Pattern of Early Neonatal Morbidities in Moderate and Late Pre-terms

Objective: The present study is an attempt to analyze the data on the pattern of early neonatal morbidities among moderate and late preterm infants of 32 full weeks of gestation to 36 +6 weeks’ gestational age in a tertiary care teaching hospital with a level III NICU, Chinna Kakani, A.P. Materials and Methods: The study was a retrospective analysis of all live born preterms of 32 +0 – 36 +6 GA, who were admitted between January, 2015 to April, 2016, over a period of 16 months. Data collected from hospital medical records of neonates were reviewed and analyzed statistically. Results: Of total of 3067 deliveries conducted, 930 babies were admitted in NICU for various reasons. Of total admissions to NICU 125 (13%) infants were termed as moderate and late preterms after checking their GA and analyzed for the spectrum of early neonatal morbidities during their stay in hospital. Of total 125 babies,58% (n=68) were moderate preterms and 45% (n=57) were late preterms, 75% (n=94) of them were AGA and 25% (n=32) were SGA. Of them, 62% (n=77) were delivered by LSCS while 38% (n=48) were delivered by NVD. Male infants comprised of 54% (n=67) while females were 46% (n=58). The mean weight at birth was 1.86 kg. Around 62% (n=78) of babies were observed for RD, of which 28% (n=35) required CPAP and 23%(n=29) for mechanical ventilation,18%(n=23) had apneas. Most common metabolic abnormality was hyper bilirubinemia at 44% (n=55) requiring phototherapy. Around 7% (N=9) received parenteral nutrition, NEC observed in 3% (n=3). Maternal co morbid conditions were associated in about 60% of cases. Conclusion: Moderate preterms were significantly at a higher risk for over all morbidities, longer duration of hospital stays and at a high risk for mortality when compared to late preterms. Moderate and late preterm infants place high demands on specialist neonatal services.


Introduction
Preterm labor is defined as live birth delivery before 37 complete weeks of gestation, and is the main determinant of neonatal morbidity and mortality around the world [1]. Gestational age can be classified as, if < 28 weeks as extreme preterm, 28-32 weeks as very preterm and 32 +0 -36 +6 weeks, as moderate to late preterm.
Prematurity is the leading cause of death in the 1 st four weeks of life and 2 nd most common cause after pneumonias in <5 yrs. Preterm birth rate continues to raise around the world mainly at the expense of late preterm newborns. Around 15 million babies are born prematurely and one million children die secondary to complications related to premature births [2]. The vast majority of (85%) global pre mature births occur in Asia and Africa where health systems are weak and access to and utilization of health services are limited, contributing to high risk of death and disabilities in preterm babies [3]. The incidence of premature birth has been increasing over recent decades across the world, and the rise is primarily the result of inclusion of a group of border line preterm infants since 2005. A new classification was created in order to focus on this group of border line infants who are still premature and as a result, should not receive care as FTI. Fetal growth and maturation occur along a continuum throughout pregnancy. For example, late preterm babies are born within the final stages of saccular stage of lung maturation (26-36 weeks of gestation). Premature birth during this critical respiratory maturation period may result in significant alteration in lung function and physiology, like wise brain maturation and the increase in brain weight are significantly higher during last trimester.
There has traditionally been lack of consensus on standard gestational age categories for infants born in the period near to term i.e. for 32-37 weeks of gestation [4]. Lack of recognition of prematurity and its importance of physical and neuro cognitive sequelae, could lead to increased comfort with early elective deliveries, less rigorous NB assessment, early discharges or inadequate monitoring.
Preterm birth is not a single entity, but a common final outcome of a heterogeneous collection of under lying maternal and fetal factors. Around 1/3 rd of all preterm births are the result of medical interventions to protect the health of mother or infant. Concern over the practice of elective induction or caesarian deliveries without medical indication prompted the March of Dimes to launch national campaign, "healthy babies are worth wait", to raise awareness among patients and providers on the importance of preventing non-indicated intervention [5].
Late preterm births comprise of 50-90% of premature births and associate with smaller but statistically significant neonatal mortality risk. During the last decade, studies showed that late and moderate preterm were at a higher risk for neonatal complications, including respiratory distress, requiring ventilation, TTN, IVH, bacterial sepsis, apneas, hypoglycemia, hyper bilirubinemia, feeding difficulties, NICU admissions and deaths [4,6,7]. More than 60% of all preterm births in Asia and Africa occur after 32 weeks of gestation and deaths in almost all these babies can be prevented by essential new born care. In areas with appropriate facilities for deliveries and post delivery care, clinical interventions such as surfactant administration and CPAP might improve survival to a large extent. Evidence based, low cost interventions were feasible for LMICs (Low and Middle income countries) and could reduce mortality related to preterm birth complications, such as antenatal steroids, KMC, and treatment of neonatal infections [2,5,8].

Methods and Materials
This is a retrospective, hospital based study, carried out byenrolling all live born preterm babies between 32 +0 -36 +6 weeks' gestational age, born in NRIGH maternity unit. It's a tertiary care teaching hospital with level-III NICU facilities catering patients from lower to upper middle class strata.
Study period: Jan 2015 -April 2016 (16 months). Study was approved by institutional ethical committee. Data collected from medical records of the preterm babies who were admitted during the study period were reviewed. Data regarding gestational age, birth weight, causes of preterm birth, duration of hospital stay, various morbidity and mortality patterns and treatment provided in the NICU were reviewed. A suitable case reporting form (CRF) was developed for the study after reviewing the files for infant particulars, risk factors, and morbidities. Gestational age was assessed by mother's last menstrual period, 1st trimester ultrasonogram, and new Ballard scoring.
Exclusion criteria: Out born, still born, and major identifiable chromosomal anomalies.
The objective was to assess the profile and magnitude of early morbidities among the moderate and late preterms admitted in our NICU. The relative frequency of individual variables were calculated.

