A Dissertation on
DIAGNOSTIC PERFORMANCE AND DISCRIMINATIVE VALUE OF SERUM FERRITIN IN PRETERM LABOUR AND PPROM
Dissertation submitted to
THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY CHENNAI-600032
With partial fulfillment of the requirements for the award of M.S.DEGREE IN
OBSTETRICS AND GYNECOLOGY (BRANCH VI)
COIMBATORE MEDICAL COLLEGE, COIMBATORE MAY 2020
UNIVERSITY REGISTER NUMBER : 221716306
DECLARATION
I Dr. SABARENAA THARINI.N solemnly declare that the dissertation entitled “DIAGNOSTIC PERFORMANCE AND DISCRIMINATIVE VALUE OF SERUM FERRITIN IN PRETERM LABOUR AND PPROM” is a bonafide work done by me at Coimbatore Medical College Hospital during the period of January 2018 to December 2018 under the guidance & supervision of Dr.R.MANONMANI M.D., DGO., Professor & Head of Department, Department of Obstetrics and Gynecology, Coimbatore Medical College & Hospital. The dissertation is submitted to Dr.MGR Medical University towards partial fulfillment of requirements for the award of MS degree branch VI Obstetrics and Gynecology.
Place: Coimbatore Dr. SABARENAA THARINI. N Date:
CERTIFICATE
This is to certify that the dissertation entitled “DIAGNOSTIC PERFORMANCE AND DISCRIMINATIVE VALUE OF SERUM FERRITIN IN PRETERM LABOUR AND PPROM” is a bonafide original work done by Dr. SABARENAA THARINI. N Postgraduate student in the Department of Obstetrics and Gynecology, Coimbatore Medical College Hospital, Coimbatore under the guidance of Dr.R.MANONMANI M.D., DGO., Professor & Head of Department, Department of Obstetrics and Gynecology, Coimbatore Medical College Hospital, Coimbatore in partial fulfillment of the regulations for the Tamilnadu DR.M.G.R Medical University, Chennai towards the award of MS., degree (Branch VI.) in Obstetrics and Gynecology.
Date : Prof.Dr.R.MANONMANI M.D DGO., Guide and HOD Department of Obstetrics and Gynecology
Date : Dr.B.Asokan, M.S., Mch.,
The Dean Coimbatore Medical College & Hospital Coimbatore
COPYRIGHT
Declaration by the Candidate
I hereby declare that The Tamilnadu DR.M.G.R Medical University, Chennai shall have the rights to preserve, use and disseminate this dissertation/thesis in print or electronic format for academic/research purposes.
Place: Coimbatore Dr. SABARENAA THARINI. N Date:
ACKNOWLEDGEMENT
I solicit my humble thanks to the Dean Dr.B.ASOKAN, M.S., Mch., Coimbatore Medical College Hospital, for allowing me to conduct the study in this hospital.
I am also immensely thankful to my guide Prof.
Dr.R.MANONMANI M.D., DGO., Professor & Head of Department, Department of Obstetrics and Gynecology, for her invaluable guidance, motivation and help throughout the study.
I express my earnest gratitude to all the Associate and Assistant Professors, Department of Obstetrics and Gynecology, without their help and guidance this work would not have been possible.
I owe a lot to my parents, my spouse Dr. M. Deepan Chakravarthy and other family members who have always been my pillar of support in all stages of my life.
My sincere thanks to my fellow post graduates who have been of immense help throughout the study period.
I am very grateful to all patients for their cooperation and participation in the study.
ABBREVIATION PTB - Preterm Labour
PPROM - Preterm Premature Rupture of Membranes NICU - Neonatal Intensive Care Unit
17P - 17 Alpha Hydroxyprogesterone Caproate AN OP - Antenatal outpatient department
IUD - IntraUterine death
GDM - Gestational Diabetes Melitus PIH - Pregnancy Induced Hypertension
Hb - Hemoglobin
WHO - World Health Organization SGA - Small for Gestational Age CRP - C-Reactive Protein
IL 6,2 - InterLeukin
TNF - Tumour Necrosis Factor
RR - Relative Risk
BMI - Body Mass Index fFN - Fetal Fibronectin
TVS - Trans Vaginal Sonography CDC - Center of Disease Control C/I - Contra Indication
ADR - Adverse Drug Reaction
GBS - Group B Streptococcal Infection
LIST OF FIGURES
S.No Figures Page
1 Features of preterm child 8
2 Outcome of preterm birth 10
3 Phenotypic components of preterm birth syndrome 13
4 Risk factors of preterm birth 14
5 Pathogenesis of infection leading to PTB 16
6 Mechanism of preterm birth 18
7 Cervical Malformations 21
8 Comparison of normal and short cervix 26
9 Fetal fibronectin 27
10 Fetal fibronectin levels throughout pregnancy 29
11 Intrauterine infection 30
12 Structure of ferritin 31
13 Amniotic fluid sludge 35
14 Secondary prevention of PTB 37
15 Cervical cerclage procedure 38
16 Cervical pessary 40
LIST OF TABLES
S.No Tables Page
1 Subcategories of preterm birth, based on gestational age
1
2 Progesterone formulation and dose for the prevention of PTB
42
3 CDC recommendations for clindamycin treatment of bacterial vaginosis in pregnancy
43
4 Pharmaceutical agents for tocolysis 45
5 Antenatal steroids for fetal lung maturation 47
6 Magnesium sulphate for neuroprotection 48
7 Antibiotic therapy in PPROM 51
8 Mean Age 53
9 Age distribution 53
10 Parity distribution 55
11 Distribution of Multi gravida among study group 56 12 Parity distribution among different age groups 57
13 Socio economic status 58
14 Distribution of multigravida in study group based on previous delivery
59
15 Distribution of PPROM 60
16 Association of Hemoglobin with parity 61
17 Association of Serum Ferritin with parity 62 18 Association of Gestational age with Hemoglobin 63 19 Association of Gestational age with serum ferritin 64
20 Association of Hemoglobin with PPROM 65
21 Association of Serum Ferritin with PPROM 66
22 Association of Hemoglobin with Socio economic status
67
23 Association of Serum Ferritin with Socio economic status
68
24 Association of Gestational age of present delivery with previous delivery
69
25 Association of multigravida in study group with Gestational age at present delivery
70
26 Association of multigravida in study group with previous delivery
71
TABLE OF CONTENTS
S.No Contents Page
1 Introduction 1
2 Aim and Objective of the study 4
3 Materials and methods 5
4 Review of literature 7
5 Observations and Results 53
6 Discussion 72
7 Limitations 76
8 Conclusion 77
9 Bibliography 10 Annexures
A – Proforma
B – Master chart
C – Consent form
ABSTRACT TITLE
DIAGNOSTIC PERFORMANCE AND DISCRIMINATIVE VALUE OF SERUM FERRITIN IN PRETERM LABOUR AND PPROM BACKGROUND AND OBJECTIVES
Preterm labour is defined as regular uterine contractions leading to cervical changes before 37 completed weeks of gestation. PTB should be distinguished from ‘prematurity’ which constitutes the deficiency of various system development at the time of birth. Preterm birth is responsible for 30-40% of neonatal mortality worldwide.
