Ministry of Health of the Republic of Moldova Public Institution [602541]

Ministry of Health of the Republic of Moldova Public Institution
“Nicolae Testemițanu” State University of Medicine and
Pharmacy of the Republic of Moldova

FACULTY OF MEDICINE nr 2
Department of Gynecology and Obstetrics

DIPLOMA THESIS
Preterm delivery management and protocols and their
influence on preterm children health consequences

Name and surname of student: [anonimizat]: 6th year, group 1636

Name and surname of scientific advisor: Ph.d Dr. Marian -Pavlenco Angela
Position and sci entific degree: doctor, associate professor

2 Content
Abbreviations ………………………………………………………………………….3
Introduction…………………………………………………………………………….5
I Bibliographical analysis ………………………………………………………………7
1.1 Definitions and prophylactic measures preterm delivery ……………….8
1.2 Contributors to preterm delivery ………………………………………….9
1.3 Diagnosis of preterm delivery …………………………………………..10
1.4 Treatment of preterm delivery …………………………………………..12
1.4.1 Protocol of preterm delivery in Moldova………………………..12
1.4.2 Protocol of preterm delivery in Israel……………………………..13
1.5 Consequences of preterm delivery ……………………………………..14
1.6 Synthesis of the bibliographic analysis…………………………………16
II Materials and research methods ……………………………………………………..18
2.1 Magnesium solphate and the benefits of th is treatment ………………..19
2.2 RSV and the benefit of the vaccination against RSV ………………….24
2.3 Israel research and statistical data regarding preemies …………………29
2.4 Moldova research and stat istical data regardi ng preemies………….…31
2.5 Synthesis of the materials and research methods………………………35
III Personal result and discussions …………………………………………………….36
3.1 Interpretation of statistical data from Israel…………………………….36
3.2 Interpretation of statistical data from Moldova…………………………39
3.3 Synthesis of the personal results………………………………………..42
Conclusions ……………………………………………………………………………44
Attachment ……………………………………………………………………………45
Bibliographic references ………………………………………………………………48

3 Abbreviations
ETC – et cetera
WHO – World’s health organization
IVF- in vitro fertilization
PROM – premature rapture of membrane
NST – non stress test
CBC – complete blood count
IGF-1 –Insulin like growth factor 1
PCR – polymera se chain reaction
WBC – leucocytes
CRP – c reactive protein
NSAID – non steroidal anti inflammatory drugs
BP- blood pressure
NEC – necrotizing entercolitis
GERD – gastroespophgel reflux disease
BPD – bronchopolmunary dysplasia
CLD – chronic lung disease
ROP – retinopathy of prematurity
CNS – central nervous system
ADHD – attention deficit – hyperactivity disorder
RSV – respiratory syncytial virus
CP- cerebral palsy
MFMU – maternal fetal medicine units
CHD congenital heart defect
C-PAP- continuous positive airway pressure
LRTI – low respiratory tract infection
FDA – food and drug administration
ICU- intensive care unit
CAP – community acquired pneumonia

4 ESPID – European society of pediatric infectious disease
IUGR – intra uterine growth restriction
NICU – neonatal inten sive care unit
RM –republic of Moldova

5 Introduction
My thesis will deal with the question of preterm delivery, the differences of the
protocol of dealing with preterm delivery in Israel and in Moldova. It will consider
which peculiarities exist in each country when dealing with this subject and which are
the main objectives which interest each country in order to study and find what could
be changed in order to optimize the treatment in preterm delivery and reduce the
morbidit y and mortality in this group of children. The actuality of this subject is
expressed by preterm delivery being between 5 -15% of deliveries in different
countries. This high number of preterm deliveries obligate as to study and explore
deeper in to this su bject in order to minim ize the complication and optimize the
treatment to prevent preterm delivery and preterm children morbidities.
You can see in my work that Israel and Moldova have different approaches in dealing
with this subject and follow different protocol. Due to this fact there is a big
differences in morbidity and mortality that makes as wonder which actions are
contributing to dealing with preterm delivery and which have an opposite effect or no
effect at all. If we study and research these sub jects we would be able to understand
deeper what needs to be changed in both of health systems to provide the best
outcome possible. In my work I will touch the subject of approaches to prevent
preterm delivery as well as in case unpreventable preterm deli very and the
possibilities to reduces to minimum as possible any outcome of this delivery as in
short run as well as in the long run. The optimization of this process as great goal not
only for the family of the patient and the patient it self but as well as for the society, a
healthier society contribute to the economic and has a social aspect as well and in the
long run will reduce costs of treating the complications possible to come from the
preterm delivery. I well look for if increasing the budget for the preterm delivery
approach will be economic and will save money when it will reduces the amount of
complications in the future and in the long term will be better for the health system of
this countries. The level of study of my work will be based on ex isting statistics in
Israel, Moldova and other countries in the world. I will show protocols which were

6 use due to some specific researches and later where changed sue to newer and more
correct data and researches which were conducted when extra possibilit ies for a better
research became available, or when some protocols where changed due to direct
results of this protocols which show no change or even a worse outcome then before
the protocol were introduced. All my work will be based on these existing rese arches
and will be only theoretical thesis from existing materials which I am using in order
to get my conclusions to the objectives I will put in my thesis.
The aim of my thesis is to show the weeks points in management of preterm delivery
that should be studied in order to optimize effectiveness of management.
The main objectives of my work will include:
1. To find out whether the current protocol of treatment of preterm delivery in
Moldova and in Israel as shown a statistical data expressing a change in
morbidity or mortalities in the years 2009 -2012
2. To exclude any other aspect that could have an impact on morbidity and
mortality as number of staff, available equipment and E TC.
3. To find out whether there is approaches in Moldova that are not used in Israel
at the moment but might have a beneficial outcome and should be considered
in Israel and vice versa.
4. To consider which fields should be studied more deeply by researches in order
to optimize the outcome of preterm delivery in both of countries.
Theoretica l importance and applied value of the work is expressed with the need
of the health system in both RM and Israel to improve and adjust to new information
and to new approaches that have shown to be beneficial in improvement in health
outcome of children bo rn prematurely. This adjustment will provide I the long run
benefit in more wide aspect and will be seen beneficial for the country as well as the
society and economical well being of the citizens. If we don’t approach this difficult
questions about proper management of preterm delivery will see a regression in the
health consequences which will influence our lives in many fields.

7 I. Bibliographic analysis
Every year, an estimated 15 million babies are born preterm (before 37 completed
weeks of gestation), and this number is rising. Over 1 million babies die annually
from preterm birth complications.
Preterm birth is the leading cause of newborn deaths ( <28 days ) and the second
leading cause of death after pneumonia in children under five years. Three -quart ers of
them could be saved with current, cost -effective interventions, even without intensive
care facilities. Across 184 countries, the rate of preterm birth ranges from 5% to 18%
of babies born. (WHO) [1]
Infants born premature are at greater risk than i nfants born mature for mortality and
variety of health and developmental problems. Complications include respiratory,
gastroenterological, immunological, central nervous system, hearing and vision
problems, as well as long term motor, cognitive, visual, he aring, behavioral, socio –
emotional, health and growth problems. The birth of a premature infant can also bring
economic and emotional costs for the family and have impaction for public -sector
services, such as health insurances, educational, and other supp ort systems.
Preterm birth is a complex cluster of problems with a set of overlapping factors of
influence. Its causes may include individual level behavioral and psychological
factors, neighborhood characteristics, environmental exposures, medical conditions,
infertility treatments, biological factors, and genetics. Many of these factors occur in
combination, particularly in those who are socioeconomically disadvantaged or who
are members of racial and ethnic minority groups. In this chapter I will discuss all the
general information about preterm delivery about its etiology, the main diagnostic
tools and tests, treatment protocols in both Israel and Moldova and the main
consequences that may lead this condition. [6]

