ISSN 1012-8875 (HONG KONG) JAN/FEB 2012 Vol. 38 No. 1 JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY Your partner in paediatric and O&G practice MAR/APR 2013 Vol. 39 No. 2 Your partner in paediatric and O&G practice www.jpog.com CME ARTICLE Cerebral Palsy & Its Causal Relationship With Birth Asphyxia JOURNAL WATCH OBSTETRICS Hypertension in Pregnancy PAEDIATRICS Evaluation of the Acute Abdomen GYNAECOLOGY The Management of Perimenopausal Menstrual Symptoms
Transcript
ISSN 1012-8875(HONG KONG)
Hong KongJAN/FEB 2012 Vol. 38 No. 1
JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
Your partner in paediatric and O&G practice
MAR/APR 2013 Vol. 39 No. 2 Your partner in paediatric and O&G practice
Hypertension is a common complication of pregnancy and remains a major cause of maternal and perinatal morbidity and mortality worldwide. Patients with hypertensive disorders of pregnancy warrant cautious care with consultant obstetric, neonatal and anaesthetic involvement to optimize both maternal and fetal outcomes.
Fergus P McCarthy, Louise C Kenny
Review ArticlePaediatrics
61 EvaluationoftheAcuteAbdomen
Evaluation of the acute abdomen in infants and children can be challenging. The authors review a structured approach to assessment and define the management of some of the more serious acute abdominal conditions seen in children such as intussusception, appendicitis, and malrotation/volvulus.
At a recent Abbott-sponsored symposium in Singapore on the ‘Impact of Nutrition on Cognitive Development in Young children’, Dr. Elizabeth Johnson, Assistant Professor at the Jean Mayer USDA Human Nutrition Research Centre on Ageing, Tufts University, USA discussed the role of nutrition, with an emphasis on lutein, in cognitive function and development during early life.
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Emerging Science on Lutein in the BrainLutein is another potentially influential nutrient with regard to brain devel-opment and cognitive function. Lutein is transported across the blood-brain barrier where it accumulates in neural tissues. It is well known that lutein concentrates in the macula which is a highly specialized area of the retina involved in relaying information to the visual cortex of the brain. The wide-spread and selective presence of these carotenoids within the visual system has led many researchers to believe that they may play a special role in visual function and protection against visual disease.1 The most recent dis-covery that lutein and zeaxanthin are the dominant carotenoids within the brain comprising 66-77 percent of the total carotenoid concentration. “Lu-tein is found in the macula at concentrations 500-1000 more than anywhere else in the body; that suggests that it may have a role in neural health,” remarked Dr Johnson.
Sources of lutein Over 500 different types of carotenoids exist in nature, but only about 30-40 are found within human sera with lutein being amongst the most abundant. Humans do not synthesize carotenoids, thus lutein must be obtained from the diet. For young infants breast milk is the sole source of lutein. Eggs, fruits, and vegetables such as spinach and kale, are the most important source of carotenoids in the human diet.1,2
How lutein works Lutein protects the eyes by absorbing potentially damaging light and acts as an antioxidant. “Specific carotenoid binding proteins exist in the reti-na which specifically binds lutein and thus it may have positive biological functions,” pointed out Dr Johnson. Lutein in the retina has been shown to enhance gap junctional communication and may be important for the development of neural circuitry in the visual system and neural functions in the brain.3,4 Lutein is found in key regions that are associated with memory and learning suggesting a preferential uptake of lutein from the circulation into neural tissue (Figure 1).
Benefits of lutein: Clinical evidence Evidence of a link between lutein and cognitive function came from two large epidemiologic studies. Older adults who consumed a diet rich in high amounts of green leafy and cruciferous vegetables (both rich sources of lutein) had slower cognitive decline than those who consumed lower amounts.5,6 Supplementation with both DHA and lutein in elderly women is strongly associated with improvements in memory, rate of learning, and learning efficiency.7 The relationship between lutein-rich macular pigment and cognitive function was examined in an ancillary study of the National In-stitute of Agingsponsored Health, Aging and Body Composition (Health ABC) study. Macular pigment and cognitive function data was analyzed for 108 subjects with a mean age of 78 years. The results indicated that higher mac-ular pigment was associated with better cognitive function. Data suggest that lutein, measured as macular pigment density, is related to cognitive function and that macular pigment is a reflection of brain lutein status. “It appears that lutein is the dominant carotenoid in the older adult brain and plays an important role in cognition,” remarked Dr Johnson. This indicates that lutein may directly impact cognitive function.8 To determine the role of lutein in infants, brain samples were obtained from a federally-funded brain and tissue bank of otherwise healthy infants who had died in their first year. The results showed that the average lutein concentration was significantly greater than all other carotenoids.8 A comparison of brain carotenoid profile of centenarians and infants during the first year of life reveals that lutein is the dominant carotenoid in both age groups, but in infant’s lutein alone, ac-counts for more than half of the carotenoid content compared to 31 percent in adults (Figure 2). This indicates lutein may have a role in neural develop-ment in addition to cognitive function as seen in adults.8,9
Breast milk has greater concentration of lutein compared to other carot-enoids. Since lutein is not produced by the body, prior to the introduction of solid foods, infants can only obtain lutein from breast milk or formulas that are supplemented with lutein. “Even though lutein concentrations are similar at birth, after one month concentrations are greater in breast fed infants,” pointed out Dr Johnson. The selective uptake of lutein in breast milk may be another reason for its dominance in the brain. A recent study provided evidence that 117 μg lutein/L, needed in formula to achieve the range of plasma levels corresponding to that of human milk-fed infants is safe and well tolerated.8
ConclusionLutein is an important phytonutrient which may play a critical role in vision, cognition, and the overall development of the brain. Conclusive evidence from several studies demonstrates that lutein, if introduced at the right time, may influence cognitive and early neural development.
References: 1. Zimmer JP, et al. Clin Ophthalmol. 2007;1(1):25-35. 2. Sommerburg O, et al. Br J Ophthalmol. 1998;82(8):907-10. 3. Stahl W, et al. Biofactors. 2001;15(2-4):95-8. 4. Bone RA, et al. Invest Ophthalmol Vis Sci. 1988;29(6):843-9. 5. Kang JH, et al. Ann Neurol. 2005;57(5):713-20. 6. Morris MC, et al. Neurology. 2006;67(8):1370-6. 7. Johnson EJ, et al. Nutr Neurosci. 2008;11(2):75-83. 8. Acta Biologica Cracoviensia Series Botanica 2011; 53(suppl. 1): 29. 9. Johnson EJ, et al. FASEB J. 2011;25:975.21.
IMPORTANT NOTICE: Breast milk is best for babies. The World Health Organisation recommends exclusive breastfeeding for the first six months of life. Unnecessary introduction of bottle feeding or other food and drinks will have a negative impact on breastfeeding. After six months of age, infants should receive age-appropriate foods while breastfeeding continues for up to two years of age or beyond. Consult your doctor before deciding to use infant formula or if you have difficulty breastfeeding.
