Effects of Types of Anesthesia on Neurobehavioral Response and Apgar Score in Neonates Delivered with Cesarean Section in Dilla University Referral Hospital

Background: Neonatal outcomes are affected by types of anesthesia and perioperative patient cares. Studies showed that neonatal neurobehavioral response and Apgar score were better in mothers who gave birth under spinal anesthesia than general anesthesia. But studies were inadequate locally and this study compared neonatal neurobehavioral response and Apgar score in mothers who undergo caesarean section. Objective: The main objective of the study was to compare Neonatal neurobehavioral response and Apgar score in neonates delivered with caesarean section under spinal vs. General anesthesia. Methods and materials: After approval from institutional review Board (IRB) of Dilla University, we studied 200 consecutive babies delivered with caesarean section under spinal and General Anesthesia from ASA I&II term pregnant mother in Dilla University Teaching and referral Hospital. Prospective effectiveness study design was employed. Mothers were randomly allocated in two equal groups 60 patients each by lottery method after informed consent. Result: There was a significant mean difference between the two groups on mean Intraoperative systolic blood pressure. More women who received spinal anesthesia had lower intraoperative systolic blood pressure as compared to women who received general anesthesia (P<0.05). Neonatal Neurologic Adaptive capacity score at 15 minutes were better in spinal as compared to General Anesthesia. There were significant association between types of Anesthesia with the majority of the tests in 15 minute and 2 hrs period. But Neonatal Neurologic Adaptive capacity score at 24 hrs didn’t show significant Association. Conclusion: Spinal Anesthesia is associated with good neonatal outcomes even in emergency caesarean section with non-touching rapid sequence spinal anesthesia technique. General anesthesia should be preserved for cases contra indicated with spinal anesthesia.


Introduction
Caesarean section is a procedure where by a baby is delivered through an incision on the abdominal wall and intact uterus of the mother under General or Spinal Anesthesia. It is usually life-saving and reserves the health of the mother and her baby [1,2].
General anaesthesia refers to the loss of ability to perceive pain associated with loss of consciousness produced by intravenous or inhalation anesthetic agents. For caesarean section, this involves the use of thiopentone for induction, tracheal intubation facilitated by suxamethonium, positive-pressure ventilation of the lungs with preoxygen plus a volatile agent, and a muscle relaxant [1].
Regional anaesthesia (spinal) refers to the use of local anaesthetic solutions to produce circumscribed areas of loss of sensation. This type of regional anaesthesia used for caesarean section involves the infiltration of a local anaesthetic agent directly into the subarachnoid space [1]. General and Regional Anesthesia for caesarean section are not ideal as each has benefits and risk to foetus. But the aim of clinician is to select the method which is harmless and most comfortable for the mother, least depressant to the new born [2].
Spinal anesthesia affects neonates either by decreasing uteroplacental perfusion secondary to sympathetic blocked induced hypotension or intratecally administered Opioids with local anesthetics that depress the respiratory center and end up with asphyxia and acidosis [3].
The outcome of Neonates delivered by Caesarean section is depending on preoperative maternal and neonatal condition, intraoperative management and postoperative care. Effective neonatal resuscitation with qualified resuscitator and adequate equipment must be provided and the Apgar score in the first minute and fifth minute and arterial oxygen saturation with pulse oximeter (89-94%) will signify adequate resuscitation minimal or no respiratory depression [4].

Incidence of Neonatal Mortality
The assessment of anaesthesia-related mortality has been employed since so many years back and defined as death of patients under, or following anesthesia within twenty four hours under the care of anesthetist [5].
Unlike other studies conducted in different parts of the world [2,4, incidence of neonatal death was reported only in one study, there were four deaths in general anesthesia and zero in spinal anesthesia [28].

Determinants of Neonatal Morbidity
Anesthesia related morbidity is any complication that could occur in patients under or following anesthesia under the care of anesthetist within twenty four hours and they are related with preoperative patient condition, intraoperative management and postoperative care [5].

Neonatal Neurobehavioral Response
Apgar sore assess the need for neonatal resuscitation and intraoperative anesthetic drugs effects are not easily appreciated [28]. As a result, the anesthesiologist and neonatologist discover new methods of assessment besides Apgar score. The neurologic and Adaptive capacity score is the one being employed because of its simplicity and feasibility.
According to a study conducted in America, the neonatal neurologic and Adaptive capacity score was much lower in babies delivered under general anesthesia than spinal anesthesia [7]. But a study conducted in Thailand showed Neonatal Adaptive Capacity Score in babies born either Spinal or general anesthesia had no significant difference [25].

