Postconceptional Age Research Articles

Increased Impact of Air Pollution on Lung Function in Preterm versus Term Infants: The BILD Study.

Rationale: Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives: We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods: In the prospective BILD (Basel-Bern Infant Lung Development) birth cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter ⩽10 μm in aerodynamic diameter (PM10) and nitrogen dioxide with lung function at 44 weeks' postconceptional age and exhaled markers of inflammation and oxidative stress response (fractional exhaled nitric oxide [FeNO]) in an explorative hypothesis-driven study design. Multilevel mixed-effects models were used and adjusted for known confounders. Measurements and Main Results: Significant associations of PM10 during the second trimester of pregnancy with lung function and FeNO were found in term and preterm infants. Importantly, we observed stronger positive associations in preterm infants (born 32-36 wk), with an increase of 184.9 (95% confidence interval [CI], 79.1-290.7) ml/min [Formula: see text]e per 10-μg/m3 increase in PM10, than in term infants (75.3; 95% CI, 19.7-130.8 ml/min) (pprematurity × PM10 interaction = 0.04, after multiple comparison adjustment padj = 0.09). Associations of PM10 and FeNO differed between moderate to late preterm (3.4; 95% CI, -0.1 to 6.8 ppb) and term (-0.3; 95% CI, -1.5 to 0.9 ppb) infants, and the interaction with prematurity was significant (pprematurity × PM10 interaction = 0.006, padj = 0.036). Conclusions: Preterm infants showed significantly higher susceptibility even to low to moderate prenatal air pollution exposure than term infants, leading to increased impairment of postnatal lung function. FeNO results further elucidate differences in inflammatory/oxidative stress response when comparing preterm infants with term infants.

Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n = 55; approximately 800–1000 IU from combined sources) or monitored therapy (n = 54; with an option of dose modification). 25-hydroxyvitamin D [25(OH)D] concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52 ± 2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (>90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p = 0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity.

Inhaled nitric oxide (INO) is used to treat hypoxic respiratory failure without clear evidence of benefit. Future trials to evaluate its use will be designed based on an understanding of the populations in which this therapy is provided and with outcomes based on patient characteristics, for example, a history of premature birth. This was a multi-center prospective observational study that evaluated subjects in the pediatric ICU who were treated with INO for a respiratory indication, excluding those treated in the neonatal ICU or treated for birth-related disease. We used logistic regression to evaluate characteristics associated with mortality and duration of mechanical ventilation. Specifically, we compared subjects born early preterm (<32 weeks post-conceptual age), late preterm (32-37 weeks post-conceptual age), and full term. A total of 163 children (median age [interquartile range], 1.8 [0.7-6.0] y) were included, 41 (25.2%) had a history of preterm birth (18 born early preterm and 23 born late preterm). INO was initiated for less-severe lung disease in the early preterm versus late preterm versus full-term subjects (median mean airway pressures, 16 vs 19 vs 19 cm H2O; P = .03), although the oxygenation index and oxygenation saturation index did not differ. The early preterm subjects had more ventilator-free days (median, 18.0, 7.0, 4.5 d; P = .02) and lower 28-d mortality (0, 26.1, 32.0%; P = .007). Lower respiratory tract disease, but not a history of prematurity, was independently associated with lower mortality. INO was used differently in early preterm subjects. Clinical trials that evaluate INO use should have standardized oxygenation deficit thresholds for initiation of therapy and should consider stratifying by early preterm status.

Neurological development and iron supplementation in healthy late-preterm neonates: a randomized double-blind controlled trial

