Bacterial vaginosis: A problematic infection from both a perinatal and neonatal perspective

Bacterial vaginosis (BV) infections are common in women of reproductive age and are easily diagnosed and treatable. Aside from being an annoyance when symptoms of discharge, odor, and pruritus occur in the gravid female, BV infections increase risk of late miscarriage, preterm labor, preterm premature rupture of membranes, and, consequently, preterm delivery. Antepartum and puerperal issues such as chorioamnionitis and endometritis are increased in the context of maternal BV. Moreover, the morbidities and mortality of preterm delivery are consequently increased as a result of BV during pregnancy. Although the pathology associated with BV appears to result from inflammation, more investigation is needed in terms of designing guidelines for appropriate screening and treatment for the prevention of adverse outcomes.     

Chorioamnionitis: a risk factor for fetal and neonatal morbidity

Despite widespread use of drugs to arrest preterm labor, there has been no decrease in the numbers of low-birth-weight or preterm infants in the last 20 years. Evidence from many sources links preterm birth to symptomatic and subclinical infections. Recently, an increasing body of evidence has suggested that not only is subclinical infection responsible for preterm birth but also for many serious neonatal sequelae, including periventricular leukomalacia, cerebral palsy, respiratory distress and even bronchopulmonary dysplasia and necrotizing enterocolitis. Proxies of intrauterine infection include clinical chorioamnionitis, histological chorioamnionitis and intraamniotic increase in cytokines, which have been found to be associated with acute neonatal morbidity and mortality and, at least to some degree, with neurological impairment, chronic lung disease and thymus involution in the preterm infant. The infectious/inflammatory mechanisms involved are not fully understood, and the types of microbes and genetic features of host adaptive and innate immune responses need to be better characterized.     

早产儿医院感染的危险因素

目的 探讨早产儿医院感染的发病情况及危险因素,为医院感染的监控和干预提供理论依据.方法回顾性调查本院2008年1月-2010年1月本院NICU 516例早产儿的临床资料,分析医院感染的危险因素.结果 1.早产儿516例中,74例发生医院感染,发生率为14.3%,共发生医院感染98例次,平均每例发生1.32次,医院感染的住院日相关发生率为8.9‰;感染部位以呼吸道为主(51.0%),其中呼吸机相关性肺炎最为多见(占36.0%),其次为皮肤软组织(26.5%)和消化道(14.3%).2.共培养出病原菌69株,革兰阴性杆菌占71.0%,以肺炎克雷伯菌最为多见(17.4%);革兰阳性球菌占18.8%,以草绿色链球菌最为多见;真菌占10.1%,主要为白色念珠菌.3.胎龄≤32周、出生体质量≤1.5 kg、羊水胎粪污染、胎膜早破≥48 h、糖尿病母亲儿、吸痰次数≥10次、气管插管次数≥3次、机械通气时间≥3 d、置胃管、静脉营养、应用抗生素时间≥2周及住院时间≥2周与医院感染率显著相关,多元Logistic回归方程显示胎龄≤32周、静脉营养、机械通气时间≥3 d及住院时间≥2周是医院感染发生的独立危险因素.结论 NICU早产儿医院感染的危险因素众多,尽量减少侵入性操作次数、缩短静脉营养及住院的时间、合理应用抗生素可有效降低医院感染发生率.     

"Getting to Zero": preventing invasive Candida infections and eliminating infection-related mortality and morbidity in extremely preterm infants

Prevention of invasive Candida infections (ICI) is an achievable goal for every NICU and supported by A-1 evidence. Due to the incidence of ICI, high infection-associated mortality and neurodevelopmental impairment, antifungal prophylaxis should be targeted to infants <1000 g or ≤ 27 weeks gestation. There is A-1 evidence for both fluconazole and nystatin prophylaxis for the prevention of ICI. Evidence currently would favour fluconazole prophylaxis in high-risk preterm infants since intravenous fluconazole prophylaxis has greater efficacy compared to enteral nystatin prophylaxis, efficacy in the most immature patients in whom mortality is the highest, requires less dosing, and can be given to infants with gastrointestinal disease or haemodynamic instability. All NICUs caring for extremely preterm infants should use antifungal prophylaxis. Even in NICUs with low rates of ICI, antifungal prophylaxis is crucial to improving survival and neurodevelopmental outcomes for this vulnerable population. For infants 1000-1500 g if there is concern for ICI in the NICU, either drug could be chosen for prophylaxis. Fluconazole prophylaxis administered at 3 mg/kg twice a week, while intravenous access is required, appears to be the safest and most effective schedule in preventing ICI while attenuating the emergence of fungal resistance. Invasive Candida infections are one group of infections we can prevent.     

