In This Issue
In This Issue
- Michael G. Ross
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- Published online by Cambridge University Press:
- 08 May 2012, p. 131
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Review
Diverse ability of maternal immune stimulation to reduce birth defects in mice exposed to teratogens: a review
- T. C. Hrubec, M. R. Prater, M. K. Mallela, R. M. Gogal, Jr, T. L. Guo, S. D. Holladay
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- 19 December 2011, pp. 132-139
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Stimulating the maternal immune system before or during pregnancy can dramatically improve morphologic outcome in mice that have been exposed to teratogens. For example, maternal immune stimulation in mice reduced craniofacial and palate defects, heart defects, digit and limb defects, tail malformations and neural tube defects caused by diverse teratogens that included chemical agents, hyperthermia, X-rays and diabetes mellitus. Several different procedures of immune stimulation were effective and included footpad injection with Freund's Complete Adjuvant, intraperitoneal (IP) injection with inert particles or attenuated Bacillus Calmette–Guerin, intrauterine injection with allogenic or xenogenic lymphocytes, or intravascular, intrauterine or IP injection with immunomodulatory cytokines. Limited information is available regarding mechanisms by which such immune stimulation reduces fetal dysmorphogenesis; however, cytokines of maternal origin have been suggested as effector molecules that act on the placenta or fetus to improve development. These collective data raise novel questions about the possibility of unrecognized maternal immune system regulatory activity in normal fetal development. This manuscript reviews the literature showing maternal immune protection against morphologic birth defects. Potential operating mechanisms are discussed, and the possibility is considered that a suppressed maternal immune system may negatively impact fetal development.
Effects of in utero conditions on adult feeding preferences
- A. K. Portella, E. Kajantie, P. Hovi, M. Desai, M. G. Ross, M. Z. Goldani, T. J. Roseboom, P. P. Silveira
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- 06 March 2012, pp. 140-152
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The fetal or early origins of adult disease hypothesis states that environmental factors, particularly nutrition, act in early life to program the risks for chronic diseases in adult life. As eating habits can be linked to the development of several diseases including obesity, diabetes and cardiovascular disease, it could be proposed that persistent food preferences across the life-span in people who were exposed to an adverse fetal environment may partially explain their increased risk to develop metabolic disease later in life. In this paper, we grouped the clinical and experimental evidence demonstrating that the fetal environment may impact the individual's food preferences. In addition, we review the feeding preferences development and regulation (homeostatic and hedonic pathways, the role of taste/olfaction and the reward/pleasure), as well as propose mechanisms linking early life conditions to food preferences later in life. We review the evidence suggesting that in utero conditions are associated with the development of specific food preferences, which may be involved in the risk for later disease. This may have implications in terms of public health and primary prevention during early ages.
Programming of the lung by early-life infection
- P. M. Hansbro, M. R. Starkey, R. Y. Kim, R. L. Stevens, P. S. Foster, J. C. Horvat
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- 14 February 2012, pp. 153-158
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Many important human diseases, such as asthma, have their developmental origins in early life. Respiratory infections in particular may alter the course of asthma and may either protect against or promote the development of this disease. It is likely that the nature of the effects depends on the type and age of infection and is determined by the impact of infection on the immune and respiratory systems. Immunity in early life is plastic and can be moulded by antigen encounter, which may enhance or reinforce the asthmatic phenotype of early life, or induce protective responses. Chlamydial respiratory infections have specific effects and may increase asthma severity in early life by promoting systemic interleukin 13 responses and causing permanent changes in lung structure. Respiratory viral infections, such as those of respiratory syncytial virus and rhinovirus, promote pro-asthmatic responses in early life that contribute to the induction of asthma. By contrast, probiotics or infection or exposure to certain bacteria, such as Streptococcus pneumoniae, may have protective effects in asthma by increasing the numbers and activity of regulatory T cells. Here, we review the impact of infections on the developmental origins of asthma. Understanding these effects may lead to new therapeutic approaches for asthma that either target deleterious infections or utilize beneficial ones.
