Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study.

BACKGROUND: Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. OBJECTIVE: We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. STUDY DESIGN: APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. RESULTS: The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. CONCLUSION: Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

Identification and validation of uterine perforation, intrauterine device expulsion, and breastfeeding in four health care systems with electronic health records.

OBJECTIVE: To validate algorithms identifying uterine perforations and intrauterine device (IUD) expulsions and to ascertain availability of breastfeeding status at the time of IUD insertion. STUDY DESIGN AND SETTING: Four health care systems with electronic health records (EHRs) participated: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Southern California (KPSC), Kaiser Permanente Washington (KPWA), and Regenstrief Institute (RI). The study included women ≤50 years of age with an IUD insertion. Site-specific algorithms using structured and unstructured data were developed and a sample validated by EHR review. Positive predictive values (PPVs) of the algorithms were calculated. Breastfeeding status was assessed in a random sample of 125 women at each research site with IUD placement within 52 weeks postpartum. RESULTS: The study population included 282,028 women with 325,582 IUD insertions. The PPVs for uterine perforation were KPNC 77%, KPSC 81%, KPWA 82%, and RI 47%; PPVs for IUD expulsion were KPNC 77%, KPSC 87%, KPWA 68%, and RI 37%. Across all research sites, breastfeeding status at the time of IUD insertion was determined for 94% of those sampled. CONCLUSIONS: Algorithms with a high PPV for uterine perforation and IUD expulsion were developed at 3 of the 4 research sites. Breastfeeding status at the time of IUD insertion could be determined at all research sites. Our findings suggest that a study to evaluate the associations of breastfeeding and postpartum IUD insertions with risk of uterine perforation and IUD expulsion can be successfully conducted retrospectively; however, automated application of algorithms must be supplemented with chart review for some outcomes at one research site due to low PPV.

Cross design analysis of randomized and observational data - application to continuation rates for a contraceptive intra uterine device containing Levonorgestrel in adolescents and adults.

BACKGROUND: To combine results from a randomized controlled study (RCT) and an observational study (OS) to evaluate discontinuation rate of a levonorgestrel-containing intrauterine contraceptive device (LNG IUD) in a real-life setting. METHODS: We included 253 parous and nulliparous women aged 21-40 years from our own phase II RCT. A total of 1607 women of all ages (including adolescents, < 20 years) were recruited from an OS. We applied the cross design synthesis (CDS) method recommended by the United States General Accounting Office. This method combines the different strengths of RCTs and OSs into one single estimate. RESULTS: Combined continuation rates for parous vs nulliparous women could be estimated more precisely as well as overall continuation rates after one (86.6%) and two years (78.5%), irrespective of age and parity. CONCLUSION: Cross design synthesis allowed more precise estimation of continuation rates of an intrauterine device.

Twelve-month discontinuation rates of levonorgestrel intrauterine system 13.5 mg and subdermal etonogestrel implant in women aged 18-44: A retrospective claims database analysis.

OBJECTIVE: To investigate the 12-month discontinuation rates of levonorgestrel intrauterine system 13.5 mg (LNG-IUS 13.5) and subdermal etonogestrel (ENG) implant in the US. STUDY DESIGN: We identified women aged 18-44 who had an insertion of LNG-IUS 13.5 or ENG implant from the MarketScan Commercial claims database (7/1/2013-9/30/2014). Women were required to have 12 months of continuous insurance coverage prior to the insertion (baseline) and at least 12-months after (follow-up). Discontinuation was defined as presence of an insurance claim for pregnancy-related services, hysterectomy, female sterilization, a claim for another contraceptive method, or removal of the index contraceptive without re-insertion within 30 days. Using Cox regression we examined the potential impact of ENG implant vs. LNG-IUS 13.5 on the likelihood for discontinuation after controlling for patient characteristics. RESULTS: A total of 3680 (mean age: 25.4 years) LNG-IUS 13.5 and 23,770 (mean age: 24.6 years) ENG implant users met the selection criteria. Prior to insertion, 56.6% of LNG-IUS 13.5 and 42.1% of ENG implant users had used contraceptives, with oral contraceptives being most common (LNG-IUS 13.5: 42.1%; ENG implant: 28.5%). Among users of LNG-IUS 13.5 and ENG implant, rates of discontinuation were similar during the 12-month follow-up (LNG-IUS 13.5: 24.9%; ENG implant: 24.0%). Regression results showed that women using LNG-IUS 13.5 vs. ENG implant had similar likelihood for discontinuation (hazard ratio: 0.97, 95% confidence interval: 0.90-1.05, p=.41). CONCLUSION: In the real-world US setting, women aged 18-44 using LNG-IUS 13.5 and ENG implant have similar discontinuation rates after 12 months. IMPLICATIONS: In the United States, women aged 18-44 using levonorgestrel intrauterine system (13.5 mg) and subdermal etonogestrel implant have similar discontinuation rates after 12 months.

