[Truncated abstract] Fetal inflammatory response syndrome (FIRS) has only recently been recognised as an important cause of spontaneous preterm delivery (PTD). In addition, it has been associated with a number of other short-term and long-term adverse neonatal outcomes, including early onset neonatal sepsis, necrotising enterocolitis, periventricular leucomalacia, cerebral palsy, and bronchopulmonary dysplasia, although the causal mechanisms are unclear. The hallmark of FIRS is histologic chorioamnionitis (HCA). Mothers with HCA are often asymptomatic and it remains unclear whether elevated maternal inflammatory markers, such as C-reactive protein (CRP) and procalcitonin (PCT), are predictive of preterm birth. Furthermore neonatal inflammatory markers such as CRP, PCT, white cell count (WCC) and absolute neutrophil count (ANC), are commonly used in clinical practice to diagnose infection in the neonatal period. Although both intrauterine inflammation and FIRS may have effects on inflammatory markers for up to 10 days following delivery, the extent to which intrauterine infection and FIRS confound these diagnostic surrogates of neonatal infection is unknown. This work addressed the hypothesis that HCA is associated with inflammatory changes that may be detected in the: (a) maternal circulation at the time of delivery, (b) umbilical cord blood at delivery and (c) post-natal circulation within the first 48 hours of life. The primary aim of this study was to investigate the relationship between the presence of HCA and maternal inflammatory markers (serum CRP and PCT on the day of delivery) as well as neonatal inflammatory markers (haematological parameters, CRP and PCT up to 48 hours following delivery). ... Cord platelet counts were likely affected by platelet activation. For both intra-rater and inter-rater reproducibility, the corrected WCC, ANC and NRBC were shown to be reliable with an ICC of >0.90 for all comparisons. However, I:T ratio was poorly reproducible. HCA appears to be a minor inflammatory insult for the mother. In the majority of cases it is asymptomatic and results in minor increases in PCT and CRP levels on the day of delivery. Conversely HCA results in significant inflammatory changes in the newborn that can be seen in the cord blood. Sensitive markers of inflammation in the cord blood are significantly higher in affected infants (CRP and PCT), while less sensitive markers, such as WCC and ANC are not significantly different. This study has shown that fetal inflammation has sustained effects on CRP and haematological parameters in early neonatal life; CRP, WCC and ANC are significantly higher in newborns exposed to HCA, peaking 24 hours following delivery. These effects may confound the interpretation of common diagnostic tests for early onset neonatal sepsis. Conclusion: HCA results in mild elevations in CRP and PCT in the cord blood. Over the subsequent 24 hours CRP, WCC and ANC increase significantly in these neonates. Intrauterine exposure to HCA may influence surrogate diagnostic markers for early onset sepsis in newborn infants. Future research to investigate novel diagnostic markers, such as CD64 and soluble triggering receptor expressed on myeloid cells (TREM-1), or enhanced microbiological molecular diagnosis, will help distinguish true invasive infection from HCA-driven inflammation in the newborn infant.

