Estimation of the reference values and decision limits for growth hormone in newborns using dried blood spots.

OBJECTIVES: Severe deficiency of growth hormone (GHD) of the newborn is a rare but potentially life-threatening disease. GH measured during the first week of life, using dried blood spots (DBS), may offer several advantages. Aim of the study was to estimate the reference values for GH in newborns by a new analytical method using DBS. METHODS: Using a new developed analytical method, GH was estimated from DBS of 1,036 healthy newborns attending the Neonatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan in the period July-October 2021. Reference values for GH deficiency were estimated by the Harrell-Davis bootstrap method, with 90 %CI calculated by the bias-corrected and accelerated bootstrap method. RESULTS: All GH measurements required 33 analytical sessions (8 months) with a CV% for calibration curve slopes equal to 6.9 %. Intermediate precision evaluated by measurement of low (3 µg/L) and high (10 µg/L) quality controls was, respectively, 14 and 6.5 %. GH reference values, estimated at percentiles 1.0st, 2.5th and 5.0th, and their 90 %CI, were, respectively, 4.5 µg/L (90 %CI 3.8-5.1), 5.9 µg/L (90 %CI 5.4-6.4) and 7.0 µg/L (90 %CI 6.7-7.3). GH levels were not associated with sex, standard deviation scores, birth weight, gestational age, type of delivery or mother's variables (age, smoking habit, gestational diabetes). CONCLUSIONS: Validation data suggest that this method can be used to measured GH in newborns using DBS. The reference values estimated in this study are in accordance with previous published works using ELISA and may help confirming the clinical suspicion of neonatal GHD.

Exclusive human milk feeding and prevalence of early adiposity rebound in ELBW infants: a retrospective cohort study.

The purpose of the present study was to evaluate the prevalence of early adiposity rebound (EAR) and factors associated with its occurrence in a cohort of extremely low birth weight infants (ELBW). We conducted a retrospective longitudinal study including ELBW infants followed-up for up to 10 years after discharge. EAR was defined as occurring before 5 years of age. A multivariate binary logistic regression analysis was performed to evaluate maternal and perinatal variables independently associated with EAR. Out of 212 ELBW infants included in the analysis, 40.6% developed EAR and 21.5% showed it before 4 years of age. Only formula milk feeding at discharge was independently associated with a higher risk of EAR. The mean BMI of children with EAR was higher than that of children without EAR. Furthermore, the prevalence of overweight and obesity was higher in the EAR group than in the timely AR group.  Conclusions: ELBW infants in our cohort developed EAR in a relatively high percentage of cases. In this already at-risk population, EAR may represent a further risk factor for an adverse metabolic outcome. Monitoring preterm infants' growth within a long-term follow-up program and promoting and supporting human milk feeding is advisable. What is Known: • Preterm-born infants are at high risk for long-term adverse health outcomes, especially cardiovascular and metabolic. • The occurrence of early adiposity rebound (EAR) is associated with the risk of later obesity and metabolic syndrome. What is New: • The occurrence of EAR in ELBW infants may represent an additional risk factor for later adverse metabolic outcomes in an already vulnerable population. • Future preventive strategies should include a long-term follow-up and the promotion of exclusive breastfeeding.

Breastmilk from COVID-19 negative lactating mothers shows neutralizing activity against SARS-COV-2.

Breastmilk protects newborns from infections through specific and nonspecific compounds. This study investigated the neutralizing activity against SARS-CoV-2 of breastmilk from SARS-CoV-2 negative, unvaccinated mothers, and compared it to that from infected nursing mothers. We enrolled women after COVID-19 swab testing results upon maternity admission, and divided them into two groups: group A, COVID-19-positive mothers, and group B, negative mothers. Breastmilk was randomly sampled at 2, 7, and 20 days postpartum. We collected 19 samples for Group A and 41 for Group B. A microneutralization assay was used to determine the 50% neutralization (NT50) titre. The presence of neutralizing antibodies was also determined. Group A had 100% neutralizing samples at 2 days postpartum (T0), declining 7 days postpartum (T1) and 20 days postpartum (T2). Group B samples exhibited neutralizing activity mostly at 7 days postpartum (T1) (90%). Negative mothers' samples showed no correlation between NT50 titres and antibodies' presence, suggesting that non-specific breastmilk components may exert antiviral action against SARS-CoV-2.

