SERUM βHCG AS A PREDICTOR OF PREGNANCY INDUCED...

SERUM βHCG AS A PREDICTOR OF

PREGNANCY INDUCED HYPERTENSION

Dissertation submitted in partial fulfilment of the

Requirement for the award of the Degree of

M.S. DEGREE – BRANCH VI

OBSTETRICS AND GYNAECOLOGY

APRIL 2017

TIRUNELVELI MEDICAL COLLEGE HOSPITAL

THE TAMIL NADU DR.M.G.R. MEDICAL UNIVERSITY,

CHENNAI,

TAMIL NADU

CERTIFICATE

This is to certify that the Dissertation entitled “SERUM βHCG AS A

PREDICTOR OF PREGNANCY INDUCED HYPERTENSION”

submitted by Dr.Jayalakshmi, MBBS., to The Tamilnadu Dr.M.G.R. Medical

University, Chennai, in partial fulfilment for the award of M.S (Obstetrics

and Gynaecology) is a bonafide work carried out by her under my guidance

and supervision during the academic year 2013-2017. This dissertation

partially or fully has not been submitted for any other degree or diploma of

this university or other.

GUIDEProf.Dr.MUTHU PRABHA, MD(OG)

Department Obstetrics andGynaecology,

Tirunelveli Medical College,Tirunelveli- 627011.

HODProf.Dr.MEENA,MD.,DGO.,DNB.,

Department Obstetrics andGynaecology,

Tirunelveli Medical College,Tirunelveli- 627011.

Dr.K.Sithy Athiya Munavarah,THE DEAN,

Tirrunelveli Medical College,Tirunelveli- 627011.

DECLARATION

I, Dr.JAYALAKSHMI.D, MBBS., solemnly declare that the

Dissertation titled “SERUM βHCG AS A PREDICTOR OF

PREGNANCY INDUCED HYPERTENSION” had been prepared by me

under the expert guidance and supervision of Prof.Dr.MUTHU

PRABHA,MD.,(OG) Professor, Department of Obstetrics and Gynaecology,

Tirunelveli Medical College Hospital, Tirunelveli.

The dissertation is submitted to The Tamilnadu Dr. M.G.R. Medical

University, Chennai in partial fulfilment of the regulation for the award of

M.S. Degree (Branch VI) in Obstetrics and Gynaecology.

It was not submitted to the award of any degree/diploma to any

University either in part or in full previously.

Place: Tirunelveli.

Date:

Dr.JAYALAKSHMI.D, MBBS.,

POST GRADUATE,

M.S. (Obstetrics and Gynaecology),

Tirunelveli Medical College,

Tirunelveli.

ACKNOWLEDGEMENT

I am very much thankful to the Dean Dr. K.Sithy Athiya Munavarah,

Triunelveli Medical College Hospital, Tirunelveli, who has granted

permission to do this study in this institution,

I take this opportunity to express my deepest sense of gratitude to

professor Dr.MEENA, M.D., DGO., DNB., Head of the Department of

Obstetrics and Gynaecology, Tirunelveli Medical College Hospital,

Tirunelveli for encouraging me and rendering timely suggestions and guiding

me throughout the course of this study. I will be forever indebted to her for

her constant support.

I sincerely thank my professor Dr.RAMALAKSHMI, M.D.,(OG).,

Dr.SHEBA ROSATTE VICTOR,M.D.,(OG)., Dr.M.SUJATHA

ALAGESAN,M.D.,(OG), Dr.VALARMATHI,MD.,(OG).,

Dr.MALLIGA, MD.,(OG)., for their support and guidance.

I am very much thankful to professor Dr.M.Saradha,M.D., (Bio-

Chemistry), Head of Department of Bio-Chemistry for providing valuable

support and guiding through the study.

I am extremely thankful to my guide Dr.MUTHU PRABHA, M.D.,

(OG) for guiding me throughout the study.

I am extremely thankful to all my Assistant Professors of the

Department of Obstetrics and Gynaecology for their guidance and support

throughout my study period in this institution.

I thank Prof. P. Arumugam statistician for their useful inputs.

I wish to express my gratitude to my parents, my brother, my husband

and my son & my sister for their support throughout my study.

I also like to express my gratitude to my friends and colleagues who

have always been a source of love, support and encouragement.

I am very much thankful to all antenatal mothers of Tirunelveli

Medical College without whom this study would not have been possible.

Lastly, I am ever grateful to God for showering his blessing in making

me a part of this noble profession and allowing me to conduct this study and

finish it in time.

CONTENTS

S.No TITLES Page No

1. Introduction 1

2. Aim of the Study 2

3. Review of Literature 5

4. Materials and Methods 56

5. Result & Analysis 59

6. Discussion 86

7. Conclusion 87

8. Summary 89

9. Bibliography

10. Annexure

ABBREVIATIONS

GHT - Gestational Hypertension

LDH - lactate Dehydrogenase

DIC - Disseminated Intravascular Coagulation

APTT - Activated Partial Thromboplastin Time

ALT - Alanine Transaminase

AST - Aspartate Transaminase

DBP - Diastolic Blood Pressure

SBP - Systolic Blood Pressure

ACOG - American College of Obstetricians and Gynaecologists

HT - Hypertension

DM - Diabetes Mellitus

IV - Intra Venous

RCOG - Royal College of Obstetricians and Gynaecologists

MM - Millimetre

% - Percentage

PG - Prostaglandins

OP - Out Patient

dL - Deciliter

DNA - Deoxy Ribonucleic Acid

ML - Millilitre

IGF - Insulin like Growth Factor

IGFBP - Insulin Like Growth Factor Binding Protein

MG - Microgram

IUGR - Intra Uterine Growth restriction

LBW - Low Birth Weight

HCG - Human Chorionic Gonadotrophin

TVMCH - Tirunelveli Medical College Hospital

OPD - Out Patient Department

PIH - Pregnancy Induced Hypertension

BP - Blood Pressure

NICE - National Institute of Health and Clinical Excellence

SLE - Systemic Lupus Erythematosus

BMI - Body Mass Index

KG - Kilogram

M2 - Meter2

PE - Pedal Edema

FSH - Follicular Stimulating Hormone

LH - Luteinising Hormone

TGFβ - Transforming Growth Factor Beta

TSH - Thyroid Stimulating Hormone

HLA-G - Human Leukocyte Antigen-G

MIC - Million International Units

TH1 - ‘T’ Helper Cells 1

TH1 - ‘T’ Helper Cells 2

IL - Interleukin

1

INTRODUCTION

Hypertensive disorders affect 7-15% of 1all gestation and form deadly

triad with haemorrhage and infection2. About 16% of maternal deaths are due to

hypertensive disorders and half of these are preventable.

Hypertensive disorders are also responsible for perinatal mortality and

morbidity. Pre-eclampsia is a risk factor for still birth, IUGR, LBW, Preterm

delivery, Respiratory distress syndrome, and admission in neonatal intensive care

unit. Hypertensive disorders account for 8-10% of all preterm births.

A variety of biochemical and biophysical markers have been proposed for

predicting the development of preeclampsia in pregnancy. Chorionic villi is the

one that is needed for development of preeclampsia. Fetus is not an important

factor. Human chorionic gonadotropin is synthesized from syncitiotrophoblast in

chorionic villi. Incomplete trophoblastic invasion that is replacement of vascular

endothelial and muscular linings by endovascular trophoblast to enlarge the

vessel diameter is incomplete.

This study is conducted to predict gestational hypertension by using serum

beta HCG and thereby to follow up the risk patients and to reduce both maternal

and perinatal morbidity and mortality.

2

AIM OF THE STUDY

To find out the sensitivity of serum beta HCG in prediction of gestational

hypertension and its severity, thereby to follow up the at risk patients and to

prevent the development of Gestational hypertension and pre-eclampsia by

prophylactic measures and to prevent its complications.

3

ABSTRACT

BACKGROUND AND AIMS

Hypertensive disorders occur in 6 %- 8% of pregnancies and contribute

significantly to stillbirths and neonatal morbidity and mortality. They are one of

the leading cause of maternal mortality- accounting for almost 15% of such

deaths. Worldwide, over half a million women die each year because of

pregnancy-related causes, and 99% of these deaths occur in the developing

world.

A variety of biochemical and biophysical markers, have been proposed for

the purpose of predicting the development of preeclampsia in pregnancy.

Screening for these factors in the second trimester of pregnancy will help in early

detection of hypertensive disorders of pregnancy, thus enabling

1. Early identification of patients at risk of developing preeclampsia and

eclampsia.

2. Prophylactic medication to prevent hypertension or to reduce its severity.

3. Prophylactic proper antenatal care.

METHODS

A prospective study was done to determine the role of βhcg in 100

pregnant women in their second trimester (13-20) weeks, attending TVMCH

OPD.Routine antenatal investigations were done. 5 ml of venous blood sample

was collected and tests were carried out. Estimation of serum beta hcg level was

done by enzyme linked fluorescence immunoassay. In antenatal clinic, the

4

patients were followed up.Their frequency of visits are once in a month till 28

weeks, once in 15 days upto 34 weeks and weekly till delivery.

RESULTS

From the study it was found, women who have elevated βHCG values in

13-20 weeks are at increased risk of developing PIH. For any test to be used as a

screening tests it should have good sensitivity, specificity and positive predictive

value.In this study β hcg had Sensitivity – 71.4% , Specificity-87.1%.

CONCLUSION

While comparing patients with normal BP and pre eclampsia - βHCG

values are elevated in patients with pre eclampsia. The sensitivity and specificity

of βHCG are very low to be useful as a mass screening marker on its own and

therefore it should be combined with other serum markers and ultrasound

parameters like Doppler study of uterine vessels, which will help in

improving its role as a screening tool.

KEYWORDS : preeclampsia, hypertensive disorder of pregnancy, β

hcg,screening.

