- Email: [email protected]
128 Third-trimester unexplained intrauterine fetal death is not associated with thrombophilia
December 2001 A m J Obstet Gynecol
$116 SMFM Abstracts 125
PREGNANCIES AFI'ER ASSISTED REPRODUCTION--HIGHER RISK FOR ADVERSE O U T C O M E UWE LANG t, J U L I O HERRERO ], A BECK l, T STALF2, C MEHNERT 2, H GIPS2; lJus tus-Liebig-Univer sitar Giessen, Obstetrics and Gynecology, Giessen, Hessen; 2Institute of Reproductive Medicine Giessen, IVF, Giessen, Hessen OBJECTIVE: Pregnancies after assisted r e p r o d u c t i o n (IVF/ICSI) are considered to be risk pregnancies. The goal of our study was to assess whether a n d in which aspects the course of these pregnancies a n d perinatal outcome after [VF differ from pregnancies not conceived through assisted reproduction. STUDY DESIGN: 406 pregnancies after IVF between 1994 a n d 1999 were examined. Data were c o m p a r e d with those of 338,737 patients without any form of sterility treatment from the statewide perinatal survey of the state of Hesse/ Germany (HEPE) for the same period. Additionally, within the IYT group, subgroups for PCO, hyperstimulation a n d other factors were formed a n d evaluated. RESULTS: 300 (73.9%) o f the p r e g n a n c i e s after 1VF were singleton pregnancies, 97 (23.9%) twin p r e g n a n c i e s a n d 9 (2.2%) triplets. After grouping HEPE data for age a n d parity to match the IVF group, in singleton pregnancies we f o u n d a high late of early vaginal bleeding (1VF 15.7%; HEPE 2.5%; P < .05), PIH (IVF: 6.3 %; HEPE 2.1%; P < .05), gestational diabetes (IVF: 4.0%; HEPE 0.8%; P < .05), a n d premature labour (IVF: 25.7%; HEPE 7.3%; P < .05) in the 1VF group. Consequently p r e g n a n c i e s after 1VF h a d a high prematurity (IVF 20.3%; HEPE 6.7%; P < .05) a n d caesarean section late (IVF 35.7%; HEPE 19.9%; P < .05). Perinatal mortality in the IVF g r o u p was 1.0% (HEPE 0.6%). Furthermore, 16.8% of the newborns after IVF were growth restricted (HEPE 8.0%; P < .05); 4.4% were severely growth restricted (<3rd Percentile). Similar results were observed c o m p a r i n g twin pregnancies. Subgroups of IVF patients h a d even higher risks for e.g. gestational diabetes, hypertension a n d prematurity. Interestingly, impaired sperm morphology was associated with an increased IUGR late. CONCLUSION: Pregnancies after 1VF therapy are high risk pregnancies when c o m p a r e d to a s t a n d a r d collective (HEPE) m a t c h e d for n u m b e r of fetuses, age a n d parity. Subgroups of IVF patients show even higher rates of specific pregnancy risks, impaired sperm morphology seems to be linked to IUGR.
