Josef Cortez

Plasma concentrations of angiogenic/anti-angiogenic factors have prognostic value in women presenting with suspected preeclampsia to the obstetrical triage area: a prospective study.

Abstract Objective: To prospectively determine the prognostic value of maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng) and soluble vascular endothelial growth factor receptors-1 and -2 (sVEGFR-1 and -2) in identifying patients with suspected preeclampsia (PE), who require preterm delivery (PTD) or develop adverse outcomes. Study design: This prospective cohort study included 85 consecutive patients who presented to the obstetrical triage area at 20–36 weeks with a diagnosis of “rule out PE.” Patients were classified as: 1) those who remained stable until term (n = 37); and 2) those who developed severe PE and required PTD (n = 48). Plasma concentrations of PlGF, sEng and sVEGFR-1 and -2 were determined by ELISA. Results: Patients with PlGF/sVEGFR-1 ≤0.05 multiples of the median (MoM) or PlGF/sEng ≤0.07 MoM were more likely to deliver preterm due to PE [adjusted odd ratio (aOR) 7.4 and 8.8], and to develop maternal (aOR 3.7 and 2.4) or neonatal complications (aOR 10.0 and 10.1). Among patients who presented <34 weeks of gestation, PlGF/sVEGFR-1 ≤ 0.035 MoM or PlGF/sEng ≤0.05 MoM had a sensitivity of 89% (16/18), specificity of 96% (24/25) and likelihood ratio for a positive test of 22 to identify patients who delivered within 2 weeks. The addition of the PlGF/sVEGFR-1 ratio to standard clinical tests improved the sensitivity at a fixed false-positive rate of 3% (p = 0.004) for the identification of patients who were delivered due to PE within 2 weeks. Among patients who had a plasma concentration of PlGF/sVEGFR-1 ratio ≤0.035 MoM, 0.036-0.34 MoM and ≥0.35 MoM, the rates of PTD <34 weeks were 94%, 27% and 7%, respectively. Conclusions: The determination of angiogenic/anti-angiogenic factors has prognostic value in patients presenting to the obstetrical triage area with suspected PE for the identification of those requiring preterm delivery and at risk for adverse maternal/neonatal outcomes.

Bacteria and endotoxin in meconium-stained amniotic fluid at term: could intra-amniotic infection cause meconium passage?

Abstract Background: Meconium-stained amniotic fluid (MSAF) is a common occurrence among women in spontaneous labor at term, and has been associated with adverse outcomes in both mother and neonate. MSAF is a risk factor for microbial invasion of the amniotic cavity (MIAC) and preterm birth among women with preterm labor and intact membranes. We now report the frequency of MIAC and the presence of bacterial endotoxin in the amniotic fluid of patients with MSAF at term. Materials and methods: We conducted a cross-sectional study including women in presumed preterm labor because of uncertain dates who underwent amniocentesis, and were later determined to be at term (n = 108). Patients were allocated into two groups: (1) MSAF (n = 66) and (2) clear amniotic fluid (n = 42). The presence of bacteria was determined by microbiologic techniques, and endotoxin was detected using the Limulus amebocyte lysate (LAL) gel clot assay. Statistical analyses were performed to test for normality and bivariate comparisons. Results: Bacteria were more frequently present in patients with MSAF compared to those with clear amniotic fluid [19.6% (13/66) versus 4.7% (2/42); p < 0.05]. The microorganisms were Gram-negative rods (n = 7), Ureaplasma urealyticum (n = 4), Gram-positive rods (n = 2) and Mycoplasma hominis (n = 1). The LAL gel clot assay was positive in 46.9% (31/66) of patients with MSAF, and in 4.7% (2/42) of those with clear amniotic fluid (p < 0.001). After heat treatment, the frequency of a positive LAL gel clot assay remained higher in the MSAF group [18.1% (12/66) versus 2.3% (1/42), p < 0.05]. Median amniotic fluid IL-6 concentration (ng/mL) was higher [1.3 (0.7–1.9) versus 0.6 (0.3–1.2), p = 0.04], and median amniotic fluid glucose concentration (mg/dL) was lower [6 (0–8.9) versus 9 (7.4–12.6), p < 0.001] in the MSAF group, than in those with clear amniotic fluid. Conclusion: MSAF at term was associated with an increased incidence of MIAC. The index of suspicion for an infection-related process in postpartum women and their neonates should be increased in the presence of MSAF.

