Background
Family history of pelvic organ prolapse among first-degree relatives is an established risk factor for pelvic organ prolapse; however, consideration of the constellation of family history that extends to distant relationships allows for more accurate determination of risk and may improve pelvic organ prolapse risk prediction estimates.
Objective
The purpose of this study was to assess risk for pelvic organ prolapse treatment based on varying family histories of pelvic organ prolapse and included number and types of affected relatives, ages of relatives at pelvic organ prolapse treatment, and whether the family history is of maternal or paternal origin.
Study Design
This was a retrospective, population-based study that involved the Utah Population Database, which is a population resource that includes extensive genealogy information linked to medical records. The study population included 453,522 total women: 4628 women with a diagnosis of treated (surgical or pessary) pelvic organ prolapse and their 15,530 first-degree relatives; 33,782 second-degree relatives, and 66,469 third-degree relatives. We estimated relative risk of treated pelvic organ prolapse based on specific family history constellations.
Results
Relative risk estimates increased with a family history of increasing numbers of treated first-degree relatives with pelvic organ prolapse (first-degree relatives, ≥1 [relative risk, 2.36; 95% confidence interval, 2.15–2.58], first-degree relatives, ≥2 [relative risk, 3.79; 95% confidence interval, 2.65–5.24], and first-degree relatives, ≥3 [relative risk, 6.26; 95% confidence interval, 1.29–18.30]). Having a family history of ≥3 affected third-degree relatives (eg, first cousins) and no affected first- or second-degree relatives was similar in risk to having 1 affected first-degree relative. Relative risk estimates decreased with increasing age of treatment for first-degree family members. Risks in individuals with a positive maternal family history for pelvic organ prolapse were consistently higher than risks in individuals with equivalent paternal family history, but paternal inheritance still played a role. Approximately 4% of the total studied female population was found to have a >2-fold risk of being treated for pelvic organ prolapse and is considered high-risk based on their family history.
Conclusion
We provide estimates for treated pelvic organ prolapse based on an extensive family history of pelvic organ prolapse using a large population-based sample. Risk for treated pelvic organ prolapse increased with increasing numbers of affected close and distant female relatives, earlier age of pelvic organ prolapse treatment in relatives, and maternal inheritance. These risk estimates may be useful for genetic studies and investigation of risk reduction strategies in those at highest risk for pelvic organ prolapse.
Pelvic organ prolapse (POP) is a disorder that results in the abnormal descent of the uterus, bladder, colon, or rectum into the vagina. The prevalence of symptomatic POP ranges from 5–10% of adult women, and the lifetime risk of surgical treatment for POP in the United States by age 80 years is 12.6% (95% confidence interval [CI], 12.4–12.7). POP is a public health problem because it imparts a significant burden on the health, quality of life, and economic strain on those impacted. , Hence, understanding the contributing risk factors for POP is of great importance because it will enable identification of those women who are at highest risk for investigation of risk reduction strategies.
Why was this study conducted?
The purpose of this study was to determine risk assessments for treated pelvic organ prolapse based on specific family history that would include numbers and types of affected relatives, earliest relative treatment age, and maternal vs paternal family history.
Key findings
Risk of prolapse treatment was associated with increasing numbers of female-affected close and distant relatives. The risk of prolapse treatment was associated with earlier age of prolapse treatment in first-degree relatives. Risk of prolapse treatment was associated with mostly maternal inheritance, but paternal inheritance still played a role.
What does this add to what is known?
Approximately 4% of women are at high risk for treated prolapse based on their family history. Family history in second- and third-degree female relatives also contributes to risk of prolapse.
The cause of POP is considered multifactorial, with the number of vaginal deliveries being the most important risk factor. However, a number of studies have observed that a family history of POP is also a significant and strong predictor of POP. Recently published risk prediction models for POP at 12 and 20 years after childbirth delivery found that a family history of POP ranked second in most models following the strongest predictor, childbirth delivery route. For those studies that assessed family history, subjects typically are asked about the existence of any symptoms or treatment for POP in either their mother or sisters. , , However, more distant relatives (eg, aunts and cousins) and paternal inheritance may also contribute to the risk of POP.
