Liggins Institute, University of Auckland and National Research Centre for Growth and Development, Auckland, New Zealand.
J Physiol. 2012 Mar 1;590(5):1273-85. doi: 10.1113/jphysiol.2011.220699. Epub 2011 Dec 19.
Size at birth is related to adult health outcomes. Twins are born smaller than singletons; this has been assumed to be secondary to limited nutrient supply in late gestation.We hypothesised that growth trajectory in twins, and the adult consequences of being conceived a twin, are determined in early gestation. Twin pregnancies in sheep were randomised to reduction of one twin on day 42 of a 148 day pregnancy by intra-thoracic KCl (Reductions, n =46) or a sham procedure (Twins, n =22). Singleton-bearing ewes also underwent a sham procedure (n =27). Ewes lambed spontaneously. Linear measures of size at birth were similar in Twins and Reductions, and significantly less than in Singletons. Birthweight was lower in Twins and Reductions than in Singletons, and less in Twins than in Reductions (means (SEM): Singletons, liveborn n =23: 6.59 (0.17) kg; Twins, liveborn n =36: 5.23 (0.16) kg; Reductions, liveborn n =27: 5.76 (0.15) kg; all comparisons P <0.05). Reductions grew most rapidly between birth and weaning (Singletons, 20.0 (0.4) g kg⁻¹ day⁻¹; Twins, 20.0 (0.3) g kg⁻¹ day⁻¹; Reductions, 21.0 (0.3) g kg⁻¹ day⁻¹, P <0.05) and were of similar weight as Singletons by weaning; Twins remained smaller by weaning but grew most rapidly thereafter (Singletons, 1.6 (0.1) g kg⁻¹ day⁻¹; Twins, 2.1 (0.1) g kg⁻¹ day⁻¹; Reductions, 1.6 (0.1) g kg⁻¹ day⁻¹, P <0.01), so that all groups had similar weight at 2 years. However, Twins and Reductions had greater percentage fat mass than Singletons at 2 years (Singletons, 11.1 (1.1)%; Twins, 14.8 (1.2)%; Reductions, 15.5 (1.1)%, P <0.05). Thus, in twins, fetal growth trajectory, linear size at birth and adult fat mass are largely determined in early gestation. If this is also true in humans, there are important implications for interventions aimed at optimising fetal growth and pregnancy outcome.
出生时的大小与成人健康结果有关。双胞胎出生时比单胎小;这被认为是由于晚期妊娠中营养供应有限所致。我们假设双胞胎的生长轨迹以及作为双胞胎受孕的成人后果是在早期妊娠中决定的。绵羊的双胞胎妊娠在妊娠 148 天的第 42 天被随机分为通过胸腔内 KCl 减少一个胎儿(减少组,n=46)或假手术(双胞胎组,n=22)。单胎妊娠的母羊也接受了假手术(n=27)。母羊自然分娩。双胞胎组和减少组的出生时大小的线性测量值相似,且明显小于单胎组。双胞胎组和减少组的出生体重均低于单胎组,且减少组的出生体重低于双胞胎组(平均值(SEM):单胎组,活产 n=23:6.59(0.17)kg;双胞胎组,活产 n=36:5.23(0.16)kg;减少组,活产 n=27:5.76(0.15)kg;所有比较 P<0.05)。减少组在出生到断奶期间生长最快(单胎组,20.0(0.4)g/kg/天;双胞胎组,20.0(0.3)g/kg/天;减少组,21.0(0.3)g/kg/天,P<0.05),并且在断奶时体重与单胎组相似;双胞胎组在断奶时仍然较小,但此后生长最快(单胎组,1.6(0.1)g/kg/天;双胞胎组,2.1(0.1)g/kg/天;减少组,1.6(0.1)g/kg/天,P<0.01),因此所有组在 2 岁时体重相同。然而,双胞胎组和减少组在 2 岁时的体脂肪百分比高于单胎组(单胎组,11.1(1.1)%;双胞胎组,14.8(1.2)%;减少组,15.5(1.1)%,P<0.05)。因此,在双胞胎中,胎儿生长轨迹、出生时的线性大小和成人脂肪量在很大程度上是在早期妊娠中决定的。如果这在人类中也是如此,那么对于旨在优化胎儿生长和妊娠结局的干预措施具有重要意义。