Documente Academic
Documente Profesional
Documente Cultură
ISSN 2411-0183
JUL/AUG 2017
VOL. 43 NO. 4
JOURNAL OF PAEDIATRICS,
OBSTETRICS & GYNAECOLOGY
GYNAECOLOGY
Colposcopy and
Cervical Intraepithelial
Neoplasia
OBSTETRICS
Analgesia in Labour
and Delivery
CME ARTICLE
Bleeding in Early
Pregnancy
MIMS JPOG JUL/AUG 2017 i
Editorial Board
CONFERENCE
Board Director, Paediatrics
American Society of Clinical Oncology
Professor Pik-To Cheung
Associate Professor, Department of Paediatrics and Adolescent Medicine (ASCO) 2017 Annual Meeting, June 2-6,
The University of Hong Kong, Hong Kong
Chicago, Illinois, US
Board Director, Obstetrics and Gynaecology
Professor Pak-Chung Ho
Director, Centre of Reproductive Medicine
The University of Hong Kong - Shenzhen Hospital, China
133
Pregnancy still possible after breast cancer
Chronic disease incidence declines over time in
Professor Biran Affandi Professor Seng-Hock Quak childhood cancer survivors
University of Indonesia, Indonesia National University of Singapore,
Singapore
Professor Hextan
Adjunct Associate Professor
JOURNAL WATCH
Yuen-Sheung Ngan
The University of Hong Kong, Hong Kong Tan Ah Moy
KK Womens and Childrens Hospital,
Professor Kenneth Kwek Singapore
KK Womens and Childrens Hospital,
Singapore Dr. Catherine Lynn Silao
University of the Philippines Manila,
Professor Kok Hian Tan Philippines 134
KK Womens and Childrens Hospital,
Singapore
Dwiana Ocviyanti, MD, PhD Autism spectrum disorder:
University of Indonesia, Indonesia
Professor Dato Updated guidelines for GPs
Dr. Karen Kar-Loen Chan
Dr. Ravindran Jegasothy The University of Hong Kong, Triponderal mass index superior to
Dean Faculty of Medicine, Hong Kong
MAHSA University, Malaysia BMI for evaluating body fat during
Dr. Kwok-Yin Leung
Associate Professor Daisy Chan The University of Hong Kong, adolescence
Singapore General Hospital, Singapore Hong Kong
Isolated maternal hypothyroxaemia
Associate Professor Raymond Dr. Mary Anne Chiong
University of the Philippines Manila,
in third trimester linked to pre-eclampsia
Hang Wun Li
The University of Hong Kong, Hong Kong Philippines
136
High prevalence of lower genital
tract infection among women in
Beijing, China
Traumatic life events affect cellular
ageing in women of reproductive
age
MIMS JPOG JUL/AUG 2017 iii
REVIEW ARTICLE
GYNAECOLOGY
CEO Yasunobu Sakai
Managing Editor Elvira Manzano
Medical Editor Elaine Soliven
Designer Sam Shum
137
Production Edwin Yu, Ho Wai Hung, Steven Cheung, Agnes Chieng
Circulation Christine Chok Colposcopy and Cervical Intraepithelial
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Advertising Coordinator Pannica Goh
Neoplasia
Cervical cancer is caused by certain
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Bleeding in Early Pregnancy 2 SKP
The Cover:
Acute Kidney Injury in Paediatric Critical Care
2017 MIMS Pte Ltd
American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, June 2-6, Chicago, Illinois, US
Elaine Soliven reports
Pregnancy still possible tients with ER-negative breast cancer, toma (HR, 0.77), acute lymphoblastic
after breast cancer through either immune system mech- leukaemia (HR, 0.86), and nonHodgkin
anisms or hormonal mechanisms, but lymphoma (HR, 0.79).
Women with a history of estrogen recep- we need more research into this, said The decline in severe health con-
tor (ER)-positive breast cancer (BC) who Lambertini. ditions in the 1990s was predominantly
subsequently got pregnant appears to due to decreased occurrence of endo-
Dr Matteo Lambertini, et al, American Society of Clinical
have similar disease-free survival (DFS) Oncology (ASCO) 2017 Annual Meeting, June 2-6, Chicago, crine conditions (4.0 percent vs 1.6 per-
Illinois, US [abstract LBA10066].
as those who did not get pregnant, ac- cent, HR, 0.66, 95 percent confidence
cording to a study. interval [CI], 0.590.73) and subsequent
Our findings confirm that preg- malignant neoplasms (2.4 percent vs
nancy after breast cancer should not Chronic disease incidence 1.6 percent, HR, 0.85, 95 percent CI,
be discouraged, even for women with declines over time 0.760.96) compared with those diag-
ER-positive cancer, said lead study au- in childhood nosed in the 1970s.
thor Dr Matteo Lambertini from the In- cancer survivors In addition, there was also a sig-
stitut Jules Bordet in Brussels, Belgium. nificant reduction in the incidence of
The multicentre, retrospective co- The incidence of chronic disease gastrointestinal and neurological con-
hort study consisted of 1,207 women, among childhood cancer survivors has ditions (HR, 0.80, 95 percent CI, 0.66
57 percent of whom had a history of decreased over the past decades and it 0.97 and HR, 0.77, 95 percent CI, 0.65
ER-positive BC. Of these, 333 women is likely due to advances in treatment, 0.91, respectively). However, there was
became pregnant after BC and were according to a study in the US. no reduction in cardiac or pulmonary
matched with 874 nonpregnant women. Our analysis marks the first com- conditions.
[ASCO 2017, abstract LBA10066] prehensive assessment of changes in The cardiac findings were con-
Researchers found no significant the rates of chronic health complications sidered surprising, noted Gibson,
difference in DFS between pregnant over time in a large group of cancer sur- given that deaths from cardiovascular
and nonpregnant women who had vivors, said lead author Dr Todd Gibson disease declined among survivors in
ER-positive BC (hazard ratio [HR], from St. Jude Childrens Research Hos- recent decades. This is a reminder
0.94, 95 percent confidence interval pital in Memphis, Tennessee, US. that survivors continue to have an in-
[CI], 0.701.26; p=0.68) or ER-neg- Researchers gathered data from creased risk for serious health prob-
ative BC (HR, 0.75, 95 percent CI, the CCSS* cohort and analysed lems compared to the general popula-
0.531.06; p=0.10) at 12.5 years from 23,601 childhood cancer survivors tion and need to be followed closely,
conception (in the matched pregnant (median age 28 years). The incidence he said.
women). of severe (grade 3), life-threatening or Overall, the findings suggest that
There was also no difference in disabling (grade 4), or fatal (grade 5) survivors who were diagnosed and
overall survival (OS) between pregnant health conditions reduced within 15 treated in more modern treatment eras
and nonpregnant women who had years of childhood cancer diagno- are doing better, said Gibson. Not only
ER-positive BC (HR, 0.84, 95 percent CI, sis at 12.7 percent in the 1970s, 10.1 are more children being cured, but they
0.601.18; p=0.32). percent in the 1980s, and 8.8 percent also have lower risk for developing se-
However, among those with in the 1990s. [ASCO 2017, abstract rious health problems due to cancer
ER-negative BC, pregnant women had LBA10500] treatment later in life.
a significantly increased OS than non- After adjusting for age and gender, *CCSS: Childhood Cancer Survivor Study
pregnant women (HR, 0.57, 95 percent a significant risk reduction was noted
Dr Todd Gibson, et al, American Society of Clinical Oncolo-
CI, 0.360.90; p=0.01). in childhood cancer survivors who had gy (ASCO) 2017 Annual Meeting, June 2-6, Chicago, Illinois,
US [abstract LBA10500].
