Heather E. Jeffery

Role of ureaplasma urealyticum in lung disease of prematurity.

AIM To examine the role of Ureaplasma urealyticum colonisation or infection in neonatal lung disease. METHODS Endotracheal aspirates from ventilated infants less than 28 weeks of gestation were cultured for U urealyticum and outcomes compared in infants with positive and negative cultures. RESULTS U urealyticum was isolated from aspirates of 39 of 143 (27%) infants. Respiratory distress syndrome (RDS) occurred significantly less often in colonised, than in non-colonised infants (p=0.002). Multivariate logistic regression analysis showed that in singleton infants, ureaplasma colonisation was the only independent (negative) predictor of RDS (OR 0.36; p=0.02). Both gestational age (OR 0.46; p=0.006) and isolation of U urealyticum (OR 3.0; p=0.05) were independent predictors of chronic lung disease (CLD), as defined by requirement for supplemental oxygen at 36 weeks of gestational age. Multiple gestation was also a major independent predictor of RDS and CLD. CONCLUSIONS Colonisation or infection with ureaplasma apparently protects premature infants against the development of RDS (suggesting intrauterine infection). However, in singleton infants, it predisposes to development of CLD, independently of gestational age. Treatment of affected infants after birth is unlikely to significantly improve the outcome and methods are required to identify and treat the women with intrauterine ureaplasmal infection, before preterm delivery occurs.

Maternal versus fetal inflammation and respiratory distress syndrome: a 10-year hospital cohort study

Objectives: To determine the impact of maternal and fetal intrauterine inflammatory responses (chorioamnionitis and umbilical vasculitis) on the development of neonatal respiratory distress syndrome (RDS) in preterm infants. Design, setting and subjects: The study included all infants <30 weeks’ gestation born at the Royal Prince Alfred Hospital, Sydney, Australia, and admitted to neonatal intensive care from 1992 to 2001. Those without placental examination were excluded. Antenatal and perinatal data were extracted from prospectively kept hospital databases and correlated with the independent, central neonatal database. Placentae were examined prospectively using a standardised, semi-quantative method. Main outcome measure: A diagnosis of neonatal RDS. Results: There were 766 eligible babies and 724 (94.5%) had placental examination. The mean (SD) gestational age of the cohort was 27.1 (1.6) weeks. Antenatal maternal steroids were given to 93.6%. Histological chorioamnionitis alone was evident in 19.1% of infants, and chorioamnionitis with umbilical vasculitis in 30.2%. Regression analysis showed that increasing gestational age (adjusted odds ratio (OR) 0.72, 95% CI 0.64 to 0.81), chorioamnionitis (adjusted OR 0.49, 95% CI 0.31 to 0.78), and chorioamnionitis with umbilical vasculitis (adjusted OR 0.23, 95% CI 0.15 to 0.35) were associated with a significant reduction in RDS. Factors associated with increased odds of RDS were multiple gestation (twin or triplet pregnancies), pregnancy-induced hypertension and an Apgar score <4 at 1 minute. Conclusions: Maternal and fetal intrauterine inflammatory responses are both protective for RDS. The presence of chorioamnionitis with umbilical vasculitis is associated with a markedly greater reduction of RDS than chorioamnionitis alone.

Late-onset infections of infants in neonatal units

Objective: To examine regional variations in the incidence of late‐onset neonatal infections in Australian and New Zealand neonatal units.

Why the Prone Position Is a Risk Factor for Sudden Infant Death Syndrome

Introduction. The laryngeal chemoreflex may explain why prone sleeping increases the risk of sudden infant death syndrome (SIDS). Swallowing and arousal are crucial to prevent laryngeal chemoreflex stimulation. Our aim was to examine these reflexes and breathing responses in healthy neonates after pharyngeal infusion of water in the supine versus the prone position, controlling for sleep state. Methods. A total of 10 term infants were recruited after parental consent and ethics approval. Polygraphic recordings included sleep state (active and quiet sleep by electroencephalogram, eye movements, breathing, and behavior), cardiorespiratory measurements (nasal airflow, chest wall movements, heart rate, and oxygen saturation), swallowing, and esophageal activity (solid state pressure catheter). Initial sleeping position was assigned randomly. Measurements were made for 1 minute before and after 0.4 mL of water was instilled into the oropharynx. To detect a 30% decrease in swallowing, power analysis indicated that ≥10 babies were required. Analysis, blinded to position, was made using nonparametric statistics. Results. Of the 164 infusions, the most commonly evoked airway protective responses to pharyngeal infusion were swallowing (95%) and arousal (54%). After infusion in active sleep, there was a significant reduction in swallowing and breathing when the prone position was compared with the supine position (prone: 21.3 [1.0] swallows/min and −9.6 [2.1] breaths/min; and supine: 32 (2.2) and −2.9 (1.5), respectively). However, there was no difference in the occurrence of arousal after water infusion. Conclusion. These data suggest that airway protection is compromised in the prone sleeping position during active sleep, even in healthy infants exposed to minute pharyngeal fluid volumes of 0.4 mL. This is because swallowing rate is reduced significantly, and there is no compensatory increase in arousal. The reduction in airway protective reflexes when in the prone position and in active sleep may be the mechanism for the increased risk of SIDS in the prone position.

