Prenatal Corticosteroid Treatment Research Articles

Evaluate the importance of giving antenatal corticosteroids in respiratory distress syndrome in preterm neonates

Respiratory distress syndrome (RDS) is one of the leading causes of early neonatal morbidity and mortality in late preterm infants (LPIs) worldwide.
 The aim: The study is intended to evaluate the importance of giving antenatal corticosteroids in decreasing respiratory distress syndrome in preterm neonates.
 Materials and methods: Prospective cohort study done in all preterms delivered in the hospital attached to those admitted in our neonatal intensive care unit during the study duration are taken as the source. All preterm babies are admitted to the neonatal intensive care unit.
 Results: The overall incidence of RDS in this study was 30 (15 %), among which 7 (7 %) were exposed to steroids, and 23 (23 %) were not exposed to steroids. Antenatal corticosteroids were significantly associated with reduced incidence of RDS in preterms (neonates born between 28–37 weeks of gestational age). The overall incidence of TTN (transient tachypnea) was found to be 46 (28 %) in this study, among which 14 (14 %) were exposed to steroids, and 32 (32 %) were not exposed to steroids. Antenatal corticosteroids were significantly associated with reduced incidence of TTN in preterms. Antenatal corticosteroids significantly reduce the need for supplemental oxygen, NICU admission, need for CPAP and mortality rate. The dose of antenatal corticosteroids was significantly associated with the incidence of RDS and TTN. 2 doses of steroids reduced RDS and TTN significantly compared to the single dose, which was just significantly associated. This study found no significance between RDS and TTN with gestational age, mode of delivery, birth weight and RDS among steroid-exposed babies.
 Conclusion: The use of antenatal corticosteroids should be promoted because they successfully lowered morbidity and mortality among premature newborns in the population studied. In order to optimise proper and timely prenatal corticosteroid treatment, this study underlines the necessity for quality improvement initiatives.

Association of Adherence to Surfactant Best Practice Uses With Clinical Outcomes Among Neonates in Sweden

While surfactant therapy for respiratory distress syndrome (RDS) in preterm infants has been evaluated in clinical trials, less is known about how surfactant is used outside such a framework. To evaluate registered use, off-label use, and omissions of surfactant treatment by gestational age (GA) and associations with outcomes, mainly among very preterm infants (GA <32 weeks). This population-based cohort study used registry data for 97 377 infants born in Sweden between 2009 and 2018. Infants did not have malformations and were admitted for neonatal care. Data analysis was conducted from June 2019 to June 2020. Timing and number of surfactant administrations, off-label use, and omission of use. Registered use was defined by drug label (1-3 administrations for RDS). Omissions were defined as surfactant not administered despite mechanical ventilation for RDS. In-hospital survival, pneumothorax, intraventricular hemorrhage grade 3 to 4, duration of mechanical ventilation, use of postnatal systemic corticosteroids for lung disease, treatment with supplemental oxygen at 28 days' postnatal age and at 36 weeks' postmenstrual age. Odds ratios (ORs) were calculated and adjusted for any prenatal corticosteroid treatment, cesarean delivery, GA, infant sex, Apgar score at 10 minutes, and birth weight z score of less than -2. In total, 7980 surfactant administrations were given to 5209 infants (2233 [42.9%] girls; 2976 [57.1%] boys): 629 (12.1%) born at full term, 691 (13.3%) at 32 to 36 weeks' GA, 1544 (29.6%) at 28 to 31 weeks' GA, and 2345 (45.0%) at less than 28 weeks' GA. Overall, 977 infants (18.8%) received off-label use. In 1364 of 3508 infants (38.9%) with GA of 22 to 31 weeks, the first administration of surfactant was given more than 2 hours after birth, and this was associated with higher odds of pneumothorax (adjusted OR [aOR], 2.59; 95% CI, 1.76-3.83), intraventricular hemorrhage grades 3 to 4 (aOR, 1.71; 95% CI, 1.23-2.39), receipt of postnatal corticosteroids (aOR, 1.57; 95% CI, 1.22-2.03), and longer duration of assisted ventilation (aOR, 1.34; 95% CI, 1.04-1.72) but also higher survival (aOR, 1.45; 95% CI, 1.10-1.91) than among infants treated within 2 hours of birth. In 146 infants (2.8%), the recommended maximum of 3 surfactant administrations was exceeded but without associated improvements in outcome. Omission of surfactant treatment occurred in 203 of 3551 infants (5.7%) who were receiving mechanical ventilation and was associated with lower survival (aOR, 0.49; 95% CI, 0.30-0.82). In full-term infants, 336 (53.4%) of those receiving surfactant had a diagnosis of meconium aspiration syndrome. Surfactant for meconium aspiration was not associated with improved neonatal outcomes. In this study, adherence to best practices and labels for surfactant use in newborn infants varied, with important clinical implications for neonatal outcomes.

