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Second-Trimester Sonographic Thymus Measurements Are Not Associated With Preterm Birth and Other Adverse Obstetric Outcomes
... In all, 258 articles were identified, 25 were assessed with respect to their eligibility for inclusion (see Supplementary material, Table S2) and 12 studies were included in the systematic review (Table 1, Figure 1) (9,10,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). These 12 studies included 1744 fetuses who had ultrasound assessment of thymus size. ...
... These 12 studies included 1744 fetuses who had ultrasound assessment of thymus size. Eleven studies were prospective (9,10,20,21,(23)(24)(25)(26)(27)(28)(29), only one was a retrospective study (22). Inclusion criteria differed among the included studies; six studies included women at risk of infectious-related complications, such as those presenting with preterm premature rupture of the membranes (PPROM) or signs of preterm labor (22)(23)(24)(27)(28)(29), whereas the remaining studies included women with no apparent risk factors (Table 1) (9,10,20,21,25,26). ...
... Eleven studies were prospective (9,10,20,21,(23)(24)(25)(26)(27)(28)(29), only one was a retrospective study (22). Inclusion criteria differed among the included studies; six studies included women at risk of infectious-related complications, such as those presenting with preterm premature rupture of the membranes (PPROM) or signs of preterm labor (22)(23)(24)(27)(28)(29), whereas the remaining studies included women with no apparent risk factors (Table 1) (9,10,20,21,25,26). ...
Introduction:
To explore the association between small fetal thymus on ultrasound and adverse obstetrical outcome.
Material and methods:
Medline, Embase, Cochrane and Web of Science databases were searched. Primary outcome was the risk of preterm birth before 37 and 34 weeks in fetuses with compared to those without a small thymus on ultrasound.
Secondary outcomes:
occurrence of chorioamnionitis, intra-uterine growth restriction, neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and pre-eclampsia.
Results:
Twelve studies including 1744 fetuses who had ultrasound assessment of thymus during pregnancy were included. Women with preterm premature rupture of the membranes (PPROM) or with preterm labour with a small fetal thymus were at higher risk of preterm birth <37 (p= 0.01), <34 (12.5 (p<0.001) weeks in fetuses with compared to those without small thymus, and the risk of chorioamnionitis was higher when the thymus was small (p<0.001). Fetuses with small thymus were not at higher risk of intra-uterine growth restriction (p= 0.3). A small thymus increased the risk of neonatal sepsis (p= 0.007) and morbidity (p= 0.003), but not the risk of pre-eclampsia (p= 0.9).
Conclusions:
A small fetal thymus is associated with a higher risk of preterm birth, chorioamnionitis, neonatal sepsis and morbidity, but not with intra-uterine growth restriction and pre-eclampsia. This article is protected by copyright. All rights reserved.
... 7 Brandt et al evaluated the association between second trimester fetal thymus measurements and adverse obstetric outcomes. 11 Their results are inconsistent with the findings of the current study and those of afore mentioned studies. These investigators found no association between thymus measurements and SGA or pregnancy-related hypertension. ...
... Brandt et al included pregnant women at GA of 18 to 23 weeks, but in the present study, pregnant women were recruited with a GA between 20 and 38 weeks. 11 It is likely that the fetal thymus size in the third trimester is more associated with IUGR and SGA. Various underlying mechanisms have been proposed for this association. ...
Objective: The objective of this study was to evaluate the association between reduced fetal thymus size and
intrauterine growth restriction (IUGR). This study was devised to determine the association between thymus size
and any abnormal Doppler indices within the fetal umbilical artery (UA), as well as the middle cerebral artery (MCA).
Materials and Methods: Forty-six pregnancies between 20 and 38 weeks of gestation with IUGR and 46 normal
pregnancies within similar gestational age (GA) range were included. The transverse diameter of fetal thymus was
measured. In the IUGR group, the fetal umbilical artery (UA) and middle cerebral artery (MCA) Doppler flow velocities
were recorded.
Results: The mean GA of fetuses with IUGR (33.5 weeks) was higher than control group (30.3 weeks). To adjust for
the effect of GA, analysis of covariance (ANCOVA) was performed. The adjusted mean thymus diameters were 19.02
mm in IUGR and 21.25 within the control group (mean difference = 2.23 mm; P = .02). The mean (±SD) thymus size
in 16 fetuses, with abnormal Doppler findings, was significantly lower than in the group with normal Doppler findings,
17.45 (±2.50) vs 22.02 (±5.39) mm; P < .001.
Conclusion: IUGR may be associated with reduced fetal thymus size, especially when coupled with abnormal Doppler
findings. The thymus size in a group of IUGR fetuses, with abnormal Doppler findings, was smaller than IUGR fetuses,
with normal Doppler findings.
... A study by Brandt et al. focused on asymptomatic pregnant women examined during routine second-trimester ultrasound screening [47]. In this study, there was no difference in the frequency of preterm births between fetuses with small and normal thymus size. ...
Objectives
The aim of this study was to compare the size of the thymus gland of healthy fetuses in twin and singleton pregnancies using the thymic-thoracic ratio (TTR). As a second objective, the TTR difference between monochorionic and dichorionic twin thymus size was examined. Finally, a possible correlation between thymus size and gestational age (GA) at birth in twin pregnancies was investigated.
Methods
The TTR was measured retrospectively using the plane of three-vessel view in prenatal ultrasound examinations. Images of 140 healthy twin fetuses (33 monochorionic and 107 dichorionic) between 19+0 and 33+2 weeks of gestation were utilized and compared to 248 healthy singleton fetuses.
Results
A significant difference in thymus size could be observed between healthy fetuses from singleton and twin pregnancies (p<0.001). Thymus size in monochorionic and dichorionic fetuses did not differ. If only comparing fetuses after 37+0 weeks of pregnancy, the difference in the TTR was no longer significant. In addition, an association between prematurity and larger thymus was established. However, the effect size of this association was small.
Conclusions
The results indicate that factors related to preterm birth, rather than the number of fetuses, are likely to influence the TTR. Utilizing fetal thymus size in ultrasound screening may hold potential for predicting adverse events like preterm birth in both singleton and twin pregnancies, but only in addition to other variables.
... It was concluded that fetal thymus screening in the second trimester cannot be used in the prediction of pregnancy complications. [22] On the other hand, in our two recent studies, it has been shown that 3D VOCAL fetal TV measurement is important in predicting the week of birth in twin pregnancies and the measurement of first trimester fetal TV in single pregnancies is important in predicting preeclampsia. [9,23] According to literature data, two-dimensional (2D) USG evaluation was performed in most of the studies investigating the possible effects of the fetal thymus. ...
Background
Intrauterine growth restriction (IUGR) refers to fetuses that are small for their gestational age. There is no effective test to predict this disease. The aim of our study is whether fetal three-dimensional (3D) ultrasonography (USG)-assisted thymus volume (TV) measurement predicts IUGR cases.
Methods
Fetal 3D USG thymus measurement between 15 and 24 weeks of gestation was performed in a total of 100 women of reproductive age. Fetal TV was measured using the virtual organ computer-assisted analysis system program. All cases were followed up in terms of pregnancy complications until delivery.
Results
IUGR was developed in six cases in total. In cases with IUGR, mean fetal TV was found to be statistically significantly lower than in healthy cases without it. When the fetal TV was taken as 0.1645, the sensitivity was calculated as 89.5% and the specificity as 50% for predicting IUGR. The use of low fetal volume parameters is a significant and good indicator for predicting IUGR according to the binary logistic regression analysis result.
Conclusion
According to the results of this study, 3D fetal TV measurement may be used in routine second-trimester sonographic anomaly screening to predict the development of fetal IUGR. In this way, fetal mortality and morbidity caused by IUGR may be reduced.
... Borgelt et al. 18 measured the anteroposterior diameter of the fetal thymus in the first trimester of pregnancy and found a positive relationship between fetal thymus and preterm birth (p<0.001). Brandt et al. 19 investigated the fetal thymus in pregnant women during the second trimester to predict prematurity. They did not observe a statistically significant association between small thymus and preterm birth. ...
Objective:
Fetal thymus involvement in prematurity has been studied, and this study aimed to evaluate its relationship with short cervix and amniotic fluid sludge in the second trimester of pregnancy.
Methods:
In this prospective cross-sectional study, 79 pregnant women (19+0 to 24+6 weeks) were included, and cervical length and the presence or absence of amniotic fluid sludge were evaluated. In the three-vessel view of the fetal thorax, the thymus was identified, and its perimeter and transverse diameter were measured and transformed to a zeta score based on gestational age.
