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Original article

Cause of premature birth as a prognostic factor of neonatal outcome and type of delivery

Smiljana Donić1, Rastko Maglić1, Vesna Mandić1, Milica Mandić1, Konstantin Kostić1, Dragana Maglić1
  • Obstetrics and Gynecology Clinic "Narodni Front", Belgrade, Serbia

ABSTRACT

Introduction: Premature birth, occurring before the 37th gestational week, is commonly attributed to uterine contractions, premature rupture of the amniotic sac, or placental abruption. In 20% – 30% cases involving maternal or fetal complications, premature birth may be induced, often due to conditions such as preeclampsia, fetal growth retardation, or severe maternal heart disease.

Aim: The study aims to determine whether the cause and time of preterm birth affect the neonatal outcome.

Material and methods: This retrospective study analyzes patients prematurely born at the Obstetrics and Gynecology Clinic Narodni Front in 2020, the cause of their premature birth, as well as the status of the fetus after birth. In the study, we compared the neonatal outcome in spontaneously induced preterm birth.

Results: Among all the births (n = 4,211), in the period between July and December 2020, there were 498 preterm births, i.e., 11.83%. Based on the data on the status of the premature infants’ vital signs, the percentage of stillborn preterm infants was 8.9% while the percentage of live births was 91.1%. The Apgar score was the highest in neonates born by vaginal birth after the 34th week of gestation, with intact fetal membranes and spontaneous contractions. According to the study, 54.1% of preterm births ended in cesarean section due to gestational age younger than 28 weeks and with a predominantly pelvic presentation of the fetus.

Conclusion: The high rate of premature births highlights a serious problem and suggests a continued rising trend, despite preventive efforts. Improved outcomes are seen in pregnancies reaching later gestational weeks, particularly after the 34th week of gestation, with intact fetal membranes and no signs of infection. Spontaneously born premature infants tend to have higher Apgar scores and better neonatal outcomes, as compared to induced births.


INTRODUCTION

Preterm birth is one of the most relevant problems of perinatal medicine today. It represents a potentially very dangerous perinatal event, primarily from the point of view of perinatal morbidity and mortality. By definition, it is a birth that occurs before the 37th week of gestation [1]. According to World Health Organization (WHO) data, based on gestational age, premature birth can be extremely preterm – before the 28th week of gestation, very preterm – between the 28th and 32nd weeks of gestation, moderate preterm – between the 32nd and 34th weeks of gestation, and late preterm – between the 34th and 37th weeks of gestation. A newborn baby born prematurely is called a premature or preterm infant. For a long time, the definition of preterm delivery was linked to the body weight of the newborn, but today it is known that the gestational age of the pregnancy and the maturity of the preterm infant are much more important for survival than the body weight at birth [1].

Prematurity is the single most important factor in neonatal morbidity, mortality, and subsequent effects on surviving infants. The outcome and course of premature birth also depend on the economic development of the country. In our region, the frequency of preterm birth is about 8% [1].

Premature babies are threatened by the immaturity of all organ systems, but the lungs and central nervous system are particularly sensitive. Complications in premature babies can occur immediately after birth. The most common and most serious are the following: intraventricular hemorrhage, respiratory distress syndrome, sepsis, and necrotizing enterocolitis. Late complications are observed during adulthood and represent permanent sequelae: retinopathy, cerebral palsy, and psychomotor and cognitive disorders. Premature babies are a significant problem, not only for individuals and families but also for society in general [1].

The etiology of premature birth is multifactorial, and we often cannot determine the exact cause of its occurrence. The causes can be categorized as variable and non-variable, as well as causes of maternal or fetal origin. The most common causes are infection, multiparity, uterine anomalies, a short period between two pregnancies, and previous premature births in the anamnesis. Lifestyle, smoking, poor diet, consumption of medicines, alcohol and drugs (especially cocaine), stress, and poor socioeconomic conditions increase the risk of premature birth. Looking at the etiological factors in general, one third of preterm births are caused by infection and premature rupture of membranes (PPROM), another third is the result of maternal and fetal factors, and the remaining third, which according to some data is up to 50% of unknown etiology, is idiopathic premature birth. The most significant risk factors related to the mother are the following: positive previous history of preterm birth, age of the pregnant woman (below 20 or over 35 years), multiple births, birth of children with low body weight, hypertensive disease in pregnancy, urinary infections, infectious diseases, febrile maternal conditions, malignant diseases, anemia, diabetes mellitus, developmental anomalies of the uterus, incompetent and insufficient lower uterine segment, increased amount of amniotic fluid, bleeding from the uterus (abruption of the placenta, placenta previa, placental insufficiency), as well as other chronic maternal diseases [1].

