Sidra Malik Outcomes of late preterm newborn

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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

FACULTY OF MEDICINE

Sidra Malik

Outcomes of late preterm newborn

A thesis submitted in part fulfillment for the

degree of Master of Medicine

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SUMMARY

Author name: Sidra Malik Title: Outcomes of late preterm newborn

Aim: The aim of the study is to evaluate morbidities, weight’s variations during the first 5 days of life and a feeding pattern in the late preterm newborns and evaluate admission to NICU.

Objectives:

1. to evaluate the rate of the major morbidities: respiratory, jaundice, hypoglycemia, hemorrhages, infections and to compare morbidities among gestational ages: 34-35-36 weeks of gestation.

2. to evaluate weight’s change during first 5 days of life and to compare among gestational ages. 3. to evaluate the pattern of feeding at a discharge time and to compare among gestational ages. Methods: This was a retrospective cohort study of all late preterm live births (340/7 to 366/7 weeks of gestation) during the 1-year period between January 2015 and December 2015 in LUHS Department of Neonatology. Late preterm newborns were divided in 3 sub-groups according to gestational age: 340/6_{, 35}0/6_{, 36}0/6 _{weeks of gestation. The incidence of major clinical outcomes was evaluated.}

Statistical analysis was performed by using Chi-Square test and Kruskal wallis test.

Results: Jaundice and respiratory morbidity occurred significantly more often in the newborn’s group of 34th GA compare with 35th GA and 36th GA. We compared morbidities, mode of delivery and gestational age and found that only newborns of 34th GA and 35th GA after vaginal delivery significantly more often had jaundice then newborns delivered by cesarean section. Significantly higher weight loss was in group 34th week. Comparing the weight loss with group 35th-36th GA, it was significantly highest weight loss on the 2nd day in the group 34th week. Breastfeeding rate was significantly higher in the group of newborns not admitted to NICU. Infants who were admitted to NICU were significantly more fed by formula.

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ACKNOWLEDGEMENTS

First of all, I want to thank my lovely family and friends in Norway as well as in Lithuania. I really appreciate all your help and moral support to go through this time.

Many thanks to my supervisor, Dr. Dalia Stonienė, who always came up with new ideas and positive input for my research that continuously motivated and pushed me to do my best. I would also like to thank my statistics teacher Jūratė Tomkevičiūtė, who helped me and guided me trough out with statically analysis’s of my thesis. Further, I would like to thank International Deans office for availability and help for every problem.

I would like also to thank my friend Marta Ejsmont. I really appreciate your help. You have been great friend during a hard time.

CONFLICT OF INTEREST

The author reports no conflicts of interest.

ETHICS COMMITTEE CLEARANCE

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ABBREVIATIONS LIST

NICU - Neonatology intensive care unit

LUHS - Hospital of Lithuanian university of health sciences Kauno klinikos

GA - Gestational age

RDS - Respiratory distress syndrome IVH - Intraventricular hemorrhage LBW - Low birth weight

VLBW - Very low birth weight ELBW - Extremely low birth weight AGA - Appropriate for gestational age SGA - Small for gestational age LGA - Large for gestational age IVF - In vitro fertilization NH - Neonatal hypoglycemia

PROM - Premature rupture of membranes PDA - Patent ductus arteriosus

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INTRODUCTION

Preterm labour is a labour which is described as consistent painful and regular contractions and cervical changes before 37th weeks of gestation (1). According to National institute of child health

and human development workshop in 2005, Late preterm infants are infants born in gestational weeks

34th 0/7 and 36th6/7. Late preterm infants were known as near term infants earlier (6,8). Its says that late preterm infants are the biggest subgroup of preterm infants and in 2009 75% of all preterm births was late preterm births (3,4). The last 25 years have showed that the birth rate of late preterm infants have raised by 33%, and this is because of its well defined gestational age (1). These late preterm newborns are considered to be physiologically and metabolically “functionally mature” due their same size and weight at birth as newborns born at term. The difference between late preterm infants and infants born at term is that term infants have fewer severe neonatal complications and less long-term neurological outcomes than infants born before 34th or till 37th weeks of gestation (1,3,7). Therefore, late preterm birth has increase risk of neonatal mortality and morbidity such as Respiratory distress syndrome (RDS), apnea, jaundice and hyperbilirubinemia, hypoglycemia, feeding difficulties, hypothermia and temperature instability, high risk for infection and sepsis, seizures, anemia, intraventricular hemorrhage (IVH), and necrotizing enterocolititis (1,6,15,). Furthermore, late preterm infants have increased rates of hospital readmission in the first year of their life and increased risk for neonatal intensive unit admission compared to infants born at term (1,10). Late preterm are 7 times more prone to have newborn morbidity compared to term infants and the morbidity rate is double by each gestational week before week 38th. Also late preterm infants born to mothers who have any maternal conditions diagnosed are at higher risk for newborn morbidity compared to term infants who are born without any risks (2). Present of morbidities in late preterm infants can effect there feeding pattern and feeding strategies (16). Feeding difficulties in late preterm infants can be due to maternal and neonates causes for example ineffective breastfeeding behaviors and delayed onset of lactation (32). Immature sucking and swallowing reflex takes part in late preterm infants feeding difficulties and this will later give effect on there weight (34,32,33).

