Epidemiology and Outcomes of Neonatal Sepsis: Experience from a Tertiary Australian NICU.

INTRODUCTION: Neonatal sepsis is associated with significant mortality and morbidity. Low-middle-income countries are disproportionately affected, but late-onset sepsis (LOS) still occurs in up to 20% of infants <28 weeks in high-income countries. Understanding site-specific data is vital to guide management. METHODS: A retrospective cohort study was conducted at King Edward Memorial Hospital (KEMH), Perth. Infants admitted between January 2012 and June 2022 were included. Data were extracted from routine electronic databases. Incidence and aetiology of sepsis were determined and the association of sepsis with neonatal outcomes analysed. RESULTS: During the study period, 23,395 newborns were admitted with a median gestation of 37 weeks and birth weight of 2,800 g. There were 370 sepsis episodes in 350 infants; 102 were early-onset sepsis (EOS) (1.6 per 1,000 live births), predominantly Streptococcus agalactiae (35, 34.3%) and Escherichia coli (27, 26.5%); 268 were LOS (0.9 per 1,000 inpatient days), predominantly coagulase-negative staphylococci (CONS) (156, 57.6%) and E. coli (30, 11.1%). The incidence of LOS declined from 2012 to 2022 (p = 0.002). Infants with EOS had increased brain injury (25.7% vs. 4.1%; p = 0.002) and mortality (18.8% vs. 1.6%; p < 0.001). Those with LOS had increased hospital stay (median 95 vs. 15 days; p < 0.001), mortality (15.3% vs. 1.6%; p = 0.018), necrotising enterocolitis (NEC) (7.4% vs. 0.5%; p < 0.001), and chronic lung disease (CLD) (58.1% vs. 5.9%; p = 0.005). Infants <28 weeks with sepsis were at increased risk of neurodevelopmental impairment compared to those without infection (43.2% vs. 30.9%, p = 0.027). CONCLUSIONS: While we observed a reduction in LOS incidence, sepsis remains associated with higher mortality, and in survivors with longer hospital stay and increased risk of brain injury, NEC, CLD, and neurodevelopmental impairment.

Neonatal Staphylococcus Aureus Sepsis: a 20-year Western Australian experience.

OBJECTIVES: The purpose of this study was to characterise neonatal Staphylococcus aureus (SA) sepsis in Western Australia (WA) between 2001 and 2020 at the sole tertiary neonatal intensive care unit (NICU), examine risk factors for sepsis in the cohort, and compare short- and long-term outcomes to control infants without any sepsis. METHODS: Retrospective cohort study at the Neonatal Directorate at King Edward Memorial Hospital (KEMH) and Perth Children's Hospital, using electronic databases and patient medical records. RESULTS: The overall incidence of SA sepsis was 0.10 per 1000 live births (62/614207). From 2001 to 2010 the incidence was 0.13/1000 live births, reducing to 0.07/1000 live births from 2011 to 2020. SA was most frequently isolated from endotracheal aspirates, and infants with SA sepsis had longer median duration of ventilatory support than those without any sepsis (31 days vs 18 days respectively, p < 0.001). In our cohort, SA sepsis was associated with worse neurodevelopmental outcomes compared to infants without any sepsis. CONCLUSIONS: The incidence of neonatal SA sepsis has reduced over the last 20 years, suggesting potential effectiveness of the preventative interventions implemented. Endotracheal tube (ETT) colonisation and prolonged ventilation may be under-recognised as potential sources of SA infection. Our study suggests SA sepsis may negatively impact neurodevelopmental outcomes.

Effect of cumulative dexamethasone dose in preterm infants on neurodevelopmental and growth outcomes: a Western Australia experience.

