Induction of Labor versus Expectant Management in Women with Preterm Prelabor Rupture of Membranes between 34 and 37 Weeks: A Randomized Controlled Trial

Background

At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term.

Methods and Findings

We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34⁺⁰ and 37⁺⁰ wk of gestation. Participants were randomly allocated in a 1∶1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate.From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported.Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM.

Conclusions

In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM.

Trial registration

Current Controlled Trials ISRCTN29313500 Please see later in the article for the Editors'' Summary     

Diagnostic Utility of Neutrophil CD64 as a Marker for Early-Onset Sepsis in Preterm Neonates

Introduction

Neutrophil CD64 has been proposed as an early marker of sepsis. This study aims to evaluate the diagnostic utility of neutrophil CD64 for identification of early-onset sepsis in preterm neonates.

Methods

The prospective study was conducted in a neonatal intensive care unit between November 2010 and June 2011. Preterm neonates in whom infection was suspected when they were <12 hours of age were enrolled. Complete blood count with differential, blood culture, neutrophil CD11b and CD64 measurement were performed. Receiver operating characteristic curve analysis was performed to evaluate the performance of neutrophil CD64 as biomarker of sepsis.

Results

A total of 158 preterm neonates was enrolled, 88 of whom were suspected infection. The suspected sepsis group was of lesser gestational age (P<0.001) and lower birth weight (P<0.001), compared with controls. The hematologic profiles of the suspected sepsis group were characterized by higher white blood cell count, neutrophil counts and C-reactive protein. The suspected sepsis neonates had significantly higher neutrophil CD64 expression compared with controls. Neutrophil CD64 had an area value under the curve of 0.869 with an optimal cutoff values of 1010 phycoerythrin molecules bound/cell and it had a high sensitivity (81.82%) and negative predictive value (77.4%). The level of neutrophil CD64 was independent of antibiotic therapy within 24 hours after the onset of sepsis in preterm neonates.

Conclusions

Neutrophil CD64 is a highly sensitive marker for suspected early-onset sepsis in preterm neonates. Our study suggests that neutrophil CD64 may be incorporated as a valuable marker to diagnose infection.     

Umbilical Cord Blood IL-6 as Predictor of Early-Onset Neonatal Sepsis in Women with Preterm Prelabour Rupture of Membranes

Objective

To evaluate umbilical cord interleukin (IL)-6 and funisitis as independent predictors of early-onset neonatal sepsis (EONS) in preterm prelabor rupture of membranes (PPROM).

Design

Prospective cohort study.

Setting

Evaluation of umbilical cord IL-6 and funisitis as predictors of early-onset neonatal sepsis in PPROM.

Population

176 women with PPROM between 23+0−36+6 weeks of gestation.

Methods

Umbilical cord IL-6 was assayed by ELISA. Funisitis was defined according to the Salafia classification. Data was adjusted by gestational age at delivery and prenatal administration of corticosteroids and antibiotics.

Main Outcome Measures

Binary logistic regression was performed to assess the independence of umbilical cord IL-6 and funisitis to predict EONS in women complicated with PPROM.

Results

The rate of EONS was 7%. Funisitis was present in 18% of women. Umbilical cord IL-6 was significantly higher in women complicated with EONS than without [median (range) 389.5 pg/mL (13.9–734.8) vs 5.2 (0.1–801–4), p<0.001]. Umbilical cord IL-6 was the only independent predictor of early-onset neonatal sepsis (odds ratio 13.6, p = 0.004).

Conclusion

Umbilical cord IL-6 was the only predictor of early-onset neonatal sepsis in PPROM. Contrary to what is reported, funisitis was not.     

Platelets Induce Apoptosis during Sepsis in a Contact-Dependent Manner That Is Inhibited by GPIIb/IIIa Blockade

Purpose

End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis.

Methods

End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score.

Measurements and Main Results

There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice.

Conclusions

In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.     

Comparative Assessment of Cytokines and Other Inflammatory Markers for the Early Diagnosis of Neonatal Sepsis–A Case Control Study

Objective

Cytokines (IL-6, IL-8 and TNF-α), sCD163, and C-reactive protein were serially measured in an attempt to identify a set of tests which can reliably confirm or refute the diagnosis of neonatal sepsis at an early stage.