Prevalencia de Hipertensión Arterial en una unidad de cuidados intensivos neonatales

La prevalencia de hipertensión arterial neonatal en las unidades de cuidados intensivos neonatales (UCIN) varía entre el 3 y el 9%, sin embargo, no existe información actualizada de Latinoamérica.Objetivo: Estimar la prevalencia de hipertensión arterial y evaluar su asociación con causas previamente relacionadas con esta condición.Pacientes y Método: Estudio transversal que incluyó a todos los niños internados en una UCIN durante un año, excluidos aquellos trasladados a cirugía cardiovascular. Se registraron variables maternas y neonatales, hipertensión arterial materna, vía de parto, edad gestacional, edad, sexo, peso de nacimiento, Apgar, antecedente de maduración pulmonar con corticoides y cateterismo de vasos umbilicales. Se consignó motivo de ingreso a UCIN, medicamentos y complicaciones durante la hospitalización. La tensión arterial se registró con oscilómetro automatizado considerando hipertensión arterial según tablas para edad gestacional. La prevalencia se expresó como porcentaje (intervalo de confianza 95%, IC95%). La estadística descriptiva se presenta como mediana (rango) o frecuencia de presentación (porcentajes) y se buscó asociación con el Test de Wilcoxon, Chi2 o Fisher según correspondiera (p &lt; 0,05).Resultados: Se reclutaron 169 pacientes (60% sexo masculino). Edad gestacional: 38 semanas (rango 26-42), 38% prematuros. Peso 3.000 g (rango 545-4.950), 32% bajo peso. Ocho pacientes presentaron hipertensión arterial (prevalencia 4,7%, IC95% 2,4-9). La presencia de hipertensión arterial se asoció con prematurez (p = 0,0003), bajo peso (p = 0,01), maduración pulmonar con corticoides (p = 0,002), cateterismo umbilical (p = 0,03), uso de ≥ 2 drogas nefrotóxicas (p = 0,02), tratamiento con cafeína (p = 0,0001), injuria renal aguda (p = 0,02) e hipertensión intracraneal (p = 0,04). Solo un paciente requirió medicación antihipertensiva y en todos los casos se normalizó durante el seguimiento.Conclusión: La prevalencia de hipertensión arterial neonatal fue de 4,7% y en todos los casos se presentó en niños prematuros con factores previamente reconocidos como asociados a esta condición.