Dose-dependent impact of human milk feeding on tidal breathing flow-volume loop parameters across the first 2 years of life in extremely low-birth-weight infants: a cohort study.

The purpose of this study is to test the hypothesis that higher consumption of human milk (HM) in preterm infants with birth weight (BW) <1000 g is associated with improved lung function in a dose-dependent manner over the first 2 years of corrected age (CA). This retrospective study at an academic medical center included infants with BW <1000g. They had lung function assessment by the tidal breathing flow-volume loop (TBFVL) follow-up visits at 0-3-, 3-6-, 6-12-, 12-18-, and 18-24-month CA. One hundred eighty infants were included in the study with a mean (SD) gestational age 26.5 (1.90) weeks and BW 772.4 (147.0) g, 50% were female, and 60% developed BPD. 62.8% of infants received HM during the NICU stay. According to a general linear model (including GA, being small for GA (SGA), sex, human milk percentage, sepsis, and BPD), on average, each week of GA resulted in a higher tPTEF/tE of 1.24 (p = 0.039) and being SGA in a lower tPTEF/tE of 5.75 (p = 0.013) at 0-3-month CA. A higher percentage of human milk out of the total enteral intake was associated with better tPTEF/tE z-scores at 0-3 months (p = 0.004) and 18-24 months of CA (p = 0.041). BPD diagnosis was associated with a relevantly worse tPTEF/tE z-score at 6-12 months of CA (p = 0.003). CONCLUSION: Preterm infants with higher consumption of HM had significantly less airway obstruction across the first 2 years, suggesting that human milk may contribute in a dose-dependent manner to improve lung function in early childhood in former preterm infants born ELBW. WHAT IS KNOWN: • Human milk feeding reduces the risk of prematurity-related morbidities, including necrotizing enterocolitis, sepsis, lower respiratory tract infections, and BPD. Both exclusive and partial human milk feeding appear to be associated with a lower risk of BPD in preterm infants. WHAT IS NEW: • This cohort study of 180 preterm infants with birth weight < 1000 g found that exposure to human milk during hospitalization improves airway obstruction markers tPTEF/tE z-score over the first 2 years of corrected age in a dose-dependent manner.

Beyond survival: the lasting effects of premature birth.

Preterm birth, defined as birth before 37 weeks of gestation, is a major public health concern. It affects about 10% of all newborns globally and is the main cause of infant death and morbidity. Prematurity increases the likelihood of respiratory distress syndrome, cerebral palsy, and developmental abnormalities. Furthermore, premature newborns are at risk of acquiring chronic noncommunicable diseases later in life due to interference with organ system development during the in-utero and perinatal period. Because of the greater risk of long-term repercussions, preterm birth should be considered a chronic disorder, and gestational age and other birth histories should be included in all medical records for patients of all ages, especially when assessing the risk of multiple chronic diseases. Conventional methods for assessing preterm infant development, as well as reliable and precise growth monitoring, can lead to the early detection of growth decline and the adjustment of feeding regimens as needed. Because of its unique composition and useful components, human milk is a powerful tool for mitigating the negative outcomes associated with prematurity. It contains a variety of growth factors that promote the development of organs and systems, counteracting the negative effects of the abrupt interruption of intrauterine development and promoting better outcomes in all altered functions. Despite its multiple benefits, human milk cannot totally restore the lasting damage caused by premature birth. Premature infants cannot be completely overcome by nutrition alone, and yet adequate nutritional intake and human milk feeding are critical to their health and development.

Feeding Difficulties in Late Preterm Infants and Their Impact on Maternal Mental Health and the Mother-Infant Relationship: A Literature Review.

Late preterm infants constitute the largest subset of premature infants and are more likely to experience feeding issues leading to delayed oral feeding independence and low breastfeeding rates. Considering the increased parental concern about their infants' nutrition and growth, we performed a literature review to provide an update on the feeding challenges faced by late preterm infants and the impact of these issues on maternal mental health and the mother-infant relationship. Based on our findings, late preterm infants have a high prevalence of feeding difficulties which need to be addressed by targeted support interventions to promote breastfeeding success and the establishment of a harmonious dyadic interaction between the mother and her infant, all of which contribute to the prevention of altered feeding behavior later in life. There is still a need for additional research to develop a standardized and shared strategy that can be proven to be effective. Should this be accomplished, it will be possible to offer appropriate support for mothers, encourage the oral skills and maturation of late preterm infants, and improve the relationship quality within the dyad.

