Novel NR5A1 Missense Mutation in Premature Ovarian Failure: Detection in Han Chinese Indicates Causation in Different Ethnic Groups

Background The etiology of most premature ovarian failure (POF) cases is usually elusive. Although genetic causes clearly exist and a likely susceptible region of 8q22.3 has been discovered, no predominant explanation exists for POF. More recently, evidences have indicated that mutations in NR5A1 gene could be causative for POF. We therefore screened for mutations in the NR5A1 gene in a large cohort of Chinese women with non-syndromic POF. Methods Mutation screening of NR5A1 gene was performed in 400 Han Chinese women with well-defined 46,XX idiopathic non-syndromic POF and 400 controls. Subsequently, functional characterization of the novel mutation identified was evaluated in vitro. Results A novel heterozygous missense mutation [c.13T>G (p.Tyr5Asp)] in NR5A1 was identified in 1 of 384 patients (0.26%). This mutation impaired transcriptional activation on Amh, Inhibin-a, Cyp11a1and Cyp19a1 gene, as shown by transactivation assays. However, no dominant negative effect was observed, nor was there impact on protein expression and nuclear localization. Conclusions This novel mutation p.Tyr5Asp, in a novel non-domain region, is presumed to result in haploinsufficiency. Irrespectively, perturbation in NR5A1 is not a common explanation for POF in Chinese.

Genetic markers, birth characteristics, and childhood leukemia risk

The cause for childhood acute lymphoblastic leukemia (ALL) remains unknown, but male gender is a risk factor, and among ethnicities, Hispanics have the highest risk. In this dissertation, we explored correlations among genetic polymorphisms, birth characteristics, and the risk of childhood ALL in a multi-ethnic sample in 161 cases and 231 controls recruited contemporaneously (2007-2012) in Houston, TX. We first examined three lymphoma risk markers, since lymphoma and ALL both stem from lymphoid cells. Of these, rs2395185 showed a risk association in non-Hispanic White males (OR=2.8, P=0.02; P interaction=0.03 for gender), but not in Hispanics. We verified previously known risk associations to validate the case-control sample. Mutations of HFE (C282Y, H63D) were genotyped to test whether iron-regulatory gene (IRG) variants known to elevate iron levels increase childhood ALL risk. Being positive for either polymorphism yielded only a modestly elevated OR in males, which increased to 2.96 (P=0.01) in the presence of a particular transferrin receptor (TFRC) genotype for rs3817672 (Pinteraction=0.04). SNP rs3817672 itself showed an ethnicity-specific association (P interaction=0.02 for ethnicity). We then examined additional IRG SNPs (rs422982, rs855791, rs733655), which showed risk associations in males (ORs=1.52 to 2.60). A polygenic model based on the number of polymorphic alleles in five IRG SNPs revealed a linear increase in risk (OR=2.00 per incremental change; P=0.002). Having three or more alleles compared with none was associated with increased risk in males (OR=4.12; P=0.004). Significant risk associations with childhood ALL was found with birth length (OR=1.18 per inch, P=0.04), high birth weight (>4,000g) (OR=1.93, P=0.01), and with gestational age (OR=1.10 per week, P=0.04). We observed a negative correlation between HFE SNP rs9366637 and gestational age (P=0.005), again, stronger in males ( P=0.001) and interacting with TFRC (P interaction=0.05). Our results showed that (i) ALL risk markers do not show universal associations across ethnicities or between genders, (ii) IRG SNPs modify ALL risk presumably by their effects on iron levels, (iii) a negative correlation between an HFE SNP and gestational age exists, which implicates an iron-related mechanism. The results suggest that currently unregulated supplemental iron intake may have implications on childhood ALL development.

A Conference on The 200th Anniversary of the Birth of Gertrud is Gómez de Avellaneda: A Celebration of Nineteenth-Century Cuban Literature

This flyer promotes the event "A Conference on The 200th Anniversary of the Birth of Gertrud is Gómez de Avellaneda: A Celebration of Nineteenth-Century Cuban Literature" cosponsored by the Cuban Research Institute and the Department of Modern Languages at Florida International University.

