a prospective study comparing pregnancy …
TRANSCRIPT
1
A PROSPECTIVE STUDY COMPARING
PREGNANCY COMPLICATIONS AND
OUTCOMES IN HAEMOGLOBIN SS AND
HAEMOGLOBIN AA WOMEN IN LAGOS,
NIGERIA
BY
DR. MONSURAT BOLANLE ADEROLU
DEPARTMENT OF OBSTETRICS AND
GYNAECOLOGY
LAGOS UNIVERSITY TEACHING HOSPITAL
(LUTH)
P.M.B. 12003, LAGOS
MAY 2016
2
ATTESTATION
This dissertation by Dr. M. B. Aderolu in part fulfilment
of the requirements for FMCOG II of The National
Postgraduate Medical College of Nigeria was supervised
by:
.......................................................
DR. B. B. AFOLABI (FRCOG, FWACS, FMCOG, DM [Notts])
...........................................................
DR OLUWOLE (MBBS, FMCOG, FWACS)
3
CERTIFICATION
This is to certify that this research was performed
by Dr. Aderolu, Monsurat Bolanle, a senior
registrar in the department of Obstetrics and
Gynaecology of the Lagos University Teaching
Hospital, Idi-araba, Lagos, Nigeria.
………………………………………………..
PROF. R. I. ANORLU
FWACS, FMCOG
Head of Department
4
Table of Contents
Title page ............................................................................................................................ iv
Conflict of interest ............................................................................................................... v
Abbreviations used in text .................................................................................................. vi
Dedication ......................................................................................................................... viii
Abstract ............................................................................................................................... ix
Introduction ......................................................................................................................... 1
Literature review .................................................................................................................. 4
Methodology ...................................................................................................................... 12
Results ............................................................................................................................... 19
Discussion .......................................................................................................................... 31
Conclusion ......................................................................................................................... 35
Acknowledgement ............................................................................................................. 36
References ......................................................................................................................... 38
Appendix ........................................................................................................................... 42
5
FMCOG PART II DISSERTATION
PROJECT TITLE:
A PROSPECTIVE STUDY COMPARING PREGNANCY
COMPLICATIONS AND OUTCOMES IN
HAEMOGLOBIN SS AND HAEMOGLOBIN AA WOMEN
IN LAGOS, NIGERIA
NAME OF CANDIDATE:
DR. MONSURAT BOLANLE ADEROLU (MBBS)
NAME OF SUPERVISORS:
Assoc. Prof. B. B. AFOLABI (FRCOG, FWACS, FMCOG, DM [Notts]) Department of Obstetrics & Gynaecology
Lagos University Teaching Hospital
DR A. A. OLUWOLE (MBBS, FMCOG, FWACS) Department of Obstetrics & Gynaecology
Lagos University Teaching Hospital
6
CONFLICT OF INTEREST
I hereby declare that there was no conflict of interest in conducting this research,
be it in terms of material gain, favoured interactions and relationships or bias
which could influence judgement in the conduct of this research, in the data
collection, analysis or interpretation of the results.
..............................................
Dr. M. B. Aderolu
7
ABBREVIATIONS USED IN TEXT
ACT artemisinine combination therapy
ANC ante-natal care
ANOVA analysis of variance
EGA estimated gestational age
ELCS elective Caesarean Section
EMCS emergency Caesarean Section
e.t.c. et ce tra
HbAS Haemoglobin AS
HbSS Haemoglobin SS
IUFD intra-uterine fetal death
Kg kilogramme
LASUTH Lagos State University Teaching Hospital
LMP last menstrual period
LUTH Lagos University Teaching Hospital
MAP Mean Arterial Blood Pressure
8
NNU Neonatal Unit
NPMCN National Post-graduate Medical College of Nigeria
% Percentage
PCV packed cell volume
PPH Post-partum Haemorrhage
RR Risk ratio
SCD Sickle Cell Disease
S.D. Standard deviation
SGA Small for Gestational Age
SVD spontaneous vaginal delivery
USA United State of America
9
DEDICATION
To all sickle cell anaemic women who despite
the dangers pregnancy poses to their health
have the courage to embark on it, with the
uncertainty associated with it in terms of the
fetomaternal outcome.
-Monsurat Aderolu
10
A PROSPECTIVE STUDY COMPARING PREGNANCY
COMPLICATIONS AND OUTCOMES IN HAEMOGLOBIN SS AND
HAEMOGLOBIN AA WOMEN IN LAGOS, NIGERIA
ABSTRACT
Introduction: Sickle cell disease in pregnancy carries an increased risk of maternal and perinatal
morbidity and mortality. The complications that have been reported include anaemia, gestational
hypertension, preeclampsia, severe crisis, postpartum haemorrhage, pulmonary diseases, preterm
delivery, low birth weight, fetal distress in labour. Past studies have been limited by relatively
small sample sizes or retrospective data, narrow geographic area and use of hospital discharge
data. This study was prospective and compared the pregnant SS women with AA controls in
order to precisely identify the complications that these women undergo.
Aim: This study aimed at determining maternal and fetal complications and outcome of
pregnancy in HbSS and HbAA pregnant women and identified associated factors.
Methodology: Pregnant women were recruited from the antenatal clinics during booking and
follow-up clinics. Information about each was collected on a proforma and subjected to statistical
analysis using Epi info.
Results: This study found that complication rate is higher in the HbSS pregnant women than the
HbAA women. The commonest complications being vaso-occlussive (bone pain) crisis (32%),
pregnancy induced hypertension (28%), urinary tract infection (13%), malaria (18%) and
intrauterine growth restriction (16%) in the HbSS pregnant women. The average duration of
labour was longer in HbSS parturients than HbAA parturients (462.4 minutes and 428.2 minutes
11
respectively). There was no maternal death recorded in both arms in this study. The incidence of
low birth weight below 2.5Kg was 38% in HbSS and 4% in HbAA subjects. There was no
statistically significant relationship between average blood pressures and maternal complications.
However the overall maternal and perinatal outcome is comparable in both groups studied.
Conclusion: Although sickle cell disease poses higher obstetric risk in pregnancy, the maternal
and perinatal outcome can be as good as in the non-sickle cell disease pregnant women if
adequate and prompt health care is given to this group of women. Health education also needs to
be given to this group of women and the need to book early for antenatal care needs to be
emphasized.
Key words: Sickle cell disease, pregnancy complications, outcome.
12
INTRODUCTION
Preamble: It is estimated that 300,000 children are born each year with sickle cell disease
(SCD), with 75% of them living in sub-Saharan Africa.1 It is the most commonly inherited
disease worldwide and is predominant in certain ethnic groups particularly African and African-
American populations.
Background to research problem: The World Health Organization at the fifty-ninth world
health assembly in 2006 estimated that half of SCD patients in sub-Saharan Africa will die
before adulthood.1,2 In Nigeria, about 24% of the population carries the sickle cell trait and
approximately 150,000 children are born annually with sickle cell anaemia, with a prevalence of
2% of newborns affected by sickle cell aneamia.2 With progressive improvement in childhood
survival, and more women growing to adulthood, the burden of sickle cell anaemia in pregnancy
will increase.
Statement of research problem: Clinically, the hallmarks of sickling episodes are periods
during which there is ischaemia and infarction in various organs. These produce clinical
symptoms predominantly pain, which is often severe. SCD is a multi-systemic disorder as there
is ischemia and infarction in various organs.
