THURSDAY 3 JANUARY 2013
MAGAZINE FOR SPECIALISTS
THURSDAY 3 JANUARY 2013
ASSISTED REPRODUCTIVE TECHNOLOGY
In vitro fertilisation
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Method Indications
PRENATAL DEVELOPMENT
Blastocyst differentiation
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Inner cell mass differentiation
Preimplantation genetic diagnosis
Live birth rate
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Dystocia (obstructed labour)
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Maternal complications
Caesarean section
Risks for the mother Risks for the child Infographic types of caesaren section
NEONATOLOGY
Neonatology Spectrum of care
Levels of care 13
15
13
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Infographic of new born
Equipment
Types Indications
Risks
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Nursing and neonatal populations
Fetal complications Intrapartum asphyxia
CAESAREAN SECTION
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Cavity formation Susceptibility Infographic of age difference
Embryo profiling
DYSTOCIA
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Implantation Susceptibility
Embryo selection Embryo transfer
Biomarkers Other factors
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Weeks development
A ntim端llerian hormone
Ovarian hyperstimulation Natural and Mild IVF Final maturation and egg retrieval Egg and sperm preparation Fertilisation
Embryo culture
Gestational age vs. embryonic age
Incubator
Qualifications and requirements Patient populations
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ASSISTED REPRODUCTIVE TECHNOLOGY
In vitro fertilisation In vitro fertilisation (IVF) is a process by which an egg is fertilised by sperm outside the body: in vitro. IVF is a major treatment for infertility when other methods of assisted reproductive technology have failed. The process involves monitoring a woman’s ovulatory process, removing ovum or ova (egg or eggs) from the woman’s ovaries and letting sperm fertilise them in a fluid medium in a laboratory. When a woman’s natural cycle is monitored to collect a naturally selected ovum (egg) for fertilisation, it is known as natural cycle IVF. The fertilised egg (zygote) is then transferred to the patient’s uterus with the intention of establishing a successful pregnancy. The first successful birth of a “test tube baby”, Louise Brown, occurred in 1978. Louise Brown was born as a result of natural cycle IVF. Robert G. Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010 they youse to do it. The term in vitro, from the Latin meaning
in glass, is used, because early biological experiments involving cultivation of tissues outside the living organism from which they came, were carried out in glass containers such as beakers, test tubes, or petri dishes. Today, the term in vitro is used to refer to any biological procedure that is performed outside the organism it would normally be occurring in, to distinguish it from an in vivo procedure, where the tissue remains inside the living organism within which it is normally found. A colloquial term for babies conceived as the result of IVF, “test tube babies”, refers to the tube-shaped containers of glass or plastic resin, called test tubes, that are commonly used in chemistry labs and biology labs. However, in vitro fertilisation is usually performed in the shallower containers called Petri dishes. One IVF method, Autologous Endometrial Coculture, is actually performed on organic material, but is still considered in vitro.
Theoretically, in vitro fertilisation could be performed by collecting the contents from a woman’s fallopian tubes or uterus after natural ovulation, mixing it with semen, and reinserting into the uterus. However, without additional techniques, the chances of pregnancy would be extremely small. Such additional techniques that are routinely used
in IVF include ovarian hyperstimulation to retrieve multiple eggs, ultrasound-guided transvaginal oocyte retrieval directly from the ovaries, egg and sperm preparation, as well as culture and selection of resultant embryos before embryo transfer back into the uterus.
IVF may be used to overcome female infertility in the woman due to problems of the fallopian tube, making fertilisation in vivo difficult. It may also assist in male infertility, where there is a defect in sperm quality, and in such cases intracytoplasmic sperm injection (ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm have difficulty penetrating the egg, and in these cases the partner’s or a donor’s sperm may be used. ICSI is also used when sperm numbers are very low. ICSI results in success rates equal to those of IVF. For IVF to be successful it typi-
cally requires healthy ova, sperm that can fertilise, and a uterus that can maintain a pregnancy. Due to the costs of the procedure, IVF is generally attempted only after less expensive options have failed. IVF can also be used with egg donation or surrogacy where the woman providing the egg isn’t the same who will carry the pregnancy to term. This means that IVF can be used for females who have already gone through menopause. The donated oocyte can be fertilised in a crucible. If the fertilisation is successful, the embryo will be transferred into the uterus, within which it may implant. IVF can also be combined with preimplantation genetic diagnosis (PGD) to rule out presence of genetic disorders. A similar but more general test has been developed called Preimplantation Genetic Haplotyping.
The sperm and the egg are incubated together at a ratio of about 75,000:1 in the culture media for about 18 hours. In most cases, the egg will be fertilised by that time and the fertilised egg will show two pronuclei. In certain situations, such as low sperm count or motility, a single sperm may be injected directly into the egg using intracytoplasmic sperm injection (ICSI). The fertilised egg is passed to a special growth medium and left
for about 48 hours until the egg consists of six to eight cells. In gamete intrafallopian transfer, eggs are removed from the woman and placed in one of the fallopian tubes, along with the man’s sperm. This allows fertilisation to take place inside the woman’s body. Therefore, this variation is actually an in vivo fertilisation, not an in vitro fertilisation.
