Background 17-alpha hydroxyprogesterone caproate for prevention of recurrent preterm birth is recommended for use in the United States. Objective To assess the clinical effectiveness of 17-alpha hydroxyprogesterone caproate to prevent recurrent preterm birth ≤ 35 weeks compared to similar births in our obstetric population prior to the implementation of 17-alpha hydroxyprogesterone caproate. Study Design This was a prospective cohort study of 17-alpha hydroxyprogesterone caproate in our obstetric population. The primary outcome was the recurrence of birth ≤ 35 weeks for the entire study cohort compared to a historical referent rate of 16.8% of recurrent preterm birth in our population. There were three secondary outcomes. First, did 17-alpha hydroxyprogesterone caproate modify a woman’s history of preterm birth when taking into account her prior number and sequence of preterm and term births? Second, was recurrence of preterm birth related to 17-alpha hydroxyprogesterone caproate plasma concentration? Third, was duration of pregnancy modified by 17-alpha hydroxyprogesterone caproate treatment compared to a prior preterm birth? Results Between January 2012 and March 2016, 430 consecutive women with prior births ≤ 35 weeks were treated with 17-alpha hydroxyprogesterone caproate. Nearly two-thirds of the women (N=267) began injections ≤ 18 weeks and 394 (92%) received a scheduled weekly injection within 10 days of reaching 35 weeks or delivery. The overall rate of recurrent preterm birth was 25% (N=106) for the entire cohort compared to the 16.8% expected rate (P = 1.0). The three secondary outcomes were also negative. First, 17-alpha hydroxyprogesterone caproate did not significantly reduce the rates of recurrence regardless of prior preterm birth number or sequence. Second, plasma concentrations of 17-alpha hydroxyprogesterone caproate were not different (P=0.17 at 24 weeks; P=0.38 at 32 weeks) between women delivered ≤ 35 weeks and those delivered later in pregnancy. Third, the mean (± standard deviation) interval in weeks of recurrent preterm birth before 17-alpha hydroxyprogesterone caproate use was 0.4 ± 5.3 weeks and the interval of recurrent preterm birth after 17-alpha hydroxyprogesterone caproate treatment was 0.1 ± 4.7 weeks (P=0.63). A side effect of weekly 17-alpha hydroxyprogesterone caproate injections was an increase in gestational diabetes. Specifically, the rate of gestational diabetes was 13.4% in 17-alpha hydroxyprogesterone caproate treated women compared to 8% in case-matched controls (P=0.001). Conclusions 17-alpha hydroxyprogesterone caproate was ineffective for prevention of recurrent preterm birth and was associated with increased rates of gestational diabetes.

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Two premature infants exhibited an acute cardiorespiratory collapse shortly after receiving a 50-fold overdose of amphotericin B (AmB). Despite aggressive intervention both infants died. Serum AmB levels were double the normal therapeutic range. We speculate that two less well-recognized toxic complications of AmB involving the cardiac and respiratory systems may have contributed to the fatal outcome.