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A comparison of placental pathology and perinatal outcome between monochorionic and dichorionic twin sets
SMFM Abstracts S137 476
477
PREVENTION OF ALCOHOL-INDUCED DELAYS IN DEVELOPMENTAL MILESTONES AND LEARNING ABNORMALITIES IN A MODEL OF FETAL ALCOHOL SYNDROME MELANIE ENDRES1, LAURA TOSO1, ROBIN ROBERSON1, JANE PARK1, VERONICA DUNLAP1, DANIEL ABEBE1, SARAH POGGI2, CATHERINE SPONG1, 1UPDN, NICHD, NIH, Bethesda, Maryland, 2Georgetown University, Obstetrics and Gynecology, Washington, District of Columbia OBJECTIVE: In utero alcohol (ALC) exposure results in developmental delay and learning impairment. Previous work demonstrated that a single novel 12 amino acid peptide prevented ALC-induced fetal death (Endres, SMFM 2003). To further evaluate the utility of this novel peptide (ADNF-12) we studied neonatal behaviors for developmental delay and adult learning using the Morris watermaze, a model of spatial learning that is specifically impaired with developmental ALC exposure. STUDY DESIGN: Timed pregnant C57Bl6/J mice on gest day 8 treated with placebo (CTL), alcohol (ALC) (30% v/v alc 0.03 mL/kg), ADNF-12 (ALC+ADNF-12) 30 min prior to alcohol, or ADNF-12 alone. Neonatal behavior tests for motor and cognitive developmental milestones were performed on postnatal days 1-21 (ALC n = 16, CTL n = 46, ALC+ADNF-12 n = 23, ADNF-12 n = 35). Adult males were tested at 8 weeks in the Morris Watermaze for learning assessment. Statistical analysis included Kruskal-Wallis and ANOVA with P ! .05 significant. RESULTS: ALC exposure resulted in significant delay in achieving developmental milestones: eye opening and cliff aversion (ability to avoid falling by stepping backwards) with ALC achieving milestones later than all other groups. Eye opening: ALC = 14.8 G 1.1d, CTL 13.8 G 0.6d, ALC + ADNF-12 13.8 G 0.6d, ADNF-12 14.1 G 0.4d, P ! .001. Cliff aversion: ALC = 9.8 G 3.3d, CTL 8.0 G 3.3d, ALC+ADNF-12 6.8 G 3.4d, ADNF-12 3.0 G 0.9d, P ! .001. Pretreatment with ADNF-12 prevented the alcohol-induced milestone delays. There was no difference between the ALC and CTL for righting, forelimb grasp, audio startle, and air righting. In the Morris watermaze, the CTL learned, decreasing their latency over 70% (46.5+/ÿ20 sec day 1 to 9.1+/ÿ7.1sec day 7, P ! .01). ALC+ADNF-12 also significantly learned, with a learning curve not different than CTL at all timepoints tested (all P O .5) and significantly better than ALC on days 4, 6 and 7 (all P ! .05). CONCLUSION: A single treatment with a novel synthetic peptide prevented ALC-induced developmental and learning abnormalities in a model of fetal alcohol syndrome.