Almost 1 million children die each year due to complications of preterm birth. Survivors are left with lifetime disabilities such as learning and hearing disabilities. Identifying pregnant women at risk of preterm delivery will enable them an early access to tertiary care centres for the management of infections and respiratory distress. An action plan to avoid preventable newborn death includes World wide access to newborn resuscitation, low cost corticosteroids, Kangaroo mother care in place of incubator. Preterm premature rupture of membranes (PPROM) is defined as amniorrhexis before the onset of preterm labour.It is the leading cause of preterm birth. Rupture of membranes is caused due to activation of enzymes such as collagenase and other mechanical factors. But PPROM and preterm
labor appears to be linked to pathologic processes such as inflammation and infection of membranes. Many biomarkers are in study to predict preterm labour. Serum ferritin is one such marker . It is an intracellular protein that is involved in iron storage. It is also an acute phase reactant which gets elevated in acute and chronic infections. This study is directed in finding the relationship between serum ferritin and preterm labour
METHODOLOGY
This is a prospective study conducted in the Department of Obstetrics and Gynecology, Coimbatore Medical College Hospital, Coimbatore during the period of January 2018 to December 2018.
This study includes100 antenatal mothers who attended Antenatal OP between 20 to 24 weeks of gestation.
After getting approval from ethical committee, patients were selected according to inclusion and exclusion criteria. Study was done after explaining the details and getting written consent from the patients. Informed written consent is obtained from them. Pregnant women with Hb levels >10 gm% are enrolled in this study.
Data regarding patient age, parity, height, weight, period of gestation are obtained.
Maternal serum samples are obtained and sent for serum ferritin estimation.
Pregnant women are followed till delivery and ferritin levels of women who deliver preterm are compared with ferritin levels of pregnant women delivered at term.
After attaining serum ferritin from all the patients , ferritin of patients with preterm labour and term delivery were compared. By using mean and standard deviation data were compared using ‘independent t test’.
Other data were analysed using chi square test. P value of <0.01 was accepted as statistically significant.
RESULTS
In this study the mean values of serum ferritin taken at Coimbatore Medical College Hospital in PPROM , preterm labour and term labour were 44.4, 43.21, 21.96 and respectively. The standard deviation of serum ferritin in PPROM, preterm labour and term labour are 14.31, 15.23 and 9.12 respectively. There is significant statistical increase in serum ferritin in the PPROM and preterm group when compared with term delivery (P < 0.05). The high values of ferritin levels in preterm labour and PPROM cases could be due to infections associated with them. In this study most women with preterm delivery in past pregnancy had preterm delivery in this current pregnancy also.
About 58.3% who had previous preterm delivery had preterm delivery in this delivery. All these data indicate that preterm delivery is multifactorial and influenced by number of factors. Anemia during the second trimester is shown to be positively linked with preterm labour although anemia later in pregnancy has a negative association. Hence in our study to overcome this variable women with anemia (hemoglobin < 10.5gm/dl) were not included.
CONCLUSION
Our Study found significant difference in serum ferritin levels between preterm labour, PPROM and normal pregnant women with same gestational age, possibly because that subclinical infection is associated with preterm delivery. Elevated ferritin concentration associated with spontaneous delivery more than 43ng/ml in second trimester as cut off point could be derived from this study. Thus from the present study serum ferritin can be used as marker in predicting the pregnant women at risk for preterm delivery and thus help obstetricians to identify pregnant women at risk and advice them for a higher centre neonatal care . The results of this study can be used for promoting further studies of ferritin in relationship with pregnancy complication.
1
INTRODUCTION
Preterm labour is defined as regular uterine contractions leading to cervical changes before 37 completed weeks of gestation 6.
Table No 1. Subcategories of preterm birth, based on gestational age
PTB should be distinguished from ‘prematurity’ which constitutes the deficiency of various system development at the time of birth.
Preterm birth is responsible for 30-40% of neonatal mortality worldwide
7. Almost 1 million children die each year due to complications of preterm birth. Survivors are left with lifetime disabilities such as learning and hearing disabilities. Identifying pregnant women at risk of preterm delivery will enable them an early access to tertiary care centres for the management of infections and respiratory distress.
Low- income countries lack the resources required for prevention and treatment of preterm labour. Babies born preterm may die of respiratory distress due to surfactant unavailability or lack of infrastructure to transport rapidly to a tertiary care facility.
2
An action plan to avoid preventable newborn death includes 1. World wide access to newborn resuscitation
2. Low cost corticosteroids
3. Kangaroo mother care in place of incubator
Preterm premature rupture of membranes (PPROM) is defined as amniorrhexis before the onset of preterm labour. It the leading cause of preterm birth. Rupture of membranes is caused due to activation of enzymes such as collagenase and other mechanical factors. But PPROM and preterm labor appears to be linked to pathologic processes such as inflammation and infection of membranes.
Administration of antenatal corticosteroids remains an important intervention to improve neonatal outcome in women presenting with preterm labour. Tocolytic agents administration provide time for the administration of antenatal steroids or transfer to a facility with NICU.
Very low birth weight neonates whose mothers were given magnesium sulphate for preterm labour or preeclampsia were found to have reduced incidence of cerebral palsy at 3 years.
Interventions such as vaginal progesterone , intramuscular 17 alpha-hydroxyprogesterone caproate (17P) and use of cervical cerclage are used to reduce the rate of preterm delivery.
3
Many biomarkers are in study to predict preterm labour2. Serum ferritin is one such marker . It is an intracellular protein that is involved in iron storage. It is also an acute phase reactant which gets elevated in acute and chronic infections.
This study is directed in finding the relationship between serum ferritin and preterm labour.
4
AIM OF STUDY
1. To study the role of maternal serum ferritin in predicting preterm labour
2. To estimate the optimal cut off point of ferritin in identifying between preterm labour and term birth.
5
MATERIALS AND METHODS
This study was conducted in the Department of Obstetrics and Gynecology, Coimbatore medical college hospital, Coimbatore during the period of January 2018 to December 2018.
Type of study Prospective study Study population
This study includes 100 antenatal mothers who attended Antenatal OP between 20 to 24 weeks of gestation.
Inclusion criteria
Age 18-40
Singleton pregnancy
Conceived spontaneously
Healthy pregnant women attending AN OP between 20 and 24 weeks of gestation.
