Preterm Prolonged Rupture Of Membranes Research Articles

Neurodevelopmental outcomes of preterm neonates receiving rescue inhaled nitric oxide in the first week of age: a cohort study

ObjectiveTo assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF).MethodsIn this retrospective cohort study, we...

Prolonged Preterm Rupture of Membranes Associated with Neonatal Disseminated Herpes Simplex Virus Type 1 at Birth: Is There a Role for Preemptive Test and Treat Strategies in High-Risk Populations?

Neonatal herpes simplex virus (HSV) prevention focuses on mothers with prior or current genital disease [1]. However, primary asymptomatic maternal HSV-1 or HSV-2 cause most cases [2–5]. Prolonged membrane rupture is a major risk [6]. This newborn was born at 29 weeks after 14 days of ruptured membranes to an asymptomatic mother. No maternal HSV testing was performed. Vesicular lesions were present at birth with HSV DNA in skin, blood, and CSF; placental histology demonstrated viral particles (Figure 1). Primary maternal HSV-1 without protective antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies and limited placental antibody transfer were documented (Table 1) [7–10]. This case highlights the need for screening and preemptive treatment of high-risk subpopulations. Financial support. This work was supported by grants from National Institutes of Health, R01AI134367, R21AI147992, R01HD098977, and the Price Family Foundation. AMM is supported by Einstein-Montefiore CTSA training grant (TL1 TR002557).

Maternal Fetal Health

Maternal Fetal Health

Diagnostic Approach to Pulmonary Hypertension in Premature Neonates.

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease in premature infants following respiratory distress at birth. With increasing survival of extremely low birth weight infants, alveolar simplification is the defining lung characteristic of infants with BPD, and along with pulmonary hypertension, increasingly contributes to both respiratory morbidity and mortality in these infants. Growth restricted infants, infants born to mothers with oligohydramnios or following prolonged preterm rupture of membranes are at particular risk for early onset pulmonary hypertension. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy, results in developmental lung arrest leading to BPD with pulmonary hypertension (PH). Early recognition of PH in infants with risk factors is important for optimal management of these infants. Screening tools for early diagnosis of PH are evolving; however, echocardiography is the mainstay for non-invasive diagnosis of PH in infants. Cardiac computed tomography (CT) and magnetic resonance are being used as imaging modalities, however their role in improving outcomes in these patients is uncertain. Follow-up of infants at risk for PH will help not only in early diagnosis, but also in appropriate management of these infants. Aggressive management of lung disease, avoidance of hypoxemic episodes, and optimal nutrition determine the progression of PH, as epigenetic factors may have significant effects, particularly in growth-restricted infants. Infants with diagnosis of PH are managed with pulmonary vasodilators and those resistant to therapy need to be worked up for the presence of cardio-vascular anomalies. The management of infants and toddlers with PH, especially following premature birth is an emerging field. Nonetheless, combination therapies in a multi-disciplinary setting improves outcomes for these infants.

Short-term and long-term outcomes of preterm neonates with acute severe pulmonary hypertension following rescue treatment with inhaled nitric oxide

ObjectiveTo describe short-term and long-term outcomes of preterm neonates with severe acute pulmonary hypertension (aPHT) in relation to response to rescue inhaled nitric oxide (iNO) therapy.DesignRetrospective cohort studyover a 6...

Risk of Early-Onset Sepsis following Preterm, Prolonged Rupture of Membranes with or without Chorioamnionitis.

This study aims to determine whether preterm prolonged rupture of membranes (PPROM) increases the risk for early-onset sepsis (EOS) in preterm infants. Retrospective cohort study of infants 30 to 34 weeks' gestation from 2005 to 2014. Exposure to PPROM (rupture of membranes ≥ 18 hours) or chorioamnionitis (maternal temperature ≥ 38°C during delivery plus notation of chorioamnionitis in the medical record) was collected. The primary outcome was proven or suspected EOS. A total of 2,192 infants were included. Overall, 1,750 (80%) were not exposed to PPROM or chorioamnionitis (group 1), 381 (17%) were exposed to PPROM without chorioamnionitis (group 2), and 61 (3%) were exposed to chorioamnionitis ± PPROM (group 3). There was no difference in the incidence of proven or suspected EOS between groups 1 and 2 (5.4 vs. 5.5%, p = 0.86). Group 3 had a higher rate of EOS (24.6%) relative to groups 1 and 2 (p < 0.001). In multivariate analysis, risk of EOS was 4.1 times higher in infants exposed to chorioamnionitis. PPROM did not increase the risk of EOS in bivariate or multivariate analysis. In the absence of chorioamnionitis, PPROM does not increase the risk of proven or clinically suspected EOS in 30 to 34 weeks' gestation infants.