8 1.1 Definitions and prophylactic measures for prevention
Preterm birth (Latin : partus praetemporaneus or partus praematurus ) is the birth of
a baby of less than 37 weeks gestational age and after 22 week of gestation ;
Premature birth is defined either as the same as preterm birth or the birth of a baby
before the developing organs are mature enough to allow normal postnatal survival.
Preterm labor is the presence of 3 criteria:
1. Gestational age from >22 <37.
2. Uterine contractions should be at least 3 times in 30 minute.
3. Cervical changes – a serial of exami nation show a change in dilation and
effacement or a single exam show dilation > 2 cm.
Preterm births have been categorized into two type one is spontaneous preter m birth
occurs as a result of preterm labor or premature rapture of membranes before 37
week s and account for 70% of preterm births. The other type is indicated preterm
birth as a result of conditions that directly threaten the health of the mother or fetus,
such as preeclampsia, placenta previa, and fetal growth restriction. [2]
Some measures have been found to be affective in preventing the preterm delivery
from occurring:
Prophylactic measure preconception:
1) Change life style(smoking, alcohol abuse)
2) Limit intrauterine surgical manipulation as minimum
3) Inform of the risk of prete rm delivery in usage of assistants technologies for
reproduction and limit the number of embryos transferred in IVF.
4) Minimal invasive techniques for cervical neoplasia treatment
Prophylactic measure prenatally:
1) Identify persons in risk group for preterm de livery and try to change the
contributing factor (smoke, drug use)
2) Give all pregnant women obligatory curs with information about how to
recognize signs of preterm delivery and to seek for medical assistance
immediately if one of this signs are present: in ferior abdominal cramps, pelvic

9 pressure, sacro -lumbar pain, change of quantity or constitution of vaginal
discharge, vaginal bleeding,
3) Cervical cerclage – is given in case of short cervical canal (insufficiency) in
absence of contraindications. Indication for effect cerclage are: monofatal
pregnancy with following situation – minimum 3 abortions in 2nd trimester or
previous preterm delivery, 2 abortions in 3rd trimester or previous preterm
delivery without any other cause except cervical insufficiency, abort ion in 2nd
trimester or previous preterm delivery with ultrasound evidence on decrease 25
cm from cervical canal.
4) Progesterone given is connected with reduction in preterm delivery risk by
44%. Indications for progesterone therapy is risk of preterm deli very or/and
presence of short cervix at 18 -24 weeks of gestation determined by
transvaginal echography. Treatment need to be given after 20 weeks of
gestation till risk of preterm delivery is eradicated.
5) Measure transvaginal ultrasound the length of cervi x as a screening test.
6) Antibiotic prophylaxis are connected with decrease the infections in preterm
children and mothers. The Recommendations are in presence of bacteria in
urine analysis more the 10×5 CD/ml and recommended to give amoxicillin
500 mg/4 a day for 3 days. For syphilis – primary, secondary and latent 2.5
million UI of benzylpenicillin 1 time and for late tertiory syphilis same dose
but 3 time 1 a week. For gonococal infection ceftriaxon 125 mg 1 time.
7) Tocolytic therapy can prolong pregnancy for 2 -7 days to allow treatment with
steroids.
1.2 Contributors to preterm birth
1) Behavioral and psychosocial contributors it has been suggested that favorable
lifestyle as been associated with favorable pregnancy ou tcomes. Those include bad
habits like tobacco smoking, drinking, using of drugs as well as incorrect nutritional
habits and inappropriate physical activity including sexual activity and some labor
activities and some psychological factors as stress and som e stressful life events and

10 emotional responses to them like depression , maternal anxiety as well as personal
racism and lack of support.
2) Socio -demographic and community factors as young maternal age, maternal status,
race and ethnicity as shown a connect ion as well as socioeconomic conditions.
Adverse neighborhood condition s as shown evidence supporting this factor role in
preterm birth rates when shown that concentrated poverty and associated
neighborhood disadvantages (lack of goods and services, health care facilities, poor
housing quality, high crime rates) has worse outcomes of pregnancy.
3) Medical and pregnancy condi tions. Illnesses of the mother for example chronic
hypertension, pregnancy diabetes mellitus, and system ic lupus can alter or limit
placen tal delivery of oxygen and nutrients to the fetus possibly resulting in growth
restrictions. As well as increase risk of preeclampsia which leads to preterm delivery.
Other conditions like underweight or obesity, family history of preterm birth, and
differ ent techniques used in infertility to achieve pregnancy can also be additional
risk factor.
4) Biological events – it is clear that the causes of premature labor are multi factorial and
vary according to the gestational age. Important common pathways leading t o
preterm birth include stress, systemic or maternal genital tract infections, placental
ischemia or vascular lesions, and uterine over distention
5) Genetic predisposition – evidence indicates that familial or intergenerational factors
influence preterm birth . This influence may reflect shared envir onmental factors or
genetic factors, or both.
6) Envir onmental toxins has been shown to have a connection to preterm birth including
air pollutants (CO2, NO, O3), agricultural chemicals, polychlorinated biphenyls,
envir onmental tobacco smoking, metals and metalloids. [3]
1.3 Diangnosis of preterm delivery
1. Gestational age <37 weeks
2. Regular uterine contractions (means at least 1 contraction each 10 minutes)
accompanied by either cervical dynamics or dilation and effacement > 2 cm. it is

11 statistical that 10% of women coming with preterm delivery will deliver in the next
week.
Anamnesis a clinical examination includes key factors and additional factors. Key
factors include – presence of factors of risk (cervical trauma, maternal infection, low
cervix, multifetal pregnancy, fetal anomalies, smoking, body mass index, home
violence), uterine contraction (1 in 10 min), PROM (usually repture before
contractions start, premature delation of cervix. Additional factors of diagnosis are
increasing in heart rate of mother or child, inferior abdominal pain or sacrolumbar,
fever, vaginal bleeding.
Test for establishment of preterm delivery include:
1) Non stress NST is initial test to establish fetal state but not specific for preterm
delivery which determine heart bite of fetus.
2) Tocography document uterine contractions – more then 1 in 10 minutes will
establish preterm delivery
3) Transvaginal ultrasound may show decreasing in cervix length – a decrease <2cm
have association with preterm delivery (60% risk)
4) Fetal fibronictin – positive test indicate a probability of preterm delivery
5) IGF -1 test a positive test may indicate PROM with sensitivity 90%.
6) CBC to determine presence of infection (increased WBC) and presence of
bleeding (decrease Hb)
7) PCR – increased in infections. Need to be done in all PROM.
8) Urine analysis should be done in all PROM to see leucocytosis for infection.
9) Urine microscopy, urine culture and antibiotic sensibility for infection in PROM.
10) Vaginal smear for group b streptococcus.
11) Nitrozin test – used to determine PROM amniotic fluid may increase vaginal PH
in this case PH will increase >6.5 will indicate PROM.
12) Vaginal liquid microscopy – crystallization of amniotic fluid gives as feri g
positive symptom and it is indication of PROM. [4]

12 1.4 Treatment protocols of preterm labor
1.4.1 Management protocol in Moldova
1) Conduction of PROM without risk of preterm delivery – Women with PROM
should my admitted to the hospital for close monitoring which would include
monitoring of cardiac rhythm, uterine sensibility, vaginal discharge, leucocytosis or
CRP increasing. Fetal heart monitoring should be done to establish tachycardia as a
sign of chorioamnionitis after 48 -72 hours of hospital monitoring may be discussed
ambulatory monitoring which will include measurement of temperature twice a day
and watching for symptoms of in fection. After diagnosis of PROM it is necessary to
administer antibiotic therapy primary option is erythromycin and clarythromycin for
15 days. In case of pregnancy on between 24 -34 weeks of gestation corticosteroid
therapy will be administered for lung m aturation and the drugs of choice are
betamethasone or dexamethasone. From 35 week of gestation there is no beneficial
result for this treatment. The dosage use is for betametasone is 12 mg i/m each 24
hour 2 times and for dexametasone 6 mg each 12 hours 4 times.
2) Conduction of preterm delivery with or without PROM – the 2 most important
factor that influence consequences are administration of corticosteroid treatment
and transportation to special center that as the abilities to manage this situation. All
preterm delivery with or without PROM will receive betametasone or dexametasone.
In Moldova in compression with other countries only women in risk for infection of
Group B streptococcus urine analysis, fever) will receive antibiotic treatment that
will include or amoxicillin 1 g i/v each 12 hours. Other option is clindamycin 900 mg
each 8 hours. Tocolytic treatment can prolong pregnancy 2 -7 days. In time of
administrat ion should be monitored mother pulse and BP each 30 min in 1st 4 hours
and each 2 hour for next 24 hours. This include nifidipine ( is a calcium canal blocker
-till 60 mg total dose), beta mimetic to block uterine contractions but has a lot of side
effects and less recommended, indometacin (NSAID prostaglandin inhibitor used till
32+6), atosiban (oxitocin antagonist) best choice today. All tocolytics should be
given as monotherapy no combinations are recommended. In Moldova primary