Exclusion criteria
Age >40 yrs
Multiple pregnancy
Pregnant women with signs of infection –fever, pain, vaginal discharge
Antenatal woman with any chronic systemic disease pertaining to cardiovascular, urogenital, oncological, endocrinological systems
Pregnant mother with any complications of pregnancy like IUD,GDM,PIH.
6
After getting approval from ethical committee ,patients were selected according to inclusion and exclusion criteria listed above. Study was done after explaining the details and getting written consent from the patients.
Methodology
● Pregnant women meeting the inclusion and exclusion criteria are enrolled in this study.
● Informed written consent is obtained from them.
● Pregnant women with Hb levels >10 gm% are enrolled in this study.
● Data regarding patient age,parity, height,weight, period of gestation are obtained.
● Maternal serum samples are obtained and sent for serum ferritin estimation.
● Pregnant women are followed till delivery and ferritin levels of women who deliver preterm are compared with ferritin levels of pregnant women delivered at term.
After attaining serum ferritin from all the patients , ferritin of patients with preterm labour and term delivery were compared. By using mean and standard deviation ,data were compared using ‘independent t test’. Other data were analysed using chi square test. P value of <0.01 was accepted as statistically significant.
7
REVIEW OF LITERATURE
In a study by Abdel-Malek K et al , serum ferritin appears to be raised in preterm labor and a cut off point of 31ng/ml between preterm labor and term labor.
In another study by Hazem F. El-Shahawy et al, there was a statistical significance in ferritin levels between term and preterm labor patients. This study concluded that serum ferritin can be used as a marker for preterm labour.
In another study by Sanoop Adathila Valappil there is significant increase in serum ferritin in PPROM cases as compared to the control group. But no significant increase in spontaneous preterm labour cases as compared to the control group.
Definition of Preterm
Preterm procured its source from Latin as prae (before) and terma (limit) from Greek 10% of the babies born around the world are preterm.
After Pneumonia, preterm is the major cause of neonatal mortality and death less than 5 years of age. The short and long term morbidity due to preterm are wide. The World Health Organisation (WHO) defines preterm as birth before 37 completed weeks of gestation or less than 259 days from the 1st day of last menstrual period .1
8
Fig No 1. Features of preterm child
Incidence and Prevalence
WHO calculated the incidence of PTB as 9.6% which accounts for 13 million annually in 2005. In 2010 the rate of PTB raised to 11.1%
accounting for 14.9 million 1. The major proportion of PTB is distributed among Asia and Africa which contributed to 60 to 85% of all PTB.
The major reason for PTB in developing countries is mainly linked to higher number of deliveries, infection, poor maternal conditions, lack
9
of availability of tocolytic drugs, heavy physical activity, lack of basic neonatal and obstetric care.1
Data across Europe for the last 10 years shows that PTB rate before 32 weeks of gestation is unchanged at 1 - 2%. The rise in PTB rate globally can be associated with increased age pregnant women, increased multiple pregnancy rate and assisted reproductive techniques, increase in iatrogenic preterm delivery and changes in registration 1. Cutting edge technologies and combined efforts of obstetricians and neonatologists has reduced PTB and its complication respectively in the last decade.
Short-term outcomes
Preterm Birth is a disruption of fetal maturation process and thus the preterm child experiences the extra uterine surroundings before its organs are fully formed. They are exposed to complications such as brain, GIT, lungs and circulatory systems immaturity 15.
Complications such as apnoea, necrotizing enterocolitis, hypoglycemia, respiratory distress, feeding difficulties, poor temperature regulation and bacterial infections are encountered by preterm babies compared with term babies 16. The risks of neonatal complications, morbidity and mortality increase with lower gestational age.
10 Long-term outcomes
There exists an exponential relationship between immaturity and neonatal mortality. Preterm babies have long term disabilities with low gestational age at birth. They are risk of cerebral palsy, vision and hearing defects, impaired mental function, asthma, epilepsy, behavioural and psychological disorders and learning disabilities 4. Children born extremely premature are at risk of early development of COPD. When the become adults they have lower educational levels 14, fewer children, lower income and are less often married. Most babies born preterm are healthy and have a normal level of function. Data from EPICure study indicates that PTB children have serious risk of disability throughout their upcoming years 13.
Fig No 2. Outcome of preterm birth
11 Classification
PTB is classified into following categories based on gestational age, clinical presentation and birth weight.
Based On Gestation Age 5
Extremely preterm: < 28 weeks
Very preterm: 28 - 31+6 weeks
The majority of PTBs occur between 32-36 weeks.
Subdivided as moderate preterm - 32 to 33+6 weeks
Late preterm (or near term) 34-36+6 weeks
Mild preterm accounts for the great majority of all PTBs
Based on Clinical Presentation According to its clinical presentation 1
Medically indicated PTB (iatrogenic or elective)
Spontaneous preterm birth
Medically indicated PTB (iatrogenic or elective) Major reasons are
antepartum haemorrhage
pregnancy-induced hypertension or preeclampsia
intrauterine growth restriction
12
non reassuring tests of foetal well-being
small for gestational age - SGA
obstetric care has become more interventional and aggressive in recent times which has mainly led to iatrogenic PTB 2.
Spontaneous PTB
Spontaneous PTBs are referred as preterm birth which occur after both prelabour rupture of the membranes (PPROM) and without rupture (with membranes intact).
PPROM is defined as spontaneous rupture of the membranes prior to 37 weeks with at least 1 hour before the start of regular uterine contractions.
Based on birth weight
Birth weight is subdivided into
1. Very low birth weight (<1500g, VlBW) 2. Low birth weight (<2500g, lBW)
3. Extremely low birth weight (<1000g, elBW).
Preterm babies may be SGA - small for gestational age - less than 10th percentile.
A Prototype Phenotypic classification
The phenotypic subdivision includes situations which are present in the index pregnancy only, but no risk factors and mode of delivery6. These information are collected meticulously from clinical records. It is found
13
that - because of overlapping of clinical conditions and presentation there exist more than one phenotype for any particular case 2,3.
This phenotypic classification helps us to understand the various causes and enhance the surveillance globally by accepting other relevant conditions to be included in the classification and doesn’t categorize a specific case to a preformed phenotype2.
Fig No 3. Phenotypic components of preterm birth syndrome
14 Risk factors
Fig No 4. Risk factors of preterm birth
The accurate predictor of PTB is difficult and combination of history of previous pregnancy events and maternal and fetal risk factors has to be involved in determining the cause of Preterm. The exact mechanism by which the risk factors are associated with PTB is unknown but defining these risk factors is significant in finding the high risk pregnant woman for initiation of prevention and interventional research regarding mechanism leading to PTB.