Ciprofloxacin in preterm neonates: case report and review of the literature

We report the use of ciprofloxacin in a preterm boy suffering from an invasive multiple resistant Enterobacter cloacae infection. The treatment was effective, after other antibiotics failed, and no adverse effects were observed during 3 years of follow up. The literature on compassionate ciprofloxacin use in 28 preterm or low birth weight infants is reviewed. Ciprofloxacin has been used to treat neonatal pneumonia, meningitis and septicaemia and was effective in all cases. Side-effects were limited to dental dyschromia and one observation on the emergence of resistance. Pharmacokinetics of ciprofloxacin were studied in seven preterm infants; iv doses ranging from 4 to 40 mg/kg per day revealed adequate serum peak concentrations (0.98–5.7 mg/l) but trough-peak ratios were high (median ratio: 32%), suggesting slower elimination in preterm infants as compared to older children. CSF concentrations were 0.10–1.45 mg/l. Conclusion Ciprofloxacin treatment of preterm or low birth weight infants may be effective and without severe side effects in infections with bacteria resistant to other antibiotics     

Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis. 2: Immunotherapy

The physiological immunodeficiency of preterm and term newborns is the major cause of their increased susceptibility to infections. Although nonspecific and specific host defence mechanisms are morphologically intact, there are functional and quantitative defects. Supportive immunotherapy is required to equalize these immunological defects. This article reviews topical possibilities for immunotherapy of neonatal sepsis (exchange transfusion, transfusion of fresh blood or fresh plasma, granulocyte transfusion, use of immunoglobulins, fibronectin, interferon and colony-stimulating factor).     

Breast milk as a source of late onset neonatal sepsis

Neonatal sepsis can be a life-threatening complication in preterm neonates. We present the clinical course of 3 preterm neonates, 1 with recurrent sepsis and 2 with late onset sepsis attributed to ingestion of breast milk containing pathogenic organisms. Breast milk should be considered as a potential source of infection in neonates with recurrent infections or when infections occur simultaneously in siblings.     

Serum Immunoglobulin Levels and Incidence of Infection During the First Year of Life in Full-term and Preterm Infants

IgG, IgM, and IgA concentrations from birth to 12 months of age, and the incidence of acute infectious processes were determined in 25 full-term and in 26 preterm infants by the single radioimmunodiffusion technique in a prospective study. Infants born at term showed significantly higher IgG levels than preterm babies up to 2 months of age (P less than 0.05) and the frequency of preterm babies with one or more acute infectious episodes during the same period of time was higher, mainly owing to pulmonary, oral mucosa, and ocular infections. The frequency of children with six or seven infectious episodes was also higher in the preterm group (P less than 0.05). IgM and IgA levels did not differ between groups. Even though preterm infants did not show serious bacterial disease or inability to produce antibodies, the incidence of infectious processes was higher in this group up to 2 months of age, a period during which serum IgG levels were lower than in the group of children born at term.     

CD64 (Fcgamma receptor I) cell surface expression on maturing neutrophils from preterm and term newborn infants

BACKGROUND: The expression of CD64 (FcgammaRI) is increased from an almost negligible to a marked level on neutrophils in patients with bacterial infections. CD64 expression on neutrophils might therefore be a potential candidate for the diagnosis of bacterial infections in infants. AIM: This study was performed to monitor changes of neutrophil expression of CD64 during the postpartum period to further evaluate the usefulness of this analysis. The possible influence on the expression of this receptor by other factors was also investigated, including respiratory distress syndrome (RDS) and preterm rupture of the membranes (PROM). METHODS: Cell surface expression of CD64 on neutrophils from preterm and term newborn infants and healthy adults was analysed by flow cytometry. The expression of the other Fcgamma receptors, CD32 and CD16, and the complement receptors CD11b/CD18 and CD35 was also analysed for comparison. RESULTS: Neutrophils from preterm newborn infants showed a moderately increased level of CD64 expression that, during their first month of life, was reduced to the level observed on neutrophils from term newborn infants and adults. In contrast, the level of neutrophil expression of CD32 and CD16 was significantly lower in preterm than term newborn infants and adults. Neutrophils from all groups indicated similar levels of CD11b expression, but the expression on neutrophils from newborn infants increased after birth. CONCLUSION: Our results showed that neutrophil expression of CD64 is moderately increased in preterm newborn infants at birth. It seems not to be influenced by RDS, PROM or other factors related to preterm birth but by bacterial infection.     

