Design and Evaluation of a Postpartum Depression Ontology

Abstract

Objective Postpartum depression (PPD) remains an understudied research area despite its high prevalence. The goal of this study is to develop an ontology to aid in the identification of patients with PPD and to enable future analyses with electronic health record (EHR) data.

Methods We used Protégé-OWL to construct a postpartum depression ontology (PDO) of relevant comorbidities, symptoms, treatments, and other items pertinent to the study and treatment of PPD.

Results The PDO identifies and visualizes the risk factor status of variables for PPD, including comorbidities, confounders, symptoms, and treatments. The PDO includes 734 classes, 13 object properties, and 4,844 individuals. We also linked known and potential risk factors to their respective codes in the International Classification of Diseases versions 9 and 10 that would be useful in structured EHR data analyses. The representation and usefulness of the PDO was assessed using a task-based patient case study approach, involving 10 PPD case studies. Final evaluation of the ontology yielded 86.4% coverage of PPD symptoms, treatments, and risk factors. This demonstrates strong coverage of the PDO for the PPD domain.

Conclusion The PDO will enable future researchers to study PPD using EHR data as it contains important information with regard to structured (e.g., billing codes) and unstructured data (e.g., synonyms of symptoms not coded in EHRs). The PDO is publicly available through the National Center for Biomedical Ontology (NCBO) BioPortal ( https://bioportal.bioontology.org/ontologies/PARTUMDO ) which will enable other informaticists to utilize the PDO to study PPD in other populations.

Keywords

ontology - knowledge representation - postpartum - depression - women's health

Background and Significance

Importance and Prevalence of Postpartum Depression

While approximately 15 to 85% of women experience the “baby blues” or some form of sadness in the 2 weeks following delivery,[1] postpartum depression (PPD) is a more severe and longer lasting mental illness that is detrimental to both the mother and newborn. PPD is classified as an episode of major depressive disorder (MDD) that can occur up to 12 months after childbirth,[2] and it affects approximately 10 to 20% of mothers.[3] [4] While unexplained crying and general sadness are common symptoms, PPD can produce more severe consequences such as feelings of hopelessness, intense anxiety,[5] suicidal ideation, thoughts about harming the baby,[6] and mother–infant bonding challenges that can affect the child's future development.[5]

Need for Increased Research on Risk Factors Underlying Postpartum Depression

The PPD field includes a considerable amount of risk factor research, with the strongest identified factors being a history of depression, anxiety during pregnancy, and depression during pregnancy;[7] however, due to the large number of variables involved in pregnancy and birth, numerous factors are understudied or not researched at all. Many risk factors, such as preeclampsia[7] [8] [9] [10] and Cesarean section,[7] [8] [9] [10] [11] lack a consensus, with separate studies reporting mixed levels of significance. Additionally, several studies[12] [13] [14] do not adjust for important confounding variables, such as a history of psychiatric illness, and therefore reduce the generalizability and usefulness of the results. Furthermore, due to the stigma associated with mental illness disclosure, studies may also suffer from recruitment or follow-up difficulties.[15] Despite electronic health record (EHR) research promoting investigation of a variety of confounding variables, assembly of large cohorts, assessment of associations among risk factor subgroups (e.g., types of Cesarean sections), and avoidance of challenges in study recruitment and follow-up,[15] very few PPD papers have utilized EHRs. Thus, it is necessary to improve PPD risk factor research by expanding the use of EHRs.

Ontologies Are Useful for Large-Research Consortiums

Large research consortiums exist, including the Observational Health Data Sciences and Informatics consortium (OHDSI; https://www.ohdsi.org/ ) along with several recent novel coronavirus disease 2019 (COVID-19)-specific consortiums such as N3C ( https://ncats.nih.gov/n3c ). While a separate initiative, N3C utilizes the same Common Data Model that OHDSI utilizes in their consortium. These consortiums are great in providing standard methods to translate individual hospital record systems into a shareable and easily computable framework that enables queries and more complex scripts to run across multiple sites simultaneously. However, these consortiums do not provide disease-specific ontology information or methods for extracting relevant patients for particular diseases, they merely provide concept sets. These concept sets include information that is largely derived from the Systematized Nomenclature of Medicine–Clinical Terms (SNOMED CT) ontology framework. They do not contain links to relevant comorbidities or diseases often confused with the disease of interest. However, a well-defined ontology would provide not only the disease codes and concepts needed to extract relevant patients but also the links and relationships between these concepts. Ideally, it would also contain relevant risk factors specific to the disease of interest.

Purpose of This Study

To support clinicians in screening for and treating patients with PPD, we aim to characterize the important clinical facets of PPD by demonstrating the relationships among confirmed (known) and potential risk factors, symptoms, comorbidities, and treatments in an ontology. We also link relevant International Classification of Diseases (ICD) code sets corresponding to the PPD risk factors to enable researchers to easily identify them in their EHR cohorts. We use a task-based approach to validate our ontology by considering whether it can identify the PPD risk factors, symptoms, and treatments present in 10 case studies of PPD patients derived from web sites,[16] [17] magazines,[18] and blogs.[19] [20] [21] [22] [23] However, we are not limited to just code sets. We also include noncore information, such as age, parity, and other relevant nondiagnostic code comorbidities, and risk factors that should be included in any PPD study.

Methods

The methods for this ontology include four parts as follows: (1) determination of the ontology's scope and survey of the literature, (2) review of existing ontologies related to PPD and evaluation of their usability in the ontology, (3) representation of the PPD knowledge base, and (4) evaluation of the ontology for correctness and usefulness. The target population for this postpartum depression ontology (PDO) includes researchers interested in using EHRs to investigate maternal mental health and medical professionals hoping to improve PPD screening and diagnosis.

