Fetal Growth Restriction - PowerPoint Presentation

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Fetal Growth Restriction

Conrad R. Chao, MD

Professor of Obstetrics and GynecologyChief of Maternal and Fetal MedicineUniversity of New MexicoSlide3

What is FGR

SGA = birthweight below 10

th percentileAssociated with higher morbidity, mortality, and subsequent adult disease (Barker hypothesis)FGR/IUGR = estimated fetal weight below 10

th

percentile

Includes many fetuses that are constitutionally small but not pathologically small

Potential for customized growth curvesSlide4
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Definition of FGR differs in

US vs Europe

EFW<10th percentileVersusEFW<10th percentile

OR

AC<10

th

percentile

Versus

Fetus that has failed to achieve its growth potential

Currently no trials of customized growth curves vs standard definitions

Adjustments for maternal weight, height, parity, ethnicitySlide7

Classification of FGR

Asymmetric

Long bone and head growth is normal but the weight is low due to small abdominal circumference (subcutaneous tissue, liver). Placental abnormality impairs nutrient and oxygen transferSymmetricAll parameters are small. Early insult to fetal growth such as aneuploidy, malformations, infectionSlide8
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Causes of FGR: Clinical Pearls

Weight variation: 20% fetal genetic, 20% maternal genetic, 60% fetal environmental

Sisters of women with FGR babies have higher incidence of FGR, but not brothersMothers who were FGR have higher risk of FGRMale fetus is 150-200 g heavierSmall influence of paternal size 100-175 gSpecific maternal genotypic disease e.g. PKU can cause FGRSlide10

Causes of FGR: Clinical Pearls

FGR is associated with congenital malformations, syndromic and non-syndromic: 22% of fetuses with anomalies have FGR

Especially common in cardiac defects2-5% of FGR infants have a chromosomal anomaly, but the rate is 20% if FGR is diagnosed in the first half of pregnancyBirthweight is lower in trisomies 21, 18, 13

Rubella, CMV, varicella, zoster, HIVSlide11
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Causes of FGR: Clinical Pearls

Effect of maternal nutrition depends on pre-pregnancy state (WW II experience with prolonged nutritional deprivation during wartime

seiges)Leningrad: preconception nutrition and gestational nutrition were poor, BW decreased 400-600gHolland: preconception nutrition was good, BW decreased only 10% and only when undernutrition occurred in third trimester

Oxygen affects BW

BW lower by 250g above 10K feet above sea level

Cyanotic heart disease and

hemoglobinopathies

reduce BWSlide13

Clinical significance of undetected FGR

Third trimester undetected IUGR is the most frequent cause of unexplained stillbirth in low risk pregnancy

43-52% of unexplained stillbirthsEFW < 10th percentile 1.5% risk of IUFD (2X BG)EFW < 5th

percentile 2.5% risk of IUFD

SGA infants – hypoglycemia, hyperbilirubinemia, hypothermia, IVH, NEC, seizures, sepsis, RDS, NND

Barker hypothesis – association with adult CV disease, diabetes, strokeSlide14
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Barker Hypothesis

David Barker, (1938-2013), British physician and epidemiologist

Adverse influences in intrauterine life can result in permanent changes in physiology and metabolismIncreased risk of disease in adulthoodBarker, et al noted that the regions in England with highest rates of infant mortality in the early 20th century had the highest risk of mortality from coronary artery disease

Highest risk of infant mortality was low birth weightSlide17

Barker Hypothesis

Studies in Sheffield and Hertfordshire showed strong relationship between death from coronary heart disease and decreasing birthweight, head circumference, or ponderal index

Intrauterine growth restriction was a greater contributor than prematurityCorrection for postnatal environmental factors such as diet, smoking, and exercise did not change relationship Multiple experimental and observational studies confirm the phenomenologySlide18
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Barker Hypothesis - mechanisms

