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Intrauterine growth retardation and preterm delivery
Intrauterine growth retardation and preterm delivery William J. Ott, MD St. Louis, Missouri OBJECTIVE: A retrospective study was undertaken to determine if premature infants had a higher incidence of intrauterine growth retardation than term infants did. If premature labor is significantly associated with intrauterine growth retardation, then defining intrauterine growth retardation with a population-specific postnatal birth weight for gestational age curve would underestimate the incidence in preterm infants. STUDY DESIGN: Data for the year 1990 were used to construct a postnatal birth weight for gestational-age curve. This curve was then used to analyze 1991 birth weight data and to determine the incidence of intrauterine growth retardation « 1oth percentile) at each week of gestation. Infants were also classified as having intrauterine growth retardation on the basis of an additional postnatal birth weight for gestational-age curve and two antenatal ultrasonic estimated fetal-weight-for-gestational-age curves. RESULTS: Analysis of the 1991 delivery data indicated that both ultrasonography curves showed a significant decrease in the incidence of intrauterine growth retardation with advancing gestational age, whereas the postnatal curves did not. CONCLUSION: The results give full support to previous reports that suggest intrauterine growth retardation is more common in preterm than in term infants and are consistent with the hypothesis that intrauterine growth retardation is significantly related to premature birth. (AM J OBSTET GVNECOL 1993;168:1710-7.)
Key words: Intrauterine growth retardation, ultrasonography, prematurity
Intrauterine growth retardation (IUGR) is a significant contributor to perinatal morbidity and mortality. 1-4 But the diagnosis and management of suspected IUGR is hampered by the heterogeneous nature of the problem and by the imprecise methods for diagnosing IUGR in the neonate. In a recent review of the subject the author pointed out that different investigators used different methods for diagnosis; this, in turn, can adversely affect the ability to diagnose IUGR in the antenatal period. I The most common method of diagnosing IUGR in the neonatal period is comparing the infant's birth weight for gestational age at birth with a standard nomogram. I -5 Because birth-weight-for-gestational-age nomograms vary from region to region and from population to population, the use of anyone particular nomogram, when applied to a different population or region, may lead to an overdiagnosis or underdiagnosis of IUGR in the study population. This has led many From the Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, St. John's Mercy Medical Center. Presented at the Sixtieth Annual Meeting of The Central Association of Obstetricians and Gynecologists, Chicago, Illinois, October 15-17, 1992. Reprint requests: William J. Ott, MD, Department of Obstetrics and Gynecology, St. John's Mercy Medical Center, 615 S. New Ballas Road, St. Louis, MO 63141-8277. Copyright © 1993 by Mosby-Year Book, 1nc. 0002-9378/93 $1.00 + .20 6/6/45991
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investigators to advocate the used of growth curves developed specifically for each region or population. 6 - lo But even this approach will not compensate for an important underlying problem in the use of postnatal birth-weight-for-gestational-age curves to diagnose IUGR. Because preterm birth (delivery at < 37 completed weeks of gestation) is considered a pathologic occurrence, some investigators have suggested that birth weight curves before 37 weeks may be in error, postulating that fetuses born prematurely may weigh less than their undelivered cohorts. I. 11-15 In other words, preterm infants may have a significantly higher incidence of IUGR that infants born at term. My experience with the use of ultrasonography-generated estimated-fetal-weight-for-gestational-age curves for the diagnosis of IUGR also supports this view. I To further study the possibility that pre term infants may have a higher incidence of IUGR than term infants, a study was designed to evaluate the rate ofIUGR in infants born before 37 completed weeks of gestation and to compare it with the rate of IUGR at term.
Material and methods Computerized discharge data from all live-born in~ fants delivered at St. John's Mercy Medical Center for 1990 and 1991 were used for analysis. The hospital primarily serves a middle- and upper-class patient pop-
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ulation. More than 80% of the patients are private, with a 10% to 15% clinic population and a 1% to 2% high-risk referral population. The hypothesis to be tested was as follows: if preterm labor is significantly associated with IUCR, then defining the presence or absence of IUCR with a populationspecific postnatal birth-weight-for-gestational-age curve (1) would underestimate the incidence of IUCR in infants born before 37 completed weeks of gestation, because infants born prematurely would have a biased overrepresentation of infants with IUCR, and (2) would overestimate the incidence of IUCR in term infants, because true IUCR would be underrepresented in this group. Data from the computerized discharge summaries for 1990 were used to construct a postnatal birth-weightfor-gestational-age curve for that patient population. The "best estimate" of gestational age at delivery was used. Because approximately 70% of the patients delivered at our institution have early ultrasonographic examinations, ultrasonographic dating would have been used for these patients. In the remainder gestational age by last menstrual period would have been used. This curve was then used to analyze the 1991 birth weight data and to determine the incidence of IUCR at each week of gestation, defined as an infant < 10th percentile of birth weight for gestational age. In addition, infants born in 1991 were also classified as having IUCR on the basis of the 10th percentile values of three other curves, one additional postnatal birth-weight-for-gestational-age curve and two antenatal ultrasonography-estimated-fetal-weight-for-gestational-age curves. Postnatal birth weight for gestational age. The postnatal birth-weight-for-gestational-age curve derived from our own delivery data for 1990 and the Brenner birth weight curve derived from a large number of deliveries at the University Hospitals of Cleveland, Ohio, was used. I6 This curve is commonly used by clinicians and investigators to define IUCR. Antenatal ultrasonographic estimated fetal weight curves. Patients who had fetal weight estimations performed at St. John's Mercy Medical Center Perinatal Laboratory and delivered of live-born, singleton infants at St. John's Mercy Medical Center after 37 completed weeks of gestation from 1987 through 1990 were used to construct an antenatal estimated-fetal-weight-forgestational-age curve. Each fetus was scanned twice during the pregnancy, and computerized discharge data were evaluated to exclude patients with medical or obstetric complications. Fetal weight was estimated by means of a previously developed formula that uses multiple ultrasonographic parameters. I Tenth percentile values calculated from these patients were used to_ define IUCR. The 10th percentile values of the recently
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Table I. Live births: St. John's Mercy Medical Center, 1990 90th percentile
No.