13 option is : nifedipine 20 mg oral maximum dose 160 mg/ day. Secondary options are
indometacin 25 mg per rectum each 6 hours for 48 hour or atosiban 6,75 mg i/v 1
min then a profusion with 6mg/hour till 48 hours.
1.4.2The protocol of treatment in Israel
Tocolitical therapy is pro ven to delay birth in no more then 48 hours when steroids
treatment can increase the neonatal result of the child. When using tocolitic treatment
is used now days in between weeks 24 till 34. Non drug therapies which are used are
rest, avoiding sexual acti vities and hydration.
After rapture of membrane with no sings of infection we can consider a tocolytic
treatment to allow therapy with steroids to improve neonatal outcomes, this therapy
may include the following groups of drugs:
1) Calcium channel blockers – proven as save and good results.
2) Prostaglandin inhibitors (indomethacin) but as side effects when used over 48 hours
like intrauterine closure of ductus arteriosus and decresment in amniotic fluids.
3) Oxytocin receptor antagonists (atosiban) very save for mo ther.
4) Beta adreno mimetic which have maternal cardiopulmonary effects as tachycardia,
dyspnea and pulmonary edema
5) Magnesium solphate – but hasn’t been proven its result as a tocolytic drugs but more
as a neuroprotector for the neonate.
The decision which t ocolytic drug to use is considered together with mother ’s
medical history, age of gestation and maternal side effects.
Maintenance therapy with tocolytics as shown to be non benefits at all.
Steroids most be given one course of this drug – 2 injections of betamethasone 12 mg
in 24 hours differences between week 24 -32 if there is a risk of preterm birth within a
week, but its still not clear as a result of this therapy in other gestational age. The
doses should not be given in closer time even if there is a high risk of closer deliver
then 24 hours.
Magnesium sulphate – as a neuroprotector should be considered if a delivery may
happen before 32 weeks or more exactly between 30 -32 week ages. If the birth didn’t

14 occur in 12 -24 hours the treatment may be stopped and renewed 6 hours after if birth
is suspected. [12]
1.5 Consequences and complications o preterm birth
Developmental immaturity affects a wide range of organ systems. I will describe the
short -term complications of preterm birth in terms of fetal development as well as
injury to fragile organ systems during the perinatal and neonatal periods. Many of
these complications have lifelong consequences for the health, growth, and
development of infants born preterm.
1.Mortality Infants born preterm are m ore likely than infants born full term to die
during the neonatal period (first 28 days) and infancy (first year), and mortality rates
increase proportionally with decreasing gestational age or birth weight. The leading
causes of infant mortality in the Un ited States are preterm birth, low birth weight, and
birth defects;
2. Lung and respiratory system that include as most common respiratory distress
syndrome which is as much as in 80% of preterm birth before 27 weeks and is due to
lack of surfacta nt the other complication is bro nchopulmunary dysplasia and chronic
lung disease a chronic disease causing inflammation, injury, and sca rring of
pulmonary tissue. Another common complication is apnea characterized by stopping
of breathing for 20 sec or more accom panied by bradycardia.
3. Gastrointestinal complications include feeding intolerance is a common
complication of preterm birth. The immature GI tract has difficulty digesting food
necessary for ongoing growth and development. Very immature and sick infants
receive parenteral nutrition with amino acids, glucose, electrolytes, and lipids.
Preterm infants below 34 to 35 weeks of postmenstrual age require tube feeding
because they cannot coordinate sucking, swallowing, or breathing. Another
complication is Necr otizing enterocolitis (NEC) is an acute injury of the small or
large intestines that causes inflammation and injury to the bowel lining and that
primarily affects preterm infants. Gastroesophageal reflux (GER) is common in
preterm and full -term infants, of ten presents as regurgitation, and may adversely

15 affect growth and health. It may also be manifested by aspiration pneumonia,
wheezing, or worsening of BPD/CLD because of an inability to protect the airway
when refluxing.
4. The skin of infants born at the lower limit of viability (i.e., 22 to 25 weeks of
gestation) is generally gelatinous, is easily injured when touched, allows tremendous
loss of fluids, and does not provide an adequate barrier to infection. Fluid and
electrolyte needs are often difficult to predict and are quite variable during the first
several days after birth, until the skin toughens. Frequent procedures and significant
infiltrates from intravenous lines lead to multiple scars in preterm infants. At the limit
of viability, skin can scar from the removal of chest monitor leads.
5. Immune system -Preterm infants have immature immune systems that are
inefficient at fighting off the bacteria, viruses, and other organisms that can cause
infections. The most serious manifestations of infections with these agents commonly
seen in preterm infants include pneumonia, sepsis, meningitis, and urinary tract
infections. As many as 65 percent of infants with birth weights of less than 1,000
grams have at least one infection during their initial hospitali zation.
6. Cardiovascular complications in preterm infants can experience a variety of
cardiovascular disorders, ranging from major morphological defects to dysfunctional
autoregulation of blood vessels. Those may include most commonly patent ductus
arteri osus, hypotension, apnea and bradycardia.
7. Hematological complications include Fetal blood loss, fetomaternal hemorrhage,
and hemolysis can all result in congenital anemia, but the most common hematologic
complication in preterm infants is anemia of prem aturity. Anemia of prematurity is an
exaggeration of the physiological anemia of infancy because of suppressed
hematopoiesis for 6 to 12 weeks after birth and is earlier in onset and symptomatic.
8. Auditory system include One to two of 1,000 newborns suff er from congenital or
perinatally acquired hearing disorders. The prevalence of neonatal hearing disorders
has been reported to be increased 10- to 50 -fold in infants at risk, which includes
preterm infants.

16 Moderate to severe bilateral hearing impairment can distort the developing child’s
perception of speech and may interfere with his or her attempt at speech production.
9. Vision complication Preterm infants are more likely than term infants to have
significant abnormalities of all parts of the visual s ystem, leading to reduced vision.
ROP is the most common eye abnormality in preterm infants. It is a neovascular
retinal disorder, and its incidence increases with decreasing gestational age and
decreasing birth weight. It is multifactorial in etiology, wi th the primary determinant
being immaturity with an avascular retina. ROP occurs in 16 to 84 percent of infants
born with gestational ages of less than 28 weeks, 90 percent of infants with birth
weights of less than 500 or 750 grams, and 42 to 47 percent o f infants with birth
weights of less than 1,000 or 1,500 grams.
10. Complications of central nervous system include incomplete formation of the
CNS makes neonates vulnerable to CNS injury, especially if the infant was born
preterm. Injury to the CNS can oc cur during pregnancy, labor, and delivery, the
transition to extra uterine life, or a subsequent illness or exposure. Most common are
intraventricular hemorrhage, intraparanchymal hemorrhage, white mat ter injury and
periventricular leukomalacia .
Neurodeve lopment disabilities may include: Cerebral palsy. Mental retardation as the
most severe but the lest severe will be language disorders, learning disabilities,
attention deficit -hyperactivity disorder (ADHD), minor neuromotor dysfunction or
developmental co ordination disorders, behavioral problems, and social -emotional
difficulties. [5]
1.6 synthesis of the bibliographical analysis
Preterm delivery is world wide problem existing in all countries no matter if its
developed or developing country. The devastating consequences attributes to preterm
children are an issue not only to the patient and his family but also to the society and
economy in a negative way. For this cause it is in our duty as doctors to find all way
possible to reduce the amount of preterm birth as well as to manage delivery the best
possible in order to reduce this impact on our lives and on the health system. In

17 addition we are able to see that different countries have different protocol in
management of preterm delivery and we can only assume it is due to specific
peculiarities present in this country or rather as shortage in new information
knowledge or maybe just due to a specific economical status characterizing this
country. In difference with the cause of this different approa ch we was make research
and match the best approach in order to get the best result.

