FETAL BRAIN PROTECTION

IN IUGR

M ADRIANES BACHNAS

HEAD OF MATERNAL-FETAL MEDICINE DIVISION

OB/GYN DEPARTMENT
FACULTY OF MEDICINE SEBELAS MARET UNIVERSITY
DR.MOEWARDI HOSPITAL
SOLO
 IUGR AND BRAIN DAMAGE

fetal growth restriction

Brain Sparing

brain structure
reduced total brain volume
altered cortical volume and structure fetal hypoxia
decreased total number of cells
myelination deficits fetal
Brain connectivity is also impaired hyponutrients
neuronal migration deficits
Placental insufficiency
reduced dendritic processes
less efficient networks with decreased long-range
connections. Fetal growth restriction (FGR)
FGR affects 3-9% of pregnancies
neurodevelopmental outcome in high-income countries

timing of the onset of FGR motor skills, cognition,

memory and
severity of FGR J Physiol. 2016 Feb 15;594(4):807-23.
neuropsychological
gestational age at delivery dysfunctions

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

BRAIN DAMAGE BEFORE BIRTH
Periventricular leukomalacia in the fetus: 23rd World Congress on Ultrasound in
prenatal imaging and diagnostic features Obstetrics and Gynecology
D. Pugash1, C. Mayer2, G. Hendson3, C.P. Dunham3
Results: A total of 38 fetuses were identified by abnormal prenatal neurosonography and/or fetal MRI. Evidence of intracranial hemorrhage
was present in 14/38 fetuses. PVHI was identified in 6 fetuses with intraventricular hemorrhage. PVL was present in 24. In 16/24 fetuses,
PVL was extensive and diffuse. Complications of monochorionic twinning were present in 6, and hydrops fetalis was present in 6. Eight
fetuses had focal PVL, and 3 of these were associated with demise of a monochorionic co-twin. Metabolic disorders and evidence of
intracranial hemorrhage were identified in 2 fetuses. Exposure to teratogens known to be associated with brain injury occurred in 2/8
fetuses. Four fetuses had focal periventricular white matter defects; these were associated with severe intraventricular hemorrhage and
presentation late in the third trimester.

Conclusions: Targeted neurosonography provides high-resolution imaging of the fetal brain and is effective in identifying fetuses with
abnormal white matter from a variety of etiological insults. This is primarily accomplished by evaluating abnormalities in transient
laminar patterns in the developing white matter of the fetal cerebrum, with or without intracranial hemorrhage.

Fetal Diagn Ther 2000;15:198208 cPVL ePVL IVH

(DOI:10.1159/000021006) less common and tended to be less severe in infants with
grade II PVL than in those with grade III PVL.

Neonatal Periventricular Leukomalacia Preceded by Fetal Periventricular Echodensity

Yamamoto N. a Utsu M. a Serizawa M. a Ohki S. b Murakoshi T. c Seguchi M. d Iwase K. d Maeda K. a,c
Objective: The purpose of this prospective study is to verify whether fetal periventricular echodensity (PVE) precedes neonatal
periventricular leukomalacia (PVL). Methods: Fetal brains were studied with transvaginal scan in 63 high-risk fetuses from 17 to 32
weeks of pregnancy, PVE echogenicity was quantified with ultrasonic histogram, and neonatal brains and clinical courses were
studied after birth. Results: No fetal cystic PVL was found, instead, fetal PVE was detected in 42 fetuses. The quantified echogenicity
value was higher in PVE than in normal brain. Four cases developed neonatal PVL among 28 preterm and 1 among 14 term births.
Neonatal PVL developed in the 23 cases of persistent fetal PVE, whereas no neonatal PVL was found when fetal PVE was negative
or disappeared. Cord compression signs were common in PVL cases. Conclusion: Neonatal PVL was preceded by antepartum
persistent fetal PVE in the present study.
dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM
BRAIN DAMAGE BEFORE BIRTH

I II
PVL
III IV
Korean J Obstet Gynecol
2012;55(4):257-260

Arch Dis Child Fetal Neonatal Ed

Postnatal brain m agnetic resonance 2001;84:F151F156
imaging: Cystic encephalomalacia
(white arrow) w ith dilated right lateral
ventricle ( black star). Large necrotic lesions cavitate in 24 weeks and remain cystic

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

BRAIN DAMAGE BEFORE BIRTH

IVH

Grant EG & S chellinger, 2001

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

IUGR AND BRAIN DAMAGE

Malinger G, Kidron D, Schreiber L, Ben-Sira L, Hoffmann C, Lev D, Lerman-Sagie T. Prenatal diagnosis of malformations of cortical
development by dedicated neurosonography. Ultrasound Obstet Gynecol 2007;29(2):17891