3 4 9 9 7 8 8 10 6 11 15 22 25 26 66 82 154 379 922 1580 1782 576 51 1 1
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44
252 308 371 442 522 611 709 817 934 1061 1198 1345 1501 1668 1844 2029 2223 2426 2637 2857 3083 3317 3557
316 387 468 559 661 773 896 1031 1175 1330 1496 1671 1854 2047 2247 2454 2667 2885 3108 3334 3563 3792 4023
349 444 555 681 823 981 1154 1342 1542 1753 1974 2202 2435 2670 2906 3140 3369 3591 3803 4005 4193 4366 4524
developed fetal growth curve of Hadlock et al. 8 were also used. The percentage of infants at each gestational age below the 10th percentile value of each curve was calculated from the 1991 data. In addition, infants were divided into two larger groups: those who were delivered before 37 weeks (preterm) and those who were delivered after 37 weeks (term). The number of infants classified as IUCR by each of the four curves was then determined for the preterm and term groups. A statistical program with linear regression analysis, with and without logarithmic transformation, was used to evaluate trends over gestational age for each of the four curves; X2 analysis was 'Jsed to determine if preterm infants had a higher incidence of IVCR when compared with term infants for each of the curves. I7 A value of p < 0.01 was considered significant in all tests. Results
There were 5757 live-born infants discharged from St. John's Mercy Medical Center during 1990. Table I lists the postnatal birth weight percentile data for these patients, and Fig. 1 shows the mathematically smoothed 10th, 50th, and 90th percentile values at each gestational age. A total of 1583 patients were entered into the antenatal ultrasonographically estimated-fetalweight-for-gestational-age curve, generating 3166 data points for analysis. Table II shows the fetal weight
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June 1993 Am J Obstet Gynecol
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percentile data from these patients. The 10th and 90th percentile values of the fetal weight curve were very similar to those of the Hadlock curve (Fig. 2). Fig. 3 compares the 10th percentile cutoffs from the four weight-for-gestational-age curves used during the study to diagnose IUCR. During 1991 5908 live-born infants were discharged from St. John's Mercy Medical Center. The percentage of infants diagnosed as having IUCR by each weight curve is listed in Table III and illustrated in Fig. 4.
Table IV shows the results of the linear regression on the percent of infants with IUCR at each gestational age for the four curves. Both ultrasonographic curves showed a significant decrease in the incidence of IUCR with advancing gestational age, whereas the postnatal St. John's Mercy Medical Center 1990 and Brenner curves did not. Logarithmic transformation of the data gave similar results. Table V shows the percentage of infants, classified as having IUCR by each of the curves, that were delivered
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Fig. 3. A comparison of 10th percentile values used for diagnosis of IUCR in study. Closed square, Hadlock antenatal ultrasonography; open square, St. John's Mercy Medical Center postnatal birth weight; closed triangle, Ott antenatal ultrasonography; open hourglass, Brenner postnatal birth weight; GA, gestational age.
Table III. Percentage of infants diagnosed with IUGR by birth weight
Table II. Normal fetal growth curve: Ultrasonographically estimated fetal weight
86 82 115 121 125 138 157 123 132 107 119 94 127 110 118 106 172 163 176 150 146 130 1I5 97 76 58 23
Weight curves
90th percentile
No.
14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
74 101 133 173 219 274 336 407 486 574 670 775 888 1009 1137 1272 1413 1560 171I 1866 2024 2185 2346 2508 2670 2830 2988
89 119 155 198 248 307 374 450 536 631 736 852 977 1112 1258 1413 1577 1751 1933 2124 2322 2527 2739 2957 3180 3407 3638
104 138 179 227 285 351 427 513 609 717 836 966 1108 1262 1428 1605 1793 1993 2203 2424 2655 2895 3144 3401 3666 3938 4216
before 37 completed weeks (preterm) or after 37 weeks (term). As listed in Table V, both ultrasonographic curves showed a significant increase in the incidence of IUGR in preterm infants « 37 weeks) compared with
Gestational age (wk)
31 32 33 34 35 36 37 38 39 40
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14.3 11.1 2.9 4.3 7.0 6.3 3.4 2.3 2.3 1.8
term infants. The Brenner curve also showed a significant difference but not as strongly as the ultrasonographic curves. The St. John's Mercy Medical Center 1990 birth weight curve did not show a significant difference. Comment
Results of the current study give full support to previous reports that suggest IUGR is more common in preterm than in term infants. 1.9. II. 13. 14 Ultrasonographically generated antenatal fetal weight curves showed a significantly higher incidence of IUGR in preterm infants than did a standard postnatal birth-weight-forgestational curve (Brenner I6 ). And, as hypothesized, a population-specific postnatal birth-weight-for-gesta-
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Fig. 4. Percent of infants diagnosed as IUGR by four weight curves discharged from St. John's Mercy Medical Center during 1991. Closed square, Hadlock antenatal ultrasonography; plus sign, St. John's Mercy Medical Center postnatal birth weight; open square, Ott antenatal ultrasonography; closed triangle, Brenner postnatal birth weight; GA, gestational age.
Table IV. Regression analysis: trend in incidence of IUCR Weight curve
Hadlock St. John's Mercy Medical Center, 1990 Ott Brenner
Table V. Preterm delivery and IUGR
Slope
R2
Significance
- 1.7079 - 0.4227
0.7917 0.0187
P = 0.0003 P = 0.3036
- 3.3503 - 0.5782
0.8793 0.1051
P = 0.0001 P = 0.1744
(NS)
(NS)
NS, Not significant.
tional-age curve (St. John's Mercy Medical Center 1990) showed no significant difference in the incidence of IUCR between preterm or term deliveries. These findings are all consistent with the basic hypothesis that IUGR is significantly related to preterm birth and that population-specific postnatal birth-weight-for-gestational-age curves will underestimate its incidence. One possible bias in the study is the estimation of gestational age. As has been mentioned by Hadlock et al. B and others,9. 14 one of the most important sources of error in birth-weight curves is the assignment of gestational age. The method of estimating gestational age at St. John's Mercy Medical Center in both the antenatal ultrasonic curve and the postnatal birth weight curve was similar to the method used in the Hadlock curve and therefore should not be a significant bias. Gestational age in the Brenner curve, however, was based entirely on last menstrual data, and this may be a significant bias.
Weight curve
% IUGR <37 wk
% IUGR >37 wk
K
7.9 6.3
1.5 4.0
79.14 4.691
23.1 6.3
8.3 2.1
Hadlock St. John's Mercy Medical Center, 1990 Ott Brenner
111.3 27.46
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P<
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P< P<
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NS, Not significant.
