IUGR Post date IUFD

Dr. Wajeih ALAali, SSCOG, ABOG, MFMConsultant OBGYN and Fetal medicine

Intrauterine Growth Restriction

❖ Definition:

Birth weight of a newborn infant is below the 10th percentile for a given gestational age

❖ Growth-restricted fetuses at risk of:

✓ meconium aspiration

✓ asphyxia

✓ polycythemia

✓ hypoglycemia

✓ mental retardation.

✓ Adult onset conditions such as hypertension, diabetes, and atherosclerosis

ETIOLOGY

❖ Maternal

❖ Placental

❖ Fetal

ETIOLOGY ❖ Maternal:

✓ poor nutritional intake

✓ cigarette smoking

✓ drug abuse✓ early cardiovascular disease

✓ hypertension & diabetes

✓ obesity

✓ alcoholism

✓ cyanotic heart disease

✓ pulmonary insufficiency

✓ antiphospholipid syndrome

✓ thrombophilias

ETIOLOGY ❖ Placental:

✓ placental insufficiency; essential hypertension, obesity (associated with leptin resistance which leads to placental dysfunction), chronic renal disease, and gestational hypertension

✓ placental or cord abnormalities ❖ Fetal

✓ Intrauterine infection (listeriosis and TORCH)

✓ Congenital anomalies.

Types of IUGR ❖ Symmetrical:

✓ Early onset

✓ HC/AC ratio may be normal

✓ Intrauterine infections, congenital fetal anomalies or chromosomal abnormality

❖ Asymmetrical:

✓ Late in pregnancy

✓ Normal head size, small AC.

✓ Inadequate nutrition, low glycogen in liver.

DIAGNOSIS

Accurate dating ❖ LMP

❖ First trimester US: CRL

❖ Clinical assessment

❖ FH Audible, FM perception

DIAGNOSIS

Ultrasound

❖ Fetal weight parameters: BPD, HC, AC, FL

❖ Serial fetal growth assessment

❖ AFI

❖ Umbilical Artery Doppler

❖ MCA Doppler

❖ DV Doppler

Figure 2: Abnormal Development of the umbilical artery

A review of 12 randomized, controlled trials of Doppler ultrasonography of the umbilical artery in high-risk pregnancies reported that, in the Doppler group, there was a significant reduction in the number of antenatal admissions (44%, 95% confidence interval (CI) 28–57%), induction of labor (20%, 95% CI 10–28%), and Cesarean

section for fetal distress (52%, 95% CI 24–69%) 37. Furthermore, the clinical action guided by Dopplerultrasonography reduced the odds of perinatal death by 38% (95% CI 15–55%). Post hoc analyses revealed a statistically significant reduction in elective delivery, intrapartum fetal distress, and hypoxic encephalopathy in the Doppler group. It was concluded that there is now compelling evidence that women with high-risk pregnancies, including pre-eclampsia and suspected intrauterine growth restriction, should be offered Doppler ultrasonographic

study of umbilical artery waveforms 37.

In terms of monitoring growth-restricted pregnancies, abnormal waveforms in the umbilical artery are an early sign of fetal impairment. For example, Bekedam et al. followed up growth-restricted fetuses longitudinally and reported thatabnormalities in the umbilical artery preceded the occurrence of cardiotocographic signs of fetal hypoxemia in more

than 90% of cases 38. The median time interval between absence of end-diastolic frequencies and the onset of late decelerations was 12 days (range 0–49 days).

Fetal arterial blood flow redistribution

In fetal hypoxemia, there is an increase in the blood supply to the brain, myocardium and the adrenal glands and reduction in the perfusion of the kidneys, gastrointestinal tract and the lower extremities (Figure 3 and 4, Table 1 )39–66. Although knowledge of the factors governing circulatory readjustments and their mechanism of action is incomplete, it appears that partial pressures of oxygen and carbon dioxide play a role, presumably through their action on chemoreceptors. This mechanism allows preferential delivery of nutrients and oxygen to vital organs, thereby compensating for diminished placental resources. However, compensation through cerebral vasodilatation islimited and a plateau corresponding to a nadir of pulsatility index (PI) in cerebral vessels is reached at least 2 weeks before the development of the fetus is jeopardized. Consequently, arterial vessels are unsuitable for longitudinalmonitoring of growth-restricted fetuses. Cardiac and venous velocity waveforms give more information regarding fetal well-being or compromise.

