Becoming pregnant

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In early pregnancy, human chorionic gonadotrophin is secreted by the embryo and placenta, and stimulates the production of oestrogen and progesterone by the mother’s ovary until around the 10th week of pregnancy when the placenta takes over. These hormones are responsible for many of the physiological changes in the mother. The first change of note is a missed period because ovulation stops. There is a change in the normal rhythmic activity of the uterine muscle with longer resting phases, under the influence of progesterone, while the womb enlarges as a result of the increasing oestrogen secretion. If there is bleeding after a missed period advice should be sought from your doctor.

During pregnancy the placenta, fetus and sac secrete several steroid and protein hormones and growth factors, so that the mother’s body will adapt for pregnancy. The hormones produced include oestrogen, progesterone, human chorionic gonadotrophin (HCG), human chorionic somato-mammotrophin (HCS), and placental adrenocorticotrophic hormone (PAH). There are also specific growth factors secreted, such as the inhibins, and insulin-like growth factors which are produced by the placenta and the mother’s ovaries.

As a result of all these changes there is a big increase in the amount of blood circulating through the body. The womb enlarges to accommodate the growing fetus. The hormones change the levels of sugar and other blood contents, so as to make it easier for the placenta to take what it needs to feed the fetus. Some hormones relax the womb and other muscles, so that the fetus can squeeze into the pelvis for delivery. A more detailed outline of what happens in pregnancy is set out below.

Physiological changes in the mother – more technical information

In the mother there is an increase in the renal tubular reabsortion of salt (sodium), which plays an important role in regulating fluid volume. The excretion of sodium is regulated by many factors, which include the effect of hormones such as progesterone, aldosterone from the adrenal gland, and the natriuretic hormones e.g. Arginine-Vasopressin (AVP). The metabolic changes in pregnancy create a tendency towards a low potassium level (hypokalaemia), but this is balanced by the potassium sparing effect of progesterone. Serum uric acid levels are decreased because renal clearance is increased during pregnancy, and renal tubular reabsorption is reduced.

The maternal red blood cell mass normally increases by about 18% during pregnancy in response to increasing erythropoietin levels. This increase is not proportional to the much higher increase in plasma volume (41-57%) and therefore results in a state of relative haemodilution during pregnancy. The total white blood cell count is increased, especially among the neutrophils, and there is a slight reduction in the platelet count. There is an increase in the clotting factors, (VII, VIII, IX and X) and a reduction in fibrinolytic activity. This results in an increased tendency towards the formation of blood clots (thrombus) during pregnancy.

Glucose metabolism is altered because of a combined gradual reduction in insulin sensitivity as pregnancy progresses, and a reduced renal threshold, making glycosuria a common finding. The metabolic rate increases, in turn reflecting the increased demands placed upon maternal cardiac and pulmonary function. This is associated with increased thyroid ctivity, and mild thyroid gland enlargement is quite common in pregnancy. The total serum tri-iodothyronine and thyroxine concentrations are increased, following an a rise in serum binding globulin levels, but there is no increase in the free hormone concentrations. There is a significantly increased positive nitrogen balance during pregnancy, and there is an increased accumulation of lipid stores and calcium and iron.

Uteroplacental physiology – more detailed information

Certain structural changes occur in the uterine blood vessels during pregnancy, which are essential to the satisfactory formation of the placenta and development of an adequate fetoplacental circulation. The pivotal change occurs within the uterine arterial circulation especially the resistance vessels, the spiral arterioles. This is a continuous process throughout pregnancy. Invasion by non-villous trophoblast occurs in the first trimester, usually before the 12th week. Trophoblastic invasion of luminal smooth muscle has usually taken place by the 20th week. The process of placentation results in the conversion of the uterine circulation from a high resistance, low flow circuit, to a low resistance, high flow system, ensuring good communication between (dilated, tortuous spiral arterioles) uteroplacental arteries and the intervillous space. The pelvic venous vasculature also undergoes a process of maeked dilation, serving as a reservoir for the circuit in later pregnancy when large amounts of blood are circulated.

Fetal physiology – more detailed information

While the fetus eventually develops some degree of autonomy during pregnancy, structurally, it is the placenta that remains in direct contact with the external environment. In practise therefore, both fetus and placenta serve as a single functional unit for the purpose of vascular, respiratory, metabolic and endocrine activity.

The human fetus increases its weight 6 billion times from conception to delivery. This is by a combination of cellular multipication, and cellular growth (hyperplasia and hypertrophy respectively). Hyperplastic growth in mainly genetically determined while hypertrophy dependxs mainly on the environment. In the first 12 weeks, the fetoplacental system is not fully developed and pregnancy is supported mainly by tubal and endometrial secretion, under stimulation from the corpus luteum and other pregnancy hormones. Once the placental unit develops, growth is accelerated significantly and depends to a major extent on the normal function of this organ.

Early pregnancy assessment

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One of the priorities of assessment of early pregnancy symptoms of pain and bleeding is to exclude an ectopic pregnancy, as it can result in loss of life. Traditionally, a history of pain disproportionate to bleeding with signs of pain on vaginal examination (cervical excitation) or reduced blood volume (hypovolaemia) will lead to a laparoscopy (See Gynaesurgeon.co.uk – Laparoscopy) to diagnose and treat the ectopic pregnancy. Over the last ten years, the introduction of routine transvaginal scanning, rapid serum HCG estimation, combined with advances in laparoscopic surgery, has led to a major change in the way that we diagnose and treat ectopic pregnancy.

Background

Approximately 1:300 pregnancies (1:100 in inner city areas) are outside the womb (extra uterine), the vast majority in the fallopian tube. The ampulla or isthmus of the tube is the most common site, typically resulting in a woman presenting with pain and bleeding (>95%) between 6 and 8 weeks gestation (dated from the first day of her last period). If the pregnancy is in the cornua of the fallopian tube, it may enlarge and present around 11 -13 weeks gestation. Where the ectopic has ruptured there will be signs of peritonism (blood in the abdomen causing irritation) or haemodynamic collapse, but the majority of women present before such catastrophic events take place.

Investigation

A positive urinary pregnancy test confirms that the patient has conceived. A careful history and examination remains an essential first step in the assessment of early pregnancy problems. Ultrasound and HCG values must always be evaluated in light of the clinical evidence, otherwise mistakes are made and unnecessary interventions or discharges take place.