Original Article
The modified obstetric metabolic equivalent (MET): finding a MET that fits in pregnancy
- C. G. Campbell, R. C. Foster, L. M. Lanningham-Foster, K. M. Smith
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- 20 February 2012, pp. 159-165
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The Compendium of Physical Activities (CPA) provides the energy expenditure (EE) for hundreds of daily activities reported in metabolic equivalents (MET). It remains to be determined if the metabolic changes of pregnancy alter the use of the CPA MET (METCPA) in this population. The energy cost of rest, activities of daily living (ADL; typing, folding laundry and sweeping) and treadmill walking [2.0, 2.5, 3.0 mph (0% incline), 3.0 mph (3% incline)] were compared with the METCPA from the 2000 and 2011 CPA in 30 pregnant women (10–14 weeks gestation) using indirect calorimetry (IC). The METCPA for each activity was compared against two measured IC values: METabsolute (3.5 ml O2/kg/min) and METratio (EEactivity/EErest). Means for both comparisons were tested by one-sample t-test. Measured MET correlated with the 2011 METCPA: METabsolutev. METCPAR2 = 0.906, P < 0.0001; METratiov. METCPAR2 = 0.861, P < 0.0001. Differences between measured MET values and the 2011 METCPA ranged from 16% underestimation to 48% overestimation. Using the absolute definition, the METCPA significantly overestimated the ADL (P < 0.0005); yet, no significant differences were found between walking at 0% grade and METCPA. Conversely, only folding laundry was significantly different with the ratio definition, whereas walking at a level grade was significantly underestimated (P < 0.0001). Similar observations were found using the 2000 CPA. The use of the METCPA to estimate EE in pregnant women can result in significant over- or underestimation, depending on the activity and the definition of the MET that is used.
Is low birth weight associated with adiposity in contemporary U.S. youth? The Exploring Perinatal Outcomes among Children (EPOCH) Study
- M. Jaiswal, T. Crume, K. Vehik, A. Scherzinger, E. Stamm, R. F. Hamman, D. Dabelea
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- 23 March 2012, pp. 166-172
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Little is known about the relationship between low birth weight (BW), as a marker of under-nutrition in utero, and childhood body mass index (BMI) and adiposity parameters, including skinfold thickness, abdominal subcutaneous (SAT) and visceral adipose tissues (VAT) and intramyocellular accumulation of lipids (IMCL). The EPOCH Study (Exploring Perinatal Outcomes among Children) explored the association between BW and markers of adiposity in contemporary, multi-ethnic children from Colorado. A total of 442 youth age 6–13 years (50% male, mean age 10.5 years) had anthropometric measurements, abdominal SAT and VAT measured by magnetic resonance imaging and IMCL deposition in the soleus muscle measured by nuclear magnetic resonance spectroscopy. BW and gestational age were ascertained from an electronic perinatal database. A weak positive association between BW and current BMI (P = 0.05) was seen, independent of demographic, perinatal, socio-economic and current lifestyle factors. When adjusted for current BMI, every one standard deviation decrease in BW (∼500 g), was associated with a 8.8 cm2 increase in SAT, independent of potential confounders. In conclusion, in a contemporary cohort of youth, BW was positively, but weakly, associated with BMI and inversely, though weakly, associated with SAT, independent of current BMI. There were no significant associations between BW and waist circumference, skinfolds, VAT and IMCL. Our results provide some support to the hypothesis that under-nutrition in utero, as reflected by lower BW, is associated with lower overall childhood body size, but an increased propensity for abdominal adiposity, reflected in this young age-group, predominantly as subcutaneous fat.