G130(P) What is the efficacy of nitric oxide in neonates with preterm prolonged rupture of membranes?

Background Preterm prolonged rupture of membranes continues to be associated with significant morbidity and mortality, predominantly as a result of respiratory failure due to pulmonary hypoplasia and/or pulmonary hypertension. Although iNO is not routinely indicated for treatment of respiratory failure in the preterm infant successful treatment with inhaled nitric oxide (iNO) has been reported in small studies. Methods Retrospective review of neonates with PPROM of latency 14 days or more at gestation less than 34 weeks at birth from June 2008–July 2014. Infants with respiratory failure who were treated with nitric oxide were compared to those who had not received iNO, and timing of treatment was correlated with outcome. Results 41 patients with PPROM (range 23 +2 –33 +5 days) were included, of whom 61% (25/41) had respiratory failure with oxygenation index >20 (OI 53.5 (IQR 38–87). Respiratory failure was associated with ultrasound confirmed oligohydramnios (p = 0.01) and male gender (p = 0.03). 64% (16/25) of infants with respiratory failure were started on iNO. Within the iNO group all patients demonstrated significant reduction in OI following iNO; 81% responding within 1 h. The median OI prior to iNO 59 (IQR 47–88) vs after iNO administration 7.3 (IQR 4.7–10.8) (p Conclusion PPROM is associated with significant mortality (22%) and morbidity with 92% BPD and 29% IVH grade 3 or above. These babies show significant respiratory failure with median OI of x in the first day of life. iNO improved OI in all cases, although there was no significant effect on BPD, IVH or mortality. Our data supports the findings of earlier studies that iNO can improve respiratory function in PPHN associated with PPROM. Further prospective trials are needed to assess long term outcomes in this subsection of babies with severe respiratory failure following preterm delivery.

A study on the outcome of neonates with sepsis at the Lagos University Teaching Hospital

Background : Neonatal morbidity and mortality are major public health challenges in our local environment with a huge percentage of deaths in the neonatal period attributable to sepsis. Aim : The aim of the study was to assess the factors that affect patients’ outcome with respect to sepsis in neonates. Methods : This was a prospective descriptive cross sectional study. Neonates with proven and suspected sepsis were recruited into the study. Outcome was assessed based on the length of hospital stay and mortality. Clinical response to treatment was also assessed. Results : Nine factors were identified as risk factors for mortality, birth weight (< 2500g P = 0.000, OR = 7.214, CI = 2.5 – 21.0), prolonged rupture of membranes (PROM) (P = 0.014, OR = 2.470, 95% CI = 1.2 -5.1), prolonged preterm rupture of membranes (PPROM) P = (0.046. OR = 2.1, 95% CI = 0.9 -4.6) multiple gestation (P = 0.009), an infectious clinical diagnosis (P = 0.046, OR = 0.480), frequent changes in antibiotics (P = 0.013). Others were a low Apgar score (P = 0.000), presence of organisms in intravenous fluids (P = 0.042, OR = 0.2, 95% CI = 0.02 – 1.3 and the presence of organisms in the blood stream (P = 0.007). Conclusion : This study determined the mortality rate in our environment due to sepsis to be 15.7%. Risk factors for a poor outcome include low birth weight, perinatal period, and maternal illness in pregnancy and isolation of a pathogen from the blood stream. Key words: Neonatal sepsis, prolonged stay, mortality, bactec 9050, microbact 12a, risk factors