Pregnancy is a serious burden to women with any of the major sickle cell haemoglobinopathies,
particularly those with haemoglobin SS disease.3 HbSS women are prone to maternal
complications during pregnancy, labour and puerperium. Several have been reported ranging
from anaemia, gestational hypertension, pre-eclampsia, severe crises, postpartum hemorrhage,
pulmonary diseases and infections as well as fetal complications like preterm delivery, low birth
weight, fetal distress in labour and increased perinatal mortality4,5. Although pre-eclampsia,
13
urinary tract infection and retained placenta were reported as being more common in some
studies;6,7 preeclampsia was not a predominant complication in one,8 while it was not identified
as a complication in an earlier study conducted in Lagos, Nigeria.9 Preeclampsia and urinary tract
infection were observed more in HbAS than HbSS women in other studies.7,10 A prospective
study would help clarify some of these discrepancies.
It has long been recognized that the blood pressure rises during labour.11,12,13 This is not
unexpected bearing in mind the stress that labour poses. In labour, there is an increase in
intravascular volume by 300 - 500mls of blood from the contracting uterus to the venous system.
Following delivery, this autotransfusion compensates for blood losses and tends to further
increase cardiac output by 50% of the delivery value. For those with heart disease and low
cardiac reserve, the increase in the work of the heart may cause ventricular failure and
pulmonary oedema.14 In HbSS individuals, several events such as vaso-occlusion, haemolysis
and sequestration with resultant increased destruction of red blood cells which already have
shorter life span than normal, predisposes them to a state of chronic anaemia and resultant
hypoxia. This hypoxic state leads to a reduction in after load with resultant tachycardia and
increase cardiac output, causing an increase in the work load of the heart leading to increased left
ventricular hypertrophy and an increased heart size.15 When blood pressure rises, the workload
on the heart worsens as the heart pumps against the elevated blood pressure in the blood vessels
further worsening the left ventricular hypertrophy which may lead to heart failure if untreated.
However blood pressure has been reported to be lower in HbSS individuals in general.16
14
Therefore this study will also check the average blood pressure in labour and relate it to
outcome.
Justification of the study: Knowledge of the likely factors like age, parity, socio-economic
class, that could predispose them to these common complications or worsen it will go a long way
in managing these patients. In this environment, most of the studies that have examined these
women have been either retrospective or low in power. An accurate determination of the
incidence of the different complications they encounter would be useful in planning prenatal,
intrapartum and postnatal care of these women.
AIM
To determine maternal and fetal complications and outcome of pregnancy in HbSS women and
identify associated factors.
OBJECTIVES
1. To compare incidence of complications such as urinary tract infection, chest infections, post
partum haemorrhage (PPH), hypertensive disorders in pregnancy, retained placenta, wound
infection, preterm births, low birth weight and stillbirth rates in HbSS and HbAA pregnant
women.
2. To compare the maternal and fetal outcome of HbSS with HbAA pregnant women.
3. To determine factors affecting the fetomaternal outcome in both groups such as age, parity,
gestational age at delivery and average blood pressure during labour.
15
Working hypothesis:
Haemoglobin SS has adverse effects on pregnancy. Therefore, the complication rates and
maternal and fetal outcome differ in pregnant haemoglobin SS and haemoglobin AA
pregnant women.
Alternate hypothesis:
There is no difference in the complication rates and pregnancy outcome of haemoglobin SS and
haemoglobin AA pregnant women.
16
LITERATURE REVIEW
Pregnancy is a serious burden to women with any of the major sickle haemoglobinopathies,
particularly those with haemoglobin SS disease.3
Epidemiology
Frequencies of the carrier state determine the prevalence of sickle cell anaemia at birth. About
5% of the world’s population carries genes responsible for haemoglobinopathies2 with the
highest prevalence among people of African, African-American, Mediterranean (Italian, Sicilian,
and Greek), Middle Eastern, East Indian, Caribbean, and Central or South American descent.17
Eight percent (8%) of African-American neonates in the U.S. are carriers of the sickle cell trait.18
In Nigeria, 24% of the population is a carrier of the mutant gene and the prevalence of sickle cell
anaemia is about 2% .2
Sickle cell anaemia (HbSS) is the commonest symptomatic haemoglobinopathy in Nigeria.19
It is also the most challenging in terms of frequency and severity of clinical manifestations.2,19
Women with sickle cell disease are at greater risk of morbidity and mortality in pregnancy. There
is also an increased risk of perinatal morbidity and mortality.8,19,20
The median age at death for women with sickle cell anaemia is 48 years,4 though a study
described patients followed from birth with 40% still alive at 60 to 87 years.21
Pathophysiology
Sickle cell anemia is a disease of the erythrocyte, a genetic disorder caused by an autosomal
recessive single gene defect in the ß-globin chain of HbA, which produces HbS.
17
HbS is formed by the substitution of valine for glutamic acid in position six of the ß-globin chain
of hemoglobin. Sickle cell anemia occurs if HbS is inherited from both parents (HbSS genotype).
Individuals who are homozygous for sickle cell hemoglobin (HbSS) have a constellation of signs
and symptoms that characterize sickle cell anemia.22-24
Erythrocytes containing mutant HbS have abnormal properties. Although the mutant ß-
hemoglobin subunits are normal in their ability to bind oxygen, they are considerably less
soluble in deoxygenated blood than normal hemoglobin. As such, and under conditions of low
oxygen tension, interaction between the abnormal valine residue and complementary regions on
adjacent molecules results in the formation of intracellular, rod-shaped polymers.25 These
abnormal hemoglobin polymers aggregate to disrupt the cytoskeleton and distort the shape of the
erythrocytes, making them brittle and poorly deformable. Thus, unlike normal erythrocytes, the
sickle-shaped cells cannot squeeze through the microcirculatory vessels, blocking blood flow and
resulting in local hypoxia. HbS is also injurious to the erythrocyte membrane, it disrupt the
attachment of the membrane to the protein cytoskeleton resulting in the exposure of trans-
membrane protein epitomes and negatively charged glycolipids that are normally found inside
the cell, which subsequently result into cellular dehydration, oxidative damage, increase
adherence to endothelial cells and the state of chronic inflammation and hemolysis.25
Repetitive cycles of sickling and polymerization however lead to membrane rigidity, and
irreversible sickle cells are eventually formed. These permanently damaged erythrocytes are then
cleared by the reticuloendothelial system. Thus, the average lifespan of the red blood cells of
sickle cell patients is 17 days compared with the 120-day lifespan of normal erythrocytes. This
results in a chronic haemolytic anaemia (haematocrit usually 20-30%) as the marrow’s capacity
to generate new red blood cells is limited.4,5,26
18
Diagnosis of sickle cell disease
Sickle cell disease can be diagnosed in newborns, as well as older persons by hemoglobin
electrophoresis, isoelectric focusing, high-performance liquid chromatography or DNA analysis.
In general, these tests have comparable accuracy. The testing method should be selected on the
basis of local availability and cost.
