Development of a Prediction Model for Surgery or Early Mortality at the Time of Initial Assessment for Necrotizing Enterocolitis.

OBJECTIVE: No available scale, at the time of initial evaluation for necrotizing enterocolitis (NEC), accurately predicts, that is, with an area under the curve (AUC) ≥0.9, which preterm infants will undergo surgery for NEC stage III or die within a week. STUDY DESIGN: This is a retrospective cohort study (n = 261) of preterm infants with <33 weeks' gestation or <1,500 g birthweight with either suspected or with definite NEC born at Parkland Hospital between 2009 and 2021. A prediction model using the new HASOFA SCORE (H: yperglycemia, H: yperkalemia, use of inotropes for H: ypotension during the prior week, A: cidemia, Neonatal S: equential O: rgan F: ailure A: ssessment [nSOFA: ] score) was compared with a similar model using the nSOFA score. RESULTS: Among 261 infants, 112 infants had NEC stage I, 68 with NEC stage II, and 81 with NEC stage III based on modified Bell's classification. The primary outcome, surgery for NEC stage III or death within a week, occurred in 81 infants (surgery in 66 infants and death in 38 infants). All infants with pneumoperitoneum or abdominal compartment syndrome either died or had surgery. The HASOFA and the nSOFA scores were evaluated in 254 and 253 infants, respectively, at the time of the initial workup for NEC. Both models were internally validated. The HASOFA model was a better predictor of surgery for NEC stage III or death within a week than the nSOFA model, with greater AUC 0.909 versus 0.825, respectively, p < 0.001. Combining HASOFA at initial assessment with concurrent or later presence of abdominal wall erythema or portal gas improved the prediction surgery for NEC stage III or death with AUC 0.942 or 0.956, respectively. CONCLUSION: Using this new internally validated prediction model, surgery for NEC stage III or death within a week can be accurately predicted at the time of initial assessment for NEC. KEY POINTS: · No available scale, at initial evaluation, accurately predicts which preterm infants will undergo surgery for NEC stage III or die within a week.. · In this retrospective cohort study of 261 preterm infants with either suspected or definite NEC we developed a new prediction model (HASOFA score).. · The HASOFA-model had high discrimination (AUC 0.909) and excellent calibration and was internally validated..

Impact of maternal infection on outcomes in extremely preterm infants.

BACKGROUND: Infants born less than 29 weeks, or extremely preterm (EPT), experience increased morbidity and mortality. We hypothesized that exposure to maternal infection might contribute to neurodevelopmental impairment (NDI) or death at 2 years of age. METHODS: We conducted a retrospective cohort study of EPT infants from January 2010 to December 2020. Maternal data extracted included maternal infections, classified as extrauterine or intrauterine. Placental pathologic and infant data were extracted. The primary outcome was NDI or death at 2 years of age. RESULTS: 548 EPT infants were born to 496 pregnant people: 379 (69%) were not exposed to any documented maternal infection prenatally, 124 (23%) to extrauterine infection, and 45 (8%) to intrauterine infection. Neither diagnosis of maternal extrauterine nor intrauterine infection was associated with NDI or death at 2 years of age (p > 0.05). Acute histologic chorioamnionitis was associated with NDI or death at 2 years of age (p = 0.033). CONCLUSIONS: Maternal infection was not associated with NDI or death at 2 years of age in EPT infants. However, acute histologic chorioamnionitis was associated with this outcome. Further work should investigate the differential influence of infection and immune response with this pathology as relates to outcomes in EPT infants. IMPACT: Maternal infection was not associated with neurodevelopmental impairment (NDI) or death at 2 years of age in extremely preterm (EPT) infants. This is reassuring support that mechanisms at the maternal-fetal interface largely protect the EPT infant. However, pathologic findings of acute histologic chorioamnionitis were associated with NDI and death at 2 years of age. Further work should investigate the differential influence of infection and immune response with acute histologic chorioamnionitis on pathology as relates to outcomes in EPT infants.

Risk Factors for Admission Hyperthermia and Associated Outcomes in Infants Born Preterm.

Maternal, placental, and neonatal factors were compared between infants born at ≤29 weeks of gestational age with admission hyperthermia (>37.5○C) and euthermia (36.5-37.5○C). Admission hyperthermia was associated with longer duration of face-mask positive-pressure ventilation and infant's temperature ≥37.5○C in the delivery room. Infants born preterm with admission hyperthermia had greater odds of developing necrotizing enterocolitis and neurodevelopmental impairment.

