Antepartum, Intrapartum, and Postpartum Exposome Impacts on Preterm Neonates
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ABSTRACT:
SUBMITTER: Catalin S. Buhimschi
PROVIDER: S-BSST210 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups).In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.).
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Project description:Lopinavir (LPV) exposure is reduced during the third trimester of pregnancy. We report the pharmacokinetics of standard LPV-ritonavir dosing (400/100 mg twice daily) in the immediate and early postpartum period when initiated during labor. In 16 human immunodeficiency virus-infected Thai women, the median (range) LPV area under the concentration-time curve and maximum and minimum concentrations in plasma were 99.7 (66.1 to 180.5) microg x h/ml, 11.2 (8.0 to 17.5) microg/ml, and 4.6 (1.7 to 12.5) microg/ml, respectively, at 41 (12 to 74) h after delivery. All of the women attained adequate LPV levels through 30 days postpartum. No serious adverse events were reported.
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Project description:Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was to analyze the pharmacokinetics of melatonin after intragastric administration in preterm infants. Preterm newborns were enrolled 24-72 h after birth, and randomly assigned to three groups receiving a single bolus of 0.5 mg·kg-1 melatonin, or 3 boluses of 1 or 5 mg·kg-1 of melatonin at 24-h intervals. Blood samples were collected before and at selective times after melatonin administration. The half-life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the curve (AUC) from 10.48 to 118.17 µg·mL-1·h-1. Our results indicate a different pharmacokinetic profile in premature newborns, compared to adults and experimental animals. The high peak plasma concentrations and the long half-life indicate that in the neonatal clinical setting, it is possible to obtain and maintain high serum concentrations using a single administration of melatonin repeated every 12/24 h.
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Project description:ObjectivesThe software "SyMRI" generates different MR contrasts and characterizes tissue properties based on a single acquisition of a multi-dynamic multi-echo (MDME)-FLAIR sequence. The aim of this study was to assess the applicability of "SyMRI" in the assessment of myelination in preterm and term-born neonates. Furthermore, "SyMRI" was compared with conventional MRI.MethodsA total of 30 preterm and term-born neonates were examined at term-equivalent age using a standardized MRI protocol. MDME sequence (acquisition time, 5 min, 24 s)-based post-processing was performed using "SyMRI". Myelination was assessed by scoring seven brain regions on quantitative T1-/T2-maps, generated by "SyMRI" and on standard T1-/T2-weighted images, acquired separately. Analysis of covariance (ANCOVA) (covariate, gestational age (GA) at MRI (GAMRI)) was used for group comparison.ResultsIn 25/30 patients (83.3%) (18 preterm and seven term-born neonates), "SyMRI" acquisitions were successfully performed. "SyMRI"-based myelination scores were significantly lower in preterm compared with term-born neonates (ANCOVA: T1: F(1, 22)?=?7.420, p?=?0.012; T2: F(1, 22)?=?5.658, p?=?0.026). "SyMRI"-based myelination scores positively correlated with GAMRI (T1: r?=?0.662, n?=?25, p???0.001; T2: r?=?0.676, n?=?25, p???0.001). The myelination scores based on standard MRI did not correlate with the GAMRI. No significant differences between preterm and term-born neonates were detectable.Conclusions"SyMRI" is a highly promising MR technique for neonatal brain imaging. "SyMRI" is superior to conventional MR sequences in the visual detection of delayed myelination in preterm neonates.Key points• By providing multiple MR contrasts, "SyMRI" is a time-saving method in neonatal brain imaging. • Differences concerning the myelination in term-born and preterm infants are visually detectable on T1-/T2-weighted maps generated by "SyMRI". • "SyMRI" allows a faster and more sensitive assessment of myelination compared with standard MR sequences.
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Project description:The involvement of the gut microbiota on weight-gain and its relationship with childhood undernutrition and growth has been reported. Thus, the gut microbiota constitutes a potential therapeutic target for preventing growth impairment. However, our knowledge in this area is limited. In this study we aimed at evaluating the relationship among early microbiota, growth, and development in preterm infants. To this end we assessed the levels of specific microorganisms by qPCR, and those of short chain fatty acids by mean of gas-chromatography, in feces from 63 preterm newborns and determined their weight-gain during the first months. The statistical analyses performed indicate an influence of the intestinal microbiota in weight-gain, with the levels of some microorganisms showing a significant association with the weight-gain of the infant. The levels of specific microbial groups during the first days of life were found to affect weight gain by the age of 1 month. Moreover, clustering of the infants on the basis of the microbiota composition at 1 month of age rendered groups which showed differences in weight z-scores. Our results suggest an association between the gut microbiota composition and weight-gain in preterm infants at early life and point out potential microbial targets for favoring growth and maturation in these infants.
