Cortical Processing of Multimodal Sensory Learning in Human Neonates.

Following birth, infants must immediately process and rapidly adapt to the array of unknown sensory experiences associated with their new ex-utero environment. However, although it is known that unimodal stimuli induce activity in the corresponding primary sensory cortices of the newborn brain, it is unclear how multimodal stimuli are processed and integrated across modalities. The latter is essential for learning and understanding environmental contingencies through encoding relationships between sensory experiences; and ultimately likely subserves development of life-long skills such as speech and language. Here, for the first time, we map the intracerebral processing which underlies auditory-sensorimotor classical conditioning in a group of 13 neonates (median gestational age at birth: 38 weeks + 4 days, range: 32 weeks + 2 days to 41 weeks + 6 days; median postmenstrual age at scan: 40 weeks + 5 days, range: 38 weeks + 3 days to 42 weeks + 1 days) with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI) and magnetic resonance (MR) compatible robotics. We demonstrate that classical conditioning can induce crossmodal changes within putative unimodal sensory cortex even in the absence of its archetypal substrate. Our results also suggest that multimodal learning is associated with network wide activity within the conditioned neural system. These findings suggest that in early life, external multimodal sensory stimulation and integration shapes activity in the developing cortex and may influence its associated functional network architecture.

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.

Pictorial review of the postmortem computed tomography in neonaticide cases.

Neonaticide is defined by the deliberate killing or homicide of a child within 24 h of its birth. In this context, three fundamental questions are generally asked of the forensic pathologist: what is the cause of death of the neonate? Was the child viable (i.e., what is the gestational age of the neonate)? Finally, was the neonate stillborn or liveborn?Postmortem imaging can help answer these questions by conducting (1) a complete lesional analysis of the body and the placenta, (2) an estimation of the gestational age by measuring the lengths of the diaphyseal long bones, and (3) an analysis of the aeration of the lungs and intestines. Using the details of 18 cases, we illustrate aspects of neonaticide cases in postmortem computed tomography (PMCT), offering detailed examples of notable postmortem changes and abnormalities, especially in the analysis of the pulmonary parenchyma. This article presents a useful iconography for the radiologist confronted with this rare yet complex forensic situation.

Newborn anthropometry, maternal capital, and altitude in the highland population from the province of Jujuy, Argentina.

OBJECTIVE: To analyze variability in newborn (NB) anthropometry among Jujenean NBs as a function of geographic altitude (500 m to ≈4000 masl), maternal anthropometry and other maternal characteristics within the maternal capital framework. MATERIALS AND METHODS: Data obtained from 41,371 mother/child pairs recorded in the Jujuy Perinatal Information System (SIP) between 2009 and 2014, including: NB and maternal weight, length/height and BMI; gestational age (corrected); maternal age, educational level, nutritional status, and marital status; birth interval; and planned pregnancy. Based on the declared place of residence, the prevalence of unsatisfied basic needs (% UBN) was determined and the data was split into two altitudinal groups: highlands (HL, >2500 masl) and lowlands (LL, <2500 masl). ANOVA, Chi-squared and Pearson tests were applied as needed. Statistical associations between the response variables-NB weight, length and BMI-and maternal and environmental variables were tested using a Generalized Additive Mixed Model (GAMM). RESULTS: All NB and maternal anthropometric variables were lower in HL compared to LL; they also presented negative correlations with altitude, except NB length. Apart from gestational age and birth interval, HL and LL presented statistically significant differences in all study variables. GAMM results showed that maternal anthropometry was the main influence on NB weight and length. DISCUSSION: Of all the maternal capital features examined, only maternal anthropometric variables were found to protect offspring against the negative impact of HL environments.

Effect of amino acid infusion during cesarean delivery on newborn temperature: a randomized controlled trial.