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There are two current main protocols for stimulating the ovaries for IVF treatment. The long protocol involves downregulation (suppression or exhaustion) of the pituitary ovarian axis by the prolonged use of a GnRH agonist. Subsequent ovarian hyperstimulation, typically using follicle stimulating hormone (FSH), starts once the process of downregulation is complete, generally after 10 to 14 days. An IVF cycle using this protocol is known as conventional IVF. The short protocol skips the downregulation part, and consists of a regimen of fertility medications to stimulate the development of multiple follicles of the ovaries. In most patients, injectable gonadotropins (usually FSH analogues) are used under close monitoring. Such monitoring frequently checks the estradiol level and, by means of gynecologic ultrasonography, follicular growth. Typically approximately 10 days of injections will be necessary. Spontaneous ovulation during the cycle is typically prevented by the use of GnRH antagonists that are used just during the last days of stimulation to block the natural surge of luteinising hormone (LH) and allow the physician to start the ovulation process by using medication, usually injectable human chorionic gonadotropins. Ovarian stimulation carries the risk of excessive stimulation leading to ovarian hyperstimulation syndrome (OHSS). This complication is life-threatening and ovarian stimulation using gonadotropins must only be carried out under strict medical supervision.
IVF can be performed by collecting a naturally selected egg from woman’s natural menstrual cycle without the use of any drugs. It is known as natural cycle IVF. The first test tube baby Louise Brown was born following natural cycle IVF. This method can be successfully used when women want to avoid taking ovarian stimulating drugs with its associated side-effects. HFEA has estimated the live birth rate to be approximately 1.3% per natural cycle IVF for women aged between 40–42. The next step-up method is called modified natural cycle IVF. In this method, medication is used for 2–4 days during woman’s natural cycle to avoid spontaneous ovulation and to make the treatment more successful. As the success rates are improved it is a widely used method of natural IVF It is
A diagram depicting the the egg retrieval process during IVF
particularly beneficial in women with very low egg reserve and in those whose ovaries do not respond to drugs. STEP 2
Further information: Final maturation (IVF) and Transvaginal oocyte retrieval When the ovarian follicles have reached a certain degree of development, induction of final oocyte maturation is performed, generally by an injection of human chorionic gonadotropin (hCG). Commonly, this is known as the “trigger shot.” hCG acts as an analogue of luteinising hormone, and ovulation would occur between 38 and 40 hours after a single HCG injection, but the egg retrieval is performed at a time usually between 34 and 36 hours after hCG injection, that is, just prior to when the follicles would rupture. This avails for scheduling the egg retrieval procedure at a time where the eggs are fully mature. HCG injection confers a risk of ovarian hyperstimulation syndrome. Using a GnRH agonist instead of hCG eliminates the risk of ovarian hyperstimulation syndrome, but with a delivery rate of approximately 6% less than with hCG.
In the laboratory, the identified eggs are stripped of surrounding cells and prepared for fertilisation. An oocyte selection may be performed prior to fertilisation to select eggs with optimal chances of successful pregnancy. In the meantime, semen is prepared for fertilisation by removing inactive cells and seminal fluid in a process called sperm washing. If semen is being provided by a sperm donor, it will usually have been prepared for treatment before being frozen and quarantined, and it will be thawed ready for use. The World Health Organization has determined an “ideal rate” of all cesarean deliveries (such as 15 percent) for a population. One surgeon’s opinion is that there is no consistency in this ideal rate, and artificial declarations of an ideal rate should be discouraged. Goals for achieving an optimal cesarean delivery rate should be based on maximizing the best possible maternal and neonatal outcomes, taking into account available medical and health resources and maternal preferences. This opinion is based on the idea that if left unchallenged.
EGG
the transfer of spermotasoa to the egg
STEP 1 Egg collection
Ovary Embrio The eggs and sperm are placed in a glass dish and incubated with careful temperature, atmospheric, and infection control for 48 to 120 hours. About 2 to 5 days after fertilization, the best fertilized eggs are selected. One to three are placed in the uterus using a thin flexible tube (catheter) that is inserted through the cervix. Those remaining may be frozen (cryopreserved) for future attempts.
EMBRIO zigotte
Uterus
STEP 3 Embryo transfer
Other determinants of outcome of IVF include: Tobacco smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%. A body mass index (BMI) over 27 causes a 33% decrease in likelihood to have a live birth after the first cycle of IVF, compared to those with a BMI between 20 and 27. Also, pregnant women who are obese have higher rates of miscarriage, gestational diabetes, hypertension, thromboembolism and problems during delivery, as well as leading to an increased risk of fetal congenital abnormality. Ideal body mass index is 19–30. Salpingectomy before IVF treatment increases chances for women with hydrosalpinges Success with previous pregnancy and/or live birth increases chances Low alcohol/caffeine intake increases success rate The number of embryos transferred in the treatment cycle. Some studies also suggest the autoimmune disease may also play a role in decreasing IVF success rates by interfering with proper implantation of the embryo after transfer. Aspirin, however, was shown by a meta-analysis to not improve pregnancy rates after IVF.