Avaliação do ganho de peso de bebês prematuros em relação ao leite materno cru e leite pasteurizado

This study aims to evaluate the weight gain of premature newborns fed with breast milk from their mothers' from those that are fed with breast milk from the milk bank. The research is the quantitative, descriptive and observational kind. It was conducted in the Neonatal Intensive Care Unit and Housing from the Maternity Hospital Escola Januário Cicco (MEJC), that is a reference for high risk pregnancy and birth in Rio Grande do Norte. The premature newborns included were following these parameters: gestational age from 26 to 37 weeks, initially hospitalized at UTIN, with oral diet, by means by gavage, cup and/or suction. Studies with premature newborns with a zero diet longer than seven days or complications that interfered in the evaluation of weight gain were excluded from this study. The sample was selected for convenience and had data of all newborns hospitalized at UTIN from the May to June of 2014 time period, followed to their discharge, ended by August of 2014 and had the inclusion parameters of the study. From the period of the data collection, 60 premature newborns entered the maternity and 39 of those were the sample of research. The project was approved by the Research Ethics Committee from UFRN, under CAAE nº 0699.0.000.294-11. The data was analyzed by means of descriptive and deduced statistics. The results indicated that the involved in the study, were born from mother with average age of 25,36 years, with less than nine years education 21 (53,8%), had the family income less than a minimum wage 24 (61,5%). Among the newborn, the female gender predominated 20 (51,3%), had cesarean delivery 25 (64,1%), had moderate prematurity 29 (74,5%), more of 1.500g 22 (556,4%). The birth weight average was 1.608,49g. The total of diets were 9.994, and an average of 256 for each newborn, in a 32,12 days of hospitalization time period. Most of the diet supplies were from the breast milk bank (50,34%), however 56,4% of the newborns had most of the diet from their mothers' milked breast milk. It was detected that 38,5% of the newborns had, in some given moment, artificial milk. The daily weight gain average of all newborns was 2,59g, but 35% of them had an average above 10g per day. From the newborn's group (n=25) that had medium weight gain, only 9 of them (36,0%) received mainly their own mothers' milked breast milk. It's been conclusive that most of the premature newborns gained weight predominantly from diets from the breast milk of the Milk Bank, showing the need of a bigger incentive to exclusive breast feeding.

Avaliação da suplementação de vitamina E sobre a concentração de alfa-tocoferol no leite materno em mulheres com partos prematuros

The term vitamin E refers to a group of eight molecular compounds which differ in structure and bioavailability, and the RRR-alpha-tocopherol more biologically active form. The composition of vitamin E in breast milk undergoes variations during lactation, colostrum and milk richer in this micronutrient compared to transitional and mature milk. Newborns, especially premature infants are more susceptible to vitamin E deficiency and to prevent the damage caused by this deficiency has been proposed supplementation of neonates with this micronutrient, however, there is no consensus to carry out this intervention. Thus, maternal supplementation with RRRalpha-tocopherol in the postpartum period can be a good alternative to try to raise the alpha-tocopherol levels in breast milk and therefore provide the premature newborn adequate amounts of vitamin E. This study to evaluate the effect of supplementation with 400 UI acetate RRR-alpha-tocopherol in women with premature births, on the concentration of alpha-tocopherol in breast milk colostrum, transitional and mature. The study included 89 healthy adult women were enrolled in the control group (n = 51) and supplemented group (n = 38). Blood samples were collected and milk colostrum soon after birth (0h milk) twenty-four hours, new rate of colostrum milk was collected (24h milk). The transitional and mature milk were collected in seven days (7d milk) and thirty days (30d milk) after delivery, respectively. Supplementation in the supplemented group was held after the collection of blood and 0h milk. The alpha-tocopherol analyzes were performed by high-performance liquid chromatography. Serum levels of alpha-tocopherol less than 516 μg/dL were considered indicative of nutritional deficiency. The average concentration of alphatocopherol in the serum of the control group mothers was 1159.8 ± 292.4 μg/dL and the supplemented group was 1128.3 ± 407.2 μg/dL (p = 0.281). All women had nutritional status in vitamin E suitable. In both groups, it was observed that the concentration of vitamin E in colostrum milk was higher compared to transitional and mature milk. In the supplemented group, the concentration of alpha-tocopherol in the milk increased 60 % after supplementation, from 1339.3 ± 414.2 μg/dL (0h milk) to 2234.7 ± 997.3 μg/dL (24h milk). While the control group values in colostrum 0h and colostrum 24h were similar (p = 0.681). In the control group the follow-on milk alphatocopherol value was 875.3 ± 292.4 μg/dL and in the group supplemented 1352.8 ± 542.3 μg/dL, an increase of 35% in the supplemented group compared to control (p <0.001). In mature milk alpha-tocopherol concentrations between the control group (426.6 ± 187.5 μg/dL) and supplemented (416.4 ± 214.2 μg/dL) were similar (p = 0.853). Only 24h milk supplemented group answered the nutritional requirement of alpha-tocopherol (4 mg/day) of the newborn. These results show that the transport of this micronutrient for milk occurs in a controlled and limited way. Thus, the native vitamin E supplementation increases the concentration of alpha-tocopherol in colostrum and milk and transition does not influence the concentration in mature milk. Only the increase in colostrum milk was sufficient to meet the nutritional requirement of premature newborns.