PTB is a multi-factorial situation. Various risk factors have been found. They are not sufficient enough to constitute bigger pool of PTBs.
15 Risk factors can be categorised into
1) Chronic stresses which includes maternal demographic risk factors like race, socio-economic status, marital status, age and maternal behavior (nutrition, smoking, etc.)
2) Acute stress like infection and immune dysregulation 17 3) Underlying genetic factors
Chronic Stress
Chronic stress is also a risk factor for PTB. Numerous chronically stressful situations have been proposed as a cause of PTB such as domestic violence, working conditions, low socioeconomic status and depression. Various researches have proved that pregnant women with features of depression and anxiousness have higher incidence of PTB.
Women who work for longer hours standing and night duties are found to have chronic stress 17 and are linked to have higher rates of PTB.
Duration and intensity of physical exertion by the pregnant mother affects pregnancy but it is difficult to quantify. Since it cannot be quantified, it cannot be used to predict the risk of PTB.
16 Infection
Infection is closely related to PTB. The increasing trend of chorioamnionitis with decreasing gestational age and increase in the rate of infection found by examination of placenta from preterm birth have proved this theory.
Fig No 5. Pathogenesis of infection leading to PTB
17 Bacterial vaginosis
Bacterial vaginosis is a frequently occurring lower genital tract infection in pregnancy and linked with PTB. Studies have proved bacterial vaginosis as an independent risk factor for PTB. However predictive value of it is limited.
Antibiotic intervention using clindamycin for the treatment of bacterial vaginosis during early pregnancy has shown some benefit in the prevention of preterm Births. In some studies usage of antibiotics such as Metronidazole in bacterial vaginosis has been found to be of less benefit and have also been related to PTB 24.
Amsel’s criteria for diagnosis of bacterial vaginosis Diagnosis requires 3 or 4 findings
1. Homogeneous, white, non-inflammatory discharge that smoothly coats vaginal wall
2. Presence of clue cells on microscopic examination 3. pH of vaginal fluid more than 4.5
4. Fishy odour of vaginal discharge after the addition of 10% KOH Asymptomatic bacteriuria
Another important infection leading to PTB is asymptomatic bacteriuria which can lead to pyelonephritis. The incidence of asymptomatic bacteriuria is 2 - 10% which accounts for less amount and thus it cannot be used as an independent predictor of PTB. But treatment of asymptomatic bacteriuria has reduced the incidence of PTB.
18 Periodontal disease
A final infectious process that has gained significant attention for its relation with PTB is periodontal disease 25. Periodontal disease is a marker that a pregnant woman is in a highly inflammatory state and may have increased risk of PTB. But the treatment periodontal disease has shown no major decrease in PTB26.
Fig No 6. Mechanism of preterm birth
19 Inflammation
Inflammation is a systematic pathway which includes many risk factors in the causation of PTB. The two major types of inflammation that have been associated with PTB are
systemic inflammation - measured in maternal serum
localized inflammation - measured in amniotic fluid or cervicovaginal secretions
There is a huge array of markers for testing inflammation in maternal serum, amninotic fluid and cervical secretion but only some has shown constant association with PTB and they cannot be taken with a high predictive value.
The most common inflammatory markers used for detection of PTB are
CRP
IL-6
Serum ferritin
IL-2, 8, 10
TNF-alpha
alkaline phosphatase
20 Genetic Risk
Genetic factors have also been associated with PTB in 25 - 40%.
These genetic risk factors are mainly of maternal origin. Pregnant women who had PTB previously and have change in partner are still at increased risk (RR = 5). But men have no increased risk for subsequent offspring.
Maternal relative with a history of PTB has also been found to increase the risk of having a PTB (RR = 1.5)18. This maternal genetic factor is further enlightened in studies of monozygotic twins who show similarities in pregnancy duration than monozygotic twins 19.
Cervical Malformations
Cervical abnormalities both congenital and iatrogenic such as arcuate uterus, unification defects, canalization defects and cervical insufficiency have been found to be associated with PTB. These women have twice the risk of PTB than women with normal uterus 20.
Pathophysiology - Partially dilated or short cervix fails in retaining intrauterine contents and allows bacteria to ascend up, where they act through toll - like receptors and stimulate activation of prostaglandins, cytokines and initiate an inflammatory response 21.
21
Fig No 7. Cervical Malformations
Women who have done uterine procedures such as cone excision, Fothergills repair also have twice the risk of PTBs 20.
Multiple Pregnancies
Multiple Pregnancies have increased risk of PTB with increasing number of fetuses 27.
Assisted reproductive therapy (ART) increase the rate of multiple pregnancy which have contributed to PTB pool.
Multiple pregnancies which occur naturally cannot be prevented but which occur due to ART leading to PTB can be reduced.
22
Weight, Diabetes and Metabolic Syndrome
Lifestyle factors such as Body Mass Index (BMI) influence the rate of PTB. Previous studies have shown that pregnant women who are underweight (BMI < 18.5) have increased risk of PTB (RR = 1.21) 28. Women on the other end of the spectrum with higher BMI (BMI > 25 to 30, 30 - 35) have reduced rates of PTB indicating a protective role. On the other hand, mothers with very high BMI of more than 35, 40 have higher risk ratios (RR = 1.33 & 2.27 respectively) 29. Women with very high BMI have increased PTB especially at 32 - 36 weeks. Meta analysis shows BMI has increased risk for both spontaneous and induced PTBs.
Metabolic diseases such as diabetes mellitus usually occur concurrent with high BMI and women with preexisting diabetes also have a high risk for both spontaneous and induced PTB.
Socio Demographic Risk Factors This includes factors such as
Maternal age
Marital status
Race/Ethnicity
Maternal Education
23 Maternal Age
It is one of obstetric risk factors associated with PTB. The average age of first born child has been considerably increased and this increase is most commonly seen in women around 35 - 39 years. Compared to mothers between 20 - 35 years adolescent mothers and mothers more than 35 years have shown a greater risk for PTB. Teenage and older mothers are reported to have a higher degree of low birth weight babies, still birth, preterm birth and fetal death and hence they require more chances of infant admission to NICU.
Marital Status
Unmarried mothers have lack of social emotional support and hence they receive less antenatal care, poor nutrition and they have more complications during pregnancy that lead to preterm delivery and low birth weight.
Race/Ethnicity
The rate of PTB in black mothers is high but it has reduced over time. Even after correcting the physiological and social risk factors racial differences exist.
Maternal Education
Lower levels of education in pregnant mother is associated with higher risk of preterm delivery. But some studies have shown no relationship between maternal education and PTB.