BACKGROUND: The effect of maternal amino acid (AA) infusion before and during cesarean delivery on neonatal temperature remains unknown. We hypothesized that thermogenic effects of AA metabolism would help maintain body temperature of newborn babies and their mothers. METHODS: Seventy-six parturients scheduled for elective singleton term cesarean delivery were equally randomized to receive intravenous 200 ml of AA or placebo approximately 1 h before subarachnoid block (infusion rate:100 ml/h). The primary outcome was the newborn rectal temperature at 0, 5 and 10 min after birth. The secondary outcomes included the maternal rectal temperature at six time-points: T0 = before starting study solution infusion, T1 = 30 min after starting infusion, T2 = one hour after starting infusion, T3 = during spinal block, T4 = half an hour after spinal block, T5 = at the time of birth and T6 = at the end of infusion, as well as maternal thermal discomfort and shivering episodes. RESULTS: There were no differences in newborn temperature between the two groups at any of the time-points (intervention-time-interaction effect, P = 0.206). The newborn temperature (mean [95%CI] °C) at birth was 37.5 [37.43-37.66] in the AA and 37.4 [37.34-37.55] in the placebo group. It showed a significant (P < 0.001) downward trend at 5 and 10 min after birth (time effect) in both groups. One neonate in the AA and five in the placebo group were hypothermic (temperature < 36.5 °C) (P = 0.20). There was a significant difference in the maternal temperature at all time points between the two groups (Intervention-time interaction effect, P < 0.001). However, after adjustment for multiplicity, the difference was significant only at T6 (P = 0.001). The mean difference [95%CI] in temperature decline from baseline (T0) till the end of infusion (T6) between the two groups was - 0.39 [- 0.55;- 0.22] °C (P < 0.0001). Six mothers receiving placebo and none receiving AA developed hypothermia (temperature < 36 °C) (P = 0.025). Maternal thermal discomfort and shivering episodes were unaffected by AA therapy. CONCLUSIONS: Under the conditions of this study, maternal AA infusion before and during spinal anesthesia for cesarean delivery did not influence the neonatal temperature within 10 min after birth. In addition, the maternal temperature was only maintained at two hours of AA infusion. TRIAL REGISTRATION: ClinicalTrials.government, Identifier NCT02575170 . Registered on 10th April, 2015 - Retrospectively registered.

Human neonates prefer colostrum to mature milk: Evidence for an olfactory bias toward the "initial milk"?

OBJECTIVES: Colostrum is the initial milk secretion which ingestion by neonates warrants their adaptive start in life. Colostrum is accordingly expected to be attractive to newborns. The present study aims to assess whether colostrum is olfactorily attractive for 2-day-old newborns when presented against mature milk or a control. METHODS: The head-orientation of waking newborns was videotaped in three experiments pairing the odors of: (a) colostrum (sampled on postpartum day 2, not from own mother) and mature milk (sampled on average on postpartum day 32, not from own mother) (n tested newborns = 15); (b) Colostrum and control (water; n = 9); and (c) Mature milk and control (n = 13). RESULTS: When facing the odors of colostrum and mature milk, the infants turned their nose significantly longer toward former (32.8 vs 17.7% of a 120-s test). When exposed to colostrum against the control, they responded in favor of colostrum (32.9 vs 16.6%). Finally, when the odor of mature milk was presented against the control, their response appeared undifferentiated (26.7 vs 28.6%). CONCLUSIONS: These results indicate that human newborns can olfactorily differentiate conspecific lacteal fluids sampled at different lactation stages. They prefer the odor of the mammary secretion - colostrum - collected at the lactation stage that best matches the postpartum age of their own mother. These results are discussed in the context of the earliest mother-infant chemo-communication. Coinciding maternal emission and offspring reception of chemosignals conveyed in colostrum may be part of the sensory precursors of attunement between mothers and infants.

Theoretical knowledge and skill retention 3 and 6 months after a European Newborn Life Support provider course.