Ultrasound

The nearer an ultrasound beam is to the organ to be investigated, the better the resolution of the images obtained.

With the introduction of transvaginal scanning, we removed the sight of distraught women with full bladders waiting for a transabdominal scan, which would often produce inconclusive results. Now women are able to have a scan immediately, which produces a conclusive result in 95% of cases. The majority of women (65 -70%) who present with and bleeding in early pregnancy will have an ongoing viable intrauterine pregnancy. Approximately 20-25% will have signs of a complete, incomplete or missed miscarriage. 1-2% will have clear signs that there is an etopic pregnancy (positive pregnancy test, empty uterus, abundant free fluid in the pelvis or occasionally, the ectopic pregnancy visualized in the tube). In about 5% of scans the diagnosis will be unclear. In these circumstances serum HCG level is obtained (2-3 hours).

HCG

Human chorionic gonadotrophin (HCG) is a hormone produced by the placenta (afterbirth) of a pregnancy. The levels of HCG rise very quickly in early pregnancy. It is usually possible to see a pregnancy sac in the womb when the level of HCG is > 2500 i.u. If there is no sac a laparoscopy is usually performed to investigate the possibility of an ectopic pregnancy. If the HCG <2000 i.u., and there is clinical suspicion that the pregnancy is ectopic, the patient may have a laparoscopy.

If there are no clinically suspicious features, it is usual practice to wait 48 hours and repeat the ultrasound and HCG level. In a small number of women, they may require more time for diagnosis to become clear.

Treatment

If the HCG level is <1000 i.u., or falling rapidly, the patient is usually managed conservatively. It is imperative that such patients are followed up every 48 hours, as it is not unusual for the HCG level to rise quickly to levels associated with tubal rupture. Occasionally in these cases, other treatments such as Methotrexate or Mifepristone may help.

Fortunately, rapid access to early pregnancy assessment means that very few women die as a result of this condition: worldwide it remains a significant cause of maternal mortality.

Early pregnancy problems

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Introduction

We traditionally divide pregnancy into three stages or trimesters, each about 13 weeks long. In the first trimester the embryo grows into a fetus, and the placenta (afterbirth) establishes itself in the uterus (womb). By the end of the first trimester the fetus is formed and the placenta is supplying the pregnancy from the mother’s circulation.

In order to make each of us unique, nature takes risks when creating a new life. If the pregnancy or body realise that the pregnancy is unlikely to result in a healthy baby, the pregnancy is stopped and the woman miscarries. Fortunately, not all bleeding in early pregnancy is a miscarriage; in fact only about a third of women who present with bleeding will have a miscarriage.

Bleeding in early pregnancy

Naturally, when a woman develops bleeding in early pregnancy, it causes concern. Not only is there the possibility of a miscarriage, there is also the small chance that the pregnancy may not be in the womb (an ectopic pregnancy). So the first trimester is a critical period in determining the outcome of a pregnancy, with miscarriage the single most common complication of pregnancy.

 

A dedicated early pregnancy unit, set up to deal with complications that present with symptoms of vaginal bleeding and abdominal pain, is invaluable in modern day practice. Following carefully established guidelines, and with dedicated medical and nursing staff, women can be investigated, using examination, biochemical testing and transvaginal ultrasound. Women with non-viable pregnancies may be cared for in a supportive environment, with the help of trained counselling staff, while those with progressing pregnancies may be reassured and special needs such as administering anti-D immunoglobulin attended to.

Miscarriage

Even though about one in four pregnancy ends in miscarriage, it is usually difficult to determine the cause. Many women are left asking the question why? and find it hard to accept that no-one can give a definite answer. It is very unlikely to have been caused by anything you did – miscarriage is very rarely anyone’s fault. If you have bleeding in early pregnancy you should attend an early pregnancy assessment unit.

The main causes of miscarriage are thought to be: Genetic problems, Hormones, Immune system, Infections, Womb problems.

  • Genetic problems: About half of all early miscarriages occur because of chromosome abnormalities. These are not usually as a result of anything being wrong with the parent’schromosomes.
  • Hormones: Women with hormonal problems find it harder to get pregnant and when they do, are more likely to miscarry.
  • Immune system: Problems with the mother accepting the pregnancy can lead to miscarriage.
  • Infections: Minor infections like colds are not harmful, but a very high temperature and some specific illnesses of infections, such as German measles, may cause miscarriage. Some researchers have found that high levels of the bacteria in the vagina (bacterial vaginosis) can also increase the risk of miscarriage.
  • Womb problems: If the cervix (neck of the womb) is weak, it may start to open as the uterus (womb) becomes heavier in later pregnancy and this may lead to miscarriage. Large fibroids may cause miscarriage in later pregnancy. An irregular-shaped uterus can mean that there is not enough room for the baby to grow in later pregnancy.

Some pregnancies are lost through ectopic pregnancy. This is when the fertilised egg implants outside the cavity of the womb, most commonly in one of the Fallopian tubes.

Recurrent miscarriage

When a woman suffers three consecutive miscarriages she is diagnosed as suffering from recurrent miscarriage, although if there are two miscarriages after a long time trying for a baby, or if the hopeful mother to be is over 35 years, investigations are often recommended before suffering three miscarriages.

The good news is that the vast majority of women who have three miscarriages will go to have a successful pregnancy and delivery of a healthy baby, but it is wise at this stage to initiate investigations to see if there is an underlying problem with carrying a pregnancy.

Investigations focus on three key areas of concern:
    – Antibody or rejection problems
    – Mother or father chromosome problems
    – Maternal hormone or uterine problems

Antibody and Rejection problems

We know that our body makes antibodies to attack foreign bacteria and viruses that can infect us. The immune system is not perfect so it is also capable of creating antibodies that can attack ourselves (known as auto antibodies). Our immune system evolved from the same system that helps us clot our blood; so some of the antibody problems women suffer from are in fact part of the coagulation or clotting process in our bodies. These problems do not often cause other problems in the early years so the first time a woman finds out about these problems is when she suffers from recurrent miscarriage.

