Multi-omics and machine learning for the prevention and management of female reproductive health

Females typically carry most of the burden of reproduction in mammals. In humans, this burden is exacerbated further, as the evolutionary advantage of a large and complex human brain came at a great cost of women’s reproductive health. Pregnancy thus became a highly demanding phase in a woman’s life cycle both physically and emotionally and therefore needs monitoring to assure an optimal outcome. Moreover, an increasing societal trend towards reproductive complications partly due to the increasing maternal age and global obesity pandemic demands closer monitoring of female reproductive health. This review first provides an overview of female reproductive biology and further explores utilization of large-scale data analysis and -omics techniques (genomics, transcriptomics, proteomics, and metabolomics) towards diagnosis, prognosis, and management of female reproductive disorders. In addition, we explore machine learning approaches for predictive models towards prevention and management. Furthermore, mobile apps and wearable devices provide a promise of continuous monitoring of health. These complementary technologies can be combined towards monitoring female (fertility-related) health and detection of any early complications to provide intervention solutions. In summary, technological advances (e.g., omics and wearables) have shown a promise towards diagnosis, prognosis, and management of female reproductive disorders. Systematic integration of these technologies is needed urgently in female reproductive healthcare to be further implemented in the national healthcare systems for societal benefit.publishedVersio

Prediction of Concurrent Hypertensive Disorders in Pregnancy and Gestational Diabetes Mellitus Using Machine Learning Techniques

Gestational diabetes mellitus and hypertensive disorders in pregnancy are serious maternal health conditions with immediate and lifelong mother-child health consequences. These obstetric pathologies have been widely investigated, but mostly in silos, while studies focusing on their simultaneous occurrence rarely exist. This is especially the case in the machine learning domain. This retrospective study sought to investigate, construct, evaluate, compare, and isolate a supervised machine learning predictive model for the binary classification of co-occurring gestational diabetes mellitus and hypertensive disorders in pregnancy in a cohort of otherwise healthy pregnant women. To accomplish the stated aims, this study analyzed an extract (n=4624, n_features=38) of a labelled maternal perinatal dataset (n=9967, n_fields=79) collected by the PeriData.Net® database from a participating community hospital in Southeast Wisconsin between 2013 and 2018. The datasets were named, “WiseSample” and “WiseSubset” respectively in this study. Thirty-three models were constructed with the six supervised machine learning algorithms explored on the extracted dataset: logistic regression, random forest, decision tree, support vector machine, StackingClassifier, and KerasClassifier, which is a deep learning classification algorithm; all were evaluated using the StratifiedKfold cross-validation (k=10) method. The Synthetic Minority Oversampling Technique was applied to the training data to resolve the class imbalance that was noted in the sub-sample at the preprocessing phase. A wide range of evidence-based feature selection techniques were used to identify the best predictors of the comorbidity under investigation. Multiple model performance evaluation metrics that were employed to quantitatively evaluate and compare model performance quality include accuracy, F1, precision, recall, and the area under the receiver operating characteristic curve. Support Vector Machine objectively emerged as the most generalizable model for identifying the gravidae in WiseSubset who may develop concurrent gestational diabetes mellitus and hypertensive disorders in pregnancy, scoring 100.00% (mean) in recall. The model consisted of 9 predictors extracted by the recursive feature elimination with cross-validation with random forest. Finding from this study show that appropriate machine learning methods can reliably predict comorbid gestational diabetes and hypertensive disorders in pregnancy, using readily available routine prenatal attributes. Six of the nine most predictive factors of the comorbidity were also in the top 6 selections of at least one other feature selection method examined. The six predictors are healthy weight prepregnancy BMI, mother’s educational status, husband’s educational status, husband’s occupation in one year before the current pregnancy, mother’s blood group, and mother’s age range between 34 and 44 years. Insight from this analysis would support clinical decision making of obstetric experts when they are caring for 1.) nulliparous women, since they would have no obstetric history that could prompt their care providers for feto-maternal medical surveillance; and 2.) the experienced mothers with no obstetric history suggestive of any of the disease(s) under this study. Hence, among other benefits, the artificial-intelligence-backed tool designed in this research would likely improve maternal and child care quality outcomes

Stillbirth risk prediction using machine learning for a large cohort of births from Western Australia, 1980–2015

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression

Stillbirth risk prediction using machine learning for a large cohort of births from Western Australia, 1980–2015

