The Impact of Maternal Asthma on the Preterm Infants' Gut Metabolome and Microbiome - The Microbiome, Atopic Disease, and Prematurity (MAP) Study

Abstract Preterm infants are at a greater risk for the development of asthma and atopic disease, which can lead to lifelong negative health consequences. This may, in part, be due to alterations that occur in the gut microbiome and metabolome during their stay in the Neonatal Intensive Care Unit (NICU). To explore the differential roles of family history (i.e., predisposition due to maternal asthma diagnosis) and hospital-related environmental and clinical factors that alter microbial exposures early in life, we looked at a unique cohort of preterm infants born £ 34 weeks gestational age from two local level III NICUs, as part of the MAP (Microbiome, Atopic disease, and Prematurity) Study. Weekly stool, milk feeds, and saliva were collected until hospital discharge, and monthly stool and milk samples were collected at home until one year of age. We also chose a sub-cohort of infants whose mothers had a history of asthma and matched gestational age and sex to infants of mothers without a history of asthma (control). We performed a prospective, paired metagenomic and metabolomic analysis of stool and milk feed samples collected at birth, 2 weeks, and 6 weeks postnatal age. Although there were clinical factors associated with shifts in the diversity and composition of stool-associated bacterial communities, maternal asthma diagnosis did not play an observable role in shaping the infant gut microbiome in the study period. There were significant differences, however, in the metabolite profile between the maternal asthma and control groups at 6 weeks postnatal age. The most notable changes occurred in the linoleic acid spectral network, which plays a role in inflammatory and immune pathways, suggesting early metabolomic changes in the gut of preterm infants born to mothers with a history of asthma. Our pilot analysis suggests that a history of maternal asthma alters a preterm infants’ metabolomic pathways in the gut as early as the first 6 weeks of life.

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“The pitch itself was no man's land:” Siege, Željezničar Sarajevo Football Club and the Grbavica Stadium

Nationalities Papers ◽

10.1080/00905992.2016.1219899 ◽

2016 ◽

Vol 44 (6) ◽

pp. 877-903

Author(s):

Richard Mills

Keyword(s):

Oral History ◽

Local Level ◽

Football Club ◽

Photographic Evidence ◽

History Of ◽

The Hague ◽

No Man's Land ◽

The Impact ◽

Football Stadium

Inspired by microhistory, this essay explores the wartime plight of a football stadium and the multi-ethnic club that called it home as a means of understanding Bosnia and Herzegovina's descent into conflict, the siege of Sarajevo, and the impact upon civilians. Like the suburb of the same name, Grbavica became part of the frontline during the siege. Deprived of its home, FK Željezničar continued to function, while players, staff, and supporters longed for a return to the shattered ground. At a local level, the organization offers a means of visualizing the development of the Grbavica suburb, from its socialist foundations to its post-Dayton reintegration. In this way, the life of the stadium and those who frequent it map onto the history of Yugoslavia, its dissolution, and the independent republic that emerged in its wake. Moreover, the wartime partition of the stadium, the club, and its supporters’ group – all of which were claimed by actors on both sides of the frontline – were representative of political developments in a state where the ethnic balance was forcibly reengineered. This reconstruction of Grbavica's war harnesses original photographic evidence, oral history, maps, contemporary journalism, and the transcripts of the Hague Tribunal.

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Low-grade intraventricular hemorrhage and neurodevelopment at 24 months of age

Scientia Medica ◽

10.15448/1980-6108.2018.3.29354 ◽

2018 ◽

Vol 28 (3) ◽

pp. 29354

Author(s):

Sara Peixoto ◽

Joana Amaral ◽

Cristina Resende ◽

Dolores Faria ◽

Adelaide Taborda

Keyword(s):

