Skip to main content
Download PDF

Predictors of adverse short-term outcomes in late preterm infants

BMC Pediatrics volume 23, Article number: 298 (2023) Cite this article

Abstract

Background

Infants born between 34 weeks and 36 weeks and 6 days of gestation are defined as late preterm infants (LPIs), and they account for approximately 74% of all premature births. Preterm birth (PB) remains the leading cause of infant mortality and morbidity worldwide.

Aim

To analyse short-term morbidity and mortality and identify predictors of adverse outcomes in late preterm infants.

Patients and methods

In this retrospective study, we evaluated adverse short-term outcomes of LPIs admitted to the Intensive Care Unit (ICU), Clinic for Children’s Diseases, University Clinical Center Tuzla, between 01.01.2020 and 31.12.2022. The analysed data included sex, gestational age, parity, birth weight, Apgar score (i.e., assessment of vitality at birth in the first and fifth minutes after birth), and length of hospitalization in NICU, as well as short-term outcome data. Maternal risk factors we observed were: age of mother, parity, maternal morbidity during pregnancy, complications and treatment during pregnancy. LPIs with major anatomic malformations were excluded from the study. Logistic regression analysis was used to identify risk factors for neonatal morbidity among LPIs.

Results

We analysed data from 154 late preterm newborns, most of whom were male (60%), delivered by caesarean Sect. (68.2%) and from nulliparous mothers (63.6%). Respiratory complications were the most common outcome among all subgroups, followed by CNS morbidity, infections and jaundice requiring phototherapy. The rate of almost all of the complications in the late-preterm group decreased as gestational age increased from 34 to 36 weeks. Birth weight (OR: 1,2; 95% CI: 0,9 − 2,3; p = 0,0313) and male sex (OR: 2,5; 95% CI: 1,1–5,4; p = 0,0204) were significantly and independently associated with an increased risk for respiratory morbidity, and gestational weeks and male sex were associated with infectious morbidity. None of the risk factors analysed herein were predictors of CNS morbidity in LPIs.

Conclusion

A younger gestational age at birth is associated with a greater risk of short-term complications among LPIs, thus highlighting the need for increased knowledge about the epidemiology of these late preterm births. Understanding the risks of late preterm birth is critical to optimizing clinical decision-making, enhancing the cost-effectiveness of endeavours to delay delivery during the late preterm period, and reducing neonatal morbidity.

Peer Review reports

Background

Preterm birth (PTB) is defined as birth before 37 gestational weeks [1, 2]. Infants born between 34 weeks and 36 weeks and 6 days of gestation are defined as late preterm infants (LPIs), and they account for approximately 74% of all premature births and 8% of total births [3]. PTB remains the leading cause of infant mortality and morbidity. Recently, increased attention has been devoted to better understanding the reasons for the high rate of late preterm birth, its causes, its short-term sequelae, and opportunities for prevention.

Research has revealed that LPIs have a slightly but significantly higher risk of adverse outcomes than those born at term.

The duration of care for LPIs is significantly greater, since they account for a large number of neonatal deaths [4].

The physiological and metabolic immaturity of LPIs makes their compensatory responses to the extrauterine environment limited compared to those born at term and predisposes these neonates to short- and long-term complications [3, 5,6,7,8,9,10].

Common perinatal outcomes associated with late prematurity include respiratory symptoms, such as respiratory distress syndrome, transient tachypnoea of the newborn (TTN),

and neonatal pneumothorax (NP) [11,12,13,14]. Respiratory distress syndrome (RDS) is a clinical diagnosis based on signs and symptoms of increased work of breathing, tachypnoea, grunting, retractions and typical X-ray findings. RDS remains one of the most common respiratory disorders affecting LPIs [1]. The higher risk of TTN among LPI is due to the immaturity of the lung epithelium in combination with the immaturity of the epithelial Na+ channel (ENaC) transition as well as lower surfactant production [15, 16]. All neonates are at risk of NP; this risk is even higher for premature infants, especially those requiring mechanical ventilation [17]. Persistent pulmonary hypertension of the newborn (PPHN) is characterized by high pulmonary vascular resistance and persistent hypoxemia after birth [18]. The treatment of RDS in LPIs often requires the use of continuous positive airway pressure (CPAP) or mechanical ventilatory support [4, 19, 20].

Sepsis accounts for up to one-third of neonatal deaths worldwide each year. The World Health Organization acknowledges neonatal sepsis as a major global health concern and that the highest burden occurs in low- and middle-income countries [21]. Due to the immaturity of the immune system, LPIs are more likely to be diagnosed with culture-proven sepsis and have a higher risk of sepsis-related mortality [5, 22, 23]. LPIs demonstrate specific infection rates, pathogen distribution, and mortality associated with sepsis [24].

LPIs are more susceptible to short- and long-term neurological morbidity. The prevalences or neonatal convulsions and electrographic-only seizures are higher among preterm newborns [25,26,27]. Hypoxic-ischaemic encephalopathy and intracranial haemorrhage mostly account for the aetiology of preterm infants [25].

Neonatal hypoglycaemia is a common metabolic disorder that can lead to adverse effects, but it can be addressed with early diagnosis and treatment [28]. The physiologic postnatal decrease in blood glucose levels is much greater in preterm infants than in term infants due to various factors, including inadequate glycogen stores, muscle protein, and body fat needed to sustain the substrates required to meet energy needs, as well as the immaturity of enzymes involved in glucose release. Inadequate compensatory mechanisms contribute to a higher risk of developing hypoglycaemia in preterm infants than in term infants [1].