OBJECTIVE: Comparing the long-term neurodevelopmental and growth outcomes of lower and higher cumulative dexamethasone exposure in preterm infants ventilated for a minimum cumulative duration of 7 days. DESIGN: A retrospective cohort medical chart review of infants born in Western Australia <29 weeks' gestation between January 2007 and May 2016 who were mechanically ventilated >7 days. INTERVENTION: No dexamethasone (controls) or a total cumulative dexamethasone dose of <2 mg/kg (lower) and ≥2 mg/kg (higher). MAIN OUTCOME MEASURES: Long-term disability at 2 and 5 years and growth measurement outcomes at 2 years of age. RESULTS: Dexamethasone was given to 104 infants (66 with cumulative dose <2 mg/kg; 38 with cumulative dose ≥2 mg/kg), and 324 infants were controls. There was no difference in odds of long-term disability in infants with any dexamethasone exposure compared with controls (aOR: 0.90, 95% CI 0.34 to 2.02, p=0.784). No difference in long-term disability was found between the lower and higher groups (p=0.494). The prevalence of cerebral palsy (Gross Motor Functional Classification System level ≥2) between the control, lower and high-dose groups did not differ significantly (5.8% vs 4.0% vs 0%). The higher dose group had lower mean weight z-score (mean effect: -0.83, 95% CI: -1.54 to -0.01, p=0.023), height z-score (mean effect: -0.63, 95% CI: -12.5 to -0.01, p=0.048) and head circumference z-score (mean effect: -0.65, 95% CI: -1.25 to -0.05, p=0.035) compared with controls. CONCLUSIONS: In our cohort, dexamethasone use was not associated with increased odds of long-term disability. Dexamethasone use was associated with lower growth measurements compared with controls.

Neonatal adaptation following intrauterine antidepressant exposure: assessment, drug assay levels, and infant development outcomes.

BackgroundAlthough a meta-analysis has confirmed the association between antidepressant exposure in utero and subsequent poor neonatal adaptation, few identified studies included drug levels or standardized measures and only two studies followed up children who developed symptoms beyond infancy.MethodsThe study draws on the Mercy Pregnancy and Emotional Wellbeing Study and reports on 42 women/infant pairs at delivery. In all, 31 women continued to take antidepressants until delivery and 11 ceased earlier in pregnancy. Poor neonatal adaptation was assessed twice daily for up to 6 days by using the Neonatal Abstinence Scoring System (NASS). Drug levels were analyzed in umbilical cord blood and maternal blood obtained at delivery.ResultsIn total, 76% (32 of 42) of neonates exposed to antidepressants had symptoms observed on the NASS. These symptoms occurred up to 5 days postpartum with 25% having symptoms that persisted for more than 3 days. The most frequent symptoms were correlated most closely to antidepressant drug levels. Elevated NASS scores were found to be associated with poorer fine motor development at 6 months of age.ConclusionsPoor neonatal adaptation may be more common than previously recognized. The NASS was observed to be an effective assessment and monitoring measure. Research following symptomatic infants beyond the neonatal period is required.

Cost effectiveness of universal umbilical cord blood gas and lactate analysis in a tertiary level maternity unit.

OBJECTIVE: There is an increasing body of literature supporting universal umbilical cord blood gas analysis (UCBGA) into all maternity units. A significant impediment to UCBGA's introduction is the perceived expense of the introduction and associated ongoing costs. Consequently, this study set out to conduct the first cost-effectiveness analysis of introducing universal UCBGA. METHODS: Analysis was based on 42,100 consecutive deliveries ≥23 weeks of gestation at a single tertiary obstetric unit. Within 4 years of UCBGA's introduction there was a 45% reduction in term special care nursery (SCN) admissions >2499 g. Incurred costs included initial and ongoing costs associated with universal UCBGA. Averted costs were based on local diagnosis-related grouping costs for reduction in term SCN admissions. Incremental cost-effectiveness ratio (ICER) and sensitivity analysis results were reported. RESULTS: Under the base-case scenario, the adoption of universal UCBGA was less costly and more effective than selective UCBGA over 4 years and resulted in saving of AU$641,532 while adverting 376 SCN admissions. Sensitivity analysis showed that UCBGA was cost-effective in 51.8%, 83.3%, 99.6% and 100% of simulations in years 1, 2, 3 and 4. These conclusions were not sensitive to wide, clinically possible variations in parameter values for neonatal intensive care unit and SCN admissions, magnitude of averted SCN admissions, cumulative delivery numbers, and SCN admission costs. CONCLUSIONS: Universal UCBGA is associated with significant initial and ongoing costs; however, potential averted costs (due to reduced SCN admissions) exceed incurred costs in most scenarios.