Evaluation of hospitalization costs and associated factors among maternity stays involving low-risk and moderate- to high-risk childbirths in the United States.

OBJECTIVES: This study aimed to assess the costs of childbirth and to identify factors associated with such hospital costs for low- and moderate/high-risk childbirth groups. METHODS: All hospitalizations for childbirth between 2010-2014 in the Premier Perspective Hospital Database were identified. Risk category for each birth was defined by the age of the subject and/or presence of specific maternal comorbidities and obstetric risk factors. Hospital childbirth costs were determined and stratified by risk groups. Factors associated with costs for each risk group were evaluated by multiple regression. RESULTS: Among 2,367,195 hospitalizations for childbirth, vaginal birth was the most common delivery method (n = 1,596,757; 68%). Among women characterized as moderate/high-risk, 42% (n = 642,495) had C-sections, while 11% (n = 90,211) of women categorized as low-risk had C-sections. The proportion of women with serious maternal morbidity among moderate/high-risk vs. low-risk women was 2% (n = 29,496) vs. 0.3% (n = 2749), respectively. The mean costs for moderate/high-risk vs. low-risk hospitalizations were $6145 (median = $5760) and $5397 (median = $5001), respectively (p < 0.0001). Factors significantly associated with costs for moderate/high-risk hospitalizations included delivery type (C-section vs. vaginal birth), LOS, urban/rural hospital status, geographic regions, calendar year of hospitalization, teaching status, payer types and serious maternal morbidity. Similar factors were found to impact costs among low-risk hospitalizations. CONCLUSIONS: Characteristics such as delivery type, LOS, geographical region, teaching status, serious maternal morbidity and hospital urban/rural status were shown to impact hospital costs of childbirth. Screening and prevention strategies of factors that negatively impact costs may aid in reducing the hospitalization costs associated with childbirths.

Two-year continuation of intrauterine devices and contraceptive implants in a mixed-payer setting: a retrospective review.

BACKGROUND: As the popularity of long-acting reversible contraception increases, so does the need for accurate data on method continuation in diverse clinical settings. We determined 2-year continuation rates for the levonorgestrel 52-mg intrauterine device, the copper T380A intrauterine device, and the 68-mg etonogestrel contraceptive implant in an academic healthcare system with mixed-payer reimbursement. OBJECTIVE: The purpose of this study was to examine the proportion and characteristics of women who continue intrauterine device and implant use to 2 years and to relate continuation to device type when controlling for patient characteristics. STUDY DESIGN: This retrospective chart review assessed University of Utah Healthcare System patients who had an intrauterine device or contraceptive implant inserted between January 1, 2004, and December 31, 2012. We identified users and dates of insertions and removals by querying billing, medication, and procedural data in the Electronic Data Warehouse. Multivariable Poisson regression was conducted to estimate incidence risk ratios and to relate the probability of 2-year continuous use to device type. RESULTS: Data on 8603 device insertions were obtained with the following distribution: levonorgestrel 52-mg intrauterine devices (6459; 75.1%), copper T380A intrauterine devices (1136; 13.2%), and 68-mg etonogestrel implant (1008; 11.7%). Two-year continuation rates were 77.8%, 73.1%, and 75.9%, respectively. There was no statistical difference in 2-year continuation between levonorgestrel 52-mg intrauterine device users (adjusted risk ratio, 1.1; 95% confidence interval, 1.0-1.1) and 68-mg etonogestrel implant users (adjusted risk ratio, 1.1; 95% confidence interval, 1.0-1.1) compared with copper device users, after we controlled for age, Hispanic ethnicity, payer type, and year of insertion. Older-age, self-pay, or public payer insurance (reference commercial payer) and Hispanic ethnicity were associated with 2-year continuation. CONCLUSION: Three-quarters of women with an intrauterine device or implant continue using it for 2 years. In this cohort, the 2-year continuation rates were 77.8%, 73.1%, and 75.9% for the levonorgestrel 52-mg intrauterine device, copper T380A intrauterine device, and 68-mg etonogestrel implant, respectively.