24 Smoking
Among the behavioral risk factors smoking shows a consistent association with PTB. There exists as a dose response relationship between PTB and smoking. Increased smoking leads to increased risk31. Thus smoking reduction programs have been introduced as a behavioural intervention for the reduction of PTB. But smoking cannot be used as a predictive tool for preterm Birth. Smoking 10 - 20 cigarettes per day has a RR = 1.5 - 2. Researchers found that women who quit smoking before 15 weeks of gestation have equally comparable rates of PTB and SGA compared to non smokers emphasizing that smoking is modifiable risk factor31.
Idiopathic causes
Only 50% of PTBs have a known cause 17. Thus preventing them with targeted therapies is difficult except in conditions like smoking and infection 30. Hence preventive measures must be undertaken in a broad spectrum.
Predicting PTB
A very important tool for prediction of PTB is previous obstetric history. Mothers with previous history of one preterm birth have 14 - 20% risk of preterm in next pregnancy and with 2 PTBs have 28 - 42%
risk and those with 3 PTBs previously have 67% risk of preterm births.
25
Further multiple pregnancy complicate this scenario. Research have contributed that prevalence of PTB in the first pregnancy is 10% and in the second pregnancy is 9.6%. The positive predictive value (PPV) is 23%. In case of spontaneous PTBs the prevalence in first pregnancy is 8.3% and in second pregnancy is 7.8%. The PTB is 20.7%.
Cervical Length
An important predictor of PTB is the length of cervix measured during pregnancy. Cervical length and strength contribute to retaining the pregnancy. The most acceptable time to measure cervical length is between 18 - 22 weeks. Measuring during early weeks and after 32 weeks has less predictive value as cervical length decreases in later weeks. It is best measured transvaginally as transabdominal measurements are not replicable. Cervical length measured at the appropriate time using the right procedure is predictive in both high risk and low risk women.
Average cervical length is 35mm. Length above 35mm is considered normal and no further evaluation is needed. Women with cervical length below 20mm have an increased risk of preterm birth 34.
26 Cervical factors scoring
Cervical length < 25 mm in TVS
Cervical score < 1.5 in digital cervical examination
Cervical score = cervical length in cm - cervical dilatation in cm at the internal OS
Fig No 8. Comparison of normal and short cervix Significance of cervical length (Limitations and advantages) 33
1. Best predictive accuracy
2. Different population show variation 3. Women with twin, triplet pregnancy
The earlier the short cervix the greater the risk of preterm birth.
27 Fetal Fibronectin
Fig No 9. Fetal fibronectin
Fetal Fibronectin (fFN) is a placental glycoprotein which is a component of extracellular matrix of chorio decidual junction, mainly produced by the trophoblast. fFN acts like a glue at the maternal - fetal interface and mediates implantation and chorio decidual attachment throughout pregnancy. fFN is normally present in cervico vaginal secretion before 20 weeks gestation because of incomplete fusion between decidua and fetal membranes. Hence the appropriate timing for testing fFN is after 22 weeks, after the fusion of membranes.
28
fFN measured in the cervico vaginal fluid is a predictor for PTB. The disruption of maternal - fetal interface by mechanical (uterine activity) or localized inflammation may lead to release of fFN. It has become invalid if the cervix is dilated, when there is bleeding per vaginum, recent sexual intercourse (< 24 hours), ruptured membranes, recent cervical examination (digital or ultrasound). Lubricants, creams, disinfectants and soaps may give a false negative result. fFN concentration more than 50ng/mL is considered positive. Though it is an indicator of PTB, it has low sensitivity in low risk population.
The American College of Obstetricians and Gynecologist (ACOG) recommends testing fFN only in symptomatic women with high risk pregnancy with following criteria; intact membranes, sampling between 24 - 34 weeks, minimum cervical dilatation (< 3cm).
The European association of perinatal medicine encourages testing fFN as a routine assessment of PTB and recommends to withhold tocolysis and prophylactic steroids when fFN is negative and cervical length by TVS is more than 2.5 cm 10.
29
Fig No 10. Foetal fibronectin levels throughout pregnancy
Maternal Inflammatory response - Evaluation of biomarkers in maternal serum
Pregnancy is a unique immunological state in which maternal immune system changes to promote fetal allograft tolerance. The balance between suppression and immune tolerance is strictly regulated by cytokines in harmony with progesterone. Switch in the Th1:Th2 cytokine ratio towards Th2 predominates in pregnancy. The aberrant Th1:Th2 profile is related to adverse pregnancy outcome such as miscarriage, preterm labour, pre-eclampsia and fetal brain injury. Mainly activation of Th1 rather than suppression of Th2 seems to be more in PTB.
30
Human labour is an inflammatory process characterized by an influx of inflammatory cells in gestational tissues and increased production of chemokines and cytokines. This inturn causes synthesis of prostaglandins which stimulates uterine contractions and increases expression of matrix metalloproteinases (MMP) leading to rupture of membranes and cervical ripening. Although this mechanism is seen both in term and preterm labour, preterm labour is characterized by asynchronous inflammatory activation.
Intrauterine Infection (IUI)
Fig No 11. Intrauterine infection
31
Evidence suggests that most intrauterine infection are chronic and subclinical and thus they are difficult to diagnose before labour or membrane rupture. A diagnostic marker for identifying these subclinical infection would be useful in PTB detection. Measurement of a single biomarker lacks efficiency in predicting in PTB because of the complex nature of PTB and the various pathway leading to PTB. Measurement of inflammatory markers in mid trimester and detection of microbial invasion of the amniotic cavity can predict PTB 4.
The various biomarkers involved in detection of PTB are described below
Serum Ferritin
Fig No 12. Structure of ferritin
32
Ferritin is an acute phase reactant released by leukocytes in response to infection. It has a role in iron homeostasis by binding and sequestering intra cellular iron. It has a spherical cell with a central cavity in which upto 4500 atoms of iron are oxidized and stored. Ferritin is a multimer with 24H (heavy) and L (light) sub units in variable proportion in different tissues, only the H subunit has feroxidize activity 45,47.
Action of ferritin as an acute phase reactant is of high importance for protection against microbial proliferation, oxidative damage and inflammation. The serum ferritin differs from intracellular protein that it is glycated and contains little or no iron46. Serum ferritin has less heavy chains and tissue ferritin has more heavy chains. It is the primary intracellular storage of iron in both prokaryotes and eukaryotes and is a diagnostic marker in a variety of acute phase reactions and inflammatory condition in high serum levels. Extracellular ferritin has important role in defence against bacteria by stimulating oxidative metabolism.
Phosphorylated insulin like growth factor binding protein 1 (PHIGFBP-1)
Insulin like growth factor produced by the liver and is involved in fetal growth and development. It is a major protein of human decidua.
