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Drug Use before and during Pregnancy in Japan: The Japan Environment and Children’s Study

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Objectives Multimorbidity is defined as the coexistence of two or more chronic physical or psychological conditions within an individual. The association between maternal multimorbidity and adverse perinatal outcomes such as preterm delivery and low birth weight has not been well studied. Therefore, this study aimed to investigate this association. Those with data on chronic maternal conditions were included in the study and categorised as having no chronic condition, one chronic condition or multimorbidities. Results Of the fetal records, 86 singleton pregnant women were analysed. The median maternal age and body mass index were 31 years and The prevalence of pregnant women with one or more chronic conditions was The prevalence of maternal multimorbidity was 6. Pre-pregnancy underweight women were the most common, observed in The risk of adverse perinatal outcomes tends to increase with a rise in the number of chronic maternal conditions. Multimorbidity becomes more prevalent among pregnant women, making our findings important for preconception counselling. No data are available. All inquiries about access to data were sent to jecs-en nies. You will be able to get a quick price and instant permission to reuse the content in many different ways. Including a wide variety of chronic conditions concerning maternal health and well-being makes the study more comprehensive. The study size is robust enough to investigate preterm birth, low birth weight and small gestational age; however, the numbers of secondary outcomes such as very preterm birth, very low birth weight and extremely low birth weight are too small to have enough statistical power. Some self-reported maternal conditions, including domestic and substance abuse, may be under-reported. Multimorbidity is usually defined as the coexistence of two or more chronic physical or psychological conditions within an individual. Consequently, the existing evidence is fragmented and often difficult to interpret. Although the prevalence of multimorbidity is highest in those aged 65 years or older, younger persons, including women of reproductive age, also represent a large proportion of those with multimorbidity, ranging from 8. The association between certain specific single maternal chronic diseases and related perinatal outcomes has been well studied; however, there are only a few studies on maternal multimorbidity and perinatal outcomes. It has been widely known that maternal physical morbidity such as hypertension, kidney disease and systemic lupus erythematosus increase the risk of preterm births PTBs and low birthweight LBW infants. Therefore, we hypothesised that the risk of adverse perinatal outcomes, such as PTB, LBW and small for gestational age SGA , would increase with the number of chronic maternal conditions present in a woman, including physical, psychological and social conditions. In Japan, the association between maternal multimorbidity and adverse perinatal outcomes has not yet been investigated. The present study aimed to determine the association between maternal multimorbidity and adverse perinatal outcomes, such as PTB, LBW and SGA, using a Japanese nationwide prospective cohort study. The JECS is an ongoing nationwide birth cohort study in Japan, the details of which have already been reported. The recruitment strategy in the JECS is shown in online supplemental appendix 1. During the study period, fetal records were included in the baseline survey of the JECS. When a mother had more than one pregnancy, only the first pregnancy was included in this study. After excluding pregnancies in the same mothers, there were 94 participants. Baseline information on the mothers, including educational level, smoking status and alcohol consumption, was collected from self-administered questionnaires applied to the enrolled pregnant women during the second or third trimesters. Maternal medical history was obtained using self-administered questionnaires and medical record transcripts during the first trimester of pregnancy. A history of domestic violence from an intimate partner was obtained from self-administered questionnaires applied to the enrolled pregnant women during the first trimester. Maternal age at delivery was calculated from the birth dates of mothers and neonates. Parity was categorised as 0, 1, 2 or higher. The categories of maternal smoking status were defined as follows: never; previously did, but quit before recognising the current pregnancy; previously did, but quit after identifying the current pregnancy; and current smoker. The categories of maternal alcohol consumption were defined as follows: never consumed; previously consumed, but quit before identifying current pregnancy; previously consumed, but quit after identifying current pregnancy; and current drinker. Maternal and neonatal medical information, such as maternal age at delivery, gestational age at delivery, neonatal birth weight and neonatal sex, were collected from the medical record transcripts at