Results:
Data from 22 women with short cervix (<25 mm) and 57 patients with normal cervix (≥25 mm) were analyzed. The transverse diameter of the fetal thymus was significantly greater in the short cervix group compared to that of the normal cervix group (z-score 2.708 vs. -0.043, p=0.003). There were no significant differences in the perimeter (z-score -0.039 vs. -0.071, p=0.890) or the transverse diameter (z-score 1.297 vs. -0.004, p=0.091) of the fetal thymus associated with the presence (n=21) or absence of sludge (n=58).
Conclusion:
A short cervix is associated with an increased transverse diameter of the fetal thymus during the second trimester of gestation.
... Caissutti et al. [17] investigated the relationship between an ultrasonographically small foetal thymus and an unfavourable obstetrical outcome. Brandt et al. [18] and Di Naro et al. [10] , including 551 foetuses, investigated the degree of relationship between a small thymus and the incidence of spontaneous PTB 37 weeks of gestation and found no significant difference between the two groups. There was no difference in the risk of PTB before 34 weeks of gestation between foetuses with and those without a small thymus. ...
... En respuesta al estrés, el timo fetal puede liberar mediadores no específicos como los corticoides endógenos, mediadores inflamatorios sistémicos y otros. (23) La deficiencia de vitaminas, minerales y proteínas de forma consistente, tiene como resultado una reducción dramática del tamaño del timo como respuesta fisiológica, en tal caso, se observan: cambios histopatológicos y retardos del crecimiento intrauterino. ...
Introducción:
el interés de la visualización sonográfica del timo fetal está relacionado con su importante función inmunológica, las posibilidades de diagnóstico que ofrecen los ecógrafos de alta resolución, y el incremento de informes de posibles afecciones durante el proceso de la gestación.
Objetivo:
determinar la frecuencia de la hipoplasia tímica fetal en gestantes de riesgo genético y relacionarla con la presencia de defectos fetales, factores de riesgo previos y aparición de efectos obstétricos adversos.
Métodos:
se realizó un estudio descriptivo prospectivo consistente en la evaluación ecográfica del timo fetal mediante el índice timo-tórax a 221 gestantes que acudieron a los servicios de referencia del Centro Provincial de Genética Médica, por presentar riesgo genético incrementado para cardiopatías.
Resultados:
se encontraron 16 fetos con un índice timo-tórax inferior o igual a 0,30, el cual se utilizó como criterio de hipoplasia tímica en este estudio, entre ellos: 4 con cardiopatías, 4 con cromosomopatías, 1 con malformación estructural aislada, 2 con preeclampsia, 1 con crecimiento intrauterino retardado, 1 pretérmino y una muerte fetal. Los motivos de referencia con mayor proporción de positividad fueron: la traslucencia nucal aumentada y la imagen de sospecha de cardiopatía congénita en ultrasonido de pesquisaje.
Conclusiones:
la determinación del índice timo-tórax permitió el diagnóstico de la hipoplasia tímica, tanto en el segundo como en el tercer trimestre de la gestación. Este tipo de investigación es relevante pues contribuye a identificar: defectos congénitos, factores de riesgo y efectos obstétricos adversos.
... Of this population, 12.3% underwent PTB; however, there was no correlation between thymus size and premature delivery. 9 It should be noted that the median gestational age at imaging was 20.5 weeks and very few of the PTBs occurred very early in gestation, hence the infective/inflammatory processes may not have commenced at the time of this initial scan. ...
Introduction:
Infection and inflammation have been implicated in the aetiology and subsequent morbidity associated with preterm birth. At present there are no tests to assess for fetal compartment infection. The thymus, a gland integral in the fetal immune system, has been shown to involute in animal models of antenatal infection, but its response in human fetuses has not been studied. This study aims to: 1) generate magnetic resonance imaging (MRI) derived fetal thymus volumes standardized for fetal weight. 2) To compare standardized thymus volumes from fetuses that delivered less than 32 weeks of gestation with fetuses that subsequently deliver at term 3) to assess thymus size as a predictor of preterm birth 4) to correlate the presence of chorioamnionitis and funisitis at delivery with thymic volumes in utero in fetuses that subsequently deliver preterm.
Material and methods:
Women at high-risk of preterm birth at 20-32 weeks of gestation were recruited. A control group was obtained from existing datasets acquired as part of three research studies. A fetal MRI was performed on a 1.5T or 3T MRI scanner: T2 weighted images were obtained of the entire uterine content and specifically the fetal thorax. A slice-to-volume registration method was used for reconstruction of 3D images of the thorax. Thymus segmentations were performed manually. Body volumes were calculated by manual segmentation and thymus:body volume ratios generated. Comparison of groups was performed using multiple regression analysis. Normal ranges were created for thymus volume and thymus:body volume ratios using the control data. Receiver operating curves (ROC) curves were generated for thymus:body volume ratio and gestation adjusted thymus volume centiles as predictors of PTB. Placental histology was analysed where available from pregnancies that delivered very preterm and the presence of chorioamnionitis/funisitis noted.
Results:
Normative ranges were created for thymus volume and thymus volume standardized for fetal size from fetuses that subsequently delivered at term, imaged 20-32 weeks gestation. Image datasets from sixteen women that delivered <32 weeks of gestation (ten with ruptured membranes and six with intact membranes) and 80 control women that delivered >37 weeks were included. Mean gestation at MRI of the study group was 28+4 weeks (SD 3.2) and the control group was 25+5 weeks (SD 2.4). Both absolute fetal thymus volumes and thymus:body volume ratios were smaller in fetuses that delivered preterm (p<0.001). Of the sixteen fetuses that delivered preterm thirteen had placental histology: eleven had chorioamnionitis and nine funisitis. The strongest predictors of prematurity were the thymus volume Z-score and thymus:body volume ratio Z-score (ROC areas 0.915 and 0.870 respectively).
Conclusions:
We have produced MR derived normal ranges for fetal thymus and thymus:body volume ratios between 20 and 32 weeks of gestation. Fetuses that deliver very preterm had reduced thymus volumes when standardized for fetal size. A reduced thymus volume was also a predictor of spontaneous preterm delivery. Thymus volume may be a suitable marker of the fetal inflammatory response although further work is needed to assess this, increasing the sample size to correlate the extent of chorioamnionitis with thymus size.
... The fetal thymus may be visualized using an ultrasound machine and is typically located in the mediastinum anterior to the great arteries and superior vena cava. In the past years, the size of the fetal thymus has served not only as a marker of genetic or heart defects but also as a predictive factor for intrauterine growth restriction (IUGR), premature birth, preeclampsia, chorioamnionitis or even neonatal sepsis [2][3][4][5][6]. Fetal thymus evaluation has become an important diagnostic and predictive tool for obstetricians, neonatologists and pediatric immunologists that may predict immunodeficiencies and qualify for further vaccination protocol. ...
Introduction
The fetal thymus may be visualized using ultrasonography (USG) and is typically located in the mediastinum. In the past years, the size of the fetal thymus has served not only as a marker of genetic or heart defects but also as a predictive factor for intrauterine growth restriction, premature birth, preeclampsia, chorioamnionitis or even neonatal sepsis.
Material and methods
A total of 410 fetuses were qualified for the study. Fetuses with heart defects were excluded from the study. The fetal thymus was evaluated with ultrasonography between the 14th and 40th week of gestation. After obtaining a standard transverse view encompassing the three great vessels, thymus measurements were attempted, i.e. maximal transverse diameter, circumference and surface area. Linear regression was used for statistical analysis, yielding 3 models, each with a different dependent variable. The confidence interval for each model was set at 80% to aid the comparison with centile grid growth charts for neonates and children. The test was regarded as statistically significant when p < 0.05.
Results
From a total of 410 fetuses the thymus transverse diameter, circumference and area were successfully measured in 410, 320 and 330 cases, respectively. The probabilities are lower than 0.0005 for each model, which means that each model is quite statistically significant.
Conclusions
The coverage of healthy thymus nomograms in the fetal population may be the basis for the identification of fetuses at risk of hypoplasia or thymic hyperplasia, which seems particularly important from the point of view of the detection of potential inborn immunological disorders
Context
Subjects with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) have subnormal adult height. There are several potential APECED-related risk factors for suboptimal height attainment during childhood.
