Intrauterine fetal growth restriction

Manuela Russu, MD, Ph.DAssociate ProfessorHead of Discipline

“Carol Davila” University of Medicine & Pharmacy“Dr. I. Cantacuzino” Clinic of Obstetrics & Gynecology

MCR, 2013

Terms Intrauterine fetal growth retardation Intrauterine fetal growth restriction Small for gestational age fetus Small for date fetus It is estimated that from 3 to 10% of infants are growth restricted

Divon MY, Hsu HW , 1992 Of interest is the observation that fetuses who deliver prematurely are smaller compared to their age-matched controls who do not deliver until term, thus implicating growth restriction in some cases of preterm birth

Hediger ML, et al, 1995

Definition Weight below the 10th percentile for the gestational age

Battaglia FC, Lubchenco LO, 1967 birthweight below the 5th percentile for the gestational age has been proposed

Seeds JW, 1984 Fetal growth standards should be based on mean values with normal limits defined by ± 2 standard deviations because this definition would limit small-for-gestational-age infants to 3% of births compared with the 10th percentile

Usher R, McLean F, 1969 Low birth weight babies: less than 2500g at term having suffered abnormal intrauterine growth

Frigoletto F, 1986

Definition From a clinical standpoint, the 3rd definition appears to be most meaningful, because most poor outcomes are in those infants with birthweights below the 3rd percentile Moreover, not all infants with birthweights < than the 10th percentile are pathologically growth restricted; some are small simply because of constitutional factors• Manning R, Hohler C (1991) & Gardosi J, et al (1992) concluded that 25 to 60% of infants conventionally diagnosed to be small for gestational age were in fact appropriately grown when determinants of birthweight such as maternal ethnic group, parity, weight, and height were considered

Normal Fetal Birthweight Lubchenco LO, Hansman C, Dressler M, Boyd E,1963

“Intrauterine growth as estimated from liveborn birth-weight

data at 24 to 42 weeks of gestation” [Pediatrics 32:793]

in Denver: fetus weight derived exclusively from white &

Hispanic women who resided at high altitude; such infants

are smaller than those born at sea level: term infants average

3400 g at sea level, 3200 g at 5000 feet, & 2900g at 10,000

feet altitude Several fetal growth curves are developed from

various populations & geographic locations in USA:Alexander GR, et al, 1996; Canada: Arbuckle TE, et al,1993

PathophysiologyPathophysiology

Mortality & Morbidity Fetal demise, birth asphyxia, meconium aspiration, neonatal hypoglycemia, hyperbilirubinemia, hypothermia are increased, prevalence of abnormal neurological development

(Paz I, et al, 1995; Piper JM, et al,1996) Long-term prognosis is related to the nature & severity of the underlying problem Timely diagnosis, appropriate obstetrical & neonatal management may reduce the risks of adverse outcome

Accelerated Maturation A 1000-g infant born at 32 wks & severely restricted physiologically functions differently in the nursery compared with a 1000-g appropriately grown infant of 27 wks

The difference is due to chronological age, and in this sense FGR confers an advantage: accelerated fetal pulmonary maturation in complicated pregnancies associated with FGR (Perelman RH, et al, 1985)

Explanation for this phenomenon: the fetus responds to a stressed environment by increasing adrenal glucocorticoid production, which leads to earlier or accelerated fetal lung maturation (Laatikainen TJ, et al, 1988)

Accelerated Maturation of IUFGR

Owen J, et al (1990) analyzed perinatal outcomes in 178 pregnancies delivered primarily because of hypertension compared with 159 pregnancies delivered because of spontaneous preterm labor or ruptured membranes They concluded that a “stressed” pregnancy, which often resulted in small-for-gestational-age infants, did not confer an appreciable survival advantage Friedman SA, et al (1995): reported similar findings were in women with FGR due to severe preeclampsia

Symmetrical Vs Asymmetrical FGR Fetal growth has been divided into 3 phases

Winick M, 1971: Am J Obstet Gynecol

Pollack RN, Divon MY , 1992: Clin Obstet Gynecol • First phase: conception early second trimester, involves cellular hyperplasia —an increase in the number of cells of all organs• Second phase: a period of continued hyperplasia and hypertrophy, involving both cell multiplication and organ growth• Third phase: beyond 32 wks, cellular hypertrophy is the dominant feature of growth. Cell size increases rapidly, there is fat deposition, and fetal weight may increase by as much as 200 g/ week

