Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs.

Gas flow is fundamental for driving tidal ventilation and, thus, the speed of lung motion, but current bias flow settings to support the preterm lung after birth do not have an evidence base. We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4-6 L/min) did not affect lung mechanics, mechanical power, or gas exchange compared with those currently used in clinical practice (8-10 L/min). Speed of pressure and volume change during inflation were faster with higher flow rates. Lower flow rates resulted in less bronchoalveolar fluid protein, better lung morphology, and fewer detached epithelial cells. Overall, relative to unventilated fetal controls, there was greater protein change using 8-10 L/min, which was associated with enrichment of acute inflammatory and innate responses. Slowing the speed of lung motion by supporting the preterm lung from birth with lower flow rates than in current clinical use resulted in less lung injury without compromising tidal ventilation or gas exchange.

Kisspeptin in the Prediction of Pregnancy Complications.

Kisspeptin and its receptor are central to reproductive health acting as key regulators of the reproductive endocrine axis in humans. Kisspeptin is most widely recognised as a regulator of gonadotrophin releasing hormone (GnRH) neuronal function. However, recent evidence has demonstrated that kisspeptin and its receptor also play a fundamental role during pregnancy in the regulation of placentation. Kisspeptin is abundantly expressed in syncytiotrophoblasts, and its receptor in both cyto- and syncytio-trophoblasts. Circulating levels of kisspeptin rise dramatically during healthy pregnancy, which have been proposed as having potential as a biomarker of placental function. Indeed, alterations in kisspeptin levels are associated with an increased risk of adverse maternal and foetal complications. This review summarises data evaluating kisspeptin's role as a putative biomarker of pregnancy complications including miscarriage, ectopic pregnancy (EP), preterm birth (PTB), foetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), gestational diabetes mellitus (GDM), and gestational trophoblastic disease (GTD).

El prematuro tardío, ¿qué sabemos desde el punto de vista perinatal? / The late premature, what do we know from the perinatal point of view?

Resumen El parto prematuro es la principal causa de morbimortalidad neonatal en Chile. Los prematuros tardíos, definidos como nacimientos entre 34 semanas con 0 días (34+0) y 36 semanas con 6 días (36+6) de gestación, representan el 70-80% de los prematuros y se asocian a baja morbilidad y excepcional mortalidad si se comparan con partos bajo 34 semanas, pero significativamente mayor al compararlos con partos de término. Los prematuros tardíos son el resultado de diversas condiciones obstétricas, tales como síndromes hipertensivos del embarazo, rotura prematura de membranas, colestasia intrahepática del embarazo y comorbilidad médica. El propósito de esta revisión es actualizar la información asociada a los prematuros tardíos y dar una visión de las tendencias en el uso de corticoides y el manejo expectante de la rotura prematura de membranas con el objetivo de disminuir las complicaciones en este grupo de prematuros.

Abstract Preterm delivery is the most important cause of neonatal morbidity and mortality in Chile. Late preterm, defined as deliveries between 34 +0 and 36+6-weeks accounts for 70-80% of preterm and is associated with non-severe morbidity and extremely low mortality when compared with deliveries below 34 weeks but significantly high when compared with full term babies. Late preterm deliveries are a result of several obstetric conditions, such a hypertensive disorder, premature rupture of membranes, intrahepatic cholestasis, and maternal medical comorbidities. The purpose of this review is to update the information associated with the risks of late preterm and to guide in the new trends in the application of steroid and expectant management for premature rupture of membranes in order to reduce the frequency of late preterm.

Furin is involved in uterine activation for labor.

The uterus undergoes distinct molecular and functional changes during pregnancy and parturition. These processes are associated with the dramatic changes in various proteins. Given that the maturation and activation of many proteins require proteolytic processing by proprotein convertases (PCs), we sought to explore the role of PCs in uterine activation for labor. First, we found that furin was the most dramatically increased PC member in myometrial tissues from the pregnant women after onset of labor at term. Using the model of cultured human myometrial smooth muscle cells (HMSMCs), we showed that furin inhibitor CMK, D6R treatment and furin siRNA transfection suppressed contractility. Inhibition of furin activity or interfering furin expression decreased connexin 43 (CX43), prostaglandin (PG) endoperoxide synthase-2 (COX-2) and PGF2α receptor (FP) expression and NF-κB activation. In mouse model, administration of furin inhibitors prolonged gestational length. However, D6R treatment did not affect RU38486- and lipopolysaccharides (LPS)-induced preterm birth. Furthermore, D6R and furin siRNA treatment reduced the release of soluble form of tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK), while furin overexpression led to an increase in soluble TWEAK release in cultured HMSMCs. D6R treatment decreased TWEAK level in blood of pregnant mice. TWEAK treatment promoted contractility and NF-κB activation, while TWEAK receptor fibroblast growth factor-inducible 14 (FN14) antagonist treatment inhibited contractility and NF-κB activation in HMSMCs. In pregnant mice, administration of FN14 antagonist prolonged gestational length. Our data suggest that furin can act as a stimulator for uterine activation for labor at term. TWEAK is one of the potential substrates which mediate furin regulation of parturition initiation.