A COMPARISON OF PLACENTAL PATHOLOGY AND PERINATAL OUTCOME BETWEEN MONOCHORIONIC AND DICHORIONIC TWIN SETS SCOTT SULLIVAN1, ROGER NEWMAN1, JANICE LAGE2, SACHIKO MINIMAGUCHI3, MYLA EBELING4, 1 Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina, 2Medical University of South Carolina, Department of Pathology & Laboratory Medicine, Charleston, South Carolina, 3Medical University of South Carolina, Pathology, Charleston, South Carolina, 4Medical University of South Carolina, Pediatrics, Charleston, South Carolina OBJECTIVE: To describe the differences in placental pathology between diamniotic dichorionic twins (di/di) and diamniotic monochorionic twins (mono/di). Perinatal outcomes by chorionicity will also be determined. STUDY DESIGN: The placentas of 247 consecutive twin gestations delivered at the Medical University of South Carolina (1999-2002) were subjected to standardized examination by a perinatal pathologist who was blinded to the obstetrical outcome. The placentas were graded on 26 separate variables reflecting major categories of cord/insertional abnormalities, hypoxia/ischemia, hemorrhage, inflammation or abruption. Outcome data was obtained from an established, research quality database. Data was analyzed using Student’s t test, c2 and Fisher’s exact test. RESULTS: There were 100 di/mo twins and 147 di/di twins. Monochorionic twins had significantly increased incidences of villous edema (P ! .01), cord insertion abnormalities (P ! .025), placental hemorrhage (P ! .01) and meconium staining (P ! .05). There were no differences seen in placental weights, acute or chronic chorioamnionitis, placental infarcts or chorangiosis between the di/mo and di/di twins. In addition to the differences in placental pathology, the monochorionic twins had lower birth weights (P ! .03), earlier delivery (P ! .05), and higher incidences of 5-minute Apgar scores !7 (P ! .05). Neonatal outcomes including death, intraventricular hemorrhage, sepsis and necrotizing enterocolitis were not associated with chorionicity. CONCLUSION: Monochorionic twin placentas demonstrate an increase in cord insertion abnormalities and other pathology consistent with villous hypoxia/ischemia but equivalent placental weights compared to dichorionic twins. These findings suggest that the placental injury seen in monochorionic twins occurs late in gestation and may be associated with a greater risk of prematurity.
478
479
PLACENTAL PATHOLOGY AND PERINATAL OUTCOME ASSOCIATED WITH SMALL FOR GESTATIONAL AGE TWINS SCOTT SULLIVAN1, ROGER NEWMAN1, JANICE LAGE2, SACHIKO MINAMIGUCHI3, MYLA EBELING4, EUGENE CHANG1, 1Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina, 2 Medical University of South Carolina, Department of Pathology & Laboratory Medicine, Charleston, South Carolina, 3Medical University of South Carolina, Charleston, South Carolina, 4Medical University of South Carolina, Pediatrics, Charleston, South Carolina OBJECTIVE: To determine the differences in placental pathology between small for gestational age (SGA) twins and appropriate for gestational age (AGA) twins. The perinatal outcomes of these twins will also be described. STUDY DESIGN: The placentas of 247 consecutive twin gestations delivered at the Medical University of South Carolina (1999-2002) were subjected to standardized examination by a perinatal pathologist who was blinded to the obstetrical outcome. The placentas were graded on 26 variables reflecting major categories of cord/insertional abnormalities, hypoxia/ischemia, hemorrhage, inflammation or abruption. SGA was defined as growth !10th percentile based on gestational age using established twin growth curves. Outcome data was obtained from a research quality perinatal database. Data was analyzed using Student’s t test, c2, and Fisher’s exact test. RESULTS: There were 57 SGA twins and 190 AGA twins. SGA twins had significantly increased incidences of cord insertion abnormalities, (P ! .025), small placental weights (P ! .001) and placental infarctions (P ! .03). There were no differences in chorionicity, chorioamnionitis, villous edema, meconium staining or villous stromal hemorrhage. In addition to the differences in placental pathology, the SGA twins had lower birthweights (P ! .03), higher rates of neonatal sepsis and higher incidences of 5-minute Apgar scores !7 (P ! .05). There were no differences in rates of death, respitory distress syndrome or intraventricular hemorrhage. CONCLUSION: SGA twins are associated with a higher incidence of cord insertion abnormalities and placental infarctions. There was a surprising absence of differences in the other findings of hypoxic/ischemic placental injury. Sepsis was the only adverse neonatal outcome increased among SGA twins but there were no differences in placental findings of chorioamnionitis.