Perfil de mães e o desfecho do nascimento prematuro ou termo

The birth or delivery under 37 weeks of pregnancy is considered a global public health problem, since it is seen as one of the main risk factors for neonatal morbidity and mortality, particularly in the first week of life. This study had the objective of analyzing the profile of mothers of premature and full-term babies for the outcome of birth. This is an analytical-descriptive and cross-sectional study, with a sample of 109 mothers of all the premature babies and 135 mothers of the randomly selected full-term babies, by drawing, occurred in the period from April to September 2015, in a public maternity. Data were organized on Microsoft Excel 2013; subsequently, there was the analysis of the analytical-descriptive statistics, through Statistica 10, through which the frequencies, proportions, p values, with 5% significance level, through the Chi-square test, were identified. The project was submitted to the Research Ethics Committee of the Federal University of Rio Grande do Norte, receiving a favorable opinion (nº 1047431/2015). This study has enabled us to identify that the socioeconomic profile of mothers of premature and full-term babies showed, in both, low schooling level and low income. In addition, our data point out in the two groups, before and during pregnancy, a high prevalence of sedentariness; statistical significance for overweight and obesity before and during pregnancy, with 42,22% prevalence before pregnancy of mothers of premature babies and 48,62% of mothers of full-term babies; with high blood pressure during pregnancy in 32,11% of mothers of premature babies and 17,04% of mothers of full-term babies. Moreover, pregnancy was only planned in 33,33%, and also unwanted by 21,1% of mothers of premature babies, while 40,37% of mothers of full-term babies planned pregnancy and 17,78% had unwanted pregnancy. With respect to the aggravating factor “illicit drugs”, there was consumption during pregnancy on the part of 8,26% of mothers of premature babies. The most frequent complications were: vaginal bleeding (in 43,12% of mothers of premature babies and 20% of mothers of full-term babies); urinary infection (in 44,95% of mothers of premature babies and 40% of mothers of full-term babies); and stressful pregnancy (in 62,96% of mothers of premature babies and 47,41% of mothers of full-term babies). Accordingly, babies were born with health problems in 58,10% of premature births and there was healthy birth in 96,30% of full-term babies. Therefore, the profile of mothers with obesity and overweight, unwanted pregnancy, user of illegal drugs during pregnancy, stressful pregnancy and vaginal bleeding may be associated with the birth of premature baby as unfavorable and hazardous event for the child’s health.

Perfil de mães e o desfecho do nascimento prematuro ou termo

The birth or delivery under 37 weeks of pregnancy is considered a global public health problem, since it is seen as one of the main risk factors for neonatal morbidity and mortality, particularly in the first week of life. This study had the objective of analyzing the profile of mothers of premature and full-term babies for the outcome of birth. This is an analytical-descriptive and cross-sectional study, with a sample of 109 mothers of all the premature babies and 135 mothers of the randomly selected full-term babies, by drawing, occurred in the period from April to September 2015, in a public maternity. Data were organized on Microsoft Excel 2013; subsequently, there was the analysis of the analytical-descriptive statistics, through Statistica 10, through which the frequencies, proportions, p values, with 5% significance level, through the Chi-square test, were identified. The project was submitted to the Research Ethics Committee of the Federal University of Rio Grande do Norte, receiving a favorable opinion (nº 1047431/2015). This study has enabled us to identify that the socioeconomic profile of mothers of premature and full-term babies showed, in both, low schooling level and low income. In addition, our data point out in the two groups, before and during pregnancy, a high prevalence of sedentariness; statistical significance for overweight and obesity before and during pregnancy, with 42,22% prevalence before pregnancy of mothers of premature babies and 48,62% of mothers of full-term babies; with high blood pressure during pregnancy in 32,11% of mothers of premature babies and 17,04% of mothers of full-term babies. Moreover, pregnancy was only planned in 33,33%, and also unwanted by 21,1% of mothers of premature babies, while 40,37% of mothers of full-term babies planned pregnancy and 17,78% had unwanted pregnancy. With respect to the aggravating factor “illicit drugs”, there was consumption during pregnancy on the part of 8,26% of mothers of premature babies. The most frequent complications were: vaginal bleeding (in 43,12% of mothers of premature babies and 20% of mothers of full-term babies); urinary infection (in 44,95% of mothers of premature babies and 40% of mothers of full-term babies); and stressful pregnancy (in 62,96% of mothers of premature babies and 47,41% of mothers of full-term babies). Accordingly, babies were born with health problems in 58,10% of premature births and there was healthy birth in 96,30% of full-term babies. Therefore, the profile of mothers with obesity and overweight, unwanted pregnancy, user of illegal drugs during pregnancy, stressful pregnancy and vaginal bleeding may be associated with the birth of premature baby as unfavorable and hazardous event for the child’s health.