126
MATERNAL AGE AND RISK O F FETAL DEATH IN TWIN GESTATIONS IN T H E UNITED STATES JOSEPH CANTERINO t, CANDE ANANTH 2, J O H N SMULIAN2, J O H N HARRIGAN 3, ANTHONY VINTZILEOS2; i UMDNJ-Rober t Wood J o h n s o n Medical School/Saint Peter's University Hospital, Obstetrics, Gynecology a n d Reproductive Sciences, New Brunswick, NJ; 2UMDNJRobert Wood J o h n s o n Medical School/Saint Peter's University Hospital, Obstetrics, Gynecology a n d Reproductive Sciences, New Brunswick, NJ; 3Jersey Shore Medical Center, Maternal-Fetal Medicine, Neptune, NJ OBJECTIVE: To evaluate the i n d e p e n d e n t contributions of y o u n g a n d advanced naaternal age on fetal death in twin gestations a n d compare these risk profiles with other c o m m o n indications for a n t e p a r t o m testing. STUDY DESIGN: Retrospective c o h o r t analysis of twin gestataions between 1995-97 in the United States using linked birth-infant death data was p e r f o r m e d . Gestational age <20 weeks a n d fetuses with anomalies were excluded. Fetal death rates with maternal ages 20-34 were c o m p a r e d with y o u n g (<20 years) a n d advanced age (35-39 years a n d _>40 years). Fetal death rates for c o m m o n indications for a n t e p a r t u m testing i n c l u d i n g c h r o n i c h y p e r t e n s i o n (CHTN), p r e g n a n c y - i n d u c e d hypertension (PIH), diabetes (DM), a n d small for gestational age (SGA) births were evaluated. I n d e p e n d e n t contributions of young a n d advanced ages, CHTN, PIH, DM a n d SGA births for the risk of fetal death were d e t e r m i n e d based on multivariable logistic regression models. Relative risk (RR) a n d 95% confidence intervals (CI) were derived f r o m these models after adjusting for b i r t h order, gravidity, race, marital status, prenatal care, education a n d smoking. RESULTS: A m o n g the 275,901 births, fetal d e a t h o c c u r r e d in 2,097 (0.8%). Fetal death rate a n d RR for maternal age categories, CHTN, PIH, DM a n d SGA are shown in the Table. W h e n the analysis was restricted to delivery _>32weeks similiar risk profiles were noted. CONCLUSION: Young maternal age is independently associated with an increased risk for fetal death. The magnitude of these risks is similiar to those of other c o m m o n indications for a n t e p a r t u m testing. Advanced maternal age appears to reduce the risk of fetal death. Table Fetal death rate in twin gestations GROUP <20 20-34 35-39 >_40 CHTN PIH DM SGA
TOTAL BIRTHS
D E A T H S (N)
RATE
19,997 207,456 40,743 7,705 2,462 23,234 9,156 25,050
260 1,546 239 52 22 115 57 620
13.0 7.5 5.9 6.7 8.9 4.9 6.2 24.8
R R (95% CI) 1.8 1.0 0.8 0.9 1.2 0.6 0.8 4.3
(1.5-2.0) (Referent) (0.7-0.9) (0.7-1.2) (0.8-1.8) (0.5-0.8) (0.6-1.1) (3.9-4.7)
127
METOCLOPRAMIDE CONCENTRATION IN BREAST MILK O F WOMEN DELIVERING BETWEEN 23-34 WEEKS GESTATION WENDY HANSEN I, STEPHEN H U N T E R 1, STEPHANIE MCANDREW ~, KATHLEEN HARRIS 3, BRIDGET ZIMMERMAN4; ÂUniversity of Iowa Hospitals a n d Clinics, Obstetrics a n d Gynecology, Iowa City, IA; 2University of Iowa Hospitals a n d Clinics, Iowa City, IA; 3University of Wisconsin Medical School, Madison, WI; 4University of Iowa College of Public Health, Biostatistics, Iowa City, IA OBJECTIVE: Metoclopramide (MC) is generally accepted to be a n effective lactagogne. We determined the concentration of MC in the breast milk of women with preterm infants (23-34 weeks gestation). STUDY DESIGN: Breast milk samples were obtained from 14 mothers taking MC who delivered p r e t e r m infants. Subjects were chosen r a n d o m l y from the experimental g r o u p (n = 34) of a larger randomized, double blind, placebo-controlled study (n = 69). Within 96 hours after birth, women took 10 m g of MC three times a day for 10 days. Breast milk samples were taken on day 10 -+ 2 a n d sent to National Medical Services (Willow Grove, PA) for a highpressure liquid c h r o m a t o g r a p h y assay of the MC levels in the milk. All samples except one were extracted from a 24-hour collection of expressed breast milk. Breast milk samples f r o m two m o t h e r s taking placebo were analyzed as controls. RESULTS: Breast milk assays of the two women in the placebo g r o u p did not detect MC. The mean level of MC excreted into the breast milk of the 14 subjects was 44.8 + 20.4 n g / m L . The median (25th-75th percentile) level of MC in breast milk was 45 (28-56) n g / m L . CONCLUSION: Mean levels of metocloplamide in preterm breast milk are similar to levels f o u n d in studies of term subjects. Breast milk levels are similar to the reported therapeutic range of 40-80 n g / m L in the plasma of adults taking 10 mg TID. We calculated the m a x i m u m possible exposure to infants in our study to be 0.011 m g / k g / d a y . This is about 3% of the recomm e n d e d daily dosage (0.5 m g / k g / d a y ) for children. This is similar to findings on term infants.