Finding
SGA twins
AGA twins
P value
Placental weight !10% Cord insertion abnormality Placental infarction
19/57 21/57 16/57
19/189 33/189 24/189
.001 .025 .025
PROTEOMIC ANALYSIS OF CERVICO-VAGINAL SECRETIONS DURING PREGNANCY IRINA BUHIMSCHI1, CATALIN BUHIMSCHI1, ERROL NORWITZ1, BEN HAMAR1, ANNA SFAKIANAKI1, MERT BAHTIYAR1, CARL P. WEINER2, CHARLES LOCKWOOD1, 1 Yale University, Ob./Gyn. & Reprod. Sci., New Haven, Connecticut, 2 University of Maryland, Baltimore, Maryland OBJECTIVE: Pregnancy is associated with increased susceptibility to ascending infection. The cervico-vaginal mucus plug is ideally positioned between the microbe-rich vagina and the normally sterile amniotic fluid cavity, suggesting a host defense function. STUDY DESIGN: The proteomic profile of cervico-vaginal secretions from 20 pregnant (P) women (GA: 26.5 G 1.0 wks) with intact membranes and no detectable uterine activity was compared to that of 7 healthy non-pregnant (NP) ovulating women. Proteomics technology (SELDI-TOF-MS) followed by immunoassay was undertaken to identify and quantify components of a proteomic fingerprint. RESULTS: The following protein biomarkers were identified in the cervicovaginal secretions: defensin-2 (3373 Da), defensin-1 (3444 Da), defensin-3 (3488 Da), calgranulin C (10,443 Da) and calgranulin A (10,834 Da) (Fig.). A nondiscriminatory ELISA for defensins 1-3 confirmed no differences between groups (P: 35.9 [32.4-41.7] vs NP: 39.0 [12.8-41.4 ng/mL, P = .97). Calgranulin C was the most abundant biomarker analyzed (P: 309.7 [61.0-1202.0] vs. NP: 110.8 [17.5-160.5 ng/mL], P = .12). Similarly, calgranulin A immunoreactivity did not differ between P and NP groups (P: 51.7 [15.9-118.6] vs NP: 64.2 [46.3-148.0] ng/ mL, P = .530). These relationships were maintained after normalizing for total protein. CONCLUSION: The cervico-vaginal proteomic fingerprint is apparently unchanged by pregnancy. The wide expression of defensins and calgranulins in both NP and P cervico-vaginal tract suggests these proteins have an important role in the innate immune defense against human genital tract infections.
477
PREVENTION OF ALCOHOL-INDUCED DELAYS IN DEVELOPMENTAL MILESTONES AND LEARNING ABNORMALITIES IN A MODEL OF FETAL ALCOHOL SYNDROME MELANIE ENDRES1, LAURA TOSO1, ROBIN ROBERSON1, JANE PARK1, VERONICA DUNLAP1, DANIEL ABEBE1, SARAH POGGI2, CATHERINE SPONG1, 1UPDN, NICHD, NIH, Bethesda, Maryland, 2Georgetown University, Obstetrics and Gynecology, Washington, District of Columbia OBJECTIVE: In utero alcohol (ALC) exposure results in developmental delay and learning impairment. Previous work demonstrated that a single novel 12 amino acid peptide prevented ALC-induced fetal death (Endres, SMFM 2003). To further evaluate the utility of this novel peptide (ADNF-12) we studied neonatal behaviors for developmental delay and adult learning using the Morris watermaze, a model of spatial learning that is specifically impaired with developmental ALC exposure. STUDY DESIGN: Timed pregnant C57Bl6/J mice on gest day 8 treated with placebo (CTL), alcohol (ALC) (30% v/v alc 0.03 mL/kg), ADNF-12 (ALC+ADNF-12) 30 min prior to alcohol, or ADNF-12 alone. Neonatal behavior tests for motor and cognitive developmental milestones were performed on postnatal days 1-21 (ALC n = 16, CTL n = 46, ALC+ADNF-12 n = 23, ADNF-12 n = 35). Adult males were tested at 8 weeks in the Morris Watermaze for learning assessment. Statistical analysis included Kruskal-Wallis and ANOVA with P ! .05 significant. RESULTS: ALC exposure resulted in significant delay in achieving developmental milestones: eye opening and cliff aversion (ability to avoid falling by stepping backwards) with ALC achieving milestones later than all other groups. Eye opening: ALC = 14.8 G 1.1d, CTL 13.8 G 0.6d, ALC + ADNF-12 13.8 G 0.6d, ADNF-12 14.1 G 0.4d, P ! .001. Cliff aversion: ALC = 9.8 G 3.3d, CTL 8.0 G 3.3d, ALC+ADNF-12 6.8 G 3.4d, ADNF-12 3.0 G 0.9d, P ! .001. Pretreatment with ADNF-12 prevented the alcohol-induced milestone delays. There was no difference between the ALC and CTL for righting, forelimb grasp, audio startle, and air righting. In the Morris watermaze, the CTL learned, decreasing their latency over 70% (46.5+/ÿ20 sec day 1 to 9.1+/ÿ7.1sec day 7, P ! .01). ALC+ADNF-12 also significantly learned, with a learning curve not different than CTL at all timepoints tested (all P O .5) and significantly better than ALC on days 4, 6 and 7 (all P ! .05). CONCLUSION: A single treatment with a novel synthetic peptide prevented ALC-induced developmental and learning abnormalities in a model of fetal alcohol syndrome.