Methods

One hundred neonates suspected to have sepsis on clinical grounds and who met the inclusion criteria were enrolled for the study. Based on the positive or negative blood culture reports they were classified as infected (n = 50) and non-infected (n = 50) neonates respectively. Fifty healthy neonates without any signs of sepsis were also included in the study as control group. The initial blood sample was taken on day 0 (at the time of sepsis evaluation) and two further samples were taken on days 1 and 2 for monitoring the clinical progress and response to treatment. In the control group the cord blood and 48 hours venous sample was collected. Plasma CRP (ng/ml), IL-6 (pg/ml), IL-8 (pg/ml), TNF-α (ng/ml) and sCD163 (ng/ml) were determined by double antibody method Enzyme Linked Immunosorbent Assay in all the three blood samples.

Results

The cut of levels for CRP at >19,689 ng/ml had a sensitivity of 68%, specificity of 92%, for IL-6 at >95.32 pg/ml had a sensitivity of 54%, specificity of 96%, for IL-8 at >70.86 pg/ml had a sensitivity of 78%, specificity of 70%, for sCD163 at >896.78 ng/ml had a sensitivity of 100%, specificity of 88% for the diagnosis of infection before antibiotics. TNF-α levels of >12.6 ng/ml showed 100% sensitivity and 72% specificity for the diagnosis of inflammation.

Conclusion

The most powerful predictor to differentiate between the non-infected and infected neonates before antibiotics was sCD163. The most powerful indicator for evaluation of prognosis is IL-6. sCD163 can be used alone to screen for sepsis in neonates before the results of blood culture are received.     

Macrophage Phenotype Is Associated with Disease Severity in Preterm Infants with Chronic Lung Disease

Background

The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation.

Objectives

To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD.

Methods

Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.

Results

Preterm birth was associated with an increase in the proportion of non-classical CD14+/CD16+ monocytes on the day of delivery (58.9±5.8% of total mononuclear cells in preterm vs 33.0±6.1% in term infants, p = 0.02). Infants with RDS were born with significantly more CD36⁺ macrophages compared with the CLD group (70.3±5.3% in RDS vs 37.6±8.9% in control, p = 0.02). At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14⁺ mononuclear phagocytes in the airway (p = 0.03), but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36 (p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung.

Conclusions

These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.     

Sequestration of Vascular Endothelial Growth Factor (VEGF) Induces Late Restrictive Lung Disease

Rationale

Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function.

Objectives

To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function.

Methods

Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1) were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model.

Measurements and Main Results

Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes.

Conclusions

These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions.     

Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

Objectives

To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis.

Methods

Historical cohort study in a population of infants born at <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997–2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley –test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis.

Results

Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4–4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5–15.9] and 3.2 [0.7–14.7], respectively.

Conclusions

We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram –negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period.     

Frequency of Retinopathy of Prematurity in Premature Neonates with a Birth Weight below 1500 Grams and a Gestational Age Less than 32 Weeks: A Study from a Tertiary Care Hospital in a Lower-Middle Income Country…

Introduction

Retinopathy of prematurity (ROP) is a treatable cause of blindness in neonates. In Pakistan, ROP is often not recognized early because screening and treatment programs are not yet in place in most neonatal units, even in tertiary care hospitals. It is hoped that this report will help inform medical professionals of the magnitude of the problem and help to design appropriate management strategies.

Objectives

The aim was to determine the frequency of ROP in premature and very low birth weight (BW) neonates (BW<1500 g and gestational age (GA) <32 weeks).

Study Design

Cross-sectional study.

Study Setting

Neonatal intensive care unit (NICU) of a tertiary care hospital in Karachi, Pakistan.

Study Duration

From June 2009 to May 2010.

Subjects and Methods

Neonates with a Birth weight (BW) <1500 g and Gestational Age (GA) <32 weeks who were admitted to the NICU and received an eye examination, or were referred for a ROP eye examination as an outpatient, were included in the study. GA was estimated from intrauterine ultrasound findings. Neonates with major congenital malformations, syndromes or congenital cataracts or tumors of the eyes, and those that died before the eye examination or did not attend the out patients department for an eye examination, were excluded. The neonatal eye examination was performed by a trained ophthalmologist at 4 or 6 weeks of age.