In spite of improved understanding of the pathophysiologic mechanisms involved in preterm labor and development of a variety of drugs to combat preterm uterine contractions, there appears to be little, if any, reduction in the overall incidence of preterm deliveries in the United States. IS Intrauterine infection, fetal congenital anomalies, and other problems appear to be significantly related to preterm birth. The current study confirms the findings of other investigators that IUGR is also associated with preterm delivery. This is consistent with the findings of Salafia et al.,'9. 20 who have shown a high rate of placental and decidual vascular abnormalities in pre term births. These findings suggest a possible interrelated cause for IUCR and pre term delivery. REFERENCES
1. Ott WJ. The diagnosis of altered fetal growth. Obstet Gynecol Clin North Am 1988;15:237-63.
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2, Villar J. deOnis M. Kestler E. et aJ. The differential neonatal morbidity of the intrauterine growth retardation syndrome, AMJ OBSTET GYNECOL 1990;163:151-7. 3. Meyers SA. Ferguson R. A population study of the relationship between fetal death and altered fetal growth. Obstet Gynecol 1989;74:325-31. 4. Fretts RC. Boyd ME. Usher RH. et al. The changing pattern of fetal death. 1961-1988. Obstet Gynecol 1992; 79:35-9. 5. Goldenberg AL. Cutter GR. Hoffman HJ. et al. Intrauterine growth retardation: standards for diagnosis. AM J OBSTET GYNECOL 1989;161:271-7. 6. Sloan GC Lorenz RP. Importance of locally derived birth weight nomograms. J Reprod Med 1991;36:598-602. 7. Secher NJ. Hansen PK. Lenstrup C. et al. Birth weight for gestational age charts based on early ultrasound estimation of gestational age. Br J Obstet Gynaecol 1986;93: 12834. 8. Hadlock FP. Harrist RB. Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991; 181: 129-33. 9. Goldenberg RL. Nelson KG. Koski JF. et al. Low birth weight. intrauterine growth retardation. and preterm delivery. AM J OBSTET GYNECOL 1985; 152:980-4. 10. Forbes FJ. Smalls MJ. A comparative analysis of birth weight for gestational age standards. Br J Obstet Gynaecol 1983;99:297-303. 11. Secher NJ. Hansen PK. Thomsen BL. et al. Growth retardation in preterm infants. Br J Obstet Gynaecol 1987;94: 115-20. 12. Weiner CPo Sabbagha RE. Vaisrub N. et al. A hypothetical model suggesting suboptimal intrauterine growth in infants delivered preterm. Obstet Gynecol 1985;65:323-6. 13. Tamura RK. Sabbagha RE. Depp R. et al. Diminished growth in fetuses born preterm after spontaneous labor or rupture of membranes. AM J OBSTET GYNECOL 1984;148: 1105-10. 14. Naeye RL. DixonJB. Distortions in fetal growth standards. Pediatr Res 1978;12:987-91. 15. Dudley NJ. Lamb MP. Hatfield JA. et al. Estimated fetal weight in the detection of the small for menstrual age fetus. J Clin Ultrasound 1990;18:387-93. 16. Brenner WE. Edelman DA. Hendricks CH. A standard of fetal growth for the United States of America. A,,,, J OBSTET GYNECOL 1976;126:555-64. 17. Statistx (version 3.5). St. Paul. Minnesota: Analytical Software. 1990. 18. Leveno KJ. Little BB. Cunningham FG. The national impact of ritodrine hydrochloride for inhibition of preterm labor. Obstet Gynecol 1990;76:12-5. 19. Salafia CM. Vintzileos AM. Bantham KF. et al. Placental pathologic findings in preterm birth. AM J OSSTET GVNECOL 1991 ;165:934-8. 20. Salafia CM. Vogen CA, Bantham KF, et al. Preterm delivery: correlation of fetal growth and placental pathology. Am J Perinatol 1992;9: 190-3.
Discussion DR. RALPH K. TAMURA, Chicago. Illinois. This study was designed by Dr. Ott to study the possibility that pre term infants may have a higher incidence of IUGR than term infants. Specifically, he hypothesized that if preterm labor is significantly associated with IUGR. then defining the presence or absence of IUGR with a population-specific postnatal birth-weight-for-gestational-age curve would (1) underestimate the incidence of rUGR in infants born before 37 completed weeks of gestation, because infants born prematurely would have a biased overrepresentation of IUGR and (2) overestimate the incidence of IUGR in term infants, because
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true IUGR would be underrepresented in these infants. The following are queries and comments regarding Dr. Ott's manuscript: I. Because the accurate assessment of gestational age is crucial to this study, how did the postnatal (pediatric) estimation of gestational age compare with the ultrasonographic estimations? Furthermore, because as many as 30% of the pregnancies were dated by menstrual history, what was the mean error in gestational age determinations? 2. What was the purpose of using both two antenatal (ultrasonographic) and two postnatal (birth weight) curves? 3. For infants delivered pre term, what were the clinical problems that necessitated a perterm delivery? rt is possible that maternal indications rather than fetal ones prompted delivery? In these cases, rUGR would not be expected (for example, severe preeclampsia without chronic hypertension). 4. Other investigations have demonstrated that a greater proportion of preterm infants (as compared with those delivered at term) are growth diminished rather than growth retarded. Perhaps Dr. Ott ought to analyze his data looking for diminished or suboptimal growth. 5. The data presented appear to convincingly show that if preterm labor is significantly associated with rUGR, then determination of the incidence of IUGR by population-specific postnatal birthweight-for-gestational-age curves would underestimate rUGR in infants born before 37 completed weeks of gestation. On the other hand, it is not clear to this reviewer how the data presented would support or refute the second half of the hypothesis, namely, that population-specific postnatal birth-weight-for-gestational-age curves would overestimate the incidence of IUGR in term infants. 6. Why did the postnatal birth weight curves fail to show a significant decrease in incidence of IUGR with advancing age? 7. Finally, what practical and clinically relevant applications are expected from these data? DR. FEDERICO G. MARIONA, Dearborn, Michigan. The author has attempted to demonstrate that the rate of IUGR in preterm infants is higher than that of term infants. This postulate was advanced by Gruenwald' and subsequently by others, including the author. The vagaries of defining fetal growth restriction are evidenced by the number of modalities and the parameters used to diagnose it. Even experienced investigators such as Ott recognize the need and potential benefit to establish local nomograms, maybe to the extent that indigenous curves may be necessary to differentiate patients by ethnic group, maternal age, parity, and even employment characteristics. Will this need represent a clinical nightmare for smaller units with limited populations and resources? Table I in the article shows that 844 of 5757 (15%) babies were born preterm during 1990. In 1991, 5908
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babies were born in his institution; however, we don't know the preterm birth prevalence for this population, only for IUGR between 31 and 40 weeks, 3 weeks past the cutoff date by the author's definition. What was in fact the total number of preterm births by gestational week included in the study? Growth restriction in the second trimester has a different significance than in the third, and I ask the author if he considers this difference in cause a possible significant factor for the validation of the relationship of fetal growth restriction with preterm birth in small groups of babies at specific gestational weeks. Because all patients with medical and obstetric complications were excluded, I'd like to see a tighter description of this population with a prevalence of 15% pre term birth. A recept report by Kempe et al." studied 397 of 16,232 very-Iow-birth-weight (2.4%) infants born in St. Louis in 1985 and 1986. This occurrence was associated with major maternal conditions. However, growth restriction was reported in 3.2%, supporting Ott's premise that a gestational age-birth weight curve will underestimate growth restriction. Indeed, the disparity in the finding of IUGR between the analysis of Kempe et al. and this paper is very important, 8.3% to 23.1% versus 3.2% in spite of patient selection. Are these populations so different? Can the author expand on the formula that uses multiple ultrasonographic parameters for fetal weight determination? Was this a best-fit relation of biometric indices or did it include the fetal ponderal index? Other groups found appropriate distribution of birth weights in a group of preterm babies, again by using a gestational age-birth weight nomogram. The use of both fetal and neonatal ponderal indices against gestational age with further adjustment of the cutoff points may provide further improvement in our ability to diagnose fetal growth restriction. Indeed, linear measurements or ratios that are strongly gestational age-dependent will continue to add to the confusion perhaps more than clarify the clinical picture. The independent use of cerebellar diameter to established gestational age separate from size represents a different approach that removes the notoriously inaccurate date of last menses parameter or a combination of last menstrual period, Dubowitz, and ultrasonic biometry. Can the author comment on this approach? Ott has a long and distinguished series of papers dealing with alterations of fetal growth. Interestingly, among the maternal risk factors for IUGR, preterm birth is not included. Is then then a purely fetal or placental factor? The placental data are soft; however, the fetal theory is, to say the least, provocative. Is the growth-restricted fetus capable of precipitating its own labor to make itself available to procure adequate caloric intake ex utero? This is just one of the magnificent intricacies of fetal development and metabolism, as Norman Kretchmer calls them. If mother and fetus exist in metabolic cooperation, is idiopathic pre term labor nonresponsive to tocolytics the maternal irrevocable answer to an inability to provide nutrients to its offspring?
