4. CONFLICT OF INTEREST

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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES FACULTY OF MEDICINE

Department of Neonatology

Title of Master’s Thesis:

MORTALITY OF FULL-TERM INFANTS IN KAUNAS PERINATAL CENTER 2001-2016

A Dissertation Submitted in Partial Fulfillment of the Requirements

for the Degree Master of Medicine Lithuanian University of Health Sciences

Author:

Marine Brochard Supervisor:

Dr Dalia Stoniene Kaunas 2019-2020

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1.SUMMARY

Author name: Marine Brochard

Research Title: Mortality of full-term infants in Kaunas Perinatal Center 2001-2016

Aim: To analyze the term newborns neonatal mortality in Kaunas Perinatal Center 2001-2016

Objectives:

1. Analyze the term newborns neonatal mortality rate in Kaunas Perinatal Center 2001-2016.

2. Analyze early mortality rates of terms infants in Kaunas Perinatal Center 2001-2016.

3. Analyze the main pathology of early neonatal deaths of term infants in Kaunas Perinatal Center 2001-2016.

Methodology: It is a retrospective cohort research carried out with the Lithuanian Medical Data of Birth from Health Information Centre of Institute of Hygiene. The study analyzed term newborns neonatal mortality rates, early mortality rates of terms infants, and main pathology of early neonatal deaths of term infants in Kaunas Perinatal Center between 2001-2016. The collected data were processed by MS Office Excel 2013.

Research Participants: All newborns and term newborns that died during the early neonatal and neonatal period in Kaunas Perinatal Center in 2001-2016.

Result: 1. Term newborn neonatal mortality rate declined from 2001 to 2003 (from 1,5% to 1,3%). In 2004 the term newborn neonatal mortality rate was significantly higher (from 1,5%

in 2001 to 1,9% in 2004) with a total number of 33 neonatal deaths. We observed a decrease in neonatal mortality rate after 2004 even if in 2006 we noticed an augmentation compare to 2005 (2005: 1,3% and in 2006: 1,6%). After 2006 neonatal mortality rates decrease till the lowest rates in 2011 and 2012 (from 1,9% in 2004 to 0,5% in 2011 and 0,5% in 2012) with a total number of 8 neonatal deaths in both 2011 and 2012.

2. We analyzed early mortality rates of terms infants whose highest rate was in 2004 (from 0,9% in 2001 to 1,3% in 2004) with a total number of 23 early neonatal deaths. The lowest

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neonatal deaths. But we can observe that the early mortality rate will increase after 2012 till 2016 (0,6% in 2013, 0,7% in 2014, 0,6% in 2015 and 0,7% in 2016)

3. The main pathology responsible for early neonatal deaths of term infants at this period was: Q00-Q99 (congenital malformations, deformations and chromosomal abnormalities).

Deaths of early neonatal term infants were higher in 2004 (with 1,3%), the most common pathology responsible for it was Q00-Q99 (0,9% with a number of 16 deaths). The second most common pathology was P20 (intrauterine hypoxia) and P21(birth asphyxia).

Conclusion:

1. The highest term newborn neonatal mortality rate was in 2004 ( 1,9%). The lowest term newborn neonatal mortality rates were in 2011 and 2012 with 0,5%.

2. The highest early mortality rates of term infants happened in 2004 (1,3%). A significant decrease in early mortality rates of term infants was noticed in 2012 (0,3%). After 2012 we could observe the mortality rate increased to 0,7%.

3. The main pathologies that caused the highest early neonatal deaths were congenital malformations, deformations and chromosomal abnormalities with 0,9% in 2004.

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2. ETHICS COMMITTEE APPROVAL

The final master‘s thesis was completed after obtaining the permit of the Bioethics Center of the Lithuanian University of Health Sciences No. BEC-MF-113. The permit was issued in 2019 , November 26th.

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3. ACKNOWLEDGEMENTS

I would like first to thanks my supervisor Dr. Dalia Stoniene for her guidance, patience and help throughout this final master thesis. She has been of immense help in the time of need to be able to reach the aim of this work.

I dedicate this thesis to my parents. I would like to express my sincere gratitude and appreciation, for their help, support no matter how far I am. They gave me the opportunity to do what I want no matter how hard it was for them. To my parents, I will never finish thank you enough for everything you did and do every day for me.

