Association of kinase insert domain-containing receptor (KDR) gene polymorphism/ haplotypes with recurrent spontaneous abortion and genetic structure

Background: Recurrent spontaneous abortion is one of the diseases that can lead to physical, psychological, and, economical problems for both individuals and society. Recently a few numbers of genetic polymorphisms in kinase insert domain-containing receptor (KDR) gene are examined that can endanger the life of the fetus in pregnant women. Objective: The risk of KDR gene polymorphisms was investigated in Iranian women with idiopathic recurrent spontaneous abortion (RSA). Materials and Methods: A case controlled study was performed. One hundred idiopathic recurrent spontaneous abortion patients with at least two consecutive pregnancy losses before 20 weeks of gestational age with normal karyotypes were included in the study. Also, 100 healthy women with at least one natural pregnancy were studied as control group. Two functional SNPs located in KDR gene; rs1870377 (Q472H), and rs2305948 (V297I) as well as one tag SNP in the intron region (rs6838752) were genotyped by using PCR based restriction fragment length polymorphism (PCR-RFLP) technique. Haplotype frequency was determined for these three SNPs’ genotypes. Analysis of genetic STRUCTURE and K means clustering were performed to study genetic variation. Results: Functional SNP (rs1870377) was highly linked to tag SNP (rs6838752) (D´ value=0. 214; χ2 = 16.44, p<0. 001). K means clustering showed that k = 8 as the best fit for the optimal number of genetic subgroups in our studied materials. This result was in agreement with Neighbor Joining cluster analysis. Conclusion: In our study, the allele and genotype frequencies were not associated with RSA between patient and control individuals. Inconsistent results in different populations with different allele frequencies among RSA patients and controls may be due to ethnic variation and used sample size.

Étude de l’impact de la prise de médicaments dans le traitement de l’arthrite juvénile sur les événements néfastes à l’accouchement chez la mère et son bébé

La plupart des femmes ayant été atteintes d’arthrite juvénile idiopathique (AJI) continuent de souffrir d’arthrite à l’âge adulte. Certains des médicaments utilisés dans le traitement de l’arthrite tels que les corticostéroïdes et les antiinflammatoires non stéroïdiens (AINS) ne sont pas recommandés durant la grossesse. Le but de ce mémoire est d’estimer l’impact de la prise de ces médicaments sur les événements néfastes à l’accouchement chez ces femmes et leur bébé. Des données administratives sur les prescriptions de médicaments et les hospitalisations d’une cohorte de 1756 femmes ayant souffert d’AJI sont utilisées. Elles ont permis de reconstruire l’historique de consommation de médicaments contre l’arthrite chez les femmes durant la grossesse et l’année précédente. Pour ce faire, deux sous-cohortes de femmes ayant souffert d’AJI ont été formées : une pour la période grossesse et une autre pour la grossesse et l’année précédant celle-ci. Les événements d’intérêt étaient : malformations congénitales, complications néonatales, complications maternelles et petit poids pour l’âge gestationnel. Les proportions de cas présentant l’un de ces événements variaient entre 11,52% et 37,08%. Les médicaments ont été modélisés en terme d’utilisation ou de durée totale de consommation durant la période d’étude. Pour chaque événement, des modèles logistiques ont été estimés pour mesurer l’association entre la prise de médicaments et l’événement, en ajustant pour des variables de confusion potentielles : hypertension avant la grossesse, âge à l’accouchement et obtention du diplôme de secondaire. La consommation de corticostéroïdes semble augmenter statistiquement significativement le risque de présenter des malformations congénitales mais n’avoir aucun impact sur les autres événements. Aucun lien statistiquement significatif n’a été observé entre la consommation de AINS et les événements d’intérêt.

Étude de l’impact de la prise de médicaments dans le traitement de l’arthrite juvénile sur les événements néfastes à l’accouchement chez la mère et son bébé

L'obtention des données a été subventionnée par CIORA (Canadian Initiative for Outcomes in Rheumatology Care). CIORA a aussi financé l'analyse des données effectuées par Justine Zehr. L'Initiative Canadienne Pour Des Resultats En Soins Rhumatologiques (ICORA) a financé l'obtention des données et une partie de l'analyse statistique présentée dans ce mémoire.

