Search

Background: Placental lesions consistent with maternal vascular underperfusion (MVU) are thought to be pathogenically linked to preeclampsia, small-for-gestational-age newborns, fetal death, and spontaneous preterm labor and delivery; yet, these lesions cannot be diagnosed antenatally. We previously reported that patients with such conditions and lesions have an abnormal profile of the angiogenic placental growth factor (PlGF) and antiangiogenic factors (eg, soluble vascular endothelial growth factor receptor [sVEGFR]-1)., Objective: The objectives of this study were to: (1) examine the relationship between the maternal plasma PlGF/sVEGFR-1 concentration ratio (referred to herein as angiogenic index-1) and the burden of histologic placental features consistent with MVU; and (2) test the hypothesis that angiogenic index-1 can identify patients in the midtrimester who are destined to deliver before 34 weeks of gestation with multiple (ie, ≥3) histologic placental features consistent with MVU., Study Design: A 2-stage case-cohort sampling strategy was used to select participants from among 4006 women with singleton gestations enrolled from 2006 through 2010 in a longitudinal study. Maternal plasma angiogenic index-1 ratios were determined using enzyme-linked immunosorbent assays. Placentas underwent histologic examination according to standardized protocols by experienced pediatric pathologists who were blinded to clinical diagnoses and pregnancy outcomes. The diagnosis of lesions consistent with MVU was made using criteria proposed by the Perinatal Section of the Society for Pediatric Pathology. Weighted analyses were performed to reflect the parent cohort; "n*" is used to reflect weighted frequencies., Results: (1) Angiogenic index-1 (PlGF/sVEGFR-1) concentration ratios were determined in 7560 plasma samples collected from 1499 study participants; (2) the prevalence of lesions consistent with MVU was 21% (n* = 833.9/3904) and 27% (n* = 11.4/42.7) of women with ≥3 MVU lesions delivered before 34 weeks of gestation; (3) a low angiogenic index-1 (<2.5th quantile for gestational age) in maternal plasma samples obtained within 48 hours of delivery had a sensitivity of 73% (n* = 8.3/11.4; 95% confidence interval [CI], 47-98%), a specificity of 94% (n* = 3130.9/3316.2; 95% CI, 94-95%), a positive likelihood ratio of 12.2, and a negative likelihood ratio of 0.29 in the identification of patients who delivered placentas with ≥3 MVU lesions at <34 weeks; (4) prospectively, at 20-23 weeks of gestation, a maternal plasma concentration of angiogenic index-1 <2.5th quantile identified 70% (n* = 7.2/10.3; 95% CI, 42-98%) of patients who delivered placentas with ≥3 MVU lesions before 34 weeks (specificity, 97% [n* = 2831.3/2918; 95% CI, 96-98%]; positive likelihood ratio, 23; negative likelihood ratio, 0.31); and (5) among women without obstetrical complications who delivered at term, angiogenic index-1 was lower in women with than without placental lesions consistent with MVU (P < .05)., Conclusion: Maternal plasma angiogenic index-1 (PlGF/sVEGFR-1) is the first biomarker for the burden of placental lesions consistent with MVU. We propose that an accumulation of these lesions in placentas delivered before 34 weeks is a histologic counterpart of an antiangiogenic profile., (Published by Elsevier Inc.)