Its possible that pregnancy Wilms tumour (hazard ratio [HR], 0.57),
could be a protective factor for pa- Hodgkin lymphoma (HR, 0.75), astrocy-
134 MIMS JPOG JUL/AUG
MIMSJPOG JUL/AUG 2017
2017 JOURNAL WATCH PEER REVIEWED
Manual of Mental Disorders (DSM-5) of body fat levels, body proportions, and
P the American Psychiatric Association. the scaling relationships among body
Although it is a lifelong condition, ASD mass, height, and percent body fat. Sta-
Paediatrics emerges in early infancy and can be relia- bility with age, accuracy in estimating
bly diagnosed as early as age 2. Possible percent body fat, and accuracy in clas-
red flags include signs of communica- sifying adolescents as overweight vs nor-
Autism spectrum disorder:
tion, social, and behavioural disturbanc- mal weight were used to determine the
Updated guidelines
es at 1224 months of age. In particular, superior index.
for GPs
children who do not babble, coo, or ges- The standard weight-to-height re-
ture by pointing, waving, or grasping by gression was not valid for finding the op-
age of 12 months, who do not say single timal body fat index since percent body
words by 16 months, and who do not say fat varied with both age and height during
any two-word phrases without prompting adolescence. Unlike BMI which increases
by age of 24 months should be referred dramatically with age, necessitating the
for specialist assessment. Any child with development of age-specific percentiles,
a loss of language or social skills at any TMI was stable between ages 8 and 17.
age should also be referred, since dete- TMI was also better at estimating percent
rioration in behaviour might indicate an body fat than BMI (R2=0.64 vs 0.38 for
acute illness in a person with ASD such boys and R2=0.72 vs 0.66 for girls), and
as an ear infection. Comorbid anxiety, at- misclassified adolescents as overweight
tention deficit hyperactivity disorder, and rather than normal weight less often than
depression are also common. However, BMI z-scores (8.4 percent vs 19.4 percent
it is important to remember that children misclassified, respectively; p<0.001). In
with ASD can present in a number of dif- addition, the index performed as well as
ferent ways depending on their current updated BMI percentiles derived from the
symptoms, cognitive ability, and educa- same data set (TMI 8.4 percent vs BMI
tional and life experiences. 8.0 percent; p=0.62), but was much sim-
pler to use since TMI does not require
Brereton AV and Tonge B., Autism spectrum disorder: An up-
date for GPs. Medicine Today 2017;18:42-48. percentile calculations.
detected during the third trimester of The researchers found that women ical failure was defined as >1,000 copies
pregnancy is strongly correlated with who were older and those who had a HIV-1 RNA/mL.
pre-eclampsia in the first large-scale in- higher pre-pregnancy body mass index At 1-year postpartum, three wom-
vestigation to undertake long-term moni- were more likely to experience hypothy- en were found to have virological fail-
toring of free thyroxin (FT4) levels in Chi- roidism. Although pregnancy-induced ure, and seven were affected by the
nese mothers with hypothyroxaemia. hypertension was not significantly corre- 18-month time point. No vertical trans-
lated with FT4, GDM, and pre-eclampsia mission of HIV-1 was noted among the
were inversely correlated with maternal 49 mother-infant pairs included in the
FT4 levels during early and late preg- DRM analysis. However, three wom-
nancy, respectively. In particular, women en had developed DRMs, and two had
with IMH during the third trimester had dual-class resistance against all recom-
an increased risk of developing pre-ec- mended first-line drugs.
lampsia. The researchers suggested that
their findings of a low DRM selection rate
Zhang Y, et al, Maternal low thyroxin levels are associated with
adverse pregnancy outcomes in a Chinese population. PLoS support the continued adoption of the
ONE 2-17;12:e0178100.
Option B+ for preventing mother-to-child
transmission of HIV-1.
(10.5 percent), and yeast infection (3.7 levels in first morning urinary specimens
G percent). HR-HPV (7 percent) was de- collected every other day for 7 weeks
tected and significantly correlated with during that same year. Child mortality
Gynaecology abnormal cervical cytology (p<0.0001). data were collected in 2000 and 2013.
Moreover, the risk of HR-HPV infection Only women who experienced child
was significantly increased by the pres- mortality were found to have shorter
High prevalence of lower ence of bacterial vaginosis (odds ra- telomere lengths with increasing age
genital tract infection among tio, 3.0, 95 percent confidence interval, (p=0.015). Notably, shorter telomere
women in Beijing, China 1.75.4; p<0.0001). length was linked to higher than average
basal cortisol levels (p=0.007) as well as
Zhang D, et al, Epidemiological investigation of the relationship
The prevalence of lower genital tract in- between common lower genital tract infections and high-risk greater variations in basal cortisol lev-
human papillomavirus infections among women in Beijing,
fection (LGTI) in Beijing is high and that China. PLoS ONE 2017;12:e0178033. els over time (p=0.053). Nonparametric
.
of co-infection is of a magnitude that war- bootstrapping analyses indicated that
rants attention by public health services, HPAA activity mediated the effect of child
according to a recent study. Traumatic life events affect mortality on telomere length.
There has been a notable increase cellular ageing in women The researchers suggested that
in the incidence of LGTI in recent years, of reproductive age more large-scale longitudinal studies are
which is of concern since the link be- required to confirm their findings.
tween high-risk human papillomavirus Women of reproductive age who suffer
Barha CK, et al, Child mortality, hypothalamic-pituitary-ad-
(HR-HPV) and other sexually transmitted a traumatic life event such as the loss renal axis activity and cellular aging in mothers. PLoS One
2017;12:e0177869.
diseases remains unclear and untreat- of a child have a faster pace of cellular
ed LGTI such as Chlamydia trachomatis ageing than those who do not, and this
may cause pelvic inflammatory disease, appears to be affected by maternal hy-
which has been linked to miscarriages, pothalamic-pituitary-adrenal axis (HPAA)
preterm birth, ectopic pregnancy, and tu- activity, say Canada-based researchers.
bal factor infertility. They tested the hypothesis that
Researchers in China analysed data psychological challenges increase the
from 1,218 married women aged 2070 age-related pace of biological ageing by
years who were resident in Beijing for at measuring telomere attrition in a cohort
least 6 months and underwent routine of Kaqchikel Mayan women living in a
annual gynaecologic health checks be- population with a high frequency of child
tween March and October 2014. Cervical mortality. The women are part of an on-
secretions and vaginal swab specimens going longitudinal study of the relation-
were tested for C. trachomatis, Neisseria ship between naturally occurring stress
gonorrhoeae, Ureaplasma urealyticum, and womens reproductive function. Ge-
yeast, clue cells, and HR-HPV. The wom- netic variability was reduced since the
en also completed a structured question- women were all Kaqchikel Mayan with at
naire that provided data on demographic least five generations of traceable ances-
status, reproductive health history, sexu- tors. Moreover, they had similar lifestyles
al behaviour, symptoms of genital tract in terms of diet, physical activity, edu-
infection, use of vaginal medications, cation, and socioeconomic status, and
and use of contraceptive methods. none smoked.