Common antibody problems include Antiphospholipid antibody and Factor V Leiden Deficiency. There is also a lot of work, which demonstrates that you are capable of having too many ‘Natural Killer’ white cells in your womb, which can also lead to miscarriage. The good news is that we can investigate you and identify if you suffer from these problems. A combination of aspirin, anticoagulant or steroids can help block these antibodies and make your body more receptive to remaining pregnant.

Chromosome problems.

About 2% of the population have chromosomes that are perfectly normal for them, but can lead to problems when trying for a baby. The most common problem is called ‘balanced translocation’ this is where a part of one chromosome splits off and attaches to another chromosome, while another piece of chromosome fills the space, which makes your chromosomes ‘balanced’. However when you produce eggs there is a much greater chance there will be a mix up and the baby will not receive a proper set of chromosomes, leading to miscarriage. A simple blood test can find out if you or your partner has any chromosome issues.

Maternal Hormone or uterine problems

The shape of a woman’s uterus or womb may make it more difficult to carry a pregnancy, but the most common problem is fibroids or myoma that interfere with the inner lining of the womb, or are large and interfere with the growth of the womb. An ultrasound scan can find out if there are any anatomical problems in the pelvis.

There are a number of hormone or endocrine problems that can affect a woman’s chances of becoming pregnant and carrying a pregnancy. For instance Polycystic ovarian syndrome [link] can interfere with ovulation and increase the chances of a woman miscarrying. A couple of blood tests can usually identify if there are any endocrine causes for recurrent miscarriage. With the right treatment nearly all the hormone problems can be rectified and a successful pregnancy follows.

Antenatal care

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Introduction

Antenatal care is the clinical assessment of mother and fetus during pregnancy, for the purpose of obtaining the best possible outcome for the mother and child.

To achieve this objective, history and examination are complemented by screening and assessment using a combination of methods, including biochemical, haematological and ultrasound. Efforts are made to maintain maternal physical and mental wellbeing, prevent preterm delivery, to anticipate difficulties and complications at delivery, ensure the birth of a live health infant, and to assist the couple in preparation for parenting.

Antenatal care traditionally involves a number of ‘routine’ visits for assessment, to a variety of healthcare professionals, on a regular basis throughout the pregnancy. This approach to antenatal care evolved as an art in an era that preceded the current, evidence-based approach to medicine.

Early monitoring and on-going care during pregnancy is associated with more favourable birth outcomes. Compared with no antenatal surveillance, some antenatal care has a beneficial effect on affect on adverse factors such as preterm delivery, low birth weight, maternal and perinatal mortality. While some traditional practices, such as strict weight-gain restriction, the use of diuretics and the liberal use of x-rays, have been discontinued, many current clinical practices fail to stand up to scientific scrutiny. Despite this, antenatal care continues to be centred about clinical assessment, with emphasis on the regularity of visits, rather than a focus on what can be achieved at key visits during the antenatal period.

Maternity care remains a mixture of both art and science, with advantages in medical technology now allowing us to focus more on the specific requirements of the mother and fetus, with an increasing drive towards the re-appraisal of current practices.

Schedule of visits during pregnancy

The pregnant woman is seen by her general practitioner as soon as possible following the first missed period and after an initial assessment is referred on to the hospital for her first (booking) hospital visit between 8-14 weeks. Hospital referrals are increasingly instituted earlier nowadays, especially among the more health conscious older educated women, who may request screening tests for the early detection of fetal abnormality. Previously, the antenatal visits were: monthly until 32 weeks gestation, then fortnightly until 36 weeks, and weekly thereafter until delivery, resulting in up to 14 hospital visits during pregnancy. Although ‘antenatal care’ improves the outcome in terms of maternal and perinatal morbidity and mortality, there appears to be little difference in outcome between a four-visit schedule and a twelve-visit schedule. Currently the trend is towards reducing the number of attendance’s, while at the same time establishing clearly defined objectives to be achieved at each visit.

The preconception visit

The ideal first ‘antenatal’ visit is at a pre-conception clinic where health education and risk assessment can be directed towards the planned pregnancy. At that time the patient’s general health and wellbeing can be fully assessed, rubella, hepatitis and HIV status can be established, and appropriate action taken where indicated.

General advice regarding nutrition and lifestyle can be given at this time. Even a single antenatal nutritional education session during pregnancy has a significant effect on birth weight.

Advice can be given regarding the avoidance of teratogens, including those linked with excesses such as vitamin A, cigarette smoking, while ensuring an optimal dietary intake of folic acid. Following the demonstration that folate supplementation reduces the risk of a subsequent neural tube defect by 72%, in those at high risk by virtue of a previous affected pregnancy, it is recommended that at least 0.4mg folic acid is taken daily during the peri-conceptional period. Abnormal blood glucose control during the peri-conceptional period is associated with increased fetal complications and this is also an ideal time to ensure that such factors have been taken care of by sound dietary education and adjustment, and where necessary, medication.

Booking Visit (8-14 weeks)

The main purpose of the booking visit to obtain a comprehensive history, establish the gestational age and identify maternal and fetal risk factors. Baseline investigations are performed.

In most centres, women are offered a first trimester ultrasound scan for pregnancy dating, the exclusion of structural fetal abnormalities and measrement of the fetal nuchal translucency.

A management plan is then drawn up for the pregnancy, based upon the risk assessment. It is by no means inflexible and is subject to alteration at subsequent visits. If the patient has a known medical problem, e.g diabetes, the patient is referred to a dedicated combined clinic. If there is a history of genetic or familial problems, referral to a feto-maternal specialist is arranged.

If this is not your first pregnancy, it is important if there were problems in a previous pregnancy that you discuss with your doctor whether any special precautions should be taken in a future pregnancy. If you are over 35, preconception planning can be particularly helpful, as the risk of problems begins to increase after this age. It is important to stress however, that the vast majority of pregnancies in older mums will be uncomplicated.

The mid-trimester risk assessment visit (20-24weeks

The results of the tests performed at the first trimester visit and at 16 weeks are reviewed with the woman. The results of the ultrasound scan for fetal abnormality are also reviewed. In some centres, Doppler ultrasound screening of the uterine arteries is used to identify women at high risk of subsequent pre-eclampsia and intra-uterine growth restriction is offered at this stage. Further care is then planned in line with risk assessment based on the ultrasound scan and other findings.

