Benha Journal of Applied Sciences (BJAS) print : ISSN 2356–9751 Vol.(5) Issue(2) Part (1) (2020), )109-115) online : ISSN 2356–976x http://bjas.journals.ekb.eg Prophylactic Antenatal Administration before Elective Cesarean Delivery at or Near Term to Improve Perinatal Outcome

S.A.El-Berry , M.A.Farag , A.A.Sharaf El-dine , R.I.Abdelaty and F.A.Abu El Fotouh Obstetrics and Gynecology Dept., Faculty of Medicine, Benha Univ., Benha, Egypt E-Mail: [email protected]. Abstract To evaluate whether giving the recommended prophylactic course of before delivery reduces the occurrence of neonatal respiratory morbidities and the need for NICU admission after elective cesarean delivery between 37and 39 weeks. This is a randomized case control retrospective study conducted at the NICU of Benha children hospital during the period started from November 2017. It reviewed the medical record of 100 neonates delivered by elective cesarean section at the period between 37and 39weeks gestation after uncomplicated and admitted to NICU due to respiratory morbidities that occur commonly after elective cesarean delivery specially TTN . The neonates were divided into 2 exposed groups whose mothers received prophylactic antenatal dexamethasone either single dose [group 2] or repeated doses [group 3], and non-exposed group [group 1] who’s mothers did not receive dexamethasone . Neonatal respiratory morbidity was compared between the three groups. Data was analysed using SPSS 19.There was no significant difference between the corticosteroid exposed groups and non-exposed groups regarding admission to NICU [p= o.570], respiratory distress syndrome [no cases of RDS have been recorded], transient tachypnea of the neonate [all cases in different groups were RD due to TTN], need for mechanical ventilation [p=0.701], final outcome, and length of hospital stay . Therefore no correlation between antenatal corticosteroid administration before elective cesarean delivery at or near term and neonatal respiratory outcome[P value=0.388].Prophylactic antenatal corticosteroid for elective cesarean delivery between 37 and 39 weeks is not effective in improving neonatal outcomes.

Keywords: Elective cesarean delivery, Antenatal cortices, Teroid , Neonatal respiratory distress.

1.Introduction When infants are delivered near or at term There is a rising trend towards elective especially by elective caesarean delivery [CS] worldwide in the past before the onset of spontaneous vaginal decades. The major contribution is pervious delivery, usually they are deprived of scar due to drastic decline in trial of vaginal necessary hormonal changes resulting in the delivery after c.s scar [34% points per year development respiratory complications from 2000 to 2009].1,2 Other reasons for this specially neonatal distress syndrome [8]. increased trend are elective Caesarean for Apart from the mode of delivery, breech presentation and maternal request. gestational age at the time of delivery also Dramatic decline in trial of scar is probably affects risk of NRM. Number of studies9,10 due to the fear that trial of labour would be have shown that the risk of NRM is inversely associated with higher risk of maternal and proportional to the gestational age at the time perinatal mortality [2-3] . of elective CS. It is 73.8/1000 at 37+6 weeks, Neonatal Respiratory Morbidity [NRM] is 42.3/1000 at 38+6 weeks and 17.6/1000 at one of the known complications of elective CS 39+6 weeks.11 This trend is particularly conducted between 37-38+6 weeks of pronounced for RDS where the risk decreases pregnancy. It ranges from transient tachypnoea from about 39/1000 for period between 37+0 [TTN] of newborn to respiratory failure. In to 37+6 to 8/1000 for period between 39+0 to 1964, the association of NRM with term 39+6 weeks, while TTN decreases from elective CS was highlighted for the first time. 7/1000at 37 to 4/1000 >39 weeks [12]. Since then large number of studies were The development of NRD leads to chain of conducted to establish their correlation. A events, including admission to neonatal recently cohort study further strengthened this intensive care unit [NICU], affecting mother- association [4] . child bonding, cost of care and complications Elective term delivery by CS is responsible from invasive procedures, including artificial for 50% of potentially avoidable causes of ventilation.13 It is also associated with the neonatal respiratory distress [NRD].10 TTN is development of asthma in childhood [14] . the most common cause of NRM followed by In order to decrease this complication, RDS.5 Iatrogenic RDS [after elective CS] guidelines issued by the American Council of persists as a cause of neonatal morbidity and Obstetricians and Gynaecologists [ACOG],15 mortality [6-7] . the Royal College of Obstetricians and Gynaecologists [RCOG] and NICE