Results

Out of 86 neonates, ROP was identified in nine neonates (10.5%) at the first eye examination. ROP was significantly associated with BW (P = 0.037), GA (P = 0.033), and chronological age (P<0.001).

Conclusions

we identified ROP in 10.5% of neonates at first eye examination. Significant associations between ROP and a GA<32 weeks and a BW<1500 g were also observed.we also stress that serial follow-up of neonates at risk for ROP is important when making a final diagnosis.     

Feasibility of Recruiting a Diverse Sample of Men Who Have Sex with Men: Observation from Nanjing,China

Background

Respondent-driven-sampling (RDS) has well been recognized as a method for sampling from most hard-to-reach populations like commercial sex workers, drug users and men who have sex with men. However the feasibility of this sampling strategy in terms of recruiting a diverse spectrum of these hidden populations has not been understood well yet in developing countries.

Methods

In a cross sectional study in Nanjing city of Jiangsu province of China, 430 MSM were recruited including 9 seeds in 14 weeks of study period using RDS. Information regarding socio-demographic characteristics and sexual risk behavior were collected and testing was done for HIV and syphilis. Duration, completion, participant characteristics and the equilibrium of key factors were used for assessing feasibility of RDS. Homophily of key variables, socio-demographic distribution and social network size were used as the indicators of diversity.

Results

In the study sample, adjusted HIV and syphilis prevalence were 6.6% and 14.6% respectively. Majority (96.3%) of the participants were recruited by members of their own social network. Although there was a tendency for recruitment within the same self-identified group (homosexuals recruited 60.0% homosexuals), considerable cross-group recruitment (bisexuals recruited 52.3% homosexuals) was also seen. Homophily of the self-identified sexual orientations was 0.111 for homosexuals. Upon completion of the recruitment process, participant characteristics and the equilibrium of key factors indicated that RDS was feasible for sampling MSM in Nanjing. Participants recruited by RDS were found to be diverse after assessing the homophily of key variables in successive waves of recruitment, the proportion of characteristics after reaching equilibrium and the social network size. The observed design effects were nearly the same or even better than the theoretical design effect of 2.

Conclusion

RDS was found to be an efficient and feasible sampling method for recruiting a diverse sample of MSM in a reasonable time.     

In Vitro Surfactant and Perfluorocarbon Aerosol Deposition in a Neonatal Physical Model of the Upper Conducting Airways

Objective

Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways.

Methods

The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4–7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted.

Results

The nebulization system produced relatively large amounts of aerosol ranging between 0.3±0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0±0.1 ml/min for distilled water (H₂Od) at 6 bar, with MMADs between 2.61±0.1 µm for PFD at 7 bar and 10.18±0.4 µm for FC-75 at 6 bar. The deposition study showed that for surfactant and H₂Od aerosols, the highest percentage of the aerosolized mass (∼65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH₂O only increased total airway pressure by 1.59 cmH₂O at the highest driving pressure (7 bar).

Conclusion

This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.     

Effect of Surfactant and Partial Liquid Ventilation Treatment on Gas Exchange and Lung Mechanics in Immature Lambs: Influence of Gestational Age

Objectives

Surfactant (SF) and partial liquid ventilation (PLV) improve gas exchange and lung mechanics in neonatal RDS. However, variations in the effects of SF and PLV with degree of lung immaturity have not been thoroughly explored.

Setting

Experimental Neonatal Respiratory Physiology Research Unit, Cruces University Hospital.

Design

Prospective, randomized study using sealed envelopes.

Subjects

36 preterm lambs were exposed (at 125 or 133-days of gestational age) by laparotomy and intubated. Catheters were placed in the jugular vein and carotid artery.

Interventions

All the lambs were assigned to one of three subgroups given: 20 mL/Kg perfluorocarbon and managed with partial liquid ventilation (PLV), surfactant (Curosurf®, 200 mg/kg) or (3) no pulmonary treatment (Controls) for 3 h.

Measurements and Main Results

Cardiovascular parameters, blood gases and pulmonary mechanics were measured. In 125-day gestation lambs, SF treatment partially improved gas exchange and lung mechanics, while PLV produced significant rapid improvements in these parameters. In 133-day lambs, treatments with SF or PLV achieved similarly good responses. Neither surfactant nor PLV significantly affected the cardiovascular parameters.