Laboratory results were available Telomere length was quantified by
for 1,195 women. Forty-seven percent qPCR of buccal specimens collected
had LGTI, most commonly U. urealyti- from 55 women in 2013, and HPAA activ-
cum (35.5 percent), bacterial vaginosis ity was assessed by quantifying cortisol
GYNAECOLOGY PEER REVIEWED MIMS JPOG JUL/AUG 2017 137
Dysplasia terminology Original CIN terminology Modified CIN terminology The Bethesda system (SIL) terminology
(1991)
Normal Normal Normal Within normal limits benign cellular
changes (infection or repair) ASCUS/AGUS
Atypia Koilocytic atypia, flat Low-grade CIN LSIL
condyloma, without
epithelial changes
Mild dysplasia or mild CIN 1 Low-grade CIN LSIL
dyskaryosis
Moderate dysplasia or CIN 2 High-grade CIN HSIL
moderate dyskaryosis
Severe dysplasia or CIN 3 High-grade CIN HSIL
severe dyskaryosis
Carcinoma in situ CIN 3 High-grade CIN HSIL
Invasive carcinoma Invasive carcinoma Invasive carcinoma Invasive carcinoma
CIN: Cervical intraepithelial neoplasia; LSIL: Low-grade squamous intraepithelial lesion; HSIL: High-grade squamous intraepithelial lesion; ASCUS: Atypical squamous
cells of undetermined significance; AGUS: Atypical glandular cells of undetermined significance.
(Reproduced with permission from IARC WHO Colposcopy Manual, Chapter 2)
colposcopy, these women will generally have ies. CIN 2 leads to dysplastic changes occurring
features of low-grade CIN. In 10% of women with in the lower half of the epithelium together with
a productive infection and very rarely in women more numerous nuclear anomalies and mitotic
with a latent infection, the viral DNA integrates bodies. Finally, in CIN 3, there is complete dis-
with the host DNA and causes expression of viral array with nuclear anomalies and mitotic bod-
E6 and E7 proteins which leads to the loss of ies through the full thickness of the epithelium
cell cycle control, mitosis, and uncontrolled cell (Figure 2).
proliferation resulting in a transforming infection The NHS Cervical Screening Programme
(Figure 1), which can subsequently lead to inva- (NHSCSP) recommends the use of the three-tier
sive cervical cancer. On cytology, histology, and terminology for the histological reporting of CIN
colposcopy, these women will generally have (CIN1, CIN2, and CIN3). The advantages of the
features of high-grade CIN. three-tier system are that it allowed direct corre-
lation with the cytological grades of dyskaryosis
CLASSIFICATION OF CIN (Table 1) and that it ensured continuity in the recording,
Traditionally, CIN has been graded as CIN 1, 2, transfer, and storage of coded data to existing lo-
and 3 depending on the degree of differentiation cal, regional, and national databases. Collection
of the cervical squamous epithelium. The diag- and analysis of this data is necessary to evalu-
nosis relies on features of nuclear abnormalities, ate the effectiveness of the cervical screening
cell stratication, and the proportion of the thick- programme.
ness of the undifferentiated epithelium. However, when providing guidance for pa-
CIN 1 demonstrates undifferentiated cells in tient management, the three-tier grading system
the basal layer of the epithelium. It has only min- is of limited value. Patient management is based
imal nuclear anomalies and sparse mitotic bod- on a two-tier grading system of low-grade CIN
140 MIMS JPOG JUL/AUG 2017 GYNAECOLOGY PEER REVIEWED
CIN progression
L1
E4
E4
L1
Viral DNA
ET
ET
E4
Viral DNA
Viral DNA
ET
ET
Figure 2. Progression of CIN from a low-grade lesion to cancer. Adjacent to this are the HPV proteins that would be expressed for such
a change. (Courtesy of Professor John Doorbar, HPV Lab, University of Cambridge)
(CIN1) and high-grade CIN (CIN2 and CIN3) ab- shown to improve the sensitivity in the diagno-
normalities. sis of transforming infection over traditional HE
The WHO histological classication of 2014 staining. This would be particularly useful in the
has modied the classication of intraepithelial medical management of younger women with a
lesions into two grades and currently classies histological diagnosis of CIN2 on traditional HE
them into low-grade CIN, which would corre- staining. Immunostaining has the potential to
spond to CIN1 or LSIL and high-grade CIN cor- differentiate between productive and transform-
responding to CIN2, CIN3, or HSIL. ing infection and thereby help to decide which
Histological grading using traditional HE of these young women need treating.
staining is complicated by 1) other conditions
such as inammation and atrophy which mimic CGIN
changes of CIN and alter the histological inter- This article would not be complete without men-
pretation; and 2) the high inter-observer variabil- tioning cervical glandular intraepithelial neopla-
ity in grading CIN. sia (CGIN). CGIN is the precursor lesion of a
With a clearer understanding of the HPV cervical adenocarcinoma. HPV 18 plays a major
viral gene expression producing different states aetiological role. However, unlike CIN, the natu-
of HPV infection (latent, productive and trans- ral history of CGIN is not well understood. The
forming infection), it is now possible to use bi- NHSCSP classication system divides glandu-
omarkers in differentiating between low-grade lar lesions into two broad categories ie, border-
(productive infection) and high-grade lesions line changes and glandular neoplasia.
(transforming infection). However, the disease burden related to
Various biomarkers can be used to iden- CGIN is on the rise. Today, approximately 20
tify E6 and E7 gene expression (p16) as well 30% of cervical cancers are classed as adeno-
as cellular proliferation (Ki-67, MCM, and E4). carcinomas. These tumours may have a more
Histological staining with these biomarkers has aggressive course and thus a poorer prognosis.
GYNAECOLOGY PEER REVIEWED MIMS JPOG JUL/AUG 2017 141
HPV vaccination is likely to prevent over 70% of all cervical cancers as well as other HPV-mediated cancers such as anal or oral cancer.
HIV-positive women should have annual cytology and if possible at the outset of the diagnosis, a colposcopy if resources permit.
the ages of 9 and 13. At present, the vaccine is Since 2013, screening is performed in Eng-
thought to be efficacious for at least 89 years land and Northern Ireland using LBC with con-
after the initial regimen and women are still rec- comitant use of HPV testing for Triage in wom-
ommended to have cervical cancer screening. en with borderline and low-grade dyskaryosis
and also as Test of Cure following treatment
Screening for CIN and CGIN. Wales and Scotland use HPV
Screening for CIN is done by cytological as- testing with LBC for Test of Cure.
sessment of cells obtained from the surface
of the cervix. This dates back to methods that Future of screening
originated with Papanicolaou in the 1940s In the near future, it is expected that the current
where cells were scraped from the cervix using method of screening using LBC and HPV testing
a spatula and smears prepared on slides for as- will be replaced by primary HPV screening.
sessment. Cytological screening has changed Following a review of results from the Eng-
since 2004 in the UK from the original method lish HPV primary screening pilot sites and inter-
using smears prepared from a cervical scrape national evidence, the UK National Screening
to liquid-based cytology (LBC). There are many Committee recommended in January 2016 that
advantages to this method including semi-au- HPV primary screening should be adopted by
tomation and uniform spread of the epitheli- the screening programme. The Public Health
al cells, meaning they are easier to read and Minister subsequently approved this in July
reduce the number of unsatisfactory samples. 2016. It is intended that the implementation of
It also allows for the concomitant use for HPV HPV primary screening will be a phased ap-
DNA testing. proach and could take until 2019.
GYNAECOLOGY PEER REVIEWED MIMS JPOG JUL/AUG 2017 143
Colposcopy
Colposcopy is the basis of secondary screen-
ing in the UK. Hans Hinselmann rst described
this method in 1925 as a way of examining the
cervix using a low-powered microscopy. It also
allows obtaining of biopsies and treating cervical
intraepithelial lesions at the time of examination.
The basis of colposcopy is to visualize un-
der magnication of the transformation zone
and its reaction to 35% acetic acid or Lugols
iodine. The transformation zone is the area
where CIN develops and is dened anatomi-
cally as the area in between the original squa-
mocolumnar junction (SCJ) which is laid down
in foetal life and the new SCJ, which is formed
when the hormonal changes of puberty lead to
eversion of the cervix and exposure of the co-
lumnar epithelium to the acidic pH of the vagi-
na, inducing metaplastic change into the squa-
mous epithelium.