LPIs have a lower nadir hematocrit compared to term neonates and nadir hematocrit is inversely proportional to GA. Normocytic, normochromic anemia is well tolerated in some LPIs while others require blood transfusion [29].

One of the most common physiological-metabolic events in neonates is hyperbilirubinemia. Hyperbilirubinemia is caused by an increased bilirubin load secondary to a short erythrocyte lifespan, immature conjugation and excretion and increased enterohepatic circulation.

More than 80% of newborns will have some degree of hyperbilirubinemia. Acute bilirubin encephalopathy and kernicterus should be prevented by monitoring all newborns, especially LPIs [30]. A lower gestational age is a risk factor for developing significant hyperbilirubinemia (i.e., the risk of hyperbilirubinemia increases with each additional week less than 40 weeks) [31]. Serious complications of hyperbilirubinemia occur far more frequently in low- and middle‐income countries. This is due to the increased prevalence of sepsis, less accessible and developed prenatal or postnatal care, as well as a lack of resources to treat neonates with severe hyperbilirubinemia [32]. Furthermore, hyperbilirubinemia is the most common reason for readmissions in preterm infants following discharge.

The health risks for both the mother and the infant are related to advanced maternal age pregnancy disorders, chronic diseases, the need for the use of assisted reproduction technology (ART), multiple births and caesarean sections, all of which may contribute to the global increase in premature births [33].

Readmission during the neonatal period and prolonged neonatal intensive care unit (NICU) stay is a substantial societal burden and a major public health problem associated with late prematurity [2, 5, 34]. Differences in practice during birth hospitalization may affect outcomes and readmission after discharge [35].

The incidence of late preterm births and associated perinatal outcomes of those treated in the intensive care unit have not been well studied in developing countries such as Bosnia and Herzegovina. There may be differences in the number of late preterm births, as well as in their early neonatal morbidity and mortality in developed and developing regions.

Thus, the aim of the current study was to estimate the effect of gestational age on short-term neonatal morbidity and mortality in LPIs treated in the intensive care unit and to identify predictors of adverse neonatal outcomes.

Patients and methods

A retrospective study of all LPIs (34 + 0/7 to 36 + 6/7 weeks of gestation) admitted to the Intensive Care Unit (ICU), Clinic for Children’s Diseases, University Clinical Center Tuzla (UKC Tuzla) during the three-year period from 1.1.2020 to 31.12.2022 was conducted.

The study protocol was approved by the Ethics Committee of UKC Tuzla.

LPIs treated in the ICU were identified by searching our Clinical computerized records database (BIS). LPIs with major anatomic malformations were excluded from the study. It is important to note that within the UKC Clinic for Gynaecology and Obstetrics, there is a department for newborns where LPIs that do not require an intensive level of care are treated. The strength of the study is that all infants were delivered and cared for at the same academic institution and it provides insight into the maternal risk factors. Another strength is that the data for all mothers and infants were pooled from 1 database. The limitation of our study is that it was retrospective.

The analysed data included sex, gestational age, parity, birth weight, Apgar score (i.e., assessment of vitality at birth in the first and fifth minutes after birth), and length of hospitalization in the ICU. Maternal risk factors we observed were: age of mother, parity, maternal morbidity during pregnancy, complications and treatment during pregnancy.

Short-term outcome data were divided into four categories: respiratory morbidity, neurological morbidity, infectious morbidity and additional outcomes.

Respiratory morbidity was defined as any of the following: the presence of respiratory distress syndrome (RDS), transient tachypnoea of the newborn (TTN), persistent pulmonary hypertension of neonate PPHN, NP or the need for ventilatory support such as mechanical ventilation and continuous positive airway pressure (CPAP). Culture-proven sepsis, pneumonia and meningitis were classified as infectious morbidities. Neonatal convulsions and intraventricular haemorrhage (IVH) were classified as central nervous system (CNS) morbidities. Additional morbidities included jaundice requiring phototherapy (indication for phototherapy based on guidelines from AAP 2004 [36]), hypoglycaemia (blood glucose level of less than < 2,2 mmol/L (40 mg/dL) in capillary or venous blood sample [9, 37]) and anaemia requiring blood transfusion.

Infant outcomes were based on clinical diagnoses made by a paediatric physician in accordance with diagnostic protocols, with ranges defined by the Department of Paediatrics.

In addition to clinical assessment, radiological diagnostic tools were used for respiratory pathology, as well as for neurological pathology. In the assessment of infection and entities that are classified as additional morbidities, laboratory and microbiological findings were used. The criteria for the diagnosis of neonatal sepsis required isolation of the microorganism from a blood culture and at least one clinical sign or symptom [38].

Statistical data analysis was conducted using the biomedical software application “MedCalc for Windows, Version 15.11.4” (MedCalc Software, Ostend, Belgium). Distribution of variables determined by the Kolmogorov‒Smirnov test. The variables with distorted distribution are shown with a median as a measure of the central value. Student’s t test and one-way analysis of variance were used to compare continuous variables between the groups, and X2 and Mann‒Whitney U tests were used for categorical variables. Multivariable logistic regression analysis was used to identify risk factors for adverse outcomes among late preterm infants. For the purpose of subgroup analysis in the late preterm group, the gestational week group was defined as the number of completed weeks of gestation. Thus, an infant born at a gestational age of 35 weeks and 6 days was included in the 35-week group. Differences were considered significant when P < 0.05.

