CORD BLOOD TGF-CORD BLOOD TGF- ββ1 1 CONCENTRATIONS IN CONCENTRATIONS IN

INTRAUTERINE GROWTH INTRAUTERINE GROWTH RESTRICTED PREGNANCIES AT RESTRICTED PREGNANCIES AT

TERMTERM

Sofia LiosiSofia Liosi 11 , Despina D. Briana, Despina D. Briana 11 , , Stavroula BakaStavroula Baka 11 , , Dimitr ios GourgiotisDimitr ios Gourgiotis 22 , Maria Boutsikou , Maria Boutsikou 11 ,,

Lamprini StamatiLamprini Stamati 22 , Dimitr ios Hassiakos, Dimitr ios Hassiakos 11 , Ariadne , Ariadne Malamitsi-PuchnerMalamitsi-Puchner 11 . .

1.1.Neonatal Division, 2nd Department of Obstetrics and Gynecology, Athens Neonatal Division, 2nd Department of Obstetrics and Gynecology, Athens University Medical School, Athens, GreeceUniversity Medical School, Athens, Greece

2.Research Laboratories, 2nd Department of Pediatrics, Athens University 2.Research Laboratories, 2nd Department of Pediatrics, Athens University Medical School, Athens, GreeceMedical School, Athens, Greece

TGF – TGF – β1β1

• A member of the transforming growth factor beta (TGF-β) family

• Three closely related isoforms TGF-β1, TGF-β2, and TGF-β3

TGF-TGF-ββ11

• inhibit ion of cell growth and transformation

• suppression of immune response • promotion of inflammation

• a crit ical regulator of trophoblast invasion and fetal growth.

Intrauterine growth Intrauterine growth restrict ion-IUGRrestrict ion-IUGR• Failure of the fetus to achieve his/her

intrinsic growth potential

• Consequence of anatomical and/or functional disorders and diseases in the feto-placental-maternal unit

• Results to increased morbidity and mortali ty in intra- and extrauterine l ife

IUGRIUGR

• abnormal trophoblast invasion

• uteroplacental vascular insufficiency

• impaired fetal growth

HYPOTHESISHYPOTHESIS

• Umbilical cord blood Umbilical cord blood concentrations of concentrations of TGFTGF-β1-β1 in IUGR cases may differ from in IUGR cases may differ from respective concentrations in appropriate-respective concentrations in appropriate-for-gestational-age (AGA) controls, due for-gestational-age (AGA) controls, due to to uteroplacental vascular insufficiency uteroplacental vascular insufficiency

AIMAIM

• Investigate cord blood TGFInvestigate cord blood TGF -β1-β1 concentrations in IUGR and AGA concentrations in IUGR and AGA pregnancies at birthpregnancies at birth

• Correlate determined concentrations Correlate determined concentrations with gestational age, gender and mode with gestational age, gender and mode of delivery.of delivery.

SUBJECTSSUBJECTS

• 160 healthy, singleton full-term 160 healthy, singleton full-term pregnanciespregnancies

- - 111010 AGA AGA (placental weight: (placental weight: 480-621480-621 g)g)- 50- 50 asymmetric IUGR asymmetric IUGR ( placental weight ( placental weight

230-230- 400g)400g)

• Apgar scores:Apgar scores: >>8 in 8 in 11 s ts t and and 55 t ht h minuteminute

Gestation Related Optimal Gestation Related Optimal Weight (GROW)Weight (GROW) computer-computer-

generated programmegenerated programme

www.gestation.net

Custom baseDaysBirthweight (g)Gestation: WeeksBooking weight (kg)Maternal height (cm)SexEthnic groupParity at booking56Customised centile =

DEMOGRAPHIC DATADEMOGRAPHIC DATA

IUGR AGAIUGR AGA• Gestational age (weeks) Gestational age (weeks) 3838 .36.36 ±1±1 .27 * .27 * 338.988.98 ±±1.07 *1.07 *

