Prolonged latency after preterm premature rupture of membranes: an evaluation of histologic condition and intracranial ultrasonic abnormality in the neonate born at <28 weeks of gestation

OBJECTIVE: The purpose of this study was to evaluate whether infants who were delivered at <28 weeks of gestation after prolonged latency in pregnancies that were complicated by preterm premature rupture of membranes are at increased risk of histologic chorioamnionitis and intracranial ultrasound abnormalities. STUDY DESIGN: A retrospective cohort analysis of 430 singleton infants born at <28 weeks of gestation in five hospitals (January 1991 through December 1993) with at least one of three protocol cranial scans read by a consensus committee and with placental pathologic evidence. Outcome variables were placental (histologic chorioamnionitis, fetal vasculitis) and neonatal (intraventricular hemorrhage, echolucencies, ventriculomegaly). Latency was divided into five intervals, and outcomes in the longer four intervals were compared with those in infants who were delivered at <1 hour after membrane rupture. Each outcome-latency relationship was evaluated in a logistic model that was controlled for confounders. RESULTS: Odds ratios and CIs for each latency interval that was controlled for confounders that included gestational age, maternal race, antenatal steroid and antibiotic administration, and delivery mode show a statistically significant increase in the risk of histologic chorioamnionitis and fetal vasculitis. Models for intraventricular hemorrhage, ventriculomegaly, and echolucencies failed to demonstrate significant differences with increasing latency. CONCLUSIONS: Ascending transcervical infection after preterm premature rupture of membranes is documented by the increasing odds ratios of placental inflammation. The odds of ultrasonically detectable brain abnormalities, however, did not increase with increasing latency.     

Proinflammatory Cytokines: A Link Between Chorioamnionitis and Fetal Brain Injury

Objective: To review the etiology of impaired fetal neurodevelopment — in particular, the relationship between chorioamnionitis, cytokines, and cerebral palsy.Data Sources: A MEDLINE search was performed for all clinical and basic science studies published in the English literature from 1966 to 2002. Key words or phrases used were chorioamnionitis, cerebral palsy, fetal brain damage, fetal CNS injury, infection in pregnancy, proinflammatory cytokines in pregnancy, proinflammatory cytokines in infection, and preterm labour or birth. All relevant human and animal studies were included.Study Selection: Fetal brain injury remains a major cause of lifelong morbidity, incurring significant societal and health care costs. It has been postulated that chorioamnionitis stimulates maternal/fetal proinflammatory cytokine release, which is damaging to the developing fetal nervous system. Elevated cytokine concentrations may interfere with glial cell development and proliferation in the late second trimester of pregnancy, when the central nervous system is most vulnerable. Increasing numbers of epidemiological and basic science studies found through MEDLINE searches support this hypothesis. Treatment options aimed at etiologic factors may lead to improved neurodevelopmental outcomes.Conclusions: Clearly, some relationship exists between chorioamnionitis, cytokines, and the development of cerebral palsy, but the severity and duration of exposure required to produce fetal damage remains unknown. Future research addressing these issues may aid in clinical decision-making. As well, the elucidation of mechanisms of cytokine action may aid in early treatment options to prevent or limit development of fetal brain injury.     

早产儿脑室周围白质软化的相关因素研究

摘要：目的　分析导致早产儿脑损伤的相关危险因素。方法　以2006年1月至2009年6月入住安徽省立儿童医院新生儿科的443例早产儿为研究对象,分为脑室周围白质软化（PVL）组（125例）与无PVL组（318例）,按PVL级别分为非囊性PVL组（116例）和囊性PVL组（9例）,采用头颅超声诊断技术早期诊断早产儿PVL,用多因素分析影响PVL及其不同级别的高危因素。 结果　单因素分析显示：胎龄、出生体重、分娩方式、低体温、生后感染、呼吸暂停、血糖、心肌酶谱、C-反应蛋白（CRP）和血清白蛋白在PVL组和无PVL组之间差异有统计学意义（P < 0.05或P < 0.01）。多因素Logistic回归分析显示：出生体重低、母亲低剖宫产率、生后感染及血清白蛋白和心肌酶谱水平高是早产儿发生PVL的危险因素,另外,生后感染是发生囊性PVL的危险因素。结论　出生体重低、母亲低剖宫产率、生后感染及血清白蛋白和心肌酶谱高是早产儿发生PVL的危险因素,另外,生后感染的早产儿发生囊性PVL的风险较高。     

