Search

Context: The positive predictive value of newborn screening for congenital adrenal hyperplasia (CAH) in New Zealand is approximately 10%. The use of a second tier liquid chromatography-tandem mass spectrometry bloodspot steroid profile test with birth weight- or gestational age-adjusted screening cutoffs may result in further screening improvements., Methods: Three years of newborn screening data with additional second-tier steroid metabolites was evaluated (n = 167 672 births). Data from babies with a negative screening test and confirmed CAH cases were compared. First- and second-tier steroid measurements were correlated with both birth weight and gestational age. Analysis of variance was used to determine birth weight and gestational age groups. Screening cutoffs were determined and applied retrospectively to model screening performance., Results: First-tier immunoassay data correlated better with gestational age than with birth weight, but there was no difference with second-tier steroid measurements. Four distinct birth weight and gestational age groups were established for 17-hydroxyprogesterone and a steroid ratio measurement. Application of 97.5th percentile second-tier birth weight- or gestational age-adjusted cutoffs would result in 10 positive tests over the period of the study with 8 true-positive screens and 2 false-positive tests. The positive predictive value of screening would be increased from 10.8% to 80%., Conclusions: The use of either birth weight- or gestational age-adjusted cutoffs for second-tier screening tests can significantly reduce the false positive rate of newborn screening for CAH in New Zealand without loss in screening sensitivity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We aimed to evaluate the association of birth weight SDS with insulin resistance, blood pressure, and auxology in children and adolescents born 23-42 weeks of gestation., Methods: We studied 143 singleton children and adolescents aged 9.3 ± 3.3 years (range 2.0-17.9 years). Clinical assessments included insulin resistance measured by HOMA2-IR, auxology, and blood pressure from sphygmomanometer measurements. Continuous associations were examined, and stratified analyses carried out. For the latter, participants were divided into those of below-average birth weight (BABW, <0 SDS) and above-average birth weight (AABW, ≥0 SDS)., Results: Irrespective of gestational age, lower birth weight SDS was associated with progressively greater HOMA2-IR (p<0.0001) and higher fasting insulin concentrations (p<0.0001). Decreasing birth weight SDS was associated with higher systolic (p = 0.011) and diastolic (p = 0.006) blood pressure. Lower birth weight SDS was also associated with decreasing stature (p<0.010). The BABW group was ~40% more insulin resistant than AABW participants (p = 0.004), with the former also displaying fasting insulin concentrations 37% higher (p = 0.004). BABW participants were 0.54 SDS shorter than those of higher birth weight (p = 0.002). On average, BABW participants had not met their genetic potential, tending to be shorter than their parents (p = 0.065). As a result, when corrected for parents' heights, BABW participants were 0.62 SDS shorter than those born of higher birth weight (p = 0.001). Sub-group analyses on participants born appropriate-for-gestational-age (n = 128) showed that associations of birth weight SDS with both insulin resistance and stature remained (although attenuated)., Conclusion: Decreasing birth weight SDS (even within the normal range) is associated with adverse metabolic profile and lower stature in children and adolescents.

