Fetal Lung Maturity Testing Research Articles

Bile-acid levels and lung maturity test in patients with intrahepatic cholestasis of pregnancy.

Prolonged fetal exposure to maternal bile acids have been linked to fetal lung injury, but it is not known if it affects production of surfactant or fetal lung maturity tests. We set out to determine if elevated total bile acid (TBA) levels predict delayed fetal lung maturity (FLM) in patients with intrahepatic cholestasis of pregnancy (ICP). A retrospective cohort study examining patients with ICP who underwent amniocentesis between 36+0 and 37+6 between 2005 and 2014. Primary goal was to identify if a relationship exists between TBA levels and FLM defined as Lecithin:Sphingomyelin >2.5, detectable Phosphatidylglycerol, or lamellar body count of >50,000. Among the 113 patients, there was no statistically significant difference in TBA levels between women with FLM and those with immaturity (31.3 [21.6, 44.5]μmol/L and 34.9 [23.9, 62.3]μmol/L respectively; p=0.16). Logistic regression performed using predefined TBA levels of 20, 30, 40 and 50μmol/L revealed that TBA levels did not predict a negative FLM test at time of amniocentesis. TBA levels do no predict presence or absence of FLM between 36+0 and 37+6weeks of gestation. Though certain pregnancy complications can affect FLM, we could not identify a correlation between TBA levels and an accelerated or delayed lung maturation process.

Role of 3D Ultrasound for Assessment of Fetal Lungs

Abstract Background: Fetal lung maturity is vital to the survival rate of neonates, and is a determinant of extra uterine life. Neonatal respiratory distress syndrome and associated com-plications account for 28% of neonatal deaths. Although the wide use of glucocorticoids has decreased the incidence of Neonatal respiratory distress syndrome, approximately 10% of neonates still develop the syndrome. Aim of Study: To study the role of 3D ultrasound for assessment of fetal lungs. Patients and Methods: A total of 50 pregnant women 34- 40 weeks gestation after a complication-free normal course of pregnancy were enrolled in the study. They were classified into 2 groups as follows: 1. Group A: (n=25) women 34-37 weeks gestation. 2. Group B: (n=25) women 37-40 weeks gestation. All the included women were subjected to: Full history taken. Ultrasound examination to confirm GA, assess Amniotic Fluid Index (AFI) and to exclude fetal anomalies. 3D ultrasound was carried out to asses fetal lung volume. After child birth, APGAR score at (1, 5 and 10min) was assessed together with occurrence of RDS and the further need for neonatal ICU admission and respiratory support measurements. Results: The mean value of fetal lung volume was signif-icantly increased in term group (52.96±4.91) when compared to preterm group (44.08±6.43) (p=0.001). In the term group the percentage of neonates which did not experience Respira-tory Distress Syndrome (RDS) was 60% compared to 24% in the preterm group (p=0.001). In the preterm group the per-centage of admitted neonates in the Intensive Care Unit (ICU) was statistically increased (68%) when compared to the term group (54%) (p=0.047). The percentage of women in the preterm group received prenatal steroids 36% was statistically higher than those in the term group 24% (p=0.047). In the present study, fetal lung volume was positively correlating with gestational age (r=0.531; p-value=0.001). In the present study, in the preterm group RDS was negatively correlated with steroids (r=–0.304; p-value=0.032). Conclusion: Ultrasound indices, including fetal lung volume may serve as useful alternatives to amniotic fluid phospholipids in analyzing fetal lung maturity. Fetal lung volume might be an accurate non-invasive predictor for the occurrence of neonatal RDS among preterm fetuses in whom the risk of RDS development deserve fetal lung maturity testing.