Impact of fetal inflammatory response on the severity of necrotizing enterocolitis in preterm infants.

OBJECTIVE: Neonates born with fetal inflammatory response (FIR) are at increased risk for adverse neonatal outcomes. Our objective was to determine whether FIR and its severity is associated with severity of necrotizing enterocolitis (NEC) in preterm infants. METHODS: A case-control retrospective study of infants <33 weeks gestational age or <1500 g birthweight, including 260 with stage I-III NEC and 520 controls matched for gestational age. Placental pathology was evaluated, and FIR progression and its severity were defined according to Amsterdam classification. RESULTS: In this study, mild FIR (i.e., stage 1 FIR) was present in 52 controls (10.0%) and 22 infants with stage I-III NEC (8.5%), while moderate to severe FIR (i.e., ≥stage 2 FIR) was present in 16 controls (3.1%) and 47 infants with stage I-III NEC (18.1%). Both stage and grade of FIR were associated with stage of NEC (P < 0.001). On multinomial logistic regression, stage III NEC was associated with stage of FIR (P < 0.001). CONCLUSION: This is the first report demonstrating the association between progression and increasing severity of FIR and stage of NEC. IMPACT: Fetal Inflammatory Response (FIR) and its progression and severity are associated with the stages of necrotizing enterocolitis (NEC). This is the first study demonstrating the impact of progression and severity of FIR on stage III NEC. These observations provide additional insight into understanding the impact of intrauterine exposure to inflammation on the severity of NEC in preterm infants.

Multi-Agent Variational Approach for Robotics: A Bio-Inspired Perspective.

This study proposes an adaptable, bio-inspired optimization algorithm for Multi-Agent Space Exploration. The recommended approach combines a parameterized Aquila Optimizer, a bio-inspired technology, with deterministic Multi-Agent Exploration. Stochastic factors are integrated into the Aquila Optimizer to enhance the algorithm's efficiency. The architecture, called the Multi-Agent Exploration-Parameterized Aquila Optimizer (MAE-PAO), starts by using deterministic MAE to assess the cost and utility values of nearby cells encircling the agents. A parameterized Aquila Optimizer is then used to further increase the exploration pace. The effectiveness of the proposed MAE-PAO methodology is verified through extended simulations in various environmental conditions. The algorithm viability is further evaluated by comparing the results with those of the contemporary CME-Aquila Optimizer (CME-AO) and the Whale Optimizer. The comparison adequately considers various performance parameters, such as the percentage of the map explored, the number of unsuccessful runs, and the time needed to explore the map. The comparisons are performed on numerous maps simulating different scenarios. A detailed statistical analysis is performed to check the efficacy of the algorithm. We conclude that the proposed algorithm's average rate of exploration does not deviate much compared to contemporary algorithms. The same idea is checked for exploration time. Thus, we conclude that the results obtained for the proposed MAE-PAO algorithm provide significant advantages in terms of enhanced map exploration with lower execution times and nearly no failed runs.

Placental clearance not synthesis tempers exaggerated pro-inflammatory cytokine response in neonates exposed to chorioamnionitis.

BACKGROUND: The source and clearance of cytokines in the fetal circulation in term pregnancies complicated by chorioamnionitis remains unclear as are the contributions of placental transport, synthesis, and clearance. The objectives of the study were to determine (1) fetal and/or placental contributions to synthesis and/or clearance of inflammatory and anti-inflammatory cytokines in term pregnancies complicated by chorioamnionitis and (2) whether this differs in pregnancies further complicated by fetal hypoxia. METHODS: Prospective cohort study of pregnancies >37 weeks gestational age that included: Group 1, uncomplicated cesarean delivery without labor (n = 20); Group 2, uncomplicated vaginal delivery (n = 30); Group 3, pregnancies complicated by chorioamnionitis (n = 10); Group 4, complicated by chorioamnionitis + fetal hypoxia (n = 10). Umbilical arterial (UmA) and venous (UmV) blood were assayed for IL-1ß, IL-2, IL-6, IL-8, TNFα, and IL-10. RESULTS: IL-6 and IL-8 were below assay detection in UmA and UmV blood in Group 1 and increased in Group 2 (P < 0.01), UmA¼UmV (P < 0.01). Their concentrations increased further in Groups 3 and 4 (P = 0.003), UmA¼UmV. Placental clearance was concentration dependent that approaches saturation in the presence of chorioamnionitis. CONCLUSIONS: Marked increases in fetal synthesis of IL-6 and IL-8 occur in chorioamnionitis. Synthesis increase further when complicated by fetal hypoxia. Cytokine removal occurs via placental concentration-dependent mechanisms, potentially contributing to adverse fetal effects. IMPACT: The source and role of the placenta in synthesis and/or clearance of inflammatory mediators in term pregnancies complicated by clinical chorioamnionitis are unclear; however, conventional wisdom suggests the placenta is their source. This is the first study demonstrating that circulating concentrations of fetal IL-6 and IL-8 in clinical chorioamnionitis ± birth asphyxia in term pregnancies are of fetal origin. Circulating fetal inflammatory cytokines are cleared by concentration-dependent placental mechanisms that are nearly saturated in chorioamnionitis ± fetal hypoxia. These observations provide additional insight into understanding the fetal immune response in term pregnancies complicated by clinical chorioamnionitis.

