1 Rollins School of Public Health, Emory University, Atlanta GA, USA
2 Mailman School of Public Health, Columbia University, New York NY, USA
3 TNO-PG, Leiden, and University Medical Center Nijmegen, Nijmegen, The Netherlands
Correspondence: LH Lumey, Department of Epidemiology, Mailman School of Public Health, Columbia University, Suite 1617A, 722 West 168 Street, New York NY 10032, USA. E-mail: lumey{at}columbia.edu
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Abstract |
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Methods We abstracted all birth records of infants born in two midwife training schools in the western Netherlands between 1 October 1944 and 31 March 1946, and compared infants whose mothers were exposed to the Dutch famine of 19441945 during specific trimesters of pregnancy with control infants born in 1943. We considered birthweight (BWT), crown-to-heel length (CHL), head circumference (HC), and ratio and regression-adjusted measures of these parameters.
Results BWT, CHL, and HC declined with famine exposure late in pregnancy. Changes in WT for CHL paralleled changes in WT alone in size and direction. Results for HC were inconsistent, varying by choice of body size adjustor (WT or CHL), and by method of adjustment (ratio or regression). BWT, CHL, and HC did not change with first trimester famine exposure.
Conclusion Even under famine conditions, birth size and body proportions vary only with late pregnancy exposure. HC for body size has the added disadvantage that late pregnancy exposure effects vary drastically with choice of measure. We do not recommend the use of birth size or body proportions as a proxy for fetal nutritional status in the study of adult disease.
Accepted 28 November 2003
Fetal programming of adult disease may be a long-term effect of fetal nutrition in gestation.1 The most widely available indicator of nutrition at birth is birthweight, but weight clearly provides only a limited perspective on fetal growth in the preceding 9 months.2 Measures of length and proportionality (Table 1) might provide additional information, and have been examined, with conflicting results.35 The use and interpretation of birth size and proportion in relation to fetal programming assumes that birth size and proportion indeed reflect specific fetal responses to specific variations in maternal nutritional status. For example, it has been suggested that under adverse nutritional conditions, fetuses maintain head size at the expense of body size (head sparing) and that this has specific implications for adult disease risk.6 We here provide empirical data on the relation between prenatal undernutrition at defined periods of gestation and birth size and body proportions, comparing births of mothers exposed to the Dutch famine of 19441945 with unexposed controls, born in 1943.
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Methods |
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We abstracted BWT, crown-to-heel length (CHL), and head circumference (HC) on singleton live births from birth records maintained at two midwife training schools in the western Netherlands, both in urban areas affected by the famine. All available records between 1 October 1944 and 31 March 1946 were abstracted, as well as a systematic sample of approximately 15 records per month per institution from 1943. (Stein et al.,8 in their previous examination of this issue, had abstracted a 50% sample of birth records from one of these institutions, with a slightly different coverage period.) Based on weekly rations, using an approach described elsewhere,13 we defined births between 1 February and 30 June 1945 as third trimester exposed, births between 1 May and 30 September 1945 as second trimester exposed, and births between 1 August and 31 December 1945 as first trimester exposed. Births between 1 November 1945 and 31 March 1946, to mothers maximally exposed to famine prior to conception, were defined as peri-conceptional exposed. There is a partial overlap between exposure in the third and second trimesters, between exposure in the second and first trimesters, and between exposure in the peri-conceptional period and the first trimester. Births in 1943 were considered unexposed.
Analytical methods
Statistical results are presented for the 1826 births between 1 October 1944 and 31 March 1946 (783 in Amsterdam, 1043 in Rotterdam) with BWT, CHL, and HC. We computed the BWT/CHL, HC/CHL, and HC/BWT ratios. We also adjusted BWT for CHL, HC for CHL, and HC for BWT using a regression approach, with the adjusted value being the residual from linear regression models run on site-specific reference groups of births in 1943. This method yields an adjusted value uncorrelated with body size. All measures were converted to Z-scores with respect to the site-specific reference group; thus the reference group always has mean = 0 and SD = 1. Trimester-specific famine effects on the direct measures, ratios, and regression residuals were tested for significance against the 1943 birth data with t-tests.
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Results |
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Second trimester exposure effects on BWT, direct measure, ratio measure, and residual measure, were similar to third trimester effects, but roughly half as big (0.3 SD). The second trimester decline in CHL was no longer significant. As with third trimester exposure, HC results varied by choice of measure; most decreasing, some increasing, some remaining stable in comparison with 1943 births.
First trimester famine exposure was not associated with changes in BWT, CHL, or HC. There was possibly a very small (0.1 SD) decrease in CHL and HC with peri-conceptional famine exposure.
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Discussion |
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Earlier reports did not systematically assess quantitative changes in body proportions. Our results show that inferences about the effect of famine on body proportions depend on the choice of proportionality measure. For instance, second trimester exposure to famine may suggest head-sparing if HC is adjusted for body size using BWT in the ratio method. Adjustment by BWT with the regression method yields a small, non-significant decline in HC. Adjustment by CHL, with either the ratio or regression method also results in declines in HC. Ratios are not recommended as a means of controlling for the denominator.15 In our data, BWT and HC/BWT are correlated (r = 0.91) and HC and HC/BWT are correlated (r = 0.26). Consequently, HC/BWT behaves as the reciprocal of BWT. We therefore do not interpret the third and second trimester exposed increases in the HC/BWT ratio as evidence for head sparing.
The very small decline in CHL and HC after peri-conceptional famine exposure may be of interest. We observed a decline in CHL among women born at the same time in the Wilhemina Gasthuis, Amsterdam.9 Recent work in sheep models has suggested that acute undernutrition in the period immediately preceding conception can trigger preterm delivery.16 While it is tempting to ascribe the human findings to the same phenomenon, we caution that the observed effect size is small and that the estimation of gestational age is especially problematic among this group, who were conceived at a time when amenorrhoea was widely prevalent.7
Many indices of body size at birth are unavailable except under special circumstances (e.g. the birth series reported by Yajnik et al.5). Our results are based on routinely collected data, albeit obtained under the stressful circumstances of war. It is possible that BWT was measured more accurately than either CHL or HC. It has been suggested that routine measures of CHL are unreliable.17 This is likely to be less of a concern in the institutions from which we obtained our data. Both were training centres for midwives, whose instructors would presumably insist on high degrees of consistency. At any rate, estimates of famine exposure effects would be reduced to the extent that an assumed, rather than actual, size was recorded.
We conclude that third trimester famine exposure depresses BWT, CHL, and HC, with a weaker and less-consistent pattern after second trimester exposure; that there are no discernible effects from first trimester exposure and only a hint of an effect after peri-conceptional exposure. Changes in BWT persisted after adjustment for CHL. Changes in HC became inconsistent after adjustment for body size, depending on both choice of body size adjustor and method of adjustment. We do not recommend the use of the HC:BWT ratio, as it is entirely driven by changes in BWT.
Even under famine conditions, birth size and body proportions vary only with late pregnancy exposure. HC for body size has the added disadvantage that late pregnancy exposure effects vary drastically with choice of measure. We do not recommend the use of birth size or body proportions as a proxy for fetal nutritional status in the study of adult disease.
KEY MESSAGES
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Acknowledgments |
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References |
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