Ontology Scope and Survey of the Literature

To determine the scope of the PDO, we conducted a survey of the PPD literature based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines[24] using PubMed and Google Scholar ([Fig. 1]). Although the PRISMA format is used, numbers are not included in [Fig. 1] because the total number of reviewed papers varied by each risk factor investigated; moreover, this was not a comprehensive systematic review or meta-analysis, but a survey of the literature for the purposes of constructing our ontology. We screened titles and abstracts of studies for conditions and their relationship to PPD or depression, then assessed each condition against the criteria for determining confirmed versus potential PPD risk factors which are delineated in [Fig. 2]. Eligibility for consideration as a confirmed PPD risk factor was determined by adjustment for important confounders; when the study was not a meta-analysis, systematic review or literature review, papers had to adjust for a history or experience during pregnancy of psychiatric illness, either prior to or during pregnancy. Confirmed risk factor papers were further required to find a statistically significant increased risk of PPD at p < 0.05 and/or an effect size that was moderate (>0.30)[25] postadjustment, include a comparison group, and have a general consensus in the field regarding the condition's relationship with PPD. In contrast, eligibility for consideration as a potential PPD risk factor from the literature survey required a statistically significant association between the condition and either PPD or depression. We noted that postnatal surveys were often given to women which introduced the potential for recall bias; however, their reported symptoms and risk factors were corroborated in other papers and case studies, leading to their inclusion in risk factor determination. Following initial review, full-text retrieval and an additional round of review followed. Studies were then synthesized to classify the risk factors.

Fig. 1 Flow diagram of paper selection process for papers involved in postpartum depression (PPD). There were many risk factors for PPD and therefore each risk factor (i.e., labeled as [Condition] in [Fig. 1]) was searched to identify further information with regards to PPD risk factor status. This step was conducted primarily because research of certain PPD risk factors is scant and the field can change over time; therefore, we wanted the most up-to-date and relevant information with regards to PPD risk factor status. We have not included numbers in [Fig. 1] because the total number of reviewed papers varies by each confirmed and potential risk factor that we investigated. The criteria for delineating confirmed versus potential PPD risk factors is further described in [Fig. 2] with paper count cutoffs.

Fig. 2 Criteria used to determine postpartum depression (PPD) risk factor status. In [Fig. 2], the eligibility criteria for a condition's consideration as a confirmed or potential PPD risk factor is shown. All confirmed risk factor papers had to adjust for psychiatric illness, either prior to or during pregnancy, excluding meta-analyses, systematic reviews and literature reviews. In determining whether to include these latter studies, three considerations were made: (1) at least one other source had to adjust for a history or experience during pregnancy of psychiatric illness, (2) these studies had a level of influence in their field as determined by citations numbering above and often beyond 200, and (3) the first authors were influential in their field with h-indexes above 40.

After identifying confirmed and potential PPD risk factors, we categorized them into four different types as follows: (1) mental condition related, (2) pregnancy or birth related, (3) instability mediated by outside factor related, and/or (4) other body condition related. Mental condition–related risk factors included mental illness diagnoses, as well as perceptions of self or others. Pregnancy- or birth-related risk factors included any complications or difficulties related to the pregnancy and delivery, while instability mediated by outside factor–related risk factors included conditions at least partially outside the mother's control such as socioeconomic status and abuse. Finally, unclassifiable risk factors were categorized as other body condition-related which included nonpregnancy issues such as asthma. Polyhierarchical modeling was used to create the ontology, allowing risk factors to be categorized as multiple risk types.

Review of Existing Ontologies in the Postpartum Depression Domain

A useful ontology must be accessible for different groups and applications,[26] so we first reviewed existing ontologies for reuse. We used the National Center for Biomedical Ontology (NCBO) BioPortal ( https://bioportal.bioontology.org/ ), Ontobee ( http://www.ontobee.org/ ), Open Biological and Biomedical Ontology Service ( http://www.obofoundry.org/ ), AberOWL ( http://aber-owl.net/#/ ), Ontology Search ( https://www.ebi.ac.uk/ols/index ), and Protégé Ontology Library ( https://protegewiki.stanford.edu/wiki/Protege_Ontology_Library ) to examine ontologies and ontology classes related to PPD. We evaluated these ontologies for their coverage of the PPD domain, as well as their ability to characterize PPD risk factors and symptoms.

More than 110 vocabulary resources were found that included depression-related classes but were not specific to PPD at the ontology level. We included information from the five most relevant sources in the PPD domain in [Table 1]. Of the vocabulary resources identified, few included PPD entries, and most entries lacked detail, further demonstrating the need to develop a PDO.

