No change in mother's own milk provision and breastfeeding rates in preterm infants during the COVID-19 pandemic.

AIM: The aim of the study was to evaluate the duration of mother's own milk (MOM) provision to preterm very low-birth weight (VLBW, <1500 g) infants during the COVID-19 pandemic. We hypothesised that COVID-19 restrictions would reduce the duration of MOM provision. METHODS: This retrospective study compared VLBW infants born at the Berlin university hospital during the pandemic (15 March 2020 to 14 March 2021, n = 108) with infants born in the pre-pandemic year (01 January 2019 to 31 January 2019, n = 121). We calculated the duration of MOM provision and analysed factors associated with its early cessation. RESULTS: During the pandemic, the rate of primiparous mothers increased from 29% to 44% while the distribution of all other parental and infants' characteristics remained similar. There were no differences in the median duration of MOM provision (47 vs. 51 days), feeding type (MOM 67% vs. 65%) and breastfeeding rates at discharge (exclusive, 8% vs. 13%; partial 69% vs. 60%). Cox proportional hazard analysis revealed smoking during pregnancy and parental school education consistently as independent risk factors for early cessation of MOM provision. CONCLUSION: Supply of MOM for VLBW infants can be upheld also during pandemic restrictions.

[Operating models and organizational structures: opportunities and challenges for human milk banking in Germany]. / Versorgungsstrukturen und Betreibermodelle: Chancen und Herausforderungen des Frauenmilchbankwesens in Deutschland.

BACKGROUND: Donor human milk is the recommended alternative for feeding preterm infants if mother's own milk is unavailable. Human milk banks collect, screen, store and distribute donated human milk according to pre-specified standard operating procedures to premature infants without mothers own milk. AIM: Herein we characterize current operating models and the structural organisation of German milk bank institutions. The analysis of current and future opportunities and challenges may support the development of a comprehensive donor milk service within Germany. MATERIAL AND METHODS: Summary of the panel discussion entitled "Operating models and organizational structures: opportunities and risks for donor human milk bank in Germany" during the 3rd Scientific Symposium of the German Human Milk Bank Initiative (FMBI), November 25th to 26th 2022, in Nuremberg, Germany. RESULTS AND DISCUSSION: Differing operator models may facilitate the use of donor human milk by incorporating unique site-specific factors, pre-existing infrastructure, and individual needs. In addition to the establishment of milk banks serving single neonatal units, high-capacity milk banks should be enabled to provide donor human milk using several hub-and-spoke systems. This may create a nationwide network for a sustainable human milk supply for preterm infants that is based on qualified breastfeeding and lactation support.

Trend over 25 years of risk factors of mother's own milk provision to very low birth weight infants at discharge.

BACKGROUND: Feeding mother's own milk (MOM) is associated with reduced morbidity of very low birth weight (VLBW) infants (<1500 g), but not all mothers are able to provide pumped breast milk or breastfeed until discharge. AIMS: To investigate the duration of MOM feeding and identify risk factors for cessation. STUDY DESIGN: Single-center retrospective cohort study. SUBJECTS: 307 VLBW infants born 2012 and 2019 surviving beyond 7 days of life. OUTCOME MEASURES: Analysis of MOM feeding at discharge, including comparison with a historical cohort of infants born 1992-1994. RESULTS: MOM feeding was initiated in 178/180 infants (98.9 %) born in 2012 and in 123/127 infants (96.9 %) born in 2019 (p = 0.132), as compared to 73/89 (82 %) infants born 1992-1994 (p < 0.001). Median [range] duration of MOM feeding was similar for infants born in 2012 (45 [0-170] days) and 2019 (50 [0-190] days) (p = 0.396), but much longer than in the historical cohort (36 [0-152] days) (p < 0.001). The overall breastfeeding rate increased up to 69.2 % and 77.2 %. Factors associated with cessation of MOM feeding were smoking during pregnancy, single-mother status, short (<12 years) duration of maternal or paternal school education (all p ≤ 0.001), natural conception, birth weight ≥ 1000 g, and gestational age ≥ 29 weeks (p < 0.05). In Cox proportional hazard multivariate analysis, smoking during pregnancy and single-mother status remained independent risk factors. CONCLUSIONS: Duration of MOM feeding and breastfeeding rates of VLBW infants during hospital stay have increased significantly during the last 30 years, while smoking and indicators of low socioeconomic status remain dominant predictors of cessation of MOM feeding.