Case 2: A Difficult Airway in the Delivery Room

A late-preterm female infant is born at 36 weeks’ gestation via spontaneous vaginal delivery to a 27-year-old, gravida 1, now para 1 mother whose pregnancy is complicated by polyhydramnios and preterm prolonged rupture of membranes. The infant has poor tone, no respiratory effort, a heart rate less than 100 beats per minute, and craniofacial abnormalities. The infant receives positive pressure ventilation and chest compressions with unsuccessful attempts at intubation by the pediatrician at 4 minutes of age. Heart rate is unresponsive to positive pressure ventilation. Laryngeal mask airway (LMA) is placed at 7 minutes of age after several unsuccessful endotracheal intubation attempts by anesthesiologists. Heart rate improves after placement of the LMA to more than 100 beats per minute. Apgar scores are 1 at 1 minute, 1 at 5 minutes, 2 at 10 minutes, 5 at 15 minutes, 6 at 20 minutes, and 7 at 25 minutes. A peripheral intravenous cannula is inserted, and a 10-mL/kg dose of normal saline bolus is given. Blood culture is performed, and arrangements are made for transfer to a tertiary care neonatal intensive care unit (NICU). A capillary blood gas is performed before transport, which reveals the following: pH, 7.05; Pco2, 73 mm Hg; Po2, 58 mm Hg; bicarbonate, 20 mEq/L (20 mmol/L); and base deficit, −10 mEq/L (−10 mmol/L). The infant receives ventilatory support with an LMA in place until arrival of the transport team. Before transport, endotracheal intubation is attempted again by the transport team with a video laryngoscope and is unsuccessful, …

Inhaled nitric oxide in preterm infants with prolonged preterm rupture of the membranes: a case series.

The available evidence does not support the routine use of inhaled nitric oxide (iNO) in the care of premature infants. We present a case series of 22 preterm infants born after prolonged preterm premature rupture of membranes and oligohydramnios with respiratory failure. Oxygenation index decreased significantly after commencement of iNO.

The influence of prolonged preterm premature rupture of the membranes on neonatal outcome of the presenting and non-presenting twin

ObjectiveTo compare the neonatal outcome in twin gestations complicated by prolonged preterm premature rupture of membranes (PPROM). Study designBetween the years 2000 and 2010 we identified 48 women with twin pregnancies who were diagnosed as having PPROM and a latency period to delivery >24h. We compared the neonatal morbidity and mortality between the presenting and non-presenting twins, assuming that the rupture occurred in the lower sac. Importantly, in 30 women we were able to identify the location of the ruptured sac by ultrasound examination demonstrating oligohydramnion. In these 30 cases, neonatal outcome of fetuses in the ruptured sac and those in the intact sac were compared. ResultsThe median gestational age was 31 weeks (range 28–33) with a median latency period between PPROM and delivery of 9 days (range 1–18).Of the identified ruptures 90% (27/30) occurred in the lower sac (presenting twin). There was no significant difference between the presenting and non-presenting twin in terms of neonatal morbidity and mortality. Moreover, no difference was found when fetuses with ruptured sac were compared to those with intact membrane sac. Importantly, the outcomes were not affected by the length of the latency period. ConclusionThe current study results demonstrated that the outcome of fetuses exposed to prolonged preterm rupture of membranes is similar to that of fetuses with intact membranes. Our data suggest that rupture of membranes per se did not cause any deleterious clinical manifestations or lead to clinical discordant inflammation and poor neonatal outcome, supporting a conservative management of twin pregnancies with PPROM.

Acute kidney injury in a single neonatal intensive care unit in Turkey

Although advances in perinatal medicine have increased the survival rates of critically ill neonates, acute kidney injury (AKI) is still one of the major causes of mortality and morbidity in neonatal intensive care units. This study aimed to determine the prevalence of AKI and analyze demographic data and risk factors associated with the mortality or morbidity. Of 1992 neonates hospitalized between January 2009 and January 2011, 168 with AKI were reviewed in the study. The diagnosis of AKI was based on plasma creatinine level >1.5 mg/dL, which persists for more than 24 hours or increases more than 0.3 mg/dL per day after the first 48 hours of birth while showing normal maternal renal function. The prevalence of AKI was 8.4%. The common cause of AKI was respiratory distress syndrome, followed by sepsis, asphyxia, dehydration, congenital anomalies of the urinary tract, congenital heart disease, and medication. The prevalence of AKI in neonates with birth weight lower than 1500 g was about three-fold higher than in those with birth weight higher than 1500 g (P<0.05). Pregnancy-induced hypertension, preterm prolonged rupture of membranes, and administration of antenatal corticosteroid were associated with increased risk of AKI (P<0.05). Umbilical vein catheterization, mechanical ventilation and ibuprofen therapy for patent ductus arteriosus closure were found to be associated with AKI (P<0.05). The overall mortality rate was 23.8%. Multivariate analysis revealed that birth weight less than 1500 g, mechanical ventilation, bronchopulmonary dysplasia, anuria, and dialysis were the risk factors for the mortality of infants with AKI. Prenatal factors and medical devices were significantly associated with AKI. Early detection of risk factors can reduce the mortality of AKI patients.