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Table V of the paper indicates a 23.1 % occurrence of fetal growth restriction before 37 weeks' gestation. This is a fourfold increased risk above estimations previously accepted. Because our ability to detect risk for preterm birth is imperfect, are we to assertively provide an acljusted energy supply to a group of patients at a 1 : 4 chance of having a growth-restricted fetus? This article "highlights the critical importance of recognizing fetal growth restriction in a large number of fetuses and, should this premise hold up as the data base expands, two critical points emerge: (1). the appropriateness of techniques used for the confirmation of suspected IUGR and (2) the validity of using tocolytic agents that otherwise have been demonstrated to have less than optimal effects to avoid pre term birth. Is the author prepared to counsel patients against heroic efforts at stopping idiopathic preterm labor? Are the fetal growth evaluation techniques currently carried out accurate enough to risk such behavior? Ott's experience may provide us sorely needed answers. REFERENCES 1. Gruenwald P. Growth of the human fetus: normal growth and its variation. AM] OBSTET GYNECOL 1966;94:1112. 2. Kempe A, Wise PH, Barkan SE, et al. N Engl ] Med
1992;327:969-73.
DR. ROBERT CARPENTER, Houston, Texas. Most ultrasonographic studies that have been performed show, at most, 50% to 65% of validity for determination ofIUGR with multiple parameters. Campbell has shown that, as have Hadlock, Deter, and multiple others. First, ponderal index was mentioned by Mariona. Was neonatal assessment of ponderal index and fat thickness performed, because the studies of Hill and others from Baylor have shown that some standard measurements, i.e., weight, will substantially underestimate IUGR. Are you suggesting that perhaps the ultrasonographic estimates detected in your population may, in fact, be like Mariona's population? I suspect fat thickness estimates on the fetus were not made. When were the upper limits of the ultrasonographic estimate compared with delivery, 48 hours or 72 hours? What was time limit from scan to delivery? Last, Deter-Rossavik has individual fetal growth assessment curves and multiple mathematic models that are difficult to understand, but there are computer programs that estimate the figures. Have you performed any modeling in your population of patients with IUGR, where two or more scans may exist between 16 and 26 weeks' gestation, to determine whether, in fact, the fetus was growing along its own individual curve? The issue of heterogeneity was mentioned, and it is absolutely true that a substantial proportion of fetuses who were said to be "growth retarded" are, in fact, not growth retarded but are at their own individual lower limits because of intrinsic genetic programming. DR. CHIN-CHU LIN, Chicago, Illinois. The previous literature and our own experience indicates that the incidence of IUGR is higher among infants of delivered
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preterm, because preterm births and IVGR (share) many high-risk factors, such as hypertension, multiple gestation, cigarette smoking, etc. Two years ago I presented an article to the association comparing symmetric and asymmetric IVGR; among our symmetric IVGR group the incidence of preterm deliveries is higher. So my question is, among your preterm group with IVGR would you see a higher incidence of symmetric IVGR compared with those term infants with IVGR? You may not have that data; but from your experience, will you see that as a clinical evidence? DR. OTT (Closing), Dr. Tamura asked why two curves were used, two antenatal and two postnataL We did that to try to get a better feel as to whether there were differences between antenatal and ultrasonic curves, I felt that using only one curve would not be adequate. I would agree with Dr. Tamura that our study did not prove the hypothesis that IVGR at term is overestimated and that greater numbers may be needed to prove that. Dr. Tamura asked what is the clinical significance of this study. I believe that the study reinforces the importance of careful evaluation of the patient in pre term labor to rule out IVGR as a cause of preterm labor. This is especially true in those patients recalcitrant to intravenous tocolytic therapy. A number of questions were asked about the differences in clinical circumstances in preterm versus term labor, clinical factors related to preterm delivery and rVGR, symmetric and asymmetric IVGR, etc. Because this study was designed only to evaluate fetal weight,
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these other parameters were not evaluated. I agree that additional studies are needed to provide further information, because our current understanding and evaluation of rVGR is deficient. Because there is significant confusion and disagreement as how to define rVGR, it is understandable that many of the studies similar to this current study have deficiencies. There was some mention of the genetic potential of each fetus and the use of projected weight (similar to the studies of Deter et aL at Baylor Vniversity) to define IVGR. Although this method of defining and evaluating rVGR shows promise, it was not evaluated in the current study. r refer you to some of our previous work in this area. 1-3 Although there are significant deficiencies in the study and by itself does not prove the relationship between rVGR and premature labor, it does give additional support to the theory. When coupled with other studies, such as umbilical artery Doppler waveform analysis, fetal fat analysis, fetal ultrasonic indices, or other studies, it will give us a better understanding of IVGR and a greater ability to diagnose it and manage it. REFERENCES 1. Ott WJ. The diagnosis of altered fetal growth. Obstet Gynecol Clin North Am 1988;15:237. 2. Ott WJ. Defining altered fetal growth. Obstet Gynecol 1990;75:1053. 3. Ott WJ. The value of fetal umbilical artery and carotid Doppler flow studies in the evaluation of suspected intrauterine growth retardation. J Mat Fetal Invest 1991; 1: 18590.
