518 Maternal gene-environment interactions and spontaneous abortion risk

$222 SMFM Abstracts 516

December 2001 A m J Obstet Gynecol

T I M I N G OF SPONTANEOUS A B O R T I O N AFTER AMNIOCENTESIS DENA TOWNER ], LINDA GREVE t, BOB CURRIER 2, FRED LOREy2; lUniversity of California, Davis, Obstetrics & Gynecology, Sacramento, G&; 2Genetic Disease Branch, DHS, Berkeley, CA OBJECTIVE: To compare, in a prenatal diagnosis population, when spontaneous abortions (SAB) occur in women accepting and declining an amniocen tesis. STUDY DESIGN: From the Calitornia State Expanded AFP program, 44,525 women with outcomes ascertained were identified where the fetal ultrasound was normal and if an aumiocentesis was pertc)rlned it was uornlal. T h e r e were 156 spontaneous abortions at < 24 weeks gestation. An amniocentesis was p e r f o r m e d in 69. The remaining 87 had declined anmiocentesis. The two groups were compared tot maternal age, gestational age (GA) at prenatal diagnosis (PDC) visit, n u m b e r of days to loss after PDC visit, GA at loss, maternal sermn AFP (MSAFP), maternal serum hCG (MShCG), and maternal seruna estriol (MSuE3). Student t test and Logrank test were used to compare the groups. RESULTS: The overall rate of SAB was 0.36%. There was no statistical difference between the two groups in the factors assessed: GA at loss was 21 weeks 2 days ~br both groups (P = .93), days until loss was 23 days with amnio and 20.4 days w,ithout (P = .29), maternal age was 30.5 years with amnio and 30.1 years in those declining (P = .72), MSAFP was 3.18 MoM in those with amnio and 2.83 MoM in those declining (P = .36), MShCG was 2.10 MoM in those having an anmio and 1.80 MoM in those declining (P = .24). The Logrank test revealed no significant difference between the groups for either GA at loss (P= .61) or days until loss (P= .40). The Figure shows the cumulative losses by GA at loss. CONCLUSION: There is no clustering of losses innnediately following anmiocentesis with the average time to loss about 3 weeks. The same pattern is present in the women declining amniocentesis, suggesting there is minimal impact of amniocentesis in this population of women. Figure GA at loss

Cumulative

518

MATERNAL GENE-ENVIRONMENT INTERACTIONS AND SPONTANEOUS A B O R T I O N RISK CYNTHIA SIMS ~, MARJORIE ROMKES 2, R1CtL&RD D. DAYs, TOMOKO NUKUI4, GAlL F. HARGER-~, NINA MARKOVIC 5, W. ALLEN HOGGE ~, ROBERTA B. NESS 6, WILLIAM L. BIGBEE4; tUniversity of Pittsburgh/Magee-Womens Research Institute, OB,GYN&RS, Pittsburgh, PA; 2University of Pittsburgh, Medicine, Pittsburgh, PA; 3University of Pittsburgh, Biostatistics, Pittsburgh, PA; 4University of Pittsburgh, Environmental & Occupational Health, Pittsburgh, PA; 5University of Pittsburgh, Epidelniology, Pittsburgh, PA; 6University of Pittsburgh/MageeWomens Research Institute, Epideufiology, Pittsburgh, PA OBJECTIVE: The objective is to evaluate the hypothesis that individual metabolic susceptibilities to environmental agents, like tobacco smoke and alcohol, increase the risk of a spontaneous abortion (SAB). STUDY DESIGN: This is an IRB approved matched (2:1) case-control study nested within a larger cohort investigation of healthy pregnant women, 1445 yeat~ old. A comprehensive questionnaire is adnfinistered in order to gather lifes~le exposures. Genmnic DNA was isolated fl'om maternal whole blood. Conditional logistic regression analysis was used to model the effects of maternal environmental exposures aud genotype on case control status. SABs were defined as a pregnancy loss < 20 weeks. RESULTS: Genomic DNA samples were available for 95 w o m e n experiencing SABs. The sociodemographic characteristics and distribution of maternal litestyle factors do not differ statistically. A statistically significant change in the likelihood ratio was obsmwed for the CYP1A2 variable but no significant changes occured when NAT2* or the CYP1A2/NAT2* interaction terms were introduced (consistent with our report). The data fur tobacco smoke exposure and alcohol consumption showed no statistically significant changes in the likelihood ratio statistic. CONCLUSION: The SAB risk significantly increased when both the potential increased activation activity and decreased detoxification is taken into account. Neither self-reported smoking or alcohol consumption were associated with an overall risk of SAB or with the genetic risk factors identified. Enzyme-mediated maternal actix~tion, detoxification and clearance, placental and fetal metabolism may impact tile level of embryonic/fetal exposure to a particular toxic substrate.