The primary objective of this study was to assess risk for treated POP based on extended family histories of POP that include the number and types of affected relatives, ages of relatives at POP treatment, and whether the family history is of maternal or paternal origin with the use of an extensive statewide genealogy database linked to medical records. Consideration of an extended family history allows for more accurate determination of risk and may improve risk prediction estimates for POP.
Materials and Methods
Utah population database (UPDB)
The UPDB includes, among other data sources, linked data from family history records dating back to the 19th century for the pioneer founders of Utah, birth and death certificates, and inpatient and outpatient electronic medical records beginning in 1994 from the University of Utah Health Sciences Center (UUHSC), an academic medical center, and Intermountain Healthcare, a not-for-profit healthcare system. The linked electronic health records from UUHSC and Intermountain Healthcare represent healthcare use for the majority of Utahns; UUHSC and Intermountain Healthcare together serve approximately 85% of the Utah population who use health care. Genealogy data for the Utah founders and descendants to the current population was obtained from 1.6 million family history records that were provided by the Genealogical Society of Utah and were extended with relationship data that were constructed from nearly 3 million Utah birth certificates. There are almost 11 million unique individuals represented in the UPDB currently. Approximately 1.3 million of them have genealogy data for at least 12 of 14 of their immediate ancestors (parents, all 4 grandparents, and at least 6 of 8 great grandparents) that connect to the Utah founding population. Women who meet these strict genealogy requirements and with linkage to healthcare records (n=453,522) were defined as probands in this study to better understand POP risks that are associated with extended relationships.
POP case definition
POP cases were defined as those individuals with an International Classification of Diseases 9th revision (ICD9) diagnosis code that indicates a diagnosis of POP (ICD9 code 618) and a Current Procedural Terminology (CPT) code that indicates treatment for POP and who also met the strict genealogy requirements and linked to healthcare records at UUHSC or at Intermountain Healthcare as described earlier. We included the following CPT procedure codes for POP: colpocleisis (57120), pessary (57160), anterior colporrhaphy (57240), posterior colporrhaphy (57250), combined anterior and posterior colporrhaphy (57260), combined anterior and posterior colporrhaphy, with vaginal repair of enterocele (57265), vaginal repair of enterocele (57268), abdominal repair of enterocele (57270), abdominal repair of vaginal vault prolapse/abdominal sacrocolpopexy (57280), vaginal repair of vaginal vault prolapse/extraperitoneal approach (57282), vaginal repair of vaginal vault prolapse/intraperitoneal approach (57283), and paravaginal repair for lateral cystocele (57284). Treated POP cases were identified from electronic medical records from 1994, when electronic medical records were first available at UUHSC and at Intermountain Healthcare, up to 2014. This study was approved by the University of Utah and Intermountain Institutional Review Boards and the Utah Resource for Genetic Epidemiological Research, which oversees the usage of UPDB data. All of the data involved in this project were deidentified, and waivers of informed consent were granted by the Institutional Review Board.
Estimation of relative risk
Relative risks were estimated for multiple different family history constellations. First-degree relatives (FDRs) include parents, children, and siblings; second-degree relatives (SDRs) include grandparents, grandchildren, aunts/uncles, nieces/nephews and half-siblings; third-degree relatives (TDRs) include great grandparents, great grandchildren, grandnieces/nephews, grand aunts/uncles, and first cousins. From among the 453,522 probands described earlier, we identified all female probands who met specific family history constellations of POP and computed their relative risk for being treated for POP. Relative risk estimates were computed as the ratio of the observed to the expected number of treated POP cases among the probands. The expected number of POP cases was estimated based on population rates of POP for women by birth state (Utah or not) and age (5-year birth year cohort). Each proband who was involved in a specific analysis was assigned their cohort-specific rate of POP. The expected number of POP cases was determined as the sum of all the cohort specific rates for all probands in that analysis. The 95% confidence interval was calculated with the method of Agresti.
