Fetal Growth and IUFGR

Question 1

Describe the historical data used to record fetal growth

Answer 1

Initial information on the actual size of the fetus, and hence on fetal growth was obtained from miscarriages of pregnancy (Figure 6.3). While the did give information of interest, this did not take account of the possible causative relationship between low fetal growth leading to miscarriage, and hence such data may be inaccurate.

It can be seen that fetal weight continues to increase during pregnancy, while fetal length changes less in the later stages.

Such summaries have now been replaced by data from in utero scanning,

Fetal length- crown rump length

Question 2

Summarise fetal growth and development during pregnancy

Answer 2

Little variation up to 16 weeks
After this- considerable variation isn size and development in terms 2 and 3
Excluding chromosomal and genetic causes, the predominant cause for fetal growth restriction corresponds to a diminished supply of nutrients.

Question 3

Describe the relationship between maternal habitus, physiology and baby size

Answer 3

Positive correlation between maternal height, uterine size and placental blood flow

Question 4

Summarise the changes in fetal weight

Answer 4

Little variation in first 16 weeks- rapid growth thereafter.

Question 5

Define Fetal Growth

Answer 5

Increase in mass that occurs between the end of embryonic period and birth

Question 6

Summarise the consequences of interrupted placental development for the fetus

Answer 6

If it occurs earlier on in the pregnancy- more likely to lead to fetal growth restriction- most organs develop in this stage

If it occurs later one- reduced weight gain

Question 7

Which two factors influence normal fetal growth

Answer 7

• Genetic potential
- derived from both parents
- mediated through growth factors eg insulin like growth factors
• Substrate supply
- essential to achieve genetic potential
- derived from placenta which is dependent upon both uterine and placental vascularity- small, infarcted and necrosed placenta will reduce the delivery of nutrients.

Question 8

Describe the relationship between genetic potential and substrate supply

Answer 8

Genetic potential: this is derived from both parents, and reflects the logical view that parents who are taller or bigger will have infants that are different in size to parents who are shorter or lighter in build. This will be mediated by factors under genetic control, including mediators such as the insulin-like growth factors.
Substrate supply: sufficient nutrients are essential to achieve genetic potential. This is primarily based on the placenta which is dependent upon both uterine and placental vascularity.

Question 9

What are the 3 subsequent phases of normal fetal growth

Answer 9

Normal fetal growth is characterised by 3 subsequent phases:

1. Cellular hyperplasia (4-20 weeks as development from embryo - fetus occurs)
2. Hyperplasia and hypertrophy (20-28 weeks)
3. Hypertrophy alone (3rd term- accumulation of fat, muscle and connective tissue).

Question 10

What is the key factor in the increase in fetal weight

Answer 10

Cellular hyperplasia (increased cell numbers): 4-20 weeks

Hyperplasia and hypertrophy (increased cell size): 20-28 weeks

Hypertrophy dominates: 28-40 weeks

As the main increase in fetal weight occurs during the final trimester of pregnancy, hypertrophy is a key factor.

Question 11

Summarise the changes in fetal growth velocity throughout the pregnancy

Answer 11

14-15 wks: 5g /day
20 wks: 10 g/day
32-34 wks: 30-35g/day
>34 wks: growth rate decreases

Question 12

Summarise fetal organ growth

Answer 12

Brain and liver increase in size the most
Heart and kidney slow and steady
growth slows after 24 weeks- when hyperplasia stops

At terms, only 20% of organ size, so growth continues throughout life

Question 13

Describe how we can measure the size of the fetus externally

Answer 13

Perhaps the simplest to understand are attempts to determine the size of the infant by palpation of the maternal abdomen.

This is the basis of determination of the Symphysis Fundal Height (SPH

This identifies the distance between the pubic symphysis and the top of the uterus, as shown in Figure 6.1.

An overview of the changes in SPH with gestational age is shown in Figure 6.2 – while this reflects generic changes in uterine size, it is vulnerable to a variety of errors that could lead to a mis-interpretation of the data.

