The role of oxygen in the development and treatment of bronchopulmonary dysplasia.

Oxygen (O2) is crucial for both the development and treatment of one of the most important consequences of prematurity: bronchopulmonary dysplasia (BPD). In fetal life, the hypoxic environment is important for alveolar development and maturation. After birth, O2 becomes a double-edged sword. While O2 is needed to prevent hypoxia, it also causes oxidative stress leading to a plethora of morbidities, including retinopathy and BPD. The advent of continuous O2 monitoring with pulse oximeters has allowed clinicians to recognize the narrow therapeutic margins of oxygenation for the preterm infant, but more knowledge is needed to understand what these ranges are at different stages of the preterm infant's life, including at birth, in the neonatal intensive care unit and after hospital discharge. Future research, especially in innovative technologies such as automated O2 control and remote oximetry, will improve the understanding and treatment of the O2 needs of infants with BPD.

Retrospective study found that outpatient care for infants exposed to drugs during pregnancy was sustainable and safe.

AIM: We determined the safety, feasibility and sustainability of an outpatient model of care for infants exposed to intra-uterine drugs. METHODS: This was a retrospective chart review of 774 drug-exposed infants born between 1998 and 2016 at the Royal Hospital for Women, Sydney, Australia. RESULTS: Most (86%) of the mothers used multiple drugs, including opioids (58%). More than three-quarters (78%) of the infants were born full term at a mean gestation of 38 weeks and hospitalised for a median of seven days. This rose to 14 days if they were medicated for neonatal abstinence syndrome (NAS). Most of the NAS patients (83%) were discharged on medication, namely morphine, and the median duration of NAS treatment was 76 (interquartile range 35-120). Three medication errors occurred: two extra doses of phenobarbitone and one infant weaned off morphine faster than prescribed. No infants were rehospitalised for NAS. Four died from sudden infant death syndrome at 2.2-5.8 months after discharge and one drowned at 15 months. None were medicated at the time of death. CONCLUSION: Outpatient care for drug-exposed infants was sustainable and had low complication rates, even for those with NAS. The optimum duration of follow-up and impact on hospital costs should be examined.

A review of international clinical practice guidelines for the use of oxygen in the delivery room resuscitation of preterm infants.

AIM: To collate and assess international clinical practice guidelines (CPG) to determine current recommendations guiding oxygen management for respiratory stabilisation of preterm infants at delivery. METHODS: A search of public databases using the terms 'clinical practice guidelines', 'preterm', 'oxygen' and 'resuscitation' was made and complemented by direct query to consensus groups, resuscitation expert committees and clinicians. Data were extracted to include the three criteria for assessment: country of origin, gestation and initial FiO2 and target SpO2 for the first 10 minutes of life. RESULTS: A total of 45 CPGs were identified: 36 provided gestation specific recommendations (<28 to <37 weeks) while eight distinguished only between 'preterm' and 'term'. The most frequently recommended initial FiO2 were between 0.21 and 0.3 (n = 17). Most countries suggested altering FiO2 to meet SpO2 targets recommended by expert committees, However, specific five-minute SpO2 targets differed by up to 20% (70-90%) between guidelines. Five countries did not specify SpO2 targets. CONCLUSION: CPG recommendations for delivery room oxygen management of preterm infants vary greatly, particularly in regard to gestational ages, initial FiO2 and SpO2 targets and most acknowledge the lack of evidence behind these recommendations. Sufficiently large and well-designed randomised studies are needed to inform on this important practice.

Acupuncture in the neonatal intensive care unit-using ancient medicine to help today's babies: a review.

Acupuncture has been used for thousands of years in Eastern medicine for a variety of conditions and illnesses, including pain. Neonatal intensive care, on the other hand, is a relatively new branch of medicine that has emerged as the pivotal influence in increasing survival of critically ill newborn infants only within the last 50 years. Unfortunately, pain is an inevitable part of treatment in a neonatal intensive care unit (NICU). The control and prevention of pain remains a major issue for clinicians despite recognition and understanding of the myriad of short- and long-term problems that are associated with both pain and its treatment within the NICU environment. In this review, we examine the potential role of acupuncture to decrease and treat pain in babies requiring neonatal intensive care and discuss future therapeutic and research implications for the use of this ancient therapy within the modern environment of the NICU.

Percutaneous Endoscopic Gastrostomy Tube in a Syncardia™ Total Artificial Heart.

