Volume 167Number 2

Elliott refers to our study and claims, "The design ofthe study appears to be inadequate in that the amountof drug administered (4g magnesium sulfate bolus and2 gm per hour infusion) has been shown to be associ­ated with subtherapeutic serum levels of magnesium."We must conclude that Elliott is far more guilty of sub­therapeutic therapy than we because we used thehigher infusion dosage more often than he did. Spe­cifically, 62% of our patients received 3 gm per hourinfusions. Moreover, we are mystified that Elliott claimstocolytic efficacy for magnesium sulfate when most ofhis patients apparently were treated with what he nowcalls a sub therapeutic dosage regimen.

Elliott also reported in 1983, "Clinically, we foundthat levels between 5.0 and 7.0 mg/dl were usually suf­ficient to inhibit contractions....'" We reported a meanmagnesium level of 6.6 mg/dl. Elliott now states that"The conclusion reached in the article by Cox et al. that'magnesium sulfate infusions resulting in maximum se­rum concentrations of magnesium equal to 6.6 mg/dlare ineffective in the prevention of preterm birth' isabsolutelytrue (emphasis added)." In an attempt to applysome logic to all this we seem unavoidably compelledto conclude that Elliott now believes his 1983 statement"... levels between 5.0 and 7.0 mg/dl were usually suf­ficient ... ", is untrue. Our real bias is that Elliott un­wittingly seems to agree with us, although we take it hewould not like this, either.

Susan M. Cox, MD, Lynne Sherman, RN, andKenneth J. Leveno, MD

Department ofObstetricsand Gynecology,Albert B. Chandler MedicalCenter, 800 Rose St., Lexington, KY 40506

REFERENCE

1. Elliott ]P. Magnesium sulfate as a tocolytic agent. AM]OBSTET GYNECOL 1983;147:277-84.

The effect of gestational age on maternal seruma-fetoprotein levels in pregnancies withDown syndromeTo the Editors: Greenberg et al. (Greenberg F, del JuncoD, Weyland B, et al. The effect of gestational age onthe detection rate of Down syndrome by maternalserum o-fetoprotein screening. AMJ OBSTET GVNECOL1991; 165: 1391-3) found that maternal serum o-feto­protein (AFP) levels were lower on average in 14 preg­nancies with Down syndrome tested at 16.5 to 17.5weeks' gestation than in 22 pregnancies tested at 14 to16.5 weeks and in 15 at 17.5 to 21.5 weeks. Expressinglevels in multiples of the median for unaffected preg­nancies of the same gestation, the mean value at eachgestation was 0.59, 0.74, and 0.69 respectively. How­ever, these differences are not borne out by summa­rizing other published studies.

Table I updates a previous summary of the literature'to include all recent publications'" in which individualmultiple of the median values according to week ofgestation are either tabulated or can be abstracted froma figure and where the serum sample was not taken

Letters 569

Table I. Maternal serum AFP levels inpregnancies with fetal syndrome according togestational age l o

'

Gestationcompleted No. of MedianAFP

(wk) pregnancies (MoM)

14 2 0.72-0.7315 26 0.7216 144 0.7217 110 0.7218 53 0.7019 29 0.7420 13 0.7721 2 0.45-1.96

14-21 379 0.72

MoM, Multiple of the median for unaffected pregnanciesof the same gestation.

after amniocentesis or chorionic villus biopsy. A totalof 379 affected pregnancies between 14 and 21 weekswere available for analysis. There was no tendency forthe median AFP level in any gestational week to differfrom the overall median value, nor did any effect ofgestation emerge when an analysis of variance of logAFP was carried out to allow for differences betweenthe various studies included. First-trimester AFP levelshave been reported in a total of 67 pregnancies withDown syndrome6

.10 and found to be similar to second­

trimester levels. The geometric mean weighted for thenumber of pregnancies in each first-trimester study was0.74 multiples of the median.

These results have implications for screening policyin centers in which AFP is the only Down syndromemarker being measured. If the same blood sample isused for both Down syndrome and neural tube defectscreening the test would need to be done at 16 to 18weeks, the gestation at which neural tube defect detec­tion is highest. If a separate blood sample can be usedor if reliance can be placed on ultrasonography forneural tube defect screening, Down syndrome screen­ing need not be restricted to 16 to 18 weeks. For centersusing multiple markers the optimal gestation will de­pend on which additional markers are used.

Howard S. Cuckle, DPhilInstitute of Epidemiology and Health Services Research, School ofMedicine, The University of Leeds, Leeds LS2 9LN, England.

REFERENCES

1. Wald N, Cuckle H. AFP and age screening for Downsyndrome. Am] Med Genet 1988;31:197-209.

2. AshwoodER, Cheng E, Luthy DA. Maternal serum alpha­fetoprotein and fetal trisomy-21 in women 35 years andolder: implications for alpha-fetoprotein screening pro­grams. Am] Med Genet 1987;26:531-9.

3. Suchy SF, Yeager MT. Down syndrome screening inwomen under 35 with maternal serum hCG. Obstet Gy­necoI1990;76:20-4.

4. Zeitune M, Aitken DA, Crossley JA, Yates]RW,Cooke A,Ferguson-Smith MA. Estimating the risk of a fetal auto­somal trisomy at mid-trimester using maternal serum al-

570 Letters

phafetoprotein and age: a retrospective studyof 142 preg­nancies. Prenat Diagn 1991;11:847-57.

5. Mancini G, Perona M, Dall'Amico D, et al. Screening forfetal Down's syndrome with maternal serum markers­An experience in Italy. Prenat Diagn 199 I ;11:245-52 .

