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Possible roles of long-chain fatty acids in preterm birth
978
Letters
sterilization failure than are women -->34 years old. A previous analysis determined that young women are also the most likely to express regret after sterilization1; for those women a reversible method of contraception may be more appropriate. The findings prompted comments that the Copper T 380A intrauterine contraceptive device (IUD), like long-acting progestins, may be an acceptable alternative to tubal sterilization for women seeking long-term contraception. The IUD is also a cost-effective contraceptive method. When Trussell et al. 2 examined the economic consequences of using contraceptive methods for 5 years, use of the Copper T IUD saved approximately $14,000, whereas tubal ligation saved approximately $12,000 compared with no contraception. In spite of its proved effectiveness, the IUD is underutilized in the United States, in part because of common misperceptions associated with IUD use. Among these is the erroneous belief that all IUDs cause ectopic pregnancies. In fact, studies have shown the Copper T 380A IUD to have a protective effect against ectopic pregnancies. In contrast, women with poststerilization pregnancy are at a significant increased risk for ectopic pregnancy. Of the 143 pregnancies that occurred after sterilization in the CREST study, 47 (33%) were ectopic. Approximately 33% of the sterilized women in the CREST study population were 18 through 27 years old. With the CREST study reporting a cumulative risk of pregnancy to be highest among this age stratification, accompanied with the knowledge that young women may regret having been sterilized, increased use of a safe and effective IUD for low-cost, long-term reversible contraception is compelling for women in this age group. Ronald T. Burkman, MD Department of Obstetrics and Gynecology, BaystateMedical Center, 259 Chestnut St., Springfield, MA 01199
REFERENCES 1. Wilcox LS, Chu S¥, Beaker ED, Zeger SL, Peterson HB. Risk factors for regret after tubal sterilization: 5 year follow-up in a prospective study. Fertil Steril 1991;33:927-33. 2. TrussellJ, Leveque JA, KoenigJD, et al. The economic value of contraception: A comparison of 15 methods. Am J Public Health 1995;85:494-503. 6/8/84734
Response declined
Abbot Purchart I (928-971) of St. Gallen--Born by postmortem cesarean section To the Editors: The postmortem cesarean section (synonyms: sectio in mortua, sectio post mortem matris) today represents a rare, mostly unpleasant occurrence in obstetrics. This procedure is indicated if fetal heartbeats are provable in the third trimester of pregnancy in a woman without signs of life.
October 1997 AmJ Obstet Gynecol
In the region of eastern Switzerland lived abbot Putchart I (928-971), famous for his commitment to fortification and urbanization of the contemporary city of St. Gallen. He had the peculiarity of being born by postmortem cesarean section because his mother, Wendilgarth, died 14 days before term. The fetus was cut out of the dead mother and wrapped in the fat of freshly slaughtered pigs. The child survived and was given by his father Ulrich to the Benedictine monastery in St. Gallen, where the monks called him "Ingenitus." In his enclosed history of that monastery Ekkehart IV wrote "At tempore labente appropinquans partui, preghans periclitatur et ante quatuordecim temporivi partus dies emoritur. Infans excisus et arvinae porci recens erute, ubi incutesceret, involutus, bone indolis cure in brevi apparuisset, baptizatur et Purchardus nominatur. ''1 Probably this historic source is the first verified description of a postmortem cesarean section in Switzerland. 2 This case report reflects an example of the early medieval medicine written down in monastic writings, which played an important role in the formation of the first universities in Europe in the following centuries. Kat~in Rothenberger, MD Depa'rCment of Obstetrics and Gynecology, Kantonsspital CH-9007 St. Gallen, Switzerland JanJanzen, MD Institute of Pathology, Ueberlingen, Lake Constance, Germany
REFERENCES 1. Ekkehart IV. Casus monasterii sancti Galli 85. Codex sangallensis 615, St. Gallen. Saeculi XI:206. 2. Jung P. Zur Geschichte der Sectio in morma in der Schweiz. Schweiz Med Wochenschr 1941;43:205-10. 6/8/84553
Possible roles of long-chain fatty acids in preterm birth To the Editors: In their article Reece et al. (Reece MS, McGregor JA, Allen KGD, Harris MA. Maternal and perinatal long-chain fatty acids: Possible roles in preterm birth. Am J Obstet Gynecol 1997;176:907-14) demonstrated a different distribution of maternal total arachidonic acid in red blood cells and plasma, red blood cell eicosapentaenoic acid, ~0-3/c0-6 ratio and docosapentaenoic acid in 37 preterms and 34 controls. In the conclusions the authors stated that higher levels of arachidonic and docosopentaneoic acids in maternal blood and trophoblast tissues are associated with an increased risk of preterm birth. We are in agreement with the physiopathologic mechanism demonstrated in the article and with the items on page 908 that put the basis for a blood screening in a next evaluation of the series. However, statistical analysis seems not to adequately describe the data set; thus it can lead to misunderstanding and reduces the value of the study. In the study design the authors used control groups at
Loiters
Volume 177, Number 4
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 performing 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 maternal 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 approach. 1 A weighted regression for the n u m b e r of measurements 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, x1 the gestational age at the time of blood drawing, x2 the preterm delivery, and (x1 • 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 d e p e n d e n t 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 x2. 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 t o o ("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 Gynecologyand 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. 6/8/84552
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. However, 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 controls 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 meaningful 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 m a n n e r 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 comparisons 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 comparisons. 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