In the case of intact fetal membranes, preterm delivery can be caused by an ascending infection from the vagina and cervix. It is a state of silent infection, when there is an intrauterine infection, but there are no clinical signs indicating its presence. Of the fetal factors, multiple pregnancies are the most common cause of premature birth, followed by fetal anomalies, intrauterine growth retardation, intrauterine death of the fetus, and anomalies of position and presentation [1].

The study aims to determine whether the cause and time of premature birth affect the neonatal outcome.

MATERIALS AND METHODS

From the database of deliveries performed during 2020 at the Obstetrics and Gynecology Clinic Narodni Front, only preterm births occurring in the period between July 1, 2020, and December 31, 2020, were included in the study. All multiple pregnancies, as well as premature births induced due to fetal anomalies, were excluded from the study. Using the methods of descriptive statistics, we described the macroscopic appearance of the amniotic fluid, the sex, the status of the newborn’s vitals, the way the delivery was completed, the structural integrity of the fetal membranes, the position of the fetus, the Apgar score at one and five minutes after birth, and noted prepartum dexamethasone therapy administered in the expectant mothers.

Statistical analysis

The data were entered into the database and processed using the IBM SPSS 25 software. Methods of descriptive and analytical statistics were applied in the study. The following methods of descriptive statistics were used: measures of central tendency, measures of variability, and relative numbers. The following methods of analytical statistics were used: methods for assessing the significance of difference, the Chi-square test, and the Mann-Whitney test, as well as methods for assessing the significance of association, Spearman’s rank correlation coefficient. A value of p < 0.05 was considered statistically significant.

RESULTS

Of the total number of births (n = 4,211), in the period between July and December 2020, there were 498 preterm births, which is 11.83% (Figure I). Based on the data on the status of the premature infants’ vital signs, the percentage of stillborn preterm infants was 8.9% while the percentage of live births was 91.1%.

Figure 1. Overview of preterm births compared to all births at the Obstetrics and Gynecology Clinic Narodni Front in the period between July 1, 2020 and December 31, 2020

Figure 1. Overview of preterm births compared to all births at the Obstetrics and Gynecology Clinic Narodni Front in the period between July 1, 2020 and December 31, 2020

According to the study, 54.1% of preterm births ended in cesarean section due to gestational age younger than 28 weeks and with a predominantly pelvic presentation of the fetus. A total of 46% of births were completed vaginally.

Most often, the fetal presentation was cephalic (41.9%), while the pelvic presentation was present in 3.4% of cases. Obstetric interventions, vacuum and internal rotation, were performed in only 0.6% of cases. Spontaneous rupture of the amniotic sac, as a cause of premature birth, was recorded in 39.7% of cases, while the amniotic sac was intact in 60.3% of all premature births. Methods of analytical statistics (p = 0.075) revealed no significant discrepancy between the mechanism of amniotic sac rupture and the status of the preterm infants’ vital signs.

The fetus, as the object of the delivery, affects the course and outcome of childbirth with its position [1]. In our study, data related to fetal position (385) indicate that there were 313 (79.2%) cases of longitudinal cephalic position, 41 (10.4%) cases of longitudinal pelvic position, 19 (4.8%) cases of breech presentation, 11 (2.8%) cases of transverse lie, 8 (2%) cases of pelvic presentation, two (0.5%) cases of occiput posterior position, and one case of (0.3%) oblique position.

First-time mothers included in the study made up 61.5% (294) of the sample, 24.9% (119) of the subjects were second-time mothers, 8.6% (41) had delivered their third baby, 3.6% (17) of the mothers had given birth for the fourth time, 1% (5) had delivered a baby for the fifth time, while for 0.4% of the subjects this was their sixth or seventh delivery.