[Truncated abstract] Pneumococcal exposure is high and life-long in developing countries including Papua New Guinea (PNG), with children under 2 years of age being at most risk for early upper respiratory tract pneumococcal carriage and infection. Deaths from pneumococcal diseases such as pneumonia and meningitis are common and likely the result of an absence of vaccination programmes. The need for effective and affordable pneumococcal vaccines has led to the testing of protein antigens including pneumolysin (Ply) and pneumococcal surface protein A (PspA) as novel vaccine antigens. Little is known on the immune responses to these proteins in humans, particularly in high-risk populations where such vaccines will be of most benefit. In this study, we examined the roles of naturally acquired antibody and cellular immune responses in mothers and newborns to Ply and PspA family 1 (PspA1) and family 2 (PspA2) in protection against or risk for early carriage in a high-risk PNG population. Antibodies to Ply, PspA1 and PspA2 were measured in plasmas of 241 mothers and 115 newborns (cords) from PNG, and 50 Australian mothers using an enzyme-linked immunosorbent assay (ELISA). Pernasal swabs were collected from PNG mothers at the time of delivery, one month post-partum, and weekly within the first month of life from their newborns to determine pneumococcal carriage. Cellular immune responses to Ply, PspA1 and PspA2, the TLR2/TLR4 ligands, LTA and LPS and to PHA were measured in cord blood mononuclear cells (CBMC) of 84 PNG versus 33 Australian newborns. Innate and T-cell cytokine responses in the PNG newborns were then analysed to determine their effect on infant pneumococcal carriage. ... No protective effect against infant pneumococcal carriage was observed with maternal and cord IgG levels for all antigens. Maternal carriage at time of delivery increased the risk for infant pneumococcal carriage in the first month of life (HR: 1.93, 95% CI 1.36 – 2.73, p = 0.001) with 70% of infants being colonised. Papua New Guinean newborns produced higher innate IL-10 and IFN-¿ (p = 0.003) and TNF-a (p < 0.001) to Ply compared to Australian newborns with no significant differences observed for IL-6 or IL-12. IFN-¿ responses to LPS and LTA (p = 0.005 and p < 0.001) were higher in PNG than Australian newborns, while IL-6, IL-10 (p < 0.001) and TNF-a (p = 0.002) to LPS with LTA-induced IL-6 and IL-10 (p < 0.001) were higher in Australian newborns. T-cell IL-5, IL-10, IL-13, IFN-¿, IL-6 and TNF-a response levels to PspA and PHA stimulation were significantly high in PNG newborns. No differences were observed for cytokine responses to Ply and PspA between PNG infant pneumococci carriers and non-carriers. Papua New Guinean infants are colonised by pneumococci very early in life and this may be influenced by high maternal carriage rates. PspA- and Ply-IgG levels are high in PNG mothers and undergo cross placental transfer but do not appear to be protective against early pneumococcal carriage. In PNG newborns, PspA elicits T-cell responses, while Ply drives more innate cellular responses, neither were demonstrated to have a protective effect against early carriage though further work is required to better define these and their relation to immune development in early childhood.

Thesis (M.S.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-04, page: 2056. Adviser: Maureen Sanderson. Includes bibliographical references.

Thesis (M.N.)--Memorial University of Newfoundland, School of Nursing, 2000. / Typescript. Bibliography: p. 100-112.

Thesis (Ph. D.)--RAND Graduate School, 1998. / Includes bibliographical references (p. 241-258).

Le système immunitaire néonatal est caractérisé par une susceptibilité accrue aux infections par des pathogènes intracellulaires et des réponses vaccinales altérées. Ces caractéristiques soulignent la capacité limitée du nouveau-né à développer des réponses immunes à médiation cellulaire.<p>Les LTγδ représentent le prototype des lymphocytes T non-conventionnels :ils sont capables de réagir très rapidement après activation et sont caractérisés par une activité qui n’est pas restreinte aux molécules du CMH. Les LTγδ qui expriment le TCR Vγ9Vδ2 constituent la population majoritaire (60-90%) de LTγδ dans le sang périphérique humain adulte. Ces cellules reconnaissent spécifiquement les phosphoantigènes, des molécules non-peptidiques de faible poids moléculaire tel que l’HMB-PP. Cet activateur naturel est un intermédiaire de la voie non-mévalonate de biosynthèse des isoprénoïdes, essentielle à de nombreux agents pathogènes. Ces cellules sont également capables de réagir aux aminobisphosphonates, drogues couramment utilisées en thérapie du cancer. Le zolédronate (Zometa) est le plus puissant des aminobisphosphonates. Grâce à leur capacité à sécréter rapidement des cytokines comme l’IFN-γ et le TNF-α ainsi qu’à leur puissante activité cytotoxique, les LT Vγ9Vδ2 jouent un rôle important dans le contrôle des infections et des cancers.