Results

During the study period, there were 8544 live births at the University Hospital Tuzla at the Clinic for Gynaecology and Obstetrics, of which 842 (9.85%) were preterm infants, including 504 (5.89%) LPIs. A total of 674 infants were admitted to the NICU of the Clinic for Children’s Diseases, University Clinical Center Tuzla, 430 (63,8%) preterm and 244 (36.2%) term infants. Out of 430 preterm infants treated in the ICU, one-third were late preterm (154; 35.2%), and out of 504 LPIs born in the studied period, 154 (30.5%) needed intensive care and treatment. LPIs were more likely to be males, delivered by caesarean section (CS) and from nulliparous mothers. Most LPIs were born at 34 gestational weeks (72; p = 0.0013) (Table 1).

Table 1 Demographic and obstetric characteristics of LPIs
Full size table

The analysis of maternal factors and late preterm birth is shown in Table 2. Maternal obstetrical factors included hypertensive disorder of pregnancy HDP (25.9%), anaemia (32.5%), hypothyroidism (5.2%), diabetes (9.7%) and infection (colpitis and vulvovaginitis, 14.9%). HDP includes chronic hypertension, pregnancy-induced hypertension, and preeclampsia. Diabetes as maternal factor included gestational and established diabetes. Other data that we presented in our study are: use of steroids (65.6%), ART (16.9%), preterm premature rupture of the membranes (PPROM) (41.6%), placental ablation (3.2%), placenta preavia (1.9%) and other obstetric factors (54.5%). Under other factors we included: polyhydramnios or oligohydramnios, fetal distress, previous cesarean section, breech presentation and maternal diseases not previously specified. Approximately 79% of mothers who had a late preterm birth had at least one of the above maternal diseases. Urgent caesarean sections was most common birth way (64.9%), followed by vaginal delivery with induction – stimulation of labour (29.9%), elective caesarean Sect. (3.2) and spontaneous vaginal delivery (1.9%).

Table 2 Association of maternal factors and late preterm birth
Full size table

Respiratory complications were the most common outcome in all subgroups, followed by CNS morbidity, infections and jaundice requiring phototherapy. The rate of almost all of the complications in the late-preterm group decreased as gestational age increased from 34 to 36 weeks. Nine neonatal deaths occurred (6%), including the same number of deaths at 34 and 36 weeks (4 infants each) (Table 3).

Table 3 Neonatal outcomes in late preterm infants
Full size table

We aimed to identify the risk factors for neonatal morbidity among LPIs. Using multivariable logistic regression analysis, only nulliparity was significantly and independently associated with an increased risk of adverse neonatal outcomes. Additionally, birth weight and male sex were significantly and independently associated with an increased risk of respiratory morbidity, and gestational weeks and male sex were associated with the risk of infectious morbidity. None of the risk factors analysed herein were predictors of CNS morbidity among LPIs (Table 4).

Table 4 Factors predicting adverse neonatal outcomes for late preterm infants
Full size table

The regression model shows that the frequency of respiratory and infectious diseases increased with gestational age, while the frequency of CNS and other diseases decreased with increasing GA (Fig. 1).

Fig. 1
figure 1

Neonatal outcomes in late preterm infants

Full size image

Discussion

Globally, the increase in the incidence of premature birth is almost entirely due to infants born late preterm [39].

The increase in late-preterm births may be attributed to the increasing use of ART. ART is associated with adverse maternal and newborn outcomes [40, 41]. The progress in obstetric practices and early recognition of foetal endangerment, more frequently result in the completion of pregnancies with infants born late preterm [42].

Of the 8544 infants born in the three-year period, there were 842 (9.85%) preterm infants, including 504 (5.89%) LPIs. Of these, 154 LPIs required intensive care and therapy in the ICU, i.e., 1.8% of all infants, 18.2% of preterm infants or 30.5% of all LPIs born in the studied period.

It is important to note that within the UKC Clinic for Gynecology and Obstetrics, there is a department for newborns where LPIs who do not require an intensive level of care are treated. In the USA, the preterm delivery rate is 12–13%; in Europe and other developed countries, the reported rates generally range from 5 to 9% [33, 43]. Increases in the singleton preterm birth rate are almost entirely due to infants born late preterm [39].

The results of our study showed that preterm infants were predominantly treated in the ICU, including 430 (63.8%) preterm and 244 (36.2%) term infants. Out of the 430 preterm infants treated in the ICU, one-third were late preterm (154; 35.2%), and the majority of them were male, similar to other studies [19, 35, 44].

Of the 154 preterm infants included in our study, 104 (68.18%) were born by CS. A higher CS rate was also reported by Tsai et al. and Ma et al. [9, 37]. On the other hand, Champion et al. [45], Aliaga et al. [35] and Liqun Lu et al. found that vaginal delivery, especially with the induction of labour, was the main mode of delivery of late preterm infants (59.6%) [46].

When making decisions regarding obstetric interventions, such as induced labour, vaginal delivery or CS, the risks of continuing the pregnancy in a suboptimal uterine environment must be compared with the risks of early delivery [47].

Neonatal morbidity is significantly higher in combination with maternal medical conditions, with the independent effect of late preterm birth on early neonatal morbidity being nearly seven times greater than the independent effect of maternal risk factors [48].

Rate od LPIs was highest among women of < 20 and > 35 years of age and lowest among women of 20–34 years of age. Due to an increased prevalence of diabetes and hypertension, as well as higher use of ART, older women may be in increased risk of having preterm birth [41]. Increased preterm risk among teens may be due to biologic immaturity, socioeconomic status, and different life habits [22, 49]. 3.9% and 6.5% of mothers who delivered late preterm infants were aged < 20 years and ≥ 35 years, respectively, compared to the study in China where 4.5% and 8.4%. There is also a difference in the method of delivery. In their study vaginal was dominant, while in ours it was an emergency caesarean section. The mentioned difference may be due to the inclusion of all late preterm infants in their study, not only those treated in the ICU [46]. Differences in the incidence of hypertension, preeclampsia and PROM can be interpreted in the same way.