To my sisters Gwladys and Samantha, and my brother Arthur, thank you for your support and love, I hope to make you proud.

I would like to thanks also my boyfriend for providing me with unfailing love and continuous encouragement throughout my years of study, the moment of crisis and through the process of researching and writing this thesis.

To all my friends, and especially my best friend Claire thank you for your

understanding and encouragement. Your friendship makes my life an enjoyable experience. I cannot list all the names here, but you are always on my mind.

4. CONFLICT OF INTEREST

The author reports no conflicts of interest.

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5. TERMS

ICD-10 Classification

Q00-Q99: congenital malformations, deformations and chromosomal abnormalities P07: disorders related to short gestation and low birth weight

P10: intracranial lacerations and hemorrhages P11: other births injuries to CNS

P20: intrauterine hypoxia P21: birth asphyxia

P22: respiratory distress of newborn P23: congenital pneumonia

P24: neonatal aspiration syndrome

P26: pulmonary hemorrhage originating in the perinatal period P28: other respiratory condition originating in the perinatal period P35: congenital viral diseases

P36: bacterial sepsis of newborn

P37: others congenital infectious and parasitic diseases P39.8: other specified infection specific to the perinatal period P39.9: infection specific to the perinatal period

P52: intracranial nontraumatic hemorrhage of newborns

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6. INTRODUCTION

Classification of a child's life into well-defined periods has become important to determine the care and interventions necessary to decrease the chances of child deaths.

Gestational age is typically discussed in terms of the number of completed weeks. The concept of "term" provides guidance to clinicians and influences the public's perceptions about the optimal timing of delivery for a healthy pregnancy. Preterm is defined as delivery before 37 weeks following the onset of the last menstrual period and post-term as after 42 weeks, term pregnancy has been defined as delivery between 37 and 42 weeks.[1]The International Classification of Diseases defines term pregnancy as delivery between 37 weeks 0 days and 41 weeks 6 days. [2] But since 2012 the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) is

recommending to use sub-categories to categorize gestational age: early term(37 0/7 weeks of gestation through 38 6/7 weeks gestation); full term(39 0/7 weeks of gestation through 40 6/7 weeks of gestation); late-term(41 0/7 weeks of gestation through 41 6/7 weeks of

gestation); and post-term(42 0/7 weeks of gestation and beyond). [3]

The neonatal period is the period from the birth of the neonate until his 28^th days of life. In 2016, neonatal mortality accounted for 46% of all deaths of children under 5 years old. [4] Neonatal period is considered to be the most vulnerable time in a child's life.

According to the World Health Organization (WHO) neonatal death can be described as

"deaths among live births during the first 28 completed days of life".[5] Neonatal deaths can be sub-categorize into early neonatal deaths (deaths between 0 and 7 completed days of birth) and late neonatal deaths (deaths after 7 days to 28 completed days of birth).[6]In 2016, 5 millions of children aged under 5 years old died, deaths of the neonates were composing the biggest amount of it with 43%. But compared to 2006, neonatal deaths decreased by 28,9% from 2006 to 2016, from 3.04 million to 2.16 million.[7]

Reducing neonatal mortality is one of the most important goal of the health system, which is reflecting the level of health and medical services in the country.

In the literature one of the most common causes of full-term neonatal deaths is congenital malformation, deformations, chromosomal abnormalities. Other causes include intrauterine hypoxia, birth asphyxia and labor complication. There is some variation between countries depending on their care configurations, their economy and environmental factors. Our research will focus on neonatal mortality and the main pathology of neonatal deaths in

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Lithuania.

The aim of this study is to analyze the term newborns neonatal mortality in Kaunas Perinatal Center 2001-2016.

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7. AIM AND OBJECTIVES OF THE THESIS

Aim of the study:

To analyze term newborns neonatal mortality in Kaunas Perinatal Center 2001-2016.

