levels of polycyclic aromatic hydrocarbons in amniotic fluid samples from smokers and nonsmokers

1
611 EFECTS OF VENO-ARTERIAL VS VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION ON HYPOXEMIC INTRAUTERINE OVINE FETUSES YASUHISA NOMURA 1 , KEIYA FUJIMORI 2 , KATSUHIKO KATO 1 , TOMOHIRO SHIROTO 1 , JHUNYA YAMADA 1 , AKIRA SATO 1 , CHIKARA ENDO 3 , 1 Fukusima Medical University, OB/GYN, Fukushima, Japan 2 Fu- kushima Medical University, OB/GYN, Fukushima, Japan 3 Endo Kikyo Maternity Clinic, Hakodate, Japan OBJECTIVE: The purpose of this study was to determine the applicability of veno-venous extracorporeal membrane oxygenation to support fetal oxygena- tion in utero. STUDY DESIGN: The ECMO system was applied to nine chronically instrumented fetal sheep with the placental circulation intact. Blood, maintaining the ECMO, was obtained through a double-lumen catheter inserted into the right atrium. After oxygenation, the blood was returned to the carotid artery through a single-lumen catheter (VA ECMO) or to the right atrium through the double-lumen catheter (VV ECMO). During continuous infusion of nitrogen into the maternal trachea, initially the VA ECMO was started to maintain fetal oxygenation and thereafter it changed to VV ECMO. Blood samples were drawn at control and initial hypoxemic periods and during hypoxemia with both types of ECMO to measure the blood gases (cranial carotid artery; CAup). RESULTS: Fetal CAup pO 2 decreased to 12.5 ± 0.4 mm Hg after reducing FiO 2 of the mother. After instituting the VA ECMO, the pO 2 was found to be 23.3 ± 2.8 mm Hg; after instituting the VV ECMO, the pO 2 was found to be 20.8 ± 1.8 mm Hg. Thus, fetal acidosis increased under both procedures. The fetal heart rate and blood pressure were not significantly altered during the experiments. CONCLUSION: Normal fetal oxygenation was maintained by VA or VV ECMO during maternal hypoxia. This study indicated that VV ECMO could more effectively and less traumatically maintain oxygenation in hypoxic fetal lambs. 612 CORD COAGULATION IN MONOCHORIONIC MULTIPLETS LATE IN GESTATION JAN DEPREST 1 , DOMINIQUE VAN SCHOUBROECK 1 , MAR- IE-VICTOIRE SENAT 2 , LIESBETH LEWI 1 , INGRID WITTERS 1 , RODRIGO RUANO 2 , YVES VILLE 2 , 1 University Hospital Gasthuisberg, Department of Obstetrics and Gynecology, Leuven, Belgium, France 2 CHI Poissy-St Germain, Poissy OBJECTIVE: Selective fetocide always raises dramatic ethical dilemmas next to local legal constraints limiting its application. We report on bipolar coagulation at advanced gestational age in highly selected circumstances of complicated monochorionic twins. STUDY DESIGN: Prospective follow-up of 8 consecutive bipolar cord occlusions performed >26 wks at two institutions. Decisions were made after careful multidisciplinary consultation and ad hoc agreement of the local ethics committee (EC). Variables were principal indication, gestational age (GA) at operation & delivery, and outcome. We discerned two groups of indications. (1) Late presentation of an anomaly not compatible with normal ex utero life and a potential threat for the co-twin following spontaneous demise. In this situation cord occlusion is preferred to early delivery and used as a rescue procedure. (2) Major congenital anomaly judged to be incompatible with reasonable life quality without immediate threat to the healthy co-twin. In this situation coagulation is selective, and when parents do not accept it, expectant management is an alternative to termination of the entire pregnancy . RESULTS: In all but 2 cases the situation presented $24 weeks but in two the diagnosis was made earlier (Table). There we proposed a later ( elective) occlusion, to avoid the risk of early PPROM, a known risk factor for fetal loss or serious postnatal morbidity. We successfully used a bipolar 3.0 mm forceps overstretching the blades to accommodate for the larger cord diameter. There was one NND related to failed therapy of pulmonary stenosis related to TTTS. CONCLUSION: Bipolar cord coagulation is feasible and effective in the third trimester of pregnancy. In countries where such a procedure is legal and in indications acceptable to parents, physicians, and the local EC, late cord occlusion can be seen as an alternative to early delivery and ex utero management, or exceptionally, a termination of the entire pregnancy. In elective circumstances it may be safer than an earlier intervention as it avoids the risks of PPROM. 