As a bridge to transplant, the Syncardia™ total artificial heart (TAH) is an option for patients who are not candidates for left ventricular assist devices (LVAD) due to right ventricular failure. The need for nutritional support in these patients is essential for a favorable outcome. Low body mass indexes and albumin levels have been associated with increased morbidity and mortality in cardiac surgery patients [Alverdy 2003]. It is not uncommon for postoperative patients to have difficulty in consuming enough calories after surgery, which is further complicated by a hypermetabolic demand due to surgical stress. Enteral nutrition has typically been favored for gut mucosal integrity and bacterial flora [Alverdy 2003] [Engleman 1999]. We describe the need for prolonged enteral nutritional support in a TAH patient that was accomplished with a percutaneous endoscopic gastrostomy (PEG) tube.

High burden of RSV hospitalization in very young children: a data linkage study.

Linked administrative population data were used to estimate the burden of childhood respiratory syncytial virus (RSV) hospitalization in an Australian cohort aged <5 years. RSV-coded hospitalizations data were extracted for all children aged <5 years born in New South Wales (NSW), Australia between 2001 and 2010. Incidence was calculated as the total number of new episodes of RSV hospitalization divided by the child-years at risk. Mean cost per episode of RSV hospitalization was estimated using public hospital cost weights. The cohort comprised of 870 314 children. The population-based incidence/1000 child-years of RSV hospitalization for children aged <5 years was 4·9 with a rate of 25·6 in children aged <3 months. The incidence of RSV hospitalization (per 1000 child-years) was 11·0 for Indigenous children, 81·5 for children with bronchopulmonary dysplasia (BPD), 10·2 for preterm children with gestational age (GA) 32-36 weeks, 27·0 for children with GA 28-31 weeks, 39·0 for children with GA <28 weeks and 6·7 for term children with low birthweight. RSV hospitalization was associated with an average annual cost of more than AUD 9 million in NSW. RSV was associated with a substantial burden of childhood hospitalization specifically in children aged <3 months and in Indigenous children and children born preterm or with BPD.

Resuscitating preterm infants with 100% oxygen is associated with higher oxidative stress than room air.

AIM: The starting fraction of inspired oxygen for preterm resuscitation is a matter of debate, and the use of room air in full-term asphyxiated infants reduces oxidative stress. This study compared oxidative stress in preterm infants randomised for resuscitation with either 100% oxygen or room air titrated to internationally recommended levels of preductal oxygen saturations. METHODS: Blood was collected at birth, two and 12 hours of age from 119 infants <32 weeks of gestation randomised to resuscitation with either 100% oxygen (n = 60) or room air (n = 59). Oxidative stress markers, including advanced oxidative protein products (AOPP) and isoprostanes (IsoP), were measured with high-performance liquid chromatography and mass spectrometry. RESULTS: Significantly higher levels of AOPP were found at 12 hours in the 100% oxygen group (p < 0.05). Increases between two- and 12-hour AOPP (p = 0.004) and IsoP (p = 0.032) concentrations were significantly higher in the 100% oxygen group. CONCLUSION: Initial resuscitation with room air versus 100% oxygen was associated with lower protein oxidation at 12 hour and a lower magnitude of increase in AOPP and IsoP levels between two and 12 hours of life. Correlations with clinical outcomes will be vital to optimise the use of oxygen in preterm resuscitation.

Do maternal opioids reduce neonatal regional brain volumes? A pilot study.

OBJECTIVE: A substantial number of children exposed to gestational opioids have neurodevelopmental, behavioral and cognitive problems. Opioids are not neuroteratogens but whether they affect the developing brain in more subtle ways (for example, volume loss) is unclear. We aimed to determine the feasibility of using magnetic resonance imaging (MRI) to assess volumetric changes in healthy opioid-exposed infants. STUDY DESIGN: Observational pilot cohort study conducted in two maternity hospitals in New South Wales, Australia. Maternal history and neonatal urine and meconium screens were obtained to confirm drug exposure. Volumetric analysis of MRI scans was performed with the ITK-snap program. RESULT: Scans for 16 infants (mean (s.d.) gestational age: 40.9 (1.5) weeks, birth weight: 3022.5 (476.6) g, head circumference (HC): 33.7 (1.5 cm)) were analyzed. Six (37.5%) infants had HC <25th percentile. Fourteen mothers used methadone, four used buprenorphine and 11 used more than one opioid (including heroin, seven). All scans were structurally normal whole brain volumes (357.4 (63.8)) and basal ganglia (14.5 (3.5)) ml were significantly smaller than population means (425.4 (4.8), 17.1 (4.4) ml, respectively) but lateral ventricular volumes (3.5 (1.8) ml) were larger than population values (2.1(1.5)) ml. CONCLUSION: Our pilot study suggests that brain volumes of opioid-exposed babies may be smaller than population means and that specific regions, for example, basal ganglia, that are involved in neurotransmission, may be particularly affected. Larger studies including correlation with neurodevelopmental outcomes are warranted to substantiate this finding.