Table 1 Relevance of existing ontologies to the PPD domain

Resource	Type of resource	PPD knowledge	Suitability to characterize PPD risk factors and symptoms	Relevance to this ontology
International Classification of Diseases, version 9-clinical modification (ICD-9-CM)	Clinical terminology	Limited coverage with no PPD-specific code, 16 MDD codes, and some symptom codes	Vague definitions and lack of codes designated for PPD limit the usefulness for characterizing PPD without clinical notes. No risk factor relationships are included	Terms in the ontology will map to ICD-9 codes
International Classification of Diseases, version 10-clinical modification (ICD-10-CM)	Clinical terminology	Reasonable coverage with 1 PPD-specific code, 22 MDD codes, and some symptom codes	Designated PPD code and many detailed MDD codes better characterize PPD as compared with ICD-9-CM. No risk factor relationships are included	Terms in the ontology will map to ICD-10 codes
Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT)	Ontology	Comprehensive coverage of MDD, maternal mental disorders, and symptoms	Suitable for ontology terms related to PPD, but conditions and symptoms are spread across the ontology No risk factor relationships are included	Terms in the ontology will map to SNOMED CT terms
Psychology Ontology (APAONTO)	Thesaurus	Limited coverage with 1 PPD entry and 1 MDD entry	Disorganized alphabetical list of psychology terms constitutes APA thesaurus. Includes definitions of depressive disorders. No risk factor relationships are included	Terms in the ontology will map to APAONTO terms
MedlinePlus Health Topics (MEDLINEPLUS)	Ontology	Limited coverage with 1 PPD entry and 28 mappings of that term	Disorganized hierarchy of health topics with annotated definitions. Does not provide more details for conditions beyond definitions. No risk factor relationships are included	Mappings to other ontologies suggest mappings for PDO

Abbreviations: APA, American Psychological Association; MDD, major depressive disorder; PDO, postpartum depression ontology; PPD, postpartum depression.

Given the lack of focus on PPD in these resources and our specific target population of EHR researchers and medical professionals, we created an ontology separate from other existing resources to best fit researchers' and medical professionals' needs. The five most relevant sources in [Table 1] were used to organize the ontology and will help to standardize future versions through mappings to established ontologies such as SNOMED CT ( https://www.nlm.nih.gov/healthit/snomedct/index.html ), a source commonly used in constructing ontologies representative of EHR data.[27]

Protégé-OWL Representation of the Postpartum Depression Knowledge Base

The PDO was written in the Web Ontology Language (OWL) using the application Protégé-OWL v.5.5.0.[28] The initial ontology was built considering pregnancy- and mental health–related ICD codes, as well as ICD codes for PPD risk factors. Symptoms of PPD included in the initial ontology were obtained from the literature review by Stewart et al.[29] Updated versions of the ontology postevaluation included treatments and other PPD-related variables.

[Supplementary Table S1] (available in the online version) includes the descriptions of the PDO's three main superclasses, as well as examples of important pregnancy, and mental health subclasses in each hierarchy. In the PDO, each class that was a confirmed or potential risk factor included the relevant ICD-9 and -10 codes as individuals. Although the ICD-10-clinical modification (CM) clinical terminology defined ICD codes as classes, they had only one logical parent class, whereas ICD codes in the PDO had relationships with multiple parent classes and therefore necessitated multiple inheritance; thus, ICD codes were designated as individuals in this ontology.

Evaluation of the Ontology for Correctness and Usefulness

The ontology was evaluated for correctness of ontology form, domain knowledge, and usability. Ontology form was evaluated using the Pellet reasoner in Protégé-OWL, while domain knowledge and usability were assessed through case review by two domain experts (R.B.M. and M.R.B.). Ten patient case studies from eight online sources were compiled,[16] [17] [18] [19] [20] [21] [22] [23] describing women presenting with various PPD phenotypes. These online sources were chosen to provide a representative set of experiences including various risk factors and symptoms that may not always be recorded in clinical notes, as well as to allow widespread sharing of results without Health Insurance Portability and Accountability Act (HIPAA) concerns. Recent work by Borland et al[30] has also demonstrated the importance of considering patient experiences in building accurate ontologies about specific conditions in addition to the traditional encyclopedic knowledge included. The two domain experts independently reviewed the first five cases to determine missing risk factors, as well as PPD symptoms and treatments. During case review, terms, and phrases (“chunks”) relevant to the mother and PPD were highlighted, then compiled and categorized by their relevant features. For example, the chunk “down feelings” was categorized by the relevant feature “symptoms of depression: depressed mood.” The chunks chosen by the domain experts were compared to compile a list of all relevant features identified. Then, duplicates were removed, and the unique relevant features were labeled as symptoms, risk factors, treatments, or other. Finally, the PDO was evaluated for its inclusion of the unique relevant features, so that necessary changes and additions to the domain knowledge could be made. A second pass using five more cases was then conducted to evaluate the updated ontology. [Fig. 3] illustrates an overview of the evaluation process, including the specific process of determining the number of unique relevant features to be analyzed against the existing ontology in each evaluation.

Fig. 3 Evaluation schema. Two postpartum depression (PPD) case study evaluations for the postpartum depression ontology (PDO) were conducted. Both evaluations consisted of extracting relevant terms and phrases from the case studies by two evaluators, comparing relevant terms, and excluding features that were not PPD symptoms, risk factors, or treatments. In [Fig. 3], the assessment of the PDO against these relevant features is shown.

Results

Postpartum Depression Ontology

The PDO was designed to formalize the PPD knowledge base in terms of ICD codes and clinical notes, including its risk factors, symptoms, treatments, comorbidities, and other related pregnancy or mental illness conditions. The ontology includes 734 classes, 13 object properties, and 4,844 individuals. The ontology has been made available on the NCBO BioPortal at https://bioportal.bioontology.org/ontologies/PARTUMDO for researchers to utilize and incorporate into their future work.

Postpartum Depression Risk Factor Identification

In total, 78 risk factors were identified, with 8 labeled as confirmed risk factors and 70 as potential risk factors. The first PPD ontology was constructed with 7 confirmed risk factors and 55 potential risk factors; however, after the initial evaluation, one confirmed risk factor was identified by the first case study evaluation and added. Furthermore, 11 potential risk factors were added, with 7 identified by the first case study evaluation and 4 by clinical expertise. The final evaluation of case studies revealed three more potential risk factors, and one potential risk factor was identified by additional clinical expertise.