613 GROWTH RESTRICTION IS ASSOCIATED WITH FETAL CARRIAGE OF A66G METHIONINE SYNTHASE REDUCTASE SNP TRACEY GLANVILLE 1 , ZOE YATES 1 , SIMON HOPKINS 1 , JAMES J. WALKER 2 , MARK LUCOCK 1 , NIGEL SIMPSON 3 , 1 Leeds General Infirmary, Feto-maternal Medicine, Leeds, United Kingdom 2 St James University Hospital, Leeds, United Kingdom 3 University of Leeds, Maternal Medicine, Leeds, United Kingdom OBJECTIVE: Methionine synthase reductase (MSR) and methionine synthase (MS) are important enzymes involved in the conversion of 5- methyltetrahydrofolate to tetrahydrofolate, a vitamin B 12 -dependent reaction that permits the conversion of homocysteine to methionine. Mutations are thought to affect secondary structure of the enzyme, resulting in altered activity, and lead to higher levels of homocysteine. Other folate gene polymorphisms have been linked with adverse pregnancy outcomes. This study set out to examine the contribution of A66G MSR and A2756G MS to fetal growth restriction. STUDY DESIGN: Growth-restricted babies ( < 2500 grams) born at term were compared to babies born of normal birth weight (3300-3800 grams). Genomic DNA was extracted from Guthrie spots and PCR amplification was performed. The amplicon was digested with the HaeIII and NdeI restriction endonucleases. Restricted products were resolved on 3% polyacrylamide gel with ethidium bromide staining and visualized under UV light. Odds ratio analyses were calculated with 95% confidence intervals. RESULTS: 236 babies were recruited to the study group, and 130, to the control group. The g allele frequencies for the MSR were 0.58 and 0.50, respectively (OR 0.73, CI 0.54-0.99). The g allele frequencies for the MS mutation were 0.21 and 0.17, respectively (OR 0.77, CI 0.52-1.14). No significant differences were observed in the combined carriage of mutant alleles for the two mutations. CONCLUSION: There is a significant difference in the carriage of the mutant allele for MSR but not for MS. These results suggest that fetal carriage of this allele could influence levels of homocysteine and thereby create an adverse environment for growth. Supported by Cereba. 614 LEVELS OF POLYCYCLIC AROMATIC HYDROCARBONS IN AMNIOTIC FLUID SAMPLES FROM SMOKERS AND NONSMOKERS STEVEN R. MYERS 1 , CHRISTOPHER CUNNINGHAM 2 , TERRY WRIGHT 2 , JONATHAN WEEKS 3 , 1 University of Louisville School of Medicine, Pharmacology and Toxicology, Louisville, KY 2 University of Louisville, Pharmacology and Toxicology, Louisville, KY 3 Society of Maternal Fetal Medicine, Louisville, KY OBJECTIVES: To evaluate the amniotic fluid levels of several tobacco smoke carcinogens (polycyclic aromatic hydrocarbons) and to determine if these levels are correlated with the level of cigarette smoke exposure. STUDY DESIGN: Amniotic fluid waste specimens were obtained between 16 and 36 weeks’ gestation. Samples were extracted and analyzed by HPLC and GC/MS (gas chromatography and mass spectroscopy) for the presence of polycyclic aromatic hydrocarbons (PAHs), including 6OH benzopyrene. Medical records were abstracted to determine the patient’s level of cigarette consumption. RESULTS: Several PAHs were detectable in amniotic fluid including 6OH Benzopyrene. Levels are clearly related to the level of maternal cigarette exposure (nonsmoker vs 1 ppd and nonsmoker vs 2 ppd, P < 0.001 and P = 0.02). CONCLUSION: Tobacco smoking during pregnancy exposes the de- veloping fetus to harmful PAHs that are known to be both mutagenic and carcinogenic. Exposure to these compounds in the first trimester and even early second trimester may place the fetus at an increased risk of DNA damage from these compounds, resulting in an elevated risk of cancer or related diseases in later life. Case series GA occlusion GA delivery Birthweight TTTS stage IV 26 32 1610 TTTS with IVH 28 36.4 NND Hydrocephaly 27.5 36.4 2810 Caudal regression 26.5 30.5 1980 Hydrocephaly 29.5 36 2770 Spina bifida 32 34 2400 TTTS stage IV 31 31.5 1150 Dandy walker 34 37 3600 Amniotic fluid 6OH benzopyrene pack/dy n mean (SD) P 0 48 1.52 (0.91) 0.5 9 6.04 (1.15) 0.3 1 23 8.32 (1.63) < 0.001 2 9 13.67 (1.51) 0.02 December 2003 Am J Obstet Gynecol S226 SMFM Abstracts