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AIM AND OBJECTIVES

The aim of the study is to evaluate morbidities, weight’s variations during the first 5 days of life and a feeding pattern in the late preterm newborns.

Objectives:

1. to evaluate the major morbidities: respiratory, jaundice, hypoglycemia, hemorrhages, infections and to compare morbidities among gestational ages: 34-35-36 weeks of gestation.

2. to evaluate weight’s change during first 5 days of life and to compare among gestational ages.

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1. LITERATURE REVIEW

Among all the European Countries, the birth rates lie between 8.2 and 15.3 births/1000 people (1). Albania and Ireland have the highest birth rate whilst Germany and Italy have the lowest (1). Most European countries have birth rates ranging from 9 to 11births/1000 people per year (1). Lithuania is number 8 among European countries, having the lowest birth rate at 9.11 births/1000 people according to the Maps of the World (1).

1.1 Newborn’s classification (term newborn and premature newborn)

Newborn’s classification is based on their gestational age and birth weight. It can be further divided into Preterm born, which is less than 37 weeks of gestation, Term born is between 37 weeks of gestation till the end of week 41 of gestation, whilst post term born is at 42 weeks of gestation or more. Preterm born is divided further into sub- divisions which are based on weeks of gestational age: Extremely preterm which is less than 8 weeks, very preterm 28 to less than 32 weeks and moderate to late preterm 32 to less than 37 weeks. A full term pregnancy is 40 weeks (2).

Classification according to birth weight is divided into low birth weight (LBW), which are newborns weighing less than 2500g, very low birth weight (VLBW) newborns weigh less than 1500g, and extremely low birth weight (ELBW) are less than 1000g.

Classification of gestational age and birth weight are two important parameters to know because it gives you information about the infant and infants outcome.

Gestational age is also divided in to three different divisions; the first one is appropriate for gestational age (AGA), were weight is suitable for the gestational age. The second one is small for gestational age (SGA), were newborn is smaller than expected and the weight falls below the 5th percentile for the gestational age. The third one is large for gestational age (LGA), were the newborn is heavier than expected and the birth weight is more than the 95th percentile for the gestational age (3).

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Preterm can be caused by conditions affecting the mother during pregnancy, such as gestational diabetes, hypertension, heart or kidney problems and infections involving the amniotic membrane, genital and urinary tracts. Plus, bleeding due to abnormal positioning of the placenta. Other cause can be mother’s life style. For example, bad nutrition, increase alcohol intake during her pregnancy and smoking. Also early deliveries caused by multiple pregnancies, very young aged woman or older woman (more than 40 years old) is very common (5).

Other risk factors for spontaneous and non-spontaneous preterm birth can be in vitro fertilization (IVF) and increased maternal body mass index (BMI) (6). However, any pregnant woman may deliver prematurely despite not having any of the known risk factors (5).

Preterm birth is the highest contributor to infant death (7). Most preterm related deaths occur among babies who are born very preterm.

Preterm birth is also a leading cause of long-term neurological disabilities in children (7). This is because during the final weeks and months of pregnancy, a developing baby will go through important growth and developments. These include changes to the brain, lungs and liver and many others organs systems, which need the final weeks of pregnancy to fully develop.

Being born very early leads to lower weight than full term newborns (7). They can have many health issues because their organs are developed incompletely (7).

The risk of serious disability or death is higher the earlier the baby is born (7). The problems that can be faced in a late preterm newborns life can be cerebral palsy, respiratory morbidities, development delay, feeding problems and vison and hearing impairment. However late preterm infants have high risk for neonatal morbidities because of there organs are immature (7).

Late preterm infants need special medical care in the hospital and in neonatal intensive care unit (NICU). In NICU it is provided all the special medical care which is needed for the infant’s growth and good development (8, 9, 5).

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However, prematurity is the main cause of death of newborns in their first 4 weeks of life after pneumonia, which is the leading cause of death in children under 5 years of age. Furthermore, in this report it mentions more than 80% of premature newborn are born between 32 and 37 weeks of gestation, and they die because of lack of necessary care such as warmth and feeding support (10). The study “Preterm birth time trends in Europe: a study of 19 countries” discusses that there is an increase rate in preterm births in Europe but the survival of late preterm infants has improved a lot over the past years due to good medical neonatal care (6). If we look at the medical data of births in Lithuania 2014, The official statistical total data number of deliveries in Lithuania were 27872 in 2014, by 779 deliveries (2.8%) more than in 2013 (38). Antenatal steroids were administered in 57.5% of preterm deliveries until 34th week of gestation and caesarean section was performed in 22% of all births in 2014; 36.6% of them were elective and 63.4% were emergency caesareans (38). Preterm neonatal mortality was 25.0 per 1000 live births, compared to 20.8 /1000 in 2011. Congenital malformations, congenital infection, respiratory distress syndrome and hypoxia fetus were the leading causes of death in both early and total mortality structures (38). Respiratory distress syndrome was diagnosed in 18.6% of premature newborns. 5.4% of all newborns in Lithuania in 2014 were born prematurely (38).