Autonomic Reflexes in Preterm Infants

ABSTRACT. Some autonomic nervous reflexes often tested in adult medicine have been studied in 21 preterm infants (25‐37 gestational weeks). The aim was to develop such tests for preterm infants and see if there were any differences in babies with recurrent apnea and bradycardia and babies who had been exposed to sympathicolytic drugs before birth. To test sympathetic nervous activity the peripheral vascular resistance was measured before and during 45° of head‐up tilting. To test parasympathetic nervous activity the degree of bradycardia was measured in response to cold face test (application of an ice‐cube on the fore‐head) and laryngeal stimulation with saline. Finally the heart rate changes after a sudden noise (85 dB) were studied as an indicator of both sympathetic and vagal activity. The peripheral resistance was found to be relatively low in these preterm infants, particularly in some infants tested at the postnatal age of about two months. Heart rate and mean blood pressure did not change during tilting, while the peripheral resistance increased significantly mainly due to lowered limb blood flow. The median decrease of the heart rate during the cold face test was 20.0% and during laryngcal receptor stimulation 23.7%. The sudden noise usually caused a biphasic heart rate response. An autonomic nervous reflex score was calculated and found to be negative (parasympathetic) in infants with recurrent prolonged apnea and bradycardia and positive in infants with clinical signs of increased sympathetic nervous activity.

Cardiovascular Stress Hyperreactivity in Babies of Smokers and in Babies Born Preterm

Background— Being born preterm, small, and to a mother who smokes are common perinatal complications with major public health implications. Evidence suggests that each affects the body’s structure and function in ways that could increase susceptibility to cardiovascular dysfunction later in life. Here, we used 2 routine stress reactivity tests to identify incipient “silent” programming of cardiovascular dysfunction associated with adverse perinatal events. Methods and Results— We studied 29 control babies born at term to nonsmokers, 18 term-born babies of mothers who smoked throughout pregnancy (mean, 15 cigarettes a day), and 31 babies born preterm to nonsmokers. All infants were compared at the same age after conception (ie, at 40 to 42 weeks), during sleep. We analyzed blood pressure (BP) and heart rate responses to breathing 4% CO2 for 4 minutes or to passive head-up tilt to 60°. BP was measured continuously from a wrist cuff. CO2 exposure raised heart rate and BP in controls by 10%, and tilt increased their BP by 5%. CO2 elicited the expected BP but no heart rate response from preterm infants but a much-greater-than-expected BP and heart rate response from babies of smokers. Tilt elicited a 3- to 4-fold greater rise in BP from preterm and tobacco-exposed babies. Conclusions— Vascular, cardiac, and blood pressure reactivity is heightened in babies born preterm or to smokers. The findings are consistent with in utero and early postnatal “programming” of human cardiovascular dysfunction by adverse circumstances. This incipient dysfunction may be an early manifestation of processes that lead to other problems or complications later on (eg, higher BP or sudden infant death syndrome).

Influence of breast versus formula milk on physiological gastroesophageal reflux in healthy, newborn infants.

The effect of milk type on physiological, gastroesophageal reflux (GER) was studied in 37 breast-fed and 37 formula-fed, healthy, term neonates aged 2–8 days. The neonates were randomly selected from the public maternity ward and studied for 4 h after their morning milk feed. GER was recorded by a pH microelectrode placed 6 cm above the gastroesophageal junction and analyzed in the third and fourth postprandial hours. Sleep state was accurately defined from the electroencephalogram, electrooculogram, electromyogram, breathing, and behavioral observations. Movement was recorded from a piezo-electric transducer. In active sleep, the breast-fed neonates demonstrated GER episodes of significantly shorter duration than the formula-fed neonates. The means and 95% confidence intervals (CI) were 3.0 (1.6,5.2) compared with 8.3 (5.0,13.3) min/h of active sleep respectively (p < 0.05). This could not be explained by greater milk volume or increased movement before or during reflux in formula-fed neonates. However, the lower median pH values for GER in breast-fed neonates, 2.0 versus 2.5, were significantly different (p < 0.05). This difference may reflect more rapid gastric emptying. The lower esophageal pH is more likely to stimulate peristalsis and thus limit the duration of reflux (shorter episodes), in the breast-fed neonates.