Pulmonary hypertension is an important co-morbidity in developmental lung diseases of infancy: Bronchopulmonary dysplasia and congenital diaphragmatic hernia.

Bronchopulmonary dysplasia (BPD) following preterm birth and congenital diaphragmatic hernia (CDH) are both forms of developmental lung disease that may result in persistent pulmonary and pulmonary vascular morbidity in childhood. The pulmonary vascular disease (PVD) which accompanies BPD and CDH is due to developmental abnormalities and ongoing perinatal insults. This may be accompanied by evidence of elevated right heart pressures and pulmonary vascular resistance, leading to diagnosis of pulmonary hypertension (PH). The development of PH in these conditions is associated with increased morbidity and mortality in the vulnerable BPD and CDH populations. We present a review of PVD pathogenesis and evaluation in BPD and CDH and discuss management of related sequelae of PH co-morbidity for affected infants.

Multimodal longitudinal respiratory function assessment in very low birth weight 7-year-old children.

PURPOSE: Preterm birth is associated with adverse pulmonary outcomes. We aimed to evaluate respiratory morbidities and lung function of very low birth weight (VLBW) Polish children followed up at the age of 7 years old, and to compare with electrical impedance segmentography (EIS) results recorded at 4 years of age. MATERIALS AND METHODS: VLBW children were compared with term controls using impulse oscillometry and spirometry. Perinatal data and current respiratory morbidities were analyzed and pulmonary function test results were compared with previous EIS results. RESULTS: We included 40 VLBW children and 30 controls in the analysis. Elevated total airway resistance and forced expiratory volume in the first second below the lower limit of normal were more prevalent in VLBW children compared with term controls (15 vs 0%; 18 vs 0%). A positive bronchodilator response was more common in VLBW children (R5 Hz: 46 vs 13.3%; R5-20 â€‹Hz: 65 vs 36.7%). Children with bronchopulmonary dysplasia (BPD) had higher total airway resistance (R5 Hz/R5 Hz pred: 1.35 vs 0.95; p â€‹< â€‹0.001), large airway resistance (R20 Hz/R20 Hz pred: 0.89 vs 0.66; p â€‹= â€‹0.001), small airway resistance (R5-20 â€‹Hz: 0.57 vs 0.34 â€‹kPa â€‹L-1 â€‹s-1; p â€‹= â€‹0.009), than controls. Strong correlation between BDR in EIS and R5 Hz/R5 Hz pred was observed in children with BPD (r â€‹= â€‹0.7). CONCLUSION: VLBW school-aged children with BPD presented with substantial respiratory morbidity and persistent reduction of lung function, affecting small and large airways and lung parenchyma. EIS may be an alternative tool for lung function assessment in children with BPD.

Fetal Exosomal Platelet-activating Factor Triggers Functional Progesterone Withdrawal in Human Placenta.

In most mammals, labor is heralded by the withdrawal of progesterone. In humans, circulating progesterone levels increase as gestation advances while placental expression of progesterone receptor A (PR-A) declines. As a result of PR-A downregulation, the non-canonical NF-κB pathway is activated, an event implicated in triggering labor. Here, we sought to identify fetal-derived mediator(s) that represses placental PR-A in human placenta leading to activation of pro-labor signaling. Lipidomic profiling demonstrated enrichment of platelet-activating factor (PAF) in exosomes originating from the human fetus. Exposure of primary cytotrophoblasts to fetal exosomes from term pregnancies reduced PR-A expression by > 50%, and PAF also reduced PR-A message levels in a dose-dependent manner. Notably, fetal exosomes from preterm pregnancies had lower PAF levels and no effect on PR-A expression. Synthetic PAF-induced DNA methylation increases by 20% at the PR-A promoter, leading to recruitment of corepressors and downregulation of PR-A in cytotrophoblast. Furthermore, suppression of PR-A by PAF-stimulated expression of the pro-labor genes, corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2), which was reversed by disruption of the DNA methyltransferases 3B and 3L. Taken together, PAF represents a novel fetal-derived candidate for initiation of labor by stimulating methylation and repression of PR-A and activating pro-labor signaling in trophoblast.