5

REVIEW OF LITERATURE

Yaron Y et al . Am J Obstet Gynecol 1999

A total of 60,040 patients underwent maternal serum screening of alpha

fetoprotein, beta HCG, Unconjugated estriol.There is a significant association

between PIH and increased serum alpha feto protein, increased serum beta HCG

and decreased unconjugated estriol.

Basirat z , et al . Saudi med J,2006

Case group : 40 term pregnant women with pre eclampsia.

Control group : 40 normal pregnancies.

Serum beta HCG is measured by Radio immune assay, and they concluded that

maternal serum beta HCG level in patients with pre eclampsia was higher than in

control group.

Preeti dubey ,kiran pandey ,sunita jain ,shilpi gupta

Prospective study(2009 - 2010) among 300 pregnant women with

gestational age between 14-24 weeks with singleton pregnancy was conducted.

They concluded that there is an association between serum HCG and the

subsequent development of pre-eclampsia.

Begum z , ARA I , TANIRA S , KEYA KA

Cross sectional case control study .A total of 74 pregnant patient with pre

eclampsia(patient were admitted in eclampsia ward in 2013) are included in this

study. 76 normotensive patients were taken as control. To identify the disease

early and to know the severity of disease βHCG is useful.

6

Sumitra yadav ,Namrata shrivastava, Sangeeta paneri,Preeti pawar (2013-

2014)

Prospective comparative study included 50 normotensive and 50 pre-

eclamptic women with gestational age of 28-40 weeks .Beta HCG is measured

by CMIA method (chemiluminescent micropartial immunoassay).They

concluded mean Beta HCG level tends to be significantly higher in pre-eclamptic

women as compared to normotensive pregnant women .

Tapas paul ,Jadab kishore phukan ,Kailash bhattacharyya (2016)

This study was conducted between 50 critically established cases of PIH

and 50 Normotensive women after 24 weeks of pregnancy.They concluded that

pregnant women with PIH have higher level of serum Beta HCG in comparison

to normotensive women.

7

GESTATIONAL HYPERTENSION

According to National High blood pressure working group and ACOG,

Hypertension in pregnancy is defined as systolic BP of 140 mm of Hg and

diastolic BP of 90 mm of Hg in a previously normotensive woman after 20

weeks of gestation,taken on two occasions 6 hours apart.3

Diastolic blood pressure is the disappearance of sounds (korotkoff

phase5). Blood pressure should be measured in sitting or in left lateral position

with the arm at the level of heart4. An appropriately sized cuff is used. If the BP

is high in one arm ,that arm is used for all BP recordings.

Classification of Hypertensive disorders5

Gestational hypertension :

Hypertension for first time during pregnancy.

No proteinuria

BP returns to normal before 12 weeks postpartum.

Pre eclampsia and eclampsia :

Hypertension diagnosed after 20 weeks gestation.

Proteinuria

May have other signs or symptoms of pre eclampsia

Eclampsia when accompanied by seizures that cannot be attributed to

other causes.

Preeclampsia superimposed on chronic hypertension :

New onset proteinuria in hypertensive women after 20 weeks gestation

8

A sudden increase in BP or proteinuria or thrombocytopenia in women

with hypertension and proteinuria before 20 weeks gestation.

Chronic hypertension :

Hypertension before pregnancy

Hypertension diagnosed before 20 weeks gestation, not attributed to

gestational trophoblastic disease or multiple pregnancy

Hypertension first diagnosed before 20 weeks gestation and persists

beyond 12 weeks postpartum

AS PER NICE GUIDELINES6

Mild gestational hypertension:

SBP of 140-149mm of Hg and DBP of 90-99mm of Hg.

Moderate gestational hypertension :

SBP of 150-159 mm of Hg and DBP of 100-109mm of Hg.

Severe gestational hypertension :

SBP of > 160mm of Hg and/ or DBP of >110 mm of Hg.

9

Preeclampsia can be classified into mild or severe:

Parameters Mild Severe

Blood pressure <160/110 >160/110

Proteinuria <2+ >3+

Headache Absent Present

Visual disturbances Absent Present

Upper abdominal pain Absent Present

Oliguria Absent Present

Thrombocytopenia Absent Present

Liver enzyme elevation Minimal Marked

Serum creatinine Normal Elevated

Fetal growth restriction Absent Present

Pulmonary edema Absent Present

Incidence :7

Nullipara 6-15 %

Multipara 2-4%

Risk factor8

Young age

Nullipara

Environmental factors

Maternal age>35 years

Multiple pregnancy

10

Molar pregnancy

Abnormal uterine artery Doppler at 18-24 weeks

High risk factor

Previous preeclampsia

Antiphospholipid antibody syndrome

Pre existing diabetes and or HT

Women with SLE

Chronic renal disease

Moderate risk factors

Multiple pregnancy

Primi

BMI >35 kg/m2

family history of pre eclampsia

maternal age >40 years

Inter pregnancy interval >10 years.

White coat hypertension

DBP >90 mm of hg in office , but <135/85 mm of hg at home (pickering

et al )

EtioPathogenesis 9

1) First time exposure to chorionic villi

2) Exposed to large amount of chorionic villi ,like twins,hydatiform mole.

3) Medical disorders in which endothelial cell activation and inflammation

may be present. ( diabetes, renal, cardiovascular diseases)

11

4) Genetic predisposition

5) Altered renin angiotensin aldosterone system (the refractoriness to

angiotensin 2 is lost).

Pre eclampsia- phenotypic expression

“Two stage disorder” – pre eclampsia theory10

Stage 1 :There is a defect in remodeling of endovascular trophoblast which leads

to stage 2 clinical syndrome.

Stage 2:Patient who were having pre existing Diabetes ,renal, cardiovascular

diseases.

Etiology:11

1) Abnormal trophoblastic invasion of uterine vessels.

2) Genetic factors

3) Inflammatory and angiogenic factors

4) Immunological intolerance between fetal and maternal tissues

12

Figure 1: Pathogenesis of pre eclampsia :

Alterations in genetic ,immunological ,environmental factors lead to changes in

regulatory factors like OH/COMT Catechol O-Methyl Transferase /2ME

Methoxy Estradiol and Angiotensin Type 1 agonistic AutoAntibodies (AT1AA),

which results in impaired VEGF /PIGF and TGF-β signaling.- Ultimately leads

to systemic endothelial dysfunction and features of preeclampsia.

13

Trophoblastic invasion abnormality:12

Normal:

Replacement of Vascular endothelial cell and muscular linings by

Endovascular trophoblasts.

Abnormal:

Trophoblasts invade decidual vessels but not the myometrium vessels

which results in high resistance flow and a small diameter vessel.

Figure 2:

There is reduced trophoblastic invasion in pre eclampsia and (IUGR) intra

uterine growth restriction compared with normal pregnancy. Hence decreased

14

bloodflow in fetoplacental unit and results in FGR Foetal Growth Restriction.

There is also systemic endothelial dysfunction and development of preeclampsia.

Genetic Factors:13

Candidate genes: polymorphism of FAS, Hypoxia inducible factor -1

alpha protein , Interleukin -1 Beta, Lymophotoxin –alpha, Apo E,TGF –

Beta14,15,16

Gene associated with preeclampsia Function

Factor V(Leiden) Factor V Leiden

MTHFR gene (6771) Methylene Tetrahydrofolate reductase

NOS3 (Glu 298 ASP) Nitricoxide production in Endothelium

AGT (M235 T) Angiotensinogen

F2(I/D at Intron16) Prothrombin (Factor II)

Inflammatory and Angiogenic factors :17

There is reduced expression of HLA-G (immune suppressive human

leucocyte Antigen-G) in women destined to be pre-eclamptic.

There is increased amount of serum antiangiogenic factor (e.g:sFLT-1 is

on chromosome -13) in women with risk for preeclampsia. Hence women

with Trisomy 13 fetus have high risk for preeclampsia.18

Th1 (Pro inflammatory Cytokines) lymphocytes activity is increased &

Th 2 (anti inflammatory Cytokines) activity is decreased.19,20

15

Figure 3 : Th1 cells and Th2 cells are derived from CD4 cells. Th1 cells are

derived from CD4 cells in the presence of IL 12. Th1 cells play a role in allograft

rejection. Th2 cells are derived from CD4 cells in the presence of IL4 and IL10.

Th2 cells play a role in allergic response. Extravillous trophoblast produces

soluble HLA-G , inducing regulatory type Tg1 cells. IL10 derived from Tg1

cells promotes maternal tolerance.

16

Immunological cause:21

Maternal immune system develops immune tolerance to fetal and

placental antigens by blocking antibodies. These blocking antibody sites are

impaired in women with high risk for preeclampsia.

Pathogenesis:

1. Vasoconstriction22

Vasoconstriction and resistance to flow are increased in response to

endothelial activation which leads to Hypertension

2. Increased response to vasopressor 23,24,25,26

Normal pregnant women—develop refractoriness to vasopressor

Preeclampsia predisposed individual –have increased sensitivity to

vasopressor.

3. Prostaglandins27,28

In preeclampsia predisposed individual prostacyclin (PGI2) level deceases,

and (TXA2) Thromboxane A2 level increases - leads to increased sensitivity

to infused vasopressor.

4. Nitric oxide29

Nitric oxide synthesis inhibition mimics the picture of preeclampsia by means

of increased mean arterial pressure and reduced heart rate.

17

5. Endothelins30,31

In normal pregnant women there is increased Endothelin -1 levels; In

preeclampsia women its levels are even more.

Increased levels of sFlt-1, sEng levels are start to increase before the

development of clinical factors.

Interestingly ,Magnesium sulphate treatment lowers ET-1 levels.

18

Pathophysiology

Cardio vascular system:32

Peripheral resistance is increased and cardiac output is decreased

Ventricular function is normal (or) Hyperdynamic.

Pulmonary oedema due to alveolar endothelial & epithelial leak,

accompanied by decreased oncotic pressure due to low serum albumin.