128
THIRD-TRIMESTER UNEXPLAINED INTRAUTERINE FETAL DEATH IS N O T ASSOCIATED WITH THROMBOPI-UI.I& RONIT BECK-FRUCHTER t, YASSER HUJEIRAT 2, STAVIT SHALEV"2, ZOHAR NAHUM 1, AMIR WEISS 1, ZEEV WEINER t, ELIEZER SHALEV'3; t H a ' E m e k Medical Center, Obstetrics a n d Gynecology, Afnla; 2 H a ' E m e k Medical Center, H u m a n Genetic Unit, Afula; 3Technion-Israel Institute of Technology, R a p p a p o r t Faculty of Medicine, Haifa OBJECTIVE: To d e t e r m i n e the frequency of i n h e r i t e d a n d a c q u i r e d thrombophilia a m o n g women with third-trimester unexplained intrauterine fetal death (IUFD). STUDY DESIGN: All women with IUFD after 24 weeks gestation in a 3-year period were initially assessed. Cases with congenital anomalies, intrauterine infection, feto-maternal bleeding or diabetes mellitus were excluded. The remaining 53 women were matched for ethnicity with 53 healthy women with a n o r m a l obstetrical history. All women, in b o t h groups were tested for mutations of factor V Leiden, p r o t h r o m b i n gene, MTHFR, for the deficiencies of protein S, protein C, anti t h r o m b i n III a n d for lupus anticoagulant a n d anticardiolipin antibodies. RESULTS: The prevalence of any t h r o m b o p h i l i a was 40% in the study g r o u p c o m p a r e d to 32% in the control g r o u p (P = .54). Inherited thrombophilia was f o u n d in 32% of the study c o m p a r e d to 21% of controls (P= .27). The late of acquired thrombophilia did not differ between the groups (20% vs. 19%, respectively). The rate of combined thrombophilias was 15% vs. 7.5% (P = .36). CONCLUSION: Third-trimester unexplained IUFD is not associated with thrombophilia.
$116 SMFM Abstracts 125
PREGNANCIES AFI'ER ASSISTED REPRODUCTION--HIGHER RISK FOR ADVERSE O U T C O M E UWE LANG t, J U L I O HERRERO ], A BECK l, T STALF2, C MEHNERT 2, H GIPS2; lJus tus-Liebig-Univer sitar Giessen, Obstetrics and Gynecology, Giessen, Hessen; 2Institute of Reproductive Medicine Giessen, IVF, Giessen, Hessen OBJECTIVE: Pregnancies after assisted r e p r o d u c t i o n (IVF/ICSI) are considered to be risk pregnancies. The goal of our study was to assess whether a n d in which aspects the course of these pregnancies a n d perinatal outcome after [VF differ from pregnancies not conceived through assisted reproduction. STUDY DESIGN: 406 pregnancies after IVF between 1994 a n d 1999 were examined. Data were c o m p a r e d with those of 338,737 patients without any form of sterility treatment from the statewide perinatal survey of the state of Hesse/ Germany (HEPE) for the same period. Additionally, within the IYT group, subgroups for PCO, hyperstimulation a n d other factors were formed a n d evaluated. RESULTS: 300 (73.9%) o f the p r e g n a n c i e s after 1VF were singleton pregnancies, 97 (23.9%) twin p r e g n a n c i e s a n d 9 (2.2%) triplets. After grouping HEPE data for age a n d parity to match the IVF group, in singleton pregnancies we f o u n d a high late of early vaginal bleeding (1VF 15.7%; HEPE 2.5%; P < .05), PIH (IVF: 6.3 %; HEPE 2.1%; P < .05), gestational diabetes (IVF: 4.0%; HEPE 0.8%; P < .05), a n d premature labour (IVF: 25.7%; HEPE 7.3%; P < .05) in the 1VF group. Consequently p r e g n a n c i e s after 1VF h a d a high prematurity (IVF 20.3%; HEPE 6.7%; P < .05) a n d caesarean section late (IVF 35.7%; HEPE 19.9%; P < .05). Perinatal mortality in the IVF g r o u p was 1.0% (HEPE 0.6%). Furthermore, 16.8% of the newborns after IVF were growth restricted (HEPE 8.0%; P < .05); 4.4% were severely growth restricted (<3rd Percentile). Similar results were observed c o m p a r i n g twin pregnancies. Subgroups of IVF patients h a d even higher risks for e.g. gestational diabetes, hypertension a n d prematurity. Interestingly, impaired sperm morphology was associated with an increased IUGR late. CONCLUSION: Pregnancies after 1VF therapy are high risk pregnancies when c o m p a r e d to a s t a n d a r d collective (HEPE) m a t c h e d for n u m b e r of fetuses, age a n d parity. Subgroups of IVF patients show even higher rates of specific pregnancy risks, impaired sperm morphology seems to be linked to IUGR.
