• 1.
  

  The gold standard test for antenatal surveillance of the pregnancy at-risk for an adverse pregnancy outcome with the lowest false negative rate is:

  
  
  
  
  • a)
    

    Biophysical Profile

    
    
  • b)
    

    CTG only

    
    
  • c)
    

    CTG and an estimation of the amniotic fluid volume

    
    
  • d)
    

    Contractions stress test

    
    
  • e)
    

    ST analysis

  
  
  
  
• 
  

  Answers

  
  
• 
  

  a) F b) F c) F d) T e) F

The biophysical profile (BPP) has a false negative rate of 0.6/1000. CTG only a false negative rate of 1.9-5/100. CTG and estimation of the amniotic fluid volume has a false negative rate of 0.8/1000. The contraction stress test has a false negative rate of 0.4/1000. ST analysis is only used intrapartum in conjunction with CTG.

• 2.
  

  The studies that have correlated ultrasound estimates of amniotic fluid volume with a dye-determined or directly measured amniotic fluid volume at the time of Caesarean delivery have observed which of the following?

  
  
  
  
  • a)
    

    The ultrasound estimate of amniotic fluid volume is correlated well with high volumes of amniotic fluid (polyhydramnios)

    
    
  • b)
    

    The ultrasound estimate of amniotic fluid volume is correlated well with low volumes of amniotic fluid volume (oligohydramnios)

    
    
  • c)
    

    The ultrasound estimate of amniotic fluid volume is correlated well with anhydramnios

    
    
  • d)
    

    The ultrasound estimate of amniotic fluid volume is correlated well with normal volumes of amniotic fluid

    
    
  • e)
    

    The ultrasound estimate of amniotic fluid volume is not correlated with low, normal, or high volumes of amniotic fluid.

  
  
  
  
• 
  

  Answers

  
  
• 
  

  a) F b) F c) F d) T e) F

Polyhydramnios is poorly identified by ultrasound. Oligohydramnios is also poorly identified by ultrasound. Normal amniotic fluid volume is correlated well with the ultrasound estimate of the amniotic fluid volume. The ultrasound estimate of amniotic fluid volume is correlated with normal amniotic fluid volume but not actual oligohydramnios or polyhydramnios

• 3.
  

  a) F b) F c) T d) T e) F

Although there is evidence that the use of umbilical artery Doppler findings can reduce the mortality by 29% in high risk pregnancies, high resistance to umbilical arterial flow can only help define growth restriction rather than predict adverse perinatal outcomes. Umbilical artery reverse flow has been shown to predict neonatal mortality. CTG interpretation in conjunction with umbilical artery Doppler velocimetry findings have been shown to reduce not only neonatal mortality but also to reduce hospital stay. Most reference charts report the umbilical artery Doppler in a free loop of cord. Impedance values are higher at the fetal end of the cord and lower at the placental end. The aetio-pathogenesis of early and late onset FGR is different; hence the pattern of deterioration of umbilical artery Doppler velocimetry is often not similar. In early onset FGR there is a reduction of villi, unlike in late onset where there is mainly impaired maturation. Therefore, the deterioration of umbilical artery Doppler waveform may not occur until very late in late onset FGR.

• 4.
  

  a) F b) T c) T d) F e) F

Whilst several studies have shown that the cerebro-placental ratio is associated with adverse perinatal outcomes in late third trimester FGR, none have shown that it is strongly predictive. The MCA – umbilical artery Doppler ratio is associated with emergency Caesarean section even in the presence of normal umbilical artery Doppler velocimetry. The MCA Doppler is a useful tool to evaluate cerebral vasodilatation and multi-centre studies have shown that it is associated with poor perinatal outcome; however, it does not inform the timing of delivery. CPR less than 1 is associated with fetal hypoxia and is present in a quarter of cases of late onset FGR prior to delivery. Although one study has shown that CPR correlates with adverse perinatal outcomes, there is still uncertainty about the interpretation of findings in association with timing of delivery.

