Volume 177, Number 4 Loiters 979 Am J Obstet Gynecol

34 weeks separated from the control groups at term. If this was done to show the difference from the preterm group, statistically eliminating the effect of gestational age on the variables of interest (fatty acids profile), then this could be reached in a simpler way without perform- ing an unclear comparison between three groups of subjects, as shown in Fig. 2 on page 911. In fact, assuming that the main aim of the article is the evaluation of fatty acids profile in preterm delivery versus controls in ma- ternal blood, then a bivariate regression to evaluate the effect of both gestational age at the time of blood drawing and preterm delivery could be a better ap- proach. 1 A weighted regression for the number of mea- surements at each gestational age could be adequate. The regression is

y = [30 -~- [31" Xl + [32" X2 -~- [33" (Xl ° X2)

where y represents each fatty acid, x 1 the gestational age at the time of blood drawing, x 2 the preterm delivery,

and (x 1 • x2) the interaction of the two variables. [31 " xl expresses the slope of the line as a dependent variable of

the gestational week. [32 " x2, used in this model as dummy variable, describes instead the effect of preterm labor on the height on the y axis or, in other words, the value of the dependent variable y when preterm labor

appears, with the gestational age constant. ½ assumes

just the values 0 (absence) or 1 (presence). [33" (xl " ½) describes the effect on the slope in the presence of x 2. This last item is a very suggestive feature because it is able to show the different effect of gestational age on the fatty

acids profile when preterm delivery occurs. In this way the authors could easily analyze the [3

coefficients and evaluate the effect of the x variables to

define the y values. Graphically it is a plot where the x

axis is gestational age and the y axis is each fatty acid. Two lines appear in the graph, the first representing the control group the other the preterm delivery group.

The last three neonatal characteristics in Table I on page 909 have no statistical sense; perhaps the use of percentiles instead of actual values could help the reader. The comparison "between groups" labeled as "c"

in Fig. 2 on page 911 is also without statistical sense, because if the first and second groups are equal ("a" comparison) and the second and the third are equal too

("b" comparison), one expects that also the first and the third groups are equal between them. The same is true

for the comparison labeled "a." Adequate post hoc test could solve this gap. We think that the article could improve its validity if these suggestions were taken into account.

Antonio Farina, MD New England Medical Center, No. 394, 750 Washington St., Boston, MA 02111

Luisa Di Luzio, MD Department of Obstetrics and Gynecology and Prenatal Pathophysiology, Bologna University School of Medicine, Bologna, Italy

Paolo Carinci, MD, PhD

Institute of Histology and General Embryology, Ferrara and Bologna Universities School of Medicine, Bologna, Italy

REFERENCE 1. Glantz SA, Slinker BK, Primer of applied regression and

analysis of variance, New York: McGraw-Hill; 1990.

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Reply

To the Editors: Regression analysis, as suggested by Farina et al:, would be a reasonable approach to examine differential effects of gestational age on essential fatty acid profiles in preterm and control populations. How- ever, in this case there are two reasons why this approach would fail to produce the suggested results. Because sampling at precisely 34 weeks of gestation was one of the primary criteria for matching prospectively sampled con- trols with preterm cases, control subjects were sampled within a very narrow range (33.4 to 34.6 weeks) yielding, essentially, one time point for analysis. Additionally, with only three exceptions, control subjects delivered within an equally narrow range (39.5 to 41 weeks). Thus only two time points are available to estimate the control slope. In preterm subjects only time points around 34 weeks (33.9 +_ 0.6 weeks) were available, and a meaning- ful slope could not be estimated. Therefore regression analysis would be precluded because [31 , designated as the average of the two slopes, would estimate the slope in controls only; [32 would estimate the preterm mean versus the average of the two control sampling times (this is not the intended, nor a useful, comparison); and [33 (the effect of preterm labor on the slope) cannot be estimated without the preterm slope.

Our Table I presented mean values + SEs (a valid statistical measure of dispersion about the mean) for weight, length, and head circumference in preterm and term neonates. The data were presented in this manner to allow the reader to draw conclusions about whether measurements were appropriate for gestational age. Clearly, presenting values instead of percentile rankings (which are derived from the actual measured values) is a matter of personal preference NOT statistical "sense."

In response tO comments regarding three-way compar- isons in our Fig. 2, in fact there are three comparisons that can be made among these means (comparisons a, b, and c). A conclusion from a versus b (or any two comparisons) does not arrive at a conclusion about a third comparison. Adequate post hoc analyses, in this case protected least-square differences subsequent to three-way analysis of variance (accepted only if the TYPE IlI sums of squares yielded p values <0.05 in the analysis of variance), were the source for these sound compari- sons.