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PRENATAL DEVELOPMENT
Gestational age vs. embryonic age
GESTATIONAL AGE is the time that has passed since the onset of the last menstruation, which generally or as standard occurs 2 weeks before the actual fertilization. Embryonic age, in contrast measures the actual age of the embryo or fetus from the time of fertilization. Nevertheless, menstruation has historically been the only means of estimating embryonal/fetal age, and is still the presumed measure if not else specified. However, the actual duration between last menstruation and fertilization may in fact differ from the standard 2 weeks by several days. Thus, the first week of embryonic age is already week three counting with gestational age. Furthermore, the number of the week is one more than the actual age of the embryo/fetus. For example, the embryo is 0 whole weeks old during the 1st week after fertilization. The following table summarizes the various expression systems during week number x of gestation. Mother’s age 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 labor period, which could potentially result in death of
the mother or fetus. Women under 16 and over 35 have a higher risk of preterm labor (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, crying, etc. There is a risk of mental retardation for infants over the age of 40 - down syndrome. Teen mothers and mother over 35 are more exposed to the risks of miscarriages, premature births, and birth defects. Drug use Eleven percent of fetus’s 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 will influence extreme irritability, crying, and risk for SIDS
number Reached age (whole weeks) Gestational x x-1 Embryonic x-2 x-3
Gestational age: 0 weeks and 0 days until to 1 week and 6 days old. 1–14 days from last menstruation. Embryonic age: -2 to -1 weeks old. (Week 1–2 of gestational age are theoretical extrapolations of embryonic age, since the fertilization hasn’t actually occurred yet.
Gestational age: 2 weeks and 0 days until 2 weeks and 6 days old. 15–21 days from last menstruation. Embryonic age: Week nr 1. 0 (whole) weeks old. 1–7 days from fertilization. Fertilization of the ovum to form a new human organism, the human zygote. (day 1 of fert.) The zygote undergoes mitotic cellular divisions, but does not increase in size. This mitosis is also known as cleavage. A hollow cavity forms marking the blastocyst stage. (day 1.5–3 of fert.) The blastocyst contains only a thin rim of trophoblast cells and a clump of cells at one end known as the “embryonic pole” which include embryonic stem cells. The embryo hatches from its protein shell (zona pellucida) and performs implantation onto the endometrial lining of the mother’s uterus. (day 5–6 of fert.) If separation into identical twins occurs, 1/3 of the time it will happen before day 5.
Gestational age: 3 weeks and 0 days until 3 weeks and 6 days old. 22–28 days from last menstruation. Embryonic age: Week nr 2. 1 week old. 8–14 days from fertilization. Trophoblast cells surrounding the embryonic cells proliferate and invade deeper into the uterine lining. They will eventu-
ally form the placenta and embryonic membranes. The blastocyst is fully implanted day 7–12 of fert. Formation of the yolk sac. The embryonic cells flatten into a disk, two cells thick. If separation into identical twins occurs, 2/3 of the time it will happen between days 5 and 9. If it happens after day 9, there is a significant risk of the twins being conjoined. Primitive streak develops. (day 13 of fert.) Primary stem villi appear. (day 13 of fert.)
Gestational age: 4 weeks and 0 days until 4 weeks and 6 days old. 29–35 days from last menstruation. Embryonic age: Week nr 3. 2 weeks old. 15–21 days from fertilization. A notochord forms in the center of the embryonic disk. (day 16 of fert.) Gastrulation commences. (day 16 of fert.) A neural groove (future spinal cord) forms over the notochord with a brain bulge at one end. Neuromeres appear. (day 18 of fert.) Somites, the divisions of the future vertebra, form. (day 20 of fert.) Primitive heart tube is forming. Vasculature begins to develop in embryonic disc. (day 20 of fert.) Embryo at 6 weeks after fertilization. The crown-rump length is about 0.2 inches. A 10mm embryo from an ectopic pregnancy, still in the oviduct. This embryo is about five weeks old (or from the seventh week of menstrual age).
Gestational age: 5 weeks and 0 days until 5 weeks and 6 days old. 36–42 days from last menstruation. Embryonic age: Week nr 4. 3 weeks old. 22–28 days from fertilization.. The embryo measures 4 mm (1/8 inch) in length and begins to curve into a C shape. The heart bulges, further develops, and begins to beat in a regular rhythm. Septum primum appears. Branchial arches, grooves which will form structures of the face and neck, form. The neural tube closes. The ears begin to form as otic pits. Arm buds and a tail are visible. Pulmonary primordium, the first traits of the lung appear. Hepatic plate, the first traits of the liver appear. Buccopharyngeal membrane ruptures. This is the future mouth. Cystic diverticulum, which will become the gallbladder, and dorsal pancreatic bud, which
THURSDAY 3 JANUARY 2013
will become the pancreas appear. Urorectal septum begins to form. Thus, the rectal and urinary passageways become separated. Anterior and posterior horns differentiate in the spinal cord Spleen appears. Ureteric buds appear. This embryo is also from an ectopic pregnancy, this one in the cornu (the part of the uterus to which the Fallopian tube is attached). The features are consistent with a developmental age of seven weeks (reckoned as the ninth week of pregnancy).
Gestational age: 6 weeks and 0 days until 6 weeks and 6 days old. 43–49 days from last menstruation. Embryonic age: Week nr 5. 4 weeks old. 29–35 days from fertilization. The embryo measures 9 mm in length. Lens pits and optic cups form the start of the developing eye. Nasal pits form. The brain divides into 5 vesicles, including the early telencephalon. Leg buds form and hands form as flat paddles on the arms. Rudimentary blood moves through primitive vessels connecting to the yolk sac and chorionic membranes. The metanephros, precursor of the definitive kidney, starts to develop. The initial stomach differentiation begins.
Gestational age: 7 weeks and 0 days until 7 weeks and 6 days old. 50–56 days from last menstruation. Embryonic age: Week nr 6. 5 weeks old. 36–42 days from fertilization. The embryo measures 13 mm (1/2 inch) in length. Lungs begin to form. The brain continues to develop. Arms and legs have lengthened with foot and hand areas distinguishable. The hands and feet have digits, but may still be webbed. The gonadal ridge begins to be perceptible. The lymphatic system begins to develop. Main development of external genitalia starts.