Preterm Infants ◽

Gestational Age ◽

Intraventricular Hemorrhage ◽

Univariate Analysis ◽

Neurodevelopmental Outcome ◽

Male Gender ◽

Low Grade ◽

Antenatal Corticosteroid ◽

The Impact ◽

Cranial Ultrasonography

AIMS: To evaluate the impact of low-grade intraventricular hemorrhage on neurodevelopmental outcome in preterm infants at 24 months of age.METHODS: We conducted a retrospective case-control study of infants with gestational age less than 34 weeks, admitted to a Neonatal Intensive Care Unit between January/2006 and December/2015. Cases were defined as those with low-grade intraventricular hemorrhage (grades I or II), diagnosed by cranial ultrasonography. For each case, a control with the same gestational age but without intraventricular hemorrhage was selected. Follow-up examinations of neurodevelopment were performed at 24 months of age in cases and controls using the Griffiths Mental Development Scale. Cerebral palsy, neurodevelopmental delay (developmental quotient <2 side deviations below the mean), hearing impairment and/or blindness were considered as severe neurodevelopmental impairment.RESULTS: The study included 172 preterm infants: 86 cases and 86 controls. In the univariate analysis, a difference between the two groups was identified for the following clinical findings: antenatal corticosteroid complete cycle (57% in cases vs. 80% in controls; p=0.001; OR: 0.33, 95%CI 0.17-0.64); male gender (63% cases vs. 41% controls; p=0.004; OR: 2.45, 95%CI 1.3-4.5); outborn (26% cases vs. 9% controls; p=0.005; OR: 3.3 95%CI 1.4-8.0); Clinical Risk Index for Babies higher than 5 (24% in cases vs. 12% in controls; p=0.029; OR: 2.4 95%CI 1.1-5.6); intubation in the delivery room (47% cases vs. 27% controls; p=0.007; OR: 2.38 95%CI 1.3-4.5); and neonatal sepsis (34% in cases vs. 20% in controls; p=0.039; OR: 2.1 95%CI 1.03-4.1). After logistic regression, differences were only maintained for antenatal corticosteroid (p=0.005; OR 0.34, 95%CI 0.16-0.72) and male gender (p=0.002; OR 2.9, 95%CI 1.4-5.8). A severe neurodevelopmental deficit was present in three cases (3.5%) and one control (1.2%). No statistically significant differences in outcome were found between cases and controls.CONCLUSIONS: In this sample, preterm infants with low-grade intraventricular hemorrhage diagnosed by cranial ultrasonography had no difference in early neurodevelopmental outcome when compared with controls.

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Evolution of circulating thyroid hormone levels in preterm infants during the first week of life: perinatal influences and impact on neurodevelopment

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0537 ◽

2019 ◽

Vol 32 (6) ◽

pp. 597-606 ◽

Cited By ~ 2

Author(s):

An Eerdekens ◽

Gunnar Naulaers ◽

Els Ortibus ◽

Johan Verhaeghe ◽

Lies Langouche ◽

...

Keyword(s):

Thyroid Hormone ◽

Preterm Infants ◽

Gestational Age ◽

Infant Development ◽

Neurodevelopmental Outcome ◽

Thyroid Stimulating Hormone ◽

Low T3 ◽

Increased Risk ◽

Total Thyroxine ◽

The Impact

Abstract Background For several decades, transient hypothyroxinemia of prematurity (THOP) has been a topic of debate. The pathophysiology is incompletely understood and consensus on the therapeutic approach is lacking. This study aimed at gaining a better insight into the pathogenesis by studying the trends in thyroid hormone (TH) levels during the first week of life. Methods This single-center prospective observational study analyzed the plasma levels of total thyroxine (T4) and free thyroxine (fT4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH) and T4-binding globulin (TBG) in cord blood and at the end of the first week of life in 120 preterm infants (gestational age [GA] <37 weeks). The change over time was calculated (delta, ∆). The impact of perinatal and subsequently postnatal variables on ∆ was studied by hierarchical multiple regression. The impact of ∆ on the neurodevelopmental outcome at the corrected ages of 9 and 24 months, measured by the Bayley Scales of Infant Development (BSID)-II, was assessed by logistic regression. Results ∆fT4 levels were negatively affected by GA and use of dopamine, whereas only GA was associated with low ∆T3 levels. Negative ∆fT4 levels were present in 75% of the extremely low-for-gestational-age infants, whereas 23.5% had a negative ∆T3 level. There was an increased risk for an abnormal mental developmental score (<85) with decreasing ∆T3 at 9 months, corrected age, but not at 24 months. Conclusions A negative evolution in circulating TH levels is principally an immaturity phenomenon, whereas dopamine can further suppress the hypothalamic-pituitary-thyroid axis. There is at least a temporary negative effect of this evolution on the infants’ neurodevelopment.

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Hypothyroxinemia Detected at 4 Weeks of Life in Preterm Infants Born at Less than 30 Weeks of Gestation

American Journal of Perinatology ◽

10.1055/s-0040-1712168 ◽

2020 ◽

Author(s):

Dinushan C. Kaluarachchi ◽

Tarah T. Colaizy ◽

Michael R. Lasarev ◽

David B. Allen ◽

Jonathan M. Klein

Keyword(s):