birth. In our study, multimorbidity was defined as the coexistence of two or more physical, psychological or social conditions in an individual according to previous reports. The chronic conditions in this study were heterogeneous because the JECS lacked information regarding the disease severity. However, the definition of multimorbidity varies among studies. This information was collected from self-reports, medical record transcripts and medication interviews. Maternal chronic conditions included allergic diseases such as asthma, anaemia, diabetes mellitus, dyslipidaemia, epilepsy, gastric or duodenal ulcer, heart disease, hepatitis, HIV infection, hypertension, inflammatory bowel disease, kidney disease, malignancy, migraine, neurological disease, other sexually transmitted diseases Chlamydia trachomatis and syphilis , psychiatric disorders, rheumatic or collagen diseases, and thyroid disease. Additionally, abnormal pre-pregnancy BMI, including underweight and obesity, physical or verbal domestic violence from intimate partners, and substance abuse were included in the maternal chronic conditions. Medication information was obtained from interviews online supplemental appendix 2. The types of medication in early pregnancy included antiallergic drugs, lipid-lowering drugs, antimigraine drugs, anti-parkinsonian drugs, antirheumatic drugs, antithyroid drugs, antiviral drugs, anticancer drugs, cardiovascular drugs, corticosteroids, gastrointestinal drugs, illegal drugs including marijuana, psychostimulant, ecstasy, thinner and toluene, insulin preparations, iron preparations, psychoactive drugs, respiratory drugs and thyroid hormone preparations. PTB was defined as a gestational age of less than 37 weeks at delivery. VPTB was defined as a gestational age of less than 34 weeks at delivery. SGA was defined as birth weight below the 10th percentile, accounting for parity, gestational age and neonatal sex according to the Japan Pediatric Society guidelines, 38 and percentiles were calculated using Excel-based clinical tools for growth evaluation of children distributed by the Japanese Society for Pediatric Endocrinology. In the SGA analyses, parity and neonatal sex were removed from the covariates. These covariates were selected based on previous studies on multimorbidity. The covariates, such as maternal age, parity, smoking status during pregnancy, drinking status during pregnancy, maternal education, household income and neonatal sex, were among the imputed missing data. Sensitivity analyses focusing on underweight, obesity, psychiatric disorders and domestic violence were performed. Each of these chronic conditions was categorised separately as included or not included in the multimorbidity category. The results of these analyses are shown in online supplemental tables Of the fetal records included in this study, 17 The main and all maternal characteristics are shown in table 1 and online supplemental table 1 , respectively. The median maternal age was 31 years range, 14—48 , and the median pre-pregnancy BMI was In the present study, The details of the maternal chronic conditions are shown in table 3. Maternal underweight The prevalence of maternal obesity was The other most frequent chronic conditions were allergic diseases 3. The association between maternal multimorbidity and adverse perinatal outcomes, using the complete dataset, is shown in online supplemental table 2. All of the trend p values were statistically significant. Online supplemental table 4 demonstrates the aOR for adverse perinatal outcomes, focusing on each disease, including underweight, obesity, psychiatric disorders and domestic violence. Regarding PTB and LBW, significant differences were found between maternal multimorbidity and no chronic conditions, regardless of the presence or absence of specific chronic conditions online supplemental table 4A—D. For SGA, maternal multimorbidity with underweight, without obesity, without psychiatric disorder, and with and without domestic violence showed significant differences compared with no chronic conditions online supplemental table 4A—D. In this study, one-third of pregnant women had one or more chronic conditions, and the prevalence of maternal multimorbidity was lower than that in previous studies. The number of chronic conditions in the mother tends to increase the risk of adverse perinatal outcomes. To our knowledge, the present study is the first to investigate the association between maternal multimorbidity, including physical, psychological and social morbidities, with perinatal outcomes. In the present study, the use of data from the JECS, including Japanese mothers and neonates, made it possible to study multimorbidities. However, this study has several limitations. First, the prevalence of maternal multimorbidity in this study was 6. However, there is no consensus on the definition of maternal multimorbidity or classification system for reporting. The risk of adverse perinatal outcomes may vary depending on the combination of the chronic conditions. Although sensitivity analyses focusing on underweight, obesity, psychiatric disorders and domestic violence demonstrated the association of adverse