Skin• Pallor
• Jaundice
• Cyanosis
• Rashes (erythema toxicum is normal)
• Birthmarks (see Chapter 51)
All newborn babies are carefully examined in the first 24 h of life to check that they are healthy and to detect congenital abnormalities, some of which may not be obvious to the parents. The baby should be fully undressed in a warm room and examined from head to toe. Ask the mother if she has any concerns and whether there is any family history of note, for example of deafness or congenital dislocation of the hips
General observation
• Weight, length and head circumference
• Maturity
• Muscle tone
• Reflexes: Moro, grasp, suck and rooting
• Is this a healthy baby who is feeding well?
Face—dysmorphic features?
• Low set or simple ears
• Inner epicanthic folds
• Mongolian or anti-Mongolian slant of eyes
• Symmetry of face and mouth
• Accessory auricles and pre-auricular pits
• Micrognathia (small chin)
Heart
• Cyanosis
• Heart failure (tachypnoea, hepatomegaly)
• Heart murmur
• Femoral pulses (coarctation)
• Apex beat (dextrocardia)
Genitalia and anus
• Hypospadias (urinary meatus on underside of penis)
• Cryptorchidism (undescended testes)
• Ambiguous genitalia: if both testes are impalpable, consider whether the baby could be a virilized female, due to congenital adrenal hypoplasia
• Imperforate anus (may have fistula to bladder or vagina)
Back and spine
• Spina bifida or posterior encephalocele
• Midline naevus, lipoma or deep sacral pit can suggest an underlying spinal abnormality
Hips
• Barlow and Ortolani tests for congenital dislocation of the hips (CDH)
• Ask about risk factors (breech, family history of CDH)
Limbs
• Talipes equinovarus (club foot)
• Polydactyly (extra digits or toes)
• Syndactyly (fused digits or toes)
• Single palmar crease and 'sandal gap' between toes (Down's syndrome)
• Contractures (oligohydramnios or congenital muscular disorder)
• Absent radii (VACTERL association)
Eyes
• Red reflex (to exclude cataract)
• Sclera (for jaundice)
• Coloboma (defect in the pupil) Head• Anterior fontanelle
• Cephalhaematoma (parietal swelling that does not cross suture lines)
• Chignon from ventouse suction cup
Mouth
• Cleft lip/palate
• Central cyanosis
• Neonatal teeth
Chest
• Respiratory rate
• Respiratory distress
• Symmetry of chest movement (pneumothorax, diaphragmatic hernia)
Abdomen
• Abdominal distension or bile-stained vomiting suggest bowel obstruction
• Palpable kidneys (hydronephrosis)
• Anterior abdominal wall defects (gastroschisis or exomphalos)
• Three vessels in umbilical cord? (normal)
Common syndromes to be aware of:
• Trisomy 21 (Down's syndrome)
• Trisomy 13 (Patau's syndrome)
• Trisomy 18 (Edwards' syndrome)
• Turner's syndrome (45 XO)
• Noonan's syndrome (lymphoedema)
• VATER and VACTERL association
• Pierre Robin sequence
Patterns of congenital abnormality
The incidence of congenital abnormalities is 10–15 per 1000 births.
The commonest are congenital heart defects (8 per 1000) (see Chapter 19). Abnormalities range from a trivial birth mark to a
genetically determined, but some may be due a combination of genetics and environment (e.g. spina bifida) or due entirely to environment (e.g. fetal alcohol syndrome).
A syndrome is a consistent pattern of dysmorphic features seen
Congenital abnormalities Moving through childhood 33 Syndromes
Down’s syndrome Trisomy 21: See Chapters 8 and 63 Patau’s syndrome Trisomy 13 Midline defects, cleft lip and
palate, cutis aplasia,
holoprosencephaly, polydactyly, heart defects (VSD, PDA, ASD)
Edward’s syndrome Trisomy 18 IUGR, polyhydramnios, rocker-bottom feet, clenched hands, prominent occiput, heart defects (VSD, PDA, ASD), apnoea Turner’s syndrome (45XO) See chapter 8.
Noonan’s syndrome Phenotypically similar to Turner’s but occurs in both sexes. Short stature, oedema, pulmonary stenosis Associations
VACTERL Vertebral, anal atresia, cardiac, tracheo-oesophageal fistula, renal, limb (absent radii)
CHARGE Coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia and ear anomalies
abnormality leads to another—for example, the small mandible (micrognathia) in Pierre Robin sequence causes posterior displace- ment of the tongue, which prevents the palate forming correctly, leading to cleft palate. An association is a non-random collection of abnormalities (see below).
Syndromes and associations
Cleft lip and palate
Cleft lip occurs in 1 in 1000 infants. 70% have a cleft lip as well.