Background: Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants. Meconium-stained amniotic fluid (MSAF) occurs in approximately 1 of every 7 pregnancies, but only 5% of neonates exposed to MSAF develop MAS. Why some infants exposed to meconium develop MAS while others do not is a fundamental question. Patients with MSAF have a higher frequency of intraamniotic inflammation/infection than those with clear fluid. We propose that fetal systemic inflammation is a risk factor for the development of MAS in patients with MSAF., Objective: We sought to investigate whether intraamniotic inflammation and funisitis, the histopathologic landmark of a fetal inflammatory response, predispose to MAS., Study Design: A prospective cohort study was conducted from 1995 through 2009. Amniotic fluid (AF) samples (n = 1281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age ≥38 weeks). Intraamniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-8 was >23 ng/mL. Funisitis was diagnosed by histologic examination if inflammation was present in the umbilical cord., Results: The prevalence of MSAF was 9.2% (118/1281), and 10.2% (12/118) of neonates exposed to MSAF developed MAS. There were no significant differences in the median gestational age or umbilical cord arterial pH at birth between neonates who developed MAS and those who did not (each P > .1). Mothers whose newborns developed MAS had a higher median of AF matrix metalloproteinase-8 (456.8 vs 157.2 ng/mL, P < .05). Newborns exposed to intraamniotic inflammation had a higher rate of MAS than those who were not exposed to intraamniotic inflammation [13.0% (10/77) vs 0% (0/32), P = .03], as did those exposed to funisitis [31.3% (5/16) vs 7.3% (6/82); relative risk, 4.3; 95% confidence interval, 1.5-12.3]. Among the 89 newborns for whom both AF and placental histology were available, MAS was more common in patients with both intraamniotic inflammation and funisitis than in those without intraamniotic inflammation and funisitis [28.6% (4/14) vs 0% (0/28), P = .009], while the rate of MAS did not show a significant difference between patients with intraamniotic inflammation alone (without funisitis) and those without intraamniotic inflammation and funisitis [10.9% (5/46) vs 0% (0/28)]., Conclusion: The combination of intraamniotic inflammation with fetal systemic inflammation is an important antecedent of MAS. This concept has implications for the understanding of the mechanisms of disease responsible for MAS and for the development of prognostic models and therapeutic interventions for this disorder., (Published by Elsevier Inc.)

Objective: Recent studies indicate that clinical chorioamnionitis is a heterogeneous condition and only approximately one-half of the patients have bacteria in the amniotic cavity, which is often associated with intra-amniotic inflammation. The objective of this study is to characterize the nature of the inflammatory response within the amniotic cavity in patients with clinical chorioamnionitis at term according to the presence or absence of 1) bacteria in the amniotic cavity and 2) intra-amniotic inflammation., Materials and Methods: A retrospective cross-sectional case-control study was conducted to examine cytokine and chemokine concentrations in the amniotic fluid (AF). Cases consisted of women with clinical chorioamnionitis at term (n=45). Controls were women with uncomplicated pregnancies at term who did not have intra-amniotic inflammation and were in labor (n=24). Women with clinical chorioamnionitis were classified according to the results of AF cultures, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and AF concentration of interleukin-6 (IL-6) into those: 1) without intra-amniotic inflammation, 2) with microbial-associated intra-amniotic inflammation, and 3) with intra-amniotic inflammation without detectable bacteria. The AF concentrations of 29 cytokines/chemokines were determined using sensitive and specific V-PLEX immunoassays., Results: 1) The AF concentrations of pro- and anti-inflammatory cytokines/chemokines such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), macrophage inflammatory protein-1 beta (MIP-1β), and interleukin-8 (IL-8) (except Eotaxin-3) were significantly higher in women with clinical chorioamnionitis at term than in controls (term labor without intra-amniotic inflammation); 2) patients with microbial-associated intra-amniotic inflammation, and those with intra-amniotic inflammation without detectable bacteria, had a dramatic differential expression of cytokines and chemokines in AF compared to patients with spontaneous labor without intra-amniotic inflammation. However, no difference could be detected in the pattern of the intra-amniotic inflammatory response between patients with intra-amniotic inflammation with and without detectable bacteria; and 3) in patients with clinical chorioamnionitis at term but without intra-amniotic inflammation, the behavior of cytokines and chemokines in the AF was similar to those in spontaneous labor at term., Conclusions: Patients with clinical chorioamnionitis who had microbial-associated intra-amniotic inflammation or intra-amniotic inflammation without detectable bacteria had a dramatic upregulation of the intra-amniotic inflammatory response assessed by amniotic fluid concentrations of cytokines. A subset of patients with term clinical chorioamnionitis does not have intra-amniotic infection/inflammation, as demonstrated by elevated AF concentrations of inflammation-related proteins, when compared to women in term labor with uncomplicated pregnancies, suggesting over-diagnosis. These observations constitute the first characterization of the cytokine/chemokine network in the amniotic cavity of patients with clinical chorioamnionitis at term.

