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Lavenia Carpenter, MD Associate Professor

Division of Maternal-Fetal Medicine Department of Obstetrics and Gynecology

Vanderbilt University

Disclosures None

Objectives Why screen

Who to screen

When to screen/when to test

What test(s) to use

Where are we going

Definitions Fetal growth restriction – Failure of a fetus to reach its

growth potential

Small for gestational age newborns – EFW < 10th% or AC< 10th%

Severe SGA - < 3rd%

LBW- < 2500 gms

WHY?

Risk of fetal death

1.5% with EFW< 10th%

2.5% with EFW < 5th%

Morbidity – Neonatal: hypoglycemia, hyperbilirubinemia, hyopthermia, IVH, NEC, seizures, sepsis, RDS ….. neonatal death

Morbidity – Childhood: congnitive delay and Adulthood: higher risk for chronic disease (Barker hypothesis)

Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Resnik, Robert, MD; Creasy, Robert K., MD.Published January 1, 2014. Pages 743-755.e4. © 2014. Morbidity and mortality in 1560 small-for-gestational-age fetuses.

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Overall stillbirth rate of 4.2/1000 but 2.4/1000 without FGR Average delivery 10 days earlier when detected

Population-Based Estimates of In-Unit Survival for Very Preterm Infants - female

Population-Based Estimates of In-Unit Survival for Very Preterm Infants - male

Balance of risks/benefits of early delivery

stillbirth

neonatal demise morbidity

Barker hypothesis

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Barker hypothesis Barker hypothesis

Thrifty phenotype

Cheryl Lyn Walker & Shuk-mei Ho; Nature Reviews Cancer 12, 479-486 (July 2012)

WHO? Maternal risk factors

History of FGR

Diabetes, hypertension, autoimmune disorders, renal disease

Tobacco or other substance use

Low pre-pregnancy birth weight

High altitude

Pregnancy course

Poor weight gain

Preeclampsia

Short fundal height

Etiologies

ENVIRONMENT Infections Altitude Nutrition

MATERNAL Chronic illnesses Substance abuse Preeclampsia Age Parity Malnutrition

FETAL Aneuploidy Genetic syndromes Multiples Gender

PL

AC

EN

TA

L

Correlation for birth weight Between r

Monozygotic twins 0.54

Full siblings 0.52

Half siblings common mother 0.58

Half siblings common father 0.10

First cousins common maternal grandparents 0.135

First cousins common paternal grandparents 0.015

Robson ER, Human growth Vol 1: Principles and prenatal growth New York: Plenum press 1978

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Maternal constraint Small breed embryo transplanted to large breed uterus

will growth larger than a small breed embryo remaining in a small breed uterus

Multiple gestation in humans

Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Resnik, Robert, MD; Creasy, Robert K., MD.Published January 1, 2014. Pages 743-755.e4. © 2014. Median growth rate curves for single and multiple births in California, 1970-1976

Maternal nutrition Starvation effect most pronounced in third trimester

(Holland example)

Starvation in the first trimester with normal birthweight daughters but small granddaughters – epigenetic effects

Fetus Genetic potential

Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Resnik, Robert, MD; Creasy, Robert K., MD.Published January 1, 2014. Pages 743-755.e4. © 2014. Weight-for-age gender-specific curves (solid line) for girls (A) and boys (B) compared with Lubchenco unisex curves ( dashed line) starting at 24 weeks.

Placenta Placental growth (mass) in first half of pregnancy with

remodeling (terminal villi) in later half of pregnancy

Fetal growth in second half of pregnancy

Fetomaternal immune cross-talk and its consequences for maternal and offspring's health Petra C Arck1, & Kurt Hecher1, Journal name:Nature Medicine Volume: 99, Pages:548–556 Year published:(2013) DOI:

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Placental surface areas at different gestational ages. () areas of intermediate villi; () areas of terminal villi. (Adapted from The Physiology of the Human Placenta, by Page K, Figure 2.7, published by UCL press).

Illustration of uterine and placental vasculature in the non-pregnant, pregnant and immediate post-partum state. Normal pregnancy is characterized by the formation of large arterio-venous shunts that persist in the immediate post-partum period. By contrast pregnancies complicated by severe preeclampsia are characterized by minimal arterio-venous shunts, and thus narrower uterine arteries characterized with “low flow and high resistance.” Red shading = arterial; blue shading = venous. Adapted from Burton et al. Placenta 2009; 30 (6), 473-482. Adapted from Placenta, Burton et al. 2009

When Maternal risk factors

Poor weight gain

Size less than dates (fundal height)

Pregnancy associated hypertension

Abnormal placentation

Abnormal serum screening

Uncertainty in dating

Timing of testing dependent upon risk factor

EGA Clinical or Sonographic +/- 2SD

IVF +/- 1 day

Ovulation induction or AI +/- 3 days

Ultrasound EGA < 8 6/7 (CRL) +/- 5 days

9-13 6/7 (CRL) +/- 7 days

14-15 6/7 (BPD, HC, AC, FL) +/- 7 days

16-21 6/7 (BPD, HC, AC, FL) +/- 10 days

22-27 6/7 (BPD, HC, AC, FL) +/- 14 days

>28 (BPD, HC, AC, FL) +/- 21 days

ACOG committee opinion Estimating Due Date No. 611 Oct 2014

Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Resnik, Robert, MD; Creasy, Robert K., MD.Published January 1, 2014. Pages 743-755.e4. © 2014. Fetal weight as a function of gestational age by selected references.