• 5.
  

  a) T b) T c) T d) F e) T

Negative IgG associated with negative IgM show the absence of past or recent CMV immunity. Of note, when CMV serology test are performed at the very beginning of symptoms, IgG might be negative with isolated positive IgM. In this case a second sample must be tested 10 days later to confirm (or not) primary infection by IgG seroconversion. CMV IgM are very sensitive and the probability of missing a recent primary infection because of false negative IgM is very low. A serological profile showing a combination of positive IgG and positive IgM is compatible with a recent primary infection. Positive CMV IgM is not specific and the presence of IgM is insufficient to diagnose recent primary infection. Indeed, detection of CMV IgM may be related to persistent specific IgM, cross reactivity of IgM related to other ongoing viral infection, non-specific stimulation of the immune system or episodes of reactivation. The measurement of IgG avidity is mandatory to confirm (or not) recent primary infection. High IgG avidity will exclude a recent primary infection in the last 3 months. Low avidity will confirm recent primary infection in the last 3 months. An intermediate avidity does not exclude a recent infection.

• 6.
  

  a) F b) T c) T d) T e) F

Timing of amniocentesis is crucial for optimal sensitivity of prenatal diagnosis. It should be done after 20 weeks’ to allow maturation of fetal urination but also at least 6 weeks after the presumed date of maternal primary infection. Therefore, in this case amniocentesis should be scheduled after 23 weeks. CMV PCR is the best technique for detection of CMV DNA in amniotic fluid. When using automated real time PCR technology the specificity and sensitivity are close to 100%. There is a residual risk of false negative prenatal diagnosis of 5 to 10%. These false negative results are in relation to trans-placental passage of the virus later than 6 weeks after maternal primary infection. Therefore, in cases of maternal primary infection, CMV detection should be performed in the newborn even if amniocentesis was negative. However, neonates found infected after a negative prenatal diagnosis have an excellent long-term prognosis. CMV-PCR in amniotic fluid collected at a timely amniocentesis has a very high negative predictive value and should not be repeated. Moreover, as seen above false negative cases have a good prognosis.

• 7.
  

  a) T b) F c) F d) T e) T

CMV fetal infection is impossible if the mother is not immune to CMV. Therefore, it is not necessary to perform CMV PCR in the amniotic fluid in seronegative women at the time of amniocentesis. A serology with positive IgG and negative IgM at 26 weeks does not exclude the occurrence of primary infection in the first trimester since IgM may have already disappeared at that time. Moreover, CMV fetal infection may occur after maternal secondary infection. A positive CMV serology 2 years before pregnancy excludes the occurrence of primary infection during the present pregnancy. However, as stated above symptomatic fetal infection may occur after maternal secondary infection. Therefore, every woman with a positive CMV IgG detection carrying a fetus presenting with symptoms compatible with CMV infection, must benefit from a amniocentesis and a CMV PCR in the amniotic fluid. If the fetus is symptomatic, CMV DNA will always be present in the amniotic fluid retrieved after 20 weeks and since PCR assays are very sensitive, a negative CMV PCR in amniotic fluid completely excludes the diagnosis of fetal infection. False positive diagnoses are exceptional with current automated real time PCR assays and a positive CMV PCR in amniotic fluid allows diagnosis of fetal infection.

