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17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies (170HP)

Primary Purpose

Preterm Birth

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
17-alpha-hydroxyprogesterone caproate injectable
Placebo
Sponsored by
Obstetrix Medical Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Preterm Birth focused on measuring Preterm Birth, Preterm Delivery, Multiple gestation, 17-alpha-hydroxyprogesterone caproate, Progesterone

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Gestational age (GA) 15-23w0d gestational age at the time of recruitment GA 16w0dk to 23w6d at the time of randomization and initiation of injections Maternal age 18 years or older One of these risk factors for spontaneous preterm birth: Twins in current pregnancy, dichorionic placentation Triplets in current pregnancy, trichorionic placentation Intact membranes Patient has had at least one detailed 2nd-trimester ultrasound examination documenting placentation, chorionicity, fetal number, fetal size, amniotic fluid volumes, and fetal anatomy. (This examination must comply with minimum standards such as those published by the American Institute of Ultrasound in Medicine, American College of Radiology, or American College of Obstetricians & Gynecologists It is NOT mandatory that this examination be performed at the research-study center.) Investigator believes patient will be reliable with follow-up visits and believes that delivery data and neonatal data are likely to be available. Exclusion Criteria: Symptomatic uterine contractions in current pregnancy Contraindication to interventions intended to prolong the pregnancy (including lethal fetal anomalies, amnionitis, preeclampsia, severe oligohydramnios, severe growth delay, fetal death appears imminent or inevitable) Risk factors for major neonatal morbidity unrelated to preterm delivery (such as monochorionic placentation in multiple gestation, major malformations, certain medication exposures) Preexisting maternal medical condition that might be worsened by progesterone therapy, including: asthma requiring medications, renal insufficiency, seizure disorder, ischemic heart disease, active cholecystitis, impaired liver function, history of thromboembolic disorder, history of breast cancer, history of major depression requiring hospitalization. Preexisting maternal medical condition associated with a high risk of preterm delivery including: refractory hypertension, diabetes with nephropathy or retinopathy, renal insufficiency, active systemic lupus erythematosus. Note that a history of prior preterm birth is NOT an exclusion. Use of progesterone or progesterone-derivative medication after 15 weeks gestation in current pregnancy. Allergy to 17OHP or oil vehicle. Placement of emergent cerclage (defined as one placed after the occurrence of cervical change such as dilation, funneling, or effacement) with this pregnancy. Prophylactic cerclage is NOT an exclusion (defined as one placed before any cervical change, for example, because of a history of cervical incompetence, or because of a prior cervical procedure such as LEEP or cone biopsy).

Sites / Locations

  • Banner Good Samaritan Hospital
  • Tucson Medical Center
  • Saddleback Memorial Medical Center
  • Long Beach Memorial Medical Center
  • University of Southern California-Irvine Medical Center
  • Good Samaritan Hospital
  • Swedish Medical Center
  • Presbyterian/St Luke's Hospital
  • Rose Medical Center
  • Skyridge Medical Center
  • Mercy Medical Center
  • Saint Luke's Hospital, Kansas City
  • Erlanger Medical Center
  • Baylor University Medical Center
  • Harris Methodist Fort Worth Hospital
  • Evergreen Hospital
  • Swedish Medical Center
  • Tacoma General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1 Test Group (170HP)

2 - Control (Normal Saline)

Arm Description

Test Group will receive weekly doses of 170HP via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.

Control Group will receive weekly doses of placebo (NS) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.