The surface of the brain is unusually smooth for a fetus at 28 weeks gestation (the Sylvian fossa is shallow and
there is no sign of the cingulate and precentral gyrus; the texture of the cortex is more irregular and echogenic
than usual.
dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM
LONG TERM NEUROLOGICAL
CONSEQUENCES OF IUGR

PEDIATRICS Volume 118, Number 1, July 2006

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM
LONG TERM NEUROLOGICAL
CONSEQUENCES OF IUGR

PEDIATRICS Volume 118, Number 1, July 2006

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM
DATING RULE OUT
ULTRASOUND MATERNAL ANOMALY
(11-14 Wks) PROBLEMS (11-13 Wks,
18-22)
GENETIC
DRIVE Volume
CALCULATION

LOW CRL

PLACENTAL
INSUFFICIENCY SERIAL BIOMETRY

EARLY INTERVENTION FINAL INTERVENTION

AND TERMINATION
PREDICTION OF INTERVENTION >34 Wks
GROWTH IMMINENT
RESTRICTION DEATH
PROGRESSION OF GROWTH RESTRICTION
22 Wks ATERM
MONITORING: USG - CTG

BRAIN PROTECTION STRATEGY

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM
PREDICTION OF
FETAL GROWTH RESTRICTION

APS antibodies:
B2-GPI, LA, ACA
LOW DOSE
ASPIRIN Vainio M, Kujansuu E, Iso-Mustajarvi M,
Maenpaa J. L ow dose acetylsalicylic acid in

Notch and PI > 1.5 56 71 %

prevention of pregnancy-induced
hypertension and intrauterine growth
retardation in women with bilateral

Papageorghiou AT, Yu CK, Bindra R, Pandis G, Nicolaides KH. Multicenter LMWH uterine artery notches. BJOG
2002;109:161-7.

screening for pre-eclampsia and fetal growth restriction by t ransvaginal uterine

artery Doppler at 23 w eeks of gestation. Ultrasound Obstet Gynecol
2001;18:441-9. 62.

Martin A M, Bindra R, Curcio P, Cicero S , Nicolaides KH. S creening for pre-

eclampsia and fetal growth restriction by uterine artery Doppler at 11-14 w eeks
of gestation. Ultrasound Obstet Gynecol 2001;18:583-6.
EARLY INTERVENTION
Yilmaz SS The Cerebroplacental Doppler Ratio and Neonatal Outcome in Suspected Small-for Gestational-Age Fetuses with Normal Umbilical Artery Doppler. The New Journal of Medicine 2013;30:248-2 51

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

MONITORING PROGRESSION OF FGR

UMBILICAL ARTERY MID CEREBRAL ARTERY

Baschat AA, Gembruch U. The cerebroplacental

CEREBRO - PLACENTAL Doppler ratio revisited. Ultrasound Obstet Gynecol
2003;21:124-7
RATIO < 1
dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM
MONITORING PROGRESSION OF FGR

Progressive decrease of single deepest

pocket - Amniotic fluid measurement

Sylvan K, Ryding EL,

Rydhstroem H.
Routine ultrasound
screening i n the
third trimester: a
population-based
study. Acta Obstet
HC/AC RATIO Gynecol Scand
2005;84:1154-8 .
> 4 weeks difference
M ADRIANES B ACHNAS
dr.SpOG(K)
Placenta Grade 3 with low EFW
SO WHAT WILL WE DO NOW ??

Gulmezoglu AM, Hofmeyr GJ. Plasma volume

expansion for suspected impaired fetal growth. Because no
Cochrane Database Syst Rev 2000: CD000167. treatment has been
Gulmezoglu AM, Hofmeyr GJ. Betamimetics for demonstrated to be
suspected impaired fetal growth. Cochrane
Database Syst Rev 2001:CD000036. 126.
of benefit for FGR
IN ALL META-ANALYSIS
Laurin J, Persson PH. The effect of bedrest in
hospital on fetal outcome in pregnancies
complicated by intra-uterine growth The assessment of fetal
retardation. Acta Obstet Gynecol Scand 1987; well-being, nutrition
66:407-11. 127. Say L, Gulmezoglu AM,
intervention, supporting
Hofmeyr GJ. Maternal oxygen administration treatment, and tmely
for suspected impaired fetal growth. Cochrane delivery remains
Database Syst Rev 2003:CD000137
as the main strategy

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

NUTRITION INTERVENTION

Journal of Nutrition June 2003

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

NUTRITION INTERVENTION
Front Biosci (Schol Ed).2011 ; 3: 428444.
Maternal amino acid supplementation for intrauterine
growth restriction Despite increases in most fetal
Laura D Brown1, Alice S G reen2, Sean W Limesand2, and Paul J Rozance1 plasma amino acids, there was no
change in fetal plasma insulin or
Amino acid concentrations in IUGR fetuses are
IGF-1 concentrations. On the other
variable, a consistent feature in both human and
hand, fetal glucagon concentrations
animal studies is reduced placental transfer of progressively increased. Thus, the
certain essential amino acids.
chronic amino acid infusion caused
The severity of IUGR correlates with the severity an increase in glucagon, a catabolic
of decreased amino acid transfer. hormone, but no increase in
anabolic hormones. Similar results
Arginine Taurine Leucine
have been found after a 24-hour
BALANCE SPECIFIC PROTEIN
fetal infusion of mixed amino acids
stimulate acute fetal insulin secretion and
muscle protein synthesis, regulates -cell following 48 hours of maternal
mass starvation in the sheep