Abnormal Development of the umbilical artery

Umbilical arteries - high pulsatility index

Umbilical arteries - high pulsatility index

Umbilical arteries - very high pulsatility index. - end diastolic velocity - pulsation in the umbilical vein

Umbilical arteries Severe cases absence of reversal of end diastolic frequencies

Management

Prevention

❖ Previous history: Uterine artery Doppler, Previous workup. Start ASA

❖ Optimise general health condition

❖ APL ASA

❖ Thombophilia LMWH

Management Antepartum

❖ Assess modifiable risks

❖ US

❖ Fetal well being tests: NST, BPP, Doppler study, Fetal kick chart

❖ Amniocentesis

❖ TORCH

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abnormalities in flow can identify fetuses with the worstoutcomes. Further research is needed to evaluate the optimaltiming of delivery with the above abnormalities in fetal bloodflow.

Fetal Kick CountsThere is insufficient evidence (no trials) to assess the effect offetal kick counts specifically for FGR fetuses.

NST/CardiotocographyMonitoring of the fetal heart rate is commonly referred to asNST, or as cardiotocography (CTG). CTG has not been well-evaluated with high-quality studies in FGR. When comparingCTG with no CTG, there is no difference in the prediction ofperinatal mortality, preventable deaths, or cesarean sections(154). Computerized CTG may improve perinatal mortalitywhen compared to traditional CTG (154). However, this anal-ysis was not limited to FGR fetuses, and the benefit of ante-natal CTG has yet to be fully investigated in this population. Inmany management schemas, CTG has been cited as a standardmonitoring tool, despite the lack of rigorous studies proving itsefficacy (1). Nonreactive and abnormal CTG has been associ-ated with acidosis and hypoxemia, (155,156) and this justifiesits use as a screening tool for fetal well-being.

Biophysical ProfileEvidence from RCTs does not support the use of BPP as a testof fetal well-being in high-risk pregnancies (157). In high-

risk pregnancies (including FGR, post-term pregnancies,hypertensive disorders, or other conditions), when comparinga BPP to other tests of fetal well-being, there is no difference inperinatal deaths or low Apgar scores (157). Although theoverall incidence of adverse outcomes was low, there is nosignificant differences between the groups in perinatal deaths(RR 1.33, 95% CI 0.60–2.98) or in Apgar score <7 at fiveminutes (RR 1.27, 95% CI 0.85–1.92). Combined data from thetwo high-quality RCTs suggest an increased risk of cesareansection in the BPP group (RR 1.60, 95% CI 1.05 to 2.44) (157).The impact of the BPP on other interventions, length of hos-pitalization, serious short-term and long-term neonatal mor-bidity and parental satisfaction requires further evaluation. InFGR alone, RCTs are lacking to prove the value of the BPP,but it is still mentioned as a surveillance tool in these preg-nancies (1). This is justified in that fetal death within one weekof a normal score on BPP testing is rare, estimated at about<0.1% in one study (158).

Estriol LevelsCompared to concealed levels, knowledge of plasma estriollevels does not affect perinatal mortality (3% in each group) inwomen with FGR, hypertension, or adverse obstetric history(159).

Interval of Fetal TestingTesting should start usually on the diagnosis of FGR. On thebasis of the evidence above, UA Doppler evaluation is

Figure 44.1 Algorithm for the management of the IUGR fetus. *Indicates at >24 weeks, deliver for category III NST/CTG. Abbreviations:wk, weeks; EFW, estimated fetal weight; BPP, biophysical profile; NST, nonstress test; MCA, middle cerebral artery Doppler; UA, umbilicalartery; AREDF, absent or reversed end diastolic flow; REDF, reversed end diastolic flow; AEDF, absent end diastolic flow; DV, ductusvenosus; MVP, maximum vertical pocket (of amniotic fluid).

FETAL GROWTH RESTRICTION 337

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Don’t forget

❖ Iatrogenic PTB and complication of prematurity

❖ Corticosteroids for fetal lung maturity

❖ Magnesium sulphate for fetal neuroprotection < 32 weeks

Post-term pregnancy

Post-term pregnancy

❖ Post term: singleton pregnancy that has lasted until ≥ 42weeks or ≥ 294 days.

❖ Postdates: singleton pregnancy that has lasted until ≥ 40 weeks, or ≥ 280 days

❖ Perinatal mortality x 3

Post-term pregnancy Risk factors/associations

❖ Wrong dating

❖ Prior post-term pregnancy

❖ Nulliparity

❖ Long (> 28 days) cycles without early ultrasound; placental sulfatase deficiency

❖ Anencephaly

❖ Male fetus.

Complication ❖ Meconium aspiration

❖ Intrauterine infection

❖ Oligohydramnios

❖ Macrosomia

❖ Non-reassuring fetal heart testing (NRFHT)

❖ Low umbilical artery pH

❖ Low 5-minute Apgar score

❖ Labor dystocia, perineal injury, and cesarean delivery

Prevention

❖ Accurate dating

❖ Stripping the membrane at 38 weeks

Interventions

❖ Initiate fetal well being tests at 40 weeks

❖ Favorable cervix:≥ 41weeks

❖ Unfavorable cervix: routine induction of labor at ≥ 41 weeks

IUFD

IUFD

❖ Fetal death after 20 weeks’ gestation but before the onset of labor.