The comprehensive management of pregnant women with major mood disorders: a case study involving phenelzine, lithium, and quetiapine.

Pregnancy in women with severe mental illness (SMI) often bring added dimensions of complexity; considering that this group of women are choosing to have children at increasing rates, more highly complex cases will require management. A 31-year-old primigravida with a diagnosis of bipolar affective disorder was treated with an antidepressant, mood stabiliser and antipsychotic. This case discusses preconception counselling, pregnancy and labour management that resulted in the delivery of a 4,200 g baby at 39 weeks by emergency caesarian section. This case highlights the collaborative approach to care that is needed in this group of women and the need for increasing awareness and knowledge in health professionals. It follows the management from preconception through to the postpartum period.

Poractant alfa versus beractant for respiratory distress syndrome in preterm infants: a retrospective cohort study.

AIM: Poractant alfa and beractant are the commonly used animal derived surfactants in preterm infants with respiratory distress syndrome. Between 2005 and 2007, poractant alfa and beractant were alternated every month in our neonatal intensive care unit for 27 months. The aim of this study was to compare the outcomes of preterm infants who received poractant alfa versus beractant. METHOD: Single-centre, retrospective cohort study of inborn preterm infants <32 weeks gestation (23-31(+6) ). RESULTS: Six hundred sixty-four preterm infants (<32 weeks) were born during the study period, of which 415 received surfactant (poractant alfa: 214; beractant: 201). Infants in the poractant alfa group were 2.8 days younger than beractant (27.0 ± 2.3 vs. 27.4 ± 2.3 weeks; P = 0.03). All other baseline characters including Clinical Risk Index for Babies II scores were similar for both groups. No significant differences were found for the following outcomes: death or chronic lung disease (78/212 vs. 59/200; P = 0.28); death (24/214 vs. 15/201, P = 0.24); moderate to severe chronic lung disease (63/212 vs. 46/200; P = 0.45) and moderate to severe disability (20/163 vs. 19/151, P = 0.98) between poractant alfa and beractant, respectively. CONCLUSIONS: The results of our study do not support the need for preferential use of poractant alfa or beractant.

Intravenous levetiracetam for treatment of neonatal seizures.

In this case series we report on eight neonates with refractory seizures who received intravenous levetiracetam when seizures did not respond to two or more conventional anticonvulsants. Six of the eight neonates had an excellent response with either cessation, or reduction in seizures by at least 80%. One neonate showed a partial response while one did not have any reduction in seizure frequency. We did not encounter any adverse effects that could be attributable to levetiracetam.

Attitudes and barriers to the introduction of umbilical cord blood gas and lactate analysis at birth.

BACKGROUND: Despite a growing body of evidence demonstrating the value of universal umbilical cord blood gas analysis (UCBGA), there remains reluctance in some maternity units to adopt universal testing. AIMS: Identify perceived barriers and benefits of universal UCBGA. METHODS: Medical and midwifery staff involved in intrapartum care at four level two maternity units (one metropolitan and three regional) completed questionnaires evaluating attitudes to UCBGA. Questionnaires included 13 statements with responses ranging from strongly agree to strongly disagree and background demographic data. RESULTS: Most respondents considered UCBGA beneficial to perinatal care (n = 72; 67.3%), with only nine individuals (8.4%) believing UCBGA had no place in perinatal care. The majority of respondents considered benefits of UCBGA to include being an effective and objective marker of neonatal status (n = 64; 59.8%), as well as playing a role in medicolegal issues (n = 74; 69.2%) and audit and teaching (n = 64; 59.8%). Respondents considered that barriers to universal UCBGA introduction included insufficient time following delivery, increased workload and encroachment of technology into birth. CONCLUSIONS: The majority of respondents indicated support for UCBGA. Information derived from this study may be useful in identifying and resolving concerns prior to the introduction of UCBGA. Further, it could be useful in the preparation of education and implementation packages necessary for introduction of UCBGA.