1.2 Morbidity among late preterm newborns

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This study shows late preterm infants are 4 times more likely than term infants to have at least one medical condition diagnosed and 3.5 times more likely to have 2 or more conditions diagnosed. Temperature instability, hypoglycemia, respiratory distress, apnea, jaundice and feeding difficulties are the common diagnosis during the birth hospitalization of late- preterm infants (16). In addition, studies show late preterm infants with short NICU stays have a higher risk of hospital re-admission after the birth hospitalization compared with all other NICU survivors (16).

Furthermore, there were studies performed where it was found that preterm born at 33rd to 36th week of gestation had a greater likelihood for hospital readmission if they stayed less than 4 days after birth in hospital and reasons for readmission were suspected sepsis (20%), jaundice (70%) and feeding difficulties (16%) (16,17). Some of the the other more common causes and readmission reasons are hyperbilirubinemia, dehydration and feeding difficulties (17). A study about prevalence and morbidity of late preterm infants in Northern Taiwan showed admission rate in NICU (including a special care nursery) was higher in late preterm infants when compared to term (36% vs.2%). It was 74%, 43% and 21% in infants born at 34th, 35th and 36th weeks of gestation. Late preterm infants had a longer hospital stay if admitted to NICU compared to the term infants (17 days vs. 10 days). They were also associated with increased risk of neonatal morbidities including RDS (18% vs. 2.02%), hypoglycemia 3% vs. 0.4%, feeding difficulty (2% vs. 0.4%) and hyperbilirubinemia needing phototherapy (14% vs. 3%) (7). The study from Pakistan about “Short-term neonatal outcome in late preterm vs. term

infants” showed that out of 10.6% were late preterm infants, among the main morbidities, RDS was at

16.5%, Hyperbilirubinemia requiring phototherapy was 37.9%, sepsis was 4.9%, growth retardation at 24.8% and NICU admission was at 18.8% (14). Another study about “Clinical outcomes of near-term

infants” says that sepsis was more frequently present in preterm infants at 36.7%, than full- term

infants (18). In study about “Neonatal morbidity in singleton late preterm infants compared with full-

term infants” it describes how late preterm infants had significant higher morbidity compared with full

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In the same way study about “Neonatal outcome of the late preterm infant (34 to 36 weeks): The

Singapore story” states that out of 12,459 deliveries, 1221 (10%) were late preterm deliveries. The

neonatal morbidity for 34th weeks vs 35th to 36th weeks for hypoglycemia was 26% vs 16%, feeding difficulties 30% vs 9%, RDS 4% vs 1%, neonatal jaundice 63% vs 24% and the length of stay 14 ± 22 days vs 4 ± 4.7 days (37).

1.3 Late preterm newborn and jaundice

“Born too soon”, the global action report on preterm birth writes, jaundice is more common

in premature newborns, because they have an immature liver and cannot easily metabolize bilirubin. If jaundiced develops, the preterm baby’s brain is at a higher risk since their blood-brain barrier is less well developed to protect the brain. However, jaundice appears twice as more in late preterm infants than term infants and have bilirubin levels increased the first five days of age (20,2). Also according to the “Iranian Journal of Neonatology” factors like mode of delivery, oxcytocin induction and neonates gender (more females than males) can be factors developing jaundice in neonates (40).

1.4 Late preterm newborn and hypoglycemia

The risk of hypoglycemia is reported to be 3 times higher in late preterm infants than in term infants and it can occur in newborn infants of all gestational ages. This is because of the insufficient metabolic response due to the sudden loss of maternal glucose supply after birth. The incidence of hypoglycemia increases with decreasing gestational age (21,22).

Newborns who are at risk of neonatal hypoglycemia (NH) is infants who are SGA, in LGA, in infants who are born to mothers who have diabetes, and in late preterm infants (23,24).

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1.5 Late preterm newborn and infection

Late preterm newborns are at an increased risk than term newborns of infections because of their immature immune system. Neonatal sepsis is more common in infants born with very low gestational age or infants with very low birth weight (12).

In preterm infants many risk factors are associated with an increased risk of sepsis. Risk factors like premature rupture of membranes (PROM), prolonged PROM´s, maternal peripartum infections, chorioamminititis, cesarean section or instrumental delivery and Apgar scores, less than 7 at 5 minutes are the most common once (11).