Outcomes

Primary Outcome Measures

Newborn Respiratory Distress Syndrome (RDS)
Newborn RDS in the twin arm is defined as compatible symptoms with radiographically confirmed hyaline membrane disease or with respiratory insufficiency of prematurity requiring ventilator support. Data expressed as mean n(%),Odds ratio, CI, and P-value were determined using repeated measures model wherein each twin/triplet within a given pregnancy is considered a repeated measure. Exceptions are comparison with 0 outcomes in one or both groups, so Fisher's Exact Test was used. Morbidity measures were based on live births with data available for the outcomes.
Use of Oxygen Therapy at 28 Days of Newborn Life
Supplemental oxygen use by the baby measured at the point that the baby reaches 28 days old (after birth)within the twin group.
Newborn Sepsis
Newborn Sepsis in the twin group was defined as the presence of positive blood culture obtained in the first week of life in association with clinical findings suggesting illness for which the neonate received antibiotics.
Newborn Pneumonia
Newborn Pneumonia in the twin group is described as compatible symptoms with diagnostic radiograph findings and positive results on blood cultures, persistent leukopenia
Newborn Intraventricular Hemorrhage Grade 3 or 4
Newborn Intraventricular hemorrhage (IVH) Stage III in the twin group is described as - IVH with ventricular dilatation. Neonatal Intraventricular hemorrhage (IVH)Stage IV in the twin group is described as - IVH with parenchymal extension.
Newborn Periventricular Leukomalacia (PVL)
Newborn Periventricular leukomalacia (PVL) in the twin group is described as the presence of more than 1 obvious hypo echoic cyst in the periventricular white matter.
Newborn Necrotizing Enterocolitis (NEC)Requiring Surgery
Newborn NEC in the twin group is described as the presence of any of the following: (1)unequivocal intramural air in abdominal radiograph; (2) perforation abdominal radiograph; (3) clinical evidence of perforation (erythema and induration of the abdominal wall or intrabdominal abscess formation); (4) characteristic findings observed at surgery or autopsy; (5) Stricture formation after an episode of suspected necrotizing enterocolitis.
Newborn Retinopathy of Prematurity (ROP)
Newborn ROP within the twin group is described as retinopathy confirmed on fundoscopic examination, felt to be due to prematurity and subsequent oxygen therapy.
Newborn Asphyxia With Ischemic Injury of Brain, Heart, Kidneys, or Liver
Newborn Asphyxia or Hypoxic-ischemic encephalopathy (HEI) within the twin group is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia (ie, hypoxia, acidosis).
Perinatal Death
Perinatal death within the twin group is described as a stillbirth, neonatal death, or miscarriage after randomization.

Secondary Outcome Measures

Individual Components of Neonatal Morbidity (RDS, IVH-III/IV, Bronchopulmonary Dysplasia(BPD), PVL, Sepsis, NEC, ROP-Stage 3/4, Perinatal Death)
Composite Neonatal Morbidity within the twin group is described as the presence of any one or more of the following neonatal morbidities (RDS, IVH-III/IV, BPD, PVL, sepsis, NEC, ROP-Stage 3/4, Perinatal Death).
Twins: Delivery Prior to 28 Weeks (Wks), 32 Wks, 34wks, and 37 Wks
Gestational age was noted at time of delivery and stratified into three categories (Twins: Delivery prior to 28 weeks (wks), 32 wks, 34 wks, and 37 wks)
Triplets: Delivery Prior to 28 Wks, 32 Wks, 35 Wks
Gestational age was noted at time of delivery and stratified into three categories (Triplets: Delivery prior to 28 wks, 32 wks, 35 wks)
Newborn Gestational Age (GA) at Delivery
Newborn Gestational age at delivery within the twin group is described as the gestational age of the baby on the day of birth.
Newborn Birthweight
Newborn Birthweight within the twins group was measure following delivery and noted in grams.
Participant Drop-out Rates
Drop-out rates in the twin group are described as any randomized participant who is withdrawn from the trial between randomization (as early at 16 weeks of pregnancy) and completion of the final dose of study medication (as late as 34 weeks of pregnancy).
Participant Side Effects Requiring Cessation of Therapy
Describe as the cessation of study related therapy for the participant within the twin group at anytime from initial study related injection until the final injection at 34 weeks of pregnancy.