Benha Journal Of Applied Sciences, Vol.(5) Issue(2) Part (1) (2020( 110 Prophylactic Antenatal Corticosteroid Administration before recommend that EL-LSCS should be planned 2.Subjects and methods at 39+0 weeks. The randomized case control study was If EL-LSCS is deemed necessary prior to conducted in the NICU of Benha children 39 weeks, prophylactic dexamethasone at least hospital and Ob./ Gyn. Department of Qwesna 48 hours prior to the date of CS will decrease central hospital during the period started from the risk of NRM.16 However, the evidence for November 2017 to November 2019 . The such recommendation is questionable. Studies protocol of the study was approved by the have shown no additional benefits of Research Committee of the Hospital. It administering to mothers after included 100 neonates who were delivered by 34 weeks [17]. EL-LSCS between 37 to 38+6 weeks of They have explained this as corticosteroids pregnancy after uncomplicated pregnancy and play an important role in final maturation of admitted to NICU due to respiratory problems by increasing number and function of that occurs commonly after elective cesarean sodium [Na]+ channels and increasing delivery specially TTN. Neonates with history production of surfactant. of antenatal diabetes mellitus [DM] While there is strong evidence that a single [gestational or overt diabetes], history of antenatal prophylactic course of corticosteroids rupture of membranes ,history of drug intake in preterm labor before 34 weeks gestation is or any chronic medical illness ,infections effective in neonatal death, RDS, including tuberculosis, congenital anomalous cerebroventricular hemorrhage, necrotizin- and intrauterine growth restriction genterocolitis, and admission to a neonatal [IUGR] were excluded. intensive care and respiratory support [18]. Patients were divided according to The question is whether these benefits might antenatal maternal steroid administration and actually extend to 37 and 38 weeks. its dose protocol into 2 exposed groups who’s The ASTEC trial has proven that incidence mothers received prophylactic antenatal of respiratory distress at 37-39 weeks of dexamethasone either single dose [group 2] or gestation are reduced to half with the use of repeated doses [group 3], and non-exposed antenatal steroids, TTN decreases from 4% to group [group 1] who’s mothers did not receive 2.1% and RDS from 1% to 0.2%. This trial dexamethasone . Neonatal medical records also showed that there is 6-fold decrease in the were reviewed with full antenatal history rate of NICU admission with NRD after giving taking from their mothers and all required antenatal corticosteroids [19]. information was documented in a structured The decreased incidence of TTN in steroid Performa whose primary outcome measure group is based on normal physiology during was to see the number of babies with NRM in labour. During labour there is a rise in each group and secondary outcome measure corticosteroids' level which encourages the was to compare difference in nursery expression of the epithelial channel gene and admission and total hospital stay in different allows the to switch from fluid secretion groups. TTN/RDS were diagnosed by to fluid absorption. ELSCS bypasses this neonatologist on the basis of clinical features mechanism, thereby predisposing to the and radiological findings. Data was analysed increased risk of NRM [20]. using SPSS 19. Baseline characteristics were There are a number of studies16,21 that compared using means and standard deviations have proven that single course of antenatal [SD] and proportions of both groups by corticosteroids is not associated with student's t test and Chi-square respectively. maternal/foetal infection and has no adverse Factors associated with TTN were explored effects on neurological or cognitive system of through student's t-test, Fisher exact and chi- the neonate. square tests whichever was appropriate. The evidence for administration of corticosteroids after 34 weeks is still 3.Results controversial since there is a lack of properly The 100 neonates included in this study 43 conducted trials of antenatal corticosteroids in of them are group 1[non exposed group] ,49 mothers delivered by elective cesarean group 2[with single steroid course] and 8 delivery at this gestational age. group 3[with multiple steroid courses] .The The current study was planned to compare three groups were comparable regarding the incidence and pattern of NRM in neonates baseline characteristics There were no delivered by planned CS between 37-38+6 significant differences between studied groups weeks after prophylactic dexamethasone to regarding baseline characteristics [ maternal mothers with those who delivered without age, parity , gestational age, indications for CS prophylactic dexamethasone. , type of anesthesia, neonatal gender& birth weight ] Table [1].

Benha Journal Of Applied Sciences, Vol.(5) Issue(2) Part (1) (2020( S.A.El-Berry , M.A.Farag , A.A.Sharaf El-dine , R.I.Abdelaty and F.A.Abu 111

Most common indication of C-section was spinal in 99 and general in 1 of the whole abdominal scar due to previous C-section. As cases of our studied groups. regarding type of anesthesia during CS it was

Table (1) Baseline characteristics of the studied groups.