<p><p>Au contraire des LTγδ de l’adulte, la fonction des LTγδ du nouveau-né est peu connue. Cependant, des évidences suggèrent que ces lymphocytes pourraient jouer un rôle particulièrement important en début de vie. Dans ce contexte, nous avons caractérisé en détail la réponse des LTγδ du sang de cordon ombilical humain après stimulation avec l’HMB-PP et le zolédronate. Contrairement à l’HMB-PP, le zolédronate induit la prolifération et la production d’IFN-γ par les LT Vγ9 du nouveau-né. L’IL-23 étant une cytokine produite de façon optimale par les DCs en début de vie, nous avons choisi d’étudier son influence sur le profil d’activation de ces cellules. L’ajout d’IL-23 au zolédronate augmente l’expression d’IFN-γ et génère une population distincte de LT Vγ9 négatifs pour l’IFN-γ et produisant de l’IL-17. De plus, l’IL-23 favorise la synthèse de plusieurs médiateurs cytotoxiques (perforine, granzymes A et B, granulysine) induits par le zolédronate. Alors que l’effet co-stimulateur de l’IL-23 sur la production d’IFN-γ et de molécules cytotoxiques est également observé au sein des LT Vγ9 de l’adulte, l’induction d’une sous-population IL-17+ IFN-γ- est unique aux LT Vγ9 du nouveau-né.<p>Afin de mieux définir les conditions requises pour induire la polarisation des LT Vγ9 du nouveau-né en cellules productrices d’IL-17, nous avons évalué l’effet de diverses cytokines ainsi que celui de dérivés microbiens sur l’activation de ces cellules au zolédronate. Le zolédronate en présence d’IL-1β ou de LPS génère une population distincte de LT Vγ9 IL-17+ IFN-γ-. De plus, l’ajout d’IL-1β au zolédronate n’augmente pas le pourcentage de LT Vγ9 producteurs d’IFN-γ. Nous avons ensuite comparé le phénotype des LT Vγ9 IL-17+ à celui des LT Vγ9 IFN-γ+. Nos résultats indiquent qu’une fraction des LT Vγ9 sécrétant l’IL-17 exprime sélectivement CCR6 contrairement aux LT Vγ9 producteurs d’IFN-γ.<p><p>En conclusion, ce travail a permis de révéler la capacité des LT Vγ9 du nouveau-né humain à se différencier en cellules productrices d’IFN-γ, d’IL-17 et de molécules cytotoxiques. Ces cellules pourraient donc constituer une première ligne de défense capable d’orchestrer une réponse immune efficace à l’encontre de dérivés microbiens ou de signaux endogènes de danger. / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

The purpose of the research was to determine the underlying contributory factors in an obstetric unit at the district hospital in Mpumalanga province, South Africa, regarding neonatal deaths and to propose strategies for midwifery practice. Quantitative, nonexperimental, descriptive, exploratory and retrospective (ex-post facto) design was used to explore and describe the factors contributing to neonatal deaths. Data collection was done using an audit tool. The conclusions drawn from this study supported the assumptions that there are factors related to antenatal, intrapartum, postnatal and neonatal care that contribute to neonatal deaths, thus emphasizing the urgency of improving the care of pregnant mothers and their babies through effective implementation of programmes and protocols / Health Studies / M.A. (Health Studies)

Bakgrund: I kompetensbeskrivningen för barnmorskor beskrivs förmågan att involvera anhöriga i samråd med patienten. Detta för att möjliggöra bästa möjliga vård och hälsofrämjande faktorer. Eftersom partners delaktighet i barnafödandet anses ha positiv betydelse för kvinnan och barnet bör barnmorskan även fråga fadern om hans upplevelser. Syfte: Syftet var att beskriva var och vad nyblivna fäder söker efter för information på internet, relaterat till barnafödande, samt hur denna information upplevs.  Metod: Datainsamlingen utfördes genom nio semistrukturerade intervjuer med nyblivna fäder. Studiens analys utfördes enligt en kvalitativ innehållsanalys med induktiv ansats som resulterade i fem kategorier. Resultat: Fäder använde internet för att få svar på sina frågor och funderingar kring graviditet, förlossning och föräldraskap. Informationen skapade en känsla av bekräftelse, trygghet, gemenskap samt fick fäderna att känna sig mer förberedda. Fäderna sökte information på faktasidor, forum, appar, poddar, youtube, ljudböcker och vetenskapliga artiklar.  