18 II. Materials and research methods
My thesis will be based on bibliographical analysis of existing researches and meta –
analysis is order to find out the main objectives that I put in the beginning of the
thesis rather then based on researches that I did myself. I will explain about
research es that where done in the last years in order to optimize the quality of
medical assistance using in preterm delivery to assure the best outcomes for preterm
children. Also I will show if this researches have shown changes in some
complications of preterm delivery. I will show analytic result showing different
outcome in different protocol using of magnesium sulphate in order to decrease cases
of cerebral palsy and other complication that could appear due to low perfusion of
brain tissue. I will speak about the researches that where done towards the
optimization of protocol of administration RSV vaccination in order to decrease the
complication of respiratory infections in preterm children and to decrease the first
year of life hospitalization among those po pulation of children.
As well I will use existing statistics about preterm delivery and consequences both in
Israel and in Moldova between the years 2008 -2013 and compare it to the specific
protocol of management of preterm delivery to see if the protocol as brought any
changes towards the outcome in this specific years. In this chapter I will show the
material and statistical data I collected in order to answer my objectives and in the
next chapter of personal result I will discuss all the point I have ga thered. From the
data I collected in this chapter and the personal result I will discuss in the next
chapter I will gather some conclusions for the last chapter. This conclusions will
include what I think from the data is the best approaches I management o f preterm
delivery and how can Israel or Moldova benefit from adding some new protocol point
in order to minimize the consequences of the preterm children I short and long run.
As well I will answer all the objectives I put to myself in this thesis from th e
corporation of all existing data.

19 2.1 Magnesium Sulphate
Preterm delivery is one of the most difficult problems in modern obstetrics. Many
doctors are willing to do anything to prevent complications that affect 4% -8% of the
preemies in very low birth w eight. In the last early there were published many
researches showing the connection between cerebral palsy (CP) of prematurity and
especially with combination with premature perinatal death , But still it is unclear
which is the best protocol for dealing w ith this problems this is why result of usage of
magnesium s ulphate and its effect on CP are not clear for shore and should be
checked more in the next years by checking the relation between levels of magnesium
in mother and in child, age of pregnancy and the long term outcomes of the children.
Of course this kind of research will be expensive and take a long time.
Cerebral Palsy is a syndrome characterized by neurologic defect leading to motor
impairment, a change in body position and different degree of m otor limitations. This
gives a high disability that has medical, emotional, and economical outcomes.
Premature birth gives a meaningful risk for CP development and is in a direct
correlation with the age of gestation at birth when a lower age means a highe r risk for
development of this syndrome and more gravid the syndrome will be. In Israel i n the
last years we can see that one third of CP cases are in children how were born
preterm but from 1995 there was pr ove that there is a decreasing in the cases of CP in
children how ’s mother was treated with magnesium sulphate close to the date of birth
with a combination of tocolytic and anticonvulsive treatment and this children were
born in very preterm. [13]
To prove this data in the last 5 years was done 5 prosp ective researches including a
large amount of cases , And last year was published a meta analysis of five of this
cases concluding all of them together in the question of the effects of Magnesium
Sulphate on decreasing cases of CP.
In all of these researche s were included children born before 34 week of gestation
when 970 children were before 34 week, 688 before 33 weeks, 2,444 before 32 weeks
and 1,255 before 30 weeks. The etiologies for the preterm delivery in these

20 researches were mostly unknown or due to premature rapture of membrane or in
mothers with preeclampsia going to delivery by induction of labor. In all these
researches the diagnosis of CP was done by a pediatrician in the age of 18 -24 weeks
of the children. The dosages, maintenance therapy and t he stop of administration was
changed in order to see different result and was in the range of 6 -4 grams at first dose
and maintenance in the range of 1 -3 grams an hour the drug was giving till the birth ,
24 hours after birth and in the case there was no b irth in 12 hours it was stopped. The
average of dose ranged from 4 -50 grams total.
The result of this researches yield that the chances of the pre emies to develop CP is
lower in the group of mothers that were treated with magnesium then in the group
that wasn’t from 3.9% in comparison to 5.6%. The amount of mothers in risk of
preterm birth needed to be treated to prevent one case of CP was 95%. The lowe st
risk for CP was watched in the group with gestational age less then 32 weeks and in
the group that the average dosage of magnesium was higher the 4 grams. There was
no evident change in the group that was treated with a lower then 4 grams therapy or
in the gestational age of less then 30 weeks in other researches was shown the
connection of the treatment with magnesium and the gravity of the CP. This research
shows a decrease in moderate and severe grades of CP in mothers treated with
magnesium in compar ison with group that didn’t re ceive this treat ment. There was a
decrease also in 26% of the risk to get mild CP in groups that were treated with
magnesium. But in general there was not shown a decrease in mortality on children
less then 2 years from any of these groups. In pregnancy with twin there was not
shown a statistic change in risk of CP with or without this treatment. As well t here
was n ot shown any side effect in any of these groups on the children except for
insignificant increase in enterocoliti s in the children that were in the gro up receiving
the treatment (6% comparison with 7.1%). A delay or motor insufficien cy was clearly
shown statistically to decrease in group receiving the treatment showing 2.6% and
4.2% in non treated child, but there wa s not shown any other changed like neurologic

21 development between the groups like mental development, psycho -motor blindness
or deafness.
Maternal side effect like mortality, cardiac arrest or respiratory arrest, pulmonary
edema, respiratory depression, h emorrhages after birth was the same in group
receiving and not receiving magnesium , but during the therapy was an increase of
50% in rate of maternal tachycardia and hypotension as a side effect of the
magnesium.
There is suffi cient evidence showing that magnesium in mothers in risk of preterm
delivery before 34 weeks reduces the risk of CP of moderate and severe forms in
30%. There was not chang e between the groups in the peri natal mortality which
could exclude the fact that mortality due to CP may be as a parameter for the
decreas ing of children with CP. No significant side effec t were watched in mother s or
children or any increasing in mortality rate of mothers or children till 2 years. [14]
Other researches showed the effect of magnesium in different us es:
1) For prevention of eclampsia – meta -analysis in 2003 showed 6 researches with 11,444
women with preeclampsia that had a decrease in development of ecalpsia with
treatment with mg2+
2) As a tocolytic – no researches as proven any change in prevention of prete rm delivery
with magnesium therapy.
3) As a neuroprotector – in different researches that included 150,000 children showed a
decrease in CP in children less the 1500 grams from 36% to 7% at least.
4) Australian collaboration trail of magnesium sulphate that had 1 200 women before 30
weeks of gestation half were treated with 4 grams plus 1 gram each hour till 24 hours
and the other half was not treated at all this research showed decrease from 22% to
17%
5) PREMAG from France showed a si ngle dose of 4 grams of magnesium can protect
from neurologic defects in gestational age less then 33 weeks. This search included
533 women expect to deliver in 24 hours with a differences of 22% and 10% of cases
of CP with and without this si ngle dose treat ment,