The relationship between 25-hydroxyvitamin D concentration in early pregnancy and pregnancy outcomes in a large, prospective cohort

Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations <75 nmol/l at 15 weeks of gestation were more likely to develop gestational diabetes mellitus than those with concentrations >75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.

Establishment and development of infant gut microbiota

The nascent gut microbiota at birth is established in concert with numerous developmental parameters. Here, in the INFAMTET study, we chronicled the impact of some factors which are key determinants of the infant gut microbiota, namely; mode of birth, gestational age, and type of feeding. We determined that the aggregated microbiota profile of naturally delivered, initially breastfed infants are relatively stable from one week to six months of age and are not significantly altered by increased duration of breastfeeding. Contrastingly, there is significant development of the microbiota profile of C-section delivered infants, and this development is significantly influenced by breastfeeding duration. Preterm infants, born by either mode of birth, initially have a high proportion of Proteobacteria, and demonstrate significant development of the gut microbiota from week 1 to later time-points. The microbiota is still slightly, but significantly, affected by birth mode at one year of age although no specific genera were found to be significantly altered in relative abundance. By two years of age, there is no effect of either birth mode or gestational age. However this does not preclude the possibility that symptoms developed later in life, which are associated with preterm or C-section birth, are as a result of the early perturbation of the neonatal gut microbiota. It is likely that the combination of relatively low exposure (breast fed), high exposure (formula fed) or delayed exposure (C-section and preterm) to specific antigens and the resulting inflammatory responses, in this crucial window of host-microbiota interaction, influence systemic health of the individual throughout life.

Efeitos ventilatórios da fisioterapia respiratória com e sem hiperinsuflação manual em recém-nascidos pré-termos sob ventilação mecânica

Atualmente, os recém-nascidos nascem cada vez mais prematuros, dependendo de cuidados intensivos neonatais. Nesse sentido, a fisioterapia respiratória tem adquirido um espaço cada vez maior, e juntamente com uma equipe multidisciplinar presta assistência a esses recém-nascidos prematuros. Entre as diversas técnicas utilizadas pelos fisioterapeutas, a hiperinsuflação manual tem tido papel fundamental na remoção de secreções brônquicas. Objetivo: Avaliar os efeitos hemodinâmicos e respiratórios da fisioterapia respiratória, com ou sem a manobra de hiperinsuflação manual em recém-nascidos prematuros. Método: Participaram deste estudo 9 recém-nascidos prematuros com idade gestacional média 32,364 semanas, nascidos no Hospital Universitário Alzira Velano, no período de abril a novembro de 2015. Os recém-nascidos foram aleatoriamente divididos em 2 grupos: B, onde se realizou a fisioterapia respiratória associada a hiperinsuflação manual; e o grupo A, em que receberam somente a fisioterapia respiratória. Foram avaliados os seguintes parâmetros: frequência cardíaca, frequência respiratória e saturação de oxigênio, 5 minutos antes da realização dos procedimentos, 1 minuto e trinta minutos após os procedimentos. Resultados: Em relação à frequência cardíaca, a fisioterapia respiratória (FR) não demonstrou diferenças estatisticamente significativas nos momentos avaliados A1 (147,80), A2 (158,40) e A3 (151,20), bem como na fisioterapia respiratória associada à hiperinsuflação manual (FR+HM) nos mesmos momentos A1 (130,75), A2 (138,50) e A3 (137,25). Na frequência respiratória também não se verificou diferenças estatisticamente significativas nos momentos A1 (53,80), A2 (50,60) e A3 (46,60) com FR e nos mesmos momentos A1 (57,00), A2 (52,25) e A3 (59,50) com FR+HM. Na saturação de oxigênio, a FR nos momentos avaliados A1 (94,80), A2 (95,60) e A3 (95,60) não demonstrou alterações estatisticamente significativas como visto também na FR+HM nos mesmos momentos avaliados A1 (94,25), A2 (92,50) e A3 (95,00).Conclusão: Verificou-se com os resultados que as frequências cardíacas e respiratórias e a saturação de oxigênio não apresentaram diferenças estatisticamente significativas pré e pós realização da fisioterapia respiratória convencional ou associada à hiperinsuflação manual.