Cannabis, the pregnant woman and her child: weeding out the myths.

To review and summarise the literature reporting on cannabis use within western communities with specific reference to patterns of use, the pharmacology of its major psychoactive compounds, including placental and fetal transfer, and the impact of maternal cannabis use on pregnancy, the newborn infant and the developing child. Review of published articles, governmental guidelines and data and book chapters. Although cannabis is one of the most widely used illegal drugs, there is limited data about the prevalence of cannabis use in pregnant women, and it is likely that reported rates of exposure are significantly underestimated. With much of the available literature focusing on the impact of other illicit drugs such as opioids and stimulants, the effects of cannabis use in pregnancy on the developing fetus remain uncertain. Current evidence indicates that cannabis use both during pregnancy and lactation, may adversely affect neurodevelopment, especially during periods of critical brain growth both in the developing fetal brain and during adolescent maturation, with impacts on neuropsychiatric, behavioural and executive functioning. These reported effects may influence future adult productivity and lifetime outcomes. Despite the widespread use of cannabis by young women, there is limited information available about the impact perinatal cannabis use on the developing fetus and child, particularly the effects of cannabis use while breast feeding. Women who are using cannabis while pregnant and breast feeding should be advised of what is known about the potential adverse effects on fetal growth and development and encouraged to either stop using or decrease their use. Long-term follow-up of exposed children is crucial as neurocognitive and behavioural problems may benefit from early intervention aimed to reduce future problems such as delinquency, depression and substance use.

Molecular characterization of bacterial colonization in the preterm and term infant's intestine.

OBJECTIVE: To further define patterns of colonising intestinal microflora in newborn infants utilising molecular methods. METHODS: Ten term and 5 preterm (<32 wk) infants born at the Royal Hospital for Women, Sydney, Australia were enrolled in the present study and followed for 6 mo post partum. Serial stools were collected, DNA was extracted and subjected to PCR-Denaturing Gradient Gel Electrophoresis using a range of primers and sequencing. The effect of gestational length, feeding and delivery method was compared to the pattern of bacterial acquisition. RESULTS: Intestinal bacterial diversity was lower in preterm compared with term infants. For term infants, bacterial DNA detection rates were not associated with feeding or delivery method, although Enterobacteria and Clostridia were commonly identified. The detection rate of Bifidobacteria was lower in preterm infants than term infants. Potential pathogens were detected in preterm infant samples. CONCLUSIONS: Preterm infants frequently have aberrant bacterial colonization of the intestine. Further research is now required to determine if this may contribute to adverse health outcomes.

Amphetamines, the pregnant woman and her children: a review.

The objective of this study is to review and summarize available evidence regarding the impact of amphetamines on pregnancy, the newborn infant and the child. Amphetamines are neurostimulants and neurotoxins that are some of the most widely abused illicit drugs in the world. Users are at high risk of psychiatric co-morbidities, and evidence suggests that perinatal amphetamine exposure is associated with poor pregnancy outcomes, but data is confounded by other adverse factors associated with drug-dependency. Data sources are Government data, published articles, conference abstracts and book chapters. The global incidence of perinatal amphetamine exposure is most likely severely underestimated but acknowledged to be increasing rapidly, whereas exposure to other drugs, for example, heroin, is decreasing. Mothers known to be using amphetamines are at high risk of psychiatric co-morbidity and poorer obstetric outcomes, but their infants may escape detection, because the signs of withdrawal are usually less pronounced than opiate-exposed infants. There is little evidence of amphetamine-induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce and difficult to extricate from the influence of other factors associated with children living in households where one or more parent uses drugs in terms of poverty and neglect. Perinatal amphetamine-exposure is an increasing worldwide concern, but robust research, especially for childhood outcomes, remains scarce. We suggest that exposed children may be at risk of ongoing developmental and behavioral impediment, and recommend that efforts be made to improve early detection of perinatal exposure and to increase provision of early-intervention services for affected children and their families.

Early postnatal surge of serum Clara cell secretory protein in newborn infants.