Solubility testing methods (Sickledex, Sick-lequik) and sickle cell preparations are inappropriate
diagnostic techniques. Although these tests identify sickle hemoglobin, they miss hemoglobin C
and other genetic variants. Furthermore, solubility testing is inaccurate in the newborn, in whom
fetal hemoglobin is overwhelmingly predominant. Solubility testing methods also fail to detect
sickle hemoglobin in persons with severe anemia.27 The sickling test is a solubility test used in
screening for sickle cell disease. It is done by adding two drops of 2% sodium metabisuphate to a
drop of blood on a slide and covering the slide with a cover slip and sealing the edges with
Vaseline to create deoxygenation. The slide is examined after 20 minutes. This test shows typical
sickling in HbSS, HbAS and HbSC patients.28,29 Haemoglobin Electrophoresis (diagnostic test) is
a method of determining the type and size of haemoglobin molecules in the blood, by observing
the rates of transit of these negatively-charged proteins in an electric field medium. It is used to
diagnose the haemoglobinothies.30 It is a blood test, and requires a few millilitres of blood from a
vein. DNA analysis provides the most accurate diagnosis in patients of any age, but it is still
relatively expensive.31
Events during pregnancy
The steady state haemoglobin level, which normally varies within a narrow range characteristic
of individual patients, falls during pregnancy reaching the lowest levels between 32 and 34
19
weeks. This fall was found to be more pronounced in sickle cell anaemia.32 The most common
manifestation of sickle cell disease is the acute painful crisis which occurs secondary to vaso-
occlusion. These painful crises can be precipitated by infection, stress, dehydration and cold
damp conditions. There is an increased risk of painful crisis during pregnancy, especially in the
latter half of pregnancy and the puerperium , and may even occur in women who have previously
had very few episodes of sickle pain.4,26,28 Data from the Cooperative study 6 (a prospective study
of the clinical course of sickle cell disease and differences among genotypes in event rates) were
at variance with these observations; this study found that painful crisis occurred in 50% of SS
pregnant mothers but that this rate did not differ from their non-pregnant experience.
Acute chest syndrome is a sudden onset of pleuritic chest pain and dyspnoea that mimics
pneumonia or pulmonary embolism and reported to occur commonly in pregnancy.4 The
syndrome arises due to sickling in the lungs, possibly combined with precipitants like infection,
marrow emboli, thromboembolism, or atelectasis. Although there are thought to be many causes,
the underlying features are not totally understood.4,26,33 The combination of albuminuria and
systolic hypertension occurring during a bone-pain crisis was recognized as having serious
significance and subsequently designated pseudotoxaemia.34 This should not be misdiagnosed as
pre-eclampsia.
In the cooperative study, eclampsia was reported in 1 per cent and pre-eclampsia in 14 per cent
of pregnancies in sickle cell disease women.6 A recent meta-analysis established an association
between sickle cell disease and pre-eclampsia.35 Pre-eclampsia is a disease of unknown
aetiology. However, some theories have been postulated which include endothelial damage,
inflammation, compromised placenta perfusion, decreased glomerular filteration rate, decreased
intravascular volume, increased central nervous system irritability and increased thromboxane A2
20
–prostacyline ratio.36,37 Most of these aetiological factors occur in HbSS patients and this might
explain why they are more likely to develop pre-eclampsia or have an exacerbation of pre-
eclampsia. However, some studies found little or no relationship between sickle cell disease and
pre-eclampsia.8,9,38,39,40,41 This might be due to smaller sample sizes, selection criteria or
geographical variations.
Clarifying an association of pre-eclamptic toxaemia with SS disease would require a large series
of patients matched with AA controls for all the factors known to be relevant to the development
of pre-eclamptic toxaemia, and consistent definitions of both pre-eclamptic toxaemia and the
pseudotoxaemia syndrome.
Other acute changes from sickling that may also occur in pregnancy include bony abnormalities
such as osteonecrosis of the femoral and humeral heads, renal medullary damage,
autosplenectomy, (and splenomegaly in other variants), hepatomegaly, ventricular hypertrophy,
pulmonary infarction, pulmonary hypertension, cerebrovascular accidents, leg ulcers and an
increased predisposition to infection and sepsis, especially due to encapsulated organisms such
as Streptococcus pneumoniae and Haemophilus influenzae.4,26,42
Blood transfusion is often necessitated in a number of HbSS patients because of anaemia which
may become severe sometimes. Occasionally exchange blood transfusion may become necessary
in those with severe vaso-occlusive crises and acute chest syndrome. The reason for exchange
transfusion is to decrease the concentration of HbS, thus increasing the overall oxygen-carrying
capacity of the blood, which will reduce the chances of sickling and therefore tissue damage,
without increasing viscosity. Exchange transfusion is usually preferred in the acutely unwell
patient with the sickle cell syndromes.19 However, controlled clinical trials on sickle cell
21
anaemia which have assessed the use of blood transfusion in the management of pregnancy, have
shown no beneficial effect on perinatal outcome, though there was a reduction in pain in the
transfused group.5,44
Delivery
Most deliveries should be by the normal vaginal route.8,9 Caesarean section has been advocated
for obstetric indications, disproportion due to pelvic outlet deformity and is increasingly used in
an attempt to decrease the high fetal wastage in deliveries and in complications.7 Deliveries have
also been reported to be complicated by retained placenta and still birth.43,45
Pregnancy outcome
Reports of maternal and fetal deaths continue to alternate with descriptions of entirely uneventful
pregnancies. Low and middle income countries generally report increased maternal and perinatal
morbidity and mortality in association with SCD,8,9, 35 Studies in high income countries generally
report more favourable fetal outcomes without appreciable risk for increased maternal
morbidity.6,39
A study carried out in the USA suggests that pregnancy in SCD is well tolerated by all the major
genotypes and the outcome of pregnancy in women with SCD is usually favourable. It was found
that infants born of SS pregnant women although at risk of being SGA, appear to be healthy. In
the study, pre-eclampsia and acute anaemia were identified as risk factors for SGA and high
hemoglobin F levels in the mother appear to protect against SGA infants.6
Another study done also in the USA where the prevalence of maternal complications among
intrapartum and postpartum women with SCD were compared with those without SCD in a large
22
geographically diverse sample found that women with SCD have increased prevalence of
pregnancy complications like deep vein thrombosis, pulmonary embolism, obstetric shock and
sepsis even when compared with a group of women with similar risk for multiple organ failure.46
A recent study done in Tanzania found very alarming maternal mortality with an incidence of
1149 death per 100,000 deliveries compared with 439 per 100,000 deliveries for non SCD. These
excessive maternal deaths were mainly attributable to infection. This study found no statistically
significant difference in prematurity rate and gestational age at delivery among SCD and non
SCD.47
A retrospective 10-year study of morbidity and pregnancy outcomes associated with sickle cell
anaemia among Saudi women found major maternal complications in the SCD group to be
anaemia, sickle cell crisis with bacterial infections and perinatal mortality rate of 77.7 per 1000
deliveries.48
A study of perinatal outcome in pregnancy with sickle cell disease done in India showed that
vaso-occlusive crisis, anaemia and pre-eclampsia were main maternal complications which led to
more preterm and caesarean deliveries, requiring more Neonatal intensive care unit admission.
Intrauterine growth restriction, intrauterine fetal death, prematurity and low APGAR scores were
found as main fetal complications in this study. Incidence of low birth weight was 100% in the
SS group.7
Placental abruption, retained placenta and pre- and postpartum infections have also been reported
to be high in a Norwegian study on pregnancy and sickle cell disease reported in the Hematology
and Oncology clinics of North America. In this study, morbidity rate was found to be high and to
include conditions such as pre-eclampsia.43
23
A similar study done on outcome of pregnancy in Jamaican women with homozygous sickle cell
disease reported retained placenta as being more common in these groups and more spontaneous
abortion.38 Yet another study done in USA on clinical care of adult patients with sickle cell
disease, showed that 29.5% of sickle cell disease pregnancies were complicated by miscarriage,
still birth or ectopic pregnancy.45
Other studies done in Nigeria had maternal death of four each out of seventy-five and sixty given
a percentage of 5.3 and 6.6 respectively.8,9 and blood transfusion was necessary in 40% and 34%
respectively in HbSS patients.8,49 One of the studies had a grandmultiparous sickle cell anaemic
patient.49
24
METHODOLOGY
STUDY DESIGN
This was a prospective comparative study of HbSS and HbAA pregnant women with no other
medical conditions conducted between October 2014 and December 2015.
