The lungs are the last fetal organ essential for extra uterine survival to achieve functional maturity. Moreover, pulmonary surfactant deficiency causes neonatal respiratory distress syndrome [12].
Prenatal diagnosis of lung maturity allow therapeutic protection against possible respiratory distress and permits delivery by planned cesarean section sufficiently early to avoid the possible complications. Some studies of ultrasound prediction of fetal lung maturity compare ultrasound parameters with tests of amniocentesis to assess that sign with lung maturity [7].
The current study was conducted to evaluate accuracy and validity of using ultrasound and Doppler to measure some fetal parameters as indicators of lung maturity in comparison to the neonatal outcome regarding the need for neonatal intensive care unit (NICU) admission due to RDS. These parameters include BPD, FL, AC, placental grading, amniotic fluid vernix (FFP) epiphyseal ossification centers of femur and tibia (DFE and PTE), fetal thalamic echogenicity, colon grading, and lung to liver echogenicity. Doppler parameters also were evaluated in this study including umbilical, middle cerebral artery pulsatility and resistive indices, and uterine and fetal main pulmonary artery resistive indices.
The current study utilized RDS as an indicator of the status of fetal lung maturity, with 19 patients (15.8% of neonates had RDS). This percentage decreased with advanced gestational age (20% at 33 weeks, reach 0% at 37 weeks). Comparable results were reported by Abdulla et al. [13] who found an RDS incidence of 12% for infants born earlier than 40 weeks gestation versus 0% for those born after 40 weeks. Similarly, Hibbard et al. [14] reported an incidence of 10.5% for infants born between 34 and 36 weeks of gestation and only 0.3% for those born at 38 weeks. Globally, a wide range of RDS incidence has been reported. Compared to the findings of the present study, much less figures were identified by other researchers, where Edwards et al. [15] found an RDS incidence of 7% and Ghafoor et al. [16] reported even lesser incidence (3.7%) among neonates at 36 weeks of gestation.
Regarding the Doppler parameters as a marker for fetal lung maturity, we evaluated the values of umbilical artery and our results showed that UA RI > 0.69 correlated with neonatal RDS.
Scopesi et al. [17] did a study to relate umbilical artery RI Doppler velocimetry to fetal and neonatal distress to establish whether umbilical artery Rl is a predictor of RDS and assess which fetal parameter is the best predictor of neonatal respiratory distress syndrome. They concluded that increased UA RI values (> 0.70) can be considered cut-off value that can predict which fetuses are at low/high risk for respiratory disorders and Doppler velocimetry analysis can provide more reliable information about fetal conditions and predict in which cases timing of delivery and unit care admission should be programmed [17].
In a study by Piazze et al. [9] where fetal lung maturity (FLM) indexes were correlated against Doppler velocimetry values, FLM was assessed by lamellar body count (LBs) in amniotic fluid by amniocentesis. They stated a positive correlation between MCA PI and LBs. MCA PI showed a trend towards lower values in neonates affected by RDS (1.36 ± 0.5 vs. 1.69 ± 0.4, NS).
They also found that a value of mean Ut RI > 0.64 correlated to a delayed biophysical FLM expressed as a decrease of LBs with a sensitivity of 90.9% and specificity of 90.3% [9].
These findings were in agreement with our results as our study also showed that MCA PI had lower values in neonates affected by RDS (0.89–1.56) vs (1.21–1.61) in non-RDS due to the brain sparing effect.
Regarding Ut RI, our results showed higher values in fetuses that were affected by neonatal RDS (0.43–0.66) vs lower values in fetuses without RDS.
In this study, the evaluation of the main pulmonary artery RI showed higher values in fetuses affected by neonatal RDS with a cut point of MPA RI > 0.78 that correlated with RDS. Laban et al. [12] reported a cut-off value of pulmonary artery (PA) RI > 0.77 for prediction of neonatal RDS in preterm fetuses and this agrees to our results.
This matched with another study done by Moety et al. [18] mentioned a cut-off value of MPA RI > 0.77 showed a sensitivity of 67.3% and specificity of 43.5% for prediction of neonatal RDS in fetuses delivered in late preterm between 34 and 36 weeks + 6 days and early term between 37 and 38 weeks + 6 days of gestation.
Conversely, a study by Khanipouyani et al. [1] found no difference in the values of PA RI between RDS fetuses and non-RDS fetuses.
This study assessed the role of epiphyseal ossification centers for prediction of fetal lung maturity. Compared to other parameters the fetal tibia epiphysis was the best indicator of lung maturity followed by the femur epiphysis, where they showed sensitivity, specificity, and accuracy of 91% vs 90%, 95% vs 84%, and 92% vs 90%, respectively.
Likewise, Abdulla et al. [13] used the sonographic epiphyseal ossification centers to assess fetal lung maturity, and they correlated these findings with the presence of neonatal RDS. The study reported high sensitivity (95.5%), specificity (91.7%), and accuracy (95%) for fetal tibial epiphysis as a predictor of lung maturity.
These data indicated that visualization and measurement of the fetal knee and shoulder epiphyseal ossification before labor could help to distinguish fetuses with a mature lung amniocentesis profile. Interestingly enough, fetuses that were positive for both distal femur epiphysis and proximal tibia epiphysis had positive outcomes.