BACKGROUND: Clara cell secretory protein (CCSP) is an anti-inflammatory mediator, but its role in neonatal lung adaptation and diseases is uncertain. OBJECTIVE: To characterize postnatal changes in serum CCSP in relation to gestation, respiratory disease (RDS) and bronchopulmonary dysplasia (BPD) in comparison with other anti-inflammatory cytokines (IL-4, -10 and -13). METHODS: Blood was collected from 76 infants (26 of 23-29 weeks' gestation, 33 of 30-36 weeks' gestation and 17 term infants) at birth (preterm cord blood); on admission; at 12, 24 and 48 h; and on days 3-4 and 7 of life. CCSP was assayed by ELISA and cytokines by Bio-Plex. RESULTS: Median serum CCSP in extremely and moderately preterm infants rose from a baseline of 13.6 and 15.9 to 33.4 ng/ml (p = 0.04) and 59.8 ng/ml (p = 0.03) at 12 h of age, respectively. CCSP levels were highest in term infants (80.7 ng/ml at 12 h). CCSP then decreased to 22.5 ng/ml on days 3-4 (p = 0.001). CCSP of 37 RDS infants fell to a lower baseline on days 4 and 7 than that of the 22 non-RDS preterms. The 8 infants who developed BPD had persistently low serum CCSP (12.7 ng/ml at 12 h). In contrast, early postnatal changes were not seen in IL-4, -10 and -13 levels, but low IL-10 and -13 levels were found on day 7 in BPD infants. CONCLUSIONS: Serum CCSP levels were characterized by an early postnatal surge. This apparent gestation-influenced surge may represent an initiation of a protective cascade against postnatal lung injury during extrauterine adaptation.

Short-term outcomes of mothers and infants exposed to antenatal amphetamines.

AIM: To determine the short-term outcomes of newborn infants and mothers exposed to antenatal amphetamines in the state of New South Wales and the Australian Capital Territory during 2004. METHODS: Amphetamine exposure was determined retrospectively using ICD-10 AM morbidity code searches of hospital medical records and from records of local drug and alcohol services. Records were reviewed on site. All public hospitals (n = 101) with obstetric services were included. RESULTS: Amphetamines were used by 200 (22.9%) of the 871 identified drug-using mothers. Most women (182, 91%) injected amphetamines intravenously. Compared with the other 669 drug users, amphetamine-using mothers were significantly more likely to use multiple classes of drugs (45.0% vs 7.8%), be subject to domestic violence (32.1% vs 17.5%), be homeless (14.8% vs 4.9%) and be involved with correctional services (19.8% vs 9.7%). The incidence of comorbid psychiatric illnesses were significantly higher (57.4% vs 41.7%) and their infants were more likely to be preterm (29.5% vs 20.4%), notified as children at risk (67.0% vs 32.8%), fostered before hospital discharge (14.5% vs 5.5%) and less likely to be breastfed (27.0% vs 41.6%). CONCLUSIONS: Amphetamine-exposed mothers and infants in public hospitals of NSW and the ACT are at significantly higher risk of adverse social and perinatal outcomes even when compared with mothers and infants exposed to other drugs of dependency. Increased vigilance for amphetamine exposure is recommended due to a high prevalence of use, especially in Australia, as a recreational drug.

Does rural or urban residence make a difference to neonatal outcome in premature birth? A regional study in Australia.

BACKGROUND: Patients living in rural areas may be at a disadvantage in accessing tertiary health care. AIM: To test the hypothesis that very premature infants born to mothers residing in rural areas have poorer outcomes than those residing in urban areas in the state of New South Wales (NSW) and the Australian Capital Territory (ACT) despite a coordinated referral and transport system. METHODS: "Rural" or "urban" status was based on the location of maternal residence. Perinatal characteristics, major morbidity and case mix adjusted mortality were compared between 1879 rural and 6775 urban infants <32 weeks gestational age, born in 1992-2002 and admitted to all 10 neonatal intensive care units in NSW and ACT. RESULTS: Rural mothers were more likely to be teenaged, indigenous, and to have had a previous premature birth, prolonged ruptured membrane, and antenatal corticosteroid. Urban mothers were more likely to have had assisted conception and a caesarean section. More urban (93% v 83%) infants were born in a tertiary obstetric hospital. Infants of rural residence had a higher mortality (adjusted odds ratio (OR) 1.26, 95% confidence interval (CI) 1.07 to 1.48, p = 0.005). This trend was consistently seen in all subgroups and significantly for the tertiary hospital born population and the 30-31 weeks gestation subgroup. Regional birth data in this gestational age range also showed a higher stillbirth rate among rural infants (OR 1.20, 95% CI 1.09 to 1.32, p<0.001). CONCLUSIONS: Premature births from rural mothers have a higher risk of stillbirth and mortality in neonatal intensive care than urban infants.