Therefore, severe infections are more common in late preterm, and premature babies are at a higher risk of dying once they get an infection. The majority of babies who die from neonatal sepsis are preterm (2). The incidence of sepsis in the neonatal period is greater than any other period of life. Studies show that between 1-5 cases per 1000 live births are in developing countries and 49-170 cases per 1000 live births in developing countries.

Study about ”Early and Late Onset Sepsis in Late Preterm Infants” shows that late preterm infants are more often diagnosed with sepsis and they have increased mortality due to sepsis and increased risk for morbidities (12).

1.6 Late preterm newborn and hemorrhages

Intraventricular Hemorrhage (IVH) occurs more often in premature newborns. Newborns who are born more than 10 weeks early have an increased risk of IVH (26).

Bleeding can be due to immature blood vessels easily rupturing in premature babies and its happens in the first four days of life in a premature newborn (27). Premature babies with respiratory distress syndrome and babies with unstable blood pressure are more likely to develop IVH compared to full term newborns (26). Other risk factors include vaginal delivery, low Apgar score, pneumothorax, hypoxia, hypercapnia, seizures, patent ductus arteriosus (PDA), thrombocytopenia, infection predispose to the development of IVH (28).

According to study about “Maternal Intrauterine Infection, Cytokines, and Brain Damage in the

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Other studies explain that approximately 12,00 premature infants develop IVH every year in United states. IVH in very low birth weight infants has declined from 40-50% in the early 1980s to 20% in the late 1980s. However, in the last two decades the occurrence of IVH has not changed. In the extremely premature infants, 500-750g, IVH occurs in about 45% of neonates (28). Mortality rate in premature infants with severe IVH is higher compared with infants without IVH (28).

1.7 Late preterm newborn and respiratory morbidity

The incidence of and risk for respiratory morbidity, including Respiratory distress syndrome (RDS), transient tachypnea of the newborn, pneumonia, respiratory failure, and the need for ventilator support, are greater in late preterm infants compared with term infants (15). RDS develops due to lung immaturity and lack of surfactant in the alveoli, which results in collapsing lungs that take extra pressure to inflate. Below 32nd weeks of gestation, the majority of babies develop RDS, although this risk can be reduced by antenatal corticosteroids injections to women at risk or preterm labor, or in preterm labor (2). Data from Wang et al studied shows that’s neonates born at 35th to 36th weeks of gestation have statistically higher proportion RDS and clinical problems compared to term neonates. Another study, Rubaltelli et aldocumented 30.8% incidence of respiratory problems in 34th to 36th week neonates compared to less than 1% at term, but also noted in another survey an incidence of respiratory problems of only 3% in late preterm neonates (30). Factors that influence neonatal respiratory outcomes can be a result of the mother’s medical condition, also the labour and type of delivery and birth weight (31). One study also claimed that caesarean delivery gives high rates for RDS in late preterm infants (36). Preterm newborns born at 34th week of gestation have 40% increased risk to develop RDS, and this risk decreases with each week of gestation till 38 weeks of gestation (31).

1.8 Late preterm newborn and weight changes and feeding issues

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Late preterm newborns weight is less than one third of a full term newborn; consequently, there is a difference between body composition and brain weight among term and preterm newborns. In late preterm newborns, feeding difficulty is the main problem because of weak and immature sucking and swallowing reflex and decreased thermoregulation (33).

Late preterm newborns are weak and fatigue and therefore can not completely empty the breast because of sleepiness and difficulty in latch (34,32).

This will cause weight loss, malnutrition and dehydration and weight loss should not exceed more than 10% of the body weight. Also delayed discharge and readmission due to feeding difficulties in preterm newborns is very common (33). Studies states that breastfeeding can effectively be done in preterm newborns, but mothers from low social class, multiple birth, smokers, and very preterm infants with low weight need extra care and help in breastfeeding (43,44). Also high practical hospital support increases the probability of breastfeeding (46).

Infants born between 34th and 35th weeks of gestation may need formula, rich in protein and minerals to increase growth. Rehydration and adequate breastfeeding are important contributors to reducing the hyperbilirubinemia in late preterm newborns in addition to phototherapy (33).

There is very little data about feeding problems and its impact in late preterm newborns. Feeding difficulties can be related to maternal and neonatal reasons. Therefore, these difficulties cause increased needs for parenteral nutrition, infusion therapy and tube feeding leading to prolonged length of stay (36, 32).

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However, study done in Massachusetts writes that preterm infants didn’t receive breast milk enough compare to term infants. Furthermore, they write that mothers who are born outside the United States breastfed more than US-born mothers either to preterm or to term infants (47).