The objectives:

1. Analyze term newborns neonatal mortality rate in Kaunas Perinatal Center 2001-2016.

2. Analyze an early mortality rate of term infants in Kaunas Perinatal Center 2001-2016.

3. Analyze the main pathology of early neonatal deaths of term infants in Kaunas Perinatal Center 2001-2016.

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8. LITERATURE REVIEW

8.1 Neonatal mortality in the neonatal period and early neonatal period

In order to increase the child’s survival, the categorization of the neonatal period in well- defined periods is important. It can help to determine which medical cares the child needs. The neonatal period is defined as the first 28 completed days of life. The highest period of fatal risk in the first year of life is the neonatal stage. Neonatal mortality is defined by the World Health Organization (WHO), as the number of neonates who die at 0-28 days (27 days 23 hours and 59 minutes) per 1,000 live births.

The neonatal mortality rate is a key indicator of health and care during pregnancy and birth. Children who die within the first 28 days of birth suffer from conditions and diseases associated with a lack of quality care at birth or skilled care and treatment immediately after birth and in the first days of life. [8] With the progress of treatments and diagnostics the neonatal mortality decreases worldwide. In 2001 the global mortality rate was 29,7/1000 compare to 2016 with 18,6 deaths per 1000 live births to 17,7/1000 live births in 2018. Some countries have achieved notable progress in reducing neonatal mortality.

Since 2001 Lithuania’s neonatal mortality rate has decreased from 4,4 deaths per 1000 live births to 2,3/1000 live births in 2016 and 2,1/1000 live births in 2018. [9] Lithuania decrease his neonatal mortality rate of 2,1% from 2001 to 2016. Which means according to UNICEF data that in 2001 worldwide there were 3.9 million neonatal deaths, in 2016 2.6 million and in 2018 2.5 million neonatal deaths. [10] In Lithuania in 2001 neonatal deaths numbers were 140, in 2016 68 and in 2018 60. [9] Five more countries have decrease in half their neonatal mortality rates between 2000 and 2010 (Turkey, Oman, Greece, Belarus and Estonia). [11] This shows the decline of global neonatal mortality.

In some other countries neonatal mortality decrease but slower, like in France, the neonatal mortality rate decreased from 2,9 deaths per 1000 live births in 2001 to 2,5/1000 live births in 2016.[12][13] This diminution in neonatal mortality may be due to the Millennium Development Goals, a plan of the United Nations in 2000 which goal was to reduce neonatal mortality by two thirds The mortality rate of children under the age of five between 2000 and 2015 by providing adequate childbirth care, timely assistance in the event of complications, vaccination, adequate nutrition of children and appropriate treatment of childhood

diseases.[14] A Nepal Demographic and Health Survey (NDHS) report revealed that over a 15-year period neonatal mortality decreased by 57%, from 91 deaths per 1000 live births in 2001 to 39 in 2016.[15]

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rate as Sub-Saharan Africa which had, on average, no significant change in neonatal mortality rate during the last decade.[16] .Further neonatal period can be subdivided into early neonatal death (0 to 7 days) and late neonatal death (7 to 28 days).[17]

Worldwide, in 2013, it was estimated that 6.3 million children died before their fifth birthday, and 44% of them died in their neonatal period. Moreover, 73% of all neonatal deaths

occurred within the early neonatal period with 36% occurring on the day of birth. [18]

8.2 Neonatal mortality in full-term newborns

The neonatal mortality rate is a key indicator of health and care during pregnancy and birth. The American College of Obstetricians and Gynecologists (also called ACOG) and the Society for Maternal-Fetal Medicine (SMFM) considered a full-term pregnancy as a

pregnancy that lasts between 39 weeks, 0 days and 40 weeks 6 days. [3] This means your pregnancy lasts between 1 week before your due date and 1 week after your due date.

Newborns full-term have the best chance of being healthy, compared with babies born earlier or later. Preterm is the leading cause of neonatal mortality worldwide. [19] [20].

Prolonged pregnancies increase newborns' mortality and morbidity due to the fact that they may be born during emergency cesarean section, aspirating meconium. Full-term neonatal mortality in 2001 in Lithuania was 1,7/1000 live births to 1,1/1000 live births in 2016. In Kaunas Perinatal Center (one of the biggest of Lithuania) full-term neonatal mortality rate in 2001 was 1,5/1000 live births to 0,9 per 1000 live births in 2016. [21] [22] A decrease of 0,6

% was observed in the full-term neonatal mortality.

