OS 215 Reproduction and Hormonal Regulation (Ob-Gyn)

High Risk Pregnancy: Hypertension in Pregnancy and Gestational DM

Lecturer: Dr. J. Santiago
Date: NOV 10, 2016 Trans: 02-07
01-01
OUTLINE  Proteinuria
I. INTRODUCTION o Urinary protein spillage of 300mg or more in 24
II. Hypertension in Pregnancy hours
A. Hypertensive Conditions o Random urine protein of at least +1 (dipstick
B. Maternal Risk Factors method)
C. Etiopathogenesis  The four general conditions encountered in
D. Etiology hypertension in pregnancy are:
E. Pathogenesis 1. Pre-eclampsia / Eclampsia
F. Pathophysiology 2. Gestational Hypertension
G. Changes in hypertensive Pregnancy 3. Chronic Hypertension
H. Prediction 4. Chronic hypertension with superimposed pre-
I. Prevention eclampsia
J. Management
K. Chronic Hypertensive disorders in Pregnancy A. Hypertensive Conditions in Pregnancy
III. Gestational Diabetes Mellitus 1. Pre-eclampsia
A. Screening and Diagnosis  Parameters:
B. Treatment Approach o BP ≥ 140/90 mmHg after 20 weeks gestation
C. Monitoring o With PROTEINURIA: ≥ 300mg/24 hours or +1
D. Labor and Delivery dipstick)
E. Carbohydrate Metabolism in Pregnancy o Platelets <100,000/uL
F. Causes of Inuslin Resistance o AST/ALT twice the normal value
G. Metabolic Effects Beyond Carbohydrate o Creatinine >1.1mg/dL
Metabolism o May be complicated with pulmonary edema and/or
H. Glucose Homeostasis in Pregnancy cerebral or visual disturbances.
IV. Fetal Implications  Hypertension should be observed at least 2 occasions at
V. Appendix least 4 hours apart. (ECOG 2013)
 However, after 20 weeks in a woman with previously
Note: Italicized notes lifted from 201x trans. normal BP or if you have new onset hypertension as high
I. INTRODUCTION as 160/110 or more, you don’t need the 2 determinations
 Diabetes and hypertension already.
o Account for patient with some co-morbid condition  For proteinuria, if you do a 24 hour urine collection and
whether it is in the pregnant or non-pregnant state.
you get a value of more than 300mg albumin that would
o Two of the most common conditions present in diagnose the patient with preeclampsia.
Filipinos.
 If albumin count not available, a creatinine ratio value of
 We study how these affect pregnancy, and how
greater than 0.3 could be used to diagnose. However, this
pregnancy affects these diseases
is not usually done.
Learning Objectives  Important parameter: use dipstick only if other methods
 Differentiate the types of hypertension are not available particularly you 24 hr urine collection.
 Identify risk factors  Classically, preeclampsia is labeled mild, moderate and
 Know more about the pathophysiological process of severe but is not done anymore (the term “mild” may
pregnancy-induced hypertension, the effects in both lead a clinician to underestimate the condition)
mother and infant, and the same for gestational diabetes  Important in diagnosing pre-eclampsia with severe
mellitus features (IMPORTANT EXAM QUESTION):
1. Diastolic and systolic that is elevated
II. HYPERTENSION IN PREGNANCY 2. Thrombocytopenia 100,000 and so forth down the
 Main causes of maternal related deaths are line
1. Hemorrhage 3. Obvious fetal growth restriction (palpation,
2. Hypertension ultrasound or other means of determining fetal
growth)
3. Infectious causes
 Hypertensive disorders based on foreign literature account
Table 1. Difference between Severe and Non-severe Preeclampsia
to 6-8% in pregnancies.
 It’s a leading cause of maternal and fetal morbidity and Abnormality Without severe With severe
mortality with as high as 16% of maternal death being features (mild) features (severe)
related to hypertension. Diastolic BP <110 mmHg >110 mmHg
 17-20% of OB admissions in PGH. Systolic BP <160 mmHg >160 mmHg
 Most common medical complication in pregnancy in the
Proteinuria None to positive None to positive
Philippines
 6000-7000 deliveries in PGH every year (about 20 per Headache Absent Present
day) Visual Absent Present
 Hypertension is diagnosed based on blood pressure Disturbances
cut- offs Upper Abdominal Absent Present
o Systolic: >=140 mmHg Pain
o Diastolic: >=90 mmHg Oliguria Absent Present
o Korotkoff V is used to get diastolic BP (favorite Convulsion Absent Present
exam question!) (Eclampsia)