Prevalence of Arterial Hypertension in a neonatal intensive care unit

The prevalence of neonatal hypertension in neonatal intensive care units (NICU) ranges between 3 and 9%. However, there is no current data on Latin America. To estimate the prevalence of neonatal hypertension and to assess its association with causes previously related to this condi tion. cross-sectional study. All patients admitted to the NICU during one year were included, excluding those transferred to the cardiovascular NICU. The following maternal and neonatal variables were registered: maternal arterial hypertension, type of delivery, gestational age, age, sex, birth weight, Apgar score, history of pulmonary maturation with corticosteroids, and umbilical vessel catheterization as well as the reason for admission to the NICU, medications, and complications during hospitalization. Blood pressure was measured with an automated oscillometric device, defining neonatal hypertension according to standards in gestational age. Prevalence was ex pressed as percentage (confidence interval 95%, CI95%). Descriptive data were reported as median (range) and frequency of presentation (percentage). Finally, we used the Wilcoxon, Chi2 o Fisher exact test to identify factors related to NH as applicable (p < 0.05). 169 patients were in cluded (60% males). Gestational age was 38 weeks (range 26-42 weeks), 38% were preterm. Birth weight was 3000 g (range 545-4950 g) and 32% presented low birth weight. Eight patients presented hypertension during hospitalization (4.7% prevalence, CI95% 2.4-9). The presence of hypertension was associated with prematurity (p = 0.0003), low birth weight (p = 0.01), prenatal corticosteroid treatment (p = 0.002), umbilical catheterization (p = 0.03), administration of ὅ 2 nephrotoxic drugs (p = 0.02), caffeine treatment (p = 0.0001), acute kidney injury (p = 0.02), and intracranial hyper tension (p = 0.04). Only one patient required antihypertensive pharmacologic treatment and in all cases, hypertension was resolved during follow-up. Prevalence of neonatal hypertension in our NICU was 4.7% and in all cases occurred in preterm newborns with previously recognized factors associated with this condition.

Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis.

BackgroundInfants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors.Methods and findingsTrials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach.Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference −0.12, 95%CI −0.18 to −0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2–5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes.ConclusionsIn this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg.

Fluorinated steroids do not improve outcome of isolated atrioventricular block

IntroductionCongenital atrioventricular block (CAVB) is a rare disorder with a significant morbidity and mortality. Consensus regarding the prescription and efficacy of prenatal corticosteroids is lacking. This nationwide study was initiated to evaluate the effects of prenatal treatment with corticosteroids on the outcome of CAVB in The Netherlands. MethodsAll fetuses identified with isolated congenital AVB-II° or AVB-III° in any of the eight academic fetal heart centers of The Netherlands between 2003 and 2013 were included and reviewed. ResultsFifty-six fetuses were included. Fourteen (25%) fetuses were treated with dexamethasone. We found no differences between the steroid-treated and untreated cases regarding in utero progression of the AVB (63% vs 67% respectively), survival to birth (86% vs 84%), pacemaker implantations (74% vs 58%) or long-term dilated cardiomyopathy (13% vs 17%). Steroid treated fetuses demonstrated more in utero growth restriction (38% vs 11%). ConclusionNo benefit from prenatal corticosteroid treatment was demonstrated for fetuses with isolated CAVB in this study. However, we found negative side effects. Our data provide no evidence to support the routine administration of corticosteroids for the treatment of fetal CAVB.

Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats.

Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required.

Repeat prenatal corticosteroid prior to preterm birth: a systematic review and individual participant data meta-analysis for the PRECISE study group (prenatal repeat corticosteroid international IPD study group: assessing the effects using the best level of evidence) - study protocol

BackgroundThe aim of this individual participant data (IPD) meta-analysis is to assess whether the effects of repeat prenatal corticosteroid treatment given to women at risk of preterm birth to benefit their babies are modified in a clinically meaningful way by factors related to the women or the trial protocol.Methods/DesignThe Prenatal Repeat Corticosteroid International IPD Study Group: assessing the effects using the best level of Evidence (PRECISE) Group will conduct an IPD meta-analysis. The PRECISE International Collaborative Group was formed in 2010 and data collection commenced in 2011. Eleven trials with up to 5,000 women and 6,000 infants are eligible for the PRECISE IPD meta-analysis. The primary study outcomes for the infants will be serious neonatal outcome (defined by the PRECISE International IPD Study Group as one of death (foetal, neonatal or infant); severe respiratory disease; severe intraventricular haemorrhage (grade 3 and 4); chronic lung disease; necrotising enterocolitis; serious retinopathy of prematurity; and cystic periventricular leukomalacia); use of respiratory support (defined as mechanical ventilation or continuous positive airways pressure or other respiratory support); and birth weight (Z-scores). For the children, the primary study outcomes will be death or any neurological disability (however defined by trialists at childhood follow up and may include developmental delay or intellectual impairment (developmental quotient or intelligence quotient more than one standard deviation below the mean), cerebral palsy (abnormality of tone with motor dysfunction), blindness (for example, corrected visual acuity worse than 6/60 in the better eye) or deafness (for example, hearing loss requiring amplification or worse)). For the women, the primary outcome will be maternal sepsis (defined as chorioamnionitis; pyrexia after trial entry requiring the use of antibiotics; puerperal sepsis; intrapartum fever requiring the use of antibiotics; or postnatal pyrexia).DiscussionData analyses are expected to commence in 2011 with results publicly available in 2012.