The phosphorylation status of IGFBP-1 differs in different sides and the non phosphorylated isoform predominates in amniotic fluid. The highly
33
phosphorylated isoform is found in cervical secretion in first and early second trimester (rarely after 23 - 37 weeks), during cervical ripening and onset of labour, as it is secreted by the decidua.
Hence prediction of PTB by rapid bedside test for the detection of PHIGFBP-1 in cervical secretion after 23 weeks can be advised.
Concentration of 30mcg/litre is required for a positive result.
Placental Alpha Macro Globulin-1 (PAMG-1) and Insulin like growth factor binding protein-1 (IGFBP-1)
Very high concentration of IGFBP-1 and PAMG-1 are found in amniotic fluid compared to blood and cervico vaginal secretions 11. Detection of IGFBP-1 and PAMG-1 are indicative of PROM in few studies. But the negative predictive value of PAMG-1 is 93.9% and IGFBP-1 is 89.5% with accuracy of both being 95 and 93% respectively.
Rapid strip test are accurate than any single clinical method but the accuracy is similar when compared with combined clinical approach which includes vaginal pooling, nitrazine test and fenning pattern and the test is also expensive. So these tests are useful in women with doubtful diagnosis of PROM.
34 Amniotic Fluid Sludge
These are aggregates of particulate matter present in amniotic fluid in close proximity to internal os. It indicates impending PTB, PPROM and microbial invasion of the amniotic cavity. It is also present in histologic chorioamnionitis in patients with spontaneous PTB and intact membranes. Bacteria can form a microbial biofilm in case of intra- amniotic infection in the form of sludge 4. Biofilms are embedded in a hydrated matrix of extracellular polymeric substances and they are implicated in 80% of chronic infections. These bacteria in biofilms are resistant to antimicrobials and difficult to isolate in culture.
Prevalence of sludge in term normal pregnancy is 1% whereas in patients with spontaneous PTB and intact membranes is 22%. In the setting of short cervix this debris seems to be a marker of PTB but there is no evidence that the management of short cervix should be altered in the presence of debris.
35
Fig No 13. Amniotic fluid sludge Prevention of Preterm Birth
The strategies involved in delaying PTB reduce the mortality and morbidity of preterm. These interventions can be primary, secondary or tertiary. Single intervention may not be effective in all cases of preterm labour.
Primary Prevention
This is directed to all women before or during pregnancy to prevent PTB. They focus on overall health and includes nutritional supplementation, screening of low risk women, smoking cessation, improved access to prenatal care, weight optimisation and avoidance of late PTB due to elective cesarean section by doing cesarean section after
36
39 weeks. More than 50% of PTB does not have obvious risk factors and many risk factors are difficult to modify (example: previous placenta previa, previous PTB), few risk factors respond to targeted intervention like smoking cessation, change in working conditions and BMI.
Nutritional supplementation role is controversial but nutritional and lifestyle adjustments in pre pregnancy period is essential to ensure BMI within normal range. Smoking cessation reduces PTB by 15% 30. Increased awareness of PTB regarding the potential avoidable risk factors and government or medical policies to limit the number of embryos transferred may reduce the rate of PTB.
Secondary Prevention
These are directed against pregnant women who are under risk of preterm labour either because of history of previous preterm delivery or the present pregnancy has risk factors. They include interventions to reduce,stop or reverse the progress of preterm labour.
37
Fig No 14. Secondary prevention of PTB Secondary prevention includes
1. Cervical Cerclage 2. Cervical pessary
3. Antenatal Progesterone
4. Antibiotic treatment of infections
38 Cervical cerclage
Fig No 15. Cervical cerclage procedure
Cervical cerclage is a surgical procedure which involves placing suture around cervix to give mechanical support to the cervix and prevents its opening. The indications of cerclage are (a)history -indicated cerclage: with previous history of PTB. It is offered between 12 and 14 weeks gestation in women with a history suggestive of cervical insufficiency (b) ultrasound indicated cerclage: a short cervix demonstrated in TVS before 24 weeks. It is performed at 14 - 24 weeks (c) physical examination-indicated cerclage : in emergency situations when pregnant women present with more than 1cm cervical dilation and
39
membranes have prolapsed. (d) Emergency cerclage: Indicated in women who present with cervical dilation with <4 cm with bulging membranes.
Rupture of membranes, dilatation > 4 cm and evidence of infection are contraindication to this procedure. Reduction in PTB after cerclage was mainly observed in women with previous history of PTB or second trimester losses and in women with short cervix 43.
Techniques for cervical cerclage 1. Transvaginal cerclage
a. McDonald suture b. Shirodkar procedure 2. Transabdominal cerclage
McDonalds procedure is the procedure of choice for cerclage. It is done under spinal or general anesthesia. Shirodkar procedure is indicated in women with previous failed McDonalds suture. A mersilene tape is used which is passed around the cervix using a specially designed Shirodkar needle
Cervical cerclage carries risks to pregnancy such that ,it causes myometrial contractions, infection or bleeding which inturn may lead to preterm labour. Hence the benefits should be carefully explained along with the risks. Studies show that there is no role for cerclage in multiple pregnancy 44.
40 Cervical pessary
Fig No 16. Cervical pessary
Cervical pessaries such as Arabin pessary have been used from the past as an effective intervention for the prevention of PTB. most commonly used is the arabin pessary . It is a flexible ring-like silicon device present in different sizes. Smaller diameter of pessary is fitted around the cervix and larger diameter faces the pelvic floor. This causes rotation of cervix towards posterior vaginal wall ,thus correcting the cervical angle. It is an out-patient procedure which is operator- independent and cost effective. This procedure does not require anesthesia and can be removed when necessary. It is not routinely used.
41 Antenatal progesterone
Mechanism of progesterone in preventing preterm labour is by reducing gap junction formation, maintaining cervical integrity, oxytocin antagonism and anti-inflammation. Role of progesterone in multiple pregnancies is less clear. Role of progesterone in threatened preterm labour is also less. Progesterone administration is beneficial in women with previous history of PTB and vaginal progesterone has shown to reduce the risk of PTB in women with short cervix36.
Women with a history of spontaneous PTB can be given intramuscular 17P weekly. After 17P is started ,it should not be discontinued as it increases the risk of recurrent preterm delivery.
Cervical length is evaluated by TVS every two weeks from 16 - 24 weeks in women with a history of PTB 32. If cervical length is less than 25mm at < 24 weeks cervical cerclage is offered. In women without a history of PTB but with short cervix should receive vaginal progesterone from the period of diagnosis till 36 weeks. Studies have shown this decreased the incidence of PTB and neonatal morbidity and mortality with this intervention 35.
