Uwe Ewald

One-year survival of extremely preterm infants after active perinatal care in sweden

CONTEXT Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling. OBJECTIVE To determine the 1-year survival in all infants born before 27 gestational weeks in Sweden during 2004-2007. DESIGN, SETTING, AND PATIENTS Population-based prospective observational study of extremely preterm infants (707 live-born and 304 stillbirths) born to 887 mothers in 904 deliveries (102 multiple births) in all obstetric and neonatal units in Sweden from April 1, 2004, to March 31, 2007. MAIN OUTCOME MEASURES Infant survival to 365 days and survival without major neonatal morbidity (intraventricular hemorrhage grade >2, retinopathy of prematurity stage >2, periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia). Associations between perinatal interventions and survival. RESULTS The incidence of extreme prematurity was 3.3 per 1000 infants. Overall perinatal mortality was 45% (from 93% at 22 weeks to 24% at 26 weeks), with 30% stillbirths, including 6.5% intrapartum deaths. Of live-born infants, 91% were admitted to neonatal intensive care and 70% survived to 1 year of age (95% confidence interval [CI], 67%-73%). The Kaplan-Meier survival estimates for 22, 23, 24, 25, and 26 weeks were 9.8% (95% CI, 4%-23%), 53% (95% CI, 44%-63%), 67% (95% CI, 59%-75%), 82% (95% CI, 76%-87%), and 85% (95% CI, 81%-90%), respectively. Lower risk of infant death was associated with tocolytic treatment (adjusted for gestational age odds ratio [OR], 0.43; 95% CI, 0.36-0.52), antenatal corticosteroids (OR, 0.44; 95% CI, 0.24-0.81), surfactant treatment within 2 hours after birth (OR, 0.47; 95% CI, 0.32-0.71), and birth at a level III hospital (OR, 0.49; 95% CI, 0.32-0.75). Among 1-year survivors, 45% had no major neonatal morbidity. CONCLUSION During 2004 to 2007, 1-year survival of infants born alive at 22 to 26 weeks of gestation in Sweden was 70% and ranged from 9.8% at 22 weeks to 85% at 26 weeks.

Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta

Background. Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results. Methods. A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of gestation. Engraftment analyses of donor cells, immunologic reaction against donor cells, and the well-being of the patient were assessed. Results. At 9 months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen. Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4% Y-positive cells (range, 6.8%–16.6%). Bone histology showed regularly arranged and configurated bone trabeculae. Patient lymphocyte proliferation against donor MSC was not observed in co-culture experiments performed in vitro after MSC injection. Complementary bisphosphonate treatment was begun at 4 months. During the first 2 years of life, three fractures were noted. At 2 years of corrected age, psychomotor development was normal and growth followed the same channel, −5 SD. Conclusions. The authors’ findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.

Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)

Aims:  The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors.

Towards universal Kangaroo Mother Care: Recommendations and report from the First European conference and Seventh International Workshop on Kangaroo Mother Care

The hallmark of Kangaroo Mother Care (KMC) is the kangaroo position: the infant is cared for skin‐to‐skin vertically between the mother’s breasts and below her clothes, 24 h/day, with father/substitute(s) participating as KMC providers. Intermittent KMC (for short periods once or a few times per day, for a variable number of days) is commonly employed in high‐tech neonatal intensive care units. These two modalities should be regarded as a progressive adaptation of the mother‐infant dyad, ideally towards continuous KMC, starting gradually and progressively with intermittent KMC. The other components in KMC are exclusive breastfeeding (ideally) and early discharge in kangaroo position with strict follow‐up. Current evidence allows the following general statements about KMC in affluent and low‐income settings: KMC enhances bonding and attachment; reduces maternal postpartum depression symptoms; enhances infant physiologic stability and reduces pain, increases parental sensitivity to infant cues; contributes to the establishment and longer duration of breastfeeding and has positive effects on infant development and infant/parent interaction. Therefore, intrapartum and postnatal care in all types of settings should adhere to a paradigm of nonseparation of infants and their mothers/families. Preterm/low‐birth‐weight infants should be regarded as extero‐gestational foetuses needing skin‐to‐skin contact to promote maturation.

Closeness and separation in neonatal intensive care

In this paper, we highlight the need for acknowledging the importance and impact of both physical and emotional closeness between the preterm infant and parent in the neonatal intensive care unit. Physical closeness refers to being spatially close and emotional closeness to parental feelings of being emotionally connected to the infant (experiencing feelings of love, warmth and affection). Through consideration of the literature in this area, we outline some of the reasons why physical closeness and emotional closeness are crucial to the physical, emotional and social well‐being of both the infant and the parent. These include positive effects on infant brain development, parent psychological well‐being and on the parent–infant relationship. The influence of the neonatal unit environment and culture on physical and emotional closeness is also discussed.

State of the art and recommendations. Kangaroo mother care: application in a high-tech environment.

Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low income settings, the original KMC model is implemented. This consists of continuous (24 h/day, 7 days/week) and prolonged mother/parent–infant skin‐to‐skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding; and, adequate follow‐up. In affluent settings, intermittent KMC with sessions of one or a few hours skin‐to‐skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high‐tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC model in all types of settings was discussed at the 7th International Workshop on KMC. Kangaroo Mother Care protocols in high‐tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents’ role, modification of the NICU environment, performance of care in KMC, and KMC in case of infant instability.

