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Fetal growth trajectories and their association with maternal and child characteristics.
Bartels, HC, O'Connor, C, Segurado, R, Mason, O, Mehegan, J, Geraghty, AA, O'Brien, E, Walsh, J, McAuliffe, F
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;(14):2427-2433
Abstract
Background: The growth of the fetus is a complex process, influenced by genetic and environmental factors. Longitudinal patterns of fetal growth are required to fully understand this process, however to date, a paucity of data exists in this area.Objective: To identify fetal growth trajectories in-utero and to assess their association with maternal and child characteristics up to 5 years postnatal.Methods: Data from 781 mother-child pairs from the ROLO longitudinal birth cohort study were analyzed. The ROLO study was a randomized control trial of a low glycemic index diet in pregnancy to prevent recurrence of macrosomia. Fetal ultrasound measurements were recorded at 20 and 34 weeks gestation, and birth weight was recorded. Abdominal circumference (AC), weight (fetal weight, or birth weight), a standardized proxy for length (femur length or birth length, individually standardized), and AC:length ratio were examined for trajectory classes using latent class trajectory mixture models. Two-, three-, four-, and five-class models were evaluated for fit, using a linear (first order) trajectory over three time-points. ANOVA and chi-square tests were applied to test associations between trajectory membership and maternal and child characteristics up to age 5.Results: For AC, two fetal growth trajectories were identified, with 29% of participants on a "slow" trajectory and 71% on a "fast" trajectory. Those on a fast trajectory had higher rates of maternal impaired glucose tolerance (28.7 versus 16.5%, p<.001) and higher rates of mean child 5-year body mass index (BMI) centiles (64th versus 58th centile, p<.05) compared to those on the slow trajectory. For estimated fetal weight, four trajectories were identified, with 4% on a "very-slow" trajectory, 63% in a "moderate-slow" trajectory, 30% in a "moderate-fast" trajectory and 3% on a "very-fast" trajectory. Mothers with a fetus on the fastest trajectory had higher antenatal serum glucose levels (p<.05), and were more likely to deliver by cesarean section (59.1 versus 20%, p<.001). At 5 years of age, children on the fastest growth trajectory had the highest mean BMI centile (86th versus 60th centile, p<.05).Conclusions: This study shows that specific fetal growth trajectories may be associated with maternal serum glucose concentrations during pregnancy, mode of delivery and child BMI at 5 years of age. Diet and lifestyle measures that target maternal glucose levels during pregnancy may have lifelong benefits for children's BMI. Identifying those on an accelerated growth trajectory during fetal life provides a unique opportunity for antenatal and infant interventions that may have long-lasting health benefits.
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Effect of metformin in addition to an antenatal diet and lifestyle intervention on fetal growth and adiposity: the GRoW randomised trial.
Poprzeczny, AJ, Louise, J, Deussen, AR, Dodd, JM
BMC endocrine disorders. 2020;(1):139
Abstract
BACKGROUND The infants born to women who are overweight or obese in pregnancy are at an increased risk of being born macrosomic or large for gestational age. Antenatal dietary and lifestyle interventions have been shown to be ineffective at reducing this risk. Our aim was to examine the effects of metformin in addition to a diet and lifestyle intervention on fetal growth and adiposity among women with a BMI above the healthy range. METHODS Women who had a body mass index ≥25 kg/m2 in early pregnancy, and a singleton gestation, were enrolled in the GRoW trial from three public maternity hospitals in metropolitan Adelaide. Women were invited to have a research ultrasounds at 28 and 36 weeks' gestation at which ultrasound measures of fetal biometry and adiposity were obtained. Fetal biometry z-scores and trajectories were calculated. Measurements and calculations were compared between treatment groups. This secondary analysis was pre-specified. RESULTS Ultrasound data from 511 women were included in this analysis. The difference in femur length at 36 weeks' gestation was (0.07 cm, 95% CI 0.01-0.14 cm, p = 0.019) and this was was statistically significant, however the magnitude of effect was small. Differences between treatment groups for all other fetal biometry measures, z-scores, estimated fetal weight, and adiposity measures at 28 and 36 weeks' gestation were similar. CONCLUSIONS The addition of metformin to dietary and lifestyle advice in pregnancy for overweight and obese women has no clinically relevant effect on ultrasound measures of fetal biometry or adiposity. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry ( ACTRN12612001277831 ).
