Extreme Prematurity Research Articles

Pathophysiology of gas exchange impairment in extreme prematurity: Insights from combining volumetric capnography and measurements of ventilation/perfusion ratio.

Infants born extremely preterm often suffer from respiratory disease and are invasively ventilated. We aimed to test the hypothesis that gas exchange in ventilated extremely preterm infants occurs both at the level of the alveoli and via mixing of fresh deadspace gas in the airways. We measured the normalised slopes of phase II and phase III of volumetric capnography and related them with non-invasive measurements of ventilation to perfusion ratio (VA/Q) and right-to-left shunt in ventilated extremely preterm infants studied at one week of life. Cardiac right-to-left shunt was excluded by concurrent echocardiography. We studied 25 infants (15 male) with a median (range) gestational age of 26.0 (22.9-27.9) weeks and birth weight of 795 (515-1,165) grams. The median (IQR) VA/Q was 0.52 (0.46-0.56) and shunt was 8 (2-13) %. The median (IQR) normalised slope of phase II was 99.6 (82.7-116.1) mmHg and of phase III was 24.6 (16.9-35.0) mmHg. The VA/Q was significantly related to the normalised slope of phase III (ρ = -0.573, p = 0.016) but not to the slope of phase II (ρ = 0.045, p = 0.770). The right-to-left shunt was not independently associated with either the slope of phase II or the slope of phase III after adjusting for confounding parameters. Abnormal gas exchange in ventilated extremely preterm infants was associated with lung disease at the alveolar level. Abnormal gas exchange at the level of the airways was not associated with quantified indices of gas exchange impairment.

Respiratory support strategies in the prevention and treatment of bronchopulmonary dysplasia.

Neonates who are born preterm frequently have inadequate lung development to support independent breathing and will need respiratory support. The underdeveloped lung is also particularly susceptible to lung injury, especially during the first weeks of life. Consequently, respiratory support strategies in the early stages of premature lung disease focus on minimizing alveolar damage. As infants grow and lung disease progresses, it becomes necessary to shift respiratory support to a strategy targeting the often severe pulmonary heterogeneity and obstructive respiratory physiology. With appropriate management, time, and growth, even those children with the most extreme prematurity and severe lung disease can be expected to wean from respiratory support.

Collaboration between Maternal-Fetal Medicine and Neonatology When Counseling at Extreme Prematurity.

Enhanced communication between maternal-fetal medicine (MFM)/obstetrics and neonatology regarding counseling at extreme prematurity remains an essential element of prenatal consultations. Together, the obstetrician and neonatologist can collaborate to provide timely and synergistic information to affected couples during a dynamic period, combining their expertise to elucidate values and formulate a plan that best supports the pregnant person and partner's goals. Such collaboration can help resolve differing perspectives between specialties, minimize redundancy and inconsistencies, and mitigate the impact of clinician bias. Best practices for joint-specialty collaboration include a precounseling clinician huddle, contemporaneous counseling by MFM specialists/obstetricians and neonatologists with the expectant parents or individualized sequential counseling if preferred by the couple, and a postcounseling clinician debrief. This approach can help establish a trusting relationship with families facing possible extremely preterm delivery and optimize the overall counseling experience. Future efforts focused on education and research, including a standardized approach to educational curricula among fellowship programs, should be emphasized.

Neonatologists' Perspectives on Exploring Parental Spirituality in Prenatal Consultations.

Values of religion, spirituality, and faith (RSF) are central to decision making for many parents facing extremely preterm labor or prenatal diagnoses of potentially life-limiting congenital anomalies. Neonatologists' opinions and comfort with discussing parental RSF are not well known. We sought to understand neonatologists' current practices and perceptions of exploring parental RSF in prenatal consultations. A retrospective chart review was performed at a single U.S. academic institution to evaluate the inclusion of spiritual terminology in documentation. All mothers who were admitted with anticipated extremely preterm delivery as well as those with prenatal diagnoses of potentially life-limiting congenital anomalies were included in analysis. After chart review, an anonymous survey was distributed to neonatology attendings and fellows to examine perspectives on exploring parental RSF. The chart review indicated that RSF terminology was absent from the documentation of all prenatal consultations performed by neonatology. Sixty-five percent of survey respondents considered RSF important in their personal lives and 47% considered RSF important in clinical practice. The three most significant barriers to exploring RSF were lack of training or education in spiritual care, differences between physicians' and patients' personal beliefs, and insufficient time. Our study highlights a gap between the goal for prenatal counseling in cases of extreme prematurity and potentially life-limiting congenital anomalies and current practices that frequently exclude the values most important to many parents. Lack of training in spiritual care is a significant barrier to neonatologists exploring parental RSF.