Effects of birth advancement in Chiari malformation in a surgical myelomeningocele model in rabbits

Background/Purpose In myelomeningocele (MMC), Chiari II malformation progresses during gestation because of the continuous loss of cerebrospinal fluid at the site of the defect. Our purpose was to assess the impact of birth advancement (BA) and prenatal corticosteroid treatment (PCT) on Chiari malformation in a surgical MMC model in rabbits. Methods A surgical MMC-like defect was created in 75 fetal rabbits. Animals were distributed into 4 groups depending on the treatment received: not treated and those undergoing BA + PCT, BA, or PCT. The degree of Chiari malformation in newborn rabbits was defined as the percentage of downward protrusion of the hindbrain between the end of the occipital bone and the beginning of the first vertebral arch. Results The degree of hindbrain herniation was 80% (8.15) in the not treated group, 36.8% (10.57) in BA + PCT, 41.8% (8.27) in BA, and 44.4% (8.32) in PCT. The BA + PCT, BA, and PCT groups showed less severe hindbrain herniation than not treated animals (mean decrease, 39.86%; SD, 10.57; P = .000). There were no significant differences between the BA + PCT, BA, and PCT groups ( P = .311). Conclusions Birth advancement and prenatal administration of corticosteroids decrease the severity of the hindbrain herniation component of Chiari II malformation in surgical MMC in fetal rabbits.

Repeat Prenatal Corticosteroid Doses Do Not Alter Neonatal Blood Pressure or Myocardial Thickness: Randomized, Controlled Trial

The goal was to determine whether repeat prenatal corticosteroid treatment alters blood pressure and myocardial wall thickness in neonates. A randomized, double-blind, placebo-controlled trial was performed in a tertiary perinatal center. Mothers with a singleton, twin, or triplet pregnancy, at a gestational age of <32 weeks, who had received initial treatment with corticosteroid > or =7 days earlier and who were considered to be at continued risk of preterm birth were assigned randomly to receive additional weekly betamethasone or placebo treatment. One hundred forty-five infants born to 120 women were studied. Blood pressure in the first 4 weeks after birth or until hospital discharge and interventricular septal thickness and left ventricular posterior wall thickness in diastole 48 to 72 hours after birth were measured. There were no differences in mean, systolic, or diastolic blood pressures between infants in the placebo and repeat steroid groups. Blood pressures of infants in both groups were similar to published normal values. There were no differences between groups in interventricular septal thickness or left ventricular posterior wall thickness in diastole. In comparison with published normal ranges, however, 24% of infants had interventricular septal thickness and 32% of infants had left ventricular posterior wall thickness of >95th percentile. Exposure to repeat prenatal corticosteroid treatment did not increase neonatal blood pressure or myocardial wall thickness in infants who remained at risk of very preterm birth > or =7 days after an initial course of corticosteroid treatment.

Urinary aquaporin-2 excretion during early human development

This study was undertaken to assess one of the determinants of kidney concentrating capacity, aquaporin-2 (AQP2), in order to understand the physiopathology of water balance in newborn babies. Urinary AQP2 excretion has been shown to be proportional to AQP2 level in the apical plasma membrane of the kidney collecting ducts and has been suggested as a marker of vasopressin (AVP) action. Urinary AQP2 excretion in the early postnatal period and at 3 weeks of age was measured in 123 neonates admitted during a 6-month period to the neonatal intensive care unit of the Children's Hospital of Toulouse, France. Clinical and biochemical data were collected for each child. During the first days after birth, higher urinary AQP2 was observed in boys than in girls (P=0.01) and positively correlated with urinary sodium/potassium (Na/K) ratio (r=0.33, P=0.01). When the babies had reached 3 weeks of age, urinary AQP2 was proportional to the gestational age at birth (r=0.33, P=0.0068) and daily weight gain (r=0.36, P=0.003). It did not correlate with urinary osmolality, which was overall very low in all babies. Urinary AQP2 was decreased in conditions of impaired renal function (r=-0.42, P=0.0005) and acidosis (P=0.03). Prenatal corticosteroid treatment had no significant impact on urinary AQP2 level. Our data show that urinary AQP2 correlates with the overall maturity of tubular function in human neonates. In babies at this early age, urinary AQP2 cannot serve as a direct marker of the renal action of AVP but reflects AQP2 expression level associated with different physiopathological conditions.