[Table 2] includes all confirmed risk factors and eight selected potential risk factors. Confirmed risk factors were strongly supported in the literature with at least two independent groups finding a statistically significant increased risk of PPD and many citations; citations for the literature supporting the eight confirmed risk factors ranged from 47 to 2,492 citations as of April 12, 2021, with each risk factor supported by at least one paper with 245 or more citations ([Table 2]). In contrast, conditions that were classified as potential risk factors often failed to include some known confounding variables, had a potentially bidirectional relationship with PPD,[31] or lacked extensive research in the field, with few papers on the subject or an established association with depression but not PPD. [Supplementary Table S2] (available in the online version) includes a complete list of the 70 potential risk factors identified from the literature, case studies, and clinical expertise. Since these additional risk factors are only “potential” due to the existence of some disagreement in the literature with regard to their role in PPD, we include them as a supplement if researchers are interested.

Table 2 Classifications and sources for confirmed PPD risk factors and eight selected potential PPD risk factors (out of 70 total potential PPD risk factors)

Risk factor[a]	Class(es) in ontology[b] [c]	Type(s)	Status[d]
History of depression[7] [8] [9] [25] [37] [38]	History_of_Major_Depressive_Disorder *Major_Depressive_Disorder	Mental condition	C
History of anxiety[25] [37]	History_of_Generalized_Anxiety_ Disorder *Generalized_Anxiety_Disorder	Mental condition	C
History of postpartum depression[9] [37] [39]	History_of_Postpartum_Depression *Postpartum_Depression	Mental condition Pregnancy or birth	C
Anxiety during pregnancy[8] [25] [50]	*Anxiety_During_Pregnancy *Generalized_Anxiety_Disorder	Mental condition Pregnancy or birth	C
Depression during pregnancy[8] [25] [50]	*Depression_During_Pregnancy *Major_Depressive_Disorder	Mental condition Pregnancy or birth	C
Abuse[37] [51]	Abuse_Violence_Type	Outside factor	C
Subjective lack of support post pregnancy[29] [38] [52] [53]	Negative_Perception_of_Support_ Postpregnancy *Negative_Perception_of_Support	Outside factor Mental condition Pregnancy or birth	C
Relationship dissatisfaction[9] [54]	Relationship_Dissatisfaction	Outside factor	C
Multiple gestation[55] [56]	Multiple_Gestation	Pregnancy or birth	P
Preeclampsia[10] [57]	Preeclampsia	Pregnancy or birth	P
Traumatic brain injury[58]	Traumatic_Brain_Injury	Outside factor Other	P
Unplanned, mistimed, or unwanted pregnancy[59]	Unplanned_Pregnancy Mistimed_Desire *Unwanted_Pregnancy	Pregnancy or birth Mental condition	P
Assisted delivery[7] [11]	Emergency_Cesarean_Section, Instrument_Assisted_Delivery	Pregnancy or birth	P
Preterm delivery (<37 weeks)[60]	Moderate_to_Late_Preterm *Preterm	Pregnancy or birth	P
**Breastfeeding intent different from reality[45]	Intent_to_Breastfeed_and_Did_Not_ Breastfeed No_Intent_to_Breastfeed_and_Did_ Breastfeed	Pregnancy or birth Mental condition	P
Gestational diabetes[7]	Gestational_Diabetes	Pregnancy or birth	P

Abbreviation: PPD, postpartum depression.

^a A double starred (**) row indicates risk factors for which there are no ICD codes (no individuals) in the ontology.

^b Since there are no International Classification of Diseases (ICD) codes with the temporal designation “history of” for depression, anxiety, and PPD, or “post pregnancy” for lack of support post pregnancy, starred (*) classes include the individuals for these conditions. Similarly, potential risk factors with starred classes indicate the ontology class under which ICD codes can be found.

^c Classes that do not specifically describe the risk factor, but which include ICD codes that could be used to identify patients with the risk factor after adjusting for necessary temporal or other relationships, are designated by a star (*) and italics. For example, a potential risk factor is Moderate_to_Late_Preterm delivery; however, there are no ICD codes specific to this time period, so the ICD codes reside under the less specific *Preterm class.

^d Above, confirmed PPD risk factors are designated “C,” whereas potential PPD risk factors are designated “P” under the Status column.

All 4,844 individuals in the ontology were subclasses of one or more of the 8 confirmed risk factor classes, or subclasses of the 47 potential risk factors for which ICD codes existed. For history of depression, anxiety, and PPD, as well as lack of support postpregnancy, there were no ICD codes with the “history of” or “post pregnancy” temporal designations. A star (*) in [Table 2] indicates the ontology class under which the ICD codes (individuals) for these conditions are located; however, the temporal relationship would need to be determined by a researcher or medical professional. For example, a patient with a history of PPD would be diagnosed with one of the ICD codes that was an individual of the Postpartum_Depression class. Researchers could then specify a time range when pulling patient codes from EHRs to determine whether patients had a history of PPD or current PPD. Furthermore, there were 23 potential risk factors for which there existed no ICD codes; thus, these risk factors are designated by a double star (**).

Postpartum Depression Ontology Object Properties

The object properties within the PDO are included in [Table 3]. Object properties were critical for demonstrating the relationships of risk factors with PPD, as well as detailing injury relationships for the investigation of traumatic brain injury (TBI) as a potential risk factor. There were 13 object properties in total with seven classified as pregnancy- or mental health–related and two specifically showing the relationships among PPD and its risk factors. There were nine object properties with the general domain class OWL: Thing due to the domain spanning the entire ontology; for example, there were risk factors in all three superclasses of the PDO.