If we summarize, late preterm infants born in gestational age 34th_{, 35}th_{and 36}th_{week of gestation have}

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2. RESEARCH METHODOLOGY AND METHODS

This was a retrospective cohort study of all late preterm live births (340/7 to 366/7 weeks of gestation) during the 1-year period between January 2015 and December 2015 in LUHS Department of Neonatology. Patients were identified, and the relevant clinical information was collected from medical records. Demographic features of the newborn included gestational age, mode of delivery, sex, birth weight (in grams obtained after delivery within 2 hours after birth), and Apgar scores at 1 and 5 minutes after birth. Late preterm newborns were divided in 3 sub-groups according to gestational age: 340/6, 350/6, 360/6 weeks of gestation. The incidence of major clinical complications was evaluated: jaundice, hypoglycemia, confirmed sepsis or probable sepsis, hemorrhages, respiratory distress syndrome. The weight’s change and pattern of feeding at discharge time were evaluated as well. It was also assessed if late preterm newborns have higher admission rate to Neonatology intensive care unit (NICU).

2.1 Statistical analysis

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3. RESULTS

3.1 Main characteristics of newborns participated in the study

A total of 3450 newborns were born in 2015 in Hospital of LUHS. 281 of them were late preterm newborns (8.14%). In our study the data was collected for 269 late preterm newborns (95.7%). 72 infants (26.8%) was born 34th week of gestation (WG), 79 infants (29.4%) was born 35th WG and 118 infants (43.9%) was born in 36th_{WG. There were no statistically significant differences of gender}

distribution among groups. (Table 3.1.1).

There was a statistically significant association between gestational age and birth weight (p<0,001) (Table 3.1.2). Newborns born 34th_{week gestational age (GA) weighed significantly less than 35}th_and

36th weeks GA and newborns 35th GA weighed less than 36th GA.

3.1.2 Characteristics of birth weight of gestational age

Evaluation by Apgar score after 1 minute didn`t show any differences between groups, but after 5 minutes significantly lowest points were in the group of 34th GA (Table 3.1.3).

Table 3.1.1 Characteristics of Gender and Gestational age

Gestational age

p=0.219 34 weeks 35 weeks 36 weeks

Gender

male

Count 36a 50a 63a

% within Gestational age 50,0% 63,3% 53,4% female

Count 36a 29a 55a

% within Gestational age 50,0% 36,7% 46,6%

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36 weeks 8.3 (1.02) 9.0 0.79) 0.149 0.009 35-36: 5min 0.114

158 (58.7%) of late preterm newborns were born by vaginal delivery and 111 (41.3%) by cesarean section. There is no statistically significantly difference between mode of delivery and gestational age groups. (Table 3.1.4).

Table 3.1.4 Mode of delivery and Gestational age groups

Gestational age

p=0.073 34 weeks 35 weeks 36 weeks

Mode of delivery

VG Count % within Gestational age 63,9% 46a 3848,1% a 7462,7% a

C/S Count % within Gestational age 36,1% 26a 4151,9% a 4437,3% a

There was statistically significance difference between mode of delivery and admission to NICU (Table 3.1.5). Newborns of 36th_{GA after cesarean section significantly more often were admitted to}

NICU compare with newborns after the vaginal delivery.

Table 3.1.5 Admission to NICU, Mode of delivery and Gestational age

3.2 The rates of major morbidities

Jaundice and respiratory morbidity occurred significantly more often in the newborn’s group

Gestational age Mode of delivery Total p VG C/S 34 weeks NICU Count 21a 12a 33 0.580 % within Mode of delivery 45,7% 46,2% 45,8%

35 weeks NICU Count % within Mode of delivery 718,4% a 614,6% a 13 16,5% 0.440

36 weeks NICU

Count 3a 11b 14

0.001

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Table 3.2.1 Morbidities and Gestational age

Newborns after vaginal delivery significantly more often had jaundice than newborns after cesarean section (Table 3.2.2.). Mode of delivery didn’t influence other morbidities.

Table 3.2.2. Morbidities and Mode of delivery

Morbidity Mode of delivery

VG (n=158) C/S (n=111)

Jaundice Count 103a 40b

% within Mode of delivery 65,2% 36,0% p=0.001

Intraventricular hemorrhages

Count 23a 12a

% within Mode of delivery 14,6% 10,8% p=0.369

Hypoglycemia Count 6a 11b

% within Mode of delivery 3,8% 9,9% p=0.43

Respiratory morbidity Count 15a 14a Morbidity Gestational age 34 weeks (n=72) 35 weeks (n=79) 36 weeks (n=118) Jaundice Count 50a 41a, b 52b

% within Gestational age 69,4% 51,9% 44,1%

p=0.003

Intraventricular hemorrhage

Count 11a 11a 13a

% within Gestational age 15,3% 13,9% 11,0% p=0.670

Hypoglycemia Count 8a 4a 5a

% within Gestational age 11,1% 5,1% 4,2% p=0.145

Respiratory morbidity Count 19a 6b 4b

% within Gestational age 26,4% 7,6% 3,4%

p=0.001

Confirmed/probable sepsis Count 4a 1_a 4_a

% within Gestational age 5,6% _1,3% _3,4%

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We compared morbidities, mode of delivery and gestational age and found that only newborns of 34th GA and 35th GA after vaginal delivery significantly more often had jaundice then newborns delivered by cesarean section (Table 3.2.3).

