American Journal of Obstetrics and Gynecology, Aug 1, 2011
Objective-17 alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). ... more Objective-17 alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms (SNPs) in the human progesterone receptor (PGR) will affect response to 17-OHPC in the prevention of recurrent PTB. Study design-Secondary analysis of a study of 17-OHPC vs. placebo for recurrent PTB prevention. 20 PGR gene SNPs were studied. Multivariable logistic regression was used to assess for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB. Results-380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. The majority (61.1%) of women were African-American. Multivariable logistic regression analysis demonstrated significant treatment-genotype interactions for African-Americans delivering <37 weeks' for rs471767 and rs578029, and for Hispanics/Caucasians delivering <37 weeks' for rs500760 and <32 weeks' for rs578029, rs503362, and rs666553. clinical efficacy of 17-OHPC for prevention of recurrent PTB may be altered by PGR gene polymorphisms. Keywords/phrases 17-alpha hydroxyprogesterone caproate; genetic polymorphisms; progesterone receptor; recurrent preterm birth * p<0.05 * p<0.05 * p<0.05 * p<0.05
American journal of obstetrics and gynecology, 2018
Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and othe... more Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and other outcomes are worse with early-term birth (37-38 weeks) even after demonstrated fetal lung maturity when compared with full-term birth (39-40 weeks). However, these studies included medically indicated births and are therefore potentially limited by confounding by the indication for delivery. Thus, the increase in adverse outcomes might be due to the indication for early-term birth rather than the early-term birth itself. We examined the prevalence and risks of adverse neonatal outcomes associated with early-term birth after confirmed fetal lung maturity as compared with full-term birth in the absence of indications for early delivery. This is a secondary analysis of an observational study of births to 115,502 women in 25 hospitals in the United States from 2008 through 2011. Singleton nonanomalous births at 37-40 weeks with no identifiable indication for delivery were included; early-t...
To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB... more To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB). A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity. Of 9,867 women, 10.4% ( = 1,038) were PTBs; 32.7% ( = 340) IPTBs and 67.3% ( = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more fr...
To compare morbidity among small-for-gestational-age (SGA; birth weight less than the 10th percen... more To compare morbidity among small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age), appropriate-for-gestational-age (AGA; birth weight 10th to 90th percentile; reference group), and large-for-gestational-age (LGA; birth weight greater than the 90th percentile) neonates in apparently uncomplicated pregnancies at term (37 weeks of gestation or greater). This secondary analysis, derived from an observational obstetric cohort of 115,502 deliveries, included women with apparently uncomplicated pregnancies of nonanomalous singletons who had confirmatory ultrasound dating no later than the second trimester and who delivered between 37 0/7 and 42 6/7 weeks of gestation. We used two different composite neonatal morbidity outcomes: hypoxic composite neonatal morbidity for SGA and traumatic composite neonatal morbidity for LGA neonates. Log Poisson relative risks (RRs) with 95% CIs adjusted for potential confounding factors (nulliparity, body mass index,...
American journal of obstetrics and gynecology, Sep 15, 2017
Infants born before 37 weeks' gestation are of public health concern since complications asso... more Infants born before 37 weeks' gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children under 5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-hydroxyprogesterone caproate (17-OHPC) reduces preterm birth by 33% in women with history spontaneous preterm birth (SPTB). We demonstrated previously that plasma concentrations of 17-OHPC vary widely among pregnant women and that women with 17-OHPC plasma concentrations in the lowest quartile had SPTB rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-OHPC plasma concentrations vary so much is unclear. 17-OHPC is predominantly metabolized by CYP3A4 and CYP3A5 enzymes. To 1) determine the relation between 17-OHPC plasma concentrations and single nucleotide polymorphisms (SNPs) in CYP3A4 and CYP3A5;...