Colposcopy is only deemed as a satisfac-
tory screening method if the entire SCJ and the
upper limit of the lesion are visualized. Only if Figure 3. (a) Colposcopic view of the cervix 60 seconds after acetic acid staining;
and (b) Same cervix as in Figure 3a with DySIS map overlaid.
both these factors are realized will appropriate
diagnosis, counselling, and treatment occur.
Colposcopic abnormalities are graded FUTURE OF COLPOSCOPY
according to the appearance of acetowhite There are multiple adjuncts that are now
change, iodine uptake, and vascular patterns available that improve the sensitivity and/or
(eg, mosaicism, punctuation, and atypical ves- specicity of colposcopy alone. These include
sels). Thus, assessments are subjective and devices such as DySIS and Niris Imaging
prone to inter-observer variability. This variation System.
is markedly reduced for high-grade (HG) le- DySIS is a digital video colposcope that
sions and the PPV of a colposcopic impression also uses dynamic spectral imaging to evalu-
of CIN3 was noted to be 78% in a systematic ate the whitening effect of acetic acid on the
review. epithelium (Figures 3a and 3b). It produces a
144 MIMS JPOG JUL/AUG 2017 GYNAECOLOGY PEER REVIEWED
Treatment of CIN
Treatment of CIN is done using a variety of meth-
ods. All methods should be efcient in eradicat-
ing the intraepithelial lesions and minimizing any
adverse effects, particularly on future pregnan-
cies, as the majority of women undergoing treat-
ment are of reproductive age.
CIN can be treated by ablative and excision-
al techniques. Both have a cure rate of >90%
and there is no difference between the two tech-
niques when it comes to treating and eradicat-
ing CIN. Both methods aim to remove the trans-
formation zone and lesion. All techniques used
should remove tissue to a depth of 710 mm so
as to ensure eradication of CIN that may involve
the gland crypt.
The technique used for treatment of CIN
relies on patient-specic factors such as the pa-
CIN can be treated by ablative and excisional techniques. tients age, colposcopic appearance, depth and
size of the lesion, type of transformation zone,
who have renal failure and require dialysis or re- and fertility status.
nal transplantation have an increased incidence CGIN in contrast to CIN should be man-
of abnormal cytology (15%). However, even with aged using excisional techniques only. Patients
this increased risk, the uptake of cervical screen- with CGIN can be managed with a conservative
ing is poor among transplant recipients. Thus, it is excision provided adequate surveillance is pos-
essential that their cervical cancer screening status sible. However, if the excision margins are in-
be reviewed at their annual transplant review. volved, a further excision should be undertaken
All women who are HIV positive should and if this fails, consideration must be given to a
have annual cytology and if possible at the out- hysterectomy.
set of the diagnosis, a colposcopy if resources Most UK centres use excisional techniques
permit. There is an increased prevalence of CIN for treatment of CIN and in particular, the LLETZ
lesions (3% vs 2040%) in HIV infected patients. procedure. Excisional techniques allow the as-
Furthermore, regression of these lesions is rare sessment of the excision margins and exclude in-
and there is a higher rate of treatment failure vasion. It is quick, easy to learn, low in cost, and
with one study demonstrating an 87% recur- well tolerated by patients. Excisional techniques
rence rate in HIV patients. are indicated in cases of suspected invasion, glan-
Women who are on cytotoxic chemotherapy dular involvement, repeat treatments, and if any
for either nongenital cancers or rheumatological discrepancy exists between cytology, colposcopy,
conditions should have screening as per national and histology. The disadvantage is with the use of
GYNAECOLOGY PEER REVIEWED MIMS JPOG JUL/AUG 2017 147
excisional techniques in a see & treat approach countries. It requires a general anaesthetic. It is
which may lead to overtreatment in some women. useful in cases of suspected invasion and glandu-
Ablative techniques destroy the cervical ep- lar disease as the lack of diathermy avoids ther-
ithelium. Hence, accurate pretreatment punch mal artefact and allows accurate assessment of
biopsy samples are required to exclude invasion excision margins. There is, however, an increased
prior to ablative treatment. Punch biopsies, how- risk of haemorrhage and an adverse impact on
ever, have a low sensitivity in excluding invasion reproductive outcomes.
and CGIN. Therefore, ablative treatments should Hysterectomy: Still retains a place in man-
only be used in selective cases where the trans- agement of CIN in patients who have coexisting
formation zone and lesion are completely visible, gynaecological problems such as menorrhagia
there is no discrepancy between cytology, col- or broids. It is also used to treat lesions where
poscopy, and histology, and there is no sugges- future fertility is not required, repeat excisions
tion of glandular or invasive lesions. are not possible due to altered cervical anatomy
as a result of previous excisions, and cytological
Ablative techniques and colposcopic surveillance is not possible due
Various ablative techniques are available such to persistently inadequate LBC or unsatisfactory
as cryocautery, cold coagulation, laser ablation, colposcopy. It is important to ensure complete ex-
and diathermy ablation. Cryocautery is the com- cision of the cervix to reduce the risk of residual
monest ablative technique used. CIN and VAIN.
Cryocautery: This technique ablates cer-
vical tissue by freezing and using probes of Treatment complications
various shapes and sizes. Cryocautery is rec- Complications of CIN treatment are rare and
ommended to be used only for the treatment of more likely with excisional techniques. Early
low-grade CIN as the rate of clearance of HG CIN complications include primary haemorrhage
is poor. A freeze-thaw-freeze technique is advo- (<1%), which is easily controlled using diather-
cated with a freeze cycle of 60 seconds, as this my or Monsels solution. In difficult cases, su-
increases the cure rate. This technique is cheap tures can be placed. Secondary haemorrhage
to perform and therefore is widely used in the usually occurs approximately 23 weeks after
developing world. the procedure. It is usually due to infection and
is effectively treated with a course of broad-spec-
Excisional techniques trum antibiotics.
Various excisional techniques are available. Late complications: Excisional treatment is
These include LLETZ/loop biopsy, NETZ/SWETZ associated with adverse reproductive outcome
(needle/straight wire excision of transformation in subsequent pregnancy in a small proportion
zone), cold knife conization, laser conization, of women and this is directly related to the depth
and hysterectomy. of excision, volume of cervical tissue removed,
LLETZ/loop biopsy (large loop excision and technique/type of excision.
of transformation zone): This is the most widely Excisional treatment of CIN does not af-
practiced technique in the UK and usually per- fect the ability to conceive or have an impact in
formed under local anaesthetic. It is safe, cheap, the first trimester of pregnancy. There is some
and easy to use, and the thermal artefact damage limited evidence that it may increase the risk of
to the specimen margins is minimal if performed second trimester miscarriages from 0.4%1.6%.
appropriately. Excisional treatment can increase the risk of
Cold knife conization: Rarely used today in preterm birth if depth of excision is more that 10
the UK but is still being used in some European mm. The absolute risk increases from 7% in the
148 MIMS JPOG JUL/AUG 2017 GYNAECOLOGY PEER REVIEWED
Analgesia in Labour
and Delivery
Andy Chu MBBS; Samson Ma BMedSci BMBS MRCP FRCA; Shreelata Datta BSc(Hons) MBBS MRCOG LLM
Management of pain during labour is very important to ensure that this is a positive experience for the woman and her partner.
requiring a particular skill set and equipment. ferent bres through the sympathetic nerves
Labour analgesia can be broadly classied into to the sympathetic chain. The pain is therefore
regional and nonregional analgesia, with a fur- felt at T10L1 dermatomes. Cervical pain is
ther sub-classication of nonregional as pharma- carried to the S2, 3 dermatomes via parasym-
cological and nonpharmacological. Early plan- pathetic pelvic splanchnic nerves. A bres are
ning and antenatal counselling are essential in thin and myelinated with a moderate speed of
a multidisciplinary clinic offering an anaesthetic signal conduction. These bres transmit acute,
opinion as well as midwifery and obstetric advice sharp pain. C bres are unmyelinated and have
for high-risk patients with multiple comorbidities a slower conduction velocity. C bres primarily
such as high BMI, difcult spinal anatomy, and transmit a deep, dissipated type of pain after
previous obstetric or anaesthetist complications. the initial injury.