Updating Clinical Practices to Promote and Protect Human Milk and Breastfeeding in a COVID-19 Era.

The COVID-19 pandemic has impacted breastfeeding and lactation globally, with clinical practices implemented early in the pandemic being mostly anti-breastfeeding, e.g., separation of mothers from their infants, and not evidence based. As the pandemic has progressed, evidence has emerged reconfirming the value of human milk and the importance of protecting and supporting breastfeeding, especially the initiation of lactation. However, it is clear that COVID-19 has changed the clinical care paradigm around breastfeeding and lactation support and, as such, it is imperative that practices adapt and evolve to maintain the emphasis on lactation support. We participated in a round table conference aiming to rescue and develop protocols and practices that support breastfeeding during the COVID-19 pandemic. One key area to target will be to maximize the use of the antenatal period. The early identification of lactation risk factors together with the development of person-centered methods to deliver breastfeeding information and education to parents-to-be will be critical. In addition, the establishment of a hospital culture that values breastfeeding and prioritizes the use of human milk will be integral for the motivation of health care professionals. That culture will also support active management of the initiation of lactation and the development of a 'back-up plan' toolkit to support the mother experiencing lactation difficulties. Post-discharge support will also be crucial with the development of both in-person and virtual lactation support programs, in particular for the immediate post-discharge period to benefit mothers who experience an early discharge process. These measures will allow for a new, adapted framework of practice that acknowledges the current COVID-19 paradigm and maintains the emphasis on the need to protect and support breastfeeding and the use of human milk.

Rate of rise of total serum bilirubin in very low birth weight preterm infants.

BACKGROUND: To assess the postnatal rate of rise (ROR) of total serum bilirubin (TSB) in very low birth weight (VLBW) preterm infants, to determine risk factors associated with a rapid rise (>90th percentile), and to compare ROR and hour-specific TSB at postnatal 12-48 h with data of term infants retrieved from the literature. METHODS: Retrospective analysis of 2430 routine TSB concentrations obtained between birth and initiation of phototherapy in 483 VLBW infants. RESULTS: TSB increased by a median (interquartile range) ROR of 0.15 (0.11-0.19) mg/dL/h. The 50th percentile of TSB was below the 40th percentile of (near-)term counterparts at 12-48 h. TSB ROR correlated with the age at initiation (RS = -0.687; p < 0.001) and the duration (RS = 0.444; p < 0.001) of phototherapy. ROR >90th percentile (>0.25 mg/dL/h) was associated with lower gestational ages [27.2 (25.4-29.3) vs. 28.4 (26.4-30.4) weeks], lower birth weights [978 (665-1120) vs. 1045 (814-1300) g], and lower 5-min Apgar scores [7 (7-8) vs. 8 (7-9)]. CONCLUSION: ROR of TSB is an indicator for early and prolonged phototherapy. While hour-specific TSB and ROR at 12-48 h are lower than those reported for (near-)term infants, TSB appears to rise more rapidly in infants with low gestational age, low birth weight, and low 5-min Apgar score.

Milk Curd Obstruction in Human Milk-Fed Preterm Infants.

BACKGROUND: Milk curd obstruction as a cause of intestinal obstruction has been known since 1959, but has nearly disappeared. However, in recent years it has experienced a revival in small premature infants. OBJECTIVE: The aim of this study was to evaluate the clinical characteristics of milk curd obstruction (lactobezoar) in preterm infants. METHODS: Data of preterm infants with milk curd obstruction cared for at a large tertiary neonatal intensive care unit between 2012 and 2016 were retrieved from the electronic registry and paper records. RESULTS: A total of 10 infants (2 girls, 8 boys) were identified: the median birth weight was 595 g (range 270-922), gestational age was 24.4 weeks (23.4-27.0), weight-for-gestational age percentile was 16 (0-62), and age at diagnosis was 28 days (16-64). Five infants (50%) were small for gestational age. All neonates had received fortified human milk (added protein 2.0 g/100 mL, range 0-2.8; added calcium 2,400 µmol/100 mL, range 0-6 844; added phosphate 2,400 µmol/100 mL, range 0-5,178). Seven neonates underwent surgery, and 2 infants died. Hyperechoic masses in extended bowel loops, visualised by abdominal ultrasound, and pale/acholic faeces were hallmarks of milk curd obstruction. CONCLUSIONS: In this study, milk curd obstruction occurred exclusively in infants with a birth weight < 1,000 g (2.2%) and < 28 weeks' gestational age (2.4%). Male and small for gestational age infants appeared to be at increased risk. Paying attention to the colour of the faeces of infants at risk might help to diagnose milk curd obstruction at an early stage.