Johnson EJ et al. Abstract FASEB J 2011;25:975.21Vishwanathan et al. Poster at 16th International Symposium on Carotenoids, Poland, July 2011
(mean + se, n=48)Serum Brain120
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CarotenesXanthophylisaSignificantly greater than other carotenoidsCryptoxanthin is the sum of α- and β-crytoxanthin
Johnson EJ et al. Abstract FASEB J 2011;25:975.21
Figure 1: Carotenoid concentrations in serum and brain
Figure 2: Brain carotenoid profile in infants and centenarians
Johnson EJ et al. Abstract FASEB J 2011;25:975.21Vishwanathan et al. Poster at 16th International Symposium on Carotenoids, Poland, July 2011
(mean + se, n=48)Serum Brain120
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CarotenesXanthophylisaSignificantly greater than other carotenoidsCryptoxanthin is the sum of α- and β-crytoxanthin
Johnson EJ et al. Abstract FASEB J 2011;25:975.21
Figure 1: Carotenoid concentrations in serum and brain
Figure 2: Brain carotenoid profile in infants and centenarians
Dr. Elizabeth JohnsonJean Mayer USDA Human Nutrition
Research Centre on Ageing,Tufts University, USA
Lutein: Potential Role in the Development of the Infant Brain
Review ArticlesComprehensive reviews providing the latest clinical information on all aspects of the management of medical conditions affecting children and women.
Case StudiesInteresting cases seen in general practice and their management.
Pictorial MedicineVignettes of illustrated cases with clinical photographs.
For more information, please refer to the Instructions for Authors on our website www.jpog.com, or contact:The EditorUBM Medica Asia Pte Ltd, 6 Shenton Way, #15-08 Tower 2, Singapore 068809Tel: (65) 6290 7400 Fax: (65) 6290 7401 E-mail: [email protected]
Review ArticleGynaecology
74 The Management of Perimenopausal Menstrual Symptoms
Abnormal bleeding around the time of the menopause is common and may be a sign of premalignancy such as endometrial hyperplasia or even endometrial carcinoma. As such, all will need uterine assessment which may include transvaginal scan combined with endometrial biopsy, hysteroscopy or a sonohysterogram. Having excluded (pre) cancer, treatment can then be offered.
John Eden, Sheila O’Neill
Continuing Medical Education
81 Cerebral Palsy and Its Causal Relationship With Birth Asphyxia
Cerebral palsy (CP) is one of the leading causes of childhood disability, with a reported incidence of 2 to 3 per 1,000 live births. With obstetric litigation often becoming an option for seeking financial compensation in CP cases, it is therefore vital for the medical profession, the legal profession and the public to understand the true reality of the causal relationships between adverse events during the delivery process and CP.
point (death, myocardial infarction, or heart failure)
was reached by 3.2% (HRT) vs 6.5% (controls), a
significant 52% reduction in the HRT group. There
was a non-significant 43% reduction in mortality
with HRT. After 16 years of follow-up, there was
still a significant difference in the proportions
reaching the primary end point (6.6% vs 10.5%),
and mortality was non-significantly 34% less in the
HRT group (5.4% vs 7.9%). There was no signifi-
cant difference in the rate of stroke between the
two groups (2.2% vs 2.8%) or in the rate of venous
thromboembolism, which was low in both groups.
The groups did not differ significantly in the inci-
dence of breast or other cancers. The rate of death
or breast cancer was significantly 46% lower in the
HRT group (4.4% vs 7.9%).
HRT begun early in the menopause reduced
cardiovascular risk without increasing the risks of
cancer or thromboembolism.
Schierbeck LL et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012; 345 (Nov 3): 16 (e 6409).
Maternal obesity and neonatal death in Africa
Overweight and obesity have become more com-
mon in developing countries. The children of obese
mothers are more likely to die perinatally, to be
admitted to the neonatal intensive care unit, to be
macrosomic, and to have low Apgar scores. Data
from 27 countries in sub-Saharan Africa have illus-
trated the dangers of maternal obesity.
Pooled data from cross-sectional Demo-
graphic and Health Surveys from the 27 countries
were analysed. Of 81,126 women, 15,518 (19%)
were overweight, among whom 4,266 (5% of the
total) were obese, 52,006 (64%) were of normal
weight, and 13,602 (17%) were underweight. Ma-
ternal obesity (body mass index, 30 kg/m2 or higher)
was associated with a 46% increase in risk of neo-
natal death in a singleton live birth in the previous
5 years. This increased risk was entirely for neona-
tal deaths within 48 hours of birth; there was no
significant association between maternal obesity
and later neonatal deaths.
In sub-Saharan Africa, maternal obesity is
associated with increased neonatal mortality with-
in 2 days of birth. Suggested mechanisms include
prematurity, intrapartum events, and infections.
Obese mothers should be advised to deliver in well-
equipped units.
Cresswell A et al. Effect of maternal obesity on neonatal death in sub-Saharan Africa: multivariable analysis of 27 national datasets. Lancet 2012; 380: 1325–1330; Nohr EA. Maternal obesity and neonatal mortality in an African setting. Ibid: 1292–1293 (comment).
Comparing drugs for tocolytic therapy
A systematic review and network meta-analysis
had addressed the question of which are the best
agents for delaying delivery when preterm birth is
threatened.
The study included 95 randomized controlled
trial. Compared with placebo, the odds ratio for de-
lay of delivery by 48 hours was 5.39 for prostaglan-
din inhibitors, 2.76 for magnesium sulfate, 2.71 for
calcium-channel blockers, 2.41 for beta mimetics,
and 2.02 for atosiban (an oxytocin receptor block-
er). Tocolytics did not reduce the risk of neonatal
respiratory distress syndrome. Side effects leading
ative likelihood ratio, 0.35). The overall probability
of non-viable pregnancy was 62.9%, increasing to
96.8% with a low progesterone level.
A single progesterone test for symptomatic
women in early pregnancy can rule out viability.
Verhaegen J et al. Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: meta-analysis of cohort studies. BMJ 2012; 345 (Oct 20): 18 (e6077).
Equity in maternal and child health interventionsAs countries strive to reach Millennium Develop-
ment Goals (MDGs) for maternal and child health,
effective interventions have been increased. Take-
up of these interventions is often greater in more
prosperous communities, leading to inequalities in
coverage. Progress towards MDGs is monitored in
75 countries by the Countdown to 2015 collabora-
tion, these countries accounting for > 95% of all
maternal and child deaths. Now, repeated surveys
in 35 countries have been used to assess the rela-
tionship between increased intervention coverage
and equity.
Data were obtained from 35 Countdown
countries with two surveys done at an average
interval of 9.1 years. Although the rich often had
greater coverage, increased coverage for skilled
birth attendants, measles vaccination, and an
increase in a composite coverage index were
associated with improved equity. For use of in-
secticide-treated bed nets by children, countries
achieving rapid progress reached rich and poor
almost equally. National increases in coverage
were mainly due to increased coverage among
the poor.
Equity needs to be taken into account as well
as total coverage in assessing progress to MDGs.