Cervical cytomegalovirus reactivation, cytokines and spontaneous preterm birth in Kenyan women.

Genital cytomegalovirus (CMV) reactivation is common during the third trimester of pregnancy. We hypothesized that cervical CMV shedding may increase risk of spontaneous preterm birth (sPTB) through the release of inflammatory cytokines in the cervix. We conducted a nested case-control analysis to determine the relationship between CMV shedding and sPTB using data and samples from a prospective cohort study in western Kenya. Women who delivered between 28 + 0 and 33 + 6 weeks gestation were matched by gestational age at sample collection to controls who delivered ≥ 37 + 0 weeks. Levels of CMV DNA and interleukin (IL)-1 beta (ß), IL-6, IL-8 and tumor necrosis factor (TNF)-α were measured in cervical swabs. We used conditional logistic regression to assess relationships between CMV shedding, cervical cytokine levels and sPTB. Among 86 cases and 86 matched controls, cervical CMV levels were not significantly associated with sPTB [odds ratio (OR) = 1·23, 95% confidence interval (CI) = 0·59-2·56], but were significantly associated with higher levels of cervical IL-6 (ß = 0·15, 95% CI = 0·02-0·29) and TNF-α (ß = 0·14, 95% CI = 0·01-0·27). In univariate analysis, higher odds of sPTB was associated with higher cervical IL-6 levels (OR = 1·54, 95% CI = 1·00-2·38), but not with other cervical cytokines. In this cohort of Kenyan women, we did not find a significant association between cervical CMV shedding and sPTB before 34 weeks.

Lung abnormalities do not influence aerobic capacity in school children born preterm.

PURPOSE: Children born preterm have impaired lung function and altered lung structure. However, there are conflicting reports on how preterm birth impacts aerobic exercise capacity in childhood. We aimed to investigate how neonatal history and a diagnosis of bronchopulmonary dysplasia (BPD) impact the relationship between function and structure of the lung, and aerobic capacity in school-aged children born very preterm. METHODS: Preterm children (≤ 32 w completed gestation) aged 9-12 years with (n = 38) and without (n = 35) BPD, and term-born controls (n = 31), underwent spirometry, lung volume measurements, gas transfer capacity, a high-resolution computer tomography (CT) scan of the chest, and an incremental treadmill exercise test. RESULTS: Children born preterm with BPD had an elevated breathing frequency to tidal volume ratio compared to term controls (76% vs 63%, p = 0.002). The majority (88%) of preterm children had structural changes on CT scan. There were no differences in peak V̇O2 (47.1 vs 47.7 mL/kg/min, p = 0.407) or oxygen uptake efficiency slope when corrected for body weight (67.6 vs 67.3, p = 0.5) between preterm children with BPD and term controls. There were no differences in any other exercise outcomes. The severity of structural lung disease was not associated with exercise outcomes in this preterm population. CONCLUSION: Children born preterm have impaired lung function, and a high prevalence of structural lung abnormalities. However, abnormal lung function and structure do not appear to impact on the aerobic exercise capacity of preterm children at school age.

Implicações da deficiência materna de vitamina D: uma revisão sistemática / Implication of maternal vitamin D deficiency: a systematic review

O estudo objetiva avaliar a relação dos níveis de vitamina D em gestantes com as principais complicações gestacionais. A pesquisa foi realizada nas bases de dados PubMed, LILACS e BIREME, sendo selecionados artigos relevantes publicados de 2013 a 2018, usando os descritores: "vitamin D" AND "maternity" OR "pregnancy". Foram revisados 14 estudos observacionais incluindo casos-controles e coortes que investigaram a relação dos níveis de vitamina D maternos com pré-eclâmpsia, diabetes mellitus gestacional e prematuridade, sendo excluídos os estudos que utilizaram suplementação de vitamina D. Os dados foram extraídos por meio de uma tabulação com as seguintes informações: autor, ano da publicação, país do estudo, score obtido no downs and black, ano da coleta da amostra, tipo do estudo, número de participantes, método de obtenção da amostra de 25(OH)D, tempo da gestação na obtenção da amostra, complicação obstétrica, fatores de confusão ajustados e os principais desfechos. Foi obtido um total de 32.505 pacientes após a soma das amostras de todos os artigos analisados. O principal resultado encontrado, abrangendo as três comorbidades analisadas, relaciona níveis menores que 30 nmol/L de vitamina D como potencial fator de risco para pré-eclâmpsia, diabetes mellitus gestacional e prematuridade.(AU)