End of the line for fetal lung maturity testing

ObjectiveDuring the last decade, guidelines published by the American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal Fetal Medicine (SMFM) have emphasized an increasingly limited role for fetal lung maturity (FLM) testing. As a reference laboratory for FLM testing, we were therefore interested in determining the impact of changing guidelines on our test volumes. MethodsWe retrospectively reviewed FLM test volume data from 2006 to 2016 for the following FLM assays: lecithin/sphingomyelin ratio, phosphatidylglycerol, disaturated lecithin, and lamellar body count. ResultsWe found that there was a precipitous decline in test volumes from 2006 to 2016; our analysis led us to discontinue providing reference laboratory FLM testing in 2016 given the very low volumes. ConclusionsThe 2019 ACOG guidelines now state that FLM testing no longer has clinical utility. Therefore, clinical laboratory directors should meet with obstetrics providers to discuss discontinuation of FLM testing at their institutions.

Neonatal Outcomes of Elective Early-term Births After Demonstrated Fetal Lung Maturity

(Am J Obstet Gynecol. 2018;219:296.e1–296.e8) Positive fetal lung maturity testing is associated with a decrease in the risk of respiratory neonatal morbidity in preterm and early-term neonates, compared with neonates who do not undergo testing. However, several studies suggest that respiratory outcomes, among others, are worse even after fetal lung maturity has been demonstrated in early-term neonates, compared with full-term neonates. This has led to a decline in fetal lung maturity testing. This study aimed to estimate the frequency and risks of adverse neonatal outcomes with early-term birth after positive fetal lung maturity testing compared with full-term birth in the absence of indications for early delivery.

Neonatal outcomes of elective early-term births after demonstrated fetal lung maturity

Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and other outcomes are worse with early-term birth (370-386 weeks) even after demonstrated fetal lung maturity when compared with full-term birth (390-406 weeks). However, these studies included medically indicated births and are therefore potentially limited by confounding by the indication for delivery. Thus, the increase in adverse outcomes might be due to the indication for early-term birth rather than the early-term birth itself. We examined the prevalence and risks of adverse neonatal outcomes associated with early-term birth after confirmed fetal lung maturity as compared with full-term birth in the absence of indications for early delivery. This is a secondary analysis of an observational study of births to 115,502 women in 25 hospitals in the United States from 2008 through 2011. Singleton nonanomalous births at 37-40 weeks with no identifiable indication for delivery were included; early-term births after positive fetal lung maturity testing were compared with full-term births. The primary outcome was a composite of death, ventilator for ≥2 days, continuous positive airway pressure, proven sepsis, pneumonia or meningitis, treated hypoglycemia, hyperbilirubinemia (phototherapy), and 5-minute Apgar <7. Logistic regression and propensity score matching (both 1:1 and 1:2) were used. In all, 48,137 births met inclusion criteria; the prevalence of fetal lung maturity testing in the absence of medical or obstetric indications for early delivery was 0.52% (n= 249). There were 180 (0.37%) early-term births after confirmed pulmonary maturity and 47,957 full-term births. Women in the former group were more likely to be non-Hispanic white, smoke, have received antenatal steroids, have induction, and have a cesarean. Risks of the composite (16.1% vs 5.4%; adjusted odds ratio, 3.2; 95% confidence interval, 2.1-4.8 from logistic regression) were more frequent with elective early-term birth. Propensity scores matching confirmed the increased primary composite in elective early-term births: adjusted odds ratios, 4.3 (95% confidence interval, 1.8-10.5) for 1:1 and 3.5 (95% confidence interval, 1.8-6.5) for 1:2 matching. Among components of the primary outcome, CPAP use and hyperbilirubinemia requiring phototherapy were significantly increased. Transient tachypnea of the newborn, neonatal intensive care unit admission, and prolonged neonatal intensive care unit stay (>2 days) were also increased with early-term birth. Even with confirmed pulmonary maturity, early-term birth in the absence of medical or obstetric indications is associated with worse neonatal respiratory and hepatic outcomes compared with full-term birth, suggesting relative immaturity of these organ systems in early-term births.

