Involvement of oxidative stress in placental dysfunction, the pathophysiology of fetal death and pregnancy disorders.

In brief: Placental oxidative stress contributes to both normal and abnormal placentation during pregnancy. This review discusses the potential consequence of oxidative stress-induced placental dysfunction on pregnancies complicated by fetal death and pregnancies with a high risk of fetal death. Abstract: The placenta is a source of reactive oxygen free radicals due to the oxidative metabolism required to meet the demands of the growing fetus. The placenta has an array of efficient antioxidant defense systems to deal with rising oxidative stress created by free radicals during pregnancy. Properly controlled physiological (low-level) free radical production is a necessary part of cellular signaling pathways and downstream activities during normal placental development; however, poorly controlled oxidative stress can cause aberrant placentation, immune disturbances and placental dysfunction. Abnormal placental function and immune disturbances are linked to many pregnancy-related disorders, including early and recurrent pregnancy loss, fetal death, spontaneous preterm birth, preeclampsia and fetal growth restriction. This review discusses the role of placental oxidative stress in both normal and pathological settings. Finally, based on previously published work, this review presents multiple lines of evidence for the strong association between oxidative stress and adverse pregnancy outcomes, including fetal death and pregnancies with a high risk of fetal death.

Health risk assessment associated with heavy metals through fractioned dust from coal and chromite mines in Pakistan.

Heavy metals exposure through dust emissions pose a health risk to workers in coal and chromite mines. The processes involved in mining are noteworthy for the generation of heavy metal-contaminated dust which causes human health implications, especially to the workers that are mainly exposed to such toxins. This study determined pollution levels in coal and chromite mines and calculated the health risk of workers being exposed to heavy metal-contaminated dust. We used fractioned dust with particle sizes < 75, 75-106, and 107-150 µm to assess the pollution levels, anthropogenic impacts, geo-accumulation index, and enrichment factor for selected coal and chromite mines. Through a probabilistic approach, Monte Carlo simulations were used to determine health risks. The findings revealed that the smallest size dust fraction (< 75 µm) contained the highest metal concentrations. Ingestion was considered a prominent exposure route contributing to health risk. In the dust fraction (< 75 µm), chromite mines exhibited the highest Cr (340.6 mg/kg) and lowest Cd (8.4 mg/kg) concentrations. In coal mines, Mn (284.9 mg/kg) and Cd (2.1 mg/kg) were measured highest and lowest, respectively. Pollution assessment revealed dust to be moderately polluted. Health risk assessment showed that Cr in chromite mines exhibited a mean HI value of 1.16E + 00 that was higher than the safe level (HI > 1) having the potential to cause significant health risk to workers. In coal mines, the estimated total HI was 6E-1. Sensitivity analysis revealed concentration and exposure time to be the most influential parameters contributing to risk. Therefore, governmental and nongovernmental organizations must develop dust pollution control guidelines and mitigation measures to safeguard the health of mineworkers by limiting heavy metal exposure.

Insights into fetal death-a patient resource.

Evidence supports a role for placental aging in the etiology of the majority of fetal deaths. This knowledge may reduce maternal feelings of guilt following fetal death that frequently exacerbates the distress caused by grief. The accompanying video may be a useful resource for women who have experienced a fetal death.

Pharyngoesophageal motility reflex mechanisms in the human neonate: importance of integrative cross-systems physiology.

Swallowing is a critical function for survival and development in human neonates and requires cross-system coordination between neurological, airway, and digestive motility systems. Development of pharyngoesophageal motility is influenced by intra- and extrauterine development, pregnancy complications, and neonatal comorbidities. The primary role of these motility reflex mechanisms is to maintain aerodigestive homeostasis under basal and adaptive biological conditions including oral feeding, gastroesophageal reflux, and sleep. Failure may result in feeding difficulties, airway compromise, dysphagia, aspiration syndromes, and chronic eating difficulties requiring prolonged tube feeding. We review the integration of cross-systems physiology to describe the basis for physiological and pathophysiological neonatal aerodigestive functions.

Differentiating esophageal sensitivity phenotypes using pH-impedance in intensive care unit infants referred for gastroesophageal reflux symptoms.