Association of Placental Pathologic Findings with the Severity of Necrotizing Enterocolitis in Preterm infants - A Matched Case-Control Study.

OBJECTIVE: To determine the association of placental pathology with the severity of necrotizing enterocolitis (NEC) in preterm infants. METHODS: This single-center matched case-control study included infants with NEC (n = 107) and gestational age and birth weight-matched controls (n = 130), born between 2013 and 2020. Placentas were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. RESULTS: Acute histologic chorioamnionitis with the fetal response was significantly more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p = 0.02). On regression model, infants with multiple placental pathologies (OR 2.16; 95% CI 1.01 - 4.73; p = 0.04) and maternal vascular malperfusion (OR 2.2; 95% CI 1.12 - 4.51; p = 0.02) had higher odds of either medical or surgical NEC than controls. CONCLUSION: Infants with multiple placental lesions, including placental inflammatory and vascular lesions, were at higher risk of medical or surgical NEC in the postnatal period.

Placental pathology associated with lenticulostriate vasculopathy (LSV) in preterm infants.

OBJECTIVE: Our aim was to examine the frequency and type of placental abnormalities in neonates with LSV. STUDY DESIGN: We prospectively reviewed cranial ultrasounds (cUS) from neonates born at ≤32 weeks of gestation at Parkland Hospital between 2012 and 2014. Our cohort included neonates with LSV and gestational age and sex matched controls with normal cUS. We retrieved placental pathology reports retrospectively and compared placental abnormalities in both groups. RESULTS: We reviewed 1351 cUS from a total of 407 neonates. Placental pathology evaluations were complete for 64/65 (98%) neonates with LSV and 68/70 (97%) matched controls. There were no significant differences for any type of placental abnormities between LSV and control groups. However, infants with highest stage LSV were more likely to have large for gestational age (LGA) placentas (p = 0.01). CONCLUSION: The association between LSV and LGA placenta may indicate a shared vascular response to an adverse prenatal environment.

Placental pathologic lesions associated with stroke in term neonates.

Objective: To determine the birth prevalence of perinatal stroke in term born infants at our high-volume delivery center and assess the frequency of both gross and histologic placental pathologies associated with perinatal stroke using the Amsterdam Placental Workshop Group Consensus Statement guidelines and definitions. Study Design: A single-center retrospective cohort study spanning 2010-2020. Results: There were 129,759 live births at Parkland Hospital during the study period and a total of 18 term born infants leading to a birth prevalence of 1 in 6,829 infants. Perinatal risk factors were found in all but one patient, and 74% presented with seizures. Pathologic placental examination was available in 56% of the cohort and only one patient had normal placental examination. Acute histologic chorioamnionitis was described in five placentas (50%) and an additional two had isolated umbilical and/or chorionic plate vasculitis with or without funisitis compared to a rate of 28% with acute inflammation in a Control group. Chronic inflammation in the form of villitis of unknown etiology was described in three of the acutely inflamed placentas and was high-grade in each of those while none of the placentas from our Control group showed evidence of any chronic lesion. Conclusion: Both acute and chronic placental inflammation are common in perinatal stroke; placental examination should be considered an essential component to the diagnostic workup.

Placental vascular malperfusion lesions in fetal congenital heart disease.