Correlation between fetal heart rate reactivity and mortality and severe neurological morbidity in extremely low birth weight infants

Objective: To determine the correlation between specific fetal heart rate (FHR) abnormalities and the incidence of death, severe (grade 3–4) intraventricular hemorrhage (IVH) and periventricular echogenicity (PVE) in extremely low birth weight infants (ELBW) within the first 4 days after birth. Methods: The study included live-born ELBW infants ≤ 30 weeks’ gestation who were born in 2000–2007 at Kaplan Medical Center, Rehovot, Israel, and, who had FHR monitoring during the 24?h before delivery and cranial ultrasound during the first 4 days of life. FHR pattern was analyzed for the presence of baseline rate, reactivity, variability and decelerations. Results: 96 infants with mean birth weight 757?±?150?g and mean gestational age 25.8?±?1.5 weeks were included. By 4 days of life, 23/96 (24%) died, 17/96 (18%) developed severe IVH and 31/96 (32%) had PVE. Absence of reactivity was significantly associated with increase in both death (p?=?0.02, OR 3.45, 95% CI: 1.22–9.47 and severe IVH (p?=?0.029, OR 3.33, 95% CI: 1.25–10) but not with PVE. Other FHR parameters were not associated with adverse outcome. Conclusion: These results suggest that FHR reactivity may be of value in predicting short-term outcome in ELBW infants. This may be helpful in counseling parents with imminent extremely preterm birth.     

早产儿囊性脑室周围白质软化症与低碳酸血症及机械通气关系

摘要】目的探讨早产儿囊性脑室周围白 质软化症(cPVL)与低碳酸血症及机械通气的关系。方法比较cPVL与非cPVL早产儿(各10例)生后3d内发生的低碳酸血症(至少2次PaCO2<3.33kPa) 情况以及每天机械通气参数，两组在胎龄、出生体重、性别及临床情况方面统计均无差异。结果cPVL组发生低碳酸血症几率为70%，明显高于非 cPVL组的20%(P=0.02)，而两组每天机械通气参数无差异。结论早产儿cPVL的发生与低碳酸血症有关，似乎与过度通气无关。     

Chorioamnionitis risk and neonatal outcome in preterm premature rupture of membranes

Objective The objective of this study was to compare the neonatal outcome in patients with preterm premature rupture of membranes with and without clinical chorioamnionitis.Study design This is a retrospective study that included 254 pregnant women with preterm rupture of membranes. The study group was divided according to the presence or absence of clinical chorioamnionitis defined as the presence of two or more of the following criteria: maternal temperature >38°C on two or more occasions 1 h apart, maternal tachycardia (120 beats/min), uterine tenderness, foul smelling amniotic fluid, maternal leukocytosis 20,000 mm^–3 with bands and positive C reactive protein. Also the study population was divided according to the use of tocolysis. Exclusion criteria included multiple pregnancy, fetal congenital anomalies, diabetes mellitus and severe preeclampsia. Amniotic fluid was collected from the cervix or from the transabdominal amniocentesis. Antibiotics and tocolysis were used according to the hospital protocols. Parametric and nonparametric statistics were used for comparisons.Results There were no significant differences in birth weight, Apgar scores at 1 and 5 min, rates of respiratory distress syndrome, intraventricular hemorrhage and necrotizing enterocolitis between patients with and without clinical chorioamnionitis or between women who received tocolysis and the ones that did not receive tocolysis. In cases of clinical chorioamnionitis and when tocolysis was used the neonates stayed longer in the neonatal intensive care unit (NICU).Conclusion Patients with preterm premature rupture of membranes and clinical chorioamnionitis have similar neonatal outcomes than the ones without clinical chorioamnionitis.     