Given this changing pattern of normal fetal growth, it has long been considered that the head and abdominal

proportions in the growth-restricted fetus would reveal both the timing & nature of the insult

leading to abnormal growth

Symmetrical Vs Asymmetrical FGR

Symmetrical restriction of anabolysm • typical for preterm babies• incomplete anabolism for GA & reduced cells number • Head development is early interested, fetal lengh is reduced as muscle mass, & fat subcutaneous stores • Infected fetuses or with genetic & anatomic defects• High risk for fetal dystress & intrapartum mortality: ~ 40- 50%: 40- 50%: Lin Lin CCCC, 1991, 1991 • Difficult to recognise in late Difficult to recognise in late pregnancy when anamnesis is pregnancy when anamnesis is

erronateerronate

Asymmetrical restriction of anabolysm

• normal cells’ number, but reduced cell’s size

• Fetal lengh is normal for GA, • Head increases in size till late in pregnancy and afterwards stagnates, being a brain protection

• Low fat & glycogen deposits, incomplete gluconeogenesis, which reduces fetal abdominal circumferences.

• High ratio: head /abdomen circumferences or femoral lengh/abdominal circumferences

• Represents 2/3 of all cases & has many causes

Symmetrical Vs Asymmetrical FGR An early insult (chemical exposure, viral infection, inherent cellular development abnormality caused by aneuploidy) could theoretically could theoretically result in a relative decrease in cell number as well as cell sizeresult in a relative decrease in cell number as well as cell size .. The resultant proportionate reduction in both head and body size has been termed symmetrical growth restriction A late pregnancy insult (placental insufficiency associated with hypertension) would affect primarily cell size. • Moreover, because placental insufficiency may result in diminished glucose transfer & hepatic storage, fetal abdominal circumference (which reflects liver size) would be reduced• Simultaneously, it is proposed that there is preferential shunting of oxygen and nutrients to the brain, which allows normal brain and head growth. This sequence of events can result in asymmetrical growth restriction with an abnormally increased relative brain size compared with the small liver• Because the fetal brain is normally relatively large and the liver relatively small, the ratio of brain weight to liver weight (usually about 3 to 1) over the last 12 weeks of pregnancy is increased to 5 to 1 or more in many severely FGR Although these generalizations about the potential pathophysiology of symmetrical vs asymmetrical growth restriction are interesting from a conceptual standpoint, there is considerable evidence that fetal growth patterns are more complex

Symmetrical Vs Asymmetrical FGR: some contradictions

Nicolaides K et al, 1991: compared the ratios of fetal head to abdominal circumference in 376 FGR with & without normal karyotypes: FGR with aneuploidy typically had disproportionately large head sizes & were therefore asymmetrically growth restricted rather than the hypothetically expected symmetrical pattern

Salafia CM, Vintzileos AM, et al, 1995: Similarly, most preterm infants with growth restriction due to preeclampsia & associated uteroplacental insufficiency demonstrate a symmetrical pattern of growth impairment rather than the hypothesized asymmetrical pattern

Symmetrical Vs Asymmetrical FGR

Crane JP, Kopta MM,, 1980

analyzed several anthropometric measurements in growth-restricted newborns & concluded that the concept of brain sparing was erroneous and could not be used to diagnose the cause of individual fetal growth restriction

Recognition of symmetrical vs asymmetrical patterns of FGR has interest in the antepartum diagnosis, because the pattern may potentially reveal the cause. This has been particularly true in the ultrasonic evaluation of FGR, where several dimensions of the fetus are now measured and can be related to each other in an attempt to evaluate proportionality of fetal structures. In practice: accurate identification of the symmetrical vs asymmetrical fetus is difficult This is probably because the concept of brain sparing in asymmetrical growth restriction is difficult to document in all but the most extreme cases

