252

253

348 SPO Abstracts

ACE INHIBITOR FETOPATHY. peter G pryde' Clark E Nugent, Aileen B Sedman.' Mason Barr Jr: Depts of OblGyn, Pathology, and Pediatrics, University of Michigan Medical Center, Ann Arbor, MI and Dept ObiGyn, Division of Repro Genetics, Hutzel HospitaVWayne State U, Detroit, MI.

The ACE·inhibitors (AI) are widely prescribed and effective antihypertensives, but are not without risk in pregnant women. Profound fetal toxicity has been reported in several animal models. Adverse human·fetal outcomes have also been reported. We describe a pallern of anomalies and physiologic atteration which can be termed AI fetopathy and report three additional infants in which this peculiar pallern is manifest (table).

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26 '1/0, 8 yr SLE, chronieHTN,on -30 '110, 9yrs cnroric HTN,onanaiapril

I ~~~bi~~ ~iM) IOlgo I ~=: I ume,

33 wk, "'tal di ..... , induction, vaginal Inech, 14409 rrale < 2.5%-~.

32 N, .. tal Islr8S1, oeser • ." section, 1480 g-<25%-ile

32 wks, letal distress, c:eser .. n Mdion, gao 9 mal. <2.S"'f..ile

sion arurie

MY.'. ~:~ng ~~~,=~u::-

Mvere profound

!'~:~18

141'r1.

I ~~~~~. ~~ ana A I N,

insuffiency, on dalysis, now 15 mo dage. IUGR, He, short linU, AlD, death@gct.0I10 ",nalfailure

These cases combined with those previously reported indicate that Als are fetotoxic. The peculiar pathophysiologic pallern cannot be ascribed to the underlying maternal disease or other medications. AI fetopathy is characterized by fetal hypotension, anuria­oligohydramnios, growth-restriction (IUGR), hypocalvaria (HC), renal tubular dysplasia (RTD), and in the most severe cases pulmonary hypoplasia (PH). In surviving neonates profound hypotension and anuria are observed which are recaicitrantto volume replacement and pressor therapy. The hypotension resolves only after dialysing off the otherwise renally secreted drug. Atthough present data do not allow inference of frequency of AI fetopathy in exposed pregnancies, these drugs should be viewed as human fetotoxins and considered only as a last resort for use during pregnancy.

FAMUAl OMPHAlOCELE (FO): CONSIDERA1l0NS IN GENE1lC COUNSEUNG. ~. NB Isada, MP Johnson', MI Evans, Dept OB/GYN, Hutzel HosplWayne State Univ, Detro~, MI

Isolated, nonsyndromic omphalocele is generally regarded as a sporadic malformation. Recurrence risks (RR) are considered negligible. Our observations on a patient in whom five consecutive pregnancies (by 2 separate nonconsanguenous partners) were complicated by FO (see table) suggests a need to aker the standard counseling for RR. Ne~her the patient nor her partners had history of relatives affected by omphalocele atthough the patients brother and his son had very large umbilical hernias requiring surgical repair. Some cases of familial isolated omphalocele have been reported. Most pedigrees are suggestive of a vertical mode of transmision although there are a few cases with only a single generation involved. In no previously reported case was a complete generation, and so many members affected. It is problematic to speculate as to the oenetic mechanism ooeratina in this familv.

Pre .11 Ka olype

not done 46,xx nol done nol done 46 xx

Deliver

25 wk.s SVD 16 INks SAb 29 wk. labor, classical CS

:. W:~-::~r ~ ~~~ (r~e:a~:l

Outcome

680 g F. omph. death @ 24 h ultrasound confirmation omph prior to Ab 1500g M, omph. repair, death @ 5 mo 1590 g M, omph, repair, death@ 24h 1650 Ii F omph, repair death@ 24 h

