Objective
The standard weekly dose of 17-alpha hydroxyprogesterone caproate (17OHP-C; 250 mg/wk) to reduce the risk of recurrent preterm birth was adopted without regard to patient characteristics. We examined the relationship between prepregnancy body mass index (BMI) and gestational age at birth after 17OHP-C prophylaxis. We hypothesized that rates of births before 32, 35, and 37 weeks of gestation would be increased in women with a BMI of 25 kg/m 2 or greater.
Study Design
A retrospective cohort study was conducted from a deidentified database of women treated with 17OHP-C for prior spontaneous preterm birth. The frequency of recurrent preterm delivery before 32, 35, and 37 weeks of gestation was investigated for women with a BMI less than 25 kg/m 2 compared with women with a BMI of 25 kg/m 2 or greater. The adjusted relative risk of preterm delivery was estimated through a modified Poisson regression approach.
Results
Of 390 women who met inclusion criteria, 60 (15.4%) delivered before 32 weeks, 89 (22.8%) before 35 weeks, and 156 (40.0%) before 37 weeks. A total of 174 women had a BMI less than 25 kg/m 2 (mean [SD], 21.2 [2.5]) and 216 had a BMI of 25 kg/m 2 or greater (mean [SD], 33.5 [6.7]). Risk of birth before 32 weeks was 1.7 times higher on average (adjusted relative risk, 1.7; 95% confidence interval, 1.05–2.77) in overweight women than in women with a BMI less than 25 kg/m 2 , adjusting for age, race, smoking, and short cervix. There was no difference in the risk of preterm birth before 35 or 37 weeks.
Conclusion
Among pregnant women receiving 17OHP-C prophylaxis for a prior preterm birth, recurrent preterm birth before 32 weeks was significantly more common in those women whose prepregnancy BMI was 25 kg/m 2 or greater than in women with BMI less than 25 kg/m 2 . This observation is consistent with pharmacological studies suggesting that dosing regimens of 17OHP-C may affect efficacy.
Preterm birth is the principal underlying cause of infant mortality in the United States, leading to 34% of all infant deaths. For those premature infants who survive past the first year, significant morbidities such as cerebral palsy, cognitive defects, and social and behavioral problems impose a great burden on these children and their families for the rest of their lives.
Prevention of prematurity has been an intense area of research in the past few decades; supplemental progesterone is a significant advance in this field. Seventeen-alpha hydroxyprogesterone caproate (17OHP-C) prophylaxis has been shown to reduce the rates of singleton preterm birth by one third in women with a prior spontaneous preterm birth.
The current recommendation for all women with a prior spontaneous preterm birth is to receive weekly injections of 250 mg 17OHP-C to reduce the risk of recurrent preterm birth. However, this guideline was adopted without consideration of patient characteristics, such as body mass index (BMI), which could influence fundamental pharmacodynamics such as drug plasma concentration and drug distribution.
17OHP-C has a high lipid solubility, suggesting a slow release from fat stores. Caritis et al demonstrated that maternal plasma concentrations of 17OHP-C vary greatly between individuals after treatment with the same recommended dosage. This study also showed a negative correlation between BMI and 17OHP-C concentrations, with the lowest 17OHP-C plasma concentrations at 3.7–8.1 ng/mL associated with an increased risk of preterm birth. Maternal BMI may therefore affect plasma concentration and efficacy of 17OHP-C therapy.
The purpose of this study was to evaluate the relationship between BMI and preterm birth rates in women who have been treated with 17OHP-C prophylaxis. We hypothesized that women with a BMI of 25 kg/m 2 or greater would have an increased risk of birth before 32, 35, and 37 weeks of gestation.
Materials and Methods
This is a retrospective cohort study of preterm birth in women who were treated with weekly intramuscular injections of 250 mg 17OHP-C initiated between 16 0/7 and 21 6/7 weeks for a history of prior spontaneous preterm birth. All data were extracted from an institutional review board–approved deidentified research database of women seen at The Ohio State University Wexner Medical Center Prematurity Prevention Clinic between January 2005 and February 2014.
17OHP-C prophylactic treatment was introduced in the clinic in 2004 and has been consistently implemented since 2005. Data on demographics, health and reproductive histories, care plans, and pregnancy outcomes were recorded in an electronic database by a single research nurse. For women with multiple recurrent preterm births in the database, only the first was included in this analysis. We excluded women with multiple gestations and uterine anomalies, populations in whom benefit of 17OHP-C has not been demonstrated.
BMI was calculated as patient reported prepregnancy weight in kilograms divided by the square of the office-measured height in meters and categorized as lean or normal weight (BMI <25.0 kg/m 2 ), overweight (≤25.0 kg/m 2 BMI <30 kg/m 2 ), or obese (BMI ≥30 kg/m 2 ).
Our initial hypotheses were to test the association between overweight or obese and preterm birth, collapsing the 2 upper categories of BMI groups. Some results are also presented for these groups separately. The primary outcomes of interest were recurrent preterm delivery before 32, 35, and 37 weeks of gestation.
Patient baseline demographic and clinical characteristics were compared via the Wilcoxon rank-sum test for continuous or ordered covariates and by the Fisher exact test for categorical characteristics. The adjusted relative risks of preterm delivery between BMI groups were estimated through a modified Poisson regression approach.