It is known that birth weight in relation to gestational age affects the morbidity and outcomes of late-preterm infants [50]. The average birth weight in our study was 2518 g and was between the 3rd and 97th percentiles of birth weight for gestational age.

Preterm birth is not a single entity but a common final outcome of underlying maternal and foetal factors. Parity (i.e., the number of offspring a female has delivered) was also found to be associated with adverse birth outcomes [51, 52]. For nulliparous mothers, late-preterm birth was significantly and independently associated with an increased risk for adverse neonatal outcomes, similar to a recent study with 837,226 singleton births conducted in the Netherlands. The mentioned study showed that the risks of PTB were significantly higher in nulliparous mothers than in mothers who had given birth at least once (RR: 1.95, 95% CI: 1.89–2.00 for PTB) [53]. In the results presented by Torres-Munoz, 41.04% of the group of cases with LPIs were primiparous women, and 54.72% were multiparous women (2–5 births), compared to the control group in which primiparous women were represented in a smaller percentage, i.e., 37.26% [54]. However, a systematic review consisting of 41 studies did not reach the same conclusion [55]. Additionally, significant heterogeneity was found among the included studies, indicating the need for more studies.

A study by De Luca et al. [27] revealed a strong age-related trend in respiratory morbidity independent of delivery mode and a > 10-fold increase in respiratory morbidity in infants born at 34 weeks GA compared with those born at term. A retrospective study in Canada by Kitsommart et al. [28] revealed significantly worse respiratory outcomes (including the prevalence of NP and the rates of positive pressure therapy, and mechanical ventilation assistance; all P < 0.001) in 1481 infants born at 34 to 36 weeks GA compared with 9332 infants born at ≥ 37 weeks GA.

The risk of adverse short-term outcomes changes with each week of gestation [19, 45, 56, 57]. Our results were fairly consistent, and the rate of almost all complications in the late-preterm group decreased as gestational age increased from 34 to 36 weeks.

Adverse short-term respiratory outcomes were the most common complications at all gestational ages. Infants born at 34 weeks had 40-fold increased odds of developing RDS versus infants born at 39 weeks [58]. In our study, the rates of RDS were 74,7%, 70,8% and 7.,6% for infants born at 34 weeks GA, 35 weeks GA and 36 weeks GA, which was similar to the rates of 70.3%, 79.5% and 70.65% in the study by McIntire et al. [11] but significantly higher than those of 22.3%, 31.5% and 32.5% in the study by Jones et al. [59]. Respiratory support was needed for up to 58,1% of infants admitted to the NICU according to Aliaga et al. [35]. The need for mechanical ventilation followed the rate of RDS in our study and was the highest in the 36th gestational week. We had more LPIs on MV at 36 weeks GA because 3 LPIs had sepsis, 1 had severe asphyxia, and 2 had a severe form of RDS with pneumothorax.

The studies by Tutdibi et al. and Derbent et al. indicate that TTN is strongly related to elective CS delivery and low GA [15, 16]. The rates of TTN and NP in our study were similar at 34 and 36 weeks GA and were present exclusively in neonates born by CS. In a study performed in 2017–2019 in the same clinic as our study, a lower gestational week and CS delivery were shown to be risk factors for NP in neonates on mechanical ventilation [60]. For PPHT, the vast majority of infants with PPHN were born at term or near term, although approximately 2% of cases were born prematurely [61]. Our study supports the claim that the highest incidence of PPH occurs at the highest GA, i.e., 25.6%.

In LPIs, treatment for suspected systemic infection is far more common than for term infants, and the diagnosis is made on the basis of clinical symptoms, laboratory findings and/or positive blood cultures [44]. Sepsis was diagnosed in 22.7% of the late-preterm infants in our study, and the literature mentions infection frequency percentages of 4,9–20,6%[11, 62]. The pattern of pathogen distribution differs from region to region as well as between developed and less developed countries due to patient demographic characteristics, the colonization of the microflora of the hospital environment and antibiotic use policies.

[38], which may explain the higher rate of sepsis in our study. Pneumonia was present in 18.8% of the LPIs, while according to Loftin et al., the frequency was 1.2% in newborns at 34 weeks GA; an overall rate of 0.7% was described in the study by Melamed et al. [7, 40], in which 2.6% of the LPIs had meningitis.

Regarding the short-term CNS morbidity outcomes, neonatal convulsions accounted for 3.9% of the LPIs in our study. Although the incidence of severe intraventricular haemorrhage is low in LPIs when compared to other preterm infants, LPIs are still at higher risk when compared to term neonates. The large variation in the reported rates of IVH is due to the lack of standard guidelines for screening neuroimaging in LPIs, so we can elucidate the reason for the high number of LPIs with IVH grade 1 and 2 in our study. McIntire et al. reported rates of IVH grade 1 and 2 in LPIs of 0.5% at 34 weeks GA, 0.2% at 35 weeks GA and 0.06% at 36 weeks GA, but when we analyse only at the data on LPIs admitted to the NICU, the percentage increases to 10.9% at 34 weeks GA. Teune et al. reviewed 22 studies and found that intracranial haemorrhage occurred more frequently in LPIs. The rate of either IVH grade 3 or 4 was extremely low in LPIs [11]; however, it remained higher than that in term neonates (0.01% vs. 0.004%) [63]. Our rate of IVH grade 3 or 4 was higher, at 2.6%, and occurred only in the 34th week of gestation. This percentage was expectedly higher, considering that Teune et al. reviewed the data of all LPIs, not only those admitted to the NICU.