Late-preterm infants (LPT) are at increased risk for long-term neurodevelopmental sequelae and iron deficiency. The aim of the study is to assess the positive effect of iron supplementation on psychomotor development in healthy LPT. We designed a randomized placebo-controlled double-blind trial dividing the newborns into two groups. Every patient was assessed using the Griffiths Mental Development Scales (GMDS)-II edition at 12-month post-conceptional age. The study was performed at the Neonatology Unit of our Hospital, in Italy. Sixty-six healthy LPT infants born between 340⁄7 and 366⁄7 weeks of gestational age were enrolled in the study. One group received martial prophylaxis from the third week of life to 6 months of post-conceptional age (2 mg/kg/day of iron pidolate), the other received placebo. Fifty-two of the enrolled infants were assessed using the GMDS at 12-month of post-conceptional age. Statistical analysis of the mean scores of the Griffiths subscales was performed. There was a difference in the mean developmental quotient (DQ) (p < 0.01) between the two groups: iron group mean DQ 121.45 ± 10.53 vs placebo group mean DQ 113.25 ± 9.70. Moreover, mean scores of the Griffiths subscales A, B, and D showed significant differences between the two groups (scale A p < 0.05, scale B p < 0.02, scale D p < 0.01, respectively).Conclusions: We recommend that all LPT neonates receive iron supplementation during the first 6 months of life in order to improve their 1-year neurodevelopmental quotient.What is Known:• Late-preterm infants (LPT) are at increased risk for long-term neurodevelopmental sequelae and also for iron deficiency.• Iron deficiency is an independent risk factor for adverse neurological outcomes.What is New:• Healthy late-preterm who received iron supplementation during the first 6 months of life achieved better neurological outcomes at 12-month post-conceptional age than LPT who received placebo.• Our study strongly supports the need for the implementation of martial prophylaxis in LPT neonates.

Weight shapes the intestinal microbiome in preterm infants: results of a prospective observational study

BackgroundThe intestinal microbiome in preterm infants differs markedly from term infants. It is unclear whether the microbiome develops over time according to infant specific factors.MethodsWe analysed (clinical) metadata - to identify the main factors influencing the microbiome composition development - and the first meconium and faecal samples til the 4th week via 16 S rRNA amplican sequencing.ResultsWe included 41 infants (gestational age 25–30 weeks; birth weight 430-990 g. Birth via Caesarean section (CS) was associated with placental insufficiency during pregnancy and lower BW. In meconium samples and in samples from weeks 2 and 3 the abundance of Escherichia and Bacteroides (maternal faecal representatives) were associated with vaginal delivery while Staphylococcus (skin microbiome representative) was associated with CS. Secondly, irrespective of the week of sampling or the mode of birth, a transition was observed as children children gradually increased in weight from a microbiome dominated by Staphylococcus (Bacilli) towards a microbiome dominated by Enterobacteriaceae (Gammaproteobacteria).ConclusionsOur data show that the mode of delivery affects the meconium microbiome composition. They also suggest that the weight of the infant at the time of sampling is a better predictor for the stage of progression of the intestinal microbiome development/maturation than postconceptional age as it less confounded by various infant-specific factors.

Long-Term Mechanical Ventilation in Neonates: A 10-Year Overview and Predictive Model.

Objectives: Significant resources are devoted to neonatal prolonged mechanical ventilation (NPMV), but little is known about the outcomes in those children. Our primary objective was to describe the NPMV respiratory, digestive, and neurological outcomes at 18 months corrected age. Our second objective was on the early identification of which patients, among the NPMV cohort, will need to be ventilated for ≥125 days, which corresponded to the 75th percentile in the preliminary data, and to describe that subgroup.Methods: In this retrospective cohort study, we included all children born between 2004 and 2013 who had a NPMV (≥21 days of invasive or noninvasive respiratory support reached between 40 and 44 weeks of postconceptional age). We used random forests, logistic regression with penalization, naive Bayes, and XGBoost to predict which patients will need ≥125 days of ventilation. We used a Monte Carlo cross validation.Results: We included 164 patients. Of which, 40% (n = 66) were female, and the median gestational age was 29 weeks [interquartile range (IQR): 26–36 weeks] with a bimodal distribution. Median ventilation days were 104 (IQR: 66–139 days). The most frequently associated diagnoses were pulmonary hypertension (43%), early pulmonary dysplasia (41%), and lobar emphysema (37%). At 18 months corrected age, 29% (n = 47) had died, 59% (n = 97) were free of any respiratory support, and 45% (n = 74) were exclusively orally fed. A moderate area under the ROC curve of 0.65 (95% CI: 0.54–0.72) for identifying patients in need of ≥125 days of ventilation at inclusion was achieved by random forests classifiers. Among the 26 measured at inclusion, the most contributive ones were PCO2, inspired O2 concentration, and gestational age. At 18 months corrected age, patients ventilated for ≥125 days had a lower respiratory weaning success (76 vs. 87%, P = 0.05), lower exclusive oral feeding proportion (51 vs. 84%, P < 0.001), and a higher neurological impairment (median Pediatric Cerebral Performance Category score 3 vs. 2, P = 0.008) than patients ventilated for < 125 days.Conclusion: NPMV is a severe condition with a high risk of mortality, neurological impairment, and oral feed delay at 18 months. Most survivors are weaned of any respiratory support. We identified the risk factors that allow for the early identification of the most at-risk children of long-term ventilation with a moderate discrimination.