The study aims to assess the relationship between vitamin D levels in pregnant women and the main gestational complications. The research was carried out in the PubMed, LILACS and BIREME databases, with the selection of relevant articles published from 2013 to 2018, using the descriptors: "vitamin D" AND "maternity" OR "pregnancy". 14 observational studies were reviewed including control cases and cohorts that investigated the relationship between maternal vitamin D levels and pre-eclampsia, gestational diabetes mellitus and prematurity, and studies that used vitamin D supplementation were excluded. Data were extracted using a tabulation with the following information: author, year of publication, country of study, score obtained in downs and black, year of sample collection, type of study, number of participants, method of obtaining the sample of 25(OH)D, time of pregnancy in obtaining the sample, obstetric complication, adjusted confounding factors and the main outcomes. A total of 32,505 patients were obtained after adding the samples of all analyzed articles. The main result found, covering the three comorbidities analyzed, lists levels below 30 nmol/L of vitamin D as a potential risk factor for pre-eclampsia, gestational diabetes mellitus and prematurity.(AU)

Preterm Labor and Birth: A Clinical Review.

When caring for women experiencing preterm labor and birth, nurses play a significant role as bedside experts, advocates, patient educators, and key members of the maternity care team. Enhanced expertise on clinical and professional knowledge of preterm labor and birth is crucial in prevention and treatment. As preterm birth rates continue to rise, perinatal nurses as well-informed clinical experts have the opportunity to offer innovative education, holistic assessments, and communication through shared decision-making models. Educating pregnant women about early recognition of preterm labor warning signs and symptoms allows for timely diagnosis, interventions, and treatment. Informed and collaborative nursing practice improves quality of clinical care based on individualized interactions. A clinical review of preterm labor and preterm birth is presented for perinatal nurses.

Postnatal dexamethasone exposure and lung function in adolescents born very prematurely.

We previously demonstrated corticosteroid administration on the neonatal intensive care unit was associated with reduced lung function at 11 to 14 years of age in children born very prematurely. The objective of this observational study was to assess if lung function remained impaired at 16 to 19 years of age in those who had received postnatal corticosteroids and whether the trajectory of lung function with increasing age differed between those who had and had not received corticosteroids. One hundred and fifty-nine children born prior to 29 weeks of gestational age had comprehensive lung function measurements; 49 had received postnatal dexamethasone. Lung function outcomes were compared between those who had and had not received postnatal dexamethasone after adjustment for neonatal factors. Forced expiratory flow at 75%, 50%, 25% and 25-75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes (total lung capacity and residual volume) were assessed. The majority of results were significantly lower in those who received dexamethasone (between 0.61 to 0.78 standard deviations). Lung function reduced as the number of courses of dexamethasone increased. Between 11 and 14 years and 16 to 19 years, lung function improved in the unexposed group, but forced expiratory flow at 75% of the expired vital capacity and forced expiratory volume in one second deteriorated in those who had received postnatal corticosteroids (p = 0.0006). These results suggest that prematurely born young people who received postnatal corticosteroids may be at risk of premature onset of chronic obstructive pulmonary disease.

Upregulation of TNF-α and IL-6 induces preterm premature rupture of membranes by activation of ADAMTS-9 in embryonic membrane cells.