6. Cuckle HS, Wald NJ, Barkai G, et al. First trimester bio­chemical screening for Down's syndrome. Lancet1988;2:851-2.

7. Scioscia A, Green J , Robinson J , Blakemore K, MahoneyM, Baumgarten A. Maternal seru m alpha-fetoprotein innormal first-trimester pregnancies and pregnancies withfetal anomalies. AmJ Hum Genet 1987;41(suppl):A285.

8. Mantigh A, Marrink J , de Wolf B, Breed ASPM, BeekhuisJR, Visser GHA. Lower maternal serum alpha-fetoproteinat 10 weeks' gestation and fetal Down 's syndrome. Br JObstet Gynaecol 1989;96:499-500.

9. Brock DJH, Barron L, Holloway S, Liston WA, Hillier SG,Seppala M. First trimester maternal serum biochemicalindicators in Down syndrome. Prenat Diagn 1990;10:245­5l.

10. Johnson A, Cowchock FS, Dar by M, Wapner R, J acksonLG. First trimester maternal serum alpha-fetoprotein andchorionic gonadotrophin in aneuploid pregnancies.Prenat Diagn 1991; 11:443-50 .

Reply

To the Editors: We are pleased to have this opportunityto emphasize the importance of pursuing improve­ments in the efficac y of the maternal serum o-fetopro­tein (AFP) screening test for Down syndrome preg­nancies. Comparing affected with unaffected pregnan­cies at our center we found that for a given maternalserum AFP cut point of 0.8 weight-adjusted multiplesof the median the detection rate was higher and thefalse-positive rate was lower between 16.5 and 17.5weeks' gestation than at earlier or later gestational ages .This suggested to us that the optimum gestational agefor maternal serum AFP screening for Down syn­drome may be similar to the optimum reported pre­viously for neural tube defect screening.' Wald andCuckle's" previous and current synthesis of maternalserum AFP multiples of the median data fro m differentcenters focus on mean or median values in Down syn­drome pregnancies. Such values relate only to detectionrates and only indirectly so. Although Cuck le did notdetect statistically significant differences among thegestational age-specific median maternal serum AFPmultiples of the median he reported, it is interestingto note that a nadir of 0.7 multiples of the median wasreported at 17 weeks' gestation in his first paper andat 18 weeks' gestation in his updated table . It is possiblethat the nadir between 17 and 18 weeks' gestation isrea l, not a result of random fluctuation, and that itimp lies a higher detection rate for Down syndromepregnancies in that time window. A similar pattern ofmaternal serum AFP multiples of the median results(with a nadir at 17 weeks' gestation) was reponed byWaller et al ." To assess accurately whether the patternsobserved by Waller and Cuckle suggest underlying de­tection rates and false-positive rates similar to ourswould require comparable analyses allowing for vari­ance in unaffected and affected pregnancies. We urgeindividual cen ters to periodically examine their mater­nal serum AFP detection rates and false-pos itive ratesin this manner. Given the quantitative advantages andpower of recent metaanalysis techniques' to properly

August 1992AmJ Obstet Gynecol

incorporate center-specific variances, we recommendthe application of these methods to assist policy dec i­sions in maternal serum AFP screening. Finally, westress the importance of appropriate tests for hetero­geneity among centers before any pooling of dataacross centers. In assessing heterogeneity as in poolingacross centers, maternal serum AFP variability in bothunaffected and affected pregnancies must be taken intoconsideration.

Deborah delJunco, PhD, Deborah Schmidt, RN,Esmie Rose, PhD , and Frank Greenberg, MD

Institutefor MolecularGeneticsand DepartmentofPediatrics, BaylorCollege of Medicine, Houston, TX 77030

REFERENCES

I. Report of United Kingdom collaborative study on alpha­fetoprotein in relation to neural-tube defects. Maternal se­rum-alpha-feto protein measurement in antenatal screen­ing for anencephaly and spina bifida in early pregnancy.Lancet 1977;1:1323-32.

2. Wald N, Cuckle H. AFP and age screening for Down syn­drome. Am J Med Genet 1988;31 :197-209.

3. Waller K, Lustig L, Hook E. Gestational age at maternalserum alpha-fetoprotein screening and the detection ofDown syndrome. AmJ Hum Genet 1990;47:581-2.

4. Laird N, Mosteller F. Some statistical methods for combin­ing experimental results. IntJ Technol Assess Health Care1990;6:5-30.

An association between placental location andnuchal cord occurrence

To the Editors: A continuing prospective study namedthe Perinatal Umbilical Cord Project made an associ­ation between placental location and nuchal cord oc­currence.' The number of entries into this private studyhas now numbered 400 cases. The purpose of this letteris to update the statistics on nuchal cord and placentallocation .

Four hundred pregnancies were prospectively stud­ied over a 3-year period. Three hund red sixty met re­quirements of a 28-week ultrasonographic examinationand manual removal of the placenta at delivery. Pla­cental location was reviewed after delivery and com­pared with the occurrence of nuchal cord. Nuchal cordis defined as the umbilical cord being 360 degreesaround the neck.

Table I summarizes the data.Among 360 pregnancies the location of the placenta

was recorded as follows: posterior, 37%; anterior, 38%;and fundal, 25%. The occurrence of a nuchal cord(14%) among all pregnancies is not the same for eachof the placental locations; it is most common among

Table I. Summary of data

Percentagewith

Placental Nu chal nuchallocation n cord cord

Posterior 134 30 22.4Anterior 137 16 11.7Fundal 89 4 4.5T OTAL 360 50 13.9