In-hospital growth and long-term neurodevelopmental outcomes of very low birth weight infants.

Background and Objectives: Very low birth weight infants (VLBW) are at risk for adverse growth and neurodevelopmental outcomes. We aimed to evaluate the association between growth during Neonatal Intensive Care Unit (NICU) stay and long-term neurodevelopmental outcomes in a cohort of preterm VLBW newborns. Methods: We conducted a longitudinal observational study in the Follow-up Service of our Clinic from January 2014 to April 2017. All preterm VLBW infants born at our hospital and enrolled in our follow-up program were considered eligible for the study. The neurodevelopmental assessment was performed using the Griffiths Mental Development Scales at 12 and 24 months corrected age. Results: Study population included 172 subjects (47.1% males) with a mean gestational age of 29 weeks and a mean birth weight of 1,117 g. A unitarian Δz-score increase in head circumference from birth to discharge was associated with a 1.6-point increase in General Quotient at 24 months corrected age. An association with subscales C and D was also found. Likewise, an increase in length Δz-score was associated with better 24-month subscale C scores although not reaching statistical significance. No relationship with the outcome at 24 months was found for weight gain. Conclusions: Growth during NICU stay appears to be related to a more favorable neurodevelopmental outcome at 24 months corrected age, especially in the hearing and language domain (subscale C). The longitudinal evaluation of auxological parameters during hospitalization can contribute to the identification of subjects at risk for adverse neurodevelopmental outcomes in the first years of life.

Mother-to-child transmission of SARS-CoV-2 infection in high-income countries: a systematic review and meta-analysis of prospective observational studies.

Mother-to-child transmission of SARS-CoV-2 has been reported since the onset of the COVID-19 pandemic. We conducted a study to summarize evidence on the risk of mother-to-child transmission in the first 30 days after birth in high-income countries and to evaluate the association between preventive measures and the risk of infection for the neonate. A systematic review and meta-analysis were undertaken following PRISMA guidelines. The National Library of Medicine, Web of Science, and Excerpta Medica databases were screened on February 26, 2022. All prospective observational studies addressing the frequency of infection in infants born to mothers SARS-CoV-2 positive were included. Twenty-six studies were included, reporting data of 2653 mothers with SARS-CoV-2 and 2677 neonates. The proportion meta-analysis pointed out an overall estimate of SARS-CoV-2 infection among infants of 2.3% (95% CI: 1.4-3.2%). Data from studies with (1.4%, 95% CI: 0.8-2) and without (1.3%, 95% CI: 0.0-2.7%) rooming-in provided similar risk of infection. Adopting at least two prevention measures during rooming-in resulted in a rate of mother-to-child infection of 1.0% (95%CI: 0.3-1.7%). The results of this study show a low rate of perinatal infection, support the rooming-in and confirm the effectiveness of preventive measures in reducing the risk of mother-to-child viral transmission.

The "Breastfeeding Paradox" as a Guide for the Assessment of Premature Infants Growth: It Is More Than Just Weigh-Ins.

One of the neonatologist's greatest challenges is ensuring that the premature infant has adequate growth and is provided with a correct supply of nutrients. Thanks to the establishment of the INTERGROWTH-21st Preterm Postnatal Growth Standards, created longitudinally and prospectively on healthy premature babies, it now appears evident that preterms' growth follows a pattern different from that of a fetus of the same gestational age. In addition to growth, defined solely as weight gain, further significance must be given to the quality of growth, that is, lean mass apposition. This should be evaluated in every clinical setting, using repeated standardized length and head circumference measurements, not only whether sophisticated dedicated equipment is available. Mother's milk, in addition to the countless already-known benefits, is also the perfect nourishment for premature babies, promoting lean mass apposition. In addition, with a still unclear mechanism called the "breastfeeding paradox," breast milk intake promotes preterms' neurocognitive development, even despite an initial lower weight gain. Since breast milk cannot always meet preterm infants' nutritional needs, breast milk fortification during hospitalization is a common practice. However, no clear benefit in continuing breast milk fortification after discharge has been demonstrated. When addressing the growth of a premature infant fed with human milk, the "breastfeeding paradox" must be taken into consideration to avoid excessive and unjustified supplementation of formula milk, both during the hospital stay and after discharge.