22 6) Research of MFMU network took 2,241 women expected to deliver between week 24
and 31 and gave half magnesium treatment and half without. The dosage was 1 dose
of 6 grams and 2 gram an hour till 12 hours if contraction where stopped treatment
was abor ted.[15]
The current recommendations by Scott:
1) To offer therapy with magnesium as a neuroprotector to all women in risk of
preterm delivery by the same crit eria done to determine the neces sity to give steroid
therapy , This include pregnancy in week 28 -32 with labor or programmed early
induction.
2) To receive an agreement from the mother after explanation of the pro and risks an
giving information about how many therapies are needed to prevent one case at least
and this ratio stand on 1/63 and can be 1/2 9 when pregnancy is below 29 week.
3) To give a loading dose of 4 -6 grams and continue 1 -2 grams/hour for 12 -24 hours.
Then to stop administration till active delivery starts.
The current recommendations in Israel are : (this is the current recommendation
but it is not the current protocol!!!)
1) The current data support the therapy is efficient as neuroprotector.
2) The indication for therapy is preterm delivery before 32 weeks
immediately.
3) The definition of preterm delivery is programmed delivery or unpreventable
delivery. For example – no reaction to tocolytic therapy and at least 2 cm
dilation and/or 80% effacement.
4) The dosage should not exceed 10 grams this is why loading dose sh ould be
4 grams and another 2 gram/ hour for 3 hours.
5) This load ing dose allows has to repeat therapy in case delivery did not
proceed at this time.
6) As it was proven that even a single dose of 4 grams is shown to be
beneficial it is also useful to give this one dose if the delivery is coming

23 very soon a nd this dose may be finished in 10 minu tes and by this will not
put the mother in any risk. [16]
Intrapartum fetal monitoring is the basic exam used today to establish the intrapartum
fetus situation and to give an idea about any suspected pathology in the fetus. When
we talk about fetal distress we mean a combination of states which can cause distress
to the fetus. The distress severity is dissuaded by the type of molecule missing (o2,
amino acids, and vitamins), the degree of deficiency, the period of def iciency, the
ability of the fetus organism to compensate this deficiency. This method to discover
fetal distress is still not sensitive enough and doesn’t have a high positive predicted
value. But still the recommendations are to provide a chart and a full description of
fetal heart. The exact criteria to establish any event during birth, which can cause
asphyxia and be as a predictor of future cerebral palsy, are:
1) Prove of metabolic acidosis in umbilical blood(ph<7)
2) Early neonatal encephalopathy symptoms in child born after 34 weeks of
gestation
3) Appearance of cerebral palsy of type spastic quadriplegic or dyskenetic.
4) Exclusion of any trauma, infection, coagulopathy or congenital
abnormalities.
All researches show that heart fetal monitoring sho uld be inter preted by periodic
patterns with clinical connections and not by momentarily findings and not forget the
monitoring is effected by drug administration during the birth. Continuous electronic
monitoring effect on the rates of CP has shown no sufficient posi tive predictive
values and a very high false positive rate. Nevertheless the current researches show
no deference in rate of CP in developed and developing countries this shows as that
continuous fetal monitoring hasn’t been a predictive value in this case , probably due
to the fact that most of events leading to CP are probably happening during delivery
itself. (See figure 1.1 and 2.1)

24 2.2 Human respiratory syncytial virus
Human respiratory syncytial virus (RSV) is a virus that causes respiratory
tract infections. It is a major cause of lower respiratory tract infections and hospital
visits during infancy and childhood. A prophylact ic medication (not a vaccine ) exists
for preterm (under 35 weeks gestation) infants, infants with certain congenital heart
defects (CHD) or bronchopulmonary dysplasia (BPD) , and infants with congenital
malformations of the airway . Treatment is limited to supportive care (for example C –
PAP), including oxygen ther apy.
In temperate climates there is an annual epidemic during the winter months.
In tropical climates , infection is most common during the rainy season.
In the United States, 60% of infants are infected during their first RSV season, and
nearly all children will have been infect ed with the virus by 2 –3 years of age. Of
those infected with RSV, 2 –3% will develop bronchiolitis , necessitating
hospitalization. Natural infection with RSV induces protective immunity which
wanes over time , possibly more so than other respiratory viral infections , and thus
people can be infected multiple times. Sometimes an infant can become
symptomatically infected more than once, even within a single RSV season. Severe
RSV in fections have increasingly been found among elderly patients. Young adults
can be re -infected every five to seven years, with symptoms looking like a sinus
infection or a cold (infections can also be asymptomatic).
RSV is a negative -sense , single -stranded RNA virus of the family Paramyxoviridae ,
which includes common respiratory viruses such as those
causing measles and mumps . RSV is a member of the paramyxovirus subfamily
Pneumovirinae. Its name comes from the fact that F proteins on the surface of the
virus cause the cell membranes on nearby cells to merge, forming syncytia .
Sing and symptoms include incubation time is 4 –5 days. For adults, RSV produces
mainly mild symptoms, often indistinguishable from common colds and minor
illnesses. The Centers for Disease Control consider RSV to be the "most common
cause of bronchiolitis and pneumonia in children under 1 year of age in the United

25 States". For some children, RSV can cause bronchiolitis , leading to severe respiratory
illness requiring hospitalization and, rarely, causing death. This is more likely to
occur in patients that are immunocompromised or infants born prematurely . Other
RSV symptoms common among infants include listlessness, poor or diminished
appetite, and a possible fever.
Recurrent wheezing and asthma are more common among individuals who suffered
severe RSV infection during the first few months of life than among
controls; whether RSV infection sets up a process that leads to recurrent wheezing or
whether those already predisposed to asthma are more l ikely to become severely ill
with RSV has yet to be determined. The main sings an d symptoms include:
 Fever (typically low -grade)
 Cough
 Tachypnea
 Cyanosis
 Retractions
 Wheezing
 Rales
 Sepsis like presentation or apneic episodes (in very young infants)
Physical examination of the infant with RSV -related LRTI may reveal the following:
 Evidence of diffuse small airway disease .
 Associated otitis media (viral, bacterial, or both) .
 Dehydration (assessed by evaluating skin turgor, capillary refill, and mucous
membranes) .
Supportive care is the mainstay of therapy for RSV infection. Although
corticosteroids are sometimes given, the available clinical data do not support their
use in the treatment of typical RSV bronchiolitis.
Pharmacologic therapies for RSV infe ction include the following:
1) Bronchodilators – These benefit at least a subset of patients with RSV -related
LRTI.

26 2) Alpha agonists – These have been used during acute bronchiolitis episodes, though
their efficacy has not been established.
3) Ribavirin – This agent is primarily reserved for patients with significant
underlying risk factors and severe acute RSV disease (eg, transplant recipients).
The following agents have been used in passive immunization to protect against RSV
infection:
1) RSV immune g lobulin intravenous (RSV -IGIV; no longer being manufactured).
2) Palivizumab (FDA -approved for prophylaxis in children at high risk for severe
RSV disease). [1]
The protocol regarding the application of vaccination in preterm child underwent
many changes in Israel. In Israel the guidelines are similar to guidelines in USA so
this evolution of protocol had similar changes in the last few years. In 2010 till the
end of this year in Israel were receiving this vaccination as part of guideline only
infant born before end of 29 weeks of gestation but in 2011 this guidelines changed.
A research done i n Soroca hosp ital in Israel by professor David G rinberg was
compared the risk of hospitalization in children department and children ICU due to
pneumonia with the pr esence of RSV as the etiology in children less then 5 years that
were born 30 -35 week of gestation in comparison with children born after 36 weeks.
During this research in between the years 2001 -2010 in this hospital were born
130,164 infants when 2,859 we re born between 30 -35 weeks of gestation. In this
research was included children bellow 5 years with community acquired alveolar
pneumonia diagnosed by chest x -ray. Pneumonia was diagnosed in 6,589 of this
children and a positive nasal culture for RSV in 2 .216 (33.6%).
The r ate of hospitalization due to C AP in the season of RSV (November -march) 26.1
to 1000 born in term and 136.1 to 1000 born between weeks 30 -35. The average risk
for premature infants in compare with term infants is 5.7.
The same hospitaliz ation in ICU department was 0.7 to 1000 n term child and 10.7 in
child born in 30 -35 weeks of gestation. And the relative risk is 17.8.

