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Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low.
Heinonen, E, Blennow, M, Blomdahl-Wetterholm, M, Hovstadius, M, Nasiell, J, Pohanka, A, Gustafsson, LL, Wide, K
European journal of clinical pharmacology. 2021;(9):1323-1331
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Abstract
PURPOSE Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. METHOD Pregnant women with moderate untreated depression were recruited in 2016-2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. RESULTS Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers', measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. CONCLUSION Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. TRIAL REGISTRATION The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.
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Effects of Maternal Vitamin D3 Supplementation on Offspring Epigenetic Clock of Gestational Age at Birth: A Post-hoc Analysis of a Randomized Controlled Trial.
Chen, L, Wagner, CL, Dong, Y, Wang, X, Shary, JR, Huang, Y, Hollis, BW, Zhu, H
Epigenetics. 2020;(8):830-840
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Vitamin D could be beneficial for healthy ageing in humans. We previously found that vitamin D supplementation may slow down epigenetic ageing in young African American adults. We tested new epigenetic clocks developed for neonates among a multiethnic population, and tested the hypothesis that maternal vitamin D supplementation would slow down the epigenetic gestational age acceleration (GAA) in newborn babies. Ninety-two pregnant women (aged 29.6 ± 4.8 y; 21% African Americans, 28% Hispanics) were randomized to receive 4000 IU/day vitamin D3 or placebo, plus prenatal vitamins containing 400 IU vitamin D3 during pregnancy in a randomized controlled trial (RCT). Cord blood genome-wide methylation analysis was performed on the Illumina Infinium MethylationEPIC Beadchip. DNA methylation gestational age was calculated based on two calculations developed by Knight and Bohlin. DNA methylation gestational ages calculated by Knight's clock and Bohlin' clock were highly correlated with the gestational age in the placebo group (correlation coefficients = 0.88, p s< 0.001, respectively). GAA was associated with higher birth weight (p = 0.039). In the entire cohort, vitamin D3 supplementation was not associated with GAA (p > 0.05). However, vitamin D3 supplementation decreased GAA by both Knight's clock (β = -0.89, p = 0.047) and Bohlin's clock (β = -0.71, p = 0.005) in the African American participants. Maternal vitamin D3 supplementation may slow down the epigenetic gestational ageing process in African American neonates. Long-term follow-up studies are warranted to determine the role of epigenetic age acceleration in the growth and development of offspring.
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Impact of nutritional supplementation during pregnancy on antibody responses to diphtheria-tetanus-pertussis vaccination in infants: A randomised trial in The Gambia.
Okala, SG, Darboe, MK, Sosseh, F, Sonko, B, Faye-Joof, T, Prentice, AM, Moore, SE
PLoS medicine. 2019;(8):e1002854
Abstract
BACKGROUND Exposure to a nutritionally deficient environment during fetal life and early infancy may adversely alter the ontogeny of the immune system and affect an infant's ability to mount an optimal immune response to vaccination. We examined the effects of maternal nutritional supplementation during pregnancy on infants' antibody responses to the diphtheria-tetanus-pertussis (DTP) vaccine included in the Expanded Programme on Immunisation (EPI). METHODS AND FINDINGS The Early Nutrition and Immune Development (ENID) trial was a randomised, partially blinded trial conducted between April 2010 and February 2015 in the rural West Kiang region of The Gambia, a resource-poor region affected by chronic undernutrition. Pregnant women (<20 weeks' gestation) with a singleton pregnancy (n = 875) were randomised to receive one of four supplements: iron-folic acid (FeFol; standard of care), multiple micronutrient (MMN), protein-energy (PE), or PE + MMN daily from enrolment (mean [SD] 13.7 [3.3] weeks' gestation) until delivery. Infants were administered the DTP vaccine at 8, 12, and 16 weeks of age according to the Gambian Government protocol. Results for the primary outcome of the trial (infant thymic size) were described previously; here, we report on a secondary outcome, infant antibody response to vaccination. The effects of supplementation on mean DTP antibody titres measured in blood samples collected from infants at 12 weeks (n = 710) and 24 weeks (n = 662) were analysed with adjustment for confounders including maternal age, compliance to supplement, and infant sex and season. At 12 weeks, following a single dose of the vaccine, compared with FeFol (mean 95% confidence interval [CI]; 0.11 IU/mL, 0.09-0.12), antenatal supplementation with MMN or MMN + PE resulted in 42.4% (95% CI 20.1-64.6; p < 0.001) and 29.4% (6.4-52.5; p = 0.012) higher mean anti-diphtheria titres, respectively. Mean anti-tetanus titres were higher by 9.0% (5.5-12.5), 7.8% (4.3-11.4), and 7.3% (4.0-10.7) in MMN, PE, and PE + MMN groups (all, p < 0.001), respectively, than in the FeFol group (0.55 IU/mL, 0.52-0.58). Mean anti-pertussis titres were not significantly different in the FeFol, MMN, and PE + MNN groups but were all higher than in the PE group (all, p < 0.001). At 24 weeks, following all three doses, no significant differences in mean anti-diphtheria titres were detected across the supplement groups. Mean anti-tetanus titres were 3.4% (0.19-6.5; p = 0.038) higher in the PE + MMN group than in the FeFol group (3.47 IU/mL, 3.29-3.66). Mean anti-pertussis titres were higher by 9.4% (3.3-15.5; p = 0.004) and 15.4% (9.6-21.2; p < 0.001) in PE and PE + MMN groups, compared with the FeFol group (74.9 IU/mL, 67.8-82.8). Limitations of the study included the lack of maternal antibody status (breast milk or plasma) or prevaccination antibody measurements in the infants. CONCLUSION According to our results from rural Gambia, maternal supplementation with MMN combined with PE during pregnancy enhanced antibody responses to the DTP vaccine in early infancy. Provision of nutritional supplements to pregnant women in food insecure settings may improve infant immune development and responses to EPI vaccines. TRIAL REGISTRATION ISRCTN49285450.