Eight-Year Outcome of Universal Screening and Intrapartum Antibiotics for Maternal Group B Streptococcal Carriers

Objectives. To report the outcome of intervention to reduce early-onset group B streptococcal disease (EOGBSD) at a tertiary maternity hospital in Sydney and to review all cases of EOGBSD since intervention to improve outcomes further. Methodology. A prospective study was made of all cases of EOGBSD in the 16 months before and 8 years after an intervention that comprised universal screening and intrapartum ampicillin for all maternal carriers of group B streptococcus. Carriers were detected by screening all women at 28 weeks, or 24 weeks with known risk factors for preterm birth, by low vaginal swab, cultured onto blood agar and treated with intravenous ampicillin in labor, 1 g every 6 hours until delivery. Women with a routine midstream urine test positive for group B streptococcus, a previous neonate with EOGBSD, or preterm labor with an unknown carrier status were also treated. EOGBSD was detected by screening all neonates with maternal and/or neonatal risk factors for sepsis. Results. The incidence of blood culture-positive EOGBSD for all live births before intervention was 1.4 per 1000 compared with a rate after intervention of 0.2 per 1000 live births. The incidence, if there were clinical signs of infection and the urine tested positive for streptococcal antigen, decreased from 3.5 per 1000 before intervention to 0.6 per 1000 live births. There was a statistically significant reduction in neonatal morbidity outcomes after intervention, including requirement for admission and treatment in a neonatal unit and the need for ventilation. An audit indicated that by the 8th year, 90% of all pregnant women were screened by a low vaginal swab at 28 weeks and 10.5% were carriers. After intervention, of the 28 neonates with EOGBSD, 64% were associated with departure from the protocol. Conclusion. The intervention has coincided with a significant decrease in the incidence of blood culture-positive EOGBSD to 0.2 and urine streptococcal antigen-positive disease to 0.6 per 1000 live births. The 84% reduction in EOGBSD has been obtained by treating 244 neonates in labor to prevent disease in one neonate. Additional reduction seems possible by improving the compliance by staff with the protocol. By contrast, before intervention and in maternity units throughout Australia with no intervention, the rates for EOGBSD remain largely unchanged at ∼2 per 1000 live births.

Is C‐reactive protein really useful in preterm premature rupture of the membranes?

Summary. In a prospective blind study 380 daily serum samples from 55 women with preterm premature rupture of the membranes were analysed for C‐reactive protein (CRP). Although the last CRP before delivery was higher in patients with histological chorioamnionitis (P= 0.007), considerable overlap between infected and non‐infected pregnancies occurred, precluding the use of CRP as a diagnostic test if published normal levels were used. When upper limits were set at 30, 35, or 40 mg/1, the last CRP before delivery proved 90, 95 and 100% specific and 88, 92 and 100% positively predictive of infection in singleton pregnancies. Such high specificities are needed to prevent inappropriate intervention based on false positive results. We therefore propose upper limits for single estimations of 30, 35, or 40 mg/1 depending on the relative risks of preterm delivery versus infection at various gestational ages. In addition, consecutive values <20 mg/1 appeared highly predictive of infection.

Airway protection in sleeping infants in response to pharyngeal fluid stimulation in the supine position.

This study was designed to evaluate upper airway protective mechanisms in response to pharyngeal fluid stimulation in healthy term and preterm infants at term equivalent age. Five term and seven preterm infants were studied and the following recorded: sleep state, cardiorespiratory function, and swallowing. Infusions of 0.9% saline and sterile water of volumes of 0.04, 0.2, and 0.35 mL were made during active (AS) and quiet sleep (QS). The effect of these variables on apnea (≥2 and ≥5 s), swallowing, and arousal was examined. After pharyngeal infusion, apnea of ≥2 and ≥5 s did not change from spontaneous rate for both term and preterm infants. The most common response to pharyngeal infusion was swallowing. In AS, swallowing occurred after 65 and 73% and in QS after and 64% of infusions in term and preterm infants, respectively. Swallowing was volume-related and occurred significantly more often in term infants after larger infusions of 0.35 and 0.2 mL (83 and 67%) compared with the 0.04 mL (19%) and after 0.2 mL compared with 0.04 mL for preterm infants (94 and 44%). At 0.2 mL, this was significantly higher in preterm compared with term infants (p < 0.01) and was the only significant difference between these infants. In response to pharyngeal fluid stimulation, airway defense in both full-term and preterm infants is maintained primarily by swallowing with no evidence of apnea.