Impact of World War 1 on placenta weight, birth weight and other anthropometric parameters of neonatal health

: Background Wars do not only affect combatant countries, populations in neutral zones can be afflicted by circumjacent conflicts as well, posing a great health burden on mothers and newborns. As neonatal health remains an ongoing cause for concern, identifying determinants that impede fetal growth is crucial. Under this pretext, the study aimed to analyze the impact of World War 1 in the neutral city of Basel on neonatal health by assessing changes in anthropometric parameters. Methods A retrospective analysis of yearly cross sections of term births in the maternity hospital of Basel from 1912 to 1923 was conducted (n = 3718). We tested adjusted anthropometry for time trends in comparison to a pre-war baseline, including birth weight, placenta weight, birth length, ponderal index and gestational age. Interrelations of placenta weights and birth weights were examined separately through birth weight to placenta weight (bw/pw) ratios and residuals of placenta weight to birth weight regressions. Results Birth weights, placenta weights and residuals were at their lowest in 1918/19, a trend not reflected in bw/pw ratios. Birth lengths remained low while ponderal indexes declined during the entire period of war, gestational age remained rather stable. Discussion 1918/19 were the pinnacle years for the population of Basel, who were suffering from general detrimental economic conditions, a food supply crisis and an outbreak of the Spanish Flu. These adverse circumstances coincided with low birth and placenta weights, residuals depicting the correlation of birth weights to placental weights more closely than bw/pw ratios. Abstract 39 Background : Wars do not only affect combatant countries, populations in neutral zones can be afflicted by 40 circumjacent conflicts as well, posing a great health burden on mothers and newborns. As neonatal health 41 remains an ongoing cause for concern, identifying determinants that impede fetal growth is crucial. Under 42 this pretext, the study aimed to analyze the impact of World War 1 in the neutral city of Basel on neonatal 43 health by assessing changes in anthropometric parameters. 44 Methods : A retrospective analysis of yearly cross sections of term births in the maternity hospital of Basel 45 from 1912 to 1923 was conducted (n = 3718). We tested adjusted anthropometry for time trends in 46 comparison to a pre-war baseline, including birth weight, placenta weight, birth length, ponderal index and 47 gestational age. Interrelations of placenta weights and birth weights were examined separately through birth 48 weight to placenta weight (bw/pw) ratios and residuals of placenta weight to birth weight regressions. 49 Results Birth weights, placenta weights and residuals were at their lowest in 1918/19, a trend not reflected in 50 bw/pw ratios. Birth lengths remained low while ponderal indexes declined during the entire period of war, 51 gestational age remained rather stable. 52 Discussion : 1918/19 were the pinnacle years for the population of Basel, who were suffering from general 53 detrimental economic conditions, a food supply crisis and an outbreak of the Spanish Flu. These adverse 54 circumstances coincided with low birth and placenta weights, residuals depicting the correlation of birth 55 weights to placental weights more closely than bw/pw ratios. 56

Background: Wars do not only affect combatant countries, populations in neutral zones can be afflicted by 40 circumjacent conflicts as well, posing a great health burden on mothers and newborns. As neonatal health 41 remains an ongoing cause for concern, identifying determinants that impede fetal growth is crucial. Under 42 this pretext, the study aimed to analyze the impact of World War 1 in the neutral city of Basel on neonatal 43 health by assessing changes in anthropometric parameters.

44
Methods: A retrospective analysis of yearly cross sections of term births in the maternity hospital of Basel 45 from 1912 to 1923 was conducted (n = 3718). We tested adjusted anthropometry for time trends in 46 comparison to a pre-war baseline, including birth weight, placenta weight, birth length, ponderal index and 47 gestational age. Interrelations of placenta weights and birth weights were examined separately through birth 48 weight to placenta weight (bw/pw) ratios and residuals of placenta weight to birth weight regressions.

49
Results Birth weights, placenta weights and residuals were at their lowest in 1918/19, a trend not reflected in 50 bw/pw ratios. Birth lengths remained low while ponderal indexes declined during the entire period of war, 51 gestational age remained rather stable.