Symmetric FGR Asymmetric FGR

Estimated Fetal growth < 10% Head circumference/ Abdomen circumference Femur lengh/ Abdomen circumference Abdomen circumference < 10%Amniotic fluidAbnormalities

YesNormal

Normal

YesNormal or

May be present

Yes

YesNormal or

-

FGR Classification

Symmetrical Growth Restriction (Zuspan F, 1990)

Assymetrical Growth Restriction (Zuspan F, 1990)

Risk Factors for FGR

Fetal factors

Placental factors

Maternal factors

Chromosomal

Congenital anomalies

Primary disorders of cartilage& bone

Infections

(TORCH, listeria,

syphilis, BK)

Multiple fetuses

Abnormal

trophoblastic invasion

Abnormal cord

insertion

Placental disc

anomalies

Lower placental

insertion

Small placenta (Leger)

Tumors

Infarcts

Social deprivation: low income & poor nutrition

Constitutionally small mothers:

low weight & hight, low weight gain

Genetics

Cardiovascular diseases, hypertension inclusive

Autoimmune diseases

(antiphospholipid antibodies) & of collagen

Diabetes mellitus

Chronic renal diseases

Hemoglobinopathies

Others: smoking, alcohol, drugs (cocaine,

heroine, methadone), fenitoin, amynopterin, trimethadione

Current obstetrical complications:

antepartum hemorrhage, postmaturity

Previous obstetrical complications:

miscarriages, congenital anormalies,

perinatal deaths, previous FGR

Additional Insights into Human FGR

The technique of fetal blood sampling via the umbilical vein for karyotyping severely GRF has permitted remarkable insights into the pathophysiology• Soothill PW, et al, 1987: measured umbilical venous PO2, PCO2, pH, lactate & glucose concentrations, nucleated red cell count, & Hb in 38 growth-restricted fetuses• The severity of fetal hypoxia correlated significantly with fetal hypercapnia, acidosis, lactic acidemia, hypoglycemia, & erythroblastosis • Economides DL, Nicolaides K, 1989: the major cause of hypoglycemia in IUFGR is reduced supply rather than increased fetal consumption or decreased endogenous glucose production. • Economides DL, et al, 1989: later found that these fetuses also had hypoinsulinemia, which they attributed to pancreatic dysfunction, as well as hypoglycemia. The degree of FGR did not correlate with plasma insulin, suggesting that it is not the primary determinant of poor fetal growth

Additional Insights into Human FGR

Economides DL, et al,1989: measured glycine/valine ratio in

umbilical vessel blood from GRF & found ratios similar to those

observed in children with protein deprivation & Kwashiorkor.

Protein deprivation correlated with fetal hypoxemiaEconomides DL, et al, 1990: measured plasma triglyceride

concentrations in small—and appropriate-for-gestational-age fetuses:

GRF demonstrated hypertriglyceridemia that was correlated with the degree of fetal hypoxemia

They hypothesized that hypoglycemic GRF mobilize adipose

tissue, and that the hypertriglyceridemia is the result of lipolysis of fetal fat stores

Van den Hof MC, Nicolaides KP, 1990: observed that GRF may be thrombocytopenic, and the degree of platelet abnormality is correlated with the degree of growth restriction, hypoxemia, & acidemia

Additional Insights into Human FGR

Varner MW, et al, 1996: described in GRF Elevations in interleukin-10, placental atrial natriuretic peptide, plasma endothelin-1 concentrations, and a defect in epidermal growth factor function, Levine et al (2000): abnormal VEGF , PlGF

These suggest a possible role for abnormal immune activation and abnormal placentation in the genesis of this condition:

Gabriel R, 1994; Heyborne KD, 1994; Kingdom JCP, 1994;

McQueen J, 1993; Neerhof MG, 1995 In animals, chronic reduction in nitric oxide- an endothelium-derived locally acting vaso-relaxant, has also been shown to result in diminished fetal growth (Diket AL, et al, 1994). In contrast, fetal umbilical venous pressure does not correlate with either fetal size or the degree of acidemia (Ville Y, et al, 1994)