“Thrifty phenotype” - early-life metabolic adaptations help in survival of the organism by selecting an appropriate trajectory of growth in response to environmental cues

Intrauterine deprivation prepares for extrauterine nutritional deprivationFetal programming – stimulus or insult during sensitive time period has irreversible long-term effects on development through permanent changes in gene expressionNutrient rich postnatal environment- genetic programming is maladaptive

Altered fetal nutrition

Increased glucocorticoid exposureSlide20

Barker Hypothesis and glucocorticoids

Sheep – increased maternal or fetal glucocorticoid concentrations are associated with elevated blood pressure in the fetus

Rats – dams given dexamethasone during pregnancy have offspring with reduced birthweight and increased blood pressure and glucose intolerance in adulthoodMediated by permanent changes in regulation of the HPA axis in the offspringNo demonstration of these effects due to a single steroid course for lung maturation

Weekly multiple courses of antenatal steroids reduce head circumference and somatic growth in humans

Single courses of antenatal steroids have neurobehavioral effects on humans who deliver at termSlide21
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Screening for FGR

Vastly different approach – ACOG versus RCOGSlide23
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Screening for FGR ACOG recommendation

Fundal height at 24-38 weeks

65-85% sensitive (32-24 weeks)96% specificACOG – special conditions in which ultrasound is recommendedFibroidsObesityWhat about: hypertension, diabetes with vascular disease, renal disease, aneuploidy, congenital malformations, lupus and other autoimmune disease, intrauterine infection, etc.?Slide25

Screening for IUGR ACOG recommendation

Fundal height at 24-38 weeks

65-85% sensitive (32-24 weeks)96% specificACOG Caveats in which US is recommendedFibroidsObesitySlide26

UK FGR Screening Summary

Historical factors are assigned odds ratios

One or more major (OR>2) risk factors are screened with fetal size and umbilical artery Doppler from 26-28 weeks 3 minor (OR <2) risk factors are screened with uterine artery Doppler at 20-24 weeksLow first trimester PAPP-A is a major risk factorEchogenic bowel requires FGR assessmentSlide27
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Diagnosis of FGR

ACOG – EFW < 10

th percentile for GARCOG – EFW < 10th percentile for GA OR AC < 10th percentile for GASlide29

Management of FGR

Identify cause

Careful search for anomaliesConsider workup for genetic or infectious causeEarly or severe onset, symmetricGenetic counseling, NIPT or amniocentesisTORCH titersSerial growth scans q 3 weeks

Antepartum surveillance – NST/SVP or BPP

Umbilical artery DopplerSlide30

How to manage abnormal testing

Evaluate context

Overall clinical pictureNR NST – CST or BPPBPP 6/10 <37 weeks – repeat within 24 hours>= 37 weeks deliverBPP <=4 deliver

Trial induction of labor is reasonableSlide31

What type of assessment of amniotic fluid volume is appropriate?

Deepest vertical pocket <2 is superior to AFI or percentile in defining oligohydramnios (SAFE Trial)

Polyhydramnios is defined as Deepest vertical pocket>8Slide32

SAFE Trial

1052 women in 4 hospitals, Germany

Women presented for a prelabor exam or for deliveryRandomized to AFI < 5 vs SVP < 2 for designation as oligohydramniosPrimary outcome measure was NICU admissionSlide33
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A few words about

Dopplers

Umbilical artery Dopplers in conjunction with standard fetal testing improves outcomes in the setting of growth restrictionThere is no evidence that UA Dopplers are helpful in management of pregnancies complicated by other high-risk conditions

There is no evidence for UA Doppler use in low-risk, normally growth fetuses

UA Doppler studies should not be undertaken in normally grown fetuses

The literature is mixed on use of UA

Dopplers

in hypertensive disorders

In the United States, use of

Dopplers

other than UA

Dopplers

for IUGR is

INVESTIGATIONALSlide36

Fetal

and umbilical Doppler ultrasound in high‐risk pregnancies

Cochrane Database of Systematic Reviews

12 NOV 2013 DOI: 10.1002/14651858.CD007529.pub3

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007529.pub3/full#CD007529-fig-00101Slide37
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Treatments for FGR