Week 9 A six week embryonic age or eight week gestational age intact human embryo.
Gestational age: 8 weeks and 0 days until 8 weeks and 6 days old. 57–63 days from last menstruation. Embryonic age: Week nr 7. 6 weeks old. 43–49 days from fertilization. The embryo measures 18 mm in length. Fetal heart tone (the sound of the heart beat) can be heard using doppler. Nipples and hair follicles begin to form. Location of the elbows and toes are visible. Spontaneous limb movements may be detected by ultrasound. All essential organs have at least begun. The vitelline duct normally closes.
The fetal period begins at the end of the 10th week of gestation (8th week of development). Since the precursors of all the major organs are created by this time, the fetal period is described both by organ and by a list of changes by weeks of gestational age. Because the precursors of the organs are formed, fetus also is not as sensitive to damage from environmental exposures as the embryo. Instead, toxic exposures often cause physiological abnormalities or minor congenital malformation.
Gestational age: 9 weeks and 0 days until 11 weeks and 6 days old. Embryonic age: Weeks nr 8–10. 7–9 weeks old. Embryo measures 30–80 mm (1.2–3.2 inches) in length. Ventral and dorsal pancreatic buds fuse during the 8th week Intestines rotate. Facial features continue to develop. The eyelids are more developed. The external features of the ear begin to take their final shape. The head comprises nearly half of the fetus’ size. The face is well formed. The eyelids close and will not reopen until about the 28th week. Tooth buds, which will form the baby teeth, appear. The limbs are long and thin. The fetus can make a fist with its fingers. Genitals appear well differentiated. Red blood cells are produced in the liver.
Gestational age: 12 weeks and 0 days until 15 weeks and 6 days old. Embryonic age: Weeks nr 11–14. 10–13 weeks old. The fetus reaches a length of about 15 cm (6 inches). A fine hair called lanugo develops on the head. Fetal skin is almost transparent. More muscle tissue and bones have developed, and the bones become harder.
The fetus makes active movements. Sucking motions are made with the mouth. Meconium is made in the intestinal tract. The liver and pancreas produce fluid secretions. From week 13, sex prediction by obstetric ultrasonography is almost 100% accurate. At week 15, main development of external genitalia is finished Fetus at 18 weeks after fertilization.
Vetebral coloumns
Gestational age: 18 weeks old. Embryonic age: Week nr 17. 16 weeks old. The fetus reaches a length of 20 cm. Lanugo covers the entire body. Eyebrows and eyelashes appear. Nails appear on fingers and toes. The fetus is more active with increased muscle development. “Quickening” usually occurs (the mother and others can feel the fetus moving). The fetal heartbeat can be heard with a stethoscope.
Uterus
Gestational age: 22 weeks old. Embryonic age: Week nr 21. 20 weeks old. The fetus reaches a length of 28 cm. The fetus weighs about 925g. Eyebrows and eyelashes are well formed. All of the eye components are developed. The fetus has a hand and startle reflex. Footprints and fingerprints continue forming. Alveoli (air sacs) are forming in lungs.
Gestational age: 26 weeks old. Embryonic age: Week nr 25. 24 weeks old. The fetus reaches a length of 38 cm. The fetus weighs about 1.2 kg (2 lb 11 oz). The brain develops rapidly. The nervous system develops enough to control some body functions. The eyelids open and close. The cochleae are now developed, though the myelin sheaths in neural portion of the auditory system will continue to develop until 18 months after birth. The respiratory system, while immature, has developed to the point where gas exchange is possible.
Gestational age: 30 weeks old. Embryonic age: Week nr 29. 28 weeks old. The fetus reaches a length of about 38–43 cm (15–17 inches).
Rectum Blader Vagina
Women between the ages of 16 and 35 have a healthier environment for a fetus than women under 16 or over 35. Women over 35 are more inclined to have a longer labor period, which could potentially result in death of the mother or fetus. 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.
The fetus weighs about 1.5 kg (3 lb 0 oz). The amount of body fat rapidly increases. Rhythmic breathing movements occur, but lungs are not fully mature. Thalamic brain connections, which mediate sensory input, form. Bones are fully developed, but are still soft and pliable. The fetus begins storing a lot of iron, calcium and phosphorus.
Gestational age: 34 weeks old.
Embryonic age: Week nr 33. 32 weeks old. The fetus reaches a length of about 40–48 cm (16–19 inches). The fetus weighs about 2.5 to 3 kg (5 lb 12 oz to 6 lb 12 oz). Lanugo begins to disappear. Body fat increases. Fingernails reach the end of the fingertips. A baby born at 36 weeks has a high chance of survival, but may require medical interventions. Fetus 38 weeks after fertilization.
Gestational age: 35 and 0 days until 39 weeks and 6 days old.
Embryonic age: Weeks nr 34–38. 33–37 weeks old. The fetus is considered full-term at the end of the 39th week of gestational age. It may be 48 to 53 cm (19 to 21 inches) in length. The lanugo is gone except on the upper arms and shoulders. Fingernails extend beyond fingertips. Small breast buds are present on both sexes. Head hair is now coarse and thickest. The development is continued postnatally with adaptation to extra uterine life and child development stages.