Postnatal growth of small for gestational age late preterm infants: determinants of catch-up growth.

BACKGROUND: Failure to recover growth is a risk reported in late preterm population. This study aimed to evaluate the auxological outcome of late preterm infants and identify factors associated with failure to recover growth. METHODS: We enrolled late preterm infants with birth weight ≤10th percentile, followed up at High-Risk Infant Follow-up Service. We collected data at birth and at follow-up visits. A logistic regression analysis was performed to assess variables independently associated with growth failure. RESULTS: The population consisted of 175 preterms. The percentage of children showing no weight recovery was 34% at 36 months. At logistic regression analysis, infants who had not regained weight at 12 months had a higher risk of not regaining weight even at 36 months. The same risk factor was highlighted for length catch-up growth. Moreover, infants fed any human milk at discharge were protected from not achieving both weight and length catch-up growth at 36 months. CONCLUSION: These results indicate that children born late preterm and small for gestational age could fail to recover weight and stature growth in the first 36 months. The protective effect of human milk on failure to thrive highlights the importance of promoting breastfeeding in this population. IMPACT: A significant number of SGA late preterms show a failure to recover weight and statural growth. Having experienced intrauterine growth restriction is associated with a greater chance of achieving statural catch-up growth. Being born singleton represents a risk factor for slower weight and height growth velocity. Breastmilk has a protective effect on failure to recover adequate weight and length in preterm SGA infants. This finding highlights the importance of promoting breastfeeding in this population.

Comparative Analysis of Docosahexaenoic Acid (DHA) Content in Mother's Milk of Term and Preterm Mothers.

Objectives and Study: Docosahexaenoic acid (DHA) plays an essential role in infants' development. Maternal diet and breastmilk are the primary DHA sources for newborns. This single-center observational study aimed to compare the DHA content in mother's milk of preterm mothers with that of term ones, and to investigate the changes in mother's milk DHA content according to the week of the gestational age. Methods: A food frequency questionnaire (FFQ) was submitted to each mother to estimate the DHA intake during the last trimester of pregnancy, and the mother's milk was collected between 24 and 96 h post-partum. Results: Women who gave birth prematurely showed a lower content of mother's milk DHA than the term ones (0.51; IQR 0.38−0.6% FA vs. 0.71; IQR 0.52−0.95% FA; p = 0.001). In the multivariate linear regression analyses, for each additional week of gestational age, there was an increase in DHA content in the mother's milk (0.046% FA; CI 95% 0.018−0.074; p < 0.001). Conclusions: Our results suggest that breast milk may not be sufficient to fully satisfy the recommended DHA intake in preterm infants. This study may represent a starting point to investigate new possible DHA supplementation strategies, especially for the late and moderate preterm infants.

Parent's Health Locus of Control and Its Association with Parents and Infants Characteristics: An Observational Study.

The Parent Health Locus of Control (PHLOC) investigates the individual's beliefs about the factors that govern their state of health and that of their children. The direct association between PHLOC and preventive health behaviours compliance has already been demonstrated in the literature. However, it is still unclear how socio-demographic variables affect the PHLOC. We investigated the Parent Health Locus of Control of parents of full-term and preterm infants and evaluated whether there were any correlations between PHLOC and socio-demographic characteristics of both parents and infants. A single-centre transverse observational study was conducted in the Neonatology Operating Unit IRCCS Ca 'Granda Foundation Ospedale Maggiore Policlinico of Milan. A self-administered questionnaire of the PHLOC scale was distributed to a sample of 370 parents of 320 full-term and 52 preterm infants attending the follow-up service. Parents under the age of 36 and with a higher level of education (bachelor's degree or above) believe less in the influence of the media on their child's health. Parents of preterm and first-child infants recognize the greater influence of health care workers, while parents of newborns that have experience complications in their clinical course, believe more in the influence of fate (Chance Health Locus of Control) and God. Younger parents with a higher level of education may be more prone to healthy preventative behaviours. Preterm birth is positively associated with an increased trust in health care professionals. The experience of disease can increase a "Chance Health Locus of Control" and risky behaviours. Assessment of PHLOC helps identify categories of parents prone to risky health behaviours and offer targeted health education interventions.