8.3 Main Pathology of neonatal deaths

In the last years neonatal mortality decreases worldwide in 2016, worldwide, the leading causes of neonatal deaths were preterm birth complications, acute respiratory infections, intrapartum-related complications, congenital anomalies, and diarrhea, but each country may have diverse causes of neonatal deaths due to their different level of health system, medical cares provided, and their economy. Providing the necessary medical care to pregnant women, mothers or newborns in a timely manner can prevent as many as 2/3 of deaths due to congenital anomalies each year. [23]. In countries where the neonatal mortality rate is high and medical cares are more difficult to provide, infections (sepsis, pneumonia, meningitis tetanus, diarrhea ) are the main causes of neonatal deaths.

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9. RESEARCH METHODOLOGY AND METHODS

A retrospective cohort study was done with data of the Kaunas Perinatal Center, collected from the Lithuanian Medical Data of Births.

Research group: all newborns and terms newborns who die during the early neonatal and neonatal period in Kaunas Perinatal Center in 2001-2016.

First our data were analyzed and collected from the Lithuanian Medical Data of Births in the period 2001-2016, then we selected the categories of our research: early neonatal and neonatal mortality rates (table 13 of the register) show in table 1.

Table 1: Neonatal mortality rates 2001-2016 in Kaunas Perinatal Center Year Live

births

Early neonatal deaths

Early neonatal deaths per 1000 live births (in %)

Neonatal deaths

Neonatal deaths per 1000 live births (in %)

2001 19246 61 3,2% 88 4,6%

2002 18231 61 3,3% 80 4,4%

2003 18521 53 2,9% 72 3,9%

2004 18090 73 4,0% 97 5,4%

2005 17545 52 3,0% 73 4,2%

2006 17380 54 3,1% 66 3,8%

2007 17536 45 2,6% 60 3,4%

2008 18717 41 2,2% 62 3,3%

2009 19216 44 2,3% 60 3,1%

2010 17929 39 2,2% 57 3,2%

2011 16885 34 2,0% 46 2,7%

2012 16588 26 1,6% 37 2,2%

2013 15759 24 1,5% 31 2,0%

2014 15819 22 1,4% 36 2,3%

2015 16366 26 1,6% 37 2,3%

2016 16123 27 1,7% 37 2,3%

A newborn's neonatal period is defined as the period starting from his birth and

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period is said to be the most vulnerable period of the life of a child. According to the WHO (World Health Organization) neonatal mortality rates can be explained as the number of newborns who die at 0-28 days (27 days 23hours and 59 minutes) per 1000 live births.

Neonatal mortality can be categorized in early neonatal deaths which is when the newborns’

deaths occur between 0 and 7 days and late neonatal deaths when newborns’ deaths occur after 7 days to 28 completed days of birth. Our study will show the neonatal mortality rates in percentage which was also collected from the Lithuanian Medical Data of Births.

Next categories to analyze from the register were: the early neonatal and neonatal mortality rates of term newborns in the period of 2001-2016 in Kaunas Perinatal Center (term newborn neonatal mortality rates were collected from table 19 of the Lithuanian Medical Data of Births and the early mortality rates of term infants were processed from table 23 of the register) shown in table 2 and table 3.

Table 2: Neonatal mortality rates of term newborns

Year Total

numbers of live births

Terms newborns

Term neonatal deaths

Term neonatal mortality rates per 1000 live births (in

%)

2001 19246 18216 28 1,5 %

2002 18231 17235 25 1,5%

2003 18521 17525 22 1, 3%

2004 18090 17153 33 1,9%

2005 17545 16526 22 1,3%

2006 17380 16388 26 1,6%

2007 17536 16507 25 1,5%

2008 18717 17593 22 1,3%

2009 19216 18135 20 1,1%

2010 17929 16948 22 1,3%

2011 16885 15890 8 0,5%

2012 16588 15575 8 0,5%

2013 15759 14835 12 0,8%

2014 15819 15011 19 1,3%

2015 16366 15526 13 0,8%

2016 16123 15278 14 0,9%

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Table 3: Early neonatal mortality rates of term newborns

A pregnancy is considered as full-term by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine when deliveries occur in the period between 39 weeks to 40 weeks and 6 days. Between 37 weeks and 38 weeks, 6 days of gestation is considered "early term." Between 41 weeks 0 days and 41 weeks, six days is

"late-term"; and 42 weeks and beyond is considered "post-term."