Associations of long interspersed nuclear element-1 DNA methylation with preterm birth in a prospective cohort study
- H. H. Burris, S. L. Rifas-Shiman, A. Baccarelli, L. Tarantini, C. E. Boeke, K. Kleinman, A. A. Litonjua, J. W. Rich-Edwards, M. W. Gillman
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- Published online by Cambridge University Press:
- 29 February 2012, pp. 173-181
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Preterm birth affects over 12% of all infants born in the United States; yet the biology of early delivery remains unclear, including whether epigenetic mechanisms are involved. We examined associations of maternal and umbilical cord blood long interspersed nuclear element-1 (LINE-1) DNA methylation with length of gestation and odds of preterm birth in singleton pregnancies in Project Viva. In white blood cells from maternal blood during first trimester (n = 914) and second trimester (n = 922), and from venous cord blood at delivery (n = 557), we measured LINE-1 by pyrosequencing [expressed as %5 methyl cytosines within the LINE-1 region analyzed (%5mC)]. We ran linear regression models to analyze differences in gestation length, and logistic models for odds of preterm birth (<37 v. ⩾37 weeks’ gestation), across quartiles of LINE-1. Mean (s.d.) LINE-1 levels were 84.3 (0.6), 84.5 (0.4) and 84.6 (0.7) %5mC for first trimester, second trimester and cord blood, respectively. Mean (s.d.) gestational age was 39.5 (1.8) weeks, and 6.5% of infants were born preterm. After adjustment for maternal age, race/ethnicity, body mass index, education, smoking status and fetal sex, women with the highest v. lowest quartile of first trimester LINE-1 had longer gestations [0.45 weeks (95% CI 0.12, 0.78)] and lower odds of preterm birth [OR 0.40 (0.17, 0.94)], whereas associations with cord blood LINE-1 were in the opposite direction (−0.45 weeks, −0.83, −0.08) and [OR 4.55 (1.18, 17.5)]. In conclusion, higher early pregnancy LINE-1 predicts lower risk of preterm birth. In contrast, preterm birth is associated with lower LINE-1 in cord blood.
Vascular programming in twins: the effects of chorionicity and fetal therapy for twin-to-twin transfusion syndrome†
- H. M. Gardiner, A. Barlas, H. Matsui, A. Diemert, M. J. O. Taylor, J. Preece, F. Gordon, S. E. Greenwald, K. Hecher
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- 20 March 2012, pp. 182-189
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We assessed vascular programming in genetically identical monochorionic twin pairs with twin-to-twin transfusion syndrome (TTTS) treated differently in utero by serial amnioreduction or fetal laser arterial photocoagulation. This case–control study re-assessed four twin groups at median 11 years comprising 20 pairs of monochorionic diamniotic twins: nine treated by amnioreduction (TTTS-amnio) and eleven by laser (TTTS-laser) with seven monochorionic and six dichorionic control pairs. Outcome measures were current blood pressure (BP), brachio-radial arterial stiffness derived from pulse wave velocity (PWV), resting microcirculation (Flux) and response to heating and post-occlusive reactive hyperaemia measured using laser Doppler. Potential confounders [PWV and BP at first study, current height, weight, heart rate and twin type (ex-recipient, ex-donor or heavier/lighter of pair)] were accounted for by Mixed Linear Models statistical methodology. PWV dichorionic > monochorionic (P = 0.024); systolic and diastolic BP dichorionic > TTTS-amnio and TTTS-laser (P = 0.004, P = 0.02 and P = 0.005, P = 0.02, respectively). Within-twin pair pattern of PWV discordance was similar in laser treated and dichorionic controls (heavier-born > lighter), opposite to TTTS-amnio and monochorionic controls. Flux monochorionic > dichorionic (P = 0.044) and heavier > lighter-born (P = 0.024). TTTS-laser and dichorionic diamniotic showed greatest hyperaemic responses (dichorionic > TTTS-amnio or monochorionic controls (P = 0.007, P = 0.025). Hyperaemic responses were slower in heavier-born twins (P = 0.005). In summary, monochorionic twins had lower BP, arterial stiffness and increased resting vasodilatation than dichorionic twins implying shared fetal circulation affects vascular development. Vascular responses in laser-TTTS were similar to dichorionic and opposite to TTTS-amnio suggesting a lasting effect of fetal therapy on vascular health.