❖ 1% of pregnancies.

Risk factors

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non-Hispanic black race, nulliparity or multiparity (>5),unmarried status, low socioeconomic status, low education,multiple gestation, assisted reproductive technology, and pastobstetric history (previous stillbirth, preterm delivery, orgrowth restriction) (6–16). Obesity, smoking, drug, and alco-hol abuse are common modifiable risk factors for fetal death.Pesticides, radiation, and fertility drugs have also been asso-ciated with fetal death. In developing countries, the mostcommon causes of stillbirths are complications of labor andinfections. Basic emergency obstetric care, births in adequatefacilities with option for safe cesarean delivery (CD), improve-ment in nutrition, and prevention and treatment of syphilisand malaria are the most feasible and cost-effective interven-tions in developing countries to decrease the incidence ofstillbirth (17).

PREVENTIONSome of the risk factors listed in Table 54.1, in particularobesity, smoking, and drug and alcohol abuse, are modifiable,and should be avoided. As the vast majority of fetal deathsoccur in developing countries, interventions should be focusedon prevention in these settings, and include (18) the following:

l Periconception folate fortificationl Insecticide-treated bed nets or intermittent preventative

treatment for malarial Syphilis detection and treatmentl Detection and treatment of hypertensive disordersl Detection and management of diabetes in pregnancyl Detection and management of FGRl Induction at 41 weeks (prevention of postterm pregnancy)l Skilled care at birthl Basic and comprehensive emergency obstetric care

PREGNANCY MANAGEMENTCounselingCounseling should include review of possible etiologies(Table 54.1), workup (Table 54.2), delivery options, as well as

Table 54.1 Associations/Risk Factors/Possible Etiologies of Fetal Death

Maternal risk factors Fetal risk factors

Chronic hypertensionPreeclampsiaDiabetes mellitus, thyroid disordersRenal diseaseSystemic lupus erythematosusAutoimmune diseaseAntiphospholipid syndromeCholestasis of pregnancyAlloimmunizationObesitySubstance abuse (especially cocaine, alcohol, coffee:>3 cups/day, etc.)

SmokingViral infections:

Parvovirus B19CytomegalovirusEnteroviruses (e.g., coxsackie virus)EchovirusesHSV-1, HSV-2HIV

Bacterial infections:Listeria monocytogenesEscherichia coliGroup B streptococciUreaplasma urealyticumTreponema pallidum

Parasitic infections:Toxoplasma gondii

Uterine malformationsAbdominal trauma

Congenital malformations (15–20%)Chromosomal/genetic abnormalities (8–13%): monosomy X,trisomy 21, trisomy 18, and trisomy 13

Single gene disorders: hemoglobinopathies (e.g., alpha-thalasse-mia); metabolic diseases (e.g., Smith–Lemli–Opitz syndrome)

Glycogen storage diseasesPeroxisomal disorders amino acid disordersConfined placental mosaicism (aneuploidy in placenta with a euploidfetus)

Placental abruption, placenta and vasa previaPlacental pathology

Chronic villitisMassive chorionic intervillositis

Complications of multifetal gestation (e.g., twin-twin transfusion, twinreversed arterial perfusion syndrome, and discordant growth)

Umbilical cord complications, fetomaternal hemorrhageFetal growth restrictionUteroplacental insufficiencyIntrauterine asphyxiaPreterm labor or rupture of membranesPostterm

In bold, most common associations.

Table 54.2 Maternal and Fetal Investigation for Fetal Death

Predeliveryl Amniotic fluid for cytogeneticsl Screen for coagulopathy (only if fetal death > 4 wk from delivery)l CBC, antibody screen, urine drug screenl Kleihauer–Betke testing or flow cytometryl Lupus anticoagulant, anticardiolipin antibodies (IgM, IgG) and

anti-b2-glycoprotein antibodies (IgM, IgG)l Parvovirus B19 titers (IgM, and IgG)a

l Syphilis testing (RPR or VDRL)l Thyroid-stimulating hormonel Glucose screening (oral glucose tolerance test, hemoglobin

A1C) (if glucose screening not done in pregnancy)l Thrombophilia workup only to be considered in cases of severe

placental infarcts, fetal growth restriction, or in the setting of apersonal history of thrombosis (factor V Leiden mutation;G20210A prothrombin gene mutation; antithrombin III)

Postdeliveryl Cord blood for cytogeneticsl Autopsy and placental examinationl Protein C, protein S activity (in selected cases as described

above for other thrombophilia workup)

aConsider workup for parvovirus especially in cases with fetal hydrops orother signs of this viral infection

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Diagnosis➡ Suspect

❖ Absence of fetal movements

❖ Uterus is small for dates

❖ Fetal heart tones are not detected

➡ Confirm by US

❖ NO FH activity

❖ Overlapping of skull bones (Spalding sign)