Amniotic fluid is an incredibly complex and dynamic milieu that changes as pregnancy progresses. It contains nutrients and growth factors, which facilitate the growth of the fetus, it provides mechanical movements of the fetus and antimicrobial effects that protect the fetus, and it allows assessment of fetal maturity and disease [2]. Of the available data for 390 preterm births, 327 (83.8%) had clear amniotic fluid, in 18 (4.6%) cases it was bloody, in 12 (3.1%) instances it was milky, and in 33 (8.5%) it had green discoloration (Figure II).

Figure 2. The frequency of different forms of amniotic fluid macroscopic appearance in preterm births (clear, green, bloody, milky)

Figure 2. The frequency of different forms of amniotic fluid macroscopic appearance in preterm births (clear, green, bloody, milky)

Despite technological progress and efforts made by doctors to preserve the health of newborns in recent years, extremely preterm infants (born before the 28th week of gestation) or with an extremely low birth weight (< 1,000 g) remain at high risk of death and disability, while female preterm infants, on average, have a better survival rate, as compared to the male sex [3]. Based on the data for 397 preterm births, 200 (50.4%) preterm males and 197 (49.6%) females were born. Using the chi-square test (p = 0.617), no statistically significant difference in the vital status of newborns was found between the male and female sex. The average weight of the total number of premature babies was 2117.67 ± 684.22 g, the average length was 44.17 ± 5.47 cm, and the mean value of head circumference was 31.05 ± 3.44 cm (Figure III). The highest frequency of premature births was in the 33rd week of gestation.

Figure 3. Body weight of premature infants included in the study, in grams

Figure 3. Body weight of premature infants included in the study, in grams

The Apgar score is a clinical assessment of the newborn’s ability to survive based on vital parameters such as skin color, heart rate, breathing, muscle tone, and reflex response. It is determined at one and five minutes after childbirth. The score can range from 0 to 10. An Apgar score of 8 – 10 is considered normal, a score of 4 – 7 indicates moderate, and a score of 0 – 3 indicates severe neuromuscular depression, which most often occurs as the result of perinatal asphyxia [1],[4].

The total number of available data regarding the Apgar score at one minute after birth is for 474 preterm infants. Of the given number, 39 (8.2%) preterm infants had a score of 0, 2 (0.4%) preterm infants had a score of 1, a score of 2 was found in 7 (1, 5%) premature babies, a score of 3 was registered in 8 (1.7%) preterm infants, 18 (3.8%) premature babies had a score of 4, a score of 5 was found in 19 (4%) premature newborns, a score of 6 was registered in 43 (9.1%) premature babies, a total of 90 (19.0%) preterm infants had a score of 7, 136 (28.7%) preterm newborns had a score of 8, 109 (23.0%) of them had a total of 9, while 3 (0.6%) premature babies scored a 10.

Today, greater importance is attached to the score at five minutes after birth, as it indicates the speed of adaptation of a healthy newborn, or the dynamics of recovery of an asphyxiated one [4]. From the database of 476 Apgar scores at five minutes after birth, a score of 0 was found in 39 (8.2%) premature babies, a score of 1 does not exist in the database, a score of 2 was recorded in one (0.2%) premature baby, a sum of 3 was found in 2 (0.4%) preterm infants, a score of 4 was determined in 8 of them (1.7%), a score of 5 was registered in 21 (4.4%) premature babies, a score of 6 was found in 19 (4.0%) premature infants, a score of 7 was registered in 47 (9.9%) cases, 116 (24.4%) premature babies had a score of 8, 129 (27.1%) of them had a score of 9, while 94 (19.7%) preterm infants scored a 10 (Figure IV). The Apgar score was the highest in newborns delivered vaginally, after the 34th week of gestation, with intact fetal membranes, and spontaneous onset of contractions. This data shows that the outcome of pregnancy is better in childbirth occurring later in gestation, after the 34th week, with intact fetal membranes and without signs of infection. A higher Apgar score in children from spontaneous versus induced premature birth also indicates a better neonatal outcome.

Figure 4. The value of Apgar scores at one and five minutes after birth, ranging from 0 to 10

Figure 4. The value of Apgar scores at one and five minutes after birth, ranging from 0 to 10

Corticosteroids are administered in order to increase the production of surfactant and accelerate fetal lung maturation in case of threat of premature birth [1]. It has been proven in numerous studies that antenatal dexamethasone treatment of parturients results in a significantly lower risk of neonatal death, without any evidence of harm to the patient or the newborn [5]. A total of 228 (45.8%) parturients included in the study received dexamethasone, while 270 (54.2%) did not (Figure V). A statistically significant difference was observed in the status of the vitals in preterm infants whose mothers received dexamethasone, as compared to those who did not receive this treatment, using the chi-square test (p < 0.001). According to our study, premature babies whose mothers received antenatal therapy had higher Apgar scores at one minute (p = 0.004) and five minutes (p = 0.046) after birth.