However, a number of critical points should be considered. Although the presence of these centers is an indication for maturity of the fetal lung, their absence does not exclude lung maturity. In addition, these epiphyseal centers must be identified with great care to avoid being confused with other adjacent cartilaginous structures. Also, DFE detection of any size may not be associated with fetal lung maturity in complicated pregnancies.
Regarding fetal thalamic echogenicity, the present study reported sensitivity, specificity, and accuracy of 77%, 79%, and 80%, respectively, for lung maturity prediction. We observed that thalamic density increased with increased fetus age in our daily practice, so the current study tried to evaluate this sign along with other ultrasound and Doppler parameters as indicators for fetal lung maturity.
Abdullah et al. [13] reported comparable results regarding thalamic echogenicity as an ultrasound marker of fetal lung maturity. Their findings showed sensitivity, specificity, and accuracy of 77.3%, 75%, and 77%, respectively.
Moreover, it was consistent with Rasheed et al. [7] who identified fetal lung maturity using thalamic echogenicity with a reported sensitivity, specificity and PPV of 63.33%, 86.53%, and 89.6%, respectively.
The present study used the amniotic fluid vernix for prediction of fetal lung maturity reporting a sensitivity of 83% and a specificity of 63%.
Comparable results were found by Rasheed et al. [7]. They found that the amniotic fluid vernix as a predictor of lung maturity had a sensitivity of 86.66% and a specificity of 48.7%.
The role of amniotic fluid particles as a predictor of fetal lung maturity has been studied by several researchers including Ram and Ram [11]. For prediction of RDS, Ram and Ram [11] reported a higher sensitivity (85.74%) and a lower PPV (66.67%) compared to our findings. Differences in the procedure used (amniocentesis vs ultrasound) or an inter-observer variation could explain this discrepancy.
Shweni and Moodley [19] reported an established lung maturity in all placental grade II and III fetuses, signifying that placental grading could be used to indicate fetal lung maturity instead of estimating lecithin/sphingomyelin (L/S) ratio, which will decrease the number of amniocenteses needed.
Loret de Mola et al. [4] reported that placental grade III had a low sensitivity (64%) and a high specificity (98%) for mature amniocentesis.
The present study found that grade III placental maturity could predict fetal lung maturity with a sensitivity of 81%, a specificity of 74%, and a PPV of 94%. Comparable results were reported by Abdullah et al. [13]. They showed that for prediction of fetal lung maturity, grade II and III placenta had sensitivity, specificity, and PPV of 60%, 75%, and 94%, respectively.
Bowerman et al. [20] established six categories of lung echogenicity relative to liver, ranging from lung much more echogenic than liver to lung less echogenic than liver and might condensed into three with little effect on the results.
Conversely, Cayea et al. [21] found echogenicity of the fetal lung /liver of essentially no value in predicting L/S or phosphatidylglycerol (PG) in amniotic fluid.
Likewise, Fried et al. [22] matched those results, as they found no clinically relevant association between fetal lung echogenicity and gestational age, L/S or presence of PG in amniotic fluid.
Our findings are in close agreement to their findings, as we could establish no significant relation between fetal lung echogenicity to liver and fetal lung maturity or neonatal RDS.
In the current study, fetal biometry as an ultrasound marker for fetal lung maturity revealed threshold values that correlated with lung maturation: BPD 82.8–93.5 mm, FL 62.7–72.1 mm, and AC 294–322 mm.
Chauhan et al. [23] did a study on estimation of fetal parts and correlated the numbers with mature L/S ratio and concluded a diagnostic threshold of BPD 84–92 mm, FL 64–72 mm, and AC 295–350 mm and those numbers are close to our results.
Regarding the BPD as a marker for fetal lung maturity, correlation of BPD > 90 mm with a positive shake test (in amniocentesis) showed 100% predictivity [3].
Loret de Mola et al. [4] reported that a grade 3 colon was 68% sensitive and 98% specific for a mature amniocentesis.
Another study by Rezaie Keikhaie et al. [24] classified the fetal intestine into 4 stages. They reported that grade 4 fetal intestine—as a predictor of fetal lung maturity—showed a low sensitivity (62.5%) and a high specificity (98.9%).
However, in the present study, the assessment of the colon grading as an ultrasound marker of fetal lung maturity showed no significant relation with fetal lung maturity.
The strengths of current study are the following: (1) Nearly the first paper—to the best of our knowledge—which discusses multiple parameters in a try to assess fetal lung maturity. (2) This study has a prospective design and minimal maternal/fetal co-morbidities in the study subjects, which could increase the applicability and validity of this technique prior to elective delivery of preterm fetuses especially in the event of NICU unavailability. (3) A single sonographer conducted all the ultrasound measurements, thus reducing the inter-observer and intra-observer variation.
(4) The researchers carried out the Doppler and ultrasound measurements within 72 h of delivery, thereby reducing the variability of the extended time period between measurement and delivery.
The limitations of this study are due to its pilot nature. We recommend the conduction of more studies to validate the results of this study in prediction of RDS in preterm fetuses.