No treatments have been demonstrated to be efficacious in well designed prospective clinical trials

Maternal oxygen therapy – some evidence of improved outcome but not clear if this was due to advanced gestational age in treated pregnanciesVitamins and fish oil are not effectiveLow dose aspirin in preeclampsia prevention trials may reduce incidence of IUGRSlide40
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Outcomes of FGR

Short-term

Neonatal asphyxia, meconium aspiration, hypoglycemia and other metabolic abnormalities, and polycythemiaPremature IUGR infant - increased risk of mortality, necrotizing enterocolitis, and need for respiratory support at 28 days of ageLong-term

50% (37/77) of SGA children had learning deficits at ages 9 to 11 years

Strong association between IUGR and spastic cerebral palsy in newborns born after 33 weeks’ gestation

Newborns who were at or above the 10th percentile for weight but had abnormal ponderal indices were also at risk for spastic cerebral palsySlide42

Customized Growth Curves

Buck Louis et al, NICHD MFM Network, 2015

Prospectively followed ultrasound growth and birthweight on racially diverse populationsPrescreened for extremes of BMI, previous IUGR, previous prematurity, substance abuse, med compAbnormal pregnancy courses were dropped e.g. preeclampsia, anomalies1737 fetuses were studiedSlide43
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FGR

US definition is EFW < 10

th percentileSymmetric vs. AsymmetricAssociated with increase in perinatal morbidity and mortalityIdentify cause if possible and workup identifiable etiologies

No effective interventions

Monitor with biophysical testing and umbilical artery Doppler

Reverse flow delivered at 32w, absent at 34w, high S/D (>95%) delivered at 37w, else deliver 38-39wSlide47

FGR

Barker hypothesis links low birth weight from IUGR with metabolic syndrome and other cardiovascular diseases in adults

Long term outcome studies suggest high incidence of neurologic abnormalitiesCustomized growth curves may be needed for diverse populationsSlide48
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MFM at UNM

Have been on site since February

At that time there were 2 perinatologistsHave completed recruitment of new staff Full-time - Luis Izquierdo

, Jacquelyn Blackstone, Evan Taber, Conrad Chao, Danielle Esters (also board-certified medical geneticist)

Part-time – William Rayburn, Luis

Curet

, Jose Gonzales, Ellen

Mozurkewich

3 MFM fellows – Brad Holbrook, Nathan Blue,

Vivek

Katukuri

Full-time diabetes educator

2 genetic counselors, 1 nurse practitioner

9 perinatal sonographers, ultrasound educatorSlide50

MFM at UNM

Expansion of clinical services – outreach to remote sites (Santa Fe, Farmington,

Crownpoint, Shiprock, Gallup), inreach (Northwest Valley, Southwest Mesa, Women’s Faculty Clinic)

Migration of services to Eubank Clinic – will continue to serve outreach,

inreach

, UNM Hospital based clinic

Gyn

ultrasound

Expand diabetes and genetic services to 5 days/week

Same day availability for ultrasound and consultationSlide51

MFM at UNM

Consolidation of UNM hospital MFM clinic into Women’s Imaging

Enhance educational opportunities – completely rewriting ultrasound and MFM curriculumRewriting all SOPsLong-term vision for MFM statewide – Statewide perinatal regionalization program, grant support, telemedicine, ECHO project for diabetes and hypertensionResearch – preeclampsia trials, basic science and clinical projects with alcohol center, tobacco project,

Tricore

screening project, ultrasound studiesSlide52

MFM at UNM

You are our customer

Focus on customer serviceExpansion of clinic and ultrasound availabilityImproved results reportingRevision of ad-hoc form to simplify orderingAMA, genetics, maternal and fetal complication referrals Feedback

Thank you!