Key words: Intrauterine growth retardation, ultrasonography, prematurity
Intrauterine growth retardation (IUGR) is a significant contributor to perinatal morbidity and mortality. 1-4 But the diagnosis and management of suspected IUGR is hampered by the heterogeneous nature of the problem and by the imprecise methods for diagnosing IUGR in the neonate. In a recent review of the subject the author pointed out that different investigators used different methods for diagnosis; this, in turn, can adversely affect the ability to diagnose IUGR in the antenatal period. I The most common method of diagnosing IUGR in the neonatal period is comparing the infant's birth weight for gestational age at birth with a standard nomogram. I -5 Because birth-weight-for-gestational-age nomograms vary from region to region and from population to population, the use of anyone particular nomogram, when applied to a different population or region, may lead to an overdiagnosis or underdiagnosis of IUGR in the study population. This has led many From the Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, St. John's Mercy Medical Center. Presented at the Sixtieth Annual Meeting of The Central Association of Obstetricians and Gynecologists, Chicago, Illinois, October 15-17, 1992. Reprint requests: William J. Ott, MD, Department of Obstetrics and Gynecology, St. John's Mercy Medical Center, 615 S. New Ballas Road, St. Louis, MO 63141-8277. Copyright © 1993 by Mosby-Year Book, 1nc. 0002-9378/93 $1.00 + .20 6/6/45991
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investigators to advocate the used of growth curves developed specifically for each region or population. 6 - lo But even this approach will not compensate for an important underlying problem in the use of postnatal birth-weight-for-gestational-age curves to diagnose IUGR. Because preterm birth (delivery at < 37 completed weeks of gestation) is considered a pathologic occurrence, some investigators have suggested that birth weight curves before 37 weeks may be in error, postulating that fetuses born prematurely may weigh less than their undelivered cohorts. I. 11-15 In other words, preterm infants may have a significantly higher incidence of IUGR that infants born at term. My experience with the use of ultrasonography-generated estimated-fetal-weight-for-gestational-age curves for the diagnosis of IUGR also supports this view. I To further study the possibility that pre term infants may have a higher incidence of IUGR than term infants, a study was designed to evaluate the rate ofIUGR in infants born before 37 completed weeks of gestation and to compare it with the rate of IUGR at term.
Material and methods Computerized discharge data from all live-born in~ fants delivered at St. John's Mercy Medical Center for 1990 and 1991 were used for analysis. The hospital primarily serves a middle- and upper-class patient pop-
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Volume 168, Number 6, Part I Am J Obstet Gynecol
ulation. More than 80% of the patients are private, with a 10% to 15% clinic population and a 1% to 2% high-risk referral population. The hypothesis to be tested was as follows: if preterm labor is significantly associated with IUCR, then defining the presence or absence of IUCR with a populationspecific postnatal birth-weight-for-gestational-age curve (1) would underestimate the incidence of IUCR in infants born before 37 completed weeks of gestation, because infants born prematurely would have a biased overrepresentation of infants with IUCR, and (2) would overestimate the incidence of IUCR in term infants, because true IUCR would be underrepresented in this group. Data from the computerized discharge summaries for 1990 were used to construct a postnatal birth-weightfor-gestational-age curve for that patient population. The "best estimate" of gestational age at delivery was used. Because approximately 70% of the patients delivered at our institution have early ultrasonographic examinations, ultrasonographic dating would have been used for these patients. In the remainder gestational age by last menstrual period would have been used. This curve was then used to analyze the 1991 birth weight data and to determine the incidence of IUCR at each week of gestation, defined as an infant < 10th percentile of birth weight for gestational age. In addition, infants born in 1991 were also classified as having IUCR on the basis of the 10th percentile values of three other curves, one additional postnatal birth-weight-for-gestational-age curve and two antenatal ultrasonography-estimated-fetal-weight-for-gestational-age curves. Postnatal birth weight for gestational age. The postnatal birth-weight-for-gestational-age curve derived from our own delivery data for 1990 and the Brenner birth weight curve derived from a large number of deliveries at the University Hospitals of Cleveland, Ohio, was used. I6 This curve is commonly used by clinicians and investigators to define IUCR. Antenatal ultrasonographic estimated fetal weight curves. Patients who had fetal weight estimations performed at St. John's Mercy Medical Center Perinatal Laboratory and delivered of live-born, singleton infants at St. John's Mercy Medical Center after 37 completed weeks of gestation from 1987 through 1990 were used to construct an antenatal estimated-fetal-weight-forgestational-age curve. Each fetus was scanned twice during the pregnancy, and computerized discharge data were evaluated to exclude patients with medical or obstetric complications. Fetal weight was estimated by means of a previously developed formula that uses multiple ultrasonographic parameters. I Tenth percentile values calculated from these patients were used to_ define IUCR. The 10th percentile values of the recently
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Table I. Live births: St. John's Mercy Medical Center, 1990 90th percentile
No.
3 4 9 9 7 8 8 10 6 11 15 22 25 26 66 82 154 379 922 1580 1782 576 51 1 1
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44
252 308 371 442 522 611 709 817 934 1061 1198 1345 1501 1668 1844 2029 2223 2426 2637 2857 3083 3317 3557
316 387 468 559 661 773 896 1031 1175 1330 1496 1671 1854 2047 2247 2454 2667 2885 3108 3334 3563 3792 4023
349 444 555 681 823 981 1154 1342 1542 1753 1974 2202 2435 2670 2906 3140 3369 3591 3803 4005 4193 4366 4524
developed fetal growth curve of Hadlock et al. 8 were also used. The percentage of infants at each gestational age below the 10th percentile value of each curve was calculated from the 1991 data. In addition, infants were divided into two larger groups: those who were delivered before 37 weeks (preterm) and those who were delivered after 37 weeks (term). The number of infants classified as IUCR by each of the four curves was then determined for the preterm and term groups. A statistical program with linear regression analysis, with and without logarithmic transformation, was used to evaluate trends over gestational age for each of the four curves; X2 analysis was 'Jsed to determine if preterm infants had a higher incidence of IVCR when compared with term infants for each of the curves. I7 A value of p < 0.01 was considered significant in all tests. Results
There were 5757 live-born infants discharged from St. John's Mercy Medical Center during 1990. Table I lists the postnatal birth weight percentile data for these patients, and Fig. 1 shows the mathematically smoothed 10th, 50th, and 90th percentile values at each gestational age. A total of 1583 patients were entered into the antenatal ultrasonographically estimated-fetalweight-for-gestational-age curve, generating 3166 data points for analysis. Table II shows the fetal weight
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June 1993 Am J Obstet Gynecol
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percentile data from these patients. The 10th and 90th percentile values of the fetal weight curve were very similar to those of the Hadlock curve (Fig. 2). Fig. 3 compares the 10th percentile cutoffs from the four weight-for-gestational-age curves used during the study to diagnose IUCR. During 1991 5908 live-born infants were discharged from St. John's Mercy Medical Center. The percentage of infants diagnosed as having IUCR by each weight curve is listed in Table III and illustrated in Fig. 4.