Full-term newborns have the best chance of being healthy, compared with babies born earlier or later. Every week of pregnancy is important for the health of the newborn; In the last few weeks, the brain and lungs are still developing. Early term delivery is associated with increased short term adverse physical morbidity, including respiratory distress syndrome, transient tachypnoea of the neonate and ventilator use, as well as an increased risk of infant mortality at 37 weeks compared to full-term delivery.

Year Term newborns Term early neonatal deaths

Early neonatal mortality rates per 1000 live births (in %)

2001 18216 17 0,9%

2002 17235 18 1%

2003 17525 13 0,7%

2004 17153 23 1,3%

2005 16526 13 0,8%

2006 16388 20 1,2%

2007 16507 19 1,2%

2008 17593 12 0,7%

2009 18135 12 0,7%

2010 16948 12 0,7%

2011 15890 6 0,4%

2012 15575 4 0,3%

2013 14835 9 0,6%

2014 15011 10 0,7%

2015 15526 8 0,6%

2016 15278 10 0,7%

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The last task was to analyze and collect data about the main pathologies of the early neonatal deaths of term infants between 2001-2016; These data are collected from the Lithuanian Medical Data of Birth (table 19 from the Lithuanian register) show in the table 4.

Table 4: Main pathology of early neonatal deaths of term infants

Year Term early neonatal mortality rates per 1000 live births

Q00- Q99

P10 P11

P20 P21

P22, P26- 28

P24 P23, P35- 37

P39.8,9

P52 P07 Others

2001 0,9% 0,4% 0% 0,2% 0% 0,1% 0,1% 0% 0% 0,1%

2002 1% 0,8% 0% 0,2% 0% 0% 0% 0% 0% 0%

2003 0,8% 0,2% 0% 0,3% 0,1% 0,1% 0% 0% 0% 0,1%

2004 1,3% 0,9% 0% 0,2% 0% 0,1% 0% 0% 0% 0,1%

2005 0,8% 0,5% 0% 0,1% 0% 0% 0% 0% 0% 0,2%

2006 1,2% 1% 0% 0 ,1% 0% 0% 0% 0% 0% 0,1%

2007 1,2% 0,5% 0% 0,4% 0% 0% 0,2% 0% 0% 0,1%

2008 0,8% 0,4% 0% 0,2% 0% 0,1% 0% 0% 0% 0,1%

2009 0,7% 0,3% 0% 0,1% 0% 0% 0,1% 0% 0% 0,1%

2010 0,7% 0,4% 0% 0,1% 0% 0% 0,2% 0% 0% 0%

2011 0,4% 0,1% 0% 0,1% 0% 0% 0,1% 0% 0% 0,1%

2012 0,3% 0,1% 0% 0,1% 0% 0,1% 0% 0% 0% 0%

2013 0,6% 0,3% 0% 0,1% 0% 0% 0,1% 0% 0% 0,1%

2014 0,7% 0,4% 0% 0,1% 0% 0% 0,1% 0% 0% 0,1%

2015 0,6% 0,2% 0% 0,2% 0% 0,1% 0,1% 0% 0% 0%

2016 0,7% 0,1% 0% 0% 0,1% 0,1% 0,2% 0% 0% 0,1%

The main pathologies responsible for the early neonatal deaths of the term newborns processed from the Lithuanian Medical Data of Births are coded according to the

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International Classification of Diseases or ICD-10-AM classification. The codes concerning our study is listed below:

Q00-Q99: congenital malformations, deformations and chromosomal abnormalities P07: disorders related to short gestation and low birth weight

P10: intracranial lacerations and hemorrhages P11: other births injuries to CNS

P20: intrauterine hypoxia P21: birth asphyxia

P22: respiratory distress of newborn P23: congenital pneumonia

P24: neonatal aspiration syndrome

P26: pulmonary hemorrhage originating in the perinatal period P28: other respiratory condition originating in the perinatal period P35: congenital viral diseases

P36: bacterial sepsis of newborn

P37: others congenital infectious and parasitic diseases P39.8: other specified infection specific to the perinatal period P39.9: infection specific to the perinatal period

P52: intracranial nontraumatic hemorrhage of newborn

Communities and decision-makers need to be informed that neonatal deaths are quite numerous and need therefore to receive adequate attention. Accurate data on neonatal mortality causes are essential for many reasons. Such data are useful for primary caregivers, for investigators because they are leading interventions, for prophylaxis and treatment, for local and national health administrators, and for decision-makers who apply and assess health care programs.