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OS 215 Hypertension in Pregnancy and Gestational DM
Serum Creatinine Normal Elevated B. Maternal Risk Factors of Preeclampsia
Thrombocytopenia Absent Present  Primiparity
(<100,000/μL)  Previous preeclampsia
Serum Minimal Marked  Chronic hypertension
Transaminase  Chronic renal disease
Elevation
 History of thrombophilia
Fetal growth Absent Obvious
Restriction  Multifetal gestation
Pulmonary edema Absent Present  Family history
 Diabetes mellitus
 Edema in preeclampsia has been ABANDONED as a  Obesity
diagnostic marker since it occurs in too many normal  SLE – puts the patient at high risk of hypertension in
women pregnancy compared to other connective tissue diseases
o Swelling of the hands or the face  Age >40 years
o Pedal edema after an overnight rest (pathologic)  IVF
 If edema is present upon waking up, it is
pathologic, as distinguished from physiologic FROM 2019: Common factor: endothelial damage
edema which appears bipedally after a period of C. Etiopathogenesis of Preeclampsia
standing/sitting up (normal)  First-time exposure to chorionic villi (primigravid)
 Exposure to superabundance of chorionic villi (twior
2. Eclampsia hydatidiform mole)
 Generalized tonic-clonic seizures (convulsions) that o Hydatidiform mole- a rare mass or growth that forms
cannot be attributed to other causes inside the womb (uterus) at the beginning of a
 Usually preceded by: pregnancy. It’s a type of gestational trophoblastic
o Headache disease where the woman presents the positive
o Visual disturbances pregnancy test but the contents of the uterus are all
o Epigastric or RUQ pain vesicular like materials (kiyawa in Tagalog)
o Altered mental status  Preexisting conditions of endothelial cell activation or
 Sometimes no prodrome inflammation (diabetes or renal or cardiovascular disease
 Preeclamptic woman is at risk for eclampsia up to 48 or chromic HPN)
hours postpartum  Genetic predisposition to hypertension developing during
pregnancy.
3. Gestational Hypertension
 Blood pressure of 140/90 for the first time after 20 D. Etiology of Preeclampsia
weeks of gestation in previously normotensive women.  Placental implantation with abnormal trophoblastic
o Important qualifier: BP cut-off should be after 20 invasion of uterine vessels
weeks and previously normotens ive  Immunological maladaptive tolerance between maternal,
 Differentiating factor: NO PROTEINURIA
paternal (placental), and fetal tissues
 BP returns to normal at less than 12 weeks postpartum.
 Maternal maladaptation to cardiovascular or inflammatory
o If BP elevates during pregnancy after 20 weeks
o If retained after 12 weeks, it’s another condition changes of normal pregnancy
already.  Genetic factors including inherited predisposing genes
 No other signs and symptoms and epigenetic influences

4. Chronic Hypertension E. Pathogenesis of Preeclampsia

 Whatever the pathologic condition present, it boils down
 BP ≥140/90mmHg before 20 weeks gestation or
to the woman developing vasospasm and
prepregnancy
endothelial damage and/or endothelial cell injury.
 With or without proteinuria
o Thromboxane A2 secretion is increased
 Persistent BP ≥140/90 mmHg 12 weeks postpartum  Ischemia
in women with gestational hypertension
 Abnormal trophoblastic invasion
5. Chronic hypertension with superimposed preeclampsia
 Development of proteinuria after 20 weeks
 Worsening proteinuria
 Sudden worsening of hypertension
 Elevation of liver enzyme to abnormal levels
 Platelet levels below 100,000 uL
 Doubling of creatinine level or ≥1.1 mg/dL
 RUQ pain
 Severe headaches
 Pulmonary congestion or edema
Figure 1. Trophoblastic invasion
 May lead to HELLP Syndrome
o Hemolysis (elevated LDH)  In preeclampsia, there is defective implantation
o Elevated Liver enzymes characterized by incomplete invasion of the spiral
o Low arteriolar wall by extravillous trophoblasts resulting in a
o Platelet small-caliber vessel with high resistance to flow
 Preeclamptic changes: endothelial damage, insudation of
plasma constituents into vessel walls, proliferation of
myointimal cells, and medial necrosis.

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OS 215 Hypertension in Pregnancy and Gestational DM
 Lipid accumulate in myointimal cells then within
macrophages  this lipid-laden cell change is called
ATHEROSIS
 Narrow spiral arteriolar lumen impairs placental blood flow
 diminished perfusion and hypoxic environment 
placental debris or microparticles are released 
systemic inflammatory response.
Renal system changes
 Decreased renal perfusion (due to vasospasm and
endothelial cell damage) – increased in normal
pregnancy
 Decreased glomerular filtration rate (due to vasospasm
and endothelial cell damage)
 Glomerular capillary endotheliosis (swelling) –
pathognomonic for preeclampsia
 Proteinuria
o Protein:creatinine ratios that are below 130 to 150
mg/g, that is, 0.13 to 0.15, indicate a low likelihood of
proteinuria exceeding 300mg/day
o Albumin is the most commonly measured protein
(our kidneys excrete other proteins, but albumin is
the one measured in tests)
 Acute tubular necrosis