Retrospective analysis of the impact of increasing access to long acting reversible contraceptives in a commercially insured population.

BACKGROUND: Unintended pregnancies have been shown to be associated with high costs for the healthcare system, among other adverse impacts, but could still account for up to 51 % of pregnancies in the US. Improvements in contraception among women are needed. Long acting reversible contraceptives (LARCs), which have proved their safety and efficacy, have been found to significantly decrease the risk of unintended pregnancy. Yet they are still marginally employed. This study aims at investigating the evolution of LARC use over 15 years and at assessing the impact of the introduction of newer LARCs on LARC use relative to all contraceptive use. METHODS: This retrospective study identified women with LARC or short acting reversible contraceptive (SARC) claims from a US insurance claims database (01/1999-03/2014). Yearly proportions of LARC users relative to all contraceptive users were reported. Generalized estimating equation models were used to assess the impact of user characteristics, such as age group (15-17, 18-24, 25-34, and 35-44), and of time periods related to the introduction of new LARCs (01/2001: Mirena, 07/2006: Implanon, 01/2013: Skyla) on LARC use. RESULTS: A total of 1,040,978 women were selected. LARC use increased yearly from 0.6 % (1999) to 16.6 % (2013) among contraceptive users. Time periods associated with the introduction of a newer LARC were significant predictors of LARC use; women in 2006-2012 and 2013-2014 were respectively 3.7-fold (95 % CI:3.57-3.74) and 6.6-fold (95 % CI:6.43-6.80) more likely to use LARCs over SARCs relative to women in 2001-2006. The increase in LARC use was especially pronounced in young women. Compared to women aged 18-24 in 2001-2006, women aged 18-24 in 2006-2012 and 2013-2014 were respectively 6.4-fold (95 % CI:5.91-6.86) and 14.7-fold (95 % CI:13.59-15.89) more likely to use LARCs over SARCs. CONCLUSIONS: This broadly representative commercial claim-based study showed that the proportion of privately insured women of childbearing age using LARCs increased over time and that the introduction of newer LARCs corresponded with significant increases in overall LARC use. Future research is needed to assess LARC use in uninsured or publicly-insured populations.

The Additional Cost Burden of Preexisting Medical Conditions During Pregnancy and Childbirth.