• BW (g) BW (g) 25250707±±264.5 * 264.5 * 33310310 ±±310.5*310.5*

• BW centile BW centile 33 .0 (0-5) 44.5 (20-99).0 (0-5) 44.5 (20-99)

• Gender (male/female) Gender (male/female) 21/29 66/4421/29 66/44

• Mode of delivery (VD/ECS)** Mode of delivery (VD/ECS)** 22/28 77/3322/28 77/33

• Parity (1Parity (1stst /other) /other) 3131 // 19 76/3419 76/34

* * values are mean ± SD**VD: vaginal delivery/ ECS: elective cesarian section **VD: vaginal delivery/ ECS: elective cesarian section

CAUSES OF IUGRCAUSES OF IUGR

• Preeclampsia (Preeclampsia ( n=6 )n=6 ) • Pregnancy induced hypertension Pregnancy induced hypertension (n=5(n=5 ))• Various diseases : Various diseases : severe type I DMsevere type I DM

(( n=5),iron deficiency anemia (n=3), n=5),iron deficiency anemia (n=3), hypothyroidismhypothyroidism (n=7)(n=7)

• Maternal smoking ( n=24 )Maternal smoking ( n=24 )

MethodsMethods

Blood collected from:Blood collected from:• Doubly-clamped umbilical cords (mDoubly-clamped umbilical cords (m ixed ixed

arteriovenous bloodarteriovenous blood ) – reflecting fetal ) – reflecting fetal statestate

• Determination of plasma Determination of plasma TGFTGF-β1-β1 concentrations by enzyme immunoassayconcentrations by enzyme immunoassay ((Human TGF-Human TGF- ββ1 ELISA, R&D OX, UK)1 ELISA, R&D OX, UK)

• Statistical analysis (non-parametric Statistical analysis (non-parametric tests)tests)

Fig. 1 Box and whiskers plots of the concentrat ions of TGF β1 UC from AGA and IUGR cases

IUGR GROUP (N=50)

AGA GROUP (N=110)

TG

FB

1 C

ON

CE

NT

RA

TIO

NS

(p

g/m

l) 30000

20000

10000

0

Results (1)Results (1)

• NoNo statistically signif icant differences in statistically signif icant differences in cord blood cord blood TGFTGF -β1-β1 concentrations concentrations between IUGR and AGA groupsbetween IUGR and AGA groups ..

Results (2)Results (2)

• In a combined groupIn a combined group

• Cord blood TGFCord blood TGF -β1-β1 concentrations were concentrations were signif icantly elevated in cases of vaginal signif icantly elevated in cases of vaginal deliverydelivery

• The effect of gender, parity and maternal The effect of gender, parity and maternal age on cord blood TGF-β1 age on cord blood TGF-β1 concentrations was not significant. concentrations was not significant.

Results (3)

• In the AGA group

• Cord blood TGF-β1 concentrations were higher in primigravidas

Results (4)

• In the IUGR group

• Cord blood TGF-β1 concentrations negatively correlated with infant’s customized centi les

Conclusions (1)Conclusions (1)

• Lack of differences in cord blood TGF-Lack of differences in cord blood TGF- ββ1 1 concentrations at term between IUGR concentrations at term between IUGR and AGA groups possibly suggests that and AGA groups possibly suggests that TGF-TGF- ββ1 may not be directly involved in 1 may not be directly involved in the pathophysiological processes the pathophysiological processes result ing in IUGRresult ing in IUGR

• Gender, parity and maternal age do not Gender, parity and maternal age do not seem to have any impact on umbil ical seem to have any impact on umbil ical cord blood TGF-cord blood TGF- ββ1 concentrations1 concentrations

Conclusions (2)Conclusions (2)

• TGF-β1 may be related to fetal growth, as indicated by the higher cord blood TGF-β1 concentrations in primigravidas and their negative correlation with infants’ customized centi les in the IUGR group

Conclusions (3)

• Stress associated with vaginal delivery may account for the higher TGF-β1 concentrations in the latter.