Labour is a physiological process which in- The second stage of labour relates to the pas-
volves delivery of the baby and placenta from the sage of the baby through the birth canal, where
uterus to the outside world. Management of pain the pain is more localized to the perineum. Pain
during labour is very important to ensure that this is afferents are A bres via the pudendal nerves,
a positive experience for the woman and her part- affecting the S2S4 dermatomes.
ner. Understanding this physiology will enhance
why certain techniques are used. Case 1: Home/midwifery led unit
The type of pain experienced relates to the A 30-year-old G3P3 woman in early labour, con-
different stages of labour: tracting moderately every 34 minutes.
The first stage relates to uterine contractions. It is possible for labouring women to require
Pain signals are transmitted via A and C af- minimal analgesia, particularly in the multiparous
OBSTETRICS PEER REVIEWED MIMS JPOG JUL/AUG 2017 151
Table 1. Contraindications for Regional Anaesthetic Blocks immediately after birth this is a recommenda-
tion by the Royal College of Obstetricians and
Gynaecologists (RCOG) to improve bonding.
Absolute Relative
Paradoxically, breastfeeding after having an epi-
Maternal refusal Signicant haemorrhage is
expected dural may be problematic. It has been found that
Local infection Untreated systemic sepsis women undergoing an epidural will have more
difficulty starting an infant on breastfeeding with-
Uncorrected hypovolaemia Certain cardiac diseases shunts,
where rapid BP changes are not in the first 24 hours. This phenomenon is not en-
tolerated tirely understood but if feeding is not established
Coagulopathy (platelets <75 Previous spinal injuries or within the first hour, these mothers run a high risk
x 109/litre, use of antiplatelet surgeries
of needing bottle supplementation instead.
agents such as clopidogrel)
Spinal tap: If the epidural catheter punc-
Raised intracranial pressure
tures an epidural vein, the LA can be injected di-
rectly to the central venous system and results in
toxicity even with small doses. This is particularly
to top-up the epidural or requiring other anal- dangerous as epidural doses of bupivacaine are
gesic techniques. of much larger quantity than spinal doses (~20
The patient must be fully consented before mL vs ~2.5 mL). If the catheter pierces the dura,
a regional block. Contraindications are listed in an excessively high block can result due to injec-
Table 1 and these apply to the other regional tion into the subarachnoid space, which at worst
techniques used. Due to the nature of the epi- can result in a total spinal block. A patient with
dural, there may be lower limb motor block. total spinal block will require ventilatory and cir-
This motor function deficit has been linked to culatory support. Epidural abscesses or haemat-
prolonged second stage of labour and increase omas are rare (under 1 in 160,000) and serious
use of instrumental deliveries. Some patients complications but should be considered if a pa-
may find this distressing as they are unable to tient still complains of motor blockade more than
mobilise. The anaesthetist will assess the effec- 6 hours after cessation of the infusion or has new
tiveness of the block looking at both the motor onset incontinence. These conditions can result
block using the Bromage scale and sensory in permanent paraplegia if not identified and
block, then adjust the dose to patient comfort treated in a timely fashion. Urgent radiological
with minimal motor blockade. A different LA imaging and discussion with the spinal team are
agent, ropivacaine instead of bupivacaine, can warranted to salvage the situation before dam-
produce less motor blockade but is not as po- age becomes permanently irreversible.
tent. Hypotension can occur due to vasodilating Epidural block: An epidural block has a
effects of preganglionic autonomic B bres inhi- similar side-effect profile to that of a spinal. There
bition. This should be anticipated and managed is a risk of infection in procedures and a spinal
as appropriate with vasopressors such as me- infection can be particularly catastrophic, requir-
taraminol or phenylephrine. ing potent and lengthy antibiotic treatment. Loss
Epidurals can provide other benets be- of sterility can be a risk during a difficult injec-
side analgesia; by blunting sympathetic nervous tion requiring multiple attempts. Direct injury to
activities they can attenuate the sympathetic the spinal cord is rare, but the majority of these
response to anxiety and pain. There is also a patients will make a full recovery from nonper-
reduced risk of thromboembolism in the lower manent nerve injuries. One point of note is that
limbs. This regional method means that women patients under regional anaesthesia are espe-
can have skin-to-skin contact with their babies cially sensitive to sedation and therefore at risk
OBSTETRICS PEER REVIEWED MIMS JPOG JUL/AUG 2017 153
The use of Entonox in labour is well established as demonstrated by its availability throughout nearly all the obstetrics units across
the United Kingdom.
tablished by using systemic pharmacological by the patient. The gas is inhaled and reaches
agents, although potentially this method is infe- a peak effect by 2030 secondsideal for inter-
rior to appropriately placed regional techniques. mittent intense pain seen in labour. The neonate
As listed before, an epidural may not be possible eliminates most of the gas within minutes of birth
in some patients. The below listed methods are so there is low risk of respiratory depression.
the commonly used ones in labour ward settings Nausea, vomiting, and disorientation are com-
and can be achieved relatively easily without mon side effects, but the major disadvantage of
specialist input. It is important to discuss the Entonox is its inability to provide complete anal-
methods with each patient appropriately as ac- gesia. Nitrous oxide is highly lipid-soluble and
ceptable analgesia does not necessarily mean will expand luminal spaces it diffuses into. Cer-
absolute absence of pain. tain circumstances such as bowel obstruction,
Entonox: Entonox is the trade name of 50% pneumothorax, ongoing middle ear infections,
oxygen and 50% nitrous oxide gas mixture. It is and decreased levels of consciousness will limit
an anaesthetic gas frequently used in hospital its use.
A&E, labour wards, and midwifery led units. The Pethidine: Pethidine, also called meperidine,
use of Entonox in labour is well established as is an opioid about one-tenth as potent as mor-
demonstrated by its availability throughout near- phine and can be given intramuscularly. Pethidine
ly all the obstetrics units across the United King- is widely used in labour and can be prescribed and
dom. One reason for its popularity is its ease of administered by midwives. Side effects of pethi-
use in the first stage of labour, although the pa- dine are similar to those of other opioids, namely
tient must be counselled on how to use it effec- respiratory depression of the mother and neonate,
tivelyit is delivered using a mouth nozzle held delayed gastric emptying, nausea, vomiting, se-
OBSTETRICS PEER REVIEWED MIMS JPOG JUL/AUG 2017 155
A patient with total spinal block will require ventilatory and circulatory support.
kidney failure. AKI is detected by a marked de- segment of the proximal tubule and the thick as-
crease in glomerular ltration rate (GFR), accom- cending limb of the loop of Henle are especially
panied by elevated levels of serum creatinine. susceptible to ischaemic insult, due to high ATP
This disease is associated with a poor prognosis demands and naturally hypoxic environment,
resulting in longer hospital and intensive care respectively. Hypoxic and nephrotoxic drug-in-
stays and higher mortality rates. It is difficult to duced injury has been found to lead to elevated
present an accurate incidence of AKI since dis- risk of CKD long-term.
ease presentation and definitions are variable, Postrenal AKI occurs due to obstruction after
however it is estimated to vary between 8% and the level of the kidneys. Typically, AKI is alleviat-
30% in paediatric intensive care units. Prognosis ed upon removal of the obstruction. Additionally,
for these patients depends on the underlying ae- if the individual has two functioning kidneys, the
tiology, ranging from full recovery to end-stage blockage must be bilateral in order to result in AKI,
renal failure (ESRF). otherwise the functional kidney will compensate.