Victoria CG et al. How changes in coverage affect equity in maternal and child health interventions in 35 Countdown to 2015 countries: an analysis of national surveys. Lancet 2012; 380: 1149–1156; Bhutta ZA, Chopra M. The Countdown for 2015: what lies ahead? Ibid: 1125–1127 (comment).
Changes in money given for maternal, newborn, and child health in Countdown countries
The global financial crisis may be affecting funding
for Millennium Development Goals 4 and 5. As part
of Countdown to 2015, recent changes in official
development assistance (ODA) to maternal, new-
born, and child health have been assessed in 74
Countdown priority countries.
Since 2003, giving to maternal, newborn,
and child health increased in all countries up to
US$6,511 million in 2009 but fell slightly for the
first time to US$6,480 million dollars in 2010. The
rate of increase in ODA for maternal and child
health has decreased since 2008. Targeting of ODA
to countries with high maternal mortality increased
between 2005 and 2010, as did targeting to child
health but to a lesser extent.
ODA may have slowed as a result of the
global financial crisis.
Hsu J et al. Countdown to 2015: changes in official development assistance to maternal, newborn, and child health in 2009–10, and assessment of progress since 2003. Lancet 2012; 380: 1157–1168; Horton R. Women’s and children’s health: no time for complacency. Ibid: 1123–1125 (comment).
in stunting. Child survival interventions – such as
insecticide-treated bed nets, improved nutrition, vi-
tamin A supplementation, appropriate treatment of
diarrhoea, improved care seeking for fever, malaria,
or pneumonia, and vaccinations – all improved.
Several programme strategies have been
important in Niger’s success: high government
priority for universal access to free primary health
care for women and children, mass campaigns for
insecticide-treated bed nets, measles vaccination
and vitamin A supplementation, and an attack on
child undernutrition.
Amouzou A et al. Reduction in child mortality in Niger: a countdown to 2015 country case study. Lancet 2012; 380: 1169–1178; Sanda S. Niger’s success in child survival. Ibid: 1127–1128 (comment).
Clinicians’ ‘gut feeling’ about serious infection in children
Serious infections in children may easily be missed
on clinical examination with potentially disastrous
results. Routine clinical assessment may be nor-
mal, but the doctor may be left with a ‘gut feeling’
that all is not well. A study in general practice has
shown the value of gut feeling.
The study included 3,369 children presenting
with an acute illness that had lasted for up to 5
days. Among children in whom other features did
not cause concern, a gut feeling that the child was
unwell increased the risk of serious infection by
a factor of 25. It had a sensitivity of 33% and a
specificity of 99%. The gut feeling was most often
based on decreased conscious level, tachypnoea,
or parental concern.
Clinicians should take their gut feelings seri-
ously.
Van den Bruel A et al. Clinicians’ gut feeling about serious infections in children: observational study. BMJ 2012; 345: (Sept 29): 14 (e6144).
Friedemann C et al. Cardiovascular disease risk in healthy children and its association with body mass index: systematic review and meta-analysis. BMJ 2012; 345: (Sept 29) 15 (e4759); Hudson L, Viner RM. Obesity in children and adolescents. Ibid: 8 (e5457) (editorial).
Physical activity interventions in children
Encouraging more physical activity in children
seems instinctively to be a worthwhile endeavour.
Current UK guidelines suggest at least 60 minutes
of moderate to vigorous exercise a day for all chil-
dren and adolescents, but few achieve it and activ-
ity levels tend to drop off in adolescence. A system-
atic review and meta-analysis has illustrated the
difficulties in encouraging exercise.
The analysis included 30 studies (6,153 chil-
dren) with physical activity measured by acceler-
ometer throughout the day at baseline and follow-
up. The pooled intervention effect was small to
negligible for total physical activity and small for
moderate or vigorous physical activity. It equated
to an extra 4 minutes of walking and running per
day.
The effects of the physical activity interven-
tions were small or negligible. Editorialists insist
that research should continue with the aim of find-
ing more effective interventions.
tervention group.
Reduced intake of sugar-sweetened drinks
was associated with reduced weight gain in
normal-weight Dutch children aged 5–12 years.
In American overweight and obese adolescents,
a 1-year programme of reduced intake of sweet-
ened drinks was associated with reduced increase
in BMI at the end of the intervention but not 1
year later. Several US organizations have called
for measures to reduce the consumption of sugar-
sweetened drinks in children and adults.
de Ruyter JC et al. A trial of sugar-free or sugar-sweetened beverages and body weight in children. NEJM 2012; 367: 1397–1406; Ebbeling CB et al. A randomised trial of sugar-sweetened beverages and adolescent body weight. Ibid: 1407–1416; Caprio S. Calories from soft drinks – do they matter? Ibid: 1462–1463 (editorial).
Classroom-based CBT for adoles-cents at risk of depression: Not effective
There is evidence that classroom-based cognitive
behavioural therapy (CBT) might prevent depres-
sion in some adolescents, but there has been no
rigorous study. Now, a study in eight schools in the
UK has shown no effect from classroom-based CBT.
The study included 5,030 school students
aged 12–16 years, among whom 1,064 (21%) were
identified as at high risk of depression. Outcome
data were available for 846 (80%) of the at-risk
group. Randomization was to classroom-based CBT,
attention control, or usual provision. At 12 months,
adjusted mean scores on the short mood and feel-
ings questionnaire were similar in the three groups.
Reported self worth and anxiety were not signifi-
cantly different between groups. There was a small
increase in negative thoughts in the CBT group.
Classroom-based CBT did not reduce symp-
toms of depression in at-risk adolescents.
Stallard P et al. Effect of classroom based cognitive behavioural therapy on symptoms of depression in high-risk adolescents: pragmatic cluster randomised controlled trial. BMJ 2012; 345 (Oct 13): 13, (e6058); Merry SN, Stasiak K. Preventing depression in adolescents. Ibid: 8 (e6720) (editorial).
Metcalf B et al. Effectiveness of interventions on physical activity of children: systematic review and meta-analysis of controlled trials with objectively measured outcomes. BMJ 2012; 345 (Sept 29): 16 (e5888); Hamer M, Fisher A. Are interventions to promote physical activity in children a waste of time? Ibid: 9 (e6320) (editorial).
High-sugar drinks and body weight in children and adolescents
High intake of sugar-sweetened drinks has been
associated with increased body mass index (BMI)
in children. Two studies reported in the New
England Journal of Medicine have shown that re-
ducing the intake of sugar-sweetened drinks may
reduce levels of obesity and overweight in children
and adolescents.
In Amsterdam, the Netherlands, an 18-month
double-blind trial included 641 normal-weight chil-
dren aged 4 years 10 months to 11 years 11 months
at eight schools. Randomization was to receive 250
mL on each school day and at weekends of either
a sugar-containing drink with 104 kcal or an arti-
and mortality. As such, it is imperative that every
effort is made to accurately classify women with
hypertension in pregnancy as having chronic hy-
pertension, non-proteinuric pregnancy-induced
hypertension or pre-eclampsia, as the aetiology
and management of the three conditions is very
different.