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Project description:Introduction and hypothesisPudendal nerve block analgesia (PNB) is used as pain relief in the final stage of childbirth. We hypothesized that PNB is associated with higher rates of postpartum urinary retention.MethodsWe performed a cohort study among primiparous women with a singleton, cephalic vaginal birth at Oslo University Hospital, Norway. Women receiving PNB were included in the exposed group, while the subsequent woman giving birth without PNB was included in the unexposed group. We compared the likelihood of postpartum urinary retention, defined as catheterization within 3 h after birth. Logistic regression analysis stratified by mode of delivery was performed adjusting for epidural analgesia, episiotomy and birth unit.ResultsOf the 1007 included women, 499 were exposed to PNB and 508 were unexposed. In adjusted analyses, women exposed to PNB did not differ in likelihood of postpartum urinary retention compared to women unexposed to PNB in either spontaneous (odds ratio[OR]: 0.82, 95% confidence interval [CI] 0.55-1.22) or instrumental (OR 1.45, 95% CI 0.89-2.39) births. Furthermore, no differences between the groups were observed with excessive residual urine volume or catheterization after > 3 h.ConclusionsPNB was associated with neither risk of postpartum urinary retention nor excessive residual urine volume and is therefore unlikely to hamper future bladder function.
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Project description:Growing evidence suggests that maternal microbiota can influence the neonates' gut colonization. However, the mechanisms of vertical bacterial transmission remain poorly defined. We believed that the first colonizers of the newborn come from the mother's gut and vagina during pregnancy and that this is independent of the mode of delivery. We conducted an observational longitudinal study to evaluate the link between the maternal gut microbiota and the meconium's microbiota in extremely and very preterm neonates. Bacterial DNA was extracted from samples and specific bacterial groups were quantified by RT-PCR. In this cohort of 117 preterm neonates, we detected bacterial DNA in 88% of meconium samples. Meconium microbiota of neonates born after 28 gestational weeks (very preterm neonates) showed stronger correlations with their mothers' fecal microbiota. However, neonates born before 28 gestational weeks (extremely preterm neonates) had more Lactobacillus - genus that dominated the vaginal microbiota - than very preterm neonates, regardless of the mode of delivery. Collectively, these data support the hypothesis that maternal bacteria from the gut and vagina can play a role in shaping neonates' gut microbiota and that mother-to-infant bacterial transmission is a controlled and time-specific process. ClinicalTrials.gov Identifier: NCT03663556.
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Project description:ContextNo consensus exists regarding the association between maternal chorioamnionitis and neurodevelopmental outcomes in preterm and very preterm neonates.ObjectivesTo investigate whether maternal chorioamnionitis affects neurodevelopmental outcomes and to identify the factors that may explain these effects.Data sourcesWe used Ovid Medline, EMBASE and Web of Science to conduct a meta-analysis of studies published in English before August 25, 2017, with titles or abstracts that discussed an association between maternal chorioamnionitis and mental/motor development.Study selectionAmong the 603 initially identified studies, we selected those that addressed an association between maternal chorioamnionitis and mental/motor development according to our preselected inclusion criteria as follows: (1) the study compared infants with and without exposure to maternal chorioamnionitis and (2) the neurodevelopmental outcome was followed up using the Bayley Scales of Infant Development 2nd edition.Data synthesisOur meta-analysis included 10 studies. According to a random effect model, infants with maternal chorioamnionitis exposure had poorer mental development (d = -2.25 [95%CI, -4.33, -0.17], p<0.05) than infants without maternal chorioamnionitis, and infants with maternal clinical chorioamnionitis exposure had poorer motor development (d = -2.37 [95%CI, -4.62 to -0.12], p<0.05) than infants without maternal clinical chorioamnionitis exposure. Factors in the meta-analysis that showed differences between the two patient groups included an MDI assessment blinded to medical history, MDI assessment at the correct age, and time of the MDI assessment.ConclusionThis study suggests that maternal chorioamnionitis may affect mental development in preterm and very preterm neonates, and that maternal clinical chorioamnionitis may affect motor development in offspring. Further studies are required to confirm these results and to detect the influence of variables across studies.
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