The most common additional short-term outcome in our study was hyperbilirubinemia, defined as jaundice that required phototherapy, as in multiple studies in which it occurred during initial hospitalization [11, 64, 65]. Very high rates of jaundice were reported by Wang et al., and more than half of the LPIs in a large-based practice report developed hyperbilirubinemia requiring phototherapy [12, 66]. Aliaga et al. reported that 33.2% of late-preterm newborns in the study group received phototherapy. More late-preterm newborns admitted to the NICU (58.3%) received phototherapy than those admitted to the newborn nursery (19.9%). Phototherapy was more common in infants born at 34 weeks GA than at 35 and 36 weeks GA (63.5 vs. 34.7 vs. 21.2%). LPIs who were treated for hyperbilirubinemia in the same way as term infants developed kernicterus and had more sequelae from hazardous hyperbilirubinemia [67]. Existing guidelines are helpful for treating hyperbilirubinemia in infants who are born at 35 weeks GA or later.

As a result of metabolic immaturity, hypoglycaemia is common among LPIs, with an overall incidence of up to 50% [7, 37, 64, 66, 67]. Our study, with a total of 26% of infants with hypoglycaemia, confirms the metabolic immaturity of preterm infants and is consistent with the results of the aforementioned studies. A meta-analysis further confirmed the increased risk of hypoglycaemia in LPIs compared with term infants [63].

In our study, 11,0% of LPIs had anaemia requiring blood transfusion, which was expected considering the morbidities of preterm infants requiring admission to the NICU. The rate of anaemia decreased as gestational age increased from 34 to 36 gestational weeks.

LPIs not requiring intensive treatment are treated at the Neonatal Department of the Clinic for Gynecology and Obstetrics. Neonates born at 35 weeks GA and 36 weeks GA who required intensive care and therapy were included in this study, which provides an explanation for the greater number of respiratory and infectious diseases in infants with older gestational age.

Conclusion

Identifying the predictors of adverse short-term outcomes in late preterm infants is of crucial importance for informing and evaluating clinical practices and guidelines aimed at reducing infant morbidity and mortality. The differences in the number of late-preterm births, as well as in the early neonatal morbidity and mortality rates in developed and developing regions, should stimulate more research to analyse risk factors for latepreterm births in underdeveloped regions.

Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

LPIs:

Late preterm infants

PTB:

Preterm birth

ICU:

Intensive Care Unit

UKC Tuzla:

University Clinical Center Tuzla

BIS:

Clinical computerized records database (BIS)

NICU:

Neonatal Intensive Care Unit

RDS:

Respiratory distress syndrome

TTN:

Transient tachypnea of the newborn

CPAP:

Continuous positive airway pressure

IVH:

Intraventricular hemorrhage

CNS:

Central nervous system

HDP:

Hypertensive disorder of pregnancy

ART:

Assisted reproduction technology

References

  1. Karnati S, Kollikonda S, Abu-Shaweesh J. Late preterm infants – changing trends and continuing challenges. Int J Pediatr Adolesc Med. 2020;7:38–46. https://doi.org/10.1016/j.ijpam.2020.02.006.

    Article  Google Scholar 

  2. Johnston KM, Gooch K, Korol E, et al. The economic burden of prematurity in Canada. BMC Pediatr. 2014;14:93. https://doi.org/10.1186/1471-2431-14-93.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Davidoff MJ, Dias T, Damus K, et al. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to 2002. Semin Perinatol. 2006;30:8–15. https://doi.org/10.1053/j.semperi.2006.01.009.

    Article  PubMed  Google Scholar 

  4. Raju TNK, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (Near-Term) Infants: a Summary of the Workshop Sponsored by the National Institute of Child Health and Human Development. Pediatrics. 2006;118:1207–14. https://doi.org/10.1542/peds.2006-0018.

    Article  PubMed  Google Scholar 

  5. Kramer MS, Demissie K, Yang H, et al. The contribution of mild and moderate Preterm Birth to Infant Mortality. JAMA. 2000;284:843–9. https://doi.org/10.1001/jama.284.7.843.

    Article  CAS  PubMed  Google Scholar 

  6. Machado LC, Passini Júnior R, Rodrigues Machado Rosa I. Late prematurity: a systematic review. J Pediatr (Rio J). 2014;90:221–31. https://doi.org/10.1016/j.jped.2013.08.012.

    Article  Google Scholar 

  7. Melamed N, Klinger G, Tenenbaum-Gavish K, et al. Short-term neonatal outcome in Low-Risk, spontaneous, Singleton, late Preterm deliveries. Obstet Gynecol. 2009;114:253–60. https://doi.org/10.1097/AOG.0b013e3181af6931.

    Article  PubMed  Google Scholar 

  8. Sharma D, Padmavathi IV, Tabatabaii SA, Farahbakhsh N. Late preterm: a new high risk group in neonatology. J Matern Fetal Neonatal Med. 2021;34:2717–30. https://doi.org/10.1080/14767058.2019.1670796.

    Article  PubMed  Google Scholar 

  9. Tsai M-L, Lien R, Chiang M-C, et al. Prevalence and morbidity of late Preterm Infants: current status in a Medical Center of Northern Taiwan. Pediatr Neonatol. 2012;53:171–7. https://doi.org/10.1016/j.pedneo.2012.04.003.

    Article  PubMed  Google Scholar 

  10. Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2005. Natl Vital Stat Rep Cent Dis Control Prev Natl Cent Health Stat Natl Vital Stat Syst. 2007;56:1–103.