Preterm Infants ◽

Gestational Age ◽

In Utero ◽

Bivariate Analysis ◽

Study Cohort ◽

Thyroid Function Tests ◽

Objective Data ◽

Postmenstrual Age ◽

History Of ◽

Multivariable Regression

Abstract Objective Data on free thyroxine (FT4) concentrations beyond first 2 weeks of preterm infants are limited. This study was aimed to describe the association between perinatal characteristics and FT4 concentrations and the incidence of hypothyroxinemia at 4 weeks. Study Design Retrospective analysis of serum thyroid function tests at 4 weeks in preterm infants <30 weeks of gestation. Association between FT4 at 4 weeks of life and perinatal characteristics were determined by bivariate analysis and multivariable regression. Incidence of hypothyroxinemia was determined using a gestational age adjusted definition based on in utero levels at the equivalent postmenstrual age. Results The study cohort consisted of 280 infants. FT4 concentrations at 4 weeks of life were significantly associated with gestational age, birth weight, gender, and maternal history of thyroid disease. Hypothyroxinemia was found in 32.8% of the study cohort. Conclusion Perinatal characteristics are associated with FT4 concentrations at 4 weeks of life. Nearly one-third of infants born <30 weeks had hypothyroxinemia at 4 weeks of life when compared with in utero levels at the equivalent postmenstrual age.

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The Impact of Hypernatremia in Preterm Infants on Neurodevelopmental Outcome at 18 Months of Corrected Age

American Journal of Perinatology ◽

10.1055/s-0040-1716845 ◽

2020 ◽

Author(s):

Heather B. Howell ◽

Matthew Lin ◽

Michele Zaccario ◽

Sadaf Kazmi ◽

Felice Sklamberg ◽

...

Keyword(s):

Birth Weight ◽

Preterm Infants ◽

Gestational Age ◽

Serum Sodium ◽

Neurodevelopmental Outcome ◽

Population Characteristics ◽

Peak Serum ◽

Fine Motor ◽

Study Objective ◽

The Impact

Objective The study objective was to assess the correlation between hypernatremia during the first week of life and neurodevelopmental outcomes at 18 months of corrected age in premature infants. Study Design A retrospective observational study of preterm infants born at less than 32 weeks of gestation who had a neurodevelopmental assessment with the Bayley scales of infant and toddler development III at 18 ± 6 months of corrected age. Serum sodium levels from birth through 7 days of life were collected. The study cohort was divided into two groups: infants with a peak serum sodium of >145 mmol/L (hypernatremia group) and infants with a peak serum sodium level of <145 mmol/L (no hypernatremia group). Prenatal, intrapartum, and postnatal hospital course and neurodevelopmental data at 18 ± 6 months were collected. Logistic regression analysis was used to assess the correlation between neonatal hypernatremia and neurodevelopment with adjustment for selected population characteristics. Results Eighty-eight preterm infants with complete neurodevelopmental outcome data at 18 ± 6 months of corrected gestational age were included in the study. Thirty-five neonates were in the hypernatremia group and 53 were in the no hypernatremia group. Maternal and neonatal characteristics were similar between the two groups except that the hypernatremia group had a significantly lower average birth weight and gestational age. Comparison of the mean neurodevelopmental scores between the two groups showed that patients in the hypernatremia group as compared with those in the no hypernatremia group had significantly lower neurodevelopmental scaled scores in the fine motor domain (p = 0.01). This difference remained significant (p = 0.03, odds ratio [OR] = 0.8, 95% confidence interval [CI]: 0.6–0.97) when adjusted for birth weight and gestational age. Conclusion Preterm infants born at less than 32 weeks of gestation with hypernatremia in the first week of life have lower fine motor scores at 18 months of corrected age. Key Points

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The impact of ibuprofen on renal clearance in preterm infants is independent of the gestational age

Pediatric Nephrology ◽

10.1007/s00467-005-1842-8 ◽

2005 ◽

Vol 20 (6) ◽

pp. 740-743 ◽

Cited By ~ 23

Author(s):

Karel Allegaert ◽

Veerle Cossey ◽

Anne Debeer ◽

Jean Paul Langhendries ◽

Bart Van Overmeire ◽

...

Keyword(s):

Renal Clearance ◽

Preterm Infants ◽

Gestational Age ◽

The Impact

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Multiparametric Analysis of Cerebral Development in Preterm Infants Using Magnetic Resonance Imaging

Frontiers in Neuroscience ◽

10.3389/fnins.2021.658002 ◽

2021 ◽

Vol 15 ◽

Author(s):

Marine Dubois ◽

Antoine Legouhy ◽

Isabelle Corouge ◽

Olivier Commowick ◽

Baptiste Morel ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Preterm Infants ◽