The use of a time-dependent control at 34 weeks of gestation was useful to validate conclusions about altered essential fatty acid metabolism in preterm birth. Unless the effect of gestational age is considered, inferences

980 Letters October 1997 Am J Obstet Gynecol

could not be drawn from differences in preterm and term profiles at delivery because it is well known that placental essential fatty acid transport is increased late in gestation to meet high fetal demands.

Mary Harris, PhD, RD, Kenneth G.D. Allen, PAl), James A. McGregor, MD, and Melanie S. Reece, PhD

Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, and Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, CO 80262

6/8/84551

No evidence to support intrauterine contraceptive device and embryo destruction To the Editors: I am writing with reference to Spinnato's article (Spinnato J. Mechanism of action of intrauterine contraceptive devices and its relation to informed con- sent Am J Obstet Gynecol 1997;176:503-6).

In his 1994 review, Croxatto a opines that there is no evidence to support the conclusion that the mechanism of action of IUD in women involves destruction of embryos. He points to the fact that very few spermatozoa reach the fallopian tubes and those that do encounter an egg are in poor condition. Indeed, there is substantial additional evidence that supports this view. If the copper content of the fluids of the uterus and fallopian tube impairs sperma- tozoa function, it would equally inhibit fertilization. Those of us with extensive laboratory and clinical experience with the fertilization process are acutely aware that even the slightest contaminant in the fluids in which the eggs and spermatozoa are placed dramatically impairs fertilization.

Spinnato provides a rather biased interpretation of the data on ovum and sperm recovery provided by Alvarez et al. In no case did the Alvarez group observe the presence of fertilized ova among women wearing the copper- containing IUD. There is no justification for Spinnato's statement that "in five of the IUD patients, the ova were actually not classifiable and could have been fertilized." It is well known that ova disintegrate in time when they are not fertilized. The conclusion of the Alvarez group was that there was no evidence of fertilized eggs in the fallopian tubes of women using IUDs. Without benefit of direct observation, Spinnato concludes the contrary. Overall, the data still support the widely held conclusion that the mechanism of action of the copper-containing IUD is directed at prefertifization events.

Luigi Mastroianni, Jr., MD

Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, 3400 Spruce St., Philadelphia, PA 19104

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Intrauterine contraceptive devices act before fertilization To the Editors: Spinnato's article (Spinnato JA. Mecha- nism of action of intrauterine contraceptive devices and

its relation to informed consent. Am J Obstet Gynecol 1997;176:503-6) addresses a complex topic. On the basis of a selective literature review, Spinnato concludes that " . . . the inhibition of implantation of the fertilized ovum remains a major if not the dominant mechanism of action of IUDs." The mechanism of IUD (intrauterine contraceptive device) action has been the subject of serious scientific attention for >30 years. A comprehen- sive review of >100 original articles on the topic was published by Croxatto et al. a Regrettably, Spinnato did no t include in his review this article, or most of the cited work that fails to support his contention, Most of us who have worked in this field acknowledge that, in spite of the massive body of literature on IUDs, the precise mecha- nism of action in the human remains uncertain. But, as Croxatto et al. conclude, " . . . the common belief that the usual mechanism of action of IUDs in women is destruc- tion of embryos is not supported by empirical evidence. The evidence establishes that in women who use [cop- per-bearing] IUDs, very few spermatozoa reach the distal segment of the Fallopian tube and those that do encoun- ter an egg in poor condition."

It cannot escape a reader's attention that the Spinnato article brings the IUD into the abortion debate in the United States. Without introducing new data, it con- cludes that contraceptive IUDs act after fertilization, implying that they could be classified as abortifacients, although there is no factual basis for th!s categorization. IUD use has been studied by every available scientific method---sperm migration, highly sensitive human cho- rionic gonadotropin determinations, ultrasonographic visualization, and ovum recovery studies--to determine whether they may work after fertilization. The data from these studies fail to provide evidence of fertilization and early development in routine users of copper-bearing IUDs.

Sheldon J. Segal, PhD

The Population Council, 1 Dag Hammarskjold Plaza, New York, NY 10017

REFERENCE 1. Croxatto HB, Ortiz ME, Valdez E. IUD mechanisms of action.

In: Bardin CW, Mishell DR Jr, editors. Proceedings of the Fourth International Conference on IUDs. Boston: Butter- worth-Heinemann; 1994.

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Reply To the Editors: My original manuscript cited 61 refer- ences. Editorial constraints (25 references) necessitated the exclusion of most of these. 1 reviewed the Cumulative Index Medicus for 1993 to 1997 and the review of Croxatto et al, was not cited.

I persist in my criticism of the study of Alverez et al. 1 The support that my colleagues have for this study and their willingness to suggest it excludes a postfertilization mechanism of action for the IUD demonstrates unrea-