Pulmonary haemorrhage and cardiac dysfunction in a neonate with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

UNLABELLED: We report on a favourable case of MCAD deficiency (homozygous 985A > G) that presented as lethargy, poor feeding, pulmonary haemorrhage and cardiac arrest without hypoglycaemia. The cessation of intralipid and the commencement of carnitine supplementation were associated with a rapid clinical improvement. CONCLUSION: Mild carnitine depletion and secondary impairment of long-chain fatty acid metabolism may have contributed to post-asphyxial myocardial dysfunction and ventricular arrhythmias. Metabolic disorders must be kept in mind as a differential diagnosis in acutely ill infants, but it must also be emphasized that carnitine therapy is not uniformly effective in all MCAD patients.

Octreotide in the treatment of congenital chylothorax.

Congenital chylothorax is the accumulation of lymphatic fluid within the pleural space. Cases unresponsive to conservative management usually require surgery. Octreotide has been used successfully to treat post-traumatic chylothoraces in the paediatric and adult population. Its exact mode of action is uncertain but it is believed to reduce lymphatic drainage by a direct action on splanchnic lymph flow. We report a case of congenital chylothorax where surgery was avoided with the compassionate trial of the somatostatin analogue, octreotide. Treatment was associated with prompt respiratory improvement prior to cessation of pleural drainage. Further studies are required to ascertain its true value in congenital chylothorax.

Attitudes of Level II obstetricians towards the care of the extremely premature infant: a national survey.

OBJECTIVE: To explore the opinions of non-tertiary obstetricians towards the care and outcome of extremely premature infants. METHODS: A structured questionnaire was mailed nationally to 232 obstetricians affiliated to maternity facilities with Level II nurseries. RESULTS: The overall response rate was 75% (n = 174) after two mailings. This included 14 obstetricians who declined to participate. The median birthweight and gestation for active resuscitation was 500 g (350-800) and 24 weeks (22-26), respectively. Factors influencing decision to transfer were: better outcomes for infants born at perinatal centres (74%), paediatric advice (10%), personal beliefs (5%), parental wishes (4%), hospital policy (3%), legal repercussions (2.5%) and past history of infertility (2%). Obstetricians in Victoria and Western Australia (WA) would transfer at 22 weeks whilst the median gestation for transfer in other states was 24 weeks (P = 0.001). Most respondents underestimated intact and infant survival rates but WA and Victorian obstetricians were less pessimistic. CONCLUSIONS: Most obstetricians in non-tertiary facilities who responded to our survey considered 500 g and 24 weeks to be the median birthweight and gestation for active resuscitation. This is similar to recent surveys of neonatologists and obstetricians in perinatal centres. There is significant underestimation of intact and infant survival at the extremes of prematurity when compared to available Australian data. Differences towards antenatal transfer between States may represent influences of local perinatal centres.

Strabismus in infants of opiate-dependent mothers.

AIM: At a follow-up clinic for infants of opiate-dependent mothers it was noted that more infants than expected developed strabismus. This study aimed to assess the prevalence of strabismus and the need for active strabismus surveillance in this population. METHODS: Consecutive infants of opiate-dependent mothers born over an 18 mo period were recalled for ophthalmological assessment by an ophthalmologist and orthoptist. Those unable to attend were surveyed by telephone using a questionnaire. RESULTS: 49 (69%) of the 71 eligible infants were recalled at a mean age of 21 mo (range 6-39); 29 had a full ophthalmological examination and the remaining 20 completed the questionnaire only. Seven (14%) of the 49 recalled infants had strabismus on examination; 4 needed glasses or patching. A further seven (14%) had a history of intermittent strabismus but declined formal examination. Another child had significant hypermetropia without strabismus. The mean age at which strabismus was observed was 8.3 mo (range birth to 19 mo). The presence of strabismus was not significantly influenced by conditions at birth, maternal drug doses, family history or need for or duration of abstinence treatment. CONCLUSION: The rate of strabismus in infants of opiate-dependent mothers was at least 10 times that in the general population. As attendance at follow-up is often poor, paediatricians should be aware of the association to encourage opportunistic assessment and ophthalmological surveillance of this population.