INTRODUCTION: The European Resuscitation Council Newborn Life Support Course (ERC- NLS) aims at training healthcare professionals, involved in perinatal care, in order to intervene efficiently and promptly to assist transition or resuscitate neonates who require help at birth. However, limited data exists for the retention of the theoretical knowledge and practical skills provided by the course. This study aims to evaluate the degree of knowledge and skill retention 3 and 6 months after the ERC-NLS provider course. METHODS: This is a prospective study. Theoretical knowledge was evaluated using the ERC-approved NLS written test (50 True/False questions). Evaluation of technical skills included performance, on an Advanced Life Support neonatal maniquin (LAERDAL), of airway management, ventilation and support of circulation (21 detailed skills). The effect of certain factors on theoretical skill retention was also evaluated. RESULTS: One hundred and sixteen (n = 116) participants were initially recruited in the study (12 males and 104 females). Theoretical knowledge was evaluated in 113 participants (3 participants missed follow-up appointments) and technical skills in 80 participants. The mean score for theoretical knowledge was 86.24% ± 5.3, 80.88% ± 7.43 and 80.04% ± 7.04 at baseline, at 3 and 6 months, respectively. This difference was significant among the three time points (baseline vs 3 months: p < 0.001; baseline vs 6 months: p < 0.001; 3 month's vs 6 months: p = 0.034). Although gender did not have an effect, doctors and participants of higher education yielded higher score of success. Regarding technical skills, 9 skills showed a continuous decline of performance from baseline to 6 months, while no difference existed for 12 skills. CONCLUSIONS: Healthcare professionals after the NLS provider course retain satisfactory levels of theoretical knowledge and technical skills even at 6 months post-training, although, there is a decline compared to baseline. Further research is needed in order to establish the proper time and type of refreshment course in order to improve outcomes.

Three kinds of caesarean sections: the foetal/neonatal perspective.

In the age of hospital births, it is commonplace to contrast the vaginal route and the abdominal route as the basic classification. From the "point of view" of the foetus/neonate, we provide reasons to contrast "birth without labour" (that is birth by pre-labour caesarean section) and all the other vaginal and abdominal modes of birth. From a great diversity of theoretical reasons, one can anticipate that babies born by pre-labour caesarean sections are different from the others. We also provide reasons to popularize the concepts of "in labour non-emergency caesarean sections" and "planned in-labour caesarean sections".

Olfactory sensory and perceptual evaluation in newborn infants: A systematic review.

Fetuses are able to process olfactory stimuli present in the womb and continue to show a preference for these odors for months after birth. Despite the accumulated knowledge about their early ability to perceive odors, there is a lack of validated scales for odor response in newborns. The evaluation of reactions of the olfactory system to environmental stimuli in infants has been defined by methodological theoretical approaches of experimental and clinical assessment tools. These approaches are mainly based on psychophysical approaches and predominantly use behavioral and physiological measures. Examples can be found in studies describing early abilities of newborn babies for behaviors or heart rate variability showing memory of maternal food preferences or mother's breast milk. This systematic review aimed to determine whether validated odor assessment tools can be feasibly used in studies. Particularly in light of the current COVID-19 pandemic and evidence of associated olfactory impairment resulting from SARS-COV-2 infection, the study is also motivated by the need for tools to assess olfactory function in neonates.

Consistency between Impedance Technique and Echocardiogram Hemodynamic Measurements in Neonates.

OBJECTIVE: The aim of this study was to validate impedance technique (IT) by investigating the agreement in cardiac output measurements performed by IT and echocardiography (ECHO). STUDY DESIGN: This is a prospective observational study, including a total of 30 neonates who underwent hemodynamic measurements by IT and ECHO. To determine the agreement between both methods, we performed IT to measure stroke volume (SV-IT) and cardiac output (CO-IT) immediately before or after ECHO to measure SV (SV-ECHO) and CO (CO-ECHO). The precision and accuracy of the IT relative to ECHO were assessed. RESULTS: SV-ECHO and SV-IT were (4.45 ± 0.78) and (4.54 ± 0.81) mL, respectively. The bias and limits of agreement of SV-IT were 0.09 mL and ( -1.92 to 1.73) mL, respectively. The true precision of SV-IT was 27.3%. Furthermore, CO-ECHO and CO-IT were (0.62 ± 0.12) and (0.61 ± 0.12) L/min, respectively. The bias and LoA of CO-IT were 0.01L/min and (-0.33 to 0.31) L/min, respectively. The true precision of CO-IT was 28.3%. CONCLUSION: Agreement between the IT and ECHO in the cardiac output measurement appeared acceptable. However, the accuracy and precision of the IT approach should be further investigated using a larger sample.

