Journal of Perinatology (2007) 27, 693–696 r 2007 Nature Publishing Group All rights reserved. 0743-8346/07 $30 www.nature.com/jp ORIGINAL ARTICLE Decreased neonatal tibial bone ultrasound velocity in term infants born after breech presentation

M Tshorny1, FB Mimouni2,3, Y Littner4, A Alper1 and D Mandel1,3 1Department of Neonatology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel; 3Sackler School of , Tel Aviv University, Tel Aviv, Israel and 4Division of Neonatology, Department of Pediatrics, Case Western Reserve University and Rainbow Babies and Children’s Hospital, Cleveland, OH, USA

such as extreme hips flexion and/or knees hyperextension.3 This Objective: found to be in the breech presentation have limited , usually maintained for days or weeks after delivery, may motion of their lower limbs. The aim of this study was to test the hypothesis affect gait and motor function up to the age of 12 to 18 months.2 that bone speed of sound (SOS) would be lower in infants born after breech Previous reports have shown that lack of motion leads to a presentation than in those born after vertex presentation. decrease in bone mineral density.4 Using the mechanostat model, 5 Study Design: We studied 127 singleton, appropriate for , Frost et al. established the importance of mechanical loading in 6 term infants delivered by a scheduled cesarean delivery at approximately the development and maintenance of bone health. Such loading 38 weeks of gestation because of breech presentation or repeat elective of the fetal skeleton in utero arises from movements against the cesarean section with vertex presentation. We used the Sunlight resistance of the uterine muscle (for example, during extension, 7 Omnisense 7000p device to measure axially transmitted SOS of the right flexion and kicking against the uterine wall). tibia within the first 96 h of life. We designed a prospective, cross-sectional study to compare bone status, assessed by bone ultrasound velocity, between infants Result: Fifty-three infants studied (42%) were born by cesarean section born after breech presentation and those born after vertex after breech presentation compared to 74 vertex controls. Bone SOS was presentation. We hypothesized that infants born after breech significantly lower in the breech presentation group, even after taking into presentation have lower bone speed of sound (SOS) than those account the effect of gender and parity (as well as gestational age at birth born after vertex presentation. and ).

Conclusion: Bone SOS is lower in infants born after breech presentation than in those born after vertex presentation. We speculate that limited Methods motion of lower limbs in fetuses found to be in the breech presentation Patients leads to a decrease in bone mineralization and strength. We enrolled 127 infants born consecutively at the Lis Maternity Journal of Perinatology (2007) 27, 693–696; doi:10.1038/sj.jp.7211809; Hospital between August 2005 and April 2006. All infants were the published online 16 August 2007 products of a term singleton delivery. Appropriateness for gestational age was determined using the intrauterine growth Keywords: ultrasonography; bone mineral content; bone speed of 8 sound; breech presentation curves of Lubchenco. In all infants, gestational age was calculated from the last menstrual period consistent ±2 weeks with early, first-trimester ultrasound evaluation, and the new Ballard scoring 9 Introduction system at birth. In our institution, nearly all breech-presenting Approximately 1 of 25 reaches term with a in the fetuses at term are delivered by a scheduled cesarean delivery at breech presentation.1,2 These fetuses usually have a limited motion approximately 38 weeks of gestation. Very few mothers agree to an of their lower limbs during the last weeks of gestation.3 Being attempt of external version and vaginal delivery in the vertex crammed in utero, these fetuses often adopt abnormal position position. Thus, we only studied breech-presenting, cesarean-delivered infants that we compared to vertex-presenting, Correspondence: Dr D Mandel, Department of Neonatology, Lis Maternity Hospital, Tel