126
MATERNAL AGE AND RISK O F FETAL DEATH IN TWIN GESTATIONS IN T H E UNITED STATES JOSEPH CANTERINO t, CANDE ANANTH 2, J O H N SMULIAN2, J O H N HARRIGAN 3, ANTHONY VINTZILEOS2; i UMDNJ-Rober t Wood J o h n s o n Medical School/Saint Peter's University Hospital, Obstetrics, Gynecology a n d Reproductive Sciences, New Brunswick, NJ; 2UMDNJRobert Wood J o h n s o n Medical School/Saint Peter's University Hospital, Obstetrics, Gynecology a n d Reproductive Sciences, New Brunswick, NJ; 3Jersey Shore Medical Center, Maternal-Fetal Medicine, Neptune, NJ OBJECTIVE: To evaluate the i n d e p e n d e n t contributions of y o u n g a n d advanced naaternal age on fetal death in twin gestations a n d compare these risk profiles with other c o m m o n indications for a n t e p a r t o m testing. STUDY DESIGN: Retrospective c o h o r t analysis of twin gestataions between 1995-97 in the United States using linked birth-infant death data was p e r f o r m e d . Gestational age <20 weeks a n d fetuses with anomalies were excluded. Fetal death rates with maternal ages 20-34 were c o m p a r e d with y o u n g (<20 years) a n d advanced age (35-39 years a n d _>40 years). Fetal death rates for c o m m o n indications for a n t e p a r t u m testing i n c l u d i n g c h r o n i c h y p e r t e n s i o n (CHTN), p r e g n a n c y - i n d u c e d hypertension (PIH), diabetes (DM), a n d small for gestational age (SGA) births were evaluated. I n d e p e n d e n t contributions of young a n d advanced ages, CHTN, PIH, DM a n d SGA births for the risk of fetal death were d e t e r m i n e d based on multivariable logistic regression models. Relative risk (RR) a n d 95% confidence intervals (CI) were derived f r o m these models after adjusting for b i r t h order, gravidity, race, marital status, prenatal care, education a n d smoking. RESULTS: A m o n g the 275,901 births, fetal d e a t h o c c u r r e d in 2,097 (0.8%). Fetal death rate a n d RR for maternal age categories, CHTN, PIH, DM a n d SGA are shown in the Table. W h e n the analysis was restricted to delivery _>32weeks similiar risk profiles were noted. CONCLUSION: Young maternal age is independently associated with an increased risk for fetal death. The magnitude of these risks is similiar to those of other c o m m o n indications for a n t e p a r t u m testing. Advanced maternal age appears to reduce the risk of fetal death. Table Fetal death rate in twin gestations GROUP <20 20-34 35-39 >_40 CHTN PIH DM SGA
TOTAL BIRTHS
D E A T H S (N)
RATE
19,997 207,456 40,743 7,705 2,462 23,234 9,156 25,050
260 1,546 239 52 22 115 57 620
13.0 7.5 5.9 6.7 8.9 4.9 6.2 24.8
R R (95% CI) 1.8 1.0 0.8 0.9 1.2 0.6 0.8 4.3
(1.5-2.0) (Referent) (0.7-0.9) (0.7-1.2) (0.8-1.8) (0.5-0.8) (0.6-1.1) (3.9-4.7)
127
METOCLOPRAMIDE CONCENTRATION IN BREAST MILK O F WOMEN DELIVERING BETWEEN 23-34 WEEKS GESTATION WENDY HANSEN I, STEPHEN H U N T E R 1, STEPHANIE MCANDREW ~, KATHLEEN HARRIS 3, BRIDGET ZIMMERMAN4; ÂUniversity of Iowa Hospitals a n d Clinics, Obstetrics a n d Gynecology, Iowa City, IA; 2University of Iowa Hospitals a n d Clinics, Iowa City, IA; 3University of Wisconsin Medical School, Madison, WI; 4University of Iowa College of Public Health, Biostatistics, Iowa City, IA OBJECTIVE: Metoclopramide (MC) is generally accepted to be a n