Effects of progesterone on hyperoxia-induced damage in mouse C8-D1A astrocytes.

INTRODUCTION: The birth of most mammals features a dramatic increase in oxygen while placenta-derived hormones such as ß-estradiol and progesterone plummet. In experimental newborn animals, transiently elevated oxygen concentrations cause death of neurons, astrocytes, and oligodendrocyte precursors. High oxygen has been associated with cerebral palsy in human preterm infants while progesterone is being used to prevent preterm delivery and investigated as a neuroprotective agent. METHODS: In this study, we investigated the effects of hyperoxia (80% O2 for 24, 48, and 72 h) on cultured C8-D1A astrocytes in the presence or absence of progesterone at concentrations ranging from 10(-9) to 10(-5) mol/L. RESULTS: Hyperoxia measured by methytetrazolium assay (MTT) reduced cell viability, increased release of lactate dehydrogenase (LDH), reduced carboxyfluorescein diacetate succinimidyl ester (CFSE)-assessed cell proliferation, and downregulated Cylin D2 expression. Progesterone did not affect any of these hyperoxia-mediated indicators of cell death or malfunctioning. Real-time PCR analysis showed that hyperoxia caused downregulation of the progesterone receptors PR-AB und PR-B. CONCLUSIONS: Our experiments showed that there was no protective effect of progesterone on hyperoxia-inducted cell damage on mouse C8-D1A astrocytes. Down regulation of the progesterone receptors might be linked to the lack of protective effects.

Transcutaneous bilirubin after phototherapy in term and preterm infants.

OBJECTIVES: To compare transcutaneous bilirubin (TcB) readings with total serum bilirubin (TSB) after phototherapy, estimating the range of TcB where confirmation through blood sampling can be avoided. METHODS: Preterm and term neonates receiving in-hospital phototherapy underwent TcB measurements (device JM-103, TcB) alongside routine TSB before and after treatment. We calculated time-dependent safety margins for transcutaneous readings to correctly assign 99% of infants not to receive phototherapy. RESULTS: Between August 2011 and December 2012, 86 newborn infants (47 preterm, 39 term) underwent a total of 189 parallel measurements. Mean difference (TcB - TSB) before treatment was -0.6 mg/dL (SD, 1.9 mg/dL). Within the first 8 hours after phototherapy, TcB levels were -2.4 mg/dL (SD, 2.1 mg/dL) below TSB. Thereafter the difference gradually returned to pretreatment values (-1.8 mg/dL in 8-16 hours, -1.1 mg/dL in 16-24 hours, and -0.8 mg/dL after 24 hours), while variations remained stable over time (SD, 1.4-1.8 mg/dL). In the first 8 hours after treatment, TcB levels of -7.3 mg/dL below the individual phototherapy threshold allowed safe rejection of confirmatory blood sampling. After 8 hours, that safety margin was reduced to approximately -5.0 mg/dL. CONCLUSIONS: TcB measurements remain a valuable tool after phototherapy when time-dependent underestimation of TcB is being accounted for.

Breastfeeding is natural but not always easy: intervention for common medical problems of breastfeeding mothers - a review of the scientific evidence.

Natural processes do not always function perfectly. In breastfeeding, problems are encountered in up to 80% of mother-infant dyads. Altogether, in Western societies, the difficulties reduce the breastfeeding rate within the first months drastically. To deal with the problems of breastfeeding efficiently requires a profound understanding of its physiology, as well as of its psychological and social determinants. This review focuses on the current knowledge of breastfeeding physiology, only touching the psychosocial factors, which are included in the promotion strategies. Subsequently, it scrutinizes definitions, incidences, prevention, and treatment of breastfeeding problems faced most frequently by nursing mothers and their consultants. Not all measures used in counseling mothers and not all treatments for the most common medical problems withstand a careful evaluation on the basis of current scientific data. However, applying proven prevention strategies will significantly improve the well being of mothers and their infants, and may contribute to an affective attitude that increases the success, frequency, and duration of breastfeeding.