Antenatal visits in the second half of pregnancy

Assessment of maternal health and fetal growth and well-being are pursued through these visits, which can take place in the community setting. Any incidental maternal symptoms are dealt with. This period is also important in ensuring the education of the woman regarding the rest of pregnancy and her delivery. Contraception and plans for the birth should also be discussed from an early stage especially with regards to sterilisation or other permanent contraception. This is in order to avoid unnecessary duress under emergency conditions if a Caesarean operative delivery is decided upon during labour.

Antenatal classes and the familiarisation hospital visit

During the antenatal visits informal education is provided for the pregnant woman and those supporting her through pregnancy. There are formal parenting (or parentcraft) classes organised in most units where the prospective parents are encouraged to discuss the pregnancy and delivery, and any apprehensions they may have. There are also usually sessions with others involved in their care to discuss topics like breast feeding, pain management during the delivery etc. The common objectives of these formal educational sessions include the promotion of good health habits, allaying anxiety, increasing the feelings of control and satisfaction with the pregnancy and delivery by the mother, preparation for the postnatal period, infant feeding, and subsequent contraception.

Antenatal visit with hospital team (usually around 36-38 weeks)

The primary objective of this visit is to anticipate any problems regarding the prospective delivery. Several factors are considered, including the past obstetric history, e.g. a previous Caesarean delivery for lack of progress in labour. Fetal malpresentation or malposistion is sought because these may also indicate a high likelihood of operative delivery. With the increasing number of planned home births, the final place of choice for the delivery is also decided. This is also a good time to finalise the discussions on planned contraception after delivery, especially sterilisation.

The postdates visits – Induction of labour (41 -42 weeks)

With accurate pregnancy dating, true postdate pregnancies are identified. At this visit a joint decision is taken as to whether an induction of labour is appropriate. This is current practice because of the reported association between postdates pregnancies and poor pregnancy outcome, particularly in order to prevent stillbirths due to the lack of an accurate, reliable test of fetoplacental reserve during those final few weeks of pregnancy. Induction of labour is usually performed by the 42nd week.

There are still two main methods of induction; amniotomy or surgical induction, and the medical methods using prostaglandin or oxytocin. When appropriately selected, there is a high probability of a safe uneventful vaginal delivery. If spontaneous labour does not occur by the 43rd week the likelihood of a Caesarean delivery is high, irrespective of the mode of onset labour. As the perinatal morbidity and mortality continue to rise at this stage, intervention is recommended.

Prenatal diagnosis and ultrasound

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Principles of screening

Patients and doctors alike are used to associating an investigation with the confirmation or exclusion of a diagnosis. It is not surprising, therefore, to find that an enormous amount of anxiety can be created by the use of screening tests, particularly in pregnancy, where so much is at stake. Screening tests simply select populations into low and high risk groups, for the purpose of planning the next level of care for a particular issue or diagnosis. They can be useful in a variety of situations in pregnancy. It is essential that the patient understands the nature of a screening test before agreeing to the investigation, so that true informed consent is obtained, to minimise the anxiety of a false positive result, and appreciate the possibility of a false negative result. The situation is made more confusing by the fact that many diagnostic tests applied to the whole population are described as ‘screening’, using the lay, rather than scientific meaning of the word.

Screening for Down’s syndrome

Our genes determine who we are, and our genes are stored in chromosomes (46 in 23 pairs). Occasionally during reproduction an extra chromosome is added, making one pair of chromosomes into a triple (trisomy). Down’s syndrome is where there are three of the 21st pair of chromosomes (Trisomy 21). There are lots of errors made in the reproduction process, but trisomy 21 remains the most common chromosome anomaly found after the first trimester, when the majority of these problems are dealt with by miscarriage (see Early pregnancy and Threatened miscarriage). A chromosomal abnormality can only be diagnosed with an invasive procedure (amniocentesis, chorion villus sampling, cordocentesis), which carry a 1% risk of miscarriage. Naturally, many women do not wish to take this risk unless they believe the risk of finding a chromosomal abnormality is high.

Screening tests, such as nuchal translucency measurement or placental hormone assay, or both, refine the calculation of risk. With this information the woman, usually in discussion with her partner, can decide if they are happy to live with risk of trisomy 21, or take the risk of an invasive procedure. There is no right and wrong answer to this dilemma. Every woman/couple have to weigh up the risks and decide for themselves.

The woman who has had four miscarriages and is 41 years of age will be much more reluctant to consider an invasive procedure, when compared to the mother who already has an affected child.

Diagnosis of abnormalities

ith the introduction of real time ultrasound it is possible to diagnose many physical abnormalities that occasionally affect a fetus. Some of these problems are not serious, some will require surgery or medical treatment, which can be planned, and a small number will be more serious, leading to major handicap or death. We traditionally rely on ultrasound at around twenty weeks to check for abnormalities, but improved technology means that we can now diagnose many problems as early as the 12 week scan.

Diagnosis of genetic disorders

It is difficult to check for gene defects unless you know precisely where the gene is. Although we have mapped the human genome, we still do not know the location of many of the more rare genetic disorders, which often happen as one off problems in a pregnancy.

More common geneteic disorders, where there is a family history and precise knowledge of the gene site, can be tested for.

The common gene defects looked for in Europe include:

  • Tay-Sachs disease (Ashkenazi Jews)
  • Sickle Cell Disease (African- Caribbean)
  • Thallassaemia (Mediterranean and middle east)

There are other common gene defects throughout the world, reflecting the local population.

Fetal hydrops and anaemia

Ultrasound

Since the introduction of ultrasound into clinical practice by Ian Donald in Glasgow in 1960, it has rapidly acquired an important place in maternity care, but this has not been without certain drawbacks and limitations due to its operator dependent nature. It has however, an established place in antenatal care in a number of areas. It is important in accurate pregnancy dating required for the purposes of monitoring fetal growth through pregnancy.

First trimester

In the first trimester, ultrasound can be used to confirm the presence of an intra-uterine pregnancy, and determine its viability.

The crown rump length measurement is used in dating until about 14 weeks, after which the biparietal diameter, head and abdominal circumferences, and femur length are used. Many of the major structural abnormalities can now be diagnosed at this stage in pregnancy. If the pregnancy is multiple, the number and chorionicity can be noted. Between 10 and 14 weeks, the fluid at the back of the neck of the fetus can measured (nuchal translucency). This is a useful screening test for predicting the likely risk of the fetus being affected by a chromosomal anomaly. If this test is unavailable, reliable dating by ultrasound is essential for biochemical screening for chromosomal abnormality, as the hormone levels vary with gestational age.