OBJECTIVES: To identify the prevalence of comorbidities in pregnant women and examine the incremental costs of these conditions on the care for mothers and their newborns. METHODS: This was a retrospective comparative cohort study of women ages 15-49 years with a documented live-birth delivery using de-identified claims from the MarketScan Research Commercial Claims and Encounters database incurred between January 1, 2007, and December 31, 2011. Total health care costs from date of first pregnancy-related claim through 3 months postdelivery were reported; pregnancy-related comorbidities prior to the pregnancy diagnosis were identified and categorized in the 12 months prior to the pregnancy diagnosis, and costs associated with each condition were compiled. A subset of newborns was matched to their mothers using a unique family identifier and their costs were captured for the three months following birth. Comparisons of costs for both mothers and newborns were made using both unadjusted and multivariate analyses between mothers with and without each condition. RESULTS: A total of 322,141 women with live births were identified; 135,572 of these mothers were linked to their newborn(s). Prevalent conditions included back disorders (8.9%), mental disorders (6.5%), headache (5.5%), allergic rhinitis (5.5%), and osteoarthritis (4.8%). Diabetes (0.97%) and hypertension (1.9%) were associated with the highest adjusted incremental costs of care in both mothers ($6,211 [95% confidence interval 5,720-6,702] and $3,367 [95% CI 2,935-3,799] respectively) and newborns ($2,067 [95% CI 1,515-2618]; and $1,210 [95% CI 725-1,695] respectively). The two most common conditions, back disorders and mental disorders, were associated with unadjusted costs of $1,895/$978 (mothers/infants) and $2,097/$1,902 (mothers/infants) respectively. CONCLUSION: Preexisting conditions common in pregnant women may result in additional resource utilization and costs for both mothers and newborns.

Knowledge and attitudes of Latin American obstetricians and gynecologists regarding intrauterine contraceptives.

BACKGROUND: Intrauterine contraceptives (IUCs), including the copper intrauterine device and the levonorgestrel-releasing intrauterine system (LNG-IUS), are among the reversible contraceptive methods with high effectiveness. However, use is low in many settings, including some Latin American countries, mainly due to the influences of myths, fears, and negative attitudes, not only of users and potential users, but also of different cadres of health care professionals. The purpose of this study was to assess the knowledge and attitudes of a group of Latin American obstetricians and gynecologists regarding IUCs. METHODS: A survey was conducted during a scientific meeting organized in Chile in 2014 to present and discuss updated information about contraception. Obstetricians and gynecologists from 12 Latin American countries, who reported that they provide daily contraception services in both the public and private sectors, participated in the meeting. Participants who agreed to take part in the survey responded to a multiple-choice questionnaire on issues regarding knowledge, use, and attitudes about IUCs. RESULTS: Of the 210 obstetricians and gynecologists participating in the meeting, the respondents to each question varied from 168 (80.0%) to 205 (97.6%). Almost 50% recognized that the failure rate of combined oral contraceptives, patches, and vaginal rings is 8%-10%. Furthermore, 10% of the participants did not recognize the high contraceptive effectiveness of long-acting reversible contraceptive methods. Additionally, almost 80% of the respondents answered that they did not offer IUCs to nulligravidas and almost 10% did not offer IUCs to adolescents, albeit almost 90% of the respondents reported that nulligravidas are candidates for an LNG-IUS. CONCLUSION: Some deficiencies and contradictions in terms of knowledge and attitudes were identified from the answers of the Latin American obstetricians and gynecologists who participated in the survey. The knowledge and attitudes of health care professionals about IUCs are important in order to provide adequate counseling and to expand the use of IUCs.

The cost of unintended pregnancies for employer-sponsored health insurance plans.

BACKGROUND: Pregnancy is associated with a significant cost for employers providing health insurance benefits to their employees. The latest study on the topic was published in 2002, estimating the unintended pregnancy rate for women covered by employer-sponsored insurance benefits to be approximately 29%. OBJECTIVES: The primary objective of this study was to update the cost of unintended pregnancy to employer-sponsored health insurance plans with current data. The secondary objective was to develop a regression model to identify the factors and associated magnitude that contribute to unintended pregnancies in the employee benefits population. METHODS: We developed stepwise multinomial logistic regression models using data from a national survey on maternal attitudes about pregnancy before and shortly after giving birth. The survey was conducted by the Centers for Disease Control and Prevention through mail and via telephone interviews between 2009 and 2011 of women who had had a live birth. The regression models were then applied to a large commercial health claims database from the Truven Health MarketScan to retrospectively assign the probability of pregnancy intention to each delivery. RESULTS: Based on the MarketScan database, we estimate that among employer-sponsored health insurance plans, 28.8% of pregnancies are unintended, which is consistent with national findings of 29% in a survey by the Centers for Disease Control and Prevention. These unintended pregnancies account for 27.4% of the annual delivery costs to employers in the United States, or approximately 1% of the typical employer's health benefits spending for 1 year. Using these findings, we present a regression model that employers could apply to their claims data to identify the risk for unintended pregnancies in their health insurance population. CONCLUSION: The availability of coverage for contraception without employee cost-sharing, as was required by the Affordable Care Act in 2012, combined with the ability to identify women who are at high risk for an unintended pregnancy, can help employers address the costs of unintended pregnancies in their employee benefits population. This can also help to bring contraception efforts into the mainstream of other preventive and wellness programs, such as smoking cessation, obesity management, and diabetes control programs.