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Multiple Micronutrients and Docosahexaenoic Acid Supplementation during Pregnancy: A Randomized Controlled Study.
Massari, M, Novielli, C, Mandò, C, Di Francesco, S, Della Porta, M, Cazzola, R, Panteghini, M, Savasi, V, Maggini, S, Schaefer, E, et al
Nutrients. 2020;(8)
Abstract
Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting-an important finding considering the essential roles of DHA and vitamin D.
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Folic Acid Supplementation throughout pregnancy: psychological developmental benefits for children.
Henry, LA, Cassidy, T, McLaughlin, M, Pentieva, K, McNulty, H, Walsh, CP, Lees-Murdock, D
Acta paediatrica (Oslo, Norway : 1992). 2018;(8):1370-1378
Abstract
AIM: To test the effect of folic acid supplements taken throughout pregnancy on children's psychosocial development. METHOD A randomised controlled trial of folic acid supplementation in pregnancy, with parental rating using the Resiliency Attitudes and Skills Profile (RASP), the Strengths and Difficulties Questionnaire (SDQ) and the Trait Emotional Intelligence Questionnaire Child Short Form (TEIQue-CSF). Children aged 6-7 whose mothers received folic acid throughout pregnancy (n = 22) were compared to those whose mothers only received it during the first trimester (n = 17). RESULTS Children whose mothers received the full-term supplement scored significantly higher on emotional intelligence and resilience. Hierarchical multiple regression analysis identified folate level at 36th gestational week as an important predictor of emotional intelligence (EI) and resilience. CONCLUSION Although conclusions must be drawn with caution, this research presents a number of potential implications, the main one being a proposed policy recommendation for women to take folic acid for the duration of pregnancy rather than stopping at the end of the first trimester. The second is the potential for future research to explore the possible psychological and social development benefits and in line with this to try and identify the explanatory mechanism involved.
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Fetal DHA inadequacy and the impact on child neurodevelopment: a follow-up of a randomised trial of maternal DHA supplementation in pregnancy.
Mulder, KA, Elango, R, Innis, SM
The British journal of nutrition. 2018;(3):271-279
Abstract
DHA is an important component of neural lipids accumulating in neural tissue during development. Inadequate DHA in gestation may compromise infant development, but it is unknown whether there are lasting effects. We sought to determine whether the observed effects of fetal DHA inadequacy on infant development persist into early childhood. This follow-up study assessed children (5-6 years) whose mothers received 400 mg/d DHA or a placebo during pregnancy. Child neurodevelopment was assessed with several age-appropriate tests including the Kaufman Assessment Battery for Children. A risk-reduction model was used whereby the odds that a child from the maternal placebo group would fail to achieve a test score in the top quartile was calculated. The association of maternal DHA intake and status in gestation with child test scores, as well as with child DHA intake and status, was also determined. No differences were detected in children (n 98) from the maternal placebo and DHA groups achieving a high neurodevelopment test score (P>0·05). However, maternal DHA status was positively related to child performance on some tests including language and short-term memory. Furthermore, child DHA intake and status were related to the mother's intake and status in gestation. The neurodevelopment effects of fetal DHA inadequacy may have been lost or masked by other variables in the children. Although we provide evidence that maternal DHA status is related to child cognitive performance, the association of maternal and child DHA intake and status limits the interpretation of whether DHA before or after birth is important.
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Vitamin D supplementation during pregnancy on infant anthropometric measurements and bone mass of mother-infant pairs: A randomized placebo clinical trial.