Table IV shows the results of the linear regression on the percent of infants with IUCR at each gestational age for the four curves. Both ultrasonographic curves showed a significant decrease in the incidence of IUCR with advancing gestational age, whereas the postnatal St. John's Mercy Medical Center 1990 and Brenner curves did not. Logarithmic transformation of the data gave similar results. Table V shows the percentage of infants, classified as having IUCR by each of the curves, that were delivered
Volume 168, Number 6, Part 1 Am J Obstet Gynecol
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Fig. 3. A comparison of 10th percentile values used for diagnosis of IUCR in study. Closed square, Hadlock antenatal ultrasonography; open square, St. John's Mercy Medical Center postnatal birth weight; closed triangle, Ott antenatal ultrasonography; open hourglass, Brenner postnatal birth weight; GA, gestational age.
Table III. Percentage of infants diagnosed with IUGR by birth weight
Table II. Normal fetal growth curve: Ultrasonographically estimated fetal weight
86 82 115 121 125 138 157 123 132 107 119 94 127 110 118 106 172 163 176 150 146 130 1I5 97 76 58 23
Weight curves
90th percentile
No.
14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
74 101 133 173 219 274 336 407 486 574 670 775 888 1009 1137 1272 1413 1560 171I 1866 2024 2185 2346 2508 2670 2830 2988
89 119 155 198 248 307 374 450 536 631 736 852 977 1112 1258 1413 1577 1751 1933 2124 2322 2527 2739 2957 3180 3407 3638
104 138 179 227 285 351 427 513 609 717 836 966 1108 1262 1428 1605 1793 1993 2203 2424 2655 2895 3144 3401 3666 3938 4216
before 37 completed weeks (preterm) or after 37 weeks (term). As listed in Table V, both ultrasonographic curves showed a significant increase in the incidence of IUGR in preterm infants « 37 weeks) compared with
Gestational age (wk)
31 32 33 34 35 36 37 38 39 40
Hadlock
14.3 11.1 17.6 8.5 7.0 6.3 3.1 l.l
1.5 1.5
St.John's Mercy Medical Center
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Brenner
14.3 11.1 5.9 4.3 7.0 5.8 3.4 1.9 2.7 6.2
33.3 27.8 26.5 23.4 11.6 14.7 8.0 4.3 4.4 7.2
14.3 11.1 2.9 4.3 7.0 6.3 3.4 2.3 2.3 1.8
term infants. The Brenner curve also showed a significant difference but not as strongly as the ultrasonographic curves. The St. John's Mercy Medical Center 1990 birth weight curve did not show a significant difference. Comment
Results of the current study give full support to previous reports that suggest IUGR is more common in preterm than in term infants. 1.9. II. 13. 14 Ultrasonographically generated antenatal fetal weight curves showed a significantly higher incidence of IUGR in preterm infants than did a standard postnatal birth-weight-forgestational curve (Brenner I6 ). And, as hypothesized, a population-specific postnatal birth-weight-for-gesta-
1714
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June 1993 Am J Obstet Gynecol
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Fig. 4. Percent of infants diagnosed as IUGR by four weight curves discharged from St. John's Mercy Medical Center during 1991. Closed square, Hadlock antenatal ultrasonography; plus sign, St. John's Mercy Medical Center postnatal birth weight; open square, Ott antenatal ultrasonography; closed triangle, Brenner postnatal birth weight; GA, gestational age.
Table IV. Regression analysis: trend in incidence of IUCR Weight curve
Hadlock St. John's Mercy Medical Center, 1990 Ott Brenner
Table V. Preterm delivery and IUGR
Slope
R2
Significance
- 1.7079 - 0.4227
0.7917 0.0187
P = 0.0003 P = 0.3036
- 3.3503 - 0.5782
0.8793 0.1051
P = 0.0001 P = 0.1744
(NS)
(NS)
NS, Not significant.
tional-age curve (St. John's Mercy Medical Center 1990) showed no significant difference in the incidence of IUCR between preterm or term deliveries. These findings are all consistent with the basic hypothesis that IUGR is significantly related to preterm birth and that population-specific postnatal birth-weight-for-gestational-age curves will underestimate its incidence. One possible bias in the study is the estimation of gestational age. As has been mentioned by Hadlock et al. B and others,9. 14 one of the most important sources of error in birth-weight curves is the assignment of gestational age. The method of estimating gestational age at St. John's Mercy Medical Center in both the antenatal ultrasonic curve and the postnatal birth weight curve was similar to the method used in the Hadlock curve and therefore should not be a significant bias. Gestational age in the Brenner curve, however, was based entirely on last menstrual data, and this may be a significant bias.
Weight curve
% IUGR <37 wk
% IUGR >37 wk
K
7.9 6.3
1.5 4.0
79.14 4.691
23.1 6.3
8.3 2.1
Hadlock St. John's Mercy Medical Center, 1990 Ott Brenner
111.3 27.46
Significance
P<
0.00001 NS
P< P<
0.00001 0.0001
NS, Not significant.
In spite of improved understanding of the pathophysiologic mechanisms involved in preterm labor and development of a variety of drugs to combat preterm uterine contractions, there appears to be little, if any, reduction in the overall incidence of preterm deliveries in the United States. IS Intrauterine infection, fetal congenital anomalies, and other problems appear to be significantly related to preterm birth. The current study confirms the findings of other investigators that IUGR is also associated with preterm delivery. This is consistent with the findings of Salafia et al.,'9. 20 who have shown a high rate of placental and decidual vascular abnormalities in pre term births. These findings suggest a possible interrelated cause for IUCR and pre term delivery. REFERENCES