Randomized placebo-controlled trial of sucrose analgesia on neonatal skin blood flow and pain response during heel lance.

Objectives:To evaluate the effect of oral sucrose on skin blood flow (SBF; perfusion units; PU) measured by Laser Doppler Imager (LDI) in term newborns and pain response (Neonatal Infant Pain Scale score; NIPS score) during heel lance; (2) determine SBF changes during heel lance; and (3) the relationship between SBF and NIPS. Materials and Methods:Term infants ⩽7 days old (n=56) undergoing routine heel lance were randomized to pretreatment with 2.0 mL oral 24% sucrose (n=29) or sterile water (n=27) in a double-blinded, placebo-controlled trial. SBF was assessed by LDI scans and NIPS scores at 10 minutes before lance, immediately after lancing, and 5 minutes after blood extraction. Mean SBF and median NIPS scores were compared between groups using General Linear Model or Kruskal-Wallis. Regressions examined the relationship between SBF immediately after heel lance and NIPS score. Results:Mean SBF and median NIPS scores immediately after heel lance were lower in sucrose-treated infants (167.9±15.5 vs. 205.4±16.0 PU, P=0.09; NIPS 1 [interquartile range 0 to 4] vs. NIPS 3 [interquartile range 0 to 6], P=0.02), although no significant difference in mean SBF. During heel lance NIPS score was predictive of SBF. An increase of 1 in NIPS score was associated with 11 PU increase in SBF (R2=0.21; P=0.09) for sucrose, and 16 PU increase for placebo-treated infants (R2=0.20; P=0.014). Conclusions:Increased SBF assessed by LDI is a pain response among term neonates after routine heel lance, which was not completely attenuated by oral sucrose administration. Increased SBF is associated with NIPS scores. Sucrose analgesic efficacy evidenced by decreased NIPS scores for the sucrose group. Association of SBF with NIPS scores suggests that LDI is potentially useful for assessing newborn procedural pain.

Secreted phospholipase A2 is increased in meconium-stained amniotic fluid of term gestations: potential implications for the genesis of meconium aspiration syndrome

Abstract Background: Meconium-stained amniotic fluid (MSAF) represents the passage of fetal colonic content into the amniotic cavity. Meconium aspiration syndrome (MAS) is a complication that occurs in a subset of infants with MSAF. Secreted phospholipase A2 (sPLA2) is detected in meconium and is implicated in the development of MAS. The purpose of this study was to determine if sPLA2 concentrations are increased in the amniotic fluid of women in spontaneous labor at term with MSAF. Materials and methods: This was a cross-sectional study of patients in spontaneous term labor who underwent amniocentesis (n = 101). The patients were divided into two study groups: (1) MSAF (n = 61) and (2) clear fluid (n = 40). The presence of bacteria and endotoxin as well as interleukin-6 (IL-6) and sPLA2 concentrations in the amniotic fluid were determined. Statistical analyses were performed to test for normality and bivariate analysis. The Spearman correlation coefficient was used to study the relationship between sPLA2 and IL-6 concentrations in the amniotic fluid. Results: Patients with MSAF have a higher median sPLA2 concentration (ng/mL) in amniotic fluid than those with clear fluid [1.7 (0.98–2.89) versus 0.3 (0–0.6), p < 0.001]. Among patients with MSAF, those with either microbial invasion of the amniotic cavity (MIAC, defined as presence of bacteria in the amniotic cavity), or bacterial endotoxin had a significantly higher median sPLA2 concentration (ng/mL) in amniotic fluid than those without MIAC or endotoxin [2.4 (1.7–6.0) versus 1.7 (1.3–2.5), p < 0.05]. There was a positive correlation between sPLA2 and IL-6 concentrations in the amniotic fluid (Spearman Rho = 0.3, p < 0.05). Conclusion: MSAF that contains bacteria or endotoxin has a higher concentration of sPLA2, and this may contribute to induce lung inflammation when meconium is aspirated before birth.