52
Discussion: 1918/19 were the pinnacle years for the population of Basel, who were suffering from general 53 detrimental economic conditions, a food supply crisis and an outbreak of the Spanish Flu. These adverse 54 circumstances coincided with low birth and placenta weights, residuals depicting the correlation of birth 55 weights to placental weights more closely than bw/pw ratios. 56 57 1. Introduction 1 2 Neonatal health remains an ongoing cause for concern [1,2]. Since the 1950s there have been 3 significantly fewer deaths of children under 5 years of age [1]. However, there are still large 4 regional differences around the world and the decline in deaths is greater among the post-neonatal 5 groups than among neonates [1]. Overall, the proportion of deaths under 1 year within deaths under 6 5 years has increased [1]. In addition, the proportion of births below 2500 g is decreasing less 7 rapidly than desired, with persisting regional differences around the world as well [2]. Thus,8 identifying determinants that impede normal development and growth are crucial to the cause of 9 ameliorating neonatal health at large. An important tool for studying impaired (or excessive) fetal 10 growth are anthropometric parameters of newborn infants [3]. They serve as a low-cost, non-11 invasive research method to record body size and proportion in both individuals and populations 12  34], and was kept in operation until its gradual resolution from 1919 47 to 1920 [34]. effect on birth weight. Our goal therefore was to exhaust the same dataset for the city of Basel, and 65 to expand the previously collected data by adding further anthropometric parameters of neonatal 66 health in order to explore in turn how they reacted during the same time period (1912 -1923). 67 We seek to contribute to the literature on the impact of perinatal exposure to political, social and 68 economic crises in a war-time environment on a regional scale. In the following paper we will focus 69 on term births in the city of Basel during the years 1912 -1923 and address the following 70 questions: What impact did World War 1 have on placenta weight, birth weight, birth weight in 71 relation to placenta weight, body length and ponderal index? Were all of the selected parameters 72 affected in the same way, or did they react differently? 73 contains precise information of the mother, the birth and the newborn. Incomplete records are very 81 rare. For this paper, the inventory Sanität X29 with 16 control books for the period from 1912 to 82 1923 was examined. Each book contains around 250 birth records. Since there was no admission 83 selection, the maternity hospital was considered a cluster unit; mothers seeking medical assistance 84 were not only from higher but also lower socioeconomic backgrounds and births ranged from 85 problem-free to complicated. The vast majority of patients (> 85 %) were residents of the city of 86 Basel, and this did not change during our observation period [33]. Regarding the years 1912 to 1923 87 approximately 50-66 % (overall 60%) of all childbirths (Appendix Table 1) and more than 90 % of 88 all hospital childbirths per year in the city of Basel took place at the maternity hospital [33]. Thus, 89 the number of childbirths occurring at the mothers home or in other hospitals were ca. 40% in the 90 case of Basel, which was ca. 20% less than in Zurich during the same time [33]. 91 However, the archived books -originally consisting of about three per year -constitute only about a 92 third of the original full records and births given in the maternal hospital during our observational 93 period (in the 1970s the archive reduced the number of books for storage reasons). As a result, our 94 data inevitably represents only about 20% of all births in the maternity hospital Basel during this 95 period, and thus about 16% of all births in the city of Basel (Appendix Table 1). There appeared to 96 be no selection pattern -in particular no seasonal selection pattern -in the presently available books 97 (see Appendix Table 1). The existing records of birth contain extensive and precise information, 98 strongly suggesting a standardized method of data collection. Unfortunately, clarifications 99 regarding the exact methods and protocols of measurement were not recorded (or those records may 100 be lost). 101 Access to the protected individual data was allowed by the Staatsarchiv Basel-Stadt upon signed 102 contractual agreement. After linking the sources and data cleaning, the data have been fully 103 anonymized. 104 105

