The relationship between postnatal hypoglycemia and umbilical artery Doppler ultrasonography in neonates with intrauterine growth restriction: A longitudinal follow-up study

Abstract Background Intrauterine growth restriction (IUGR) refers to fetuses with an estimated ultrasonography weight below the 10% percentile. Hypoglycemia is a major concern in neonates with IUGR. Objective To investigate the relationship between umbilical artery (UA) Doppler ultrasonography and neonate hypoglycemia and IUGR. Materials and Methods This was a longitudinal follow-up study consisting of 114 neonates (gestational age of 28-40 wk) born with IUGR in the third trimester of pregnancy at Shahid Sadoughi Hospital, Yazd, Iran between May 2016 and October 2017. The neonates were assigned into three subgroups of normal UA Doppler, absent end-diastolic flow (EDF) in UA Doppler, and reverse EDF in UA Doppler. The blood glucose of the neonates was checked one, two, three, six, 12, 24 and 48 hr after birth, and the neonates were placed in the hypoglycemia or euglycemia groups according to guidelines. Results Out of the 114 neonates included in the study, 75 (65.8%) had normal UA Doppler, 29 (25.4%) had absent EDF in UA Doppler, and 10 (8.8%) had reverse EDF in UA Doppler. There was a significant difference in the mean blood glucose in the first hr between the normal UA Doppler group and the reverse EDF in UA Doppler group (p < 0.01). Conclusion Postnatal hypoglycemia in neonates with IUGR is associated with the result of UA Doppler ultrasonography during pregnancy.


Introduction
Intrauterine growth restriction (IUGR) or fetal growth restriction is a condition in which the fetus (unborn baby) is unable to achieve their potential and expected growth based on their gestational age due to environmental or genetic factors (1,2).
The placenta plays a key role as a mediator in the relationship between the mother and fetus in embryo development. Therefore, fetal insufficiency for any reason can be the main mechanism of growth restriction. Fetal insufficiency leads to a negative effect on general blood nutrients and active oxygen exchange and reduces the synthesis of glucose, proteins, and lipids (3,4). At the time of delivery, newborns with IUGR usually look like the gestational age of an unborn baby (5).
The most common complications of growth restriction include hypoglycemia, asphyxia, hypoxic-ischemic encephalopathy, gastrointestinal bleeding, polycythemia, maternal malformations, pulmonary bleeding, apnea, congenital heart diseases, and disseminated intravascular coagulation. Growth restriction is also associated with higher morbidity and mortality (6,7). Therefore, research on IUGR is a global priority.
Umbilical artery (UA) Doppler indicates the resistance in blood perfusion at the placenta-fetus level (8). Placental and maternal conditions can lead to the closure of small muscular arteries in tertiary chorionic villi, and progressive reduction in the end-diastolic flow (EDF), absent EDF, or reverse EDF in the UA Doppler (9). Reverse EDF in the UA blood flow indicates a developed condition of the fetus and may indicate a closure of more than 70% of the arteries in the tertiary chorionic villi (10,11). Absent or reverse EDF in the UA is commonly associated with severe IUGR or oligohydramnios (12,13). Therefore, in cases of suspected fetal growth restriction, UA Doppler is a reasonable measure. Although there are few methods available for UA Doppler, the systolic to diastolic ratio and pulsatility index are commonly used to treat suspected cases of IUGR (14).
Hypoglycemia is a major concern in neonates with growth restriction. Hypoglycemia reduces the level of consciousness and can lead to seizures followed by neonatal hypoxia (15). Therefore, blood

Materials and Methods
In this longitudinal follow-up study, 114 infants born with IUGR in the third trimester of pregnancy It is worth noting that blood sugar was checked in all neonates in the first hr after birth, but blood sampling at the second and third hr was only done for neonates with abnormal blood sugar levels. For neonates with normal blood sugar in the first hr, sampling in the following hr was not performed.

Ethical considerations
This study was approved by the Ethical

Statistical analysis
The data were analyzed using the Statistical

Results
From a total of 138 neonates who were born in the third trimester of pregnancy and were diagnosed with IUGR using UA Doppler  (Table IV). There was a significant difference in the rate of AFI across the three groups of Doppler ultrasonography, and the difference was seen between the normal and reverse UA Doppler groups (p = 0.01, Table V).
There was no significant difference in the weight estimated by ultrasonography (EFW) between the three groups based on first-hr mean glucose level (p = 0.11, Table VI). There was no significant difference between the three groups of Doppler ultrasonography (p = 0.05).

Conclusion
Based on the results of this study, it can be concluded that postnatal hypoglycemia in neonates with IUGR is associated with UA Doppler ultrasonography during pregnancy.
Reverse EDF in UA Doppler ultrasonography is significantly associated with an increased probability of hypoglycemia in the first hr of birth. It is recommended that blood glucose be closely monitored after birth in neonates with IUGR, especially if the UA Doppler is reverse.
In this situation, the risk of hypoglycemia is