Figure 2. Decreased Placental Perfusion

F. Pathophysiology of Preeclampsia

Table 2. Pathophysiology of Pre-eclampsia

Functional Compromise Clinical Manifestation
A. Integrity of
Proteinuria and edema
Intravascular Space
Increased vascular
B. Modulation of vessel resistance and sensitivity
and vascular Tone to vasopressors; poor
organ perfusion Figure 3. Renal vascular changes in preeclampsia
C. Maintenance of Anti- Subtle indications of Hepatic Changes
coagulation activated coagulation
 RUQ or midepigastric pain
 Elevated serum hepatic transaminase levels
 These changes ultimately result in multi-organ  Hepatic infarction  hepatic hematoma  subcapsular
involvement with a clinical spectrum ranging from an hematoma
attenuated manifestation to one of cataclysmic o These hepatic changes are late signs. Usually when
deterioration that is life threatening for both mother and there is RUQ or midepigastric pain it is already an
fetus. indication to terminate the pregnancy
 Acute fatty liver of pregnancy must be ruled out (managed
G. Changes in Hypertensive Pregnancy differently)
 HELLP Syndrome – associated with increased risk for
Cardiovascular System adverse outcomes:
 Increased cardiac afterload caused by hypertension o Subcapsular hematoma
 Cardiac preload, which is affected negatively by o Placental abruption
pathologically diminished hypervolemia of pregnancy and o Acute kidney injury
is increased by intravenous crystalloid or oncotic solutions o Pulmonary edema
 Endothelial activation with interendothelial extravasation o Stroke
of intravascular fluid into the extracellular space and o Coagulopathy
importantly into the lung o Acute respiratory distress syndrome
o Sepsis
Hematological Changes  With HELLP Syndrome, deliver very soon or you might
 Typically, there’s thrombocytopenia in normal pregnancy. lose both the mother and the baby
If it becomes very decreased such that it reach levels of
100,000 or less, this will now be called severe features of Cerebrovascular System
pre-eclampsia.  Visual changes
 Derangements in the plasma clotting factors - prolonged  Transient blindness associated with hypertension:
clotting time and bleeding time amaurosis fugax
 Abnormalities in RBC morphology and hemolysis  Cerebral edema
 Hemolysis: RBC destruction  Hyperemia
o Increased serum lactate dehydrogenase (LDH)  Focal anemia
levels
 Thrombosis
o Decreased haptoglobin levels
o HELLP SYNDROME  Hemorrhage
 H- hemolysis
Uteroplacental perfusion
 Measure serum LDH
 Oligohydramnios – because of decreased perfusion
 EL- elevated liver enzymes
 LP – low platelet count  Fetal growth restriction – because of decreased perfusion