Conclusion

SF therapy response was more effective in the older gestational age group whereas the effectiveness of PLV therapy was not gestational age dependent.     

Determinants and Causes of Neonatal Mortality in Jimma Zone,Southwest Ethiopia: A Multilevel Analysis of Prospective Follow Up Study

Background

Ethiopia is among the countries with the highest neonatal mortality with the rate of 37 deaths per 1000 live births. In spite of many efforts by the government and other partners, non-significant decline has been achieved in the last 15 years. Thus, identifying the determinants and causes are very crucial for policy and program improvement. However, studies are scarce in the country in general and in Jimma zone in particular.

Objective

To identify the determinants and causes of neonatal mortality in Jimma Zone, Southwest Ethiopia.

Methods

A prospective follow-up study was conducted among 3463 neonates from September 2012 to December 2013. The data were collected by interviewer-administered structured questionnaire and analyzed by SPSS V.20.0 and STATA 13. Verbal autopsies were conducted to identify causes of neonatal death. Mixed-effects multilevel logistic regression model was used to identify determinants of neonatal mortality.

Results

The status of neonatal mortality rate was 35.5 (95%CI: 28.3, 42.6) per 1000 live births. Though significant variation existed between clusters in relation to neonatal mortality, cluster-level variables were found to have non-significant effect on neonatal mortality. Individual-level variables such as birth order, frequency of antenatal care use, delivery place, gestation age at birth, premature rupture of membrane, complication during labor, twin births, size of neonate at birth and neonatal care practice were identified as determinants of neonatal mortality. Birth asphyxia (47.5%), neonatal infections (34.3%) and prematurity (11.1%) were the three leading causes of neonatal mortality accounting for 93%.

Conclusions

This study revealed high status of neonatal mortality in the study area. Higher-level variables had less importance in determining neonatal mortality. Individual level variables related to care during pregnancy, intra-partum complications and care, neonatal conditions and the immediate neonatal care practices were identified as determinant factors. Improving antenatal care, intra-partum care and immediate neonatal care are recommended.     

Culture of Airway Epithelial Cells from Neonates Sampled within 48-Hours of Birth

Introduction

Little is known about how neonatal airway epithelial cell phenotype impacts on respiratory disease in later life. This study aimed to establish a methodology to culture and characterise neonatal nasal epithelial cells sampled from healthy, non-sedated infants within 48 hours of delivery.

Methods

Nasal epithelial cells were sampled by brushing both nostrils with an interdental brush, grown to confluence and sub-cultured. Cultured cells were characterised morphologically by light and electron microscopy and by immunocytochemistry. As an exemplar pro-inflammatory chemokine, IL-8 concentrations were measured in supernatants from unstimulated monolayers and after exposure to IL-1β/TNF-α or house dust mite extract.

Results

Primary cultures were successfully established in 135 (91%) of 149 neonatal samples seeded, with 79% (n  =  117) successfully cultured to passage 3. The epithelial lineage of the cells was confirmed by morphological analysis and immunostaining. Constitutive IL-8 secretion was observed and was upregulated by IL-1β/TNF-α or house dust mite extract in a dose dependent manner.

Conclusion

We describe a safe, minimally invasive method of culturing nasal epithelial cells from neonates suitable for functional cell analysis offering an opportunity to study “naïve” cells that may prove useful in elucidating the role of the epithelium in the early origins of asthma and/or allergic rhinitis.     

Risk of Vertical Transmission of Human Papillomavirus throughout Pregnancy: A Prospective Study

Objective

Much controversy still exists about maternal-to-infant transmission of human papillomavirus (HPV) infection, specifically about the magnitude of the risk and the route and timing of such vertical transmission. This prospective cohort study examines the risk of vertical transmission of maternal HPV in each trimester of pregnancy.

Study design

One hundred fifty three healthy pregnant women were followed longitudinally throughout pregnancy and cervical swabs obtained in each trimester and postpartum for HPV detection. Cord blood, neonatal nasopharyngeal aspirates, and placental biopsies were collected at delivery. DNA isolation, polymerase chain reaction, and hybridization were performed using the GG HPV Genotyping Chip Kit (Goodgene Inc., Seoul, Korea). Detection of HPV in neonates was defined as the presence of HPV DNA in either cord blood or neonatal nasopharyngeal aspirate.