Reducing neonatal mortality by improving the care and interventions during pregnancies is one of the most important aims of the health system which is reflecting the level of health and medical services in the country. By the establishment of more Perinatal Center, better care of mothers and newborns can be done.

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10. RESULTS

10.1 Neonatal mortality rates

According to the Lithuanian Medical data of Births, the neonatal mortality rates in the period between 2001-2016 in Kaunas Perinatal Center were the highest in 2004 with a mortality rate of 5,4 per 1000 live births and the lowest in 2013 with a neonatal mortality rate of 2 per 1000 live births. (Graph 1) During our analysis we noticed that from 2001 till 2003 the mortality rates decrease progressively with a range from 4,6 to 3,9 cases per 1000 live births but in 2004 the mortality increased sharply to 5,4 cases per 1000 live births. After 2004 the neonatal mortality rates decreased drastically with the lowest rates of 2/1000 per live births in 2013. Finally, from 2013 to 2014 the neonatal mortality rates increased from 2 to 2,3 and from 2014 to 2016 no noticeable changes have been observed

Graph 1: Neonatal mortality rates in Kaunas Perinatal Center in the period 2001-2016

0.00%

1.00%

2.00%

3.00%

4.00%

5.00%

6.00%

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

NEONATAL MORTALITY RATES

Early neonatal deaths per 1000 live births (in %) Neonatal deaths per 1000 live births (in %)

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During our analysis we noticed that from 2001 till 2003 the mortality rates decrease progressively with a range from 4,6 to 3,9 cases per 1000 live births but in 2004 the mortality increased sharply to 5,4 cases per 1000 live births. After 2004 the neonatal mortality rates decreased drastically with the lowest rates of 2/1000 per live births in 2013. Finally from 2013 to 2014, the neonatal mortality rates increased from 2 to 2,3 and from 2014 to 2016 no

noticeable changes have been observed.

10.2: Neonatal mortality rates of term infants

In this task, we analyzed the neonatal mortality rates of term newborns of Kaunas Perinatal Center between 2001 to 2016 which was more important in 2004 with 1,9 cases per 1000 live births. From 2001 to 2003 the deaths rates of term newborns decrease slowly from 1,5% to 1,3%. Two peaks appeared in 2004 (1,9 cases per 1000 live births) and 2006 (with a rate of 1,6 per 1000 live births) then the mortality rates decreased till the lowest rates in 2011 and 2012 with 0,5%. (Graph 2) After 2012 the mortality starts to increase again but without reaching the level of mortality rates of the year 2004.

Graph 2: Neonatal mortality rates of term infants in Kaunas Perinatal Center in the

0.00%

0.20%

0.40%

0.60%

0.80%

1.00%

1.20%

1.40%

1.60%

1.80%

2.00%

0 5 10 15 20 25 30 35

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Neonatal mortality rates of term newborns

Term neonatal deaths

NEONATAL MORTALITY RATE OF TERM NEWBORNS

Term neonatal deaths Term neonatal mortality rates per 1000 live births ( in %)

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According to our analysis and data from the Lithuanian Medical Data of Births, early neonatal deaths rates of terms infants in Kaunas Perinatal Center ranged between 0,3 to 1,3 cases per 1000 live births. The higher mortality rate was describe in 2004 with a percentage of 1,3 per 1000 live births and the lowest in 2012 with 0,3. As in our previous analyze the mortality from 2001 to 2003 (from 0,9% to 0,7%°) decreased progressively with a peak of newborns neonatal mortality in 2004. After 2004 the rates continue to decrease till the lowest one in 2012. However after 2012 the mortality rates of early neonatal newborns increase till 0,7 cases per 1000 live births in 2016. ( Graph 3)

Graph 3: Early neonatal mortality rates of term newborns in Kaunas Perinatal Center in the period 2001-2016

0.00%

0.20%

0.40%

0.60%

0.80%

1.00%

1.20%

1.40%

0 5 10 15 20 25

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Term early neonatal mortality rates