Objective: The diagnosis of clinical chorioamnionitis is based on a combination of signs [fever, maternal or fetal tachycardia, foul-smelling amniotic fluid (AF), uterine tenderness and maternal leukocytosis]. Bacterial infections within the amniotic cavity are considered the most frequent cause of clinical chorioamnionitis and an indication for antibiotic administration to reduce maternal and neonatal morbidity. Recent studies show that only 54% of patients with the diagnosis of clinical chorioamnionitis at term have bacteria in the AF and evidence of intra-amniotic inflammation. The objective of this study was to examine the performance of the clinical criteria for the diagnosis of chorioamnionitis to identify patients with microbial-associated intra-amniotic inflammation (also termed intra-amniotic infection)., Materials and Methods: This retrospective cross-sectional study included 45 patients with the diagnosis of clinical chorioamnionitis at term, whose AF underwent analysis for: 1) the presence of microorganisms using both cultivation and molecular biologic techniques [polymerase chain reaction (PCR) with broad primers], and 2) interleukin (IL)-6 concentrations by enzyme-linked immunosorbent assay. The diagnostic performance (sensitivity, specificity, accuracy, and likelihood ratios) of each clinical sign and their combination to identify clinical chorioamnionitis were determined using microbial-associated intra-amniotic inflammation [presence of microorganisms in the AF using cultivation or molecular techniques and elevated AF IL-6 concentrations (≥2.6 ng/mL)] as the gold standard., Results: The accuracy of each clinical sign for the identification of microbial-associated intra-amniotic inflammation (intra-amniotic infection) ranged between 46.7% and 57.8%. The combination of fever with three or more clinical criteria did not substantially improve diagnostic accuracy., Conclusion: In the presence of a fever during labor at term, signs used to diagnose clinical chorioamnionitis do not accurately identify the patient with proven intra-amniotic infection (i.e., those with microorganisms detected by culture or molecular microbiologic techniques and an associated intra-amniotic inflammatory response).

Objective: We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a "multi-hit" model of neonatal white matter injury (WMI)., Methods: This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) live-born singleton neonates delivered at Hutzel Women's Hospital, Detroit, MI, from 2006 to 2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation., Results: A total of 425 live-born singleton neonates delivered before the 32nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [odds ratio (OR) 4.7; 95% confidence interval (CI) 1.4-15.8 vs. OR 1.3; 95% CI 0.7-2.6]. Similarly, newborns with funisitis who developed neonatal inflammation-initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6 (95% CI 1.5-8.3) vs. OR 1.7 (95% CI 0.5-5.5)]. The greater the number of these three types of inflammation documented, the higher the risk of VE (P<0.0001)., Conclusion: Chronic placental inflammation, acute fetal inflammation, and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm.

Purpose: To evaluate the feasibility of performing fetal brain magnetic resonance venography using susceptibility weighted imaging (SWI)., Materials and Methods: After obtaining informed consent, pregnant women in the second and third trimester were imaged using a modified SWI sequence. Fetal SWI acquisition was repeated when fetal or maternal motion was encountered. The median and maximum number of times an SWI sequence was repeated was four and six respectively. All SWI image data were systematically evaluated by a pediatric neuroradiologist for image quality using an ordinal scoring scheme: 1. diagnostic; 2. diagnostic with artifacts; and 3. nondiagnostic. The best score in an individual fetus was used for further statistical analysis. Visibility of venous vasculature was also scored using a dichotomous variable. A subset of SWI data was re-evaluated by the first and independently by a second pediatric neuroradiologist. Kappa coefficients were computed to assess intra-rater and inter-rater reliability., Results: SWI image data from a total of 22 fetuses were analyzed. Median gestational age and interquartile range of the fetuses imaged were 32 (29.9-34.9) weeks. In 68.2% of the cases (n = 15), there was no artifact; 22.7% (n = 5) had minor artifacts and 9.1% (n = 2) of the data was of nondiagnostic quality. Cerebral venous vasculature was visible in 86.4% (n = 19) of the cases. Substantial agreement (Kappa = 0.73; 95% confidence interval 0.44-1.00)) was observed for intra-rater reliability and moderate agreement (Kappa = 0.48; 95% confidence interval 0.19-0.77) was observed for inter-rater reliability., Conclusion: It is feasible to perform fetal brain venography in humans using SWI., (© 2013 Wiley Periodicals, Inc.)