Question 14

Describe the use if symphysis fundal height to measure the size of the fetus

Answer 14

SFH: distance over the anterior abdominal wall from the symphysis to the top of the uterus
12 w: at symphysis pubis
20 w: at umbilicus
20-34w: GA +/- 2 cm
36-38w: GA +/- 3 cm
>38w: GA +/- 4 cm- larger error as it descends into the pelvis

Question 15

What can give a smaller value for SFH

Answer 15

If small: wrong dates, small for GA, reduced fluid (OLIGOHYDRAMINOS) or transverse lie

Question 16

What can give a larger value for SFH

Answer 16

If large: wrong dates, large for GA, multiple pregnancy, increased fluid (polyhydraminos) or fibroids , molar pregnancy

Question 17

What is a molar pregnancy

Answer 17

Molar pregnancy is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term. A molar pregnancy is a gestational trophoblastic disease which grows into a mass in the uterus that has swollen chorionic villi

Question 18

What are the pros of SFH

Answer 18

Simple and inexpensive

Question 19

What are the cons of SFH

Answer 19

• Low detection rate: 50-86%
Great inter-operator variability
• Influenced by a number of factors (BMI, fetal lie, amniotic fluid, fibroids)

This simple and inexpensive measurement may identify gross changes in size, and hence gross complications in the pregnancy, but is generally of limited use, thanks to the many confounders, which include the problems listed above, as well as considerable inter-operator variability.

Question 20

If SFH detects a small or large baby- what should be done

Answer 20

Obstetric Ultrasound Examination

Question 21

Describe some of the innacruacies in dating the pregnancy by LMP

Answer 21

Dating by LMP:

Inaccurate (irregular periods; abnormal bleeding; oral contraceptives, breastfeeding)

Question 22

Describe the importance of correct dating in the pregnancy

Answer 22

Importance of correct dating:
• SGA or LGA confusion
• Inappropriate inductions (if LGA, may want to induce labour)
• Steroids in preterm delivery- to boost surfactant production

Question 23

How should all pregnancies be dated

Answer 23

All pregnancies should be dated by CRL except IVF pregnancies CRL should be between 45-84mm
CRL measured using obstetric ultrasound examination.

Question 24

When is the pregnancy dated by head circumference

Answer 24

HC is used if first scan is done after 14 weeks (CRL>84mm)

Question 25

Describe the ultrasound assessment of fetal growth

Answer 25

Fetal growth is assessed by 4 biometrical parameters:

Biparietal diameter (BPD), Head Circumference (HC), Abdominal Circumference (AC) and Femur Length (FL). They are combined to give the Estimated Fetal Weight (EFW).
• Normal growth curves constructed from ultrasound measurements are expressed in centiles
• They are used clinically to identify a normal intrauterine growth and detect risk of obstetric and neonatal complications
In many cases, it is not single measurements that are most important, but sequential measurements.

Note that ultrasound can also be used to assess fetal wellbeing, which can be a more important use of the technology

Question 26

What are the key landmarks used to standardise BPD and HC

Answer 26

Mid-echo line
Posterior horn of lateral ventricle and choroid plexus
cavum septum pellucidum

Question 27

Describe the key landmarks used to standardise AC

Answer 27

Stomach bubble
Transverse view of spine
Rib
Descending aorta
Intra-hepatic vein 1/3rd way from abdominal was

Question 28

What should be done with the data from obstetric ultrasound scans

Answer 28

For any infant, the changes in each parameter can be plotted, and the growth over time visualised. In a normal pregnancy, each parameter is expected to follow a centile, showing steady increases in size. The use of the centiles is important, because this allows compensation for different sizes of infants that are growing and developing normally.

Figure 6.9 shows two infants that were delivered at term: the infant on the left is normal but big, and the infant on the right is normal but small. These differences are most likely to be due to genetic effects, most notably the size of the parents. If the parents are both on the 95th centile for height, then their infant would be expected to be of a similar size.