AIM: To investigate the role of thrombospondin motifs 9 (ADAMTS9) in preterm premature rupture of membranes (pPROM). MATERIALS AND METHODS: ADAMTS9 levels were measured in amnion cells from 24 patients of different groups (preterm vs. full-term birth, with vs. without PROM). ADAMTS9 was suppressed in human amnioblasts to investigate its effects on embryonic membrane cells and inflammation-induced cell damage. Pregnant mouse models were used to assess whether inflammation regulates ADAMTS9 by upregulating TNF-α and IL-6, contributing to the preterm birth occurrence. KEY FINDINGS: We found that ADAMTS9 protein and gene expression levels significantly differed among various groups (pPROM > full-term PROM > preterm non-PROM > full-term non-PROM). After ADAMTS9 suppression in human amnioblast WISH cells, TNF-α- and IL-6-induced apoptosis was decreased. In addition, TNF-α, IL-6, and ADAMTS9 protein and gene expression levels were increased in the embryos of mice treated with LPS compared with controls. In agreement, the rate of preterm birth was higher in the LPS group compared with controls. SIGNIFICANCE: Taken together, these in vitro and in vivo findings suggest that TNF-α and IL-6 secreted by macrophages during inflammation regulate ADAMTS9 and induce pPROM.

Pregnancy-Related Complications in Patients With Fibromuscular Dysplasia: A Report From the European/International Fibromuscular Dysplasia Registry.

Current literature suggests a higher risk of pregnancy-related complications in patients with renal fibromuscular dysplasia (FMD). The aim of our study was to assess the nature and prevalence of pregnancy-related complications in patients subsequently diagnosed with FMD. A call for participation was sent to centers contributing to the European/International FMD Registry. Patients with at least 1 pregnancy were included. Data on pregnancy were collected through medical files and FMD characteristics through the European/International FMD Registry. Data from 534 pregnancies were obtained in 237 patients. Despite the fact that, in 96% of cases, FMD was not diagnosed before pregnancy, 40% of women (n=93) experienced pregnancy-related complications, mostly gestational hypertension (25%) and preterm birth (20%), while preeclampsia was reported in only 7.5%. Only 1 patient experienced arterial dissection and another patient an aneurysm rupture. When compared with patients without pregnancy-related complications, patients with complicated pregnancies were younger at FMD diagnosis (43 versus 51 years old; P<0.001) and had a lower prevalence of cerebrovascular FMD (30% versus 52%; P=0.003) but underwent more often renal revascularization (63% versus 40%, P<0.001). In conclusion, the prevalence of pregnancy-related complications such as gestational hypertension and preterm birth was high in patients with FMD, probably related to the severity of renal FMD. However, the prevalence of preeclampsia and arterial complications was low/moderate. These findings emphasize the need to screen hypertensive women for FMD to ensure revascularization before pregnancy if indicated and appropriate follow-up during pregnancy, without discouraging patients with FMD from considering pregnancy.

Antenatal Corticosteroids and Outcomes in Preterm Twins.

OBJECTIVE: To estimate whether improvement in outcomes from antenatal corticosteroid treatment in extremely and very preterm twins is similar to that observed in singletons, and to investigate whether antenatal corticosteroid treatment has different effects according to chorionicity or birth order. METHODS: This population-based study was based on an analysis of data collected by the Neonatal Research Network of Japan from 2003 to 2015 of neonates weighing 1,500 g or less at birth, from gestational ages of 24 0/7 to 31 6/7 weeks of gestation. After propensity score matching, univariate logistic and interaction analyses were performed to compare short-term (neonatal period) and medium-term (3 years of age) outcomes of the children of mothers who received antenatal corticosteroids with those of children of mothers who did not receive antenatal corticosteroids. We focused on differences between singletons and twins, between monochorionic and dichorionic twins and between the first and second twin. RESULTS: The study comprised 23,502 singletons and 6,546 twins. Antenatal corticosteroid treatment was associated with significant decreased short-term neurologic outcomes in both singletons and twins. However, antenatal corticosteroid treatment was associated with significantly decreased mortality (odds ratio [OR] 0.61; 95% CI 0.53-0.70), respiratory distress syndrome (OR 0.71, 95% CI 0.67-0.76), and cerebral palsy (OR 0.85, 95% CI 0.72-0.99) in singletons but not in twins (OR 0.89, 95% CI 0.68-1.17; OR 0.99, 95% CI 0.87-1.12; and OR 0.82, 95% CI 0.61-1.11, respectively). No association was found between chorionicity and the efficacy of antenatal corticosteroid treatment on outcomes. Further, no association was found between birth order and the efficacy of antenatal corticosteroid treatment on outcomes, except for periventricular leukomalacia and necrotizing enterocolitis (interaction: P=.02 and P=.04, respectively). CONCLUSION: Antenatal corticosteroid treatment in twins was associated with a beneficial effect on short-term neurologic outcomes only, without improvement in other short-term and medium-term outcomes. There was no difference related to chorionicity.