BACKGROUND: To identify esophageal sensitivity phenotypes relative to acid (SAcid), bolus (SBolus), acid and bolus (SAcid+Bolus), and none (SNone) exposures in infants suspected with gastroesophageal reflux disease (GERD). METHODS: Symptomatic infants (N = 279) were evaluated for GERD at 42 (40-45) weeks postmenstrual age using 24-h pH-impedance. Symptom-associated probability (SAP) for acid and bolus components defined esophageal sensitivity: (1) SAcid as SAP ≥ 95% for acid (pH < 4), (2) SBolus as SAP ≥ 95% for bolus, (3) SAcid+Bolus as SAP ≥ 95% for acid and bolus, or (4) SNone as SAP < 95% for acid and bolus. RESULTS: Esophageal sensitivity prevalence (SAcid, SBolus, SAcid+Bolus, SNone) was 28 (10%), 94 (34%), 65 (23%), and 92 (33%), respectively. Emesis occurred more in SBolus and SAcid+Bolus vs SNone (p < 0.05). Magnitude (#/day) of cough and emesis events increased with SBolus and SAcid+Bolus vs SNone (p < 0.05). SAcid+Bolus had increased acid exposure vs SNone (p < 0.05). Distributions of feeding and breathing methods were distinct in infants with SBolus vs SNone (both, p < 0.05). Multivariate analysis revealed that arching and irritability events/day were lesser at higher PMAs (p < 0.001) and greater for infants on NCPAP (p < 0.01) with SBolus and SAcid+Bolus (p < 0.05). Coughs/day was greater at higher PMAs (p < 0.001) for infants with gavage and transitional feeding methods (p < 0.02) with SBolus and SAcid+Bolus (p < 0.05) but lesser with Trach (p < 0.001). Number of emesis events/day were greater with SBolus and SAcid+Bolus (p < 0.001). Sneezes/day decreased for infants on Trach (p = 0.02). CONCLUSIONS: Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. We differentiated esophageal sensitivity phenotypes in NICU infants referred for GERD symptoms using pH-impedance. Acid sensitivity alone was rare, which may explain poor response to acid suppressives; aerodigestive symptoms were predominantly linked with bolus spread. Magnitude of esophageal acid exposure and esophageal sensitivity to bolus spread may explain the pathophysiological basis for symptoms. IMPACT: Objective GERD diagnosis and reasons for symptoms in NICU infants remains unclear. Differentiation of esophageal sensitivities by acid and bolus components of GER reveal distinct symptom profiles, specifically the bolus component of GER significantly contributes to symptom occurrence. Acid only sensitivity to GER is rare, and acid-suppressive therapy alone may not improve symptoms in a majority of NICU infants. Magnitude of esophageal acid exposure and esophageal sensitivity to any bolus spread may explain the pathophysiological basis for symptoms. Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. GERD treatments should be individualized to the patient's GERD phenotype and likely also target the bolus component of GER.

Is there a role for placental senescence in the genesis of obstetric complications and fetal growth restriction?

The placenta ages as pregnancy advances, yet its continued function is required for a successful pregnancy outcome. Placental aging is a physiological phenomenon; however, there are some placentas that show signs of aging earlier than others. Premature placental senescence and aging are implicated in a number of adverse pregnancy outcomes, including fetal growth restriction, preeclampsia, spontaneous preterm birth, and intrauterine fetal death. Here we discuss cellular senescence, a state of terminal proliferation arrest, and how senescence is regulated. We also explore the role of physiological placental senescence and how aberrant placental senescence alters placental function, contributing to the pathophysiology of fetal growth restriction, preeclampsia, spontaneous preterm labor/birth, and unexplained fetal death.

Evidence that fetal death is associated with placental aging.

BACKGROUND: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. OBJECTIVE: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. STUDY DESIGN: We collected placentas from women at 37-39 weeks' gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. RESULTS: Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. CONCLUSION: Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue.

Additive effect of lipid lowering drug (simvastatin) in combination with antidiabetic drug (glibenclamide) on alloxan induced diabetic rats with long term dyslipidemia.