Frequency of Otitis Media Based on Otoendoscopic Evaluation in Preterm Infants

Objective This study was conducted to determine the frequency of otitis media in preterm neonates using otoendoscopy and tympanometry. Study Design Prospective study. Setting Wayne State University, Hutzel Women’s Hospital Neonatal Intensive Care Unit. Subjects and Methods Eighty-six preterm infants were included (gestational age <36 weeks). Otoendoscopy and tympanometry were performed to detect the presence of otitis media. Kappa statistic and logistic regression were used for statistical analysis. Results Otoendoscopy was performed in 85 patients. The frequency of otoendoscopy-diagnosed otitis media was 72.9% (62/85). Tympanometry could be performed on 69.76% of the ears. There was 73.5% agreement between the findings of tympanometry and those of otoendoscopy. The association between the presence of otitis media and gestational age at birth was statistically significant. The lower the gestational age, the higher the frequency of otoendoscopy-diagnosed otitis media (P = .001). Conclusion Otoendoscopically diagnosed otitis media is frequent in preterm neonates. There was agreement between the results of tympanometry and those of otoendoscopy. The frequency of otitis media increased with lower gestational age.

Near Infrared Spectroscopy as a Biomarker for Necrotising Enterocolitis following Red Blood Cell Transfusion

Red blood cell transfusions (RBCTs) have been associated with necrotising enterocolitis (NEC) in preterm infants (PTIs). The objective of this report is to evaluate the use of regional cerebral (cRSO2) and splanchnic (sRSO2) tissue oximetry measured using near infrared (NIR) spectroscopy as biomarkers to evaluate the association between RBCT and NEC in a secondary analysis of a hypothesis-generating Phase I exploratory study of biomarker development. cRSO2 and sRSO2 were monitored in PTIs receiving RBCTs. Three time periods were defined: pre-RBCT (12 h prior to RBCT), during RBCT and post-RBCT (24 h after RBCT). Three groups were defined: absence of NEC within ±7 days of index RBCT (Group 1); NEC within 7 days prior (Group 2) and within 7 days after RBCT (Group 3). Mean hourly sRSO2 and cRSO2 were compared between groups across RBCT periods using the mixed effect method. Neonatal postnatal morbidities and treatments were included as covariates. Fifty-seven infants (median gestational age 27 weeks) received 147 RBCTs (Group 1 = 120, Group 2 = 19, and Group 3 = 8) during NIR spectroscopy monitoring. In the adjusted analysis, there was a significant change in sRSO2 during the course of RBCT (p = 0.0405) with significant interaction with group (p < 0.0001) such that in Groups 1 and 2, sRSO2 increased over RBCT periods, whereas in Group 3, sRSO2 declined over RBCT periods. cRSO2 increased during the course of the RBCT (p < 0.0001) with significant interaction with group (p = 0.0258). cRSO2 and sRSO2 increased significantly following RBCT in infants without NEC or NEC diagnosed prior to RBCT. Post-RBCT sRSO2 decreased in infants who were subsequently diagnosed with NEC in this exploratory secondary analysis of a Phase I Biomarker study. sRSO2 response may potentially be a biomarker to identify infants who are likely to develop NEC post-RBCT that needs to be validated in larger prospective “hypothesis-testing” randomised controlled trials.