Accurate prediction of hypoxic-ischaemic encephalopathy at delivery: a cohort study.

OBJECTIVE: Hypoxic-ischaemic encephalopathy (HIE) is a major acute neurologic manifestation of perinatal asphyxia associated with significant mortality and morbidity. The study aimed to develop a simple, accurate method of predicting HIE at delivery. METHODS: Between January 2003 and December 2009, all HIE cases were identified from the 38,404 deliveries at a single tertiary centre. Receiver operating curve (ROC) analysis and multivariate logistic regression assessed the ability of clinical and biochemical assessments to predict HIE. RESULTS: Sixty neonates met the HIE criteria: 39 were moderate-severe HIE. Univariate analyses identified clinical neonatal markers (Apgar scores and neonatal resuscitation level) to be better HIE predictors than biochemical markers (umbilical artery pH, base excess and lactate values). Multivariable models using two to four predictors had areas under ROC curves up to 0.98, sensitivities up to 93% and specificities up to 99%. For moderate-severe HIE, the most effective predictor was neonatal resuscitation level and arterial lactate (ROC 0.98, sensitivity 85%, specificity 99%). CONCLUSION: The combination of umbilical arterial lactate and neonatal resuscitation level provides a rapid and accurate method of predicting moderate-severe HIE that can identify neonates at birth that may benefit from tertiary care and neuroprotective therapies.

Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis in preterm infants.

BACKGROUND: Histologic chorioamnionitis (HCA) is implicated in the onset of preterm labor and delivery. Chorioamnionitis is a known risk factor for early-onset sepsis and may modulate postnatal immunity. Preterm infants are at greatly increased risk of late-onset sepsis (LOS), particularly with coagulase-negative staphylococci (CoNS), but the impact of HCA on the risk of LOS is unknown. METHODS: Eight hundred thirty-eight preterm infants born at <30 weeks gestational age at a single tertiary center were included. Histologic examination of placenta and extraplacental membranes was performed, and clinical data were extracted from hospital databases. The influence of HCA on the incidence of early-onset sepsis and LOS was examined using logistic regression analysis and Cox proportional hazards regression. RESULTS: Mean gestational age was 26.9 ± 1.9 weeks, and mean birth weight was 936 ± 277 g. Two hundred and seventy-six (33%) of 838 infants developed LOS. The presence of fetal or maternal HCA, or maternal HCA and fetal HCA alone, was associated with a significantly decreased risk of LOS with any organism. Histologic chorioamnionitis correlated with a significantly decreased risk of CoNS LOS. CONCLUSIONS: HCA is associated with a significantly reduced risk of acquiring LOS, both with CoNS and other bacteria. Perinatal inflammation may enhance the functional maturation of the preterm immune system and provide protection against LOS in high-risk preterm infants.

Estimation of rac-amisulpride transfer into milk and of infant dose via milk during its use in a lactating woman with bipolar disorder and schizophrenia.

This case describes the transfer of the antipsychotic drug amisulpride into milk and the estimation of infant exposure via breastfeeding. The dyad investigated was a 28-year-old lactating woman and her 13-month-old daughter. The woman had been taking 400 mg of amisulpride daily for 9 days and provided eight milk samples and one blood sample over a 24-hour dose interval. Amisulpride concentrations in these samples were measured by high-performance liquid chromatography, and infant dose was calculated by standard methods. The infant's health and progress were evaluated by a neonatal pediatrician. Transfer of amisulpride into milk was high, with a milk:plasma distribution ratio of 19.5 (5,188 µg/L in milk and 266 µg/L in plasma). The average amisulpride concentration in milk was 3,562 µg/L, which, when multiplied by an average milk intake of 0.15 L/kg/day, gave an absolute infant dose of 534 µg/kg/day. The relative infant dose was 10.7% of the maternal weight-adjusted dose (5,000 µg/kg/day), which is slightly above the usual 10% safety recommendation. The infant was in good health with an appropriate Denver development score for her age. She showed no acute drug-related adverse effects. Given that the infant had already benefited from 13 months of breastfeeding, that amisulpride has potential adverse effects, and that its relative infant dose was 10.7%, we recommended cessation of breastfeeding in the near-term.