Failure SCr 3 times baseline or 4 mg/dL; <0.3 mL/kg/hour (oliguria) for 24 hours Highly specific
GFR 75% (or anuria for 12 hours)
0.3 mg/dL within 48 hours, or UO equal to or Table 2. AKIN Guidelines from Mehta, et al, 2007
less than 0.5 mL/kg/hour over 6 hours. See Table
3 for guidelines.
Stage Serum creatinine Urine output
pRIFLE 1 SCr 0.3 mg/dL or 1.52.0 <0.5 mL/kg/hour for >6 hours
times baseline value
In children specically, a paediatric adaptation of RI-
2 SCr >2.03.0 times baseline <0.5 mL/kg/hour for >12 hours
FLE was created, known as pRIFLE. pRIFLE differs
a
from typical RIFLE classications in that the classi- 3 SCr 4.0 mg/dL with acute <0.3 mL/kg/hour for 24 hours
cation is based on changes in estimated creatinine increase of 0.5 mg/dL or or anuria for 12 hours
SCr >3.0 times baseline
clearance or UO, instead of change in SCr which is a
Any patients being treated with RRT automatically are placed into stage 3.
used in adult RIFLE. There are three classications:
Risk, Injury, and Failure. This is because children
are rapidly growing, which can lead to changes in
SCr independent of actual onset of AKI. Table 3. KDIGO Guidelines from KDIGO AKI Work Group 2012
AKI IN SEPSIS
Studies report 4570% of AKI to be induced by Stage Serum creatinine (SCr) Urine output
sepsis. AKI and sepsis independently increase 1 SCr 0.3 mg/dL or 1.51.9 <0.5 mL/kg/hour, 612 hours
mortality, but combined sepsis and AKI shows a times baseline value
staggering mortality of 5766%. Septic AKI oc- 2 SCr 2.02.9 times baseline <0.5 mL/kg/hour, 12 hours
curs due to a combination of alterations in mi- a
3 SCr 4.0 mg/dL or 3.0 times <0.3 mL/kg/hour, 24 hours or
crovascular blood ow, ion balance, oxidative baseline or in patients under anuria for 12 hours
stress, and inammation. Traditionally, the ide- 18 years, eGFR to <35 mL/
ology that renal ischaemia is the major cause of minute/1.73 m2
a
AKI lead to the thought that restored perfusion Any patients being treated with RRT automatically are placed into stage 3.
AKI is detected by a marked decrease in GFR, accompanied by elevated levels of serum creatinine.
Endothelin is a potent vasoconstrictor that space of the glomerulus, constricting the glo-
has also been shown to play an active role in merular capillary tuft. Crescent formation is initi-
the complex pathophysiology of sepsis. TNF- ated by holes in the glomerular basement mem-
causes endothelin release, which acts on vascu- brane (GBM), Bowmans capsule, and walls of
lar endothelial cells and causes microvascular glomerular capillaries allowing macrophages
uid leakage. Inammation also plays a central and coagulation factors to trigger cleavage of
role in septic AKI. Inammatory cytokines lead brinogen to brin. Earlier commencement of
to heterogeneous upregulation of inducible NO medical intervention will help to avoid long-term
synthase, damaging various regions of the mi- damage.
crovasculature.
NEPHROTOXIC AKI
RAPIDLY PROGRESSIVE Nephrotoxic medications are substantial cause
GLOMERULONEPHRITIS of AKI, reported as 16% of AKI in hospitalized
Rapidly progressive glomerulonephritis (RPGN) paediatric patients. Certain antibiotics, antivirals,
is indicated by decreased renal function and is antifungals, angiotensin converting enzyme in-
often associated with haematuria, proteinuria, hibitors (ACEIs), nonsteroidal anti-inammatory
and decreased UO. This condition is frequent- drugs (NSAIDs), calcineurin inhibitors, chemo-
ly referred to as crescentic glomerulonephritis therapeutic agents, and radiographic contrast
(CGN), since it is marked by development of substances induce nephrotoxic AKI.
glomerular crescents. Glomerular crescents are Cisplatin is a platinum-based chemother-
nonspecic response to glomerular injury, ap- apeutic agent typically utilized in the manage-
pearing as 2 layers of cells in the Bowmans ment and treatment of solid, malignant neo-
PAEDIATRICS PEER REVIEWED MIMS JPOG JUL/AUG 2017 165
syndrome (HRS) with regards to haemodynam- completely understood at this point in time, so
ic shifts, as well as liver impairment resulting in children must be treated based on adult models
hypoalbuminaemia, uid leakage from capillar- of disease.
ies, splanchnic vasodilation, and hypovolaemia AKI in cirrhotic patients tends to be either
in the intravascular compartment. Chemothera- prerenal or intrarenal. Depending on the aetiolo-
peutic drugs commonly utilized in BMT are also gy, uid management will differ: in prerenal AKI,
a source of AKI due to nephrotoxicity. Norepi- uid supplementation is necessary to elevate
nephrine from the activated hepatorenal sym- the intravascular volume while in intrarenal AKI
pathetic nervous system constricts the afferent decreasing uids may be necessary. If ascites
renal arteriole, depressing GFR, and retaining is severe, abdominal compartment syndrome
salt. The prognosis of SOS-AKI is poor, and could be the cause. Many traditional biomarkers
thus treatment usually is supportive: treatment will overestimate renal function due to problems
for the kidneys mirrors treatment of HRS, and rooted in declining hepatic function, and more
debrotide tends to be the drug of choice. accurate markers such as inulin are unrealistic
in practice due to high cost and feasibility of
AKI IN LIVER DISEASE use. However, the Modication of Diet in Renal
AKI in liver disease can occur in patients with Disease (MDRD) Study equation can be used in
acute liver failure (ALF), chronic liver disease, patients with liver cirrhosis.
acute on chronic liver failure, and post-transplan- HRS causes prerenal AKI in patients with
tation. The most important point to bear in mind ascites and cirrhosis of the liver. The whole pro-
is that AKI in these patients is not always hepa- cess is precipitated by portal hypertension which
torenal syndrome (HRS). In fact, of all the caus- causes bacterial translocation and release of vas-
es of AKI in patients with liver disease, majority odilators especially nitric oxide. The kidneys will
are caused by prerenal or acute tubular necro- attempt to salvage as much perfusion as possible
sis and HRS constitutes only a small part. ALF by arteriole vasodilation via prostaglandins. How-
is a rare condition, indicated by new onset liver ever, with low cardiac output state, activation of
dysfunction with coagulopathy which in children renin-angiotensin-aldosterone system leads to re-
may or may not be accompanied by encepha- nal vasoconstriction and eventual ascites due to
lopathy, AKI, and ALF often occur concurrently, sodium and water retention.
especially with specic aetiologies: nephrotoxic
medications, acetaminophen overdose, HRS, AKI IN CARDIAC DISEASE
sepsis, and hypovolaemia. AKI commonly occurs in patients undergoing car-
As liver disease progresses, there are se- diac surgeries, with increased mortality and mor-
vere vascular haemodynamic complications bidity, as well as increasing costs of healthcare
that disturb renal processes, leading to imbal- overall. Incidence of AKI after cardiac surgery
anced electrolyte levels and ascites. Frequent- ranges from 3% to 30%. A large retrospective
ly, changes in vascular compliance and renal cohort study seeking to determine the incidence
perfusion culminate in AKI, common in patients of AKI in the cardiac postoperative paediatric
with chronic liver disease (CLD). CLD causes population found that patients with AKI were
haemodynamic uctuations, unbalancing uids more likely to have had a more complex surgery
and electrolytes, and leaving the kidneys highly requiring lengthier cardiopulmonary bypass,
susceptible to damage. Ascites is an indicator cyanosis, and requirement of mechanical venti-
of this disease state in both children and adults, lation. Of this subset of patients, 15% required
and serves as a mortality predictor. However, RRT for AKI, and those patients additionally have
the pathophysiology of ascites in children is not a heightened mortality rate of 60%.