Neonatal Intensive Care Unit (NICU) Admission and Hospital Stay
The factors contributing for long duration of hospital stay and NICU admission varies with preoperative maternal and neonatal condition, types of anesthesia administered intraoperative management and postoperative care.
According to an observational study conducted in Pakistan, babies delivered under general anesthesia had long duration of hospital stay and required neonatal Intensive care Unit Admission [22].
A study conducted in Turkey showed that neonatal ICU admission had no significant difference in mothers who received either spinal or general anesthesia [10].
According to another study conducted in Italy, rates of neonatal admission and need for oxygen ventilation were higher in babies delivered under general anesthesia. But the overall neonatal outcomes were not significant [24].

Apgar Score
The immediate neonatal outcome is usually measured with a tool called Apgar score in the first minute and fifth minutes after delivery.
A study conducted in Ethiopia showed that neonatal outcomes were affected by uterine incision to delivery time. Neonates delivered in uterine incision to baby out less than three minute had better Apgar score [6].
During review of the literature, we found out many clinical trials and observational studies comparing neonatal outcomes delivered with caesarean section. However, still there are controversies on selection of types of anesthesia and effects of each on neonatal outcomes. Besides, there are no studies in Ethiopia comparing neonatal outcomes delivered with caesarean section in clinical trial or prospective observational study.
Apgar score is employed to confirm the need for resuscitation of the baby. However, Apgar score doesn't confirm effects of maternal preoperative and intraoperative administered drugs on neonatal neurologic effects. Anesthesiologists and pediatricians used different techniques to assess neurobehavioral response of neonates delivered with caesarean section. Neurologic and Adaptive capacity score is the recent techniques employed by Anesthesiologists. There were many clinical trials and observational studies conducted to assess the Apgar score of neonates delivered with caesarean section [4,6,8,10,12,14,[17][18][19][20][21][22][23][24][25]. These studies showed that babies delivered under spinal anesthesia had better outcomes as compared to general anesthesia. Though studies conducted on effects of types of anesthesia to Neurobehavioral response of neonates were scarce worldwide, they showed that babies delivered under General anesthesia had low neurobehavioral response than Spinal anesthesia groups [2,7,13,16].

Methods and Materials
After approval from institutional review Board (IRB) of Dilla University, we studied 200 consecutive babies delivered with cesarean section under spinal and General Anesthesia from ASA I&II term pregnant mother in Dilla University Teaching and referral Hospital. Prospective effectiveness study design was employed. Mothers were randomly allocated in two equal groups 60 patients each by lottery method after informed consent. Mothers with spinal Anesthesia group was preloaded with 1-1.5 litres of crystalloids before spinal Anesthesia and Spinal Anesthesia was given with 2-2.5 ml of 0.5% bupivacaine in sitting position with strict aseptic technique. General Anesthesia was induced with rapid sequence induction with 3.5 mg/kg of thiopental and 1-2 mg/kg succinylcholine. General Anesthesia was maintained with 1-1.5 v% halothane, 0.1 mg/kg of vecronium and 1.5-2 mg/kg of Pethdine.

Data collection method and measurement of variables
Data were collected using a pre-tested structured questionnaire. The trained data collectors managed the data in intraoperative and postoperative period who were not responsible for the anesthetic management for that particular subject.
Preoperatively, the socio-demographic characteristics, ASA status, preoperative hematocrit and blood pressure were taken. Intraoperatively, the maternal blood pressure was taken every three minutes until delivery of the baby and the induction to delivery time also recorded. Just after delivery, the first and the fifth minute Apgar scores were recorded. The Apgar score was assessed with a standard table format which contains five parameters (Table 1) [10].  Postoperatively, the baby was sent to ward along with his/her mother and the neurobehavioral response of the baby was assessed with Neonatal neurologic and Adaptive capacity score at 15 minutes, 2 and 24 hrs. The Neonatal Neurologic and Adaptive capacity score contains five assessment areas i.e. adaptive capacity, Active tone, Passive tone, primary reflexes and general neurologic status. Each criterion was given a score of 0 for absent or abnormal, 1 for slightly abnormal and 2 for normal and the maximum score will be 40 (

Data processing and analysis
Chi square test and odds ratio were used to determine the association between hypothesized independent and dependent variables. Finally, multivariate analysis was used to control possible confounders and identify independent predictor of Neurobehavioral response and Apgar score.

Results
A total of 200 Neonates delivered with caesarean section from a term pregnant women were followed perioperatively for twenty and the response rate of the participants were hundred percent.

Socio-demographic characteristics
Data on maternal age, weight, height, Body Mass Index, and neonatal weight were summarized in Table 3.

Maternal preoperative Characteristics
Data on maternal preoperative hematocrit, previous cesarean section and qualification of the anesthetist who provided anesthesia were shown in Table 4.