Estimation of desvenlafaxine transfer into milk and infant exposure during its use in lactating women with postnatal depression.

This study characterises the extent of desvenlafaxine transfer into milk and provides data on infant exposure to desvenlafaxine via breast milk in ten women with postnatal depression and their breastfed infants. Desvenlafaxine concentration in milk and plasma was measured chromatographically in milk and in maternal and infant plasma collected at steady state. Theoretic and relative infant doses via milk were estimated and the per cent drug in infant versus mother's plasma was calculated. Theoretic infant dose via milk was 85 (53-117) µg kg(-1) day(-1) (mean and 95% confidence interval) and relative infant dose was 6.8% (5.5-8.1%). The ratio of drug in infant/maternal plasma also gave an infant exposure estimate of 4.8% (3.5-6.2%) for all ten infants and 5.3% (4.2-5.7%) in the eight infants who were exclusively breastfed. No adverse effects were seen in the infants. The relative infant dose was similar to that for previous studies using venlafaxine and was supported by a separate exposure measure using the ratio of drug in the infant's plasma relative to that in the mother's plasma. The theoretic infant dose of desvenlafaxine was 41-45% of that for venlafaxine and its metabolite desvenlafaxine in previous studies, reflecting the lower recommended maternal dose for desvenlafaxine. Although our data for desvenlafaxine use in lactation are encouraging and there are supporting data from venlafaxine studies, more patients and their infants need to be studied before the safety of desvenlafaxine as a single therapeutic agent can be fully assessed.

Assessment of infant dose through milk in a lactating woman taking amisulpride and desvenlafaxine for treatment-resistant depression.

This study presents the case of a 35-year-old breastfeeding mother who delivered her fourth child 5 months previously and was prescribed 100 mg amisulpride twice daily and 250 mg desvenlafaxine in the morning for treatment-resistant depression. Arriving at this regimen took approximately 2 months postbirth. Because she was keen to continue breastfeeding her infant, and published data on the use of amisulpride and desvenlafaxine were very limited, the clinical team sought assistance from the therapeutic drug monitoring laboratory to quantify infant dose-exposure to guide consideration of continuing breastfeeding. A sampling schedule for milk and plasma from mother and plasma from her infant was agreed and drug concentrations were measured by high-performance liquid chromatography. Absolute (theoretic) infant dose (µg/kg/d) was calculated as the product of the average concentration in milk and an assumed milk intake of 0.15 L/kg/day (294 mg/kg/day for desvenlafaxine and 183 mg/kg/day for amisulpride), and relative infant dose was estimated as absolute infant dose expressed as a percentage of the maternal dose in µg/kg/day (7.8% for desvenlafaxine and 6.1% for amisulpride). Consistent with the infant being partially breastfed, the ratio of drug in the infant's plasma to that in mother's plasma was lower at 1.7% for desvenlafaxine and 3.9% for amisulpride. A pediatric assessment of the infant found achievement of expected developmental progress for age and no detectable drug-related adverse effects. Assessing the safety of breastfeeding was difficult because it involved simultaneous use of two drugs for which there was limited previous experience. However, after discussion of the infant dose-exposure data and lack of adverse effects, the mother elected to continue partial breastfeeding for the next few months. The clinical team plans a reassessment of the infant's progress in 3 months.

Benefits of introducing universal umbilical cord blood gas and lactate analysis into an obstetric unit.