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression

Clinical risk modelling with machine learning: adverse outcomes of pregnancy

As a complex biological process, there are various health issues that are related to pregnancy. Prenatal care, a type of preventative healthcare at different points in gestation is comprised of management, treatment, and mitigation of such issues. This also includes risk prediction for adverse pregnancy outcomes, where probabilistic modelling is used to calculate individual’s risk at the early stages of pregnancy. This type of modelling can have a definite clinical scope such as in prenatal screening, and an educational aim where awareness of a healthy lifestyle is promoted, such as in health education. Currently, the most used models are based on traditional statistical approaches, as they provide sufficient predictive power and are easily interpreted by clinicians. Machine learning, a subfield of data science, contains methods for building probabilistic models with multidimensional data. Compared to existing prediction models related to prenatal care, machine learning models can provide better results by fitting more intricate nonlinear decision boundary areas, improve data-driven model fitting by generating synthetic data, and by providing more automation for routine model adjustment processes. This thesis presents the evaluation of machine learning methods to prenatal screening and health education prediction problems, along with novel methods for generating synthetic rare disorder data to be used for modelling, and an adaptive system for continuously adjusting a prediction model to the changing patient population. This way the thesis addresses all the four main entities related to predicting adverse outcomes of pregnancy: the mother or patient, the clinician, the screening laboratory and the developer or manufacturer of screening materials and systems.Kliinisen riskin mallinnus koneoppimismenetelmin: raskaudelle haitalliset lopputulemat Raskaus on kompleksinen biologinen prosessi, jonka etenemiseen liittyy useita terveysongelmia. Äitiyshoito voidaan kuvata ennalta ehkäiseväksi terveydenhuolloksi, jossa pyritään käsittelemään, hoitamaan ja lievittämään kyseisiä ongelmia. Tähän hoitoon sisältyy myös raskauden haitallisten lopputulemien riskilaskenta, missä probabilistista mallinnusta hyödynnetään määrittämään yksilön riski raskauden varhaisissa vaiheissa. Tällä mallinnuksella voi olla selkeä kliininen tarkoitus kuten prenataaliseulonta, tai terveyssivistyksellinen tarkoitus missä odottavalle äidille esitellään raskauden kannalta terveellisiä elämäntapoja. Tällä hetkellä eniten käytössä olevat ennustemallit perustuvat perinteiseen tilastolliseen mallinnukseen, sille ne tarjoavat riittävän ennustetehokkuuden ja ovat helposti tulkittavissa. Koneoppiminen on datatieteen osa-alue, joka pitää sisällään menetelmiä millä voidaan mallintaa moniulotteista dataa ennustekäyttöön. Verrattuna olemassa oleviin äitiyshoidon ennustemalleihin, koneoppiminen mahdollistaa parempien ennustetulosten tuottamisen sovittamalla hienojakoisempia epälineaarisia päätösalueita, tehostamalla datakeskeisten mallien sovitusta luomalla synteettisiä havaintoja ja tarjoamalla enemmän automaatiota rutiininomaiseen mallien hienosäätöön. Tämä väitös esittelee koneoppimismenetelmien evaluaation prenataaliseulonta-ja terveyssivistysongelmiin, ja uusia menetelmiä harvinaisten sairauksien datan luomiseen mallinnustarkoituksiin ja jatkuvan ennustemallin hienosäätämisen järjestelmän muuttuvia potilaspopulaatiota varten. Näin väitös käy läpi kaikki neljä asianomaista jotka liittyvät haitallisten lopputulemien ennustamiseen: odottava äiti eli potilas, kliinikko, seulontalaboratorio ja seulonnassa käytettävien materiaalien ja järjestelmien kehittäjä tai valmistaja

Machine Learning in Fetal Cardiology: What to Expect

In fetal cardiology, imaging (especially echocardiography) has demonstrated to help in the diagnosis and monitoring of fetuses with a compromised cardiovascular system potentially associated with several fetal conditions. Different ultrasound approaches are currently used to evaluate fetal cardiac structure and function, including conventional 2-D imaging and M-mode and tissue Doppler imaging among others. However, assessment of the fetal heart is still challenging mainly due to involuntary movements of the fetus, the small size of the heart, and the lack of expertise in fetal echocardiography of some sonographers. Therefore, the use of new technologies to improve the primary acquired images, to help extract measurements, or to aid in the diagnosis of cardiac abnormalities is of great importance for optimal assessment of the fetal heart. Machine leaning (ML) is a computer science discipline focused on teaching a computer to perform tasks with specific goals without explicitly programming the rules on how to perform this task. In this review we provide a brief overview on the potential of ML techniques to improve the evaluation of fetal cardiac function by optimizing image acquisition and quantification/segmentation, as well as aid in improving the prenatal diagnoses of fetal cardiac remodeling and abnormalities