42
Table No 2. Progesterone formulation and dose for the prevention of PTB
Indication Progestogen Dosing
Prior PTB 17 alpha -
hydroxyprogesterone caproate
250mg IM weekly from 16 - 36 weeks
No prior PTB, cervical length < 25mm at <24 weeks
Vaginal progesterone gel 90mg
Vaginal progesterone capsule 200 mg
Daily from diagnosis of short cervix till 36 weeks
The OPPTIMUM study - dOes Progesterone Prophylaxis To prevent preterm labour IMprove oUtcoMe - is a randomized trial vaginal progesterone 200mg daily from 22 - 24 to 34 weeks of gestation. Primary outcome of this study was to assess the immediate obstetrical and childhood outcomes. The results were that vaginal progesterone was not associated with lower risk of preterm birth or composite neonatal adverse outcomes 37,38,39.
Management of Infection
Routine screening and treatment of bacterial vaginosis to reduce PTB does not significantly reduce the risk of PTB. Possible reasons for antibiotic failure are
43
Antibiotic might not effectively treat or prevent chorioamnionitis
Host factors such as diet, smoking might influence the risk of PTB irrespective of antibiotics
Treatment protocol differs in many aspects such as methods of diagnosing, timing, dosing and choice of antibiotic.
However, some studies have shown that administration of clindamycin to women (<22 weeks) reduce the rate of PTB compared to placebo 24.
Table No 3. CDC recommendations for clindamycin treatment of bacterial vaginosis in pregnancy
Treatment Dosage
Clindamycin cream 2% 1 full applicator (5g) intravaginally at bed time - 7 days
Alternative Regimens
Clindamycin 300mg Orally twice daily - 7 days
Clindamycin ovules 100mg Intravaginally once at bedtime - 3 days
Routine screening of asymptomatic bacteriuria with urine culture is recommended at 12 - 16 weeks gestation which will identify 80% of women with infection. Currently the gold standard for diagnosis is quantitative culture of mid stream or clean catch urine. Criteria for
44
diagnosis of asymptomatic bacteriuria is 2 (or more) consecutive clean catch urine samples both giving positive cultures of the same bacterial strain in quantitative counts of at least 105 colony forming units (cfu) per ml. Escherichia coli is the most common causative organism identified other than gram negative bacteria and group B streptococci. Various antibiotics are available for the treatment of asymptomatic bacteriuria in pregnancy and the treatment should depend upon antimicrobial susceptibility testing. Periodontal disease is associated with PTB but antenatal treatment does not affect the pregnancy outcome.
Tertiary Prevention
Most interventions are aimed at tertiary prevention - prevention after symptoms develops. It includes antenatal transfer, regionalized perinatal care, tocolytic agents, antenatal administration of corticosteroids.
Tocolysis
Tocolytic drugs are used for short term prolongation of pregnancy (upto 48 hours) with the goal of allowing time for administration of antenatal steroids, magnesium sulphate for neuroprotection, antibiotics for group B streptococcal infection and maternal transfer if needed. After cessation of labour there is evidence of long term tocolysis benefits for the prolongation of the pregnancy. Wide variety of tocolytic agents have been used for suppressing uterine contraction - beta agonists, oxytocin
45
receptor antagonists, calcium channel blockers, prostaglandin synthetase inhibitor and magnesium sulphate. The ideal tocolytic agent must be inexpensive, easy to administer, without maternal, fetal or neonatal side effects and effective in delaying PTB long enough for the administration of antenatal steroids 40,41.
Table No 4. Pharmaceutical agents for tocolysis
Drug (class) Dose Comments Contra indication and
adverse effects Nifedipine
(calcium channel blocker)
30mg oral loading dose, 10 - 20mg every 4-6 hours
Decreased incidence of neonatal respiratory
distress syndrome, necrotising
enterocolitis, intraventricular hemorrhage, jaundice
C/I - maternal hypotension
ADR - flushing, dizziness, headache, transient hypotension.
No fetal adverse effects
Terbutaline (beta mimetic)
0.25mg
subcutaneously every 20min - upto 3 doses
Neonatal
outcomes are variable and maternal adverse effects are common
C/I - heart disease, thyrotoxicosis, purely controlled diabetes ADR - Cardiac arrhythmia,
pulmonary edema, hypotension,
46
tachycardia, hyperglycemia, hyperinsulinemia, hypokalemia,
hallucination, tremor.
Fetal and neonatal ADR - tachycardia, hyperglycemia,
hypocalcemia, intraventricular haemorrhage.
Indomethacin (NSAID)
50mg rectally/50 - 100mg orally - loading dose
25 - 50 mg orally every 4 hours - for 48 hours - maintenance dose
Efficacy appears similar to other agents. Other
NSAIDs -
ketorolac,
sulindac may also be used
C/I - Renal or hepatic impairment, active peptic ulcer disease, oligohydramnios Maternal ADR - heartburn, nausea
Fetal ADR -
Constriction of ductus arteriosus, pulmonary hypertension,
intraventricular haemorrhage,
hyperbilirubinemia, necrotizing
enterocolitis.
47
Antenatal Administration of corticosteroids
Trials confirmed that treatment with steroids reduces the risk of respiratory distress syndrome (RDS), intraventricular hemorrhage, necrotizing enterocolitis, early sepsis, need for respiratory support, NICU admission and neonatal death. Antenatal steroids enhances the benefit of postnatal surfactant and reduces the need for blood pressure support.
They are administered routinely to accelerate fetal lung maturation in pregnant women at risk of PTB 48,49.
Table No 5. Antenatal steroids for fetal lung maturation
Corticosteroid Dose
Betamethasone Two Doses - 12mg IM given 24 hours apart
Dexamethasone 4 doses - 6mg IM given every 6 hours
In general both betamethasone and dexamethasone shows similar results in terms of respiratory distress and perinatal mortality. But 1 meta - analysis showed that dexamethasone has decreased in intraventricular hemorrhage and NICU stay when compared to betamethasone. Evidence shows that even a single dose of either gives benefit, so it is recommended that the first dose be given even if it is unlikely that patient will receive the following doses. However there is no evidence of improved outcome with accelerated dosing.
48 Magnesium sulphate for neuroprotection
Magnesium sulphate can be administered immediately before and at the time of delivery of a preterm infant. It decreases the rate of cerebral palsy (RR = 0.68) 50. Various trials have proved its benefits but have varied in regimens used. A 2012 Cochrane review showed that no superiority of any regimen over the other. It is administered to women between 24 - 32 weeks at high risk of delivery within 24 hours.
Table No 6. Magnesium sulphate for neuroprotection
Loading Dose Maintenance Dose Repeat Treatment 4gm over 20-30 min 1gm/hr till birth or 24
hours
No immediate repeat doses
BEAM study - Beneficial Effects of Antenatal Magnesium sulphate - A placebo controlled trial in 2 - 41 women at imminent risk of preterm birth between 24 and 31 week. A 2 year follow up was done which concluded that magnesium sulphate infusion prevents cerebral palsy regardless of the gestational age at which therapy is given.