The prevalence of complications and healthcare costs during pregnancy.

OBJECTIVE: To study the economic burden of pregnancy in the US, common complications during pregnancy, and the incremental costs attributable to these complications. METHODS: A retrospective comparative cohort study was conducted of pregnant women aged 15-49 years using de-identified medical and pharmacy claims from the Truven Health MarketScan Commercial Claims and Encounters database incurred between January 1, 2007 and December 31, 2011. The total healthcare costs are reported (adjusted to 2011 dollars) from the date of the first pregnancy-related claim through to 3 months post-delivery and these costs were compared to matched controls of non-pregnant women. Pregnancy-related complications were categorized, and the incremental costs associated with each complication were estimated using multivariate analyses. RESULTS: A total of 322,141 eligible women with live births were studied. Compared to matched controls, the average costs of care for pregnant women were nearly $13,000 higher through 3 months post-delivery. A total of 46.9% of women had at least one pre-specified pregnancy complication; the most commonly observed were fetal abnormality (24.7%) and early or threatened labor (16.3%). Multiple gestation (1.9%) resulted in the highest adjusted incremental cost ($12,212; 95% CI = 11,298, 13,216); hypertension ($6152; 95% CI = 5312, 6992) and diabetes ($5081; 95% CI = 4244, 5918) were also among those complications that led to high incremental costs of care. CONCLUSION: Pregnancy and delivery are frequently compounded by complications that lead to increased costs and resource utilization.

Costs of Newborn Care Following Complications During Pregnancy and Delivery.

The aim of this study is examine the impact of pregnancy and delivery complications on the healthcare costs of newborns during the first 3 months of life. We conducted a retrospective cohort study of newborns born to women ages 15-49 using de-identified medical and pharmacy claims from the Truven Health MarketScan Commercial Claims and Encounters database incurred between January 1, 2007 and December 31, 2011. Total healthcare costs and resource utilization were examined and compared for the first 3 months of life between cohorts of newborns either with or without evidence of categorized maternal complications. Incremental costs were also determined using multivariable analysis for the conditions found to be the most prevalent in the study population. A total of 137,040 infants were studied, 75.4% of which were born to mothers who had experienced at least one complication during pregnancy or delivery. Fetal abnormalities (26.2%), early or threatened labor (16.6%), and hemorrhage (10.8%) were the most frequently observed complications. Diabetes (8.0%) and hypertension (7.7%) were also common, with the majority of other conditions present in 1% or less of the study population. Adjusted analyses found significant differences for seven conditions where incremental costs ranged from $987 to $10,287. Complications are common during pregnancy and delivery and some complications may lead to increased healthcare costs for newborns immediately following birth.

Ovarian cysts: presence and persistence with use of a 13.5mg levonorgestrel-releasing intrauterine system.