OP05.07: Prediction and utility of neonatal respiratory morbidity by quantitative lung texture analysis in pregnancies at risk for preterm/early term delivery

Prediction of neonatal respiratory morbidity can be useful to plan timing and place of delivery in complicated pregnancies and the justification of a first or repeat dose of antenatal corticosteroid in patients at risk for preterm & early term deliveries. This is especially so in resource and access restricted populations. The limited positive predictive performance of current diagnostic tests together with the risks of an invasive procedure, limits the use of fetal lung maturity assessment. This study was undertaken to evaluate the prediction and utility of information provided by a new method of quantitative ultrasound texture analysis (quantusFLM®) of fetal lung maturity in preterm and early term (<39.0 weeks) deliveries. Plans for intervention in pregnancies at risk for preterm and early term deliveries were analysed before and after information from a quantitative test for fetal lung maturity was made available to the clinician. Information was provided to multiple centres from a centralised imaging facility. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation in the 48 hours prior to planned delivery, stored in DICOM format and analysed with quantusFLM®. Perinatal neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, was recorded. The performance of the test in altering decisions of timing and place of delivery and the specificity, negative predictable value of the test to predict neonatal respiratory morbidity were evaluated. A total of 100 patients were assessed. Quantitative textural analysis of the lung predicted neonatal respiratory morbidity with a specificity of 97% and a negative predictive value of 97%. Post test decision making was significantly altered in about one in three patients. quantusFLM® predicted neonatal respiratory morbidity with a higher accuracy than that of previously reported other tests with the advantage of being a non-invasive method.

Contemporary practice patterns in the use of amniocentesis for fetal lung maturity

Purpose: Fetal lung maturity (FLM) testing has been performed to help direct delivery timing in complex obstetrical conditions. We explored current practice patterns of FLM testing attempting to identify factors affecting its use.Materials and methods: We distributed a 31-question survey to obstetricians and perinatologists that examined practice characteristics potentially affecting FLM usage. Logistic regression measured associations between these factors and test utilization. Weighted averages were calculated for conditions in which respondents considered FLM testing helpful.Results: Three hundred four surveys were completed. The response rate for respondents actively practicing obstetrics was 52%. The majority of respondents utilize FLM testing; however, 80% reported a decline in use over the past five years with 64% citing “published guidelines” as the reason. Respondents found FLM testing most applicable for poorly dated pregnancies. After an immature FLM test, 44% of respondents administer antenatal corticosteroids in the late-preterm period. None of the factors surveyed were significantly associated with FLM testing use.Conclusion: The majority of respondents use FLM testing although significant factors contributing to its use were not identified. We discover a high frequency of antenatal corticosteroid administration beyond 34 weeks gestational age in response to immature FLM indices that may be an area for future study.

The effect of freezing amniotic fluid on lamellar body count fetal lung maturity testing.

The effect of freezing amniotic fluid on lamellar body count fetal lung maturity testing.

Actualización en la evaluación de la madurez pulmonar fetal por ultrasonido

El síndrome de dificultad respiratoria (SDR) del recién nacido persiste como una de las principales causas de morbilidad y mortalidad en neonatos prematuros. A pesar que la evidencia científica reciente cuestiona la utilidad de las pruebas para evaluar la madurez pulmonar fetal para determinar el momento más adecuado para el parto en ciertas complicaciones obstétricas, existe un conjunto de indicaciones relativas en las cuales una prueba no invasiva puede encontrar aplicación. El objetivo del presente trabajo es revisar los trabajos publicados en la literatura sobre el empleo de la ecografía como método para predecir la morbilidad respiratoria neonatal, utilizando la evaluación Doppler de la arteria pulmonar y el análisis cuantitativo de la textura ecográfica del pulmón fetal.