STUDY LOCATION
The study was conducted at the Obstetrics Department of Lagos University Teaching Hospital
Idi Araba, Lagos State and the two General Hospitals (located at Isolo and Ifako-ijaiye) being
utilized by the Obstetrics and Gynaecology department of the Lagos State University Teaching
Hospital, Ikeja. Pregnant women were recruited from the antenatal clinics during booking and
follow-up clinics.
SAMPLE SIZE DETERMINATION
Considering the prevalence of sickle cell disease in pregnancy to be 2% in Nigeria from previous
study,2 and prevalence of pseudotoxaemia and post partum haemorrhage (PPH) to be 1.3% and
1.9% respectively in an earlier study in Nigeria,8 the minimum sample size for this study was
calculated as shown below using the formula.50
n = z2pq
d2
Where:
n = the desired sample size.
25
z = the standard normal deviate (usually 1.96) which corresponded to
95% confidence level.
p = the proportion of target population estimated to have a particular
characteristics (2% in this case which was equivalent to 0.02).
q = 1.0 – p (which was 1.0 – 0.02 = 0.98 in this case).
d = the degree of accuracy desire (usually 0.05).
Therefore, substituting the above figures in the formula,
n = (1.96)² X 0.02 X0.98
(0.05)²
= 30
Hence a minimum sample size of 30 was required to give an appreciable statistical power to this
study. However taking 20% attrition into consideration which was equal to 6, the required
sample size was thus 30+6=36. In this study, a total sample size of 100 was used, of which 50
were pregnant women with HbSS and 50 were HbAA pregnant women who served as controls.
SELECTION OF PATIENTS
The study population consisted of pregnant women who register and have antenatal care and
delivery at the hospitals mentioned above. Every consenting HbSS pregnant woman that met the
criteria was recruited into the study. Similarly, HbAA pregnant women matched for age, parity
and gestational age at booking were recruited at each antenatal clinic as controls.
Selection based on age was done using age grouping as follows: 16-20, 21-25, 26-30, 31-35, 36-
40, 41-45 years. Parity was categorized as follows: Para 0, Para 1, Para 2-4 and Para 5 and
26
above. Gestational age at booking was grouped as follows: 16 and below, 17-20, 21-24, 25-28,
29-32, 33-36, above 36 completed weeks.
Where more than one participant in an antenatal clinic qualified as control for a particular case,
the final selection was done by simple balloting.
Inclusion criteria
1. Pregnant women between the age range 18 years to 45 years.
2. Women who gave written consent.
3. Pregnant women with genotype HbSS and HbAA diagnosed in LUTH and LASUTH.
Exclusion criteria
1. Women with diabetes mellitus, renal failure, heart diseases, chronic essential
hypertension, human immunodeficiency virus positive and other medical disorders.
2. Women who did not give informed consent.
3. Women with multiple gestations.
STUDY PROCEDURE AND DATA COLLECTION
participants were recruited at booking. Data was collected using a well structured questionnaire
administered by the investigator, to obtain participants’ personal information. The participants
were informed about the purpose of the study and written consent obtained. Thereafter, their
phone numbers were collected and the investigator’s phone number was given to the participants.
The participants were informed to give a call anytime they are admitted into the hospital. They
27
were also called every week to see how they were doing. They were seen in the labour ward to
get other information from them and from their case notes whenever they were on admission.
This information included the antenatal visits, packed cell volume progression, any previous
crisis and treatment for urinary tract infection, chest infection, anaemia, e.t.c. While in labour,
their blood pressures were measured using a digital blood pressure monitor. Blood pressure was
recorded in the first and second stages of labour, immediate post-partum and 6 hours post-
partum. They were further seen in the postnatal ward for further information.
The primary outcome measures were major obstetric-related complications including
hypertensive disorders in pregnancy, post-partum haemorrhage, intrauterine growth restriction
(IUGR), retained placenta and intrauterine fetal death; sickling-related complications such as
vaso-occlusive, acute chest syndrome, pseudotoxaemia and hemolytic crisis; medical disorders in
pregnancy like urinary tract infection, malaria, severe anaemia and vaginal candidiasis; maternal
mortality and perinatal mortality. A complication is defined as a disease or injury that develops
during the treatment of a pre-existing disorder.51 The secondary outcome measures were non-
obstetric related complications like wound status and incidence of puerperal complications like
breast engorgement; maternal indices like admission frequency during pregnancy, duration of
labour, caesarean section rate and blood loss at delivery; perinatal indices like birth weight,
APGAR score, incidence of stillbirth and neonatal unit (NNU) admission rate. Birth asphyxia is
defined as an insult to the fetus or newborn due to failure to breath or breathing poorly, leading
to decrease oxygen to various organs52 and is represented by an APGAR score of 6 and below in
this study.
28
DATA ANALYSIS:
All data collected were subjected to statistical analysis using Epi Info statistical package, version
3.5.1. Student t-test, ANOVA, chi-square test and kruskal-wallis test were used where
applicable. A p-value of less than 0.05 was considered to be statistically significant.
QUALITY ASSURANCE
I ensured all recruited participants in the study fulfilled the eligibility criteria.
I ensured that these women were well monitored on phone for necessary information.
I ensured that the control group was properly matched.
ETHICAL CONSIDERATION
This study was approved by the Health Research and Ethics Committee of the Lagos University
Teaching Hospital (Approval number ADM/DCST/HREC/1768) and the Health Service
Committee for Lagos State Hospitals to utilize Lagos State University Teaching Hospital
(LASUTH) patients. Participants were only recruited after giving informed written consent.
Informed consent to participate and withdrawal from study
The purpose of the study was explained to all the potential participants. The volunteers signed an
informed consent form. They were informed of their freedom to withdraw or refuse to partake in
the study without prejudice to their usual expected standard of care.
29
Confidentiality of data
All information including history, physical findings and results obtained from the participants
were kept strictly confidential. The participants were assured that their identity will be kept in
confidence by the investigator.
Beneficence of the study
The results obtained from this study will help in formulation of evidence-based policy for
optimal management of sickle cell anaemia in pregnancy and in puerperium.
Non-Malficence
This study did not include any form of interventional measures that was harmful to the women,
either then or in the future.
Justice
The participants continued to enjoy equal attention and optimal care throughout this study.
Method of participants’ selection was scientifically objective and ensured fairness.
Dissemination of Findings
The results of this study are hereby submitted as part fulfillment of the requirements for the Part
II Fellowship examination of the Faculty of Obstetrics & Gynaecology of the National
postgraduate Medical College of Surgeon. Information obtained will be given to medical staff
and patients in the antenatal clinic and wards as part of continuing education and protocols can
be developed from these findings also. The study will also be sent for publication after award of
the fellowship.
30
LIMITATIONOF THE STUDY
1. There was the possibility that some participants may already have chronic undiagnosed
medical conditions.
2. Some of the outcome measures such as estimated blood loss at delivery are subjective
and liable to observer error.
JOB DESCRIPTION
At the antenatal clinic and ward, I was involved in recruiting subjects for the study, review of
records and administering questionnaires. Measuring their blood pressure.
31
RESULTS
Sociodemographic characteristics of study population: A total of 100 participants
were studied, of which 50 were HbAA and 50 HbSS. They were predominantly married
women (96% of HbAA and 92% of HbSS), with mean age ± S.D. of 29.8 ± 4.19 years for
HbAA and 29.8 ± 5.09 years for HbSS. There was no statistically significant difference in
both groups studied in terms of age group (p = 0.9997), social class (p = 0.3922) and parity
(p = 0.9610) in both groups studied. A greater proportion of participants (90%) booked after
16 weeks gestational age. Table I summarizes the sociodemographic characteristics of the
two groups studied.
