International conference «Actual approaches to the extremely preterm babies: International experience and Ukrainian realities» (Kyiv, Ukraine, March 5-6, 2013)

1. Implementation of
neurodevelopmental monitoring
service for high risk newborns:
Republic of Moldova experience
A.М. Kurtyanu
Mother and Child Healthcare
Research Institute
Kishinev, Republic of Moldova

2. Report goals
• Abstract on psychomotor development of
preterm infants on the basis of literature
data
• Structure and functions of Republican
Diagnostics and monitoring Service for
high risk neonates (Neonatal Follow-up).
• Internal study results

3. The highest obsterical risks - annual results
Preterm labour 13 000 000
Costs 26 000 000 000 US$
Preterm
labour rates
10-12 % 5,5 – 11,4 %
≥ 30%
% of preterm labours in R. of Moldova,
1990-2012
5,2
5,1 5
5
4,79 12,1%
4,8 4,68
4,5
4,6
4,37
4,4
4,2
4 Tracy SK et al, BJOG 2007,Langhoff-Roos, J et al BMJ 2006,
1990. 2000. 2005. 2010. 2011. 2012. Grijbovski AM, Public Heath 2005
According to findings of the study held in 184 countries (2010), the rates are as follow: R..
Moldova (11,0%), Ukraine (6,5%), Romania (7,3%), Switzerland (7,4%), USA (12,0%), Russia 3
(12,0%) worldwide (11,1%) (Born Too Soon: The Global Action Report on Preterm Birth, 2012).

4. Prematurity & low birth weight (%)
Characteristic RM Ukraine Romania USA Russia
< 1,000 g 0,4 0,4 0,3 0,7 0,28
Most of the (99,3%)
preterm infants
(live-born)
1,000-2,500 g 63,9% 5,6 4,7 5,6 7,2 5,48
-preterm infants
> 2,500 g 94,0 94,3 91,1 92,1 94,2
7,6% - preterm infants

5. Survival rates of newborns with different weight
categories in R. of Moldova (2000-2012)
0,98 0,985 0,988
0,947 0,961 0,96 0,959
0,934 0,945
0,919
0,841 85% 0,863
0,814
0,806
0,777
1500-1999
0,601 2000-2499
500-999
0,522
42,70% 1000-1499
0,399
0,369
0,317
0,0538
0,0164
2000. 2005. 2009. 2010 2011. 2012.

6. Survival of neonates in MACH RI at different
gestational age , 2012
100
100 100
80 94,9 98 97,9 95,9 100
80 91 92,9
50 50 65,2
60 68
32
40 50 50 34,8 49 50 51 47
42
20 48 54
20 0 23 22
0
02 5 8 14 25 Mortalitatea
Mortalitate
0 0 nascuti
9 7,1 6,1 Nașteri
Supravetuirea
22 s.g.
2
23 s.g.
Supravețuirea
24 s.g.
0 2,1
25 s.g.
4,1
26 s.g.
27 s.g.
28 s.g.
0
29 s.g.
30 s.g.
31 s.g.
32 s.g.
33 s.g.
34 s.g.
35 s.g.
36 s.g.
Concluzii: supravețuirea invers proporțională termenului de gestație:
Conclusions: inverse proportion is observed between survival and gestational age
22 - 23 s.g. – supravețuire – 0% 26 – 28 s.g. – supravețuire - 61,0%
22-23 weeks – 0% 26-28 weeks – 61%
24 - 25 s.g. – supravețuire – 35,0% 29 – 32 s.g. – supravețuire - 96,2%
24-25 weeks – 35% 29-32 weeks – 96.2% 89,8%

7. Abstract on psychomotor development
of preterm infants on the basis of
literature data
Psychomotor, neurosensory , cognitive and behavioural
disfunctions.