OBJECTIVE: The aim of this study was to assess the presence of ovarian cysts in women using a new low-dose levonorgestrel-releasing intrauterine contraceptive system (LNG-IUS 13.5mg [total content]). STUDY DESIGN: A Phase 3 study assessed LNG-IUS 13.5mg use in healthy women with regular menstrual cycles who requested contraception. Transvaginal ultrasonography was performed at screening, baseline, and 3, 6, 9, 12, 18, 24, 30, and 36 months after placement. RESULTS: A total of 1432 women, mean age 27.2±4.8 years, were studied. A total of 10,446 transvaginal ultrasound examinations were performed over 3 years. Ovarian cysts were present in 1.6, 1.1, 2.3, 2.1, 2.4, 2.0, 2.1, 2.2, 1.9, and 2.1% of participants at screening, baseline, and Months 3, 6, 9, 12, 18, 24, 30, and 36, respectively. One hundred first-time ovarian cysts were identified from baseline through Month 9. The size distribution through Month 12 was ≤30 mm (13%), >30 to ≤50 mm (74%), >50 to ≤80 mm (11%), and >80 mm (0%). The overall persistence of ovarian cysts from one examination to the next in Year 1 was 12% (11/90 with follow-up). Cyst persistence was 36% from baseline to 3 months, 13% from 3 to 6 months, 10% from 6 to 9 months, and 0% from 9 to 12 months. The likelihood of cyst persistence increased for cysts >50mm (36%) as compared to those ≤50 mm (8%). CONCLUSION: Ovarian cysts were present in 1.6% of women at screening, 2.0 to 2.4% of LNG-IUS 13.5mg users during Year 1, and 1.9 to 2.1% during Years 2 and 3. The majority were >30 to ≤50 mm in size. The small and diminishing number of persistent cysts-decreasing to 0% from 9 to 12 months-suggests that they were functional in nature. IMPLICATIONS: Transvaginal ultrasound follow-up of women during a 3-year clinical trial of LNG-IUS 13.5mg showed that ovarian cysts were present in 1.6% of participants at screening and 1.1-2.4% at each subsequent visit. Eighty-eight percent were ≤5cm, with none >8cm. No ovarian cysts persisted beyond Month 9, suggesting a functional etiology.

Medicaid spending on contraceptive coverage and pregnancy-related care.

OBJECTIVE: Up to 50% of pregnancies are unintended in the United States, and the healthcare costs associated with pregnancy are the most expensive among hospitalized conditions. The current study aims to assess Medicaid spending on various methods of contraception and on pregnancy care including unintended pregnancies. METHODS: We analyzed Medicaid health claims data from 2004 to 2010. Women 14-49 years of age initiating contraceptive methods and pregnant women were included as separate cohorts. Medicaid spending was summarized using mean all-cause and contraceptive healthcare payments per patient per month (PPPM) over a follow-up period of up to 12 months. Medicaid payments were also estimated in 2008 per female member of childbearing age per month (PFCPM) and per member per month (PMPM). Medicaid payments on unintended pregnancies were also evaluated PFCPM and PMPM in 2008. RESULTS: For short-acting reversible contraception (SARC) users, all-cause payments and contraceptive payments PPPM were respectively $365 and $18.3 for oral contraceptive (OC) users, $308 and $19.9 for transdermal users, $215 and $21.6 for vaginal ring users, and $410 and $8.8 for injectable users. For long-acting reversible contraception (LARC) users (follow-up of 9-10 months), corresponding payments were $194 and $36.8 for IUD users, and $237 and $29.9 for implant users. Pregnancy cohort all-cause mean healthcare payments PPPM were $610. Payments PFCPM and PMPM for contraceptives were $1.44 and $0.54, while corresponding costs of pregnancies were estimated at $39.91 and $14.81, respectively. Payments PFCPM and PMPM for contraceptives represented a small fraction at 6.56% ($1.44/$21.95) and 6.63% ($0.54/$8.15), respectively of the estimated payments for unintended pregnancy. CONCLUSIONS: This study of a large sample of Medicaid beneficiaries demonstrated that, over a follow-up period of 12 months, Medicaid payments for pregnancy were considerably higher than payments for either SARC or LARC users. Healthcare payments for contraceptives represented a small proportion of payments for unintended pregnancy when considering the overall Medicaid population perspective in 2008.

The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: dietary and blood assessments.