Results
During the study period of sixteen months, a total of 3067 deliveries were conducted in the maternity unit of NRIGH, of which 930 babies (30% of all deliveries) were admitted to NICU due to various reasons, out of these 125 babies (13%) were selected after checking their gestational ages between 32/o -36/6 weeks and termed as moderate and late preterm babies. These infants were analyzed for pattern of early morbidities during their hospital stay till their discharge. Of total 125 babies, 58% (n=68) were moderate preterm and 45 % (n=57) were late preterm, 75% (n=94) of the total were AGA (appropriate for gestational age), and 25% (n=32) were SGA (small for gestational age).
1. Mode of delivery: 62% (n=77) of them were delivered by LSCS while 38% (n=48) were delivered by NVD (Normal Vaginal Delivery).     Mean duration of stay for moderate preterms was 14 days while for late preterms it was 6.5 days. Amongst the 32-34 weeks GA, the observed mortality due to various reasons was 2.5% (n=3), while no mortalitywas observed in 34-36 weeks GA. during their stay in NICU.

Discussion
Late and moderate preterm infants are both physiologically and developmentally immature and have higher risks for morbidity and mortality compared with infants born at term. The major findings of our study were that the risk for any short-term morbidity in moderate and late preterm infants is clearly related to gestational age.
The most commonly observed morbidities were hyperbilirubinemia, respiratory problems and need for parenteral nutrition. Previous studies compared late preterm infants outcome with term infants [4,9,1]. However, the differences between those born at 32-36 weeks suggest that it is inappropriate to regard moderate and late-preterm infants as a homogeneous group with respect to neonatal morbidity and mortality [11].
Our study shows that the rate of admissions for 32+0 -36+6 weeks gestation was 40/1000 live births with an incidence of 4%. Of which 2.2% were moderate preterms and 1.8% were late preterms.
There was a higher rate of LSCS in this study population probably because of high risk expectant mothers being referred to our tertiary care maternity unit. There were more male infants observed; however, this was similar to previous studies [12].
Gestational age and maternal co-morbidities were risk factors for adverse neonatal outcome [13]. Around 60% of the study group had associated maternal comorbidities that led to either spontaneous or induced labour culminating into preterm labour.
In our study around 60% of infants (especially moderate preterms) experienced respiratory compromises requiring ventilation, CPAP, apneas, similar to study by Kirby [14], which demonstrates the immaturity of their respiratory systems. The incidence of respiratory complications was higher in the 32-34 weeks GA group compared to the 34-36 weeks of GA group (table 2).
A significant number (44%) had hyperbilirubinemia requiring photo therapy. The level of hyperbilirubinemia was higher and needed longer duration of phototherapy in the moderate preterm infants group compared to late preterm infantsgroup. These findings weresimilar to the observations found in revious studies [10,15,16]. A quarter of the study group were classified as SGA, which might be secondary to poor maternal health status, poor socio economic status or associated co morbidities like pregnancy induced HTN, eclampsia etc.
According to UNICEF 'the state of worlds children 2010' report 28% of the neonates are born with low birth weight in India. Pulver et al. [17] reported that the risk of death during 1st month of life was 40 times greater among late preterms classified as SGA than among the late preterms with AGA.
The estimated prevalence of SGA is highest in South Asia and Africa. India has the world's largest number of SGA births, 12.8 million in 2010, due to the large number of births and the high proportion, 46.9%, of births that are SGA [18].
In addition to feeding problems secondary to immaturity of GIT, impaired sucking and deglutition mechanisms are often barriers to establish successful breast feeding leading to excessive weight loss, and longer stay in NICU. About 7% of the study group received parenteral nutrition, except for one baby from late preterm, all of them belong to moderate preterms.
Hypoglycemia was a rare event in our study, except for a few instances in infants of diabetic mother's, as most of them were either on venous infusions or breast feeds depending on their clinical condition.
About 50% of the admitted babies were treated for clinical sepsis, though culture proven sepsis was about 5%. Several studies show variable incidence like Wang et al. [4] 36%, Jaiswal et al. [16] 4% and Melamed et al. [10] 19%. Our study also shows significant difference between moderate and late preterm morbidities, in spite of receiving antenatal steroids and surfactant, their requirement for respiratory support, incidence of neonatal jaundice, sepsis, neurological morbidities, feeding difficulties were high, requiring close monitoring compared to late preterm infants [19].

Conclusion
The high rate of neonatal morbidity in our study may be attributed to the inclusion of moderate preterms who had outnumbered the late preterms. Moderate preterms had shown to have more difficult transition to extra uterine life and required to stay longer in NICU and need extra attention and special care to prevent adverse events.
The guidelines for these babies need to be reviewed, looking for possible causes as well as developing evidence based protocols for close monitoring to minimize the morbidity and to bring awareness among obstetricians about the risks of premature birth related morbidities.
Limitations: Major limitation is its retrospective design, relatively small sample size, single center study. Since its a tertiary care referral center, number of high risk mothers were referred with antenatal complications.
Majority of our study group comprised of moderate preterms. Hence high incidence of morbidities may be observable and most of the patients had a low socioeconomic status, the results of this study may not reflect the actual burden which is prevalent in the community as a whole.