The near-term (late preterm) human brain and risk for periventricular leukomalacia: a review

Historically the major focus in neonatal neurology has been on brain injury in premature infants born less than 30 gestational weeks. This focus reflects the urgent need to improve the widely recognized poor neurological outcomes that occur in these infants. The most common underlying substrate of cerebral palsy in these premature infants is periventricular leukomalacia (PVL). Nevertheless, PVL also occurs in near-term (late preterm), as well as term, infants, as documented by neuroimaging and autopsy studies. In both very preterm and late preterm infants, gray matter injury is associated with PVL. In this review, we discuss the cellular pathology of PVL and the developmental parameters in oligodendrocytes and neurons that put the late preterm brain at risk in the broader context of brain development and injury close to term. Further research is needed about the clinical and pathologic aspects of brain injury in general and PVL in particular in late preterm infants to optimize management and prevent adverse neurological outcomes in these infants that, however subtle, may be currently underestimated.     

Death or survival with major morbidity in VLBW infants born at Brazilian neonatal research network centers

Objective: To analyze unfavorable outcomes at hospital discharge of preterm infants born at Brazilian public university centers.

Methods: Prospective cohort of 2646 inborn infants with gestational age 23–33 weeks and birth weight 400–1499?g, without malformations, born at 20 centers in 2012–2013. Unfavorable outcome was defined as in-hospital death or survival at hospital discharge with ≥1 major morbidities: bronchopulmonary dysplasia (BPD) at 36 corrected weeks, intraventricular hemorrhage (IVH) grades 3–4, periventricular leukomalacia (PVL) or surgically treated retinopathy of prematurity (ROP).

Results: Among 2646 infants, 1390 (53%) either died or survived with major morbidities: 793 (30%) died; 497 (19%) had BPD; 358 (13%) had IVH 3–4 or PVL; and 84 (3%) had ROP. Logistic regression adjusted by center showed association of unfavorable outcome with: antenatal steroids (OR 0.70; 95%CI 0.55–0.88), C-section (0.72; 0.58–0.90), gestational age <30 (4.00; 3.16–5.07), being male (1.44; 1.19–1.75), small for gestational age (2.19; 1.72–2.78), 5th-min Apgar <7 (3.89; 2.88–5.26), temperature at NICU admission <36.0?°C (1.42; 1.15–1.76), respiratory distress syndrome (3.87; 2.99–5.01), proven late sepsis (1.33; 1.05–1.69), necrotizing enterocolitis (3.10; 2.09–4.60) and patent ductus arteriosus (1.69; 1.37–2.09).

Conclusions: More than half of the VLBW infants born at public university level 3 Brazilian hospitals either die or survive with major morbidities.     

Chorioamnionitis increases neonatal morbidity in pregnancies complicated by preterm premature rupture of membranes

OBJECTIVE: To compare morbidities of neonates born to women who developed chorioamnionitis after premature preterm rupture of membranes versus those who did not. STUDY DESIGN: We reviewed outcomes in singleton pregnancies with confirmed premature preterm rupture of membranes at 24 weeks or beyond that resulted in delivery less than 37 weeks. Management of premature preterm rupture of membranes included the use of antibiotics, betamethasone if less than 32 weeks, and expectant management with induction at 34 weeks or greater. Composite neonatal major and minor morbidity rates were compared between pregnancies complicated by chorioamnionitis and those that were not. RESULTS: From August 1998 to August 2000, 430 cases of premature preterm rupture of membranes were identified among 6003 deliveries (7.2%). Thirteen percent of women (56/430) with premature preterm rupture of membranes developed chorioamnionitis. The incidence of chorioamnionitis increased significantly with decreasing gestational age. The composite neonatal major morbidity rate was significantly higher in neonates whose mothers developed chorioamnionitis (55%) versus those who did not (18%, P < .0001). In a multiple logistic regression model, chorioamnionitis ( P < .0001), infant gender ( P = .007), latency ( P = .03), and gestational age at delivery ( P < .0001) were significantly associated with composite neonatal morbidity. CONCLUSION: Neonatal morbidities are significantly higher among pregnancies with premature preterm rupture of membranes complicated by chorioamnionitis when compared with pregnancies that were not.     