Objective: To determine if there is an association between cervical strain, evaluated using ultrasound elastography, and spontaneous preterm delivery (sPTD) <37 weeks of gestation., Methods: One hundred and eighty nine (189) women at 16-24 weeks of gestation were evaluated. Ultrasound elastography was used to estimate cervical strain in three anatomical planes: one mid-sagittal in the same plane used for cervical length measurement, and two cross sectional images: one at the level of the internal cervical os, and the other at the level of the external cervical os. In each plane, two regions of interest (endocervix and entire cervix) were examined; a total of six regions of interest were evaluated., Results: The prevalence of sPTD was 11% (21/189). Strain values from each of the six cervical regions correlated weakly with cervical length (from r=-0.24, P<0.001 to r=-0.03, P=0.69). Strain measurements obtained in a cross sectional view of the internal cervical os were significantly associated with sPTD. Women with strain values ≤25th centile in the endocervical canal (0.19) and in the entire cervix (0.14) were 80% less likely to have a sPTD than women with strain values >25th centile [endocervical: odds ratio (OR) 0.2; 95% confidence interval (CI), 0.03-0.96; entire cervix: OR 0.17; 95% CI, 0.03-0.9]. Additional adjustment for gestational age, race, smoking status, parity, maternal age, pre-pregnancy body mass index, and previous preterm delivery did not appreciably alter the magnitude or statistical significance of these associations. Strain values obtained from the external cervical os and from the sagittal view were not associated with sPTD., Conclusion: Low strain values in the internal cervical os were associated with a significantly lower risk of spontaneous preterm delivery <37 weeks of gestation.

Objective: Massive perivillous fibrin deposition (MPFD) and maternal floor infarction (MFI) are related placental lesions often associated with fetal death and fetal growth restriction. A tendency to recur in subsequent pregnancies has been reported. This study was conducted to determine whether this complication of pregnancy could reflect maternal antifetal rejection., Methods: Pregnancies with MPFD were identified (n = 10). Controls consisted of women with uncomplicated pregnancies who delivered at term without MPFD (n = 175). Second-trimester maternal plasma was analyzed for panel-reactive anti-HLA class I and class II antibodies. The prevalence of chronic chorioamnionitis, villitis of unknown etiology, and plasma cell deciduitis was compared between cases and controls. Immunohistochemistry was performed on available umbilical vein segments from cases with MPFD (n = 4) to determine whether there was evidence of complement activation (C4d deposition). Specific maternal HLA-antibody and fetal HLA-antigen status were also determined in paired specimens (n = 6). Plasma CXCL-10 concentrations were measured in longitudinal samples of cases (n = 28 specimens) and controls (n = 749 specimens) by ELISA. Linear mixed-effects models were used to test for differences in plasma CXCL-10 concentration., Results: (i) The prevalence of plasma cell deciduitis in the placenta was significantly higher in cases with MPFD than in those with uncomplicated term deliveries (40% versus 8.6%, P = 0.01), (ii) patients with MPFD had a significantly higher frequency of maternal anti-HLA class I positivity during the second trimester than those with uncomplicated term deliveries (80% versus 36%, P = 0.01); (iii) strongly positive C4d deposition was observed on umbilical vein endothelium in cases of MPFD, (iv) a specific maternal antibody against fetal HLA antigen class I or II was identified in all cases of MPFD; and 5) the mean maternal plasma concentration of CXCL-10 was higher in patients with evidence of MPFD than in those without evidence of MFPD (P < 0.001)., Conclusion: A subset of patients with MPFD has evidence of maternal antifetal rejection., (© Published 2013. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: The objective of this study was to determine whether maternal plasma concentrations of soluble α-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM)., Methods: A cross-sectional study was conducted to include women in the following groups: i) PTL with MIAC (n=14); ii) PTL without MIAC (n=79); iii) pPROM with MIAC (n=30); and iv) pPROM without MIAC (n=33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 h of maternal blood collection. Plasma concentration of soluble α-klotho was determined by ELISA., Results: i) The median plasma concentration (pg/mL) of soluble α-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; P<0.001). ii) Among patients with PTL, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (787.0 vs. 1138.9; P=0.007). iii) Among patients with pPROM, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (766.4 vs. 1001.6; P=0.045). iv) There was no significant difference in the median plasma concentration of soluble α-klotho between PPROM without MIAC and PTL without MIAC (1001.6 pg/mL vs. 1138.9 pg/mL, respectively; P=0.5). v) After adjustment for potential confounders (maternal age, tobacco use, gestational age at venipuncture), soluble α-klotho remained significantly associated with MIAC (P=0.02); and vi) Among patients without MIAC, smoking was significantly associated with a lower median plasma concentration soluble α-klotho than in non-smokers (794.2 pg/mL vs. 1382.0 pg/mL, respectively; P<0.001); however, this difference was not observed in patients with MIAC., Conclusions: Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble α-klotho. Moreover, among patients without infection, the plasma concentration of α-klotho was lower in smokers.

Objective: To determine the relation of neonatal cranial ultrasound abnormalities to autism spectrum disorders (ASD) in low birth weight (LBW) adult survivors, a population at increased ASD risk., Study Design: This is a secondary analysis of a prospectively-followed regional birth cohort of 1105 LBW infants systematically screened for perinatal brain injury with cranial ultrasound in the first week of life and later assessed for ASD using a two-stage process [screening at age 16 years (n = 623) followed by diagnostic assessment at age 21 years of a systematically selected subgroup of those screened (n = 189)]; 14 cases of ASD were identified. For this analysis, cranial ultrasound abnormalities were defined as ventricular enlargement (indicative of diffuse white matter injury), parenchymal lesions (indicative of focal white matter injury), and isolated germinal matrix/intraventricular hemorrhage., Results: Compared with no cranial ultrasound abnormalities, any type of white matter injury (ventricular enlargement and/or parenchymal lesion) tripled the risk for screening positively for ASD [3.0 (2.2, 4.1)]. However, the risk of being diagnosed with ASD depended on type of white matter injury. With ventricular enlargement, the risk of ASD diagnosis was almost seven-fold that of no cranial ultrasound abnormality [6.7 (2.3, 19.7)], and no elevated risk was found for parenchymal lesion without ventricular enlargement [1.8 (0.2, 13.6)]. Isolated germinal matrix/intraventricular hemorrhage did not increase risk for a positive ASD screen or diagnosis., Conclusion: In LBW neonates, cranial ultrasound evidence of ventricular enlargement is a strong and significant risk factor for subsequent development of rigorously-diagnosed ASD., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To determine whether maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) at 30-34 weeks of gestation can identify patients at risk for stillbirth, late preeclampsia, and delivery of small-for-gestational-age (SGA) neonates., Study Design: A prospective cohort study included 1269 singleton pregnant women from whom blood samples were obtained at 30-34 weeks of gestation and who delivered at >34 weeks of gestation. Plasma concentrations of PlGF, sEng, and sVEGFR-1 were determined by enzyme-linked immunosorbent assay., Results: The prevalence of late (>34 weeks of gestation) preeclampsia, severe late preeclampsia, stillbirth, and SGA was 3.2% (n = 40), 1.8% (n = 23), 0.4% (n = 5), and 8.5% (n = 108), respectively. A plasma concentration of PlGF/sEng <0.3 MoM was associated with severe late preeclampsia (adjusted odds ratio, 16); the addition of PlGF/sEng to clinical risk factors increased the area under the receiver-operating characteristic curve from 0.76 to 0.88 (P = .03). The ratio of PlGF/sEng or PlGF/sVEGFR-1 in the third trimester outperformed those obtained in the first or second trimester and uterine artery Doppler velocimetry at 20-25 weeks of gestation for the prediction of severe late preeclampsia (comparison of areas under the receiver-operating characteristic curve; each P ≤ .02). Both PlGF/sEng and PlGF/sVEGFR-1 ratios achieved a sensitivity of 74% with a fixed false-positive rate of 15% for the identification of severe late preeclampsia. A plasma concentration of PlGF/sVEGFR-1 <0.12 MoM at 30-34 