    Google Scholar 

  11. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008;111:35–41. https://doi.org/10.1097/01.AOG.0000297311.33046.73.

    Article  PubMed  Google Scholar 

  12. Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics. 2004;114:372–6. https://doi.org/10.1542/peds.114.2.372.

    Article  PubMed  Google Scholar 

  13. Clark RH. The epidemiology of respiratory failure in neonates born at an estimated gestational age of 34 weeks or more. J Perinatol Off J Calif Perinat Assoc. 2005;25:251–7. https://doi.org/10.1038/sj.jp.7211242.

    Article  Google Scholar 

  14. Dani C, Corsini I, Piergentili L, et al. Neonatal morbidity in late preterm and term infants in the nursery of a tertiary hospital. Acta Paediatr Oslo Nor 1992. 2009;98:1841–3. https://doi.org/10.1111/j.1651-2227.2009.01425.x.

    Article  CAS  Google Scholar 

  15. Derbent A, Tatli MM, Duran M, et al. Transient tachypnea of the newborn: effects of labor and delivery type in term and preterm pregnancies. Arch Gynecol Obstet. 2011;283:947–51. https://doi.org/10.1007/s00404-010-1473-6.

    Article  PubMed  Google Scholar 

  16. Tutdibi E, Gries K, Bücheler M, et al. Impact of labor on outcomes in transient tachypnea of the newborn: population-based study. Pediatrics. 2010;125:e577–583. https://doi.org/10.1542/peds.2009-0314.

    Article  PubMed  Google Scholar 

  17. Colin AA, McEvoy C, Castile RG. Respiratory morbidity and lung function in Preterm Infants of 32 to 36 weeks’ gestational age. Pediatrics. 2010;126:115–28. https://doi.org/10.1542/peds.2009-1381.

    Article  PubMed  Google Scholar 

  18. Singh Y, Lakshminrusimha S. Pathophysiology and management of Persistent Pulmonary hypertension of the Newborn. Clin Perinatol. 2021;48:595–618. https://doi.org/10.1016/j.clp.2021.05.009.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Consortium on Safe Labor, Hibbard JU, Wilkins I, et al. Respiratory morbidity in late preterm births. JAMA. 2010;304:419–25. https://doi.org/10.1001/jama.2010.1015.

    Article  Google Scholar 

  20. Ramaswamy VV, Abiramalatha T, Bandyopadhyay T, et al. Surfactant therapy in late preterm and term neonates with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2022;107:393–7. https://doi.org/10.1136/archdischild-2021-322890.

    Article  PubMed  Google Scholar 

  21. Popescu CR, Cavanagh MMM, Tembo B, et al. Neonatal sepsis in low-income countries: epidemiology, diagnosis and prevention. Expert Rev Anti Infect Ther. 2020;18:443–52. https://doi.org/10.1080/14787210.2020.1732818.

    Article  CAS  PubMed  Google Scholar 

  22. Shapiro-Mendoza CK, Tomashek KM, Kotelchuck M, et al. Risk factors for neonatal morbidity and mortality among “healthy,” late preterm newborns. Semin Perinatol. 2006;30:54–60. https://doi.org/10.1053/j.semperi.2006.02.002.

    Article  PubMed  Google Scholar 

  23. Tomashek KM, Shapiro-Mendoza CK, Weiss J, et al. Early discharge among late preterm and term newborns and risk of neonatal morbidity. Semin Perinatol. 2006;30:61–8. https://doi.org/10.1053/j.semperi.2006.02.003.

    Article  PubMed  Google Scholar 

  24. Cohen-Wolkowiez M, Moran C, Benjamin DK, et al. Early and late Onset Sepsis in Late Preterm Infants. Pediatr Infect Dis J. 2009;28:1052–6.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Glass HC, Shellhaas RA, Tsuchida TN, et al. Seizures in Preterm Neonates: a Multicenter Observational Cohort Study. Pediatr Neurol. 2017;72:19–24. https://doi.org/10.1016/j.pediatrneurol.2017.04.016.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pisani F, Facini C, Bianchi E, et al. Incidence of neonatal seizures, perinatal risk factors for epilepsy and mortality after neonatal seizures in the province of Parma, Italy. Epilepsia. 2018;59:1764–73. https://doi.org/10.1111/epi.14537.

    Article  PubMed  Google Scholar 

  27. Pisani F, Prezioso G, Spagnoli C. Neonatal seizures in preterm infants: a systematic review of mortality risk and neurological outcomes from studies in the 2000’s. Seizure - Eur J Epilepsy. 2020;75:7–17. https://doi.org/10.1016/j.seizure.2019.12.005.

    Article  Google Scholar 

  28. Bülbül A, Bahar S, Uslu S, et al. Risk factor Assessment and the incidence of neonatal hypoglycemia in the postnatal period. Şişli Etfal Hastan Tıp Bül. 2019;53:389–94. https://doi.org/10.14744/SEMB.2019.08634.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Von Kohorn I, Ehrenkranz RA. Anemia in the preterm infant: Erythropoietin versus erythrocyte transfusion — it’s not that simple. Clin Perinatol. 2009;36:111–23. https://doi.org/10.1016/j.clp.2008.09.009.

    Article  Google Scholar 

  30. Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the Newborn Infant 35 or more weeks of Gestation. Pediatrics. 2004;114:297–316. https://doi.org/10.1542/peds.114.1.297.

    Article  Google Scholar 

  31. Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice Guideline Revision: management of Hyperbilirubinemia in the Newborn Infant 35 or more weeks of Gestation. Pediatrics. 2022;150:e2022058859. https://doi.org/10.1542/peds.2022-058859.