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DYSTOCIA
Obstructed labour Approximately one fifth of human labours have dystocia. Dystocia may arise due to incoordinate uterine activity, abnormal fetal lie or presentation, absolute or relative cephalopelvic disproportion, or (rarely) a massive fetal tumor such as a sacrococcygeal teratoma. Oxytocin is commonly used to treat incoordinate uterine activity, but pregnancies complicated by dystocia often end with assisted deliveries, including forceps, ventouse or, commonly, caesarean section. Recognized complications of dystocia include fetal death, respiratory depression, hypoxic ischaemic encephalopathy (HIE), and brachial nerve damage. A prolonged interval between pregnancies, primigravid birth, and multiple birth have also been associated with increased risk for labor dystocia. Shoulder dystocia is a dystocia in which the anterior shoulder of the infant cannot pass below the pubic symphysis or requires significant manipulation to pass below it. It can also be described as delivery requiring additional manoeuvres after gentle downward traction on the head has failed to deliver the shoulders. A prolonged second stage of labour is another type of dystocia whereby the fetus has not been delivered within three hours in a nulliparous woman, or two hours in multiparous woman, after her cervix has become fully dilated. Synonyms for dystocia include difficult labour, abnormal labour, difficult childbirth,
abnormal childbirth, and dysfunctional labour. Acute fatty liver of pregnancy (or hepatic lipidosis of pregnancy) usually manifests in the third trimester of pregnancy, but may occur any time in the second half of pregnancy, or in the puerperium, the period immediately after delivery. On average, the disease presents during the 35th or 36th week of pregnancy. The usual symptoms in the mother are non-specific including nausea, vomiting, anorexia (or lack of desire to eat) and abdominal pain; however, jaundice and fever may occur in as many as 70% of patients. In patients with more severe disease, preeclampsia may occur, which involves elevation of blood pressure and accumulation of fluid (termed edema). This may progress to involvement of additional systems, including acute renal failure, hepatic encephalopathy, and pancreatitis. There have also been reports of diabetes insipidus complicating this condition. Many laboratory abnormalities are seen in acute fatty liver of pregnancy. Liver enzymes are elevated, with the AST and ALT enzymes ranging from minimal elevation to 1000 IU/L, but usually staying in the 300500 range. Bilirubin is almost universally elevated. Alkaline phosphatase is often elevated in pregnancy due to production from the placenta, but may be additionally elevated.
Vaginal birth injury with visible tears or episiotomies are common. Internal tissue tearing as well as nerve damage to the pelvic structures lead in a proportion of women to problems with prolapse, incontinence of stool or urine and sexual dysfunction. Fifteen percent of women become incontinent, to some degree, of stool or urine after normal delivery, this number rising considerably after these women reach menopause. Vaginal birth injury is a necessary, but not sufficient, cause of all non hysterectomy related prolapse in later life. Risk factors for significant vaginal birth injury include: A baby weighing more than 9 pounds. The use of forceps or vacuum for delivery. These markers are more likely to be signals for other abnormalities as forceps or vacuum are not used in normal deliveries. The need to repair large tears after delivery. Pelvic girdle pain. Hormones and enzymes work together to produce ligamentous relaxation and widening of the symphysis pubis during the last trimester of pregnancy. Most
girdle pain occurs before birthing, and is known as diastasis of the pubic symphysis. Predisposing factors for girdle pain include maternal obesity. Infection remains a major cause of maternal mortality and morbidity in the developing world. The work of Ignaz Semmelweis was seminal in the pathophysiology and treatment of puerperal fever and saved many lives. Hemorrhage, or heavy blood loss, is still the leading cause of death of birthing mothers in the world today, especially in the developing world. Heavy blood loss leads to hypovolemic shock, insufficient perfusion of vital organs and death if not rapidly treated. Blood transfusion may be life saving. Rare sequelae include Hypopituitarism Sheehan’s syndrome. The maternal mortality rate (MMR) varies from 9 per 100,000 live births in the US and Europe to 900 per 100,000 live births in Sub-Saharan Africa. Every year, more than half a million women die in pregnancy or childbirth.
Risk factors for fetal birth injury include fetal macrosomia (big baby), maternal obesity, the need for instrumental delivery, and an inexperienced attendant. Specific situations that can
contribute to birth injury include breech presentation and shoulder dystocia. Most fetal birth injuries resolve without long term harm, but brachial plexus injury may lead to Erb’s palsy or Klumpke’s paralysis.
Intrapartum asphyxia is the impairment of the delivery of oxygen to the brain and vital tissues during the progress of labour. This may exist in a pregnancy already impaired by maternal or fetal disease, or may rarely arise de novo in labour. This can be termed fetal distress, but this term may be emotive and misleading. True intrapartum asphyxia is not as common as previously believed, and is usually accompanied by multiple
other symptoms during the immediate period after delivery. Monitoring might show up problems during birthing, but the interpretation and use of monitoring devices is complex and prone to misinterpretation. Intrapartum asphyxia can cause long-term impairment, particularly when this results in tissue damage through encephalopathy.