8. Survival and short-term morbidity in
preterm infants
Mercer BM. Obstet Gynecol 2003;101:178-93

9. Healthresults for preterm infants
• Long-term • Intrauterine programming
– 1 of 5 with mental – Weaker reproductive
development delay health
– 1 of 3 with poor vision – High risk of preterm
– 50% of infants with labour for descendants
cerebral palsy – Diabetes mellitus
– 5 times higher risk of – Ishemic heart desease
infant mortality: RR 1.5
• boys (22-32 weeks)
• girls (22-28 weeks)
Spong CY et al, Obstet Gynecol 2009

10. Preterm infants health results
Survival with 23 weeks of GA.:
1/3 cerebral palsy with blindness/deafness.
Suvival with 24 weeks of GA.:
Psychomotor development delay 22 - 45%.
Suvival with 25 weeks of GA.:
Multiple disfunctions of severe psychmotor
development 12 - 35%.
These rates have not changed since 90-ies!!!
Hack M; Fanaroff A

11. Psychomotor development deficit in preterm
infants born with extremely low birth weight
(ELBW) - global trends
Age at Values
GA,
Country / authors Years examination,
weeks Number %
years
Conclusion: cerebral palsy value varies per country

12. Number of neonates with severe form of psychomotor
development depending on GA <26 s.g.
Cerebral palsy Confidence
Age, weeks.
distribution, % interval
23 34 Insufficient data
24 22-45 6-48, 28-64
25 12-35 3-27, 15-59
Total value 31
12 studies which investigated correlation between psychomotor
development and GA, at 12 and 36 month of corrected age

13. Health results of preterm infants born live with
ELBW at 18-22 month
Incomplete FU
Discontinued
Died
Severe disorders
Mild disorders
Normal develoment

14. Mortality, morbidity and survival without
severe adverse outcomes
Prospective study (120 days of life) from 01.1990 to 12.2002 in 16 centres of National Institute of Child
Health & Human Development Neonatal Research Network.
NICHD Neonatal Research Network centers (n = 16) [Fanaroff et all 2007]

15. Survival factors
• Gestational age: inverse ratio
• Birth weight: infants with SBW have the weakest results
• Gender: survival ↑ for girls
• Labours at third level institutes: ↑ survival
• Antenatal steroids: ↑ survival ; number of disabled is the same, at
postnatal period 
• Labour conditions and intensive care: proper ↑ survival
• Treatment with surfactant: ↑ survival; number of disabled is the same
• Hypothermia prevention
• Postnatal steroids administration decrease: ↓IVH
• Monocyesis
• Weight growth
• Multiple birth: ↓ survival and ↑ morbidity
• Sepsis: ↓ survival
• Cesarean section (pelvic presentation): controversial data
[4446 births at 22-25 weeks of GA Tyson et all 2008]

16. Factors that affect the development
of cerebral damage
• Its development is influenced by the start,
duration and severity of injury
– Term / preterm infant
– Extensive / local injury
– Acute / chronic
– Number of available injuring mechanisms
(strokes)

17. Prognosis factors MDI < 70
NICHD Data -- 1151 infants < 1000 g.

18. Prognosis factors PDI < 70
NICHD Data -- 1151 infants < 1000 g.

19. Cerebral development phases
Structuring of neurons
Migration
Myelination
Proliferation
Glial cells differentiation
Subplate
Cortical folding
Weeks 10 15 20 25 30 35 40
of gestation
23 40 Latal, 2003

20. Cortical development and
differentiation
Preterm infant (25 weeks) Term infant
(IRM ponderee T2)

21. Cortical development (surface)
27 weeks 32 weeks 35 weeks

22. Effects of clinical interventions on CNS
development
• More detailed studies are needed to investigate
the effectiveness and damaging impact of clinical
interventions on CNS
– For example, the use of corticosteroids at postnatal period
Cerebral cortical gray matter volumes.
300
Cerebralcortical gray matter volume (cc)
250
200
150
100
50
0
Cortical gray matter volume 35% in Term Preterm @ Term Preterm @ Term
preterm infant treated with No Steroids Steroids
dexametazone
Murphy BP et al 2001

23. Other factors affecting the
development of CNS
• Future development depends rather on
gestational age than on the birth weight (BW)
– The literature is mostly based on BW, which influences
the results accuracy of the studies (bias)
• The range and severity of development disorders are
often underestimated if observation stops in the early
childhood.
– EPICURE ( 26 weeks of gestation):
• No severe adverse effects at 30 months : 76% vs
63% at 6 years (sustainable result stays by 11
years)
[Marlow et al 2009]

24.  Mortality /  morbidity
• Antenatal corticosteroid therapy:
– 20%: 1990-1991
– 79%: 1997-2002
• Ante/ intrapartum antibiotic therapy:
– 31%: 1990-1991
– 70% 1997-2002
• I (1982–1989) (n = 496)
• II (1990–1999) (n = 749)
• III (2000–2002) (n = 233)
– At 20 months of corrected age
• Between I and II:  survival from 49% to 68% =  morbidity
• Between II и III:  CP from 13% to 5%   morbidity from 35% to 23%
[Wilson-Costello et al 2007]