1. Ott WJ. The diagnosis of altered fetal growth. Obstet Gynecol Clin North Am 1988;15:237-63.
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2, Villar J. deOnis M. Kestler E. et aJ. The differential neonatal morbidity of the intrauterine growth retardation syndrome, AMJ OBSTET GYNECOL 1990;163:151-7. 3. Meyers SA. Ferguson R. A population study of the relationship between fetal death and altered fetal growth. Obstet Gynecol 1989;74:325-31. 4. Fretts RC. Boyd ME. Usher RH. et al. The changing pattern of fetal death. 1961-1988. Obstet Gynecol 1992; 79:35-9. 5. Goldenberg AL. Cutter GR. Hoffman HJ. et al. Intrauterine growth retardation: standards for diagnosis. AM J OBSTET GYNECOL 1989;161:271-7. 6. Sloan GC Lorenz RP. Importance of locally derived birth weight nomograms. J Reprod Med 1991;36:598-602. 7. Secher NJ. Hansen PK. Lenstrup C. et al. Birth weight for gestational age charts based on early ultrasound estimation of gestational age. Br J Obstet Gynaecol 1986;93: 12834. 8. Hadlock FP. Harrist RB. Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991; 181: 129-33. 9. Goldenberg RL. Nelson KG. Koski JF. et al. Low birth weight. intrauterine growth retardation. and preterm delivery. AM J OBSTET GYNECOL 1985; 152:980-4. 10. Forbes FJ. Smalls MJ. A comparative analysis of birth weight for gestational age standards. Br J Obstet Gynaecol 1983;99:297-303. 11. Secher NJ. Hansen PK. Thomsen BL. et al. Growth retardation in preterm infants. Br J Obstet Gynaecol 1987;94: 115-20. 12. Weiner CPo Sabbagha RE. Vaisrub N. et al. A hypothetical model suggesting suboptimal intrauterine growth in infants delivered preterm. Obstet Gynecol 1985;65:323-6. 13. Tamura RK. Sabbagha RE. Depp R. et al. Diminished growth in fetuses born preterm after spontaneous labor or rupture of membranes. AM J OBSTET GYNECOL 1984;148: 1105-10. 14. Naeye RL. DixonJB. Distortions in fetal growth standards. Pediatr Res 1978;12:987-91. 15. Dudley NJ. Lamb MP. Hatfield JA. et al. Estimated fetal weight in the detection of the small for menstrual age fetus. J Clin Ultrasound 1990;18:387-93. 16. Brenner WE. Edelman DA. Hendricks CH. A standard of fetal growth for the United States of America. A,,,, J OBSTET GYNECOL 1976;126:555-64. 17. Statistx (version 3.5). St. Paul. Minnesota: Analytical Software. 1990. 18. Leveno KJ. Little BB. Cunningham FG. The national impact of ritodrine hydrochloride for inhibition of preterm labor. Obstet Gynecol 1990;76:12-5. 19. Salafia CM. Vintzileos AM. Bantham KF. et al. Placental pathologic findings in preterm birth. AM J OSSTET GVNECOL 1991 ;165:934-8. 20. Salafia CM. Vogen CA, Bantham KF, et al. Preterm delivery: correlation of fetal growth and placental pathology. Am J Perinatol 1992;9: 190-3.
Discussion DR. RALPH K. TAMURA, Chicago. Illinois. This study was designed by Dr. Ott to study the possibility that pre term infants may have a higher incidence of IUGR than term infants. Specifically, he hypothesized that if preterm labor is significantly associated with IUGR. then defining the presence or absence of IUGR with a population-specific postnatal birth-weight-for-gestational-age curve would (1) underestimate the incidence of rUGR in infants born before 37 completed weeks of gestation, because infants born prematurely would have a biased overrepresentation of IUGR and (2) overestimate the incidence of IUGR in term infants, because
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true IUGR would be underrepresented in these infants. The following are queries and comments regarding Dr. Ott's manuscript: I. Because the accurate assessment of gestational age is crucial to this study, how did the postnatal (pediatric) estimation of gestational age compare with the ultrasonographic estimations? Furthermore, because as many as 30% of the pregnancies were dated by menstrual history, what was the mean error in gestational age determinations? 2. What was the purpose of using both two antenatal (ultrasonographic) and two postnatal (birth weight) curves? 3. For infants delivered pre term, what were the clinical problems that necessitated a perterm delivery? rt is possible that maternal indications rather than fetal ones prompted delivery? In these cases, rUGR would not be expected (for example, severe preeclampsia without chronic hypertension). 4. Other investigations have demonstrated that a greater proportion of preterm infants (as compared with those delivered at term) are growth diminished rather than growth retarded. Perhaps Dr. Ott ought to analyze his data looking for diminished or suboptimal growth. 5. The data presented appear to convincingly show that if preterm labor is significantly associated with rUGR, then determination of the incidence of IUGR by population-specific postnatal birthweight-for-gestational-age curves would underestimate rUGR in infants born before 37 completed weeks of gestation. On the other hand, it is not clear to this reviewer how the data presented would support or refute the second half of the hypothesis, namely, that population-specific postnatal birth-weight-for-gestational-age curves would overestimate the incidence of IUGR in term infants. 6. Why did the postnatal birth weight curves fail to show a significant decrease in incidence of IUGR with advancing age? 7. Finally, what practical and clinically relevant applications are expected from these data? DR. FEDERICO G. MARIONA, Dearborn, Michigan. The author has attempted to demonstrate that the rate of IUGR in preterm infants is higher than that of term infants. This postulate was advanced by Gruenwald' and subsequently by others, including the author. The vagaries of defining fetal growth restriction are evidenced by the number of modalities and the parameters used to diagnose it. Even experienced investigators such as Ott recognize the need and potential benefit to establish local nomograms, maybe to the extent that indigenous curves may be necessary to differentiate patients by ethnic group, maternal age, parity, and even employment characteristics. Will this need represent a clinical nightmare for smaller units with limited populations and resources? Table I in the article shows that 844 of 5757 (15%) babies were born preterm during 1990. In 1991, 5908
1716 Ott
babies were born in his institution; however, we don't know the preterm birth prevalence for this population, only for IUGR between 31 and 40 weeks, 3 weeks past the cutoff date by the author's definition. What was in fact the total number of preterm births by gestational week included in the study? Growth restriction in the second trimester has a different significance than in the third, and I ask the author if he considers this difference in cause a possible significant factor for the validation of the relationship of fetal growth restriction with preterm birth in small groups of babies at specific gestational weeks. Because all patients with medical and obstetric complications were excluded, I'd like to see a tighter description of this population with a prevalence of 15% pre term birth. A recept report by Kempe et al." studied 397 of 16,232 very-Iow-birth-weight (2.4%) infants born in St. Louis in 1985 and 1986. This occurrence was associated with major maternal conditions. However, growth restriction was reported in 3.2%, supporting Ott's premise that a gestational age-birth weight curve will underestimate growth restriction. Indeed, the disparity in the finding of IUGR between the analysis of Kempe et al. and this paper is very important, 8.3% to 23.1% versus 3.2% in spite of patient selection. Are these populations so different? Can the author expand on the formula that uses multiple ultrasonographic parameters for fetal weight determination? Was this a best-fit relation of biometric indices or did it include the fetal ponderal index? Other groups found appropriate distribution of birth weights in a group of preterm babies, again by using a gestational age-birth weight nomogram. The use of both fetal and neonatal ponderal indices against gestational age with further adjustment of the cutoff points may provide further improvement in our ability to diagnose fetal growth restriction. Indeed, linear measurements or ratios that are strongly gestational age-dependent will continue to add to the confusion perhaps more than clarify the clinical picture. The independent use of cerebellar diameter to established gestational age separate from size represents a different approach that removes the notoriously inaccurate date of last menses parameter or a combination of last menstrual period, Dubowitz, and ultrasonic biometry. Can the author comment on this approach? Ott has a long and distinguished series of papers dealing with alterations of fetal growth. Interestingly, among the maternal risk factors for IUGR, preterm birth is not included. Is then then a purely fetal or placental factor? The placental data are soft; however, the fetal theory is, to say the least, provocative. Is the growth-restricted fetus capable of precipitating its own labor to make itself available to procure adequate caloric intake ex utero? This is just one of the magnificent intricacies of fetal development and metabolism, as Norman Kretchmer calls them. If mother and fetus exist in metabolic cooperation, is idiopathic pre term labor nonresponsive to tocolytics the maternal irrevocable answer to an inability to provide nutrients to its offspring?