BACKGROUND: Fetuses with congenital heart disease are at increased risk of perinatal morbidity and mortality, which is highly influenced by their prenatal health. Placental function is vital for the health of the fetus, but increased rates of pathologic lesions of the placenta have been observed in pregnancies complicated by fetal congenital heart disease. OBJECTIVE: This study aimed to determine the prevalence of both gross and histologic placental pathologies in a cohort of pregnancies complicated by fetal congenital heart disease vs healthy controls using the Amsterdam Placental Workshop Group Consensus Statement sampling and definitions of placental lesions. STUDY DESIGN: This single-center retrospective cohort study included placental examinations from pregnancies diagnosed prenatally with fetal congenital heart disease between 2010 and 2019; moreover, control placentas were collected from pregnancies without maternal or fetal complications. Placentas were sampled and evaluated according to the Amsterdam Placental Workshop Group Consensus Statement and gross and histopathologic diagnoses determined. RESULTS: Approximately 80% of fetuses diagnosed with congenital heart disease (n=305) had a placental examination for comparison with controls (n=40). Of note, 239 placentas (78%) in the group with fetal congenital heart disease had at least 1 gross or histopathologic lesion compared with 11 placentas (28%) in the control group (P<.01). One-third of placentas complicated by fetal congenital heart disease met the criteria for small for gestational age, and 48% of placentas had one or more chronic lesions, including maternal vascular malperfusion (23% vs 0%; P<.01), villitis of unknown etiology (22% vs 0%; P<.01), fetal vascular malperfusion (20% vs 0%; P<.01), and other chronic lesions (16% vs 0%; P<.01). Acute inflammation was equally present in both the group with fetal congenital heart disease and the control group (28% vs 28%; P=1.00). Although gestational age and birthweight z score were similar between the 2 groups, birth head circumference was 1.5 cm less in pregnancies complicated by fetal congenital heart disease with a significantly lower z score compared with the control group (-0.52±1.22 vs 0.06±0.69; P<.01). CONCLUSION: Vascular malperfusion lesions and chronic forms of inflammation occur at markedly higher rates in placentas complicated by fetal congenital heart disease, which may contribute to the decreased head circumference at birth. Further work in neuroplacentology is needed to explore connections among cardiac defects, placental vascular malperfusion lesions, and fetal brain development.

Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes.

Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta-heart-brain connection. IMPACT: Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.

Electrocardiogram for heart rate evaluation during preterm resuscitation at birth: a randomized trial.

BACKGROUND: Although electrocardiogram (ECG) can detect heart rate (HR) faster compared to pulse oximetry, it remains unknown if routine use of ECG for delivery room (DR) resuscitation reduces the time to stabilization in preterm infants. METHODS: Neonates <31 weeks' gestation were randomized to either an ECG-displayed or an ECG-blinded HR assessment in the DR. HR, oxygen saturation, resuscitation interventions, and clinical outcomes were compared. RESULTS: During the study period, 51 neonates were enrolled. The mean gestational age in both groups was 28 ± 2 weeks. The time to stabilization, defined as the time from birth to achieve HR ≥100 b.p.m., as well as oxygen saturation within goal range, was not different between the ECG-displayed and the ECG-blinded groups [360 (269, 435) vs 345 (240, 475) s, p = 1.00]. There was also no difference in the time to HR ≥100 b.p.m. [100 (75, 228) vs 138 (88, 220) s, p = 0.40] or duration of positive pressure ventilation (PPV) [345 (120, 558) vs 196 (150, 273) s, p = 0.36]. Clinical outcomes were also similar between groups. CONCLUSIONS: Although feasible and safe, the use of ECG in the DR during preterm resuscitation did not reduce time to stabilization. IMPACT: Although feasible and apparently safe, routine use of the ECG in the DR did not decrease time to HR >100 b.p.m., time to stabilization, or use of resuscitation interventions such as PPV for preterm infants <31 weeks' gestational age. This article adds to the limited randomized controlled trial evidence regarding the impact of routine use of ECG during preterm resuscitation on DR clinical outcomes. Such evidence is important when considering recommendations for routine use of the ECG in the DR worldwide as such a recommendation comes with a significant cost burden.

New Modified Recombinant Botulinum Neurotoxin Type F with Enhanced Potency.