Blood Volume:33

Usually in GHT, normal blood volume is maintained

In preeclampsia –women have decreased blood volume

Coagulation Abnormalities 34,35

Thrombocytopenia

LDH levels are elevated

Schistocytosis, spherocytosis, reticulocytosis in peripheral blood.

Elevated liver enzymes (because of hepato cellular necrosis).

Fibronectin level is elevated36

19

Liver:37

Haemorrhage & infarction in Liver leads to right epigastric pain and

tenderness.

There may a chance of development of hepatic hematoma. This may

further extend and form subcapsular hematoma.

20

Kidney:38,39

Decreased filtration due to glomerular endotheliosis causes increased

serum creatinine levels.

Urine sodium concentration is elevated & urine calcium is decreased.

Plasma uric acid is increased

Proteinuria

21

Placenta:40a,b

MACROSCOPIC APPEARANCE OF PLACENTA IN NORMAL AND

PREECLAMPTIC PREGNANCY

Figure 5: Normal placenta and placenta in pre eclamptic patients (Reduced

thickness)

Chorionic villi congestion

Proliferative endarteritis

Increased incidence of infarcts, haematomas

Syncitial knots increased , cytotrophoblastic cellular proliferation .

22

MICROSCOPIC APPEARANCE OF PLACENTA

Figure 6 :Increased levels of syncytial knots in placeta of the patient with pre

eclampsia.

Brain:41,42

There is vasoconstriction of cerebral vessels due to autoregulation which

leads to cytotoxic oedema. When this fails—leads to vasodilatation and

vasogenic oedema.

Foci of infarction may be seen

Cerebral haemorrhage may be seen with chronic hypertension with

eclampsia

23

MRI should be performed in severe hypertensive disease of pregnancy

with complications.43

Management:44a

Evaluation

Urine examination – proteinuria

Hb% increased

Platelet – decreased

Peripheral smear – schistioscytes

INR, APTT- increased (in DIC) – This is done if platelet count and LDH

are abnormal.44b

Serum Creatinine –higher

ALT, AST, LDH, Bilirubin – higher

Albumin-lower

Fundus examination

Pre conceptional advice:

Angiotensin converting enzyme inhibitors, Atenolol, Statins, Thiazides

should be discontinued because of teratogenic effect.

Antepartum Management45a

According to NICE45b guidelines women with at least one high and two

moderate risk factors of preeclampsia should be given 75mg of aspirin

from 12 weeks of pregnancy till the delivery of the baby

24

Reduced physical activity

Regular blood pressure monitoring & ante natal visit (weekly or two

weekly)

Anti-hypertensive therapy

According to NICE guidelines ,women with mild to moderate HT with

comorbid condition –start antihypertensives.

Admission is advised in women with preeclampsia and complication

Out patient management if the disease does not worsen

Criteria for home management of mild preeclampsia.

Ability to comply with recommendations

DBP < 100 mm Hg

SBP < 150 mm Hg

Normal laboratory tests and no maternal symptoms

Reassuring fetal status with appropriate growth

Urine protein of 1 g or less in 24 hours.

Intrapartum management:46,47

Hourly Blood pressure monitoring

Aim is to maintain diastolic BP at or below 110mmHg and Systolic BP at

or below 160mmHg.

Mild hypertension with severe disease or organ dysfunction- start Anti

Hypertensives. Women with mild to moderate HT with co-morbid

condition- Treat with Anti Hypertensives.

25

Eclampsia prophylaxis given in women with severe preeclampsia or

impending eclampsia

Continuous fetal heart monitoring

Vaginal delivery should be considered except for obstetric indications

In case of poor bishop score, induction should be done with

prostaglandins

Ergometrin should be avoided; Active management of third stage of

labour (AMTSL) should be followed.

Indication for caesarean delivery:

Timing of Delivery(ACOG)

The outcome of Labour induction > 37 weeks in mild preeclampsia, was

better compared to expectant management (Koopmans et al 2009)

For women with controlled HT (With drugs)- 37 to 39 weeks

With severe HT -36 to 37 weeks.

Treatment of Hypertension:

SOGC Guidelines (2008) suggest that with Anti-hypertensive therapy 48

Hypertensive women without comorbid conditions should have DBP

between 80-105 mmHg

Hypertensive women with comorbid conditions (DM, Renal disease)

should have SBP 130-139 mm of Hg and DBP 80-89mm of Hg

In patients with severe HT, maintain SBP of 140 -150mm of Hg and DBP

of 90-100mm of Hg.

26

Recommended management of mild Gestational Hypertentension or

Preeclampsia

27

Recommended management of severe preeclampsia

28

DRUGS

1. LABETALOL-- Adrenoceptor blocker ; 100-400 mg bd- tds (maximum

of 1200mg/day) . Side effects – postural Hypotension, tiredness

2. METHYL DOPA --Centrally acting alpha adrenergic agonist ; 250 -

500mg tds-qid(maximum of 2g/day). Side effects – headache, dizziness,

hypotension .

3. NIFEDIPINE -- calcium channel blockers ; 10-20mg bd. Side effects-

Hypotension, head ache, and nasal congestion .

4. HYDRALAZINE- i.v boluses ; starting at 5mg and increasing by 5mg

every 20 minutes upto 20 mg.49

CORTICOSTEROIDS:

Women with preeclampsia before 34 weeks should have steroids for fetal

lung maturity.

12 mg of Betamethasone given in 24 hours apart as2 doses .(RCOG –

2010) 50

Complications:

Maternal:

1. Eclampsia

2. Cerebro vascular Accident (May occur due to intracerebral haemorrhage )

3. Placental abruption

4. HELLP Syndrome51

29

Haemolysis

Abnormal peripheral smear (schistocytes, burr cells

LDH> 600 U/L

Bilirubin >1.2 mg/dl

Elevated Liver Enzymes

AST > 70 U/L

LDH> 600 U/L

Low Platelet count

Platelet count < 100 000 /mm3

5. Pulmonary oedema with or without acute left ventricular failure

6. Acute Renal failure

7. Micro angiopathic haemolytic Anaemia.

8. Disseminated intravascular coagulation (DIC)

9. Drug related side effects

Foetal:

1. Intra uterine fetal growth restriction

2. Oligohydramnios

3. Prematurity (more likely to be iatrogenic in preeclampsia due to

termination in severe Preeclampsia, Eclampsia, Abruption)

4. Antepartum and intrapartum asphyxia mostly due to poor placental blood

flow, maternal hypoxia induced by Eclampsia (or) sedative effect by

anticonvulsant

30

5. Intra uterine death

6. Fetal side effects of antihypertensive drugs.

Eclampsia:

Eclampsia is defined as the development of seizures that can not be

attributed to other causes and/ or unexplained coma during pregnancy or

puerperium in a woman with pre-eclampsia

Maternal mortality in Eclampsia is 1 to 5 %

Perinatal mortality occurs in about 5-12% of the cases.52

Impending Eclampsia:

It is suggested in women with following signs and symptoms

Headache (occipital or frontal)

Blurring of vision

Epigastric pain and or right upper quadrant pain

Nausea/ vomiting

Oliguria

Laboratory evidence of disseminated intra vascular coagulation

It presents as generalised tonic-clonic convulsions and or coma in a pre-

eclamptic woman.

Management:53,53a,b,c

Magnesium sulphate is for prevention and treatment.

31

Clearing the airways, oral suctioning, oxygen

Controlling the blood pressure

Delivering the baby

MAGNESIUM SULPHATE

Loading dose: 4g of 20% magnesium sulphate is given i.v slowly over 5

minutes, followed by 10 g of 50% magnesium suphate solution, one half (5g)

i.m injected deeply into each gluteal region.

Maintenance dose:5 g magnesium sulphate (50% solution) every 4 hours into

alternate buttock intramuscularly.

Monitor:

Respiratory rate

Patellar reflexes

Urinary output before giving repeat doses.

In case of magnesium toxicity give 1 g calcium gluconate (10 ml of 10%

solution) i.v slowly

DELIVERY

In case of preeclampsia – must be delivered with in 24 hours

In case of Eclampsia – with in 12 hours in a patient who has Convulsions.

If the cervix is favourable – Amniotomy or labour induction with PG, Oxytocin

If the cervix is unfavourable & fetus is alive – caesarean section

32

Risk of recurrence:54

In women with GHT:

GHT-16 to 17%

Pre-eclampsia- 2 to 7 %

In women with Pre-eclampsia

GHT-13-53%

Pre-eclamplsia-16%

In women with Eclampsia or HELLP

Preeclampsia -25 to 55 %

PREDICTION AND PREVENTION

SCREENING TESTS FOR PREECLAMPSIA

I. Alteration in the function of placental perfusion and resistance in vessels

Mean arterial blood pressure

Doppler ultrasound

Roll over test

Angiotensin infusion test

Isometric exercise test

Platelet angiotension II binding

Platelet calcium response to arginine vasopressin

Renin

33

24-hours Ambulatory blood pressure monitoring

II.Alteration in the function of Fetoplacental unit

Human chorionic gonadotrophin

Alpha fetoprotein

Inhibin A

Pregnancy-associated plasma protein A – decreased

Estriol

III. Alteration in the function of Renal parameters

Elevated Serum uric acid

Increased Microalbuminuria

Kallikrein in urine

Elevated Microtransferrinuria

IV.Alteration in the function of Endothelial & oxidant stress

Fibronectin-elevated

Endothelin-elevated

Thromboxane-elevated

Homocysteine-elevated,

The various predictors can be broadly classified as non laboratory methods and

laboratory methods.

34

NON LABORATORY METHODS:

1. History : High risk factors associated with preeclampsia includes

· Primigravida

· Extremes of maternal age

· Obesity

· Multifetal gestation

· Prior pregnancy complicated by preeclampsia

· Ethnicity.