Measurement of Blood Pressure
Blood pressure should be measured with the wom-
an rested and seated at a 45-degree angle with the
arm at the level of the heart. It is imperative that an
appropriately sized cuff should be used. To avoid in-
correct measurement of blood pressure, if the mid-
arm circumference is greater than 33 cm, a large
cuff should be used. Korotkoff phase 1 should be
used to measure systolic blood pressure, and Korot-
koff 5 is the appropriate measurement of diastolic
blood pressure. The method used to record blood
pressure should be consistent and documented.
Pregnancy-induced Hypertension
Gestational or pregnancy-induced hypertension is a
rise in the blood pressure in the absence of protein-
uria after 20 weeks’ gestation. True non-proteinuric
pregnancy-induced hypertension does not appear to
be associated with an increase in maternal or fetal
morbidity. However, the risk of progression from
pregnancy-induced hypertension to pre-eclampsia
is approximately 20–30% and therefore vigilance
is required. This rate increases to approximately
50% when pregnancy-induced hypertension de-
velops before 32 weeks’ gestation. As a result of
this risk of progression to pre-eclampsia, weekly
urinalysis and blood pressure checks are generally
recommended in women with pregnancy-induced
hypertension.
Chronic Hypertension
Chronic hypertension is defined as hypertension
preceding pregnancy. Blood pressure falls in the
first and second trimesters. Therefore, women with
high blood pressure before the 20th week of preg-
nancy are assumed to have pre-existing or essen-
tial hypertension. As many women of reproductive
age only present for the first time when pregnant,
chronic hypertension is often revealed in the first
half of pregnancy. Approximately 90–95% of cases
of chronic hypertension are considered to be es-
sential. Secondary causes which account for ap-
proximately 5–10% are listed in Table 1. In women
presenting with hypertension in the first half of
pregnancy, it is important to look for an underlying
cause. These investigations should at least include:
• urine analysis (looking for blood, protein or
glucose)
• ureaandelectrolytes
• renaltractultrasound.
Women with underlying renal disease are at sig-
nificantly increased risk of poor pregnancy outcome
and require multidisciplinary care.
Box 1. Classification of hypertension in pregnancy
A. New-onset hypertension and/or proteinuria in pregnancy 1. Gestational hypertension (without proteinuria) 2. Gestational proteinuria (without hypertension) 3. Pre-eclampsia (hypertension with proteinuria)B. Chronic hypertension and renal disease 1. Chronic hypertension without proteinuria 2. Chronic renal disease (proteinuria with or without hyper- tension) 3. Chronic hypertension with superimposed pre-eclampsia (ie, with new-onset proteinuria in pregnancy)C. Unclassified 1. Hypertension and/or proteinuria noted when first presen- tation is after 20 weeks 2. As above, when noted for the first time during pregnancy, labour or puerperium, and there are insufficient backgro- und data to permit a diagnosis from category A or B above
Screening • Women should be screened for signs of hypertension using blood pressure checks and urinalysis monthly until 30
weeks’ gestation, fortnightly from 30 weeks’ gestation and weekly from 36 weeks’ gestation • If elevated blood pressure +/– proteinuria, refer for admission or monitoring in antenatal day unit
Maternal assessment • Repeat (at least 4-hourly) blood pressure measurement • Quantitative measurement of protein in urine (pre-eclampsia = 0.3 g protein 24-hour urine collection) • Platelet count, serum uric acid concentration, and tests of liver function (alanine and aspartate aminotransferase
levels) • Coagulation screen if altered liver function
Antihypertensive therapy • Consider admission, monitor closely and treat if blood pressure is persistently above 160/100 mm Hg
Anticonvulsant therapy • If convulsions occur, use magnesium sulphate, intravenously or intramuscularly • In cases of severe pre-eclampsia, consider prophylactic magnesium sulphate
Fetal management • Give prophylactic steroids if the duration of gestation is less than 34 weeks • Perform an ultrasound assessment of fetal weight on initial presentation and repeat fortnightly • Doppler ultrasonographic assessment of umbilical blood-flow velocity if evidence of growth restriction • Regular cardiotocography (non-stress tests) • Ultrasonography at least twice a week for liquor volume • Multidisciplinary approach regarding timing and mode of delivery
Postpartum care • Continued close monitoring of the mother by experienced carers • If on magnesium therapy, continue for at least 24 hours post partum until stable • Careful fluid balance (total 80 mL/h intake) and early use of diuretics if pulmonary oedema secondary to fluid
overload is suspected • Decrease dose of antihypertensive agents as indicated. Avoid sudden cessation immediately post partum as rebound
hypertension likely
Follow-up • Long-term follow-up to make sure that the blood pressure falls (within 6 weeks post partum), and suitable referral if it
does not • Discussion about the illness and the significance for the future • Recommend pre-conceptual counselling for future pregnancies
cated as the first-line anticonvulsant. Formal clini-
cal review should occur every 4 hours, observing
for side effects (motor paralysis, absent reflexes,
respiratory depression and cardiac arrhythmia).
The antidote is 10 mL 10% calcium gluconate given
slowly intravenously. Of the magnesium sulphate,
97% is excreted in the urine. Oliguria (< 80 mL per
24 hours) can thus lead to toxicity. Therefore, in the
presence of oliguria, magnesium sulphate should be
reduced or withheld. If magnesium is not excreted,
levels should not fall. Box 3 highlights key manage-
ment steps in the treatment of patients with severe
pre-eclampsia.
Eclampsia
Eclampsia refers to the occurrence of one or more
generalized convulsions and/or coma in the setting
of pre-eclampsia and in the absence of other neu-
rological conditions. The UK Obstetric Surveillance
System (UKOSS) report gives an estimated inci-
dence of 27.5 cases per 100,000 maternities with
a case fatality rate estimated to be 3.1%. This was
Box 4. Diagnostic criteria used for eclampsia
Any woman with convulsion(s) during pregnancy or in the first 10 days post partum, together with at least two of the follow-ing features within 24 hours of the convulsion(s):• Hypertension (a booking diastolic pressure of < 90 mm Hg, a
maximum diastolic of ≥ 90 mm Hg and a diastolic increment of ≥ 25 mm Hg)
• Proteinuria (at least + protein in a random urine sample or ≥ 0.3 g in a 24-hour collection)
• Thrombocytopenia (platelet count of less than 100 × 109/L)• Raised plasma alanine aminotransferase concentration
(≥ 42 IU/L) or an increased plasma aspartate aminotransferase concentration (≥ 42 IU/L)
Box 3. Key points in the management of the severe pre-eclamptic patient
• Insert an indwelling catheter and measure hourly urine output until stable
• Record blood pressure and pulse every 15 minutes until stable and then half hourly
• Oxygen saturation should be measured continuously and charted with the blood pressure. If saturation falls below 95%, then medical review is essential to outrule pulmonary oedema and other complications
• Strict fluid balance should be recorded with detailed input and output measurements
• Respiratory rate should be measured hourly. A reducing respi-ratory rate may indicate magnesium toxicity
• Temperature should be measured 4-hourly• When present, central venous pressure and arterial lines should
be measured continuously and charted with the blood pressure• Neurological assessment should be performed hourly using
either the AVPU (alert/verbal/painful/ unresponsive) or Glasgow Coma scales
• Fetal well-being should be monitored using a cardiotocography• Blood tests should be repeated at least every 12 hours whilst
on the magnesium sulphate protocol. In the event of compli-cations such as haemorrhage or abnormal or deteriorating haematological and/or biochemical parameters, more frequent blood tests should be taken, eg, every 4–8 hours Evidence from the HYPITAT
with significant maternal morbidity, in particular
cerebrovascular events (2.3%). The benefit of
magnesium sulphate in the prevention of eclamp-
sia has been well demonstrated, and magnesium
sulphate has been shown to halve the risk of ec-
lampsia among women with pre-eclampsia. Box
4 indicates the diagnostic criteria for eclampsia.