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Page 1: Levels of polycyclic aromatic hydrocarbons in amniotic fluid samples from smokers and nonsmokers

611 EFECTS OF VENO-ARTERIAL VS VENO-VENOUS EXTRACORPOREALMEMBRANE OXYGENATION ON HYPOXEMIC INTRAUTERINE OVINEFETUSES YASUHISA NOMURA1, KEIYA FUJIMORI2, KATSUHIKO KATO1,TOMOHIRO SHIROTO1, JHUNYA YAMADA1, AKIRA SATO1, CHIKARAENDO3, 1Fukusima Medical University, OB/GYN, Fukushima, Japan 2Fu-kushima Medical University, OB/GYN, Fukushima, Japan 3Endo KikyoMaternity Clinic, Hakodate, Japan

OBJECTIVE: The purpose of this study was to determine the applicability ofveno-venous extracorporeal membrane oxygenation to support fetal oxygena-tion in utero.

STUDY DESIGN: The ECMO system was applied to nine chronicallyinstrumented fetal sheep with the placental circulation intact. Blood,maintaining the ECMO, was obtained through a double-lumen catheterinserted into the right atrium. After oxygenation, the blood was returned tothe carotid artery through a single-lumen catheter (VA ECMO) or to the rightatrium through the double-lumen catheter (VV ECMO). During continuousinfusion of nitrogen into the maternal trachea, initially the VA ECMO wasstarted to maintain fetal oxygenation and thereafter it changed to VV ECMO.Blood samples were drawn at control and initial hypoxemic periods and duringhypoxemia with both types of ECMO tomeasure the blood gases (cranial carotidartery; CAup).

RESULTS: Fetal CAup pO2 decreased to 12.5 ± 0.4 mm Hg after reducingFiO2 of the mother. After instituting the VA ECMO, the pO2 was found to be23.3 ± 2.8 mm Hg; after instituting the VV ECMO, the pO2 was found to be20.8 ± 1.8 mm Hg. Thus, fetal acidosis increased under both procedures. Thefetal heart rate and blood pressure were not significantly altered during theexperiments.

CONCLUSION: Normal fetal oxygenation was maintained by VA or VVECMO during maternal hypoxia. This study indicated that VV ECMO couldmore effectively and less traumatically maintain oxygenation in hypoxic fetallambs.

612 CORD COAGULATION IN MONOCHORIONIC MULTIPLETS LATE INGESTATION JAN DEPREST1, DOMINIQUE VAN SCHOUBROECK1, MAR-IE-VICTOIRE SENAT2, LIESBETH LEWI1, INGRID WITTERS1, RODRIGORUANO2, YVES VILLE2, 1University Hospital Gasthuisberg, Department ofObstetrics and Gynecology, Leuven, Belgium, France 2CHI Poissy-StGermain, Poissy

OBJECTIVE: Selective fetocide always raises dramatic ethical dilemmas nextto local legal constraints limiting its application. We report on bipolarcoagulation at advanced gestational age in highly selected circumstances ofcomplicated monochorionic twins.

STUDY DESIGN: Prospective follow-up of 8 consecutive bipolar cordocclusions performed >26 wks at two institutions. Decisions were made aftercareful multidisciplinary consultation and ad hoc agreement of the local ethicscommittee (EC). Variables were principal indication, gestational age (GA) atoperation & delivery, and outcome. We discerned two groups of indications. (1)Late presentation of an anomaly not compatible with normal ex utero life anda potential threat for the co-twin following spontaneous demise. In this situationcord occlusion is preferred to early delivery and used as a rescue procedure. (2)Major congenital anomaly judged to be incompatible with reasonable life qualitywithout immediate threat to the healthy co-twin. In this situation coagulation isselective, and when parents do not accept it, expectant management is analternative to termination of the entire pregnancy .

RESULTS: In all but 2 cases the situation presented $24 weeks but in twothe diagnosis was made earlier (Table). There we proposed a later ( elective)occlusion, to avoid the risk of early PPROM, a known risk factor for fetal loss orserious postnatal morbidity. We successfully used a bipolar 3.0 mm forcepsoverstretching the blades to accommodate for the larger cord diameter. Therewas one NND related to failed therapy of pulmonary stenosis related to TTTS.

CONCLUSION: Bipolar cord coagulation is feasible and effective in thethird trimester of pregnancy. In countries where such a procedure is legal and inindications acceptable to parents, physicians, and the local EC, late cordocclusion can be seen as an alternative to early delivery and ex uteromanagement, or exceptionally, a termination of the entire pregnancy. Inelective circumstances it may be safer than an earlier intervention as it avoids therisks of PPROM.