Incidence of complications in HbSS and HbAA pregnant women: Complication rate in
pregnancy was 38% for HbAA and 92% for HbSS participants and this difference was
statistically significant (table II). The commonest complications amongst the HbSS pregnant
women were vaso-occlusive crisis (32.0% of HbSS), pregnancy induced hypertension
(28.0% of HbSS), urinary tract infection (26.0% of HbSS), malaria (18.0% of HbSS) and
intrauterine growth restriction (16.0% of HbSS). When compared with the HbAA sub-group,
it was observed that the following complications occurred more frequently amongst the
HbSS pregnant women: pregnancy induced hypertension (p = 0.0078), pre-eclampsia (p =
0.3588), intrauterine growth restriction (p = 0.0099), urinary tract infection (p = 0.0015),
upper respiratory tract infection (p = 0.2065), wound dehiscence (p = 0.2410), retained
placenta (p = 0.3588), malaria (p = 0.1239), preterm delivery (p = 0.0414) and post partum
haemorrhage (p = 0.7124), table III.
32
Maternal outcome in HbSS and HbAA pregnant women: Maternal outcome measures in
this study were number of admissions during pregnancy, complication rate, mode of delivery,
wound status following caesarean section, average duration of labour and maternal mortality
rate. The average blood loss at delivery was significantly higher in HbSS group parturients
compared to their HbAA counterparts, the mean value ± S.D. being 500.00 ± 461.32mls in
the HbSS and 302.00 ± 223.28mls in the HbAA participants (p = 0.0018). Table II
summarizes the maternal outcome in each group. Although there was no maternal death
reported in this study, it is worthwhile mentioning that 3 out of the pregnant women with
sickle cell anaemia who were managed in LUTH during the study period died from various
complications, specifically acute chest syndrome, cardiomyopathy and septicaemia
respectively. These 3 women were not recruited for this study as they did not meet the
inclusion criteria. One of them had twin gestation and cardiomyopathy, another was
unbooked and the third had a pre-existing hypertension.
Blood pressure pattern in HbSS and HbAA pregnant women during labour and early
puerperium: Mean systolic blood pressure drops slightly and progressively during labour
and puerperium in HbAA patients, whereas it rises progressively in labour and immediate
puerperium and then drops by 6 hours post partum in HbSS patients. The mean diastolic
blood pressure rises progressively in labour and early puerperium and then drops below the
value in first stage of labour in HbAA participantss, while it rises progressively but slowly all
through labour and early puerperium in HbSS participants. In the early puerperium in HbSS
women, the average mean arterial blood pressure (MAP) drops only slightly and is still
higher than the MAP in the first stage while in HbAA participantss, it drops below that of
first stag (Tables V and VI).
33
Fetal outcome in HbSS and HbAA pregnant women: Fetal outcome measures in this
study were APGAR score, fetal birth weight, admission rate into neonatal unit and perinatal
mortality rate. The HbSS pregnant women were more likely to deliver at a lower gestational
than their HbAA counterparts. The mean ± S.D. of gestational age at delivery was 36.95 ±
2.22 weeks in HbSS pregnant women and 38.25 ± 1.60 weeks in HbAA pregnant women and
this was statistically significant (p = 0.0032). The incidence of preterm delivery among the
HbSS was 28% in this study versus 10% for HbAA and this was statistically significant, p =
0.0414 (table II). Birth asphyxia is more likely to occur amongst babies of HbSS mothers
(table VII). The HbSS participants had significantly lighter babies (mean birth weight ± S.D.
of 2.58 ± 0.62Kg) compared to HbAA participants (mean birth weight ± S.D. of 3.27 ±
0.52Kg), p = 0.0000. The incidence of low birth weight below 2.5Kg was 38% in HbSS and
4% in HbAA participants, p = 0.0015. Incidence of neonatal unit admission was 42% for
babies of HbSS mothers and 4% for babies of HbAA mothers and this difference was
statistically significant, p = 0.0002. The risk ratio of the baby of an HbSS parturient being
admitted into the neonatal unit was found to be 1.65 times that of an HbAA woman (table
VII). The perinatal death rate was 2% in each group studied (table III). One intrauterine fetal
death was recorded in each group, both occurring preterm (32 weeks in the HbSS parturient
and at 34 weeks in the HbAA participants).
Factors affecting maternal outcome in HbSS and HbAA pregnant women: The
relationship between age, parity and gestational age at delivery versus maternal complication
rate was assessed. It was found that there was no statistically significant relationship between
age and maternal complication (p = 0.5439), parity and maternal complication (p = 0.7932)
and gestational age at delivery and maternal complication (p = 0.0642) when both groups
34
were assessed together. Maternal complication rate in HbSS women alone was found to be
unaffected by frequency of admissions in pregnancy (p = 0.4236), gestational age at delivery
(p = 0.3213), total duration of labour (p = 0.3326) and blood loss at delivery (p = 0.9313) in
this study. There was also no statistically significant relationship between maternal
complication in pregnant HbAA women alone when compared with frequency of admissions
in pregnancy (p = 0.2332), gestational age at delivery (p = 0.1479), total duration of labour (p
= 0.3559) and blood loss at delivery (p = 0.3707).There was no statistically significant
relationship between average blood pressures and maternal complication.
Factors affecting fetal outcome in HbSS and HbAA pregnant women: The relationship
between age, parity and gestational age at delivery versus perinatal outcome was also
assessed. It was found that was no statistically significant relationship between age and
perinatal outcome (p = 0.7248) and between parity and perinatal outcome (p = 0.0843) but
there was a statistically significant relationship between gestational age at delivery and
perinatal outcome when both groups were assessed together (p = 0.0004) and also when each
group was assessed alone (HbSS group, p = 0.0214 and HbAA group, p = 0.0000). Only
average diastolic blood pressure in first stage of labour has statistically significant
relationship with fetal outcome in both groups (p = 0.0038).
35
Table I: Sociodemographic characteristics of study population
PARAMETER HbAA, n = 50 HbSS, n = 50 Total ____
Age (years)
16 – 20 1 (2.0 %%) 1 (2.0%) 2 (2.00%)
21 – 25 7 (14.0 %%) 7 (14.0%) 14 (14.0%)
26 – 30 21 (42.0%) 21 (42.0%) 42 (42.0%)
31 – 35 16 (32.0%) 16 (32.0%) 32 (32.0%)
36 – 40 4 (8.0%) 4 (8.0%) 8 (8.0%)
41 – 45 1 (2.0%) 1 (2.0%) 2 (2.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100.0%)
ϰ2 = 0.1309, p = 0.9997
Marital status
Single 2 (4.0%) 4 (8.0%) 6 (6.0%)
Married 48 (96.0%) 46 (92.0%) 94 (94.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100%)
ϰ2 = 0.0000, p = 1.0000
Socioeconomic class
I 17 (34.0%) 14 (28.0%) 31 (31.0%)
II 10 (20.0%) 17 (34.0%) 27 (27.0%)
III 15 (30.0%) 15(30.0%) 30 (30.0%)
IV 8 (16.0%) 4 (8.0%) 12 (12.0%)
V 0 (0.0%) 0 (0.0%) 0 (0.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100%)
ϰ2 = 2.9964, p = 0.3922
Parity
0 15 (30.0%) 15(30.0%) 30 (30.0%)
1 23 (46.0%) 23 (46.0%) 46 (46.0%)
2 – 4 12 (24.0%) 12 (24.0%) 24 (24.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100%)
ϰ2 = 0.0797, p = 0.9610
Gestational age at booking
12 – 16 5 (10.0%) 5 (10.0%) 10 (10.0%)
17 – 20 19 (38.0%) 19 (38.0%) 38 (38.0%)
21 – 24 7 (14.0%) 7 (14.0%) 14 (14.0%)
25 – 28 8 (16.0%) 8 (16.0%) 16 (16.0%)
29 – 32 9 (18.0%) 9 (18.0%) 17 (17.0%)
33 – 36 2 (4.0%) 2 (4.0%) 4 (4.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100%)
ϰ2 = 2.0000, p = 0.9197
NOTE: Figures are presented as frequency percentage of individual group, p < 0.05 is considered to be statistically
significant. Grade I is the highest social class while grade V is the lowest social class.