Gestational Age ◽

Brain Maturation ◽

Resonance Imaging ◽

Equivalent Age ◽

Very Preterm ◽

Extremely Preterm ◽

The Impact

ObjectivesThe severity of neurocognitive impairment increases with prematurity. However, its mechanisms remain poorly understood. Our aim was firstly to identify multiparametric magnetic resonance imaging (MRI) markers that differ according to the degree of prematurity, and secondly to evaluate the impact of clinical complications on these markers.Materials and MethodsWe prospectively enrolled preterm infants who were divided into two groups according to their degree of prematurity: extremely preterm (<28 weeks’ gestational age) and very preterm (28–32 weeks’ gestational age). They underwent a multiparametric brain MRI scan at term-equivalent age including morphological, diffusion tensor and arterial spin labeling (ASL) perfusion sequences. We quantified overall and regional volumes, diffusion parameters, and cerebral blood flow (CBF). We then compared the parameters for the two groups. We also assessed the effects of clinical data and potential MRI morphological abnormalities on those parameters.ResultsThirty-four preterm infants were included. Extremely preterm infants (n = 13) had significantly higher frontal relative volumes (p = 0.04), frontal GM relative volumes (p = 0.03), and regional CBF than very preterm infants, but they had lower brainstem and insular relative volumes (respectively p = 0.008 and 0.04). Preterm infants with WM lesions on MRI had significantly lower overall GM CBF (13.3 ± 2 ml/100 g/min versus 17.7 ± 2.5, < ml/100 g/min p = 0.03).ConclusionMagnetic resonance imaging brain scans performed at term-equivalent age in preterm infants provide quantitative imaging parameters that differ with respect to the degree of prematurity, related to brain maturation.

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Risk Factors for Early Wheezing in Preterm Infants: A Retrospective Cohort Study

10.21203/rs.3.rs-42409/v1 ◽

2020 ◽

Author(s):

Xun Chen ◽

Minjing Yang ◽

Shengzhu Huang ◽

Xiaolian Qin ◽

Zhijian Pan ◽

...

Keyword(s):

Risk Factors ◽

Family History ◽

Preterm Infants ◽

Gestational Age ◽

Premature Delivery ◽

Related Factors ◽

Recurrent Wheezing ◽

History Of ◽

Group A ◽

Group B

Abstract Background: The related factors that cause recurrent wheezing in children are complex, and premature delivery may be one of the reasons. Little is known about early wheezing in preterm infants. Methods: Data sourced from 1616 children born between 2007 and 2013 from 8 hospitals of Guangxi in China. All children were followed by telephone or questionnaire through the sixth year of life. Children were grouped by characters of age: Group A: gestational age (GA) ≤ 32 weeks, Group B: 32 weeks < GA < 37 weeks, Group C: 37 weeks ≤ GA < 42 weeks. Results: The incidence and the risk factors of early wheezing in preterm infants were analyzed. The incidence of early wheezing: Group A > Group B > Group C. In Group A, the proportion of small-for-gestational-age (SGA) infant was higher in early wheezing group than in normal group (P = 0.005). Male (95% CI: 1.611 to 4.601) and family history of allergy (95% CI: 1.222 to 3.411) were the risk factors for early wheezing in Group B. Conclusions: Newborns with younger GA had a higher risk of early wheezing. SGA was a possible factor influencing early wheezing in preterm infants with GA≤ 32 weeks. Male and family history of allergy were the risk factors for early wheezing in preterm infants with 32 weeks < GA < 37 weeks.

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Impact of Carbon Dioxide on Cerebral Oxygenation and Vital Parameters in Stable Preterm and Term Infants Immediately after Birth

Neonatology ◽

10.1159/000519636 ◽

2021 ◽

pp. 1-8

Author(s):

Christina Helene Wolfsberger ◽

Marlies Bruckner ◽

Bernhard Schwaberger ◽

Lukas Peter Mileder ◽

Berndt Urlesberger ◽

...

Keyword(s):

