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HYPERCHOLESTEROLEMIA IN PREGNANCY

AS A PREDICTOR OF ADVERSE PREGNANCY


OUTCOME
Introduction
Pregnancy is an unique and physiologically normal episode in a women's life. All

pregnancies are at risk, while most pregnancies are uneventful. About 15% of pregnant

women may develop a potentially life-threatening complication in turn may require a

obstetrical intervention to survive.1

Labour is naturally occurring phenomenon which usually starts on its own. It is defined

as spontaneous onset of regular and painful uterine contraction associated with a

progressive effacement with dilatation of cervix and descent of presenting part, with or

without a show of ruptured membrane.2

Preterm Labour is defined by WHO as the onset of labour after the period of viability,

that is after 28 weeks of gestation and before 37 completed weeks.2

Pre- term birth is associated with significant perinatal morbidity and mortality rates. It is

associated with an increased risk of adverse metabolic outcomes in later life such as

type 2 Diabetes mellitus, hypertension, CAD and stroke.3


The mothers who delivered preterm infants also appeared to have increased risk

metabolic diseases later in life.

LIPIDS metabolism

The major serum lipids includes free (unesterified) fatty acids, lysophospholipids,

triglycerides, cholesterol and phospholipids. Lipids are insoluble in aqueous solution

and are transported in plasma complexed with specific proteins or apoproteins. Free

fatty acids and lysophospholipids bound by albumin , cholesterol, cholesterol esters

and phospholipids exist as large lipid protein complexes called lipoproteins.

Four major classes of lipids are:

1.Chylomicrons

2.B-LDL

3.Pre B LDL

4.Alpha LDL

Chylomicrons-These are assembeled in intestinal mucosa cells from dietary lipids,

primarily through triacylglycerol, which are degraded by lipoprotein lipase.


VLDL- produced in the liver, composed predominantly of endogenous triacylglycerol.

Their function is to carry this lipid from the liver to peripheral tissues.

LDL – These have a high concentration of cholesterol and cholesterol esters. Its

primary function is to provide cholesterol to peripheral tissues or return it to the liver.

HDL- These lipoproteins are present in the liver, small intestine. They take up

cholesterol from non-hepatic tissues and return it to liver by reverse transport, which is

primary mechanism by which LDL protects from atherosclerosis.

Apolipoproteins function as structural components of lipoprotein particles , co-factors

for enzymes ,ligands for cell surface receptors and determine the metabolic fate of

particle on which they reside.

Six major classes of apolipo-proteins:

APO A1 -Major protein of HDL

APO A2-unknown

APO A5- Biochemical and Genetic marker of increased triglyceride concentration.

APO B48 – Main lipoprotein of chylomicrons and LDL


APO B100- Structural protein of VLDL, IDL, LDL for LDL receptor

APO C2- activates lipoprotein lipase ,liberating fatty acid and monoglyceride from

chylomicron.

APO D- Component of HDL

APO E- involved in receptor recogniozition of IDL, chylomicron remenant by the liver.

LIPIDS IN NORMAL PREGNANCY

During pregnancy there is a physiological increase in total cholesterol and triglyceride

plasma concentration, due to increased insulin resistance, oestrogens, progesterone

and placental lactogen.

Triglycerides Total cholesterol

Normal value:less than Normal value: less than 200

150 Pregnancy : upto 350 mg/dl.

Pregnancy upto

300mg/dl
When cholesterol concentration exceeds the 95th percentile, there is a predisposition

to oxidative stress in foetal vessels, exposing new-born to a greater fatty streaks

formation and high risk of atherosclerosis.

High maternal serum cholesterol level is associated with preterm delivery / Low birth

weight in term infants.

Preterm birth and foetal growth restriction affect over 10% of all pregnancies and leads

to Significant neonatal morbidity and mortality.

Maternal cholesterol is essential for both hormonal and physiological changes of early

pregnancy.

Circulating low density lipoprotein cholestrol is chief substrate for placetal progesterone

biosynthesis.

According to some study total cholesterol increases substantially during second and

third trimester in pregnancy.