BACKGROUND: Current evidence suggests that umbilical arterial pH analysis provides the most sensitive reflection of birth asphyxia. However, there's debate whether umbilical cord blood gas analysis (UC-BGA) should be conducted on some or all deliveries. AIM: The aim of this study was to evaluate the impact of introducing universal UC-BGA at delivery on perinatal outcome. METHODS: An observational study of all deliveries > or =20 weeks' gestation at a tertiary obstetric unit between January 2003 and December 2006. Paired UC-BGA was performed on 97% of deliveries (n = 19,646). Univariate and adjusted analysis assessed inter-year UC-BGA differences and the likelihood of metabolic acidosis and nursery admission. RESULTS: There was a progressive improvement in umbilical artery pH, pO(2), pCO(2), base excess and lactate values in univariate and adjusted analyses (P < 0.001). There was a significant reduction in the newborns with an arterial pH <7.10 (OR = 0.71; 95%CI 0.53-0.95) and lactate >6.1 mmol/L (OR = 0.37; 95%CI 0.30-0.46). Utilising population specific 5th and 95th percentiles, there was a reduction in newborns with arterial pH less than 5th percentile (pH 7.12; OR = 0.75; 95%CI 0.59-0.96) and lactate levels greater than 95th percentile (6.7 mmol/L; OR = 0.37; 95%CI 0.29-0.49). There was a reduction in term (OR = 0.65; 95%CI 0.54-0.78), and overall (OR = 0.75; 95%CI 0.64-0.87) nursery admissions. These improved perinatal outcomes were independent of intervention rates. CONCLUSIONS: These data suggest that introduction of universal UC-BGA may result in improved perinatal outcomes, which were observed to be independent of obstetric intervention. We suggest that these improvements might be attributed to provision of biochemical data relating to fetal acid-base status at delivery influencing intrapartum care in subsequent cases.

Congenital Mycoplasma pneumoniae pneumonia in a neonate.

A fatal case of vertical transmission of Mycoplasma pneumoniae manifesting as congenital pneumonia in a neonate is presented. The diagnosis was based on the detection of DNA by polymerase chain reaction on the neonatal nasopharyngeal aspirates and placenta and rising titers of maternal anti Mycoplasma antibodies by complement fixation test.

Transfer of dexamphetamine into breast milk during treatment for attention deficit hyperactivity disorder.

AIMS: To investigate dexamphetamine transfer into milk, infant doses and effects in the breast-fed infant. METHODS: Four women taking dexamphetamine, and their infants were studied. RESULTS: The median maternal dexamphetamine dose was 18 mg day(-1) (range 15-45 mg day(-1)). Median (interquartile range) descriptors were 3.3 (2.2-4.8) for milk/plasma ratio, 21 microg kg(-1) day(-1) (11-39) for absolute infant dose and 5.7% (4-10.6%) for relative infant dose. No adverse effects were seen. In three infants tested, dexamphetamine in plasma was undetected in one (limit of detection 1 microg l(-1)) and present at 18 microg l(-1) and 2 microg l(-1) in the other two. CONCLUSION: Dexamphetamine readily transfers into milk. The relative infant dose was <10% and within a range that is generally accepted as being 'safe' in the short term.

Quetiapine and breast feeding.

OBJECTIVE: To quantify the relative infant dose of quetiapine during breast feeding, describe the milk:plasma (M:P) ratio, and determine the well-being of the exposed infant. CASE SUMMARY: A 26-year-old mother and her 3-month-old son were studied over a 24 hour quetiapine dose interval at steady-state. Quetiapine concentrations were quantified by high-performance liquid chromatography. Infant exposure was calculated as the concentration in milk multiplied by an estimated milk production of 0.15 L/kg/day and normalized to the weight-adjusted maternal dose. The average concentration in milk was 41 microg/L, the M:P ratio (measured using average concentrations in the elimination phase) was 0.29, and the relative infant dose was 0.09% of the maternal weight-adjusted dose (7273 microg/kg/day). The infant plasma concentration of 1.4 microg/L was some 6% of the corresponding maternal plasma concentration. No adverse effects were noted in the infant. DISCUSSION: Our findings of an infant exposure to quetiapine of less than 0.1% of the maternal dose and a lack of adverse effects confirm and extend the findings of 2 previous studies. CONCLUSIONS: Although limited, the data shown here support the prescription of quetiapine to a breast-feeding mother following a careful individual risk/benefit analysis. We suggest regular monitoring of infant progress and occasional measurement of quetiapine in the infant's plasma.