Blood Pressure Variability and Baroreflex Sensitivity in Premature Newborns-An Effect of Postconceptional and Gestational Age.

Introduction: Cardiovascular system is the vitally important system in the dynamical adaptation process of the newborns to the extrauterine environment. To reliably detect immaturity in the given organ system, it is crucial to study the development of the organ functions in relation to maturation process.Objectives: The objective was to determine the changes in the spontaneous short-term blood pressure variability (BPV) and baroreflex sensitivity (BRS) reflecting various aspects of cardiovascular control during the process of maturation in preterm babies and to separate effects of gestational age and postnatal age.Methods: Thirty-three prematurely born infants without any signs of cardio-respiratory disorders (gestational age: 31.8, range: 27–36 weeks; birth weight: 1,704, range: 820–2,730 grams) were enrolled. Continuous peripheral blood pressure signal was obtained by non-invasive volume-clamp photoplethysmography method during supine rest. The recordings of 250 continuous beat-to-beat blood pressure values were processed by spectral analysis of BPV (assessed measures: total power, low frequency and high frequency powers of systolic BPV) and BRS calculation. For each infant we also assessed systolic, diastolic and mean blood pressures, heart rate and respiratory rate.Results: With the postconceptional age, BPV measures decreased (for total power: Spearman correlation coefficient rs = −0.345, P = 0.049; for low frequency power: rs = −0.365, P = 0.037; for high frequency power rs = −0.349; P = 0.046); and BRS increased significantly (rs = 0.448, P = 0.009). The further analysis demonstrated that these effects were more attributable to gestational age than to postnatal age. BRS correlated negatively with BPV magnitude (rs = −0.479 to −0.592, P = 0.001–0.005). Mean blood pressure and diastolic blood pressure increased during maturation (rs = 0.517 and 0.537, P = 0.002 and 0.001, respectively) while heart rate and respiratory rate decreased (rs = −0.366 and −0.516, P = 0.036 and 0.002, respectively).Conclusion: We conclude that maturation process is accompanied by an increased involvement of baroreflex buffering of spontaneous short-term blood pressure oscillations. Gestational age plays a dominant role not only in BPV changes but also in BRS, mean blood pressure, diastolic blood pressure and heart rate changes.

Neighborhood Disadvantage and Early Respiratory Outcomes in Very Preterm Infants with Bronchopulmonary Dysplasia

To investigate the impact of neighborhood conditions on respiratory-related hospital admissions in the first year after discharge from the neonatal unit in a population of infants born very preterm with bronchopulmonary dysplasia (BPD). Very preterm infants (gestational age <33 weeks) who had BPD at 36 weeks postconceptional age and who received follow-up in a French regional medical network were included. Socioeconomic context was estimated using a neighborhood-based Socioeconomic Deprivation Index. Poisson regression analysis was used to identify risk factors associated with rehospitalization. The study included 423 infants with a mean gestational age of 27 ± 2 weeks and mean birth weight of 941 ± 277 g; 51% of the population lived in a disadvantaged area. The hospital admission rate was increased by 8.8% for infants living in affluent areas and by 24% for those living in disadvantaged areas (P<.01) and reached 30% in extremely preterm infants from disadvantaged areas. After adjusting for perinatal characteristics, home oxygen therapy, and season of birth, the respiratory-related hospitalization rate was almost 3-fold higher in infants living in disadvantaged areas, with an adjusted incidence rate ratio of 2.79 (95% CI, 1.29-6.09; P <.01). Disadvantaged neighborhoods adversely impact early respiratory outcomes in infants born very preterm with BPD. The social context should be considered in routine follow-up care of children born preterm. Further studies investigating the underlying mechanisms are warranted for implementing preventive strategies.