Changes in the prevalence of breast feeding in preterm infants discharged from neonatal units : a register study over 10 years

Objective: There are indications that the prevalence of exclusively breastfed preterm infants is decreasing in Sweden. The objective was to investigate trends in exclusive breast feeding at discharge from Swedish neonatal units and associated factors in preterm infants. Design, setting and participants: This is a register study with data from the Swedish Neonatal Quality Register. Data from 29 445 preterm infants (gestational age (GA) <37 weeks) who were born during the period 2004–2013 were retrieved. Data included maternal, perinatal and neonatal characteristics. Data were analysed for the whole population as well as for 3 GA groups. Results: From 2004 to 2013, the prevalence of exclusive breast feeding decreased, in extremely preterm (GA 22–27 weeks) from 55% to 16%, in very preterm (GA 28–31 weeks) from 41% to 34% and in moderately preterm infants (GA 32–36 weeks) from 64% to 49%. The decline was statistically significant (p<0.001) in all 3 GA groups. This decline remained significant when adjustments were made for factors negatively associated with exclusive breast feeding and which became more prevalent during the study period, that is, small for GA (all groups) and maternal mental illness (very preterm and moderately preterm infants). Conclusions: In the past 10 years, Sweden has experienced a lower rate of exclusive breast feeding in preterm infants, especially in extremely preterm infants. The factors analysed in this study explain only a small proportion of this decline. The decline in exclusive breast feeding at discharge from neonatal units raises concern and present challenges to the units to support and promote breast feeding.

Impact de trois interventions: méthode mère kangourou, massage en incubateur et massage en position kangourou sur la croissance et le développement des enfants prématurés nés à moins de 33 semaines d’âge gestationnel

Cette recherche vise à étudier l’impact d’interventions réalisées par les parents dans l’unité néonatale de soins intensifs. Plus spécifiquement, le premier objectif est de documenter les effets différentiels de la Méthode Mère Kangourou « MMK » accompagnée ou non du Massage en incubateur «MI » ou du Massage en Position Kangourou « MPK » et des Soins Traditionnels «ST » accompagnés ou non du massage dans l’incubateur sur la croissance physique mesurée par le poids, la taille et le périmètre crânien pendant une période de 5 et 15 jours dans l’unité néonatale et l’impact à 40 semaines d’âge gestationnel. Le second objectif est de comparer, chez des enfants qui bénéficient de la « MMK » la valeur ajoutée du « MPK » ou du «MI » sur le neuro-développement à 6 et 12 mois d’âge corrigé de l’enfant. Un échantillon total de 198 enfants et leur famille a été recruté de la façon suivante dans trois hôpitaux de Bogota. Dans chaque hôpital, 66 sujets ont été répartis aléatoirement à deux conditions. Ces hôpitaux ont été choisis afin de tester les effets de diverses conditions expérimentales et de diminuer les bais de sélection. Dans chaque hôpital, deux techniques ont été assignées aléatoirement. Il s’agit, dans le premier, de la « MMK & MPK » vs « MMK & MI ». Dans le second, « MMK sans massage » vs « MMK & MI ». Dans le troisième, « MI » a été comparé aux « ST » ce qui implique une absence de contact physique continu des bébés avec leurs parents. Les résultats rapportés dans le premier article sont à l’effet que, dans le premier hôpital, il y a un effet compensatoire de l’intervention « MMK & MPK » sur la perte physiologique du poids de l’enfant prématuré dans les 15 premiers jours de vie avec un impact sur le poids à 40 semaines d’âge gestationnel, sur la durée du portage kangourou et sur la durée d’hospitalisation totale. Aucun effet sur le périmètre crânien ou la taille n’est apparu. Dans le deuxième hôpital, aucune différence significative n’est rapportée pour le poids sauf quand l’intervention est commencée après le 10ième jours de vie alors que l’enfant « MPK» semble grossir mieux que le «MMK avec MI». Finalement, dans le troisième hôpital il n’y a aucun effet du massage sur les variables anthropométriques, le groupe avec MI grossissant moins vite avec un léger impact sur le poids à 40 semaines. Cela pourrait être dû à la perte de chaleur due à l’ouverture de l’incubateur quand l’enfant est très immature. Dans le second article, les 66 enfants de l’hôpital sont répartis aléatoirement dans le groupe « MMK & MPK» vs le groupe « MMK & MI», ont complété, à 6 et 12 mois d’âge corrigé, un test de neuro-développement, le Griffiths. Les résultats à 6 mois ne montrent aucune différence entre les 2 interventions, mais a 12 mois le IQ semble dépendant du nombre de jours d’hospitalisation de l’enfant, cette durée d’hospitalisation correspond au temps que met l’enfant à se stabiliser physiquement et correspond également au temps que mettent la mère et l’enfant à s’adapter à la méthode kangourou. Une fois, l’adaptation kangourou réussie, la dyade mère enfant sort avec l’enfant toujours en position kangourou. Le temps d’hospitalisation correspond au temps que met l’enfant à être éligible à l’apprentissage de la MMK par la mère. À 12 mois les deux groupes montrent des résultats équivalents, mais des différences positives sont apparues pour le groupe « MMK & MPK» dans les sous échelle Coordination Oculo Manuelle et Audition et Langage du test Griffiths. Dans l’ensemble, les résultats suggèrent que la pratique des deux interventions non traditionnelles peut contribuer à une meilleure croissance physique dans nos cohortes. Le gain de poids du bébé, notamment, est affecté par l’intervention MPK (Hôpital 1) ou sans l’ajout du Massage (Hôpital 2). Par ailleurs, le massage en incubateur n’a pas de différence significative en comparaison aux soins traditionnels, ces interventions ont toutefois un impact mineur (tendances) sur le neuro développement à 6 et 12 mois d’âge corrigé dans cette étude.