OBJECTIVE: To assess the folate status of US women in a study of a folate-fortified oral contraceptive (OC) using the Short Folate Food Frequency Questionnaire and plasma and red blood cell (RBC) folate samples. DESIGN: Sub-analysis from a multi-centre, randomised, double-blind, controlled contraceptive trial with assessments at baseline and 6 months. We calculated dietary folate equivalents (DFE) consumed and the proportion of participants meeting folate adequacy benchmarks. SETTING: Eight centres in the USA. SUBJECTS: Healthy women aged 18-40 years requesting contraception with no contraindications for OC use. RESULTS: Overall, 385 participants were randomised to either a novel folate-fortified OC or a marketed OC. The 262 (68 %) participants compliant with the protocol were included in the analysis set. Baseline daily DFE consumption was 529·8 (sd 342·1) µg and similar in both groups. At follow-up, the fortified OC group had higher intake than the conventional OC group (1225·9 (sd 346·2) µg compared with 500·6 (sd 361·2) µg). Mean plasma folate level increased from 44·5 (sd 17·2) to 55·8 (sd 21·1) nmol/l. Mean RBC folate level increased from 996·7 (sd 369·8) to 1311·9 (sd 436·0) nmol/l. The proportion meeting selected folate adequacy benchmarks increased in the fortified OC group (P < 0·001). CONCLUSIONS: Lack of adequate folate intake in reproductive-aged women from dietary sources or supplements alone suggests the need for novel approaches. Use of folate-fortified OC ensures adequate folate levels and meeting of folate benchmarks.

Healthcare-related characteristics of low vs normal folate levels among women of child-bearing age.

OBJECTIVE: Despite the institution of mandatory folic acid fortification in the US, folate deficiencies still occur and are associated with an increased risk of several conditions. Since little is known regarding the relationship between folate status and other clinical, demographic, and healthcare-related characteristics, the objective of the study was to compare healthcare-related characteristics among US child-bearing age women with low vs normal red blood cell (RBC) folate levels. RESEARCH DESIGN AND METHODS: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used to conduct a retrospective cohort study. Women (aged 18-45 when surveyed) were categorized in two cohorts for comparison: normal RBC folate level (≥ 140 ng/ml, NFL) and low RBC folate level (<140 ng/ml, LFL). RESULTS: Of the 2816 subjects, 5.9% were assigned to the LFL cohort and were significantly younger (28 vs 30 years, p=0.01); a greater proportion were 18-25 years old (55.7% vs 39.9%, p<0.001) or African-American (55.1% vs 22.3%, p<0.01). A lower proportion of LFL women were insured (67.3% vs 75.5%, p=0.01) with low rates of private insurance (39.5% vs 53.1%, p<0.01), while Medicaid/SCHIP coverage was similar (16.8% vs 15.1%, p=0.56). Predictors of low folate levels included aged 36-45 years (OR: 2.14 [95% CI: 1.04, 4.39]) and never being married (2.65 [1.34, 5.24]), while a household income ≥ $75,000 reduced the likelihood of having low folate levels (0.20 [0.06, 0.73]). LIMITATIONS: The proportion of women with low folate levels was small, with the sample size limiting the ability to adjust for other factors during analysis. Medical histories were based on patient interviews and are subject to recall bias. CONCLUSION: LFL women are younger and have low rates of private insurance coverage compared to women with normal folate levels. Differences in age, marital status, and household income are associated with folate status.

Use of drospirenone/ethinyl estradiol (DRSP/EE) among women with acne reduces acne treatment-related resources.