Cholestasis impairs gut microbiota development and bile salt hydrolase activity in preterm neonates

ABSTRACT Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops in extreme prematurity and how cholestasis alters this maturation, we conducted a nested case-control study collecting 124 stool samples longitudinally from 24 preterm infants born at mean 27.2 ± 1.8 weeks gestation and 946 ± 249.6 g, half of whom developed physiologic cholestasis. Samples were analyzed by whole metagenomic sequencing, in vitro BSH enzyme activity assays optimized for low biomass fecal samples, and quantitative mass spectrometry to measure the bile acid metabolome. In extremely preterm neonates, acquisition of the secondary bile acid biosynthesis pathway and BSH genes carried by Clostridium perfringens are the most prominent features of early microbiome development. Cholestasis interrupts this developmental pattern. BSH gene abundance and enzyme activity are profoundly reduced in cholestatic neonates, resulting in decreased quantities of unconjugated bile acids. UDCA restores total fecal bile acid levels in cholestatic neonates, but this is due to a 522-fold increase in fecal UDCA. A majority of bile acids in early development are atypical positional and stereo-isomers of bile acids. We report novel associations linking isomeric bile acids and BSH activity to neonatal growth trajectories. These data highlight deconjugation of bile acids as a key microbial function that is acquired in early neonatal development and impaired by cholestasis.

Safety of performing classical versus low transverse caesarean sections in extremely preterm and very preterm births: Maternal and neonatal complications.

Improved survivability of extremely preterm infants has led to increased rates of caesarean sections. Short-term maternal and neonatal risks of classical caesarean sections (CCS) in the context of extreme prematurity remain unclear. The aim was to examine maternal and neonatal complications associated with CCSs versus low transverse caesarean sections (LTCS) at extremely preterm (23 0/7-27 6/7 weeks) and very preterm gestational ages (28 0/7-31 6/7 weeks). A retrospective cohort study was conducted at Royal Brisbane and Womens Hospital, Queensland, Australia between 2016 and 2020. Maternal and neonatal outcomes were examined using univariate and multivariate statistical analysis. CCSs (extremely preterm: n=93; very preterm: n=83) were associated with higher estimated blood loss than LTCS (extremely preterm: n=70; very preterm: n=287) in very preterm births (CCS: 638 ± 410 mL; LTCS: 556 ± 397 mL; P=0.01). There was no significant difference in composite maternal outcomes between CCS and LTCS for extremely preterm (adjusted odds ratio (aOR): 1.11; 95% confidence interval (CI): 0.58-2.12; P=0.75) or very preterm births (aOR: 1.08; 95% CI: 0.63-1.94; P=0.79) after accounting for multiple pregnancy, placenta accreta and non-cephalic fetal presentations. Although CCSs were associated with lower Apgar scores at 1min post-birth than LTCSs at very preterm gestational ages (CCS: 5.58 ± 2.10; LTCS: 6.25 ± 2.14; P=0.02), there was no statistical difference in the rates of intraoperative neonatal injuries or composite outcomes when corrected for low birth weight. Short-term maternal and neonatal outcomes do not significantly differ between CCS and LTCS for extremely preterm or very preterm births.