Peri and neonatal mortality of FGRPeri and neonatal mortality of FGR

Intrapartum fetal dystress

Hypothermia

Polycythemia

Hypoglycemia

Hypocalcemia

Meconium aspiration

Pulmonary hemorrhage

Fetal demise in utero

Screening & Identification of FGR Early establishment of GA Attention to maternal weight gain Careful measurements of uterine height throughout pregnancy will serve to identify many cases of abnormal fetal growth in women without risk factors Identification of risk factors, including a previously growth-restricted fetus, should raise the possibility of growth restriction during the current pregnancy In women with significant risk factors, consideration should be given to serial sonography to detect abnormal fetal growth; the frequency of examinations will vary depending upon clinical circumstances, an initial dating examination (first trimester) followed by a second examination at 32 to 34 wks, should serve to identify many cases of FGR

If clinical findings suggest inadequate fetal growth prior to this time, earlier sonography is necessary Definitive diagnosis usually cannot be made until delivery

Screening & Identification of FGR

Uterine Fundal Height A tape calibrated in centimeters is applied over the abdominal curvature from the top of the symphysis to the top of the uterine fundus, which is identified by palpation or percussion. Between 18 and 30 wks, the uterine fundal height in centimeters coincides with wks of gestation. If the measurement is more than 2 to 3 cm from the expected height, inappropriate fetal growth may be suspected

Carefully performed serial fundal height measurements throughout gestation are a simple, safe, inexpensive, and reasonably accurate screening method that may be used to detect many small-for-gestational-age fetuses Imprecision is the principal problem

Predictive value for fetal sizes at birth Predictive value for fetal sizes at birth of uterine fundal height: of uterine fundal height: Benson CB,

1986

Below 10 percentile (%)

Over 90 percentile

(%)

Sensitivity

Specificity

Positive predictive value

Negative predictive value

70/263 (27)

2337/2656 (88)

70/ 389 (18)

2337/2530 (92)

104/277 (38)

2321/2642 (88)

104/ 425 (25)

2321/2494 (93)

Screening & Identification of FGR

Ultrasonic Measurements Routine screening incorporates an ultrasound examination at 16 to 20 wks to establish: GA & rule out visible anomalies, and then follow-up imaging at 32 to 34 wks to evaluate fetal growth The optimal ultrasonographic method of estimating fetal size, and therefore FGR, has been reviewed by Manning R, 1995 Combining head, abdomen, & femur dimensions should in theory enhance the accuracy of predictions of fetal size Abdominal circumference measurements have been accepted by experienced ultrasonographers as the most reliable index of fetal size

Snijders RJM, Nicolaides KP, 1994; Manning R, 1995

Ultrasonic Measurements Small abdominal circumferences are linked to biochemical abnormalities such as hypoxia & acidemia Larsen T, et al, 1992:

• performed ultrasound after 28 wks and every 3 wks thereafter in 1000 pregnancies at risk for FGR

• Revealing the results of ultrasonic estimates of fetal growth during the third trimester significantly increased diagnosis of small-for-gestational-age fetuses. In this same group, elective deliveries also increased, but without overall improvement in neonatal mortality or morbidity

• Thus, this method of screening improved the diagnosis, but did not improve fetal outcome Goldenberg RL, et al, 1989: as the percentage of pregnancies undergoing ultrasound increased, fetal growth restriction decreased This was attributed to accurate GA information obtained using ultrasound

Ultrasonic Measurements An association between oligohydramnios and pathological fetal growth restriction has long been recognized (AF measurement in 4 quadrants) The smaller the vertical dimension of sonographically measured pocket of amnionic fluid, the greater the perinatal mortality The likely explanation for oligohydramnios is diminished fetal urine production due to hypoxia and centralisation of circulation Bladder volume measurements may give relations to diminished fetal urine production when circulation centralisation (Campbell S, Wladimiroff JW, Dewhurst CJ, 1973) When symmetrical FGR: IIIrd degree placental helps to differentiate from prematurity (Kazzi GM, Gross TL, FillyRA, 1983)

Placental degree

(Granum P, Berkovitz R, Hobbins J, 1979)

Conclusion: Sonography indicates IUFGR

when:

1. Fetal weight is estimated below 10 percentile for given gestational age

2. Increase ratio HC/AC more signifiant than 2 SD compared to average: 85% will have IUFGR

3. FL/AC more than 23.5

4. Diminished of fetal bladder volume

5. Diminished of amniotic fluid

6. High degree of placental maturation

Doppler Velocimetry in FGR (1(1))

Umbilical Artery: estimates blood flow and placental vascular resistence- Blood flow is present during all cardiac Blood flow is present during all cardiac cycle; normal S/D ratio cycle; normal S/D ratio < 3,5 after 30 wks after 30 wks

ForouzanForouzan et al. et al. 1991 1991

- - Abnormal aspect is associated to a high risk Abnormal aspect is associated to a high risk of fetal acidosis- proved by cordocentesisof fetal acidosis- proved by cordocentesis

- - Low (absence) of end- diastolic flow (by Low (absence) of end- diastolic flow (by reducing arterioles number/ tertiary villosity) reducing arterioles number/ tertiary villosity) is previous with 7 days to NST alterationis previous with 7 days to NST alteration- Reverse diastolic end- flow is more Reverse diastolic end- flow is more dangerous, being predictive for developing dangerous, being predictive for developing brain damages (during school years)brain damages (during school years) Valcamonico A, et al, 1994Valcamonico A, et al, 1994- Abnormal Umbilical Doppler aspects are Abnormal Umbilical Doppler aspects are better correlated to fetal acidosis than NSTbetter correlated to fetal acidosis than NST- Umbilical Artery Doppler assesssments are Umbilical Artery Doppler assesssments are proposed as screening for: FGR, HBP and not proposed as screening for: FGR, HBP and not in normal pregnancyin normal pregnancy- These conditions are frequently seen in These conditions are frequently seen in association with fetal aneuploidy & other association with fetal aneuploidy & other malformationsmalformations (Rizzo G, et al, 1994)(Rizzo G, et al, 1994)

Umbilical Artery Doppler Velocimetry

In high-risk populations, sensitivities in the range of 75- 95% have been reported Conversely, in screening programs involving general obstetrical populations, sensitivities in the range of 15 - 30% are more common

Beattie RBBeattie RB, et al 1989; , et al 1989; Bruinse HWBruinse HW, et al 1989 , et al 1989

Kay JJKay JJ, et al 1991; , et al 1991; Trudinger BJTrudinger BJ, et al, 1985, et al, 1985 Perinatal deaths reduction (Odd Ratio: 0.71; CI: Perinatal deaths reduction (Odd Ratio: 0.71; CI: 0.50- 1.01)0.50- 1.01) Less labor inductions: (Odd Ratio: 0.83; IC: 0.74- Less labor inductions: (Odd Ratio: 0.83; IC: 0.74- 0.93)0.93) Less days for hospitalisation, with adverse events Less days for hospitalisation, with adverse events (Odd Ratio : 0.56; CI:0.43- 0.72)(Odd Ratio : 0.56; CI:0.43- 0.72)

Fetal Doppler Velocity (2)(2)

Medium Cerebral ArteryMedium Cerebral Artery

- - When hypoxy & hypercapnia, fetal end-diastolic blood flow is increased, and Pulsatility Index is reduced, phenomenon known as”brain sparing”- These changes may be previous to the change of S/D ratio on umbilical artery or pulsatility

index - The measurement of maxim systolic peak is predictor for severe fetal anemia instead of invasive techniques when Rh isoimmunisation

FGR Doppler VelocityFGR Doppler Velocity (3)

- Depiction of: FGR, fetal hydrops, heart and liver defects, diafragmatic hernia, tranfuser-transfused syndrome in gemelarity - When fetal hypoxy is increased the umbilical venous flow which cross the ductus venosus, uncertain if it is because central venous pressure increase or vasodilation

- In fetal hypoxemia, through ductus venosus the resistence is reduced, because of retrograde velocity in umbilical vein during artrial contractions, which when present during fetal breathing movements imposes great attention

Ductus venosusDuctus venosus

--DV plays a role in venous blood flow regulation between inferior vena cava and umbilical vein

Fetal Doppler AspectsFetal Doppler Aspects (4)(4)