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Caesarean section
There are several types of Caesarean section (CS). An important distinction lies in the type of incision (longitudinal or latitudinal) made on the uterus, apart from the incision on the skin. The classical Caesarean section involves a midline longitudinal incision which allows a larger space to deliver the baby. However, it is rarely performed today, as it is more prone to complications. The lower uterine segment section is the procedure most commonly used today; it involves a transverse cut just above the edge of the bladder and results in less blood loss and is easier to repair. An unplanned Caesarean section is performed once labour has commenced due to unexpected labor complications. A crash/emergent/emergency Caesarean section is performed in an obstetric emergency, where complications of pregnancy onset suddenly during the process of labour, and swift action is required to prevent
the deaths of mother, child(ren) or both. A planned caesarean (or elective/scheduled caesarean), arranged ahead of time, is most commonly arranged for medical reasons and ideally as close to the due date as possible. This may be done in cases of intractable bleeding or when the placenta cannot be separated from the uterus. Traditionally, other forms of Caesarean section have been used, such as extraperitoneal Caesarean section or Porro Caesarean section. A repeat Caesarean section is one that is done when a patient had a previous Caesarean section. Typically it is performed through the old scar. In many hospitals, especially in Argentina, the United States, United Kingdom, Canada, Norway, Sweden, Finland, Australia, and New Zealand, the mother’s birth partner is encouraged to attend the surgery to support the mother and share the experience. The anaesthetist will usually lower the drape temporarily as the child is delivered so the parents can see their newborn. Cesarean section can be performed with
single or double layer suturing of the uterine incision. A Cochrane review came to the result that single layer closure compared with double layer closure was associated with a statistically significant reduction in mean blood loss.
A
Classic
B
Transverse incisions
C
previous uterine rupture prior problems with the healing of the perineum (from previous childbirth or Crohn’s disease) Bicornuate uterus Rare cases of posthumous birth after the death of the mother
Risks
Caesarean section is recommended when vaginal delivery might pose a risk to the mother or baby. Not all of the listed conditions represent a mandatory indication, and in many cases the obstetrician must use discretion to decide whether a Caesarean is necessary. Some indications for Caesarean delivery are: Complications of labor and factors impeding vaginal delivery, such as: prolonged labour or a failure to progress (dystocia) fetal distress cord prolapse uterine rupture increased blood pressure (hypertension) in the mother or baby after amniotic rupture
Types of caesaren section Low vertical
increased heart rate (tachycardia) in the mother or baby after amniotic rupture placental problems (placenta praevia, placental abruption or placenta accreta) abnormal presentation (breech or transverse positions) failed labour induction
failed instrumental delivery (by forceps or ventouse (Sometimes a trial of forceps/ ventouse delivery is attempted, and if unsuccessful, it will be switched to a Caesarean section.) large baby weighing >4000g (macrosomia) umbilical cord abnormalities (vasa previa, multilobate including bilobate and succenturiate-lobed placentas, velamentous insertion) Other complications of pregnancy, preexisting conditions and concomitant disease, such as: pre-eclampsia hypertension multiple births previous (high risk) fetus HIV infection of the mother Sexually transmitted infections, such as genital herpes (which can be passed on to the baby if the baby is born vaginally, but vcan usually be treated in with medication and do not require a Caesarean section) previous transverse Caesarean section
The mortality rate for both Caesarian sections and vaginal birth, in the Western world, continues to drop steadily. In 2000, the mortality rate for Caesareans in the United States were 20 per 1,000,000.The UK National Health Service gives the risk of death for the mother as three times that of a vaginal birth. However, it is misleading to directly compare the mortality rates of vaginal and Caesarean deliveries. Women with severe medical conditions, or higherrisk pregnancies, often require a Caesarean section which can distort the mortality figures. A study in the Canadian Medical Association Journal found the absolute difference in rates of severe maternal morbidity (e.g. cardiac arrest, wound hematoma, or hysterectomy) was small (18.3 additional cases in 1000 or three times the risk) and the difference in maternal mortality was nonsignificant, but this additional risk over vaginal delivery should be considered by women contemplating an elective Caesarean delivery and by their physicians. As with all types of abdominal surgeries, a Caesarean section is associated with risks of postoperative adhesions, incisional hernias (which may require surgical correction) and wound infections. If a Caesarean is performed under emergency situations, the risk of the surgery may be increased due to a number of factors. The patient’s stomach may not be empty, increasing the anaesthesia risk. Other risks include severe blood loss (which may require a blood transfusion) and postdural-puncture spinal headaches. A study published in Obstetrics and Gynecology found women who had multiple
Caesarean sections were more likely to have problems with later pregnancies, and recommended women who want larger families should not seek Caesarean section as an elective. The risk of placenta accreta, a potentially life-threatening condition, is only 0.13% after two Caesarean sections, but increases to 2.13% after four and then to 6.74% after six or more surgeries. Along with this is a similar rise in the risk of emergency hysterectomies at delivery. The findings were based on outcomes from 30,132 Caesarean deliveries. It is difficult to study the effects of Caesarean sections because it can be difficult to separate out issues caused by the procedure itself versus issues caused by the conditions that require it. For example, one study found women who had just one previous Caesarean section were more likely to have problems with their second birth. Women who delivered their first child by Caesarean delivery had increased risks for malpresentation, placenta previa, antepartum hemorrhage, placenta accreta, prolonged labor, uterine rupture, preterm birth, low birth weight, and stillbirth in their second deliveries. However, the authors concluded some risks may be due to confounding factors related to the indication for the first Caesarean, rather than due to the procedure itself.