Group 1 Group 2 Group 3 [no steroid] [single course] [2 courses] Test P value No= 43[%] No= 49[%] No=8[%] Age[years] 28.4±4.5 26.18±4.08 26.81±2.92 F test= [mean±SD] 0.083 [20-37] [20-35] [24-33] 2.806 Range parity 6[14] 4[8.2] 0[0] primi-gravida 1.806* 0.403 37[86] 45[91.8] 8[100] multi-gravida Gestational 38.1±5d 37.8±4d 38.4±6d age[weeks] F test= [37-38+6] [37-38+6] [37-38+6] 0.141 [mean±SD] 2.214

Range Indication of CS 1ry infertility 1[2.3%] 0[0%] 0[0%] ECS[CPD] 2[4.7%] 4[8.2%] 0[0%] 6.412 0.372 ECS[old age] 3[7%] 0[0%] 0[0%] CS scar 37[86%] 45[91.8%] 8[100%] Type of anaesthesia General 0[0%] 1[2%] 0[0%] 1.246 0.591 spinal 43[100%] 48[98%] 8[100%]

Gender: 10[23.3%] 15[30.4%] 2[25%] female 0.647 0.572 33[76.7%] 34[69.6%] 6[75%] male

Post- delivery weight: 3283.2±337.2 3210.1±356.4 3188.2±317.4 F Test= [mean±SD] [2700-4100] [2700-4200] [2800-3700] 0.410 0.620 Range

The number of neonates being admitted to need for mechanical ventilation [4[9.8%]in NICU with respiratory morbidities after group 1, 4[8.2%]in group 2 &0[0%]in group elective CS was slightly lower in group1 [no 3][P value 0.701]. One neonate of all cases corticosteroid] when compared to group 2& died because of pneumothorax as a 3[corticosteroid exposed groups] [43% vs. complication during application of CVP line, 3 57% respectively from the total number of the complicated by sepsis & rest of all babies were studied 100 neonates].Antenatal discharged home. In all groups, majority of administration of dexamethasone was not babies remained in NICU for less than 48 associated with reduction in the risk of hours . neonatal admission to PCBU. Table (2). There was no statistically significant All neonates were admitted by RD of difference between studied groups with regard different grades due to transient tachypnea of to final outcome, requirement for mechanical newborn . No cases of RDS was recorded ventilation and length of hospital stay Table between studied cases. Therefore no [2]. statistically significant difference between the Therefore no correlation between antenatal studied groups with regard to cause of NICU corticosteroid administration before elective admission [P value o.570] and the risk of cesarean delivery at or near term and neonatal neonatal RDS after elective CS at term. Table respiratory outcome[R=0.087, P value=0.388]. (2). Table (3). There was no significant difference between different groups regarding rate of

Benha Journal Of Applied Sciences, Vol.(5) Issue(2) Part (1) (2020( 112 Prophylactic Antenatal Corticosteroid Administration before

Table (2) Comparison between the studied groups according to usage of antenatal steroids regarding neonatal outcome.

Group 1 Group 2 Group 3 Fisher Exact test P value [no [single [2 courses] steroid] course] No=8 No= 43 No= 49 Causes of 0.797 0.570 NICU 4[9.3%] 4[8.2%] 0[0%] admission 39[90.7%] 45 [91.8%] 8[100%] malignant TTN TTN V support No 39[90.2%] 45[91.8%] 8[100%] 2.246 0.701 yes 4[9.8%] 4[8.2%] 0[0%] Hospital stay 23.254 0.401 <6h 15[34.8%] 16[32.6%] 5[62.5%] 6-48h 14[32.5%] 14[28.5%] 2[25%] >48h 14[32.5%] 19[38.7%] 1[12.5%] Fetal outcome: 4.321 0.362 Discharge 43[100%] 45[91.8%] 8[100%] Sepsis 0[0%] 3[6.1%] 0[0%] died 0[0%] 1[2.1%] 0[0%]

Table (3) Correlation between antenatal steroid use and fetal outcome.

Parameter R P value Steroid use 0.087 0.388

4.Discussion from alveoli; and increase in pulmonary blood The increase in elective CS rates in the past perfusion. decades has highlighted the need to reduce Recent evidence indicates that apart from respiratory complications associated with this traditional mechanical concept of vaginal high rate of CS. In developing countries squeeze, molecular mechanism predominantly resources are scarce and it is difficult to lung, Na+ channels promote alveolar fluid provide expensive treatment as neonatal care. drainage and these channels may be This leads to financial burden on the state as underactive in fetuses not exposed to the well as the individual in the form of expensive process of labour.8 The expression of these neonatal care, parental anxiety, separation of channels is regulated by several factors such as newborn from the mother and increased risk of endogenous catecholamines, oxygen, thyroid neonatal morbidity secondary to NICU hormones and, finally, by glucocorticoids. admission. Among these, the most important factor for Overall incidence of NRD is estimated at induction of Na reabsorption in the foetal lungs 2.8% and the main risk factors are gestational and surfactant production in advanced age at the time of delivery and mode of gestational age are catecholamines and delivery [2]. glucocorticoids. Glucocorticoids increase the There is 4-fold increase in respiratory number and function of these Na+ channels as distress and 5-fold increased risk of serious well as responsiveness to catecholamines and respiratory morbidity in EL-LSCS compared to thyroid hormones, providing rationale for their .4 Although at term, risk of exogenous administration in cases of EL- NRM is low [2-fold] but not negligible, LSCS. therefore it is important to take best possible In the current study, the effects of action to decrease this complication. administering corticosteroids to mothers who In the absence of stress of labour there is were planned to have elective C-section after lack of catecholamines and corticosteroids 37 weeks gestation, were evaluated in terms of release which is mandatory for final maturation neonatal respiratory morbidity requiring of fetal lungs. Basically there are two oxygen supplementation and the requirement mechanisms required to ensure neonatal lung for admission to NICU. maturity at term: elimination of excessive fluid