Second trimester

The second trimester ultrasound scan is usually done between 18 and 22 weeks gestation. This involves a search for morphological abnormalities, including anomalies associated with chromosomal disorders (markers), and an assessment of fetal growth. Doppler ultrasound of the uterine arteries is performed between 20 and 24 weeks gestation. Abnormal uterine artery Doppler waveform patterns are predictive of uteroplacental complications that may occur later in the pregnancy.

Third trimester

In the third trimester, or when the fetus becomes potentially viable, ultrasound can be use to monitor growth, or help in the diagnosis of fetal growth restriction. In addition to the growth of the fetus, ultrasound allows us to investigate its environment in utero, and determine the ability of the fetus to cope with adverse situations. Biophysical assessment, including liquor estimation and assessment of body and breathing movement, fetal heart rate analysis, and umbilical artery Doppler are accepted tests of wellbeing, performed throughout the world. Doppler assessment of the fetal circulation provides more specific information regarding the fetal condition in-utero, but is not routinely available.

The safety of ultrasound examinations during pregnancy has naturally been questioned. The consensus of opinion is that no detrimental effects of ultrasound use have been reported during pregnancy. At the levels of power and intensity currently used, there are numerous benefits derived but no known complications.

Diagnostic invasive procedures

Amniocentesis

A small needle is inserted, under ultrasound guidance, into the amniotic fluid that surrounds the fetus. Some cells from the fetus are in the fluid. These are then either amplified (with a technique known as PCR) and/or cultured, so that the chromosomes in the cells can be looked at. As with all invasive procedures there is approximately 1% risk of miscarriage.

Chorionic villi sampling (CVS)

A small needle is inserted, under ultrasound guidance, into the placenta. The cells in the placenta have the same genes and chromosomes as the fetus. These are then either amplified (with a technique known as PCR) and/or cultured, so that the chromosomes in the cells can be looked at. There are more cells obtained with CVS, compared to amniocentesis, so this technique is usually preferred when looking for genetic anomalies. As with all invasive procedures there is approximately 1% risk of miscarriage.

Cordocentesis (Fetal blood sampling)

A small needle is inserted, under ultrasound guidance, into the umbilical cord of the fetus. The fetal blood cells can then be either amplified (with a technique known as PCR) and/or cultured, so that the chromosomes in the cells can be looked at. There is approximately 1% – 5% risk of miscarriage, depending on the indication for the fetal blood sampling.

Ultrasound

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Ultrasound scanning in early pregnancy

Assessment of early pregnancy is dealt with elsewhere, as the complication encountered most often relates to threatened miscarriage.

The 11 – 13 week first trimester scan

As we approach the end of the first trimester the developing embryo has now become a fetus, attaining the form and shape of a small human (12wk1). At this stage of pregnancy we can now discover much about a pregnancy:

  1. Confirm viability – the majority of miscarriages will have taken place by the end of the first trimester. If the fetus appears healthy at this stage of the pregnancy, the risk of subsequent miscarriage is very low (~1%). In a small number of pregnancies a missed miscarriage may be found (the pregnancy is not viable but the placenta or afterbirth continues to be active, having missed the fact.
  2. Confirm gestational age. When we count the number of weeks pregnant from the first day of the last period, we assume that conception took place exactly two weeks later. This is often not the case. The ultrasound measurement provides a more accurate estimate of gestational age, though we usually don’t redate unless there is more than a week in the difference between the menstrual and ultrasound dates.
  3. Confirm number of fetuses – This is the best time to check for twins and for the chorionicity of the twins.
  4. Identify abnormalities – Many abnormalities can be seen at this stage, particularly the more severe abnormalities.
  5. Screening for Chromosomal anomalies – Our genes are carried on our chromosomes, which are in every cell in our body. The natural process is not perfect, and sometimes there are too many or too few chromosomes, leading to problems such as mental retardation. The only way of being certain whether a fetus has a chromosomal anomaly or not is to perform an invasive procedure, such as amniocentesis, placental biopsy (CVS) or fetal cord blood sampling (see prenatal diagnosis). These tests carry a 1% risk of miscarriage, so many women only wish to consider an invasive test if they are high risk. Screening tests, looking at the fluid at the back of the neck of the fetus (translucent neck – nuchal translucency) (12wk2) and biochemistry assay of placental hormones. The most popular of these tests is the combined Nuchal/biochemistry test, performed around 11 – 13 weeks gestation.

The mid-pregnancy ultrasound assessment (16 wk)

At this stage of pregnancy we can now discover much about a pregnancy:

    1. Confirm gestational age. If dates, viability and number of pregnacies have not been confirmed by the 11 – 13 weeks scan (see back), they can be permed at this time. Identify abnormalities – Many abnormalities which cannot be seen can be seen at this stage, particularly the more severe abnormalities (holo 4)
    2. Identify abnormalities – Many abnormalities cannot be seen at 11 – 13 weeks, so they can be identified at about 20 weeks gestation (see prenatal diagnosis).
    3. Screening for Chromosomal anomalies – Our genes are carried on our chromosomes, which are in every cell in our body. The natural process is not perfect, and sometimes there are too many or too few chromosomes, leading to problems such as mental retardation. The only way of being certain whether a fetus has a chromosomal anomaly or not is to perform an invasive procedure, such as amniocentesis, placental biopsy (CVS) or fetal cord blood sampling.
    4. These tests carry a 1% risk of miscarriage, so many women only wish to consider an invasive test if they are high risk. If the patient has not had nuchal translucency or biochemical screening (see above) markers or possible signs can be sought on the 20-week scan. If earlier screening has taken place, many of the original markers do not substantially alter the risk. If there is more than one marker a careful review by a Fetal Medicine Specialist is recommended.
    5. Screening for pre-eclampsia and IUGR – These conditions carry great risks for the mother and fetus later in the pregnancy. These tests carry a 1% risk. Using ultrasound blood flow and biochemistry tests, it is possible to identify women who are at increased risk of these conditions.
    6. Screening for preterm labour – Preterm labour and delivery is one of the biggest causes of death and handicap in the newborn (see common obstetric problems). A weak cervix or neck of the womb is one cause of preterm labour. Ultrasound measurement of the cervix between 20 and 26 weeks can be helpful in spotting some of the women that will deliver their baby early.