weeks of gestation had a sensitivity of 80%, a specificity of 94%, and a likelihood ratio of a positive test of 14 for the identification of subsequent stillbirth. Similar findings (sensitivity 80%; specificity 93%) were observed in a separate case-control study., Conclusion: Risk assessment for stillbirth and severe late preeclampsia in the third trimester is possible with the determination of maternal plasma concentrations of angiogenic and antiangiogenic factors at 30-34 weeks of gestation., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Massive perivillous fibrin deposition (MPFD) is associated with serious complications of pregnancy including recurrent spontaneous abortion, fetal growth restriction, and fetal demise. The aim of this study was to determine whether maternal plasma concentrations of angiogenic/antiangiogenic factors in MPFD differ from those of uncomplicated pregnancies., Study Design: This retrospective longitudinal case-control study included MPFD cases (n = 10) and control patients (n = 175) with uncomplicated pregnancies who were enrolled in a longitudinal study and delivered at term. Serial plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 were determined by an enzyme-linked immunosorbent assay (cases, n = 28 samples; controls, n = 723 samples). Individual analyte concentrations were averaged across gestational age at specimen collection intervals. Linear mixed models were used to test for differences in log-transformed mean analyte concentrations both overall and as a function of time., Results: The following results were found: (1) patients with MPFD had a lower mean plasma PlGF concentration (P = .03) and higher mean plasma concentrations of sVEGFR-1 and sEng (both P < .01) than controls, adjusted for potential confounders; (2) the mean plasma concentration of PlGF differed further among cases and controls as a function of gestational age interval (P < .0001); however, mean sVEGFR-1 and sEng group differences as a function of gestational age interval approached but did not reach significance (P = .09 and P = .11, respectively); (3) patients with MPFD had lower mean plasma concentrations of PlGF/sVEGFR-1 (P < .0001) and PlGF/sEng (P < .001): both of these relationships differed further as a function of gestational age interval (both P < .0001); and (4) differences in mean sVEGFR-1, sEng, and the ratios of PlGF to sVEGFR-1 and PlGF to sEng were observed before 20 weeks of gestation., Conclusion: An imbalance of angiogenic/antiangiogenic factors is present in patients with MPFD prior to the diagnosis. We propose that these changes participate in the mechanisms responsible for adverse pregnancy outcomes in patients with MPFD., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To investigate the rate of transient thyroid deficiency and treatment compliance among cases with congenital hypothyroidism diagnosed and followed-up after age 3 years by newborn screening (NBS)., Study Design: Cases detected by Michigan NBS between October 1, 2003, and December 31, 2007, and followed-up after age 3 years were included. The χ(2) and Fisher exact tests were used to test differences among followed and lost cases. Logistic regression models were used to investigate predictors of treatment cessation., Results: Roughly 45% of eligible cases were lost to follow-up, and disease state (transient or permanent congenital hypothyroidism) could not be determined for 12 cases (7.9%). Of the 72 followed cases, 34 (47%) were considered permanent congenital hypothyroidism based on thyroid imaging findings (n = 7) or an increase in medication dosage over time (n = 27). One-quarter of followed cases with congenital hypothyroidism were no longer being treated, and of these, just over 83% stopped treatment without medical supervision. Of 23 cases that underwent a medically supervised trial without thyroid hormone medication, treatment was reinstated in 20. Laboratory confirmation of euthyroidism was available for 6 of 18 cases clinically deemed transient. After adjustment, black race was the strongest predictor of treatment cessation (OR, 9.86; 95% CI, 1.82-53.31). Treatment cessation was also more common among low birth weight infants and those admitted to the neonatal intensive care unit at birth., Conclusion: We recommend that NBS programs include long-term follow-up through at least age 3 years to determine treatment compliance and disease permanence. Further research is needed to determine ideal follow-up program operations and reassessment methods for congenital