Placental measurements associated with intelligence quotient at age 7 years
- D. P. Misra, C. M. Salafia, A. K. Charles, R. K. Miller
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- 20 March 2012, pp. 190-197
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We hypothesized that placental villous branching that is measured by disk chorionic plate expansion and disk thickness is correlated with factors also involved in regulation of branching growth of other fetal viscera (e.g. lung, kidney) including neuronal dendrites, and thus may be associated with variation in childhood intelligence quotient (IQ). IQ at age 7 years was assessed using the Wechsler Intelligence Scale for Children. Placental measures [placental weight (g), thickness (mm), chorionic plate surface diameters (cm), area (cm2), shape, and cord length and cord eccentricity] were independent variables in regression analyses of age 7-year IQ in 12,926 singleton term live born infants with complete placental data. Analyses were stratified on gender with adjustment for socioeconomic status, race, parity, gestational age, exact age at testing and centered parental ages. After adjustment for covariates, placental measurements were independently associated with IQ at age 7 years but results varied by gender. Chorionic plate diameters were only associated with higher IQ in girls. Placental thickness was positively associated with higher IQ for boys and girls. We have previously shown that placental measures affect age 7-year body mass index and diastolic blood pressure. Here we demonstrate that specific measures, placental chorionic plate diameters in girls and disk thickness, independent of gender, are correlated with age 7-year IQ. Further exploration of the possible interaction of these factors on the placental villous arborization reflected by the chorionic plate expansion and placental thickness that correlate with age 7-year IQ, as well as other age 7 somatic features as previously addressed, is indicated.
Altered adipocyte structure and function in nutritionally programmed microswine offspring
- E. A. DuPriest, P. Kupfer, B. Lin, K. Sekiguchi, T. K. Morgan, K. E. Saunders, T. T. Chatkupt, O. N. Denisenko, J. Q. Purnell, S. P. Bagby
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- 25 April 2012, pp. 198-209
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Adipose tissue (AT) dysfunction links obesity of any cause with cardiometabolic disease, but whether early-life nutritional deficiency can program adipocyte dysfunction independently of obesity is untested. In 3–5-month-old juvenile microswine offspring exposed to isocaloric perinatal maternal protein restriction (MPR) and exhibiting accelerated prepubertal fat accrual without obesity, we assessed markers of acquired obesity: adiponectin and tumor necrosis factor (TNF)-α messenger ribonucleic acid (mRNA) levels and adipocyte size in intra-abdominal (ABD-AT) and subcutaneous (SC-AT) adipose tissues. Plasma cortisol, leptin and insulin levels were measured in fetal, neonatal and juvenile offspring. In juvenile low-protein offspring (LPO), adipocyte size in ABD-AT was reduced 22% (P = 0.011 v. controls), whereas adipocyte size in SC-AT was increased in female LPO (P = 0.05) and normal in male LPO; yet, adiponectin mRNA in LPO was low in both sexes and in both depots (P < 0.001). Plasma leptin (P = 0.004) and cortisol (P < 0.05) were reduced only in neonatal LPO during MPR. In juveniles, correlations between % body fat and adiponectin mRNA, TNF-α mRNA or plasma leptin were significant in normal-protein offspring (NPO) but absent in LPO. Plasma glucose in juvenile LPO was increased in males but decreased in females (interaction, P = 0.023); plasma insulin levels and insulin sensitivity were unaffected. Findings support nutritional programming of adipocyte size and gene expression and subtly altered glucose homeostasis. Reduced adiponectin mRNA and adipokine dysregulation in juvenile LPO following accelerated growth occurred independently of obesity, adipocyte hypertrophy or inflammatory markers; thus, perinatal MPR and/or growth acceleration can alter adipocyte structure and disturb adipokine homeostasis in metabolically adverse patterns predictive of enhanced disease risk.