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Neonatal respiratory morbidity is increased On the contrary to our study; The by various risk factors including gender of the Antenatal Steroids for Term Elective Cesarean newborn, birth weight, type of anesthesia given Section study, by Stutchfield et al, examined to mother at the time of C-section, maternal the use of antenatal corticosteroids given to medical conditions like premature rupture of women who planned to deliver at 37 weeks of membranes [PROM], maternal fever, and gestation or greater by elective cesarean. history of maternal use.22,23 But Although the investigators found a significant in this study, all those babies who were born to difference in the rate of RDS between the mothers with history of PROM and other treatment and control groups [1.1 and 0.2%, medical disorders were excluded. All the C- respectively], they had similar numbers of sections except one c.s were performed under admissions to neonatal intensive care for both spinal anesthesia. There was no statistically groups [26 and 32, respectively], indicating significant difference between the different that although antenatal corticosteroids may groups in our study as far as birth weight and have decreased the incidence of respiratory gender of the neonates were concerned. morbidity, other neonatal morbidities still The result of the present study showed no necessitated intensive care. significant relationship of dexamethasone with Also the data presented by Stutchfield et al NRM i.e revealed no beneficial effect of show that delaying non-urgent elective antenatal administration of steroids for caesarean section until 39 weeks is much more parturients scheduled for elective cesarean effective in avoiding neonatal admission than delivery between 37 and 39 weeks of gestation giving steroids. For the 15% or so of such regarding reduction of respiratory morbidity , women who will go into labour between 37 NICU admission or need for mechanical and 39 weeks, the inconvenience of having ventilation . All neonates were admitted to their caesarean “out of hours” is likely to be NICU with RD due to TTN and the number less than that of having their baby admitted to of babies admitted in nursery with respiratory special care. Most will only be in early labour, distress was higher in dexamethasone exposed avoiding the complications of an acute Groups [2+ 3] than non exposed Group[1] intrapartum emergency [19] . [57% vs. 43% respectively from the total given before elective number of the studied 100 neonates]. caesarean section at term reduces respiratory The result of the present study coming in distress and admission to a special care baby agreement with a study carried out by unit [26]. The benefit falls with increasing Hutchson, who showed that antenatal gestation, supporting the recommendation to corticosteroids have no role in reducing the delay elective caesarean section until the 39th neonatal respiratory morbidity as well as NICU week. Nevertheless, the benefits of antenatal admission.20 He has found that the total steroids persist till 39 weeks [27]. number of babies admitted in the Many other studies are also in agreement betamethasone group was 26/467 and in the with a Cochrane systematic review 2009 which control group 32/475, with no statistically is in contrast with our current study and stated significant difference in the overall rate of that there was a reduction in NICU admission admissions to PCBU [24]. for babies whose mothers received antenatal A study of 362 neonates born at 34 weeks corticosteroids.26 However, the same review of gestation or more found that even if did not find any statistically significant immature fetal lung indices were detected, difference as far as the respiratory morbidity administration of antenatal corticosteroids did was concerned. not reduce respiratory morbidity in neonates Other recent studies born at 34 weeks of gestation or more [17]. [28],[29],[30],[31],[32] with the most recent A recent trial published similar results update of Cochrane Systematic Reviews [33] showing that conclusions antenatal treatment concluded that Steroid cover significantly with corticosteroids at 34-36 weeks of reduced the risk of respiratory morbidity and pregnancy does not reduce the incidence of admission to NICU in babies delivered by respiratory disorders in newborn infants [25] . elective cesarean section between 37-39 Although the previous 3 studies focused on weeks. However, the authors described the a different gestational age from that of the quality of evidence, was low and very low for present study, still a great similarity occurs the outcomes of RDS, TTN and admission to between both studies and the mechanism of NICU for respiratory morbidity, indicating that Steroid action after 34 weeks either late the true effect could potentially be preterm [34-36+6] or early term[37-38+6] the substantially different from the found estimate same. of effect. Also the unblinded design of the studies[as no placebo was used in 3 of the 4

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