Sagital view : aortic arch and isthmus (white triangle) connects the 2 fetal parallel circulatory systems (right & left ventricles)Velocity in aortic

isthmus:a) normal pattern in

uncomplicated pregnancy;

b) anterograde flow (anterograd/retrograd ratio of 2)

c) retrograde flow corresponding to a value of 0.54 in pregnancies complicated with placental inssuficiency

Fetal Doppler AspectsFetal Doppler Aspects (5)(5) In normal pregnancies, there is a In normal pregnancies, there is a small retrograde flow at the end of small retrograde flow at the end of pregnancy, which shows a small pregnancy, which shows a small increase of placental vascular increase of placental vascular resistence or of fetal peripheric resistence or of fetal peripheric circulationcirculation

Fouron et al, 1994 Fouron et al, 1994

RasanenRasanen et al, 1996et al, 1996 Brain oxygen deliver is ensured Brain oxygen deliver is ensured when there is anterograde flow. when there is anterograde flow. When retrograde flow- brain oxygen When retrograde flow- brain oxygen deliver decreases even if blood flow deliver decreases even if blood flow in cerebal arteries is increasedin cerebal arteries is increased

Fouron et al, 1999Fouron et al, 1999 Blood flow in aortic isthmus is changed previous damages in velocity of umbilical arteries

BonninBonnin et al, 1993et al, 1993

Antenatal FGR depictionAntenatal FGR depiction Fetal Doppler assessmentsFetal Doppler assessments (7)(7)

As fetal Doppler assessments may bring uncertain As fetal Doppler assessments may bring uncertain informations, informations,

which can induce which can induce unproper clinical decisions, it is imperative that unproper clinical decisions, it is imperative that

Doppler measurements & interpretations to be done by Doppler measurements & interpretations to be done by skilled opperatorsskilled opperators, ,

who know the significance of registered changes and who who know the significance of registered changes and who practice adequate techniquespractice adequate techniques

Management of FGR

Once a small-for-gestational-age fetus is suspected, intensive efforts should be made to determine if

• growth restriction is present and,

• if so, its type and the etiology In the presence of sonographically detectable anomalies, cordocentesis may be performed for rapid karyotyping The detection of a lethal aneuploidy may obviate cesarean section for fetal indications Efforts are made to ensure delivery, when possible, of an infant who will subsequently thrive and achieve normal potential

Management of FGR

Growth Restriction Near Term

Prompt delivery is likely to afford the best outcome for the fetus who is considered growth restricted at or near term

In the presence of significant oligohydramnios, most fetuses will be delivered if GA has reached 34 wks or beyond

• Assuming that the fetal heart rate pattern is reassuring (with LAT), vaginal delivery may be attempted• Unfortunately, such fetuses often tolerate labor less well than their appropriately grown counterparts, & CS is indicated for intrapartum fetal compromise Importantly, uncertainty about the diagnosis of fetal growth restriction should preclude intervention until fetal lung maturity is assured

Management of FGR

Growth Restriction Remote from Term

Observation is recommended → a growth-restricted fetus is diagnosed prior to 34 wks, & amnionic fluid volume & antepartum fetal surveillance is normal, Sonography is repeated at intervals of 2 to 3 wks• As long as there is continued growth & fetal evaluation remains normal, the pregnancy is allowed to continue until fetal maturity is achieved otherwise, delivery is effected • At times, amniocentesis for assessment of pulmonary maturity may be helpful in clinical decision making

• A sonographic search should be made for fetal anomalies, and consideration should be given to obtaining umbilical blood for karyotyping, especially if a chromosomal anomaly is suspected

• Uniform indications for such testing have not been established

Pearce JMF, Campbell S (1985) recommend screening for toxoplasmosis, rubella, CMV, herpes, and other viral agents, not all researchers found this to be productive in most cases of suspected growth restriction

Management of FGR

In FGR remote from term, there is In FGR remote from term, there is no specific treatment that will ameliorate the condition1. Although there is no evidence that bed rest actually results in accelerated fetal growth or improved outcome in growth-restricted fetuses, many clinicians advise a program of modified rest in the lateral recumbent position in which maternal cardiac output—and presumably placental perfusion—is maximized