Non-medically indicated (elective) childbirth before 39 weeks gestation “carry significant risks for the baby with no known benefit to the mother.” Complications from elective cesarean before 39 weeks include: newborn mortality at 37 weeks may be 2.5 times the number at 40 weeks, and was elevated compared to 38 weeks of gestation. These “early term” births were also associated with increased death during infancy, compared to those occurring at 39 to 41 weeks (“full term”). Researchers in one study and another review found many benefits to going full term, but “no adverse effects” in the health of the mothers or babies. In one recent study, neonates born before 39 weeks may experienced 2.5 times more of complications compared with those delivered at 39 to 40 weeks.
THURSDAY 3 JANUARY 2013
NEONATOLOGY
Neonatology Neonatology is a subspecialty of pediatrics that consists of the medical care of newborn infants, especially the ill or premature newborn infant. It is a hospital-based specialty, and is usually practiced in neonatal intensive care units (NICUs). The principal patients of neonatologists are newborn infants who are ill or requiring special medical care due to prematurity, low birth weight, intrauterine growth retardation, congenital malformations (birth defects), sepsis, pulmonary hyperplasia or birth asphyxias.
Rather than focusing on a particular organ system, neonatologists focus on the care of newborns who require Intensive Care Unit (ICU) hospitalization. They may also act as general pediatricians, providing well newborn evaluation and care in the hospital where they are based. Some neonatologists, particularly those in academic settings, may follow infants for months or even years after hospital discharge to better assess the long term effects of health problems early in life. Some neonatologists perform clinical and basic science research to further our understanding of this special population of patients.
A neonatal intensive care unit (NICU) is an intensive care unit specializing in the care of ill or premature newborn infants. The first official ICU for neonates was established in 1961 at Vanderbilt University Mildred Stahlman, officially termed a NICU when Stahlman used a ventilator off-label for a baby with breathing difficulties, for the first time ever in the world. A NICU is typically directed by one or more neonatologists and staffed by nurses, nurse practitioners, pharmacists, physician assistants, resident physicians, and respiratory therapists. Many other ancillary disciplines and specialists are available at larger units. The term neonatal comes from neo, “new”, and natal, “pertaining to birth or origin”.
Healthcare institutions have varying entrylevel requirements for neonatal nurses. Neonatal nurses are Registered Nurses (RNs), and therefore must have an Associate of Science in Nursing (ASN) or Bachelor of Science in Nursing (BSN) degree. Some countries or institutions may also require a midwifery qualification. Some institutions may accept newly-graduated RNs who have passed the NCLEX exam; others may require additional experience working in adult-health or medical/surgical nursing. Some countries offer postgraduate degrees in neonatal nursing, such as the Master of Science in Nursing (MSN) and various doctorates. A nurse practitioner may be required to hold a postgraduate degree. The National Association of Neonatal Nurses recommends two years’ experience working in a NICU before taking graduate classes. As with any registered nurse, local licensing or certifying bodies as well as employers
may set requirements for continuing education. There are no mandated requirements to becoming an RN in a NICU, although neonatal nurses must have certification as a Neonatal Resuscitation Provider. Some units prefer new graduates who do not have experience in other units, so they may be trained in the specialty exclusively, while others prefer nurses with more experience already under their belt. Intensive care nurses endure intensive didactic and clinical orientation, in addition to their general nursing knowledge, to provide highly specialized care for critical patients. Their competencies include the administration of high-risk medications, management of high-acuity patients requiring ventilator support, surgical care, resuscitation, advanced interventions such as extracorporeal membrane oxygenation or hypothermia therapy for neonatal encephalopathy procedures, as well as chronic-care management or lower acuity cares associated with premature infants such as feeding intolerance, phototherapy, or administering antibiotics.
In the United Kingdom, in 2008, the Caesarean section rate was 24%. In Ireland the rate was 26.1% in 2009. The Canadian rate was 26% in 2005–2006. Australia has a high Caesarean section rate, at 31% in 2007. In Italy the incidence of Caesarean sections is particularly high, although it varies from region to region. In Campania, 60% of 2008 births reportedly occurred via Caesarean sections. In the Rome region, the mean incidence is around 44%, but can reach as high as 85% in some private clinics. In the United States the Caesarean rate has risen 48% since 1996, reaching a level of 31.8% in 2007. A 2008 report found that fully one-third of babies born in Massachusetts in 2006 were delivered by Caesarean section. In response, the state’s Secretary of Health and Human Services, Dr. Judy Ann Bigby, announced the formation of a panel to investigate the reasons for the increase and the implications for public policy. China has been cited as having the highest rates of C-sections in the world at 46% as of 2008 Studies have shown that continuity of care
with a known carer may significantly decrease the rate of Caesarean delivery but there is also research that appears to show that there is no significant difference in Caesarean rates when comparing midwife continuity care to conventional fragmented care. More emergency Caesareans—about 66%—are performed during the day rather than during the night. Analyzing the rise in Caesarean section rates. The World Health Organization officially withdrew its previous recommendation of a 15% C-section rates in June 2010. Their official statement read, “There is no empirical evidence for an optimum percentage. What matters most is that all women who need caesarean sections receive them.” The US National Institutes of Health says rises in rates of Caesarean sections are not, in isolation, a cause for concern, but may reflect changing reproductive patterns: The World Health Organization has determined an “ideal rate” of all cesarean deliveries (such as 15 percent) for a population. One surgeon’s opinion is that there is no consistency in this ideal rate, and artificial declarations of an ideal rate should be discouraged.
THURSDAY 3 JANUARY 2013
Levels of care Level 1: Basic neonatal care
Normal new born
Level 1a: Evaluation and postnatal care of healthy newborn infants; and Phototherapy
h) or continuous positive airway pressure. Intravenous infusion, total parenteral nutrition, and possibly the use of umbilical central lines and percutaneous intravenous central lines.