Aviv cesarean-delivered infants. In the latter group, the only acceptable Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. indication for cesarean delivery was repeat cesarean delivery in a E-mail: [email protected] Received 27 March 2007; revised 5 June 2007; accepted 26 June 2007; published online mother who refused an attempt of vaginal delivery. In addition, 16 August 2007 vertex-presenting infants were generally delivered at Neonatal tibial bone ultrasound velocity in term infants M Tshorny et al 694 approximately 38 weeks of gestation. In both groups, we excluded Statistical methods all infants born to mothers treated with medications potentially The Minitab statistical program was utilized for analyses (Minitab, affecting bone mass (for example, steroids, anticoagulants, State College, PA, USA). We used the Kruskal–Wallis test for antidepressants and so on) or suffering from diseases that may nonnormally distributed variables, and the t-test for normally affect the mother or her infant’s bone mass (for example, distributed variables. Backward stepwise logistic regression was used gestational diabetes, metabolic bone disease and so on). to determine the effect of breech versus vertex presentation over bone SOS while taking into account potential confounders such as Design gender, gestational age at birth and parity. Results are expressed as This study was approved by our Institutional Review Board. mean±s.d., or n (%). P-values of <0.05 were considered A written informed consent was obtained from at least one of significant. the legal guardians of the infants. As per protocol, all infants were studied within the first 96 h of life. Results Biophysical methods The Sunlight Omnisense 7000p device (Tel-Aviv, Israel) that Table 1 depicts significant demographic characteristics of the measures axially transmitted SOS was used. The instrument population studied, as well as bone SOS results. A total of 127 generates inaudible high-frequency pulsed acoustic waves at a mothers agreed to participate in the study. Fifty-three infants center frequency of 1.25 MHz. Ultrasonic waves are successively studied (42%) were born by cesarean section after breech transmitted and received by transducers embedded in the presentation. There were no significant differences between the two ultrasound probe. By measuring the propagation times along the groups in terms of gestational age, birth weight, head different trajectories, the SOS of the bone is determined. The axial circumference, knee-sole length and 1- and 5-min Apgar scores. transmission of ultrasound enables to eliminate soft-tissue effect There were proportionally more boys in the vertex than in the and is not affected by soft-tissue thickness since the distance is breech group. The ‘breech’ group had a significantly lower constant.10 As ultrasound waves pass through a medium, the speed, gravidity and parity than the ‘vertex’ group. Bone SOS was dispersion and attenuation of the signals are strongly influenced by significantly lower in the breech presentation group. In backward the density, elasticity and cohesiveness of that medium. The higher stepwise logistic regression, presentation was still found to the density of the medium, the more cohesive is its microstructure; significantly affect bone SOS (P ¼ 0.03) even after taking into the greater its modulus of elasticity, the faster the speed of account the effect of gender (P ¼ 0.012), gestational age at birth propagation. (nonsignificant), birth weight (nonsignificant) and parity A single investigator (MT) measured bone SOS in all infants. (nonsignificant). For the purpose of bone SOS measurement in infants, a small probe (1.4 cm  2.7 cm  11 cm), 900 to 1000 kHz was utilized. Measurements of bone SOS were obtained on the right tibia as Discussion previously described.11–14 Using this instrument at the tibial We have shown that, in support of our hypothesis, bone SOS is site, our coefficients of variation (within-measurement and lower in infants born after breech presentation than in those born between-measurements) was below 0.5%. after vertex presentation. We believe that this decrease is likely to