25. Differences between the studies (I)
Characteristic EPICURE EPICURE EPIPAGE Suede Ulm
(short-term) (long-term) (long-term) 1992-1998 1996-
1995 1997 1999
Survival rate at 424 424 119 103 48
25 weeks of GA
Examination age 30 months 6 years 5 years 3 years 5.6 years
No poor 142 (76%) 118 (63%) Data available 70 (89%) 29 (71%)
outcomes within only for 24-28
study period ( % of SA group total :
infants admitted to 92% (out of
NICU)
examined infants)
No poor 35 (24%) Data available
outcomes ( % of only for 24-28
examined neonates) SA group total
52%
Mid-term and long-term results in infants born at 25 weeks of GA in population studies and in one
specialized centre

26. Differences between the studies (II)
• Severe retardation is often diagnosed
– < 2 years
– by a well-trained pediatrician
• Mild and moderate underdevelopment are
diagnosed later and should be discovered
– Specialized consultation

27. Results / cerebral palsy
• Severe retardation - Cerebral palsy
about 10%
• Moderate and mild • < 1500 g
development deficit - – 5%
30 - 50%
• No retardation
• < 1000 g
– 15-20%
• Decreasing?
[ Platt MJ et al 2007]

28. Chronic lungs desease and survival in 385 neonates
with ELBW in 11 centres of South America
100%
According to the
90% studies
development is
80%
mostly influenced
70% by
50% respiratory
60% disfunctions than
50% by cerebral ones
40%
30% Survival at RDS
30%
20% BPD
10% 20%
Mortality
0%
A B C D E F G H I J K TOTAL
GRUPO COLABORATIVO NEOCOSUR, J. Perinatol 2002;22:2-7

29. Structure and functions of Republican
Diagnostics and Monitoring Service for
neonates from high risk groups (Neonatal
Follow-up).
3 development phases
1. Establishment
2. Regionalizitation and reinforcement
3. Monitoring of functions as a part of
Early Intervention Service

30. Implementation of advanced technologies into
intensive and routine neonatal care system
1/01/2008, the Rupublic of Moldova adopted WHO and EU criteria and standards
of live-born neonates registration

31. 1. Standards.
Documents issued within the framework of Neonatal
Diagnostics and Monitoring Service
• As a result, Order No. 455/137/131 of December 10, 2007 was
jointly issued by the Ministry of Healthcare, Ministry of
Information Technologies and National Bureau of Statistics in
order to start official statistical registration of labours and
neonates with birth weight over 500 g and gestational age
over 22 weeks.
• In order to comply with the requirements of Declaration of
Millenium Development Goals and according to the activities
regulated by National Healthcare Policy for 2007-2021 and
Healthcare System Development Strategy for 2008-2017, there
was a Republican Neonatal Diagnostics and Monitoring
Service established and implemented according to the Order
No. 118 of 19/02/2010 of the Ministry of Healthcare which
covered high risk infants groups up to 2 years of corrected
age.

32. Standards (2).
Documents issued within the framework of Neonatal
Diagnostics and Monitoring Service
1. Regulations on the Republican Neonatal Monitoring
System for infants up to two years.
2. Functional responsibilities of the person in charge from
the Centre of Family Physicians who coordinates the
operation of Neonatal Monitoring System.
3. Instructions for family doctor and pediatrician
regulating their responsibilities within the Neonatal
Monitoring System.
4. Documents regulating the introduction of Neonatal
Monitoring Service into early development system for
children up to five years.