perinatal outcomes with the presence or absence of each condition, no further detailed studies were conducted because the main aim of this study was not to examine the impact of each chronic condition. Third, some self-reported biases may exist. Self-reported body weight may be underestimated for underweight and overestimated for obesity. This study was insufficient to investigate these severe adverse outcomes. Conducting studies on maternal multimorbidity has been challenging because there is no agreed definition or uniform measurement tool for multimorbidity. Moreover, most studies on multimorbidity conducted in the general population predominantly used questionnaires. As this method was based on self-report, it might present the disadvantage of assigning equal weight to both major and minor chronic conditions. However, our method may have decreased the prevalence of multimorbidities. This study comprised 23 chronic conditions, which included not only physical morbidity, but also psychological and social morbidity. A systematic review of multimorbidity by Fortin et al 3 suggested using a list of at least the 12 most prevalent chronic conditions to conduct studies on multimorbidity. In a previous study by Admon et al 13 on maternal multimorbidity, only seven physical and one social morbidity were defined as chronic conditions, and the prevalence of one chronic condition and multimorbidity was 8. These values are much lower than those of our results. Although it has been controversial which chronic conditions should be included in maternal multimorbidity, our study may have reduced the chance of missing pregnant women at a potential risk of adverse perinatal outcomes. In a study on chronic diseases in pregnant women in Germany, pregnant women with at least one chronic condition had an increased risk of PTB. In maternal multimorbidity, medication during pregnancy may affect perinatal outcomes. The present study defined a physical or psychological condition as one that required medical attention during pregnancy. The study on the exposure to medication for hypertension, diabetes and autoimmune disease during pregnancy reported that the ORs of PTB, LBW and SGA were higher in the antihypertensive and corticosteroid-exposed group compared with those in the unexposed group. Chronic physical conditions such as hypertension, kidney disease, systemic lupus erythematosus and abnormal pre-pregnancy BMI are associated with adverse perinatal outcomes. Additionally, maternal infections, such as HIV, malaria, syphilis and tuberculosis, have been reported to be associated with adverse perinatal outcomes. Although the prevalence of psychiatric disorders was 0. In the present study, domestic violence from intimate partners was the second most frequent chronic condition at Multimorbidity with and without domestic violence was significantly associated with PTB, LBW and SGA, although the point estimate of the aOR for multimorbidity with domestic violence was slightly smaller than the aOR for those without domestic violence in this study. Social morbidity, including domestic violence, has been highlighted as a risk factor associated with adverse perinatal outcomes. The mechanism by which maternal multimorbidity affected perinatal outcomes was not clear in the present study. However, maternal multimorbidity appears to affect perinatal outcomes as both an intermediate and direct factor. For example, abnormal maternal BMI, such as underweight and obesity, is known to be an independent risk factor for PTB. After all, both maternal obesity and pre-eclampsia are regarded as risk factors for PTB. PTB is considered a syndrome initiated by multiple mechanisms, including infection or inflammation, uteroplacental ischaemia or haemorrhage, uterine overdistension, stress and other immunologically mediated processes. The risk of adverse perinatal outcomes tends to increase as the number of chronic maternal conditions increases. Since the number of reproductive-aged women with multimorbidity has been increasing as the maternal population ages, preconception care for maternal multimorbidity is becoming increasingly important. Our findings provide essential information for preconception counselling in women with multimorbidities. All the participants provided written informed consent. We would like to express our gratitude to all the JECS participants and all staff members involved in data collection. We would like to thank Editage www. This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author s and has not been edited for content. Contributors KNakanishi and YSaijo designed the study. KNakanishi and YSaijo conducted the data analysis. KNakanishi drafted the manuscript. YSaijo made critical revisions. YSaijo is responsible for the overall content as guarantor. All authors reviewed and commented on the manuscript. All authors approved the final manuscript. Funding This study was funded by the Ministry of Environment of Japan. Provenance and peer review Not commissioned; externally peer reviewed. Supplemental material This content has been supplied by the author s. Any opinions or recommendations discussed are solely those of the author s