Bronchopulmonary Dysplasia in Extremely Premature Infants: A Scoping Review for Identifying Risk Factors

Over the years, bronchopulmonary dysplasia (BPD) affects the pulmonary function of infants, resulting in chronic health burdens for infants and their families. The aim of this scoping review was to screen available evidence regarding perinatal risk factors associated with the development and severity of BPD. The eligibility criteria of the studies were year of publication between 2016 and 2021; setting of a developed country; English or Japanese as the study language; and randomized controlled, cohort, or case-control design. The titles and abstracts of the studies were screened by independent reviewers. Of 8189 eligible studies, 3 were included for severe BPD and 26 were included for moderate BPD. The risk factors for severe BPD were male sex, iatrogenic preterm birth, maternal hypertensive disorders of pregnancy (HDP), low gestational age, small-for-gestational-age (SGA) birth weight, mechanical ventilation on day 1, and need for patent ductus arteriosus (PDA) management. The risk factors for moderate or severe BPD included male sex, premature rupture of membranes, clinical chorioamnionitis, maternal HDP, SGA birth weight, bubbly/cystic appearance on X-ray, and PDA management. We identified several risk factors for BPD. We plan to confirm the validity of the new classification using the existing dataset.

Extremely premature birth bioethical decision-making supported by dialogics and pragmatism

Moral values in healthcare range widely between interest groups and are principally subjective. Disagreements diminish dialogue and marginalize alternative viewpoints. Extremely premature births exemplify how discord becomes unproductive when conflicts of interest, cultural misunderstanding, constrained evidence review, and peculiar hierarchy compete without the balance of objective standards of reason. Accepting uncertainty, distributing risk fairly, and humbly acknowledging therapeutic limits are honorable traits, not relativism, and especially crucial in our world of constrained resources. We think dialogics engender a mutual understanding that: i) transitions beliefs beyond bias, ii) moves conflict toward pragmatism (i.e., the truth of any position is verified by subsequent experience), and iii) recognizes value pluralism (i.e., human values are irreducibly diverse, conflicting, and ultimately incommensurable). This article provides a clear and useful Point-Counterpoint of extreme prematurity controversies, an objective neurodevelopmental outcomes table, and a dialogics exemplar to cultivate shared empathetic comprehension, not to create sides from which to choose. It is our goal to bridge the understanding gap within and between physicians and bioethicists. Dialogics accept competing relational interests as human nature, recognizing that ultimate solutions satisfactory to all are illusory, because every choice has downside. Nurturing a collective consciousness via dialogics and pragmatism is congenial to integrating objective evidence review and subjective moral-cultural sentiments, and is that rarest of ethical constructs, a means and an end.

Comparison of Premature, Extremely Premature, and Older Adults With Coronary Artery Disease in Pakistan.

Comparison of Premature, Extremely Premature, and Older Adults With Coronary Artery Disease in Pakistan.

The Triple Aim Quality Improvement Gold Standard Illustrated as Extremely Premature Infant Care.

The Triple Aim is widely regarded as the quality improvement gold standard that enhances population health, lowers costs, and betters individual care. There have been no large-scale, sustained demonstrations of such improvement in healthcare. Illustrating the Triple Aim using relevant extremely premature infant outcomes might highlight interwoven proficiency and efficiency complexities that impede sustained value progress. Ten long-term collaborating neonatal intensive care units (NICU) in the Vermont Oxford Network calculated the Triple Aim in 230/7 to 276/7-week infants using three surrogate measures: (1) population health/x-axis-eight major morbidity rates as a composite, risk-adjusted metric; (2) cost/y-axis-total hospital length of stay; and (3) individual care/z-axis-mortality, then illustrated this relationship as a sphere within a three-dimensional cube. Three thousand seven hundred six infants born between January 1, 2014 and December 31, 2019, with mean (standard deviation) gestational age of 25.7 (1.4) weeks and birth weight of 803 (208) grams were analyzed. Triple Aim three-axis cube positions varied inconsistently comparing NICUs. Each NICUs' sphere illustrated mixed x- and z-axis movement (clinical proficiency), and y-axis movement (cost efficiency). No NICU demonstrated the theoretically ideal Triple Aim improvement in all three axes. Backward movement in at least one axis occurred in eight NICUs. The whole-group Triple Aim sphere moved forward along the x-axis (better morbidities metric), but moved backward in the y-axis length of stay and z-axis mortality measurements. Illustrating the Triple Aim gold standard as extreme prematurity outcomes reveals complexities inherent to simultaneous attempts at improving interwoven quality and cost outcomes. Lack of progress using relevant Triple Aim parameters from our well-established collaboration highlights the difficulties prioritizing competing outcomes, variable potentially-better-practice applications amongst NICUs, unmeasured biologic interactions, and obscured cultural-environmental contexts that all likely affect care. Triple Aim excellence, if even remotely possible, will necessitate scalable, evidence-based methodologies, pragmatism regarding inevitable trade-offs, and wise constrained-resource decisions. · The Triple Aim gold standard is elusive. There is no demonstration of sustained, large-scale success in healthcare and our quality improvement network has previously published benchmark extreme prematuritymorbidity improvements.. · Extreme prematurity outcomes illustrated as the Triple Aim show uneven results in relevant surrogate parameters and Triple Aim achievement, if even possible, will necessitate evidence-based methodologies that are scalable.. · Pragmatism, inevitable trade-offs, and wise constrained-resource decisions are required for Triple Aim success..

