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A Mature Pseudoprimid with Hypertension in Pregnancy and History of
                       Subfertility for four years.
                   By: Muhamad Na’im B Ab Razak, Universiti Sains Malaysia


38 years old Malay lady, gravida two, para 0 + 1(miscarriage) was referred to HUSM at 38
week + 3 days from District Hospitals in view of elevated blood pressure during the ante
antenatal check up at 38 week period of amenorrhea. Patient was initially noted to have high
blood pressure during booking at 13 week of pregnancy but not started on anti hypertensive
medication as blood pressure normalize throughout pregnancy. Currently the hypertension is
controlled with tab Methyldopa 100 mg t.d.s. There is no sign and symptoms of impending
eclampsia. Apart from that, noted problem list include advance maternal age, nulliparity and
history of infertility for four years (however current pregnancy is by spontaneous pregnancy).

                                           ~~~~~~~~~~~~~

'Mature' is a term used to coin pregnancy in older obstetric patient. The first attempt to be made
in defining 'older' obstetric patient is by The International Federation of Obstetricians and
Gynaecologists (FIGO) in the year of 1958. According to the definition by the FIGO, it refers to
the maternal age over 35 years old. Other term that is been used includes 'advanced maternal
age', 'very advanced' and 'geriatric'. Improvements in women’s general health have led to the
term 'Advanced maternal age' to be reserved for pregnancies in women at or over 40 years of
age.[ Mehrnoosh Aref-Adib et al, 2007]

Pseudo primid is rather a confusing term but occasionally being used to refer patient who has
never completed a pregnancy beyond the period of fetal viability which is 24 week. Although,
some may define period of viability as 22 weeks depending on the advancement of neonatology
medicine. The correct word is nulliparous, nulli para or can be simply being put as para 0.

Hypertension is defined as persistent elevation of systolic BP of 140 mmHg or greater and/or
diastolic BP of 90 mmHg or greater. [Malaysian CPG for Management of hypertension, 2008]. In pregnant lady,
this medical problem complicates 2-3% [Paul Gibson] of pregnancy. It is further classified into four
categories according to National High Blood Pressure Education Program Working Group on
High Blood Pressure in Pregnancy. The classification includes 1) chronic hypertension, 2)
preeclampsia-eclampsia, 3) preeclampsia superimposed on chronic hypertension, and 4)
gestational hypertension.

To say that patient is having pregnancy induced hypertension, it should follow the definition
which is BP more than or equal to 140/90 mmHg in previously normotensive patient, or a rise in
systolic BP of > 30 mmHg or diastolic BP > 15 mmHg compared with pre-conception or first
trimester value in two recording of at least 4 Hour apart.

Pre eclampsia is hypertension unique to pregnancy, diagnosed after 20W of gestation and
associated with new onset proteinuria; Eclampsia if seizure occurs. HELLP syndrome
(Hemolysis, Elevated liver enzyme, low platelet) is a variant of PE with involvement of liver
giving rise to tender epigastric pain, and finally DIC.

If the mother already having pre existing Hypertension but after 20 week, she develops new
onset proteinuria, sudden increase in BP, thrombocytopenia or elevated liver enzymes, then Pre
eclampsia with superimposed on chronic hypertension must be suspected.

Finally, for the definition of subfertility or infertility. It is being defined as the failure of a couple
of reproductive age to conceive after at least 1 year of regular coitus without contraception.
Primary infertility exists when a woman has never been pregnant. Secondary infertility occurs
when a woman has a history of one or more previous pregnancies [The Johns Hopkins Manual of Gynecology
3rd ed].


In approaching this patient, a close attention need to be paid as this might be the last pregnancy
for her. Patient took almost four years to conceive after the miscarriage in the first pregnancy.
The fertility rate of woman reduce half after the age of 35 years old. Furthermore, this pregnancy
also being complicated by hypertension.

Advanced maternal age is associated with a significantly increased risk of obstetric
complications and intervention. It is associated with miscarriage, ectopic pregnancy,
chromosomal disorder in fetal, placenta abnormalities (Pre Eclampsia, Abruptio placenta,
Placenta Previa), multiple pregnancy, medical condition like Hypertension, DM and anemia,
aneuploidy and fetal anomalies, increase maternal mortality. [I. Ataullah & T. Freeman-Wang, 2005]

In a study by Ilse Delbaere et al, hypertension during pregnancy together with advanced maternal
age is significantly important risk factor for preterm birth and low birth weight. This might be
due to the poor placenta function. T’sang-T’ang Hsieh et al also reported that adverse perinatal
outcomes in older women in Asian population can be attributed to the increased frequency of
coexisting pregnancy complication including hypertension.