❖ Gas shadow in fetal heart (Robert sign)

Management

❖ Expectant management: weekly coagulation

❖ IOL: Prostaglandin, Misoprostol

Work up

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non-Hispanic black race, nulliparity or multiparity (>5),unmarried status, low socioeconomic status, low education,multiple gestation, assisted reproductive technology, and pastobstetric history (previous stillbirth, preterm delivery, orgrowth restriction) (6–16). Obesity, smoking, drug, and alco-hol abuse are common modifiable risk factors for fetal death.Pesticides, radiation, and fertility drugs have also been asso-ciated with fetal death. In developing countries, the mostcommon causes of stillbirths are complications of labor andinfections. Basic emergency obstetric care, births in adequatefacilities with option for safe cesarean delivery (CD), improve-ment in nutrition, and prevention and treatment of syphilisand malaria are the most feasible and cost-effective interven-tions in developing countries to decrease the incidence ofstillbirth (17).

PREVENTIONSome of the risk factors listed in Table 54.1, in particularobesity, smoking, and drug and alcohol abuse, are modifiable,and should be avoided. As the vast majority of fetal deathsoccur in developing countries, interventions should be focusedon prevention in these settings, and include (18) the following:

l Periconception folate fortificationl Insecticide-treated bed nets or intermittent preventative

treatment for malarial Syphilis detection and treatmentl Detection and treatment of hypertensive disordersl Detection and management of diabetes in pregnancyl Detection and management of FGRl Induction at 41 weeks (prevention of postterm pregnancy)l Skilled care at birthl Basic and comprehensive emergency obstetric care

PREGNANCY MANAGEMENTCounselingCounseling should include review of possible etiologies(Table 54.1), workup (Table 54.2), delivery options, as well as

Table 54.1 Associations/Risk Factors/Possible Etiologies of Fetal Death

Maternal risk factors Fetal risk factors

Chronic hypertensionPreeclampsiaDiabetes mellitus, thyroid disordersRenal diseaseSystemic lupus erythematosusAutoimmune diseaseAntiphospholipid syndromeCholestasis of pregnancyAlloimmunizationObesitySubstance abuse (especially cocaine, alcohol, coffee:>3 cups/day, etc.)

SmokingViral infections:

Parvovirus B19CytomegalovirusEnteroviruses (e.g., coxsackie virus)EchovirusesHSV-1, HSV-2HIV

Bacterial infections:Listeria monocytogenesEscherichia coliGroup B streptococciUreaplasma urealyticumTreponema pallidum

Parasitic infections:Toxoplasma gondii

Uterine malformationsAbdominal trauma

Congenital malformations (15–20%)Chromosomal/genetic abnormalities (8–13%): monosomy X,trisomy 21, trisomy 18, and trisomy 13

Single gene disorders: hemoglobinopathies (e.g., alpha-thalasse-mia); metabolic diseases (e.g., Smith–Lemli–Opitz syndrome)

Glycogen storage diseasesPeroxisomal disorders amino acid disordersConfined placental mosaicism (aneuploidy in placenta with a euploidfetus)

Placental abruption, placenta and vasa previaPlacental pathology

Chronic villitisMassive chorionic intervillositis

Complications of multifetal gestation (e.g., twin-twin transfusion, twinreversed arterial perfusion syndrome, and discordant growth)

Umbilical cord complications, fetomaternal hemorrhageFetal growth restrictionUteroplacental insufficiencyIntrauterine asphyxiaPreterm labor or rupture of membranesPostterm

In bold, most common associations.

Table 54.2 Maternal and Fetal Investigation for Fetal Death

Predeliveryl Amniotic fluid for cytogeneticsl Screen for coagulopathy (only if fetal death > 4 wk from delivery)l CBC, antibody screen, urine drug screenl Kleihauer–Betke testing or flow cytometryl Lupus anticoagulant, anticardiolipin antibodies (IgM, IgG) and

anti-b2-glycoprotein antibodies (IgM, IgG)l Parvovirus B19 titers (IgM, and IgG)a

l Syphilis testing (RPR or VDRL)l Thyroid-stimulating hormonel Glucose screening (oral glucose tolerance test, hemoglobin

A1C) (if glucose screening not done in pregnancy)l Thrombophilia workup only to be considered in cases of severe

placental infarcts, fetal growth restriction, or in the setting of apersonal history of thrombosis (factor V Leiden mutation;G20210A prothrombin gene mutation; antithrombin III)

Postdeliveryl Cord blood for cytogeneticsl Autopsy and placental examinationl Protein C, protein S activity (in selected cases as described

above for other thrombophilia workup)

aConsider workup for parvovirus especially in cases with fetal hydrops orother signs of this viral infection

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Questions ?