Uterine artery Doppler is discussed in greater detail later in this chapter.

Scanning in the second half of pregnancy

In the U.K. the majority of women will have had an ultrasound scan to confirm viability, number of fetuses and to check for any obvious anomalies (first trimester scan). The purpose of scanning in the second half of pregnancy is to help diagnose and manage pregnancies at risk of obstetric complications. We use ultrasound to:

      1. Measure the fetus and assess growth.
      2. Assess fetal wellbeing by looking at fetal movement and liquor (amniotic fluid) volume (3trim1)
      3. Check the fetal blood flow, to check for reduced flow or redistribution of flow (associated with a reduced oxygen supply to the fetus).

Where there is normal growth, activity and liquor, there is generally no cause for concern. The assessment is less useful for women who go beyond their due date, as the risk of unexpected serious events is greater in this group of women.

If there is a reduction in growth, poor movement or reduced liquor, or changes in the blood flow, there is cause for concern. Further scans or early delivery (often by Caesarean Section) is required.

The 11 – 13 week first trimester scan – more detailed information.

Throughout the nineties we have sought to identify the best use of ultrasound in the first half of pregnancy, differentiating between the limitations of ultrasound and its users, constantly trying to provide the most accurate data on the capability of this investigation. Ultrasound manufacturers have taken advantage of revolutionary developments in computer technology to produce machines and transducers with ever-greater resolution, particularly at higher frequencies.

These machines, whether transabdominal or transvaginal, have made routine investigation in early pregnancy a reality. Early pregnancy dating, confirmation of viability, diagnosis of multiple pregnancy and abnormality, can now be attained with a 10-14 week scan. It is therefore apparent that much of what is currently achieved at the mid-pregnancy assessment can be fulfilled by the 12-14 week scan. Although earlier diagnosis includes pregnancies that would have been lost through the process of natural wastage, it allows women to make decisions about their pregnancy at a much earlier stage than before. Invasive prenatal diagnostic testing can also be offered at this stage, accepting the potential dangers of early chorionic villous sampling and early amniocentesis.

Nuchal translucency is a transient finding in early pregnancy, observed at a time when dramatic changes are occurring in the uteroplacental and fetal circulations. The transient nature probably reflects the completion of these changes in uteroplacental and fetal haemodynamics. Within a few weeks the fetal circulation adapts and the fluid typically disappears. The confirmation that increased fetal nuchal translucency is associated with an increased risk of chromosomal abnormality, as well as structural; particularly cardiac and genetic, syndromes, raises the possibility of adapting (or applying) the early scan to meet the needs of the original mid-pregnancy assessment. Two important issues then arise; the true ability of the early pregnancy scan to achieve these objectives, and the future role, if any, of the second trimester scan.

Lively discussions take place at every scientific meeting regarding the true capability of the early pregnancy assessment. It is now generally agreed that the estimation of gestational age is best done using ultrasound, early in the pregnancy. The detection of anomalies, whether using transvaginal or transabdominal probes, continues to improve, again through the use of better training and technology. We are still learning about the best means of exploiting the relationship between increased nuchal translucency, placental biochemistry and chromosomal and fetal abnormality.

The mid-pregnancy ultrasound assessment – more detailed information

The timing of the original pregnancy scan arose because of several factors. The initial quality of early ultrasound machines made diagnosis of anomalies difficult in the early stages of pregnancy, although reasonably accurate dating was possible before the inception of real-time B-mode scanning. With the introduction of amniocentesis for advanced maternal age, an ultrasound scan between 16 and 19 weeks gestation became more valuable, as not only could dates be confirmed, but the optimal site for the introduction of the amniocentesis needle could also be identified. Biochemical screening, initially for neural tube defects, and later for Down’s syndrome, rely on ultrasound dates to provide an accurate gestational age.

It is a sign of the pace of change in the use of ultrasound in pregnancy, that we are discussing the changing shape of mid pregnancy assessment, when the issues surrounding the original use of such an application are yet to be resolved. The use of a mid-pregnancy ultrasound assessment, where gestational age can be confirmed, and structural anomalies and markers of chromosomal aneuploidy can be recognised, is still debated. The assessment of newer imaging methods is easier than proving the value of older, well established ones.

The reports in the literature suggest that, given skilled staff and adequate equipment it is possible to confirm dates, identify most major structural anomalies, and through the use of morphological markers, achieve limited success in identifying pregnancies at increased risk of aneuploidy.

Unfortunately the combination of skilled personnel and modern equipment can be hard to come by, and ultrasonography remains one of the most operator dependent of diagnostic technologies. Any perceptions regarding the evolution of the mid-pregnancy scan must be considered in this context.

Throughout the nineties we have sought to find the true value of the mid-pregnancy scan, differentiating between the limitations of ultrasound and its users, constantly trying to provide the most accurate data on the capability of this investigation. Ultrasound manufacturers have taken advantage of revolutionary developments in computer technology to produce machines and transducers with even greater resolution, particularly at higher frequencies.

This evokes the question of the future of the mid pregnancy assessment, in terms of both its timing and what is to be achieved by the investigation (if a detailed first trimester scan has been performed).

The paucity of anomalies left after first trimester anomaly and nuchal translucency screening, has lead us to reconsider the term ‘anomaly scan’ at 20 weeks gestation. In addition, the detailed early scan annuls the significance of ‘soft markers’ of aneuploidy e.g. mild hydronephrosis at the mid pregnancy scan. It is also more difficult to justify its use for this purpose in terms of cost benefit analysis. A scan at this time however, is likely to be most useful in the prediction of complications such as pre-term delivery and utero-placental disorders that present later in the pregnancy.

Colour Doppler technology has greatly improved access to the use of Doppler ultrasound, without necessarily resulting in a corresponding improvement in the skill of the operator. This problem can only be addressed by proper training and meticulous attention to detail. While the reproducibility of uterine artery Doppler ultrasound screening in pregnancy varies, it is generally accepted that there is a strong relationship between elevated uterine artery resistance and perinatal complications, particularly pre-eclampsia. The finding of elevated resistance in both uterine arteries (bilateral notches) at 20 or 24 weeks gestation identifies a cohort of women at considerable risk of early delivery as a result of uteroplacental problems. The next logical step is to identify and introduce interventions that will prevent or palliate such complications; studies are currently being conducted to address the issue.