Objective
To determine the growth patterns in children with APECED.
Methods
This retrospective longitudinal study included 59 children with APECED from the Finnish national APECED cohort and assessed length/height and weight z-scores from birth to the end of prepuberty.
Results
Collectively, 59 children (30 [51%] girls) were included. Their median birth weight z-score (−0.60) was below the population average; 12 (20%) patients were born small for gestational age. Height attainment progressively declined from birth until the end of prepuberty (z-score −1.95), whereas weight-for-height z-score did not (+0.26). Of the 59 patients, 38 (64%) had all height z-scores below 0 during prepuberty, and 7 (12%) had z-scores below −2.0. Age at the end of prepuberty, number of APECED manifestations, duration of glucocorticoid treatment, and growth hormone deficiency correlated negatively with height z-score at the end of prepuberty (P < .0001; P = .041; P = .013; P = .034, respectively).
Conclusion
Children with APECED had a progressive growth impairment from birth through prepuberty. Multiple predisposing risk factors were recognized, including disease severity and growth hormone deficiency. Timely interventions are needed to ensure optimal height attainment and new treatment options need to be developed.
Background/aim
The thymus is essential for developing the fetal immune system and may show involution upon exposure to acute stress. Early detection of intrauterine infection is urgently needed to avoid fetal affection and sepsis. The present study aims to correlate the fetal thymus size with the infection parameters in pregnancies complicated with preterm premature rupture of membranes (PPROM).
Subjects and methods
The present study recruited pregnant women who fulfilled the inclusion criteria in a ratio of 1 case to 4 controls according to the study design; Group 1 of twenty cases presenting in PPROM, and Group 2 of eighty cases of women without PPROM. The primary outcome of the study was to measure fetal thymus size by abdominal ultrasound and its correlation with maternal total leukocytic count (TLC) and its differential count, C-reactive protein (CRP), and maternal fever. The secondary outcomes involved the correlation of the fetal thymus size with fetal distress, the occurrence of neonatal infection, Apgar neonatal score, and histological examination of the placenta and membranes for evidence of chorioamnionitis.
Results
Group 1 had a significantly higher CRP level ( P <0.001), higher TLC level ( P =0.035), and higher Staff ( P <0.001). On the contrary, group 2 had significantly higher AFI ( P =0.022), greater Thymus perimeter ( P <0.001), and greater thymus transverse diameter ( P <0.001). In addition, the pathological examination of the placenta revealed positive signs of infection in group 1 in only 65% of cases. Group 1 had a positive correlation between Thymus perimeter and APGAR score of the neonates ( r =0.658, P =0.002), Thymus perimeter and birth weight ( r =0.741, P <0.001), Thymus transverse diameter and APGAR score of the neonates ( r =0.741, P <0.001), and finally Thymus transverse diameter and birth weight ( r =0.734, P <0.001). Group 2 showed a significant positive correlation between the Thymus perimeter and neonatal APGAR score ( r =0.232, P =0.039) and Thymus transverse diameter and birth weight ( r =0.320, P =0.004). In Group 1, Cases with placental signs of infection (n=13) had higher CRP levels ( P =0.046), higher TLC levels ( P =0.014), higher Staff ( P <0.001), but lower AFI ( P =0.032).
Conclusion
The assessment of the fetal thymus during the routine second- and/or third-trimester scan could be a predictive measure for intra-amniotic infection. However, there is no association between small fetal thymus and adverse perinatal outcomes in uncomplicated pregnancies. Further larger studies with different demographic, maternal characteristics, and different inflammatory processes with and without active management to summarize whether fetal thymus can be used in clinical practice to avoid infection-related fetal morbidities or not.
Introduction:
The purpose was to compare thymus size measured during second trimester screening of fetuses who were subsequently small for gestational age at birth (weight below 10th percentile, SGA group) with fetuses with normal birth weight (control group). We hypothesized that measuring the fetal thymic-thoracic ratio (TT ratio) might help predict low birth weight.
Methods:
Using three-vessel view echocardiograms from our archives, we measured the anteroposterior thymus size and the intrathoracic mediastinal diameter (IMD) to derive TT ratios in the SGA (n=105) and control groups (n=533) between 19+0 and 21+6 weeks of gestation. We analyzed the association between TT ratio and SGA adjusted to week of gestation using logistic regression. Finally, we determined the possible TT ratio cut-off point for discrimination between SGA and control groups by means of receiver operating characteristics (ROC) curve analysis.
Results:
The TT ratio was significantly higher in the SGA group than in the control group (p<0.001). An increase of the TT ratio by 0.1 was associated with a 3.1-fold increase in the odds of diagnosing SGA. We determined that a possible discrimination cut-off point between SGA and healthy controls was achieved using a TT ratio of 0.390 (area under the ROC-curve 0.695).
Conclusion:
An increased TT ratio may represent an additional prenatal screening parameter that improves the prediction of birth weight below the 10th percentile. Prospective studies are now needed to evaluate the use of fetal thymus size as predictive parameter for adverse fetal outcome.
Background:
Ultrasonographic evaluation of fetal thymus size may be used to predict the adverse perinatal outcome in pregnant women with vasculitis.
Aim:
To compare fetal thymus size in pregnant women with vasculitis and healthy pregnant women and to evaluate whether fetal thymus size predicts the adverse perinatal outcome.
Methods:
Twenty-two pregnant women with previously diagnosed vasculitis, 18 of them with Behçet's disease, three with Takayasu arteritis, and one with Wegener's granulomatosis, were included in the case group. The control group comprised 66 healthy pregnant women whose gestational ages matched the case group. Thymic thoracic ratio (TTR) was measured to assess fetal thymus size in the view of three vessels and trachea.
Results:
In the case group, fetal TTR was significantly lower (0.32±0.03 vs. 0.36±0.02, p=<.001). Fetal TTR was significantly lower in those using prednisone than those not (p=.001) in the case group. There was no significant difference in fetal TTR between colchicine used and not used (p=.078) in the case group. Also, for the TTR, a sensitivity of 100% and a specificity of 92% were achieved with a cut-off value of 0.33 for predicting adverse perinatal outcomes.
Conclusion:
The fetuses of pregnant women with maternal vasculitis had a smaller TTR. The small fetal thymus may alert clinicians to possible adverse perinatal outcomes and, with other supporting risk factors, may help predict adverse perinatal outcomes in pregnant women with vasculitis.
Aim:
This study aimed to evaluate the difference in fetal thymus diameter, which we measured ultrasonographically, between the healthy pregnant group and the pregnant group with gestational diabetes.
Method:
Fetal thymus and thymus/thorax ratio parameters were assessed in this case-control study. Patients were examined in two groups. They included 49 diabetics (study group) women and 71 nondiabetic (control group). We performed a binary logistic regression analysis to determine the predictive value of ultrasonographic measurements. We completed the receiver curve characteristic analysis to evaluate the cut-off thymus diameter.
Results:
The median age of pregnant women was 27. Thymus diameter and thymus-thorax ratio were smaller in fetuses of diabetic mothers than in the nondiabetic group (p <0.05). Thymus diameter was found to be more predictive of gestational diabetes prediction (p: 0.019). There was no correlation between fasting blood glucose and thymus diameter.
Conclusion:
Decreased fetal thymus anterior-posterior diameter seems to be associated with diabetic pregnancy.
Objective
The objective of this study was to evaluate the association between reduced fetal thymus size and intrauterine growth restriction (IUGR). This study was devised to determine the association between thymus size and any abnormal Doppler indices within the fetal umbilical artery (UA), as well as the middle cerebral artery (MCA).
Materials and Methods
Forty-six pregnancies between 20 and 38 weeks of gestation with IUGR and 46 normal pregnancies within similar gestational age (GA) range were included. The transverse diameter of fetal thymus was measured. In the IUGR group, the fetal umbilical artery (UA) and middle cerebral artery (MCA) Doppler flow velocities were recorded.
Results
The mean GA of fetuses with IUGR (33.5 weeks) was higher than control group (30.3 weeks). To adjust for the effect of GA, analysis of covariance (ANCOVA) was performed. The adjusted mean thymus diameters were 19.02 mm in IUGR and 21.25 within the control group (mean difference = 2.23 mm; P = .02). The mean (±SD) thymus size in 16 fetuses, with abnormal Doppler findings, was significantly lower than in the group with normal Doppler findings, 17.45 (±2.50) vs 22.02 (±5.39) mm; P < .001.