    Article  PubMed  Google Scholar 

  32. Horn D, Ehret D, Gautham KS, Soll R. Sunlight for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates. Cochrane Database Syst Rev. 2021;2021:CD013277. https://doi.org/10.1002/14651858.CD013277.pub2.

    Article  PubMed Central  Google Scholar 

  33. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet Lond Engl. 2008;371:75–84. https://doi.org/10.1016/S0140-6736(08)60074-4.

    Article  Google Scholar 

  34. Health issues of the late preterm infant - PubMed. https://pubmed.ncbi.nlm.nih.gov/19501692/. Accessed 10 Nov 2022.

  35. Aliaga S, Boggess K, Ivester TS, Price WA. Influence of neonatal practice variation on outcomes of late preterm birth. Am J Perinatol. 2014;31:659–66. https://doi.org/10.1055/s-0033-1356484.

    Article  PubMed  Google Scholar 

  36. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114:297–316. https://doi.org/10.1542/peds.114.1.297.

    Article  Google Scholar 

  37. Ma X, Huang C, Lou S, et al. The clinical outcomes of late preterm infants: a multi-center survey of Zhejiang, China. J Perinat Med. 2009;37:695–9. https://doi.org/10.1515/JPM.2009.130.

    Article  PubMed  Google Scholar 

  38. Shim GH, Kim SD, Kim HS, et al. Trends in Epidemiology of neonatal Sepsis in a Tertiary Center in Korea: a 26-Year longitudinal analysis, 1980–2005. J Korean Med Sci. 2011;26:284–9. https://doi.org/10.3346/jkms.2011.26.2.284.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2009. Natl Vital Stat Rep Cent Dis Control Prev Natl Cent Health Stat Natl Vital Stat Syst. 2010;59:1–19.

    Google Scholar 

  40. Loftin RW, Habli M, Snyder CC, et al. Late Preterm Birth. Rev Obstet Gynecol. 2010;3:10–9.

    PubMed  PubMed Central  Google Scholar 

  41. Sunderam S, Chang J, Flowers L, et al. Assisted reproductive technology surveillance–United States, 2006. Morb Mortal Wkly Rep Surveill Summ. 2009;Wash DC 2002:58–1.

    Google Scholar 

  42. Shapiro-Mendoza CK, Lackritz EM. Epidemiology of late and moderate preterm birth. Semin Fetal Neonatal Med. 2012;17:120–5. https://doi.org/10.1016/j.siny.2012.01.007.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Slattery MM, Morrison JJ. Preterm delivery. Lancet Lond Engl. 2002;360:1489–97. https://doi.org/10.1016/S0140-6736(02)11476-0.

    Article  Google Scholar 

  44. Hamidović LD, Babović A. (2017) Rizici Kasnog Prematuriteta Novorođenčadi Hospitalizirane U Jedinici Intenzivne Njege. 70–4. https://doi.org/10.5457/429.

  45. Champion V, Durrmeyer X, Dassieu G. [Short-term respiratory outcome of late preterm newborn in a center of level III]. Arch Pediatr Organe Off Soc Francaise Pediatr. 2010;17:19–25. https://doi.org/10.1016/j.arcped.2009.10.002.

    Article  CAS  Google Scholar 

  46. Lu L, Qu Y, Tang J, et al. Risk factors associated with late preterm births in the underdeveloped region of China: a cohort study and systematic review. Taiwan J Obstet Gynecol. 2015;54:647–53. https://doi.org/10.1016/j.tjog.2014.05.011.

    Article  PubMed  Google Scholar 

  47. Reddy UM, Ko C-W, Raju TNK, Willinger M. Delivery indications at Late-Preterm Gestations and Infant Mortality Rates in the United States. Pediatrics. 2009;124:234–40. https://doi.org/10.1542/peds.2008-3232.

    Article  PubMed  Google Scholar 

  48. Shapiro-Mendoza CK, Tomashek KM, Kotelchuck M, et al. Effect of late-preterm birth and maternal medical conditions on newborn morbidity risk. Pediatrics. 2008;121:e223–232. https://doi.org/10.1542/peds.2006-3629.

    Article  PubMed  Google Scholar 

  49. Strobino DM, Ensminger ME, Kim YJ, Nanda J. Mechanisms for maternal age differences in birth weight. Am J Epidemiol. 1995;142:504–14. https://doi.org/10.1093/oxfordjournals.aje.a117668.

    Article  CAS  PubMed  Google Scholar 

  50. Pulver LS, Guest-Warnick G, Stoddard GJ, et al. Weight for gestational age affects the mortality of late preterm infants. Pediatrics. 2009;123:e1072–1077. https://doi.org/10.1542/peds.2008-3288.

    Article  PubMed  Google Scholar 

  51. Hinkle SN, Albert PS, Mendola P, et al. The association between parity and birthweight in a longitudinal consecutive pregnancy cohort. Paediatr Perinat Epidemiol. 2014;28:106–15. https://doi.org/10.1111/ppe.12099.

    Article  PubMed  Google Scholar 

  52. Schimmel MS, Bromiker R, Hammerman C, et al. The effects of maternal age and parity on maternal and neonatal outcome. Arch Gynecol Obstet. 2015;291:793–8. https://doi.org/10.1007/s00404-014-3469-0.

    Article  CAS  PubMed  Google Scholar 

  53. Koullali B, van Zijl MD, Kazemier BM, et al. The association between parity and spontaneous preterm birth: a population based study. BMC Pregnancy Childbirth. 2020;20:233. https://doi.org/10.1186/s12884-020-02940-w.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Torres-Muñoz J, Jiménez-Fernandez CA, Ortega RR et al. (2020) Factors Associated with Late Prematurity in the University Hospital of Valle Cali, Colombia during 2013–2014. Front Public Health 8.