High blood glucose level, elevated level of liver enzyme, necrosis and shrinkage of islets of Langerhans has been implicated in the pathogenesis of type 2 diabetes. High blood glucose cause oxidative stress, production of free radical as well as elevated SGPT and SGOT level. Both glibenclamide and simvastatin in fixed dose used as antihyperglycemic antidyslipidemic and antioxidative agents for type 2 diabetes treatment. This study therefore aimed to evaluate the antihyperglycemic, antidyslipidemic and antioxidative effect of fixed dose combination of glibenclamide (0.6 mg/70 kg body weight) and simvastatin (5 mg/70 kg body weight) on long term alloxan induced diabetic rats with cardiovascular disease using various diagnostic kits as a parameter of phamacotherapeutic and pharmacological effect. The study was carried out using 96 Swiss Albino male rats weighing about 200-220 g. Combination therapy induced a significant decrease in blood glucose level in alloxan induced diabetic rats, from 33.75 ± 1.65 to 5.80 ± 0.07 mmol/l 2 h after last dose administration, after 4 weeks treatment. In case of dyslipidemic effect, combination therapy reduced total cholesterol (45 %), triglyceride (36 %) and low density lipoprotein-cholesterol (32 %) levels significantly and increased high density lipoprotein-cholesterol level (57 %) in comparison with their respective diabetic control groups. Results of this study showed that combination therapy effectively decreased SGPT (ALAT) (55 %) and SGOT (ASAT) (51 %) in comparison with diabetic control group. It was also observed that catalase and superoxide dismutase enzyme activity was increased by 58 and 91 % respectively in comparison with diabetic control group after 4 weeks treatment with combination of both drugs. In conclusion, these findings of combination therapy (glibenclamide and simvastatin) on alloxan induced diabetes in rats are significantly better than monotherapy using single drug. The results of the present study suggest that, combination of the fixed dose of glibenclamide and simvastatin might be efficacious in patients with diabetic dyslipidemia and increased oxidative stress. Furthermore, this combination therapy offer dosage convenience to the patients and by virtue of its dual mode of action might be a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidemia and oxidative stress.

Characteristics of esophageal refluxate and symptoms in infants compared between pre-treatment and on treatment with proton pump inhibitors.

OBJECTIVE: To examine longitudinal pH-impedance characteristics from those infants who remained on proton pump inhibitors therapy for gastroesophageal reflux disease (GERD) as parents/providers refused to discontinue therapy after 4 weeks. STUDY DESIGN: Eighteen infants with acid reflux index >3% underwent treatment, and pH-impedance data were compared prior to and on proton pump inhibitors at 42 ± 1 and 46 ± 1 weeks' postmenstrual age, respectively. Esophageal acid and bolus exposure, symptoms and swallowing characteristics were examined. RESULTS: Proton pump inhibitors reduces the acid-mediated effects of reflux but modifies impedance and clearance mechanisms (P < 0.05). Prolonged therapy did not reduce symptoms (P > 0.05). Infants evaluated while on proton pump inhibitors were 1.8 times more likely to have swallows before and after reflux. CONCLUSIONS: Prescription of proton pump inhibitors for objectively determined GERD should have time limits, as prolonged treatment can result in prolonged esophageal bolus clearance time without relieving symptoms.

Comparison of direct effects of rice-thickened formula vs routine feeds on symptoms and gastroesophageal reflux indices: A crossover cohort study.

BACKGROUND: We compared the direct effects of routine vs rice-thickened formula on 24-h pH-impedance and symptom characteristics and then examined if dietary effects were modified by acid reflux index severity in infants. METHODS: Forty infants under consideration for gastroesophageal reflux disease and therapies were evaluated at 43 ± 1 weeks postmenstrual age. Each infant was equally fed routine diet and thickened formula during evaluations. Postprandial sessions were analyzed for acid reflux index, reflux events, clearance times, distal baseline impedance, and symptoms. RESULTS: Thickened formula has no effect (P ≥ 0.05) on acid reflux events' characteristics or overall symptom frequency. However, refluxate height and frequency of weakly acidic events and cough were decreased (P < 0.05). Prolonged bolus clearance and a decrease in distal baseline impedance were noted with thickened feeds (vs routine feeds) when acid reflux index was >7 (P < 0.05). CONCLUSION: Our pH-impedance testing protocol identifies direct effects of potential therapies at the point of care. Acutely, thickened formula does not impact acid-specific reflux indices but decreases full-column reflux and cough reflexes. In those with an acid reflux index of >7, thickened formula prolongs the distal esophageal bolus clearance (the mechanisms of which are uncertain). Clinical trials are needed to clarify objective indications and therapeutic use of thickened formulas for infants with gastroesophageal reflux disease, along with short- and long-term side effects.