Tidal Breathing Parameters Measured by Structured Light Plethysmography in Newborns: Is It Feasible in Neonatal Intensive Care Unit?

OBJECTIVE: Structured light plethysmography (SLP) is a novel and noncontact respiratory assessment technique. It provides tidal breathing measurement in patients difficult to cooperate. In this study, we aimed to determine data for tidal breathing parameters measured by SLP in newborns. STUDY DESIGN: Infants between 2 and 5 days of life without having any respiratory symptoms were eligible for this observational study. In total, 5 minutes of tidal breathing was recorded using SLP (Thora-3Di, PneumaCare Ltd, Cambridge, U.K.) in each infant. Various tidal breathing parameters including timing indices, flow-based parameters, and regional parameters were obtained from SLP data. RESULTS: A total of 57 infants underwent measurements in the study. Evaluable recordings from 42 term and 11 late preterm infants were analyzed. Median gestational age and birthweight of the infants were 38 (37-39) weeks and 3,195 (2,790-3,585) g, respectively. In terms of flow-based parameters, "tidal inspiratory flow at 50% of inspiratory volume divided by tidal expiratory flow at 50% of expiratory volume" was 1.29 (1.13-1.53). Relative contribution of the thorax to each breath in percentage was measured as 38.67 (28.21-43.60). Median values of left-right hemithoracic asynchrony and thoraco-abdominal asynchrony were 6.92 (5.35-9.04) and 17.96 (12.98-36.44) degrees in the study population, respectively. There were no differences in tidal breathing parameters except "hemithoracic asynchrony" between term and late preterm infants. Hemithoracic asynchrony was significantly lower in term neonates than late preterms. CONCLUSION: SLP was found to be feasible to obtain measures of tidal breathing parameters in newborns and it could be performed successfully even in the first days of life.

The association between maternal and foetal factors with birth weight discordance in twins from Yucatan, Mexico.

Birth weight discordance (BWD) is not an uncommon event in twin pregnancies and can be associated with maternal and newborn characteristics. We aimed to analyse the association between maternal sociodemographic and newborn characteristics with BWD in twin infants born in Yucatan, Mexico, during 2008-2017 (n = 2091 pairs). BWD was calculated as the percentage of birth weight of the heavier twin. We defined three categories of BWD: concordant twins: <15%, mild-discordant: 15-24%, and severe discordant: ≥25%. A multinomial logistic regression model was used to analyse the association between maternal sociodemographic and newborn characteristics with BWD. Seventy-four percent (n = 1547) of twin pairs were classified as concordant, 17% (n = 356) met the criteria for mild-discordance and 9% (n = 188) for severe discordance. The odds for mild-discordance were significantly lower for mothers with medium level of education and in the highest quartile of total twin birth weight (TBW). Opposite-sex twin pairs showed increased odds for mild-discordance compared with same-sex pairs. The odds for severe discordance increased as mothers were in older age groups and decreased as TBW increased. Our rates of BWD are similar to those reported in populations from wealthier countries and maternal age and education, infants' sex, and TBW are associated with BWD.

The role of gasotransmitters in neonatal physiology.