Results
A total of 4628 female subjects with a diagnosis of treated POP between 1994 and 2014 was included in this analysis. Of this number, 786 women (17%) were treated only with pessary (no surgery). These individuals had 15,530 female FDRs, 33,782 female SDRs, and 66,469 female TDRs.
First-degree family history of treated POP
Table 1 shows relative risk estimates of POP for probands, defined by varying numbers of FDRs that had been treated for POP. The Table includes the number of probands with the family history specified, the observed number of probands diagnosed with POP, the expected number of POP cases, the relative risk, the significance of the relative risk test of hypothesis, and the 95% CI for the relative risk. For example, there were 719 probands with ≥2 FDRs who were treated for POP; of these individuals, 36 probands had also been treated for POP, whereas only 9.51 cases were expected based on the UPDB population-based cohort rates for POP. The relative risk estimate, 3.79, was significant at P <.00001 (95% CI, 2.65–5.24), which means that individuals with ≥2 FDRs who were treated for POP were 3.79 times more likely to also be treated for POP, compared with the expected number of women who were treated for POP in Utah, based on population rates of the disease. Relative risk estimates increased with increasing numbers of FDRs who had been treated for POP.
| Relative risk estimates for pelvic organ prolapse | Probands | Observed | Expected | Relative risk | P value | 95% Confidence interval |
|---|---|---|---|---|---|---|
| Based on FDR family history, SDRs and TDRs ignored | ||||||
| 0 | 622,108 | 4,122 | 4,396.77 | 0.94 | <.00001 | 0.91–0.97 |
| ≥1 | 18,258 | 477 | 202.23 | 2.36 | <.00001 | 2.15–2.58 |
| ≥2 | 719 | 36 | 9.51 | 3.79 | <.00001 | 2.65–5.24 |
| ≥3 | 35 | <5 | <5 | 6.26 | .013 | 1.29–18.30 |
| Based on SDR family history; FDR (n=0) and TDRs ignored | ||||||
| 0 | 577,439 | 3,814 | 4,146.66 | 0.92 | <.00001 | 0.89–0.95 |
| ≥1 | 44,669 | 308 | 250.10 | 1.23 | .0003 | 1.10–1.38 |
| ≥2 | 3,895 | 23 | 17.86 | 1.29 | .23 | 0.82–1.93 |
| ≥3 | 321 | <5 | <5 | 2.14 | .24 | 0.26–7.71 |
| Based on SDR family history; FDRs (n=1) and TDRs ignored | ||||||
| 0 | 15,404 | 395 | 174.2 | 2.27 | <.00001 | 2.05–2.50 |
| 1 | 1,911 | 42 | 16.83 | 2.50 | <.00001 | 1.80–3.37 |
| ≥2 | 250 | <5 | <5 | 2.00 | .14 | 0.55–5.12 |
| Based on TDR family history; FDR (n=0) and SDR (n=0) | ||||||
| 0 | 489,431 | 3,087 | 3,470.42 | 0.89 | <.00001 | 0.86–0.92 |
| ≥1 | 88,008 | 727 | 676.25 | 1.08 | .052 | 1.00–1.16 |
| ≥2 | 14,478 | 121 | 107.30 | 1.13 | .19 | 0.94–1.35 |
| ≥3 | 2,782 | 35 | 15.71 | 2.23 | <.00001 | 1.55–3.10 |
| ≥4 | 674 | 5 | 2.57 | 1.94 | .20 | 0.63–4.54 |
| Based on TDR family history; FDR (n=1) and SDRs ignored | ||||||
| ≥1 | 3,472 | 109 | 40.49 | 2.69 | <.00001 | 2.21–3.25 |
| ≥2 | 650 | 38 | 7.48 | 5.08 | <.00001 | 3.59–6.97 |
| Based on TDR family history; FDR (n=1) and SDR (n=1) | ||||||
| ≥1 | 549 | 14 | 4.74 | 2.96 | .0004 | 1.62–4.96 |
| ≥2 | 134 | 3 | 0.99 | 3.02 | .079 | 0.62–8.84 |
| ≥3 | 45 | <5 | <5 | 5.70 | .049 | 1.01–20.58 |
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