American Journal of Obstetrics and Gynecology, 2016
Background-Although preterm birth less than 37 weeks gestation is the leading cause of neonatal m... more Background-Although preterm birth less than 37 weeks gestation is the leading cause of neonatal morbidity and mortality in the United States, the majority of data regarding preterm neonatal outcomes come from older studies, and many reports have been limited to only very preterm neonates. Delineation of neonatal outcomes by delivery gestational age is needed to further clarify the continuum of mortality and morbidity frequencies among preterm neonates. Objective-We sought to describe the contemporary frequencies of neonatal death, neonatal morbidities, and neonatal length of stay across the spectrum of preterm gestational ages. Study Design-Secondary analysis of an obstetric cohort of 115,502 women and their neonates who were born in 25 hospitals nationwide, 2008-2011. All live born non-anomalous singleton preterm (23.0-36.9 weeks of gestation) neonates were included in this analysis. The frequency of neonatal death, major neonatal morbidity (intraventricular hemorrhage grade III/IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II/III, bronchopulmonary dysplasia, persistent pulmonary hypertension), and minor neonatal morbidity (hypotension requiring treatment, intraventricular hemorrhage grade 1/2, necrotizing enterocolitis stage 1, respiratory distress syndrome, hyperbilirubinemia requiring treatment) were calculated by delivery gestational age; each neonate was classified once by the worst outcome they met criteria for. Results-8,334 deliveries met inclusion criteria. There were 119 neonatal deaths (1.4%). 657 (7.9%) neonates had major morbidity, 3,136 (37.6%) had minor morbidity, and 4,422 (53.1%) survived without any of the studied morbidities. Deaths declined rapidly with each advancing week of gestation. This decline in death was accompanied by an increase in major neonatal morbidity, which peaked at 54.8% at 25 weeks of gestation. As frequencies of death, and major neonatal morbidity fell, minor neonatal morbidity increased, peaking at 81.7% at 31 weeks of gestation. The frequency of all morbidities fell beyond 32 weeks. Neonatal length of hospital stay decreased significantly with each additional completed week of pregnancy; among babies delivered from 26 to 32 weeks of gestation, each additional week in utero reduced the subsequent length of neonatal hospitalization by a minimum of 8 days. The median post-menstrual age at discharge nadired at 35.7 weeks post-menstrual age for babies born at 32-33 weeks of gestation. Conclusions-Our data show that there is a continuum of outcomes, with each additional week for gestation conferring survival benefit while reducing the length of initial hospitalization. These contemporary data can be useful for patient counseling regarding preterm outcomes.
To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertensio... more To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertension and the relationship with pregnancy outcomes. This was a secondary analysis of a multicenter trial of vitamin C and E for prevention of pregnancy-associated hypertension in low-risk nulliparous women. Laboratory abnormalities included: platelets less than 100,000/mm, aspartate aminotransferase 100 units/L or greater, creatinine 1.5 mg/dL or greater, lactate dehydrogenase 600 units/L or greater, total bilirubin 1.2 mg/dL or greater, or evidence of hemolysis on peripheral smear. Mild pregnancy-associated hypertension was defined as blood pressure 140-159/90-109 mm Hg. Severe pregnancy-associated hypertension was defined as persistent blood pressure 160/110 mm Hg or greater, acute antihypertensive treatment, or any blood pressure elevation associated with clinical signs of end-organ dysfunction (one or more of headache, epigastric pain, blurred vision, pulmonary edema, eclampsia, or oligu...
Objective-To examine maternal and infant outcomes after a vaginal delivery of twin A and a cesare... more Objective-To examine maternal and infant outcomes after a vaginal delivery of twin A and a cesarean delivery of twin B, and to identify whether the second twin experienced increased shortterm morbidity as part of a combined route of delivery. January 1, 1999 and December 31, 2000, a prospective cohort study of all cesarean deliveries was conducted at 13 university centers. This secondary analysis was limited to women with twin gestations who experienced labor and underwent cesarean delivery. We compared outcomes of the second twin in women who had vaginal delivery of the first twin and a cesarean delivery of the second twin to those who had cesarean delivery of both twins. Results-One-thousand twenty-eight twin pregnancies experienced labor and underwent cesarean delivery, 179 (17%) had a combined vaginal/cesarean delivery. Gestational age at delivery was 34.6 weeks in both groups (p = 0.97). The rupture of membranes to delivery interval was longer in the combined group (3.2 vs 2.3 hrs, p < 0.001). Endometritis and culture proven sepsis in the second twin were more common in the combined group, respectively (n=24, OR 1.6, 95% CI, 1.0 -2.7), (n=15, OR 1.8, 95% CI, 1.0 -3.4). These differences were not significant after logistic regression analysis. There were no statistically significant differences in an arterial cord pH of less than 7.0, Apgar less than or equal to 3 at 5 minutes, seizures, grade 3 or 4 IVH, HIE or neonatal death. Conclusion-Combined twin delivery may be associated with endometritis and neonatal sepsis when compared to a twin delivery where both are delivered by cesarean in twin pregnancies