Exocrine Pancreatic Maturation in Pre-term and Term Piglets Supplemented With Bovine Colostrum

Pre-term infants have an immature digestive system predisposing to short- and long-term complications including feeding intolerance, maldigestion and necrotizing enterocolitis (NEC). Optimal feeding strategies are required to promote maturation of the gut including the exocrine pancreas. Little is known about age- and diet-related development of pancreatic exocrine enzymes following pre-term birth. Currently, bovine colostrum supplementation is investigated in clinical trials on pre-term infants. Using pigs as models for infants, we hypothesized that pancreatic enzyme content is (1) immature following pre-term birth, (2) stimulated by early colostrum supplementation, and (3) stimulated by later colostrum fortification. Thus, using piglets as models for infants, we measured trypsin, amylase, lipase and total protein in pancreatic tissue collected from piglets delivered by cesarean section either pre-term (90% gestation) or close to term. Experiment 1:Pre-term and term pigs were compared at birth and 11 days. Experiment 2: Pre-term and term pigs were either enterally supplemented with bovine colostrum or fed total parenteral nutrition for 5 days, followed by exclusive milk feeding until day 26. Experiment 3: Pre-term pigs were fed bovine's milk with or without colostrum fortification until 19 days. The results showed that pancreatic trypsin, amylase and total protein contents were reduced in pre-term vs. term pigs. Trypsin mainly increased with advancing post-conceptional age (2-fold), while amylase was affected predominantly by advancing post-natal age, and mostly in pre-term pigs from birth to 11 or 26 days. Colostrum feeding in both term and pre-term piglets decreased trypsin and increased amylase contents. Lipase activity decreased with advancing gestational age at birth and post-natal age, with no consistent responses to colostrum feeding, with lipase activities decreasing relative to total pancreatic protein content. In summary, key pancreatic enzymes, amylase and trypsin, are immature following pre-term birth, potentially contributing to reduced digestive capacity in pre-term neonates. Rapid post-natal increases occurs within few weeks of pre-term birth, partly stimulated by enteral colostrum intake, reflecting a marked adaptation capacity. Alternatively, lipase is less affected by pre-/post-natal age and feeding. Thus, there is a highly enzyme-specific and asymmetric perinatal development of the exocrine pancreas.

The Effect of an Eyelid Speculum on Intraocular Pressure Measurement in Newborns

To evaluate the effect of an eyelid speculum on intraocular pressure (IOP) measurements in newborns. A total of 54 eyes of 27 newborns were involved in the study. The IOP measurements were obtained under topical anesthesia with the Icare PRO (Icare Finland Oy) before and after inserting the infant type of Barraquer wire eyelid speculum. A paired t test was used to compare the measurements. The mean IOP without the eyelid speculum was 9.04 ± 2.13 mm Hg (range: 6.00 to 13.20 mm Hg) in the right eye and 9.26 ± 1.59 mm Hg (range: 7.10 to 13.00 mm Hg) in the left eye. With the eyelid speculum in place, the mean IOP was 11.91 ± 2.23 mm Hg (range: 9.10 to 15.80 mm Hg) in the right eye and 11.70 ± 1.89 mm Hg (range: 8.40 to 14.50 mm Hg) in the left eye (P ≤ .001). The mean differences in IOP between measurements with and without the eyelid speculum were 2.87 ± 2.23 mm Hg (range: 0.20 to 5.20 mm Hg) in the right eye and 2.44 ± 1.48 mm Hg (range: 0.00 to 4.90 mm Hg) in the left eye. The mean difference in IOP between measurements with and without the eyelid speculum for all eyes was 2.65 ± 1.89 mm Hg (range: 0.00 to 5.20 mm Hg). There was no correlation between the difference in IOP after the placement of the eyelid speculum and postconceptual age or weight at the examination (r = 0.11, P = .41, r = 0.32, P = .14, respectively). The Barraquer wire eyelid speculum caused an increase in IOP in newborns under topical anesthesia without a significant difference between postconceptual age and sex in both eyes. The average IOP rise after the eyelid speculum was inserted was 2.65 mm Hg. This effect should be considered when interpreting IOP measurements in newborns. [J Pediatr Ophthalmol Strabismus. 2022;59(1):13-16.].