Neonatal GBS prophylaxis
The incidents of neonatal GBS infection and its mortality has decreased significantly after the acceptance of CDC guidelines for the prevention of GBS disease. GBS reminds the leading cause of neonatal
49
mortality due to infection. Use of clindamycin and cefazolin in penicillin allergic patients for treatment of PTB and PPROM is recommended. A vaginal - rectal swab for GBS culture should be obtained when a woman presents with PPROM or preterm labour if results from last 5 weeks testing is not available. Intrapartum antibiotics (Penicillin or ampicillin) should be started on admission until birth or until it is confirmed that women is not in true preterm labour or a negative GBS culture is available. Clindamycin and vancomycin are used as a last resort for women with serious penicillin allergy. It is not routinely practised in india.
Preterm rupture of membranes (PPROM)
PPROM is the amniorrhexis before 37 completed weeks. 25 - 30%
of PTB are preceded by PPROM1.Collagen fibers contributed to the tensile strength of membranes. Matrix metalloproteinase (collagenase activity is increased due to the result of infection or inflammation and leads to final common pathway ending in membrane rupture. Risk factors for PPROM are similar to those of preterm labour with intact membranes.
Delivery is likely to occur within a week of rupture in 13 - 16% of cases there is clinically evident intra-amniotic infection. Digital vaginal examination increases the likelihood of this infection. Intrauterine complications are abruption of the placenta, umbilical cord compression, pulmonary developmental abnormalities and infection.
50
Evaluation of the patient with suspected PPROM includes accurate dating, sterile speculum examination, ultrasound evaluation of oligohydramnios, assessment of fetal lung maturity (by amniocentesis or vaginal amniotic fluid testing for lamellar body count and phosphatidylglycerol between 32-36 weeks), screening for infection and fetal monitoring (electronic fetal heart rate and uterine contraction monitoring).
Management of PPROM
The management of PPROM necessitates a balance between advantage of delaying delivery and risk of prolonged fetal exposure to potentially hostile environment.
1. Monitored for clinical infection - maternal fever, uterine tenderness and fetal tachycardia are signs of infection
2. Antepartum fetal testing - the non - stress test and biophysical profile are used to assess the fetal condition
3. Antibiotic therapy - management with antibiotics between 24 - 32 weeks prolonged pregnancy and decreases chorioamnionitis, fetal morbidity and maternal infection
51
Table No 7. Antibiotic therapy in PPROM
Antibiotic Dosage
Initial therapy
Ampicillin 2gm IV every 6 hours for 48 hours Erythromycin 250 mg IV every 6 hours for 48 hours Follow up therapy
Amoxicillin 250mg orally every 8 hours for 5 days Erythromycin base 333mg orally every 8 hours for 5 days
4. Cortical steroids - Antenatal corticosteroids administration in the setting of PPROM decreases the risk of neonatal RDS, necrotising enterocolitis and intraventricular haemorrhage. The incidence of maternal and neonatal infection is not found to be increased.
5. Tocolysis - As opposed to antibiotics and steroid treatment, tocolysis in view of PPROM lacks evidence of benefit
6. Magnesium sulphate for neuroprotection
52
Management of PPROM according to gestational age
1. 34 weeks or more - plan delivery - labour induction unless contraindicated. Single cotico steroid course may be considered upto 36+6 weeks in those who have not received a previous course of steroids.
2. 32 - 33 completed weeks - expectant management, single corticosteroids, antimicrobials to prolong latency
3. 24 - 31 completed weeks - expectant management, single corticosteroids course, tocolytics, antimicrobial to prolong latency, magnesium sulphate for neuroprotection
4. < 24 weeks - expectant management or induction of labour, antimicrobials
53
OBSERVATIONS AND RESULTS Table No 8. Mean Age
N Minimum Maximum Mean SD
Age 100 17 38 25.54 4.217
Study group consists of 100 patients who attended our AN OP for routine second trimester antenatal check up. Most of the patients were around the age of 25.
Table No 9. Age distribution
Groups Frequency Percent (%)
<20 years 12 12.0
21-25 years 40 40.0
26-30 years 37 37.0
>31 years 11 11.0
Total 100 100
Teenage pregnancy constituted about 12% of the study population.
Most of the patients were around 21 - 25 years which constitutes 40%.
Elderly gravida were around 11% and antenatal mothers between 26 and 30 years constituted about 37%
54
55
Table No 10. Parity distribution
Groups Frequency Percent (%)
PRIMI 48 48.0
MULTI 52 52.0
Total 100 100
This study has a combination of primigravida and multigravida.
Multigravida constituted most of the study population which is about 52% and primigravida constituted about the remaining 48%. Pregnant women with previous history of abortion were classified according to thier parity level as either primigravida or multigravida.
56
Table No 11.Distribution of Multi gravida among study group
Groups Frequency Percent (%)
L1 49 94.2
L2 2 3.8
L3 1 2
Total 52 100
Multigravida are further divided into L1,L1,L3 based on the number of living children they have. Most multigravida were P1L1 occupying 94.2% of multigravida population.
57
Table No 12. Parity distribution among different age groups
Groups PRIMI MULTI P value
<20 years 5(41.7%) 7(58.3%)
.158 21-25 years 11(27.5%) 29(72.5%)
26-30 years 9(24.3%) 28(75.7%)
>31 years 3(27.3%) 8(72.7%)
Multigravida constituted most of the study population with 58.3%
in the teenage group. In 21 - 25 years group 72.5% were multi and 27.5%
were primigravida. In 26 - 30 year group 75.7% were multi and 24.3%
only were primi. In the elderly group majority were multi with 72.7% and primigravida were only 27.3%.
58
Table No 13. Socio economic status
Groups Frequency Percent (%)
CLASS III 9 9.0
CLASS IV 50 50.0
CLASS V 41 41.0
Total 100 100
Pregnant women were grouped according to Kuppusamy modified scale into different socioeconomic status. Most of the pregnant women belong to class IV socio economic status which constitutes about 50%.
The remaining were distributed between class III and V.
59
Table No 14. Distribution of multigravida in study group based on previous delivery
Groups Frequency Percent (%)
PREVIOUS TERM 40 76.9
PREVIOUS PRETERM 12 23.1
Total 52 100
The multigravida in study group were also classified based on previous delivery as previous preterm and previous term. 23.1% multigravida had previuos history of a preterm delivery.
60
Table No 15. distribution of PPROM
Groups Frequency Percent (%)
POSITIVE 31 31.0
NEGATIVE 69 69.0
Total 100 100
In our study, 31% of women had PPROM and the rest 69% did not have PPROM.