Vaziri, F, Dabbaghmanesh, MH, Samsami, A, Nasiri, S, Shirazi, PT
Early human development. 2016;:61-68
Abstract
INTRODUCTION Based on the essential role of vitamin D in the regulation of calcium metabolism, we evaluated the effects of 2000IUvitamin D/day in late pregnancy on infant's anthropometric measurements and bone mass parameters of mother-infant pairs. MATERIAL AND METHODS In this randomized clinical trial, the main inclusion criteria were: aged 18 or older, no history of internal diseases and pregnancy complications, and a singleton live fetus. The intervention group received two 1000IU vitamin D3 pills (2000IU) daily from weeks 26-28 until childbirth. Maternal serum 25-hydroxyvitamin D, infants' anthropometric measurements (at birth, 4th and 8th weeks postnatal), and maternal and infant bone mass parameters were examined. RESULTS The two groups were not statistically different in relation to baseline 25-hydroxyvitamin D concentrations. However, there was a significant difference between the study groups with regard to change in vitamin D status over time (p<0.001). In cross-sectional analysis, the two groups were not different with respect to anthropometric measurements in three time points. Also, in repeated measure analysis, the two groups did not show any statistical differences concerning the infants' anthropometric measurements. The bone mass measurements of all the 28 mothers who belonged to the two study groups were not different. Finally, the bones mass measurements of the infants in the two study groups were not different. CONCLUSION Ingestion of 2000IUvitamin D3/day during late pregnancy did not improve anthropometric measurements of infants from birth until the 8th week postnatal, nor improve the maternal and infant bone mass measurements.
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The Effects of Fetal Gender on Maternal and Fetal Insulin Resistance.
Walsh, JM, Segurado, R, Mahony, RM, Foley, ME, McAuliffe, FM
PloS one. 2015;(9):e0137215
Abstract
OBJECTIVE Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort. STUDY DESIGN This is a secondary analysis of a cohort from the ROLO randomized control trial of low GI diet in pregnancy. Serum insulin, glucose and leptin were measured in early pregnancy and at 28 weeks. At delivery cord blood C-peptide and leptin were measured. A comparison of maternal factors, fetal biometry, insulin resistance and leptin was made between male and female offspring. A multivariate regression model was built to account for the possible effects of maternal BMI, birthweight and original study group assignment on findings. RESULTS A total of 582 women were included in this secondary analysis, of whom 304 (52.2%) gave birth to male and 278 (47.8%) gave birth to female infants. Compared to male infants at birth, female infants were significantly lighter, (3945 ± 436 vs. 4081± 549g, p<0.001), shorter in length (52.36 ± 2.3 vs. 53.05 ± 2.4cm, p<0.001) and with smaller head circumferences (35.36 ± 1.5 vs. 36.10 ± 1.1cm, p<0.001) than males. On multiple regression analysis, women pregnant with female fetuses were less insulin resistant in early pregnancy, i.e. had lower HOMA indices (B = -0.19, p = 0.01). Additionally female fetuses had higher concentrations of both cord blood leptin and C-peptide at birth when compared to male offspring (B = 0.38, p<0.001 and B = 0.31, p = 0.03 respectively). CONCLUSION These findings suggest gender is a risk factor for insulin resistance in-utero. Additionally, carrying a female fetus decreases the risk of insulin resistance in the mother, from as early as the first trimester.
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DHA supplementation and pregnancy outcomes.
Carlson, SE, Colombo, J, Gajewski, BJ, Gustafson, KM, Mundy, D, Yeast, J, Georgieff, MK, Markley, LA, Kerling, EH, Shaddy, DJ
The American journal of clinical nutrition. 2013;(4):808-15
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BACKGROUND Observational studies associate higher intakes of n-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy with higher gestation duration and birth size. The results of randomized supplementation trials using various n-3 LCPUFA sources and amounts are mixed. OBJECTIVE We tested the hypothesis that 600 mg/d of the n-3 LCPUFA docosahexaenoic acid (DHA) can increase maternal and newborn DHA status, gestation duration, birth weight, and length. Safety was assessed. DESIGN This phase III, double-blind, randomized controlled trial was conducted between January 2006 and October 2011. Women (n = 350) consumed capsules (placebo, DHA) from <20 wk of gestation to birth. Blood (enrollment, birth, and cord) was analyzed for red blood cell (RBC) phospholipid DHA. The statistical analysis was intent-to-treat. RESULTS Most of the capsules were consumed (76% placebo; 78% DHA); the mean DHA intake for the treated group was 469 mg/d. In comparison with placebo, DHA supplementation resulted in higher maternal and cord RBC-phospholipid-DHA (2.6%; P < 0.001), longer gestation duration (2.9 d; P = 0.041), and greater birth weight (172 g; P = 0.004), length (0.7 cm; P = 0.022), and head circumference (0.5 cm; P = 0.012). In addition, the DHA group had fewer infants born at <34 wk of gestation (P = 0.025) and shorter hospital stays for infants born preterm (40.8 compared with 8.9 d; P = 0.026) than did the placebo group. No safety concerns were identified. CONCLUSIONS A supplement of 600 mg DHA/d in the last half of gestation resulted in overall greater gestation duration and infant size. A reduction in early preterm and very-low birth weight could be important clinical and public health outcomes of DHA supplementation. This trial was registered at clinicaltrials.gov as NCT00266825.
