenic drugs (Table 1), the median pregnant women’s own teratogenic risk perception value decreased from 33.0% (interquartile range 15.0 - 50.0) to 4.0% (1.0 - 10.0). This change was statistically significant (p < 0.01).
Assessment of pregnancy outcomes, performed by postcard survey, revealed that 97.1% (661/681) of subjects continued their pregnancy, resulting in 617 live births, 2 stillbirths, and 42 miscarriages. The remainder (2.9%, 20/681) discontinued pregnancy (induced abortion).
68
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Fig. 3. Status prior to counseling.
4. Discussion
possibility that pregnant women’s own teratogenic risk perception was overestimated.
4.1. Current status of pregnant women 4.2. Effect of counseling
In our study, pregnant woman’s own teratogenic risk perception prior to counseling was high at 33.0%. Even after excluding cases of consultation on teratogenic drugs (Table 1), the pregnant women’s own teratogenic risk perception before the counseling was no change. In TIS in other countries, pregnant women’s own teratogenic risk perception prior to counseling has been reported as 24.0% in pregnant women exposed to drugs, chemicals, or radiation [8]; 37.5% in pregnant women exposed to cocaine [9]; 22.3% in pregnant women with depression [13]; and 45.0% in pregnant women who were counseled about non-teratogenic drugs [14]. As in other countries, pregnant women in Japan overestimate the risk of medication exposure during pregnancy. Differences are probably due to different populations in different countries with different risk perceptions. Pregnant women who responded with a pregnant women’s own teratogenic risk perception of 50.0% accounted for approximately 20.0% of all subjects. Because many pregnant women may report a 50% risk if they cannot judge the risk to the fetus, we considered the
4.2.1. Decrease in pregnant women’s own teratogenic risk perception, increase in intention to continue pregnancy Pregnant woman’s own teratogenic risk perception decreased from 33.0% to 5.0% (p < 0.01) and Intention to continue pregnancy increased from 86.0% to 100.0% (p < 0.01) after counseling (Fig. 2). This is consistent with the results of TIS studies in other countries [8,9,13,14]. In addition, this finding indicates that Japan Drug Information Institute in Pregnancy counseling effectively decreased pregnant woman’s own teratogenic risk perception and increased Intention to continue pregnancy. 4.2.2. Convergence of variability There was large variability in pregnant woman’s own teratogenic risk perception and Intention to continue pregnancy before counseling, but both variabilities decreased after counseling. This finding suggests that pregnant woman’s own teratogenic risk perception initially varied 69
Reproductive Toxicology 79 (2018) 66–71
N. Yakuwa et al.
%
%
100
100
90
90
80
80
70
70
p<0.01
60 50
50
40
40
30
30
20
20
10
10
0
p<0.01
60
0
before
before
after
after
Fig. 4. Pregnant women’s own teratogenic Risk Perception and Intention to Continue Pregnancy median values and interquartile ranges before vs. after counseling. The median pregnant women’s own teratogenic risk perception value decreased from 33.0% (interquartile range 16.0–50.0) to 5.0% (2.0–11.0) (p < 0.01) The median Intention to continue pregnancy value increased from 86.0% (50.0–100.0) to 100.0% (95.0–100.0) (p < 0.01)
Funding
Table 2 Postcard survey of pregnancy outcomes.
Japan Drug Information Institute in Pregnancy is managed by the Ministry of Health, Labor and Welfare project expenses. This study was conducted based on the operating expenses of Japan Drug Information Institute in Pregnancy.
N sending of the postcard questionnaire no answer to the postcard questionnaire ineligible due to gestational age at counseling women who could survey of outcome Outcome: continued pregnancy livebirth stillbirth miscarriage discontinued pregnancy
823 111 31 681
Conflict of interest declaration
661 617 2 42 20
All authors declare no conflict of interest. Acknowledgements We thank all the women who participated in the study.
among participants, but that a certain level of understanding was obtained after counseling. Intention to continue pregnancy also varied among participants before counseling, but became less variable after counseling. The reduction in the variability of pregnant woman’s own teratogenic risk perception was associated with a smaller variability in Intention to continue pregnancy after the counseling. Taken together, these findings suggest that pregnant woman’s own teratogenic risk perception affects Intention to continue pregnancy.
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4.2.3. Survey on pregnancy outcomes We investigated actual pregnancy outcomes. In other countries, such investigations of actual pregnancy results have been limited. Koren et al [15] analyzed the association between the results of an attitude survey of the likelihood to continue pregnancy and actual pregnancy outcome, before and after counseling, in pregnant women who indicated that they were less than 50% likely to continue the pregnancy. In our study, almost all (97.1%) participants continued their pregnancies. We confirmed that our counseling not only was effective in increasing Intention to continue pregnancy, but also was associated with actual pregnancy continuation. 5. Study limitations Pregnant women who received consultation may have had greater anxiety than pregnant women in general. 70
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