Finding suitable prophylactic therapies has proved more difficult than originally envisaged. There remains a nagging suspicion that aspirin, given in adequate amounts, can improve the outcome in certain high-risk pregnancies. Other regimens may also prove useful in this regard. For example, while glyceryl trinitrate, a nitric oxide donor, has a limited benefit as a single treatment, it may be of use in combination therapy. Meanwhile reports outlining the link between short cervical length and an increased risk of preterm delivery have been published. This opens a new debate as to whether screening for cervical length should be incorporated into the second trimester scan assessment.

Ultrasound in the management of high-risk pregnancies – more detailed information

Work undertaken in the nineties1, 2,3,4,9 have demonstrated the relationship between hypoxaemia/acidaemia and redistribution of the fetal arterial circulation. Abnormal venous waveforms (a reflection of cardiac dysfunction have been strongly linked to the development of acidaemia and impending heart failure, the final sequence seen in the fetus compromised by chronic utero-placental insufficiency (figure 1).5,6,7,8.

Umbilical arterial resistance typically informs us about placental resistance, whereas fetal growth, arterial and venous flow patterns provide an insight into the fetal response to inadequate placental supply of oxygen and other nutrients.

So where does this leave the fetal physician? How best is he or she to investigate and manage the at risk fetus? The first and most important point is to recognise that there is no “magic” score or figure that can be applied to all situations. Gestational age and fetal size are critical factors in any decision regarding delivery of the compromised fetus. Furthermore, Doppler indices are in some respects “gestational age conditional”: it is unusual to see abnormal venous flows at term, and the umbilical artery pulsatility index, nearly always elevated in preterm IUGR, can be normal in the term or post-term fetus that is compromised.

In our practice we use a combination of relevant medical and obstetric history, abnormal uterine-artery Doppler and referral on clinical suspicion of IUGR/pre-eclampsia as a signal to perform an initial assessment. If fetal growth, movement and amniotic fluid are normal, fetal Doppler or fetal heart rate analysis is not routinely performed. The decision regarding follow up is based on the findings at scan, in addition to the original indication for referral.

Where there is evidence of a reduction in growth velocity or evidence of growth restriction, where the amniotic fluid is reduced or no fetal movements recorded, a more detailed assessment of the fetus is undertaken. (All patients will typically have had an anomaly scan before 24 weeks gestation). If the umbilical and middle cerebral artery Doppler results are normal, we do not go on to perform venous flow or Doppler fetal heart rate assessment. Where there is evidence of compromise (cessation of growth, oligohydramnios, abnormal fetal arterial redistribution) a decision regarding delivery or further assessment is made, taking the gestational age, estimated fetal weight, biophysical and Doppler parameters into consideration.

When there is clear evidence of compromise e.g. cessation of growth, oligohydramnios, abnormal fetal arterial Doppler, the gestational age and estimated fetal size must be taken into account when making a decision regarding intervention. If the fetus is greater than 1500g and more than 34 weeks mature, it is difficult to find a good reason to continue with the pregnancy, particularly if the epidemiological data on size and subsequent complications holds true.

Between 32 and 34 weeks gestation other factors such as availability of neonatal and community services are additional important points when making a decision for continuing the pregnancy or arranging delivery.

Between 28 and 32 weeks gestation, with the fetus greater than 750g, the balance between gestational age and fetal compromise makes each decision unique. The risk of death or cerebral palsy reduces as each week goes by, but if delivery is delayed until there is fetal circulatory collapse (very abnormal venous blood flows), the risk of death is also increased. There are no easy answers in this situation. The patient, the neonatologist and the perinatologist have to weigh up each case and determine the optimum time for intervention on an individual basis. In these cases it would seem prudent to consider delivering the fetus, before venous blood flow patterns or short-term fetal heart rate variation become grossly abnormal, although we only have anecdotal clinical experience to support this approach.

With extreme prematurity, the decisions become even more difficult. The risk of death or handicap from immaturity is considerably greater in this group, when compared to later gestations. Fortunately, the small immature fetus often appears able to cope far better with hypoxia and acidaemia than its bigger and more mature equivalent. Here, the use of the computerised fetal heart rate analysis, Doppler the fetal arterial and venous circulation, in addition to growth and liquor, play a part in determining the frequency of assessments and the final decision to deliver.

Umbilical venous blood flow may be a useful method of assessing changes before there are frankly abnormal venous Doppler waveforms. On occasions a condition may be so severe as to consider not delivering at all, but allowing nature to takes its inevitable course. Of course on other occasions, the maternal condition e.g. pre-eclampsia precludes such a decision and requires the pregnancy to be ended as quickly as possible, in the mother’s interests.

In the absence of clear scientific data to support precise criteria for delivery, we must rely on clinical experience, interpreting all the available evidence to provide us with the best decision possible at the time. Where technology and the skill to utilise it is available, it would be irresponsible to base decisions on a limited range of information.