** measurement of blood velocity through certain vessels

(uterine arteries) via Doppler ultrasound

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OS 215 Hypertension in Pregnancy and Gestational DM
H. Prediction of Preeclampsia Initial work up
 Maternal high risk factors  CBC with platelet count
 Uterine artery Doppler velocimetry  Serum Creatinine
 Serum biomarkers  AST, ALT, LDH
 24H urine protein
Maternal high risk factors  Biometry
 Primiparity
 Biophysical profile
 Previous preeclampsia
 Amniotic fluid index
 Chronic HPN
 NST
 Chronic Renal Disease
 Doppler velocimetry of umbilical artery if growth restricted
 History of thrombophilia
 Multifetal gestation Mild gestational hypertension & Preeclampsia without severe
 Family History features
 DM  Weekly
 Obesity o CBC with platelet count
 Age > 40 years o AST ASLT LDH
 IVF o Serum creatinine
o Amniotic fluid index
Uterine artery Doppler velocimetry o NST (2x/week if with severe features)
 Doppler analysis that has the potential to predict  Every 3 weeks
pregnancy complications associated with uteroplacental o Biometry
insufficiency before the onset of clinical features o Doppler velocimetry as necessary
 For almost 30 years, procedure has been utilized as a  Delivery at 37 weeks is recommended
screening tool for uteroplacental insufficiency  If before 37 weeks, do expectant management
 Usually used during second trimester (weeks 18-24)
 Presence of diastolic notching beyond 24-25 weeks Preeclampsia with severe features
 Increased resistance or pulsatility indices (PI)  Delivery at 34 weeks AOG
 Abnormal PI  Unstable maternal or fetal status
o Prediction of early- onset preeclampsia  Stabilize maternal condition first before delivery
 92% specific
Long term consequences of preeclampsia
 48% sensitive
 The earlier preeclampsia is diagnosed in pregnancy, the
o Prediction at any AOG more likely will be its recurrence in future pregnancies
 93% specific
 Recurrence is higher for multiparous women who develop
 26% sensitive
preeclampsia
Serum Biomarkers  Earlier onset is also a greater risk for underlying
Notice: Refer to appendix for comprehensive table that the thrombophilias
lecturer presented in class  Recurrent pregnancy HPN is an increased risk for chronic
HPN and subsequent renal disease
I. Prevention of Preeclampsia  Occurrence of preeclampsia places a woman at risk for
 Aspirin chronic HPN, ischemic heart disease, and stroke later in
o 17% reduction of risk in high-risk women life
o 8% reduction in preterm birth
o 14% reduction in fetal/neonatal death K. Chronic HPN disorders of pregnancy
o 10% in IUGR/SGA Chronic HPN
st
o Aspirin 60-80 mg OD starting late 1 trimester  Early prenatal care
 Calcium  Ideally during prepregnancy to rule out end-organ damage
o Risk reduction of 36% in women with low calcium  Basic workup
intake o Serum creatinine
o Risk reduction of 22% in high-risk women o Electrolytes
o Ca supplementation of <1g/day has 38% RR o Uric acid
 No evidence of benefit o Platelet count
o Vitamin C and E and D o Urine protein
o Exercise  Antihypertensives started once SBP ≥ 160 mmHg or DBP
o Low salt diet ≥ 105 mmHg
o Bed rest  May opt to discontinue if BP is well-controlled prior to
pregnancy
J. Management  Maintain BP at 120-160/80-105 mmHg
Principles:
 Consider the ff factors Chronic HPN with superimposed preeclampsia
o Severity of disease Signs:
o Maternal and fetal status  Development of proteinuria after 20 weeks
o AOG  Worsening of proteinuria and sudden worsening of HPN
o Membrane status  Elevation of liver enzyme to abnormal levels
o Uterine contractions and cervical dilatation  Platelet levels below 100,000/uL
o Patient’s preference  Doubling of creatinine level or ≥ 1.1 mg/dL
o Maternal and fetal safety  RUQ
 Severe headaches
 Pulmonary congestion or edema

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OS 215 Hypertension in Pregnancy and Gestational DM
For patients without severe features, deliver at 37 weeks AOG Table 4. Anti-HPN drugs and doses

Deliver fetus for women with the following once condition is DRUG (FDA risk) DOSE
stabilized: Methyldopa (B) 500-3000 mg/day in 2 or 3 divided
doses
 Uncontrolled severe HPN Labetalol (C) 200-2400 mg/day in 2 or 3 divided
 Eclampsia doses
 Pulmonary edema Nifedipine (C) 30-120 mg/day of a slow-release
 Placental abruption preparation
 DIC Hydralazine (C) 50-300 mg/day in 2-4 divided
 Nonreassuring fetal status doses
B-blockers (C) Depends on specific agent
HELLP Syndrome
Hydrochlorothiazide (C) 25 mg/day
 Progressive and sudden deterioration of maternal and
fetal outcomes
Sample use with nifedipine according to sir’s slides
 Higher rates or maternal morbidity and mortality
 BP ≥160/110
 Prompt delivery if 34 weeks AOG and beyond  Nifedipine 10 mg oral
 Before 34 weeks, delivery may be delayed for 24-48 hours  Repeat BP after 20 mins
for corticosteroid administration if stable maternal-fetal  If BP still ≥ 140/90, nifedipine 20 mg oral
status  Repeat BP after 20 mins
Timing of Delivery  If still 140/90, nifedipine 20 mg oral
Table 3. Timing of Delivery  If BP persists, give labetolol 20 mg IV every 2 minutes and
CONDITION TIME OF DELIVERY refer to other specialists (IM, anesthesia, critical care, etc)
Mild gestational hypertension 37 weeks  Give additional anti-HPN per specific order
Preeclampsia without severe 37 weeks  Once BP is controlled, monitor every 10 minutes for an
features hour, then every 15 minutes for an hour, then every 30
Preeclampsia with severe 34 weeks minutues for 1 hour, then every 4 hours.
features Seizure prophylaxis
Chronic hypertension (stable) 38 weeks  Magnesium sulfate proven to halve the risk of eclampsia
CH with superimposed and reduce risk of maternal death
preeclampsia:  No excess of death nor disability after 2 years
Without severe features 37 weeks  Only patients with severe preeclampsia should be given
With severe features 34 weeks MgSO4
HELLP syndrome ≥ 34 weeks Immediate delivery after
maternal stabilization Table 5. Dosage of MgSO4
HELLP syndrome from age of Delivery after administration Pritchard
Loading Dose Maintenance Dose
viability to 33 6/7 weeks of corticosteroids
4g IV 20% solution over 5 to 10 5g IM every 4h in alternate
min (PLUS) buttock till 24 hrs after the last
seizure or delivery whichever is
Control of blood pressure 10g IM (5g 50% solution deep IM later
 Reduction of risk of stroke and/or myocardial infarction in each buttock)
 Antihypertensives only recommended if BP ≥ 160/110 Zuspan
 Safe level of lowering blood pressure in pregnancy is not Loading Dose Maintenance Dose
well studied 4g IV 20% solution over 5 to 10 1 to 2 g/ h by controlled infusion
min pump x 24 h after the last seizure
 Goal: BP of 140-150/90-100 mmHg
Administration of maintenance dose:
According to Cochrane database (anti-HPN meds)
 Before next dose, check if
 50% reduction in development of severe HPN
o RR is at least 16/min
 no clear benefit in reducing fetal and neonatal death,
o Patellar reflexes are present
preterm deliveries, nor IUGR
o Urinary output is at least 30 mL/hr over 4 hours
 Give 5 grams of MgSO4 50% solution together with 1 mL
New England Journal of Medicine (Less tight control vs tight
of 2% lignocaine in the same syringe via deep IM injection
control of HPN for women with GHPN and non-proteinuric
into alternate buttocks every 4 hours
CHPN)
 Withhold or delay if
 tight (DBP of 85)
o RR falls below 16.min
 less tight (DBP of 100)
o Absent paterllar reflexes
 no significant difference in pregnancy loss, high-level o Urinary output below 30 mL per hour from prior 4
NICU care, IUGR/SGA babies, maternal complications hours
 more women with BP ≥ 160/110 in less tight control group  Incase of respiratory arrest, assist ventilation with mask
Cochrane Database on choice of Anti-HPN drug and bag; administer calcium gluconate 1g (10mL of 10%
 No drug shown to be superior to others solution) IV slowly until respiration begins
 Should be based on clinician’s experience, knowledge of  Record drug administration and other pertinent details
adverse effects, and patient preference
Eclampsia
 New-onset generalized tonic-clonic seizures in a woman
with preeclampsia
 Can occur before, during, or after labor
 Other causes need to be ruled out