• 8.
  

  a) F b) F c) F d) T e) F

Dating of any pregnancy, unless conceived by ART, should be done by CRL measurement in the first trimester. In case of discordant CRL, the gestational age is determined by the largest CRL since most first trimester pathologies are associated with reduced CRL, not enlarged CRL. The typical sonographic appearance of the inter-twin membrane in monochorionic diamniotic pregnancies changes from the early first trimester, when the amniotic sacs can be visualised separately, to the late first trimester where the membranes become fused and attached to the single surrounding chorion but with an empty lambda sign where the amniotic membranes reach the placental surface, to the true t-sign in the second trimester. Discordant NT as well as discordant CRL are associated with an increased chance of various pathologies, including TTTS. However the predictive values are too low to be used in clinical practice. Any monochorionic twin should be regarded as at risk for TTTS and followed with serial ultrasound. At 11 weeks’ gestation, a lambda sign in which chorionic tissue can be seen between the membranes is a strong predictor of dichorionicity, while an empty lambda sign is only present in monochorionic diamniotic twins. Color Doppler in first trimester twins can show twin reversed arterial perfusion (TRAP) sequence, in which the direction of flow in the aorta of the acardiac twin is upwards towards the usually underdeveloped upper body and head. In most cases, no heartbeat is seen in the acardiac twin, and skin edema is common. Moving lower limbs are often the first clue to the diagnosis. Spontaneous TRAPS usually occurs late in the second trimester, and requires measurement of the middle cerebral artery peak systolic velocity in both twins.

• 9.
  

  a) T b) F c) F d) F e) T

Gratacos staging using the Doppler blood flow profile in the umbilical artery of the smaller twin is useful to estimate prognosis. An abnormal ductus venosus waveform in the smaller twin is associated with a particularly poor prognosis. Currently, the best treatment option for sFGR is unknown. Laser surgery is technically more difficult than in TTTS, and associated with a high risk of death of the smaller twin. It may however protect the larger twin from developing brain damage. The option needs to be discussed based on many individual parameters and the views of parents, and should be done in an experienced fetal therapy centre. Referring sFGR pregnancies is certainly a good idea, however, the decision on any intervention should be left to the fetal therapy center and the parents. In many sFGR pregnancies, AA-anastomoses are present. Especially in Gratacos type III, the AA is typically large. The intermittent blood flow in the umbilical artery point towards such a presence. With careful color Doppler examination, the AA may be visualised, however this is time-consuming and clinically irrelevant, since staging and prognosis are best done using the pulsed wave Doppler patterns in the umbilical artery and ductus venosus. Brain damage in sFGR cases is not uncommon, especially in Gratacos type III. The highest risk is in surviving twins after co-twin demise. MRI usually only becomes abnormal at least 3–4 weeks after the ischemic event. There is a lack of information on early fetal brain imaging abnormalities and long term neurological outcome. Currently, outside of research settings, routine MRI in monochorionic twins is not advised, unless ultrasound shows brain lesions or one twin has died several weeks before. The best management of sFGR patients is referral to specialised tertiary care centres, where all possible intervention options are available, and experienced clinicians can evaluate and counsel the patient. These centres can also participate in prospective studies, which are urgently needed in this complex, high risk clinical situation.

• 10.
  

  a) T b) T c) F d) F e) F

Discordant structural anomalies are 3–5 times more frequent in monoamniotic twins as compared to monochorionic diamniotic twins, likely related to the late splitting of the embryo. TTTS occurs in 3% of monoamniotic twins, and obviously, discordant amniotic fluid volumes are not present. Polyuria of the recipient causes overall polyhydramnios, and the donor will show absence of bladder filling. There is general consensus that monoamniotic twins are best delivered by elective caesarean section. The virtually always present cord entanglement poses a great danger in case of a vaginal birth, with acute tightening of the knot after birth of the first twin. In addition to answer (c) it is important to realise that the absence of an inter-twin membrane means that in the inadvertent event of a vaginal birth of the first twin, the second one has no amniotic fluid which makes version and extraction difficult and often impossible. The entangled cords can lead to compression of one or both cords and their arteries, which can be shown by specific Doppler waveform changes described as notches in the post-systolic part of the wave. Whether this should prompt immediate delivery is unknown, and certainly gestational age has to be taken into account. Most centres start more frequent monitoring at 28 weeks, since delivering the twins earlier has a high likelihood of death or neurologic impairment related to prematurity. More research into the clinical value of the umbilical artery notch is needed to advise on its place in the fetal monitoring in monoamniotic twins.