PAEDIATRICS PEER REVIEWED MIMS JPOG JUL/AUG 2017 167
FLUID MANAGEMENT
Fluid management plays a major role in preven-
tion and subsequent treatment of AKI. When the
balance between intravascular and extracellular
uid compartments is disturbed, redistribution Fluid management plays a major role in prevention and subsequent treatment of AKI.
of uids may be hindered. The primary endpoint
of uid treatment is to restore renal perfusion traditionally many practitioners have attempt-
via increasing intravascular volume. The gener- ed to cure AKI by supplying the patient with
al types of uids are colloids, albumin, gelatin, large volumes of uids to restore intravascular
and crystalloids. The debate as to which type of volume and renal function. However, this course
uid to use has always been a matter of debate. of treatment may cause uid overload (FO), es-
Hypertonic uids are more likely to remain in pecially when oligoanuric. Although it is unclear
the intravascular compartment, and most likely whether oedema caused by FO has any direct
prove to be more effective than hypotonic uids causal effect on AKI, oedema causing abdom-
in patients with depleted intravascular volume. It inal compartment syndrome can cause tubule
is suggested that synthetic colloids are avoided compression, further retention of water and salt,
in patients with AKI or at risk for AKI and that and diminished renal blood ow, inducing AKI.
balanced salines are the best mode of uids for To manage FO, the goal is to initiate a neu-
AKI treatment. tral or negative uid balance. Current treatment
approaches include diuretics and RRT. Howev-
Fluid overload in patients with AKI er, each has its own disadvantages. Patients
It is believed that AKI ensues due to systemic hy- may develop diuretic resistance, imbalanced
potension with resultant renal ischaemia. Thus, electrolytes, and further decline in renal integ-
168 MIMS JPOG JUL/AUG 2017 PAEDIATRICS PEER REVIEWED
reduced consciousness if AKI is severe enough 2017 Elsevier Ltd. All rights reserved. Initially published in Paediatrics and
Child Health 2017;27(5):233237.
during acute phase of disease. Serum potas-
sium and ECG should be monitored closely About the Authors
Rupesh Raina is a Consultant Nephrologist in the Department of Pediatric
for hyperkalaemia and ensure levels over 6.5 Nephrology at Akron Children Hospital, Akron and Akron General Medical
Center, Cleveland Clinic Foundation, Akron, OH, USA. Conict of interest:
mmol/litre are quickly treated. Monitoring of ac- none declared.
id-base balance is essential as well, and one Abigail Chauvin is a Second-Year Medical Student at Northeast Ohio Medical
University of Rootstown, Ohio, USA. Conict of interest: none declared.
may administer IV bicarbonate for treatment of
Akash Deep is a Consultant Paediatric Intensivist at Kings College Hospital,
acidosis in the face of persistence despite cor- Denmark Hill, London, UK. Conict of interest: none declared.
CONTINUING MEDICAL EDUCATION MIMS JPOG JUL/AUG 2017 169
Pun Ting Chung MBBS, FHKAM (O&G), FRCOG; Yung Shuk Fei Sofie MBBS, FHKAM (O&G); Wan Hei Lok Tiffany MBBS, FHKAM (O&G)
INTRODUCTION
Vaginal bleeding commonly occurs in
pregnancy. More than 20% of preg-
nant women with successful deliveries
experienced vaginal bleeding during
the antenatal course.1 Two of the most
important differential diagnoses for pa-
tients presenting with bleeding in early
pregnancy are miscarriage and ectopic
pregnancy.
ASSESSMENT OF BLEEDING
IN EARLY PREGNANCY
For patients admitted to the ward
through the Accident & Emergency De-
partment, the general condition should
be assessed before taking history and
performing examination. Resuscitation
of the patients should be performed as
appropriate.
History should be directed to es-
tablish the possibility of pregnancy. As- Vaginal bleeding commonly occurs in pregnancy. More than 20% of pregnant women
sociated symptoms including abdom- with successful deliveries experienced vaginal bleeding during the antenatal course.
inal pain and passage of tissue mass
should be asked. Risk factors of ectopic bleeding or abdominal pain. Remov- gations. A negative pregnancy test would
pregnancy such as history of previous al of products of conception from the rule out pregnancy related complications.
ectopic pregnancy, pelvic inflammatory cervix may stop bleeding. It will also The single most useful investigation for a
disease, tubal surgery, and use of as- ameliorate vasovagal shock as a result patient with bleeding in early pregnancy
sisted reproduction techniques should of distension of the cervical os. There is transvaginal ultrasound examination.
be explored. are other advantages of vaginal exami- The other important investigation is the
Abdominal examination is an in- nations. Local causes of vaginal bleed- serum human chorionic gonadotropin
dispensable assessment. Apart from ing like cervical ectropion and cervical (hCG) level.
helping to make the diagnosis, pres- polyp can be diagnosed. Opportunis-
ence of free fluid or peritoneal signs tic screening for carcinoma of cervix MISCARRIAGE
often indicates surgical treatment. The can also be done. The authors are of Miscarriage is the preferred term for
value of performing routine vaginal ex- the opinion that a vaginal examination pregnancy loss before 24 weeks.4 This
amination is challenged.2-3 However, should be done. should replace the term abortion in a
vaginal examination would be impor- To make a definitive diagnosis, series of related conditions (Table 1). The
tant for patients with severe vaginal most patients would need further investi- term silent miscarriage is better because
170 MIMS JPOG JUL/AUG 2017 CONTINUING MEDICAL EDUCATION
Table 1. Recommended Terminology for Early Pregnancy Loss and Related ultrasound should be done to confirm
Conditions the foetal viability by detecting the foe-
tal pulsation. Cardiac activity can be
documented at around 5 weeks and 5
Old terminology Recommended terminology days gestation.7 However, a substan-
Spontaneous abortion Miscarriage tial proportion of pregnancies miscar-
Threatened abortion Threatened miscarriage ried after detection of cardiac activity.