Transient Defect in Nitric Oxide Generation after Rupture of Fetal Membranes and Responsiveness to Inhaled Nitric Oxide in Very Preterm Infants with Hypoxic Respiratory Failure

To study antenatal risk factors and inflammatory responses during hypoxic respiratory failure (HRF) in infants of very low gestational age (VLGA, ≤32.0 weeks). Of a cohort of 765 VLGA infants, 144 required mechanical ventilation. Airway specimens from these patients were prospectively studied. Infants who developed HRF (oxygenation index >25) with echocardiographic diagnosis of pulmonary hypertension were treated with inhaled nitric oxide (iNO). Three gestation comparison groups were formed on the basis of specific antenatal complications: prolonged preterm rupture of membranes (PPROM), spontaneous preterm birth, and preeclampsia. Chest radiographs were studied and airway specimens were analyzed for concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-8, IL-10, IL-12p70, IL-1β, and nitrite + nitrate over 4 days. Seventeen (2.2% of all VLGA infants) developed HRF. In all 17 cases, PPROM complicated the antenatal course; these infants responded to iNO, regardless of infection or PPROM. The chest radiographs of HRF and non-HRF PPROM infants were similar. Airway proinflammatory cytokines and nitrite + nitrate levels were low in infants with HRF, but they increased during iNO treatment and remained elevated after discontinuation of iNO. Each of the 3 comparison groups had different and characteristic patterns of airway cytokines and nitrite + nitrate levels. Seven percent of VLGA infants with preterm rupture of membranes and 15% of those with PPROM developed HRF, characterized by pulmonary hypertension that acutely responds to iNO. These infants may have a transient deficiency in the inflammatory response, including a defect in nitric oxide generation in airspaces.

A case of neonatal sepsis with acute liver failure

Baby JR was born by caesarean section at 34 weeks gestation fter premature rupture of membranes (ROM) which lasted ∼48h, ccompaniedbyclinical concernsofmaternal chorioamnionitisdue o raised white cell count (WCC) and C reactive protein (CRP). The aby was initially well with no respiratory distress. However, due o the prolonged preterm ROM and signs of maternal chorioamionitis the baby was transferred to special care baby unit (SCBU) nd given benzylpenicillin and gentamicin. Over the next 4 days the child remained well. Blood cultures ere negative and CRP remained normal. Consequently, the empircal antibiotics that had been commenced at birth were stopped nd he was discharged from special care to be cared for on he postnatal ward with his mother. At this time the neonatal eam were made aware of the maternal history of Chlamydia trahomatis (see below), so an eye swab was taken and sent to the aboratory for C. trachomatis, Herpes Simplex Virus (HSV) 1 and and adenovirus testing by real time Polymerase Chain Reacion (PCR) assays. The sample was negative for all pathogens ested. Onday6of life thebabybecameunwellwith lethargy, pallor and uskiness during feeds. Hewas therefore readmitted to special care

Dry Lung Syndrome: A Distinct Clinical Entity

Infants with preterm prolonged rupture of membranes can present with immediate onset of pulmonary insufficiency and need aggressive ventilatory support. Dry lung syndrome remains an under-recognised clinical entity and very few cases are reported in the literature, though a working definition has been previously proposed. The proposed underlying etiopathogenesis for this is functional hypoplasia of the lung where higher than usual ventilatory pressure for initial 1-2days can improve oxygenation. This study presents two cases which had similar antenatal and immediate postnatal course, but had diametrically opposite outcomes. Strategies to optimise outcomes in the setting of early premature rupture of the membranes should include antenatal assessment of mothers with monitoring of the liquor volume as well as the strength of foetal breathing movements, in-utero transfer with delivery in perinatal centres and attendance by neonatal staff of appropriate experience.