BACKGROUND AND OBJECTIVE: Acne is a common dermatologic condition that extends into middle age, particularly among women, and is associated with substantial healthcare resource utilization. Drospirenone (DRSP), a synthetic progestin, has anti-androgenic activity, and women using DRSP 3.0 mg/ethinyl estradiol (EE) 0.02 mg as a 24/4 regimen (DRSP/EE-24/4) for contraception also may use it for treatment of moderate acne. The study used a US national healthcare database to assess acne-related healthcare resource utilization among women aged 18-45 years before (pre-index) and after (post-index) initiation of DRSP/EE-24/4. METHODS: Resource utilization and costs were evaluated by age group (18-25, 26-35, or 36-45 years) and by type of acne medication (systemic antibiotic, topical, or anti-androgen). RESULTS: Data for 1340 women were evaluated. Overall, drug costs, medical costs, and total costs were decreased by 38%, 37%, and 37%, respectively (p<0.0001 for all) between the pre-index and post-index periods; significant differences were evident across age groups and acne medication categories. Total costs were significantly decreased for patients (41%) and healthcare plans (36%; p<0.0001 for both) overall and across age groups and drug classes. Acne-related claims and number of days using acne medication were reduced (by 37% each; p<0.0001 for both). STUDY LIMITATIONS: The study was retrospective in design and had a limited follow-up period. Database limitations restricted assessment of medication compliance and adherence. CONCLUSION: DRSP/EE-24/4 use was associated with substantial reductions in acne-related healthcare resource utilization, and reductions occurred regardless of age or type of acne medication. DRSP/EE-24/4 therefore represents a cost-effective option for the treatment of acne among women using DRSP/EE-24/4 for oral contraception.

Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States.

OBJECTIVE: The objective of the study was to estimate the potential reduction of neural tube defects (NTDs) through the use of Metafolin-fortified oral contraceptives (OCs) in the United States. STUDY DESIGN: A population-based decision analytic model was developed to estimate the benefits of increased red blood cell (RBC) folate levels through the use of Metafolin-fortified OCs on NTD risk during pregnancy. We modeled women who began the year taking Metafolin-fortified or traditional OCs. Folate levels were derived from the National Health and Nutrition Examination Survey and clinical trial data. NTD risk was estimated by applying a published risk equation to respective RBC folate levels. RESULTS: The number of predicted NTD cases declined by 23.7% to 31.4%, depending on median baseline folate levels in women taking a fortified OC compared with taking a traditional OC. CONCLUSION: Metafolin-fortified OCs have the potential to reduce the number of folate-dependent NTDs among current and recent OC users.

Premenstrual dysphoric disorder symptom cluster improvement by cycle with the combined oral contraceptive ethinylestradiol 20 mcg plus drospirenone 3 mg administered in a 24/4 regimen.

BACKGROUND: A combined oral contraceptive comprising ethinylestradiol (EE) 20 mcg/drospirenone 3 mg in a 24/4 regimen has been clinically shown to alleviate the symptoms associated with premenstrual dysphoric disorder (PMDD). However, previous studies did not report data according to cycle-by-cycle improvement. STUDY DESIGN: This was a subanalysis of a Phase III, double-blind, multicenter, United States-based study. Women with confirmed PMDD were randomized to EE 20 mcg/drospirenone 3 mg 24/4 or placebo for three treatment cycles. Ten of the 21 emotional and physical items on the Daily Record of Severity of Problems scale were grouped to define three symptom clusters: (a) negative emotions, (b) food cravings and (c) water retention-related symptoms. The change from baseline at each treatment cycle was compared between groups using a weighted analysis of covariance model. RESULTS: The full analysis set comprised 449 women. Daily Record of Severity of Problems scores for each symptom cluster were significantly reduced from baseline with both EE 20 mcg/drospirenone 3 mg 24/4 and placebo (p<.0001 for all). The greatest symptom improvements were achieved within the first cycle of treatment and continued throughout cycles 2 to 3. The mean between-treatment difference was significant in favor of EE 20 mcg/drospirenone 3 mg 24/4 for all three symptom clusters in all three treatment cycles (p≤.0001 vs. placebo in percent change from baseline). CONCLUSION: Ethinylestradiol 20 mcg/drospirenone 3 mg 24/4 improved commonly recognizable PMDD symptom clusters relating to negative emotions, food cravings and water retention-related symptoms to a significantly greater extent than placebo during all three cycles of treatment.