36
Table II: Maternal outcome in HbAA and HbSS pregnant women
PARAMETER HbAA, n = 50 HbSS, n = 50 Total________
Number of admissions
0 39 (78.0 %%) 14 (28.0%) 53 (53.0%)
1 10 (20.0 %%) 22 (44.0%) 32 (32.0%)
2 1 (2.0%) 9 (18.0%) 10 (10.0%)
3 0 (0.0%) 5 (10.0%) 5 (5.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100.0%)
ϰ2 = 21.1418, p = 0.0001
Mode of delivery
ElC/S 9 (18.0%) 6 (12.0%) 15 (15.0%)
EmC/S 8 (16.0%) 34 (68.0%) 42 (42.0%)
Forceps 1 (2.0%) 0 (0.0%) 1 (1.0%)
SVD 32 (64.0%) 10 (20.0) 42 (42.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100.0%)
ϰ2 = 24.2264, p = 0.0000
Complication rate
Yes 19 (38.0%) 46(92.0%) 65 (65.0%)
No 31 (62.0%) 4 (8.0%) 35 (35.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100.0%)
ϰ2 = 24.2308, p = 0.0000
Wound status post-caesarean section
Satisfactory 17 (100.0%) 37 (92.5%) 54 (94.7%)
Wound dehiscence/infection 0 (0.0%) 3 (7.5%) 3 (5.3%)
Total 17 (100.0%) 40 (100.0%) 57 (100.0%)
ϰ2 = 23.4818, p = 0.2410
Mean duration of labour (minutes)
1st stage 402.81 458.00 p = 0.2085
2nd stage 12.96 51.25 p = 0.0004
3rd stage 13.35 10.89 p = 0.2260
Total duration 428.15 462.38 p = 0.3457
Gestational age at delivery (weeks)
28 - 36 5 (10.0%) 14(28.0%) 19 (19.0%)
37 - 42 45 (90.0%) 36 (72.0%) 81 (81.0%)
>42 0 (0.0%) 0 (100.0%) 0(0.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100.0%)
ϰ2 = 4.1585, p = 0.0414
NOTE: Figures are presented as frequency percentage of individual group, p < 0.05 is considered to be statistically
significant.
37
Table III: Incidence of non-sickling related complications in HbAA and HbSS pregnant
women
COMPLICATIONS HbAA, n = 50 HbSS, n = 50 Total
Preterm delivery 5 (10.0%) 14 (28.0%) 19 (19.0%)
Pregnancy induced hypertension 3 (6.0%) 14 (28.0%) 17 (17.0%)
Urinary tract infection 1 (2.0%) 13 (26.0%) 14 (14.0%)
Malaria 3 (6.0%) 9 (18.0%) 12 (12.0%)
Intrauterine growth restriction 0 (0.0%) 8 (16.0%) 8 (8.0%)
Post-partum haemorrhage 3 (6.0%) 5 (10.0%) 8 (8.0%)
Upper respiratory tract infection 1(2.0%) 5 (10.0%) 6 (6.0%)
Pre-eclampsia 1 (2.0%) 4 (8.0%) 5 (10.0%)
Retained placenta 1 (2.0%) 4 (8.0%) 5 (5.0%)
Vaginal candidiasis 1 (2.0%) 3 (6.0) 4 (4.0%)
Eclampsia 1 (2.0%) 3 (6.0%) 4 (4.0%)
Breast engorgement 3 (6.0%) 1 (2.0%) 4 (4.0%)
Wound dehiscence/infection 0 (0.0%) 3 (6.0%) 3 (3.0%)
Preterm contractions 1 (2.0%) 1 (2.0%) 2 (2.0%)
Intrauterine fetal death (IUFD) 1 (2.0%) 1 (2.0%) 2 (2.0%)
Acute kidney injury 0 (0.0%) 2 (4.0%) 2 (2.0%)
Osteomyelitis 0 (0.0%) 1 (2.0%) 1 (1.0%) Asymptomatic bacteriuria 0 (0.0%) 1 (2.0%) 1 (1.0%)
Cardiomyopathy 0 (0.0%) 1 (2.0%) 1 (1.0%)
Pneumonia 0 (0.0%) 1 (2.0%) 1 (1.0%)
Abruptio placentae 0 (0.0%) 1 (2.0%) 1 (1.0%)
HELLP syndrome 0 (0.0%) 1 (2.0%) 1 (10.0%)
Fetal hypospadia 1 (2.0%) 0 (0.0%) 1 (1.0%)
Gluteal abscess 0 (0.0%) 1 (2.0%) 1 (1.0%)
Preterm rupture of membrane 0 (0.0%) 1 (2.0%) 1 (1.0%)
NOTE: Figures in paracentesis and in black are presented as frequency percentage of individual group.
Table IV: Incidence of sickling related complications in HbSS pregnant women
COMPLICATIONS HbSS, n = 50
Vaso-occlusive crisis 16 (32.0%)
Acute chest syndrome 3 (6.0%)
Pseudotoxaemia 3 (6.0%)
Sequestration crisis 1 (2.0%)
Haemolytic crisis 1 (2.0%)
Severe anaemia 1 (2.0%)
NOTE: Figures in paracentesis and in black are presented as frequency percentage.
38
Table V: Blood pressure pattern in labour and early puerperium in HbAA pregnant
women
Average blood pressure in HbAA in labour and
puerperium
Systolic
(mmHg)
Diastolic
(mmHg)
MAP
(mmHg)
1st stage 127 78 94
2nd stage 126 79 95
Immediate post-partum 125 81 95
6 hours post-partum 121 75 88
Table VI: Blood pressure pattern in labour and early puerperium in HbSS pregnant
women
Average blood pressure in HbSS in labour and puerperium Systolic
(mmHg)
Diastolic
(mmHg)
MAP
(mmHg)
1st stage 125 73 90
2nd stage 126 75 92
Immediate post-partum 132 78 96
6 hours post-partum 128 79 95
39
Table VII: Fetal outcome in HbAA and HbSS pregnant women
PARAMETER HbAA, n = 50 HbSS, n = 50 Total ________
APGAR score at 1 minute
0 – 3 0 (0.0%) 4 (8.2%) 4 (4.1%)
4 – 5 2 (4.1%) 11 (22.4%) 13 (13.3%)
6 3 (6.1%) 10 (20.4%) 13 (13.3%)
7 – 10 44 (89.8%) 24 (49.0) 68 (69.4%)
Total 49 (100.0%) 49 (100.0%) 98 (100%)
ϰ2 = 23.4818, p = 0.0000
APGAR score at 5 minutes
0 – 3 0 (0.0%) 0 (0.0%) 0 (0.0%)
4 – 5 0 (0.0%) 0 (0.0%) 0 (0.0%)
6 0 (0.0%) 5 (10.2%) 5 (5.1%)
7 – 10 49 (100.0%) 44 (89.8) 93 (94.9%)
Total 49 (100.0%) 49 (100.0%) 98 (100%)
ϰ2 = 23.4818, p = 0.0000
Fetal birth weight (Kg)
1.00 – <1.50 0 (0.0%) 3(6.0%) 3 (3.0%)
≥1.50 – <2.50 2 (4.0%) 16 (32.0%) 18 (18.0%)
≥2.50 – <4.00 43 (86.0%) 31 (62.0%) 74 (74.0%)
≥4.00 5 (10.0%) 0 (0.0%) 5 (5.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100%)
ϰ2 = 15.4395, p = 0.0015
Admission into neonatal unit
Yes 2 (4.0%) 21 (42.0%) 23 (23.0%)
No 48 (96.0%) 29 (58.0%) 77 (77.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100%)
ϰ2 = 13.5289, p = 0.0002, RR = 1.6522
Perinatal outcome
Alive 49 (98.0 %%) 49 (98.0%) 98 (98.00%)
Dead 1 (2.0 %%) 1 (2.0%) 2 (2.0%)
Total 50 (100.0%) 50 (100.0%) 100 (100.0%)
Fisher exact test, p = 0.7532
NOTE: Figures are presented as frequency percentage of individual group, p < 0.05 is considered to be statistically
significant.