519

INCIDENCE OF ADVERSE OUTCOME AFTER GENETIC AMNIOCENTESIS JONATHAN GILLEN-GOLDSTEIN~, STEVEN A KLEIN~, ANDREW P MACKENZIEl, BRUCE YOUNG-~: tNew York University, New York, NY; ~Madonna Perinatal Center, Mineola, NY; 3NewYork University, Obstetrics and Gynecology, NewYork, NY OBJECTIVE: To detemfine the incidence of adverse outcomes and their natural course "after midtrimester amniocentesis for genetic diagnosis. STUDY DESIGN: A retrospective review of a computerized database to identify all patients presenting for genetic aumiocentesis from 1993 to 2001. Outcomes were con, piled from review of medical records. Outcome criteria included rupture of membranes (ROM) within one week of ainnioceutesis, diagnosed by patient complaint of leaking fluid and physician observed vaginal pooling of fluid +/- a >50% decrease in AFI, spontaneous abortion (SAB), intrauterine fi:tal denfise (IUFD), and clinically a n d / o r culture documented infection. RESULTS: During the study period, genetic amniocentesis was performed 9105 times. There were a total of 47 adverse outcomes including 24 ROM, 13 SAB, and 10 IUFD (see Table). We report a ROM rate after genetic aumiocemesis of 0.26% (24/9105), or apwoximately 1 in 400 amniocentesis. Of the 24 cases of ROM, 20 (83%) had spontaneous resealing of the membranes. All resealed within 14 days, with 17 by 7 days and 19 by 10 days. The 4 cases that did not reseal all developed evidence of infection after at least 10 days had passed. We also report a fetal loss rate after amnio of 0.3% (27/9105), or less than l in 300 anmiocentesis. CONCLUSION: Adverse outconles from anmiocentesis are rare. Conservative m a n a g e m e n t may facilitate spontaneous resolution in the majority of cases. After 7-10 days, infection becomes a serious risk when resealing has not occurred spontaneously, lntmwention to seal the membranes surgically may be a consideration during this brief window of opportunity in the small n u m b e r of patients in this high risk group. Table

Losses

800% 60 0%

400%

;!

~o 0% 00% Gestat~onal Age at Loss from 122 to 167 days

517

ELEVATED MATERNAL SERUM ALPHA FETOPROTEIN, BUT N O T MATERNAL SERUM HUMAN C H O R I O N I C G O N A D O T R O P I N IS ASSOCIATED W I T H PRETERM DELIVERY DENA TOWNER t , LINDA GREVE 1, BOB CURRIER -°, FRED LOREY2, ]University of California, Davis, Obstetrics & Gynecology, Sacramento, CA 2Genetic Disease Branch, DHS, Berkeley, CA OBJECTIVE: To evaluate the median maternal serum alpha fetoprotein (MSAFP), maternal serum h u m a n chorionic gonadotropin (MShCG) and maternal serum unconjugated estriol (MsuE3) values by gestational age (GA) at delivery and distribution of gestations: ages at delivery in women with an apparently false positive result from rile California Expanded AFP Program. STUDY DESIGN: Gestational age at delivery was determined for 14,536 women that were screen positive in the California Expanded AFP program, who all had a normal ultrasound and karyotype. The majority (60%) of these w o m e n were initially seen for elevated MSAFP. Median values tot MSAFP, MShCG, and MSuE3 were calculated for each week of delivery. Multiple regression was used to evaluate the median analyte values by weeks of GA at delivery. The percent of deliveries occurring each week of gestation was calculated and compared to the latest CDC reported rate in 1999. RESULTS: Elevated MSAFP was associated with p r e t e r m delivery (P < .001), but MShCG ( P - .75) and MSuE3 (P= .084) were not. The trend with MSuE3 was to have lower values with advancing gestation. The percent of deliveries prior to 37 weeks was 12.4%, which is similar to the latest CDC reported rate of 11.8%. CONCLUSION: This data confirms the association of unexplained elevations of MSAFP with p r e t e r m deliver},, but does not confirm an association with unexplained elevations of MShCG. In this highly selected group of women, the rate of preterm delivery is not apparently different than that of the general US population. Further studies are need to define the predictive value of an unexplained elevation of MK~cFE Figure Deliveries and analyte medians by week ; ~

. tNuntbero -

percent !MSAFP]MShCO MSuE3 J

~½~ ~ - i --8.2~-~7~-~.-~i----02-~-~ 2s ........~. &S~; i zr~ 1 ~i~a KT~ i 27 __4~44

1 L1%

..... 3i-.7 7 ~5-- i 32 34

96

2.84 i C01 2,Sl ~

i ~;4~ "~

86

0.85 1

~:i7

o.~q

I.~2

0.84

ezo% ] o.se ! ~,a~

0.oe

~ I089 L l & ~

~ 1,88

2~7

96.0%

1

T 0,7§ i 1,93 = 064

_!. ~oo:o~ i.i,

# OF CASES

TOTAL # OF AMNIOCENTESIS

INCIDENCE

24 20 4 10 13

9105 9105 9105 9105 9105

0.26% 0.22% 0.04% 0.11% 0.14%

0.g7

T--2-2-~b', $sYn'og-TZ~-!-i77:,,-E:t-uq

:'0 ! ~o~ 4~

.......

3.5%

222 ~ 6 %

a~ 37

i

', 2 7 6 ! 1.70 : 0.73 ]

.t,8_~_..o:~....

Total ROM Resealed Not resealed IUFD Spent. Ab