In the present study, 90 pregnant mothers and their neonates born prematurely were examined. The mean age of the mothers who participated in the current study was 30.82 (±6.93) years, their mean weight was 87.72 (±11.59) kg, and their neonatal mean birth weight was 1576.64 (±447.26) gr. Among these mothers, 25 women experienced their first pregnancy, 34 women had their second pregnancy, 28 women had their third pregnancy, and 3 women experienced their fourth pregnancy (67 women had no previous abortions, while 19 women had one abortion and 4 women had two abortions). Out of these 90 pregnant mothers, 33 women (36.7%) had a normal vaginal delivery and 57 women (63.3%) had a cesarean section. When examining the umbilical artery Doppler, 48 women (53.3%) had a normal Doppler, 25 women (27.8%) had an absent Doppler, and 17 women (18.9%) had a reverse Doppler. Among the 33 neonates born by normal vaginal delivery, 26 neonates (78.7%) had a normal Doppler and 7 neonates (21.3%) had an absent Doppler. None of the neonates had a reverse Doppler. Out of the 57 neonates born by cesarean section, 22 neonates (38.5%) had a normal Doppler, 18 neonates (31.5%) had an absent Doppler, and 17 neonates (30%) had a reverse Doppler. The mean platelet count was 237170, 108000, and 67000 in the normal group, the absent group, and the reverse group, respectively (Table 1). The P-value analysis revealed a value of less than 0.05 (P=0.004); therefore, it can be concluded that the neonates’ mean platelet counts were different in various sonographic indices.
   The mean hemoglobin level was 17.17, 17.59, and 18.42 in the normal, absent, and reverse Doppler groups, respectively (Table 1). The P-value analysis indicated a value of greater than 0.05; therefore, it can be concluded that the neonates’ mean hemoglobin levels did not differ in various sonographic indices. The mean white blood cell (WBC) count was 14.81, 9.36, and 5.58 in the normal, absent, and reverse Doppler groups, respectively (Table 1). The P-value analysis showed a value of greater than 0.05; therefore, it can be concluded that the neonates’ mean WBC counts did not differ in various sonographic indices. The mean NRBC was 92.68, 399.71, and 511.67 in the normal, absent, and reverse Doppler groups, respectively (Table 1). The P-value analysis indicated a value of less than 0.05 (P=0.002); therefore, it can be concluded that the neonates’ mean NRBC blood levels were different in various sonographic indices. Assessing the arterial blood gases showed that the mean pH was 7.29, 7.01, and 6.89 in the normal, absent, and reverse Doppler groups, respectively (Table 1). The P-value analysis showed a value of ​​less than 0.05 (P=0.001), demonstrating a significant association between the levels of blood pH and sonographic indices of umbilical artery Doppler. Five neonates died before the third day after birth and before performing the cerebral ultrasound. Of the remaining 85 neonates, 1 neonate was born by normal vaginal delivery and 15 neonates were born by cesarean section developed IVH. Of these 16 neonates with IVH, 13 neonates (81.3%) were in the reverse Doppler group and 3 neonates (18.7%) were in the absent Doppler group (Table 1). None of the neonates in the normal Doppler group developed IVH. The P-value analysis showed a value of less than 0.05 (P=0.001); therefore, it can be concluded that there was a correlation between the incidence of IVH and Doppler sonographic indices.
   Five neonates died before the third day after birth and before measuring their bilirubin levels. Of the remaining 85 neonates, 20 neonates born by normal vaginal delivery and 21 neonates born by cesarean section developed hyperbilirubinemia. Of the 41 neonates with hyperbilirubinemia, 15 neonates were in the reverse Doppler group (36.6%), 12 neonates were in the absent Doppler group (29.3%), and 14 neonates were in the normal Doppler group (34.1%) (Table 1). The P-value analysis revealed a value of more than 0.05; therefore, it can be concluded that there was no difference between hyperbilirubinemia and Doppler sonographic indices.

This study aimed to evaluate blood cells and hematological indices in the neonates with IUGR and examine their associations with prenatal Doppler ultrasound findings.
The analyses performed revealed that there was a correlation between decreased platelet count and Doppler sonographic findings and the platelet counts decreased in the IUGR neonates who had an abnormal umbilical artery Doppler ultrasound (absent and/or reverse). Moreover, there was a direct relationship between the severity of thrombocytopenia and the severity of umbilical artery Doppler. Severe (<50,000) and moderate (<100,000) thrombocytopenia were prevalent in the neonates with reverse Doppler, while mild thrombocytopenia (<150,000) was common in the neonates with absent Doppler.
 