Table 3 Ontology object properties

Domain class	Object property	Conjunction	Range class	Related to mental health, pregnancy, or other
owl:Thing	has_PPD_risk_factor_status	only	Postpartum_Depression_ Risk_Status	Pregnancy Mental health
owl:Thing	has_PPD_risk_type	only some	Postpartum_Depression_ Risk_Type	Pregnancy Mental health
owl:Thing	has_ICD_version	NA	ICD_Code_Version	Pregnancy
owl:Thing	is_symptom_of	some	Postpartum_Depression	Pregnancy Mental health
Inviable_ Pregnancy_ Condition	causes_living_status	only	Infant_or_Fetus_ Inviability	Pregnancy
owl:Thing	has_postpartum_psychosis_ risk_factor_status	only	Postpartum_Psychosis_ Risk_Status	Pregnancy Mental health
owl:Thing	has_psychotic_status	only	Psychotic_Status	Mental health
Injury_Type	has_injury_depth	only	Injury_Depth	Other
Injury_Type	has_injury_trauma_type	only	Injury_Trauma	Other
TBI_Related_ Injury	has_injury_area	only	Injury_Area	Other
owl:Thing	is_during	only	Condition_Time	Other
owl:Thing	has_condition_type	only	Condition	Other
owl:Thing	has_procedure	only	Medical_Procedure_ Encounter_or_Treatment	Other

Abbreviations: ICD, International Classification of Diseases; PPD, postpartum depression.

Pregnancy- and Mental Health–Related Object Properties

The PPD risk factors spanned the ontology and were categorized as several distinct types, leading to general owl:Thing domain classes for both PPD-related object properties. To differentiate among the types of risk factors, the object property has_PPD_risk_type was created with a range of Postpartum_Depression_Risk_Type. This class was further subdivided into the four risk factor type classes. To demonstrate whether the literature supported classes as confirmed or potential risk factors, the object property has_PPD_risk_factor_status was formed with a range of Postpartum_Depression_Risk_Status. This class included three subclasses identifying variables as confirmed, potential or not risk factors; this latter categorization included the class Mistaken_for_PPD which contained conditions with symptoms similar to those of PPD that could lead to an incorrect diagnosis.

The object property has_PPD_risk_factor_status required the use of the conjunction ‘only’ to relate it to a class and exclude the possibility of a confirmed risk factor also being a potential risk factor or not a risk factor. For example, Abuse_Violence_Type—the class representing all forms of abuse—had the object property relationship has_PPD_risk_factor_status ‘only’ Confirmed_PPD_Risk_Factor. In contrast, the object property has_PPD_risk_type allowed the conjunctions ‘only’ and ‘some’ to relate classes due to the polyhierarchical structure of the PDO. Abuse_Violence_Type had the object property relationship has_PPD_risk_type ‘only’ Instability_Mediated_by_Outside_Factor_Related_PPD_Risk_Type because it could not be classified as one of the other three types. However, History_of_Postpartum_Depression used the conjunction ‘some’ because it could be considered both a mental condition and pregnancy- or birth-related risk type, and ‘some’ specifies an “at least one” relationship.[32] [Fig. 4] shows an example of the relationships and individuals for the confirmed risk factor abuse and, more specifically, sexual abuse.

Fig. 4 Individuals and the has_PPD_risk_factor_status object property showing abuse as an example. In [Fig. 4], blue arrows show a has subclass relationship, the yellow arrow shows a has_PPD_risk_factor_status only relationship with the Confirmed_PPD_Risk_Factor class, and the purple arrows signify a has individual relationship. ICD codes for sexual abuse are shown here, with two overlapping the Physical_Abuse class. ICD, International Classification of Disease; PPD, postpartum depression.

Three more pregnancy- or mental health–related object properties were particularly important in the ontology. The object property has_ICD_version was used among the 4,844 individuals of the PPD risk factors to show whether the codes were from version ICD-9 or -10; no specified conjunction was necessary because the object property connected individuals. [Fig. 5] represents the other object property illustrating the variety of PPD symptoms included in the final version of the PDO. The is_symptom_of object property had a range of Postpartum_Depression, and the conjunction ‘some’ was used because these symptoms are at least related to Postpartum_Depression, yet they could also be related to other conditions. Any symptoms and signs with synonymous or similar descriptions were included using the rdfs:label annotation.

Fig. 5 Symptoms of PPD as shown in the PDO. In [Fig. 5], a representation of several PPD symptoms is visualized, in which the blue arrows show a has subclass relationship and the orange arrows signify an is_symptom_of some relationship with the Postpartum_Depression class. The yellow boxes show clustering of synonyms and similar terms under the rdfs:label annotation. PDO, postpartum depression ontology; PPD, postpartum depression.

Other Object Properties

There were six object properties classified as “Other.” Due to the relationship among traumatic injury, TBI, physical abuse, and depression,[33] [34] [35] a clinical expert (M.R.B.) recommended that we include TBI in the ontology as a potential PPD risk factor. Thus, the injury class required three object properties to relate five important subclasses of the injury superclass: Injury_Type, Injury_Area, Injury_Depth, Injury_Trauma, and TBI_Related_Injury. The class Injury_Type was related to the classes Injury_Depth and Injury_Trauma by the object properties has_injury_depth and has_injury_trauma_type, respectively, while TBI_Related_Injury was related to Injury_Area by the object property has_injury_area. All used the conjunction ‘only’ to exclude false injury descriptions; for example, the class Traumatic_Brain_Injury used the conjunction ‘only’ to provide closure to the object property has_injury_trauma_type ‘only’ Traumatic_Injury such that a nontraumatic cause of a brain injury was excluded.