Nutrition for Infant Feeding.

It has long been demonstrated that nutrition in the first 1000 days of life can affect health outcomes later in life [...].

Modulating Role of Breastfeeding Toward Long COVID Occurrence in Children: A Preliminary Study.

The SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus-2) pandemic has forced the global health system to face new challenges both in the acute management of COVID-19 (Coronavirus Disease 2019) patients and in its consequences. In particular, the long-term effects of this new virus, especially in children, are still poorly understood. Scientific research is currently trying to understand the mechanisms underlying the so called "long COVID syndrome". Since the beginning of the pandemic, breastmilk has been studied for its antiviral and immunomodulatory properties. Based on these assumptions, we conducted a preliminary study in order to investigate the prevalence of long COVID in a cohort of Italian children with previously detected SARS-CoV-2 infection and evaluate if breastfeeding might play a role in modulating long COVID occurrence.

Newborn Weight Loss as a Predictor of Persistence of Exclusive Breastfeeding up to 6 Months.

Objectives: To investigate the association between neonatal weight loss and persistence of exclusive breastfeeding up to 6 months. Study Design: An observational cohort study in the setting of a Baby Friendly Hospital, enrolling 1,260 healthy term dyads. Neonatal percentage of weight loss was collected between 48 and 72 h from birth. Using a questionnaire, all mothers were asked on the phone what the infant's mode of feeding at 10 days, 42 days and 6 months (≥183 days) from birth were. The persistence of exclusive breastfeeding up to 6 months and the occurrence of each event that led to the interruption of exclusive breastfeeding were verified through a logistic analysis that included 40 confounders. Results: Infants with a weight loss ≥7% were exclusively breastfed at 6 months in a significantly lower percentage of cases than infants with a weight loss <7% (95% CI 0.563 to 0.734, p < 0.001). Weight loss ≥7% significantly increases the occurrence of either sporadic integration with formula milk (95% CI 0.589 to 0.836, p < 0.001), complementary feeding (95% CI 0.460 to 0.713, p < 0.001), exclusive formula feeding (95% CI 0.587 to 0.967, p < 0.001) or weaning (95% CI 0.692 to 0.912, p = 0.02) through the first 6 months of life. Conclusions: With the limitations of a single-center study, a weight loss ≥7% in the first 72 h after birth appears to be a predictor of an early interruption of exclusive breastfeeding before the recommended 6 months in healthy term exclusively breastfed newborns.

The hidden universe of human milk microbiome: origin, composition, determinants, role, and future perspectives.

Although traditionally considered sterile, human milk is currently recognized as an alive ecosystem that harbors not only bacteria, but also viruses, fungi and yeasts, and minor genera, collectively known as the human milk microbiome (HMM). The seeding of HMM is a complex phenomenon whose dynamics are still a matter of research. Many factors contribute to its determination, both maternal, neonatal, environmental, and related to human milk itself. The transmission of microorganisms to the infant through breastfeeding may impact its present and future health, mainly shaping the GI tract microbiome and immune system. The existence and persistence of HMM as a conserved feature among different species may also have an evolutionary meaning, which will become apparent only in evolutionary times. CONCLUSION: The complexities of HMM warrant further research in order to deepen our knowledge on its origin, determinants, and impact on infants' health. The practical and translational implications of research on HMM (e.g., reconstitution of donor human milk through inoculation of infant's own mother milk, modulation of HMM through maternal dietary supplementation) should not be overlooked. WHAT IS KNOWN: • Human milk harbors a wide variety of microorganisms, ranging from bacteria to viruses, fungi and yeasts, and minor genera. • Human milk microbiome is shaped over time by many factors: maternal, neonatal, environmental, and related to human milk itself. • The transmission of microorganisms through breastfeeding may impact the infant's present and future health. WHAT IS NEW: • We provide an overview on human milk microbiome, hopefully encouraging physicians to consider it among the other better-known breastfeeding benefits. • Further studies, with standardized and rigorous study designs to enhance accuracy and reproducibility of the results, are needed to deepen our knowledge of the human milk microbiota and its role in newborn and infant's health.