Botulinum neurotoxins (BoNTs) are notorious toxins and powerful agents and can be lethal, causing botulism, but they are also widely used as therapeutics, particularly to treat neuromuscular disorders. As of today, the commercial BoNT treatments available are from native A or B serotypes. Serotype F has shown efficacy in a clinical trial but has scarcely been used, most likely due to its medium duration of effect. Previously, the uniqueness of the light chain of the F7 subtype was identified and reported, showing an extended interaction with its substrates, VAMPs 1, 2 and 3, and a superior catalytic activity compared to other BoNT/F subtypes. In order to more extensively study the properties of this neurotoxin, we engineered a modified F7 chimera, mrBoNT/F7-1, in which all the regions of the neurotoxin were identical to BoNT/F7 except the activation loop, which was the activation loop from BoNT/F1. Use of the activation loop from BoNT/F1 allowed easier post-translational proteolytic activation of the recombinant protein without otherwise affecting its properties. mrBoNT/F7-1 was expressed, purified and then tested in a suite of in vitro and in vivo assays. mrBoNT/F7-1 was active and showed enhanced potency in comparison to both native and recombinant BoNT/F1. Additionally, the safety profile remained comparable to BoNT/F1 despite the increased potency. This new modified recombinant toxin F7 could be further exploited to develop unique therapeutics to address unmet medical needs.

TeleNICU: Extending the reach of level IV care and optimizing the triage of patient transfers.

BACKGROUND: The use of telemedicine to provide care for critically ill newborn infants has significantly evolved over the last two decades. Children's Health System of Texas and University of Texas Southwestern Medical Center established TeleNICU, the first teleneonatology program in Texas. OBJECTIVE: To evaluate the effectiveness of Tele Neonatal Intensive Care Unit (TeleNICU) in extending quaternary neonatal care to more rural areas of Texas. MATERIALS AND METHODS: We conducted a retrospective review of TeleNICU consultations from September 2013 to October 2018. Charts were reviewed for demographic data, reasons for consultation, and consultation outcomes. Diagnoses were classified as medical, surgical, or combined. Consultation outcomes were categorized into transferred or retained. Transport cost savings were estimated based on the distance from the hub site and the costs for ground transportation. RESULTS: TeleNICU had one hub (Level IV) and nine spokes (Levels I-III) during the study period. A total of 132 direct consultations were completed during the study period. Most consultations were conducted with Level III units (81%) followed by level I (13%) and level II (6%) units. Some common diagnoses included prematurity (57%), respiratory distress (36%), congenital anomalies (25%), and neonatal surgical emergencies (13%). For all encounters, 54% of the patients were retained at the spoke sites, resulting in an estimated cost savings of USD0.9 million in transport costs alone. The likelihood of retention at spoke sites was significantly higher for medical diagnoses compared to surgical diagnoses (89% vs. 11%). CONCLUSION: Telemedicine effectively expands access to quaternary neonatal care for more rural communities, helps in the triage of neonatal transfers, promotes family centered care, and significantly reduces health care costs.

A stability perspective of bioinspired unmanned aerial vehicles performing optimal dynamic soaring.

The phenomenon of dynamic soaring, as exhibited by soaring birds, has long been a biological inspiration for aerospace and control engineers. If this fascinating phenomenon, which allows soaring birds to perform almost unpowered flight using wind shear, can be mimicked by unmanned aerial vehicles (UAVs), then there is substantial potential for technological and economic enhancement of UAV performance. Although there has been a considerable amount of research covering the modeling, optimization, control and simulation aspects of different UAVs performing dynamic soaring, there is little to no conclusive work analyzing the stability of such UAVs in soaring orbits. In this paper we present a comprehensive framework for determining the stability of soaring UAVs utilizing both linear (Floquet-based) and nonlinear (contraction theory-based) techniques. Floquet stability analysis was inconclusive, which led to the use of a nonlinear contraction formulation to reach a conclusive stability assessment for an actual nonlinear fixed-wing UAV performing dynamic soaring. Furthermore, parametric variation along with numerical simulations were conducted to ascertain the response of the actual nonlinear system when perturbed from the nominal motion studied in this paper. The analysis and simulations revealed that the system possesses instability as the UAV motion diverges from its nominal trajectory and follows an undesirable path. From this result we conclude, for the first time in the literature as far as we are aware, that UAVs performing dynamic soaring in an optimal way to reduce wind shear requirements are inherently unstable. The results of this work suggest that mimicking of dynamic soaring by UAVs will require careful investigation of tracking and regulatory controls that need to be implemented.

Vulnerable child syndrome in the neonatal intensive care unit: A review and a new preventative intervention with feasibility and parental satisfaction data.