Length of stay in a neonatal intensive care unit and its association with low rates of exclusive breastfeeding in very low birth weight infants

OBJECTIVE: To identify the inpatient maternal and neonatal factors associated to the weaning of very low birth weight (VLBW) infants. METHODS: One hundred nineteen VLBW (<1500 g) infants were monitored from July 2005 through August 2006, from birth to the first ambulatory visit after maternity discharge. This maternity unit uses the Kangaroo Method and the Baby Friendly Hospital Initiative. Out of 119 VLBW infants monitored until discharge, 88 (75%) returned to the facility, 22 (25%) were on exclusive breastfeeding (EB), and 66 (75%) were weaned (partial breastfeeding or formula feeding). RESULTS: Univariate analysis found an association between weaning and lower birth weight, longer stays in the neonatal intensive care unit (NICU), and longer hospitalization times, in addition to more prolonged enteral feeding and birth weight recovery period. Logistic regression showed length of NICU stay as being the main determinant of weaning. CONCLUSION: The negative repercussion on EB of an extended stay in the NICU is a significant challenge for health professionals to provide more adequate nutrition to VLBW infants.

Length of stay in a neonatal intensive care unit and its association with low rates of exclusive breastfeeding in very low birth weight infants

OBJECTIVE: To identify the inpatient maternal and neonatal factors associated to the weaning of very low birth weight (VLBW) infants. METHODS: One hundred nineteen VLBW (<1500 g) infants were monitored from July 2005 through August 2006, from birth to the first ambulatory visit after maternity discharge. This maternity unit uses the Kangaroo Method and the Baby Friendly Hospital Initiative. Out of 119 VLBW infants monitored until discharge, 88 (75%) returned to the facility, 22 (25%) were on exclusive breastfeeding (EB), and 66 (75%) were weaned (partial breastfeeding or formula feeding). RESULTS: Univariate analysis found an association between weaning and lower birth weight, longer stays in the neonatal intensive care unit (NICU), and longer hospitalization times, in addition to more prolonged enteral feeding and birth weight recovery period. Logistic regression showed length of NICU stay as being the main determinant of weaning. CONCLUSION: The negative repercussion on EB of an extended stay in the NICU is a significant challenge for health professionals to provide more adequate nutrition to VLBW infants.

Thalidomide and birth defects

Apologies to the many papers we were unable to cite, due to space constraints. We thank Lynda Erskine, Shaunna Beedie and Chris Mahony for helpful discussions. Lucas Rosa Fraga is funded by a PhD scholarship from the Science without Borders program - CNPq Brazil - INAGEMP/ Grant CNPq 573993/2008-4. Alex J. Diamond is funded by a BBSRC DTP PhD Scholarship.

Thalidomide and birth defects

Apologies to the many papers we were unable to cite, due to space constraints. We thank Lynda Erskine, Shaunna Beedie and Chris Mahony for helpful discussions. Lucas Rosa Fraga is funded by a PhD scholarship from the Science without Borders program - CNPq Brazil - INAGEMP/ Grant CNPq 573993/2008-4. Alex J. Diamond is funded by a BBSRC DTP PhD Scholarship.

Cumulative live birth rates after one or more complete cycles of IVF : a population-based study of linked cycle data from 178 898 women

© The Author 2016. 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.

Childhood intelligence predicts premature mortality : Results from a 40-year population-based longitudinal study

Acknowledgements This study was supported by a grant from the Luxembourg Fonds National de la Recherche (VIVRE FNR/06/09/18) and a PhD scholarship awarded to the first author by the Fonds National de la Recherche.

Home birth in Ireland 1993-1997: a review of community midwifery practice

To date little is known about the practices of domiciliary midwives and the outcomes of home birth in Ireland. The purpose of this review is to provide some background information on the situation for women seeking a home birth and to document the outcomes of home births in Ireland between 1993 -1997. Design: Descriptive analysis of prospective data collected from domiciliary midwives regarding women who requested a home birth between 1993 and 1997. Participants: The questionnaire was distributed to 15 domiciliary midwives; this included all the domiciliary midwives known to the authors to be practising in Ireland at that time. Findings: During this period, 585 women planned to give birth in their home with the assistance of midwives, 500 women achieved this. The spontaneous vaginal delivery rate for women who commenced their labour at home was 96.9% (n = 554). These women gave birth without medications or other interventions. 544 (93%) of the women breastfed their babies and 538 (92%) were still breastfeeding at 6 weeks. This is the first review of domiciliary midwifery practice in Ireland in recent years. They obtained data from 11 independent midwives on 585 women who planned home births. Findings showed high rates of spontaneous vaginal delivery and breastfeeding. There were 500 babies born at home with three perinatal deaths, including one undiagnosed breech delivery, one infant with abnormal lungs on post-mortem and one infant with Potter's Syndrome who was stillborn.