Postnatal Head Growth Deficit Among Premature Infants Parallels Retinopathy of Prematurity and Insulin-like Growth Factor-1 Deficit

BACKGROUND. We hypothesized that in premature infants, retinal vascular growth retardation between birth and postmenstrual age of ∼30 to 32 weeks that initiates retinopathy of prematurity is paralleled by brain growth retardation. METHODS. In a prospective longitudinal study, we measured postnatal head growth, retinopathy of prematurity stage, protein and energy intake, severity of illness and serum insulin-like growth factor-1 levels in 58 preterm infants (mean gestational age at birth: 27.6 weeks) from birth until postmenstrual age of ∼40 weeks. RESULTS. Premature infant head growth decelerates dramatically after birth until postmenstrual age of ∼30 weeks. Head growth retardation coincides with retinal vascular growth suppression. Accelerated growth follows between post menstrual ages of ∼30 to 32 weeks and ∼40 weeks. The degree of head growth retardation up to postmenstrual age of 31 weeks corresponds to the degree of retinopathy of prematurity and to the degree of suppression of serum levels of insulin-like growth factor-1. At postmenstrual age of 31 weeks, if a child’s head circumference SD is below −2.5, then the probability of also developing at least stage 3 retinopathy of prematurity increases fivefold compared with head circumference above −2.5 SD (32% vs 6%) suggesting parallel processes in brain and retina. Serum insulin-like growth factor-1 levels correlate positively with head circumference SD score and with the degree of retinopathy of prematurity. CONCLUSIONS. The correlation between head and retinal growth is consistent with insulin growth factor-1 being one of the postnatal growth factors involved in this multifactorial process and also suggests that factors that contribute to retinopathy of prematurity during this critical period may also affect neurological dysfunction. Additional studies are required to establish this connection.

Neutrophils from Term and Preterm Newborn Infants Express the High Affinity Fcγ-Receptor I (CD64) During Bacterial Infections

The high affinity Fcγ-receptor I (FcγRI, CD64) is normally expressed only to a very low extent by neutrophils. During bacterial infections, however, neutrophils from adult patients significantly increase their expression of FcγRI. Stimulation through FcγRI is a highly effective way to improve various aspects of neutrophil function, including phagocytosis. In our study the expression of FcγRI on neutrophils from preterm (n = 9) and term (n = 3) newborn infants, children (n = 14), and adults (n = 6) during the early phase of an acute bacterial infection was investigated. Our results showed that neutrophils from newborn infants with bacterial infection expressed FcγRI to a significantly higher extent than both noninfected preterm (p < 0.001) and term (p < 0.001) newborn infants and that neutrophils from preterm neonates expressed FcγRI to the same extent as neutrophils from term neonates and older infants, children, and adults. No difference in the neutrophil cell surface expression of FcγRI during bacterial infections was found among newborn infants, children, and adults. Expression of FcγRI probably represents an important mechanism to improve neutrophil phagocytosis as well as other aspects of neutrophil function during bacterial infections, especially in preterm infants. Our study indicates that measurement of cell surface expression of FcγRI on neutrophils could be a useful indicator of severe bacterial infections in preterm and term neonates, as well as in older children and adults.

Positive Effect of Kangaroo Mother Care on Long‐Term Breastfeeding in Very Preterm Infants

OBJECTIVE To investigate the use of Kangaroo Mother Care (KMC) and its association with breastfeeding at 1 to 6 months of corrected age in mothers of very preterm (VPT) and preterm (PT) infants. DESIGN Prospective longitudinal study. SETTING Neonatal Intensive Care Units in four counties in Sweden. PARTICIPANTS The study included 103 VPT (< 32 gestational weeks) and 197 PT (32-36 gestational weeks) singleton infants and their mothers. METHODS Data on KMC, measured in duration of skin-to-skin contact/day during all days admitted to a neonatal unit, were collected using self-reports from the parents. Data on breastfeeding were obtained by telephone interviews. RESULTS VPT dyads that breastfed at 1, 2, 5, and 6 months had spent more time in KMC per day than those not breastfeeding at these times. A trend toward significance was noted at 3 and 4 months. In the PT dyads no statistically significant differences were found in the amount of KMC per day between those dyads that breastfed and those that did not. CONCLUSIONS This study shows the importance of KMC during hospital stay for breastfeeding duration in VPT dyads. Hence, KMC has empowering effects on the process of breastfeeding, especially in those dyads with the smallest and most vulnerable infants.

Pre- and Postnatal Transplantation of Fetal Mesenchymal Stem Cells in Osteogenesis Imperfecta: A Two-Center Experience

Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same‐donor MSCs. We have previously reported on prenatal transplantation for OI type III. This patient was retransplanted with 2.8 × 106 same‐donor MSCs per kilogram at 8 years of age, resulting in low‐level engraftment in bone and improved linear growth, mobility, and fracture incidence. An infant with an identical mutation who did not receive MSC therapy succumbed at 5 months despite postnatal bisphosphonate therapy. A second fetus with OI type IV was also transplanted with 30 × 106 hfMSCs per kilogram at 31 weeks of gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. The patient followed her normal growth velocity until 13 months of age, at which time longitudinal length plateaued. A postnatal infusion of 10 × 106 MSCs per kilogram from the same donor was performed at 19 months of age, resulting in resumption of her growth trajectory. Neither patient demonstrated alloreactivity toward the donor hfMSCs or manifested any evidence of toxicities after transplantation. Our findings suggest that prenatal transplantation of allogeneic hfMSCs in OI appears safe and is of likely clinical benefit and that retransplantation with same‐donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive and that further studies are required.