Asfixia perinatal y proteína S100B

La asfixia perinatal es la principal causa de muerte en la primera semana de vida la nivel mundial, los niños que sufren esta complicación y sobreviven pueden presentar trastornos neurológicos de diferente nivel de compromiso que inciden en su desarrollo personal y social. Las cifras de muerte por este problema de salud han disminuido de manera importante, sin embargo en el reporte de la Organización Mundial de Salud (OPS) del 2010, la asfixia perinatal es causa del 29% de muertes infantiles en los países de América Latina y el Caribe 2. Es necesario conocer además la extensión del daño neurológico que sufren estos niños, con este fin se desarrolló un estudio piloto en el Hospital Universitario Mayor Mederi de Bogotá, en el cual se determinó la concentración de un marcador metabólico de daño cerebral, la proteína S100B en suero de 60 recién nacidos sanos, con el objetivo de analizar la asociación del mismo con el peso al nacer, la edad gestacional y el diagnóstico. Los resultados no mostraron diferencias significativas entre este marcador y las variables analizadas que puede asociarse al pequeño número de pacientes, sin embargo han sentado las bases para el desarrollo de un estudio que incluya varios hospitales de Bogotá y sobre todo la determinación del mismo en recién nacidos con diagnóstico de hipoxia en el período perinatal, lo cual aportará información del grado de la alteración que puedan tener a nivel cerebral y contribuya al mejor manejo evolutivo con la aplicación de medidas de intervención en estadios tempranos de la vida.

Diclofenaco comparado con ibuprofeno para el cierre de Ductus arterioso persistente, en recién nacidos prematuros

Introducción: El Ductus arterioso persistente (DAP), es uno de los defectos congénitos cardiacos más comunes, requiere manejo farmacológico y/o quirúrgico; presenta complicaciones hemodinámicas, respiratorias y muerte. Los medicamentos de elección para su manejo son indometacina e ibuprofeno, pero su costo y accesibilidad llevo al uso de diclofenaco como alternativa de manejo en algunos hospitales. Objetivo: Comparar respuesta al tratamiento con diclofenaco vs ibuprofeno en cierre de DAP. Materiales y Métodos: Estudio observacional analítico retrospectivo, que compara los resultados obtenidos al usar Diclofenaco e Ibuprofeno para el cierre del DAP en recién nacidos pretérmino. Se recolecto información de pacientes hospitalizados en la Unidad Neonatal de un Hospital II nivel de Bogotá. Se revisaron las historias clínicas de pacientes de edad gestacional entre 24 y 36 semanas por Ballard con los criterios para diagnóstico de DAP y recibieron tratamiento farmacológico con una de las siguientes opciones: Ibuprofeno 10 mg/Kg dosis inicial después 5mg/Kg a las 24 48 horas, o Diclofenaco 0.2 mg/Kg dosis cada 12 horas tres dosis. Se comparó el Diclofenaco y el Ibuprofeno para el tratamiento farmacológico de DAP en recién nacidos prematuros. Resultados: Fueron evaluados 103 pacientes, el diagnóstico de DAP se realizó con ecocardiograma transtorácico, el 66.6 % de los pacientes presentó cierre farmacológico con Diclofenaco y 69 % con Ibuprofeno, La mortalidad fue de 17.65 % con Diclofenaco y 11.54 % con ibuprofeno; en ambos casos asociadas a la prematurez. Conclusiones: El éxito farmacológico fue similar en ambos grupos, el diclofenaco es una alternativa interesante cuando la terapia convencional no esté disponible.

