Racial and ethnic disparities in use of 17-alpha hydroxyprogesterone caproate for prevention of preterm birth.

Racial/ethnic disparities in preterm birth remain a major public health challenge in the United States. While 17-alpha hydroxyprogesterone caproate (17OHP-C) is recommended for preterm birth prevention in women with a prior preterm birth, non-Hispanic black women continue to experience higher rates of recurrent preterm birth than white women receiving the same treatment. Further investigation of disparities in 17OHP-C use and adherence is warranted. We sought to evaluate whether racial and ethnic disparities exist in the use of and adherence to 17OHP-C within a population of eligible women. This was a retrospective cohort study of women with a prior spontaneous, singleton preterm birth who were eligible for 17OHP-C for preterm birth prevention and received care at a single institution from 2010 through 2014. Associations between self-identified race/ethnicity (non-Hispanic black vs women in all other racial/ethnic groups) and documented counseling about 17OHP-C, receipt of any 17OHP-C, and adherence to 17OHP-C administration were each estimated by bivariable analysis and multivariable logistic regression. Adherence to 17OHP-C was defined as not >1 missed dose, initiation <20 weeks' gestational age, and continuation until 37 weeks or delivery. Of 472 women who were clinically eligible for 17OHP-C, 72% (N = 296) had documented 17OHP-C counseling and 48.9% (N = 229) received 17OHP-C. There were no differences in likelihood of 17OHP-C counseling or receipt of 17OHP-C based on race/ethnicity. While overall 83% (N = 176) of women were adherent to 17OHP-C, only 70% (N = 58) of non-Hispanic black women were adherent, compared to 91% (N = 118) of all other women (P < .001). Non-Hispanic black women had more missed doses (2.4 vs 0.4 doses, P < .001) and later initiation of care (12.0 vs 10.2 weeks, P < .001) than women in other racial/ethnic groups. After adjustment for potential confounders, non-Hispanic black women were significantly less likely to be adherent to 17OHP-C (adjusted odds ratio, 0.16; 95% confidence interval, 0.04-0.65). A significant interaction between non-Hispanic black race/ethnicity and public insurance was identified (adjusted odds ratio, 0.16; 95% confidence interval, 0.05-0.52). In a diverse cohort of women eligible for preterm birth prevention, non-Hispanic black women are at an increased risk of nonadherence to 17OHP-C. Non-Hispanic black women with public insurance are at a particularly increased risk of nonadherence.

Yee LM ，Liu LY ，Sakowicz A ，Bolden JR ，Miller ES ... -  《-》

Disparities in 17-Hydroxyprogesterone Caproate Offer and Uptake in Pregnancies at a Risk of Preterm Birth.

To evaluate the offer, acceptance, uptake, and patient experience with 17-hydroxyprogesterone caproate (17OHP-C) over the course of 10 years. This is a retrospective cohort study with a qualitative component. We identified all women with spontaneous preterm deliveries with subsequent births in our hospital between 2005 and 2015. We used linear regression to calculate unadjusted odds ratios for 17OHP-C offer, acceptance, and doses received associated with predictors of interest, and multivariable modeling further adjusted for potential confounders. A grounded theory approach was used to glean recurrent themes surrounding the patient experience. A total of 265 women fit the eligibility criteria; 39.6% were offered 17OHP-C and 83.8% accepted 17OHP-C. The mean number of documented 17OHP-C doses was 15.7 ± 5.4. Women were less likely to be offered 17OHP-C if they had public insurance or if their earliest preterm birth was of greater gestational age. Non-Hispanic black women were documented to have received four fewer doses than white women. We also identified recurrent themes that hindered acceptance and adherence to 17OHP-C: insurance difficulties, unstable housing, lack of childcare, and job inflexibility. Women at a risk of preterm birth are more likely to be offered and receive 17OHP-C if they have private insurance and have had an earlier preterm birth. Non-Hispanic black women were documented to have received fewer doses of 17OHP-C than white women. Further inquiry into the structural causes that lead to disparities in care for women at a risk for preterm birth is important.

Berhie SH ，Riley LE ，Bryant AS 《-》

Nonresponse to 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention: clinical prediction and generation of a risk scoring system.