Slutsats: Det framkom att fäder inte tog upp sina frågor och funderingar med barnmorskan och därför sökte på internet. En medvetenhet om detta kan underlätta för barnmorskan att göra fadern delaktig, genom att tillgodose faderns informationsbehov samt rekommendera tillförlitliga internetsidor för informationshämtning. / Background: The competence description for midwives describes the ability to involve relatives in consultation with the patient. This is to enable the best possible care and health promoting factors. Since partner´s participation in childbirth is considered to have a positive impact on the woman and child, the midwife also should ask the father about his experiences. Purpose: The purpose was to describe where and what kind of information fathers to newborn infants are searching for on the internet, related to childbirth, and how this information is experienced. Method: The data collection was conducted through 9 semi-structured interviews with fathers to newborn infants. The study's analysis was performed according to a qualitative content analysis with inductive approach that resulted in 5 categories. Results: Fathers used the internet to answer their questions and concerns about pregnancy, childbirth and parenthood. The information created a sense of affirmation, security, community and made the fathers feel more prepared. The fathers sought information on fact pages, forums, apps, podcasts, youtube, audiobooks and scientific articles. Conclusion: It emerged that fathers did not express their questions and thoughts which resulted in them searching information on the internet. An awareness of this can help the midwife to involve the father, by meeting the father's information needs and recommending reliable internet sites for information retrieval.

Thesis (M.Med. (Paediatrics and Child Health)) -- University of Limpopo, 2019 / Objectives To determine the prevalence and survival rate; and to assess the maternal risk factors as well as complications of prematurity, associated with the mortality of very low and extremely low birth weight infants in the Neonatal Intensive Care Unit (NICU) of Mankweng Hospital. Materials and Methods A retrospective descriptive study was conducted at the NICU of Mankweng Hospital for a 7-month period from 1st January to 31st July 2015. The patient medical records and the Perinatal Problem Identification Programme (PPIP) data were used for the study. Results Prevalence of prematurity was 23%, Infants weighing between 500g-1499g represented 6.3% of the total live births and 25% of the admissions to the NICU; of which 4.9% were classified as extremely low birth weight (ELBW). Overall 77% of the study population survived until discharge. From the medical records, the survival to discharge of infants with weight 500g - 999g was 52%; and 84% for those with weight 1000g-1499g. Multivariable analysis found that improved survival was associated with an increase in gestational age (p <0.001), as well as birth weight (p <0.001) and prolonged length of stay. Variables associated with poor survival were spontaneous preterm labour (p = 0.031), low Apgar score at 1 and 5 minutes (p <0.001), sepsis (p = 0.001), respiratory distress syndrome (p <0.001), pulmonary hemorrhage (p <0.001), hypothermia (P = 0.005), resuscitation at birth (p = 0.002) and necrotising enterocolitis (p =0.044). Antenatal steroids were not associated with survival (p =0.111), however this was not documented in 53%(134/252) of the records, so the non-significance to outcome in this study may not be a true reflection. The use of NCPAP or SiPAP only was associated with improved survival of up to 69% and high mortality rates were recorded in babies who required invasive ventilator support. Multi-organ immaturity was found to be the most common cause of death, followed by sepsis. Conclusion: The prevalence and survival rates of very low and extremely low birth weight, found in this study are comparable to those found in other tertiary hospitals in South Africa. The survival rate of ELBW babies is low and must be improved. Reliable data and further research should address effective steps to prevent preterm labour, extreme prematurity and hypothermia. The documentation and provision of antenatal steroids is encouraged. KEY CONCEPTS: Prematurity, Extremely low and Very low birth weight, Risk factors, Prevalence, Survival, Neonatal mortality rate.