Carbon Dioxide ◽

Oxygen Saturation ◽

Preterm Infants ◽

Gestational Age ◽

Oxygen Extraction ◽

Arterial Oxygen ◽

Secondary Outcome ◽

Tissue Oxygen ◽

Term Infants ◽

The Impact

Introduction: Carbon dioxide (pCO2) induces changes in the tone of cerebral vessels. The aim of the present study was to evaluate the impact of pCO2 on cerebral regional tissue oxygen saturation (crSO2), cerebral fractional tissue oxygen extraction (cFTOE), and cerebral tissue oxygen extraction (cTOE), measured with near-infrared spectroscopy (NIRS), in preterm and term infants 15 min after birth. Methods: Post hoc analyses of secondary outcome parameters of prospective observational studies were performed. Stable preterm and term infants with cerebral NIRS monitoring (INVOS 5100C) until minute 15 after birth and a blood gas analysis, performed between minutes 14–18 after birth, were included. Heart rate (HR) and arterial oxygen saturation (SpO2) were recorded. pCO2 was correlated with crSO2, cFTOE, cTOE, SpO2, HR, and partial pressure of oxygen (pO2). Results: Eleven preterm infants with a median (IQR) gestational age of 34.8 (32.7–36.1) weeks were analyzed. Mean ± SD pCO2 was 53.5 ± 4.2 mm Hg. At minute 15 after birth, crSO2 was 82.6 (74.3–91.3)%, cFTOE 0.15 ± 0.09, cTOE 14.6 ± 8.4%, SpO2 97.4 ± 2.1%, and HR 152 (136–167) bpm. pCO2 correlated negatively with crSO2 (p = 0.012) and positively with cFTOE (p = 0.035) and cTOE (p = 0.037). Eighty-four term infants with a gestational age of 39.0 (38.5–38.9) weeks were analyzed. pCO2 was 53.5 ± 6.3 mm Hg. At minute 15 after birth, crSO2 was 84.4 (80.8–85.1)%, cFTOE 0.14 ± 0.08, cTOE 13.6 ± 7.9%, SpO2 96.5 ± 2.6%, and HR 155 (153–163) bpm. pCO2 did only negatively correlate with pO2 (p = 0.034) in term infants. Conclusion: In preterm infants, higher pCO2 was associated with lower crSO2 and higher cFTOE/cTOE. In term infants, no associations were observed. The present findings suggest that the vasodilatative effect of pCO2 is less pronounced in preterm infants during immediate postnatal transition.

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Respiratory Syncytial Virus Associated Hospitalizations in Infants of 33 to 42 Weeksʼ Gestation: Does Gestational Age Matter?

Klinische Pädiatrie ◽

10.1055/a-0868-0004 ◽

2019 ◽

Vol 231 (04) ◽

pp. 206-211 ◽

Cited By ~ 1

Author(s):

Bernhard Resch ◽

Charlotte Wörner ◽

Selma Özdemir ◽

Magdalena Hubner ◽

Claudia Puchas ◽

...

Keyword(s):

Risk Factor ◽

Preterm Infants ◽

Gestational Age ◽

Respiratory Illness ◽

Late Preterm ◽

Term Infants ◽

History Of ◽

Near Term ◽

Syncytial Virus ◽

Older Siblings

Abstract Background To evaluate rates and characteristics of respiratory syncytial virus hospitalizations (RSV-H) in infants of 33 to 42 weeks of gestational age (GA). Patients All infants with a history of neonatal hospitalization and a GA of 33 to 42 weeks born between 2005 and 2015 and follow-up at least over one RSV season (first year of life). Infants with congenital heart disease and other congenital anomalies were excluded. Methods Retrospective single-center cohort STROBE compliant study. Data were collected regarding demographic data and re-hospitalization characteristics due to respiratory illness and due to RSV infection; and data were compared between moderate-late preterm, near term, term, and post term infants, respectively. Results A total of 81.656 live born infants were registered in our catchment area with gestational age from 33 to 42 weeks during the study period; and 2188 of 2356 preterm infants and 1004 of 1168 term infants with history of neonatal hospitalization were included for analysis. Rehospitalizations due to respiratory illness occurred in 301 preterm (13.8%) and 136 term (13.5%) infants for 381 and 183 times, respectively. In total 84 of 3192 infants (2.6%) were tested RSV positive, 61 of 2188 preterm (2.8%) and 23 of 1004 term (2.3%). Preterm infants without history of neonatal hospitalization had a RSV hospitalization (RSV-H) rate of 1.7% (61/3488) and term infants of 1.3% (967/74.644) that were significantly lower compared to study infants (p=0.004 and 0.002, respectively). Moderate and late preterm (2.8%), near term (3.1%) and post term (3.5%) infants had significantly higher RSV-H rates compared to term infants (1.2%). Risk factors for RSV-H in preterm infants included discharge during RSV season (4.2 vs. 2.0%, p=0.017) and presence of older siblings (4.2 vs. 2.1%, p=0.023), in term infants presence of older siblings (p=0.019). The course of RSV disease did not differ between groups. Discussion Interestingly, we did not observe decreasing RSV-H rates with increasing GA. Term infants represented the group with lowest RSV-H rates. Neonatal hospitalization was a risk factor for RSV-H for both preterm and term infants. Near term infants do more resemble the late preterm than term infants regarding RSV-H rates. Conclusion We found comparable higher RSV-H rates in all groups compared to term infants without differences in the course of disease and identified neonatal hospitalization as an independent risk factor.

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