40
DISCUSSION
It was found in this study that complication rate is higher in the HbSS pregnant women
compared to their HbAA counterpart. An earlier study conducted at the Lagos University
Teaching Hospital, Lagos,Nigeria by Odum CU et al9 between 1995 – 1997 found a
complication rate of 96.6% in pregnant HbSS women. These findings thus emphasize the fact
that pregnancy in HbSS women is high risk, especially in this environment.
The commonest complications in HbSS pregnant women as was observed in this study were
vaso-occlusive (bone pain) crisis (32%), pregnancy induced hypertension (28%), urinary tract
infection (26%), malaria (18%) and intrauterine growth restriction (16%). The incidence of bone
pain crisis in this study is slightly higher than was reported in earlier study by Afolabi BB et al at
Lagos University Teaching Hospital, in 1996 – 2000 (25.3%),8 but much lower than the
incidence reported by Cardoso PSR et al (77.8%).40
We found that pregnancy induced hypertension, pre-eclampsia, intrauterine growth restriction,
urinary tract infection, retained placenta and malaria occurred more frequently among the HbSS
pregnant women compared to their HbAA counterpart. This observation is similar to findings in
other studies.9,38 One of the cases of pre-eclampsia in the HbSS group was complicated with
HELLP syndrome. This finding is consistent with other reports in the literature.8,53 Malaria is
common in HbSS individual because the vast majority of sickle cell disease patients live in
underdeveloped nations with high prevalence and transmission rates of infections, they tend to
have lower immunity and do have autosplenectomy resulting from recurrent vaso-occlusive
infarcts within the spleen and are thus generally more prone to infections.54 More so chronic
transfusion therapy which is often indicated in treatment of sickle cell disease complications
41
such as severe anemia and acute chest syndrome also predisposes them to transfusional
malaria.54 The increased risk of IUGR in HbSS pregnant women could be caused by chronic
maternal anaemia and increased blood viscosity or degree of sickling and vaso-occlussion in the
placenta circulation with resultant chronic hypoxia and placental insufficieny. 55
A study done in Saudi Arabia has also corroborated a finding of 3 out of 57 HbSS participants
(5.26%) with acute chest syndrome in pregnancy which is also similar to the finding in this study
(3 out of 50).41 However, studies done in Bahrain in Brazil and USA found lower incidences of
1.2% and 0.06% respectively.56 The co-operative study reported a higher incidence of acute chest
syndrome in the general non-pregnant population, being 12.8% in the HbSS individuals and
5.5% in the HbSC; the peak incidence being between the age 2 and 4, with an incidence of
25.3% in children and 8.8% in adults. 57 The findings of the co-operative study is contrary to the
expectation that acute chest syndrome may be commoner in the pregnant than non-pregnant
sickle cell disease women because of the changes that occur in the cardiovascular system in
pregnancy and the fact that pregnancy suppresses immunity predisposing to higher risk of
infection. No study was found in the literature to have reported the incidence of acute chest
syndrome in strictly non-pregnant women of reproductive age group. The reason for this
difference is thus not clear cut and this calls for further research. The participants who developed
acute chest syndrome in this study were admitted to the intensive care unit, managed by partial
exchange blood transfusion, oxygen supplementation, good hydration, antibiotics coverage and
aggressive pulmonary therapy.
The HbSS women are more likely to deliver preterm compared to their HbAA counterparts
probably because of a higher complication rate in them which may necessitate early delivery. A
42
recent meta-analysis found that there was a more than 2 fold increased risk in preterm delivery in
women with HbSS compared to women without sickle cell disease.35
Unlike several studies that have reported increased incidence of spontaneous miscarriages, still
birth and ectopic pregnancy in HbSS pregnant women, this study did not record any of these
complications.7,38,45 This is probably because the women studied booked after the first trimester
above 16 weeks, when the risk of spontaneous miscarriages and ectopic pregnancies are less. The
fact that they were all booked patients might explain why none of them had stillbirth. This study
also found that the HbSS parturients are more likely to have stable haematocrit post-partum
probably because of the low threshold for blood transfusion in this category of women after
delivery even before they become haemodynamically unstable. This practice is reflected in this
study by the higher incidence of blood transfusion in the HbSS women compared to their HbAA
counterparts (26% versus 4%).
This study did not report any maternal death unlike previous studies6,7,8,9,53 probably because of
the selection criteria which excluded high risk pregnant women with other co-morbidites except
sickle cell disease. More so, the participants recruited were all booked and managed in tertiary
institutions where they have access to multidisciplinary care.
In this study, there is no increased risk of IUFD in both groups which is similar to findings in
previous recent studies41,58, probably due to improved antenatal care, fetal monitoring and
prompt intervention. Low birth weight is one of the most consistent findings in neonates born to
mothers with sickle cell disease7,59,60. Almost half of the neonates in this study were low birth
weight which reflected in the number of neonatal unit admissions. This study showed that HbSS
pregnant women are more likely to have babies with birth asphyxia according to APGAR scores.
43
An improvement in the 5-minuteAPGAR score in both groups is a reflection of the neonatal care
offered to these groups of people as they were managed in tertiary institutions. There was no
neonatal death reported in both groups studied.
Contrary to earlier reports that blood pressure tend to be lower in HbSS individuals16, this study
found that mean systolic, diastolic and mean arterial blood pressures increase slightly in labour
and early puerperium in HbSS women, hence, the need to be more careful in this group of
women in labour knowing that the increase in the work of the heart that occurs in labour due to
the increased intravascular volume from the contracting uterus to the venous system may cause
ventricular failure and pulmonary oedema for those with underlying heart disease and low
cardiac reserve. Whereas systolic blood pressure falls in HbAA pregnant women in labour and
immediate puerperium while there is a slight increase in the mean diastolic blood pressure and
average mean arterial blood pressure. Bearing in mind the fact that systolic blood pressure is
commonly affected by emotional issues, anixiety and stress, the increase in systolic blood
pressure in labour and immediate puerperium in the HbSS parturient may be attributable to the
higher level of anxiety and stress that labour and delivery poses on this group of women. This
finding further emphasizes the need to shorten second stage of labour in this group of parturient.
Despite the increased complication rates reported among HbSS pregnant women compared to
their HbAA counterpart as reported in this study, the overall maternal and early perinatal
outcomes were comparable. Despite the increased risk of complications in HbSS pregnant
women reported generally in most studies, Sun PM et al39 in a study also found no significant
difference in perinatal outcome of HbSS compared to HbAA individual and there was no
maternal death reported in the study. However, it is important to be vigilant at all times while
managing HbSS pregnant women as complications can arise at anytime. Preconception care
44
should be emphasized for this category of women (HbSS pregnant women) and multidisciplinary
approach and prompt intervention are highly recommended to minimize perinatal and maternal
deaths.