A COMPARISON OF PLACENTAL PATHOLOGY AND PERINATAL OUTCOME BETWEEN MONOCHORIONIC AND DICHORIONIC TWIN SETS SCOTT SULLIVAN1, ROGER NEWMAN1, JANICE LAGE2, SACHIKO MINIMAGUCHI3, MYLA EBELING4, 1 Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina, 2Medical University of South Carolina, Department of Pathology & Laboratory Medicine, Charleston, South Carolina, 3Medical University of South Carolina, Pathology, Charleston, South Carolina, 4Medical University of South Carolina, Pediatrics, Charleston, South Carolina OBJECTIVE: To describe the differences in placental pathology between diamniotic dichorionic twins (di/di) and diamniotic monochorionic twins (mono/di). Perinatal outcomes by chorionicity will also be determined. STUDY DESIGN: The placentas of 247 consecutive twin gestations delivered at the Medical University of South Carolina (1999-2002) were subjected to standardized examination by a perinatal pathologist who was blinded to the obstetrical outcome. The placentas were graded on 26 separate variables reflecting major categories of cord/insertional abnormalities, hypoxia/ischemia, hemorrhage, inflammation or abruption. Outcome data was obtained from an established, research quality database. Data was analyzed using Student’s t test, c2 and Fisher’s exact test. RESULTS: There were 100 di/mo twins and 147 di/di twins. Monochorionic twins had significantly increased incidences of villous edema (P ! .01), cord insertion abnormalities (P ! .025), placental hemorrhage (P ! .01) and meconium staining (P ! .05). There were no differences seen in placental weights, acute or chronic chorioamnionitis, placental infarcts or chorangiosis between the di/mo and di/di twins. In addition to the differences in placental pathology, the monochorionic twins had lower birth weights (P ! .03), earlier delivery (P ! .05), and higher incidences of 5-minute Apgar scores !7 (P ! .05). Neonatal outcomes including death, intraventricular hemorrhage, sepsis and necrotizing enterocolitis were not associated with chorionicity. CONCLUSION: Monochorionic twin placentas demonstrate an increase in cord insertion abnormalities and other pathology consistent with villous hypoxia/ischemia but equivalent placental weights compared to dichorionic twins. These findings suggest that the placental injury seen in monochorionic twins occurs late in gestation and may be associated with a greater risk of prematurity.