2. Provocative pressor tests: These tests are based on increased vascular

sensitivity to vasopressor stimuli in women those destined to be hypertensive

during pregnancy

a. Angiotensin II infusion test- Talledo et al.1968

This test is done between 28-30 weeks

An increase in the diastolic BP more than 20 mmHg during the Angiotensin

infusion predicts preeclampsia with a sensitivity of 90% , specificity of 87%,

positive predictive value of 78% in high risk population

Disadvantage:

· Difficulty to do as a mass screening procedure.

· Time consuming

· Expensive

· Unreliable

35

b. Roll over Test-Grant et al

This test is done between 28-32 weeks of pregnancy. First the blood

pressure is recorded with the patient in left lateral position. An increase in

diastolic BP of more than 20mmHg, when the patient lies on the supine

position is regarded as positive test.

Sensitivity - 0-88%

Specificity - 5-95%

Positive predictive value - 0-93%

This test is of no clinical use due to gross variation in results.

c. Isometric handgrip test: Dagani et al.55

This test is done between 28-32 weeks of gestation.

Suggested a threshold increase of 20mmHg in diastolic BP when patient

Squeezes a hand ball for 3 minutes

Sensitivity 81%

Specificity 96%

Positive predictive value 81%

d. Mean Arterial pressure:

Page and Christians on suggested that patients with mean arterial pressure

more than 90 mmHg in second trimester are at high risk for pre-eclampsia. But

predictive value vary greatly.

36

Doppler USG: Campbell and associates

Doppler velocimetry of uterine umbilical vessels can predict pre-

eclampsia as early as 18 weeks. There is a characteristic notching of diastolic

waveform, suggesting increased peripheral resistance due to impaired

trophoblastic invasion of spiral arterioles in patients with risk to develop pre-

eclampsia. It is not useful for screening pregnant women -Bowel and colleagues

(1993)

Sensitivity 78%

Positive predictive value 28%

LABORATORY TESTS :

Fetal placental unit – endo crine dysfunction

HCG, Alpha Fetoprotein , Estriol ,PAPPA, inhibin A , activin A,

Placental protein 13 , Corticotropin releasing hormone .

Markers of endothelial dysfunction

Serum fibronectin

Plasminogen activator inhibitors,cell adhesion molecules, serum

thrombomodulin,endothelin-1

coagulation factors and platelets

serum uric acid

Atrial natriuretic peptide, Haematocrit.

37

Urinary assays:

a. Microalbuminuria

b. Urinary calcium excretion56

c. Urinary calcium / creatinine ratio57

d. Urine kallikrien / creatinine ratio

e. Fasting urine albumin/ creatinine ratio

Proteinuria

Proteinuria means protein levels in urine of >150 mg/day.

In O.P settings, Dipstick method is used.

False positive results with

1. Hematuria

2. Drugs like penicillin ,sulphanamides

3. Pus,semen and vaginal secretions.

False negative reports in

1. Diluted urine

2. Other nonalbumin or LMW protein

The results are graded as

negative (less than 10 mg per dL),

Trace (10 to 20 mg per dL),

1+ (30 mg per dL),

2+ (100 mg per dL),

3+ (300 mg per dL)

4+ (1,000 mg per dL).

38

This method preferentially detects albumin and it is less sensitive to globulins

or parts ofglobulins (heavy or light chains or Bence Jones proteins).

Angiogenic factors

Decrease in proangiogenic factors like vascular endothelial growth factors

(VEGF) and placental growth factors (PlGF)

Increase in antiangiogenic factors like sFlt -1 and sEng

Cell free fetal DNA: 58,59

Fetal maternal cell trafficking is increased in pregnancies complicated by

preeclmpsia. Conde concluded that cell free-fetal DNA quantification is

not yet useful for prediction of preeclampsia.

Serum uric acid:

Serum uric acid concentration is raised in preeclampsia due to decreased

clearance. Serum level correlates with disease severity and fetal outcome.

The rise in serum levels occurs relatively late in the course of the disease. Hence

not reliable as a predictor. Sensitivity ranged from 0-55% and specificity 77-

95%. Raised serum uric acid is probably better regarded not as a predictive,

diagnostic or specific feature of preeclampsia, but as a sensitive indicator of

impaired renal function.

39

SERUM FIBRONECTION:

Fibronectin is a glycoprotein that has a important role in cellular

adhesions, migration, phagocytosis and homeostasis. It is a component of

connective tissue and basement membrane. Following endothelial injury, it is

released from endothelial cells and extracellular matrix into circulation.

Cellular fibronectin levels of> 3.8 ug/mL within 22 to 26 weeks of gestation was

proposed to be helpful in the early detection of preeclampsia in primigravida.

Sensitivity, specificity and positive & negative predictive values were

inconsistent among different studies. Systemic review concluded that neither

cellular nor total fibronectin was clinically useful to predict

PIH.

Hyperhomocysteinemia:

Homocysteine causes oxidative stress and endothelial cell dysfunction and

it is found to be elevated in preeclampsia. Although women with elevated serum

homocysteine levels at 14-16 weeks of pregnancy had a 3 – 4 fold risk of

developing preeclampsia, 80 it has not shown consistent results.

Serum inhibin A activin A:

Their role in etiology of preeclampsia is not clear. They are secreted by

trophoblast cells of placenta, levels peak at 8 weeks and then declines to rise

again at term. They have a formation of placental bed in invasion of trophoblast.

Maternal serum levels are increased between 13-18 weeks in patients who later

develop preeclampsia.

40

Alpha-Fetoprotein (AFP):

Origin from ,

i. Yolk sac

ii. Fetal liver

iii. Gastro intestinal tract

Maternal serum AFP increases until 30 weeks of gestation.there is a association

between high maternal AFP and preeclampsia or GHT have been demonstrated

in several studies. In fetal serum AFP reaches a peak value of 3mg/ml at 12

weeks of gestation and declines thereafter.

Pregnancy Associated Plasma Protein – A (PAPP-A):

IGF have a role in regulation of fetal growth. PAAP-A is a protease for

IGFBP1 and IGFBP2. Hence ,

Low level of PAPP-A

Elevated IGFBP1 and IGFBP2

Low level of IGF

IGF have also role in trophoblastic invasion of deciduas by controlling the

uptake of glucose and aminoacids.

Low maternal PAPP-A at 10-14 weeks

Marker of inadequate placentation

Associated with GHT and FGR

41

Angiogenic and antiangiogenic factors:

Several proangiogenic and antiangiogenic substances are involved in

placental vascular development. Factors like Vascular Endothelial Growth Factor

(VEGF) placental growth factor (PLGF) are decreased in preeclampsia. This

difference is consistently not seen in early pregnancy. Study demonstrated that

placental growth factor is not a good marker for subsequent development of

severe preeclampsia. Excessive amounts of antiangiogenic factors are stimulated

by worsening hypoxia at the uteroplacental interface. Trophoblastic tissue of

women destined to develop preeclampsia over produces at least 2 antiangiogenic

peptides that enter the maternal circulation.

i. Soluble Fms – like tyrosine kinase (sFlt-1) is a receptor for placental

growthfactor (PLGF) and Vascular Endothelial Growth Factor (VEGF).

ii. Soluble endoglin (sEng) is a placental derived molecule that blocks

iii. Endoglin, a co-receptor for TGFB. It inhibits binding of TGFB to

endothelial receptors and results in decreased endothelial nitric oxide

dependent vasodilatation. The cause of placental overproduction of

antiangiogenic proteinss remains enigma.

iv. Soluble endoglin and soluble fms like tyrosine kinase 1 (SFlt-1) are

increased prior to onset of clinical disease. Until better substantiated, their

clinical usefulness is not recommended,

URINE TESTS

A number of investigators have evaluated the potential value of

microalbuinuria as a predictive test. Microalbuminuric phase precedes clinical

42

proteinuric phase. The developmentof a radioimmunoassay for albumin has

made it possible to detect microalbuminuria in women who have not yet

developed proteinuria as demonstrated by clinical methods.87 Pregnant women

with mircoalbuminuria (> 12.04 ugm/ml) at 16-22 weeks are at risk of

developing hypertensive disorder Sensitivity 9% and specificity 29% with poor

predictive value.

Urinary calcium excretion:

Hypocalciuria occurs early and persists throughout the pregnancy affected

with preeclampsia. Taufield et al measured 24 hours urinary calcium excretion

and found lower total and fractional excretion in women with preeclampsia as

compared to normotensive pregnant women.

Urinary calcium creatinine ratio:

Rodrigtiez et al compared the microalbuminuria and calcium creatinine as

predictive test.

Microalbuminuria ≥11µg/ml

Calcium creatinine ratio≤0.04µg/ml

They concluded Calcium creatinine ratio is superior to microalbuminuria. But

still large number of studies are required.

Urinary Kallikreins excretion:

Kallikreins are proteases with indirect vasomotor effects mediated by

kinins and by the renin-angiotensin system. Urinary Kallikreins excretion has

been shown to increase in normotensive pregnancy, whereas in preeclampsia

reduced levels as compared to non-pregnant subjects have been found.

43

In Millar et al study, the ratio between inactive urinary Kallikreins and urinary

creatinine concentrations at 16-20 weeks as predictor test to diagnose

preeclampsia. This test does not have any significant sensitivity and specificity.

But have some prognostic significant in development of PIH.

Difficulties with assay techniques have impeded assessment of Kallikrein-kinin

system in PIH.

Microtransferrinuria :

Urinary microtransferrin levels in pregnant women who subsequently

developed severe PE and eclampsia were significantly higher than those of the

pregnant women who remained normotensive. With sensitivity 93.5%,

specificity 65%, it can be a potential predictor of preeclampsia.

As of ACOG (2004), there is no clinically useful screening test to predict

the development of preeclampsia. Further, prospective longitudinal studies are

needed.

44

Prevention

There is a considerable literature devoted to the prevention of

preeclampsia. However, there is some controversy over whether or not

prevention of preeclampsia per se is a worthy goal, rather than the prevention of

the complications of preeclampsia.