Letters
sterilization failure than are women -->34 years old. A previous analysis determined that young women are also the most likely to express regret after sterilization1; for those women a reversible method of contraception may be more appropriate. The findings prompted comments that the Copper T 380A intrauterine contraceptive device (IUD), like long-acting progestins, may be an acceptable alternative to tubal sterilization for women seeking long-term contraception. The IUD is also a cost-effective contraceptive method. When Trussell et al. 2 examined the economic consequences of using contraceptive methods for 5 years, use of the Copper T IUD saved approximately $14,000, whereas tubal ligation saved approximately $12,000 compared with no contraception. In spite of its proved effectiveness, the IUD is underutilized in the United States, in part because of common misperceptions associated with IUD use. Among these is the erroneous belief that all IUDs cause ectopic pregnancies. In fact, studies have shown the Copper T 380A IUD to have a protective effect against ectopic pregnancies. In contrast, women with poststerilization pregnancy are at a significant increased risk for ectopic pregnancy. Of the 143 pregnancies that occurred after sterilization in the CREST study, 47 (33%) were ectopic. Approximately 33% of the sterilized women in the CREST study population were 18 through 27 years old. With the CREST study reporting a cumulative risk of pregnancy to be highest among this age stratification, accompanied with the knowledge that young women may regret having been sterilized, increased use of a safe and effective IUD for low-cost, long-term reversible contraception is compelling for women in this age group. Ronald T. Burkman, MD Department of Obstetrics and Gynecology, BaystateMedical Center, 259 Chestnut St., Springfield, MA 01199
REFERENCES 1. Wilcox LS, Chu S¥, Beaker ED, Zeger SL, Peterson HB. Risk factors for regret after tubal sterilization: 5 year follow-up in a prospective study. Fertil Steril 1991;33:927-33. 2. TrussellJ, Leveque JA, KoenigJD, et al. The economic value of contraception: A comparison of 15 methods. Am J Public Health 1995;85:494-503. 6/8/84734
Response declined
Abbot Purchart I (928-971) of St. Gallen--Born by postmortem cesarean section To the Editors: The postmortem cesarean section (synonyms: sectio in mortua, sectio post mortem matris) today represents a rare, mostly unpleasant occurrence in obstetrics. This procedure is indicated if fetal heartbeats are provable in the third trimester of pregnancy in a woman without signs of life.
October 1997 AmJ Obstet Gynecol
In the region of eastern Switzerland lived abbot Putchart I (928-971), famous for his commitment to fortification and urbanization of the contemporary city of St. Gallen. He had the peculiarity of being born by postmortem cesarean section because his mother, Wendilgarth, died 14 days before term. The fetus was cut out of the dead mother and wrapped in the fat of freshly slaughtered pigs. The child survived and was given by his father Ulrich to the Benedictine monastery in St. Gallen, where the monks called him "Ingenitus." In his enclosed history of that monastery Ekkehart IV wrote "At tempore labente appropinquans partui, preghans periclitatur et ante quatuordecim temporivi partus dies emoritur. Infans excisus et arvinae porci recens erute, ubi incutesceret, involutus, bone indolis cure in brevi apparuisset, baptizatur et Purchardus nominatur. ''1 Probably this historic source is the first verified description of a postmortem cesarean section in Switzerland. 2 This case report reflects an example of the early medieval medicine written down in monastic writings, which played an important role in the formation of the first universities in Europe in the following centuries. Kat~in Rothenberger, MD Depa'rCment of Obstetrics and Gynecology, Kantonsspital CH-9007 St. Gallen, Switzerland JanJanzen, MD Institute of Pathology, Ueberlingen, Lake Constance, Germany
REFERENCES 1. Ekkehart IV. Casus monasterii sancti Galli 85. Codex sangallensis 615, St. Gallen. Saeculi XI:206. 2. Jung P. Zur Geschichte der Sectio in morma in der Schweiz. Schweiz Med Wochenschr 1941;43:205-10. 6/8/84553
Possible roles of long-chain fatty acids in preterm birth To the Editors: In their article Reece et al. (Reece MS, McGregor JA, Allen KGD, Harris MA. Maternal and perinatal long-chain fatty acids: Possible roles in preterm birth. Am J Obstet Gynecol 1997;176:907-14) demonstrated a different distribution of maternal total arachidonic acid in red blood cells and plasma, red blood cell eicosapentaenoic acid, ~0-3/c0-6 ratio and docosapentaenoic acid in 37 preterms and 34 controls. In the conclusions the authors stated that higher levels of arachidonic and docosopentaneoic acids in maternal blood and trophoblast tissues are associated with an increased risk of preterm birth. We are in agreement with the physiopathologic mechanism demonstrated in the article and with the items on page 908 that put the basis for a blood screening in a next evaluation of the series. However, statistical analysis seems not to adequately describe the data set; thus it can lead to misunderstanding and reduces the value of the study. In the study design the authors used control groups at
Loiters
Volume 177, Number 4
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 performing 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 maternal 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 approach. 1 A weighted regression for the n u m b e r of measurements 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, x1 the gestational age at the time of blood drawing, x2 the preterm delivery, and (x1 • 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 d e p e n d e n t 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 x2. 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 t o o ("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 Gynecologyand 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. 6/8/84552
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. However, 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 controls 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 meaningful 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 m a n n e r 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 comparisons 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 comparisons. 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