Effects of delayed intraventricular TLR7 agonist administration on long-term neurological outcome following asphyxia in the preterm fetal sheep.

In the preterm brain, accumulating evidence suggests toll-like receptors (TLRs) are key mediators of the downstream inflammatory pathways triggered by hypoxia-ischemia (HI), which have the potential to exacerbate or ameliorate injury. Recently we demonstrated that central acute administration of the TLR7 agonist Gardiquimod (GDQ) confers neuroprotection in the preterm fetal sheep at 3 days post-asphyxial recovery. However, it is unknown whether GDQ can afford long-term protection. To address this, we examined the long-term effects of GDQ. Briefly, fetal sheep (0.7 gestation) received sham asphyxia or asphyxia induced by umbilical cord occlusion, and were studied for 7 days recovery. Intracerebroventricular (ICV) infusion of GDQ (total dose 3.34 mg) or vehicle was performed from 1-4 hours after asphyxia. GDQ was associated with a robust increase in concentration of tumor necrosis factor-(TNF)-α in the fetal plasma, and interleukin-(IL)-10 in both the fetal plasma and cerebrospinal fluid. GDQ did not significantly change the number of total and immature/mature oligodendrocytes within the periventricular and intragyral white matter. No changes were observed in astroglial and microglial numbers and proliferating cells in both white matter regions. GDQ increased neuronal survival in the CA4 region of the hippocampus, but was associated with exacerbated neuronal injury within the caudate nucleus. In conclusion, our data suggest delayed acute ICV administration of GDQ after severe HI in the developing brain may not support long-term neuroprotection.

Duration of neonatal oxygen supplementation, erythropoiesis and blood pressure in young adults born preterm.

BACKGROUND: Although erythropoiesis is impaired and anaemia frequent in neonates born preterm, haematopoiesis in adults born preterm has not been previously studied. OBJECTIVE: We, thus, aimed to evaluate haemoglobin and erythropoietin levels in young adults born preterm, to identify neonatal events associated with erythropoiesis in adulthood and to examine the relationships of haemoglobin levels with respiratory function and blood pressure. METHODS: We assessed a cohort of 101 young adults (ages 18-29) born preterm (≤29 weeks of gestation), in comparison to 105 full-term controls. We measured haemoglobin, erythropoietin levels and blood pressure. We also assessed respiratory function using spirometry. RESULTS: Compared with controls, tobacco use and sex-adjusted haemoglobin levels were 5.3 (95% CI 2.9 to 7.7) g/L higher in preterm-born individuals, but erythropoietin levels were similar. Duration of oxygen supplementation in the neonatal period was independently associated with higher haemoglobin levels in the preterm group. In young adults born preterm with bronchopulmonary dysplasia, airflow limitation was associated with higher haemoglobin levels. Both systolic (SBP) and diastolic (DBP) blood pressure were increased in individuals born preterm (p=0.042 and p=0.0008, respectively). Higher haemoglobin levels were associated with higher SBP and DBP, independently of term or preterm status. Mediation analysis suggests that haemoglobin increase contributes to 37% and 32% of the effect of preterm birth on SBP and DBP, respectively. CONCLUSIONS: Haemoglobin levels are higher in young adults born preterm, while erythropoietin levels are similar, especially in case of bronchopulmonary dysplasia and airflow limitation, and haemoglobin increase is associated with elevated blood pressure in this population.

Early life factors for endometriosis: a systematic review.