Postnatal respiratory compliance among premature ventilated neonates associated with variable timing and dosing of antenatal steroids

BACKGROUND Antenatal steroids (ANSs) improve the respiratory compliance of premature infants. Many premature neonates are born before the administration of a complete course of ANS. OBJECTIVE The objective of this study was to evaluate the respiratory system compliance (Crs) of premature (≤ 32 weeks gestation), intubated neonates in relation to the dose, and timing of ANS administration. STUDY DESIGN Neonates (n = 61) were divided into four groups based on the dose and timing of ANS exposure: Group 1: no ANS; Group 2: partial course (one dose of betamethasone); Group 3: complete course (two doses of betamethasone administered within 2 weeks of delivery); and Group 4: remote course (two doses of betamethasone administered > 2 weeks before delivery). Crs was measured by single-breath occlusion technique. RESULTS Indexed respiratory compliance ± standard error of the mean (mL/cmH2O/kg) adjusted for gestational ages were 0.359 ± 0.074, 0.366 ± 0.080, 0.625 ± 0.038, and 0.505 ± 0.060 for Groups 1 to 4, respectively. The mean indexed Crs in complete ANS was significantly higher than that of no ANS (0.266 ± 0.085; p = 0.016) as well as partial ANS group (0.259 ± 0.086; p = 0.025). CONCLUSIONS Crs after birth was significantly higher among premature intubated neonates born to mothers who received a complete course of ANS within 2 weeks, compared with no ANS or a partial course of ANS.

Auditory Brainstem Response and Distortion-Product Otoacoustic Emission Studies in Neonates at High-Risk for Hearing Loss:

Objectives: 1) Recognize that preterm infants less than 1300g have a well-described and markedly increased incidence of hearing loss, possibly attributed to reversible early middle ear pathology. 2) Analyze if distortion product oto-acoustic emissions (DPOAE) and/or auditory brainstem response (ABR) could be useful adjuncts when used in addition to tympanometry and otoendoscopy in evaluation of neonatal hearing and middle ear. Methods: Institutional review board approved prospective study at a tertiary care center neonatal intensive care unit with subjects undergoing ABR, DPAOE, tympanometry, and otoendoscopy studies within 72 hours of birth and in scheduled increments until discharge. From January 2010 to date, 77 neonates have been examined. Results: Our results confirmed that DPOAE could be a reliable and repetitive study from 24 weeks of gestational age and onward. When comparing traditional tympanometry to DPOAE, 85.7% of examinations with type B or C tympanometry also had an abnormal DPOAE result. Conversely, 62.5% of patients with type A tympanometry had a normal DPOAE result. Furthermore, in patients with a clinical diagnosis of AOM or OME, 66.7% percent had an abnormal DPAOE result. Regarding ABR threshold studies, there were several limitations with data acquisition due to incubator interference and background noise; thus, the potential of ABR in this population remains to be determined. Conclusions: This study suggests that DPOAE can be used as a reliable hearing evaluation in the neonatal population. Additionally, it may serve as a useful adjunct and insight into evaluating neonatal middle ear pathology, especially when combined with tympanometry and otoendoscopy.

Incidence of Otitis Media in Preterm Infants

Objectives: 1) Determine if objective tympanometry findings correlate with the subjective endoscopy finding in diagnosing middle ear disease (AOM or OME) in premature infants. 2) Determine if the incidence of middle ear disease increases with lower gestational weight in premature infants. Methods: Our prospective study includes 76 preterm infants, (< 36wks) admitted to the Neonatal Intensive Care Unit (NICU) at Harper Hospital. Endoscopic otoscopy and tympanometry were performed to detect the presence of otitis media within the first 4 days of birth. The Fisher exact test was used for statistical analysis. Results: 1) 44 ears had normal otoendoscopic findings, of which 35 had normal tympanometry findings (79.54 %). 63 ears had middle ear disease, of which 48 showed abnormal reading on tympanometry (76.19 %). 2) 26 babies weighed less than 1300 grams at birth (average gestational age 26.99 weeks), 23 of which had middle ear disease on otoendoscopy. 25 babies weighed more than 1300 grams (average gestational age 31.85 weeks), 12 of which had middle ear disease on otoendoscopy. A P value of 0.0025 suggests a significant correlation between low birth weight and middle ear disease. Conclusions: We demonstrate that endoscopic otoscopy technique correlates with objective tympanometry data, although there are several limitations to comparing these techniques. We provide evidence that the incidence of otitis media in LBW preterm infants is higher based on otoendoscopy.