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1.
Maternal and Perinatal Factors Associated With Kawasaki Disease Among Offspring in Taiwan.
Chang, CL, Lin, MC, Lin, CH, Ko, TM
JAMA network open. 2021;(3):e213233
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Abstract
This case-control study investigates the association of perinatal factors and maternal autoimmune diseases with the development of Kawasaki disease using the Taiwan Maternal and Child Health Database.
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Association of Maternal DNA Methylation and Offspring Birthweight.
Kheirkhah Rahimabad, P, Arshad, SH, Holloway, JW, Mukherjee, N, Hedman, A, Gruzieva, O, Andolf, E, Kere, J, Pershagen, G, Almqvist, C, et al
Reproductive sciences (Thousand Oaks, Calif.). 2021;(1):218-227
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Abstract
This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.
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Effect of Maternal Smoking on Plasma and Urinary Measures of Vitamin E Isoforms in the First Month after Extreme Preterm Birth.
Stone, C, Qiu, Y, Kurland, IJ, Slaughter, JC, Moore, P, Cook-Mills, J, Hartert, T, Aschner, JL
The Journal of pediatrics. 2018;:280-285.e3
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We examined the effect of maternal smoking on plasma and urinary levels of vitamin E isoforms in preterm infants. Maternal smoking during pregnancy decreased infant plasma alpha- and gamma-tocopherol concentrations at 1 week and 4 weeks, with 45% of infants of smokers deficient in alpha-tocopherol at 1 month after birth.
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Association of Maternal Gestational Weight Gain With the Infant Fecal Microbiota.
Robinson, A, Fiechtner, L, Roche, B, Ajami, NJ, Petrosino, JF, Camargo, CA, Taveras, EM, Hasegawa, K
Journal of pediatric gastroenterology and nutrition. 2017;(5):509-515
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Abstract
OBJECTIVES Pregnancy characteristics may influence the infant fecal microbiota during early life. We aimed to examine associations of maternal gestational weight gain with infant fecal microbiota composition, bacterial community richness, and Shannon diversity index. METHODS We analyzed data from a prospective cohort study of healthy infants. We collected prenatal data, including report of mother's gestational weight gain, and infant fecal samples from 84 infant-mother dyads. By applying 16S rRNA gene sequencing and an unbiased clustering by partitioning around medoids using Bray-Curtis distances, we identified 4 fecal microbiota profiles, and examined the associations of maternal gestational weight gain with the 4 fecal microbiota profiles, bacterial community richness, and Shannon diversity index. RESULTS Overall, the median age of infants was 4.0 months and 43% were girls. The mothers of the 84 infants gained a mean of 14.2 kg (standard deviation, 5.4 kg) during pregnancy. We identified 4 distinct microbiota profiles: Bifidobacterium-dominant (42%), Enterobacter/Veillonella-dominant (23%), Bacteroides-dominant (19%), and Escherichia-dominant (17%). Infants whose mothers had higher gestational weight gain were less likely to have a Bacteroides-dominant profile, corresponding to a relative risk ratio of 0.83 (95% confidence interval, 0.71-0.96; P = 0.01) per 1 kg increase in weight. In addition, higher gestational weight gain was also associated with lower bacterial community richness and Shannon diversity index (P < 0.05). CONCLUSIONS In this prospective cohort study of healthy infants, maternal gestational weight gain was associated with the infant fecal microbiota profiles, bacterial community richness, and Shannon diversity index.
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CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment.
Llop, S, Tran, V, Ballester, F, Barbone, F, Sofianou-Katsoulis, A, Sunyer, J, Engström, K, Alhamdow, A, Love, TM, Watson, GE, et al
Environment international. 2017;:34-42
Abstract
BACKGROUND Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. OBJECTIVES We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. METHODS The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age, 2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). RESULTS There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p<0.05) in European cohorts only. CONCLUSIONS Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.
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Mild gestational diabetes mellitus and long-term child health.