Elevated maternal cholesterol may have disproportionate impact during critical periods

for placentation and early neuroepithelial expansion.


Studies have reported a possibly increased risk for prematurity and impaired foetal

growth with very high maternal cholesterol levels.

This study will investigate effect of higher than normal level of maternal serum
cholesterol and other parameters of Lipid profile during gestation on two important
adverse outcomes (Preterm births and low birth weight).

In this study, Lipid profile along with other routine investigation will be done.

In this cases with normal lipid profile who will have term babies will be noted and
cases who have abnormal lipid profile and have preterm babies or low birth weight
babies will be noted.

Association of S. cholesterol levels, HDL levels, LDL levels, triglyceride levels will also
be noted and correlated.

Parity of the women will also be correlated with deranged lipid profile.

BMI correlation with lipid profile.

Diet correlation with lipid profile will be done.

Babies of mothers with deranged lipid profile undergoing NICU admissions will be
noted.

Effect of maternal S. cholesterol leading to diabetes or pre-eclampsia in mothers will


be studied.

AIM OF THE STUDY

• To establish relationship between Elevated Lipid profile at 28-36week of gestation in


uncomplicated pregnancy and Preterm delivery.

• To establish relationship between Elevated Lipid profile and Low birth weight in term
babies.
OBJECTIVE OF STUDY

• To determine the association between Hyperlipidemia in pregnancy and Pre-term


births.

• Correlation between hyperlipidaemia and hypothyroidism.


• Incidence of low birth weight in term babies.

MATERIAL AND METHODS

Study design- Prospective cross sectional study

• Duration of study-18months
• Sample size- 300 cases
• Source of data- Study sample consists of antenatal mothers coming to GEMS
medical college and hospital for regular antenatal care.

The Study group includes 300 healthy pregnant women, fasting cholesterol levels
during 28 to 36 week Gestational age, who have come for antenatal check up at the
Department of Obstetrics and Gynaecology, Great Eastern Medical School and
Hospital.
Inclusion Criteria:
1) Singleton gestation between gestational age of 28-36 weeks.
2) Age- 20-35 years
3) With known LMP, confirmed by USG.

Exclusion criteria:
1) Multiple gestation.
2) Gestational Diabetes Mellitus
3) Hypertension
4) HIV
5) Current or previous history of smoking or other substance abuse.
6) Previous abnormal pregnancy history.
7) Previous history of preterm delivery.
8) Cervical incompetence / history of cervical cerclage.
9) Renal disorder
10) Congenital anomalies of fetus.
11) Pre-existing Medical disease

Study method:
The design of the study prospective study. In all these antenatal mothers detailed
history with special reference to diet and habits, followed by complete general and
obstetric examination were done. The purpose of investigation and investigation was
explained to every patient and her informed consent obtained.

General and Systemic Examination:


Height, weight, pulse, Blood pressure, edema, anemia,cardiovascular,Respiratory and
central nervous system disorder were examined.

Investigations
• Hb, Blood grouping and typing BT/CT.

• Thyroid profile

• HIV,HBsAg,HCV,VDRL

• RBS/OGCT

• Urine :Albumin,sugar,Microscopy

• Lipid profile

• Antenatal scan.
Review of literature

• Lawoyin TO et al, prospective study on some factors which influence the delivery of
low birth weight babies in developing country, Nigeria, 600 random gravid women
presented to antenatal booking clinics, incidence of low birth weight with maternal
weight gain was noted and with increase maternal weight incidence of low birth weight
was significantly noted.
• Janet M Catov et al, association of maternal cardiovascular disease and preterm
delivery, Pittsburgh, 446 women were enrolled, women who delivered preterm infant
had higher prevalence of CVD as compared to who delivered term infants.
• Dorothy J Vanderjat et al, compare levels of serum lipids in healthy women and
women with preeclampsia, nigeria, 43 women with preeclampsia and 130 healthy
women served as control. this study showed pre-eclampsia is associated with
decrease HDL levels.
• Robin J Edison et al , to assess whether low maternal serum cholestrol during
pregnancy is assosciated with preterm delivery, impaired fetal growth, South carolina,
cohort of 9338 women taken from prenatal clinics for routine second -trimester serum
screening. Prevalence of preterm delivery among mothers with low Total cholestrol
was found.