Influence of Postconceptional Age on the Renal Biomarkers in Very-Low-Birth-Weight Infants

Influence of Postconceptional Age on the Renal Biomarkers in Very-Low-Birth-Weight Infants

A Case of Preterm Ovarian Hyperstimulation Syndrome Presenting With Vaginal Bleeding

Abstract Background: Preterm ovarian hyperstimulation syndrome (POHS) is a rare syndrome described in preterm female infants. This is associated with high serum estradiol and gonadotropin levels, multiple follicular ovarian cysts, and edema of the hypogastric, labial and upper leg regions. This usually occurs at 30 to 39 weeks post-conceptional age (PCA). Vaginal bleeding may or may not be present. We present an unusual case of POHS that had a delayed presentation at 5 months of age (45 weeks PCA) with vaginal bleeding. Case presentation: An extremely premature female infant presented with vaginal bleeding at 5 months of age. Workup revealed pubertal gonadotropins indicating ovarian hyperstimulation. She had mild swelling in the hypogastric region. No breast buds were palpable and there was no clitoromegaly. At the time LH (22.2 mu/ml), FSH (8.3 mu/ml), Estradiol (502.2 pg/mL), and Testosterone (111 ng/dL) were all highly elevated. Multiple ovarian follicles were visualized on her pelvic ultrasound, with generous ovarian dimensions: right ovary (3.6 x 1.6 x 1.9 cm, volume 5.7 cc) and left ovary (2.5 x 2.4 x 1.5 cm, volume 4.7 cc). The largest follicle measured 8.8 mm. The uterus was 3.3 x 1.3 x 1.7 cm, with endometrial stripe thickness of 3 mm. There was no endometrial or adnexal mass. Cosyntropin test showed adequate peak cortisol (32.6 mcg/dL). Her newborn screen had been normal. Serial monitoring of her lab work showed a decrease in her gonadotropin and estradiol levels. She had a recurrence of vaginal bleeding about 3 weeks after initial presentation. By 50 weeks PCA the bleeding had resolved and the LH (1.2 mu/ml), FSH (1.5 mu/ml), estradiol (36 pg/ml) had reduced considerably. Complete normalization of LH (1.2 mu/ml), FSH (1.5 mu/ml), E (36 pg/ml), and testosterone (&amp;lt;7 ng/dl) was demonstrated by 55 weeks PCA. Conclusion: POHS has been attributed to the immaturity of the hypothalamic-pituitary-gonadal axis in preterm infants. Vaginal bleeding has been described in one case [1] several weeks after breast enlargement and swelling of clitoral hood, labia majora, hypogastrium and upper legs. In our case the baby presented with vaginal bleeding at 45 weeks that recurred about 3 weeks later and resolved by 50 weeks, with only minimal swelling. This case underlines the need to be aware of this etiology and its varied presentation. [1] Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report. Altuntas et al. J Pediatr Endocr Met; 273(3-4):355-358.

PHYSICAL AND NEUROPSYCHIC DEVELOPMENT IN INFANTS DEPENDING ON THE VITAMIN D LEVEL IN THE UMBILICAL CORD BLOOD

In order to investigate the role of prenatal sufficiency of 25-hydroxyvitamin D3 (25(OH)D3) in the postnatal development of infants, a dynamic assessment of physical (PD) and neuropsychic development (NPD) was carried out in comparison with the level of 25(OH)D3 in umbilical cord blood in newborns, upon reaching 40 weeks of post-conceptual age (PCA); at 3, 6 and 12 months of corrected age (CA). Materials and Methods: A prospective observational study of 118 children born between 24 and 41 weeks of gestational age was carried out, of which 52 were premature (group 1) and 66 were term infants (group 2). Evaluation of 25(OH)D3 level in cord blood serum was carried out. using an immunochemical analyzer UniCel DxI600 Beckmancoulter, USA. To assess PD indicators (body weight, height, head circumference), the Intergrowth-21st nonparametric method was selected using an online postnatal growth calculator. NPD was assessed according to the CAT/CLAMS and Zhurba -Mastyukova's scales. Comparing the developmental age with the actual age, the developmental coefficient was calculated as a percentage, the value of which &gt;75 % indicated that the NPD corresponded to the actual or corrected age of the child. Research results and discussion: The median of the 25(OH)D3 indicator in the 1st group was 17,63 ng/l, 95 % CI / Q1-Q3: 10,07-21,39; in group 2 - 23,76 ng/l, 95 % CI / Q1-Q3: 17,2-39,34 (p &lt; 0,001). Severe deficiency of 25(OH)D3 (below 10 ng/ml) was observed more often in premature infants (25 %) and only in 9,1% of term infants (p = 0,03). A direct statistical dependence of the growth rates in both full-term and premature infants in compare of 25(OH)D3 in cord blood after they reach 12 months of CA (p = 0,049, p = 0,036, respectively) was proved. In the group of premature infants a statistically significant relationship between speech developmental disorders (coefficient of speech development CAT/CLAMS 75 % in compare of the age norm. The sensitivity and specificity of the method were 75,3 and 55 %, respectively. Conclusions: In order to produce preventive measures it is necessary to continue further study of low vitamin D prenatal supply influence on PD and NPD in the near and long-term prognosis in children.