33. 2. Regionalization of Diagnostics and Monitoring Service for
high risk neonates.
3. Equipment supply
Kishinev
Bălţi
MACH RI
Republican Centre of
Regional Centre Neonatal Diagnostics
and Monitoring
Kishinev
Municipal Hospital No.
1,
Municipal Centre
Ceadir-Lunga
Cahul
Regional
Regional Centre
Centre

34. Structure of the Republican Centre of
diagnistocs and monitoring for high-risk
neonates
Low and very low birth weight
Neonatal neurologic
Doctor's room.
neonates care unit
Database
unit
Active invitation
Pediatric examination Pediatric examination
room with BSID tools room with BINS tools
Screening cabinet
Ultrasound screening EEG examination (audiometry and
room room ophthalmoscopy)

35. 4. Medical personnel training
• Theoretical and practical workshop on Neurological
pathologies in term and preterm neonates, 2007- 40
neonatologists (33%)
• 2 workshops on Neural development assessment for
neonates discharged from NICU (with support of US
instructors)
– Giuleşti Hospital, Bucharest, Romania, 2007 – 3 specialists
– MACHI, 2009 - 25 neonatologists and neonatal neurologists
• 2 internships (1 neurologist) on EEG use - Giulesti hospital,
Bucharest, Romania (2007), Follow up, clinical and social
rehabilitation of neonates from hight risk groups, France - 1
month.
• 1 training in the Centre Follow up, RCIT, Jaşi, Romania –
3 specialists
• Visit that included theoretical and practical training at
the working place (Dr. R.Ha Vin Leutcher, HUG,
Switzerland, (2010), 12 specialists from MACI, HospitalNo. 1
Kishinev, and Beltz Rehabilitation Centre

36. 4. Materials for medical personnel
1. Neonatal observation map
2. Booklet on Neonatal Diagnostic and Monitoring
Centre operation
3. Poster on Neonatal Diagnostic
and Monitoring Centre

37. 4. Materials for medical personnel and
mothers (1)
4. Preterm infants care basics
5. Kinetic therapy for preterm infants
6. Guideline for mothers of preterm infants

38. Goals of the Republican Centre of diagnistocs
and monitoring for high-risk neonates
↝ Specialized medical support for infants with high risk of
poor neurological outcomes.
↝ Definition of poor neurological outcomes risks using
BINS and BSID tools.
↝ Admission of infants with medium or high risk of poor
neurological outcomes to the monitoring programme.
↝ Specialized neural examination of infants having high risk
of poor neurological outcomes
↝ Paraclinical examinations: ultrasound, EEG, audiometry,
ophthalmoscopy.

39. The list of high risk neonates eligible for
Monitoring Programme
↝ Preterm infants with birth ↝ Periventricular leukomalacia
weight ≤ 1500g
↝ Severe hyperbilirubinemia
↝ Fetal growth and development (170 mmol/l within 24 hours or
delay (two standard 300 mmol/l within 48 hours
deviations) after delivery)
↝ Visual and audial disorders ↝ CNS infections (meningitis,
↝ Hypoxic-ishemic encephalitis)
encephalopathy (Sarnat II-III) ↝ Ulcerous necrotizing
↝ Seaizures at neonatal period enterocolitis
↝ Respiratory support (ALV or ↝ Bronchopulmonary dysplasia
CPAP ) ↝ Clear neurological symptoms
↝ Intraventricular hemorrhage at discharge
(grades III-IV)

40. Personnel of the Republican Centre of
diagnistocs and monitoring for high-risk
neonates
• Neonatologist
• Neurologist
• Rehabilitation / kinetic therapy specialist
• Audiologist
• Ophthalmologist
• Ultrasound diagnostician
• EEG specialist
• Psychologist
• Speech therapist

41. Follow-up neonatal Database
(2009-2012)
• Total number of infants included into the database -
1265
• Including 527 (41,7%) preterm infants with birth
weight <1500 g
• Number of infants who did not visit the centre
"Follow-up neonatal" – 320 (25,3%)
• 631 (49,8%) infants who survived up to 24 month of
corrected age
• 40 (31.6%) dead infants out of those who were
included into the Follow-up

42. Poor neurologic outcomes assessment
tools - BINS and BSID
Screening tests for risk
Neurologic functions (muscle
assessment
tone, movement /
(1-24 months)
asymmetry)
Expressive functions (motor
functions)
Receptive functions (visual,
audial, speech)
Cognitive functions

43. Infants development scale
(1-42 months)
The test includes 5 Cognitive functions
components:
Communication (receptive,
expressive)
Motor function
Social-emotional status
Adaptive status

44. Neonatal examinations calendar
• At admission to resuscitation unit and at discharge
• 3 months
• 6 months
• 12 months
• 18 months
• 24 months
Corrected age is calculated for preterm infants at 34
weeks of gestation.
Corrected age = Actual age + Gestational age - 40 weeks

45. Psychomotor development results in infants at
24 months of corrected age (155 cases) in RM.
Internal study results

46. Goal / Materials and methods
• Goal: to study the outcomes of neurological
development in preterm infants with BW ≤ 1500
g at 2 years of corrected age.
• Methods. Design. Retrospective descriptive
study at MACH RI from 01/01/2008 to 31/12/
2009.
• Analysis of health records of 93 newborns and 6
follow-up visits with the last one at 24 months.