27 Also the relative risk to receive pneumonia due to RSV in pret erm child and in term
is by 6.4 and the relative risk to g et to ICU due to RSV was 31.3.
This increased risk was seen in children born in weeks 30 -31 as well as week 32 as
well as weeks 33 -35. Also is important to mention there was an increase in risk even
in late premature infant as well. It most be mentioned th at is the years there was not
reported any cases of pneumonia in children that received this vaccination for RSV.
This research was presented in the 2011 conference of ESPID. [18]
After this research the Israel government changes its protocol and recommend ation
regarding the administration of the RSV vaccination and the recombination were
changed to:
The vaccination called abbosinagys and by its generic name palivizumab which is
produced by genetic engineering and contains monoclonal antibodies for RSV . This
antibodies stay in blood for 30 days this vaccination is giving every month in
between the active month s of the virus which are November till March and giving in
the following groups of children:
1) Any children born preterm till 2 years of age that suffer from chronic
lung disease and are re ceiving oxygen therapy.
2) Children till 1 year that were born prematurely and had been diagnosed
with bronchopulmunary dysplasia. This diagnosis must be done by chest
x-ray and with clinical signs after the reaching to fix ed age of 36 weeks.
In addition they must have been needed for at least one of these
therapies: oxygen, diuretics, steroids, bronchotolytics.
3) Preterm born till 32+6 weeks and haven’t reach to 1 year in the season of
RSV
4) Preterm till 34+6 weeks and haven’t reach to 6 month of age at the
season of RSV.
5) Children suffering from congenital heart disease and with one of the
following criteria: are treated for CHF, infant with moderate to severe
pulmonary hypertension, or cyanotic heart defect.

28 6) Children how haven’ t reached to one year and were born less the 1 kg
without relation to the gestational age.
7) Children how are not 1 year and suffer from sever chronic pulmonary
disease without relation to age they were born. [19]
Today there is an essential update regarding the prophylaxis for RSV.
By new data that has been established this year in America there is considerable
amount of information that changes completely the current view on vaccine
prophylaxis. The American Academy of Pediatrics has released updated guidelines
addressing palivizumab prophylaxis for respiratory syncytial virus (RSV).
According to the updated recommendations, palivizumab prophylaxis for RSV
should be limite d to infants born before 29 weeks' gestation and to infants with
chronic illness such as congenital heart disease or chronic lung disease. Other
recommendations include the following:
 Give infants who qualify for prophylaxis in the first year of life no mo re than
five monthly doses of palivizumab (15 mg/kg per dose) during the RSV season
 In the second year of life, palivizumab prophylaxis is recommended only for
children who needed supplemental oxygen for 28 days or more after birth and who
continue to need medical intervention (supplemental oxygen, chronic corticosteroid,
or diuretic therapy). [17]

29 “Table 1.1”
2.3 Israel data and statistics regarding preterm children and there care.
subject 2008 2009 2010 2011 2012
Num of birth 156923 161,042 166255 166800 170940
Num of preterm
(till 36+6) 14123
(8.9%) of
child
birth 14493
(8.9%) 14963
(9%) 15012
(9%) 15385
(9%)
very preterm
(till 33+6) 2825
(20%) of
preterm 2899
(20%) 2993
(20%) 3002
(20%) 3077
(20%)
Preterm Born between
34-37 week 11298 11594 11970 12010 12308
Born <1.5kg
They are 10% of
preterm birth 1571
(1%) of
birth 1654 (1%) 1626
(1%) 1668
(1%) 1709
(1%)
Born >1.5 kg 12552 12839 13337 13344 13676
Num of preterm born
between 30 -35 week
how had infection 887
(13,6%) 910
(13,6%) 940
(13,6%) 943
(13,6) 966
(13,6%)
Num of preterm <1.5kg
how had sepsis in first
hospitalization 388
(26,7%)
of <1.5
kg 361
(24,2%) 345
(23,6%) 322
(22,8%)

30 Preterm born <1.5 kg
how died in hospital in
first hospitalization 245
(15%) of
<1.5 kg 298 (18%) 295
(18%) 237
(15,3%)
Num of neonatologist
shortage in the health
system -173 -173 -173 -180 -180
Num of nurses
shortage in preterm
children ICU -700 -700 -700 -700 -700
Number of beds
shortage in
neonatological
department -240 -240 -240 -195 -150
Preterm infant no
receiving the correct
guidance and food
adjustment to there
needs -11,298 -11,594 -11,970 -12,010 -12,308
Num of children how
should receive RSV
vaccination (35+6) 6,837 7,016 7,245 7,269 7,443
Num of children that
should but don’t
receive RSV vaccine -6,069 -5,412 -4,961 -4,978 -4,833
[17]
T- term infant/P – preterm infant

31 “Table 1.2”
2.4 Moldova data and statistics regarding preterm children
subject 2009 2010 2011 2012 2013
Num of birth alive 40803 40474 38979 39879 39259
Num of preterm 4.8% 5% 4.7% 5% 4.8%
From women gave
birth had previously
preterm delivery 1011
2.6% 1407
3.5% 583
1,5%
From women gave
birth had previously
term baby with
<2.5kg 465
1.2% 1194
3% 369
0.9%
Num of born with 5
min Apgar score > 6 304
0.8% 276
0.7% 256
0.6%
Num of birth with
emotional support 22713
58.3% 29040
72.8% 24216
61.7%
Num of new born
with blood infection 291
0.7% 150
0.4%
Num of affection in
new born at
term/preterm
In 1000 from: T:183
P:1997 T:239
P:1715 T:206
P:1963 T:306
P:1932 T:325
P:1704
Respiratory
affection T:0.3
P:0.5 T:0.2
P:0.5 T:0.2
P:2.4 T:1
P:7.1 T:0.1
P:2.3
Pneumonia T:1.1
P:12.7 T:2.6
P:15.4 T:1.2
P:6.5 T:3.3
P:6.5 T:1.4
P:8.6
Skin infection T:1.4
P: T:1.1
P:1.6 T:0.8
P: T:0.5
P:0.5 T:0.2
Congenital T:16.2 T:17.8 T:16 T:15.4 T:15.9

32 malformations P:58 P:51 P:52 P:29.4 P:37.6
Other specific
affection during
perinatal period T:135.9
P: 1784 T:189
P:1489 T:206
P: T:222
P:1659 T:241
P:1518
IUGR T:35
P:526 T:55
P:678 T:47.7
P:821 T:40
711 T:54
607
Intracranial
hemorrhage during
labor T:1.4
P:1.6 T:0.4
P:3.2 T:0.7
P:1.8 T:0.9
P:2.2 T:1.6
P:4
Other labor
affection of CNS T:8
P:11.1 T:6
P:18.1 T:5.9
P:16.6 T:5.7
P:8.2 T:4.9
P:6.4
Intrauterine hypoxia
and labor asphyxia T:17.4
P:100.7 T:17.4
P:99.8 T:17.7
P:82 T:16.2
P:71 T:13.8
54.8
Respiratory
insufficiency T:8.9
P:145 T:8.1
P:144 T:8.3
P:147 T:11.9
P:141.4 T:12.9
P:157.4
Congenital
pneumopathy T:20.3
P:220 T:23.3
P:210 T:30.8
P:177 T:17.7
P:135.9 T:20
P:124.9
Bacterial infection T:1.5
P:22 T:1.7
P:28 T:1.9
P:27.8 T:1.4
P:21.8 T:0.7
P:16
Non labor
intracranial
hemorrhage T:2.9
P:48 T:2.2
P:15 T:2.1
P:21.9 T:1.9
P:13.6 T:0.6
P:11.4
Hemolytic newborn
disease T:16.7
P:59 T:11.6
P:48 T:14,8
P:66.8 T:11.3
P:11.4 T:14.3
P:13.1

[7],[8],[9],[10],[11].
T- term infant/P – preterm infant

33

“Fig.1.1 Dynamics of preterm delivery in Moldova 1990 -2012”

In republic of Moldova in 2012 was registered preterm delivery 4.68% by department
of statistics of RM. “ Born Too Soon : The Global Action Report on Preterm Birth ,
2012 ” that did a report on 184 contries reports that in 2012 RM had a rate of 11% of
preterm delivery.