Impaired intrauterine growth, inability of the fetus to achieve the required growth potential, contributes to a higher burden of neonatal morbidity and mortality. Intrauterine growth is an inferred process and small for gestational age is considered a rough estimate of impaired intrauterine growth that requires reliable gestational age data. Due to sparse data and measurement errors in gestational age, researchers rely on markers such as birth weight, birth length, and birth head circumference to infer fetal growth. While the etiology of impaired fetal growth is multifactorial, maternal anemia and undernutrition contribute substantially to impaired fetal growth and are prioritized in 2030 global nutrition goals by the World Health Assembly. Nutrition supplements such as lipid-based nutrient supplements, multiple micronutrients, and iron or folic acid during pregnancy are presumed to improve maternal anemia. But the effect of the supplements during pregnancy on fetal growth appears to be small to negligible, which has shifted the researcher’s focus to the pre-conception period. However, prior reviews on the preconception period have either synthesized the evidence from observational studies, or have explored outcomes such as congenital anomalies (e.g., neural tube defects), neurodevelopment disorders, or only birth weight. Hence the evidence from existing randomized controlled trials (RCTs) evaluating the effect of preconception nutrition supplements on maternal anemia and all markers of fetal growth including birth weight, birth length, and birth head circumference has not been systematically summarized and synthesized. We bridged this knowledge gap in the current dissertation (Aim 1). The Women First (WF) Preconception Nutrition Trial found that lipid-based nutrient supplementation started preconception or during pregnancy conferred greater benefits for birth weight and birth length among mothers who were anemic (Hemoglobin (Hb) < 12 g/dL) than among mothers who were non-anemic (Hb ≥ 12 g/dL) pre-pregnancy. However, by dichotomizing women into anemic and non-anemic women, we may miss high-risk women with specific Hb levels who may obtain greater benefits for intrauterine growth associated with the supplements. Assessing the effect of preconception nutrient supplements across a range of pre-pregnancy Hb levels will help us identify women with specific Hb cut-offs who may have the greatest potential to respond to the supplements (Aim 2). Additionally, there are major gaps in understanding the mechanisms of how nutrient supplements, consumed either before or during pregnancy, improve intrauterine growth. A better understanding of the underlying mechanisms would allow for fine-tuning of nutrition interventions for greater efficacy. Here, we examined whether Hb during pregnancy could be a potential mechanism through which nutrition supplements improve intrauterine growth (Aim 3). For Aim 1, we undertook a systematic review and meta-analysis of the RCTs evaluating the effect of preconception nutrition supplements on maternal hemoglobin and markers of intrauterine growth including birth weight, birth length, birth head circumference, and small for gestational age. Additionally, we examined preterm birth as an important perinatal outcome. We searched electronic databases including PubMed, Web of Science, Embase, CINAHL, and Cochrane Central. We computed pooled mean differences and risk ratios (RR) with 95% confidence intervals (CIs) using random-effect models. We employed I2 and Cochran’s Q test statistics to assess heterogeneity. We used the GRADE (grading of recommendations, assessment, development, and evaluations) tool to assess the quality of evidence. For Aim 2 and Aim 3, we leveraged the existing data from a large multi-country Women First (WF) Preconception Nutrition Trial conducted in Pakistan, India, Guatemala, and the Democratic Republic of Congo. Women in the WF trial were randomized to consume a lipid-based nutrient supplement (LNS) at least three months before and during pregnancy (Arm 1- preconception), only during pregnancy (Arm 2- during), or not at all (Arm 3 - control). The outcome was weight, length, and head circumference within 48 hours of birth expressed as Z-scores. For Aim 2, we analyzed the WF trial data on 2443 women-newborn dyads. For each site, we computed adjusted mean differences in these Z-scores between