Full Information

First Posted
September 9, 2005
Last Updated
March 11, 2016
Sponsor
Obstetrix Medical Group
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1. Study Identification

Unique Protocol Identification Number
NCT00163020
Brief Title
17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies
Acronym
170HP
Official Title
17-Alpha-Hydroxyprogesterone Caproate for Reduction of Neonatal Morbidity Due to Preterm Birth in Twin and Triplet Pregnancies - A Concurrent Randomized Double-blinded Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
November 2004 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Obstetrix Medical Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Hypothesis: Among women with twin or triplet pregnancies, weekly injections of 17-alpha-hydroxyprogesterone caproate (17OHP), started before 24 weeks of gestation, will reduce neonatal morbidity by reducing the rate of preterm delivery. This study involves two concurrent double-blinded randomized clinical trials of 17OHP versus placebo. Each trial will test the efficacy and safety of 17OHP in women with a specific risk factor for preterm birth. The two risk factors to be studied are: Twin pregnancy Triplet pregnancy
Detailed Description
Prematurity is a leading cause of neonatal morbidity and mortality in the USA. Nationally, 12% of all babies deliver before term and 3% deliver before 32 wks gestational age (GA). Recent studies suggest that 17OHP and other progesterone derivatives may reduce the rate of preterm birth among women with a history of prior preterm birth. However, it has not been demonstrated that this reduction in preterm birth is accompanied by a clinically significant reduction in neonatal complications. Further, most women who deliver preterm have no history of a prior preterm birth. Little is known about whether progesterone treatment is effective in women with other risk factors for preterm birth such as multiple gestation. The proposed study will assess the role of 17OHP in women with twin or triplet pregnancies and will assess the impact on neonatal health, not merely the impact on gestational age at delivery. Prior studies were not designed to be large enough to have statistical power to assess effects on neonatal morbidity. In the 6 trials combined in the Goldstein meta-analysis, only 279 women were treated with 17OHP and only 73 women had a preterm delivery. The NICHD study presented by Meis approximately doubles the world-wide experience, with 306 women under treatment, of whom 73 delivered prior to 35 wks. Yet, this study was not designed to have power to show a reduction in neonatal complications but only a reduction in preterm birth rates. The present study is the first to be specifically designed to have adequate power to test whether 17OHP reduces neonatal morbidity among women with one of two specific risk factors for preterm birth.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preterm Birth
Keywords
Preterm Birth, Preterm Delivery, Multiple gestation, 17-alpha-hydroxyprogesterone caproate, Progesterone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
321 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 Test Group (170HP)
Arm Type
Active Comparator
Arm Description
Test Group will receive weekly doses of 170HP via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.
Arm Title
2 - Control (Normal Saline)
Arm Type
Placebo Comparator
Arm Description
Control Group will receive weekly doses of placebo (NS) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.
Intervention Type
Drug
Intervention Name(s)
17-alpha-hydroxyprogesterone caproate injectable
Other Intervention Name(s)
170HP
Intervention Description
250mg of 17-alpha-hydroxyprogesterone caproate (+ preservatives) injectable weekly starting as early as 19wks gestation until 34.0wks gestation of delivery which ever comes first.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal Saline
Intervention Description
Weekly doses of placebo (NS + preservatives) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.
Primary Outcome Measure Information:
Title
Newborn Respiratory Distress Syndrome (RDS)
Description
Newborn RDS in the twin arm is defined as compatible symptoms with radiographically confirmed hyaline membrane disease or with respiratory insufficiency of prematurity requiring ventilator support. Data expressed as mean n(%),Odds ratio, CI, and P-value were determined using repeated measures model wherein each twin/triplet within a given pregnancy is considered a repeated measure. Exceptions are comparison with 0 outcomes in one or both groups, so Fisher's Exact Test was used. Morbidity measures were based on live births with data available for the outcomes.
Time Frame
Measured from delivery until 30 days after baby was discharged from the hospital
Title
Use of Oxygen Therapy at 28 Days of Newborn Life
Description
Supplemental oxygen use by the baby measured at the point that the baby reaches 28 days old (after birth)within the twin group.
Time Frame
Measured at 28 days after birth.
Title
Newborn Sepsis
Description