Elevación transitoria de TSH neonatal asociada a factores de riesgo de parto pretérmino

Introducción: La hipotiroxinemia es una alteración transitoria frecuente en el prematuro que resuelve sin medicación, es importante conocer los factores que se asocian con esta alteración para disminuir el tratamiento inoportuno y el aumento de costos en atención en salud que puede implicar un diagnóstico errado de hipotiroidismo congénito. Por medio de este estudio se evaluó la asociación entre elevación transitoria de la TSH neonatal y algunas variables asociadas a parto pretérmino en pacientes atendidos en la Clínica Materno Infantil Colsubsidio nacidos entre Enero 2014 a Abril de 2015. Metodología: Se realizó un estudio de casos y controles, analítico, retrospectivo. Los casos fueron prematuros con elevación de TSH sin hipotiroidismo congénito, los controles fueron prematuros con TSH normal, seleccionados de manera aleatoria 70 casos, 140 controles con una relación 1:2. Se realizaron asociaciones mediante prueba de chi cuadrado y análisis multivariado para controlar factores de confusión. Resultados: La edad gestacional promedio para casos fue 34.6±1.8, para controles 34.2±2.4. Ambas poblaciones fueron comparables. Los factores con resultados estadísticamente significativos fueron: Pielonefritis (p 0.04), hipertensión inducida por el embarazo (p 0.00), presencia de anemia (p 0.02) y embarazo múltiple (p0.03). Los resultados de regresión logística establecieron que la pielonefritis, hipertensión y anemia son factores de riesgo con resultados estadísticamente significativos. Discusión: Los resultados permitieron documentar que existen factores de riesgo para prematurez, como la pielonefritis, anemia materna e hipertensión inducida por el embarazo, que influyen en los valores de TSH de cordón umbilical que no necesariamente conllevan al desarrollo de hipotiroidismo congénito

Neonatal outcomes following maternal SARS-CoV-2 infection in pregnancy - longitudinal follow-up and assessment of transplacental antibody transfer

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in pregnancy has been associated with multiple adverse pregnancy outcomes, including the risk of in utero mother-to-child transmission. Short- and long-term outcomes of SARS-CoV-2 exposed neonates and the extent to which maternal SARS-CoV-2 antibodies are transferred to neonates are still unclear. METHODS: Prospective observational study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy, between April 2020-April 2021. Neonates were evaluated at birth and enrolled in a 12-month follow-up. SARS-CoV-2 IgG transplacental transfer ratio was assessed in mother-neonate dyads at birth. Maternal derived IgG were followed in infants until negativizing. RESULTS: Of 2745 neonates, 106 (3.9%) were delivered by mothers with SARS-CoV-2 infection in pregnancy. Seventy-six of 106 (71.7%) mothers were symptomatic. Median gestational age and mean birth weight were 39 weeks (range 25+5-41+4) and 3305 grams (SD 468). Six of 106 (6%) neonates were born preterm, without significant differences between asymptomatic and symptomatic mothers (P=0.67). No confirmed cases of in utero infection were detected. All infants had normal cerebral ultrasound and clinical evaluation at birth and during follow-up, until a median age of 7 months (range 5-12). All mothers and 96/106 (90.5%) neonates had detectable SARS-CoV-2 IgG at birth. Transplacental transfer ratio was higher following second trimester maternal infections (mean 0.940.46 versus 1.070.64 versus 0.750.44, P=0.039), but was not significantly different between asymptomatic and symptomatic women (P=0.20). IgG level in infants progressively decreased after birth: at 3 months 53% (51/96) and at four months 68% (63/96) had lost maternal antibodies respectively. The durability of maternal antibodies was positively correlated to the IgG level at birth (r=0.66; P<0.00001). CONCLUSIONS: Maternal SARS-CoV-2 infection was not associated with increased neonatal or long-term morbidity. No cases of confirmed in utero infection were detected. Efficient transplacental IgG transfer was found following second trimester maternal infections.