Pilot Feasibility Study of a Hospital-Based Post-Natal Educational Intervention on New Mothers in a BFHI-Compliant Tertiary Referral Center for Neonatal Care.

The immediate post-partum period offers a valuable opportunity for parental education on various health topics. The aim of this study was to pilot test the feasibility in a tertiary referral center for neonatal care of a post-natal educational intervention (the Diary) designed to provide mothers with basic information concerning newborn care and breastfeeding. Furthermore, we aimed to evaluate its effect on exclusive breastfeeding rates at discharge and at 48 h post-discharge, and on maternal perceived support during hospital stay, compared to standard care. A single-center two-phase interventional study was carried out from 1 December 2018 to 2 June 2019. The Diary was given to mothers enrolled in Phase 2, together with the Nurse-Parent Support Tool (NPST). The Diary-NPST couples analyzed were 269. The Diaries filled out and returned were 62.2%. Overall, mothers rated the information received through the Diary as "clear and comprehensive". Exclusive breastfeeding rates at discharge resulted in being higher in Phase 1 than in Phase 2 (80.6% vs. 72.5%, p = 0.04), whereas no difference emerged in terms of exclusive breastfeeding rates at 48 h. In both phases, the median NPST total score (4.05) was high. In conclusion, we propose a new instrument of in-hospital post-natal maternal education and, in line with the current literature, we support well-designed written educational materials to promote mothers' knowledge and satisfaction with post-partum hospital assistance. Further studies that are multicentric and with a longer follow-up period are needed to evaluate the potential impact of the Diary on exclusive breastfeeding duration.

Human Milk, More Than Simple Nourishment.

Human breast milk not only has nutritional properties but also holds a functional role. It contains various bioactive factors (lactoferrin, lysozyme, leukocytes, immunoglobulins, cytokines, hormones, human milk oligosaccharides, microbiome, microRNAs and stem cells) shown to contribute to several short- and long-term health outcomes. Some of these factors appear to be involved in the infant's neuro-cognitive development, anti-oncogenic processes, cellular communication and differentiation. Furthermore, breast milk is increasingly recognized to have dynamic characteristics and to play a fundamental role in the cross-talking mother-neonate. This narrative review aims to provide a summary and an update on these bioactive substances, exploring their functions mainly on immunomodulation, microbiome and virome development. Although the knowledge about breast milk potentiality has significantly improved, leading to discovering unexpected functions, the exact mechanisms with which breast milk exercises its bioactivity have not been completely clarified. This can represent a fertile ground for exploring and understanding the complexity behind these functional elements to develop new therapeutic strategies.

Effect of human milk and other neonatal variables on lung function at three months corrected age.

OBJECTIVE: To evaluate the impact of human milk and different neonatal variables on tidal breathing flow-volume loop (TBFVL) parameters within three months' corrected age (CA) in infants born ≤32 wks or weighing <1500 g. METHODS: We retrospectively studied 121 infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) <1500 gr who had lung function assessment within three months' CA by TBFVL analysis between June 2009 and April 2018. We investigated the impact of GA, gender, being Small for GA (SGA), sepsis, days of mechanical ventilation (MV) and human milk feeding (HMF) on later respiratory function, both in the entire group and according to BW ( ≤1000 g and >1000 g). RESULTS: The mean(SD) z-score for tidal volume (Vt) and time to peak expiratory flow to expiratory time (tPTEF/tE) were respectively -4.3 (2.5) and -0.8 (2.0) for the overall population with no significant differences between infants <1000 g or ≥1000 g. The mean(SD) Vt standardized for body weight was 6.2(2.0) ml/kg. Being female was associated with better Vt/Kg, whereas longer MV or being born SGA were associated with worst tPTEF/tE. For infants with BW < 1000 gr, tPTEF/tE was positively associated with HMF. CONCLUSION: An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW <1000 g has emerged, which deserves further investigation.