the randomized arms across six pre-pregnancy Hb categories (8-8.9, 9-9.9, 10-10.9, 11-11.9, 12-12.9, and ≥13g/dL) based on Hb distributions. We pooled site-specific effect measures using meta-analysis. For Aim 3, hemoglobin measured at 12 (n=2075) and 32 weeks of gestation (n=2157) was a mediator. We employed causal mediation analysis under a counterfactual approach to estimate direct and indirect effects. For Aim 1, we identified 20 eligible RCTs (n=27,659 women). Preconception nutrition supplements (iron and folic acid, multiple micronutrients, and a lipid-based nutrient supplement) increased maternal hemoglobin by 0.30g/dL ((0.03, 0.57); I2=79%). However, we did not find a significant effect of the supplements on birth weight (12.47gm ((-33.14, 58.08); I2=58%)), birth length (0.15cm (-0.26, 0.56); I2=68%; n=5), birth head circumference (-0.23cm (-0.88, 0.43); I2=84%), small for gestational age (RR: 0.91 (0.80,1.04); I2=31%), or preterm birth (RR: 0.93 (0.69,1.25); I2=57%). Overall, the quality of evidence was assessed as moderate and very low for maternal hemoglobin and three markers of intrauterine growth including birth weight, birth length, and birth head circumference, respectively. In Aim 2, we found that the effect of LNS on birth weight, length, and head circumference varied by pre-pregnancy Hb categories. Pooled mean differences in the Z-scores for birth length (0.60 (0.03, 1.23)), birth weight (0.50, (0.11, 0.89)), and birth head circumference ((0.26, (0.02, 0.51)) were greatest for Arm 1-preconception vs. Arm 3-control women with Hb 9-9.9g/dL. Women with Hb 10-10.9g/dL also benefited from preconception LNS. However, compared to controls, the effects of preconception LNS on birth weight, birth length, and birth head circumference attenuated for women with Hb 10-10.9g/dL. Compared to Arm 3-control, LNS during pregnancy (Arm 2) improved birth length, birth weight, and birth head circumference for women with Hb 8-10.9g/dL. Preconception LNS (Arm1) vs. LNS during pregnancy (Arm 2) improved the three markers of intrauterine growth only for women with Hb 9-9.9g/dL. Women with nearly normal (11-11.9 g/dL) and normal Hb (≥12g/dL) did not appreciably benefit from LNS, offered before and or during pregnancy. For Aim 3, Hb at 12 or 32 weeks of gestation did not mediate the relationship between the LNS and intrauterine growth. Indirect effects of preconception LNS (Arm 1) vs. Arm 3, mediated by Hb at 12 weeks, were 0.02 (-0.02, 0.01), 0.01 (-0.01, 0.02), and 0.01 (-0.01, 0.02) for length, weight, and head circumference Z-scores, respectively. The corresponding direct effects, not mediated by Hb, were 0.18 (0.09, 0.33), 0.12 (0.03, 0.23), and 0.06 (-0.03, 0.20), respectively. Site-specific and gestational age-adjusted data analyses both at 12 and 32 weeks of gestation confirmed the findings of negligible mediation by Hb during pregnancy. All types of preconception nutrition supplements studied to date appear to reduce maternal anemia. However, it is uncertain whether there are beneficial effects of preconception nutrition supplements on markers of intrauterine growth. Low quality of evidence from the RCTs examining the markers of intrauterine growth warrants future well-designed RCTs to produce solid scientific data, particularly on the benefits of a more comprehensive package of preconception nutrition supplements that include both macro- and micronutrients. The findings from the WF trial suggest that the benefits of preconception LNS on fetal growth are mainly confined to women with pre-pregnancy Hb 9-9.9g/dL. Compared to controls, women with Hb 10-10.9g/dL also benefited from preconception LNS, albeit the magnitude of effect on three markers of intrauterine growth was modest for women with Hb 10-10.9g/dL. However, LNS, started during pregnancy, appeared to improve markers of intrauterine growth for women with a wider range of Hb 8-10.9g/dL. Women with Hb ≥ 11g/dL did not benefit from LNS started either pre-conception or during pregnancy. These findings suggest that prioritizing women with specific pre-pregnancy Hb categories for targeted nutrition interventions may be advisable. This would target limited resources most efficiently in LMICs. Lastly, negligible mediation by Hb during pregnancy suggests that alternative pathways that potentially mediate the relationship between LNS and intrauterine growth need to be investigated.