• Vinod k mishra et al,to estimate influence of variation in maternal serum lipid levels
on variation in infant birth weight,143 gravidas taken .Effects of maternal serum lipid
levels on infant Birth weight was analyzed. Inverse association between birth weight
and HDL was found.

References
• Lawoyin TO, Oyediran AB. A prospective study on some factors which influence the
delivery of low birth weight babies in a developing country. Afr J Med Med Sci. 1992
Oct;21(1):33-9. PMID: 1288241.

• Catov JM, Newm an AB, Roberts JM, Kelsey SF, Sutton-Tyrrell K, Harris TB,
Colbert L, Rubin SM, Satterfield S, Ness RB; Health ABC Study.
Preterm delivery and later maternal cardiovascular disease risk.
Epidemiology. 2007 Nov;18(6):733-9. Doi :
10.1097/EDE.0b013e3181567f96. PMID: 17917602.V

• Vanderjagt DJ, Patel RJ, El-Nafaty AU, Melah GS, Crossey MJ, Glew RH. High-
density lipoprotein and homocysteine levels correlate inversely in preeclamptic
women in northern Nigeria. Acta Obstet Gynecol Scand.
2004 Jun;83(6):536-42. doi: 10.1111/j.1600-0412.2004. 00513. X. PMID:
15144334.
• Edison RJ, Berg K, Remaley A, Kelley R, Rotimi C, Stevenson RE, Muenke M.
Adverse birth outcome among mothers with low serum cholesterol.
Pediatrics. 2007 Oct;120(4):723-33. doi: 10.1542/peds.2006-1939. PMID:
17908758.

• Misra VK, Trudeau S, Perni U. Maternal serum lipids during pregnancy and infant
birth weight: the influence of prepregnancy BMI. Obesity (Silver Spring). 2011
Jul;19(7):1476-81. doi: 10.1038/oby.2011.43. Epub 2011 Mar 10. PMID: 21394096.
PROFORMA
Case No. -----------OP/IP NO. ----------------- Date : ------------------
1. a) Name of the Patient: b) Age: c) Address:
2. a) Occupation: Housewife/Office work/Sedentary work/Hard work
b) Socioeconomic status: Lower class/ Middle class/Upper class
c) Gravida & Parity: Gravida-------, Para-------, Living issue--------,
Last childbirth -
3. Complaints:
4. Menstrual History: LMP_______________________ EDD ________________
Gestational age:
5. Obstetric History:
b) Past medical/surgical history:
c) Family history:
d) Personal history:
diet -veg,/ Non veg
6. History of present pregnancy from Antenatal records:
a. Pallor, icterus, edema, jaundice
b) BP: mmHg
c) Pulse: /Min
d)BMI-
e)Surgical and medical: disorders, if any:
f) Temp: Raised/Normal/Subnormal
g)CVS:
h) RS:
8. Obstetrical Examination:
a. Presentation: Cephalic
b. Position: LOA/ROA/LOT/ROT/ROP
c. Height of fundus: wks/term size
d. AF: Normal/Scanty/Excess
e. Fetal heart rate: <120/ 120-160/ >160/M
f. Pelvis: Average/Borderline/CPD
g. Uterine contraction: Normal/Abnormal
9. USG
a) Gestational age: wks Days
b) AFI: cm.
d)Expected date of delivery in USG:
10. NST during labour: Reactive/Nonreactive
General Investigation
Hb%: TC : Platelet count: RBS:
Blood GP & Rh typing: Urine: Albumin RBCs Sugar
HbsAg: Microscopy:
HIV : VDRL:
TSH:
Special investigation:
Lipid profile-
Total cholestrol: LDL: HDL: VLDL: Triglycerides:
NST test: Reactive/ Non-reactive
Gestational age weeks days Placenta location
AFI:
BPP:
Maternal co-morbidities: GDM/Pre-Eclampsia/PROM/PPROM
Delivery Details: Normal delivery/ LSCS
21. condition of baby at birth
APGAR score: i) at one mt.__________/10________ ii) at five mt.______/10
Birth weight: kg
Sex: Male/Female
preterm/term
Birth weight-
Resuscitation, if any: Nasopharyngeal suction/Oxygen
inhalation/Medication/
Newborn Baby: By mother side / at NICU
Perinatal death-
GREAT EASTERN MEDICAL SCHOOL &
HOSPITAL
(Promoted by Aditya Educational Society)
DEPARTMENT OF OBSTETRICS AND GYNECOLOGY