Results

HPV DNA was detected in 14%(22/153) of healthy women in the first trimester, 18%(22/124) in the second trimester, and 10%(15/153) in the third trimester; 24%(37/153) were positive for HPV DNA on at least one occasion in pregnancy. At birth, 5.2%(8/153) of neonates were HPV DNA positive. Seven of these eight infants were born to HPV-positive mothers. Placental HPV DNA was positive in 3.3%(5/152) of cases, and all five cases were from mothers with at least one HPV-positive test. Detection of HPV DNA in neonates was associated with detection of HPV in mothers during any of the three trimesters of pregnancy.

Conclusion

HPV DNA was detected at birth in 5.2%(8/153) of neonates born to healthy women, and was associated with the detection of HPV in mothers during any of the three trimesters of pregnancy.     

Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ

Background

Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants.

Methodology/Principal Findings

We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Gram-positive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-γ. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-γ.

Conclusion/Significance

Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressively matures in the last three months in utero. Ex vivo treatment of leukocytes from premature neonates with interferon-γ reversed their innate immune responses deficiency to bacteria. These data represent a promising proof-of-concept to treat premature newborns at the time of delivery with pharmacological agents aimed at maturing innate immune responses in order to prevent neonatal sepsis.     

Automatic Quantitative MRI Texture Analysis in Small-for-Gestational-Age Fetuses Discriminates Abnormal Neonatal Neurobehavior

Background

We tested the hypothesis whether texture analysis (TA) from MR images could identify patterns associated with an abnormal neurobehavior in small for gestational age (SGA) neonates.

Methods

Ultrasound and MRI were performed on 91 SGA fetuses at 37 weeks of GA. Frontal lobe, basal ganglia, mesencephalon and cerebellum were delineated from fetal MRIs. SGA neonates underwent NBAS test and were classified as abnormal if ≥1 area was <5^th centile and as normal if all areas were >5^th centile. Textural features associated with neurodevelopment were selected and machine learning was used to model a predictive algorithm.

Results

Of the 91 SGA neonates, 49 were classified as normal and 42 as abnormal. The accuracies to predict an abnormal neurobehavior based on TA were 95.12% for frontal lobe, 95.56% for basal ganglia, 93.18% for mesencephalon and 83.33% for cerebellum.

Conclusions

Fetal brain MRI textural patterns were associated with neonatal neurodevelopment. Brain MRI TA could be a useful tool to predict abnormal neurodevelopment in SGA.     

Paediatric Acute Kidney Injury in a Tertiary Hospital in Nigeria: Prevalence,Causes and Mortality Rate

Background

The modest decline in child mortality in Africa raises the question whether the pattern of diseases associated with acute kidney injury (AKI) in children in Nigeria has changed.

Methods

A database of children, aged between one month and 16 years, with AKI (using modified pediatric RIFLE criteria) was reviewed. The cause of AKI was defined as the major underlying disease. The clinical and laboratory features of children with AKI who survived were compared to those who died.

Results

Of the 4 015 children admitted into Lagos University Teaching Hospital between July 2010 and July 2012, 70 episodes of AKI were recorded equalling 17.4 cases per 1000 children. The median age of the children with AKI was 4.8 (range 0.1–14.4) years and 68.6% were males. Acute kidney injury was present in 58 (82.9%) children at admission with 70% in ‘failure’ category. Primary kidney disease (38.6%), sepsis (25.7%) and malaria (11.4%) were the commonest causes. The primary kidney diseases were acute glomerulonephritis (11) and nephrotic syndrome (8). Nineteen (28.4%) children with AKI died. Need for dialysis [odds ratio: 10.04 (2.94–34.33)], white cell >15 000/mm³ [odds ratio: 5.72 (1.65–19.89)] and platelet <100 000/mm³ [odds ratio: 9.56 (2.63–34.77)] were associated with death.

Conclusion

Acute kidney injury is common in children admitted to hospitals. The common causes remain primary kidney diseases, sepsis and malaria but the contribution of sepsis is rising while malaria and gastroenteritis are declining. Acute kidney injury-related mortality remains high.