Cerebral haemorrhage has been reported to be the
most common cause of death in patients with ec-
lampsia, and stroke is known to be the most com-
mon cause of death (45%) in women with HELLP
syndrome.
POSTPARTUM MANAGEMENT OF HYPERTENSION IN PREGNANCY
Blood pressure rises progressively over the first
five postnatal days, peaking on days 3–6 after
delivery. Research has focused on the antenatal
complications, for both mother and baby, and the
risks and benefits of administering antihyperten-
sive therapy prior to delivery. There is very little
information on how best to manage postpartum
hypertension, regardless of type or severity, to
optimize maternal safety and minimize hospital
stay. Women with postpartum hypertension may
also experience longer hospital stays and, pos-
sibly, heightened anxiety about their recovery.
General NICE recommendations for postnatal care
of women with hypertension in pregnancy include
stopping methyldopa within 2 days of birth and
asking the woman about severe headache and
epigastric pain every time blood pressure is meas-
ured. In cases of mild or moderate pre-eclampsia
platelet count, transaminases and serum creati-
nine should be measured 48–72 hours after birth
or step-down. These do not need to be repeated
if results are normal. In most cases of gestational
hypertension and pre-eclampsia, there is a rapid and
complete resolution within 6 weeks of delivery of
the fetus. Patients requiring antihypertensives can
be weaned off slowly, and medications should not be
stopped suddenly as there may often be a rebound
hypertension.
Postnatal Follow-up
All women who have had pre-eclampsia should be
offered a medical review at the postnatal review
(6–8 weeks) after the birth. Women who have had
pre-eclampsia should be educated regarding their
increased risk of development of cardiovascular
disease, renal disease and cardiovascular risk fac-
Practice points
• Automated blood pressure devices may underestimate the blood pressure in pregnancy and therefore caution should be exercised in their use
• An appropriately sized blood pressure cuff should be used. If the mid-arm circumference is > 33 cm, a large cuff should be used
• Labetalol remains the antihypertensive of choice. Methyldopa and nifedipine may be used as second- or third-line agents
• Systolic blood pressures over 150 mm Hg should be treated• Anaesthetists should anticipate an additional rise in blood
pressure at intubation in women with severe pre-eclampsia who are undergoing caesarean section under general anaes-thesia and take measures to avoid a speed that compromises maternal well-being, even when there are concerns about fetal well-being
• If the platelet count is < 20 × 109/L, a platelet transfusion is recommended prior to caesarean section or vaginal delivery
• Following delivery, the patient should be fluid restricted to ≤ 80 mL total fluid per hour until a natural dieresis occurs
• Ergometrine/oxytocin should not be given for the active management of the third stage if the mother is hypertensive or her blood pressure has not been checked
• Postpartum, women should be counselled appropriately regard-ing their risk of recurrence of pre-eclampsia as well as their increased risk of developing cardiovascular and renal disease
severe pre-eclampsia have an increased risk of re-
currence in their next pregnancy (about 1 in 6 [16%]
pregnancies) but the disorder is generally less
severe and manifests 2–3 weeks later than in the
first pregnancy. This risk increases to about 1 in 4
(25%) pregnancies if the pre-eclampsia was com-
plicated by severe pre-eclampsia, HELLP syndrome
or eclampsia and led to birth before 34 weeks. The
risk of recurrence is about 1 in 2 (55%) pregnancies
if the pre-eclampsia led to birth before 28 weeks’
gestation. Women with essential hypertension
should be encouraged to present for pre-conceptual
counselling as antihypertensive medications such
as ACE inhibitors are contraindicated in pregnancy
and should be changed pre-conceptually. The use
of low-dose aspirin in women with chronic hyper-
tension moderately reduces the risk of developing
superimposed pre-eclampsia, intrauterine growth
retardation and perinatal death, and should be of-
fered to all women at an early booking visit. The
findings from the CLASP trial do not support routine
treatment with aspirin of all women at risk of pre-
eclampsia.
CONCLUSION
Hypertensive disorders are one of the commonest
complications of pregnancy and may be associated
with significant maternal and fetal morbidity and
mortality. Although the aetiology of these disor-
ders is becoming increasingly better understood,
interventions to prevent hypertensive disorders
of pregnancy have had poor results. The mainstay
of treatment remains the use of antihypertensive
medications, the use of magnesium sulphate in the
prevention of eclampsia, and multidisciplinary input
to ensure a timely delivery.
FURTHER READING
Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihy-pertensive drug therapy for mild to moderate hyperten-sion during pregnancy. Cochrane Database Syst Rev 2007(1):CD002252.
Centre for Maternal and Child Enquiries (CMACE). Saving moth-ers’ lives: reviewing maternal deaths to make motherhood safer: 2006–08. The eighth report on confidential enqui-ries into maternal deaths in the United Kingdom. BJOG 2011;118(suppl 1):1–203.
Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988;158:892–898.
Hypertension in pregnancy. The management of hypertensive disorders during pregnancy. National Institute for Health and Clinical Excellence, www.nice.org.uk/guidance/CG107; August 2010.
Knight M, Kurinczuk J, Spark P, Brocklehurst P. United Kingdom Obstetric Surveillance System (UKOSS) annual report. Oxford: National Perinatal Epidemiology Unit; 2007.
Knight M. Eclampsia in the United Kingdom 2005. BJOG 2007;114:1072–1078.
Koopmans CM, Bijlenga D, Groen H, et al. HYPITAT study group. Induction of labour versus expectant monitoring for gesta-tional hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet 2009;374:979–988.
Milne F, Redman C, Walker J, et al. The pre-eclampsia community guideline (PRECOG): how to screen for and detect onset of pre-eclampsia in the community. BMJ 2005;330:576–580.
Smith GC, Pell JP, Walsh D. Pregnancy complications and mater-nal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births. Lancet 2001;357:2002–2006.
Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010;376:631–644.
von Dadelszen P, Payne B, Li J, et al. PIERS Study Group. Predic-tion of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet 2011;377:219–227.
About the AuthorsFergus P McCarthy is Specialist Registrar in obstetrics and gynaecology and Post Doctoral Research Fellow at The Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland. Louise C Kenny is Professor of Obstetrics and Consultant Obstetrician and Gynaecologist, The Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland.