Effects of sevoflurane on primary neuronal cultures of embryonic rats.

BACKGROUND AND OBJECTIVE: Commonly used anaesthetics can cause neurodegeneration in the developing brain. Sevoflurane, a widely used substance in paediatric anaesthesia, has not been analysed thus far. This study was carried out to investigate the effects of sevoflurane on neuronal cell viability. METHODS: Primary cortical neuronal cultures were prepared from Wistar rat embryos (E18), kept in 100 microl Gibco-Neurobasal-A medium and exposed to 4 and 8 Vol.% sevoflurane for up to 48 h. Cell viability was assessed using the methyltetrazolium assay and was related to untreated controls. To evaluate the role of gamma-aminobutyric acid type A receptors, untreated cells were preincubated with the receptor antagonists gabazine or picrotoxin and were subsequently exposed to 8 Vol.% sevoflurane and the receptor antagonist. Cell viability was assessed and compared with that of sevoflurane-treated controls. RESULTS: Up to 6 (8 Vol.%) and 12 h (4 Vol.%) of exposure to sevoflurane, cell viability was equal when compared with untreated controls. Only longer exposure times led to significantly lowered cell viability. After 12 h of exposure, no significant differences in cell viability were found between these two series. Cell viability of cultures treated with sevoflurane and the receptor antagonists showed no significant differences when compared with sevoflurane-exposed controls. CONCLUSION: These results suggest that sevoflurane does not cause neurodegeneration in primary cortical neurons of the rat following clinically relevant exposure times and concentrations.

Ibuprofen augments bilirubin toxicity in rat cortical neuronal culture.

Premature infants are at risk for bilirubin-associated brain damage. In cell cultures bilirubin causes neuronal apoptosis and necrosis. Ibuprofen is used to close the ductus arteriosus, and is often given when hyperbilirubinemia is at its maximum. Ibuprofen is known to interfere with bilirubin-albumin binding. We hypothesized that bilirubin toxicity to cultured rat embryonic cortical neurons is augmented by coincubation with ibuprofen. Incubation with ibuprofen above a concentration of 125 microg/mL reduced cell viability, measured by methylthiazole tetrazolium reduction, to 68% of controls (p < 0.05). Lactate dehydrogenase (LDH) release increased from 29 to 38% (p < 0.01). The vehicle solution did not affect cell viability. Coincubation with 10 microM unconjugated bilirubin (UCB)/human serum albumin in a molar ratio of 3:1 and 250 microg/mL ibuprofen caused additional loss of cell viability and increased LDH release (p < 0.01), DNA fragmentation, and activated caspase-3. Preincubation with the pan-caspase inhibitor z-val-ala-asp-fluoromethyl ketone abolished ibuprofen- and UCB-induced DNA fragmentation. The study demonstrates that bilirubin in low concentration of 10 microM reduces neuron viability and ibuprofen increases this effect. Apoptosis is the underlying cell death mechanism.

17beta-estradiol attenuates hyperoxia-induced apoptosis in mouse C8-D1A cell line.

In premature infants, oxygen free radicals generated following neonatal resuscitation are associated with subsequent diseases such as retinopathy of prematurity and bronchopulmonary dysplasia. Recent studies in brain tissue samples have shown that nonphysiologic oxygen levels play a key role in induction of apoptosis in the developing brain. Estrogen is a well-established agent in neuroprotection and, therefore, is thought to be neuroprotective even in the premature brain. Astrocytes appear to have a critical role in protection and survival of neurons in the brain. As one of the glial cell types, they have a great potential for possible involvement in the mediation of estrogen neuroprotective effects. The aim of our study was to analyze whether astrocytes in cell cultures are damaged by hyperoxia and whether 17beta-estradiol (E2) can protect them against apoptosis. Additionally, we investigated the mechanism of the protection by E2, hypothesizing that it is mediated through extracellular signal-regulated kinase (ERK1/2). Cells underwent eightfold more apoptosis when cultivated in hyperoxia compared with normoxia. Addition of E2 reduced apoptosis in hyperoxia by more than 50%. Levels of ERK1/2 and phosphorylated ERK1/2 were increased after hyperoxia compared with normoxia. Preincubation with E2 prior to exposure to hyperoxia resulted in decreased levels of ERK1/2 and pERK1/2. Hyperoxia induces apoptosis in C8-D1A cells, and E2 seems to be a protecting factor for astrocytes in hyperoxia. This effect is not mediated through up-regulation of pERK1/2.