American Journal of Obstetrics and Gynecology, Aug 1, 2011
Objective-17 alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). ... more Objective-17 alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms (SNPs) in the human progesterone receptor (PGR) will affect response to 17-OHPC in the prevention of recurrent PTB. Study design-Secondary analysis of a study of 17-OHPC vs. placebo for recurrent PTB prevention. 20 PGR gene SNPs were studied. Multivariable logistic regression was used to assess for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB. Results-380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. The majority (61.1%) of women were African-American. Multivariable logistic regression analysis demonstrated significant treatment-genotype interactions for African-Americans delivering <37 weeks' for rs471767 and rs578029, and for Hispanics/Caucasians delivering <37 weeks' for rs500760 and <32 weeks' for rs578029, rs503362, and rs666553. clinical efficacy of 17-OHPC for prevention of recurrent PTB may be altered by PGR gene polymorphisms. Keywords/phrases 17-alpha hydroxyprogesterone caproate; genetic polymorphisms; progesterone receptor; recurrent preterm birth * p<0.05 * p<0.05 * p<0.05 * p<0.05
American journal of obstetrics and gynecology, 2018
Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and othe... more Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and other outcomes are worse with early-term birth (37-38 weeks) even after demonstrated fetal lung maturity when compared with full-term birth (39-40 weeks). However, these studies included medically indicated births and are therefore potentially limited by confounding by the indication for delivery. Thus, the increase in adverse outcomes might be due to the indication for early-term birth rather than the early-term birth itself. We examined the prevalence and risks of adverse neonatal outcomes associated with early-term birth after confirmed fetal lung maturity as compared with full-term birth in the absence of indications for early delivery. This is a secondary analysis of an observational study of births to 115,502 women in 25 hospitals in the United States from 2008 through 2011. Singleton nonanomalous births at 37-40 weeks with no identifiable indication for delivery were included; early-t...
To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB... more To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB). A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity. Of 9,867 women, 10.4% ( = 1,038) were PTBs; 32.7% ( = 340) IPTBs and 67.3% ( = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more fr...
To compare morbidity among small-for-gestational-age (SGA; birth weight less than the 10th percen... more To compare morbidity among small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age), appropriate-for-gestational-age (AGA; birth weight 10th to 90th percentile; reference group), and large-for-gestational-age (LGA; birth weight greater than the 90th percentile) neonates in apparently uncomplicated pregnancies at term (37 weeks of gestation or greater). This secondary analysis, derived from an observational obstetric cohort of 115,502 deliveries, included women with apparently uncomplicated pregnancies of nonanomalous singletons who had confirmatory ultrasound dating no later than the second trimester and who delivered between 37 0/7 and 42 6/7 weeks of gestation. We used two different composite neonatal morbidity outcomes: hypoxic composite neonatal morbidity for SGA and traumatic composite neonatal morbidity for LGA neonates. Log Poisson relative risks (RRs) with 95% CIs adjusted for potential confounding factors (nulliparity, body mass index,...
American journal of obstetrics and gynecology, Sep 15, 2017
Infants born before 37 weeks' gestation are of public health concern since complications asso... more Infants born before 37 weeks' gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children under 5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-hydroxyprogesterone caproate (17-OHPC) reduces preterm birth by 33% in women with history spontaneous preterm birth (SPTB). We demonstrated previously that plasma concentrations of 17-OHPC vary widely among pregnant women and that women with 17-OHPC plasma concentrations in the lowest quartile had SPTB rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-OHPC plasma concentrations vary so much is unclear. 17-OHPC is predominantly metabolized by CYP3A4 and CYP3A5 enzymes. To 1) determine the relation between 17-OHPC plasma concentrations and single nucleotide polymorphisms (SNPs) in CYP3A4 and CYP3A5;...