Conclusion
IUGR may be associated with reduced fetal thymus size, especially when coupled with abnormal Doppler findings. The thymus size in a group of IUGR fetuses, with abnormal Doppler findings, was smaller than IUGR fetuses, with normal Doppler findings.
Objectives
The aim of this study was to compare the second trimester thymus-thorax-ratio (TTR) between fetuses born preterm (study group) and those born after 37 weeks of gestation were completed (control group).
Methods
This study was conducted as a retrospective evaluation of the ultrasound images of 492 fetuses in the three vessel view. The TTR was defined as the quotient of a.p. thymus diameter and a.p. thoracic diameter.
Results
Fetuses that were preterm showed larger TTR (p<0.001) the second trimester than those born after 37 weeks of gestation were completed. The sensitivity of a binary classifier based on TTR for predicting preterm birth (PTB) was 0.792 and the specificity 0.552.
Conclusions
In our study, fetuses affected by PTB showed enlarged thymus size. These findings led us to hypothesize, that inflammation and immunomodulatory processes are altered early in pregnancies affected by PTB. However, TTR alone is not able to predict PTB.
Background/aims:
To evaluate the diagnostic accuracy of fetal thymus transverse diameter (FTTD) in predicting fetal infection in preterm premature rupture of membranes (PPROM) and compare its accuracy with cord blood tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).
Methods:
Forty consecutive pregnancies complicated with PPROM between 26(1/7) and 36(6/7) gestational weeks were evaluated prospectively. Serial fetal ultrasonography follow-ups with 3-day intervals were performed beginning on the admission day. The FTTD was recorded on every ultrasonographic examination. Cord blood TNF-α and IL-6 values were measured after delivery.
Results:
FTTD was decreased below 5% according to nomograms compared to the initial measurement in 45% of all PPROM cases. Decreased FTTD had a sensitivity of 100%, specificity of 73%, positive predictive value of 55%, and negative predictive value of 100% in predicting early neonatal sepsis. Cord blood TNF-α had a sensitivity of 80% and specificity of 90%, whereas IL-6 had a sensitivity of 90% and specificity of 63.3% in predicting early neonatal sepsis.
Conclusions:
Assessment of the decrease in FTTD by serial ultrasonographic examinations is a promising 'prenatal' method for the early detection of early neonatal sepsis.
Abstract Objective: To predict histological chorioamnionitis (CA) in the cases of preterm premature rupture of membranes by using fetal thymus transverse and anteroposterior diameters and areal measurements. Methods: Fifty healthy and 50 patients diagnosed with preterm premature rupture of membranes (PPROM) between 24 to 37 weeks of gestation were included in the study. Fetal thymus measurements were done and repeated on a weekly basis until delivery, Furthermore white blood cell, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured every other day until delivery, too. Following delivery, all patients' placentas were sent to pathology. Results: Histological CA was detected in 48% of the PPROM patients. There were no patients in either group with clinical CA. Thymus transverse diameter had 91% sensitivity, 81% specificity, 82% PPV, and 91% NPV in predicting histological CA in PPROM patients. No linear relationship was found between thymus anteroposterior diameter measurements and gestational age. Thymus area measurements have sensitivity of 75%, specificity of 81%, PPV of 78%, NPV of78% in determining CA in patients with PPROM. Conclusion: Both thymus transverse diameter and area measurement are more significant than sedimentation and CRP values in predicting histological CA. Fetal thymus measurements can be used in early diagnosis of infections among high risk patients.
Objective: Our primary objective was to determine whether there was an association between levels of antenatal maternal serum soluble RAGE (sRAGE), drawn at the time of presentation with preterm labor (PTL), and subsequent preterm birth (PTB). Secondary objectives were to determine whether levels of sRAGE – analyzed from both antenatal maternal serum (MS) and postpartum umbilical cord serum (CS) – were associated with neonatal sepsis. Methods: Nested case-control analyses were performed within a prospective cohort of patients at risk for PTB. MS was obtained at enrollment and CS at delivery. The sRAGE levels were analyzed. Non-parametric calculations and receiver-operator analyses were performed. Results: Overall, 39.8% of patients delivered < 37 weeks (n = 498) and 15% had neonatal sepsis (n = 193). In comparing cases and controls, sRAGE was significantly lower in those with than those without an adverse event (PTB: median MS-sRAGE 771.79 versus 948.485 pg/mL, p = 0.004; neonatal sepsis: 25-centile CS-sRAGE 1220.49 versus 2244.41 pg/mL, p = 0.0013). Adding MS-sRAGE to models of clinical variables significantly enhanced the ability of the model to predict both PTB (area under the curve [AUC] 0.71 versus 0.79, p = 0.004) and neonatal sepsis (AUC 0.65 versus 0.75, p = 0.04). The negative predictive value of CS-sRAGE for neonatal sepsis was very strong (NPV = 0.91). Conclusions: The sRAGE can be used to help predict adverse perinatal outcomes. Patients with higher levels of sRAGE – who therefore may have an enhanced capability to regulate their immune response – appear less likely to experience PTB and neonatal sepsis.
To establish reference ranges for the fetal thymic-thoracic ratio (TT-ratio) and to compare results with those from fetuses with congenital heart defects (CHD) with and without microdeletion 22q11 (del.22q11), a condition known to be associated with a hypoplastic thymus.
TT-ratio was defined as the quotient of the anteroposterior thymic to the intrathoracic mediastinal diameters measured in the three vessels and trachea view. This ratio was measured in a prospective cross-sectional study of 302 normal healthy fetuses between 15 and 39 weeks' gestation. The study group comprised two groups: one group (CHDn) consisted of 90 fetuses with CHD and a normal karyotype with no del.22q11 and the other group (CHD(22)) included 20 fetuses with CHD and a normal karyotype but with proven del.22q11.
The TT-ratio of the normal fetuses did not show any statistically significant change during gestation, with a mean value of 0.44. The values of all 90 fetuses of the CHDn group were within the normal range and no different from normal fetuses. However, 19 of the 20 (95%) fetuses in the CHD(22) group had a significantly smaller TT-ratio (P < 0.001) compared with both the CHDn group and the normal fetuses, having a mean value of 0.25.
The TT-ratio is reliable and easy to obtain during fetal echocardiography. Fetuses with CHD and a low TT-ratio can be considered at high risk of having microdeletion del.22q11.
To determine sonographically the transverse diameter of the fetal thymus and present nomogram for the transverse diameter of the fetal thymus in uncomplicated singleton pregnancies between 19 and 38 weeks of gestation. Setting: Department of Obstetrics and Gynecology, Charles University in Prague, Faculty of Medicine Hradec Kralove, University Hospital Hradec Kralove, Czech Republic.
A prospective study was performed. The transverse diameter of the fetal thymus was measured by the one experienced examiner in 198 healthy fetuses between 19 and 38 weeks of gestation.
The transverse diameters of the fetal thymus were obtained from 183 of the 198 subjects. The regression equation was expressed as a function of gestational age: the transverse diameter of the fetal thymus (mm) = 1.001 × gestational age (week) - 0.932 or 0.143 × day - 1.34. Both the correlation coefficients, r=0.91 for weeks and r=0.92 for days were found to be highly statistically significant (p<0.0001).
This study presents normative data (mean, 5th and 95th) for the ultrasound measurements of the transverse diameter of the fetal thymus in healthy singleton pregnancies.
To assess whether the analysis of high sensitivity C-Reactive Protein (hsCRP), a biomarker of inflammation, and placental growth factor (PlGF), a biomarker of placental dysfunction, could help identify patients at risk for preterm birth (PTB).
We performed a prospective cohort study of women with symptoms of preterm labor (22-33 6/7 weeks). Maternal serum was analyzed for hsCRP and PlGF. Median biomarker values were used as analytic cut-points. We performed chi-square tests of association between biomarkers and PTB, nonparametric tests to compare medians, and logistic regression to determine the odds of PTB associated with biomarker values. Test characteristics of each biomarker were calculated.
56.3% of the cohort (N = 96) delivered preterm. Median hsCRP (N = 78) was 4.34 mg/L, and median PlGF (N = 86) was 558.25 mg/l. In the setting of inflammation (high hsCRP), women with low PlGF had a 6.84-fold (95%CI: 1.57-29.80) increased risk of PTB. In the setting of placental dysfunction (low PlGF), women with high hsCRP had a 5.97-fold (95%CI: 1.52-23.43) increased risk of PTB.