AbbreviatIOnS: omph_ ISOlated omphalooele, M_ male, F_ female, SAb- spontaneous abortion. L res.. low transverse oe.rean section, SVO. spontaneous .... ginal deNvery

Because the defect occurred with two separate fathers a monogenic autosomal recessive mechanism is unlikely. However, the finding of a large umbilical hernia in the patient's brother and his son, makes an autosomal dominant mechanism With variable expresslvlly a tenable explanation. A polygenic-multifactorial mechanism which might be suggested as an alternative explanation is not satisfying in light of the 100% transmission through 5 siblings. With present data and diagnostic limitations the true mechanism operating cannot be elucidated. Undoubtedly it is largely genetiC. These cases emphasize omphalocele heterogeneity and caution in counseling RR.

January 1992 Am.J Obslct Gynecol

254 DETERMINANTS FOR PARENTAL DECISION TO ABORT (DTA) OR CONTINUE FOR NON-ANEUPLOID ULTRASOUND DETECTED ABNORMALTIES. PG pryde.' AE Odgers: NB Isada. MP Johnson, MI Evans. Dept OB/GYN, Reprod. Genetics, Hutzel Hosp~allWayne State U, Detroit, MI.

Decision to abort an otherwise wanted pregnancy because of fetal anomalies is complex. This study evaluates DTA after finding maHormations on ultrasound in the karyotypically normal fetus. All pregnancies managed on our service complicated by ukrasound abnormalities from 4/90-8/91 were included (n=262). Cases with associated karyotypic abnormalities (KA) were excluded (n=35) as were cases in which a diagnosis was made after the legal gestational age (GA) limit for abortion (24 wks, n-65). The remaining 159 cases were stratified into prognosis groups of severe, uncertain, and mild. Data were analyzed using ANOVA with decision to continue (C) or terminate (T) as the dependent variable. Results: Mothers age. gravity, parity, and gestational age at diagnosis were not significantly different between groups. Severity of the ultrasound abnormality was stronaly correlated wjth PTA (p- 0001)

Mild Uncertain Severe Totals T 2.8% 11.1% 65.6% 30.2% C 97.1 % 88.9% 34 . .4% 69.8% Total 100% 100% IOWo 100% Conclusions: 1. In non-aneuploid pregnancies with ukrasound diagnosis of fetal abnormality, the major predictor of DTA is sever~y of prognosis. 2. Contrary to previous assertions by other authors, but in agreement with our previous study in KA fetuses. the GA at the time of diagnOSis is not an important variable in DTA. 3. Contrary to widely held opinion, most parents having fetuses with significant anomalies which carry uncertain prognoses opted to continue pregnancy. This was particularly true for defects potentially correctable by in-utero intervention (eg. bladder shunt, data not shown).

255 ANTENATAL DIAGNOSIS USING AMPLIFICATION OF FETAL DNA FROM MATERNAL BLOOD. C. Chambersx, A. EyreX , K. Ward, Dept Ob/Gyn, Univer­sity of Utah School of Medicine, Salt Lake City, UT

To determine the practicality of testing fetal cells present in the maternal circulalion for genetic diagnosis, a model testing for the Y chromosome was selected. 50 maternal blood samples were obtained from gestations rang;ng from 6 weeks to term. DNA was extracted from the samples. The polymerase chain reaction was used to search for V-specific sequences (of fetal origin) using eilher nested primers (Lo el ai, Lancet 1990) which detect a single copy region or primers to Y alphoid repeats (Witt et aI., Hum Genet 1989). Results were compared to the neonatal sex recorded at delivery. Sensitivity (ability to correctly identify male fetuses) was 80-100%, increaSing with each successive trimester of pregnancy. Specificity varied from 20-92% depending on the primer set and the assay conditions. False positives occurred predominantly with samples from multiparous patients who had previously delivered a male child. This model suggests that amplification of paternal specific markers from maternal blood could reduce the need for invasive diagnostic procedures in order to perform DNA testing, especially in nulliparous gestations.