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OS 215 Hypertension in Pregnancy and Gestational DM
 Treat a pregnant woman with seizures as eclampsia, III. GESTATIONAL DM IN PREGNANCY
unless proven otherwise  Overt diabetes
 Incidence of .89% in PGH and .28% worldwide according  GDM
to WHO (both are 2013 statistics)  Carbohydrate intolerance that begins or is first recognized
 DO NOT deliver if mother is unstable even in the during pregnancy
presence of fetal distress  Includes previously undiagnosed overt diabetes
 Control seizures, HPN, and hypoxia first before delivery in  Maternal complications
the event of eclampsia o Obstetric trauma
o CS
SYMPTOMS: o Type 2 DM in later life
 Impending eclampsia o Metabolic syndrome
o Persistent occipital or frontal headache  Fetal complications
o Blurred vision o LGA
o Photophobia o Macrosomia
o Epigastric or RUQ pain o Cardiomyopathy
o Altered mental status  Neonatal
o Birth trauma
Associated complications o RDS
 Abruptio placenta o Hypoglycemia
 Aspiration pneumonia o Hypocalcemia
 Pulmonary edema o Hypomagnesemia
 Neurologic deficits o Polycythemia
 Renal failure  Child/Adult
 Cardiopulmonary arrest o Obesity
o Type 2 DM
OTHER NOTES o Metabolic syndrome
 Do not restrain an actively convulsing patient, just keep  Prevalence of <2% in Sweden, as high as 14% in high-
her from injuring herself or other people risk populations
 Respirations increase after an episode as a response to  Prevalence in PH: 1.9% but may perhaps be
hypercarbia, lactic acidosis, and hypoxia underreported
 Fetal bradycardia is not unusual and usually recovers in
Table 6. Diagnostic tests for GDM in Pregnancy
3-5 minutes
 Once an episode ends, labor usually begins Thresholds by time interval
Diagnostic Modified
 If cervix is favorable, membranes should be ruptured and Test Criteria
Plasma glucose (in mg/dL)
labor should be induced using oxytocin or prostaglandins Fasting 1-hour 2-hour 3-hour
≥130
 If vaginal delivery is not anticipated within 24 hours, and if 50-g GCT
≥140
there is a presence of fetal heart abnormalities, or if cervix 100-g OGTT ≥105 ≥190 ≥165 ≥145
is unfavorable, a CS delivery should be performed NDDG
≥95 ≥180 ≥155 ≥140
Carpenter-
 After childbirth: Coustan
o Anti-convulsion therapy continued for 24 hours 75-g OGTT ≥95 ≥180 ≥155
75-g OGTT WHO ≥126 ≥140
o Anti-HPN drugs should be continued if DBP is higher
than 110, and urinary output should be monitored
A. Screening and Diagnosis
 Steroids should be given to aid fetal lung maturity if less 1. International Association of Diabetes and Pregnancy Study
than 34 weeks AOG Groups (2010)
 Ultimately, decision to deliver immediately or wait a bit *Memorize values
depends on clinical circumstances
Table 7. Diagnosis of Gestational Diabetes Mellitus
Considerations in HPN disorders in pregnancy 75-g OGTT (only 1 value needed for diagnosis)
Delivery: Fasting 92 mg/dL (5.1 mmol/L)
 Vaginal delivery can still be attempted 1-hour 180 mg/dL (10.0 mmol/L)
 Can use either spinal or epidural anesthesia 2-hour 153 mg/dL (8.5 mmol/L)
Pospartum:
 NSAIDS may contribute to increased BP Table 8. Diagnosis of Overt Diabetes
 BP monitored for at least 72 hours 75-g OGTT (only 1 value needed for diagnosis)
 Follow up BP monitoring 7-10 days postpartum Fasting  126 mg/dL (7.0 mmol/L)
 Instruct patient on signs and symptoms of preeclampsia Random  200 mg/dL (11.1 mmol/L)
and eclampsia HbA1C  6.5%
 MAGSO4 for women with new onset HPN with headaches
or blurred vision
 Restart/start anti-HPN if BP is persistent at  150/100