Our results suggest an interplay between inflammation and placental dysfunction in the pathogenesis of PTB. Analyzing biomarkers that reflect different pathways of PTB may hold promise for identifying patients at greatest risk.
The thymus is a primary lymphoid organ with both endocrine and immune functions. There is a large body of evidence indicating the existence of a complex neuroendocrine control of the thymus physiology. This is supported by the historic observation that the thymus becomes involuted during the response to stress. The thymus is dramatically affected by the acute phase response (APR), a systemic reaction to tissue injury and/or infection accompanied by profound neuroendocrine and metabolic changes. The APR comprises alterations in behavior, body temperature, and production and release of cytokines, particularly interleukin (IL)-1, IL-6 and TNFalpha, and glucocorticoids (GCs) and is characterized by suddenly increased production of so-called acute phase proteins (APPs). The stimulation of APR activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the suppression of specific immunity, which might serve to protect the organism from adverse immune reactions; the immunostimulatory hormones (e.g., PRL, GH, IGF-1) are suppressed, whereas the production of APPs in the liver is stimulated by IL-6, catecholamines and GCs. The most striking effect of the latter on the immune system is the induction of apoptosis in the thymus. In concert with GCs, elevated levels of catecholamines also selectively suppress immune response mechanisms. APR may be regarded as an emergency response that represents a switch of the host defense from the adaptive immune response which is slow to develop and is commanded by the thymus and T-lymphocytes to a less specific, but more rapid and intense reaction. Here we discuss the immunoregulatory changes during the APR with a special emphasis on the role of thymus in this process.
Emerging evidence indicates a relationship between bronchopulmonary dysplasia (BPD) and chorioamnionitis. Recent data provide evidence of an acute thymic involution in very low birth weight (VLBW) preterm infants and fetuses with histologic chorioamnionitis. We tested the hypothesis that a small thymus detected at birth on the routine chest radiograph is a predictor of BPD in VLBW infants.
A prospective study was conducted on 400 VLBW preterm infants who survived >4 weeks (mean gestational age: 27.5 weeks [range: 24-30]; mean birth weight: 1010 g [range: 450-1450]). Thymic size was measured on routine chest radiographs taken in the first 6 hours after birth and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina and that of the thorax (CT/T). The accuracy of CT/T for identifying infants with BPD was tested using receiver operating characteristic curve analyses and multivariate logistic regression.
Fifty-one VLBW infants (12.7%) subsequently developed BPD. A small thymus (CT/T <0.28) was observed in 94.1% of the infants with BPD versus 2.9% of the infants without BPD. A small thymus at birth identified infants with BPD with 94.1% sensitivity and 98.3% specificity (odds ratio: 17.8; 95% confidence interval: 5.7-55.4).
A small thymus at birth on the standard chest radiograph can accurately identify VLBW infants who subsequently develop BPD.
The Fetal Inflammatory response Syndrome (FIRS) describes a state of extensive fetal multi organ involvement during chorioamnionitis, and is associated with grave implications on perinatal outcome. The syndrome has been linked to the preterm parturition syndrome and is associated with inflammation/ infection processes in most of the fetal organs. The fetal thymus, a major organ in the developing immune system involutes during severe neonatal disease and has been shown to be smaller in fetuses with FIRS. Various methods for imaging of the fetal thymus and measurement are described. Currently the only method to diagnose FIRS prenatally is through amniocentesis. We suggest that women who are admitted with preterm labor with intact membranes and those with PPROM should have a detailed sonographic examination of the fetal thymus as a surrogate marker of fetal involvement in intrauterine infection/inflammation processes. This article is protected by copyright. All rights reserved.
This article reviews risk factors for preterm delivery, with special attention to previous preterm birth and a short cervix. Strategies for minimizing the risk of preterm birth among high-risk women, including progesterone supplementation and cerclage, are discussed. ForewordThis Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.StageA woman presents for prenatal care in the first trimester of her third pregnancy. Her first child was born at 30 weeks of gestation after preterm labor. Her second pregnancy ended in delivery at 19 weeks of gestation. How would you recommend reducing the risk of preterm birth in this pregnancy? The Clinical Problem In the United States, the annual rate of preterm births (before 37 weeks of gestation) reached a peak of 12.8% in 2006 and was 11.7% in 2011.(1) The rate in the United States remains nearly twice the rate in European nations.(2) Premature birth in the ... Prevention of Preterm Parturition Despite advances in neonatal care, preterm birth remains a leading cause of infant death in the United States, especially among blacks. Systemic changes in reproductive health care to reduce the incidence of multifetal pregnancies and scheduled births before 39 weeks of gestation that lack a medical indication have been temporally associated with decreased preterm birth rates. Strategies to identify and treat medical risk factors in early pregnancy (e.g., genitourinary infection and poor nutrition) have not been effective in reducing preterm birth rates. Previous preterm birth and a short cervix (20 mm, as measured by transvaginal ultrasonography) are major risk factors for preterm birth. The use of progesterone supplementation in women with a previous preterm birth, a short cervix, or both was shown in randomized trials to reduce the frequency of preterm birth and is recommended for women with these risk factors. Cervical cerclage reduces the risk of recurrent preterm birth among women with a short cervix.
Thymic size can be affected by both exogenous and endogenous glucocorticoids. The risk of respiratorydistress syndrome is reduced after maternal steroid administration. To find whether fetal lung maturity correlates with size of the thymus, the cardiothymic: thoracic ratio was measured in 167 newborn infants with and without RDS. Mean CT/T was significantly greater (0.40 vs 0.35; P<0.001) in those babies with RDS. This relation was independent of gestational age, although an increase in CT/T with advancing gestational age was shown. Prepartum maternal steroid administration did not result in significant involution of the cardiothymic shadow when compared with control infants with and without RDS. The CT/T may be of use in predicting which premature babies are more likely to develop RDS.
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An abstract is unavailable. This article is available as HTML full text and PDF.
Objective
We aim to test the hypothesis that two-dimensional (2-D) fetal adrenal gland volume (AGV) measurements offer similar volume estimates as volume calculations based on 3-D technique. Methods
Fetal AGV was estimated by three-dimensional (3-D) ultrasound (VOCAL) in 93 women with signs/symptoms of preterm labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula derived from 2-D measurements of the same blocks (0. 523×length×width×depth). Comparisons were performed by intraclass correlation coefficient (ICC), coefficient of repeatability, and Bland-Altman method. The corrected AGV (cAGV; AGV/fetal weight) was calculated for both methods and compared for prediction of preterm birth (PTB) within 7 days. ResultsAmong 168 volumes, there was a significant correlation between 3-D and 2-D methods (ICC=0.979; 95% confidence interval [CI]: 0.971 to 0.984). The coefficient of repeatability for the 3-D was superior to the 2-D method (intraobserver 3-D: 30.8, 2-D:57.6; interobserver 3-D:12.2, 2-D: 15.6). Based on 2-D calculations, cAGV433 mm3/kg was best for prediction of PTB (sensitivity: 75%, 95% CI=59 to 87; specificity: 89%, 95% CI=82 to 94). Sensitivity and specificity for the 3-D cAGV (cutoff420 mm3/kg) was 85% (95% CI=70 to 94) and 95% (95% CI=90 to 98), respectively. In receiver-operating-curve curve analysis, 3-D cAGV was superior to 2-D cAGV for prediction of PTB (z=1.99, p=0.047). Conclusion2-D volume estimation of fetal adrenal gland using ellipsoid formula cannot replace 3-D AGV calculations for prediction of PTB.
Three large randomized controlled trials investigating the efficacy of universal cervical length screening and treatment with vaginal progesterone or cervical cerclage to prevent preterm delivery have been published over the past several years. None of these trials demonstrate proven efficacy for universal cervical length screening and cerclage placement in women with short cervical length. However, universal cervical length screening and treatment with daily vaginal progesterone in women with short cervical length reduces the risk of preterm birth, but large numbers of women must be screened to prevent a relatively small number of preterm deliveries. Issues that should be considered while implementing universal cervical length screening include: (1) standards of quality and reproducibility for transvaginal ultrasound cervical length ascertainment; (2) implications of screening on the application of therapeutic strategies to populations not known to benefit (so-called "indication creep"); and (3) willingness of obstetricians to prescribe vaginal progesterone formulations that are not approved by the US Food and Drug Administration for preterm birth prevention. Optimal strategies to employ cervical ultrasound and progesterone treatment might be revealed by additional studies investigating cervical length cutoffs, frequency of screening, selective screening in higher-risk groups, and the use of transabdominal cervical length screening as a surrogate for transvaginal cervical length screening.