The gasotransmitters, nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO), are endogenously-produced volatile molecules that perform signaling functions throughout the body. In biological tissues, these small, lipid-permeable molecules exist in free gaseous form for only seconds or less, and thus they are ideal for paracrine signaling that can be controlled rapidly by changes in their rates of production or consumption. In addition, tissue concentrations of the gasotransmitters are influenced by fluctuations in the level of O2 and reactive oxygen species (ROS). The normal transition from fetus to newborn involves a several-fold increase in tissue O2 tensions and ROS, and requires rapid morphological and functional adaptations to the extrauterine environment. This review summarizes the role of gasotransmitters as it pertains to newborn physiology. Particular focus is given to the vasculature, ventilatory, and gastrointestinal systems, each of which uniquely illustrate the function of gasotransmitters in the birth transition and newborn periods. Moreover, given the relative lack of studies on the role that gasotransmitters play in the newborn, particularly that of H2S and CO, important gaps in knowledge are highlighted throughout the review.

Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island.

BACKGROUND: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. METHODS: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex. RESULTS: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (ß = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (ß = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (ß = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (ß = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (ß = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (ß = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (ß = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (ß = 0.14 mm, 95%CI = 0.002, 0.28). CONCLUSIONS: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

Assessment of breath sounds at birth using digital stethoscope technology.

Newborn transition is a phase of complex change involving lung fluid clearance and lung aeration. We aimed to use a digital stethoscope (DS) to assess the change in breath sound characteristics over the first 2 h of life and its relationship to mode of delivery. A commercially available DS was used to record breath sounds of term newborns at 1-min and 2-h post-delivery via normal vaginal delivery (NVD) or elective caesarean section (CS). Sound analysis was conducted, and two comparisons were carried out: change in frequency profiles over 2 h, and effect of delivery mode. There was a significant drop in the frequency profile of breath sounds from 1 min to 2 h with mean (SD) frequency decreasing from 333.74 (35.42) to 302.71 (47.19) Hz, p < 0.001, and proportion of power (SD) in the lowest frequency band increasing from 0.27 (0.11) to 0.37 (0.15), p < 0.001. At 1 min, NVD infants had slightly higher frequency than CS but no difference at 2 h.Conclusion: We were able to use DS technology in the transitioning infant to depict significant changes to breath sound characteristics over the first 2 h of life, reflecting the process of lung aeration.What is Known:• Lung fluid clearance and lung aeration are critical processes that facilitate respiration and mode of delivery can impact this• Digital stethoscopes offer enhanced auscultation and have been used in the paediatric population for the assessment of pulmonary and cardiac soundsWhat is New:• This is the first study to use digital stethoscope technology to assess breath sounds at birth• We describe a change in breath sound characteristics over the first 2 h of life and suggest a predictive utility of this analysis to predict the development of respiratory distress in newborns prior to the onset of symptoms.

Neonatal Iron: Factors Influencing its Level and Associated Complications - a Review Article.

BACKGROUND: Iron is an essential micronutrient which plays a significant role, particularly vital for early brain growth and function. Maternal iron condition influences the iron status of neonates since iron transferred from the mother is the only source for fetal iron. A depletion in iron as a result of rapid growth leads to iron deficiency which is common in neonates. Although there are inconsistencies with regard to the normal reference ranges for neonatal iron level, the current review summarized literature to provide compressive information about neonatal iron status and factors that influence its level. METHODS: This is a narrative review on the basis of relevant literatures mainly on neonatal iron from peer-reviewed journals. Electronic databases such as PubMed, PMC, Scopus, Science Direct, Google scholar, Google, and Yahoo were used to retrieve relevant literatures using key terms like "newborn iron, neonatal iron, iron overload, maternal factors, complication, iron level and neonates" separately and in combination. RESULTS: Several factors had been postulated as factors associated with neonatal iron status. The current review figured out that maternal obesity, gestational diabetes mellitus, preterm delivery, placental transferrin receptor, inappropriate iron supplementation, use of iron fortified formula, uses of recombinant erythropoietin therapy, smoking, maternal iron deficiency anemia, umbilical cord clamping, and transfusion are the major factors which can influence neonatal iron level. These factors may have either positive or negative effects on neonatal iron level. Both iron deficiency and iron overload at some stage in the fetal development or at early stage of neonatal development cause abnormal functions of multiple organ system of neonates and subsequently contributed to neonatal and childhood morbidity and mortality. CONCLUSIONS: By one and other means insufficient, late and extra maternal iron supplementation, early and delayed umbilical cord clamping have negative effects on the iron level of neonates. Therefore, careful prenatal and antenatal follow-up need to be strengthened with due emphasis for maternal iron assessment.