Newborn Sepsis in the twin group was defined as the presence of positive blood culture obtained in the first week of life in association with clinical findings suggesting illness for which the neonate received antibiotics.
Time Frame
measured during the first week following birth
Title
Newborn Pneumonia
Description
Newborn Pneumonia in the twin group is described as compatible symptoms with diagnostic radiograph findings and positive results on blood cultures, persistent leukopenia
Time Frame
measure during the first 28 days after birth.
Title
Newborn Intraventricular Hemorrhage Grade 3 or 4
Description
Newborn Intraventricular hemorrhage (IVH) Stage III in the twin group is described as - IVH with ventricular dilatation. Neonatal Intraventricular hemorrhage (IVH)Stage IV in the twin group is described as - IVH with parenchymal extension.
Time Frame
measured during the first 28 days after birth
Title
Newborn Periventricular Leukomalacia (PVL)
Description
Newborn Periventricular leukomalacia (PVL) in the twin group is described as the presence of more than 1 obvious hypo echoic cyst in the periventricular white matter.
Time Frame
measured in the first 28 days after birth.
Title
Newborn Necrotizing Enterocolitis (NEC)Requiring Surgery
Description
Newborn NEC in the twin group is described as the presence of any of the following: (1)unequivocal intramural air in abdominal radiograph; (2) perforation abdominal radiograph; (3) clinical evidence of perforation (erythema and induration of the abdominal wall or intrabdominal abscess formation); (4) characteristic findings observed at surgery or autopsy; (5) Stricture formation after an episode of suspected necrotizing enterocolitis.
Time Frame
measured in the first 28 days after birth
Title
Newborn Retinopathy of Prematurity (ROP)
Description
Newborn ROP within the twin group is described as retinopathy confirmed on fundoscopic examination, felt to be due to prematurity and subsequent oxygen therapy.
Time Frame
measured during the first 28 day after birth
Title
Newborn Asphyxia With Ischemic Injury of Brain, Heart, Kidneys, or Liver
Description
Newborn Asphyxia or Hypoxic-ischemic encephalopathy (HEI) within the twin group is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia (ie, hypoxia, acidosis).
Time Frame
measured during the first 28 days after delivery
Title
Perinatal Death
Description
Perinatal death within the twin group is described as a stillbirth, neonatal death, or miscarriage after randomization.
Time Frame
measured from randomization to 28 days after birth.
Secondary Outcome Measure Information:
Title
Individual Components of Neonatal Morbidity (RDS, IVH-III/IV, Bronchopulmonary Dysplasia(BPD), PVL, Sepsis, NEC, ROP-Stage 3/4, Perinatal Death)
Description
Composite Neonatal Morbidity within the twin group is described as the presence of any one or more of the following neonatal morbidities (RDS, IVH-III/IV, BPD, PVL, sepsis, NEC, ROP-Stage 3/4, Perinatal Death).
Time Frame
measured as any event noted in the first 28 day following birth.
Title
Twins: Delivery Prior to 28 Weeks (Wks), 32 Wks, 34wks, and 37 Wks
Description
Gestational age was noted at time of delivery and stratified into three categories (Twins: Delivery prior to 28 weeks (wks), 32 wks, 34 wks, and 37 wks)
Time Frame
Gestational age noted at time of birth
Title
Triplets: Delivery Prior to 28 Wks, 32 Wks, 35 Wks
Description
Gestational age was noted at time of delivery and stratified into three categories (Triplets: Delivery prior to 28 wks, 32 wks, 35 wks)
Time Frame
noted at delivery
Title
Newborn Gestational Age (GA) at Delivery
Description
Newborn Gestational age at delivery within the twin group is described as the gestational age of the baby on the day of birth.
Time Frame
determined at the time of birth
Title
Newborn Birthweight
Description
Newborn Birthweight within the twins group was measure following delivery and noted in grams.
Time Frame
measure following delivery
Title
Participant Drop-out Rates
Description
Drop-out rates in the twin group are described as any randomized participant who is withdrawn from the trial between randomization (as early at 16 weeks of pregnancy) and completion of the final dose of study medication (as late as 34 weeks of pregnancy).
Time Frame
any time from randomization to completion of final dose of study medication
Title
Participant Side Effects Requiring Cessation of Therapy
Description
Describe as the cessation of study related therapy for the participant within the twin group at anytime from initial study related injection until the final injection at 34 weeks of pregnancy.
Time Frame