478
479
PLACENTAL PATHOLOGY AND PERINATAL OUTCOME ASSOCIATED WITH SMALL FOR GESTATIONAL AGE TWINS SCOTT SULLIVAN1, ROGER NEWMAN1, JANICE LAGE2, SACHIKO MINAMIGUCHI3, MYLA EBELING4, EUGENE CHANG1, 1Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina, 2 Medical University of South Carolina, Department of Pathology & Laboratory Medicine, Charleston, South Carolina, 3Medical University of South Carolina, Charleston, South Carolina, 4Medical University of South Carolina, Pediatrics, Charleston, South Carolina OBJECTIVE: To determine the differences in placental pathology between small for gestational age (SGA) twins and appropriate for gestational age (AGA) twins. The perinatal outcomes of these twins will also be described. STUDY DESIGN: The placentas of 247 consecutive twin gestations delivered at the Medical University of South Carolina (1999-2002) were subjected to standardized examination by a perinatal pathologist who was blinded to the obstetrical outcome. The placentas were graded on 26 variables reflecting major categories of cord/insertional abnormalities, hypoxia/ischemia, hemorrhage, inflammation or abruption. SGA was defined as growth !10th percentile based on gestational age using established twin growth curves. Outcome data was obtained from a research quality perinatal database. Data was analyzed using Student’s t test, c2, and Fisher’s exact test. RESULTS: There were 57 SGA twins and 190 AGA twins. SGA twins had significantly increased incidences of cord insertion abnormalities, (P ! .025), small placental weights (P ! .001) and placental infarctions (P ! .03). There were no differences in chorionicity, chorioamnionitis, villous edema, meconium staining or villous stromal hemorrhage. In addition to the differences in placental pathology, the SGA twins had lower birthweights (P ! .03), higher rates of neonatal sepsis and higher incidences of 5-minute Apgar scores !7 (P ! .05). There were no differences in rates of death, respitory distress syndrome or intraventricular hemorrhage. CONCLUSION: SGA twins are associated with a higher incidence of cord insertion abnormalities and placental infarctions. There was a surprising absence of differences in the other findings of hypoxic/ischemic placental injury. Sepsis was the only adverse neonatal outcome increased among SGA twins but there were no differences in placental findings of chorioamnionitis.
Finding
SGA twins
AGA twins
P value
Placental weight !10% Cord insertion abnormality Placental infarction
19/57 21/57 16/57
19/189 33/189 24/189
.001 .025 .025
PROTEOMIC ANALYSIS OF CERVICO-VAGINAL SECRETIONS DURING PREGNANCY IRINA BUHIMSCHI1, CATALIN BUHIMSCHI1, ERROL NORWITZ1, BEN HAMAR1, ANNA SFAKIANAKI1, MERT BAHTIYAR1, CARL P. WEINER2, CHARLES LOCKWOOD1, 1 Yale University, Ob./Gyn. & Reprod. Sci., New Haven, Connecticut, 2 University of Maryland, Baltimore, Maryland OBJECTIVE: Pregnancy is associated with increased susceptibility to ascending infection. The cervico-vaginal mucus plug is ideally positioned between the microbe-rich vagina and the normally sterile amniotic fluid cavity, suggesting a host defense function. STUDY DESIGN: The proteomic profile of cervico-vaginal secretions from 20 pregnant (P) women (GA: 26.5 G 1.0 wks) with intact membranes and no detectable uterine activity was compared to that of 7 healthy non-pregnant (NP) ovulating women. Proteomics technology (SELDI-TOF-MS) followed by immunoassay was undertaken to identify and quantify components of a proteomic fingerprint. RESULTS: The following protein biomarkers were identified in the cervicovaginal secretions: defensin-2 (3373 Da), defensin-1 (3444 Da), defensin-3 (3488 Da), calgranulin C (10,443 Da) and calgranulin A (10,834 Da) (Fig.). A nondiscriminatory ELISA for defensins 1-3 confirmed no differences between groups (P: 35.9 [32.4-41.7] vs NP: 39.0 [12.8-41.4 ng/mL, P = .97). Calgranulin C was the most abundant biomarker analyzed (P: 309.7 [61.0-1202.0] vs. NP: 110.8 [17.5-160.5 ng/mL], P = .12). Similarly, calgranulin A immunoreactivity did not differ between P and NP groups (P: 51.7 [15.9-118.6] vs NP: 64.2 [46.3-148.0] ng/ mL, P = .530). These relationships were maintained after normalizing for total protein. CONCLUSION: The cervico-vaginal proteomic fingerprint is apparently unchanged by pregnancy. The wide expression of defensins and calgranulins in both NP and P cervico-vaginal tract suggests these proteins have an important role in the innate immune defense against human genital tract infections.