Primary prevention

Primary prevention though best, is possible only when the exact etiology

is known. Primary prevention is possible to some extent by modification of some

of the risk factors. As the disease process more common in nulliparous women or

in mutliparous women with change of partners, it is recommended to have

pregnancies with low risk men, to stay with same partner and to have children at

an age when the endothelium is still able to cope with the inflammatory stress

associated with the pregnancy state. Prevention &/or effective control of

obesity could significantly result in the frequency of preeclampsia.

Similarly women with diabetes, chronic hypertension, renal and other

medical disorders should have their primary condition under control before

attempting conception. However it applies only to minority of patients.

Secondary prevention

The basic requirements for secondary prevention are

1) knowledge of pathophysiological mechanisms

2) availability of screening methods

3) means of intervention and modification of the pathophysiology.

45

None of the 3 criteria are available for effective secondary prevention.

Many screening tests suffer from poor sensitivity and specificity.

Non pharmacological interventions

1. Bed rest

2. Life style changes

3. Regular physical activity

Nutritional interventions

1. Dietary sodium restriction

2. Dietary protein and energy intake

3. Control of obesity.

4. Change in dietary habits

5. Fist oil-some studies have shown beneficial effects of omega-3 fatty

acids in the prevention of preeclampsia. The large European multicentre

Fish Oil supplementation. Trial (FOTIP) concluded that fish oils are

unlikely to beneficial in prevention of preeclampsia.

6. Alcohol intake.

7. Arginine supplementation – found to be beneficial but it was an

isolated study.

8. Japanese Herbal medicine Toki-shakuyuku-san (TS) – may be

beneficial in the

treatment and prevention of preeclampsia.

46

Pharmacological Interventions

1 Antihypertensive drugs.

2 Diuretics

3 Zinc supplementation.

4 Magnesium

5 Folic acid and other B vitamins – there is no scientific data that any of B

vitamins are beneficial in the prevention of preeclampsia.

6 Low dose aspirin: Low dose aspirin 50-150mg/day therapy during

pregnancy selectively inhibits platelet thromboxane A2 (TX-A2)

biosynthesis with minimal effects on prostacyclin. Largest trial to date is

CLASP (collaborative low dose aspirin) study. Overall the use of low

dose aspirin was associated with 12% reduction in the incidence of

preeclampsia (non significant) and it reduced the incidence of preterm

delivery (19.7% v/s 22.3% in placebo group). Aspirin treated women has

slightly higher risk of abruptio placentae (STATISTICALLY NOT

SIGNIFICANT). Meta analysis of antiplatelet agents for the prevention of

preeclampsia did not find difference between treatment and control group.

The results of available trials do not support the widespread and routine

prophylactic or therapeutic use of aspirin therapy for women judged to be

at risk for preeclampsia. The only group where low dose aspirin may be

justified is in women at risk of developing early onset preeclampsia.

7 Heparin and low dose aspirin – for only women with anti phospholipids

antibody syndrome and not for routine recommendation.

47

8 Calcium supplementation – There is inverse relation between calcium

intake and the frequency of preeclampsia. The largest trial conducted

(2g/day supplementation) by Levind did not find any benefit. However

Cochrane review observed a modest reduction in preeclampsia and the

effect was greatest in high risk women with low calcium intake.

9 Nitric oxide (NO) donors – NO synthesis is impaired in preeclampsia.

10 The data on effects of NO donors in prevention of preeclampsia are

limited and conflicting. A large multicentric trial is currently underway.

11 Antioxidants – Various antioxidants like Vitamin C, E, Iycopene,

selenium, N-acetylcysteine and garlic are used in many studies with

encouraging results. However the Cochrane review 2008 finds that

antioxidant supplementation may not affect risk of preeclampsia or

clinical outcomes (level 2 evidence).

Diet:60,61

Low salt diet

Calcium and fish oil containing foods

Exercise:

Cardiovascular drugs:

Diuretics

antihypertensive drugs

Anti-oxidants62,63,64

Vitamin C, Vitamin E, Vitamin D

48

Anti-thrombotic agents:65,66

Low dose Aspirin

Aspirin/ Dipyridamole

Aspirin + Heparin

Aspirin + Ketanserin

HUMAN CHORIONIC GONADOTROPIN

Human chorionic gonadotropin is a glycoprotein a peptide frame

work to which carbohydrate side chains are attached.

Half-life – 24 to 36 hours

Alpha (92 amino acids)

HCG consists of -2 subunits

Beta (145 amino acids)

These 2 subunits are linked by disulphide bonds

α subunit is identical to –FSH,LH,TSH

β subunit is unique and specificity in immunoassay is attributed to the molecular

and carbohydrate differences in β subunit

In β subunit, there is a unique carboxy terminal tail piece of 23 amino

acids groups that allow production of highly specific immunologic assays.

Molecular weight :36000 Daltons .

49

Biosynthesis of HCG:

1) α subunit originates from one single gene on chromosome 6

50

2) β subunit originates from 8 separate genes for beta subunits of different

glycoprotein hormone on chromosome 19.

3) Secreted by trophoblasts

Before 5 weeks syncytiotrophoblasts and cytotrophoblasts produce HCG.

Later produced exclusively by syncytiotrophoblasts.

It acts via plasma membrane LH-HCG receptors

Regulation of HCG synthesis:

HCG Secretion is probably regulated by

1. Placental GnRH (Gonadotrophin releasing hormone) and CRH

(corticotropic releasing hormone)

2. Activin, Endorphin, inhibin

3. Butylated cyclic AMP

4. Interleukin 1, and interleukin 6

5. Transforming growth factor ( TGF- Beta )

6. Fibroblast growth factor

7. Tumour necrosis factor (TNF)

Exact mechanism by which regulation occurs is not known

51

Clearance:

Renal clearance accounts for 30% of HCG clearance.

Remaining is likely cleared by metabolism in liver

Molecular forms in plasma and urine

HCG exists in multiple forms

Intact HCG

Hyperglycosylated HCG

Nicked HCG

Free subunits

HCG concentration in serum:

HCG concentration is approximately 100 IU/L at time of expected but

missed menses. The maximum level of about 1,00,000 IU/L in maternal

circulation is reached at 8-10 weeks gestation. HCG levels decrease to about

10,000 -20,000 IU/L by 18-20 weeks of gestation and remain at that level until

delivery.

Doubling time approximately 3 days (1.4 to 3.5 days)

Levels are elevated in : multiple gestation

Down’s syndrome fetus

Gestational trophoblastic disease

52

Decreased levels seen in:

Ectopic pregnancy

Impending miscarriage

Functions of HCG:

Supports corpus luteum of pregnancy till placenta takes over

Stimulates fetal leydig cells to produce testosterone

May promote uterine muscle relaxation and vasodilatation

Promotes secretion of relaxin by corpus luteum

Serum HCG levels Throughout normal pregnancy67s

53

3 weeks LMP : 5-50 m IU/ml




7-8 weeks LMP : 7650 -229,000 m IU/ml

9-12 weeks LMP : 25700-2,88,000 m IU/ml

13-16 weeks LMP : 13,300-2,54,000 m IU/ml

17-19 weeks LMP : 4,060 -1,65,400 m IU/ml

25-40 weeks LMP : 3640-117,000 m IU/ml

Non pregnant females < 5 m IU/ml

Numerous different assays for quantitative estimation of HCG have been

developed that differ in methodology (Radio- immunoassay, Enzyme

immunoassay,Fluorescent immunoassay), sensitivity and specificity.68

HCG in preeclampsia:

Placenta is the main source for HCG synthesis and measurement of

plasma HCG levels has proven to be effective screening tool for pregnancies

with altered placental function.

placenta

Impairedangiogenesis

High hormone levels inmaternal circulation

Insufficiencyof spiralarteries Hypersecretion of

placental hormones

Hyperplasia oftrophoblast cells

Hypoxia

54

In normal pregnancy:

low oxygen tension in first trimester.

TGF beta mediated prevention of trophoblast into invasive phenotype

Between 10 and 12 weeks The physiological increase in

oxygen tension decrease of TGF-Beta

trophoblast to differentiate into a more invasive type.

In preeclamptic patients:

TGF-Beta levels remains high

Immature trophoblast development

Development of hypersecretory state in response to hypoxia

Elevated placental hormones

Placental hormones are elevated prior to the development of preeclampsia.

ELIZA (ENZYME LINKED IMMUNOSORBANT ASSAY):

It is useful for quantification of extremely small amounts of Beta-HCG.

ELIZA test uses monoclonal antibodies bound to a solid phase support which

binds the HCG in the sample. A second antibody is added to sandwich the test

sample Beta-HCG. The second antibody is linked with an enzyme such as

Alkaline phosphatase. When the substrate for this enzyme is added blue colour

develops. The intensity of which is proportional to the amount of enzyme and

55

thus to the amount of second antibody bound. This in turn is a function of the

amount of Beta-HCG in the test sample. The sensitivity of the test is 25-50

mU/ml.

56

METHODOLOY

INTRODUCTION

The primary aim of antenatal care is to achieve a healthy mother and

healthy baby .Nowadays there are many investigations and treatment modalities

are available. Although advances in antenatal care, Hypertensive disorder in

pregnancy contribute to increased maternal mortality and morbidity and thereby

accounts for increased perinatal morbiditiy and mortality. Major causes of

maternal mortality includes haemorrhage, sepsis, hypertension, obstructed

labour abortion and other conditions.

Placentation abnormality is one of the main event in disease

formation.There is immunological changes in trophoblast which leads to

secretory response. This is seen as rise seen in β hcg levels. This study was

conducted to find out the association between β hcg and development of GHT.

AIM

To test the hypothesis that women with high serum beta-HCG levels in

early pregnancy are at higher risk of developing PIH.

METHODS

Serum beta-HGC estimation was done by ELISA method in 100 women

between 13 and 20 weeks of gestation, selected randomly for this study from

Aug2014 to Jul2015.