Human placenta releases extracellular vesicles carrying corticotrophin releasing hormone mRNA into the maternal blood.

The human placenta releases diverse extracellular vesicles (EVs), including microvesicles (100-1000 nm) and exosomes (30-150 nm), into the maternal blood for feto-maternal communication. Exosomes and microvesicles contribute to normal pregnancy physiology and major pregnancy pathologies. Differences in miRNA expressions and protein content in placental exosomes have been reported in complicated pregnancies. During human pregnancy, Corticotropin-Releasing Hormone (CRH) is produced and released by the placenta into the maternal blood. CRH is involved in regulating gestational length and the initiation of labour. CRH mRNA levels in the maternal plasma rise with gestation. High levels of CRH mRNA are reported to be associated with preeclamptic and preterm pregnancies. However, the underlying mechanism of placental CRH mRNA secretion remains to be elucidated. We hypothesise that the placenta releases CRH mRNA packaged within extracellular vesicles (EVs) into the maternal blood. In this study, placental EVs (microvesicles and exosomes) were isolated from human term healthy placentas via villus washes and from explant culture media by differential centrifugation and purified by density gradient ultracentrifugation using a continuous sucrose gradient (0.25-2.5 M). Western blotting using placenta- and exosome-specific markers and electron microscopy confirmed exosomes and microvesicles in the placental wash and explant media samples. Real-time quantitative RT-PCR data detected CRH mRNA in placenta-derived EVs from placental washes and explants. We also sorted placenta-secreted EVs in maternal plasma samples (≥37 weeks) by high-resolution flow cytometry using a fluorescent-labelled PLAP antibody. CRH mRNA was demonstrated in placental EVs obtained from maternal blood plasma. We therefore show that human placental EVs carry CRH mRNA into the maternal blood. Our study implies that measuring CRH mRNA in placental EVs in the maternal plasma could beused for monitoring pregnancy.

The impact of FDI on the agriculture sector: A case study from Bangladesh.

This paper aims to inspect the relationship between Foreign Direct Investment (FDI) and the agricultural sector of Bangladesh. This study is based on time series data from 1972 to 2021. The Auto Regressive Distributed Lag (ARDL) model and F-Bound test are used to examine the relationship between the variables under study. The empirical finding suggests that FDI has a considerable negative influence on the agricultural sector in Bangladesh in the long term. Moreover, this is also found by the study that FDI has no effect in the short run on the country's agricultural sector. This study recommends that governments should adopt agriculture-friendly policies, and should adopt some training facilities for the farmer to increase their farming skills so that FDI can develop the agricultural sector.

Extracellular vesicles- crucial players in human pregnancy.

Extracellular vesicles (EVs) are lipid-bilayer enclosed membrane vesicles released by cells in physiological and pathological states. EVs are generated and released through a variety of pathways and mediate cellular communication by carrying and transferring signals to recipient cells. EVs are specifically loaded with proteins, nucleic acids (RNAs and DNA), enzymes and lipids, and carry a range of surface proteins and adhesion molecules. EVs contribute to intercellular signalling, development, metabolism, tissue homeostasis, antigen presentation, gene expression and immune regulation. EVs have been categorised into three different subgroups based on their size: exosomes (30-150 nm), microvesicles (100-1000 nm) and apoptotic bodies (1-5 µm). The status of the cells of origin of EVs influences their biology, heterogeneity and functions. EVs, especially exosomes, have been studied for their potential roles in feto-maternal communication and impacts on normal pregnancy and pregnancy disorders. This review presents an overview of EVs, emphasising exosomes and microvesicles in a general context, and then focusing on the roles of EVs in human pregnancy and their potential as diagnostics for adverse pregnancy outcomes.

How do migration decisions and drivers differ against extreme environmental events?