Table 3.2.3. Morbidities, Mode of delivery and Gestational age

3.3 The weight changes during first 5 days of life

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Table 3.3.1 Weight loss during the first 5 days of life compared with gestational ages

3.4 The pattern of feeding at a discharge time

Weight loss 34th week (n=72)

weight loss1 weight loss 2 weight loss 3 weight loss 4 weight loss 5 Mean 3,8 5,5 5,8 5,6 5,0 Std. Deviation 3,41 3,12 3,48 3,99 4,40 Minimum -2,4 -3,3 -6,1 -6,9 -8,4 Maximum 16,5 14,5 17,8 17,9 17,0 Percentiles 25 1,066 3,374 3,969 3,554 3,183 50 3,485 5,387 5,767 5,388 4,894 75 5,902 6,986 7,639 7,852 6,927

weight loss1 weight loss2 weight loss3 weight loss4 weight loss5 Mean 2,9 3,8 4,4 4,5 4,0 Std. Deviation 2,92 3,76 3,51 3,95 4,47 Minimum -9,9 -12,8 -11,5 -11,7 -15,4 Maximum 10,2 10,0 9,5 12,3 10,0 Percentiles 25 1,211 2,509 3,226 3,203 2,218 50 2,316 4,194 5,051 5,469 5,107 75 4,637 6,024 6,247 6,806 6,886

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Mode of delivery significantly influenced feeding at discharged. Newborns after vaginal delivery were significantly more often breastfed than newborns delivered by cesarean section (Table 3.4.2).

Table 3.4.2 Feeding at discharge and mode of delivery

Mode of delivery p=0.001 VG C/S Fe ed in g at d is ch ar ge breastfeeding Count 112a 58b

% within Mode of delivery 70,9% 52,3%

bottle+mother's milk

Count 31a 28a

% within Mode of delivery

19,6% 25,2%

formula

Count 6a 14b

% within Mode of delivery _3,8% _12,6%

formula+mother's milk

Count 9a 11a

% within Mode of delivery

5,7% 9,9%

Admission to NICU had significant influence on feeding type before newborn’s discharge at home. Breastfeeding rate was significantly higher in the group of newborns not admitted to NICU. Infants who were admitted to NICU were significantly more fed by formula. (Table 3.4.3).

Table 3.4.1 Feeding at discharge in gestational ages

Gestational age

p=0.001

34 weeks 35 weeks 36 weeks

Fe ed in g at d is ch ar ge breastfeeding Count 33a 52b 85b % within Gestational age 45,8% 65,8% 72,0%

bottle+mother's milk Count 27a 15b 17b

% within Gestational age 37,5% 19,0% 14,4% formula Count 10a 4a 6a

% within Gestational age 13,9% 5,1% 5,1% formula+mother's

milk

Count 2a 8a 10a

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Table 3.4.3 Feeding at discharge and admission to NICU NICU Total yes no Fe ed in g at d is ch ar

ge breastfeeding Count _{% within NICU} 21_35,0%a 149_71,3%b 170 _63,2% bottle+mother's milk Count _{% within NICU} 27_45,0%a 32_15,3%b 59 _21,9% formula Count 11a 9b 20

% within NICU 18,3% 4,3% 7,4% formula+mother's milk Count 1a 19a 20

% within NICU 1,7% 9,1% 7,4%

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DISCUSSION OF THE RESULTS

The growing interest about late preterm newborns in the medical literature encourage me to evaluate outcomes of late preterm infants in the Hospital of LUHS. During 2015 in this hospital total number of newborns was 3450, among them 281 (8.14%) were born late preterm 34th, 35th and 36th weeks of gestation (WG). In our study the data was collected for 269 (95.7%) late preterm newborns. If we compare the total number of late preterm newborns with other countries in the world, for example in Pakistan there was born 326 late preterm newborns (14), in Northern Taiwan during a 2 year periods it was born 1491 late preterm newborns (7) and in United States total registered birth was 3932,181, where 11.39% was total preterm newborns and 7.99% late preterm newborns (13). As we can see that numbers of late preterm newborn are higher in other countries compare to hospital of LUHS and Lithuania is seeing to be number 8 among European countries having the lowest birth rate (1). Also if look at the medical data of births in Lithuania in 2014, the total data number od deliveries were 27872 and among them 5.4% of newborns were born prematurely (38).

There was a statistically difference between the gestational ages and the birth weight in late preterm newborns. Late preterm newborns born 34th_{week GA weighted less than late preterm newborns born}

35th and 36th (p=<0.001). The same was for late preterm newborns born week 35th GA weighted less than late preterm newborns born in week 36th GA (p=0.001). Gestational age is important for the newborn to develop and explains about there size and weight. As long the infant stay inside the womb it will grow and get bigger. Late preterm born as early will have less weight compare to the other late preterm gestational ages (32,33,15).