• 11.
  

  a) F b) F c) F d) F e) T

The average rate for a high income country is 3–4 per 1,000 and all rates fall within the range 1–9 per 1,000. In high income countries, intrapartum stillbirth does account for 5–10% of all stillbirths. However, the proportion is much higher in low and middle income countries and 98–99% of all stillbirths occur in such countries. Overall, it is estimated that <20% of the variation in stillbirth risk is explained by maternal characteristics. The exact proportion of stillbirths estimated to be due to growth restriction depends on the method used, but generally it is in the region of 30–50%. Hence, better screening for growth restriction would only impact on a minority of stillbirths. The cause of most stillbirths is not known. There are many associations, particularly in relation to placental histopathology. However, many of these are also seen in completely normal pregnancies. Hence, the actual cause of death is not known for many stillbirths.

• 12.
  

  a) T b) F c) F d) F e) F

A PAPP-A level of <0.4 multiples of the median is associated with an increased risk of stillbirth and the majority in this group are associated with fetal growth restriction, placental abruption or preeclampsia. The use of biochemical tests of placental function were both introduced and withdrawn in the absence of clear evidence of effectiveness (or ineffectiveness). Raised msAFP is associated with these structural abnormalities but elevated second trimester levels are also associated with an increased risk of non-anomalous stillbirth, particularly at early gestational ages and associated with placental causes. The data on PAPP-A and stillbirth relate to first trimester measurement, and there is an absence of evidence in relation to late pregnancy measurements. The sFlt-1/PlGF ratio has been described as a test for maternal pre-eclampsia, but there is limited evidence regarding its association with stillbirth.

• 13.
  

  a) F b) T c) T d) T e) F

Delivery at 37–38 weeks is referred to early term. It is associated with increased risks of short term and long term complications. Hence, it is generally only indicated if the balance of risks of expectant management exceed these risks. Although induction of labour is associated with higher rates of caesarean delivery in observational studies, the reverse is apparent in RCTs. This suggests that the observational associations are due to confounding by the indication for induction. This is a key finding of the meta-analysis. The explanation is that once a baby is delivered it is no longer at risk of stillbirth. Hence, shortening the pregnancy reduces the risk of stillbirth. However, from 38 weeks onwards, there is no further decline in the risk of neonatal death with advancing gestational age. Level 1 evidence indicates that, among nulliparous women aged 35 and above, routine induction of labour had no effect on the risk of Caesarean delivery. This was the key finding of the 35/39 trial, published in NEJM 2016. Elective induction (i.e. without a medical indication) can be considered from 39 weeks onwards. Reduced fetal movements commonly precede stillbirth. Hence, induction of labour should be offered to women who present with reduced fetal movements from 39 weeks onwards.

• 14.
  

  a) F b) F c) T d) F e) T

The current meta-analysis of RCTs fails to demonstrate any benefits of universal ultrasound. The current meta-analysis is too small to be adequately powered to detect a reduction in perinatal death with plausible estimates of screening test and interventional effectiveness. A number of countries have implemented universal late pregnancy ultrasound in the absence of trial evidence. False positive diagnoses have significant potential to cause harm. For example, if a woman has a scan and the baby is wrongly diagnosed as being large for dates, she is at increased risk of emergency caesarean during labour. A level 1 study of diagnostic effectiveness published in the Lancet is 2015 demonstrated a 20% rate of detection with selective ultrasound and a 57% rate of detection with universal ultrasound. However, for every 1 additional true positive for SGA, there were 2 additional false positives.