Perfil ecográfico de madurez pulmonar fetal: quince años de experiencia en el Hospital Nacional Arzobispo Loayza

Objective: To evaluate the predictive capacity of Sonographic Fetal Lung Maturity Profile compared to the Clements test to reliably predict the Fetal Maturity, avoiding potential complications of amniocentesis, and constraints that exist in our environment for the use of markers prediction biochemical fetal maturity test as lecithin / sphingomyelin among others. Material and Methods: Descriptive, prospective study evaluating diagnostic parameters to determine fetal lung maturity using ultrasound and amniocentesis procedures, and comparing perinatal outcome as the gold standard. 1200 pregnant women hospitalized with high obstetric risk at Hospital Nacional Arzobispo Loayza from December 1995 to December 2010 were studied. They underwent sonographic profile of lung maturity with five parameters; liver, distal femoral epiphysis, and gestational age composed of multiple biometrics. All had an amniocentesis test to determine clement test in amniotic fluid (three tubes). If, by obstetric indication, pregnancy was ended within 48 hours of testing, perinatal outcome was evaluated. Results: 1251 newborns were studied, as there were 50 multiple pregnancies. The most common diagnosis was preeclampsia. Average gestational age by Capurro was 34.4 + 1.6 weeks (range 27-36 weeks), the weight of the newborns, in average, was 2136 + 580 gr (range 1050-2840 g). In total 80 newborns presented Hyaline Membrane Disease, diagnosed by clinical and radiological criteria. The prediction results for both sonographic fetal lung maturity and Clements test were: specificity (97.35%, 85.74%), sensitivity (86.25%, 75.0%), negative (69.0%, 26.43%) predictive value, positive predictive value (99.04%, 98.04%) respectively. Conclusion: Sonographic fetal lung maturity has a high predictive ability of fetal lung maturity, to be more specific and sensitive relative to Clements test, with the advantage of being easily repeatable and reproducible, it is noninvasive, fast, cheaper and can be done as an outpatient, predicting lung maturity better.

Intrahepatic cholestasis of pregnancy and timing of delivery

Objective: We examined the morbidities from delivery at earlier gestational ages versus intrauterine fetal demise (IUFD) for women with intrahepatic cholestasis of pregnancy (ICP) to determine the optimal gestational age for delivery.Methods: A decision-analytic model was created to compare delivery at 35 through 38 weeks gestation for different delivery strategies: (1) empiric steroids; (2) steroids if fetal lung maturity (FLM) negative; (3) wait a week and retest if FLM negative; or (4) deliver immediately. Literature review identified 18 studies that estimated IUFD in ICP; we used the mean rate, 1.74%, and assumed a uniform distribution from 34 to 40 weeks gestation. Large cohort data was used to calculate neonatal morbidity rates at each gestational age. Maternal and neonatal quality-adjusted life years (QALYs) were combined. Univariate sensitivity and Monte Carlo analyses were performed to test for robustness.Results: Immediate delivery at 36 weeks without FLM testing and steroid administration was the optimal strategy as compared to delivery at 36 weeks with steroids (+47 QALYs) and as compared to immediate delivery at 35 weeks (+210 QALYs). Our results were robust up to a 30% increase in the rate of IUFD.Conclusion: Immediate delivery at 36 weeks in women with ICP is the optimal delivery strategy.

Predicting Fetal Lung Maturity Using the Fetal Pulmonary Artery Doppler Wave Acceleration/Ejection Time Ratio

Objective: To determine whether the acceleration/ejection time ratio of the fetal main pulmonary artery Doppler waveform (PATET) can accurately predict the results of fetal lung maturity testing in amniotic fluid. Methods: We prospectively studied pregnant women attending our ultrasound unit for clinically indicated fetal lung maturity testing. An ultrasound examination that included measurement of the PATET was performed before the results of the amniocentesis were reported. The results of the PATET and the surfactant/albumin ratio were compared, and a receiver operating characteristic curve was used to determine the PATET cutoff with the optimal sensitivity and specificity for predicting surfactant/albumin ratio results. p < 0.05 was considered statistically significant. Results: Forty-three patients were included in this study. The receiver operating characteristic curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93% (95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58-96%) for predicting immature surfactant/albumin ratio results. Conclusion: The PATET may provide a noninvasive means of determining fetal lung maturity with acceptable levels of sensitivity, specificity, and predictive values.