Of the remaining three object properties classified as “Other,” the is_during object property was particularly important. Since the ontology was created to represent the PPD knowledge base, time was defined relative to pregnancy and delivery. The is_during object property was used to form many complex class expressions which have more than one conjunction. For example, the class Gestational_Diabetes was equivalent to Diabetes ‘and’ is_during ‘only’ Time_During_Pregnancy. In other words, gestational diabetes is a type of diabetes that only occurs during pregnancy. In another example, the object property defined the meaning of a very preterm baby, which is a baby born between 28 weeks of gestation up to 31 weeks 6 days gestation.[36] In this case, the object property would be used as follows: Very_Preterm is_during ‘only’ (28_Weeks_Gestation ‘or’ 29_Weeks_Gestation ‘or’ 30_Weeks_Gestation ‘or’ 31_Weeks_Gestation).

Evaluation Results

Case Study Evaluation Results

The case study evaluation was performed in two rounds of five case studies by R.B.M. and M.R.B ([Supplementary Table S3], available in the online version). In the first set of 158 sentence chunks ([Fig. 3]), 60 chunks (38%) were identified as relevant features by the two evaluators, and all 60 were annotated similarly. The remaining 98 chunks (62%) were only identified by one evaluator due to varying expertise; these were discussed to reach a consensus opinion for all. This process was repeated for the second set of case studies with 214 sentence chunks ([Fig. 3]). Of these,106 chunks (49.5%) were identified as relevant features by both evaluators with 96 annotated similarly and 10 without consensus. This lack of consensus was due to differing interpretations of the sentence chunks. For example, “I wasn't eating or drinking enough water, which meant my body wasn't making breastmilk” was interpreted by R.B.M. as “breastfeeding difficulties,” whereas M.R.B. interpreted this as “nutrition issues.” For these 10 chunks and 108 (50.5%) identified by only one evaluator, a second discussion led to a consensus on classification of relevant features.

[Table 4] shows the results of the analysis comparing the unique relevant features identified through case studies to the PDO in both rounds of evaluation. During the initial evaluation, 79 unique relevant features were analyzed. In total, 30.4% of all unique relevant features were explicitly included in the first PPD ontology; when similar classes for unique relevant features without an explicit class in the ontology were considered, 45.6% of the unique relevant features were covered. All 14 PPD treatments in the initial evaluation were not encapsulated, so they were added to a new class of features called PPD_Treatment. Furthermore, of the 11 PPD risk factors that were not already included, 10 were potential risk factors and one—History_of_Anxiety—was identified as a confirmed risk factor. A subsequent survey of the literature on History_of_Anxiety was performed to fulfill the criteria required in [Fig. 2].

Table 4 Case study evaluation results for PPD symptoms, risk factors, and treatments

	Initial evaluation (n = 79)[a]		Final evaluation (n = 88)[b]
Unique relevant feature type	Included in first version of PDO	Total	Included in final version of PDO	Total
PPD symptoms	13 (30.2%)	43	31 (67.4%)	46
PPD risk factors	11 (50.0%)	22	27 (90.0%)	30
PPD treatments	0 (0.0%)	14	10 (83.3%)	12

Abbreviations: PDO, postpartum depression ontology; PPD, postpartum depression.

^a The initial evaluation involved assessing the first version of PDO against n = 79 unique relevant features obtained from the first set of five case studies.

^b The final evaluation involved assessing the second version of PDO against n = 88 unique relevant features obtained from the second set of five case studies.

The final evaluation involved 88 unique relevant features of which 77.3% were already explicitly included in the second PPD ontology and 86.4% were covered when similar classes were evaluated. Interestingly, only three new potential risk factors were identified out of the 30 risk factor chunks, demonstrating a 90.0% accuracy in the ontology's goal of characterizing PPD risk factors. Most treatments were already included (83.3%), whereas several new symptoms were identified.

The Pellet Reasoner Evaluation Results

We used the Pellet reasoner to evaluate the final ontology and 154 inconsistencies were found. All inconsistencies resulted from multiple inheritance of ICD code individuals under the three disjoint superclasses: Condition, Maternal_Descriptor, and Medical_Procedure_Encounter_or_Treatment ([Supplementary Table S1], available in the online version).

One major source of inconsistencies were ICD codes describing high-risk pregnancies which are classified as a descriptor of pregnancy risk in the ontology. For example, ICD-10 code O09.811, which is defined as “Supervision of pregnancy resulting from assisted reproductive technology, first trimester,” is an individual of the High_Risk and Assisted_Reproductive_Technology_Cycle classes. However, these are located under the Maternal_Descriptor and Medical_Procedure_Encounter_or_Treatment superclasses, respectively. ICD codes classified as multiple gestations also exhibited many inconsistencies. The ICD-9 code V27.3, which is defined as “Outcome of delivery, twins, one liveborn and one stillborn,” exhibited multiple inheritance of the classes Infant_Stillbirth (Condition) and Multiple_Gestation (Maternal_Descriptor).