Intraoperative maternal characteristics
There was a significant mean difference between the two groups on mean Intraoperative systolic blood pressure. More women who received spinal anesthesia had lower intraoperative systolic blood pressure as compared to women who received general anesthesia (P<0.05). Severe reduction in blood pressure decreased placental perfusion which results in fetal acidosis and asphyxia. However, neonates delivered from spinal anesthesia with lower blood pressure and Normal blood pressure didn't show any difference (

Neonatal characteristics
There was no neonatal death in this study. The number of neonates required resuscitation was higher in general anesthesia, 24/100 and 14/10 respectively. But the mean difference was not significant (P>0.071) (Figure 1).

Apgar score
There were significant mean difference on the mean first and fifth minute Apgar score (P<0.05). The Apgar score of neonates in the first minute less than seven was lower in general Anesthesia as compared to spinal anesthesia. Thirty one neonates from hundred had lower first minute Apgar score less than seven in General Anesthesia when compared to spinal Anesthesia groups which was only eleven neonates from hundred with lower first minute Apgar score less than seven (

Neurologic adaptive capacity score
Neonates delivered under General and spinal Anesthesia was assessed with Neurologic Adaptive Capacity score to determine the effect of Anesthetic drug on neonatal immediate outcomes in 15 minute, 2 hrs and 24 hrs.
Neonates delivered under spinal anesthesia had highest score in 15 minutes when compared to babies delivered under General Anesthesia. There were significant association between types of anesthesia with the majority of the tests especially in 15 minute and 2 hrs period. However, there was no significant difference in 24 hrs assessment (

Determinants of neonatal Apgar scores
To determine the predictor of lower Apgar score, bivariate and Multivariate logistic regression was conducted and the results was described below (Table 8).
Neonates born under General Anesthesia were more likely to have higher figures of Apgar score less than seven when compared to spinal anesthesia, (AOR=0.275, 95% CI=[0.129, 0.285]).
Neonates born with greater than three minutes from uterine incision to baby out were half times more likely to be asphyxiated (AOR=0.453, 95% CI= [0.224, 0.917]) as compared to babies born with less than three minutes from uterine incision to baby out.

Variables
Apgar

Discussion
The mean Apgar score at first minute was lower in neonates delivered under general Anesthesia when compared to spinal Anesthesia groups. This study is in line with many studies conducted elsewhere [2,10,11,13,17,18,20,21,24]. However, the mean fifth minute Apgar score didn't show significant mean difference in these studies.
But a study conducted other areas showed a significant mean difference at first and fifth minute [6,12,23,25].
In this study Neonatal Neurologic Adaptive Capacity Score in the 15 minute and 2 hrs time were higher in neonates delivered under spinal Anesthesia when compared to General Anesthesia. This study finding is in line with a study conducted in America [7]. However, the 24 hrs Neurologic Adaptive capacity score didn't show significant different. This significant difference in the first couple of hours might be due to  [25].
A systemic review and meta-analysis on effects of types of anesthesia on maternal and neonatal outcomes also showed that neonatal Neurologic Adaptive Capacity Score didn't significant different (P>0.4) [2].
Neonatal resuscitation and intensive care Admission is higher in babies delivered under general Anesthesia as compared to Spinal Anesthesia but there was no significant mean difference (p>0.071). This study finding is in line with a study conducted in Turkey in which neonatal Intensive care Admission was 5 vs. 6 for spinal and general anesthesia respectively [10].
Another study in Turkey also showed that respiratory support didn't show any significant association (P>1) [22].
A study conducted in America showed that immediate neonatal intensive care Admission didn't have any significant difference. However, a study conducted in Pakistan showed that there were higher number of neonatal Admission in general anesthesia when compared to spinal Anesthesia, [28] vs. 6 respectively, P<0.001. These discrepancies might be due to longer induction delivery time with potent lipid soluble intravenous agents and/or more emergency cases with fetal distress in the sample of a study conducted in Pakistan.
Greater induction to delivery time is associated with low Apgar score. This study is in line with a study conducted in Gondar University.

Conclusion
The findings in this study revealed that the mean first minute and fifth minute Apgar score is much better in babies delivered under spinal Anesthesia when compared to general Anesthesia.
Apgar score less than seven at first minute was better in neonates delivered under spinal anesthesia. Neonatal Apgar score had a significant association with induction delivery time.
Neonatal Neurologic Adaptive Capacity Score was higher in neonates delivered under Spinal Anesthesia in 15 minute and 2 hrs when compared to General Anesthesia.
The neonatal respiratory support and Neonatal Intensive care Admission didn't show any significant difference between the groups.
Overall, spinal Anesthesia is associated with minimal neonatal outcomes even in emergency caesarean section with non-touching rapid sequence spinal anesthesia technique. General anesthesia should be preserved for cases contra indicated with spinal anesthesia.