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OS 215 Hypertension in Pregnancy and Gestational DM
Table 11. Recommended pregnancy weight gain (IOM)
nd
Weight Gain in 2 and
Category Total Weight rd
3 Trimesters
(BMI) Gain Range (lb)
Mean in lb/wk (range)
Underweight
28-40 1 (1-1.3)
(<18.5)
Normal weight
25-35 1 (0.8-1)
(18.5-24.9)
Overweight
15-25 0.6 (0.5-0.7)
(25.0-29.9)
Obese
11-20 0.5 (0.4-0.6)
(30.0)

 Exercise during pregnancy

o At least 30 mins of daily moderate intensity exercise
o Resistance exercises also effective

3. Pharmacologic Therapy
Figure 4. Flowchart in diagnosing diabetes  Human insulin
o Drug of choice
 Even if normal, still reassess o Long history of safety
o Check risk factors: first degree relative with diabetes, o No significant transplacental passage
previously delivered a macrosomic baby, a lot of o Initial dosage
unexplained fetal death, previous pregnancy is GDM st
 1 trimester: 0.7-0.8 U/kBW
o If no risk factors, you can do a 2-hour 75-g OGTT at 
nd
2 trimester: 1.0 U/kBW
24-28 weeks 
rd
3 trimester: 1.2 U/kBW
o NPH insulin
B. Treatment Approach
 2/3 dose before breakfast
 Patient Education
 1/3 dose before dinner
 Glucose Monitoring
 Oral hypoglycemic agents
 Medical nutrition therapy
o Biguanide (Metformin)
 Pharmacologic therapy
 500 mg/tab 2x a day
1. Glucose Monitoring  Maximum of 3000mg/day
 Self-monitoring of blood glucose (SMBG)  Dec hepatic glucose production
o Those on Medical Nutrition Therapy (Diabetic diet) –  Dec glucose intestinal absorption
4x a day  Inc insulin action
 1 fasting  Crosses the placenta
 3 postprandial (breakfast, lunch, dinner) o Glyburide (glibenclamide)
o Those on pharmacologic therapy (up to 6x a day)  2.5 mg tab once a day
 3 preprandial (B,L, D)  Maximum dose of 20 mg daily (10mg BID)
 3 postprandial (B,L,D) 
nd
2 generation sulfonylurea
 HbA1C  Inc insulin secretion
Table 9. Treatment goals for women with GDM
 Insignificant placental passage (4%)
Therapeutic goal o No significant differences found in oral
Preprandial or hypoglycemic agents vs insulin in management of
≤ 95 mg/dL (5.3 mmol/L)
Fasting gestational diabetes
1-hour  Fasting or postprandial glycemic control
≤ 140 mg/dL (7.8 mmol/L)
postprandial  Large for gestational age babies
2-hour 
≤ 120mg/dL (6.7 mmol/L) Cesarean section rates
postprandial
 Neonatal hypoglycemia
Table 10. Treatment goals for women with preexisting DM C. Monitoring
Therapeutic goal 1. Antenatal fetal surveillance
Pre-meal, bedtime  Ultrasonography
60-99 mg/dL (3.5-5.4 mmol/L) st
o 1 trimester: fetal viability
and Overnight fast
nd
Peak postprandial 100-129 mg/dL (5.4-7.1 mmol/L) o 2 trimester: congenital anomaly screening
rd
HbA1C ≤ 6.0% o 3 trimester: fetal growth, fetal well-being
 Tests of fetal well-being