Question 29

Describe the confounding factors and impracticalities of using LMP to date the pregnancy

Answer 29

Confounding factors include: Irregular length of periods; abnormal endometrial bleeding; the use of oral contraceptives; breastfeeding. There are also other practicalities, in that a couple hoping to start a family are likely to take careful note of LMP timings, whereas in the case of an unplanned pregnancy, maternal information on her last menstrual period may not be so precise.

Question 30

Summarise the importance of dating the pregnancy correctly

Answer 30

Correct dating is very important, as a change in the dates may lead to a pregnancy being inappropriately identified as Large or Small for gestational age. Clinical decisions about delivery timings and methods (induction or Caesarean section) may not be correct; glucocorticoids are given prior to preterm delivery to enhance lung surfactant production and subsequent lung function.

Best practice is therefore to date the pregnancy by ultrasound, determining the Crown-Rump length of the fetus, preferably towards the end of the first trimester; variations in fetal size are more limited at this stage of development, so the gestational age of the infant can be estimated more precisely.

Question 31

Describe how poverty can influence fetal growth

Answer 31

Poverty has been linked to poor prenatal care and has been an influence on prenatal development. Women in poverty are more likely to have children at a younger age, which can result in low birth weight. Many of these expecting mothers have little education and are therefore less aware of the risks of smoking, alcohol, and drugs – other factors that influence the growth rate of a fetus. Women in poverty are more likely to have diseases that are harmful to the fetus.

Question 32

Describe how the Mother’s age can influence fetal growth

Answer 32

Women between the ages of 16 and 35 have a healthier environment for a fetus than women under 16 or over 35. Women between this age gap are more likely to have fewer complications. Women over 35 are more inclined to have a longer labour period, which could potentially result in death of the mother or fetus. Women under 16 and over 35 have a higher risk of preterm labour (premature baby), and this risk increases for women in poverty, African Americans, and women who smoke. Young mothers are more likely to engage in high risk behaviors, such as using alcohol, drugs, or smoking, resulting in negative consequences for the fetus. Premature babies from young mothers are more likely to have neurological defects that will influence their coping capabilities – irritability, trouble sleeping, constant crying for example. There is increased risk of Down syndrome for infants born to those aged over 40 years. Young teenaged mothers (younger than 16), and mothers over 35, are more exposed to the risks of miscarriages, premature births, and birth defects.

Question 33

Describe how drug use can influence Fetal Growth

Answer 33

Eleven percent of fetuses are exposed to illicit drug use during pregnancy. Maternal drug use occurs when drugs ingested by the pregnant woman are metabolized in the placenta and then transmitted to the fetus. When using drugs (narcotics), there is a greater risk of birth defects, low birth weight, and a higher rate of death in infants or stillbirths. Drug use may lead to extreme irritability, crying, and risk for SIDS once the fetus is born. The chemicals in drugs can cause an addiction in the babies once they are born. Marijuana will slow the fetal growth rate and can result in premature delivery. It can also lead to low birth weight, a shortened gestational period and complications in delivery. Heroin will cause interrupted fetal development, stillbirths, and can lead to numerous birth defects. Heroin can also result in premature delivery, creates a higher risk of miscarriages, result in facial abnormalities and head size, and create gastrointestinal abnormalities in the fetus. There is an increased risk for SIDS, dysfunction in the central nervous system, and neurological dysfunctions including tremors, sleep problems, and seizures. The fetus is also put at a great risk for low birth weight and respiratory problems. Cocaine use results in a smaller brain, which results in learning disabilities for the fetus. Cocaine puts the fetus at a higher risk of being stillborn or premature. Cocaine use also results in low birthweight, damage to the central nervous system, and motor dysfunction.