57

INCLUSION CRITERA

Pregnant women with

1. Non proteinuric

2. Normotensive

3. Primi/Multi gravida

4. Singleton

5. Gestational age 13-20 weeks as determined by last menstrual period or

ultrasound scan.

EXCLUSION CRITERIA

Chronic hypertension.

Molar Pregnancy.

Diabetes mellitus.

Anomalous foetus.

Multiple pregnancy.

METHODS

All the women were subjected to detailed history regarding age, parity,

past obstetric history, medical history, and family history. Height, weight, blood

pressure were measured.

Routine antenatal investigation was done. 5 ml of venous blood sample

was collected andtests were carried out. Estimation of serum β hcg level was

done by enzyme linked fluorescence immunoassay.

58

The cases were followed up in antenatal clinic and were examined 4

weekly till 28 weeks, fortnightly upto 34 weeks and thereafter weekly till

delivery. At every visit, blood pressure was recorded and urine was examined for

albumin.PIH included gestational hypertension and preeclampsia. Gestational

hypertension was defined as blood pressure _ 140/90 mmHg on two occasions at

least 6 hours apart after 20 weeks of gestation. Preeclampsia was defined as

gestational hypertension and proteinuria of atleast 1 + on dipstick. The patients

who developed preeclampsia were followed till 6 weeks after delivery.

59

RESULTS AND ANALYSIS

Data analysis and interpretation:

The data were analysed and interpreted according to the type of variables.

The continuous variables were analysed in terms of mean and interpreted by

student’s t test. The discontinuous variables were described in terms of

percentages and interpreted by χ2 (Chi-square) test. The cut point for prediction

of βHCG as an indicator of PIH was done by ROC curve approach. The level of

significance was fixed as 5% and the P-values less than or equal to 0.05 (P≤0.05)

were considered as statistically significant.

Results:

Similarity of study subjects:

The study subjects namely normal and PIH mothers were compared in

terms of their age, SBP and DBP at the time of Ante- natal registration.

60

Table-1:Comparison of PIH and Normal mothers in respect of their age:

Age groupNormal

Pregnancy Induced

Hypertension

Total

Frequency % Frequency % No %

15-19 1 1.2 0 0.0 1 1.01

20-24 21 24.7 3 21.4 24 24.24

25-29 51 60.0 10 71.4 61 61.62

30-34 8 9.4 1 7.2 9 09.09

35-39 4 4.7 0 0.0 4 04.04

Total 85 100.0 14 100.0 99 100

Mean ± SD 26.2 ± 4.5 26.1 ± 2.2

Significance “t” = 0.094, df= 97 and P>0.05.

0

10

20

30

40

50

60

70

80

15-19 20-24 25-29 30-34 35-39

1.2

24.7

60

9.44.7

0

21.4

71.4

7.20

Normal Pregnancy Induced Hypertension

61

The above table-1 states the similarity of PIH and Normal mothers in

respect of their age at the time of booking. The mean age of normal was 26.2 ±

4.5 years and that of PIH mothers was 26.1 ± 2.2 years. The difference of age

between them was not statistically significant (P>0.05).

15-191%

20-2424%

25-2962%

30-349%

35-394%

TOTAL

62

Table-2: Comparison of Socio economics status between the Normal and PIH

mothers.

Economic

Status

PIH Normal Totalχ2 df Significance

No % No % No %

III 0 0.0 4 4.7 4 4.1

1.072 1 P>0.05IV 4 28.6 30 35.3 34 34.3

V 10 71.4 51 60.0 61 61.6

Total 14 100.0 85 100.0 99 100.0

The above table -2 compares the economic status between the PIH and

normal mothers. There was statistically significant similarity between them

(P>0.0).

0

10

20

30

40

50

60

70

80

III IV V

0

28.6

71.4

4.7

35.3

60

PIH Normal

63

III4%

IV34%

V62%

Total

64

Table-3: Comparison of homogeneity between the PIH and Normal mothers in

respect of their gravida.

Gravida.PIH Normal Total χ2 df Significance

No % No % No %

0.287 1 P>0.05Primi 6 42.9 43 50.6 49 49.5

Multi 8 57.1 42 49.4 50 50.5

Total 14 100.0 85 100.0 99 100.0

The PIH and Normal mothers were compared in respect of their gravid in

the above table-3. The primi and multi gravid mothers were 49.5% and 50.5%

respectively. The gravid of mothers had not been statistically significant between

the two categories of mothers (P>0.05).

0

10

20

30

40

50

60

Primi Multi

42.9

57.1

50.6 49.4

PIH Normal

65

49%51%

Total

Primi

Multi

66

Table-4: Comparison of systolic and diastolic blood pressure between PIH and

Normal mothers at the time of booking:

Blood

Pressure

PIH Normal Differ b/w

means“t” df Sig

Mean SD Mean SD

SBP 107.9 9.7 112.0 9.1 4.1 1.563 97 P>0.05

DBP 70.7 6.2 72.0 7.4 1.3 0.618 97 P>0.05

The systolic and diastolic blood pressures of the PIH and normal mothers

were compared in the above table-4. The mean SBP of PIH mothers was 107.9

±9.7mm/Hg and that of normal mothers was 112.0 ± 9.12mm/Hg .The difference

between them was not statistically significant (P>0.05). The mean DBP of PIH

mothers was 70.7±6.2mm/Hg and that of the normal mothers was 72.02±

7.4mm/Hg. The difference between them was also not statistically significant

(P>0.0).

Increase of SBP and DBP from booking to delivery:

The study subjects were compared within the PIH and normal mothers

from booking to delivery.

67

SBP DBP

112

72

107.9

70.7

Normal PIH

68

Table-5: Comparison of SBP and DBP within the PIH mothers from booking

to delivery.

Blood

Pressure

At Booking At delivery Increase“t” df Sig

Mean SD Mean SD Mean SD

SBP 107.8 9.7 149.3 10.7 41.2 15.1 10.253 13 P<0.001

DBP 70.7 6.2 95.7 7.6 25.0 8.5 10.942 13 P<0.001

The increase of SBP and DBP were compared within the PIH mothers

from booking to delivery in the above table-5. The mean SBP of them at booking

was 107.8 ± 9.7mm/Hg and that of at delivery was 149.3±10.7mm/Hg. The mean

increase was 41.2±15.1mm/Hg. The increase of SBP was statistically very highly

significant (P<0.001). The mean DBP of them at booking was 70.7 ± 6.2mm/Hg

and that of at delivery was 95.7±7.6mm/Hg. The mean increase was

25.0±8.5mm/Hg. The increase of DBP was statistically very highly significant

(P<0.001).

0

20

40

60

80

100

120

140

160

SBP DBP

107.8

70.7

149.3

95.7

At Booking At delivery

69

0

20

40

60

80

100

120

SBP DBP

112

72

116.4

74.6

At Booking At delivery

Table-6: Comparison of SBP and DBP within the Normal mothers from

booking to delivery.

Blood

Pressure

At Booking At delivery Increase“t” df Sig

Mean SD Mean SD Mean SD

SBP 112.0 9.1 116.4 7.8 4.4 11.9 3.373 84 P<0.01

DBP 72.0 7.4 74.6 6.6 2.6 9.7 2.471 84 P<0.01

The increase of SBP and DBP were compared within the normal mothers

from booking to delivery in the above table-6. The mean SBP of them at booking

was 112.0 ± 9.1mm/Hg and that of at delivery was 116.4±7.8mm/Hg. The mean

increase was 4.4±11.9mm/Hg. The increase of SBP was statistically y highly

significant (P<0.01). The mean DBP of them at booking was 72.0 ± 7.4mm/Hg

and that of at delivery was 74.6±6.6mm/Hg. The mean increase was

2.6±9.7mm/Hg. The increase of DBP was statistically highly significant

(P<0.01).

70

Table-7:Comparison of Increased SBP and DBPbetween PIH and Normal

mothers:

Blood

Pressure

PIH Normal Differ

b/w

means

“t” df SigMean SD Mean SD

SBP 41.4 15.1 4.4 11.9 37.0 10.385 97 P<0.001

DBP 25.0 8.5 2.6 9.7 22.4 8.167 97 P<0.001

The increase of SBP and DBP between the PIH and normal mothers was

compared in the above table-7. The mean increase of SBP of PIH mothers was

41.4±15.1mm/Hg. The mean increase of SBP of Normal mothers was

4.4±11.9mm/Hg. The difference between them was statistically very highly

significant (P<0.001). Similarly, the DBP mean increase of PIH mothers was

25.0±8.5mm/Hg. The mean increase of DBP of Normal mothers was

2.6±9.7mm/Hg. The difference between them was statistically very highly

significant (P<0.001).

Increase of Urine albumin from booking to delivery:

The incidence of urine albumin was found in the booking status in both

groups. But at delivery there was an incidence of urine albumin in both groups.

71

SBP DBP

41.4

25

4.42.6

PIH Normal

72

Table-8: Urine albumin incidence between the PIH and normal mothers at

delivery.

Mothers

U. Alb

present

U. Alb not

presentTotal χ2 df Significance

No % No % No %

82.902 1 P<0.001PIH 13 13.1 1 1.0 14 14.1

Normal 0 0.0 85 85.9 85 85.9

Total 13 13.1 86 86.9 99 100.0

The table-8 shows the presence of the urine albumin at the time of

delivery. There was no urine albumin present in the normal deliveries and 13.1%

of PIH had urine albumin in their urine. The presence was statistically very

highly significant (P<0.001).

Elevation of Serum βHCG:

The β HCG level was compared between the PIH and normal mothers.

P I H N O R M A L

130

1

85

U. Alb present U. Alb not present

73

Table-9: Comparison of βHCGbetween thePIH and normal mothers:

Variabl

e

PIH Normal Differb/

w means“t”

D

fSig

Mean SD Mean SD

β HCG54297.