早产儿新生儿期疾病的流行病学调查

目的：探讨住院早产儿新生儿期疾病分布情况及影响其转归的因素。方法：对长沙市三家医院2008年961例住院早产儿资料进行调查。结果：呼吸系统疾病最常见,占73.8%,其次为新生儿感染（败血症）（39.4%）和神经系统疾病（38.3%）。不同胎龄、不同出生体重早产儿循环系统疾病的发生率差异无统计学意义（P>0.05）,但呼吸系统疾病、新生儿感染（败血症）、神经系统疾病等其他疾病的发生率及生后28 d治愈、好转率各组间差异均有统计学意义（P<0.05）。胎龄、出生体重增加是住院早产儿生后28 d结局的保护因素,新生儿窒息、高胆红素血症、新生儿硬肿症等是危险因素。结论：住院早产儿新生儿期常见疾病为呼吸系统疾病、新生儿感染（败血症）、神经系统疾病;随胎龄、出生体重增加,多数疾病的发生率呈下降趋势,治愈、好转率呈上升趋势。住院早产儿生后28 d转归的保护因素是胎龄和出生体重增加,危险因素有新生儿窒息、高胆红素血症、新生儿硬肿症等。     

Acute apparently life threatening events in 62 infants: anamnestic and clinical data

Among 62 infants admitted to our hospital after an acute and apparently threatening event which according to the parents required active intervention either by tactile stimulation, or shaking or mouth to mouth ventilation were 21 previously preterm babies, 12 of whom with additional perinatal risk factors, and 41 fullterm infants, 3 of them being subsequent siblings of a SIDS victim. More than 80% of the ALTEs occurred during presumed sleep while the remaining 20% were observed during wakefullness, mostly during or shortly after feeding. The majority was said to be found pale or blue, floppy and mostly unreactive. The parents or caretakers, however, were unable to give reliable information concerning the type of breathing i.e. whether the infants were apneic or not. On admission, 71% of the pre- and 63% of the fullterms showed abnormal signs and symptoms. A total of 14 infants had symptoms of respiratory tract infections, involving the lungs in only 6 cases. An other 10 infants developed moderate enteritis after admission only; 8 of them had stool cultures positive for rotavirus antigen. On the basis of the anamnestic and clinical data including the results of the diagnostic work-up in 14 (34%) of the fullterm and 3 (14%) of the preterm infants a so far unrecognized disorder was diagnosed which in many cases gave access to a specific therapy. If the cases of infections - not including those with only mild respiratory tract involvement often found in cases of SIDs or near miss SIDS - are included in this group their number increased to 27 (43,5%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transplacental transport of IgG antibodies to preterm infants: a review of the literature

Newborn infants, especially preterm infants, have an immature immune system, which is not capable to actively protect against vaccine-preventable infections. Therefore, the newborn is dependent on transplacental transport of Immunoglobulin G (IgG), an active, FcRn receptor mediated process. Fetal IgG rises from approximately 10% of the maternal concentration at 17-22 weeks of gestation to 50% at 28-32 weeks of gestation. If transplacental acquired IgG is lower in preterm than in term infants, preterm infants are especially at risk for these vaccine-preventable diseases.The aim of this study was to review the transplacental transfer of IgG against vaccine-preventable diseases (measles, rubella, varicella-zoster, mumps, Haemophilus influenza type B, diphtheria, tetanus, pertussis and polio) to (pre)term infants and to identify factors that influence the transplacental transfer of these antigens.After selection, 18 studies on transplacental transport to preterm infants were included. In general, these studies showed for all antibodies that preterm infants have lower antibody concentrations compared with term infants. Maternal and infants antibody concentrations showed a strong correlation in 7 of the included studies. Infant antibody concentration was not associated with parity, maternal age, height or weight. Infants of vaccinated mothers had lower anti-measles antibody titers than infants of natural immunized mothers. IgG titers of preterm infants decrease earlier in life below protective antibody titers than term infants. Combined with their immature immune system, this puts preterm infants at increased risk for vaccine-preventable diseases.     