Airway basal stem cells generate distinct subpopulations of PNECs.

SUMMARYPulmonary neuroendocrine cells (PNECs) have crucial roles in airway physiology and immunity by producing bioactive amines and neuropeptides (NPs). A variety of human diseases exhibit PNEC hyperplasia. Given accumulated evidence that PNECs represent a heterogenous population of cells, we investigate how PNECs differ, whether the heterogeneity is similarly present in mouse and human cells, and whether specific disease involves discrete PNECs. Herein, we identify three distinct types of PNECs in human and mouse airways based on single and double positivity for TUBB3 and the established NP markers. We show that the three PNEC types exhibit significant differences in NP expression, homeostatic turnover, and response to injury and disease. We provide evidence that these differences parallel their distinct cell of origin from basal stem cells (BSCs) or other airway epithelial progenitors.

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BackgroundNeonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. MethodsWe performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. ResultsTracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. ConclusionsThe results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registrationNCT02350348.

Nicotinic Receptors in the Brainstem Ascending Arousal System in SIDS With Analysis of Pre-natal Exposures to Maternal Smoking and Alcohol in High-Risk Populations of the Safe Passage Study.

Pre-natal exposures to nicotine and alcohol are known risk factors for sudden infant death syndrome (SIDS), the leading cause of post-neonatal infant mortality. Here, we present data on nicotinic receptor binding, as determined by 125I-epibatidine receptor autoradiography, in the brainstems of infants dying of SIDS and of other known causes of death collected from the Safe Passage Study, a prospective, multicenter study with clinical sites in Cape Town, South Africa and 5 United States sites, including 2 American Indian Reservations. We examined 15 pons and medulla regions related to cardiovascular control and arousal in infants dying of SIDS (n = 12) and infants dying from known causes (n = 20, 10 pre-discharge from time of birth, 10 post-discharge). Overall, there was a developmental decrease in 125I-epibatidine binding with increasing postconceptional age in 5 medullary sites [raphe obscurus, gigantocellularis, paragigantocellularis, centralis, and dorsal accessory olive (p = 0.0002–0.03)], three of which are nuclei containing serotonin cells. Comparing SIDS with post-discharge known cause of death (post-KCOD) controls, we found significant decreased binding in SIDS in the nucleus pontis oralis (p = 0.02), a critical component of the cholinergic ascending arousal system of the rostral pons (post-KCOD, 12.1 ± 0.9 fmol/mg and SIDS, 9.1 ± 0.78 fmol/mg). In addition, we found an effect of maternal smoking in SIDS (n = 11) combined with post-KCOD controls (n = 8) on the raphe obscurus (p = 0.01), gigantocellularis (p = 0.02), and the paragigantocellularis (p = 0.002), three medullary sites found in this study to have decreased binding with age and found in previous studies to have abnormal indices of serotonin neurotransmission in SIDS infants. At these sites, 125I-epibatidine binding increased with increasing cigarettes per week. We found no effect of maternal drinking on 125I-epibatidine binding at any site measured. Taken together, these data support changes in nicotinic receptor binding related to development, cause of death, and exposure to maternal cigarette smoking. These data present new evidence in a prospective study supporting the roles of developmental factors, as well as adverse exposure on nicotinic receptors, in serotonergic nuclei of the rostral medulla—a finding that highlights the interwoven and complex relationship between acetylcholine (via nicotinic receptors) and serotonergic neurotransmission in the medulla.

Earlier preterm birth is associated with a worse neurocognitive outcome in a rabbit model.

Preterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo's the clinical neurocognitive phenotypes of early and late PTB. Time mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age. PTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits. In this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.

DNA methylation perturbations may link altered development and aging in the lung.