Study Question: Are childhood measures of phenotype associated with peri-conception parental, IVF treatment and/or embryonic characteristics of IVF children?, Summary Answer: Birthweight, childhood body mass index (BMI) and height of pre-pubertal IVF children were strongly associated with peri-conception factors, including follicular and embryonic characteristics., What Is Known Already: A growing number of studies have identified a range of phenotypic differences between IVF and naturally conceived pre-pubertal children; for example, birthweights are lower following a fresh compared with a thawed embryo transfer., Study Design, Size, Duration: This retrospective cohort study included IVF children (n = 96) born at term (>37 weeks) after a singleton pregnancy from the transfer of either fresh or thawed embryos in New Zealand. Between March 2004 and November 2008, these children were subjected to clinical assessment before puberty., Participants/materials, Setting, Methods: Clinical assessment provided anthropometric measures of children aged 3.5-11 years old. Peri-conception factors (n = 36) derived retrospectively from parental, treatment, laboratory and embryonic variables (n = 69) were analysed using multiple stepwise regression with respect to standard deviation scores (SDSs) of the birthweight, mid-parental corrected BMI and height of the IVF children. Data from children conceived from fresh (n = 60) or thawed (n = 36) embryos, that met inclusion criteria and had high-quality data with >90% completeness, were analysed., Main Results and the Role of Chance: Embryo treatment at transfer was identified as a predictor of birthweight with thawed embryos resulting in heavier birthweights than fresh embryos [P = 0.02, 95% confidence interval (CI) fresh minus thawed: -1.047 to -0.006]. Birthweight SDS was positively associated with mid-parental corrected BMI SDS (P = 0.003, slope 0.339 ± 0.100). Four factors were related (P < 0.05) to mid-parental corrected height SDS. In particular, child height was inversely associated with the diameter of lead follicles at oocyte retrieval (P < 0.0001, slope -0.144 ± 0.040) and with the quality score of embryos at transfer (P = 0.0008, slope -0.425 ± 0.157), and directly associated with the number of follicles retrieved (P = 0.05, slope 1.011 ± 0.497). Child height was also positively associated with the transfer of a fresh as opposed to thawed embryo (P < 0.001, 95% CI 0.275-0.750)., Limitations, Reasons for Caution: More than one embryo was transferred in most cycles so mean development and quality data were used. The large number of variables measured was on a relatively small sample size. Large cohorts from multiple clinics using a variety of treatment protocols and embryology methods are needed to confirm the associations identified and ultimately to test these factors as possible predictors of phenotype., Wider Implications of the Findings: This is the first study to directly associate peri-conception measures of IVF treatment with a pre-pubertal child's phenotype. Demonstration that peri-conception measures relate to a pre-pubertal child's phenotype extends the range of factors that may influence growth and development. These findings, if corroborated by larger studies, would provide invaluable information for practitioners, who may want to consider the impact of ovarian stimulation protocols as well as the quality of the embryo transferred on a child's growth and development, in addition to their impact on pregnancy rate., Study Funding/competing Interests: This work was supported by grants from the National Research Centre of Growth and Development New Zealand (grant 3682065) and the Australasian Paediatric Endocrine Group (APEG; grant 3621994), as well as a fellowship from Fertility Associates New Zealand awarded to M.P.G. In terms of competing interest, J.C.P is a shareholder of Fertility Associates. M.P.G. currently holds the position of Merck Serono Lecturer in Reproductive Biology. W.S.C. and P.L.H. have also received grants and non-financial support from Novo Nordisk, as well as personal fees from Pfizer that are unrelated to the current study. The other authors have no conflict of interest to declare., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. Lifestyle interventions in pregnancy such as antenatal exercise, are proposed to improve both short- and long-term health of mother and child. We hypothesise that regular moderate-intensity exercise during the second half of pregnancy will result in improved maternal and offspring outcomes, including a reduction in birth weight and adiposity in the offspring, which may be protective against obesity in later life., Methods/design: The IMPROVE (Improving Maternal and Progeny Risks of Obesity Via Exercise) study is a two-arm parallel randomised controlled clinical trial being conducted in Auckland, New Zealand. Overweight and obese women (BMI ≥25 kg/m2) aged 18-40 years, with a singleton pregnancy of <20 weeks of gestation, from the Auckland region, are eligible for the trial. Exclusion criteria are ongoing smoking or medical contra-indications to antenatal exercise.Participants are randomised with 1:1 allocation ratio to either intervention or control group, using computer-generated randomisation sequences in variable block sizes, stratified on ethnicity and parity, after completion of baseline assessments. The intervention consists of a 16-week structured home-based moderate-intensity exercise programme utilising stationary cycles and heart rate monitors, commencing at 20 weeks of gestation. The control group do not receive any exercise intervention. Both groups undergo regular fetal ultrasonography and receive standard antenatal care. Due to the nature of the intervention, participants are un-blinded to group assignment during the trial.The primary outcome is offspring birth weight. Secondary offspring outcomes include fetal and neonatal body composition and anthropometry, neonatal complications and cord blood metabolic markers. Maternal outcomes include weight gain, pregnancy and delivery complications, aerobic fitness, quality of life, metabolic markers and post-partum body composition., Discussion: The results of this trial will provide valuable insights on the effects of antenatal exercise on health outcomes in overweight and obese mothers and their offspring., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12612000932864.

Context & Objective: A recent paper by our group reported that regular aerobic exercise during pregnancy led to lower foetal IGF-I and IGF-II concentrations and a modest reduction in offspring birth weight when compared with the offspring of nontraining control participants. Maternal hormonal alterations in response to exercise training may be associated with the regulation of nutrient availability for foetal growth through placental regulation of maternal metabolism., Objective: To determine whether the reduction in offspring size was associated with changes in the maternal IGF axis [including placental growth hormone (PGH)], leptin and/or free fatty acids (FFA) in response to aerobic exercise training in the second half of pregnancy., Design and Setting: A randomized, controlled trial of exercise in pregnancy., Patients: Eighty-four healthy nulliparous women (mean±SD age 30±4 year, BMI 25·5±4 kg/m(2) )., Measurements: Serum samples were drawn at 19 and 35 weeks gestation to determine serum IGF-I, IGF-II, IGF-binding protein-1, IGF-binding protein-3, PGH, leptin and FFA., Results: Exercise training in pregnancy had no impact on the pregnancy-related changes in the maternal IGF axis. Women in the exercise group experienced a 29% increase in leptin in late gestation (P=0·026 vs control) and a trend towards lower FFA (P=0·07 vs control). Late pregnancy changes in maternal leptin were inversely related to offspring birth weight (r= -0·24, P<0·05) and BMI (r= -0·25, P<0·05)., Conclusions: An increase in leptin in exercising pregnant women may reflect subtle changes within the placenta in response to regular exercise and may contribute to the reduction in offspring size previously reported in this cohort., (© 2011 Blackwell Publishing Ltd.)