HIGH PROTEIN HIGH CALORIE 1) competitive inhibition of transport among essential

amino acids across the placenta,
When increasing amounts of dietary protein are used to 2) mismatch of increased fetal amino acid supply with
supply this energy, poor fetal weight gain and adverse persistently low fetal anabolic hormone concentrations,
and
perinatal outcomes occur
3) preferential utilization of increased fetal amino acids
Therefore, high dietary protein supplementation ONLY for oxidative metabolism rather than protein synthesis
can be viewed as toxic to the fetus and accretion.
Prematurity Lower birth weight
dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM
DHA Brain Protection
JOURNAL OF NEUROTRAUMA 28:21132122 (October 2011) a Mary Ann Liebert, Inc.
DOI: 10.1089/neu.2011.1872

The Salutary Effects of DHA Dietary Supplementation on Cognition,

Neuroplasticity, and Membrane Homeostasis after Brain Trauma
Aiguo Wu,1 Zhe Ying,1 and Fernando Gomez-Pinilla 1,2

The pathology of traumatic brain injury (TBI) is characterized by the

decreased capacity of neurons to metabolize energy and sustain
synaptic function, likely resulting in cognitive and emotional disorders.
Based on the broad nature of the pathology, we have assessed the
potential of the omega-3 fatty acid docosahexaenoic acid (DHA) to
counteract the effects of concussive injury on important aspects of
neuronal function and cognition. Fluid percussion injury (FPI) or sham
injury was performed, and rats were then maintained on a diet high in
DHA (1.2% DHA) for 12 days. We found that DHA supplementation,
which elevates brain DHA content, normalized levels of brain-derived
neurotrophic factor (BDNF), synapsin I (Syn-1), cAMP-responsive
element-binding protein (CREB), and calcium/calmodulin-dependent
kinase II (CaMKII), and improved learning ability in FPI rats. It is known
that BDNF facilitates synaptic transmission and learning ability by
modulating Syn-I, CREB, and CaMKII signaling. The DHA diet also
counteracted the FPI-reduced manganese superoxide dismutase
(SOD) and Sir2 (a NAD + -dependent deacetylase). Given the
involvement of SOD and Sir2 in promoting met- abolic homeostasis,
DHA may help the injured brain by providing resistance to oxidative
stress. Furthermore, DHA normalized levels of calcium-independent
phospholipase A2 (iPLA2) and syntaxin-3, which may help preserve
membrane homeostasis and function after FPI. The overall results
emphasize the potential of dietary DHA to counteract broad and
fundamental aspects of TBI pathology that may translate into
preserved cognitive capacity.

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

MgSO4 Brain Protection

4 g iv (slow)
Continued
by 1 g/h
For 24 hour

MgSO4
increases
BDNF in
fetus

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

BRAIN PROTECTION - RESUME

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

 RAWAT JALAN:
WHEN TO KTG tiap minggu DHA
DELIVER ? USG tiap 2 minggu Balanced
Lacak etiologi Protein
modifikasi
2 kali px biometri
pertumbuhan tetap Gambaran abnormal < 34 Mg MgSO4 +
doppler ringan: CPR <1
Tanpa BPPS/KTG buruk
Deksametason
TBJ <10 pst
RAWAT
AC <5 pst INAP
BPPS +
HC/AC : 4 minggu
DOPPLER
Cairan Amnion: > 34 Mg Terminasi
SDP < 2
Plasenta Grade 3
(aterm) TBJ < 2.5 kg
Tes Maturasi
Paru
BPPS 4/10
Atau kurang

Abnormalitas doppler berat:

6/10 dengan
A/R EDF A.umb
oligohidramion
V umb pulsasi

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

 BRAIN PROTECTION STRATEGY
1. DEFINING THE REAL GROWTH RESTRICTED FETUS
2. PREDICTION ON RESTRICTED GROWTH:
EARLY INTERVENTION
3. MONITORING (US CTG) AND NUTRITIONAL
INTERVENTION (BALANCED PROTEIN DHA)
WHILE RESTRICTION PROGRESSING
4. PRECISION IN TIME TO DELIVER:
MgSO4 Dexametasone FOR BRAIN PROTECTION

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM

Thank You

dr. M Adrianes Bachnas, SpOG (K)FM Fetomaternal FK UNS-RSDM