anytime from initial injection to final injection at 34 weeks.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Gestational age (GA) 15-23w0d gestational age at the time of recruitment GA 16w0dk to 23w6d at the time of randomization and initiation of injections Maternal age 18 years or older One of these risk factors for spontaneous preterm birth: Twins in current pregnancy, dichorionic placentation Triplets in current pregnancy, trichorionic placentation Intact membranes Patient has had at least one detailed 2nd-trimester ultrasound examination documenting placentation, chorionicity, fetal number, fetal size, amniotic fluid volumes, and fetal anatomy. (This examination must comply with minimum standards such as those published by the American Institute of Ultrasound in Medicine, American College of Radiology, or American College of Obstetricians & Gynecologists It is NOT mandatory that this examination be performed at the research-study center.) Investigator believes patient will be reliable with follow-up visits and believes that delivery data and neonatal data are likely to be available. Exclusion Criteria: Symptomatic uterine contractions in current pregnancy Contraindication to interventions intended to prolong the pregnancy (including lethal fetal anomalies, amnionitis, preeclampsia, severe oligohydramnios, severe growth delay, fetal death appears imminent or inevitable) Risk factors for major neonatal morbidity unrelated to preterm delivery (such as monochorionic placentation in multiple gestation, major malformations, certain medication exposures) Preexisting maternal medical condition that might be worsened by progesterone therapy, including: asthma requiring medications, renal insufficiency, seizure disorder, ischemic heart disease, active cholecystitis, impaired liver function, history of thromboembolic disorder, history of breast cancer, history of major depression requiring hospitalization. Preexisting maternal medical condition associated with a high risk of preterm delivery including: refractory hypertension, diabetes with nephropathy or retinopathy, renal insufficiency, active systemic lupus erythematosus. Note that a history of prior preterm birth is NOT an exclusion. Use of progesterone or progesterone-derivative medication after 15 weeks gestation in current pregnancy. Allergy to 17OHP or oil vehicle. Placement of emergent cerclage (defined as one placed after the occurrence of cervical change such as dilation, funneling, or effacement) with this pregnancy. Prophylactic cerclage is NOT an exclusion (defined as one placed before any cervical change, for example, because of a history of cervical incompetence, or because of a prior cervical procedure such as LEEP or cone biopsy).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kimberly Maurel, RN, MSN, CNS
Organizational Affiliation
Obstetrix Medical Group, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Andrew Combs, MD
Organizational Affiliation
Obstetrix Medical Group, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner Good Samaritan Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Tucson Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
Saddleback Memorial Medical Center
City
Laguna Hills
State/Province
California
ZIP/Postal Code
92653
Country
United States
Facility Name
Long Beach Memorial Medical Center
City
Long Beach
State/Province
California
ZIP/Postal Code
90801-1428
Country
United States
Facility Name
University of Southern California-Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Good Samaritan Hospital
City
San Jose
State/Province
California
ZIP/Postal Code
95124
Country
United States
Facility Name
Swedish Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80110
Country
United States
Facility Name
Presbyterian/St Luke's Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Rose Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Facility Name
Skyridge Medical Center
City
Lonetree
State/Province
Colorado
ZIP/Postal Code
80124
Country
United States
Facility Name
Mercy Medical Center
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
Saint Luke's Hospital, Kansas City
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Erlanger Medical Center
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Harris Methodist Fort Worth Hospital
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Evergreen Hospital
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122-4307
Country
United States
Facility Name
Tacoma General Hospital
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
2653414
Citation
Goldstein P, Berrier J, Rosen S, Sacks HS, Chalmers TC. A meta-analysis of randomized control trials of progestational agents in pregnancy. Br J Obstet Gynaecol. 1989 Mar;96(3):265-74. doi: 10.1111/j.1471-0528.1989.tb02385.x.
Results Reference
background
PubMed Identifier
12592250
Citation
da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003 Feb;188(2):419-24. doi: 10.1067/mob.2003.41.
Results Reference
background
PubMed Identifier
12802023
Citation
Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. doi: 10.1056/NEJMoa035140. Erratum In: N Engl J Med. 2003 Sep 25;349(13):1299.
Results Reference
background
Citation
American College of Obstetricians & Gynecologists. Special problems of multiple gestation. Educational Bulletin 253, 1998.
Results Reference
background

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17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies

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