June 1993 Am J Obstet Gynecol
Table V of the paper indicates a 23.1 % occurrence of fetal growth restriction before 37 weeks' gestation. This is a fourfold increased risk above estimations previously accepted. Because our ability to detect risk for preterm birth is imperfect, are we to assertively provide an acljusted energy supply to a group of patients at a 1 : 4 chance of having a growth-restricted fetus? This article "highlights the critical importance of recognizing fetal growth restriction in a large number of fetuses and, should this premise hold up as the data base expands, two critical points emerge: (1). the appropriateness of techniques used for the confirmation of suspected IUGR and (2) the validity of using tocolytic agents that otherwise have been demonstrated to have less than optimal effects to avoid pre term birth. Is the author prepared to counsel patients against heroic efforts at stopping idiopathic preterm labor? Are the fetal growth evaluation techniques currently carried out accurate enough to risk such behavior? Ott's experience may provide us sorely needed answers. REFERENCES 1. Gruenwald P. Growth of the human fetus: normal growth and its variation. AM] OBSTET GYNECOL 1966;94:1112. 2. Kempe A, Wise PH, Barkan SE, et al. N Engl ] Med
1992;327:969-73.
DR. ROBERT CARPENTER, Houston, Texas. Most ultrasonographic studies that have been performed show, at most, 50% to 65% of validity for determination ofIUGR with multiple parameters. Campbell has shown that, as have Hadlock, Deter, and multiple others. First, ponderal index was mentioned by Mariona. Was neonatal assessment of ponderal index and fat thickness performed, because the studies of Hill and others from Baylor have shown that some standard measurements, i.e., weight, will substantially underestimate IUGR. Are you suggesting that perhaps the ultrasonographic estimates detected in your population may, in fact, be like Mariona's population? I suspect fat thickness estimates on the fetus were not made. When were the upper limits of the ultrasonographic estimate compared with delivery, 48 hours or 72 hours? What was time limit from scan to delivery? Last, Deter-Rossavik has individual fetal growth assessment curves and multiple mathematic models that are difficult to understand, but there are computer programs that estimate the figures. Have you performed any modeling in your population of patients with IUGR, where two or more scans may exist between 16 and 26 weeks' gestation, to determine whether, in fact, the fetus was growing along its own individual curve? The issue of heterogeneity was mentioned, and it is absolutely true that a substantial proportion of fetuses who were said to be "growth retarded" are, in fact, not growth retarded but are at their own individual lower limits because of intrinsic genetic programming. DR. CHIN-CHU LIN, Chicago, Illinois. The previous literature and our own experience indicates that the incidence of IUGR is higher among infants of delivered
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Volume 168, Number 6, Part 1 Am J Obstet Gynecol
preterm, because preterm births and IVGR (share) many high-risk factors, such as hypertension, multiple gestation, cigarette smoking, etc. Two years ago I presented an article to the association comparing symmetric and asymmetric IVGR; among our symmetric IVGR group the incidence of preterm deliveries is higher. So my question is, among your preterm group with IVGR would you see a higher incidence of symmetric IVGR compared with those term infants with IVGR? You may not have that data; but from your experience, will you see that as a clinical evidence? DR. OTT (Closing), Dr. Tamura asked why two curves were used, two antenatal and two postnataL We did that to try to get a better feel as to whether there were differences between antenatal and ultrasonic curves, I felt that using only one curve would not be adequate. I would agree with Dr. Tamura that our study did not prove the hypothesis that IVGR at term is overestimated and that greater numbers may be needed to prove that. Dr. Tamura asked what is the clinical significance of this study. I believe that the study reinforces the importance of careful evaluation of the patient in pre term labor to rule out IVGR as a cause of preterm labor. This is especially true in those patients recalcitrant to intravenous tocolytic therapy. A number of questions were asked about the differences in clinical circumstances in preterm versus term labor, clinical factors related to preterm delivery and rVGR, symmetric and asymmetric IVGR, etc. Because this study was designed only to evaluate fetal weight,
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these other parameters were not evaluated. I agree that additional studies are needed to provide further information, because our current understanding and evaluation of rVGR is deficient. Because there is significant confusion and disagreement as how to define rVGR, it is understandable that many of the studies similar to this current study have deficiencies. There was some mention of the genetic potential of each fetus and the use of projected weight (similar to the studies of Deter et aL at Baylor Vniversity) to define IVGR. Although this method of defining and evaluating rVGR shows promise, it was not evaluated in the current study. r refer you to some of our previous work in this area. 1-3 Although there are significant deficiencies in the study and by itself does not prove the relationship between rVGR and premature labor, it does give additional support to the theory. When coupled with other studies, such as umbilical artery Doppler waveform analysis, fetal fat analysis, fetal ultrasonic indices, or other studies, it will give us a better understanding of IVGR and a greater ability to diagnose it and manage it. REFERENCES 1. Ott WJ. The diagnosis of altered fetal growth. Obstet Gynecol Clin North Am 1988;15:237. 2. Ott WJ. Defining altered fetal growth. Obstet Gynecol 1990;75:1053. 3. Ott WJ. The value of fetal umbilical artery and carotid Doppler flow studies in the evaluation of suspected intrauterine growth retardation. J Mat Fetal Invest 1991; 1: 18590.