  55. Shah PS, Knowledge Synthesis Group on Determinants of LBW/PT births. Parity and low birth weight and preterm birth: a systematic review and meta-analyses. Acta Obstet Gynecol Scand. 2010;89:862–75. https://doi.org/10.3109/00016349.2010.486827.

    Article  PubMed  Google Scholar 

  56. Dimitriou G, Fouzas S, Georgakis V, et al. Determinants of morbidity in late preterm infants. Early Hum Dev. 2010;86:587–91. https://doi.org/10.1016/j.earlhumdev.2010.07.011.

    Article  PubMed  Google Scholar 

  57. Demestre Guasch X, Raspall Torrent F, Martínez-Nadal S, et al. Prematuros tardíos: una población de riesgo infravalorada. An Pediatría. 2009;71:291–8. https://doi.org/10.1016/j.anpedi.2009.06.011.

    Article  Google Scholar 

  58. Ventolini G, Neiger R, Mathews L, et al. Incidence of respiratory disorders in neonates born between 34 and 36 weeks of gestation following exposure to antenatal corticosteroids between 24 and 34 weeks of gestation. Am J Perinatol. 2008;25:79–83. https://doi.org/10.1055/s-2007-1022470.

    Article  PubMed  Google Scholar 

  59. Jones JS, Istwan NB, Jacques D, et al. Is 34 weeks an acceptable goal for a complicated singleton pregnancy? Manag Care Langhorne Pa. 2002;11:42–7.

    Google Scholar 

  60. Hadzic D, Skokic F, Husaric E, et al. Risk factors and outcome of neonatal pneumothorax in Tuzla Canton. Mater Socio-Medica. 2019;31:66–70. https://doi.org/10.5455/msm.2019.31.66-70.

    Article  Google Scholar 

  61. Kumar VH, Hutchison AA, Lakshminrusimha S, et al. Characteristics of pulmonary hypertension in preterm neonates. J Perinatol Off J Calif Perinat Assoc. 2007;27:214–9. https://doi.org/10.1038/sj.jp.7211673.

    Article  CAS  Google Scholar 

  62. Robertson PA, Sniderman SH, Laros RK, et al. Neonatal morbidity according to gestational age and birth weight from five tertiary care centers in the United States, 1983 through 1986. Am J Obstet Gynecol. 1992;166:1629–41. https://doi.org/10.1016/0002-9378(92)91551-k. discussion 1641–1645.

    Article  CAS  PubMed  Google Scholar 

  63. Teune MJ, Bakhuizen S, Gyamfi Bannerman C, et al. A systematic review of severe morbidity in infants born late preterm. Am J Obstet Gynecol. 2011;205:374e1–9. https://doi.org/10.1016/j.ajog.2011.07.015.

    Article  Google Scholar 

  64. Celik IH, Demirel G, Canpolat FE, Dilmen U. A common problem for neonatal intensive care units: late preterm infants, a prospective study with term controls in a large perinatal center. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2013;26:459–62. https://doi.org/10.3109/14767058.2012.735994.

    Article  Google Scholar 

  65. Lubow JM, How HY, Habli M, et al. Indications for delivery and short-term neonatal outcomes in late preterm as compared with term births. Am J Obstet Gynecol. 2009;200:e30–33. https://doi.org/10.1016/j.ajog.2008.09.022.

    Article  PubMed  Google Scholar 

  66. Medoff Cooper B, Holditch-Davis D, Verklan MT, et al. Newborn clinical outcomes of the AWHONN late preterm infant research-based practice project. J Obstet Gynecol Neonatal Nurs JOGNN. 2012;41:774–85. https://doi.org/10.1111/j.1552-6909.2012.01401.x.

    Article  PubMed  Google Scholar 

  67. Bhutani VK, Johnson L. Kernicterus in late preterm infants cared for as term healthy infants. Semin Perinatol. 2006;30:89–97. https://doi.org/10.1053/j.semperi.2006.04.001.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Authors and Affiliations

  1. Pediatric Department, Health and Educational Medical Center Tuzla, Tuzla, Bosnia and Herzegovina

    Nina Mekic & Amra Serak

  2. Clinic for Children’s Diseases Tuzla, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina

    Amela Selimovic, Almira Cosickic, Devleta Hadzic & Evlijana Zulic

  3. Clinic for Internal Medicine, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina

    Majda Mehmedovic

  4. Polyclinic for Laboratory Diagnostics University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina

    Sehveta Mustafic

Authors
  1. Nina Mekic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amela Selimovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Almira Cosickic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Majda Mehmedovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Devleta Hadzic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Evlijana Zulic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sehveta Mustafic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amra Serak
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NM and AS contributed to the conception and design of the study; NM, AS, DH, EZ, SM and AS collected and analyzed data; NM, AS and MM wrote the manuscript; AS and AC revised the manuscript. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Nina Mekic.

Ethics declarations

Ethics approval and consent to participate

This study was designed in accordance with the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of University Clinical Center Tuzla. Informed consent was obtained from all the legal representatives or the guardians of the child participants involved in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mekic, N., Selimovic, A., Cosickic, A. et al. Predictors of adverse short-term outcomes in late preterm infants. BMC Pediatr 23, 298 (2023). https://doi.org/10.1186/s12887-023-04112-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12887-023-04112-z

Keywords

BMC Pediatrics

ISSN: 1471-2431

Contact us