Apgar score defines how well the breathing process is in the infant and how the infant its doing outside mother’s womb (39). From our result, Apgar score after 5 minutes was lowest in 34th GA. Late preterm newborns born this early will have difficulties to breath because their lungs are not fully matured and will have adjusting problems to environment because of being born early (2,7).

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Newborns of 36th GA after cesarean section were more often admitted to NICU compare with newborns after vaginal delivery (p=<0.001). Previous studies have shown that after caesarean delivery there is an increase risk for late preterm admission to NICU because these infants have respiratory problems (7,14,36). Also study from Northern Taiwan and Pakistan found that late preterm newborns had higher rate of admission to NICU and had increased risk of RDS (7,14).

We compared morbidities among gestational ages 34th_,35th_{, and 36}th_{and it showed that jaundice and}

respiratory morbidity occurred more often in late preterm infants born in 34th week GA (p=<0.001) comparing to newborns born at 35th and 36th week GA. If we compare this results to the literature many studies claimed that respiratory and jaundice morbidity has high rates to develop among the late preterm infants (7,14,19,36,37) and that respiratory problems have higher incidence in week 34th GA (30,31). Other neonatal morbidities in the form of intraventricular hemorrhage (34 vs 35 vs 36: 15.3% vs 13.9% vs 11.0%) hypoglycemia (11.1% vs 5.1% vs 4.2%) and confirmed/probable sepsis (5.6% vs 1.3% vs 3.4%) were not significantly different between the 3 groups.

Also late preterm infants after vaginal delivery had more often jaundice than newborns after caesarean section. Mode of delivery didn’t influence other morbidities. Further more, we compared morbidities, mode of delivery and gestational age where we found out that only newborns born in 34th GA and 35th GA after vaginal delivery significantly had higher incidence of jaundice then the newborns delivered by cesarean section. Also, the “Iranian Journal of Neonatology” found that vaginal delivery had influence on developing jaundice (40).

We evaluated weight changes during first 5 days of life and compared among the gestational groups, it was found that it was significantly higher weight loss by percentile in the group from 34th week of newborns. Comparing the weight loss from birth by percentiles, it was determined that significantly highest weight loss was on 2nd day in the group of newborn of 34th GA comparing with the group 35th and 36th_{GA. Late preterm newborns are at higher risk of requiring nutrition support and specially is}

they are small for gestational age or born 34th_{weeks of gestation. This is because of feeding difficulty}

(28)

We compared the pattern of feeding at a discharge time and to compare among gestational ages. Among late preterm infants 170 (63.2%) were breastfed, 59 (21.9%) of them were fed by bottle and mothers milk, 20 (7.4%) late preterm infants were fed by formula and 20 (7.4%) late preterm infants were given formula and mothers milk. Breastfeeding rate at discharge was significantly higher in the group of 36th_{GA. Late preterm newborns born in group 36}th_{GA have better sucking and swallowing}

reflex, and have better latch compare to the other two groups, 34th_{and 35}th_{GA late preterm newborns}

(32,33,34). Study have shown that Also high practical hospital support increases the probability of breastfeeding (46), which is one of the things neonatology department in LUHS is working on. Also according to study and the results we found infants born between 34th and 35th weeks of gestation may need formula (33).

We checked if mode of delivery had any influence on feeding at discharge. Mode of delivery were significantly influenced on feeding at discharge. Newborn who were after vaginal delivery were significantly more often breastfed than newborns delivered by cesarean section. comparing the results with studies done, it shows that mothers with vaginal delivery have better bonding between mother-child and also starting early breastfeeding postpartum increases breastfeeding rates (2, 48). Late preterm newborns born by cesarean section was more often admitted to NICU compare with newborns after vaginal delivery and therefor it can be difficult with breastfeeding and mother-child bonding, which is better achieved in late preterm newborns born with vaginal delivery.

(29)

CONCLUSIONS

1. Respiratory morbidity and jaundice was significantly associated with lower gestational age and mode of delivery. Newborns of 34th GA had significantly higher risk of developing respiratory morbidity and jaundice. Newborns of 34th – 36th GA and delivered by natural way had significantly higher risk of developing jaundice.

2. Newborns of 34th GA had significantly higher weight loss on the 2nd day of life compare with newborns of 35th-36th GA.