The inconsistencies identified by the Pellet reasoner demonstrated that the three superclasses of the PDO should not be disjoint; some ICD codes are both descriptive in nature, as well as indicate a condition or procedure. All inconsistencies were deemed to be valid from a logical and clinical perspective, and we modified the ontology accordingly. The finalized ontology available on NCBO reflects the latest and most correct and updated version of the ontology. If any changes are made postpublication of this manuscript, those will also be shared with the community via the NCBO BioPortal at: https://bioportal.bioontology.org/ontologies/PARTUMDO . For an overview of the entire ontology's hierarchy please see [Fig. 6].

Fig. 6 A graphical overview of the Postpartum Depression Ontology Superclasses and Direct Subclasses of the Ontology.

Discussion

As the first PPD-specific ontology to our knowledge, the PDO was built inclusive of ICD codes to represent the PPD knowledge domain in an EHR-accessible format for researchers and medical professionals. After a literature search and two rounds of evaluation, the ontology encompasses treatments, symptoms, risk factors, and other related conditions, as well as personal descriptors and procedures. Most importantly, the PDO compiles 78 known and potential PPD risk factors that were identified through the literature, case studies, and clinical expertise. To date, no studies have considered all of these factors together, yet understanding the totality of risk factors is critical given the high prevalence of PPD[3] [4] and its serious consequences.[5] [6] The PDO developed here designates eight variables as confirmed risk factors and 70 as potential risk factors in an effort to inform not only diagnoses but also to identify and improve prevention strategies.

The literature search revealed many risk factors, yet very few had sufficient evidence to support a causal relationship with PPD. Despite agreement among most papers reviewed that a history of mental illness was one of the strongest risk factors for PPD development,[7] [8] [9] [25] [37] [38] [39] other variables investigated often had contradictory significance levels, indicating the possibility of a bidirectional relationship or an absence of sufficient evidence. Given the importance of understanding risk factors and the lack of agreement in the field, we designed this ontology as a resource to discover which areas in the field required further research. Thus, the object property and class combination of “has_PPD_risk_factor_status ‘only’ Potential_PPD_Risk_Factor” directs researchers to identify conditions that have not been adequately studied and promotes investigation of these conditions to add to the field through the inclusion of the relevant ICD codes.

The confirmed risk factor section of the ontology promotes adjustment for factors as confounding variables in future risk factor studies, as well as helps medical professionals to identify patients at risk. Since ICD codes were included in the ontology for each of the confirmed PPD risk factors, medical professionals may offer more individualized care by using these codes to supplement screening tools such as the PPD-specific Edinburgh Postnatal Depression Scale (EPDS),[40] the Center for Epidemiologic Studies Depression (CES-D) scale,[41] the Beck Depression Inventory,[42] and the Patient Health Questionnaire-9 (PHQ-9).[43] Additionally, researchers can now more easily identify larger cohorts of women at risk for PPD by using the ICD codes included in EHRs; this population is a critical target for future intervention studies.

While the PDO incorporates ICD codes for EHR analyses, it was important to include information beyond its coverage of medical diagnoses and the information typically included in EHRs such as age and weight. Specifically, we added classes characterizing the mother's intentions and perceptions of support, self, and the pregnancy that may only be present in clinical notes or not at all. This type of information is rarely—if ever—included in ontologies with mental health sections, yet negative perceptions of reality and illusions often influence mental health unfavorably.[44] Furthermore, outcomes that differ from the mother's expectations, such as intent to breastfeed but inability to do so, have been linked to an increased risk of PPD;[45] thus, this type of information is crucial to include. While perceptions of reality may be difficult to diagnose, this PDO can improve the current self-assessment screening tools[40] [41] [42] [43] that may suffer from self-reporting bias,[46] as well as suggest topics about intentions and perceptions to discuss with patients such as expecting to lose pregnancy weight quickly.

In addition to classes that were added to characterize intentions, perceptions, and other variables missing from ICD codes, the use of polyhierarchical modeling and multiple inheritance was crucial in building the PDO. The polyhierarchy was particularly important for risk factor classification; simply creating a list of risk factors would have been insufficient, as this would not allow the categorization of risk factors into multiple risk types. In addition, multiple inheritance was critical for ICD codes which often had more than one parent class. For example, the ICD-10 code T74.11XA, which is defined as “Adult physical abuse, confirmed, initial encounter,” had the parent classes Abuse_Violence_Type, Adult_Victim, Confirmed_Abuse, and Physical_Abuse. It was necessary to identify each aspect of the code—confirmed abuse, abuse type, and victim age—because these variables could play a role in risk factor research, such as determining age of sustained abuse or type of sustained abuse as carrying a greater risk of developing PPD. Thus, the development of the PDO through these modeling choices allowed the characterization of the PPD knowledge domain's complexity.

During the evaluation of the PDO, clinical case studies provided a unique focus on PPD treatments and symptoms that were often absent from the literature and ICD codes. None of the treatments identified from the first set of case studies were included in the ontology which partially accounts for the low total percent coverage (30.4%); when treatments were removed from analysis, there was a small increase to 36.9% coverage. Further, comprehensive coverage of PPD symptoms was difficult because many of the symptom names used in the case studies were similar to other symptoms described by different women. Even though the coverage of symptoms doubled between evaluations, there was only 67.4% coverage in the final evaluation, suggesting the need to continue updating the ontology with more symptoms and to increase the use of the rdfs:label annotation. Moreover, despite their absence from ICD codes, which limits EHR research, these symptoms may be included in clinical notes or screening results that could aid in the development of better screening tools or in the choice of treatments by medical professionals.