Prenatal use of indomethacin for preterm labor and renal function among very low birth weight infants.

Indomethacin is administered as a tocolytic agent for threatening preterm labor <28weeks of gestation. Only a few, not conclusive, studies have investigated its nephrotoxicity in very low birth weight (VLBW) infants. We investigated whether indomethacin increases the incidence of acute kidney injury (AKI) among VLBW infants. This is a retrospective study including all VLBW infants born at our center between January 1, 2005, and December 31, 2013. Indomethacin was administered to women with preterm labor and intact membranes. Neonatal AKI was defined according to KDIGO classification. Univariate analyses were performed comparing VLBW infants exposed to and not exposed to indomethacin. In the multivariable model, the association of indomethacin and AKI was adjusted for patent ductus arteriosus, use of nephrotoxic medications, birth weight, and gestational age. Five hundred seventy-five VLBW infants were included, 49 (8.5%) of whom were exposed to indomethacin in utero. The univariate analysis showed that infants exposed to indomethacin had lower birth weight, lower gestational age, and higher incidence of AKI than infants not exposed. The multivariable model adjusted for confounding factors confirmed an increased risk of AKI in relation to gestational age at birth <27 weeks, but not to indomethacin. Our data suggest that extreme prematurity, but not the use of indomethacin, is associated with AKI.

Burden of Treatments for Respiratory Complications in Extremely Premature Infants: Interviews with Caregivers

Introduction: Extremely premature (EP) infants (<28 weeks gestational age) with respiratory conditions after discharge from the neonatal intensive care unit (NICU) impose a significant burden on caregivers. This study explored caregiver burden post-NICU discharge and perceptions of meaningful change in infant chronic respiratory morbidity. Methods: Adult primary caregivers of EP infants 3–14 months corrected age were recruited through patient advocacy organizations or hospital centers in the USA, Northern Ireland, Germany, and Japan and interviewed by phone. Interviews explored caregiver experiences with infants with respiratory conditions, associated treatment burden, and meaningful change in infant respiratory morbidity as measured by treatment use. Qualitative analysis of interview data was performed using MAXQDA software. Sociodemographic data were summarized using descriptive statistics. Results: Forty-five caregivers (95.6% female) of EP infants were interviewed. Respiratory morbidities post-NICU discharge included coughing (78%), breathing difficulties (76%), wheezing (58%), and bronchopulmonary dysplasia/chronic lung disease of prematurity (56%). Respiratory medications were required by 87% of infants, 80% used home respiratory technology support (e.g., supplemental oxygen), 38% were re-hospitalized, and 33% had emergency department visits. Caregivers considered visits to the emergency department to be the most burdensome treatment requirement they experienced, and reduction in the number of emergency department visits was considered the most meaningful change in treatment use. Conclusion: These findings underscore the significant burden faced by caregivers of EP infants with respiratory morbidities. Development of treatments for respiratory complications should take into consideration the concerns and preferences of caregivers in order to provide a meaningful benefit.

