- Email: [email protected]
Evaluation of 17-alpha hydroxyprogesterone caproate efficacy
Accepted Manuscript Evaluation of 17-alpha hydroxyprogesterone caproate efficacy Alisse Hauspurg, MD, Raman Venkataraman, PhD, Steve N. Caritis, MD PII:
S0002-9378(17)31133-X
DOI:
10.1016/j.ajog.2017.09.018
Reference:
YMOB 11850
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 16 August 2017 Accepted Date: 19 September 2017
Please cite this article as: Hauspurg A, Venkataraman R, Caritis SN, Evaluation of 17-alpha hydroxyprogesterone caproate efficacy, American Journal of Obstetrics and Gynecology (2017), doi: 10.1016/j.ajog.2017.09.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Alisse HAUSPURG1, MD
RI PT
Evaluation of 17-alpha hydroxyprogesterone caproate efficacy
SC
2
Raman VENKATARAMAN , PhD
M AN U
Steve N. CARITIS1, MD
1
Magee-Womens Hospital of University of Pittsburgh Medical Center Division of Maternal-Fetal Medicine Department of Obstetrics, Gynecology and Reproductive Sciences
Department of Pharmaceutical Sciences School of Pharmacy and Department of Pathology, School of Medicine, University of Pittsburgh
EP
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2
Corresponding Author: Alisse Hauspurg 300 Halket Street Pittsburgh, PA 15213 Telephone:412-641-3950 (office) 908-672-7522 (cell) Email: [email protected]
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50
The authors report no conflicts of interest.
ACCEPTED MANUSCRIPT
51
We read with interest the recently published study by Nelson, et al regarding the efficacy of 17-alpha hydroxyprogesterone caproate (17-OHPC) for prevention of recurrent preterm birth
53
(PTB)1. The primary outcome in this study was the rate of recurrent PTB ≤ 35 weeks.
54
Additionally, three secondary outcomes were evaluated, two of which compared the
55
contemporary cohort to a historical cohort. The third one evaluated the relationship between 17-
56
OHPC concentrations and PTB.
RI PT
52
We have reservations regarding the conclusions reached in this study, which compares
58
obstetrical outcomes from a contemporary cohort of women receiving 17-OHPC with those of a
59
historical cohort (1988-2011) who did not receive 17-OHPC. To compare rates of preterm birth
60
in a historical cohort from as early as 1988 to the rates in a contemporary cohort is fraught with
61
potential biases given the changes in the composition and characteristics of patients receiving
62
prenatal care over time. Obesity, drug abuse, age at conception, medical complications,
63
assisted reproductive technologies and immigrant status are a few factors that have increased
64
over the last three decades; all of these factors may impact rates of recurrent PTB. Limited data
65
are provided comparing the characteristics of the cohorts. The contemporary cohort is 80%
66
Hispanic, which not only limits the external validity but also raises questions about a differential
67
response to 17-OHPC based on progesterone receptor polymorphisms, which have been
68
previously shown by Manuck et al to vary by race2. No data are provided about the rates of
69
recurrent PTB among contemporaneous women who did not receive or refused 17-OHPC. Such
70
a cohort would provide a better comparator of PTB risk than a historical cohort.
M AN U
TE D
EP
AC C
71
SC
57
The third secondary outcome is not constrained by the use of historical cohort. No
72
relationship between plasma concentration of 17-OHPC and PTB rates was observed, contrary
73
to our secondary analysis of the Omega-3 study2. These results are potentially important but
74
require further clarification to enable comparison to our findings. Specifically, the authors
75
should indicate what adjustments were made in their analysis for covariates that impact the rate
ACCEPTED MANUSCRIPT
of PTB. Likewise, information should be provided on factors that impact plasma concentration
77
such as compliance and timing of the blood draw in relationship to the administration of 17-
78
OHPC. A relationship between plasma concentration and PTB rate suggests efficacy whereas a
79
lack of relationship challenges that conclusion. More studies are needed that focus on the
80
relationship between plasma concentrations of 17-OHPC and preterm birth rates.
RI PT
76
AC C
EP
TE D
M AN U
SC
81 82
ACCEPTED MANUSCRIPT
83 84
References 1. Nelson DB, McIntire DD, McDonald J, et al. 17-alpha Hydroxyprogesterone caproate did
86
not reduce the rate of recurrent preterm birth in a prospective cohort study. Am J Obstet
87
Gynecol 2017;216:600.e1-9.
RI PT
85
2. Manuck TA, Lai Y, Mies PJ, et al. Progesterone receptor polymoprhisms and clinical
89
response to 17-alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol 2011;
90
205(2): 135.e1-135.39.
3. Caritis SN, Venkataramanan R, Thom E, et al. Relationship between 17-alpha
M AN U
91
SC
88
92
hydroxyprogesterone caproate concentration and spontaneous preterm birth. Am J
93
Obstet Gynecol. 2014;210(2):128.e1-128.