Figure 5. The frequency of mothers who did not receive dexamethasone therapy and those who did receive dexamethasone therapy

Figure 5. The frequency of mothers who did not receive dexamethasone therapy and those who did receive dexamethasone therapy

DISCUSSION

A study conducted by Goldenberg et al., in 2008, in the United States of America (USA), indicates that the frequency of preterm births is about 12% - 13% in the United States and 5% - 9% in many other developed countries. However, the rate of premature birth also depends on the geographical location, mainly due to increased risk factors, as well as due to premature births resulting from multiple IVFs [6]. Common causes of preterm delivery include preeclampsia or eclampsia and intrauterine growth retardation. Of the total number of preterm births, the frequency of induced births is 30% - 35%, the frequency of spontaneous preterm births is 40% - 45%, and the frequency of PPROM is 25% - 30% [6]. Spontaneous labor and PPROM are collectively referred to as spontaneous preterm labor [6]. In our study, the frequency of preterm births, during the observed period of six calendar months, was 11.83%, while spontaneous births were observed in 39.7%, and induced births in 60.3% of cases.

The risks decrease with increasing gestational age [1]. Before the 34th week, more than half of preterm neonates have some complication, while after the 36th week, complications occur in about 16% of preterm infants.

According to a study conducted by Mayo et al., in 2017, in the United States of America, extremely young nulliparous women are at higher risk of preterm birth, but the mechanism has not been clearly established [7]. A retrospective cohort study included nulliparae aged 13 to 20 years who had a single pregnancy terminated prematurely, in the period between 2007 and 2011 [7]. The results show that the highest prevalence, i.e. 14.5% of preterm births, is among the youngest nulliparae, aged 13, while the lowest prevalence of preterm deliveries was among the oldest in the observed group, i.e. among twenty-year-old women (6.7%) [7]. Namely, the risk of spontaneous preterm birth is significantly higher in subjects younger than 16 years [7].

Our study correlates with the evidence pointing to an increased risk of premature delivery in nulliparous women, who account for as many as 61.5% (294) cases, while women giving birth for the second time make up 24.9% (119) of the cases, women delivering their third child account for 8.6% (41) of preterm deliveries, those delivering their fourth child make up 3.6% (17) of cases, women having their fifth child constitute 1% (5) of all cases, and those delivering their sixth or seventh child contribute with only 0.4%, but we do not have data on the age of the mothers.

A 2017 UK study by Roberts et al. supports evidence that antenatal corticosteroids accelerate fetal lung development in case of the threat of premature birth [5]. The study included 7,774 parturients and 8,158 preterm infants [5]. Antenatal corticosteroid therapy, as compared to placebo or no treatment, clearly reduces some of the most serious complications in preterm infants, such as perinatal mortality, neonatal mortality, respiratory distress syndrome, intravascular hemorrhage, necrotizing enterocolitis, the need for mechanical ventilation, and systemic infection in the first 48 hours of life [5]. Based on the available data, we compared the status of the vitals of neonates with the use of dexamethasone in parturients, in 394 cases. In the group of patients who received dexamethasone therapy (172), mortality was recorded in only 1 neonate, which is 0.6%, while 171 (99.4%) neonates survived. On the other hand, in the group of female patients who did not receive this treatment (222), there were 34 (15.3%) deceased neonates while 188 (84.7%) survived.