Prenatal prediction of neonatal haemodynamic adaptation after maternal hyperoxygenation.

The reactivity of the pulmonary vascular bed to the administration of oxygen is well established in the post-natal circulation. The vasoreactivity demonstrated by the fetal pulmonary artery Doppler waveform in response to maternal hyperoxia has been investigated. We sought to investigate the relationship between the reactivity of the fetal pulmonary arteries to hyperoxia and subsequent neonatal cardiac function in the early newborn period. METHODS: This explorative study with convenience sampling measured pulsatility index (PI), resistance index (RI), acceleration time (AT), and ejection time (ET) from the fetal distal branch pulmonary artery (PA) at baseline and following maternal hyperoxygenation (MH). Oxygen was administered for 10 min at a rate of 12 L/min via a partial non-rebreather mask. A neonatal functional echocardiogram was performed within the first 24 h of life to assess ejection fraction (EF), left ventricular output (LVO), and neonatal pulmonary artery AT (nPAAT). This study was conducted in the Rotunda Hospital, Dublin, Ireland. RESULTS: Forty-six women with a singleton pregnancy greater than or equal to 31 weeks' gestational age were prospectively recruited to the study. The median gestational age was 35 weeks. There was a decrease in fetal PAPI and PARI following MH and an increase in fetal PAAT, leading to an increase in PA AT:ET. Fetuses that responded to hyperoxygenation were more likely to have a higher LVO (135 ± 25 mL/kg/min vs 111 ± 21 mL/kg/min, p < 0.01) and EF (54 ± 9% vs 47 ± 7%,p = 0.03) in the early newborn period than those that did not respond to MH prenatally. These findings were not dependent on left ventricular size or mitral valve (MV) annular diameter but were related to an increased MV inflow. There was no difference in nPAAT. CONCLUSION: These findings indicate a reduction in fetal pulmonary vascular resistance (PVR) and an increase in pulmonary blood flow and left atrial return following MH. The fetal response to hyperoxia reflected an optimal adaptation to postnatal life with rapid reduction in PVR increasing measured cardiac output.

Acid Sphingomyelinase Inhibition Attenuates Cell Death in Mechanically Ventilated Newborn Rat Lung.

RATIONALE: Premature infants subjected to mechanical ventilation (MV) are prone to lung injury that may result in bronchopulmonary dysplasia. MV causes epithelial cell death and halts alveolar development. The exact mechanism of MV-induced epithelial cell death is unknown. OBJECTIVES: To determine the contribution of autophagy to MV-induced epithelial cell death in newborn rat lungs. METHODS: Newborn rat lungs and fetal rat lung epithelial (FRLE) cells were exposed to MV and cyclic stretch, respectively, and were then analyzed by immunoblotting and mass spectrometry for autophagy, apoptosis, and bioactive sphingolipids. MEASUREMENTS AND MAIN RESULTS: Both MV and stretch first induce autophagy (ATG 5-12 [autophagy related 5-12] and LC3B-II [microtubule-associated proteins 1A/1B light chain 3B-II] formation) followed by extrinsic apoptosis (cleaved CASP8/3 [caspase-8/3] and PARP [poly(ADP-ribose) polymerase] formation). Stretch-induced apoptosis was attenuated by inhibiting autophagy. Coimmunoprecipitation revealed that stretch promoted an interaction between LC3B and the FAS (first apoptosis signal) cell death receptor in FRLE cells. Ceramide levels, in particular C16 ceramide, were rapidly elevated in response to ventilation and stretch, and C16 ceramide treatment of FRLE cells induced autophagy and apoptosis in a temporal pattern similar to that seen with MV and stretch. SMPD1 (sphingomyelin phosphodiesterase 1) was activated by ventilation and stretch, and its inhibition prevented ceramide production, LC3B-II formation, LC3B/first apoptosis signal interaction, caspase-3 activation, and, ultimately, FLRE cell death. SMPD1 inhibition also attenuated ventilation-induced autophagy and apoptosis in newborn rats. CONCLUSIONS: Ventilation-induced ceramides promote autophagy-mediated cell death, and identifies SMPD1 as a potential therapeutic target for the treatment of ventilation-induced lung injury in newborns.