Alloo J, Gerstle T, Shilyansky J, Ein SH. Appendicitis in children less than 3 years of age: a 28-year review. Pediatr Surg Int 2004;19:777–779.
Bailey B, Bergeron S, Gravel J, Bussières JF, Bensoussan A. Effi-cacy and impact of intravenous morphine before surgical consultation in children with right lower quadrant pain suggestive of appendicitis: a randomized controlled trial. Ann Emerg Med 2007;50:371–378.
Becker T, Kharbanda A, Bachur R. Atypical clinical features of pediatric appendicitis. Acad Emerg Med 2007;14:124–129.
Bhatt M, Joseph L, Ducharme FM, Dougherty G, McGillivray D. Prospective validation of the pediatric appendicitis score in a Canadian pediatric emergency department. Acad Emerg Med 2009;16:591–596.
Choong CK, Beasley SW. Intra-abdominal manifestations of Henoch–Schönlein purpura. J Paediatr Child Health 1998;34:405–409.
Doria AS, Moineddin R, Kellenberger CJ, et al. US or CT for diagnosis of appendicitis in children in adults? A meta-analysis. Radiology 2006;241:83–94.
Goldman RD, Carter S, Stephens D, Antoon R, Mounstephen W, Langer JC. Prospective validation of the pediatric appen-dicitis score. J Pediatr 2008;153:278–282.
Green R, Bulloch B, Kabani A, Hancock BJ, Tenenbein M. Early analgesia for children with acute abdominal pain. Pediat-rics 2005;116:978–983.
Laje P, Martínez-Ferro M. Acute abdomen. In: Sinha C, Davenport M, eds. Handbook of pediatric surgery. London: Springer; 2010:173–176.
Samuel M. Pediatric appendicitis score. J Pediatr Surg 2002;37:877–881.
Shew B. Surgical concerns in malrotation and midgut volvulus. Pediatr Radiol 2009;39(suppl 2):S162– S171.
Shlamovitz GZ, Mower WR, Bergman J, et al. Lack of evidence to support routine digital rectal examination in pediatric trauma patients. Pediatr Emerg Care 2007;23:537–543.
Waseem M, Kotlus Rosenberg H. Intussusception. Pediatr Emerg Care 2008;24:793–800.
Williams H. Green for danger! Intestinal malrotation and volvu-lus. Arch Dis Child Educ Pract Ed 2007;92:ep87–91.
been published, but in the end, if endometrial hy-
perplasia is suspected, then the endometrium will
need to be assessed and most will require at least
transvaginal pelvic ultrasound (TVUS).
Risk factors for endometrial hyperplasia or
cancer include obesity, age over 40 years, polycys-
tic ovary syndrome, exposure to unopposed oestro-
gen therapy, tamoxifen usage, and postmenopausal
bleeding. Many will present with AUB. It is not the
intent of this review of perimenopausal menstrual
symptoms to describe the management of endo-
metrial hyperplasia; although it needs to be stated
that any degree of atypia will usually necessitate
hysterectomy because of the risk of small occult
carcinoma being already present as well as the sig-
nificant risk of progression to carcinoma.
INVESTIGATIONS
The guidelines of the American College of Obstetri-
cians and Gynecologists mandate that all women
over 35 years with AUB should have an endometrial
assessment (ACOG Committee on Practice Bulle-
tins 2001). The tests available will vary according
to location but include TVUS, endometrial biopsy
(EB), sonohysterogram (SHG; or saline infusion so-
nogram), dilation and curettage (D&C), and hyster-
oscopy.
Historically, D&C was the mainstay of endo-
metrial assessment. However, its main drawbacks
include the need for a general anaesthetic, missed
pathology, or incomplete removal of an intra-cavity
lesion, free floating tissue left in situ, and a high
false-negative rate. Complications included uterine
perforation and intrauterine adhesions.
EB COMBINED WITH TVUS
Office EB using the Pipelle device is a cost-effec-
tive tool for investigating AUB especially when
combined with TVUS. Endometrial hyperplasia and
carcinoma are unlikely if the endometrial thickness
(ET) is 4 mm or less. This is very useful for assess-
ing postmenopausal bleeding (later), but unfortu-
nately many perimenopausal women will have thick
ET because of unopposed oestrogen surges and so
some form of tissue sampling is very helpful in this
group (the National Institute for Clinical Excellence
recommends EB in all cases of AUB, age > 40). The
Pipelle device can provide a histological diagnosis
of most endometrial pathologies with some limita-
tions (Table 1). Typically, the Pipelle system is very
good at detecting pathologies that involve most of
the endometrial cavity but can miss small focal le-
sions, including cancers. In one study, Pipelle sam-
pling was done prior to hysterectomy for known
endometrial cancer. Over 95% of the sample were
Table 1. Limitations of endometrial biopsy
Factors that might make it difficult to perform an endometrial biopsy:• Cervical stenosis (cervical surgery, multiple caesarean sections)• Pain• Sharply anteverted or retroverted uterus
Has the cavity been adequately sampled? Considerations:• Uterine shape and size (eg, bicornuate uterus)• Location of a lesion (eg, it is difficult to sample a cornual
lesion)• Size of lesion• Is the lesion affecting most of the endometrium or localized?
other times long and variable flow. Thus, treatment
goals are usually menstrual regulation, reduction of
menstrual loss, and the prevention of endometrial
hyperplasia. The next section will focus on the LG-
IUS, OCPs, sequential HT, and endometrial ablation.
LEVONORGESTREL-CONTAINING INTRAUTERINE SYSTEM
The LG-IUS is an excellent option for menstrual
control for many perimenopausal women. Irregular
bleeding is common immediately after insertion, but
this can be minimized if the ET is thin at insertion.
This can be achieved by either inserting the device
just after menstruation or by pre-treatment with a
progestin or contraceptive pill. In the long term,
the LG-IUS reduces menstrual blood loss by over
90%. It works best in those with a normal uterus,
although it can control a fibroid uterus, especially if
there are no sub-mucus lesions, and if the uterus is
not too large. There may be a higher expulsion rate
if fibroids are present.
If menopausal symptoms such as hot flushes are
present, then concomitant oestrogen can be given
as the LG-IUS will prevent endometrial hyperplasia.
Systematic reviews have shown that the LG-IUS and
endometrial ablation gave similar results for heavy
menstrual loss if sub-mucus fibroids are not present.
CONTRACEPTIVE PILLS
If there are no contraindications (Table 2), then a
low-dose OCP can control both the irregular cycle
and the symptoms of the perimenopause. Long-
cycle regimens can be used to ‘skip’ periods. There
are scant data on the use of OCP in women over 50
years, although OCPs containing oestradiol, rather
than ethinyl-oestradiol, are now available. Theo-
retically, these should be safer for perimenopausal
women, although definitive data are not yet avail-
able.