592 - Early hyperglycemia in extreme prematurity is associated with pulmonary and pancreatic dysfunction

592 - Early hyperglycemia in extreme prematurity is associated with pulmonary and pancreatic dysfunction

The Role of Lung Function in Determining Which Children Develop Asthma

Longitudinal studies have demonstrated that altered indices of airway function, assessed shortly after birth, are a risk factor for the subsequent development of wheezing illnesses and asthma, and that these indices predict airway size and airway wall thickness in adult life. Pre- and postnatal factors that directly alter early airway function, such as extreme prematurity and cigarette smoke, may continue to affect airway function and, hence, the risks for wheeze and asthma. Early airway function and an associated asthma risk may also be indirectly influenced by immune system responses, respiratory viruses, the airway microbiome, genetics, and epigenetics, especially if they affect airway epithelial dysfunction. Few if any interventions, apart from smoking avoidance, have been proven to alter the risks of developing asthma, but vitamin C supplementation to pregnant smokers may help decrease the effects of in utero smoke on offspring lung function. We conclude that airway size and the factors influencing this play an important role in determining the risk for asthma across the lifetime. Progress in asthma prevention is long overdue and this may benefit from carefully designed interventions in well-phenotyped longitudinal birth cohorts with early airway function assessments monitored through to adulthood.

Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: a pooled analysis of randomised controlled trials

In a phase 2b trial and the phase 3 MELODY trial, nirsevimab, an extended half-life, monoclonal antibody against respiratory syncytial virus (RSV), protected healthy infants born preterm or at full term against medically attended RSV lower respiratory tract infection (LRTI). In the MEDLEY phase 2-3 trial in infants at higher risk for severe RSV infection, nirsevimab showed a similar safety profile to that of palivizumab. The aim of the current analysis was to assess the efficacy of nirsevimab using a weight-banded dosing regimen in infants born between 29 weeks gestational age and full term. Infants enrolled in the phase 2b and MELODY trials were randomised (2:1) to receive a single intramuscular injection of nirsevimab (infants weighing <5 kg received 50 mg; those weighing ≥5 kg received 100 mg) or placebo before the RSV season. Infants in MEDLEY were randomised (2:1) to receive one dose of nirsevimab (infants weighing <5 kg received 50 mg; those weighing ≥5 kg received 100 mg) followed by four monthly placebo doses, or five once-a-month intramuscular doses of palivizumab. We report a prespecified pooled efficacy analysis assessing the weight-banded dosing regimen proposed on the basis of the phase 2b and MELODY trials, in addition to extrapolated efficacy in infants with chronic lung disease, congenital heart disease, or extreme preterm birth (<29 weeks' gestational age) based on pharmacokinetic data from the phase 2-3 MEDLEY safety trial. For the pooled efficacy analysis, the primary endpoint was incidence of medically attended RSV LRTI through 150 days post-dose. The secondary efficacy endpoint was number of admissions to hospital for medically attended RSV LRTI. The incidence of very severe RSV LRTI was an exploratory endpoint, defined as cases of hospital admission for medically attended RSV LRTI that required supplemental oxygen or intravenous fluids. We also did a prespecified exploratory analysis of medically attended LRTI of any cause (in the investigator's judgement) and hospital admission for respiratory illness of any cause (defined as any upper respiratory tract infection or LRTI leading to hospital admission). Post hoc exploratory analyses of outpatient visits and antibiotic use were also done. Nirsevimab serum concentrations in MEDLEY were assessed using population pharmacokinetic methods and the pooled data from the phase 2b and MELODY trials. An exposure target was defined on the basis of an exposure-response analysis. To successfully demonstrate extrapolation, more than 80% of infants in MEDLEY had to achieve serum nirsevimab exposures at or above the predicted efficacious target. Overall, 2350 infants (1564 in the nirsevimab group and 786 in the placebo group) in the phase 2b and MELODY trials were included in the pooled analysis. Nirsevimab showed efficacy versus placebo with respect to the primary endpoint of medically attended RSV LRTI (19 [1%] nirsevimab recipients vs 51 [6%] placebo recipients; relative risk reduction [RRR] 79·5% [95% CI 65·9-87·7]). Consistent efficacy was shown for additional endpoints of RSV LRTI hospital admission (nine [1%] nirsevimab recipients vs 21 [3%] placebo recipients; 77·3% [50·3-89·7]) and very severe RSV (five [<1%] vs 18 [2%]; 86·0% [62·5-94·8]). Nirsevimab recipients had fewer hospital admissions for any-cause respiratory illness (RRR 43·8% [18·8-61·1]), any-cause medically attended LRTI (35·4% [21·5-46·9]), LRTI outpatient visits (41·9% [25·7-54·6]), and antibiotic prescriptions (23·6% [3·8-39·3]). Among infants with chronic lung disease, congenital heart disease, or extreme preterm birth in MEDLEY, nirsevimab serum exposures were similar to those found in the pooled data; exposures were above the target in more than 80% of the overall MEDLEY trial population (94%), including infants with chronic lung disease (94%) or congenital heart disease (80%) and those born extremely preterm (94%). A single dose of nirsevimab protected healthy infants born at term or preterm from medically attended RSV LRTI, associated hospital admission, and severe RSV. Pharmacokinetic data support efficacy extrapolation to infants with chronic lung disease, congenital heart disease, or extreme prematurity. Together, these data suggest that nirsevimab has the potential to change the landscape of infant RSV disease by reducing a major cause of infant morbidity and the consequent burden on caregivers, clinicians, and health-care providers. AstraZeneca and Sanofi.