In preeclampsia the maternal adaptive immune system undergoes specific changes, which are different from the physiological processes associated with healthy pregnancy. Whether preeclampsia also affects the fetal immune system is difficult to investigate, due to limited access to the fetus. We hypothesized that if preeclampsia affects the fetal adaptive immune system this might be associated with early changes in thymic growth. In this case-control study, 53 preeclamptic and 120 healthy control pregnancies were matched for maternal age, gestational age and smoking. Fetal thymus diameter was measured as the greatest width perpendicular to a line connecting sternum and spine based on ultrasound images taken at 17-21 weeks gestation. Independent of fetal and maternal anthropometric measures, thymuses were found to be smaller in preeclamptic pregnancies than healthy controls (16.2 mm versus 18.3 mm, respectively, mean difference=2.1 mm, 95% CI: 0.8-3.3, p<0.001), and the odds of developing preeclampsia was estimated to be 0.72 (95% CI: 0.60-0.86, p<0.001) lower for each 1 mm increase in thymus diameter. There was no correlation between the onset of preeclampsia and fetal thymus size. This is the first study to suggest that fetal thymus growth is reduced before the clinical onset of preeclampsia and precedes any described fetal anomalies or maternal immunological changes associated with preeclampsia. We propose that the fetal adaptive immune system is either passively affected by maternal processes preceding clinical preeclampsia or is actively involved in initiating preeclampsia in later pregnancy.
To investigate the risk of preterm birth (delivery at less than 37 weeks of gestation) by evaluating the fetal adrenal gland volume, hallmark of activation of the fetal hypothalamic-pituitary-adrenal axis, measured by 3-dimensional ultrasonography.
We performed 3-dimensional ultrasound examination of the fetal adrenal gland volume in 126 singleton fetuses, prospectively comparing those born to mothers with signs or symptoms of preterm labor (n=53) to control subjects (n=73). Multiplanar technique with rotational methods for measurement of fetal adrenal gland volume was performed by using Virtual Organ Computer-Aided Analysis (VOCAL) technology.
The fetal adrenal gland volume was successfully examined in 86.5% of the cases. There was a direct relationship between the fetal adrenal gland volume and estimated fetal weight. A corrected adrenal gland volume of greater than 422 mm3/kg was best in predicting preterm birth within 5 days from the time of the measurement. The sensitivity, specificity, and positive and negative likelihood ratios were 92%, 99%, 93.5, and 0.08, respectively. Multiple logistic regression analysis showed that the corrected adrenal gland volume was the only significant independent predictor factor of preterm birth within 5 days of measurement.
Corrected adrenal gland volume measurement may identify women at risk for impending preterm birth. This information can be generated noninvasively and in time for clinical decision making.
II.
To compare measurements of the fetal thymus obtained by magnetic resonance imaging (MRI) and ultrasound (US).
Written informed consent was obtained from the patients that participated in this Institutional Review Board-approved observational study. The study population consisted of 17 pregnant women carrying fetuses between 21 and 34 weeks of gestation with suspected abnormalities. The transverse diameter and perimeter of the thymus were measured in these fetuses at the level of an axial view of the thorax that includes the pulmonary, aorta, and superior vena cava. The degree of agreement between MRI and US measurements was determined using Lin's concordance correlation coefficient and Bland-Altman analysis.
The mean (standard deviation, SD) gestational age at the time of the prenatal evaluation was 28.4 weeks (3.6). The thymus was measured by MRI and US in all cases. Comparison of the measurements from these two imaging modalities demonstrated a relatively good reproducibility with no evidence of systematic error.
MRI and US measurements of the fetal thymus during the second half of pregnancy are comparable. This finding suggests that MRI can become a useful adjuvant to US for assessment of the fetal thymus.
Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.
This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat.
Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups.
The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.
To determine whether the thymus is smaller in fetuses of pre-eclamptic mothers than in those of normal controls.
This was a cross-sectional, prospective, comparative study of sonographically determined fetal thymus measurements in 39 pregnancies with pre-eclampsia and 70 healthy pregnancies.
Both the diameter and the perimeter of the fetal thymus were smaller in pregnancies with pre-eclampsia than in healthy controls. The means of the thymus diameters were 28.6 ± 5.9 and 32.9 ± 4.5 mm and of thymus perimeters 80.9 ± 16.5 and 93.1 ± 16.6 mm for pre-eclamptic and healthy pregnancies, respectively (P < 0.001). General linear models showed that smaller fetal thymuses in pre-eclampsia were independent of gestational age, estimated fetal weight, small for gestational age status and antenatal steroid use.
Pre-eclampsia is associated with smaller fetal thymuses.
How do we do it?
Practical advice on imaging-based techniques and investigations
Our objectives were to compare the size and volume of the developing fetal thymus obtained by two-dimensional ultrasound (2D-US) and three-dimensional ultrasound (3D-US), develop normative data for thymus volume (TV), and investigate TV in fetuses with congenital heart disease (CHD) and normal twin gestations.
We studied 321 fetuses (gestational age (GA): 17-39 weeks) including 238 normal singletons, 64 normal twins and 19 singleton fetuses with CHD. We used 2D-US to assess fetal thymus maximum transverse diameter (MTD), maximum transverse area (MTA), anteroposterior diameter (APD) and superoinferior diameter (SID). TV was obtained by 3D-US using virtual organ computer-aided analysis. Measurements were adjusted for estimated fetal weight where appropriate. Linear regression analysis, general linear models and Fisher's Z-transformation were used where appropriate. A nomogram of fetal TV based on singleton gestations was produced according to previously published methods.
Ultrasound assessment of the fetal thymus was possible in 95.3% (306/321) of cases. Both 3D-US and 2D-US measurements were significantly correlated with GA (TV r = 0.989; MTA r = 0.918; MTD r = 0.884; APD r = 0.849; and SID r = 0.816; all P < 0.05). After Fisher's Z-transformation, the correlation between the TV and GA was significantly stronger than that between any individual 2D-US measurement and GA (P < 0.05). Normal twin fetuses had TVs similar to those of singletons adjusted for estimated fetal weight and GA (P = 0.85). TV adjusted for estimated fetal weight and GA was significantly lower in fetuses with CHD than in normal singletons (P < 0.05).
2D-US and 3D-US are useful tools for evaluation of the size and volume of the human fetal thymus through gestation. Fetal TV by 3D-US seems to reflect normal development of the thymus in utero better than do 2D-US measurements. Lower TV should be expected in association with CHDs.
The main objective of this study was to determine whether fetal thymic measurements could be obtained in twins, with a secondary goal to determine whether thymic measurements from uncomplicated singleton and twin pregnancies are comparable.
The transverse diameter and perimeter of the fetal thymus were measured prospectively in 678 singleton and 56 twin pregnancies, and their relationships with gestational age were determined and compared between groups.
Thymic measurements were possible in 757 (95.8%) of the 790 fetuses. Measurements were not possible in 19 of 678 singletons (2.8%) and in 14 of the 112 (12.5%) twins (P < 0.001). After construction of nomograms for the transverse diameter and perimeter of the fetal thymus, similar measurements were noted for singletons and twins.
These results suggest that sonographic measurements of the thymus are feasible in twin pregnancies and that, in uncomplicated pregnancies, these measurements are similar to those noted for singletons. These findings pave the way for future studies aimed at determining the clinical utility of thymic measurements in complicated singleton and twin pregnancies.
We assessed the risk of adverse pregnancy outcomes (preterm birth [PTB], preeclampsia [PRE], fetal growth restriction [FGR], or perinatal death) in women with periodontal disease (PD) compared to those without.
A multicenter prospective cohort study enrolled women from 3 sites between 6 and 20 weeks' gestation. The presence of PD was defined as periodontal attachment loss > or = to 3 mm on 3 or more teeth. The primary binary composite outcome included PRE, PTB, FGR, or perinatal death. Multivariable logistic regression (MVLR) was used to control for confounders.
Three hundred eleven patients with and 475 without PD were included. There was no association between PD and the composite outcome, PRE, or PTB in unadjusted analyses. There was no association between PD and the composite outcome (adjusted odds ratio [AOR], 0.81; 95% confidence interval [CI], 0.58-1.15; P = .24), preeclampsia (AOR, 0.71; 95% CI, 0.37-1.36; P = .30), or preterm birth (AOR, 0.77; 95% CI, 0.49-1.21; P = .25) after adjusting for relevant confounders.