PROGESTINS AND SEQUENTIAL HT
Progestins have anti-oestrogenic, anti-proliferative
and atrophying effects on the endometrium. Their
impact depends upon the type, dose and regimen
used. These can be given alone or in combination
with oestrogens as in the OCP or HT. Continuous
progestins, in adequate dosage, can completely
suppress menstruation (eg, depot injection of me-
droxyprogesterone acetate), but most commonly
progestins are given cyclically. Ten days of luteal
Table 2. Contraindications to the contraceptive pill
History of venous or arterial thrombosis or other cardiovascular events
Uncontrolled hypertensionAdvanced diabetes or liver diseaseHeadaches with neurological manifestationsSmokers older than 35 years of ageWomen with known or suspected breast, endometrial, vaginal or cervical cancer
Undiagnosed abnormal vaginal bleeding
Caution and additional counselling may be required:Family history of breast cancerPersonal history of atypical breast lesionMigraine, diabetes, hyperlipidaemia (especially hypertriglyceridae-mia)
Depression (some progestins can aggravate depression)Gallbladder, liver, heart or kidney disease, hypertension
an examination, all will need some type of uterine
assessment. For most, this will be an EB backed up
with a TVUS. SHG is a cost-effective method for as-
sessing the endometrium. If a focal lesion is found on
imaging, then hysteroscopy and biopsy will be indi-
cated. Having excluded endometrial hyperplasia and
uterine carcinoma, polyps and sub-mucus fibroids in
particular, medical options will usually be the first-
line treatment. Of these, the most effective is the LG-
IUS, although some women will prefer to try an oral
medication first such as tranexamic acid, a low-dose
OCP, or cyclic progestins. HT has not been adequately
evaluated as a treatment for AUB.
Surgery is usually a second-line option; howev-
er, if sub-mucus fibroids or polyps are present, then
these can be resected hysteroscopically. Endometrial
ablation and the LG-IUS have been shown to give
similar results for most patients with heavy men-
strual bleeding.
FURTHER READING
Bradley LD. Diagnosis of abnormal uterine bleeding with biopsy
or hysteroscopy. Menopause: J North Am Menopause Soc
2011;18:425–433.
de Kroon CD, de Bock GH, Dieben SWM, Jansen FW. Saline
contrast hysterosonography in abnormal uterine bleeding:
a systematic review and meta-analysis. Br J Obstet
Gynaecol 2003;110:938–947.Farquahar C, Ekeroma A, Furness S, Arroll B. A systematic
review of transvaginal ultrasonography, sonohysterogra-phy and hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women. Acta Obstet Gynecol Scand 2003;82:493–504.
Hammond R, Johnson J. Endometrial hyperplasia. Curr Obstet Gynaecol 2004; 14: 991–1003.
Kaunitz AM, Meredith S, Pirjo I, Kubba A, Sanchez-Ramos L. Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis. Obstet Gynecol 2009;113:1104–1116.
Munro MG, Critchley HOD, Fraser IS. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil Steril 2011;95:2204–2208.
Pinkerton JV. Pharmacological therapy for abnormal uterine bleeding. Menopause: J North Am Menopause Soc 2011;18:453–461.
RCOG. Standards in gynaecology – report of a working party. RCOG, June 2008.
Soules MR, Sherman S, Parott E, et al. Executive summary: stages of reproductive aging workshop (STRAW). Climacteric 2001;4:267–272.
van Dongen H, de Kroon CD, Jacobi CE, Trimbos JB, Jansen FW. Diagnostic hysteroscopy in abnormal uterine bleed-ing: a systematic review and meta-analysis. Br J Obstet Gynaecol 2007;114:664–675.
About the AuthorsJohn Eden is Associate Professor of Reproductive Endocrinol-
ogy at the University of New South Wales; Director at the
Barbara Gross Research Unit, Royal Hospital for Women;
Director of Women’s Health and Research Institute of Austra-
lia; Medical Co-Director of Gynaecology, Royal Hospital for
Women, Randwick, New South Wales, Australia. Sheila
O’Neill is Clinical Associate Professor at the Graduate School
of Medicine, University of Wollongong, Wollongong, New
South Wales, Australia and Visiting Medical Officer at the
Menopause Clinic, Royal Hospital for Women, Randwick, New
South Wales, Australia.
Practice points
• Non-steroidal anti-inflammatory drugs, tranexamic acid, oral contraceptive pills and cyclic progestins given for at least 21 days are effective oral medical options for heavy menstrual bleeding
• The most effective medical option for abnormal uterine bleeding is the levonorgestrel-releasing intrauterine systems
• For most patients, endometrial ablation and the levonorg-estrel-releasing intrauterine systems give similar results
• Hormone therapy is not an effective treatment for abnormal uterine bleeding
• Infants with signs of intrauterine growth restriction
• Reduced fetal heart rate variability from the onset of labour
• Microcephaly at birth (head circumference less than the third centile)
• Major antenatal placental abruption
• Extensive chorioamnionitis
• Congenital coagulation disorders in the child
• Presence of other major antenatal risk factors for cerebral palsy – eg,
preterm birth < 34 weeks’ gestation, multiple pregnancy, or autoim-
mune diseases
• Presence of major potential risk factors for cerebral palsy – eg, post-
natal encephalitis, prolonged hypotension, or hypoxia due to severe
respiratory disease
• A sibling with cerebral palsy, especially of the same typeaAdapted by permission from BMJ Publishing Group Limited. (BMJ; MacLennan A; 319: 1054–1059; copyright 1999)23
1. Bax M, Flodmark O, Tyderman C. Definition and classification of cerebral palsy: from syndrome toward disease. Dev Med Child Neurol Suppl 2007;109:39–41.
2. Cans C, De-la-Cruz J, Mermet MA. Epidemi-ology of cerebral palsy. Paediatr Child Health 2008;18:393–398.
3. Johnson SL, Blair E, Stanley FJ. Obstetric mal-practice litigation and cerebral palsy in term in-fants. J Forensic Leg Med 2011;18:97–100.
4. Kruse M, Michelsen SI, Flachs EM, Bron-num-Hansen H, Madsen M, Uldall P. Lifetime costs of cerebral palsy. Dev Med Child Neurol 2009;51:622–628.
5. MacLennan AH, Spencer M. Projections of Australian obstetricians ceasing practice and the reasons. Med J Aust 2002;176:425–428.
6. Wood E, Rosenbaum P. The gross motor func-tion classification system for cerebral palsy: a study of reliability and stability over time. Dev Med Child Neurol 2000;42:292–296.
7. American College of Obstetricians and Gy-necologists. Inappropriate use of the terms fetal distress and birth asphyxia. ACOG Committee Opinion No. 326. Obstet Gynecol 2005;106:1469–1470.
8. Nelson KB, Grether JK. Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight. Am J Obstet Gynecol 1998;179:507–513.
9. McCarty SM, James PS, Berninger VW, Gans BM. Assessment of intelligence functioning across the life span in severe cerebral palsy. Dev Med Child Neurol 1986;28:369–372.
10. Garne E, Dolk H, Krageloh-Mann I, Holst Ravn S, Cans C; SCPE Collaborative Group. Cerebral palsy and congenital malformations. Eur J Pae-diatr Neurol 2008;12:82–88.