References

    1. Soothill PW, Nicolaides KH, Campbell S. Prenatal asphyxia, hyperlacticaemia, hypoglycemia and erythroblastosis in growth retarded fetuses. BMJ 1987; 294: 1051-53.
    2. Bilardo C, Nicolaides KH, Campbell S. Doppler measurements of fetal and uteroplacental circulations: Relationship with umbilical venous blood gases measured at cordocentesis. Am J Obstet Gynecol 1990; 162: 115-20.
    3. Hecher K, Snijders R, Campbell S, Nicolaides K. Fetal venous, intracardiac and arterial blood flow measurements in intrauterine growth retardation: relationship with fetal blood gases. Am J Obstet Gynecol 1995; 173: 10-15.
    4. Rizzo, G., Capponi, A., Arduini, D., Romanini, C. (1996). Doppler indices from inferior vena cava and ductus venosus in predicting pH and oxygen tension in umbilical blood at cordocentesis in growth-retarded fetuses. Ultrasound Obstet Gynecol; 7: 401-10.
    5. Baschat AA, Gembruch U, Reiss I, Gortner L, Diedrich K. Demonstration of fetal coronary blood flow by Doppler ultrasound in relation to arterial and venous flow velocity waveforms and perinatal outcome-the “heart sparing effect”. Ultrasound Obstet Gynecol 1997; 8: 82-86.
    6. Harrington K, Thompson MO, Carpenter RG, Nguyen M, Campbell S. (1999) Doppler fetal circulation in pregnancies complicated by pre-eclampsia or delivery of a small for gestational age baby: 2. Longitudinal analysis. Br J Obstet Gynaecol, 106, 453-66.
    7. Kiserud T, Eik-Ness SH, Blaas H-G, Hellevik LR. (1994) Ductus venosus blood velocity and the umbilical circulation in the seriously growth retarded fetus. Ultrasound Obstet Gynecol; 4: 109-114.
    8. Gudmunsson S, Tulzer G, Huhta JC, Marsal K. (1996) Venous Doppler velocimetry in fetuses with absent end-diastolic blood velocity in the umbilical artery. Ultrasound Obstet Gynecol; 7: 262-7.
    9. Hecher K, Campbell S, Doyle P, Harrington K, Nicolaides K. Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies. Circulation 1995; 91: 129-38.

Twins and more

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Introduction

Multiple pregnancies have their own problems at each stage of a pregnancy. Twins are the most common multiple pregnancy, with triplets and quadruplets etc. much less common. One of the reasons for an increase in the attention afforded multiple pregnancy has been the rise in these pregnancies as a result of assisted conception and ovulation stimulation techniques.

Types of multiple pregnancy and their importance

Twins and more can be identical or mono -zygotic (where the twins come from the same egg and sperm) or non-identical or dizygotic (where they arise from two or more eggs and sperm). When non-identical twins implant in the womb they always have two separate sacs and placentas (dichorionic, chorion being one of the sac membranes). If the twins are identical, they may or may not share a sac; it depends how long after conception the split takes place.

For instance if the embryo divides into two in the first couple of days, each fetus will have a separate sac and placenta. If they split after more than five days they will share the sac and placenta (mono-chorionic). If they leave it too late to split they can end up as conjoined or siamese twins.

The reason this is important is because monochorionic twins account for roughly a third of twin pregnancies, but about two thirds of the increased risk associated with being a multiple pregnancy. For this reason monochorionic pregnancies tend to be monitored more closely in pregnancy. For instance, the risk of very preterm delivery (see Preterm labour and delivery), i.e. delivery before 32 weeks gestation is about 1% for singleton, 2% for dichorionic and 10% for monochorionic pregnancies. As preterm delivery is the biggest cause of perinatal death and handicap you can see the importance of knowing which type of twin pregnancy you have. An ultrasound scan at the end of the first trimester (11 – 13 weeks) is the best time to check on the chorionicity of a multiple pregnancy.

Complications

Multiple pregnancies are at greater risk of:

  1. Chromosomal abnormalities (see Prenatal diagnosis). Dizygotic twins are more common in older women, who have a greater risk of chromosomal problems, and each egg carries its own risk. Special counselling is advisable regarding this issue in multiple pregnancy.
  2. Fetal abnormalities. The risk for the non-identical (dizygotic) twins is the same as a singleton, but identical twins have a four-fold increase in the risk of finding an abnormality.
  3. Common obstetric problems. There is an increased risk of developing antepartum and postpartum haemorrhage (see Haemorrhage), hypertension www.pregnancycare.co.uk/hypertension diabetes, anaemia and deep venous thromboembolism (see Major symptoms) among other problems in twin pregnancy.
  4. Death of one twin can affect the chances of the remaining twin staying alive or being handicapped.
  5. Twin-twin transfusion syndrome. This can happen if the twins share the same sac and placenta. One fetus gets too much blood, becomes big and has extra fluid around it (polyhydramnios), while the other receives too little, is small and has no fluid around it (oligohydramnios – stuck twin). If the extra fluid around the recipient (big twin) becomes too much for the uterus the woman presents with a rapidly swelling, painful abdomen. She may require drainage of the fluid or laser to the vessels communicating from one side of the placenta to the other.

Delivery

Because many twins deliver early, and because it is not considered safe to allow a multiple pregnancy to labour if there has been previous uterine surgery, e.g. Caesarean section, the section rate for twins is higher than for singletons. If the delivery is vaginal, the experience of the operator is essential in ensuring that not only the first, but also the second twin is delivered safely.

Drinking alcohol

Excessive drinking, combined with poor nutrition can lead to a condition known as fetal alcohol syndrome, where the baby is born with a small head and an unusual facial appearance, among other problems. It is not known exactly what quantity of alcohol consumption is safe or at what stage of pregnancy that consumption is harmful to the unborn child. Most studies do not report any adverse outcome from women drinking up to 8 units (I unit = 1 glass of wine, 1 glass of beer) per week. It is assumed that the alcohol is taken as part of a meal, and not all at the same time. Where possible the best choice is to avoid alcohol entirely during pregnancy.

Heavy drinking can reduce a man’s sperm count

Nutrition

An adequate diet is just as important prior to conception as it is during pregnancy. It is good a idea to try to attain weight that is appropriate for your height before you get pregnant. Special diets may not be appropriate for the first few months of pregnancy. Talk to your counsellor about a plan that’s right for you.

Common sense is your best guide – you should have something from each of the following food groups every day.

  • Milk and dairy products
  • Meat, poultry, fish, eggs, nuts and beans
  • Wholegrain or enriched bread and cereal
  • Fruits and vegetables

Today the government recommends that all women of childbearing age should be told about folic acid and how to obtain it, because research shows that, neural tube defects, such as spina bifida and hydrocephalus, may be prevented by taking the folic acid vitamin.

A healthy adult needs 200µg (0.2mg) of folic acid every day, but women who are considering pregnancy need to take more – an extra 400µg (0.4mg) to make a total of 600µg (0.6mg) – This can be bought over the counter at any pharmacy.

Exercise

Regular exercise will not only make you feel better but will also help during your pregnancy and labour. Building muscles in the lower back, stomach and legs will be especially helpful in making yours a more comfortable and active pregnancy. Use the time before you conceive to start an exercise programme that suits your lifestyle. If you don’t exercise already, walking and swimming are excellent choices.