Comparison of antibiotic regimens in preterm premature rupture of membranes: neonatal morbidity and 2-year follow-up of neurologic outcome

Objectives: The objective of this study was to compare neonatal morbidity and neurologic outcome at 2 years between groups treated with antibiotics regimens consisting clarithromycin and erythromycin in preterm premature rupture of the membranes (pPROM) patients delivered before 32 weeks of gestation.

Methods: This was a retrospective study comparing neonatal morbidity as primary outcome measures and the neurological outcome at 2 years as secondary outcome.

Results: A total of 166 women were included: 80 treated with erythromycin and 86 treated with clarithromycin. The median gestational age at delivery was greater in clarithromycin group (p?=?0.005). There was no significant difference in latency (p?=?0.77). The incidence of histological chorioamnionitis was significantly lower in clarithromycin group (p?=?0.004). By multivariable analysis adjusting confounding variables, the incidence of bronchopulmonary dysplasia and intraventricular hemorrhage (≥Grade 3) was lower in clarithromycin group (BPD; OR 0.34, 95% CI [0.13–0.90]), IVH; OR 0.23, 95% CI [0.06–0.91], respectively). Other morbidities and neurologic outcome at 2 years’ corrected age showed no statistically significant difference between two groups.

Conclusion: We suggest that clarithromycin-based regimen may be worth considering as an alternative choice of erythromycin in pPROM patients.     

Significant intraventricular hemorrhage is more likely in very preterm infants born by vaginal delivery: a multi-centre retrospective cohort study

Objectives: The objective of this study is to determine the association between mode of delivery (vaginal delivery [VD] versus cesarean section [CS]) and the rate of significant intraventricular hemorrhage (sIVH) in preterm infants.

Methods: A multicenter retrospective cohort study, based on data collected from the Vermont Oxford Network database. Infants born between 23 and 31⁺⁶ weeks of gestational age between 2001 and 2014 were identified. Exposure was the mode of birth (VD versus CS). Primary outcome was development of sIVH. Data were analyzed using univariate and multivariate statistical methods.

Results: A total of 1575 infants were eligible. Nine hundred and two infants were born by CS and 673 by VD. Univariable analysis showed that infants born vaginally were more likely to have sIVH (p?p?p?=?.010) and have a longer hospital stay (p?=?.006). After adjusting for available confounders, multivariable analysis persistently showed that infants between 23 and 27 weeks born by CS were less likely to develop sIVH [OR 1.61 (1.01–2.58), p?=?.049].

Conclusions: sIVH is less common in very preterm infants (23–27 weeks of gestation) delivered by CS. However, neurodevelopmental risks associated with survival at this early age, as well as increased maternal morbidities must also be considered.     

Method of delivery and intraventricular haemorrhage in extremely preterm infants

Objectives.?It has been reported that caesarean delivery (CD) protects against intraventricular haemorrhage (IVH) in the extremely preterm infant, but it is not known whether this effect involve the more severe grades of IVH. Thus, our aim was to confirm the correlation between the occurrence of IVH and the mode of delivery, and to evaluate this correlation for each grade of IVH.

Methods.?All infants with gestational age (GA)?≤?28 weeks admitted to the neonatal intensive care unit of a tertiary hospital were studied for each grade IVH and major complications rate.

Results.?We found that vaginally born infants had a higher rate of each grade of IVH, but the increase was statistically significant only for grade 3 IVH (18% vs. 2%, p?<?0.0001) and all grades IVH (45% vs. 20%, p?<?0.0001). Multivariate analysis demonstrated that CD (RR: 0.42, 95% CI 0.28–0.63), birth weight?≥?800?g (RR: 0.48, 95% CI 0.32–0.73), 27–28 weeks of GA (RR: 0.38, 95% CI 0.25–0.60) and antenatal steroids (0.66, 95% CI 0.22–0.46) decrease independently the risk of developing IVH.

Conclusions.?Our study demonstrates that CD decreases the risk of developing IVH in extremely preterm infants including the most severe grades of IVH.     