Studio prospettico osservazionale sull'interruzione volontaria farmacologica di gravidanza: fattori predittivi di dolore pelvico durante il trattamento

INTRODUZIONE Pochi studi in Letteratura hanno indagato la correlazione tra la sintomatologia dolorosa associata all’interruzione farmacologica di gravidanza (IVG) e i livelli d’ansia pre-trattamento. L’obiettivo primario del nostro studio è stato di valutare la correlazione tra la sintomatologia dolorosa in corso di IVG farmacologica e i livelli d’ansia pre-trattamento. Inoltre, sono stati indagati i fattori predittivi di dolore e la correlazione con l’epoca gestazionale. MATERIALI E METODI È stato condotto uno studio osservazionale, prospettico, multicentrico presso l’Unità Operativa di Ostetricia e Ginecologia dell’Azienda USL e presso l’Unità Operativa di Ginecologia dell’IRCCS Sant’Orsola Malpighi di Bologna. Sono state incluse le pazienti sottoposte a IVG farmacologica tra giugno 2021 e novembre 2021, che rispettassero i criteri di inclusione ed esclusione. Sono stati somministrati 5 questionari (GHQ-12, GAD-7, STAI-6, VAS) e raccolti i dati anamnestici ed ecografici. I potenziali fattori di rischio sono stati, quindi, selezionati per l’inclusione nell'analisi di regressione multivariata. RISULTATI Delle 242 pazienti incluse, il 38,0% ha riferito una sintomatologia dolorosa severa (VAS >70). Dall’analisi di regressione multivariata, la dismenorrea intensa è risultata essere il fattore di rischio più forte per il dolore (OR = 6,30, IC 95% 2,66 – 14,91), seguita da alti livelli di ansia valutati mediante il punteggio del GHQ-12 > 9 (OR = 3,33, IC 95% 1,43 – 7,76). Al contrario, la nostra analisi ha confermato che un precedente parto vaginale rappresentava una caratteristica protettiva contro il dolore (OR 0,26, IC 95% 0,14 – 0,50). CONCLUSIONI Nel nostro studio alti livelli d’ansia pre-trattamento e la dismenorrea sono associati ad intensa sintomatologia dolorosa, mentre il parto vaginale è risultato protettivo. L’IVG farmacologica è una metodica efficace e sicura, ma spesso associata a sintomatologia dolorosa. È quindi fondamentale delineare fattori di predittivi di dolore ed individuare le pazienti a maggior rischio a cui somministrare un’idonea terapia antalgica.

Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age

Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD) fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein) or normal protein diet (18% casein; NPD) was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively), throughout gestation (LPD, NPD) or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD). LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD). LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr) and insulin-like growth factor I receptor (Igf1r) in retroperitoneal fat was significantly elevated in Emb-LPD females (P&0.05), whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1) gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring health. © 2011 Watkins et al.

The effect of gestational and lactational age on the human milk metabolome

Human milk is the ideal nutrition source for healthy infants during the first six months of life and a detailed characterisation of the composition of milk from mothers that deliver prematurely (<37 weeks gestation), and of how human milk changes during lactation, would benefit our understanding of the nutritional requirements of premature infants. Individual milk samples from mothers delivering prematurely and at term were collected. The human milk metabolome, established by (NMR) spectroscopy, was influenced by gestational and lactation age. Metabolite profiling identified that levels of valine, leucine, betaine, and creatinine were increased in colostrum from term mothers compared with mature milk, while those of glutamate, caprylate, and caprate were increased in mature term milk compared with colostrum. Levels of oligosaccharides, citrate, and creatinine were increased in pre-term colostrum, while those of caprylate, caprate, valine, leucine, glutamate, and pantothenate increased with time postpartum. There were differences between pre-term and full-term milk in the levels of carnitine, caprylate, caprate, pantothenate, urea, lactose, oligosaccharides, citrate, phosphocholine, choline, and formate. These findings suggest that the metabolome of pre-term milk changes within 5-7 weeks postpartum to resemble that of term milk, independent of time of gestation at pre-mature delivery.