Context: Epidemiological studies have identified the importance of the in utero environment in providing a healthy start to life. Previous studies have suggested that the maternal environment, in particular a reduction in maternal insulin sensitivity, contributes significantly to fetal growth. Regular aerobic exercise, through an effect on maternal insulin sensitivity, may influence offspring size by regulating nutrient supply to the fetus., Objective: The aim of the study was to determine the effects of aerobic exercise training in the second half of pregnancy on maternal insulin sensitivity and neonatal outcomes., Design and Setting: We conducted a community-based, randomized, controlled trial of exercise in pregnancy., Participants: Eighty-four healthy nulliparous women (mean +/- sd, age, 30 +/- 4 yr; body mass index, 25.5 +/- 4 kg/m(2)) participated in the study., Intervention: Subjects participated in a home-based stationary cycling program from 20 wk gestation to delivery., Main Outcome Measures: Maternal insulin sensitivity, neonatal auxology, body composition, and growth-related peptides in cord blood were measured., Results: Offspring of exercisers had lower birth weight (sd score, control, 0.23 +/- 0.8; exercise, -0.19 +/- 0.9; P = 0.03) and body mass index at birth (sd score, control, 0.40 +/- 0.9; exercise, -0.01 +/- 0.09; P = 0.04). The reduction in maternal insulin sensitivity in late gestation was not affected by exercise (P = 0.45) and was unrelated to offspring size. Exercise offspring had lower cord serum IGF-I (P = 0.03) and IGF-II (P = 0.04)., Conclusions: Regular exercise was associated with lower birth weights and reduced cord concentrations of growth-related peptides, suggesting an influence of exercise on endocrine regulation of fetal growth. These effects on offspring growth were not associated with an exercise training effect on maternal insulin sensitivity.

Growth hormone (GH) therapy is often associated with adverse side effects, including impaired insulin sensitivity. GH treatment of children with idiopathic short stature does not lead to an optimized final adult height. It has been demonstrated that FFA reduction induced by pharmacological antilipolysis can stimulate GH secretion per se in both normal subjects and those with GH deficiency. However, to date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using a model of maternal undernutrition in the rat to induce growth-restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At postnatal day 28, male offspring of normally nourished mothers (controls) and offspring born with low birth weight [small for gestational age (SGA)] were treated with saline, GH, or GH (5 mg.kg(-1).day(-1)) in combination with acipimox (GH + acipimox, 20 mg.kg(-1).day(-1)) or fenofibrate (GH + fenofibrate, 30 mg.kg(-1).day(-1)) for 40 days. GH plus acipimox treatment significantly enhanced linear body growth in the control and SGA animals above that of GH, as quantified by tibial and total body length. Treatment with GH significantly increased fasting plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA animals but was not significantly different between saline and GH-plus-acipimox-treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment in both control and SGA animals, concomitant with a significant reduction in fasting plasma FFA and insulin concentrations. This is the first study to show that GH plus acipimox combination therapy, via pharmacological blocking of lipolysis during GH exposure, can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects.

Objective: To assess whether antenatal exercise in overweight/obese women would improve maternal and perinatal outcomes.Design: Two-arm parallel randomised controlled trial.Setting: Home-based intervention in Auckland, New Zealand.Population and Sample: Pregnant women with body mass index ≥25 kg/m(2) .Methods: Participants were randomised to a 16-week moderate-intensity stationary cycling programme from 20 weeks of gestation, or to a control group with no exercise intervention.Main Outcome Measures: Primary outcome was offspring birthweight. Perinatal and maternal outcomes were assessed, with the latter including weight gain, aerobic fitness, quality of life, pregnancy outcomes, and postnatal body composition. Exercise compliance was recorded with heart rate monitors.Results: Seventy-five participants were randomised in the study (intervention 38, control 37). Offspring birthweight (adjusted mean difference 104 g; P = 0.35) and perinatal outcomes were similar between groups. Aerobic fitness improved in the intervention group compared with controls (48.0-second improvement in test time to target heart rate; P = 0.019). There was no difference in weight gain, quality of life, pregnancy outcomes or postnatal maternal body composition between groups. However, compliance with exercise protocol was poor, with an average of 33% of exercise sessions completed. Sensitivity analyses showed that greater compliance was associated with improved fitness (increased test time (P = 0.002), greater VO2 peak (P = 0.015), and lower resting heart rate (P = 0.014)), reduced postnatal adiposity (reduced fat mass (P = 0.007) and body mass index (P = 0.035)) and better physical quality of life (P = 0.034).Conclusions: Maternal non-weight-bearing moderate-intensity exercise in pregnancy improved fitness but did not affect birthweight or clinical outcomes.Tweetable Abstract: Moderate-intensity exercise in overweight/obese pregnant women improved fitness but had no clinical effects. [ABSTRACT FROM AUTHOR]