Table 1 Demographic and clinical characteristics of the study participants

Breech presentation (n ¼ 53) Vertex presentation (n ¼ 74)P-value

Gravidity 1.7±1.0 2.8±1.7 <0.001 Parity 0.7±0.8 1.3±1.2 0.003 Gestational age (weeks) 38.7±0.77 (37–41) 38.8±1.1 (37–41) NS Birth weight (g) 3152.0±286.0 (2640.0–3676.0) 3162.6±375.4 (2525.0–3876.0) NS Gender (Male/female) 22:31 41:27 <0.05 Head circumference (cm) 34.67±1.16 (32–37.5) 34.32±1.15 (32–36.5) NS Knee–sole length (cm) 11.80±0.71 (10–13) 11.47±0.70 (10–13) NS 1-min Apgar score 8.96±0.52 (5–9) 8.91±0.30 (7–9) NS 5-min Apgar score 10.0±0 (10–10) 9.86±0.39 (8–10) NS Bone SOS at birth (m sÀ1) 3069.6±134.0 (2821–3383) 3122.8±129.2 (2898–3475) 0.03

Abbreviations: NS, not significant; SOS, speed of sound. Data expressed as mean±s.d., range or n (%), except gender.

Journal of Perinatology Neonatal tibial bone ultrasound velocity in term infants M Tshorny et al 695 reflect a decrease in bone mineralization and strength, as bone SOS that the effect of presentation (breech versus vertex) upon bone measurement, a noninvasive method of evaluation of bone status, SOS remained significant even after taking into account gender is highly predictive of bone mineral content and of bone and gravidity or parity. Also, in spite of the fact that there were no strength.15,16 significant differences between groups in gestational age or birth Our results support the speculation that limited motion of lower weight, because of the potential effect of these variables on body limbs in fetuses found to be in the breech presentation leads to a composition and bone SOS; we also took them into account in decrease in bone mineral density. A similar speculation was logistic regression. Once again, the effect of presentation (breech suggested by Regev et al.,17 who found that bone strength was versus vertex) upon bone SOS remained significant even after significantly decreased in infants of gestational diabetic mothers taking into account the latter variables. compared to healthy controls. In the latter study, neonates with Nevertheless and whatever is the mechanism, tibial bone SOS is higher birth weight had lower bone SOS. Regev et al. suggested significantly reduced in infants with a breech presentation. that reduced bone strength in infants of gestational diabetic Whether or not this decrease might be significant from a clinical mothers may be the result of reduced intrauterine fetal mobility, standpoint (increased risk of obstetric fractures) remains to be presumably due to mechanical limitation of fetal movements. investigated. Similarly, in a previous study we have demonstrated that in infants of nondiabetic mothers, those born large for gestational age have lower bone SOS than those born appropriate for gestational age.13 References It is also possible that relative lack of motion in large-for- 1 Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR, Term Breech gestational-age fetuses, due to reduced space in the uterine cavity, Trial Collaborative Group. Planned versus planned vaginal birth for leads to a decrease in bone SOS by a similar mechanism. This breech presentation at term: a randomised multicentre trial.. Lancet 2000; 356: explanation is strengthened by the Frost’s mechanostat theory,5,6 1375–1383. 2 Goffinet F, Carayol M, Foidart JM, Alexander S, Uzan S, Subtil D et al., PREMODA which implies that bone cell action is coordinated by the Study Group. Is planned vaginal delivery for breech presentation at term still an mechanical requirements of the bone. In support of this theory are option? Results of an observational prospective survey in France and Belgium. Am J several recent studies showing that in preterm infants, 4 or 8 weeks Obstet Gynecol 2006; 194: 1002–1011. of assisted range-of-motion exercise attenuates the postnatal 3 Sival DA, Prechtl HF, Sonder GH, Touwen BC. The effect of intra-uterine breech decrease in bone strength18 or even increases bone mineral content position on postnatal motor functions of the lower limbs. Early Hum Dev 1993; 32: 19,20 161–176. and density; results that are consistent with recent reports 4 Turner CH, Robling AG. Mechanisms by which exercise improves bone strength. emphasizing the importance of intrauterine movements on fetal J Bone Miner Metab 2005; 23(Suppl): 16–22. 3 bone development. When mechanical challenges exceed an 5 Frost HM. 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A simplified score for assessment of fetal maturation of strength than of bone mineral content.10,15,16 This is particularly newly born infants. J Pediatr 1979; 95: 769–774. 15 10 Njeh CF, Hans D, Wu C, Kantorovich E, Sister M, Fuerst T et al. An in vitro true for small bones as shown by Wright et al. who in her investigation of the dependence on sample thickness of the speed of sound along the cardinal work showed that breakability of bones in vitro was better specimen. Med Eng Phys 1999; 21: 651–659. predicted by ultrasound velocity than by mineral content even 11 Littner Y, Mandel D, Mimouni FB, Dollberg S. Bone ultrasound velocity of infants born measured by actual ash weight, although actual ash weight and small for gestational age. J Pediatr Endocrinol Metab 2005; 18: 793–797. ultrasound velocity were also correlated. However, we must warn 12 Littner Y, Mandel D, Cohen S, Mimouni FB, Dollberg S. Bone ultrasound velocity of that the methodology used by Wright et al. was not exactly similar appropriately grown for gestational age concordant twins. Am J Perinatol 2004; 21: 269–273. to that used in our study. Indeed, Wright et al. used a prototype of 13 Littner Y, Mandel D, Mimouni FB, Dollberg S. Bone ultrasound velocity curves of newly an instrument (which was never produced commercially) that born term and preterm infants. J Pediatr Endocrinol Metab 2003; 16: 43–47. measured horizontally propagated ultrasound wave, rather than 14 Littner Y, Mandel D, Mimouni FB, Dollberg S. Decreased bone ultrasound velocity in longitudinal propagated as with the instrument we used. large-for-gestational-age infants. J Perinatol 2004; 24: 21–23. A potential limitation of our study is that, in spite of the fact 15 Wright LL, Glade MJ, Gopal J. The use of transmission ultrasonics to assess bone status in the human newborn. 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17 Regev RH, Dolfin T, Eliakim A, Arnon S, Bauer S, Nemet D et al. Bone speed of sound 19 Moyer-Mileur L, Luetkemeier M, Boomer L, Chan GM. Effect of physical activity on in infants of mothers with gestational diabetes mellitus. J Pediatr Endocrinol Metab bone mineralization in premature infants. J Pediatr 1995; 127: 620–625. 2004; 17: 1083–1088. 20 Moyer-Mileur LJ, Brunstetter V, McNaught TP, Gill G, Chan GM. Daily physical activity 18 Litmanovitz I, Dolfin T, Arnon S, Regev RH, Nemet D, Eliakim A. Assisted exercise and program increases bone mineralization and growth in preterm very low birth weight bone strength in preterm infants. Calcif Tissue Int 2007; 80: 39–43. infants. Pediatrics 2000; 106: 1088–1092.

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