Desenvolvimento da linguagem de crianças prematuras extremas ao nascimento: orientação aos pais

ABSTRACT Purpose: to analyze the linguistic development of extremely premature children at birth, through the Initial Speech and Language Acquisition Scale, and to verify the knowledge of these children's parents about language. Methods: the study included 21 parents of extremely premature children at birth. A booklet on the development of children's language and a questionnaire was prepared for the study, in order to investigate the efficiency of guidance to parents. Initially, the children were assessed using the Initial Speech and Language Acquisition Scale, and then, the parents received oral guidance on how to stimulate their children's language. Therefore, the questionnaire was applied to verify the impact of the guidelines on their knowledge. The data obtained through the scale were related to the answers obtained through the questionnaire applied to the parents, through descriptive percentages and Mann-Whitney test, with p&lt;0.05. Results: most of the children performed as expected for their age in the evaluated aspects. The questionnaire showed that most parents had guidance on the general development of their children, but only half of them had knowledge about language. All participants felt contemplated with the educational material. Conclusion: despite the extreme prematurity, most children performed as expected for their age in terms of language, and parents had moderate knowledge on language.

A case report of an unusual and rare social cause of extreme prematurity in a newborn

The most frequent factors contributing to newborn mortality include prematurity and low birth weight. Prematurity has been linked to a number of well-known reasons, including maternal health, intrauterine infections, uteroplacental insufficiency, and psychosocial causes. The period of pregnancy is important for parental decision-making. Here, we report an intriguing, unique example of poor judgment and irrational reasoning that resulted in the birth of twins who were severely preterm and underweight. The couple when conceived spontaneously gave birth to a healthy baby, and then, they donated the baby to the elder brother under social and cultural pressure. The couple thought that they would not be able to take care of a baby and finally decided not to have any kids. Once more, they changed their minds and went for the pregnancy. However, they later decided to terminate the baby and finally chose a tubectomy. After a while, they decided they wanted to start a family again and underwent tubal recanalization. She chose in vitro fertilization (IVF) since she was unable to conceive naturally. Twins of gestational age 28–30 weeks were born through an emergency cesarean section after spending a lot of money. Both the babies required surfactant, ventilation, and intensive care for a long period due to their severe prematurity. Despite our best efforts and good nursing care, we still lost both the babies. The death of any baby in a hospital may be a mental trauma for the parents as well as health professionals. This case report is all about how wrong decision-making in the antenatal period regarding child adoption, donation of children, abortion, family planning, recanalization, and IVF treatment leads to birth of extremely low birth weight and severely premature babies.

Follow-up of premature babies – what should the family doctor know?

Once discharged from the neonatology unit, the preterm baby should be signed up to be surveyed by a family doctor, to prevent and reduce the risk of developmental delay through early identification of risk factors and guidance towards appropriate treatment programs. The number of newborns at risk discharged from the Neonatal Intensive Care Unit (NICU) is growing due to improvement in in­ten­sive care techniques and build-up of field experience. Etio­lo­gic risk factors for extreme prematurity are low so­­cio­eco­no­mical status, extreme mother’s age (underage and over 35-40 years old) and the increase in pregnancies ob­tained through assisted reproductive techniques. When the preterm baby surpasses acute complications and is dis­charged from intensive care, we have to take into con­si­de­ra­tion chronic complications of prematurity, that can have an impact on all organs and systems. The family doc­tor has a dual role, to prevent preterm birth through careful mo­ni­to­ring pregnancies, as well as the follow-up of former preterm new­born.

Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates

Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population. To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates. This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin in extremely premature neonates conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 874 extremely premature neonates born at 24 to 27 weeks' gestation who were enrolled in the PENUT study. Secondary analysis was performed in November 2021. Primary exposure was peak FB during the first 14 postnatal days. The FB was calculated as percent change in weight from birth weight (BW) as a surrogate for FB. The primary outcome was mechanical ventilation on postnatal day 14. The secondary outcome was a composite of severe bronchopulmonary dysplasia (BPD) or death. A total of 874 neonates (449 [51.4%] male; mean [SD] BW, 801 [188] g; 187 [21.4%] Hispanic, 676 [77.3%] non-Hispanic, and 11 [1.3%] of unknown ethnicity; 226 [25.9%] Black, 569 [65.1%] White, 51 [5.8%] of other race, and 28 [3.2%] of unknown race) were included in this analysis. Of these 874 neonates, 458 (52.4%) received mechanical ventilation on postnatal day 14, and 291 (33.3%) had severe BPD or had died. Median peak positive FB was 11% (IQR, 4%-20%), occurring on postnatal day 13 (IQR, 9-14). A total of 93 (10.6%) never decreased below their BW. Neonates requiring mechanical ventilation at postnatal day 14 had a higher peak FB compared with those who did not require mechanical ventilation (15% above BW vs 8% above BW, P < .001). On postnatal day 3, neonates requiring mechanical ventilation were more likely to have a higher FB (5% below BW vs 8% below BW, P < .001). The median time to return to BW was shorter in neonates who received mechanical ventilation (7 vs 8 days, P < .001) and those with severe BPD (7 vs 8 days, P < .001). After adjusting for confounding variables, for every 10% increase in peak FB during the first 14 postnatal days, there was 103% increased odds of receiving mechanical ventilation at postnatal day 14 (adjusted odds ratio, 2.03; 95% CI, 1.64-2.51). In this secondary analysis of a randomized clinical trial, peak FB was associated with mechanical ventilation on postnatal day 14 and severe BPD or death. Fluid balance in the first 3 postnatal days and time to return to BW may be potential targets to help guide management and improve respiratory outcomes. ClinicalTrials.gov Identifier: NCT01378273.

Burden of Comorbidities and Healthcare Resource Utilization Among Medicaid-Enrolled Extremely Premature Infants

Background: The effect of gestational age (GA) on comorbidity prevalence, healthcare resource utilization (HCRU), and all-cause costs is significant for extremely premature (EP) infants in the United States. Objectives: To characterize real-world patient characteristics, prevalence of comorbidities, rates of HCRU, and direct healthcare charges and societal costs among premature infants in US Medicaid programs, with respect to GA and the presence of respiratory comorbidities. Methods: Using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes, diagnosis and medical claims data from 6 state Medicaid databases (1997-2018) of infants born at less than 37 weeks of GA (wGA) were collected retrospectively. Data from the index date (birth) up to 2 years corrected age or death, stratified by GA (EP, ≤28 wGA; very premature [VP], &gt;28 to &lt;32 wGA; and moderate to late premature [M-LP], ≥32 to &lt;37 wGA), were compared using unadjusted and adjusted generalized linear models. Results: Among 25 573 premature infants (46.1% female; 4462 [17.4%] EP; 2904 [11.4%] VP; 18 207 [71.2%] M-LP), comorbidity prevalence, HCRU, and all-cause costs increased with decreasing GA and were highest for EP. Total healthcare charges, excluding index hospitalization and all-cause societal costs (US dollars), were 2 to 3 times higher for EP than for M-LP (EP $74 436 vs M-LP $27 541 and EP $28 504 vs M-LP $15 892, respectively). Conclusions: Complications of preterm birth, including prevalence of comorbidities, HCRU, and costs, increased with decreasing GA and were highest among EP infants during the first 2 years in this US analysis.