Using Machine Learning to Predict Complications in Pregnancy:A Systematic Review

Introduction: Artificial intelligence is widely used in medical field, and machine learning has been increasingly used in health care, prediction, and diagnosis and as a method of determining priority. Machine learning methods have been features of several tools in the fields of obstetrics and childcare. This present review aims to summarize the machine learning techniques to predict perinatal complications. Objective: To identify the applicability and performance of machine learning methods used to identify pregnancy complications. Methods: A total of 98 articles were obtained with the keywords “machine learning,” “deep learning,” “artificial intelligence,” and accordingly as they related to perinatal complications (“complications in pregnancy,” “pregnancy complications”) from three scientific databases: PubMed, Scopus, and Web of Science. These were managed on the Mendeley platform and classified using the PRISMA method. Results: A total of 31 articles were selected after elimination according to inclusion and exclusion criteria. The features used to predict perinatal complications were primarily electronic medical records (48%), medical images (29%), and biological markers (19%), while 4% were based on other types of features, such as sensors and fetal heart rate. The main perinatal complications considered in the application of machine learning thus far are pre-eclampsia and prematurity. In the 31 studies, a total of sixteen complications were predicted. The main precision metric used is the AUC. The machine learning methods with the best results were the prediction of prematurity from medical images using the support vector machine technique, with an accuracy of 95.7%, and the prediction of neonatal mortality with the XGBoost technique, with 99.7% accuracy. Conclusion: It is important to continue promoting this area of research and promote solutions with multicenter clinical applicability through machine learning to reduce perinatal complications. This systematic review contributes significantly to the specialized literature on artificial intelligence and women’s health

Prediction Models for Intrauterine Growth Restriction Using Artificial Intelligence and Machine Learning: A Systematic Review and Meta-Analysis

Background: IntraUterine Growth Restriction (IUGR) is a global public health concern and has major implications for neonatal health. The early diagnosis of this condition is crucial for obtaining positive outcomes for the newborn. In recent years Artificial intelligence (AI) and machine learning (ML) techniques are being used to identify risk factors and provide early prediction of IUGR. We performed a systematic review (SR) and meta-analysis (MA) aimed to evaluate the use and performance of AI/ML models in detecting fetuses at risk of IUGR. Methods: We conducted a systematic review according to the PRISMA checklist. We searched for studies in all the principal medical databases (MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane). To assess the quality of the studies we used the JBI and CASP tools. We performed a meta-analysis of the diagnostic test accuracy, along with the calculation of the pooled principal measures. Results: We included 20 studies reporting the use of AI/ML models for the prediction of IUGR. Out of these, 10 studies were used for the quantitative meta-analysis. The most common input variable to predict IUGR was the fetal heart rate variability (n = 8, 40%), followed by the biochemical or biological markers (n = 5, 25%), DNA profiling data (n = 2, 10%), Doppler indices (n = 3, 15%), MRI data (n = 1, 5%), and physiological, clinical, or socioeconomic data (n = 1, 5%). Overall, we found that AI/ML techniques could be effective in predicting and identifying fetuses at risk for IUGR during pregnancy with the following pooled overall diagnostic performance: sensitivity = 0.84 (95% CI 0.80–0.88), specificity = 0.87 (95% CI 0.83–0.90), positive predictive value = 0.78 (95% CI 0.68–0.86), negative predictive value = 0.91 (95% CI 0.86–0.94) and diagnostic odds ratio = 30.97 (95% CI 19.34–49.59). In detail, the RF-SVM (Random Forest–Support Vector Machine) model (with 97% accuracy) showed the best results in predicting IUGR from FHR parameters derived from CTG. Conclusions: our findings showed that AI/ML could be part of a more accurate and cost-effective screening method for IUGR and be of help in optimizing pregnancy outcomes. However, before the introduction into clinical daily practice, an appropriate algorithmic improvement and refinement is needed, and the importance of quality assessment and uniform diagnostic criteria should be further emphasized