Adjustment covariates were chosen a priori based on the previous literature. These included age, race, smoking status, and short (<21 mm) cervical length before 24 weeks’ gestation (a major risk factor for preterm birth defined as a cervical length measurement less than 21 mm via transvaginal ultrasound), and the gestational age at the patient’s earliest preterm birth.
All analyses were performed in STATA 13.0 (StataCorp, 2013, Stata Statistical Software: Release 13; StataCorp LP, College Station, TX). All reported P values and confidence intervals (CIs) are 2 sided and unadjusted for multiple comparisons.
Results
Of the 390 women who met inclusion criteria, 174 (44.6%; mean [SD], 21.2 [2.5]) had a prepregnancy BMI less than 25 kg/m 2 ; 216 (55.4%; mean [SD], 33.5 [6.7]) had a prepregnancy BMI of 25 kg/m 2 or greater. Table 1 summarizes the demographic and clinical data. Smoking was more prevalent in women with low and normal BMI (47.1%) than in women who were overweight or obese (36.6%) (Fisher exact test P = .039). Women with a BMI of 25 kg/m 2 or greater were significantly more likely to have a short cervix before 24 weeks’ gestation (39.4% vs 25.3%, Fisher exact test, P = .004) than women with a BMI less than 25 kg/m 2 . Cervical cerclage, a common surgical treatment for short cervix, was used more often in the women in the high BMI group than in the women in the normal BMI group (30.6% vs 20.7%, Fisher exact test, P = .028).
| Demographic | BMI <25 kg/m 2 (n = 174) | BMI ≥25 kg/m 2 (n = 216) |
|---|---|---|
| BMI, kg/m 2 | ||
| Mean (SD) | 21.2 (2.5) | 33.5 (6.7) |
| Median (minimum, maximum) | 21.5 (15.3, 24.9) | 31.9 (25.0, 53.9) |
| Overweight, n (%) | 75 (35.0) | |
| Obese, n (%) | 141 (65.0) | |
| Age, y | ||
| Mean (SD) | 25.6 (5.3) | 26.8 (5.1) |
| Median (minimum, maximum) | 25.0 (16, 41) | 26 (17,41) |
| Gravidity, median (minimum, maximum) | 4.0 (2, 13) | 4.0 (2, 14) |
| Parity, median (minimum, maximum) | 2.0 (0, 12) | 2.0 (0, 11) |
| GA, wks, of earliest PTB | ||
| Mean (SD) | 28.0 (6.0) | 25.3 (6.1) |
| Median (minimum, maximum) | 29.25 (16.0, 36.5) | 24.0 (15.0, 36.5) a |
| GA, wks, of most recent birth | ||
| Mean (SD) | 29.7 (6.3) | 27.7 (7.0) |
| Median (minimum, maximum) | 32.0 (16, 40) | 28.0 (13, 40) a |
| GA, wks, at first office visit | ||
| Mean (SD) | 15.2 (4.4) | 14.3 (4.4) |
| Median (minimum, maximum) | 15.1 (6.0, 26.0) | 14.1 (5.0, 28.6) a |
| GA, wks, at first CL | ||
| Mean (SD) | 16.9 (2.7) | 16.5 (2.8) |
| Median (minimum, maximum) | 16.5 (11, 26) | 15.8 (11.2, 28.6) a |
| First CL, mm | ||
| Mean (SD) | 31.7 (8.3) | 31.8 (9.2) |
| Median (minimum, maximum) | 32.0 (0, 48) | 33.0 (3, 58) |
| Total number of visits | ||
| Mean (SD) | 6.7 (2.8) | 6.9 (3.0) |
| Median (minimum, maximum) | 6.0 (1, 16) | 7.0 (1, 17) |
| GA, wks, at delivery | ||
| Mean (SD) | 36.4 (3.8) | 35.6 (5.4) |
| Median (minimum, maximum) | 37.5 (19, 41) | 37.5 (17.2, 41.1) |
| Race | ||
| Nonblack, n (%) | 78 (44.8) | 84 (38.9) |
| Black, n (%) | 96 (55.2) | 132 (61.1) |
| Insurance | ||
| No insurance, n (%) | 11 (6.3) | 17 (7.9) |
| Medicaid, n (%) | 127 (73.0) | 155 (71.8) |
| Private insurance, n (%) | 36 (20.7) | 44 (20.4) |
| Smoking during pregnancy, n (%) | 82 (47.1) | 79 (36.6) a |
| Cerclage, n (%) | 36 (20.7) | 66 (30.6) a |
| Indicated PTB, n (%) | 19 (10.9) | 23 (10.7) |
| CL ≤21 mm before 24 wks (%) | 44 (25.3) | 85 (39.4) a |
Among the 390 pregnancies studied, there were 60 births before 32 weeks (15.8%), 89 births before 35 weeks (22.4%), and 159 births before 37 weeks of gestation (40.0%). The rates of preterm birth in each BMI category are summarized in Table 2 . Women who were overweight or obese had a 1.7 times higher risk of recurrent preterm birth before 32 weeks, adjusted for age, race, and smoking status (adjusted relative risk [aRR], 1.72; 95% CI, 1.07–2.79; P = .028) when compared with those women who had normal/underweight BMIs. This effect was attenuated with further adjustment for short cervical length measured before 24 weeks’ gestation (aRR, 1.51; 95% CI, 0.93–2.45).
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