8

22302.

7

27018.

2

11255.

727279.6

7.12

297

P<0.00

1

The β HCG levels of PIH and normal mothers were compared in the

above table-9. The mean β HCG of PIH group mothers was 54297.8± 22302.7

and that of normal group mothers was27018.2 ± 11255.7. The difference

between the means was statistically very highly significant (P<0.001).

β HCG

54297.8

27018.2

Normal PIH

74

Table-10:Correlation between β HCG with booking SBP and DBP and with at

delivery SBP and DBP:

Time Variable-1 Variable-2 “r” Sig r2 %

At

booking

β HCG SBP -.067 P>0.05 .0045 0.45

β HCG DBP -.027 P>0.05 .00073 0.073

At

delivery

β HCG SBP +.606 P<0.001 .3672 36.7

β HCG DBP +.507 P<0.001 .257 25.7

The above table -10 correlates the blood pressure with the β HCG at

booking and delivery. At booking there was no significantly correlated between

the β HCG with either SBP or DBP (P>0.05). But at delivery the β HCG was

very highly correlated with both SBP and DBP(P<0.001). At delivery the β HCG

determined SBP 36.7% and DBP 25.7%.

Prediction of Urine albumin and Cut point of β HCG:

The urine albumin of study subjects were determined by screening test

and cut points of β HCG were determined by ROC curve approach.

75

Table-11: Prediction of Urine albumin:

PredictionMothers

PIH Normal Total

Urine

Albumin

Positive 13 0 13

Negative 1 85 86

Total 14 85 99

The above table -11 predicts the positive and negative of urine albumin

among the PIH and Normal mothers.

1. The sensitive of the test was 92.9%.

2. The specificity of the test was 100%

3. The false positive was 0%

4. The false negative was 1.2%.

Fixation of cut point:

The cut points were calculated by ROC curve approach.

76

Fig-1: Fixation of cut point for β HCG diagnosis with reference to PIH.

Area Under the Curve

Test Result Variable: Serum β HCG

Area Std. Error Asymptotic Sig.

Asymptotic 95% Confidence

Interval

Lower Bound Upper Bound

0.845 0.060 P<0.001 0.728 0.963

In the above Fig -1: the cut point of βHCG for predicting PIH was 42263 with

Sensitive 71.4% and Specificity 87.1%. The area under the curve was 84.5% and the

test is best fit.

77

Fig-2: Fixation of cut point for β HCG diagnosis with reference to Urine

Albumin.

Area Under the Curve

Test Result Variable: Serum β HCG:

Area Std. Error Significant95% Confidence Interval

Lower Bound Upper Bound

0.877 0.054 P<0.001 0.771 0.984

In the above Fig -2: the cut point of β HCG for predicting PIH was 42263

with Sensitive 76.9% and Specificity 87.2%. The area under the curve was

87.7% and the test is best fit.

The above two figures reveal that the same cut point of βHCG as 42263

with non- significant differences between the sensitivity and specificity of two

tests.

78

Maternal outcome of study subjects:

The maternal outcomes of subjects namely PIH and normal mothers were

compared in the following tables.

Table-12:Comparison of mode of delivery between the PIH and normal:

Type of

delivery

PIH Normal Totalχ2 df Sig

No % No % No %

Normal 3 3.0 39 39.4 42 42.4

3.578 2 P>0.05Forceps 0 0.0 2 2.0 2 2.0

LSCS 11 11.1 44 44.4 55 55.6

Total 14 14.1 85 85.9 99 100.0

The table -12 compares the mode of deliveries between the PIH and

normal mothers. The normal, forceps and LSCS deliveries among the total

mothers were 42.4%, 2.0% and 55.6% respectively. The difference between the

PIH and normal mothers was not statistically significant (P>0.05).

0

5

10

15

20

25

30

35

40

45

Normal Forceps LSCS

30

11.1

39.4

2

44.4

PIH Normal

79

42%

2%

56%

Total

Normal

Forceps

LSCS

80

Table-13:Comparison of term of babies between the PIH and normal

Mothers:

Term/Preterm

delivery


No % No % No %

Pre term 7 7.1 5 5.1 12 12.1

21.964 1 P<0.001Term 7 7.1 80 80.8 87 87.9

Total 14 14.1 85 85.9 99 100.0

The table -13 compares the term of babies between the PIH and normal

mothers. The pre and term among the total mothers were 12.1%, and87.9%

respectively. The difference between the pre and term babies among the PIH and

normal wasvery highly statistically significant (P>0.001).

0

10

20

30

40

50

60

70

80

90

Pre term Term

7.1 7.15.1

80.8

PIH Normal

81

12%

88%

Total

Pre term

Term

82

Table-14:Comparison of peri natal outcome between the PIH and normal

Mothers:

Perinatal

outcome


No % No % No %

APO 6 6.1 5 5.1 11 11.1

21.964 1 P<0.001NPO 8 8.1 80 80.8 88 88.9

Total 14 14.1 85 85.9 99 100.0

The table -14 compares the peri natal outcome between the PIH and

normal mothers. The pre and term among the total mothers were 11.1%, and

88.9% respectively. The difference between the APO and NPO of babiesbetween

the PIH and normal mothers was very highly statistically significant (P>0.001).

0

10

20

30

40

50

60

70

80

90

APO NPO

6.1 8.15.1

80.8

PIH Normal

83

11%

89%

Total

APO

NPO

84

Table-15:Comparison of Maternaloutcome between the PIH and normal

Mothers:

Maternal

Outcome


No % No % No %

Complicated 4 4.0 0 0.0 4 4.0

18.476 1 P<0.001Normal 10 10.1 85 85.9 95 96.0

Total 14 14.1 85 85.9 99 100.0

0

10

20

30

40

50

60

70

80

90

Complicated Normal

410.1

0

85.9

PIH Normal

85

The table -15 compares the maternal outcome between the PIH and

normal mothers. The complicated and normal outcome among the total mothers

was 4.0%, and 96.0% respectively. The difference between the complicated and

normal outcome between the PIH and normal mothers was very highly

statistically significant (P>0.001).

4%

96%

Total

Complicated

Normal

86

DISCUSSION

1. The PIH and normal mothers of study were not differed in respect of

their demographic, economic, gravid status and blood pressure level at

the time of booking was not significantly differed.

2. The increase of β HCG among the PIH mothers was significantly

greater than the counterpart of normal mothers.

3. The urine albumin all subject was nil at the booking and the same was

present among the PIH cases.

4. The cut points β HCG by ROC curve.

5. The maternal outcome by means of mode of delivery was not

significant.

6. The number of preterm babies and abnormal perinatal outcome was

significantly more in PIH mothers than the normal mothers.

7. The maternal complications among the PIH mothers were significantly

more than the normal mothers.

The prediction of PIH through β HCG which is simple procedure will help

the mothers early detection and treatment.

87

CONCLUSION

This study was done to examine the possibility of using serum beta hcg to

predict PIH.

100 pregnant women between 13-20 weeks gestation with singleton

pregnancy were selected randomly and serum β hcg were estimated.

Regular follow up of the cases was done till delivery.

Patients who have elevated β hcg levels, in second trimester are at

increased risk of developing PIH.

The mean β HCG of PIH group mothers was 54297.8± 22302.7 and that

of normal group mothers was27018.2 ± 11255.7. The difference between

the means was statistically very highly significant (P<0.001).

For any test to be used as a screening tests it should have good sensitivity,

specificity and positive predictive value.

This study had Sensitivity – 71.4% ,Specificity –87.1% .

Hence instead of single serum marker, it is advised to do multiple serum

analysis, such as AFP, uterine artery Doppler (bilateral notching), along

with βhcg, which has the potential to minimize unwarranted

inconvenience and morbidity and mortality associated with false positive

results.

According to RCOG ,2008 NICE GUIDELINES ,further research using large

prospective studies should be conducted into the effectiveness and cost

effectiveness of using alpha fetoprotein ,beta human chorionic gonadotropin ,

88

fetal DNA in maternal blood and uterine artery dopplers ,or potentially a

combination of these ,to detect women at risk of developing preeclampsia.

89

SUMMARY

This study was done to examine the possibility of using serum beta hcg to

predict PIH.

100 pregnant patients were included in the study between 13-20 weeks of

getational age with singleton pregnancy.

Regular follow up of the cases was done till delivery.

Systolic, diastolic, mean blood pressure at the time of booking between

PIH and normotensive patients did not vary significantly.

From this study we found that βhcg levels were elevated in patients

having preeclampsia,compared with patients who remained normotensives

throughout pregnancy, but while significant effects reported in this study are too

modest compared with natural variability and also sensitivity and positive

predictive value of βhcg are too low to be useful as mass screening marker on its

own and therefore it should be combined with other serum markers and

ultrasound parameters like Doppler study of uterine vessels, which will help in

improving its role as a screening tool.