<10th% <3rd%

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WHAT (test to use)? Cardiotocography or NST

Biophysical profile

Doppler studies

Nonstress test (NST)

Moderate variability Accelerations associated with maternal palpation FMs (accelerations graded for gestation) on 20-minute NST

FM and accelerations not coupled Insufficient accelerations, absent accelerations, or decelerative trace Minimal or absent variability

Devoe, L, Glob. libr. women's med., (ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10210

Fetal Variable Normal Behavior (score = 2) Abnormal Behavior (score = 0)

Fetal breathing movements (FBMs)

Intermittent, multiple episodes of more than 30 sec within a 30-min biophysical profile (BPP) time frame Hiccups count If continuous FBMs for 30 min, rule out fetal acidosis

Continuous breathing without cessation Completely absent breathing or no sustained episodes

Body or limb movements

At least three discrete body movements in 30 min Continuous, active movement episodes equal a single movement Includes fine motor movements, rolling movements, and so on, but not rapid eye movements or mouthing movements

Three or fewer body or limb movements in a 30-min observation period

Fetal tone or posture

Demonstration of active extension with rapid return to f lexion of fetal limbs and brisk repositioning or trunk rotation Opening and closing of hand or mouth, kicking, and so on

Low-velocity movement only Incomplete f lexion, f laccid extremity positions, abnormal fetal posture Must score 0 when fetal movement (FM) is completely absent

Amniotic f luid evaluation

At least one pocket larger than 2 cm with no umbilical cord (text discusses subjectively decreased f luid)

No cord-free pocket greater than 2 cm or multiple definite elements of subjectively reduced amniotic f luid volume

Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Bahtiyar, Mert Ozan, MD; Copel, Joshua A., MD.Published January 1, 2014. © 2014.

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Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Bahtiyar, Mert Ozan, MD; Copel, Joshua A., MD.Published January 1, 2014. © 2014.

BPP – gradual hypoxia concept NST and FBM

Movement

Tone

AFV (chronic)

Vintzileos et al. Obstet Gynecol 1987;70:196

BPP and cord pH

BPP Interpretation Predicted PNM/1000 * Recommended Management

10/10, 8/8, 8/10 (AFV normal)

No evidence of fetal asphyxia

Less than 1/1000

No acute intervention on fetal basis; serial testing indicated by disorder-specific protocols

8/10-oligo Chronic fetal compromise likely (unless ROM is proved)

89/1000

For absolute oligohydramnios, prove normal urinary tract, disprove undiagnosed ROM, consider antenatal steroids, and then deliver

6/10 (AFV normal) Equivocal test; fetal asphyxia is not excluded

Depends on progression (61/1000 on average)

Repeat testing immediately, before assigning final value If score is 6/10, then 10/10, in two continuous 30-minute periods, manage as 10/10 For persistent 6/10, deliver the mature fetus, repeat within 24 hr in the immature fetus, then deliver if less than 6/10

4/10 Acute fetal asphyxia likely

91/1000 Deliver by obstetrically appropriate method, with continuous monitoring If AFV-oligo, acute on

chronic asphyxia very likely

2/10 Acute fetal asphyxia likely with chronic decompensation

125/1000 Deliver for fetal indications (frequently requires cesarean section)

0/10 Severe, acute asphyxia virtually certain

600/1000 If fetal status is viable, deliver immediately by cesarean section

Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Bahtiyar, Mert Ozan, MD; Copel, Joshua A., MD.Published January 1, 2014. © 2014.

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BPP and medications Beta andrenergics

Possible increase in FBM

Steroids Reduction in FBM and FM and non-reactive NST has been

described

Magnesium sulfate Possible decrease in FBM and NST

Opiods

Fasting Hyperglycemia may increase FBM in presence of acidemia

fasting may decrease FBM

Signore C, Freeman R and Spong C. Obstet Gynecol. Mar 2009; 113(3): 687–701

Risk for mortality morbidity due to prematurity http://www.nichd.nih.gov/about/org/der/branches/p

pb/programs/epbo/pages/epbo_case.aspx

http://www.nichd.nih.gov/about/org/der/branches/ppb/programs/epbo/pages/epbo_case.aspx

<10th% <3rd%

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Umbilical artery

Doppler studies Umbilical artery

Middle cerebral artery

Ductus venosus

Uterine artery

http://www.vanderbilthealth.com/includes/healthtopics/calc.php?

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Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Bahtiyar, Mert Ozan, MD; Copel, Joshua A., MD.Published January 1, 2014. © 2014.

Middle cerebral artery

Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Bahtiyar, Mert Ozan, MD; Copel, Joshua A., MD.Published January 1, 2014. Pages 211-217.e1. © 2014.

Cerebroplacental ratio (CPR) in relation to gestational age. The curves indicate the 5th, 10th, 90th, and 95th percentile values for pregnancies with and without morbidity and perinatal complications. The interval between Doppler imaging and delivery was less than 2 weeks. Open circles, <10th percentile, no morbidity; filled circles, <10th percentile, with morbidity.

Abnormal MCA

Abnormal umbilical

artery

Abnormal

ductus venosus

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TRUFFLE 2011 “Although the difference in proportion of infants

surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age.”

Where? Expansion in use of customized fetal growth charts

Cell free fetal DNA for evaluation of genetic syndromes

Biochemical markers to help distinguish small normal from placental dysyfunction

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Placenta on chip

For Immediate Release: Thursday, June 18, 2015 Researchers design placenta-on-a-chip to better understand pregnancy http://www.nih.gov/news/health/jun2015/nichd-18.htm

THANK YOU!