Term early neonatal deaths

EARLY NEONATAL MORTALITY RATES OF TERM NEWBORNS

Term early neonatal deaths Early neonatal mortality rates per 1000 live births (in %)

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10.3 Pathologies of early neonatal deaths of term infants

In the period of 2001-2016 in Kaunas Perinatal Center, the first pathology causing early neonatal deaths of term newborns was: congenital malformations, deformations, chromosomal abnormalities according to the Lithuanian Medical Data of Births, coded Q00- Q99 by the ICD-10. Previously we observed that 2004 registers the highest percentage of early neonatal mortality with 1,3 cases per 1000 live births and congenital malformation, deformations and chromosomal abnormalities caused by 0,9% of these cases. (Graph 4) The second most common cause of deaths according to our analysis is intrauterine hypoxia and birth asphyxia, coded P20 and P21. Their highest rate was in 2007 when they caused 0,4%

of the 1,2 deaths per 1000 live births.

Graph 4: Main pathologies of early neonatal deaths of term infants

0.00%

0.20%

0.40%

0.60%

0.80%

1.00%

1.20%

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Main pathology of early neonatal death of term infants

Q00-Q99 P10 P11 P20 P21 P22, P26-28 P24 P23,P35-37 P39.8,9 P52 P07 others

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11. DISCUSSION OF THE RESULTS

Neonatal mortality in full-term newborns

In our study, we analyzed the neonatal mortality rates in the early and neonatal period in the period 2001-2016 which will be compared to other studies from different authors.

According to the Office for National Statistics, England mortality rates ranged from 2,7 deaths per 1000 live births to 3,6 cases per 1000 live births. The highest rate was in 2001 with 3,6% and remains unchanged till 2004 where it starts to decrease till its lowest rates in 2013 with 2,7% and till 2016 remain unchanged. Comparing to our study we also observed that the period between 2001 and 2004 registers the highest rates of deaths of newborns and then from 2004 a progressively decrease of the neonatal mortality rates is noticed with lowest rates in 2013.

Euro-Peristat made a project to collect data from some countries of the European Union plus Norway between 2004 and 2010. They study the neonatal mortality changes in these different countries between 2004-2010 and observed a slow decrease in the rates as in the Czech Republic with 1,9 cases per 1000 live births in 2004 to 1,6 cases per 1000 live births in 2010, also in Denmark in 2004 the rate was at 3,0% and in 2010 it decreased to 1,5%. In Estonia the neonatal mortality rates decreased drastically from 3,9 in 2004 to 1,3 cases per 1000 live births as Latvia which decrease in total of 2,2% from 2004 to 2010. [24]

In comparison with our study of the Kaunas Perinatal Center neonatal mortality its neonatal mortality rate also decreases by 2,2 %.

In the US between 2000 and 2010 they did a report on neonatal mortality with the different gestational age, we focused on full-term neonatal mortality which means infants that were born at 39 weeks to 40 weeks and 6 days. In 2000 the mortality rates of full-term

newborns were 2,24 cases per 1000 live births then in 2006 the mortality rates were 2,05%

and finally in 2010 the full-term neonatal mortality rates decreased to 1,87 cases per 1000 live births. [25]

The data obtained in our study are in agreement with the data of the following studies, we noticed that since 2000 in many countries the neonatal mortality rates and neonatal mortality rates of full-term newborns had decrease progressively especially after 2004.

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Main causes of neonatal deaths

In our study we describe the main pathologies found in Kaunas Perinatal Center from 2001 to 2016 that caused the deaths of full-term newborns as congenital malformations, deformations and chromosomal abnormalities, intrauterine hypoxia, birth asphyxia, congenital pneumonia, congenital viral diseases or others infections.

In Canada a cohort study was done on infant mortality at term and the causes of it.