Spontaneous preterm birth remains a leading cause of neonatal morbidity and mortality among nonanomalous neonates in the United States. Spontaneous preterm birth tends to recur at similar gestational ages. Intramuscular 17-alpha hydroxyprogesterone caproate reduces the risk of recurrent spontaneous preterm birth. Unfortunately, one-third of high-risk women will have a recurrent spontaneous preterm birth despite 17-alpha hydroxyprogesterone caproate therapy; the reasons for this variability in response are unknown. We hypothesized that clinical factors among women treated with 17-alpha hydroxyprogesterone caproate who suffer recurrent spontaneous preterm birth at a similar gestational age differ from women who deliver later, and that these associations could be used to generate a clinical scoring system to predict 17-alpha hydroxyprogesterone caproate response. Secondary analysis of a prospective, multicenter, randomized controlled trial enrolling women with ≥1 previous singleton spontaneous preterm birth <37 weeks' gestation. Participants received daily omega-3 supplementation or placebo for the prevention of recurrent preterm birth; all were provided 17-alpha hydroxyprogesterone caproate. Women were classified as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest previous spontaneous preterm birth. Responders were women with pregnancy extending ≥3 weeks later compared with the delivery gestational age of their earliest previous preterm birth; nonresponders delivered earlier or within 3 weeks of the gestational age of their earliest previous preterm birth. A risk score for nonresponse to 17-alpha hydroxyprogesterone caproate was generated from regression models via the use of clinical predictors and was validated in an independent population. Data were analyzed with multivariable logistic regression. A total of 754 women met inclusion criteria; 159 (21%) were nonresponders. Responders delivered later on average (37.7±2.5 weeks) than nonresponders (31.5±5.3 weeks), P<.001. Among responders, 27% had a recurrent spontaneous preterm birth (vs 100% of nonresponders). Demographic characteristics were similar between responders and nonresponders. In a multivariable logistic regression model, independent risk factors for nonresponse to 17-alpha hydroxyprogesterone caproate were each additional week of gestation of the earliest previous preterm birth (odds ratio, 1.23; 95% confidence interval, 1.17-1.30, P<.001), placental abruption or significant vaginal bleeding (odds ratio, 5.60; 95% confidence interval, 2.46-12.71, P<.001), gonorrhea and/or chlamydia in the current pregnancy (odds ratio, 3.59; 95% confidence interval, 1.36-9.48, P=.010), carriage of a male fetus (odds ratio, 1.51; 95% confidence interval, 1.02-2.24, P=.040), and a penultimate preterm birth (odds ratio, 2.10; 95% confidence interval, 1.03-4.25, P=.041). These clinical factors were used to generate a risk score for nonresponse to 17-alpha hydroxyprogesterone caproate as follows: black +1, male fetus +1, penultimate preterm birth +2, gonorrhea/chlamydia +4, placental abruption +5, earliest previous preterm birth was 32-36 weeks +5. A total risk score >6 was 78% sensitive and 60% specific for predicting nonresponse to 17-alpha hydroxyprogesterone caproate (area under the curve=0.69). This scoring system was validated in an independent population of 287 women; in the validation set, a total risk score >6 performed similarly with a 65% sensitivity, 67% specificity and area under the curve of 0.66. Several clinical characteristics define women at risk for recurrent preterm birth at a similar gestational age despite 17-alpha hydroxyprogesterone caproate therapy and can be used to generate a clinical risk predictor score. These data should be refined and confirmed in other cohorts, and women at high risk for nonresponse should be targets for novel therapeutic intervention studies.

Manuck TA ，Stoddard GJ ，Fry RC ，Esplin MS ，Varner MW ... -  《-》

Spontaneous preterm birth in African-American and Caucasian women receiving 17α-hydroxyprogesterone caproate.

To determine if the rates of recurrent spontaneous preterm birth in women receiving 17α-hydroxyprogesterone caproate (17P) differ according to maternal race. Retrospective analysis of a cohort of women enrolled in outpatient 17P administration at < 27 weeks. Maternal characteristics, obstetric history, and rates of recurrent preterm birth were determined using chi-square and multivariable Cox proportional hazards regression at two-tailed α = 0.05. Primary study outcome was defined as having a spontaneous preterm birth < 34 weeks. African-American women initiated 17P injections later (19.6 versus 18.9 weeks, p < 0.001) and discontinued injections earlier (33.2 versus 34.1 weeks, p < 0.001) than Caucasian women. Spontaneous recurrent preterm birth < 34 weeks was higher in African-Americans versus Caucasians receiving 17P (odds ratio 2.1; 95% confidence interval 1.7, 2.4). After adjusting for other significant factors, African-American race retained the strongest association with recurrent spontaneous preterm birth < 34 weeks. Within each racial group, short cervical length < 25 mm before 27 weeks' gestation had the highest hazard of recurrent spontaneous preterm delivery. Despite treatment with 17P, African-American women have higher rates of recurrent preterm birth.

Timofeev J ，Singh J ，Istwan N ，Rhea D ，Driggers RW ... -  《-》

Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth.

Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response. We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate "responder." This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with ≥1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended ≥3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression. One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32% (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95% confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95% confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95% confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort. Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention.

Manuck TA ，Esplin MS ，Biggio J ，Bukowski R ，Parry S ，Zhang H ，Huang H ，Varner MW ，Andrews W ，Saade G ，Sadovsky Y ，Reddy UM ，Ilekis J ，Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR) ... -  《-》