2. Medical Nutrition Therapy (MNT) 2. Congenital anomaly screening

 First strategy in achieving glycemic control  Mandatory for women with overt diabetes
 Weight loss during pregnancy is NOT recommended  GDM patients, screening if HbA1C  7.0% or FBS > 120
 33-40% carbohydrates, 20% protein, 40% fats mg/dL
 3 meals, 3 snacks  Fetal 2D echocardiography for women with overt DM
 75-80% of women with GDM will reach glycemic goals
 For most women, MNT for 2 weeks before shifting to 3. Doppler velocimetry
pharmacologic therapy if glycemic goals not met  Not routine
 Indications
o Preeclampsia
o Intrauterine growth restriction
o Vasculopathy

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OS 215 Hypertension in Pregnancy and Gestational DM
4. Monitoring of fetal growth Table 14. Postpartum testing throughout lifetime
 Focus on fetal abdominal circumference TIME TEST PURPOSE
 May be assessed every 2-4 weeks Fasting or
 Other strategies for fetal well-being Detect persistent, overt
Post-delivery random plasma
o Fetal movement counting diabetes
glucose
o Fetal biophysical profile (FBP) Early Postpartum
 If normal biophysical score in diabetic patients, 75-g 2-hour
postpartum (6- classification of glucose
the FBP should be done twice weekly OGTT
12 weeks) metabolism
1 year 75-g 2-hour Assess glucose
D. Labor and Delivery postpartum OGTT metabolism
 Study: Elective delivery in diabetic pregnant women. Fasting plasma Assess glucose
Cochrane Database of Systemic Reviews Annually
glucose metabolism
o Induction at 38 weeks reduced frequency of LGA 75-g 2-hour Assess glucose
and babies weighing > 4000g Every 3 years
OGTT metabolism
o However, no reduction in rate of Cesarean sections 75-g 2-hour Classify glucose
and neonatal morbidities Prepregnancy
OGTT metabolism
o Potential reduction in rate of macrosomia and
shoulder dystocia
 Preparing for oral glucose tolerance test (OGTT)
o Active management appears to reduce the rates of
macrosomia and its complications o Have an unrestricted diet ( 150 grams of carbs per
day) for at least 3 days prior to the testing
 POGS recommendations
o Observe an overnight (at least 8 hours, but not more
o Optimal time for delivery on or after 38 week
than 14 hour) fast prior to the teasting
o Delivery before 38 weeks for compelling maternal or
o The glucose solution should be consumed in less than
fetal indications
5 mins
o Elective Cesarean delivery at 39 weeks
o Remain seated and should not smoke during the test
o Expectant management for well-controlled DM until
40 weeks
E. Carbohydrate Metabolism in Pregnancy
o Vaginal delivery still the preferred route
o DM is NOT an indication for Cesarean delivery  Adjusts to provide adequate nutrition for both the
mother and growing fetoplacental unit
o DM is NOT a contraindication for trial of labor after
Cesarean  “Fasting Hypoglycemia” or “Accelerated Starvation”
o First half of pregnancy
Table 12. Considerations with respect to fetal weight o ↑ Estrogen and Progesterone → β-Cell Hyperplasia
→ ↑ Insulin Response
< 4000g 4000-4499g >= 4500g
o ↑ Peripheral utilization of glucose  “Fasting
Consider past history, Hypoglycemia” or “Accelerated Starvation”
clinical pelvimetry, Cesarean o Compensatory response: protein catabolism and
Trial of labor evidence of body-to- delivery MAY be accelerated gluconeogenesis from amino acids
head disproportion and considered  “Diabetogenic state”
progression of labor o Second half of pregnancy
o Usually in 24 – 28 weeks (ideal time to screen for
1. Intrapartum glucose management DM)
 Plasma or capillary glucose monitored every 1-4 hours o Hormonal changes to ensure adequate nutrition for
 During labor, glycemic targets are both mother and growing fetoplacental unit
o Plasma glucose: 80-120mg/dL o Characterized by an exaggerated rate and amount
o Capillary glucose: 70-110mg/dL of insulin release
 Start short-acting intravenous insulin infusion at 0.5-1.0 o ↓ Sensitivity to insulin (of the peripheral cells)
U/hour (discontinued prior to delivery) at cellular level - “insulin resistance” due to
 D50-50 if hypoglycemic placental “contra-insulin” hormones