12. Beaino G, Khoshnood B, Kaminski M, et al. Pre-dictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study. Dev Med Child Neurol 2010;52:e119–e125.
13. Ancel PY, Livinec F, Larroque B, et al; EPIPAGE Study Group. Cerebral palsy among very preterm children in relation to gestational age and neona-tal ultrasound abnormalities: the EPIPAGE cohort study. Pediatrics 2006;117:828–835.
14. Platt MJ, Cans C, Johnson A, Topp GSM, Torriolo MG, Krageloh-Mann. Trends in cerebral palsy among infants of very low birthweight (<1500 g) or born prematurely (<32 weeks) in 16 European centres: a database study. Lancet 2007;369:43–50.
15. O’Callaghan ME, MacLennan AH, Gibson CS; Australian Collaborative Cerebral Palsy Research Group. Obstet Gynecol 2011;118:576–582.
16. Topp M, Langhoff-Roos J, Uldall P, Kristensen J. Intrauterine growth and gestational age in pre-term infants with cerebral palsy. Early Hum Dev 1996;44:27–36.
18. Drougia A, Giapors V, Krallis N, Theocharis P, Nikaki A, Tzoufi M, Andronikou S. Incidence and risk factors for cerebral palsy in infants with perinatal problems: a 15-year review. Early Hum Dev 2007;83:541–547.
20. Thomas W, Speer CP. Chorioamnionitis: impor-tant risk factor or innocent bystander for neonatal outcome? Neonatology 2011;99:177–187.
21. Gilbert WM, Jacoby BN, Xing G, Danielsen B, Smith LH. Adverse obstetric events are associ-ated with significant risk of cerebral palsy. Am J Obstet Gynecol 2010;203:328.e1–e5.
22. Martinez-Biarge M, Madero R, Gonzalez A, Quero J, Garcia-Alix A. Perinatal morbidity and risk of hypoxic-ischemic encephalopathy associ-ated with intrapartum sentinel events. Am J Ob-stet Gynecol 2012;206:148.e1–e7.
23. MacLennan A. A template for defining a caus-al relation between acute intrapartum events and cerebral palsy: international consensus state-ment. BMJ 1999;319:1054–1059.
24. Hankins GDV, Speer M. Defining the patho-genesis and pathophysiology of neonatal en-cephalopathy and cerebral palsy. Obstet Gynecol 2003;102:628–636.
25. Phelan JP, Korst LM, Martin GI, Applica-tion of criteria developed by the Task Force on Neonatal Encephalopathy and Cerebral Palsy to acutely asphyxiated neonates. Obstet Gynecol 2011;118:824–830.
26. Graham EM, Ruis KA, Hartman AL, Northing-ton FJ, Fox HE. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008;199:587–595.
27. Rouse DJ, Hirtz DG, Thom E, et al; Eunice Ken-nedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Eng J Med 2008;359:895–905.
28. Constantine MM, Weiner SJ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mor-tality in preterm infants: a meta-analysis. Obstet Gynecol 2009;114:354–364.
29. Nelson KB, Chang T. Is cerebral palsy prevent-able? Curr Opin Neurol 2008;21:129–135.
30. Steer PJ. Has electronic fetal heart rate moni-toring made a difference. Semin Fetal Neonatal Med 2008;13:2–7.
31. Shankaran S, Pappas A, McDonald SA, et al; Eunice Kennedy Shriver NICHD Neonatal Research Network. Childhood outcomes after hypothermia for neonatal encephalopathy. N Eng J Med 2012;366:2085–2092.
32. Azzopardi D, Strohm B, Linsell L, et al; UK TOBY Cooling Register. Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK – analysis of national data. PloS One 2012;7:e38504.
33. Greenwood C, Newman S, Impey L, Johnson A. Cerebral palsy and clinical negligence litiga-tion: a cohort study. BJOG 2003;110:6–11.
34. Muraskas JK, Morrison JC. A proposed evi-dence-based neonatal work-up to confirm or re-fute allegations of intrapartum asphyxia. Obstet Gynecol 2010;116:261–268.
and were often not scheduled at optimal
times.34 Obviously, full documentation of
various parameters would be extremely
useful to refute or support the allegation.
For instance, the presence of thrombocy-
topenia, elevated haemoglobin, haemato-
crit, and elevated lymphocyte counts in the
newborn would point to chronic hypoxia in
utero that antedates labour, while serial
nucleated red cell counts in the first few
days of life showing delayed clearance
would not support a diagnosis of acute in-
trapartum hypoxia. Cerebral oedema dem-
onstrated by ultrasound on the first day of
life would point against acute intrapartum
asphyxia as oedema usually only appears
24 hours after the asphyxia event. Simi-
larly, neuroimaging at optimal times may
be helpful in approximating a window of
time when the injury might have occurred
(as there is usually a delay of 2–3 weeks)
and in demonstrating whether the pat-
tern of lesions would be more suggestive
of prolonged partial asphyxia in utero or
acute total asphyxia. Moreover, in addi-
tion to performing appropriate tests such
as cord arterial pH, electroencephalogram
or magnetic resonance brain imaging to
establish or refute the essential criteria
for the diagnosis of acute intrapartum hy-
poxia, every effort should also be made to
look for and confirm possible alternative
diagnoses for CP.
About the Author
Dr To is consultant obstetrician and maternal fetal medi-cine subspecialist in the Department of Obstetrics and Gynaecology, United Christian Hospital, Hong Kong.
This continuing medical education service is brought to you by the Medical Progress Institute, an institute dedicated to CME learning. Read the article ‘Cerebral Palsy and Its Causal Relationship With Birth Asphyxia’ and answer the following questions. This JPOG article has been accredited for CME by the Hong Kong College of Obstetricians and Gynaecologists.
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CME Article
Cerebral Palsy and Its Causal Relationship With Birth Asphyxia
Answer True or False to the questions below.
1. The incidence of cerebral palsy (CP) is around 2 per 1,000 live births.
2. The development of CP in a neonate born before 34 weeks’ gestation is more likely the result of an acute intrapartum event rather than the complications of prematurity.
3. A small-for-gestational-age neonate born at 32 weeks is more likely to suffer from CP than an appropriate-for-gestation neonate born at the same gestation.
4. There is a trend towards a decreasing incidence of cerebral palsy in preterm neonates in the recent decade or so.
5. In infants suffering from CP due to acute intrapartum asphyxia, a sentinel event is present in less than 20% of the cases.
6. An infant with hemiplegic spastic CP is likely to have suffered from antenatal ischaemic stroke rather than from an acute intrapartum hypoxic event.
7. Electronic fetal heart monitoring during labour has been shown to decrease the incidence of CP.
8. There is no evidence that antenatal exposure of the fetus to magnesium sulphate would be neuroprotective against CP.
9. In over 90% of CP cases that satisfy all the essential criteria for an acute intrapartum hypoxic event, the patients will sue for medical negligence.
10. The finding of severe histological chorioamnionitis from placental examination in a neonate with a normal cord blood pH at delivery is insufficient to refute the diagnosis of acute intrapartum hypoxia.