Cerebral palsy in preterm infants: a population-based case-control study of antenatal and intrapartal risk factors

Previous studies have indicated that foetomaternal infection increases the risk of spastic cerebral palsy (CP) in term infants, whereas this association appears to be less evident in preterm infants. The aim of this study was to analyse infection-related risk factors for spastic CP in preterm infants. A population-based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57 moderately preterm (32-36 wk), born in 1983-90, were included and matched with a control group (n = 296). In total, 154 maternal, antenatal and intrapartal variables were retrieved from obstetric records. In the entire group, histological chorioamnionitis/pyelonephritis, long interval between rupture of membranes and birth, admission-delivery interval <4 h and Apgar scores of <7 at 1 min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and 10 min were strongly associated with an increased risk. Abruptio placentae, Apgar scores <7 at 1 min and pathological non-stress test (reason for delivery) were significant risk factors of CP only in the moderately preterm and hemiplegic groups, whereas fever before delivery was a significant risk factor in the very preterm and spastic diplegic groups. Antibiotics during pregnancy was associated with CP only in the spastic diplegic CP group. Conclusion: Antenatal infections marginally increased the risk of CP. Low Apgar score and abruptio placentae were associated with CP, especially in moderately preterm infants with hemiplegic CP.     

早产儿侵袭性真菌感染的预防和治疗

新生儿,特别是早产儿是侵袭性真菌感染的高危人群,造成早产儿相关疾病的发病率和病死率的增加,如何预防和治疗侵袭性真菌感染,减少其对早产儿的损伤,成为新生儿科医生关注的热点.本文主要对早产儿侵袭性真菌感染的预防和治疗作重点阐述.     

早中期早产儿神经发育不良相关的感染因素分析

目的 探讨与早中期早产儿在校正18月龄时神经发育不良相关的感染因素。方法 以2015年6月至2018年12月入住新生儿重症监护病房并在早产高危儿门诊随访的胎龄28~ < 34周早产儿为研究对象。校正18月龄时采用修订版Bayley婴幼儿发展量表进行神经发育评估,运用单因素和多因素logistic回归分析探讨对神经发育产生影响的感染相关因素。结果 纳入早中期早产儿138例,其中校正18月龄时神经发育不良者59例。单因素logistic回归分析显示早中期早产儿神经发育不良与晚发感染、血培养阳性、其他系统感染有关（P < 0.05）;多因素logistic回归分析显示晚发感染是神经发育不良的独立危险因素（OR=1.510,95% CI：1.133~3.600,P < 0.05）。结论 晚发感染可增加早中期早产儿神经发育不良的风险。     

Neutrophils from term and preterm newborn infants express the high affinity Fcgamma-receptor I (CD64) during bacterial infections.

The high affinity Fcgamma-receptor I (FcgammaRI, CD64) is normally expressed only to a very low extent by neutrophils. During bacterial infections, however, neutrophils from adult patients significantly increase their expression of FcgammaRI. Stimulation through FcgammaRI is a highly effective way to improve various aspects of neutrophil function, including phagocytosis. In our study the expression of FcgammaRI on neutrophils from preterm (n = 9) and term (n = 3) newborn infants, children (n = 14), and adults (n = 6) during the early phase of an acute bacterial infection was investigated. Our results showed that neutrophils from newborn infants with bacterial infection expressed FcgammaRI to a significantly higher extent than both noninfected preterm (p < 0.001) and term (p < 0.001) newborn infants and that neutrophils from preterm neonates expressed FcgammaRI to the same extent as neutrophils from term neonates and older infants, children, and adults. No difference in the neutrophil cell surface expression of FcgammaRI during bacterial infections was found among newborn infants, children, and adults. Expression of FcgammaRI probably represents an important mechanism to improve neutrophil phagocytosis as well as other aspects of neutrophil function during bacterial infections, especially in preterm infants. Our study indicates that measurement of cell surface expression of FcgammaRI on neutrophils could be a useful indicator of severe bacterial infections in preterm and term neonates, as well as in older children and adults.     

Thymic size in preterm neonates: a sonographic study

AIM: To assess the variation in size of the thymus in vivo in preterm neonates and to identify relations between thymic size and gestational age (GA), birthweight, occurrence of postnatal infections and maternal alcohol and tobacco intake during pregnancy. METHODS: Eighty preterm neonates with a GA between 24 and 36 wk, and a birthweight between 490 and 4110 g were examined between days 0 and 19 after birth. The thymic size was assessed by sonography as a volume estimate, the so-called thymic index (Ti). The median Ti was 5.2 (1.2-17.9). Ti was positively correlated with birthweight and GA and negatively correlated with occurrence of postnatal infection (p < 0.01, p = 0.03, p = 0.05, R2 = 0.68). A correlation between thymic size and maternal alcohol and tobacco intake was not demonstrated. CONCLUSION: It is possible to assess the size of the thymus by sonography in very low-birthweight and preterm neonates. A normal range for Ti in preterm neonates has been established. The sonographic method is a safe and effective technique for measuring the size of the thymus in preterm infants.     