Level 1b: Care for infants with corrected gestational age greater
Level 3: Intensive neonatal care
than 34 weeks or weight greater than 1800 g who have mild illness expected to resolve quickly or who are convalescing after intensive care; Ability to initiate and maintain intravenous access and medications Nasal oxygen with oxygen saturation monitoring (e.g., for infants with chronic lung disease needing long-term oxygen and monitoring).
Level 2: special care newborn nursery Level 2a: Care of infants with a corrected gestational age of 32
weeks or greater or a weight of 1500 g or greater who are moderately ill with problems expected to resolve quickly or who are convalescing after intensive care Peripheral intravenous infusions and possibly parenteral nutrition for a limited duration Resuscitation and stabilization of ill infants before transfer to an appropriate care facility Nasal oxygen with oxygen saturation monitoring ( for infants with chronic lung disease needing long-term oxygen and monitoring).
44%
Level 2b: Mechanical ventilation for brief durations (less than 24
Continuing transitional care, additional nursing care by mother’s side
26%
Level 3a: Care of infants of all gestational ages and weights; Mechanical ventilation support, and possibly inhaled nitric oxide, for as long as required Immediate access to the full range of subspecialty consultants.
Special Care Baby Unit Basic acre (1level )
Level 3b: Comprehensive on-site access to subspecialty consultants; Performance and interpretation of advanced imaging tests, including computed tomography, magnetic resonance imaging and cardiac echocardiography on an urgent basis Performance of major surgery on site but not extracorporeal membrane oxygenation, hemofiltration and hemodialysis, or surgical repair of serious congenital cardiac malformations that require cardiopulmonary bypass.
Level 3c: Extracorporeal membrane oxygenation, hemofiltration
18%
Intermediate care Specialty. Including high dependency care. Expanded Intermediate care includes short-term intencive care ( 2 level )
10%
and hemodialysis, or surgical repair of serious congenital cardiac malformations that require a cardiopulmonary bypass.
Intensive care Subspeciality, tertiary NICU ( 3 level )
2%
Equipment An incubator (or isolette) is an apparatus used to maintain environmental conditions suitable for a neonate (newborn baby). It is used in preterm births or for some ill full-term babies. Possible functions of a neonatal incubator are: Oxygenation, through oxygen supplementation by head hood or nasal cannula, or even continuous positive airway pressure (CPAP) or mechanical ventilation. Infant respiratory distress syndrome is the leading cause of death in preterm infants, and the main treatments are CPAP, in addition to administering surfactant and stabilizing the blood sugar, blood salts, and blood pressure. Observation: Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation, and brain activity. Protection from cold temperature, infection, noise, drafts and excess handling: Incubators may be described as bassinets enclosed in plastic, with climate control equipment designed to keep them warm and limit their exposure to germs. Provision of nutrition, through intravenous catheter or NG tube. Administration of medications. Maintaining fluid balance by providing fluid and keeping a high air humidity to prevent too great a loss from skin and respiratory evaporation.
A transport incubator is an incubator in a transportable form, and is used when a sick or premature baby is moved, e.g., from one hospital to another, as from a community hospital to a larger medical facility with a proper neonatal intensive care unit. It usually has a miniature ventilator, cardio-respiratory monitor, IV pump, pulse oximeter, and oxygen supply built into its frame.
Common diagnosis and pathologies in the NICU include: Anemia Apnea Bradycardia Bronchopulmonary dysplasia (BPD) Hydrocephalus Intraventricular hemorrhage (IVH) Jaundice Necrotizing enterocolitis (NEC) Patent ductus arteriosus (PDA) Periventricular leukomalacia (PVL) Infant respiratory distress syndrome (RDS) Retinopathy of prematurity (ROP)
Healthcare institutions have varying entry-level requirements for neonatal nurses. Neonatal nurses are Registered Nurses (RNs), and therefore must have an Associate of Science in Nursing (ASN) or Bachelor of Science in Nursing (BSN) degree. Some countries or institutions may also require a midwifery qualification. Some institutions may accept newly-graduated RNs who have passed the NCLEX exam; others may require additional experience working in adult-health or medical/surgical nursing. Some countries offer postgraduate degrees in neonatal nursing, such as the Master of Science in Nursing (MSN) and various doctorates. A nurse practitioner may be required to hold a postgraduate degree.
The National Association of Neonatal Nurses recommends two years’ experience working in a NICU before taking graduate classes. As with any registered nurse, local licensing or certifying bodies as well as employers may set requirements for continuing education. There are no mandated requirements to becoming an RN in a NICU, although neonatal nurses must have certification as a Neonatal Resuscitation Provider. Some units prefer new graduates who do not have experience in other units, so they may be trained in the specialty exclusively, while others prefer nurses with more experience already under their belt. Intensive care nurses endure intensive di-
dactic and clinical orientation, in addition to their general nursing knowledge, to provide highly specialized care for critical patients. Their competencies include the administration of high-risk medications, management of high-acuity patients requiring ventilator support, surgical care, resuscitation, advanced interventions such as extracorporeal membrane oxygenation or hypothermia therapy for neonatal encephalopathy procedures, as well as chronic-care management or lower acuity cares associated with premature infants such as feeding intolerance, phototherapy, or administering antibiotics. NICU RNs undergo annual skills tests and are subject to additional training to maintain contemporary practice.