BACKGROUND: Despite its high prevalence and health burden, many aspects of endometriosis remain unclear, including risk factors and the underlying biological mechanisms. Exposures during early life, including in utero, are thought to play an important role in the subsequent onset of the condition. To date, however, much of the evidence from studies on early life exposures and diagnosed endometriosis appears mixed and difficult to assess. OBJECTIVE AND RATIONALE: This study aims to provide a systematic review of the epidemiologic evidence on early life factors associated with the subsequent diagnosis of endometriosis. In utero and early life exposures have previously been linked to a range of adult health outcomes, including infertility. SEARCH METHODS: A systematic review of case-control, cross-sectional and cohort studies was conducted using the search terms 'endometriosis'[MeSH] AND ('risk factors'[MeSH] OR 'protective factors'[MeSH]) AND ('in utero', 'fetal', 'neonatal, 'perinatal', 'developmental origins', 'early life', 'childhood' OR 'life course') in Embase, PubMed and Scopus databases. The review included articles published in English until 10 June 2018 with original data from studies with diagnosed endometriosis. The quality of primary studies was evaluated using the Newcastle-Ottawa Scale by both authors independently. Due to the degree of inconsistency in the measurements and study methods, a qualitative assessment of findings was undertaken rather than meta-analysis. OUTCOMES: The search retrieved 70 records without duplicates that contained 20 records on human case-control, cross-sectional or cohort studies, from which 11 papers/studies were selected based on their assessment score. The majority of studies found that women born with low birthweight (<2.5 kg or <5.5 lb) were more likely to be diagnosed with endometriosis. For other early life factors, the evidence is mixed or limited, with further research needed on the association of endometriosis with preterm birth, in utero exposure to diethylstilbestrol and to maternal smoking, passive smoking in early life, and infant formula feeding (compared with breastfeeding). WIDER IMPLICATIONS: While the weight of evidence points to low birthweight as a risk factor for diagnosis of endometriosis, future research is warranted on this and other key early life exposures where the findings are mixed to provide more robust evidence and for insights on potential causal pathways. Such research, however, needs to address current methodological issues, such as the use of prospective data from large population-based studies, better diagnostic methods to confirm disease free status, more consistent definitions of variables and consideration of potential biological mechanisms to guide the analyses. The improvements will advance the future synthesis of evidence to support clinically relevant risk assessment for a more timely diagnosis and treatment of endometriosis.

Kidney-Detrimental Factors and Estimated Glomerular Filtration Rate in Preterm Newborns: The Role of Nutrition.

: Background: Kidney function in preterm newborns may be impaired by many factors. METHODS: 71 newborns with gestational age (GA) < 32 weeks were enrolled. Serum creatinine (sCr), cystatin C (CysC), beta-trace protein (BTP) and urea were measured at T0 (3rd day of life) and T36 (GA 36 weeks), and estimated glomerular filtration rate (eGFR) was calculated according to different formulas at T36. Pre-natal and post-natal kidney injury risk scores were calculated. RESULTS: Newborns with GA ≤ 28 weeks had higher sCr at T0, and lower sCr, BTP and higher urea levels at T36 (p = 0.007, p = 0.005 and p = 0.029, respectively). eGFR values were not different according to GA when calculated by the formulas using only CysC, but were higher in subjects with GA ≤ 28 weeks according to the other formulas. The post-natal score was positively correlated with eGFR according to sCr-based formulas, but the correlations did not persist when adjusted for urea levels and GA. CONCLUSIONS: CysC-based eGFR values are not influenced by GA. Post-natal score shows a direct correlation with eGFR according to sCr-based formulas, not persisting after adjustment for GA and urea levels, implying the importance of the nutritional status, since more premature subjects receive a more aggressive nutritional regimen, testified by higher urea levels.

Nutrients and Microbiota in Lung Diseases of Prematurity: The Placenta-Gut-Lung Triangle.

Cardiorespiratory function is not only the foremost determinant of life after premature birth, but also a major factor of long-term outcomes. However, the path from placental disconnection to nutritional autonomy is enduring and challenging for the preterm infant and, at each step, will have profound influences on respiratory physiology and disease. Fluid and energy intake, specific nutrients such as amino-acids, lipids and vitamins, and their ways of administration -parenteral or enteral-have direct implications on lung tissue composition and cellular functions, thus affect lung development and homeostasis and contributing to acute and chronic respiratory disorders. In addition, metabolomic signatures have recently emerged as biomarkers of bronchopulmonary dysplasia and other neonatal diseases, suggesting a profound implication of specific metabolites such as amino-acids, acylcarnitine and fatty acids in lung injury and repair, inflammation and immune modulation. Recent advances have highlighted the profound influence of the microbiome on many short- and long-term outcomes in the preterm infant. Lung and intestinal microbiomes are deeply intricated, and nutrition plays a prominent role in their establishment and regulation. There is an emerging evidence that human milk prevents bronchopulmonary dysplasia in premature infants, potentially through microbiome composition and/or inflammation modulation. Restoring antibiotic therapy-mediated microbiome disruption is another potentially beneficial action of human milk, which can be in part emulated by pre- and probiotics and supplements. This review will explore the many facets of the gut-lung axis and its pathophysiology in acute and chronic respiratory disorders of the prematurely born infant, and explore established and innovative nutritional approaches for prevention and treatment.