2. Postpartum glucose management F. Causes of Insulin Resistance

 Plasma glucose monitored every 4-6 hours  Human Chorionic Somatomammotropin (hCS), also
 Subcutaneous insulin may be given as needed known as human Placental Lactogen (hPL)
 To know whether GDM or overt diabetes postpartum, use o Main hormone with anti-insulin effect
75-g OGTT 6-12 weeks postpartum (preferably at 6  Human Placental Growth Hormone
weeks)  Cortisol
 Need to monitor patient forever  Progesterone
 Estrogen
Table 13. 75-g OGTT 6-12 weeks postpartum
Impaired G. Metabolic Effects Beyond Carbohydrate Metabolism
Diabetes
Normoglycemia glucose
Mellitus  First half: Hyperinsulinemia → promotes lipogenesis and
tolerance
↓ lipolysis
Fasting < 100 mg/dL 110-125 mg/dL  126 mg/dL
 Second half: high level Human Placental Lactogen →
2-hour < 140 mg/dL 140-199 mg/dL  200 mg/dL stimulation of lipolysis → release of FFA from adipose
Symptoms of tissues
DM and RBS  Normally, hypoglycaemia does not occur because of the
 200 mg/dL adequate levels of insulin
 At the cellular level, in the maternal compartment, there
is RIR → increase glucose levels
 This gets transmitted to the placental barrier causing
increase

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OS 215 Hypertension in Pregnancy and Gestational DM
H. Glucose Homeostasis in Pregnancy F. Congenital Defects Most Characteristic of Diabetic
 Normal: Embryopathy
o Postprandial hyperglycemia vs. fasting  Cardiovascular
hypoglycemia: Increasing mean 24-hr glucose  Musculoskeletal
levels - maintained by ↑ insulin levels, prevents  Urogenital
hypoglycemia  CNS
o Borderline pancreatic reserve: inadequate
 Gastrointestinal
endogenous insulin production
 Role of placenta in maternal metabolism:  Chromosomal
o Produces most hormones that alter metabolism
G. Etiology of Congenital Malformations: Maternal
o Controls transport of nutrients to the fetal
Hyperglycemia
compartment
 Primary metabolic factor responsible
o Insulin enhances glucose and amino acid transport
 Mechanism
III. FETAL IMPLICATIONS o Inhibition of glycolysis
A. Fetal Complications of Pregnancies in Mothers with o Functional deficiency of arachidonic acid
Diabetes
H. Altered Fetal Growth: Macrosomia
1. Spontaneous abortion
 Predisposes fetus to shoulder dystocia, traumatic birth
2. Preterm Delivery
injury & asphyxia
3. Malformations
 BW > 4000 to 5000g
4. Altered Fetal Growth
 ↑ adiposity, ↑ muscle mass & organomegaly
5. Unexplained fetal demise
6. Polyhydramnios  Pederson Concept: Maternal hyperglycemia → fetal
7. Neonatal effects hyperglycemia & hyperinsulinemia → ↑ excessive fetal
8. Respiratory Distress Syndrome growth
9. Metabolic Effects
END OF TRANSCRIPTION
10. Cardiomyopathy

B. Fetal Death
 In pregnancies not receiving optimal care
 After 36 weeks gestation in patients with:
o Vascular disease
o Poor glycemic control
o Hydramnios
o Fetal macrosomia
o Preeclampsia
 Prevented by: Close fetal surveillance and Scheduled
delivery

C. Chronic Fetal Hypoxia

 Cited as likely cause of fetal death in DM
 Supported by observation of:
o Extramedullary hematopoiesis in stillborns
o “Relative fetal erythemia” & lactic academia in cord
blood sampling

D. Factors that reduce fetal oxygenation in DM pregnancies

 Maternal:
o Alterations in oxyhemoglobin dissociation curve
o Ketoacidosis
 Placental
o ↓ Uteroplacental blood flow
 Hyperglycemia
 Ketoacidosis
 Preeclampsia
o ↓ Oxygen transfer - ↑ diffusion distance
 Fetal
o Hyperglycemia
o Hyperinsulinemia
o Ketonemia

E. Congenital Malformations
 ↑ Significant cause of perinatal death
 Higher risk if:
o Poor glycemic control preconceptionally
o Long-standing Type 1 diabetics
o Vasculopathy also present
 Due to genetic susceptibility and intrauterine
environmental factors

th
Insult probably prior to 7 week gestation

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OS 215 Reproduction and Hormonal Regulation (Ob-Gyn)
High Risk Pregnancy: Hypertension in Pregnancy and Gestational DM
Lecturer: Dr. J. Santiago
Date: NOV 10, 2016 Trans: 02-07
APPENDIX 01-01

Serum Biomarkers for Preeclampsia

Detection rates using multiparametric models for preeclampsia

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