34

“Fig.1.2 Proportion of preterm birth in RM in years 2000 -2012 in different
group of wight at birth ”

In the last 10 years the number of preterm birth with birth weight less then 1.5 kg as
decreased in 30%. Number of birth between 1.5 -2 kg has increased in 20%.

“Fig.1.3 Newborn survivals in different weight categories in years 2000 -2012”

35 2.5 Syntheses of the materials and research methods
The materials I have collected in my work have showed me a great deal of changes
occurring in the past years in regards to preterm delivery. This change attributes to
different changes in management protocol as well as to difference in statistical data
regarding the variety of consequences following the preterm delivery. This large vary
in statistical data show that each country tries the best to optimize the outcome of this
population of children by adapting to new information and researches as maximum as
possible with regard of the countries financial and professional abilities. But still
there is a visible delay in new information integration into the health system seen in
RM with the help of this statistics . Its shown the most of the new information for
example as RSV vaccination and Magnesium sulphate effectiveness as not been fully
incorporated into the health system and it might take a while until this information
will be used for adjustment to a better c are of this population of children.

36 III Personal results and discussion
3.1Table 1.1 interpretation
This is the report of preterm infant situation in Israel for the years 2008 -2012. This
report gives a comprising scanning of the situation of all preterm infants in this 5
years and pay attention to different spectrums connect to health and quality of life of
the preterm infants and their families. The most import finding of this report are:
1) The number of preterm delivery and always increasin g
2) There is a stop in increase of the preterm infant death – as they were increasing
in the last years but you can see that in 2011 already died 237 which much less
by 58 then previous year.
3) There is a severe and consistent shortage in doctors, nurses, beds in ICU
departments that does not fit the increasing rate in child birth
4) There is a decreasing in cases of sepsis but the cases of respiratory infection are
left the same. Pneumonia is evident in 1 of each 8 preterm in the first 5 years of
there life w hich is 5 time as much as term child.
5) In 2012 , 145 more preterm infant were entitled of the RSV vaccination which
left 4,833 preterm infant not entitled although there chances to get RSV are
completely the same. (weeks 34 -35)
6) 80% of preterm infant are not receiving the appropriate initial care, the correct
adjustment of food to there needs, and the guidance of a professional during
there hospitalization.
Most of the researches in the world regarding the different groups of preterm infants
as in different we eks and different weights point out that the preemie s born close to
term (weeks 34 -37) most get a very similar treatment as other group of preterm
infant. For this reason today the international definition for preterm is before 37
weeks of gestation.
Morbi dity and mortality
The rates of morbidity don’t show any improvement in year 2008. But most be
mentioned a small improvement in the rates of sepsis in the last years. The

37 rehospitalization with respiratory infection in children shows the worse scenario fo r
the morbidity of preterm children. One out of 8 children born between 30 -35 weeks
of gestation will return for rehospitalization in the first 5 years of there life due to
pneumonia. And this rate is higher 5 times then in term children. We most mention
that the rate of receiving an infection in preterm ICU during first hospitalization is
higher in Israel in 50% more then other developed countries. In 2008 till 2010 we so
increasing rate of mortality in infant born <1.5kg from 15.6% till 18% but it was sto p
in 2011. But even thought the mortality of very low birth weight in Israel is still
higher then in other developed countries. And stand on for 2013 on 12.4%. We most
mention that the rate of mortality in Israel for preterm infant is calculated only
regarding children born <1.5 kg because the rest of preterm children mortality rates
go under calculation with the term infant mortality rate.
Shortage in staff
Neonatology in Israel today is considered one of specialties most i n distress due to its
shortage on staff, equipment and infrastructure. By the report of medical management
of ministry of health of Israel in November 2010 was recommended to add 173
doctors, 700 nurses, 240 beds to the NICU this is the minimum number need to NICU
to allow appropriate care of the preterm infants to reduce the morbidity and mortality
among this population. This recommendation was calculated by an estima te that
should be one nurse for each 1.5 NCIU beds. From all the shortage of 180
neonatolo gists for all infant: 2008 -2010 the shortage for preterm NICU specialist is –
87 and in 2011 -2012 is -75. Due to this severe situation the health department
decided to do some changes in 2013 and gave an extra 29 doctors, 30 nurses, and 40
beds.
Entitlement to primary care of newborn
Preterm born under 34 weeks will be admitted to NICU, were there will be staff
specialist in this field of preterm delivery, when a newborn born after 34 weeks will
go to a regular children department of term children where ill be treated as a term
child! In comparison to a preterm child which can be kept for few month in the

38 hospital the newborn born after 34 weeks will stay only 72 hours as all term children
although he his premature. There is a high importance that preterm inf ant will be in
NICU where there are specialist which studied the peculiarities and the specific
disease, there pathogenesis, and there unique treatment characterizing the preterm
infants. In NICU the conditions of hospitalization are very sterile to preven t
infections and give the optimal environment needed for the preemies. In addition the
correct medical equipment for preemies is only found in the NICU. A preemie born
after 34 weeks gets nursery there he his treated as all children when 304 nurses take
care of 60 beds, what makes it hard to give personal attention and doesn’t allow
alertness regarding to any change in the state of the preemie. There is not optimal
condition or the correct equipment to deal with the specific peculiarities of preterm
infant therapy.
The entitlement for RSV vaccination
The RSV virus is the most common cause of pneumonia in children under 5 years
and for admission in NICU and for ventilation. The hospitalization also will increase
child risk for nosocomial infection. In additi on children without this vaccination we
see an increase in asthma and wheezing development that cause more absences from
school, lose of work days and diminished quality of life. Most of the preterm infants
don’t get this vaccination due to the fact them d on’t stand in the criteria for receiving
it but still in the same risk to get RSV like other preterm children. Today in Israel
only a third of the preterm children that should receive the vaccine stand in the
criteria for receiving it. This means that only children born at 23+6 and 33+6 how do
not have 6 month of age at November will get the vaccine and not all children till
35+6 that should have it by the last research data. And they are 1/3 of this population
of preterm children and that is despite the fa ct that all children till 37 weeks haven’t
got there lung developed yet! This is the reason that the non vaccinated children have
increase in hospitalization and pneumonia.

39 The way of calculation: number of children till 35+6 are 7,443 (2012 ), children til l
32+6 and 33+6 ( not 6 month age till November) are 2,610(2012). This make the 35%
of the children how should receive the vaccine.
Another example is 7,260(35+6) in 2011 and had received by criteria only
2,291(2011) this is 31% of children how should have received .
3.2 Table 1.2 interpretation
1) 1st thing I noticed is the decreasing of live birth in Moldova. This is not the
subject of my thesis but I do consider it to be due to negative immigration and
decrease I population in Moldova and not due to any medical reason.
2) Number of preterm delivery is q uit stable in the last years at a rate of 5% by
Moldavian statistical data but as I mentioned in “fig 1.1” it is not considered to
be true by “ Born Too Soon : The Global Action Report on Preterm Birth , 2012 ”
which insist that by there statistical data in RM it is a rate of 11% of preterm
delivery i cant explain the reseon for this deifferances but i can assume it is due
to inaproppriate collection of data espacially in rural areas which are probably
not done by the book or at all.
3) Another point is the decre asing of secondary cases of preterm delivery in
women how had previously preterm delivery or a baby burn <2.5 kg. This I
consider to be an example of correct management in the field of prophylaxis
and more specifically in education of women for correct ass essment of signs
and symptoms that might become preterm delivery if not treated.
4) Although I can see by statistical data the significant decrease in pneumonia
among the children born preterm which can be attributed to the antibiotic
protocol given in management of preterm delivery in Moldova I see on the
other hand stable number in the lung affection section which include more
affections then only pneumonia. This may include bronchitis and bronchiolitis
which can be defiantly connected to RSV and the a bsence of the prophylaxis
against this virus. As you can see in the 3 chapter this virus constitute the main