INFORMED CONSENT FORM

Title of the study: HYPERLIPIDEMIA IN PREGNANCY AS A PREDICTOR OF


ADVERSE PREGNANCY OUTCOME.

Name of the principal investigator:

Patient IP No: Date:


Name: Age/Gender:
I have read or had read to me and understood the purpose of this study and the confidential nature
of the information that will be collected and disclosed during the study in the language that well
known to me.
I have had the opportunity to ask my questions regarding the various aspects of this study and
my questions have been answered to my satisfaction.
I, the undersigned agree to participate in this study and authorize the collection and disclosure
of my personal information as outlined in this consent form. I understood that I will be not
incurring any extra cost because of this research project.
I understand that I remain free to withdraw from this study at any time and this will not change
my future care.
I voluntarily agree to participate in this research. I allow my details to store and use for any future
study.

Participant’s Name & signature Date

Signature of the witness Date

Signature of the principal investigator Date

D.No. 3-351, Ragolu,Srikakulam Dist., Andhra Pradesh 532484. Phone(08942) 398398/278301,Fax: 278501
Email: gems_sklm@yahoo.co.in/principal@gems.edu.in www.gems.edu.in
(Recognized by Medical Council of India/ Govt. of India, Affiliated to Dr.NTR University of Health Sciences, Vijayawada, Andhra Pradesh)
గ్రేట్ ఈస్ర్న
ట ్ మెడికల్ స్కూ ల్ & హాస్పి టల్
(ఆదిత్య ఎడ్యయ కేషనల్ సొసైటీ గ్రోత్స హించింది)
గ్రరస్కతి మరియు గైనకాలజీ విభాగిం

స్మాచారిం కన్స ింట్ ఫారిం

అధ్య యనిం యొకూ శీరి ిక. HYPERLIPIDEMIA IN PREGNANCY AS A PREDICTOR OF ADVERSE PREGNANCY
OUTCOME.

గ్రరధాన రరిశోధ్కుడి పేరు:

రోగి IP స్ింఖ్య : తేదీ:


పేరు: వయస్సస / లింగిం:
నేను చదివాను లేదా చదివాను మరియు ఈ అధ్య యనిం యొకూ ఉద్దశ్ ే య ిం మరియు నాకు బాగా తెలస్పన భాషలో అధ్య యనిం
స్మయింలో సేకరిించబడిన మరియు బహర గత్ిం చేయబడే స్మాచారిం యొకూ రహస్య స్వ భావాన్న్ అర థిం చేస్సకునా్ ను.
ఈ అధ్య యనిం యొకూ వివిధ్ అింశాలకు స్ింబింధించ నా గ్రరశ్్ లను అడిే అవకాశ్ిం నాకు లభించింది మరియు నా
స్ింత్ృప్తికి నా గ్రరశ్్ లకు స్మాధానిం ఇవవ బడిింది.
నేను, స్ింత్కిం చేస్పనవారు ఈ అధ్య యనింలో పాల్గగనడాన్నకి అింగీకరిస్సినా్ రు మరియు ఈ స్మమ తి రూరింలో చెప్తి నట్లుగా నా
వయ కిగత్
ి స్మాచారాన్న్ సేకరిించడాన్నకి మరియు బహర గత్ిం చేయడాన్నకి అధకారిం ఇస్తిరు. ఈ రరిశోధ్న గ్రపాజెక్ట టవలు నాకు
అదనపు ఖ్రుు ఉిండదు అన్న నేను అర థిం చేస్సకునా్ ను.
నేను ఎపుి డైనా ఈ అధ్య యనిం నుిండి వైదొలగడాన్నకి సేవ చఛ గా ఉనా్ నన్న మరియు ఇది నా భవిషయ త్ స్ింరక్షణను మారు దన్న
నేను అర థిం చేస్సకునా్ ను.
ఈ రరిశోధ్నలో పాల్గగనడాన్నకి నేను స్వ చఛ ిందింగా అింగీకరిస్సినా్ ను. భవిషయ త్ వివరాల కోస్ిం నా వివరాలను న్నలవ
చేయడాన్నకి మరియు ఉరయోగిించడాన్నకి నేను అనుమతిస్తిను.