and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Skip to main content. Log In More Log in via Institution. Log in via OpenAthens. Log in using your username and password For personal accounts OR managers of institutional accounts. Forgot your log in details? Register a new account? Forgot your user name or password? Search for this keyword. Advanced search. Latest content Archive For authors About Browse by collection. Log in via Institution. Email alerts. Article Text. Article menu. Original research. Abstract Objectives Multimorbidity is defined as the coexistence of two or more chronic physical or psychological conditions within an individual. Data availability statement No data are available. Statistics from Altmetric. Lack of information on the severity of maternal morbidity is a limitation. Introduction Multimorbidity is usually defined as the coexistence of two or more chronic physical or psychological conditions within an individual. Figure 1 Flow diagram of the study participants. Patient and public involvement This study did not involve patients or the public. Maternal and neonatal baseline information Baseline information on the mothers, including educational level, smoking status and alcohol consumption, was collected from self-administered questionnaires applied to the enrolled pregnant women during the second or third trimesters. Exposure: maternal multimorbidity In our study, multimorbidity was defined as the coexistence of two or more physical, psychological or social conditions in an individual according to previous reports. Results Of the fetal records included in this study, 17 View this table: View inline View popup. Discussion In this study, one-third of pregnant women had one or more chronic conditions, and the prevalence of maternal multimorbidity was lower than that in previous studies. Ethics statements Patient consent for publication Not required. Acknowledgments We would like to express our gratitude to all the JECS participants and all staff members involved in data collection. Multimorbidity in general practice: prevalence, incidence, and determinants of co-occurring chronic and recurrent diseases. J Clin Epidemiol ; 51 : — The Academy of Medical Science. A systematic review of prevalence studies on multimorbidity: toward a more uniform methodology. Ann Fam Med ; 10 : — Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet ; : 37 — Association between pre-pregnancy multimorbidity and adverse maternal outcomes: a systematic review. J Multimorb Comorb ; 12 : Causes and consequences of comorbidity: a review. 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PloS One ; 12 : e BMC Public Health ; 14 : J Epidemiol ; 28 : 99 — Measuring multimorbidity beyond counting diseases: systematic review of community and population studies and guide to index choice. BMJ ; : m Burden of physical, psychological and social ill-health during and after pregnancy among women in India, Pakistan, Kenya and Malawi. BMJ Glob Health ; 3 : e Suzuki S. Optimal pre-pregnancy body mass index cut-offs for obesity in Japan. Maternal body mass index and breastfeeding non-initiation and cessation: a quantitative review of the literature. Nutrients ; 12 : Child Abuse Negl ; 90 : — Pharmacy Basel ; 5 : Introduction of the new standard for birth size by gestational ages. J Jpn Pediatr Soc : — Endocrinology TJSfP. Kowarik A , Templ M. Imputation with the R package VIM. J Stat Soft ; 74 : 1 — Missing data imputation using statistical and machine learning methods in a real breast cancer problem. 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BJOG ; : — Impact of maternal pre-pregnancy body mass index on maternal, fetal and neonatal adverse outcomes in the worldwide populations: a systematic review and meta-analysis. Obes Res Clin Pract ; 15 : — OpenUrl CrossRef. Perinatal outcomes in women living with HIV-1 and receiving antiretroviral therapy-a systematic review and meta-analysis. Acta Obstet Gynecol Scand ; : — Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem. Lancet Infect Dis ; 18 : e — Adverse pregnancy outcomes associated with maternal syphilis infection. J Matern Fetal Neonatal Med ; 35 : — Tuberculosis TB in pregnancy - a review. Prevalence and associated factors of common mental disorders in women: a systematic review. Public Health Rev ; 42 : Symptoms of antenatal common mental disorders, preterm birth and low birthweight: a prospective cohort study in a semi-rural district of Vietnam. Trop Med Int Health ; 18 : — Experiences of violence before and during pregnancy and adverse pregnancy outcomes: an analysis of the Canadian maternity experiences survey. BMC Pregnancy Childbirth ; 11 : Maternal prepregnancy body mass index and risk of spontaneous preterm birth. Paediatr Perinat Epidemiol ; 28 : — Clinical risk factors for preeclampsia in the 21st century. Obstet Gynecol ; : — Epidemiology and causes of preterm birth. Lancet ; : 75 — Supplementary materials Supplementary Data This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author s and has not been edited for content. Data supplement 1. Competing interests None declared. Read the full text or download the PDF:. Log in.

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