Serum βHCG as a Predictor of Pregnancy Induced Hypertension

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SERUM β HCG 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,

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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.

GUIDE

Prof.Dr.MUTHU PRABHA, MD(OG)

Department Obstetrics and

Gynaecology,

Tirunelveli Medical College, Tirunelveli- 627011.

HOD

Prof.Dr.MEENA,MD.,DGO.,DNB.,

Department Obstetrics and

Gynaecology,

Tirunelveli Medical College, Tirunelveli- 627011.

Dr.K.Sithy Athiya Munavarah, THE DEAN,

Tirrunelveli Medical College,

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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.

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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.

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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.

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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.

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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.

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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

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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 studyβhcg 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.

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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

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Sumitra yadav ,Namrata shrivastava, Sangeeta paneri,Preeti pawar (2013- 2014)

Prospective comparative study included 50 normotensive and 50 preeclamptic 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.

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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.

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 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.

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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



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 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 )

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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

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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.

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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:

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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 – Beta^14,15,16

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.



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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.

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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 vasopressor23,24,25,26

Normal pregnant women—develop refractoriness to vasopressor

Preeclampsia predisposed individual –have increased sensitivity to vasopressor.

3. Prostaglandins^27,28

In preeclampsia predisposed individual prostacyclin (PGI2) level deceases, and (TXA2) Thromboxane A2 level increases - leads to increased sensitivity

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5. Endothelins^30,31

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.

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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

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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.

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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

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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 .

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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

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 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 Management^45a

 According to NICE^45b guidelines women with at least one high and two

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 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

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 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 therapy⁴⁸

 Hypertensive women without comorbid conditions should have DBP between 80-105 mmHg

 Hypertensive women with comorbid conditions (DM, Renal disease)

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Recommended management of mild Gestational Hypertentension or Preeclampsia

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Recommended management of severe preeclampsia

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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:

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 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)

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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

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 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.

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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

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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.

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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:

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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:

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Doppler USG: Campbell and associates

Doppler velocimetry of uterine umbilical vessels can predict preeclampsia 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 preeclampsia. 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



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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),

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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

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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

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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

(52)

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

(53)

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.

(54)

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.

(55)

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

(56)

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.

(57)

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

(58)

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



(59)

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

(60)

(61)

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)

(62)

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

(63)

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 pregnancy^67s

(64)

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 Impaired

angiogenesis

High hormone levels in maternal circulation

Insufficiency of spiral

(65)

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.

(66)

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.

(67)

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 βhcg 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.

(68)

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

(69)

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.

(70)

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.

(71)

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

Age group

Normal

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.

40 50 60 70 80

60 71.4

(72)

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).

15-19

1% 20-24

24%

25-29 62%

30-34 9%

35-39 4%

TOTAL

(73)

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

Economic Status

PIH Normal Total

χ² df Significance

No % No % No %

III 0 0.0 4 4.7 4 4.1

1.072 1 P>0.05

IV 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).

30 40 50 60 70 80

28.6

71.4

35.3

60

(74)

4%III

34%IV

V 62%

Total

(75)

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>0.05

Primi 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).

20 30 40 50 60

42.9

57.1

50.6 49.4

(76)

49%

51%

Total

Primi Multi

(77)

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.

(78)

SBP DBP 112

72 107.9

70.7 Normal PIH

(79)

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).

120 140 160

107.8

149.3

95.7

(80)

20 40 60 80 100

120 112

72 116.4

74.6

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).

(81)

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

Blood Pressure

PIH Normal Differ

b/w means

“t” df Sig

Mean 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.

(82)

SBP DBP 41.4

25

4.4 2.6

PIH Normal

(83)

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

Mothers

U. Alb present

U. Alb not present

Total χ² df Significance

No % No % No %

82.902 1 P<0.001

PIH 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.

U. Alb present U. Alb not present

(84)

Table-9: Comparison ofβHCGbetween thePIH and normal mothers:

Variabl e

PIH Normal Differb/

w means

“t”

D f

Sig

Mean SD Mean SD

β HCG

54297.

8

22302.

7

27018.

2

11255.

7

27279.6

7.12 2

97

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

(85)

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.

(86)

Table-11: Prediction of Urine albumin:

Prediction

Mothers

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.

(87)

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

(88)

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 Significant

95% 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.

(89)

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 Total

χ² df Sig

No % No % No %

Normal 3 3.0 39 39.4 42 42.4

3.578 2 P>0.05

Forceps 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).

30 35 40

45 39.4

44.4

(90)

42%

2%

56%

Total

Normal Forceps LSCS

(91)

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

Term/Preterm delivery

PIH Normal Total

χ² df Sig

No % No % No %

Pre term 7 7.1 5 5.1 12 12.1

21.964 1 P<0.001

Term 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).

30 40 50 60 70 80

90 80.8

(92)

12%

88%

Total

Pre term Term

(93)

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

Perinatal outcome

PIH Normal Total

χ² df Sig

No % No % No %

APO 6 6.1 5 5.1 11 11.1

21.964 1 P<0.001

NPO 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).

30 40 50 60 70 80

90 80.8

(94)

11%

89%

Total

APO NPO

Serum βHCG as a Predictor of Pregnancy Induced Hypertension