effective lactagogne. We determined the concentration of MC in the breast milk of women with preterm infants (23-34 weeks gestation). STUDY DESIGN: Breast milk samples were obtained from 14 mothers taking MC who delivered p r e t e r m infants. Subjects were chosen r a n d o m l y from the experimental g r o u p (n = 34) of a larger randomized, double blind, placebo-controlled study (n = 69). Within 96 hours after birth, women took 10 m g of MC three times a day for 10 days. Breast milk samples were taken on day 10 -+ 2 a n d sent to National Medical Services (Willow Grove, PA) for a highpressure liquid c h r o m a t o g r a p h y assay of the MC levels in the milk. All samples except one were extracted from a 24-hour collection of expressed breast milk. Breast milk samples f r o m two m o t h e r s taking placebo were analyzed as controls. RESULTS: Breast milk assays of the two women in the placebo g r o u p did not detect MC. The mean level of MC excreted into the breast milk of the 14 subjects was 44.8 + 20.4 n g / m L . The median (25th-75th percentile) level of MC in breast milk was 45 (28-56) n g / m L . CONCLUSION: Mean levels of metocloplamide in preterm breast milk are similar to levels f o u n d in studies of term subjects. Breast milk levels are similar to the reported therapeutic range of 40-80 n g / m L in the plasma of adults taking 10 mg TID. We calculated the m a x i m u m possible exposure to infants in our study to be 0.011 m g / k g / d a y . This is about 3% of the recomm e n d e d daily dosage (0.5 m g / k g / d a y ) for children. This is similar to findings on term infants.
128
THIRD-TRIMESTER UNEXPLAINED INTRAUTERINE FETAL DEATH IS N O T ASSOCIATED WITH THROMBOPI-UI.I& RONIT BECK-FRUCHTER t, YASSER HUJEIRAT 2, STAVIT SHALEV"2, ZOHAR NAHUM 1, AMIR WEISS 1, ZEEV WEINER t, ELIEZER SHALEV'3; t H a ' E m e k Medical Center, Obstetrics a n d Gynecology, Afnla; 2 H a ' E m e k Medical Center, H u m a n Genetic Unit, Afula; 3Technion-Israel Institute of Technology, R a p p a p o r t Faculty of Medicine, Haifa OBJECTIVE: To d e t e r m i n e the frequency of i n h e r i t e d a n d a c q u i r e d thrombophilia a m o n g women with third-trimester unexplained intrauterine fetal death (IUFD). STUDY DESIGN: All women with IUFD after 24 weeks gestation in a 3-year period were initially assessed. Cases with congenital anomalies, intrauterine infection, feto-maternal bleeding or diabetes mellitus were excluded. The remaining 53 women were matched for ethnicity with 53 healthy women with a n o r m a l obstetrical history. All women, in b o t h groups were tested for mutations of factor V Leiden, p r o t h r o m b i n gene, MTHFR, for the deficiencies of protein S, protein C, anti t h r o m b i n III a n d for lupus anticoagulant a n d anticardiolipin antibodies. RESULTS: The prevalence of any t h r o m b o p h i l i a was 40% in the study g r o u p c o m p a r e d to 32% in the control g r o u p (P = .54). Inherited thrombophilia was f o u n d in 32% of the study c o m p a r e d to 21% of controls (P= .27). The late of acquired thrombophilia did not differ between the groups (20% vs. 19%, respectively). The rate of combined thrombophilias was 15% vs. 7.5% (P = .36). CONCLUSION: Third-trimester unexplained IUFD is not associated with thrombophilia.