Migration is often understood to be a livelihood strategy to cope with the effects of environmental threats and climate change. Yet, the extent to which migration decisions differ due to the type, severity, and frequency of environmental events has been little explored. This paper employs household surveys in southwestern Bangladesh to explore this research gap. A multinominal regression model is used to simulate reported future migration decisions (200 sample households) in the context of both rapid-onset (i.e. cyclone and flood) and slow-onset (salinity, siltation, and riverbank erosion) environmental phenomena. Results show: i) previous disaster experience and increasing conflict in the community motivate migration in the near future in the context of slow-onset phenomena (salinity); (ii) economic strength and self-efficacy increase non-migration intention in both contexts of sudden and slow-onset events; and (iii) the extent and pattern of these influences on migration differ across demographics, including education, religion, and age. Importantly, this analysis shows that the relationship between migration decisions and the type, severity, and frequency of environmental events is influenced by socioeconomic conditions. Therefore, this research supports future adaptation planning specifically tailored to the type and exposure of extreme environmental events.

In harm's way: Non-migration decisions of people at risk of slow-onset coastal hazards in Bangladesh.

Non-migration is an adaptive strategy that has received little attention in environmental migration studies. We explore the leveraging factors of non-migration decisions of communities at risk in coastal Bangladesh, where exposure to both rapid- and slow-onset natural disasters is high. We apply the Protection Motivation Theory (PMT) to empirical data and assess how threat perception and coping appraisal influences migration decisions in farming communities suffering from salinization of cropland. This study consists of data collected through quantitative household surveys (n = 200) and semi-structured interviews from four villages in southwest coastal Bangladesh. Results indicate that most respondents are unwilling to migrate, despite better economic conditions and reduced environmental risk in other locations. Land ownership, social connectedness, and household economic strength are the strongest predictors of non-migration decisions. This study is the first to use the PMT to understand migration-related behaviour and the findings are relevant for policy planning in vulnerable regions where exposure to climate-related risks is high but populations are choosing to remain in place.

Symptom Scores and pH-Impedance: Secondary Analysis of a Randomized Controlled Trial in Infants Treated for Gastroesophageal Reflux.

BACKGROUND AND AIMS: To evaluate and compare gastro-esophageal reflux (GER) symptom scores with pH-impedance and test the effects of acid-suppressive medications with or without feeding modifications on pH-impedance in high-risk infants. METHODS: Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) and 24-hour pH-impedance data were analyzed from 94 infants evaluated in a tertiary care setting for GER disease. Longitudinal data from 40 infants that received randomized GER therapy (proton pump inhibitor [PPI] with or without feeding modifications) for 4 weeks followed by 1-week washout were analyzed. Relationships between I-GERQ-R and pH-impedance metrics (acid reflux index, acid and bolus GER events, distal baseline impedance, and symptoms) were examined and effects of treatments compared. RESULTS: (A) Correlations between I-GERQ-R and pH-impedance metrics were weak. (B) I-GERQ-R sensitivity, specificity, and positive predictive values were suboptimal when correlated with pH-impedance metrics. I-GERQ-R negative predictive value (NPV) was high for acid symptom-association probability (NPV = 84%) and distal baseline impedence (NPV = 86%) thresholds. (C) PPI with feeding modifications (vs PPI alone) did not alter pH-impedance metrics or symptom scores (P > .05); however, bolus clearance metrics worsened for both treatment groups (P < .05). CONCLUSIONS: In high-risk infants (1) I-GERQ-R may be a helpful clinical screening tool to exclude acid-GER disease diagnosis and minimize unnecessary acid-suppressive treatment, but further testing is needed for diagnosis. (2) Acid-suppressive therapy with feeding modifications has no effect on symptom scores or pH-impedance metrics. Clearance of refluxate worsened despite PPI therapy, which may signal development of pharyngoesophageal dysmotility and persistence of symptoms. (3) Placebo-controlled trials are needed in high-risk infants with objective pH-impedance criteria to determine efficacy, safety, and underlying mechanisms. Clinicaltrials.gov ID: NCT02486263.

Evaluation of SIMESON, a training program to improve access to quality health care for pregnant women and newborn in different healthcare facilities of northern Bangladesh.