Accuracy of the lamellar body count in amniotic fluid contaminated by meconium

Objective: To determine whether meconium-contaminated amniotic fluid falsely elevates the lamellar body count in fetal lung maturity testing.Methods: Thirty mothers undergoing amniocentesis for fetal lung maturity testing were prospectively consented. A 2 mL portion of the patient’s sample was mixed with a 10% meconium solution and the meconium-stained sample was then run in tandem with the patient’s sample used in clinical management. Pure meconium samples without amniotic fluid were also run through the cell counter for analysis.Results: Following meconium contamination, the lamellar body count value increased in 67% of the cases, decreased in 23% and remained the same in 10%. There were 13 test results that had “immature” values in the uncontaminated patient management sample group and nine of these (69%) became elevated to a “mature” level (a false elevation) following the addition of meconium. All of the 10 pure liquid meconium samples devoid of amniotic fluid processed by the cell counter identified and quantified some particle the size of platelets.Conclusions: The lamellar body count test result is not reliable in meconium-stained amniotic fluid specimens. There is some unknown particle found in meconium that is the size of platelets/lamellar bodies that can falsely elevate the test result. Currently, the only reliable fetal lung maturity test in meconium-stained amniotic fluid is the presence of phosphatidylglycerol.

Advances in prenatal diagnostics.

Advances in prenatal diagnostics.

Fetal lung maturity testing: the end of an era.

Respiratory distress syndrome is a major cause of neonatal morbidity and mortality that is most commonly caused by a deficiency in lung surfactant in premature infants. Therefore, laboratory tests were developed to measure the presence and/or concentration of lung surfactant in amniotic fluid in order to estimate maturity of the fetal lung. Although these tests were once widely employed, their utilization by physicians has decreased in recent years. Several studies have shown that demonstration of a mature fetal lung index by antenatal testing does not improve neonatal outcomes. Instead, decreased respiratory and nonrespiratory morbidities are most highly correlated with gestational age of the fetus. Therefore, fetal lung maturity testing may have passed the point of being clinically useful.

Neonatal morbidity occurs despite pulmonary maturity prior to 39 weeks gestation

ObjectiveTo compare outcomes among late-preterm or early-term neonates according to fetal lung maturity status.Study DesignWe conducted a retrospective cohort study of 234 eligible singletons delivered after fetal lung maturity (FLM) testing prior to 39 weeks gestation at our center over a two year time period. A primary composite neonatal outcome included death and major morbidities.ResultsThe overall rate of primary composite morbidity was 25/46 (52.2%) and 61/188 (32.4%) in the immature/transitional and mature groups, respectively. After adjustment for confounders including gestational age, the composite outcome was not significantly different; aOR 1.4 (CI 0.7-3.0). The rate of respiratory distress syndrome was significantly higher in the immature/transitional group; OR 3.4 (CI 1.1-10.3) as expected.ConclusionsFLM status did not correlate with the spectrum of neonatal morbidities in late preterm and early term births. Neonatal complications remained common in both groups.

136: A prospective study of fetal lung maturity tests in twins based on birth order and weight

136: A prospective study of fetal lung maturity tests in twins based on birth order and weight

The Effect of Freezing of Amniotic Fluid on the Lamellar Body Count Fetal Lung Maturity Test

The study purpose was to determine if amniotic fluid that is inadvertently frozen falsely elevates the lamellar body count (LBC) fetal lung maturity test. Because the TDx-FLM test is no longer available, many laboratories are converting to the LBC test. Studies to date on the effect of freezing prior to running the test are limited by small numbers; used …

Discordance in Lamellar Body Counts Between Sysmex XS-1000 and Sysmex XE-5000 Analyzers

Respiratory distress syndrome, the ninth leading cause of newborn mortality in the US, is caused by fetal lung immaturity due to pulmonary surfactant deficiency. Accordingly, the American College of Obstetrics and Gynecology recommends fetal lung maturity (FLM) testing at <39 weeks gestation. Lamellar body counts (LBC) are often employed for FLM assessment. Most studies established …

427: Blood contaminated amniotic fluid and the lamellar body count fetal lung maturity test

427: Blood contaminated amniotic fluid and the lamellar body count fetal lung maturity test