Prenatal Corticosteroids

After completing this article, readers should be able to: 1. Describe the standard of care for prenatal corticosteroids for women in preterm labor prior to 34 weeks’ gestation. 2. Describe the effects of prenatal corticosteroids on the fetus. 3. List the preferred corticosteroid for prenatal treatments. 4. Explain the recommendation regarding not using repetitive courses of prenatal corticosteroids. Prenatal glucocorticoids are standard of care for women at high risk of preterm delivery prior to 34 weeks’ gestation because randomized, controlled trials and extensive meta-analyses demonstrate decreased death and improved outcomes, primarily related to less respiratory distress syndrome (RDS) and a decreased incidence of intraventricular hemorrhages (IVH) (Fig. 1). (1) However, it is worth remembering that the benefits of prenatal corticosteroids initially were demonstrated in 1972, and most of the trials were completed before 1985. Most infants in the trials were delivered after 28 weeks’ gestation and in the presurfactant era, when mortality rates for infants whose birthweights were less than 1 kg were high and when obstetric management differed from current practice. Maternal corticosteroid therapy is validated practice, but care strategies proven to be effective may lose effectiveness as other aspects of care change and the target population most likely to benefit changes. This review asks a series of questions to frame the overriding question of how antenatal corticosteroids should be used in 2006. Figure 1. Meta-analysis of randomized controlled trials of prenatal corticosteroids. Adapted from Crowley. (1) The current recommendations come from the 1994 National Institutes of Health (NIH) Consensus Conference and were reinforced by a second NIH Consensus Conference in 2000. (2) The key points from the guidelines are: 1. The benefits of prenatal corticosteroids outweigh any risks that have been identified. The benefits include decreased death and decreased incidence of RDS and IVH. 2. All fetuses at 24 to 34 weeks’ gestation are candidates …

Neonatal complications following preterm birth

Improvements in neonatal intensive care during the last 20 years have increased the survival of the most immature newborns at 23 weeks from 0% to 65% at some centres, although rates vary widely among neonatal care centres. University of Utah, USA data show that each week in utero after week 23 raises survival by 6–9%, to 90% by 27–28 weeks and 95% by 33 weeks. Provision of care in specialised centres to provide high‐risk obstetric and neonatal intensive care, prenatal treatment with corticosteroids, postnatal treatment with surfactant and nitric oxide, and improvements in respirators and equipment to care for extremely immature infants all contribute to these changes. The increased rate of survival for extremely premature newborns has not been accompanied by an increased rate of severe intraventricular haemorrhage or neurological impairment, such as cerebral palsy. Regardless, intraventricular haemorrhage remains a significant problem, especially if associated with post‐haemorrhagic hydrocephalus, leading to long‐term neurological impairment and decreased survival. Necrotising enterocolitis (NEC) is more common in premature than in term newborns and is the most frequent cause of short bowel syndrome in infancy. Survival after surgery for NEC has improved during the last two decades, but complications of nutritional support produce many long‐term problems. Retinopathy of prematurity (ROP) remains a frequent cause of neurosensory impairment for extremely premature newborns. Laser photocoagulation for advanced ROP is more effective than cryotherapy for preventing retinal detachment and improving visual outcomes. Despite prenatal corticosteroid treatment and postnatal surfactant administration, many extremely premature newborns still develop bronchopulmonary dysplasia. Abnormal pulmonary function may persist into adulthood, but newer ventilators and management schemes appear to be reducing this long‐term morbidity. Many changes in neonatal care occur each year, but carefully controlled outcome studies are needed to evaluate the effectiveness of these newer styles of neonatal intensive care.