Maternal omega-3 fatty acid supplementation protects against lipopolysaccharide-induced white matter injury in the neonatal rat brain

Objectives: Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants, and no specific treatment currently exists for this condition. We have evaluated whether maternal omega-3 fatty acid (ω3 FA) treatment reduces endotoxin-induced PVL in the developing rat brain. Methods: Wistar rats with dated pregnancies were fed a standard diet or a diet enriched in ω3 FA (70% docosahexaenoic acid + 30% eicosapentaenoic acid mixture) during gestation. Intraperitoneal injection of lipopolysaccharide (LPS) was administered consecutively on the 18th and 19th embryonic days to establish the endotoxin-induced PVL rat model. The animals were divided into four groups: (i) control, (ii) PVL, (iii) PVL+low-dose ω3 FA and (iv) PVL+high-dose ω3 FA. At day P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments. Results: High-dose maternal ω3 FA treatment reduced brain weight loss. Maternal ω3 FA treatment given either in low or high doses greatly decreased caspase-3 immunoreactivity and increased myelin basic protein immunoreactivity, indicating a decrease in apoptosis and hypomyelination. Conclusion: Considering that no specific treatment is available for PVL, maternal ω3 FA supplementation may provide a nutritional strategy to limit periventricular white matter damage caused by infections during pregnancy.     

Maternal blood endotoxin activity in pregnancies complicated by preterm premature rupture of membranes

Objective: To compare maternal blood endotoxin activity (EA) in women with preterm premature rupture of membranes (PPROM) with gestational age (GA) matched controls; to evaluate serial EA till birth in PPROM and its correlation with latency to delivery.

Methods: We followed singleton preterm pregnancies from admission with PPROM until birth. Uncomplicated, GA-matched pregnancies served as controls. Demographics, birth and neonatal outcomes were collected. EA (EAA?) was assessed serially in PPROM and at study entry in controls. EA was compared using Mann Whitney and Wilcoxon tests, p value <.05 was considered significant.

Results: We recruited 20 cases of PPROM and 20 controls. Demographics were similar between groups. Mean GA of PPROM was 29.0?±?2.2 weeks and median latency was 7.5 (IQR 14.1) weeks. Median EA at admission following PPROM was significantly elevated over controls (0.43 (0.18) versus 0.36 (0.2); p?p?=?.2) following PPROM. However, on comparing cases with latency to delivery ≤7 days (n?=?10) versus >7 days (n?=?10), there was a significant drop in EA in the latter group (0.44 (0.2) versus 0.34 (0.2); p?相似文献   

Neurodevelopmental outcomes of premature infants with severe intraventricular hemorrhage

Objective: Our objective was to determine the neurodevelopmental outcome at 18–24 months’ of corrected age (CA) in preterm infants with severe intraventricular hemorrhage (IVH).

Methods: This was a retrospective cohort study of all preterm infants who were <37 weeks’ gestation, had Grade 3–4 IVH, were admitted between January 2009 and December 2010 and discharged. The cohort was divided into three groups. Group 1 was defined as infants born with a birth weight (BW) less than 1000?g, group 2 was defined as infants born with a BW between 1000 and 1500?g and group 3 was defined as infants born with a BW between 1501 and 2500?g. Severe IVH was defined as the presence of grade 3–4 IVH on cranial ultrasound. Cranial ultrasound was performed in the first week of life and subsequently at weekly intervals by a radiologist. A comprehensive assessment including hearing, vision, neurological and developmental evaluation with Bayley Scales of Infant Development, Second edition was performed by the experienced researchers at 18–24 months’ CA. Neurodevelopmental impairment (NDI) was defined as at the presence of one or more of the following: cerebral palsy; Mental Developmental Index score lower than 70; Psychomotor Developmental Index score lower than 70; bilateral hearing impairment; or bilateral blindness.

Results: From January 2009 to December 2010, a total of 138 infants were diagnosed as severe IVH (grade 3–4). Of them, 74 (71.1%) infants (group 1?=?31, group 2?=?29 and group 3?=?14 infants) completed the follow-up visit and evaluated at 18–24 months’ CA. Median Apgar score (p?p?p?p?p?p?p?=?0.014, respectively). The duration of hospitalization and mortality rates consistent with the degree of prematurity were significantly higher in group 1 compared to groups 2 and 3 (p?=?0.03 and p?=?0.01). Among the long-term outcomes, the rates of CP and NDI did not differ between the groups (p?=?0.68 and p?=?0.068).