Fetal perturbations in DNA methylation during lung development may reveal insights into the enduring impacts on adult lung health and disease during aging that have not been explored altogether before.We studied the association between genome-wide DNA-methylation and post-conception age in fetal-lung (n=78, 42 exposed to in-utero-smoke (IUS)) tissue and chronological age in adult-lung tissue (n=160, 114 with Chronic Obstructive Pulmonary Disease) using multi-variate linear regression models with covariate adjustment and tested for effect modification by phenotypes. Overlapping age-associations were evaluated for functional and tissue-specific enrichment using the Genotype-Tissue-Expression (GTEx) project.We identified 244 age-associated differentially methylated positions and 878 regions overlapping between fetal and adult-lung tissues. Hyper-methylated CpGs (96%) were enriched in transcription factor activity (FDR adjusted P=2x10-33) and implicated in developmental processes including embryonic organ morphogenesis, neurogenesis and growth delay. Hypo-methylated CpGs (2%) were enriched in oxido-reductase activity and VEGFA-VEGFR2 Signaling. Twenty-one age-by-sex and eleven age-by-pack-years interactions were statistically significant (FDR<0.05) in adult-lung tissue.DNA methylation in transcription factors during development in fetal lung recapitulates in adult-lung tissue with aging. These findings reveal molecular mechanisms and pathways that may link disrupted development in early-life and age-associated lung diseases.

English

BACKGROUND Retinopathy of prematurity (ROP) also known as retrolental fibroplasia is a vasoproliferative retinopathy which affects the retinal blood vessels in developing state. ROP is one of the major causes of preventable blindness in children. It usually occurs in very low birth weight premature infants. Its presentation varies from complete regression in some, to leaving long term sequelae in others. Our aim was to find the prevalence of ROP in Ganjam district, Odisha. METHODS A prospective study was undertaken in M.K.C.G. Medical College and Hospital along with Christian Hospital and City Hospital, Berhampur, from 01/10/2016 to 30/09/2018. Babies fulfilling the inclusion criteria were screened after 3rd week of life or post-conceptional age of 31 - 33 weeks whichever was at a later date, and followed till 45 weeks of gestation according to stage. The babies were screened by indirect ophthalmoscopy and 28 D lens with the help of infant speculum and scleral depressor after instilling topical anaesthetic 2 % proparacaine. The pupil was dilated with 0.4 % tropicamide and 2.5 % phenylephrine. Analysis of qualitative data was done by chi-square test. RESULTS Out of 123 babies examined, 26 were lost to follow up and 19 out of 97 babies (19.58 %) developed ROP (inclusive of all stages). Low birth weight, low gestational age, duration of oxygen exposure &gt; 2 days, exchange transfusion, septicaemia with positive CRP value were found to be significant risk factors in development of ROP. Hyperbilirubinemia, gender and multiple gestation were found to be insignificant in the development of ROP. CONCLUSIONS Timely screening, regular follow-up, early detection and intervention are the best ways to reduce the prevalence of ROP. Neonatal intensive care unit (NICU) should follow strict guidelines for screening of new-borns. Proper counselling and motivation of parents for regular screening of at-risk infants are the need of the hour. KEYWORDS Retinopathy of Prematurity, Low Birth Weight, Low Gestational Age, Oxygen Exposure, Exchange Transfusion

Normative Values for Auditory Brainstem Responses and Wave V Thresholds in Indian Neonates and Infants.

Click-evoked auditory-brainstem-response (ABR) is widely used for hearing screening in neonates and infants. However, their normative values are based on small studies. This retrospective study was done at a tertiary-care centre where click-ABR based screening is done in all newborns. ABR records (Nihon-Kohden machine, model MEB-9400K) of 420 healthy neonates (preterm 75; full-term 32) and infants (113) done over a period 4years (2014-2018) were analysed retrospectively. Sick neonates and those with Wave V threshold > 40dbnHL were excluded. Infants were divided into four groups based on post-conceptual age, Group A (75): 34-36 weeks; Group B (44): 37-40weeks; Group C (188):41weeks-1 month; and Group D (113): 1-6months. The mean absolute latencies for wave I, wave III, and wave V varied from 1.45-1.56 milliseconds (ms), 4.14-4.37ms, and 6.36-6.81ms respectively. Interpeak latencies for I-V and I-III varied from 4.91ms to 5.22ms and 2.69ms to 2.81ms respectively. Older infants had lower absolute and interpeak latencies. Late preterm babies were not different from term babies suggesting early maturation of brainstem pathways.