40 reason for preterm lung affection and by today researches need to be
prophylactically treated.
5) Congenital malformations and IUGR are varying these years between
decreasing and increasing all the time. A contribute this fact to that in Moldova
1st screening of pregnant women is done after 18 weeks of gestation. In Israel
in comparison 1st screening is done between 14 -16 weeks and the 2nd and more
detailed is done between 18 -24 weeks. The current data in Israel show that in
the 1st screening 75% of congenital anatomical anomalies are found and given
the women a choice of stopping pregnancy in an early stage as possible. This
factor does no t exist today in RM and it what contributes to the increasing or
stability of congenital malformations and IUGR.
6) Intracranial hemorrhage during labor and other CNS affections during labor
tripled in the last 5 years in RM, by my opinion for a few reasons. One will be
the aggressive induction of labor with cytotec due to the fact that in Moldova
doesn’t exist small doses of cytotec pill and this fact cause doctors to break
manually the pill into two or four which cause an unsupervised dosage of the
drug whic h can be a as a consequence of aggressive contractions leading to
trauma of the fetus intrapartum. The other cause is due to increasing in use of
additional instrumentation in labor more frequently due to either loss of
patience of the doctor or of the pat ient during labor which was not present or
not so regular previous years.
7) A decreasing in half is shown in intrauterine hypoxia and labor asphyxia which
in my opinion can be thanks to non stop cardiac monitoring which as
developed and inserted in institut ed of RM in the past years more beneficially.
8) Respiratory insufficiency remains a problem for RM. Although in the
management protocol of preterm delivery is implied glucocorticosteroid
therapy in all women with suspicion on preterm delivery or only with PR OM.
We should consider which could be the factor that brings this problem. Is the
incorrect dosage of corticosteroids? Or maybe this protocol is not applied in all

41 institutes? What could be other factors that may cause respiratory
insufficiency? Or maybe t here is incorrect combination of tocolytic therapy
with corticosteroid therapy? This is a question that remains to be discussed
9) Bacterial infections are defiantly decreasing and this is due to prophylactic
treatment with antibiotics and a correct managemen t of PROM
10) Hemolytic disease of newborn as decreased in 4 times that is due to education
of women and screening test to identify women with potential risk and correctly
educating them about the possible outcomes of secondary pregnancy and the
possibilit y to give immunological therapy in 1st pregnancy to prevent
complications after.
“Table 1.3”
Differences between RM and Israel 2012 with preterm children
Israel Moldova
Num of birth 170940 39879
% of preterm birth 9% 5%
<1.5 kg of all preemies 10% of preterm or 1% of
all birth 1% of all birth
% of preterm infant with
infection in hospital 13.6% 21%
% of preterm infant how
died in hospital <1.5kg 15% 20%

In this table I used table (1.1 and 1.2) with addition of figures (1.2 and 1.3) and
established a comparison between Moldova and Israel in order to may some
conclusions. As you can see the rate of preterm delivery is different but this is a
matter of discussion in Moldova as statistics there very disconnected to statistics
done in Europea n countries as regards to Moldova. Category of preterm less then
1.5 kg is the same in both countries and may be attributed to the fact that

42 prophylactic measures in both countries to prevent preterm delivery are still in
they’re 1st steps. There is still a better management protocol for the premature
infants and for labor management which contribute for the slight difference
between mortality rate of <1.5kg category of preemies and in rate of infection of
these infants. This should be discussed in more det ails and look for ways of
improvement in order to maximize outcome of this infants in both countries.
3.3 syntheses of personal results
1) For the 1st objective I found out that the current protocol in management of
preterm delivery is showing a change in the outcome in the past few years. To
elaborate I am talking about antibiotic treatment which has shown a great
improvement in the rate of infant infections in Moldova. Although in Israel the
rate didn’t change but it is lower then in Moldova for many years so maybe
there is a place for additional protocol reassessment to see some changes in the
infection rates. The other point is the cortico steroid protocol used in Moldova
which haven’t shown a change in rate of respiratory insufficiency among
preterm infant and should be reconsidered to be added or changed. The new
protocol in Moldova about magnesium sulphate has no statistical data in this
country yet but in Israel it has already successful trails showing the beneficial
outcome of this treatment in prevention of cerebral palsy and must be adjusted
in Moldova to the worldwide used protocol regarding this therapy and its
application. Another p oint is the usage of RSV vaccine which shows in many
researches a beneficial effect in decreasing rate of respiratory infection among
the preterm population. Unfortunately it is yet to enter the Moldova protocol
and It is a must to be discussed.
2) If we wan t to exclude other aspect which could interfere with correct
management of preterm delivery and its outcome we should look at the Israel
statistic and see that regarding the presence of world wide used protocol there
hasn’t been change in statistic in the past few years in the field of infection of
preterm children, the among in regard to all birth, in the survival rate of this

43 infants and in the number of cases of sepsis. All of this can be attributed to
other aspects including the factors that there hasn’ t been change in the shortage
of staff in the hospital, in the shortage of beds in NICU, in the shortage of
correct guidance and food adjustment for this population of infants and in the
among of preterm children which should receive RSV vaccination and st ill
don’t. all this factors can attribute to the stability and no good or bad change in
statistical data in Israel.
3) The approaches to consider to add in Moldova from my statistical point o view
is to consider adding the RSV vaccination to minimize the resp iratory
complications in children of prematurity in the form of administration as it this
mentioned in my thesis. Another important topic is to increase the knowledge
in all institutes regarding the good results of Magnesium Sulphate treatment
and to add i t in all hospitals in the country in the recommended doses by the
researches I have mentioned in the chapter about Magnesium Sulphate.
Approaches that should be considered in Israel from Moldova are if in fact the
data established by Moldova statistic rega rding the number of preterm birth
from all birth is the correct data then Israel should look for a reason that can
explain the low rate in order to corporate it into her own protocol. We should
consider if this difference is mainly due to education and mat ernal knowledge
which is better in Moldova or is it due to another influencing factor? An
example of this kind of factor may be the low medium age of mother during
pregnancy in Moldova in comparison with a high medium age in Israel as a
risk factor for pre maturity.
4) The last point I want to consider is my conclusion about which field should be
researched better and in this point I recommend to research more deeper the
effects of RSV vaccination and its beneficially, the optimization of tocolytic
therapy to e nlarge the prolongation of pregnancy as possible and the field of
corticosteroid therapy and to find the best approach that will show as maximal
improvement in the long run.

44 Conclusions
1. The current protocol of management of preterm delivery both in Israel
and in RM as shown many changes in the past years some of that
changes are beneficial but a big part still shows a need for farther
investigation of this field.
2. I found that there are many aspect that could interfere with the correct
establishment of manag ement preterm delivery that are not part of the
management but are big influence on the consequences of child health.
(example is staff, equipment, economical state.)
3. I found approaches that exist in Israel and should be integrated in the
health system in Moldova and should be revised (example is addition of
RSV vaccination, applying magnesium sulphate protocol, revising
protocol of labor induction.)
4. I found that both in RM and in Israel there are unclear result about
children born premature health and the management of this population
needs to be overviewed with the questions of making changes with
relation to new data established in last years in order to optimize the
consequences and receive the best outcome.

45 Attachments

“Fig.1.4 results of meta analysis”

46

“Fig.1.5 results a 5 randomized trails on magnesium sulphate"

47

I hereby declare that the diploma thesis entitled " Preterm delivery management
and protocols and their influence on preterm children health consequences ” Is
written by me and has not been presented before at another college or institution of
Higher education in the country or abroad. Also, I declare that all sources used,
Including the Internet sources, are indicated in the paper, considering the rules for
avoiding plagiarism:
– All text fragments are reproduced exactly, even the proper translations from other
Languages are written in quotes and have detailed reference source;
– paraphrasing in own words of text written by other authors has detailed reference;
– Summary of the ideas of other authors has a detailed reference to the original text.

Date _______________

Name and surname of student: Korotkov Zoya
fdddddddddddddddddddddddddddddddddddddfddddddddddddddddd __________

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