Landon, MB, Rice, MM, Varner, MW, Casey, BM, Reddy, UM, Wapner, RJ, Rouse, DJ, Biggio, JR, Thorp, JM, Chien, EK, et al
Diabetes care. 2015;(3):445-52
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OBJECTIVE To evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity. RESEARCH DESIGN AND METHODS Follow-up study of children (ages 5-10) of women enrolled in a multicenter trial of treatment versus no treatment of mild GDM. Height, weight, blood pressure, waist circumference, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were measured. RESULTS Five hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5-6 and 7-10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels. CONCLUSIONS Although treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose.
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Does magnesium exposure affect neonatal resuscitation?
Drassinower, D, Friedman, AM, Levin, H, Običan, SG, Gyamfi-Bannerman, C
American journal of obstetrics and gynecology. 2015;(3):424.e1-5
Abstract
OBJECTIVE Research on immediate neonatal resuscitation suggests that maternal magnesium exposure may be associated with increased risk of low Apgar scores, hypotonia, and neonatal intensive care unit admission. However, not all studies support these associations. Our objective was to determine whether exposure to magnesium at the time of delivery affects initial neonatal resuscitation. STUDY DESIGN This is a secondary analysis of the Randomized Controlled Trial of Magnesium Sulfate for the Prevention of Cerebral Palsy that evaluated whether the study drug (magnesium or placebo) that was administered at the time of delivery was associated with increased risk for a composite adverse neonatal resuscitation outcome (5-minute Apgar score <7, oxygen administration in the delivery room, intubation, chest compressions, hypotension, and hypotonicity). A subgroup analysis was performed among patients who delivered at ≥30 weeks of gestation. Log-linear regression was used to control for possible confounders. RESULTS Data for 1047 patients were analyzed, of whom 461 neonates (44%) were exposed to magnesium. There was no increased risk for the primary composite outcome associated with magnesium exposure. Individual adverse neonatal outcomes and other secondary short-term neonatal outcomes that were evaluated also did not demonstrate an association with magnesium exposure. CONCLUSION Exposure to magnesium sulfate did not affect neonatal resuscitation or other short-term outcomes. These findings may be useful in planning neonatal care and patient counseling.
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Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: a prospective cohort study.
Zhu, K, Whitehouse, AJ, Hart, PH, Kusel, M, Mountain, J, Lye, S, Pennell, C, Walsh, JP
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;(5):1088-95
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It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results; none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study. Maternal serum samples collected at 18 weeks gestation were assayed for 25-hydroxyvitamin D (25OHD). Outcomes were total body bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry in offspring at 20 years of age. The mean (± SD) maternal serum 25OHD concentration was 57.2 ± 19.2 nmol/L; 132 women (38.7%) were vitamin D-deficient (25OHD <50 nmol/L). After adjustment for season of sample collection, maternal factors, and offspring factors (sex, birth weight, and age, height, lean mass, and fat mass at 20 years), maternal 25OHD concentration was positively associated with total body BMC and BMD in offspring, with a mean difference of 19.2 (95% confidence interval [CI], 5.6-32.7) g for BMC and 4.6 (95% CI, 0.1-9.1) mg/cm(2) for BMD per 10.0 nmol/L of maternal 25OHD. Maternal vitamin D deficiency was associated with 2.7% lower total body BMC (mean ± SE) (2846 ± 20 versus 2924 ± 16 g, p = 0.004) and 1.7% lower total body BMD (1053 ± 7 versus 1071 ± 5 mg/cm(2) , p = 0.043) in the offspring. We conclude that vitamin D deficiency in pregnant women is associated with lower peak bone mass in their children. This may increase fracture risk in the offspring in later life.
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Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years.
Meador, KJ, Baker, GA, Browning, N, Cohen, MJ, Bromley, RL, Clayton-Smith, J, Kalayjian, LA, Kanner, A, Liporace, JD, Pennell, PB, et al
JAMA pediatrics. 2014;(8):729-36
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IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may be harmful. We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES Differential Ability Scales IQ was the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS In total, 42.9% of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95% CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95% CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95% CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95% CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95% CI, 0-7] points higher for breastfed children, P = .03). CONCLUSIONS AND RELEVANCE No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00021866.