The most common pathologies of neonatal deaths are congenital anomalies, asphyxia, immaturity, infection, sudden infant death, and injury. [26]

In Israel, a tertiary care hospital did a study on full-term mortality of infants during the first month of life in the period from 2000 to 2005 and describe the causes of deaths of these full-term infants. The main cause of death was congenital anomalies (64,5%), other causes were chromosomal anomalies or syndromes with (12,9%), labor complications (12,9%), infections (3,2%), metabolic disorders (3,2%) and congenital diseases (3,2%). [27]

In Poland, a study was done on early neonatal deaths in the period 2007-2009, they describe the main causes of these neonatal deaths. The most of deaths cases were caused by malformations 30.8%, then disorders occurring during pregnancy 35.4% and in third place - respiratory disorders 13%. [28]

A cohort study of women of a region of South Denmark was done, they investigate the causes of early neonatal deaths from 2010 to 2014. They found that most deaths cases were unknown (62.1%). The second most common cause of death was congenital anomalies (10.5%), fetal, genetic, structural and karyotypic anomalies (11.6%). [29]

In the US in the period 2010-2012 a study was done on preterm and full-term neonatal specific causes of deaths, what they noticed is that sudden unexpected death in infancy and congenital malformations were the two most common causes of neonatal deaths full-term infants. [30]

We can conclude that we can’t compare the different causes of neonatal deaths among the different countries because each country had different major causes of neonatal deaths, but what we can notice is that congenital anomalies is a cause of death which is occurring quite often as the different studies showed.

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12. CONCLUSIONS

1. Neonatal mortality in Kaunas Perinatal Center in 2001-2016 ranged from 2,0 to 5,4 cases per 1000 live births. 2004 was the year with the most neonatal deaths (97 death) with 5,4% and the lowest was in 2013 (31 deaths) with 2%. It's after 2004 that the neonatal mortality decreased the most. From 2004 to 2016 the neonatal mortality decreased by 3,4%.

2. The early neonatal mortality in Kaunas Perinatal Center was also the highest in 2004 with a mortality rate of 4 cases per 1000 live births and 2013 showed the lowest mortality rate with 1,5 cases per 1000 live births. In the period from 2004 to 2016 the early neonatal mortality rate decreased by 2,5%. In general, we can conclude that the neonatal mortality rate since 2001 has drastically decreased.

3. In neonatal mortality of full-term newborns an increase was also proved in 2004 with 1,9% which is the highest rate in the period 2001-2016 and the lowest was describe in 2011 and 2012 with 0,5%. But after 2012 the mortality rates re-increasing.

4. Early neonatal mortality rate in full-term infants was the lowest in 2012 with 0,3 cases per 1000 live births and 2004 recorded the biggest mortality rate with 1,3 cases per 1000 live births.

5. The main pathologies causing early neonatal deaths of full-term newborns in Kaunas Perinatal Center were: congenital malformations, deformations, chromosomal abnormalities, intrauterine hypoxia and birth asphyxia.

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13. PRACTICAL RECOMMENDATIONS

In Kaunas Perinatal Center in order to decrease the rate of neonatal mortality we should focus on the pathologies causing the deaths of the newborns. In the case of congenital anomalies, genetic counseling should be more recurrent in case of gross

congenital anomaly early abortion may be proposed by the obstetricians. Neonatal infections can be minimized by the obstetricians if they take care of any suspicious vaginal discharge in the antenatal period.

To avoid intrauterine asphyxia, careful monitoring of the mother and fetus should be done, with the new technologies like fetus electrocardiography and prophylactic exchange can help to detect and treat intrauterine hypoxia.

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11GGlobal, regional, and national 2016.

global, regional, and national age-sex specific mortality for 264 causes of death, 1980- 2016: a systematic analysis for the Global Burden of Disease Study 2016.

Global, regional, and national age-sex specific mortality for , regional, and

4. CONFLICT OF INTEREST

TABLE OF CONTENTS

1.SUMMARY

2. ETHICS COMMITTEE APPROVAL

3. ACKNOWLEDGEMENTS

4. CONFLICT OF INTEREST

5. TERMS

6. INTRODUCTION

7. AIM AND OBJECTIVES OF THE THESIS

8. LITERATURE REVIEW

9. RESEARCH METHODOLOGY AND METHODS

10. RESULTS

NEONATAL MORTALITY RATES

NEONATAL MORTALITY RATE OF TERM NEWBORNS

EARLY NEONATAL MORTALITY RATES OF TERM NEWBORNS

Main pathology of early neonatal death of term infants

11. DISCUSSION OF THE RESULTS

12. CONCLUSIONS

13. PRACTICAL RECOMMENDATIONS

14. REFERENCES