Risk score to stratify miscarriage risk levels in preconception women

www.nature.com/scientificreports OPEN Risk score to stratify miscarriage risk levels in preconception women Xin Hui Choo1,16, Chee Wai Ku2,3,16, Yin Bun Cheung4,5, Keith M. Godfrey6,7, Yap‑Seng Chong1,8, Lynette Pei‑Chi Shek9,10, Kok Hian Tan2,11, Thiam Chye Tan3, Sadhana Nadarajah12, Fabian Kok Peng Yap2,13, Marjorelee T. Colega8, Mary Foong‑Fong Chong8,14, Shiao‑Yng Chan8,15, See Ling Loy2,12,16* & Jerry Kok Yen Chan2,12,16* Spontaneous miscarriage is one of the most common complications of pregnancy. Even though some risk factors are well documented, there is a paucity of risk scoring tools during preconception. In the S-PRESTO cohort study, Asian women attempting to conceive, aged 18-45 years, were recruited. Multivariable logistic regression model coefficients were used to determine risk estimates for age, ethnicity, history of pregnancy loss, body mass index, smoking status, alcohol intake and dietary supplement intake; from these we derived a risk score ranging from 0 to 17. Miscarriage before 16 weeks of gestation, determined clinically or via ultrasound. Among 465 included women, 59 had miscarriages and 406 had pregnancy ≥ 16 weeks of gestation. Higher rates of miscarriage were observed at higher risk scores (5.3% at score ≤ 3, 17.0% at score 4–6, 40.0% at score 7–8 and 46.2% at score ≥ 9). Women with scores ≤ 3 were defined as low-risk level (< 10% miscarriage); scores 4–6 as intermediate-risk level (10% to < 40% miscarriage); scores ≥ 7 as high-risk level (≥ 40% miscarriage). The risk score yielded an area under the receiver-operating-characteristic curve of 0.74 (95% confidence interval 0.67, 0.81; p < 0.001). This novel scoring tool allows women to self-evaluate their miscarriage risk level, which facilitates lifestyle changes to optimize modifiable risk factors in the preconception period and reduces risk of spontaneous miscarriage. Spontaneous miscarriage is one of the most common complications of pregnancy, occurring in 12–26% of recognized pregnancies1. Spontaneous miscarriage is multifactorial in aetiology, with biological, environmental, obstetric and lifestyle factors being shown to play a r ole2. Chromosomal aberrations, such as aneuploidies, account for up to 40–50% of all miscarriages3. To effectively reduce or prevent spontaneous miscarriage, studies have emphasized the importance of assessing risk factors which are modifiable—namely lifestyle and behavioural factors4–6. These include pre-pregnancy underweight, overweight or obesity, cigarette smoking, alcohol intake, caffeine intake and lack of dietary supplementation, such as folic acid and multivitamins, which have been found 1 Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119228, Singapore. 2Duke-NUS Medical School, Singapore 169857, Singapore. 3Department of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital, Singapore 229899, Singapore. 4Program in Health Services & Systems Research and Center for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857, Singapore. 5Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University, 33014 Tampere, Finland. 6Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton SO16 6YD, UK. 7National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton SO16 6YD, UK. 8Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore 117609, Singapore. 9Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119228, Singapore. 10Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, National University Health System, Singapore 119074, Singapore. 11Department of Maternal Fetal Medicine, KK Women’s and Children’s Hospital, Singapore 229899, Singapore. 12Department of Reproductive Medicine, KK Women’s and Children’s Hospital, 100, Bukit Timah, Singapore 229899, Singapore. 13Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore 229899, Singapore. 14Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore 117549, Singapore. 15Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119228, Singapore. 16These authors contributed equally: Xin Hui Choo, Chee Wai Ku, See Ling Loy and Jerry Kok Yen Chan. *email: ; Scientific Reports | (2021) 11:12111 | https://doi.org/10.1038/s41598-021-91567-8 1 Vol.:(0123456789) www.nature.com/scientificreports/ to increase the risk of m iscarriage2,4,7. Shift work, particularly night shifts, and occupations requiring heavy lifting, have also been shown to increase the risk of miscarriage8,9. Most studies that assessed pre- or early-pregnancy risk factors contributing to miscarriage were conducted during early pregnancy1,10,11. Recall bias could be a confounding factor especially in determining pre-pregnancy information. Given that most miscarriages occur in the early weeks of gestation, sometimes even before women recognize that they are p regnant1, evaluation of these factors in early pregnancy might be too late for any intervention or treatment to have an impact on the miscarriage outcome. This highlights the need to identify at-risk women prior to pregnancy for appropriate risk-modifying interventions. To date, relevant studies conducted during the preconception period have been l imited12–16. These studies mainly focused on identifying individual risk factors for miscarriage, but not on defining the overall risk level based on the presence of multiple risk factors. Understanding the risk level (e.g. low-, intermediate-, high-risk) facilitates the design of cost-effective targeted interventions with varied intensity for those in different risk g roups17. Using data from the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) prospective cohort study, we aimed to develop a risk score based on a set of preconception maternal risk factors, which could be used to identify the risk levels for miscarriage among women planning to conceive. These risk factors were easily understood, readily available and did not require invasive procedures, thus increasing its acceptability and accessibility to all women of reproductive age. Most importantly, priority was given to lifestyle and behavioural factors which were modifiable, making this an attractive initiative for implementation in the general population. Methods Study participants. Between February 2015 and October 2017, 1032 women planning to conceive within the next 12 months were recruited from the general population of Singapore. Part (...truncated)