Despite the body of literature suggesting an association between PD and adverse pregnancy outcomes in urban populations, this large prospective study failed to demonstrate an association.
To test the hypothesis that intrauterine growth restriction (IUGR) is associated with decreased thymus size in the human fetus.
The thymus perimeter was measured in 60 consecutive IUGR fetuses at prenatal ultrasound examination. IUGR was defined as an abdominal circumference (AC) <5(th) centile. Sixty controls were identified by selection of the next consecutive appropriately grown fetus of similar gestational age (+/-1 week). To exclude fetal size effects, ratios between thymus perimeter and fetal biometry measurements including biparietal diameter (BPD), AC and femur length (FL), as well as estimated fetal weight (EFW) were compared between IUGR fetuses and controls.
The proportion of fetuses with thymus perimeter <5(th) centile for gestation was significantly higher in IUGR fetuses than in controls (58/60 vs. 7/60, P < 0.0001). The mean thymus perimeter/BPD ratio (0.87 +/- 0.20 vs. 1.13 +/- 0.13, P < 0.0001), thymus perimeter/AC ratio (0.28 +/- 0.06 vs. 0.35 +/- 0.03, P < 0.0001), thymus perimeter/FL ratio (1.18 +/- 0.26 vs. 1.51 +/- 0.19, P < 0.001) and thymus perimeter/EFW ratio (0.05 +/- 0.01 vs. 0.06 +/- 0.01, P = 0.02) were significantly lower in IUGR fetuses than in controls. There was a significant positive correlation between the observed-to-expected mean for gestation thymus perimeter ratio and the enrollment-to-delivery interval (r = 0.44, P < 0.001).
IUGR is associated with a disproportionately small thymus. This supports the hypothesis that thymic involution may be part of the fetal neuroendocrine response to intrauterine starvation.
The purpose of this study was to determine whether the size of the thymus is different in male and female fetuses.
In this prospective study, the transverse diameter and perimeter of the thymus were measured in healthy fetuses between 24 and 37 weeks' gestation. The means of the study variables from male and female fetuses were compared by the Student t test, and the relationships between the transverse diameter and perimeter of the thymus and gestational age and other common fetal biometric parameters were determined by linear regression modeling.
No differences were noted between male and female fetuses for the means of the study variables. After the relationship between the transverse diameter and perimeter of the thymus and gestational age was confirmed (R(2) = 0.8 and 0.75, respectively; both P < .01), the 95% confidence interval-predicted changes were calculated, and the scatterplots of the measurements suggested that sex did not affect the size of the thymus. Bland-Altman plots were used to analyze intraobserver variability and showed good agreement for both of these thymic measurements for male and female fetuses.
These results suggest that fetal sex does not affect the size of the thymus and, together with previous reports, support the hypothesis that a quantitative reduction in fetal thymus size could serve as an indirect marker of abnormal thymopoiesis and congenital thymic insufficiency.
The thymic weights of 20 growth-retarded babies dying at or about birth were found to be less than normal for their birth weights. It is suggested that small-for-dates babies that survive may be immunodeficient as are children who suffer from extrauterine malnutrition.
Thymic size can be affected by both exogenous and endogenous glucocorticoids. The risk of respiratory distress syndrome is reduced after maternal steroid administration. To find whether fetal lung maturity correlates with size of the thymus, the cardiothymic:thoracic ratio was measured in 167 newborn infants with and without RDS. Mean CT/T was significantly greater (0.40 vs 0.35; P less than 0.001) in those babies with RDS. This relation was independent of gestational age, although an increase in CT/T with advancing gestational age was shown. Prepartum maternal steroid administration did not result in significant involution of the cardiothymic shadow when compared with control infants with and without RDS. The CT/T may be of use in predicting which premature babies are more likely to develop RDS.
A prospective study was performed in 340 obstetric sonograms to evaluate the sonographic characteristics of the fetal thymus. The thymus was identified as a homogeneous structure in the anterior fetal mediastinum in 251 cases (74%). The thymus was categorized as either hyperechoic, isoechoic, or hypoechoic relative to fetal lung. Seventy one of 115 cases (62%) prior to 27 weeks gestation were hyperechoic relative to fetal lung whereas 100 of 136 cases (73%) after 27 weeks were hypoechoic relative to lung (p less than .0001). Thymic measurements and shape were also recorded. The anterior-posterior AP thickness, measured in the midline at the sternum, ranged from 2 mm at 14 weeks to 20.8 mm at term. This study demonstrates that the thymus can be imaged in most fetuses.
To develop a current national fetal growth curve that can be used as a common reference point by researchers to facilitate investigations of the predictors and consequences of small and large for gestational age delivery.
Single live births to United States resident mothers in 1991 (n = 3,134,879) were used for the development of this curve, which was compared with four previously published fetal growth curves. Techniques were developed to address cases with implausible birth weight-gestational age combinations and to smooth fetal growth curves across gestational age categories.
In general, the previously published fetal growth curves underestimated the 1991 United States reference curve. This underestimation is most apparent during the latter weeks of gestation, approximately 33-38 weeks.
Our findings indicate that the prevalence of fetal growth restriction (FGR) will vary markedly, depending on the fetal growth curve used. Furthermore, many previously published fetal growth curves no longer provide an up-to-date reference for describing the distribution of birth weight by gestational age and for determining FGR that is consistent with the most recent live birth data for the entire United States.
The three-vessel view is a transverse view of the fetal upper mediastinum is as simple to obtain as the four-chamber view. It demonstrates the main pulmonary artery, ascending aorta and superior vena cava in cross- or oblique sections. The purposes of this study were to describe the normal anatomy of the three-vessel view and to analyze what anatomical changes would occur in this view when there are lesions of the ventricular outflow tracts and/or great arteries. Sonograms of 29 fetuses with lesions involving the ventricular outflow tracts and/or great arteries were reviewed. Three-vessel views were evaluated in terms of vessel size, number, arrangement and alignment.
Twenty-eight of 29 fetuses showed an abnormal three-vessel view that included abnormal vessel size (n = 12), abnormal alignment (n = 8), abnormal arrangement (n = 7) and abnormal vessel number (n = 3). The vessel size was abnormal in obstructive lesions of the right (n = 4) or the left (n = 8) side of the heart. An abnormal alignment was seen in tetralogy of Fallot (n = 6) and double-outlet right ventricle (n = 2) that showed anterior displacement of the aorta. An abnormal arrangement was seen in complete (n = 4) and corrected (n = 1) transpositions, double-outlet right ventricle (n = 1) and pulmonary atresia with ventricular septal defect (n = 1). Only two vessels were seen in truncus arteriosus (n = 1). Four vessels were seen in persistent left superior vena cava (n = 2). A fetus with pulmonary atresia and intact ventricular septum showed a normal three-vessel view.
In conclusion, most of the lesions involving the ventricular outflow tracts and/or great arteries showed an abnormal three-vessel view. Copyright © 1997 International Society of Ultrasound in Obstetrics and Gynecology
Labor is the physiologic process by which a fetus is expelled from the uterus to the outside world. Labor is defined as an increase in myometrial activity or, more precisely, a switch in the pattern of myometrial contractility from irregular contractures (long-lasting, low-frequency activity) to regular contractions (high-intensity, high-frequency activity),1 resulting in effacement and dilatation of the uterine cervix. In normal labor, there appears to be a time-dependent relation between the biochemical changes in the connective tissue in the cervix that usually precede uterine contractions and cervical dilatation. All these events usually occur before the spontaneous rupture of the fetal . . .
Chorioamnionitis, a major cause of preterm birth with significant neonatal morbidity and mortality, frequently occurs in mothers who are free of symptoms. A combined clinical, radiologic, and pathologic study of 129 very low birth weight infants indicated a significant association between a markedly decreased thymic size at birth and subclinical chorioamnionitis.
A retrospective study was conducted to assess radiographically the thymus size in well and sick neonates and to search for a possible relationship to perinatal events. Thymus size was expressed as cardiothymic:thoracic ratio (CT/T) by measuring the width of the cardiothymic shadow at the level of carina and dividing it by the width of the thorax at the costophrenic angles. The CT/T was measured on chest radiographs obtained on day 1 in well term neonates consecutively born in our nursery and sick neonates with meconium staining of the amniotic fluid, meconium aspiration syndrome or respiratory distress syndrome (RDS). Neonates with congenital anomalies, congenital heart disease or intrauterine growth retardation were excluded. There were no significant relationships between CT/T and sex, birth route, birthweight or gestational age in well and sick term neonates. The CT/T were comparable among well and sick term neonates and were significantly greater in the preterm neonates with RDS than in the preterm neonates without RDS. The CT/T was correlated to the birth route only in the preterm neonates.