In a study conducted by Li et al., in 2013, in China, it was demonstrated that the Apgar score system has a continuous, significant value for predicting neonatal outcomes, both for term and preterm infants [8]. Preterm births had about a 10 to 20 times higher incidence of low 5-minute Apgar scores (< 7) than term births, although a vast majority of preterm births had a score greater than 7 [8]. The neonatal mortality rate decreased with the increase of the Apgar score. The analysis included preterm births occurring between the 24th and the 36th gestational week [8]. Apgar score values at five minutes after birth were as follows: a score of 1 in 0.43% of premature infants with a neonatal mortality rate of 581.86; a score of 2 in 0.293% of premature babies with a mortality rate of 334.68; a score of 3 in 0.38% of premature babies with a mortality rate of 192.42; a score of 4 in 0.57% of premature infants, whose mortality rate was 121.28; a score of 5 in 1% of premature babies with a mortality rate of 74.58; a score of 6 in 2.31% of premature babies who had a mortality rate of 43.47; a score of 7 in 5.2% of premature babies with a mortality rate of 18.91; a score of 8 in 16% of premature babies with the mortality rate of 4.39; a score of 9 in 69.60% of premature babies with a mortality rate of 0.59; and a score of 10 in 4.23% of premature infants who had a neonatal mortality rate of 0.37 [8].

However, the Apgar score has its limitations [8]. Numerous factors can affect the Apgar score, such as drugs, trauma, congenital anomalies, infections, hypoxia, and hypovolemia, especially in premature births [8]. To date, there are but several consistent data on the significance of the Apgar score in preterm infants [8]. Because score components such as tone, color, and reflex excitability depend in part on the physiological maturity of infants, this situation may cause a healthy preterm infant without evidence of asphyxia to score lower, simply because of its current immaturity [8].

In our study, at five minutes after birth, we recorded an Apgar score of 0 in 8.2% of premature babies, a score of 1 does not exist in the database, a score of 2 was found in 0.2% of the cases, a score of 3 was recorded in 0.4% of premature babies, a score of 4 was registered in 1.7% of preterm infants, a score of 5 was recorded in 4.4% of the babies, a score of 6 occurred in 4.0% of cases, a score of 7 was observed in 9.9% of preterm infants, a score of 8 occurred in 24.4 % of cases, a score of 9 was present in 27.1% of premature infants, while a score of 10 was recorded in 19.7% of cases. Limitations of the research include the insufficient number of subjects and the short observation period.

CONCLUSION

A significant frequency of premature births (11.8%) in the total number of births indicates the seriousness of the problem and the further tendency of the number of premature births to increase despite the implementation of all preventive measures. The high frequency of vital newborn infants (91%) indicates that, with adequate and timely therapy, as well as with an appropriate choice in the way that early premature delivery is completed, the perinatal outcome of the newborn improves.

A high incidence of cesarean section (54.1%) in preterm births is caused by the gestational age of the pregnancy that is younger than the 28th week as well as the predominant pelvic presentation of the fetus.

Intact fetal membranes in more than half of premature births indicate that the most common cause of premature deliveries is spontaneously initiated uterine activity in primiparous mothers, which suggests the need for better information dissemination and wider implementation of preventive measures.

Clear amniotic fluid (83.8%) indicates that infection was not the dominant cause of preterm birth in our study.

The Apgar score was the highest in newborns delivered vaginally, after the 34th week of gestation, with intact fetal membranes and spontaneous onset of contractions. This data indicates that the pregnancy outcome is better in late gestation, after the 34th week, with intact fetal membranes and no signs of infection. A higher Apgar score in children from spontaneous, compared to induced premature birth, indicates a better neonatal outcome. A better Apgar score in newborns whose mothers received dexamethasone indicates that we significantly improve the perinatal outcome with its application.

The frequency of preterm births is still increasing and is therefore a challenge for perinatologists and neonatologists. We emphasize the importance of implementing preventive measures at the level of primary health care in order to establish control over premature births.

  • Conflict of interest:
    None declared.

Informations

March 2024

Pages 64-74
  • Keywords:
    preterm birth, premature infant, Apgar score
  • Received:
    08 March 2024
  • Revised:
    11 March 2024
  • Accepted:
    18 March 2024
  • Online first:
    25 March 2024
  • DOI:
  • Cite this article:
    Donić S, Maglić R, Mandić V, Mandić M, Kostić K, Maglić D. Cause of premature birth as a prognostic factor of neonatal outcome and type of delivery. Serbian Journal of the Medical Chamber. 2024;5(1):64-74. doi: 10.5937/smclk5-49715
Corresponding author

Smiljana Donić
Obstetrics and Gynecology Clinic Narodni Front
62 Kraljice Natalije Street, 11000 Belgrade, Serbia
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


1. Plećaš D, Stanimirović B, Stanković A, Vasiljević M. Pretermiski porođaj i posttermiski porođaj. Ginekologija i akušerstvo - Udžbenik za studente medicine, 5. izdanje, Beograd: Medicinski fakultet u Beogradu; 2019. p. 256-258.