Conclusion: Our results demonstrated that long-term outcomes of preterm infants did not differ between the groups classified according to the BW at two years of age. This has leaded to the conclusion that severe IVH is alone represents a significant risk factor for poor neurodevelopmental outcome in this already high-risk population.     

Delayed cord clamping and inotrope use in preterm infants

Objective: To evaluate the impact of delayed cord clamping (DCC) on need for inotropic support and mean arterial blood pressure (MABP).

Methods: This is a single-center, prospective case-control study of premature infants, born <32 weeks gestation, who underwent DCC in comparison to a matched control group who underwent immediate cord clamping (ICC). The primary outcomes were the differences in MABP and inotropic medication used over the first week of life. Secondary outcomes included the admission hemoglobin, need for blood transfusion, and rates of intraventricular hemorrhage (IVH). Infants were matched on EGA, birth weight, sex, antenatal corticosteroid and magnesium exposure, and presence of chorioamnionitis.

Results: Hundred and fifty-eight infants (DCC n?=?79, ICC n?=?79) were included. Demographic factors were similar between groups. DCC infants had a higher admission hemoglobin (p?p?=?.03), fewer median transfusions (p?=?.03), and were discharged at an earlier post-menstrual age (p?=?.04). When controlling for other factors, DCC was not associated with a reduction in inotrope use (p?=?.22) but was associated with a reduction in high-grade IVH (p?=?.01). There was no difference in MABP between the groups.

Conclusions: DCC is not associated with a reduction in the use of inotropes or a difference in MABP.     

Placental villous hypermaturation is associated with idiopathic preterm birth

Abstract

Objective: Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB.

Methods: Secondary analysis of 82 placental samples from women with PTB obtained from a multicenter trial of repeat versus single antenatal corticosteroids. Samples were centrally reviewed by a single placental pathologist masked to clinical outcomes. The histopathologic criterion for infection was the presence of acute chorioamnionitis defined as neutrophils marginating into the chorionic plate. Placental villous hypermaturation (PVH) was defined as a predominance of terminal villi (similar to term placenta) with extensive syncytial knotting. Idiopathic PTB comprised a group without another known etiology such as preeclampsia, IUGR or infection.

Results: Acute chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The frequency of PVH in idiopathic PTB (26/31?=?84%) was similar to cases with IUGR or preeclampsia (16/18?=?89%), but significantly more common than PVH in the group with acute chorioamnionitis (10/33?=?30%) (p?<?0.001).

Conclusions: PVH, which is a histologic marker of relative placental insufficiency, is a common finding in idiopathic PTB.     

Placental histologic patterns and neonatal seizure,in preterm premature rupture of membrane

Objective: To investigate the relationship between placenta and perinatal outcomes, in preterm infants born to mothers with preterm premature rupture of fetal membrane (PPROM).

Methods: We report detailed histology of placentas and perinatal outcomes of infants from 79 PPROM pregnancies. Placental histologic pattern and adverse perinatal outcomes were assessed by logistic regression, adjusting for gestational age at birth, birth weight and interval from rupture of membrane to delivery.

Results: Mean gestational age at membrane rupture was 29.5?±?3.4 weeks. The incidence of histologic chorioamnionitis (HCA), fetal inflammatory response (FIR) and vascular thrombotic abnormalities in placental histologic examination were 63.3, 25.3 and 78.5%, respectively. Neonates with FIR showed significantly higher incidence of periventricular leukomalacia (PVL) (85% versus 59.3%, p?=?0.0364) at brain ultrasonography, than neonates without FIR, in univariate analysis, but not in logistic regression analysis. In logistic regression analysis, the odds ratio of low Apgar score at 1?min in the neonates with clinical chorioamnionitis was 5.009 (95% CI, 1.242–20.195). The odds ratio of neonatal seizure in the neonates with FIR and vascular thrombotic problem was 7.486 (95% CI, 1.617–34.653).

Conclusions: Our findings support the association between FIR with vascular thrombotic problem in placenta and neonatal seizure, in pregnancies with PPROM.