BJOG Exchange
DOI: 10.1111/1471-0528.12856 www.bjog.org
Risk factors for miscarriage from a prevention perspective: a nationwide follow-up study
Sir, We wish to comment that the recently published article in BJOG by Feodor Nilsson et al. provides meaningful research information in the field of reproductive medicine.1 Pregnancy-related metabolic disorder(s), including spontaneous abortions/miscarriages, are emerging as major public health problem(s) worldwide; therefore, costeffective screening strategies with observational follow-up intervention(s) and/or early identification of modifiable risk factors for precise estimation of a preventable proportion of miscarriages are essential significantly to prevent the increasing burden of adverse pregnancy-related events, including miscarriages in susceptible women. The research group conducted a nationwide observational follow-up study in Danish population (n = 91 427 pregnancies/Danish National Birth Cohort: 1996–2002). The methodology included a large sample size; 88 373 pregnancies had complete clinical/ demographic information on relevant covariates, thereby enhancing the overall study quality. Pre-/post-pregnancyrelated data on modifiable risk factors were collected using computer-assisted telephone interviews/linkage with Danish registers; a comprehensive follow-up of pregnancy outcome proved to be a major study strength, without loss of a significant proportion of Danish women to clinical follow-up(s). Sophisticated sta-
tistical tools, primarily multiple Cox regression analysis, were used in the study for estimation of population attributable fractions/identification of modifiable risk factors. The main study outcome measure was miscarriage before 22 completed weeks of gestation; interestingly, age ≥30 years at conception, underweight and obesity were pre-pregnant risk factors associated with increased risk of miscarriage, whereas alcohol consumption, excess daily weight lifting (>20 kg) and night work were modifiable risk factors during pregnancy. The findings demonstrated that 25.2% of the miscarriages might be prevented by overall reduction of these risk factors. Risk of miscarriages before and during pregnancy may be reduced to 14.7 and 12.5%, respectively, by modification of risk factors. We would like to suggest that the authors could have included more risk-/ co-factors such as blood type(s), presence of genital tuberculosis (multiplex-DNA PCR detection for Mycobacterium tuberculi) and/or human papillomavirus infection (FDA-approved Hybrid Capture-2 assay for HPV titre evaluation and HPV detection), blood pressure, caffeine, tobacco status (active/passive smoker/tobacco chewer), endometrial thickness and anti-Mullerian hormone/Mullerian inhibiting substance (AMH/MIS) levels of Danish women before and during pregnancy. Furthermore, use of smokeless tobacco during pregnancy had adverse effect on the woman’s reproductive physiology and the pregnancy outcome.2 Altered AMH/MIS levels
ª 2014 Royal College of Obstetricians and Gynaecologists
were reportedly associated with diminished ovarian reserve,3 thus predisposing reproductive age women to adverse pregnancy outcomes, including miscarriages and/or clinical infertility. Future epidemiological research could use a multicentre cohort-based intervention with face-to-face questionnaire-based interviews for unbiased risk assessment, along with trimester-based biochemical evaluation(s) of maternal serum biomarkers and uterine artery Doppler imaging as possible valuable predictive factors governing pregnancy outcomes, including prediction/prevention of miscarriages in women of ethnically disparate populations. & References 1 Feodor Nilsson S, Andersen PK, Strandberg-Larsen K, Nybo Andersen A-M. Risk factors for miscarriage from a prevention perspective: a nationwide follow-up study. BJOG 2014;121:1375–85. 2 Kumar S. Tobacco and areca nut chewing-reproductive impairments: an overview. Reprod Toxicol 2013;36:12–17. 3 Seifer DB, Baker VL, Leader B. Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril 2011; 95:747–50.