hypothyroidism disease permanence. Guidelines that provide evidence-based reassessment methods would be beneficial for the healthcare providers of children with congenital hypothyroidism., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To evaluate Michigan newborn screening for congenital hypothyroidism (CH) protocol changes., Methods: This population-based study includes infants born and screened in Michigan (January 1, 1994-June 30, 2010). Screening performance is compared across 4 periods defined by the dried blood spot testing method: (1) thyroxine (T4) with backup thyrotropin, (2) tandem T4 and thyrotropin, (3) primary thyrotropin testing without serial testing, and (4) primary thyrotropin plus serial testing for births weighing <1800 g. Logistic regression is used to test for differences across periods., Results: Thyrotropin testing exhibited greater specificity overall and greater likelihood of detection with serial testing relative to primary T4 testing. Tandem T4 and thyrotropin testing appeared more sensitive relative to other protocols, yet it produced significantly more false-positives, and detection may have been affected by overdiagnosis and misclassification. Central CH was no longer detected once T4 testing ceased., Conclusions: Primary thyrotropin plus serial testing for infants at risk for later rising thyrotropin outperformed other newborn screening strategies for classic CH, although 2 false-negatives occurred among normal birth weight infants admitted to the NICU during this testing period. Tandem T4 and thyrotropin screening outperformed other strategies for detection of both classic and central CH combined, although it is associated with increased operating costs. Additional research is necessary to weigh the benefits of increased sensitivity against additional program operating costs.

Objectives: Asthma is one of the more common reasons for children's visits to the emergency departments (EDs). Many studies show that the level of asthma care and self-management in children before an ED visit for asthma is often inadequate; however, most of these studies have been conducted in the inner cities of large urban areas. Our objectives were to describe asthma care and management in children treated for asthma in 3 EDs located in an urban, suburban, or rural setting., Methods: We studied a prospective patient cohort consisting of children aged 2 to 17 years who presented with an acute asthma exacerbation at 3 EDs in western Michigan. An in-person questionnaire was administered to the parent or guardian during the ED visit. Information was collected on demographics; asthma history; usual asthma care; frequency of symptoms during the last 4 weeks; current asthma treatment, management, and control; and past emergency asthma care. A telephone interview conducted 2 weeks after the ED visit obtained follow-up information. The 8 quality indicators of asthma care and management were defined based on recommendations from national guidelines., Results: Of 197 children, 70% were enrolled at the urban site, 18% at the suburban site, and 12% at the rural site. The average age was 7.9 years; 60% were male, and 33% were black. At presentation, nearly half (46%) of the children had mild intermittent asthma, 20% had mild persistent asthma, 15% had moderate persistent asthma, and 19% had severe persistent asthma. One quarter of the children had been hospitalized for asthma, and two thirds had at least 1 previous ED visit in the past year. At least 94% had health insurance coverage and 95% reported having a primary care provider. Less than half of the children had attended at least 2 scheduled asthma appointments with their regular asthma care provider in the past year. Although only 5% of the subjects reported that the ED was their only source of asthma care, at least 30% reported that they always went directly to the ED when they needed urgent asthma care. Only 3 in 5 children possessed either a spacer or a peak-flow meter, whereas approximately 2 in 5 reported having a written asthma action plan. Among those with persistent asthma, there was considerable evidence of undertreatment, with 36% not on either an inhaled corticosteroid or a suitable long-term control medication. Only 20% completed a visit with their regular asthma care provider within 1 week of their ED visit., Conclusions: Despite very high levels of health care coverage and access to primary care, the overall quality of asthma care and management fell well short of that recommended by national guidelines.