Variables 106
The birth records contained numerous data concerning the mother, the birth and the newborn, only 107 slightly restricting the variety of possible variables to be included in this study. that the intercept is not zero, meaning the ratio of BW/PW will change along the regression line 135 [51]. This artifact of ratios may lead to interpretation errors, e.g. histologically immature placentas 136 at term appeared to be more "efficient" at birth according to the ratio [51]. Instead, the use of 137 residuals of a regression of birth weight on placental weight is proposed. This method requires a 138 sample of births and cannot be calculated for an individual birth, but it is less prone to artefacts 139 [51]. We chose to include BW/PW ratio as well as residuals of regressions, in order to compare the 140 results and examine their sensitivity to fluctuations of birth and placental weights. 141 Size of the infant and of the placenta at birth not only reflects fetal growth but also duration of 142 gestation [3]. BW/PW ratio at term is known to increase with GA, as the proportion of increase in 143 BW is higher than PW [14,48]. This corresponds to the association of small-for-gestational age 144 infants and increased ratios due to increased placental size and decreased BW, which pose a risk 145 factor of increased neonatal morbidity [52,53]. In our data, GA was calculated as the difference 146 between date of birth of the child and reported last menstruation of the mother. 147 In order to provide a context for the specific variables mentioned above, we examined the socio-148 economic environment of the mother through data that we gathered over the birth register 149 significantly lower in relation to our baseline), BWs are significantly lower than expected for the 262 measured PWs, reflected in significantly lower residuals of that year. Contrarily, ratios did not 263 significantly change in respect to the baseline, BWs not being low enough to affect the ratio. In the 264 year 1920, PWs were significantly higher with regard to the baseline, however BWs were as to be 265 expected based on the regression, reflected in the residuals (Appendix Figure 3), as they show no 266 significant deviation to the baseline. The ratio, on the other hand, shows significantly lower values, 267 as the large placental weights lead to a rather large denominator, generating a low ratio. Gestational 268 age (3D) presents an oscillating development around the baseline 1912-1913, with minima in 1915 269 and 1916, corresponding with increased preterm (Figure 2, B) and fetal loss rates (Figure 2, A). As  hospital. In general, the rate of fetal loss and premature births in the maternity hospital were slightly 341 higher than in published figures for the entire canton. It must remain unclear whether this could 342 point towards a selection bias (i.e., more complicated pregnancies and births in the hospital) and/or 343 underreporting of fetal loss delivered at home. While low placenta weight has been indicated as a 344 risk factor of stillbirth [68], the relationship remains unknown, and while comparatively lower 345 placenta weights were found in 1919, a causal connection could not be made. 346

347
With the intention of examining the correlation between birth weights and placenta weights, a rather 348 remarkable finding was reached by direct comparison of variations in BW/PW ratio and residuals 349 from regression of PW to BW. In 1918, birth weights were lower than expected for the measured 350 placental weights, reflected in significantly lower residuals. According to current theory, where 351 ratio is used as a proxy for placental efficiency [13, 69], our findings would imply a reduced 352 placental efficiency, however ratios are not significantly lower in comparison to the baseline. 353 Furthermore, low ratios were found in 1920, in response to high placental weights, indicating a 354 reduction in placental efficiency of that year. However, residuals in 1920 did not significantly 355 deviate from the baseline i.e. birth weights were as to be expected for the given placental weights, 356 implying that placental efficiency did not lessen in comparison to the baseline. 357 358 Our analysis confirms Christians et. al.
[51] conclusion that ratios are subjected to undesirable 359 properties, as changes in BW/PW ratio are a result of the intercept not being zero, thus creating an 360 artefact. Instead, the use of residuals as a measure of placental efficiency is proposed, and our 361 findings support this suggestion. Furthermore Hayward et.al. called attention to the fact that the 362 ratio alone only offers limited insight into placental efficiency, therefore considering if it is the 363 weight of the fetus or the placenta that is higher or lower than the norm is crucial, and offers greater 364 insight into the probability of incidence of abnormal placental function [13]. Another remarkable 365 finding was the high placental weights recorded during the year of 1920. As records stating the 366 exact protocols of measurements could not be found in the archives, it is possible that the high 367 measures are the result of a measurement and/or reporting bias (e.g. method of measurement or 368 change of scales). However, the high measurement may also be an expression of compensatory 369 effect of the placenta due to the low birth weights in the years before. In order to examine this 370 hypothesis a larger basis would be necessary. 371

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There are some limitations to this study. Firstly, birth records are not complete for each year (only 373 one third of the original records were available, and our data represents only about 20% of all births 374 given in the maternity hospital at that time), suggesting our study could be subject to a selection 375 bias as the births may have been influenced by other factors not included in this study, e.g. seasonal 376 influences. As a sensitivity analysis, we reran our main regressions as linear random effect models 377 to control for the variance within and between the months of birth and found similar patterns. For 378 that reason, we assume that the month of birth, and thus the selection of the book, did at least not 379 vastly influence our results. Secondly, the specific methods of measurement could not be traced in 380 other documents of the archives, as for the comparison of our data with further studies it would be 381 relevant to know how birth weight or placenta weight were measured (if the placenta was weighed 382 trimmed or untrimmed [10,70]). Specifically information on the methods of measurement may 383 have made it possible for us to explain the unusual placenta weight data we collected for the year 384 1920. Thirdly, direct measures of maternal nutrition intake and stress would be insightful for a 385 deeper understanding of their effects on neonatal anthropometric parameters. Fourthly, we were 386 unable to isolate the effects of war versus the effects of infection from the Spanish flu, which hit 387 Basel from early July 1918. Since our archival source for the year 1918 covers only births that took 388 place before May, these pregnancies and births cannot have been influenced by the Spanish flu.