(30)

LITERATURE LIST

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7. Tsai ML e. Prevalence and morbidity of late preterm infants: current status in a medical center of Northern Taiwan. - PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov. 2016 [cited 13 December 2015]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22770105

8. Preterm Birth | Maternal and Infant Health | Reproductive Health | CDC [Internet]. Cdc.gov.

2016 [cited 14 December 2015]. Available from:

http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm

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10. [Internet]. Apps.who.int. 2016 [cited 7 January 2016]. Available from: http://apps.who.int/iris/bitstream/10665/44864/1/9789241503433_eng.pdf?ua=1

(31)

14. Haroon A e. Short-term neonatal outcome in late preterm vs. term infants. - PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov. 2016 [cited 12 January 2016]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24411540

15. Late preterm infants [Internet]. Uptodate.com. 2016 [cited 11 January 2016]. Available from:

http://www.uptodate.com/contents/late-preterm-infants?source=machineLearning&search=morbidity+preterm&selectedTitle=2~150&sectionR ank=1&anchor=H8#H8

16. Engle W, Tomashek K, Wallman C. "Late-Preterm" Infants: A Population at Risk. PEDIATRICS [Internet]. 2007 [cited 10 January 2016];120(6):1390-1401. Available from: http://pediatrics.aappublications.org/content/120/6/1390#abstract-1

17. GJ E. The neonatal "sepsis work-up": personal reflections on the development of an evidence-based approach toward newborn infections in a managed care or... - PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov. 2016 [cited 14 January 2016]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9917478

18. Wang M, Dorer D, Fleming M, Catlin E. Clinical Outcomes of Near-Term Infants. PEDIATRICS [Internet]. 2004 [cited 7 January 2016];114(2):372-376. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15286219

19. Leone A, Ersfeld P, Adams M, Meyer Schiffer P, Bucher H, Arlettaz R. Neonatal morbidity in singleton late preterm infants compared with full-term infants. Acta Paediatrica [Internet]. 2011

[cited 7 January 2016];101(1):e6-e10. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/21895764

22. Evidence-based Care Management of the Late Preterm Infant [Internet]. Medscape. 2016 [cited 16 January 2016]. Available from: http://www.medscape.com/viewarticle/734234_12)

(32)

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27. Intraventricular Hemorrhage [Internet]. Stanfordchildrens.org. 2016 [cited 14 January 2016]. Available from: http://www.stanfordchildrens.org/en/topic/default?id=intraventricular-hemorrhage-90-P02608

28. Ballabh P. Intraventricular Hemorrhage in Premature Infants: Mechanism of Disease. Pediatr Res [Internet]. 2010 [cited 26 January 2016];67(1):1-8. Available from: http://www.nature.com/pr/journal/v67/n1/full/pr20101a.html#CONCLUSION

29. Dammann OLeviton A. Maternal Intrauterine Infection, Cytokines, and Brain Damage in the Preterm Newborn. Pediatr Res [Internet]. 1997 [cited 19 March 2016];42(1):1-8. Available from: http://www.nature.com/pr/journal/v42/n1/full/pr19972261a.html#close

30. Respiratory Morbidity in Late Preterm Births. JAMA [Internet]. 2010 [cited 20 February 2016];304(4):419. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146396/ 31. Respiratory Morbidity in Late Preterm Births. JAMA [Internet]. 2010 [cited 12 February

2016];304(4):419. Available from:

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32. Giannì M, Roggero P, Piemontese P, Liotto N, Orsi A, Amato O et al. Is nutritional support needed in late preterm infants?. BMC Pediatrics [Internet]. 2015 [cited 8 December 2015];15(1). Available from: http://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-015-0511-8#CR5

33. Whyte R. Safe discharge of the late preterm infant. Paediatrics & Child Health [Internet]. 2010

[cited 14 February 2016];15(10):655. Available from:

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34. Breastfeeding the preterm infant [Internet]. Uptodate.com. 2016 [cited 10 January 2016]. Available from: http://www.uptodate.com/contents/breastfeeding-the-preterm-infant?source=machineLearning&search=feeding+in+late+preterms+infants&selectedTitle=2~ 150&sectionRank=3&anchor=H16#H16

(33)

39. Updated by: Neil K. Kaneshiro a. Apgar score: MedlinePlus Medical Encyclopedia [Internet].

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https://www.nlm.nih.gov/medlineplus/ency/article/003402.htm

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and Maternal and Neonatal Factors 2016; 7 (1):1

http://ijn.mums.ac.ir/article_6663_9bb7af7d47aa91a1b565c95c961afe37.pdf

41. Shapiro-Mendoza C, Tomashek K, Kotelchuck M, Barfield W, Nannini A, Weiss J et al. Effect of Late-Preterm Birth and Maternal Medical Conditions on Newborn Morbidity Risk. PEDIATRICS. 2008;121(2):e223-e232.

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Sidra Malik Outcomes of late preterm newborn

LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

FACULTY OF MEDICINE

Sidra Malik

Outcomes of late preterm newborn

A thesis submitted in part fulfillment for the

degree of Master of Medicine

TABLE OF CONTENTS

SUMMARY

ACKNOWLEDGEMENTS

CONFLICT OF INTEREST

ETHICS COMMITTEE CLEARANCE

ABBREVIATIONS LIST

INTRODUCTION

AIM AND OBJECTIVES

1. LITERATURE REVIEW

2. RESEARCH METHODOLOGY AND METHODS

3. RESULTS

DISCUSSION OF THE RESULTS

CONCLUSIONS

LITERATURE LIST