To date, this PDO evaluation is limited by the relatively low number of case studies reviewed and the use of two evaluators. Another limitation is that one of the evaluators (R.B.M.) was the developer of the ontology; however, the second evaluator (M.R.B) produced similar results in the evaluation and a consensus opinion with regard to correctness was derived from comparison of the evaluations, demonstrating the usability and reliability of the ontology independent of the developer. Future work will involve a secondary evaluation with additional case studies and new evaluators to assess the strength of the ontology in its inclusion of all information relevant to a PPD diagnosis. Newly constructed ontologies will be assessed for relevance to the PDO and new terms will be included; one such example is the semantic-based verbal autopsy framework for maternal death[47] which includes many pregnancy complications that could increase the risk of PPD in cases of maternal survival. Additionally, further refinement of PPD symptoms and treatments is required, as the number of relevant features in those categories added after the two rounds of evaluation suggest that there are more PPD features. However, we are confident that most treatments, symptoms, and risk factors are included either explicitly or through a similar feature in the ontology due to the final evaluation yielding 86.4% coverage. In fact, the inclusion of 90.0% of risk factors—which is the most important category for the PDO's target population—demonstrates that these are sufficiently characterized.

Beyond a deeper exploration and evaluation of the current PDO, our future work will involve incorporating more relevant ICD codes into the PDO. Currently, the ICD-9 and -10 codes included as individuals in the ontology are categorized under the eight confirmed PPD risk factors and the 47 potential PPD risk factors for which there are relevant ICD codes. As the literature expands, future iterations of the ontology will be updated with additional risk factors and their ICD codes,[48] as well as include codes from ICD version 11. ICD-11 will be available to Member States in 2022 to replace earlier versions;[49] thus, the relevant ICD codes from all versions must be included as individuals, so that researchers can identify the most up-to-date codes to use in EHR studies. Finally, the terms in the PDO will be mapped to SNOMED CT, ICD-9-CM, and ICD-10-CM to improve accessibility and standardization of resources.

Conclusion

The PDO is a comprehensive ontology of the PPD knowledge base designed to include information needed for a PPD diagnosis. We made our ontology readily accessible via the NCBO BioPortal (available at: https://bioportal.bioontology.org/ontologies/PARTUMDO ) for researchers to utilize and incorporate into their future work. Our evaluation focused on the use of case studies to demonstrate its coverage and usefulness. Interestingly, the PDO adds a new dimension to the knowledge base by compiling researched risk factors and designating them as confirmed (known) or potential PPD risk factors, with ICD codes used in EHRs included for these risk factors. The PDO can therefore illuminate areas of PPD that require further investigation, as well as supplement the current PPD screening techniques employed, promoting more clarity in the field for researchers and potentially improving the standard of care provided by medical professionals. As an ontology, the PDO provides much more detail than would typically be available in disease concept sets because it provides relationships between concepts and other useful information for conducting research studies on PPD.

Clinical Relevance Statement

Postpartum pepression (PPD) remains an understudied research area despite its high prevalence. This study contributes an ontology to aid in the identification of patients with PPD and to enable future analyses with electronic health record (EHR) data. In addition to PPD, relevant comorbidities that have been reported in the literature that are related to PPD are included. The ontology is freely available on the NCBO BioPortal web site and was constructed using Protégé-OWL. Our ontology will enable future researchers to study PPD using EHR data as it contains important information with regards to structured (e.g., billing codes) and unstructured data (e.g., synonyms of symptoms not coded in EHRs) and also the connections between diseases and comorbidities. The PDO is publicly available through the National Center for Biomedical Ontology (NCBO) BioPortal ( https://bioportal.bioontology.org/ontologies/PARTUMDO ) which will enable other informaticists to utilize the PDO to study PPD in other populations.

Multiple Choice Questions

1. What public database houses publicly available ontologies, including our postpartum depression ontology?

   • NCBO BioPortal

   • PubMed Central

   • Entrez

   • GitHub

   Correct Answer: The correct answer is option a. Our ontology is made freely available on the NCBO BioPortal web site. The NCBO was founded as one of the National Centers for Biomedical Computing supported by the NHGRI, NHLBI, and the NIH Common Fund.

2. Which of the following International Classification of Diseases (ICD) versions are included in terms of codes in the Postpartum Depression Ontology?

   • ICD-9

   • ICD-10

   • ICD-11

   • ICD-9 and ICD-10

   Correct Answer: The correct answer is option d. Our ontology includes diagnostic codes for both ICD-9 and ICD-10 for researchers using those terminologies. These can be easily mapped to SNOMED-CT using existing OHDSI Common Data Model mappings.

3. Postpartum depression is a diagnosis code in which clinical terminologies?

   • ICD-9

   • ICD-10

   • ICD-9, ICD-10

   • ICD-10, ICD-11

   Correct Answer: The correct answer is option d. While ICD-9 has diagnosis codes for depression, there is no explicit code for “postpartum depression.” However, in ICD-10, an explicit code for postpartum depression appears, and ICD-11 also contains specific codes.

Conflict of Interest

None declared.

Protection of Human and Animal Subjects

This research did not involve human subjects.

Author Contribution

Conceived study design: R.B.M. and M.R.B. Developed methodology: R.B.M., B.A.D'A., and M.R.B. Provided clinical advice pertinent to study problem: A.L.C.S. and A.C.B. Wrote paper: R.B.M. and M.R.B. Reviewed, edited, and approved final manuscript: R.B.M., A.C.B., B.A.D'A., S.P.C., A.L.C.S., and M.R.B.

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Publication History

Received: 20 August 2021

Accepted: 04 January 2022

Article published online:
09 March 2022