AIM: The study aims to explore the current knowledge and skills of healthcare providers already trained by SIMESON (simulation for essential skills for obstetrical and neonatal care), in reviewing perinatal health situations including current status of healthcare facilities and cost estimation. DESIGN: It was an observational study. METHODS: Cost estimation following both quantitative and qualitative approaches was also attempted. RESULT: Knowledge and skills of 88 healthcare providers about the provision of normal delivery and immediate postpartum care, management of postpartum haemorrhage (PPH), retained placenta and use of bag and mask ventilation to help a baby breathe were found to be considerably strengthened following SIMESON training. During the 6 months after training, there were 477 PPH cases managed successfully with only one death; neonatal deaths observed were 6.6/1,000 live births; twice the number of facility deliveries; and 80% use rate of Ambu bag for helping baby breathe. The estimated cost per trainee was 395.68 USD, and 5.85 USD per beneficiary.

Studying the effects of profenofos, an endocrine disruptor, on organogenesis of zebrafish.

Profenofos is an endocrine-disrupting chemical that can enter into the aquatic ecosystem either through surface runoff or through percolation of a toxicant from the soil. In order to clarify the effect of profenofos on the developmental stages of zebrafish, the embryos were treated with serial dilutions of profenofos (0%, 10%, 25%, and 50% of LC50). Embryos were treated with profenofos for 7 days or until hatching. The toxic endpoints assessed include hatching time, survival, malformation, and heartbeats of the embryos. In a 96-h test on zebrafish embryos, the LC50 of profenofos was 0.057 mg/L. Profenofos considerably lowered survival, increased abnormalities at different ontogenetic stages, and developed malformations of different organs in a concentration-dependent fashion. The identified developmental malformations were fluid accumulation, impaired jaw, short tail, ruptured pectoral and caudal fin, curved body, thin yolk sac tube, and deformed heart. The way of looping arrangement of the heart at the early stage of embryos was significantly influenced by the higher concentration of profenofos. Heartbeat is also reduced significantly in a concentration-dependent fashion. The results show that the zebrafish are susceptible to profenofos even at lower concentrations in the initial stage. Therefore, when used in agricultural areas adjacent to the aquatic environment, endocrine-disrupting chemicals should be used in an appropriate manner.

Mechanisms and management considerations of parent-chosen feeding approaches to infants with swallowing difficulties: an observational study.

Videofluoroscopy swallow studies (VFSS) and high-resolution manometry (HRM) methods complement to ascertain mechanisms of infant feeding difficulties. We hypothesized that: (a) an integrated approach (study: parent-preferred feeding therapy based on VFSS and HRM) is superior to the standard-of-care (control: provider-prescribed feeding therapy based on VFSS), and (b) motility characteristics are distinct in infants with penetration or aspiration defined as penetration-aspiration scale (PAS) score ≥ 2. Feeding therapies were nipple flow, fluid thickness, or no modification. Clinical outcomes were oral-feeding success (primary), length of hospital stay and growth velocity. Basal and adaptive HRM motility characteristics were analyzed for study infants. Oral feeding success was 85% [76-94%] in study (N = 60) vs. 63% [50-77%] in control (N = 49), p = 0.008. Hospital-stay and growth velocity did not differ between approaches or PAS ≥ 2 (all P > 0.05). In study infants with PAS ≥ 2, motility metrics differed for increased deglutition apnea during interphase (p = 0.02), symptoms with pharyngeal stimulation (p = 0.02) and decreased distal esophageal contractility (p = 0.004) with barium. In conclusion, an integrated approach with parent-preferred therapy based on mechanistic understanding of VFSS and HRM metrics improves oral feeding outcomes despite the evidence of penetration or aspiration. Implementation of new knowledge of physiology of swallowing and airway protection may be contributory to our findings.

Approach to Feeding Difficulties in Neonates and Infants: A Comprehensive Overview.

Deglutition disorders (DD) can be transient and considered as physiologic during normal maturation. However, when oral feeding milestones are impaired and bothersome symptoms and aerodigestive consequences are associated, it is interpreted as DD with varying specific entities, such as feeding difficulties, swallowing disorders, aerodigestive illness, and aspiration syndromes. Symptoms related to DD are heterogeneous and managed empirically. This article clarifies current controversies, explains the potential role of safe feeding and physiologic and pathophysiologic perspectives, and highlights current advances in the field. Evidence basis for diagnostic strategies is discussed, and involves evaluation for structure and function tests, and nutrition and feeding assessment.