We conclude that thymus involution in the perinatal period is a complex process and the response is different between term and preterm neonates.
Chorioamnionitis represents the leading cause of preterm birth and related pathologic conditions as well as of fetal death and frequently occurs in symptom-free mothers. Recent radiologic findings have indicated that thymus size is significantly reduced in preterm infants born to mothers with subclinical, histologically proven chorioamnionitis. However, an accurate morphologic description of the thymus gland in fetuses and neonates with chorioamnionitis is lacking, although it is known that infection and other stress processes may cause lymphocyte depletion in the thymuses of infants and older babies (acute stress involution). We describe morphologic modifications in the thymus of fetuses with histologically proven chorioamnionitis and newborn infants with chorioamnionitis and proven sepsis. The main findings included (1) decreased organ volume (ANOVA, P < .0024); (2) reduced corticomedullary ratio (P < 10(-6)); (3) significant changes in the relationship between thymic parenchyma and thymic interstitial tissue with resulting increased organ complexity (P = .03); (4) severe reduction of thymocytes; and (5) other degenerative processes such as monocyte/macrophage infiltration of Hassall's bodies. These results indicate that chorioamnionitis, with or without sepsis, is associated with significant morphologic modifications in the thymus. We wish to note that the described thymic pathology is only one aspect of the fetal systemic inflammatory response syndrome with which chorioamnionitis is associated.
Coronary heart disease remains the leading cause of morbidity and mortality in the industrialized world. Clinical and laboratory studies have shown that inflammation plays a major role in the initiation, progression, and destabilization of atheromas. C-Reactive protein (CRP), an acute phase reactant that reflects low-grade systemic inflammation, has been studied in a variety of cardiovascular diseases.
Findings from prospective clinical trials were examined to determine the prognostic utility of CRP in acute coronary syndromes, and observations from epidemiological studies were reviewed to determine the ability of CRP to predict future first coronary events. The analytical considerations of CRP measurement in these clinical applications were also examined.
In patients with established coronary disease, CRP has been shown to predict adverse clinical events. In addition, prospective studies have consistently shown that CRP is a strong predictor of future coronary events in apparently healthy men and women. The relative risk associated with CRP is independent of other cardiovascular disease risk factors. High-sensitivity CRP (hs-CRP) assays are needed for risk assessment of cardiovascular disease. Such assays are currently available but may require further standardization because patients' results will be interpreted using population-based cutpoints. Preventive therapies to attenuate coronary risk in individuals with increased hs-CRP concentrations include aspirin and statin-type drugs.
hs-CRP has prognostic utility in patients with acute coronary syndromes and is a strong independent predictor of future coronary events in apparently healthy subjects.
To present the normative data of the transverse diameter of the developing fetal thymus.
In this prospective study, the maximum transverse diameter of the thymus was measured by one sonologist in 376 normal fetuses between 19 and 38 weeks of gestation. We assessed the relationship of the transverse thymic diameter with gestational age (GA), biparietal diameter, femur length and abdominal circumference using general linear regression modeling. The predicted mean and 95% reference range of thymic diameter at each GA were calculated from the regression equation.
Measurements of the transverse diameter were possible in 352 of the 376 (94%) fetuses. The transverse diameter of the fetal thymus increased with increasing GA and fetal size parameters in a linear manner. The regression equation for transverse diameter of the thymus as a function of GA was: thymic diameter (cm) = 0.15 x GA (weeks) - 1.59 (r(2) = 0.86, P < 0.001).
The transverse diameter of the fetal thymus is easy to measure; this study presents normative data.
Emerging evidence indicates that chorioamnionitis is associated with a significant decrease in thymic size at birth in very low birth weight (VLBW) preterm infants. The aim of this study was to determine whether decreased fetal thymus size is associated with histological or clinical chorioamnionitis in patients with preterm premature rupture of membranes (PROM).
Twenty-one patients between 24 and 35 weeks of gestation with preterm PROM were included. Serial ultrasound examinations were performed during the latency period, and measurements of the fetal thymus size were obtained. Small thymus was defined as a thymus perimeter < or = 5th percentile according to a fetal thymus nomogram, which was based on measurements of 403 fetuses. Diagnosis of chorioamnionitis was made using neonatal clinical parameters and histological examinations of the placentas.
In our study 13 patients presented with thymus size below the 5th percentile. Among the 13 patients with small thymus, nine (69%) had clinical or histological findings consistent with the diagnosis of chorioamnionitis. All eight women with a normal-sized thymus had no evidence of clinical or histological chorioamnionitis. Fetal thymus perimeter < or = 5th percentile yielded a sensitivity of 100%, specificity of 66.7%, a positive predictive value of 69% and a negative predictive value of 100% for identifying chorioamnionitis in patients with preterm PROM.
Fetal thymus size is decreased in women with preterm PROM and chorioamnionitis. Measurement of the fetal thymus might allow an early diagnosis of chorioamnionitis in cases of preterm PROM. Normal thymus size might be used to rule out latent intrauterine infection.
Previous randomized trials have shown that progesterone administration in women who previously delivered prematurely reduces the risk of recurrent premature delivery. Asymptomatic women found at midgestation to have a short cervix are at greatly increased risk for spontaneous early preterm delivery, and it is unknown whether progesterone reduces this risk in such women.
Cervical length was measured by transvaginal ultrasonography at a median of 22 weeks of gestation (range, 20 to 25) in 24,620 pregnant women seen for routine prenatal care. Cervical length was 15 mm or less in 413 of the women (1.7%), and 250 (60.5%) of these 413 women were randomly assigned to receive vaginal progesterone (200 mg each night) or placebo from 24 to 34 weeks of gestation. The primary outcome was spontaneous delivery before 34 weeks.
Spontaneous delivery before 34 weeks of gestation was less frequent in the progesterone group than in the placebo group (19.2% vs. 34.4%; relative risk, 0.56; 95% confidence interval [CI], 0.36 to 0.86). Progesterone was associated with a nonsignificant reduction in neonatal morbidity (8.1% vs. 13.8%; relative risk, 0.59; 95% CI, 0.26 to 1.25; P=0.17). There were no serious adverse events associated with the use of progesterone.
In women with a short cervix, treatment with progesterone reduces the rate of spontaneous early preterm delivery. (ClinicalTrials.gov number, NCT00422526 [ClinicalTrials.gov].).
To assess the relation between sonographic fetal thymus size and the components of fetal inflammatory response syndrome (FIRS) in women with preterm prelabour rupture of membranes (PPROM).
Prospective cohort study.
University hospital from January through October 2006.
Fifty-six women with PPROM.
In these women, fetal thymus perimeter was measured sonographically. At birth, cord venous plasma interleukin-6 (IL-6) level estimation and histopathological examination of the placentas and umbilical cords were performed.
Small thymus size (< 5th percentile for gestational age) and its association with FIRS.
From the 56 women with PPROM, 54% had chorioamnionitis (CA), 23% had funisitis. IL-6 level was > 11 pg/ml in 52% of women and > 18 pg/ml in 41%. A small thymus was more associated with male fetuses, shorter preterm prelabour rupture of membranes delivery interval, higher IL-6 level, higher frequency of funisitis and CA. When data were regressed for confounding, only IL-6 level and funisitis remained significant independent factors that influence the thymus size. In the subset of women (n = 19) who delivered within 1 week of first measurements, a small thymus had sensitivity and positive predictive value of 93%, specificity and negative predictive value of 75% and accuracy of 89% in the identification of FIRS (IL-6 >18 pg/ml and/or funisitis).
An association exists between fetal thymic involution and components of FIRS in women with PPROM. Small fetal thymus size may be considered a reliable sonographic marker of fetal involvement in the inflammatory response.
Progesterone and the risk of preterm birth among women with a short cervix
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- Brandt
Brandt et al-Second-Trimester Thymus Measurements Are Not Associated With Preterm Birth
J Ultrasound Med 2016; 35:989-997
Fetal adrenal gland volume: a novel method to identify women at risk for impending preterm birth
- Turan