Neonatal complications following preterm birth

Improvements in neonatal intensive care during the last 20 years have increased the survival of the most immature newborns at 23 weeks from 0% to 65% at some centres, although rates vary widely among neonatal care centres. University of Utah, USA data show that each week in utero after week 23 raises survival by 6–9%, to 90% by 27–28 weeks and 95% by 33 weeks. Provision of care in specialised centres to provide high-risk obstetric and neonatal intensive care, prenatal treatment with corticosteroids, postnatal treatment with surfactant and nitric oxide, and improvements in respirators and equipment to care for extremely immature infants all contribute to these changes. The increased rate of survival for extremely premature newborns has not been accompanied by an increased rate of severe intraventricular haemorrhage or neurological impairment, such as cerebral palsy. Regardless, intraventricular haemorrhage remains a significant problem, especially if associated with post-haemorrhagic hydrocephalus, leading to long-term neurological impairment and decreased survival. Necrotising enterocolitis (NEC) is more common in premature than in term newborns and is the most frequent cause of short bowel syndrome in infancy. Survival after surgery for NEC has improved during the last two decades, but complications of nutritional support produce many long-term problems. Retinopathy of prematurity (ROP) remains a frequent cause of neurosensory impairment for extremely premature newborns. Laser photocoagulation for advanced ROP is more effective than cryotherapy for preventing retinal detachment and improving visual outcomes. Despite prenatal corticosteroid treatment and postnatal surfactant administration, many extremely premature newborns still develop bronchopulmonary dysplasia. Abnormal pulmonary function may persist into adulthood, but newer ventilators and management schemes appear to be reducing this long-term morbidity. Many changes in neonatal care occur each year, but carefully controlled outcome studies are needed to evaluate the effectiveness of these newer styles of neonatal intensive care.

Longitudinal Assessment of Pituitary-Thyroid Axis and Adrenal Function in Preterm Infants Raised by ‘Kangaroo Mother Care’

Objective: To assess whether complete kangaroo mother care (KMC), a skin-to-skin contact intervention, would affect longitudinal/developmental patterns of hormonal change. Method: An open randomized controlled trial was conducted in a large tertiary care hospital, comparing KMC and traditional care for newborn infants weighing less than 2,001 g. Eighty-seven healthy preterm (<37 weeks gestational age) infants from this study provided three blood-spot samples on filter paper: at randomization (postnatal age 1–5 days), 2 weeks later, and at calculated term (41 weeks gestational age). They met a number of additional inclusion criteria including discharge from the hospital within the first postnatal week. The levels of 17α-hydroxy-progesterone (17-OHP), thyroxine-stimulating hormone (TSH) and thyroxine (T₄) were assessed by radioimmunoassay. Birth weight (<1,800 or ≧1,800 g) and prenatal maternal corticosteroid treatment were taken into account in the analysis. Interventions: Complete KMC includes early discharge, positioning the infant on the parent’s chest in an upright position, 24 h/day in skin-to-skin contact, and breast-feeding. In the traditional care group, infants were discharged according to routine hospital practice. Results: Levels of 17-OHP and TSH decreased significantly from eligibility to calculated term while T₄ levels did not change significantly over time. Most importantly, overall, treatment (KMC) did not interact with the pattern of physiological change. Conclusions: Maturation of the pituitary-thyroid axis and adrenal function is apparently not compromised by KMC, at least in healthy preterm infants.

The effect in premature infants of prenatal corticosteroids on endogenous surfactant synthesis as measured with stable isotopes.