Cleft lip may be diagnosed antenatally, allowing the parents to receive counselling. After birth a cleft palate is confirmed by pal- pating and observing the defect in the palate. A submucosal cleft is palpable but not visible. Cleft palate is best managed by a multi- disciplinary team including plastic surgeon, orthodontist and speech therapist. Repair of the lip is performed at 3 months and the palate at 9 months. The cosmetic appearance following plastic surgery is excellent. Showing the parents ‘before and after’ photo- graphs (see figure) can help allay anxiety. Expected difficulties include feeding difficulty, milk aspiration, conductive hearing loss and speech and dental problems. Regular audiological assessments are essential.
Neural tube defects (spina bifida)
Failure of the neural tube to close normally in early pregnancy causes spina bifida. It used to be a major cause of disability, but folic acid supplementation in early pregnancy has reduced the incidence by 75%. Antenatal ultrasound screening and selective termination has made open spina bifida a rare condition. Neural tube defects are always midline. The severity depends on the extent to which the neural tube has failed to develop:
• Anencephaly. The cranial part of the neural tube does not exist and the brain cortex does not develop. Infants die soon after birth.
a) Cleft lip (before surgery)
Source: Queen Victoria Hospital NHS Foundation Trust
b) Cleft lip repaired
• Myelomeningocele. An open lesion where the spinal cord is covered by a thin membrane of meninges. There is severe weakness of the lower limbs with bladder and anal denervation and an associated hydrocephalus. Survivors have severe disability.
• Meningocele. The spinal cord is intact but there is an exposed sac of meninges which can rupture, with the risk of meningitis.
• Spina bifida occulta. A ‘hidden’ neural tube defect where the vertebral bodies fail to fuse posteriorly. Some degree may be present in 5–10% of normal infants. The only clue may be a tuft of hair, naevus, lipoma or deep sacral pit in the midline over the lower back. A spinal ultrasound is indicated.
Developmental dysplasia of the hip
Developmental dysplasia of the hip (DDH) occurs in 1% of infants.
The acetabulum is shallow and does not adequately cover the femoral head, leading to the hip joint being, dislocatable or dis- clocated. Risk factors are breech position, family history, female sex and impaired limb movement. There is an association with talipes. True congenital dislocation of the hip (CDH) occurs in 2 per 1000 infants. Examination includes observation of symmetri- cal skin creases and leg length, the Ortolani test (a dislocated hip will not abduct fully, and ‘clunks’ as it relocates into the acetabu- lum) and the Barlow test (feeling a clunk as a dislocatable hip slips out of the acetabulum). Babies with risk factors or abnormal examination should have an ultrasound of the hip joint before 12 weeks. Treatment involves wearing a harness or splint to hold the joint in flexion and abduction for several months.
Ortolani test
• Abducting the hips to try to relocate hip
• Fingers push femur forwards into acetabulum
Barlow test
• Pushing backwards to try to dislocate hip
8 Screening and genetics
Chorionic villus sampling (11–13 weeks)
• Biopsy of placenta performed in fetal medicine clinic. Fetal cells extracted and examined
• 2 in 100 chance of miscarriage
• Diagnosis of chromosomal disorder or gene testing
Amniocentesis (from 15 weeks)
• Ultrasound guided sample of amniotic fluid taken and fetal cells extracted
• 1 in 100 risk of miscarriage Maternal blood test (0–10 weeks)
• Sickle cell
• Thalassaemia
Genetic tests in Newborn
• Karyotype (structural chromosomal disorders e.g. trisomy 13, deletions e.g. 5p-)
• Molecular cytogenetic techniques to identify chromosomal deletions or rearrangements
• Specific gene testing (e.g. cystic fibrosis, haemophilia)
Genetic testing to confirm clinical diagnosis:
• CTG repeats in myotonic dystrophy
• 22q deletion in DiGeorge syndrome Karyotype demonstrating trisomy 21 Down syndrome
• Biochemical screening (triple test = AFP, hCG, oestriol) alone or combined with ultrasound nuchal translucency measurement at 11–13 weeks
• Offered to all pregnant women
• If screen positive offered invasive testing (CVS or amniocentesis)
Newborn hearing screening (birth)
• Otoacoustic emissions at cot-side
• Brainstem evoked potentials if high risk or missed newborn screen
Newborn bloodspot screen (day 5–8)
• (see table opposite) Newborn physical examination
• At 72 h and 6 weeks (see Chapter 6|)
• Hips, heart, eyes, testes (boys)
School screening
• Vision, growth and obesity (at entry)
• Obesity (at age 11 years) Congenital anomaly screen
• Detailed ultrasound examination at 18–20 weeks
• Skeletal abnormality
• CNS abnormality
• Neural tube defects
• Structural heart defects (major)
• Cleft lip
• Renal agenesis or obstruction
• Congenital lung malformation
Weeks 0
8 11
13 15 18 20
36
40 Birth
Screening timeline (UK) Genetic testing timeline
Pre-conception
• Pre-conception genetic counselling
• Carrier screening of parents
• Pre-implantation testing (IVF)
Screening and genetics Moving through childhood 35
Screening
Screening aims to identify unrecognized disease in apparently well people. Cost must be considered and balanced against that of treatment if the problem presents later. Conditions suitable for screening should:
• Be identifiable at a latent or early symptomatic stage
• Be treatable.