పాల్గగనేవారి పేరు & స్ింత్కిం: తేదీ

స్తక్షి తేదీ స్ింత్కిం:

గ్రరధాన రరిశోధ్కుడి స్ింత్కిం: తేదీ

D.No. 3-351, Ragolu,Srikakulam Dist., Andhra Pradesh 532484. Phone(08942) 398398/278301,Fax: 278501
Email: gems_sklm@yahoo.co.in/principal@gems.edu.in www.gems.edu.in
(Recognized by Medical Council of India/ Govt. of India, Affiliated to Dr.NTR University of Health Sciences, Vijayawada,
Andhra Pradesh)
GREAT EASTERN MEDICAL SCHOOL & HOSPITAL

(Promoted by Aditya Educational Society)

DEPARTMENT OF OBSTETRICS AND GYNECOLOGY

INFORMED CONSENT FORM

Title of the study: HYPERLIPIDEMIA IN PREGNANCY AS A PREDICTOR OF ADVERSE PREGNANCY


OUTCOME.

प्रमु ख अन्वेषक का नाम:


रोगी IP नहीीं: दिनाीं क:
नाम: आयु / द ीं ग:
मैं समझता हीं दक मैं इस अध्ययन से दकसी भी समय वापस े ने के द ए स्वतींत्र हीं और यह मे रे भदवष्य की िे खभा को नहीीं
बि े गा।
मैं ने इस अध्ययन के उद्दे श्य और उस जानकारी के गोपनीय स्वरूप को पढ़ या समझ द या है, जो उस भाषा में अध्ययन के
िौरान एकदत्रत और प्रकट की जाने वा ी जानकारी का गोपनीय स्वरूप होगा जो मु झे अच्छी तरह से ज्ञात है ।
मु झे इस अध्ययन के दवदभन्न पह ु ओीं के बारे में अपने प्रश्न पूछने का अवसर दम ा है और मे रे प्रश्नोीं का उत्तर मे री सींतुदि के
द ए दिया गया है ।
मैं , अधोहस्ताक्षरी इस अध्ययन में भाग े ने के द ए सहमत हीं और इस सहमदत के रूप में उल्लिल्लखत मे री व्यल्लिगत
जानकारी के सींग्रह और प्रकटीकरण को अदधकृत करता हीं । मु झे समझ में आ गया दक इस शोध पररयोजना के कारण मैं
कोई अदतररि ागत नहीीं गाऊींगा।
मैं स्वे च्छा से इस शोध में भाग े ने के द ए सहमत हीं । मैं अपने दववरण को भदवष्य के दकसी भी अध्ययन के द ए सींग्रहीत
और उपयोग करने की अनुमदत िे ता हीं ।

प्रदतभागी का नाम और हस्ताक्षर की तारीख

साक्षी दतदि का हस्ताक्षर

प्रधान अन्वेषक का हस्ताक्षर दिनाीं क

D.No. 3-351, Ragolu,Srikakulam Dist., Andhra Pradesh 532484. Phone(08942) 398398/278301,Fax: 278501
Email: gems_sklm@yahoo.co.in/principal@gems.edu.in www.gems.edu.in
(Recognized by Medical Council of India/ Govt. of India, Affiliated to Dr.NTR University of Health Sciences, Vijayawada, Andhra Pr adesh)

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