• 15.
  

  a) F b) F c) F d) T e) F

The 1F state in a normal fetus can last for up to 120 minutes. A trace showing 2 accelerations in 10 minutes is as predictive as one showing 3 accelerations in 20 minutes. Single isolated decelerations on an otherwise reactive trace do not make the trace pathological. The false positive rate for a reactive trace with 24 hours is 0.03%

• 16.
  

  a) F b) F c) F d) T e) F

In the 2F state fetal gross body movements elicit heart rate accelerations. An understanding of the behavioural states is critical to the definition of the unreactive trace, and critical to the interpretation of the 4F state where a baseline is difficult to identify as the excessive movements lead to heart rate of 180–200bpm. The 1F state commonly has variability of < 2bpm.

• 17.
  

  a) T b) F c) F d) F e) F

After 30 weeks an increasing number of fetuses have a mature pattern of heart rate acceleration that is equivalent to that seen at term. The baseline of the preterm fetus is higher than the term fetus. Given an understanding of the immature heart rate accelerative pattern in fetuses < 30 weeks, a reactive pattern can be identified in normal fetuses. V shaped decelerations lasting approximately 15 seconds are common changes seen on the baseline and are benign. Unfortunately there is no published data on CTG traces in preterm pregnancies and outcome.

• 18.
  

  a) T b) F c) F d) T e) F

The CPR is an independent predictor of the risk of stillbirth, and combined with the estimated fetal weight and uterine Doppler in the third trimester can identify the majority of fetuses at risk of stillbirth. There is an inverse relationship between the uterine artery Doppler PI in the third trimester the CPR values. The CPR is calculated as the MCA PI divided by the umbilical artery PI. The CPR can identify the fetus at risk among both small and appropriately-sized babies

• 19.
  

  a) F b) T c) F d) F e) T

A proportion of the small fetuses suffer from FGR. FGR is a risk factor for stillbirth, perinatal mortality and neonatal morbidity, hypoxic ischemic encephalopathy and cerebral palsy. The CPR is emerging as a marker of failure to reach growth potential. Being small in size (weight less than the 10 ^th centile) is not an essential criteria to define FGR. Reduced growth velocity is likely to be a better indicator of FGR than the EFW at term. The majority of the fetuses with FGR at term demonstrate normal umbilical artery Doppler

• 20.
  

  a) F b) F c) T d) F e) T

The uterine artery Doppler, whether recorded in the first, second or third trimester, is significantly associated with the risk of stillbirth. It is true that in longitudinal studies, the uterine artery Doppler recorded in the third trimester is likely to be a better predictor of the fetuses at risk at term, when compared to the second trimester uterine artery Doppler. The uterine artery Doppler is a better predictor of FGR when recorded in the second, compared to the first, trimester. The uterine artery Doppler recorded in the third trimester has an additive value in identifying the fetuses at risk at term. The uterine artery Doppler is significantly associated with the risk of stillbirth, but not after adjusting for estimated fetal weight and CPR

• 21.
  

  a) F b) T c) T d) T e) F

Reduced amniotic fluid can occur due to many reasons and reduced fetal movements seen on scan similarly. All the other parameters are required to distinguish FGR and SGA.

• 22.
  

  a) F b) F c) F d) T e) F

The aetio-pathogenesis of early and late onset FGR is different; hence the pattern of deterioration of umbilical artery Doppler velocimetry is often not similar. In early onset FGR there is a reduction of villi, unlike in late onset where there is mainly impaired maturation. Therefore, the deterioration of umbilical artery Doppler waveform may not occur until very late in late onset FGR.

• 23.
  

  a) F b) F c) T d) T e) F

According to the criteria described in the manuscript and currently accepted by most experts and guidelines, a very low estimated fetal weight centile (<3rd) indicates a higher risk of abnormal perinatal outcome, regardless of Doppler results. Consequently, and following the same criteria, the case should be classified as fetal growth restriction. Since we have reached term, elective delivery is recommended.