Neonatal incubator or artificial womb? Distinguishing ectogestation and ectogenesis using the metaphysics of pregnancy.

A 2017 Nature report was widely touted as hailing the arrival of the artificial womb. But the scientists involved claim their technology is merely an improvement in neonatal care. This raises an under-considered question: what differentiates neonatal incubation from artificial womb technology? Considering the nature of gestation-or metaphysics of pregnancy-(a) identifies more profound differences between fetuses and neonates/babies than their location (in or outside the maternal body) alone: fetuses and neonates have different physiological and physical characteristics; (b) characterizes birth as a physiological, mereological and topological transformation as well as a (morally relevant) change of location; and (c) delivers a clear distinction between neonatal incubation and ectogestation: the former supports neonatal physiology; the latter preserves fetal physiology. This allows a detailed conceptual classification of ectogenetive and ectogestative technologies according to which the 2017 system is not just improved neonatal incubation, but genuine ectogestation. But it is not an artificial womb, which is a term that is better put to rest. The analysis reveals that any ethical discussion involving ectogestation must always involve considerations of possible risks to the mother as well as her autonomy and rights. It also adds a third and potentially important dimension to debates in reproductive ethics: the physiological transition from fetus/gestateling to baby/neonate.

Significant deviations in sonographic fetal weight estimation: causes and implications.

PURPOSE: To allocate parameters associated with significant deviations in sonographic estimated fetal weight (EFW) and evaluate labor outcomes in such circumstances. METHODS: Retrospective case-control study of women with a singleton gestation who underwent sonographic EFW within a week prior to delivery in a single tertiary university-affiliated medical center (2012-2018). The study group was comprised of 177 pregnancies in which sonographic EFW was at least ± 20% of actual birth weight, matched to 354 pregnancies with an accuracy of ± 1% of sonographic EFW to actual birth weight. Matching was based on age, gravidity, parity, and gestational age at delivery. Placental location, fetal presentation, spine position and amniotic fluid volumes during the ultrasound evaluation, as well as pregnancy outcomes, were compared between groups. RESULTS: Median gestational age at delivery (37.0 vs. 38.0 weeks, p < 0.001), median estimated fetal weight (2591 vs. 3198 g, p < 0.001) and median birth weight (2916 vs. 3158 g, p = 0.001) were all lower in the non-accurate compared to the accurate weight estimation group. Ultrasound parameters significantly differed between groups. Women in the non-accurate, compared to accurate weight estimations group, presented higher rates of breech presentation (20.34 vs. 9.89%, p = 0.001), lower rates of anterior placenta (44.6 vs. 53.67%, p = 0.002) and lateral spine position (80.23 vs. 88.42%, p < 0.021). Multivariate analysis was utilized to control potential confounders, non-lateral spine position was found to be an independent risk factor for inaccuracies in EFW [OR = 2.505, 95% CI 1.159-5.416, p = 0.0196]. Obstetric parameters did not differ between groups. Higher rates of neonatal intensive care unit admission (20.34 vs. 11.02%, p = 0.003) and neonatal respiratory complications (7.34 vs. 3.39%, p = 0.042) were observed in the non-accurate EFW subgroup. Multivariate analysis demonstrated that inaccuracy in sonographic EFW was an independent risk factor for NICU admission (OR = 2.4, 95% CI 1.034-5.577, p = 0.041). CONCLUSION: Accuracy in sonographic EFW depends on fetal presentation, spine position and placental location. Non-accuracy is associated with adverse neonatal outcomes.