In one series of patients after assisted
Inevitable abortion Inevitable miscarriage
reproduction treatment, 12.2% of preg-
Incomplete abortion Incomplete miscarriage nancies miscarried afterward.8 The
Complete abortion Complete miscarriage efficacy of treatment of patients with
threatened miscarriage with progester-
Missed abortion Silent miscarriage
one is inconclusive.9
Septic abortion Miscarriage with infection
MSD <25 mm with Perform a second scan, a of silent miscarriage is made, there
no visible foetal pole minimum of 7 days after the first are three options to further manage-
MSD 25 mm with Seek a second opinion on the ment. Expectant management for 12
no visible foetal pole viability and/or perform a second weeks is the preferred management
scan, a minimum of 7 days after
because this would minimise the risk of
the first
terminating a viable pregnancy. Also,
Transabdominal Visible foetal pole with Record the size of the CRL and
scan no visible heartbeat perform a second scan, a minimum expectant management is probably
of 14 days after the first the most cost effective.10 The Nation-
Visible intrauterine with Record the size of the MSD al Institute for Health and Care Excel-
no visible foetal pole and perform a second scan, a lence (NICE) suggested that an ultra-
minimum of 14 days after the first
sound examination should be done if
Adapted from NICE Clinical Guideline 154.9 bleeding and pain have not started, or
CRL: Crown-rump length; MSD: Mean sac diameter
bleeding or pain are persisting and/or
increasing after 3 weeks. If bleeding
missed miscarriage is considered a Threatened miscarriage and pain of the patient have subsided,
mouthful to enunciate . The other alter-
5
The amount of bleeding is usually not a pregnancy test should be done at the
native term is delayed miscarriage but heavy. There is usually no abdomi- end of 3 weeks.9 It is important to note
this term could imply fault on the part of nal pain and the uterine size is corre- that these recommendations are not
the woman or her doctors.6 sponding to the gestational age. Pelvic supported by sufficient clinical stud-
CONTINUING MEDICAL EDUCATION MIMS JPOG JUL/AUG 2017 171
ies.11 Medical treatment is the second Table 3. Three Options of Management of Miscarriage
acceptable option. This is also cost-ef-
fective12 and avoids the risk of evacu-
ation of uterus. An 800 mcg of miso- Expectant Medical Surgical
management management management
prostol can be administered vaginally.
Treatment - Single dose of Evacuation under
The dose can be repeated if there is no
800 mcg vaginal MAC or GA
bleeding or abdominal pain the next misoprostol
day. NICE suggested that a pregnan- Contraindications Evidence Evidence of -
cy test should be done after 3 weeks. of infection infection
Again, this recommendation is only Haemodynamic
Haemodynamic instability
based on expert recommendation. The instability
Allergy to
third option is surgical evacuation of the Suspicion misoprostol
uterus, either through electric or manu- of ectopic Suspicion
al vacuum aspiration. A comparison of pregnancy of ectopic
pregnancy
the three options can be found in Table
3. The final decision should be made Advantages Noninvasive Less invasive Quickest, highest
success rate;
by the patient in the absence of con-
traindications. Tissue mass obtained in Shortest duration
of bleeding
the course of treatment should be sent
Disadvantages Increased Compared with Anaesthetic and
for histological assessment to confirm
need for blood surgical treatment: surgical risks
intrauterine pregnancy and exclude transfusion,
- Gastrointestinal
unsuspected gestational trophoblastic unplanned side effects
disease.4 admission, and
intervention; - Longer duration
of pain and
Longer duration of bleeding
Intrauterine pregnancy of
bleeding - More
uncertain viability unplanned
A woman is considered to have an in- admissions
trauterine pregnancy of uncertain via- Success rate 1447% (silent 85% 95%
bility if transvaginal ultrasonography miscarriage);
shows an intrauterine gestational sac 85% in 2 weeks
with no embryonic heartbeat and no (incomplete
miscarriage)
findings of definite pregnancy failure.13
Anti-RhD No, if No Yes
NICE suggested that an ultrasound ex- prophylaxis for spontaneous At least 250 IU
amination can be repeated in a week nonsensitised miscarriage anti-D Ig
following a transvaginal scan. The find- RhD-negative occurs and no
women intervention
ings of a prospective observational
needed
multicentre study supported this rec-
Cost Most cost Second most Most costly
ommendation.14 effective cost effective
MAC: Monitored anaesthesia care
Incomplete miscarriage
The patient usually has a history of
passage of tissue mass apart from is usually smaller than the gestation- of endometrial thickness or volume
vaginal bleeding. There may also be al age. There is no consensus on the cannot differentiate between retained
history of abdominal pain. The cer- ultrasound diagnostic criteria for in- products of gestation and decidua.15
vical os is open and the uterine size complete miscarriage. Measurement The value of morphological criteria are
172 MIMS JPOG JUL/AUG 2017 CONTINUING MEDICAL EDUCATION
USG diagnostic or
probably diagnostic of ectopic
pregnancy
Medical treatment
Patient to check Weekly hCG
(Methotrexate IMI
pregnancy test at 3 weeks till normal
50 mg/m)
and reassess if positive
ectopic pregnancies. The diagnosis be the cause of the bleeding and the eas- tress and consider appropriate interven-
and management of nontubal ectopic iest way to make the diagnosis is to per- tion as necessary.
pregnancy are different and the authors form a vaginal speculum examination.
would like to refer to other publications CONCLUSION
for more information.25-26 OTHER MANAGEMENT ISSUES Bleeding in early pregnancy is a com-
It is important to give an anti-D rhesus mon condition. The most important dif-
OTHER DIAGNOSES prophylaxis at a dose of 250 IU (50 mi- ferential diagnoses include miscarriage
There are other causes of bleeding in crograms) to all nonsensitized rhesus and ectopic pregnancy. Apart from histo-
early pregnancy. negative women who have a surgical ry and physical examination, ultrasound
Molar pregnancy is a condition procedure to manage ectopic pregnan- examination and measurement of se-
which can be associated with serious cy or miscarriage. There is no need for
9
rum hCG are mostly required to make a
sequelae. This is the reason why all tis- patients who receive solely medical diagnosis and guide management.
sue mass obtained in the course of man- management for ectopic pregnancy or
agement should be sent for pathological miscarriage, threatened miscarriage, About the authors
Dr Pun Ting Chung is Consultant Gynaecologist in the
examination. complete miscarriage, or pregnancy of Department of Obstetrics & Gynaecology, Queen Mary
Hospital and Hon Clinical Associate Professor, The
Cervical ectropion is more common- unknown location. University of Hong Kong, Hong Kong.
ly found. It was found in more than 10% Different patients can have a very Dr Yung Shuk Fei Sofie is a Clinical Assistant Professor
in the Department of Obstetrics and Gynaecology, The
of patients. Cervical polyp was found in different reactions after suffering from University of Hong Kong, Hong Kong.
2% of patients.3 In fact, in many of these bleeding in early pregnancy. The doc-
Dr Wan Hei Lok Tiffany is a specialist in Obstetrics and
patients, a normal intrauterine pregnancy tor should be very sensitive towards the Gynaecology in the Department of Womens Health &
Obstetrics, the Hong Kong Sanatorium & Hospital, Hong
was found. The ectropion or polyp could possibility of developing emotional dis- Kong.
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176 MIMS JPOG JUL/AUG 2017 CME QUESTIONS
1. There is no need to perform pelvic examination in patients suffering from bleeding in early pregnancy
because of the accuracy of ultrasound examination.
2. Delayed miscarriage is a better term than silent miscarriage because most patients would have some
symptoms and therefore cannot be silent.
3. Silent miscarriage can be diagnosed if foetal pulsation is not detected after 6 weeks maturity.
4. Expectant management is the preferred management for silent miscarriage because the risk of
terminating a viable pregnancy would be minimised with other treatments.
5. It is proven that repeating a vaginal scan after 7 weeks is the most cost effective approach for intrauterine
pregnancy of uncertain viability.
6. Endometrial thickness of less than 1 cm confirmed the diagnosis of complete miscarriage.
7. The presence of an inhomogenous adnexal mass or extrauterine sac-like structure and absence of an
intrauterine gestational sac confirm the diagnosis of ectopic pregnancy.
8. An hCG level of more than 2,000 IU/L without evidence of intrauterine gestation on transvaginal
ultrasound examination is not compatible with a normal intrauterine pregnancy.
9. Expectant management is not an option for the management of ectopic pregnancy.
10. Laparoscopic salpingotomy should be considered the surgical treatment of choice because of the
superior reproductive outcome.