Considering the NRBC count, there was a direct relationship between increased NRBC count and abnormal umbilical artery Doppler. The NRBC count were higher in the neonates with abnormal Doppler. However, there was no significant relationship between the severity of Doppler ultrasound (reverse or absent) and increased NRBC.

As has been shown in previous studies (9,10), fetal erythropoiesis and increased NRBC count in the fetal blood circulation are markers for intrauterine hypoxia. With increase umbilical artery resistance and fetal blood flow slowing and chronic hypoxia platelet production increased in the liver and bone marrow. This finding is similar to previous studies (9,10,11,12,13). Increased NRBC count can also differentiate between hypoxia and acute neurologic injury or neurological injury following chronic hypoxia so that in chronic lesions, NRBC count increase.
About WBC count and Hb level there was no significant difference between different groups. These findings were different from those of previous studies (9,10,11,12) but similar with one study (13). This difference may be due to genetic differences in the Iranian neonates. The other reason that can explain this result is a decrease in RBC life time in the IUGR neonate with absent or reverse Doppler. Despite the increase of NRBC count, because of RBC lysis, Hb level do not increase with hypoxia. This may explain hyperbilirubinemia in IUGR neonates.
About IVH incidence we found significant difference between neonates with Absent or Reverse Doppler and neonates with normal Doppler. These findings are consistent with an increase severity of thrombocytopenia concurrently with an increase severity of Doppler disorder.
There is no obvious relationship between hyperbilirubinemia and absent or reverse Doppler in our study. This finding is different with previous studies (9,11,15). The reason for this difference may be the low Hb level in neonates in our study.

 

Modern perinatology tries to reduce perinatal mortality and morbidity but every year many neonates are born with cerebral pulsy and hypoxic-ischemic disorders. IUGR is the common problem in perinatology and one of the main reason for perinatal mortality and morbidity. One of The main challenge for perinatologists is to reduce this mortality and morbidity like intra uterine fetal death and neurological problem.
Increase NRBC level and decrease platelet level in fetus can predict IUGR before birth and even before Doppler sonography. In animal models, NRBC levels increase 2 to 3 days after hypoxia; therefore, the increase may indicate hypoxia before the labor initiation.

Increased NRBC levels are associated with adverse neonatal outcomes, including increased ICU admission, respiratory distress, and increased need for mechanical ventilation.

The incidence of thrombocytopenia is associated with an increased rate of neurological complications. The presence of placental pathology in IUGR fetus and increased resistance to fetal blood flow lead to platelet aggregation, decreased platelet levels, increased placental microthrombosis, and exacerbation of placental insufficiency. Therefore, early diagnosis of this abnormality and initiation of treatment with drugs, such as aspirin, which inhibit thromboxane A2, improve placental blood circulation, prevent IUGR progress, and improve pregnancy outcomes.  
Furthermore, we found that the rate of IVH incidence increased significantly as the abnormal umbilical artery Doppler (reverse compared to absent) got severe. This finding is consistent with the fact that an increase in the severity of thrombocytopenia concurrently occurred with an increase in the severity of abnormal Doppler. As the severity of thrombocytopenia got worse, the incidence of IVH increased in the neonates.

One of the major problems seen in IUGR neonates which can have long-term consequences is IVH. It is clear that identifying risk factors for its occurrence before delivery can have significant benefits, including administering prenatal treatments (such as magnesium sulfate), choosing the type of delivery and pregnancy termination time, and providing quick postpartum care. The present and previous studies have shown that prenatal Doppler ultrasound can be a strong predictor of IVH. Finally, finding the relationship of uterine-placental blood circulation with hematological indices and perinatal outcomes plays an important role in managing the pregnancy, considering the proper time for pregnancy termination, and providing postpartum care.

 

1. The absence of control group in our study because some complications may be due to prematurity in neonates

2. Mother disease like preeclampsia, hypertension and diabetes are not included in our study.

The authors would like to thank the Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS), Tehran, Iran for their cooperation and support throughout the period of study.

 

The authors declared that there are no conflicts of interest.