47. Profiles of the study population
Total of premature infants with weight
≤ 1500 g born or referred to IIIrd level -
337
Died during neonatal Survived / dishcarged - 288
period - 49 Enrolled in Follow up program - 265
Died during Follow up Lost to Follow-up program Enrolled in
period 159 follow-up
13
study at 2 y -
93
Never 1 visit
Never Came Came ≥ 35
came 58
came 11 once 1 once l
2 visits
28
NDFU <1 y- 56 3 visits
15
4 visits
NDFU ≥1 y - 45 18
5 visits
5

48. Gestational age of newborns enrolled in the
study
GA, weeks Number %
34-32 17 18,2
31-29 44 47,3
77,4%
28-27 28 30,1
26-25 4 4,3
Total 93 100

49. Morbidity of examined newborns at
discharge
Pathology abs. nr. %
Early sepsis 13 13,9
16%
Late-onset sepsis 2 2,1
Meningitis 7 7,2
Pneumonia 66 70,9
NEC 4 4,3
RDS: Severe 8 8,6 47,3%
Medium 36 38,7
Mild 18 19,4
IVH gr. I 16 17,2
IVH gr. II 12 12,9
15%
IVH gr. III 2 2,1
PVL 2 2,1

50. Results of psychological assessment using BSID III
at 2 years of corrected age, 93 infants
Motor
Cognitiv Speech
Test Explanation function
Nr. % Nr. % Nr. %
>85 Norm 79 84,9 73 78,4 80 85,4
70-84 Development 5 5,3 11 11,8 2 2,1
delay
69 Severe 9 9,6 9 9,6 11 11,8
psychomotor
delay
Conclusions: at 24 month of corrected age mostly cognitive (14.9%) and
speech (21.4%) functions have been observed, 85.4% of examined
participants had normal neurological development.

51. Neurological disorders discovered at 12, 18 and 24
months
Nr. Pathology 12 months 18 months 24 months
abs % abs % abs %
1 Healthy 69 53% 83 63,8% 100 76,9%
2 Minimal brain dysfunction 25 19,2% 24 18,4% 13 10 %
3 Moderate disorders (of 18 13,8% 7 5,3% 1 0,7%
muscle tone)
4 Severe disorders 18 13,8% 16 12,3% 16 12,3%
--- Cerebral palsy 9 6,9% 10 7,6% 11 8,4%
---Hydrocephalus/ 5 3,8% 3 2,3% 3 2,3%
Ventriculomegaly
5 ROP 2 1,5%
6 Partial atrophy of optic nerve 0 3 2,6% 3 3,2%
--- Microcephaly 1 0,7% 1 0,7% 1 0,7%
--- Psihomot. retard. 3 2,3% 2 1,5% 1 0,7%
Minimal and moderate dysfunctions discovered at 12,18 and 24 dynamically decrease
and by 2 years of corrected age transform into the norm in 76.9% of all cases. Severe
disorders discovered at 1 year stay unchanged by 2 years. Morbidities observed most
often: cerebral palsy, ventriculomegaly / hydrocephalus.

52. Conclusions
• Survival of preterm neonates at ultimate vitality (over 26 weeks of
gestation) is low (~5,4% in 2005 and 42,7% in 2012).
• Development of national management standards for women with
high risk of preterm labour and deeply premature newborns (from
GA of 22-26 weeks) allowed to improve medical services quality,
lower adverse effects including poor neurological outcomes for
these neonates.
• In our study of neural development disorders we received the
results comparable with other authors which were influenced by
low number of infants with GA before 26 weeks.
• In terms of implementation of advanced technologies into
resuscitation service and ELBW infants care, to establish
Diagnostics and Monitoring System for high risk groups of infants
is an important stage in supporting their psychomotor and somatic
development.
• Integration of Follow-up centres into early intervention service will
improve and diversify these services, while regionalization of
Follow-up service will contribute to lower numbers of disabled
children.

53. Thank you for
attention!