Question 34

Describe how alcohol can influence fetal growth

Answer 34

Alcohol use leads to disruptions of the fetus’s brain development, interferes with the fetus’s cell development and organization, and affects the maturation of the central nervous system. Alcohol use can lead to heart and other major organ defects, such as small brain, which will affect the fetus’s learning behaviors. Alcohol use during pregnancy can cause behavioral problems in a child, mental problems or retardation and facial abnormalities – meaning smaller eyes, thin upper lip, and little groove between the nose and lips. Use can also increase the risk of miscarriages and stillbirths, or low birth weight. Fetal alcohol syndrome (FAS) is a developmental disorder that is a consequence of too much alcohol intake by the mother during pregnancy. Children with FAS have a variety of distinctive facial features, brain abnormalities, and cognitive deficits. The debate on whether ANY alcohol during pregnancy can impact on fetal development is on-going.

Question 35

Describe how smoking and nicotine can influence fetal growth

Answer 35

When a mother smokes during pregnancy the fetus is exposed to nicotine, tar, and carbon monoxide. Nicotine results in less blood flow to the fetus because it constricts the blood vessels. Carbon monoxide reduces the oxygen flow to the fetus. The reduction of blood and oxygen flow results in stillbirth, low birth weight, and ectopic pregnancy. There is an increase of risk of sudden death syndrome (SIDS) in infants. Nicotine also increases the risk for miscarriages and premature births or infant mortality. There has been a link from smoking during pregnancy that led to asthma in childhood. Low birth weight and premature births can also increase the risk of asthma if a mother smoked during pregnancy because of the effects on the respiratory system of the fetus.

Question 36

Describe how maternal disease can influence Fetal Growth

Answer 36

If a mother is infected with a disease, the placenta cannot always filter out pathogens. Babies can be born with venereal diseases transmitted by the mother.

– hypertension – diabetes
– coagulopath

Question 37

Describe how the mother’s diet and physical health can influence Fetal Growth

Answer 37

An adequate nutrition is needed for a healthy fetus. A lack of iron results in anemia in the fetus, the lack of calcium can result in poor bone and teeth formation, and the lack of protein can lead to a smaller fetus and mental retardation.

Question 38

Describe the impact of maternal prenatal depression on fetal growth

Answer 38

A study found that mother’s prenatal depression was associated with adverse perinatal outcomes such as slower fetal growth rates. It appears that prenatal maternal cortisol levels play a role in mediating these outcomes.

Question 39

Describe the impact of environmental toxins on Fetal Growth

Answer 39

Exposure to environmental toxins in pregnancy lead to higher rates of miscarriage, sterility, and birth defects. Toxins include fetal exposure to lead, mercury, and ethanol or hazardous environments.

Question 40

Summarise the feto-placental factors influencing fetal growth

Answer 40

Genotype potential
• Gender (B>G)
• Hormones
• Previous pregnancy
-
placental
   –
genetic

Question 41

Describe the impact of gender and previous pregnancies on fetal growth

Answer 41

Males are usually bigger than females.

Previous pregnancy: Generally infants are heavier in second and subsequent pregnancies, but this is based on large patient groupings, so extrapolating to an individual pregnancy is difficult, due to all the other potential variables.

Question 42

Summarise the effects of hormones on fetal growth

Answer 42

Hormones have an important role in the control of fetal growth. They act on both tissue accretion and differentiation and enable a precise and orderly pattern of growth to occur during late gestation. In part, their actions on growth may be mediated by other growth factors such as the insulin-like growth factors (IGFs). Insulin stimulates fetal growth by increasing the mitotic drive and nutrient availability for tissue accretion. It has little effect on tissue differentiation. In contrast, the main effects of cortisol in utero are on tissue differentiation and maturation.

Question 43

Describe the effects of cortisol and thyroxine on fetla growth

Answer 43

Cortisol appears to act directly on the cells to alter gene transcription or post-translational processing of the gene products. Cortisol may also initiate the transition from the fetal to the adult modes of growth regulation by inducing the switch from IGF-II to IGF-I gene expression in the fetal liver. Thyroxine affects both tissue accretion and differentiation in the fetus by a combination of metabolic and non-metabolic mechanisms.