American Journal of Obstetrics and Gynecology, 2016
Background-Although preterm birth less than 37 weeks gestation is the leading cause of neonatal m... more Background-Although preterm birth less than 37 weeks gestation is the leading cause of neonatal morbidity and mortality in the United States, the majority of data regarding preterm neonatal outcomes come from older studies, and many reports have been limited to only very preterm neonates. Delineation of neonatal outcomes by delivery gestational age is needed to further clarify the continuum of mortality and morbidity frequencies among preterm neonates. Objective-We sought to describe the contemporary frequencies of neonatal death, neonatal morbidities, and neonatal length of stay across the spectrum of preterm gestational ages. Study Design-Secondary analysis of an obstetric cohort of 115,502 women and their neonates who were born in 25 hospitals nationwide, 2008-2011. All live born non-anomalous singleton preterm (23.0-36.9 weeks of gestation) neonates were included in this analysis. The frequency of neonatal death, major neonatal morbidity (intraventricular hemorrhage grade III/IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II/III, bronchopulmonary dysplasia, persistent pulmonary hypertension), and minor neonatal morbidity (hypotension requiring treatment, intraventricular hemorrhage grade 1/2, necrotizing enterocolitis stage 1, respiratory distress syndrome, hyperbilirubinemia requiring treatment) were calculated by delivery gestational age; each neonate was classified once by the worst outcome they met criteria for. Results-8,334 deliveries met inclusion criteria. There were 119 neonatal deaths (1.4%). 657 (7.9%) neonates had major morbidity, 3,136 (37.6%) had minor morbidity, and 4,422 (53.1%) survived without any of the studied morbidities. Deaths declined rapidly with each advancing week of gestation. This decline in death was accompanied by an increase in major neonatal morbidity, which peaked at 54.8% at 25 weeks of gestation. As frequencies of death, and major neonatal morbidity fell, minor neonatal morbidity increased, peaking at 81.7% at 31 weeks of gestation. The frequency of all morbidities fell beyond 32 weeks. Neonatal length of hospital stay decreased significantly with each additional completed week of pregnancy; among babies delivered from 26 to 32 weeks of gestation, each additional week in utero reduced the subsequent length of neonatal hospitalization by a minimum of 8 days. The median post-menstrual age at discharge nadired at 35.7 weeks post-menstrual age for babies born at 32-33 weeks of gestation. Conclusions-Our data show that there is a continuum of outcomes, with each additional week for gestation conferring survival benefit while reducing the length of initial hospitalization. These contemporary data can be useful for patient counseling regarding preterm outcomes.
To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertensio... more To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertension and the relationship with pregnancy outcomes. This was a secondary analysis of a multicenter trial of vitamin C and E for prevention of pregnancy-associated hypertension in low-risk nulliparous women. Laboratory abnormalities included: platelets less than 100,000/mm, aspartate aminotransferase 100 units/L or greater, creatinine 1.5 mg/dL or greater, lactate dehydrogenase 600 units/L or greater, total bilirubin 1.2 mg/dL or greater, or evidence of hemolysis on peripheral smear. Mild pregnancy-associated hypertension was defined as blood pressure 140-159/90-109 mm Hg. Severe pregnancy-associated hypertension was defined as persistent blood pressure 160/110 mm Hg or greater, acute antihypertensive treatment, or any blood pressure elevation associated with clinical signs of end-organ dysfunction (one or more of headache, epigastric pain, blurred vision, pulmonary edema, eclampsia, or oligu...
Objective-To examine maternal and infant outcomes after a vaginal delivery of twin A and a cesare... more Objective-To examine maternal and infant outcomes after a vaginal delivery of twin A and a cesarean delivery of twin B, and to identify whether the second twin experienced increased shortterm morbidity as part of a combined route of delivery. January 1, 1999 and December 31, 2000, a prospective cohort study of all cesarean deliveries was conducted at 13 university centers. This secondary analysis was limited to women with twin gestations who experienced labor and underwent cesarean delivery. We compared outcomes of the second twin in women who had vaginal delivery of the first twin and a cesarean delivery of the second twin to those who had cesarean delivery of both twins. Results-One-thousand twenty-eight twin pregnancies experienced labor and underwent cesarean delivery, 179 (17%) had a combined vaginal/cesarean delivery. Gestational age at delivery was 34.6 weeks in both groups (p = 0.97). The rupture of membranes to delivery interval was longer in the combined group (3.2 vs 2.3 hrs, p < 0.001). Endometritis and culture proven sepsis in the second twin were more common in the combined group, respectively (n=24, OR 1.6, 95% CI, 1.0 -2.7), (n=15, OR 1.8, 95% CI, 1.0 -3.4). These differences were not significant after logistic regression analysis. There were no statistically significant differences in an arterial cord pH of less than 7.0, Apgar less than or equal to 3 at 5 minutes, seizures, grade 3 or 4 IVH, HIE or neonatal death. Conclusion-Combined twin delivery may be associated with endometritis and neonatal sepsis when compared to a twin delivery where both are delivered by cesarean in twin pregnancies
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Papers by Ronald Wapner