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Consumption of a DHA-containing functional food during pregnancy is associated with lower infant ponderal index and cord plasma insulin concentration.
Courville, AB, Harel, O, Lammi-Keefe, CJ
The British journal of nutrition. 2011;(2):208-12
Abstract
DHA (22 : 6n-3) in pregnancy has previously been shown to benefit infant brain and retinal development. Fatty acid consumption during pregnancy may also have an impact on infant adipose tissue development. The objective of the present study was to assess the prenatal impact of a DHA-containing functional food (DHA-FF) on infant intra-uterine growth. This was a longitudinal, randomised, double-blinded, placebo-controlled trial. Pregnant women were assigned to consume a DHA-FF or placebo bar from 24 weeks' gestation until delivery. Blood samples were collected from mothers at baseline and delivery and from the umbilical cord at delivery. Plasma and erythrocyte fatty acids were analysed by GLC and plasma insulin concentrations were analysed using a commercially available ELISA kit. Infant birth weight and length were obtained at delivery and ponderal index (weight (g)/length (cm)3 × 100) was calculated. A total of forty-seven mothers completed the study. Infants of mothers consuming the DHA-FF during the last half of pregnancy had lower ponderal indices (β = 0.198, P < 0.05) and umbilical cord blood insulin concentrations (β = 0.743, P < 0.05) than infants of mothers consuming the placebo. Thus, DHA consumption during pregnancy may be advantageous with respect to infant body composition at birth and insulin sensitivity.
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Long-term effects of hydrolyzed protein infant formulas on growth--extended follow-up to 10 y of age: results from the German Infant Nutritional Intervention (GINI) study.
Rzehak, P, Sausenthaler, S, Koletzko, S, Reinhardt, D, von Berg, A, Krämer, U, Berdel, D, Bollrath, C, Grübl, A, Bauer, CP, et al
The American journal of clinical nutrition. 2011;(6 Suppl):1803S-1807S
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BACKGROUND Previous analysis in a prospective, population-based cohort reported reduced weight gain in children fed extensively hydrolyzed casein (eHF-C) formula during the first year of life but showed no effect on growth between 1 and 6 y of life. No studies have been conducted in children up to the age of 10 y. OBJECTIVE The objective was to investigate potential differences in body mass index (BMI) over the first 10 y of life between infants fed within the intervention period of the first 16 wk of life with partially hydrolyzed whey (pHF-W), extensively hydrolyzed whey (eHF-W), eHF-C, or cow-milk formula (CMF) and infants exclusively breastfed (BF) within the intervention period. DESIGN This was a prospective, randomized, double-blind trial in full-term neonates with atopic heredity in the German birth cohort German Infant Nutritional Intervention (GINI) followed through the first 10 y of life. Analyses of absolute and World Health Organization (WHO)-standardized BMI trajectories for 1840 infants [pHF-W (n = 253), eHF-W (n = 265), eHF-C (n = 250), CMF (n = 276), and BF (n = 796)] were conducted according to intention-to-treat principles. RESULTS Except for the previously reported slower BMI gain in infants fed with eHF-C formula within the first year of life, no significant differences in absolute or WHO-standardized BMI trajectories were shown between the pHF-W, eHF-W, eHF-C, CMF, and BF groups thereafter up to the age of 10 y. CONCLUSIONS Extension of the follow-up period from 6 to 10 y for this randomized controlled trial showed no long-term consequences on BMI for the 4 infant formulas considered. These data need to be confirmed in future studies.