Question 44

Describe the role of GHs and IGF-1 on fetal growth

Answer 44

Pituitary growth hormone, on the other hand, appears to have little part in the control of fetal growth, unlike its role postnatally. Fetal hormones, therefore, promote growth and development in utero by altering both the metabolism and gene expression of the fetal tissues. These hormonal actions ensure that fetal growth rate is commensurate with the nutrient supply and that prepartum maturation occurs in preparation for extrauterine life.

The IGFs are mitogenic, stimulating the fetal metabolism and coordinating the feto-placental metabolism. IGF-II regulates early embryonic development while IGF-I is responsible for the growth of the newborn.

Fetal insulin plays an indirect role in the regulation of fetal growth. It modulates the expression of the fetal IGF. On the other hand, it has direct effects on the adipose tissue and the proliferation of the cells within the fetus. Its effects, though, on the differentiation of the tissue and thus on prenatal maturation are small.

Question 45

Describe the role of fetal glucoocorticoids on fetal growth

Answer 45

Fetal glucocorticoid affects tissue differentiation and prenatal development of the organs such as, for example, lungs (maturation of the surfactant), liver (control of glycemia), as well as the intestines (maturation of the expression of digestive enzymes and proliferation of the villi). In addition glucocorticoid, together with thyroid gland hormones, affects the maturation of the lungs and the nervous system.

Growth hormone (GH) has no effects on prenatal growth. This explains the absence of growth deficiencies in congenital hypopituitarism.

Question 46

Describe the effect of some other hormones on fetal growth

Answer 46

Other growth factors exist that affect the proliferation, differentiation and maturation of the cells. They play an important role in embryogenesis, summarised below:

EGFs (epidermal growth factors) are strongly mitogenic and form a group of molecules that bind to the same receptors (tyrosine kinase).

TGFs (transforming growth factors) form a super-family that numbers more than 30 members (TGFb, activin, BMP [bone morphogenetic proteins], GDNF [glial-derived neurotropic factor]).

FGFs (fibroblast growth factors) of which around 20 are known.

Embryonic cholinesterase (ChE) is an enzyme that is active in morphogenesis. Depending on their developmental stage embryonic cells express muscarinic receptors on their surfaces for acetylcholine and synthesize cholinesterase, which is able to inactivate neurotransmitters.

The interleukins 1 form a family that belongs to the cytokines. They play an important role during implantation.

Sexual hormones of embryonic origin are essential for differentiation of reproductive tissues

Question 47

Summarise the different fetal hormones

Answer 47

Pituitary - somatotrophin - yes (small?), partly via hepatic growth factors
prolactin -no
FSH/LH- yes, via gonadal steroid production

pancreas- insulin- yes

adrenals- androgens -yes
gonads- androgens- yes
thyroid- iodothyronines- yes, probably by third trimester

Question 48

Describe the importance of customised growth charts

Answer 48

The customised standard defines the individual fetal growth potential by three underlying principles:

1. Adjustedtoreflectmaternalconstitutionalvariation maternal ht, wt, ethnicity, parity
2. Optimised by presenting a standard free from pathological factors such as diabetes and smoking
3. Based on fetal weight curves derived from normal pregnancies

Question 49

Summarise normal vs abnormal fetal growth

Answer 49

Normal but big Normal but small
Growth Restriction Macrosomia
Neonatal Hydrocephalus
Achondroplasia

Question 50

Summarise obstetric ultrasound examination

Answer 50

• Assessment of fetal “wellness” not just size - movement, size and amniotic fluid
• Looking at trends in growth- measure again in 10-14 days- to see if falling of centile or not
• Predicting fetal metabolic compromise- baby will stop moving as it diverts blood to major organs
• Anticipating the need to deliver prematurely - stops growing at 32 weeks- deliver early to prevent adverse outcome
• Liaising with Neonatal Services- get tertiary unit ready if premature