Most in vitro studies show that prenatal administration of corticosteroids stimulates the synthesis of surfactant phosphatidylcholine (PC), but studies in animals are controversial. Whether prenatal corticosteroids stimulate surfactant PC synthesis in humans has not been studied. We studied endogenous surfactant PC synthesis in relation to prenatal corticosteroid treatment in 27 preterm infants with respiratory distress syndrome. Infants received a 24-h infusion of the stable isotope [U-(13)C]glucose, starting approximately 5 h after birth. We measured (13)C-incorporation into palmitic acid in surfactant PC from serial tracheal aspirates and in plasma triglycerides and phospholipids by isotope-ratio mass spectrometry. Premature infants had received either zero (n = 11), one (n = 4), or two doses (n = 12) of prenatal betamethasone (12 mg intramuscularly). The fractional synthesis rate (FSR) of surfactant PC from glucose was 1.7 +/- 0.3%/d without corticosteroid treatment, 2.9 +/- 1.4%/d with one dose of prenatal corticosteroid, and 5.8 +/- 1.3%/d after two doses of prenatal corticosteroid. Using multiple regression analysis, we found that the FSR of surfactant PC increased by 40% (confidence interval: 7 to 82%/d, p < 0.02) per dose of corticosteroid and doubled after two doses of corticosteroid. The (13)C-enrichment of plasma triglycerides and phospholipids was not increased by corticosteroid. These data show for the first time that prenatal corticosteroid treatment stimulates surfactant synthesis in the preterm infant.

Pharmacologic Enhancement of Fetal Lung Maturation

During the 22 years since the first clinical reports of prenatal corticosteroid treatment to enhance fetal lung maturation, this treatment has been studied in thousands of preterm newborns. These studies demonstrated that prenatal steroid treatment reduces RDS among premature newborns at 26 to 33 weeks gestation. The potent fluorinated steroids, betamethasone and dexamethasone, are more effective in accelerating lung maturation than are the less potent corticosteroids, cortisol, cortisone, and prednisone. No immediate or long-term adverse effects have been demonstrated for the newborn or fetus. With PROM, mothers may have an increased risk of endometritis without a clear increase in overall frequency of infection, at the same time steroids significantly decrease the frequency of RDS in the newborns. During these 22 years of evaluation and application of prenatal steroid treatment to reduce RDS, the survival of the very low birth weight (< 1501 g) newborn has increased dramatically. Major morbidities, however, impact significantly on the quality of life for these survivors with birth weights as low as 500 g and gestations as short as 22 to 23 weeks. Prenatal steroid treatment reduces the frequency of PDA, intraventricular hemorrhage, NEC, and bronchopulmonary dysplasia. These are the most important and frequent morbidities that reduce the quality of life for the very low birth weight survivor. Without clearly demonstrable and major adverse effects for the mother or child from corticosteroid treatment, the cost/benefit ratio strongly and clearly favors treatment when preterm delivery is anticipated. Hopefully, obstetricians will use corticosteroids more often in the management of preterm labor because this treatment may markedly improve the quality of survival for many premature newborns.

Prenatal diagnosis and corticosteroid treatment of diffuse neonatal hemangiomatosis: case report.

Prenatal diagnosis and corticosteroid treatment of diffuse neonatal hemangiomatosis: case report.

Corticosteroids, Thyrotropin-Releasing Hormone, and Antioxidant Enzymes in Preterm Lamb Lungs

Forty-three twin lamb fetuses of 121 +/- 1 d gestation were catheterized and received i.v. saline (n = 8), 0.75 mg/kg/h cortisol for 60 h (n = 15), 5 micrograms/kg thyrotropin-releasing hormone (TRH) every 12 h for five doses (n = 9), or cortisol and TRH (n = 11) before delivery at 128 +/- 1 d. After delivery, the lambs were randomized for natural sheep surfactant treatment or sham treatment, ventilated for 75 min, and killed. Superoxide dismutase, catalase, and glutathione peroxidase activities were measured in fetal lung tissue. Superoxide dismutase and catalase activities were increased in both the corticosteroid (p less than 0.001) and the corticosteroid with TRH (p less than 0.01) groups. Glutathione peroxidase activity was higher after prenatal corticosteroid treatment, but statistical significance was not reached (p = 0.06). Although prenatal exposure to corticosteroids increased superoxide dismutase, catalase, and glutathione peroxidase activities, TRH alone or TRH added to corticosteroids provided no additional benefit. Lambs treated with surfactant had higher lung catalase activities than lambs that did not receive surfactant, probably secondary to the presence of catalase activity in the surfactant preparation. Increased pulmonary antioxidant enzyme activity may be an additional feature of the overall beneficial effect of corticosteroids on fetal lung development.