Granulocyte function in premature infants before the 34th week of pregnancy and in mature newborn infants]

BACKGROUND: Preterm and term neonates have an increased risk to develop severe bacterial infections. Impairment of neutrophil function may be responsible for this increased risk. Other diseases related to prematurity like retinopathia of prematurity (ROP) or broncho-pulmonary dysplasia (BPD) on the other hand may be due to poorly controlled O2-radical production. PATIENTS AND METHODS: Blood samples of 112 premature (34 weeks of gestation and older) and term neonates were analysed. Blood samples of 23 healthy adults (18 to 50 years old) served as controls. O2-radical production and phagocytosis of neutrophils were determined by flow cytometry, using a commercial test system. RESULTS: Under the experimental conditions applied, the capacity to produce O2-radicals following vigorous stimulation (E. coli) is comparable between neutrophils of preterm/term neonates and healthy adults. However, unstimulated or weakly stimulated (fMLP) neutrophils of preterm and term neonates show a statistically higher O2-radical production as neutrophils of the control group. The production of oxygen radicals increases during the first 10 days of the life. The capability of neutrophils to phagocytose E. coli is significantly lower in newborns (preterm and term) compared to the adult controls. CONCLUSIONS: The values reported here for phagocytosis and O2-radical production utilizing a commercially available test system may serve as "preliminary normal values" for neonates. No differences were found between the groups of neonates with and without infection. Impaired neutrophil-phagocytosis possibly contributes to the increased risk of preterm and term neonates to acquire bacterial infections. The increased spontaneous O2-radical production, on the other hand, may play a role for the development of so called "free radical diseases" such as ROP or BPD. However, our results cannot add further proof to this hypothesis.     

Low thymic size in preterm infants in the neonatal intensive care unit,a possible marker of infection? A prospective study from birth to 1 year of age

Aim: To study the growth of the thymus in preterm infants. Methods: Ultrasonographic thymic size (Ti) was studied in 80 preterm infants (gestational age 24–36 weeks) from birth to discharge from the neonatal intensive care unit (NICU). Thirty‐three of these infants were followed to 1 year of age. Results: At birth, the median Ti was 5.2 compared with 11.8 in term infants. At discharge, the median Ti was 10.0 and not significantly different from Ti in term infants at birth (p = 0.22). The size of the thymus was significantly associated with postmenstrual age and weight (both p < 0.01). Infections during admission were negatively associated with the size of the thymus (p < 0.01). During the first 3 months after discharge, preterm infants had a significantly higher frequency of infections than did term infants (p = 0.002); hereafter, the preterm infants had significantly fewer infections than term infants (p = 0.002). The median Ti in preterm infants and term infants at 1 year of age was 21.1 and 17.3, respectively. This difference was not statistically significant (p = 0.41). Conclusions: Growth of thymus was not compromised by preterm birth. Ti is negatively associated with the frequency of infections in preterm neonates submitted to NICU.     

Underlying maternal and pregnancy‐related conditions account for a substantial proportion of neonatal morbidity in late preterm infants

Aim

We studied the impact of maternal and pregnancy‐related conditions and the effect of gestational age itself, on the health of infants born late preterm.

Methods

Singletons born in gestational weeks 34 + 0 to 41 + 6 in 1995–2013 in the southern region of Sweden were identified from a perinatal register. We found 14 030 infants born late preterm and 294 814 born at term. A hierarchical system was developed to examine the impact of pregnancy complications. The outcomes studied were as follows: neonatal death, central nervous system (CNS) or respiratory disease, infection, neonatal admission and respiratory support. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained using logistic regression analyses.

Results

Late preterm infants were at increased risk for all outcomes compared to term infants, with adjusted ORs from 13.1 (95% CI: 12.7–13.6) for neonatal admission to 2.3 (95% CI: 1.8–2.9) for infections. Late preterm birth after preterm prelabour rupture of membranes was associated with an overall lower risk compared to late preterm births due to other causes. Exposure to antepartum haemorrhage or maternal diabetes increased the risk for CNS and respiratory morbidity.

Conclusion

Morbidity decreased in late preterm infants with increasing gestational age. Underlying conditions accounted for a substantial part of the morbidity.