CONCLUSION:
Although sickle cell disease poses higher obstetric risk in pregnancy, the maternal and perinatal
outcome can be as good as in the non- sickle cell disease pregnant women if adequate and
prompt health care is given to this group of women.
Comprehensive care may promote awareness of Sickle Cell Disease among affected women to
present early for booking, assessment and management of symptoms.
It is hoped that the results of this study will contribute to the existing knowledge about Sickle
Cell Anaemia in pregnancy and help to strengthen the monitoring, management and follow up of
this group of patient.
45
ACKNOWLEDGEMENT
I thank all my consultants for the knowledge they impacted on me and for their constructive
criticisms during the course of my training. My appreciation also goes to my past and current
Head of Departments, Prof. B. A. Oye-Adeniran and Prof. R. I Anorlu respectively.
I hereby express my sincere thanks to my supervisors for their patience in supervising and
reading my work. To Dr. B. B. Afolabi, for her kind and extra effort in enhancing my academics.
To Dr. A. A. Oluwole, for his understanding and guidance.
I will forever be grateful to Dr. O. A. Babah, who has always been there for me, creating time
out of her tight schedule to read my works and offer guidance since the beginning of my
residency programme. I thank her for her contributions towards my professional upliftment.
I am primary indebted to my parents Dr and Mrs I. A. Tijani for their love, support and inspiring
encouragements over the years. I also thank my husband for his love, persistent motivation and
understanding. I thank my children for their endurance whenever I am away from home during
the course of my residency training. I sincerely appreciate my cousin Muslima, who has been a
trusted caregiver to my children whenever I am not around in the course of my residency
training.
I am grateful to my colleagues for sharing their experiences with me. My gratitude also go to the
matron in-charge of the antenatal clinic, CNO Lawal, the nurses and medical records officers in
the antenatal clinics for informing me of newly booked sickle cell anaemic patients. To all the
nursing staff in the labour ward and labour ward theatre especially matron Shittu for contacting
me on phone whenever the patients are admitted into the labour ward. To the nursing staff in the
46
neonatal unit for giving me information and update about the neonates of the recruited patients
admitted into their facililty.
To my colleagues at the Lagos State University Teaching Hospital (LASUTH), Dr Durojaiye and
Dr Jimoh who served as my contacts in the two General Hospitals utilized for this study.
Most especially I am grateful to the almighty God for everything.
47
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APPENDIX
CONSENT FORM
A PROSPECTIVE STUDY COMPARING PREGNANCY
COMPLICATIONS AND OUTCOMES IN HAEMOGLOBIN SS AND
HAEMOGLOBIN AA WOMEN IN LAGOS, NIGERIA
LUTH HREC Approval number ADM/DCST/HREC/1768
Dear Ma,
INTRODUCTION
This consent form contains information about the research named above. To ensure you are well
informed about your participation in this research, kindly read this consent form. In case there
are words that you do not understand, please ask us to explain. If you choose to participate in this
study, we would like you to sign this consent form.
REASON FOR THE RESEARCH
Pregnancy is a serious burden to women with any of the major sickle cell haemoglobinopathies,
particularly those with haemoglobin SS disease. HbSS women are prone to maternal
complications during pregnancy, labour and puerperium. . This study will compare the pregnant
SS women with AA controls in order to more precisely identify the complications that these
women undergo. Knowledge of the likely factors that could predispose them to these common
complications or worsen it will go a long way in managing these patients.
WHAT YOU NEED TO DO:
If you agree to be in this study, you will need to:
Sign this consent form
Answer some simple questions (will take about 10 minutes).
Allow your blood pressure to be measured when necessary.
53
Your case note will be accessed to retrieve information.
POSSIBLE RISKS
There is no danger to you or your baby from your participating in this study.
POSSIBLE BENEFIT
You will be told about the result if you so wish. You will also be contributing to knowledge
which may potentially benefit several women and their babies in the future.
CONFIDENTIALITY
We will protect information about you and your participation in this research to the best of our
ability. Your name or any personal information about you will not be made public or be in any
research report If you refuse any part of this examination, it will not affect the care that will be
provided in the future.
CONTACT INFORMATION
NAME: DR. M.B ADEROLU
DEPARTMENT: OBSTETRICS AND GYNAECOLOGY
PHONE NO: 08035507441
E-MAIL: [email protected].
LUTH Health Research Ethics Committee
Room 107, Administrative Block
Lagos University Teaching Hospital
54
VOLUNTEER AGREEMENT
I understand what I need to do to be part of this study titled “Prospective study of pregnancy
complications and outcome of haemoglobin SS women in Lagos” and all questions that I asked
have been answered.
I also understand that I can withdraw from the study at anytime without affecting any of the
medical benefits I require.
I hereby agree to participate in the study.
…………………………………….. ………………………………….
Name of Participant Signature/Thumbprint of Participant
………………………………..
Date
……………………………….. ………………………………………
Name of Witness Signature of Witness and date
55
STUDY PROFORMA
A PROSPECTIVE STUDY COMPARING PREGNANCY
COMPLICATIONS AND OUTCOMES IN HAEMOGLOBIN SS AND
HAEMOGLOBIN AA WOMEN IN LAGOS, NIGERIA
LUTH HREC Approval number ADM/DCST/HREC/1768
Bio-data
Initials _____________________________
Hospital No ___________________________
Age ___________________________
Occupation
Husband ___________________ Wife ____________________
Educational status
Husband__________________ Wife ____________
Socio economic class i ii iii iii iv v
Tribe __________________________
Marital Status ___________________________
Parity ________________________________
LMP ________________________________
Booking status Booked Unbooked
Weight at Booking ________________
EGA at booking _____________
EGA at delivery _______________
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Index Pregnancy/ delivery history:
Was it spontaneously conceived; Yes No
No of gestation: I ii iii iv v
No of crisis in pregnancy
Infection in pregnancy/Acute crisis syndrome/number of admission
________________ __________________ _________________
Heamatinics ______________________
P C V progression ____________________
Mode of delivery SVD forceps vacuum
ELCS EMCS Destructive operation
Duration of labour
1st Stage _________________________hours
2nd Stage _________________________hours
3rd Stage _________________________hours
Total duration of labour ____________________ hours
Blood pressure in labour
1st Stage __________________________hours
2nd Stage __________________________hours
Immediate post partum _________________________________
6 hours post partum _____________________________________
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Drug use in labour and delivery
Ergot _________________________________
Oxytocin _______________________________
Misoprostol_____________________________
Analgesics______________________________
Others__________________________________
Episiotomy given? Yes No
Estimated blood loss _________________
Post partum PCV ____________
Blood transfusion? Yes No
Maternal Complications during pregnancy, delivery and puerperium (list)
1. …………………………………………
2. …………………………………………
3. …………………………………………
4. …………………………………………
5. …………………………………………
Fetal Outcome
Sex: Male Female
Outcome: Alive Dead
Fetal birth weight ______________________
If alive, was baby admitted in NNU? Yes No
APGAR 1min 5min
58
If dead, cause of death _______________________________________
Puerperium:
Breast feeding? Yes No
History of breast engorgement in puerperium: Yes No
Does patient have chronic hypertension? Yes No
Any other medical condition_________________________________________
If caesarean, wound status _______________________________________________
ANC Blood pressure
Lowest ______________________________________________
Highest _______________________________________________
Post partum blood pressure
Lowest______________________________________________
Highest______________________________________________