S Pandeya,b & R Tyagia,c a
Infertility Clinic/Laboratory, Javitri Hospital & Test-tube Baby Centre, Lucknow, U.P., India bDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA cInfertility & Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
Accepted 15 March 2014. DOI: 10.1111/1471-0528.12856
1439
DOI: 10.1111/1471-0528.12856 www.bjog.org
Risk factors for miscarriage from a prevention perspective: a nationwide follow-up study
Sir, We wish to comment that the recently published article in BJOG by Feodor Nilsson et al. provides meaningful research information in the field of reproductive medicine.1 Pregnancy-related metabolic disorder(s), including spontaneous abortions/miscarriages, are emerging as major public health problem(s) worldwide; therefore, costeffective screening strategies with observational follow-up intervention(s) and/or early identification of modifiable risk factors for precise estimation of a preventable proportion of miscarriages are essential significantly to prevent the increasing burden of adverse pregnancy-related events, including miscarriages in susceptible women. The research group conducted a nationwide observational follow-up study in Danish population (n = 91 427 pregnancies/Danish National Birth Cohort: 1996–2002). The methodology included a large sample size; 88 373 pregnancies had complete clinical/ demographic information on relevant covariates, thereby enhancing the overall study quality. Pre-/post-pregnancyrelated data on modifiable risk factors were collected using computer-assisted telephone interviews/linkage with Danish registers; a comprehensive follow-up of pregnancy outcome proved to be a major study strength, without loss of a significant proportion of Danish women to clinical follow-up(s). Sophisticated sta-
tistical tools, primarily multiple Cox regression analysis, were used in the study for estimation of population attributable fractions/identification of modifiable risk factors. The main study outcome measure was miscarriage before 22 completed weeks of gestation; interestingly, age ≥30 years at conception, underweight and obesity were pre-pregnant risk factors associated with increased risk of miscarriage, whereas alcohol consumption, excess daily weight lifting (>20 kg) and night work were modifiable risk factors during pregnancy. The findings demonstrated that 25.2% of the miscarriages might be prevented by overall reduction of these risk factors. Risk of miscarriages before and during pregnancy may be reduced to 14.7 and 12.5%, respectively, by modification of risk factors. We would like to suggest that the authors could have included more risk-/ co-factors such as blood type(s), presence of genital tuberculosis (multiplex-DNA PCR detection for Mycobacterium tuberculi) and/or human papillomavirus infection (FDA-approved Hybrid Capture-2 assay for HPV titre evaluation and HPV detection), blood pressure, caffeine, tobacco status (active/passive smoker/tobacco chewer), endometrial thickness and anti-Mullerian hormone/Mullerian inhibiting substance (AMH/MIS) levels of Danish women before and during pregnancy. Furthermore, use of smokeless tobacco during pregnancy had adverse effect on the woman’s reproductive physiology and the pregnancy outcome.2 Altered AMH/MIS levels
ª 2014 Royal College of Obstetricians and Gynaecologists
were reportedly associated with diminished ovarian reserve,3 thus predisposing reproductive age women to adverse pregnancy outcomes, including miscarriages and/or clinical infertility. Future epidemiological research could use a multicentre cohort-based intervention with face-to-face questionnaire-based interviews for unbiased risk assessment, along with trimester-based biochemical evaluation(s) of maternal serum biomarkers and uterine artery Doppler imaging as possible valuable predictive factors governing pregnancy outcomes, including prediction/prevention of miscarriages in women of ethnically disparate populations. & References 1 Feodor Nilsson S, Andersen PK, Strandberg-Larsen K, Nybo Andersen A-M. Risk factors for miscarriage from a prevention perspective: a nationwide follow-up study. BJOG 2014;121:1375–85. 2 Kumar S. Tobacco and areca nut chewing-reproductive impairments: an overview. Reprod Toxicol 2013;36:12–17. 3 Seifer DB, Baker VL, Leader B. Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril 2011; 95:747–50.
S Pandeya,b & R Tyagia,c a
Infertility Clinic/Laboratory, Javitri Hospital & Test-tube Baby Centre, Lucknow, U.P., India bDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA cInfertility & Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
Accepted 15 March 2014. DOI: 10.1111/1471-0528.12856
1439