Differing Prevalence and Diversity of Bacterial Species in Fetal Membranes from Very Preterm and Term Labor

BackgroundIntrauterine infection may play a role in preterm delivery due to spontaneous preterm labor (PTL) and preterm prolonged rupture of membranes (PPROM). Because bacteria previously associated with preterm delivery are often difficult to culture, a molecular biology approach was used to identify bacterial DNA in placenta and fetal membranes.Methodology/Principal findingsWe used broad-range 16S rDNA PCR and species-specific, real-time assays to amplify bacterial DNA from fetal membranes and placenta. 74 women were recruited to the following groups: PPROM <32 weeks (n = 26; 11 caesarean); PTL with intact membranes <32 weeks (n = 19; all vaginal birth); indicated preterm delivery <32 weeks (n = 8; all caesarean); term (n = 21; 11 caesarean). 50% (5/10) of term vaginal deliveries were positive for bacterial DNA. However, little spread was observed through tissues and species diversity was restricted. Minimal bacteria were detected in term elective section or indicated preterm deliveries. Bacterial prevalence was significantly increased in samples from PTL with intact membranes [89% (17/19) versus 50% (5/10) in term vaginal delivery p = 0.03] and PPROM (CS) [55% (6/11) versus 0% (0/11) in term elective CS, p = 0.01]. In addition, bacterial spread and diversity was greater in the preterm groups with 68% (13/19) PTL group having 3 or more positive samples and over 60% (12/19) showing two or more bacterial species (versus 20% (2/10) in term vaginal deliveries). Blood monocytes from women with PTL with intact membranes and PPROM who were 16S bacterial positive showed greater level of immune paresis (p = 0.03). A positive PCR result was associated with histological chorioamnionitis in preterm deliveries.Conclusion/SignificanceBacteria are found in both preterm and term fetal membranes. A greater spread and diversity of bacterial species were found in tissues of women who had very preterm births. It is unclear to what extent the greater bacterial prevalence observed in all vaginal delivery groups reflects bacterial contamination or colonization of membranes during labor. Bacteria positive preterm tissues are associated with histological chorioamnionitis and a pronounced maternal immune paresis.

Aerosolized Iloprost in the Treatment of Pulmonary Hypertension in Extremely Preterm Infants: A Pilot Study

In premature infants with preterm prolonged rupture of membranes, death after birth is often due to persistent pulmonary hyper-tension. Aerosolized iloprost was used to treat pulmonary hypertension due to prolonged preterm rupture of fetal membranes (7-56 days) in four extremely low-birthweight neonates (23-25 weeks' gestation, weight 448-645 g) under spontaneous breathing supported by nasal continuous positive airway pressure. Inhalation dose was 2 microg/kg b.w. and between 44 and 65 inhalations were performed in each patient starting within the first hour of life over a total of several days. Single inhalations lasted 5 min and were not repeated until 60 min had elapsed. After the first inhalation, the PaO2/FiO2 mean ratio increased from 65 (range 35-114) to 194 (148-250) mmHg and oxygenation requirements decreased within the next 7 days. Echocardiography similarly showed reduction in pulmonary resistance. We observed no severe side effects on blood pressure or prolonged bleeding time during inhalation. Iloprost inhalation might therefore be an additional treatment for improving oxygenation in cases of persistent pulmonary hypertension in extremely low-birthweight infants under spontaneous breathing. Further randomized clinical studies are required to establish the role of iloprost in this setting.

Antenatal inflammation and infection in chronic lung disease of prematurity.

In spite of improved neonatal care, chronic lung disease of prematurity (CLD) remains a major cause of morbidity and mortality in extremely preterm infants. Our current understanding is that antenatal infection can trigger intra-uterine inflammation which then promotes preterm labour. Recent studies suggest that antenatal infection and inflammation can also increase the preterm infant's susceptibility to develop CLD. It may be that exposure of the fetal lung to high concentrations of pro-inflammatory cytokines is the cause of this increased susceptibility. One candidate for initiating intra-uterine inflammation is ascending infection by the vaginal commensal Ureaplasma urealyticum (Uu). Antibiotics administered to mothers prior to delivery appear to improve the neonatal outcome in cases of preterm prolonged rupture of membranes, but not in cases of preterm labour with intact membranes. Uu can be transmitted vertically to the airways of the preterm infant, but the role of Uu in causing CLD remains uncertain. Small trials of antibiotics given to preterm infants after delivery have not shown any consistent benefit in reducing CLD. Although CLD remains a significant problem for the extremely preterm infant, it is likely that molecular biology techniques, such as the polymerase chain reaction, will enhance the detection of antenatal infection and further our understanding of the pathogenesis of CLD.

Fetal growth rates in patients with preterm prolonged rupture of membranes

Fetal growth rates in patients with preterm prolonged rupture of membranes