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Intimate Partner Violence, Depression, and Child Growth and Development.
Neamah, HH, Sudfeld, C, McCoy, DC, Fink, G, Fawzi, WW, Masanja, H, Danaei, G, Muhihi, A, Kaaya, S, Smith Fawzi, MC
Pediatrics. 2018;(1)
Abstract
BACKGROUND Evidence on the relationship between maternal depression and exposure to intimate partner violence (IPV) with child physical growth and development is equivocal. Our aim in the current study is to examine these relationships among women and their children in Tanzania. METHODS The Bayley Scales of Infant Development and anthropometric measures were used to assess children 18 to 36 months of age (n = 1031). Maternal exposure to IPV and depression were assessed using the Tanzania Demographic and Health Survey questionnaire and the Patient Health Questionnaire-9, respectively. We used linear regression models to calculate standardized mean differences (SMDs) for developmental outcomes and generalized linear models to estimate the associations with nutritional status. RESULTS Mild depressive symptoms in mothers (Patient Health Questionnaire-9 ≥5) and exposure to physical and sexual IPV were associated with lower SMDs for motor skills (-0.14 [P = .023] and -0.23 [P < .01], respectively), expressive communication (-0.13 [P = .187] and -0.23 [P < .01], respectively), receptive communication (-0.19 [P < .009] and -0.16 [P = .03], respectively), and cognitive development (-0.08 [P = .245] and -0.12 [P = .07], respectively). Exposure to physical and sexual IPV was associated with higher risk for stunting (relative risk = 1.6; P < .001). CONCLUSIONS This study reveals that maternal depressive symptoms and IPV are associated with adverse child nutritional and developmental outcomes. Further research is needed to develop programs to address IPV and depression among women and enhance the growth and development of their children.
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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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Antenatal administration of vitamin K1: relationship to vitamin K-dependent coagulation factors and incidence rate of periventricular-intraventricular hemorrhage in preterm infants; Egyptian randomized controlled trial.
El-Ganzoury, MM, El-Farrash, RA, Saad, AA, Ali, MS, El-Bhbiti, AR, Selem, AM
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. 2014;(8):816-20
Abstract
OBJECTIVES To determine the effect of maternal antenatal administration of vitamin K1 on activity level of vitamin K-dependent coagulation factors and on the occurrence of periventricular-intraventricular hemorrhage (PIVH). METHODS This study was conducted on 90 infants who were classified into; Group A: 30 preterm whose mothers received antenatal vitamin K1, Group B: 30 preterm whose mothers did not receive antenatal vitamin K1, and Group C: 30 healthy full term newborns as a control group. All newborns were subjected to measurement of the activity level of vitamin K-dependent coagulation factors (FII, FVII, FIX and FX). Cranial ultrasound was done on the 1st, 3rd and 7th days of life. RESULTS Group B showed significantly lower activity level of FII and FX with higher incidence of PIVH compared with group A. Neonates who developed PIVH by the 7th day in both group A and B had significantly lower activity level of vitamin K-dependent coagulation factors. CONCLUSION when antenatal vitamin K1 was given to pregnant women at imminent risk of preterm labor, their preterm neonates were able to achieve a clotting status approaching that of full term neonates and are less liable to develop PIVH.
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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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Auditory- and visual-evoked potentials in Mexican infants are not affected by maternal supplementation with 400 mg/d docosahexaenoic acid in the second half of pregnancy.
Stein, AD, Wang, M, Rivera, JA, Martorell, R, Ramakrishnan, U
The Journal of nutrition. 2012;(8):1577-81
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The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18-22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26-0.43; all P < 0.001) and left-right visual-evoked potentials were strongly correlated (range, 0.79-0.94; all P < 0.001) within any assessment. Correlations across visits were modest to moderate (range, 0.09-0.38; all P < 0.01). The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure (all comparisons P > 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo.
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Provision of micronutrient-fortified food from 6 months of age does not permit HIV-exposed uninfected Zambian children to catch up in growth to HIV-unexposed children: a randomized controlled trial.
Filteau, S, Baisley, K, Chisenga, M, Kasonka, L, Gibson, RS, ,
Journal of acquired immune deficiency syndromes (1999). 2011;(2):166-75
Abstract
BACKGROUND HIV-exposed, uninfected (HIV-EU) children represent a large proportion of children in southern Africa. The reasons for their poorer growth and higher morbidity and mortality than their HIV-unexposed peers are unclear. OBJECTIVE We compared anthropometry of 125 HIV-EU with 382 HIV-unexposed young Zambian children participating in a trial of micronutrient-fortified complementary/replacement food. DESIGN The randomized controlled trial provided children from age 6 to 18 months with a porridge flour containing either a basal or a rich level of micronutrients. Weight and length were measured 3 monthly and head and arm circumferences and triceps and subscapular skinfolds 6 monthly. RESULTS There were no significant anthropometric differences between the 2 treatment groups. In unadjusted analyses, most anthropometric Z scores of HIV-EU children were lower than those of HIV-unexposed children; after adjustment for treatment arm, socioeconomic factors, breastfeeding and sex, head and arm circumference Z scores remained lower. Subscapular skinfold Z scores were lower among HIV-EU than HIV-unexposed children at 6 months but not 18 months. CONCLUSIONS Socioeconomic factors accounted for some but not all of the impaired growth of HIV-EU children. Micronutrient malnutrition may not be the socioeconomic factor responsible for the growth faltering. Factors acting earlier in life had irreversible effects.