• 24.
  

  a) T b) T c) T d) T e) F

Fetal macrosomia may be arbitrarily defined as a birth weight >4000 g and complicates over 10% of all pregnancies in the United States of America. It is associated with increased risks of Caesarean section and trauma to the birth canal and fetus. Prediction of fetal macrosomia may be performed using clinical and ultrasonographic evaluation. Clinical evaluation is based on maternal fundal height assessment. When fundal height assessment is performed on an individual basis using a customized chart, greater accuracy can potentially be obtained. Similarly, ultrasound estimation of fetal weight (EFW) may not be accurate, resulting in an increased rate of false positive tests.

• 25.
  

  a) T b) T c) T d) F e) F

Inaccurate prediction of fetal macrosomia has resulted in a high number of unnecessary procedures, since early induction of labor to limit fetal growth may result in a substantial increase in the Caesarean section rate because of failed inductions or respiratory complications in newborns. For these reasons, it could be suggested that pregnancies complicated by fetal macrosomia might be best managed expectantly. There is no known relationship with chorioamnionitis and fetal birth injury is related to macrosomia itself not the inaccurate prediction of it.

• 26.
  

  a) T b) T c) T d) T e) T

Fetal macrosomia may be arbitrarily defined as a birth weight >4000g and is associated with increased risks of Caesarean section and trauma to the birth canal and fetus.

• 27.
  

  a) T b) T c) T d) T e) T

A direct correlation has been observed between maternal weight gain and the incidence of secondary Caesarean section when vaginal delivery was initially planned; in addition, a direct correlation between increasing birth weight and a higher incidence of secondary Caesarean section and assisted vaginal delivery has been reported. Gestational diabetes mellitus (GDM) is a known clinical risk factor associated with fetal macrosomia and represents 90% of all types of diabetes occurring in pregnancy. In women diagnosed with GDM, the main complication is fetal macrosomia. The rationale for performing an elective Caesarean section includes a potential reduction in perinatal complications, especially those related to macrosomia. Using multiple logistic regression models in 181,479 deliveries, comparing birth outcome of women with and without familial history of DM, it has been shown that women with a familial history of DM (n= 13,813) had a higher rate of fetal macrosomia, defined as a birth weight >4000 g, compared with controls (p < 0.001) and a 1.3-fold increase in the risk for Caesarean section (p < 0.001).

• 28.
  

  a) F b) F c) F d) T e) T

According to the National Vital Statistics in the United States, the prevalence of newborns weighing at least 4000 g has decreased by 10% in seven years (10.2% in 1996 and 9.2% in 2002) and 19% for newborns weighing >5000 g (0.16% and 0.13%, respectively). Bayesian calculations indicate that the post-test probability of detecting a macrosomic fetus in an uncomplicated pregnancy is variable, ranging from 15% to 79% with ultrasound estimation of birth weight, and 40% to 52% with clinical estimates. Among diabetic patients the post-test probability of identifying a newborn weighing >4000 g clinically and by ultrasound is over 60%.

• 29.
  

  a) T b) T c) T d) T e) T

Macrosomia defined as a fetal weight exceeding the 95th centile or > 2 standard deviations (SD) above the mean for expected gestational age has multifactorial causes. Genetic, environmental and constitutional factors as well as metabolic disorders, e.g. diabetes mellitus have a significant impact on the occurrence of fetal macrosomia. Constitutional factors like pre-gestational body mass index (BMI), excessive weight gain during pregnancy and pre-gestational as well as GDM are recognized as independent risk factors for fetal macrosomia.

• 30.
  

  a) T b) F c) F d) T e) T

It has been demonstrated that fasting plasma glucose (FPG) in late pregnancy (30–32 weeks of gestation) but not fasting plasma insulin or insulin resistance, is a determinant of newborn macrosomia. Moreover, if an increase in FPG is observed from early to late pregnancy, these women had a 4.5-fold increase in risk of newborn macrosomia. Among women with GDM, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 years, adjusting for maternal pre-pregnancy BMI.