Vulnerable Child Syndrome (VCS) occurs in the setting in which a child recovers from a life-threatening illness, as result of which the parent develops heightened parental perceptions of child vulnerability (PPCV). This leads to a pattern of overprotective parenting which may result in adverse neurodevelopmental and behavioral outcomes in the child over time. Parents of premature infants have been shown to be at increased risk of developing raised PPCV while their infants may develop symptoms of VCS. The PreVNT trial is a randomized controlled trial designed to test the efficacy of a 5-session manualized Cognitive Behavioral Therapy (CBT) intervention to reduce PPCV. Results of a pilot study of parents of premature infants (n = 41) demonstrate that the intervention can be delivered with high ratings of treatment fidelity and with a completion rate of 100% during the NICU admission, and 78% at 6 months post term. Ratings of parental satisfaction ranged between 4.9 and 5 out of 5 demonstrating high satisfaction with the intervention. Pilot feasibility and maternal satisfaction data are presented for a group of 22 intervention families, which suggest a CBT model for understanding VCS is feasible and deemed helpful by parents. This review is gauged to summarize risk of VCS development, diagnosis of VCS, and effective treatments for VCS through Cognitive Behavioral Therapy. We also present a paradigm shift in a therapeutic approach by introducing the PreVNT Trial. Given that VCS can interfere with the long-term outcomes of both infant and family, it is important to understand VCS and address its involvement in NICU and post NICU discharge care. Further research is needed in this area.

Autism spectrum disorders in extremely preterm infants and placental pathology findings: a matched case-control study.

BACKGROUND: The prevalence of autism spectrum disorders (ASD) is 5-fold higher in preterm (PT) infants born ≤28 weeks gestational age (GA) as compared to the general population. The relationship between placental pathologic lesions and ASD in PT infants has not been studied. OBJECTIVES: The objective of this study was to determine the association of placental pathology with the occurrence of ASD in PT infants born ≤28 weeks GA. STUDY DESIGN: A matched case-control study to identify confirmed ASD cases (n = 16) and matched controls (n = 48) born at Parkland Hospital between January 2012 and December 2015. Patients were matched using known variables associated with increased risk of ASD in PT infants. Placental histology from all births was reviewed. RESULTS: Children with ASD had 2-fold greater incidence of multiple placental pathologic lesions vs. matched controls [11/16 (69%) vs.16/48 (33%), respectively; P = 0.01]. In contrast, single placental pathologic lesions were not associated with ASD [5/16 (31%) vs. 21/48 (43%), respectively; P = 0.1]. CONCLUSIONS: In this study, we have demonstrated an association between the increasing complexity of histologic placental lesions and the later risk for ASD in infants born ≤28 weeks GA. Thus, placental pathology findings may be valuable in further understanding the prenatal pathologic processes underlying ASD in PT infants. IMPACT: PT infants with ASD have a 2-fold greater incidence of multiple placental pathologies. This is the first study to report an association between the complexity of histologic placental lesions and later risk of ASD in infant born extremely PT (i.e., ≤28 weeks GA). This study reiterates the importance of examining placental pathologic lesions, since placental evidence of antenatal insults correlates with postnatal morbidities and mortality in PT infants.

Placental origins of neonatal diseases: toward a precision medicine approach.

The placenta is the single most reliable source for precise information on intrauterine environment, as well as maternal and fetal health. It mediates the physiology of two distinct yet highly interconnected individuals. The pathology that develops in the placenta, and the adaptations the placenta undergoes to mitigate this pathology, may influence the later life health of the mother and baby. Pathological placental examination provides a unique opportunity to explore and understand the intrauterine environment, as well as providing a record of events that may be associated with adverse pregnancy outcomes. A number of placental lesions have been described in association with various neonatal morbidities. The purpose of this review is to summarize the evidence for the association of placental pathologic lesions with neurodevelopmental outcomes infants with specific neonatal morbidities, including (1) neonatal encephalopathy, (2) bronchopulmonary dysplasia, (3) congenital heart diseases, and (4) autism spectrum disorders. For each of these disease processes, we will also propose specific research priorities in future studies. We conclude with a hospital-specific protocol for triaging which placentas should receive histological evaluation as a fundamental first step for the field of neuroplacentology to guide precision-based therapeutic approaches in the affected newborns. IMPACT: The purpose of this review is to summarize the evidence for placental origins of neonatal diseases. We propose specific research priorities in the field of neuroplacentology in future studies. We also present a targeted hospital-based approach for triaging which placentas should receive histological evaluation.