• Have a better prognosis if treated early.
Screening of newborns and children in the UK is outlined oppo- site and in the box below. Further information is available at http://www.screening.nhs.uk/england.
Genetic disorders
Most disorders that are screened for in newborns have a genetic basis. Molecular genetic techniques are increasingly used to iden- tify abnormal genes or chromosomes. It is vital that families receive appropriate counselling so that they understand the impli- cations of an abnormal result. Genetic tests can be performed at various times:
• Pre-implantation testing is only available with in-vitro fertiliza- tion techniques, but can allow screening prior to implantation.
• Antenatal genetic testing via chorionic villus sampling or amnio- centesis allows the possibility of termination of pregnancy. Some families choose to continue the pregnancy despite a positive result and this allows them time to come to terms with the diagnosis.
• Newborn genetic testing may be performed to confirm a clinical diagnosis (e.g. Down’s syndrome or congenital myotonic dystro- phy) or following a positive screening test (e.g. CF gene testing fol- lowing an abnormal IRT result on the newborn blood spot screen).
• Genetic testing of older children may be needed to confirm a diagnosis presenting later in childhood (e.g. fragile X or Duchenne muscular dystrophy). In general children must not be tested for adult-onset genetic disorders without their own informed consent unless it is going to alter their treatment during childhood.
Genetic inheritance
Many genetic disorders occur sporadically with no preceding family history or are multifactorial, with an environmental element
(e.g. diabetes), but some single-gene disorders show a clear inherit- ance pattern:
• Autosomal recessive: both parents carry an abnormal copy of the gene (carrier). 25% of their children will inherit both abnormal genes and be affected. 50% of offspring inherit one abnormal gene and are themselves carriers and usually unaffected. 25% of off- spring do not inherit either abnormal gene.
• Autosomal dominant: inheriting even a single copy of the abnormal gene from either parent means the child is affected.
These conditions sometimes present earlier or more severely in successive generations (anticipation). Sometimes the effect of a gene mutation will depend on which parent it is inherited from (imprinting).
• Sex-linked inheritance: gene disorders on the X chromosome usually only present in boys, as the presence of a second normal X chromosome in girls prevent them being severely affected.
Examples include haemophilia A and fragile X syndrome.
• Chromosomal disorders: these are usually sporadic due to non- disjunction of chromosomes during meiosis (trisomy 21, 18 or 13) or due to rearrangement of major parts of the chromosome (trans- locations). In Turner’s syndrome there is deletion of one X chro- mosome (45 XO). In some cases there is deletion of part of a chromosome, e.g. cri du chat syndrome (5p- deletion).
Screening for Down’s syndrome
Down’s syndrome affects 1 in 1000 live births (1 in 600 fetuses).
There is an association with increased maternal age (1 in 880 at 30 years rising to 1 in 100 at age 40 years). 95% are due to non- disjunction during meiosis and 3% to an unbalanced translocation.
1% are mosaics, with only a proportion of cells within the body having trisomy 21. About 55% of affected fetuses are detected antenatally, through screening. In those diagnosed antenatally, only 5% of couples choose to continue with the pregnancy. Ante- natal screening involves measurement of AFP, hCG and oestriol (the ‘triple’ test) and other markers, with nuchal fold (subcutane- ous tissue at back of the neck) thickness in the fetus. This gives a calculated risk, which if high may prompt diagnostic testing via chorionic villus sampling or amniocentesis.
Notes
The midwife will collect bloodspots from the heel of every newborn baby on day 5–8 of life on to an absorbent card. These are analysed and also stored for further diagnostic tests if necessary
Congenital hypothyroidism Screen detects high TSH level but will miss hypothyroidism secondary to pituitary dysfunction. Thyroid replacement allows normal development
Sickle cell disease Universal screening to all pregnant women aims to identify at-risk couples. Newborn blo odspots are analysed by HPLC for all sickle cell variants
Phenyketonuria (PKU) A phenylalanine assay has replaced the original ‘Guthrie’ test. Babies PKU need urgent advice on starting a low-phenylalanine diet and long-term follow-up to prevent learning disability from phenylalanine metabolites
Cystic fibrosis (CF) A high immunoreactive trypsin (IRT) on the newborn blood spot is followed up with DNA testing for common CF mutations
Medium-chain acylcarnitine deficiency (MCAD)
A fatty acid oxidation defect that can lead to significant hypoglycaemia during periods of illness. Acylcarnitine abnormalities can be detected by tandem mass spectrometry. MCAD is a preventable cause of sudden death in infancy. Frequent feeds prevent the need for breakdown of fatty acids