2. In most cases of FGR diagnosed prior to term, neither a precise etiology nor a specific therapy is apparent Management decisions in such cases hinge upon an assessment of the relative risks of fetal damage or death with continued prenatal evaluation versus the risks due to preterm delivery

3. Although reassuring tests of fetal well-being will in many cases allow safe observation & continued maturation of significantly preterm growth-restricted fetuses, concern exists for their long-term neurological outcome

Blair E, Stanley F, 1990 Although it is generally believed various tests of fetal well-being appear to be effective in reducing the risks of fetal death, some investigators challenge this belief

Management of Fetal Growth Management of Fetal Growth RestrictionRestriction

4. By way of contrast::• three large prospective trials of low-dose aspirin did not confirm these findings:• Sibai BM, et al, 1993• Italian Study of Aspirin in Pregnancy, 1993 • CLASP, 1994 5. Rajhvajn B, et al (1991): reported improved fetal growth with the maternal administration of high concentrations of oxygen in cases of severe, unexplained FGR

Kurjak A, Zmijanac J, 1992: : appropriately emphasize that prospective clinical trials are necessary

Labor and DeliveryAbnormalities of fetal heart rate must be monitored because will evidence compromise of fetuses suspected of being GR throughout labor, spontaneous or induced FGR is commonly the result of insufficient placental function as a consequence of faulty maternal perfusion, ablation of functional placenta, or both These conditions are likely aggravated by labor

Lin CC, et al, 1991 Importantly, diminished amnionic fluid also predisposes to cord compression and its dangers Cesarean delivery is also increased in FGR because breech presentation occurs more commonly

Sherer DM, et al, 1996

Subsequent Development of the GRF

o Vohr BR,et al, 1979: reported that preterm, small-for-gestational-age infants had similar outcomes at 18 to 24 months, compared with appropriate-for-gestational-age preterm infants

o Vohr BR, Oh W, 1983: a longer follow-up of preterm small-for-gestational-age infants also supported the view that a long-term favorable outcome may be expected• In contrast to this favorable outlook:

• Low JA, et al, 1992: in a 9- to 11-year follow-up study, demonstrated learning deficits in almost half of growth-restricted infants

• Blair E,Stanley F (1990, 1992) reported a significant association between FGR and subsequent cerebral palsy

Subsequent Development of the GRF

Subsequent growth of the individual newborn who is GR cannot be predicted reliably from anthropometric measurements obtained at birth • In general, prolonged symmetrical, or generalized, fetal growth restriction is likely to be followed by slow growth after birth

• By contrast, the asymmetrically growth-restricted fetus, is more likely to catch up after birth (Brook CGD, 1983) The subsequent neurological & intellectual capabilities of the infant who was GR in utero cannot be predicted precisely, & conflicting reports are available

FGR in Subsequent FGR in Subsequent PregnanciesPregnancies

The risk of recurrent fetal growth restriction is increased in pregnant women who have previously had this complication

Bakketeig LS, et al, 1986Bakketeig LS, et al, 1986 This is particularly true in women with a history of FGR and a continuing medical complication

Patterson RM, et al, 1986Patterson RM, et al, 1986

Labor and Delivery

It can be anticipated that the infant may need expert assistance in making a successful transition to air breathing The fetus is at risk of being born hypoxic & of having aspirated meconium It is essential that care for the newborn be provided immediately by someone who can skillfully clear the airway below the vocal cords, especially of meconium, & ventilate the infant as needed The severely growth-restricted newborn is particularly susceptible to hypothermia and may also develop other metabolic derangements such as serious hypoglycemia, polycythemia, hyperviscosity

D. Barker’s Hypothesis D. Barker’s Hypothesis for long term sequellae

“Fetal and Infant Origins of Adult Diseases” (1992) GRFs have as risks during adult life:

HypertensionHypertension Diabetes MellitusDiabetes Mellitus AtherosclerosisAtherosclerosis

Hubinette A, et al (2001); Huxley R, et al, 2002: reports on relationship between FGR & hypertension

Smith GCS , et al, 2002: risk of ischemic heart disease in mothers of low birthweight fetuses