Maturation-dependent oligodendrocyte apoptosis caused by hyperoxia.

In the immature human brain, periventricular leukomalacia (PVL) is the predominant white matter injury underlying the development of cerebral palsy. PVL has its peak incidence during a well-defined period in human brain development (23-32 weeks postconceptional age) characterized by extensive oligodendrocyte migration and maturation. We hypothesized that the dramatic rise of oxygen tissue tension associated with mammalian birth and additional oxygen exposure of the preterm infant during intensive care may be harmful to immature oligodendrocytes (OLs). We therefore investigated the effects of hyperoxia on rat oligodendroglia cells in vitro and in vivo. Immature OLs (OLN-93), their progenitors [preoligodendrocytes (pre-OL)], and mature OLs were subjected to 80% hyperoxia (24-96 hr). Flow cytometry was used to assess cell death. Cell viability was measured by metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT). In addition, 6-day-old rat pups were subjected to 80% oxygen (24 hr) and then sacrificed, and their brains were processed for immunfluorescence staining. Apoptosis was detected at various stages (annexin-V, activated caspase-3) after 24-48 hr of incubation in 80% oxygen in pre- and immature OLs. Mature OLs were resistant to oxygen exposure. These results were confirmed by MTT assay. This cell death was blocked by administration of the pan-caspase inhibitor zVAD-fmk. Degeneration of OLs was confirmed in 7-day-old rat brains by positive staining for activated caspase-3. Hyperoxia triggers maturation-dependent apoptosis in immature and pre-OLs and involves caspase activation. This mechanism may be relevant to the white matter injury observed in infants born preterm.

Antigen-positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT).

Neonatal alloimmune thrombocytopenia (NAIT) is a fetomaternal incompatibility most commonly induced by maternal anti-HPA-1a, IgG alloantibodies against a polymorphic epitope of the glycoprotein IIb/IIIa complex in approximately 97.5% of white patients. Current guidelines recommend transfusion of immunologically compatible platelets to prevent cerebral hemorrhage, the most severe complication in affected newborns. Such platelet concentrates, however, are often not readily available. In a retrospective analysis in German and Canadian centers, 27 newborns with NAIT were identified who received platelets from random donors. Unexpectedly, 24 of 27 newborns showed an increase above a threshold of 40 x 10(9) platelets per liter, with moderate (n = 8) or significant (n = 16) platelet count increments (more than 80 x 10(9)/L). We conclude that transfusion of platelet concentrates from random donors is an appropriate strategy in the management of unexpected, severe NAIT predominantly in first pregnancies, pending the availability of compatible platelets.

Neuronal damage after moderate hypoxia and erythropoietin.

Both mild hypoxia and exogenous erythropoietin may protect the brain against subsequent severe hypoxia, and the conditioning effect of transient hypoxia is partly mediated by hypoxia-induced endogenous erythropoietin. We now observed in several experimental models that combining transient hypoxia and exogenous erythropoietin may cause neuronal damage. High-dose erythropoietin (40 IU/ml) profoundly impeded synaptic transmission of rat hippocampal slice cultures when used in conjunction with moderate hypoxia (10% O2 for two 8-h periods). Addition of erythropoietin increased viability of cultured rat embryonic cortical neurons at 21% O2 but decreased viability under hypoxic conditions (2% O2) in a dose-dependent fashion. Death of human neuronal precursor cells challenged by oxygen and glucose deprivation was increased by erythropoietin when cells were cultured under hypoxic but not under normoxic conditions. In neonatal rats exposed to moderate hypoxia plus erythropoietin, numbers of degenerating cerebral neurons were increased, as compared to controls or rats subjected to either hypoxia or erythropoietin alone. Thus, erythropoietin may aggravate rather than ameliorate neuronal damage when administered during transient hypoxia.