2. Underwood MA, Gilbert WM, Sherman MP. Amniotic Fluid: Not Just Fetal Urine Anymore. J Perinatol. 2005; 25, p. 341–348. [CROSSREF]

3. Glass HC, Costarino AT, Stayer SA, Brett CM, Cladis F, Davis PJ. Outcomes for Extremely Premature Infants. Anesth Analg.2015; 120(6):1337-51. [CROSSREF]

4. Perišić V, Janković B. Neonatologija. Pedijatrija - Udžbenik za studente medicine, 3. izdanje, Beograd: Medicinski fakultet u Beogradu; 2019. p. 109-115.

5. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev, 2017;(3): CD004454. [CROSSREF]

6. Goldendenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008; 371(9606): 75–84. [CROSSREF]

7. Mayo JA, Shachar BZ, Stevenson DK, Shaw GM. Nulliparous teenagers and preterm birth in California, J Perinatal Med. 2017; 45(8):959-967. [CROSSREF]

8. Li T, Wu T, Lei X, Zhang H, Mao M, Zhang J. The Apgar Score and Infant Mortality, PLoS One.2013; 8(7):e69072. [CROSSREF]


REFERENCES

1. Plećaš D, Stanimirović B, Stanković A, Vasiljević M. Pretermiski porođaj i posttermiski porođaj. Ginekologija i akušerstvo - Udžbenik za studente medicine, 5. izdanje, Beograd: Medicinski fakultet u Beogradu; 2019. p. 256-258.

2. Underwood MA, Gilbert WM, Sherman MP. Amniotic Fluid: Not Just Fetal Urine Anymore. J Perinatol. 2005; 25, p. 341–348. [CROSSREF]

3. Glass HC, Costarino AT, Stayer SA, Brett CM, Cladis F, Davis PJ. Outcomes for Extremely Premature Infants. Anesth Analg.2015; 120(6):1337-51. [CROSSREF]

4. Perišić V, Janković B. Neonatologija. Pedijatrija - Udžbenik za studente medicine, 3. izdanje, Beograd: Medicinski fakultet u Beogradu; 2019. p. 109-115.

5. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev, 2017;(3): CD004454. [CROSSREF]

6. Goldendenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008; 371(9606): 75–84. [CROSSREF]

7. Mayo JA, Shachar BZ, Stevenson DK, Shaw GM. Nulliparous teenagers and preterm birth in California, J Perinatal Med. 2017; 45(8):959-967. [CROSSREF]

8. Li T, Wu T, Lei X, Zhang H, Mao M, Zhang J. The Apgar Score and Infant Mortality, PLoS One.2013; 8(7):e69072. [CROSSREF]

1. Plećaš D, Stanimirović B, Stanković A, Vasiljević M. Pretermiski porođaj i posttermiski porođaj. Ginekologija i akušerstvo - Udžbenik za studente medicine, 5. izdanje, Beograd: Medicinski fakultet u Beogradu; 2019. p. 256-258.

2. Underwood MA, Gilbert WM, Sherman MP. Amniotic Fluid: Not Just Fetal Urine Anymore. J Perinatol. 2005; 25, p. 341–348. [CROSSREF]

3. Glass HC, Costarino AT, Stayer SA, Brett CM, Cladis F, Davis PJ. Outcomes for Extremely Premature Infants. Anesth Analg.2015; 120(6):1337-51. [CROSSREF]

4. Perišić V, Janković B. Neonatologija. Pedijatrija - Udžbenik za studente medicine, 3. izdanje, Beograd: Medicinski fakultet u Beogradu; 2019. p. 109-115.

5. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev, 2017;(3): CD004454. [CROSSREF]

6. Goldendenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008; 371(9606): 75–84. [CROSSREF]

7. Mayo JA, Shachar BZ, Stevenson DK, Shaw GM. Nulliparous teenagers and preterm birth in California, J Perinatal Med. 2017; 45(8):959-967. [CROSSREF]

8. Li T, Wu T, Lei X, Zhang H, Mao M, Zhang J. The Apgar Score and Infant Mortality, PLoS One.2013; 8(7):e69072. [CROSSREF]


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