AC C
EP
TE D
94 95
S0002-9378(17)31133-X
DOI:
10.1016/j.ajog.2017.09.018
Reference:
YMOB 11850
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 16 August 2017 Accepted Date: 19 September 2017
Please cite this article as: Hauspurg A, Venkataraman R, Caritis SN, Evaluation of 17-alpha hydroxyprogesterone caproate efficacy, American Journal of Obstetrics and Gynecology (2017), doi: 10.1016/j.ajog.2017.09.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Alisse HAUSPURG1, MD
RI PT
Evaluation of 17-alpha hydroxyprogesterone caproate efficacy
SC
2
Raman VENKATARAMAN , PhD
M AN U
Steve N. CARITIS1, MD
1
Magee-Womens Hospital of University of Pittsburgh Medical Center Division of Maternal-Fetal Medicine Department of Obstetrics, Gynecology and Reproductive Sciences
Department of Pharmaceutical Sciences School of Pharmacy and Department of Pathology, School of Medicine, University of Pittsburgh
EP
TE D
2
Corresponding Author: Alisse Hauspurg 300 Halket Street Pittsburgh, PA 15213 Telephone:412-641-3950 (office) 908-672-7522 (cell) Email: [email protected]
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50
The authors report no conflicts of interest.
ACCEPTED MANUSCRIPT
51
We read with interest the recently published study by Nelson, et al regarding the efficacy of 17-alpha hydroxyprogesterone caproate (17-OHPC) for prevention of recurrent preterm birth
53
(PTB)1. The primary outcome in this study was the rate of recurrent PTB ≤ 35 weeks.
54
Additionally, three secondary outcomes were evaluated, two of which compared the
55
contemporary cohort to a historical cohort. The third one evaluated the relationship between 17-
56
OHPC concentrations and PTB.
RI PT
52
We have reservations regarding the conclusions reached in this study, which compares
58
obstetrical outcomes from a contemporary cohort of women receiving 17-OHPC with those of a
59
historical cohort (1988-2011) who did not receive 17-OHPC. To compare rates of preterm birth
60
in a historical cohort from as early as 1988 to the rates in a contemporary cohort is fraught with
61
potential biases given the changes in the composition and characteristics of patients receiving
62
prenatal care over time. Obesity, drug abuse, age at conception, medical complications,
63
assisted reproductive technologies and immigrant status are a few factors that have increased
64
over the last three decades; all of these factors may impact rates of recurrent PTB. Limited data
65
are provided comparing the characteristics of the cohorts. The contemporary cohort is 80%
66
Hispanic, which not only limits the external validity but also raises questions about a differential
67
response to 17-OHPC based on progesterone receptor polymorphisms, which have been
68
previously shown by Manuck et al to vary by race2. No data are provided about the rates of
69
recurrent PTB among contemporaneous women who did not receive or refused 17-OHPC. Such
70
a cohort would provide a better comparator of PTB risk than a historical cohort.
M AN U
TE D
EP
AC C
71
SC
57
The third secondary outcome is not constrained by the use of historical cohort. No
72
relationship between plasma concentration of 17-OHPC and PTB rates was observed, contrary
73
to our secondary analysis of the Omega-3 study2. These results are potentially important but
74
require further clarification to enable comparison to our findings. Specifically, the authors
75
should indicate what adjustments were made in their analysis for covariates that impact the rate
ACCEPTED MANUSCRIPT
of PTB. Likewise, information should be provided on factors that impact plasma concentration
77
such as compliance and timing of the blood draw in relationship to the administration of 17-
78
OHPC. A relationship between plasma concentration and PTB rate suggests efficacy whereas a
79
lack of relationship challenges that conclusion. More studies are needed that focus on the
80
relationship between plasma concentrations of 17-OHPC and preterm birth rates.
RI PT
76
AC C
EP
TE D
M AN U
SC
81 82
ACCEPTED MANUSCRIPT
83 84
References 1. Nelson DB, McIntire DD, McDonald J, et al. 17-alpha Hydroxyprogesterone caproate did
86
not reduce the rate of recurrent preterm birth in a prospective cohort study. Am J Obstet
87
Gynecol 2017;216:600.e1-9.
RI PT
85
2. Manuck TA, Lai Y, Mies PJ, et al. Progesterone receptor polymoprhisms and clinical
89
response to 17-alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol 2011;
90
205(2): 135.e1-135.39.
3. Caritis SN, Venkataramanan R, Thom E, et al. Relationship between 17-alpha
M AN U
91
SC
88
92
hydroxyprogesterone caproate concentration and spontaneous preterm birth. Am J
93
Obstet Gynecol. 2014;210(2):128.e1-128.
AC C
EP
TE D
94 95