613 GROWTH RESTRICTION IS ASSOCIATED WITH FETAL CARRIAGE OFA66G METHIONINE SYNTHASE REDUCTASE SNP TRACEY GLANVILLE1,ZOE YATES1, SIMON HOPKINS1, JAMES J. WALKER2, MARK LUCOCK1,NIGEL SIMPSON3, 1Leeds General Infirmary, Feto-maternal Medicine,Leeds, United Kingdom 2St James University Hospital, Leeds, UnitedKingdom 3University of Leeds, Maternal Medicine, Leeds, United Kingdom

OBJECTIVE: Methionine synthase reductase (MSR) and methioninesynthase (MS) are important enzymes involved in the conversion of 5-methyltetrahydrofolate to tetrahydrofolate, a vitamin B12-dependent reactionthat permits the conversion of homocysteine to methionine. Mutations arethought to affect secondary structure of the enzyme, resulting in altered activity,and lead to higher levels of homocysteine. Other folate gene polymorphismshave been linked with adverse pregnancy outcomes. This study set out toexamine the contribution of A66G MSR and A2756G MS to fetal growthrestriction.

STUDY DESIGN: Growth-restricted babies ( < 2500 grams) born at termwere compared to babies born of normal birth weight (3300-3800 grams).Genomic DNA was extracted from Guthrie spots and PCR amplification wasperformed. The amplicon was digested with the HaeIII and NdeI restrictionendonucleases. Restricted products were resolved on 3% polyacrylamide gelwith ethidium bromide staining and visualized under UV light. Odds ratioanalyses were calculated with 95% confidence intervals.

RESULTS: 236 babies were recruited to the study group, and 130, to thecontrol group. The g allele frequencies for the MSR were 0.58 and 0.50,respectively (OR 0.73, CI 0.54-0.99). The g allele frequencies for the MSmutation were 0.21 and 0.17, respectively (OR 0.77, CI 0.52-1.14). No significantdifferences were observed in the combined carriage ofmutant alleles for the twomutations.

CONCLUSION: There is a significant difference in the carriage of themutant allele for MSR but not for MS. These results suggest that fetal carriage ofthis allele could influence levels of homocysteine and thereby create an adverseenvironment for growth.

Supported by Cereba.

614

Case series

GA occlusion GA delivery Birthweight

TTTS stage IV 26 32 1610TTTS with IVH 28 36.4 NNDHydrocephaly 27.5 36.4 2810Caudal regression 26.5 30.5 1980Hydrocephaly 29.5 36 2770Spina bifida 32 34 2400TTTS stage IV 31 31.5 1150Dandy walker 34 37 3600

December 2003Am J Obstet Gynecol

S226 SMFM Abstracts

LEVELS OF POLYCYCLIC AROMATIC HYDROCARBONS IN AMNIOTICFLUID SAMPLES FROM SMOKERS AND NONSMOKERS STEVEN R.MYERS1, CHRISTOPHER CUNNINGHAM2, TERRY WRIGHT2, JONATHANWEEKS3, 1University of Louisville School of Medicine, Pharmacology andToxicology, Louisville, KY 2University of Louisville, Pharmacology andToxicology, Louisville, KY 3Society of Maternal Fetal Medicine, Louisville, KY

OBJECTIVES:To evaluate the amniotic fluid levels of several tobacco smokecarcinogens (polycyclic aromatic hydrocarbons) and to determine if these levelsare correlated with the level of cigarette smoke exposure.

STUDY DESIGN: Amniotic fluid waste specimens were obtained between16 and 36 weeks’ gestation. Samples were extracted and analyzed by HPLC andGC/MS (gas chromatography and mass spectroscopy) for the presence ofpolycyclic aromatic hydrocarbons (PAHs), including 6OH benzopyrene.Medical records were abstracted to determine the patient’s level of cigaretteconsumption.

RESULTS: Several PAHs were detectable in amniotic fluid including 6OHBenzopyrene. Levels are clearly related to the level of maternal cigaretteexposure (nonsmoker vs 1 ppd andnonsmoker vs 2 ppd, P < 0.001 and P = 0.02).

CONCLUSION: Tobacco smoking during pregnancy exposes the de-veloping fetus to harmful PAHs that are known to be both mutagenic andcarcinogenic.

Exposure to these compounds in the first trimester and even early secondtrimester may place the fetus at an increased risk of DNA damage from thesecompounds, resulting in an elevated risk of cancer or related diseases in laterlife.

Amniotic fluid 6OH benzopyrene

pack/dy n mean (SD) P

0 48 1.52 (0.91) —0.5 9 6.04 (1.15) 0.31 23 8.32 (1.63) < 0.0012 9 13.67 (1.51) 0.02