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: aderolu.monsurat@yahoo.com.

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______________________________________________