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Early fetal growth and birth outcome
- Tim J Cole (25 April 2007)
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Re: Early fetal growth and birth outcome
- Neeru Gupta (1 May 2007)
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Authors' response
- Radek Bukowski, Gordon CS Smith (25 May 2007)
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Tim J Cole, Professor of medical statistics UCL Institute of Child Health, WC1N 1EH
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Bukowski et al (21 April) show in women with a known date of conception a strong positive association between fetal crown-rump length at <14 weeks gestation and both birth weight and pregnancy duration. The first of these associations is unsurprising, in that a fetus that has grown rapidly in the first 13 weeks is likely to be relatively heavy later. But the second, that larger fetuses at 13 weeks tend to have longer gestations, is harder to explain. The authors themselves restate the finding in the Discussion, but without further comment. They point out that an inverse association would be expected if delayed implantation was playing a role, and clearly this is ruled out, but why a positive association? One possible explanation might be iatrogenic, in that smaller babies are more likely to be induced and larger babies more likely to be delivered naturally. But personally I doubt that this explains much of the association. Can anyone suggest a better explanation? On a separate note, the figures show an obviously nonlinear relationship between the two outcomes and fetal size. The smallest fetuses, where <delta>GA is -5 or -6 days, are much more affected than the other fetuses, and again this is not commented on. Might there be another process operating here, over and above the reduced fetal growth? Competing interests: None declared |
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Neeru Gupta, Assistant Director General Indian Council of Medical Research, Ansari Nagar, New Delhi-110029.
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I perfectly endorse the two observations made by Professor Tim J. Cole. There are two comments in order to react to Prof.Tim J. Cole queries: one, that mode of delivery could have been an additional information in the two groups one with Intra Uterine Growth Retardation (IUGR) and other with no IUGR and should have been commented upon (that may also be related to early fetal growth). And, second that what were the types of IUGRs (proportions of symmetrical IUGR and assymetrical IUGR) observed with each day deficit or surplus in actual growth from that of expected, till 14 weeks? In other words, how many pregnancies were ended in spontaneous labour and how many were induced or had instrumental delivery or caesareans? If the length of pregnancy differed in those with spontaneous labour with each day difference between observed and expected gestational age (ÄGA) and if there is a definitive association observed, that will suggest that early foetal growth may have some repercussions on mechanism of labour. Otherwise, the induced and instrumental/ caesarean deliveries would be obviously iatrogenic and more in IUGR categories. Symmetrical IUGRs are known to occur in cases where intrauterine insult takes place in early pregnancy whereas the asymmetrical IUGRs occur when the insult occurs in late pregnancy and prognosis in post-neonatal growth and development also differ in the two groups1,2,3. The type of IUGR would have been an additional information. It might be a pertinent information and possible explanation regarding the growth trajectories/pattern, including that of ÄGA of –5 or –6 days, in later pregnancy. References: 1. Deorari AK, Aggarwal R, Paul VK. Management of infants with intra- uterine growth restriction. : Indian J Pediatr. 2001 Dec;68(12):1155-7. 2. Lapillonne A, Peretti N, Ho PS, Claris O, Salle BL. Aetiology, morphology and body composition of infants born small for gestational age. Acta Paediatr Suppl. 1997 Nov;423:173-6; discussion 177. 3. Takagi K. [Limit of antenatal management of intrauterine growth retarded fetus][Article in Japanese] Nippon Sanka Fujinka Gakkai Zasshi. 1993 Aug;45(8):808-14. Competing interests: None declared |
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Radek Bukowski, Associate Professor University of Texas Medical Branch 301 University Blvd. Galveston, TX 77555, USA, Gordon CS Smith
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Dear Editor, Professor Cole suggested that the finding of an association between early fetal growth and later birth weight was "unsurprising". This study replicates the finding of an earlier report of spontaneous conceptions1 which other researchers felt was unlikely to be explained by early fetal growth2. Hence, the current report is clearly informative. Regarding the association with the timing of delivery, we and others have shown that preterm delivery is associated with growth impairment at birth, even in the absence of maternal or fetal complications3;4. Thus it is plausible that fetuses with impaired growth evident already in the first trimester of pregnancy are born earlier than ones of normal growth. This hypothesis is further supported by animal experiments which demonstrated that dietary restriction in the periconceptional period is associated with early delivery5. The apparent non-linear association between early fetal growth (deltaGA) and birth weight or risks of delivering small for gestational age infant is likely due to small numbers of fetuses with extreme growth impairment of -5 or -6 days at 8 to 12 weeks post conception. We tested for non-linearity of those relationships using fractional polynomials up to the fourth order6. These demonstrated no improvement of fit compared with the assumption of linearity. Analysis performed after exclusion of growth impairment of -5 or -6 days did not result in a significant change of the regression co-efficient. Dr. Gupta suggested that premature delivery due to pregnancy complications would be more often associated with growth restriction and result in shorter duration of pregnancy. Our findings have shown that the relationship between early fetal growth and duration of pregnancy was not significantly changed after adjustment for pregnancy complications which would make up the indications for premature delivery and would potentially affect fetal growth. Thus it is unlikely that observed association between first trimester growth and duration of pregnancy could be due to elective preterm delivery. First trimester growth has an positive association with Ponderal index (birth weight / birth length3) a measure of asymmetricity of fetal growth. Although significant, this relationship was weak suggesting that early fetal growth is associated with symmetrical later growth. However, one cannot infer from this relationship that early onset of growth impairment resulted in symmetricity of later growth impairment, as fetal chromosomal abnormalities have been shown to be associated with asymmetrical growth impairment7. This and other findings indicate that study of early fetal growth appears to provide important biological and clinical insights into the fetal growth and pregnancy outcome. R. Bukowski
Reference List 1. Smith GC, Smith MF, McNay MB, Fleming JE. First-trimester growth and the risk of low birth weight. N.Engl.J.Med. 1998;339:1817-22. 2. Gardosi J,.Francis A. Early pregnancy predictors of preterm birth: the role of a prolonged menstruation-conception interval. BJOG. 2000;107:228-37. 3. Tamura RK, Sabbagha RE, Depp R, Vaisrub N, Dooley SL, Socol ML. Diminished growth in fetuses born preterm after spontaneous labor or rupture of membranes. Am.J.Obstet.Gynecol. 1984;148:1105-10. 4. Bukowski R, Gahn D, Denning J, Saade G. Impairment of growth in fetuses destined to deliver preterm. Am.J.Obstet.Gynecol. 2001;185:463-7. 5. Bloomfield FH, Oliver MH, Hawkins P, Campbell M, Phillips DJ, Gluckman PD et al. A periconceptional nutritional origin for noninfectious preterm birth. Science 2003;300:606. 6. Royston P,.Altman DG. Regression Using Fractional Polynomials of Continuous Covariates - Parsimonious Parametric Modeling. Applied Statistics-Journal of the Royal Statistical Society Series C 1994;43:429- 67. 7. Falcon O, Cavoretto P, Peralta CF, Csapo B, Nicolaides KH. Fetal head-to-trunk volume ratio in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound Obstet.Gynecol. 2005;26:755-60. Competing interests: None declared |
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