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SBP DBPURINE

AlbuminSBP DBP

URINE

AlbuminVAGINAL

CAESAREAN

SECTION1 Sudalimathi 27 59972 IV G2P1L1 100 70 nil 42280 140 90 1+ V T NPO

2 Peratchi 28 39450 V primi 110 70 nil 37492 120 70 nil C T NPO

3 Saral 25 39752 V G3P1L1A1 120 80 nil 17150 110 70 nil C T NPO

4 Lalitha 29 43190 IV primi 110 70 nil 38974 130 80 nil C T NPO

5 Sumathi 29 51538 III G2P1L1 110 60 nil 48106 120 70 nil C T NPO

6 Jeeva 27 36192 IV primi 130 80 nil 71595 130 80 nil C T NPO

7 Packiya lakshmi 26 2878 IV primi 110 70 nil 32432 120 60 nil C T NPO

8 Lakshmi 25 60044 IV primi 120 80 nil 45292 120 70 nil C P APO

9 Jayalakshmi 28 59743 IV primi 100 80 nil 27644 130 70 nil C T NPO

10 Anandha Valli 28 41864 V G2P1L1 110 70 nil 32250 110 80 nil C T NPO

11 Poomari 23 59584 V G2P1L1 110 70 nil 32190 130 80 nil C T NPO

12 Mumthaj banu 29 42055 IV G4P3L2 100 70 nil 12220 120 80 nil C T NPO

13 Rathina mani 32 40868 V G2P1L1 120 80 nil 22190 110 70 nil C T NPO

14 Pudhiya lakshmi 21 40896 IV G2P1L0 100 70 nil 21990 120 70 nil V P APO

15 Karthiga 26 36414 V G2P1L1 110 70 nil 62250 150 90 1+ C T NPO

16 Benazir 25 60705 IV G2P1L1 100 70 nil 22210 130 80 nil C T NPO

17 Srirangam 27 41823 IV G2P1L1 110 70 nil 42270 140 90 1+ C T

18 Banumathi 28 39539 V G2P1L1 100 70 nil 23864 120 80 nil C T

19 Selvi 24 39126 V G2P2L0 110 80 nil 32430 110 70 nil C T

20 Mala 26 40521 IV primi 120 70 nil 38772 120 70 nil V T

21 Sivakani 25 41764 V primi 110 70 nil 70500 160 100 2+ C P APO

22 Andal 27 41764 IV G3P1L1A1 110 70 nil 42256 130 80 nil V T

23 Sivasundari 29 20221 IV G2P1L1 100 80 nil 20390 120 80 nil V T

24 Veena 25 38083 V primi 110 60 nil 29810 110 80 nil C T NPO

25 Femila 29 65728 III primi 120 70 nil 56934 110 70 nil C T NPO

26 Surya 25 720247 IV primi 120 80 nil 29852 110 70 nil V T NPO

27 Sudha 27 72403 IV primi 120 80 nil 45280 120 70 nil V T NPO

28 Mariswari 26 42000 V primi 110 80 nil 22176 120 80 nil V T NPO

29 Vasanthi 23 42379 V G2A1 120 70 nil 22240 120 80 nil V T NPO

30 Gowri 20 40129 IV G2P1L1 110 70 nil 22210 110 80 nil V T NPO

31 Murugalakshmi 26 42690 V G2P1L1 120 80 nil 12230 120 80 nil V T NPO

32 Samuthira Kani 23 42671 V primi 100 60 nil 12220 140 90 nil C T NPO

33 Chandra 27 42631 V primi 100 70 nil 12260 120 70 nil V T NPO

34 Rajathi 24 61482 V G3P1L1 110 70 nil 22080 110 80 nil V P APO

35 Maheswari 20 42688 V primi 100 70 nil 22260 110 80 nil V T NPO

36 Mymoon Begam 28 40568 V G2P1L1 120 80 nil 31520 120 70 nil C T NPO

37 Esakiyammal 26 40262 IV G3P1L1A1 110 70 nil 13400 110 80 nil C T NPO

38 Ramalakshmi 29 37702 V G4P2L1 120 60 nil 13511 120 80 nil C T NPO

39 Murugeswari 23 49892 V G2P1L1 120 80 nil 34000 110 70 nil V T NPO

40 Samuthira valli 28 49555 V primi 130 80 nil 45200 150 100 2+ C T APO

41 Esakiyammal 25 49905 V primi 100 70 nil 72400 170 110 4+ C P APO

42 Selvi 35 49352 V G2P1L1 110 60 nil 42400 110 80 nil V T NPO

43 V.R. Gomathi 28 59812 IV primi 100 70 nil 32170 120 80 nil C T NPO

Normal

Perinatal

outcome

Abnormal

Perinatal

outcome

AT DELIVERY

AGE PretermTerm

BirthNAMES.NO

SERUM

βHCGPARITYI.P NUMBER

AT BOOKINGSocioecono

mic Status

MODE OF DELIVERY

44 Sornalega 29 41747 IV G2P1L1 130 70 nil 22270 110 60 nil C T NPO

45 Kasthuri 25 62724 V G4P3L3 100 70 nil 32110 110 80 nil V T NPO

46 Thenmathi 27 62421 IV primi 110 70 nil 42220 130 80 nil V P NPO

47 Sudhi 28 48447 V primi 120 80 nil 12640 120 70 nil Forceps T NPO

48 Ambika 25 48537 V primi 110 70 nil 37200 110 70 nil Forceps T APO

49 Prabha 27 48872 IV G2P1L1 120 80 nil 50500 110 80 nil C T NPO

50 Murugalakshmi 33 50707 V G3P1L1A1 110 80 nil 31400 120 80 nil V T NPO

51 Arunachalam 25 51144 V primi 100 60 nil 36400 100 70 nil V T NPO

52 Jeyabharathi 23 51502 IV G2A1 110 70 nil 10300 110 60 nil V T NPO

53 Muthu petchi 23 47223 V primi 120 80 nil 23850 150 100 2 + C T NPO

54 Selva 25 24204 V primi 120 80 nil 23090 110 80 nil C T NPO

55 Eswari 26 25375 V primi 110 80 nil 19760 120 80 nil V T NPO

56 Muthumani 26 44357 V primi 100 60 nil 33060 120 60 nil C T NPO

57 Dhana lakshmi 25 44686 IV primi 110 60 nil 19470 110 80 nil C T NPO

58 Priya 30 13891 V G2P1L1 100 70 nil 22700 140 90 1 + C P APO

59 Yamuna 30 36119 IV primi 110 80 nil 23980 120 70 nil C T NPO

60 Princy 29 65827 III primi 110 80 nil 30650 110 80 nil C T NPO

61 Indhumathi 29 72304 III primi 130 80 nil 22079 100 80 nil V T NPO

62 Vijitha 31 71882 IV primi 130 70 nil 25357 110 70 nil C T NPO

63 Esaki thai 31 49583 V G2P1L1 120 70 nil 24240 120 70 nil V T NPO

64 Gomathi 24 48675 V G2A1 110 80 nil 49602 110 70 nil V T APO

65 Saranya 25 48997 V primi 110 70 nil 42206 120 80 nil C T NPO

66 Lilly 27 47999 V G2P1L1 110 70 nil 44970 110 80 nil V T NPO

67 Maharasi 27 47796 V G2P1L1 100 80 nil 37124 150 90 1 + C P NPO

68 Punitha 21 43042 IV primi 100 60 nil 32260 130 70 nil V T NPO

69 Chinnathai 29 41873 V primi 110 70 nil 22250 120 80 nil V T NPO

70 Selva Kani 30 38092 V G2P1L1 100 60 nil 12270 110 80 nil C T NPO

71 Maheswari 20 42688 V primi 120 80 nil 22210 120 80 nil V T NPO

72 Nancy 27 57964 IV primi 130 80 nil 12250 120 80 nil V T NPO

73 Amala 23 62588 IV primi 120 70 nil 32200 140 100 2 + C P NPO

74 Rani 28 62857 V primi 100 60 nil 22220 110 70 nil C T NPO

75 Mariyammal 28 38503 V G3P2L2 100 70 nil 82220 170 110 4 + V P APO

76 Chinnathangam 32 43823 V G2P1L1 110 70 nil 52270 130 70 nil C T NPO

77 Prema 25 43757 V primi 120 80 nil 12240 120 70 nil V T NPO

78 Mariessakki 20 36062 V G2P1L1 110 80 nil 12270 120 80 nil V T NPO

79 Umamaheswari 24 36345 V G3P1L1A1 110 60 nil 22200 130 80 nil C T NPO

80 Parameswari 27 43871 V primi 100 70 nil 32250 120 70 nil V T NPO

81 Priya 24 43346 IV G2P1L1 110 70 nil 32220 110 80 nil V T NPO

82 Gnanamani 24 43827 V primi 100 60 nil 22210 110 80 nil V T NPO

83 Muthurathi 26 43796 V primi 120 80 nil 12630 130 80 nil C T NPO

84 Valarmathi 32 43929 V primi 130 80 nil 12580 120 70 nil C T NPO

85 Mariyammal 23 44071 IV primi 120 70 nil 42640 110 80 nil C T NPO

86 Avudai ganapathi 23 42018 V primi 100 60 nil 22595 110 60 nil V T NPO

87 Mari 24 38728 V primi 110 70 nil 22535 110 70 nil V T NPO

88 Kavitha 29 44365 IV G3P1L1A1 120 80 nil 12550 110 60 nil V T NPO

89 Ramalakshmi 35 44460 V G4P1L1A2 130 80 nil 12555 130 80 nil C T NPO

90 Baby 28 43180 V G4P1L0A2 110 60 nil 72575 150 90 1+ V P APO

91 Santhabeula 27 44766 V primi 100 60 nil 23635 110 60 nil V T NPO

92 Mahalakshmi 29 35587 V G2P1L1 110 70 nil 32585 120 70 nil C T NPO

93 Packia thai 25 43719 V G2P1L1 120 70 nil 22600 100 80 nil V T NPO

94 Sakunthala 25 64962 IV primi 120 80 nil 12530 120 80 nil C T NPO

95 Arumugakani 35 64336 V G3P1L0A1 100 80 nil 32600 100 70 nil C P T NPO

96 Thangamani 25 44814 IV G2P1L1 100 70 nil 12595 140 90 1+ C T NPO

97 Rajeswari 23 44819 V G2P1L1 110 60 nil 17300 120 70 nil C T NPO

98 Kaleeswari 19 43958 V primi 120 80 nil 15200 120 60 nil C T NPO

99 Sankarammal 37 44172 V G2P1L1 110 70 nil 24400 110 80 nil C T NPO

100 Mariyammal 24 45295 IV G3P2L2 100 60 nil 19670 110 80 nil C T NPO

SERUM βHCG AS A PREDICTOR OF PREGNANCY INDUCED...

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Transcript of SERUM βHCG AS A PREDICTOR OF PREGNANCY INDUCED...