In this patient, the blood pressure is normalized throughout pregnancy. These could be attribute
to the normal changes in pregnancy in which although cardiac output rises in pregnancy,
however there is relative greater fall in peripheral resistance [Kumar& Clark 6th edition]. Therefore, the
decision not to start anti hypertensive in the early pregnancy is justifiable as it will cause
hypotension and ultimately resulting in poor placenta function.
After the 20 week of pregnancy, the baby is growing in size and the big uterus may cause the
aortocaval compression, leading to maternal hypotension. As a compensatory response, there
will be increased in sympathetic tone causing vasoconstriction and tachycardia and diversion of
blood flow from the lower limbs through the vertebral plexus and the azygos veins to reach the
right heart. This may explain why this patient have high blood pressure again at term.[Berhard H.
Heidemann]


In managing hypertension in pregnancy ACE inhibitors and Angiotensin Receptor Blockers are
contraindicated as it may cause renal dysgenesis of the fetus. beta blocker is also contra indicated
as it can cause Intrauterine growth restriction. Methyldopa and labetolol is the drug of choice in
managing hypertension in pregnancy although nifedipine may be used as well. in the presence of
hypertensive crisis, IV hydrallazine or IV labetolol may be used. Magnesium sulphate infusion
can be used in pre eclampsia patient as a prophylaxis for eclampsia or if eclampsia occurs

Monitoring of both mother and fetal condition is important in determining the next management.
Pregnancy is allowed until estimated date of delivery if both mother and fetus in good condition.
If patient develop pre eclampsia or eclampsia, then delivery is recommended.

In this patient, induction of labour is justifiable because of advanced maternal age and
hypertension. Furthermore, patient is already at 39 weeks of pregnancy. If she wants to wait,
therefore she need close monitoring by daily CTG and weekly ultrasound as well as blood
pressure readings.

If she agrees to induction of labour, PGE(2) induction of labor is successful in approximately
75% of patients with hypertensive disorders and unfavorable cervix, with apparently no serious
maternal or fetal complications. [Ben-Haroush A et al, 2005] Other method like membrane sweep and
scratch, pitocin induction may be appropriated..


Reference:

    1.       Ataullah & T. Freeman-Wang, "The older obstetric patient", Current Obstetrics &
             Gynaecology, Volume 15, Issue 1, Pages 46-53, Elsevier, 2005
    2.       Bernhard H Heidemann, "Changes in Maternal Physiology During Pregnancy",
             Update in Anaesthesia, 2005
    3.       Ben-Haroush A, Yogev Y, Glickman H et al, "Mode of delivery in pregnant women
             with hypertensive disorders and unfavorable cervix following induction of labor with
             vaginal application of prostaglandin E.", Acta Obstet Gynecol Scand. 2005
4.   Clinical Practice Guidelines: Management of Hypertension 3rd edition, Ministry of
     Health Malaysia, 2008
5.   Mehrnoosh Aref-Adib, Theresa Freeman-Wang & Ifat Ataullah, "The older obstetric
     patient", Onstetrics, Gynaecology and Reproductive Medicine 18:2, Elsevier, 2007
6.   Parveen Kumar & Michael Clark, " Clinical Medicine 6th ed", Elsevier Saunders,
     2005
7.   T’sang-T’ang Hsieh, Jui-Der Liou, Jenn-Jeih Hsu et al, "Advanced maternal age and
     adverse perinatal outcomes in an Asian population", European Journal of Obstetrics
     & Gynecology and Reproductive Biology 148: 21–26, 2010

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A mature pseudoprimid with hypertension in pregnancy and history of subinfertility for four years

  • 1. A Mature Pseudoprimid with Hypertension in Pregnancy and History of Subfertility for four years. By: Muhamad Na’im B Ab Razak, Universiti Sains Malaysia 38 years old Malay lady, gravida two, para 0 + 1(miscarriage) was referred to HUSM at 38 week + 3 days from District Hospitals in view of elevated blood pressure during the ante antenatal check up at 38 week period of amenorrhea. Patient was initially noted to have high blood pressure during booking at 13 week of pregnancy but not started on anti hypertensive medication as blood pressure normalize throughout pregnancy. Currently the hypertension is controlled with tab Methyldopa 100 mg t.d.s. There is no sign and symptoms of impending eclampsia. Apart from that, noted problem list include advance maternal age, nulliparity and history of infertility for four years (however current pregnancy is by spontaneous pregnancy). ~~~~~~~~~~~~~ 'Mature' is a term used to coin pregnancy in older obstetric patient. The first attempt to be made in defining 'older' obstetric patient is by The International Federation of Obstetricians and Gynaecologists (FIGO) in the year of 1958. According to the definition by the FIGO, it refers to the maternal age over 35 years old. Other term that is been used includes 'advanced maternal age', 'very advanced' and 'geriatric'. Improvements in women’s general health have led to the term 'Advanced maternal age' to be reserved for pregnancies in women at or over 40 years of age.[ Mehrnoosh Aref-Adib et al, 2007] Pseudo primid is rather a confusing term but occasionally being used to refer patient who has never completed a pregnancy beyond the period of fetal viability which is 24 week. Although, some may define period of viability as 22 weeks depending on the advancement of neonatology medicine. The correct word is nulliparous, nulli para or can be simply being put as para 0. Hypertension is defined as persistent elevation of systolic BP of 140 mmHg or greater and/or diastolic BP of 90 mmHg or greater. [Malaysian CPG for Management of hypertension, 2008]. In pregnant lady, this medical problem complicates 2-3% [Paul Gibson] of pregnancy. It is further classified into four categories according to National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. The classification includes 1) chronic hypertension, 2) preeclampsia-eclampsia, 3) preeclampsia superimposed on chronic hypertension, and 4) gestational hypertension. To say that patient is having pregnancy induced hypertension, it should follow the definition which is BP more than or equal to 140/90 mmHg in previously normotensive patient, or a rise in
  • 2. systolic BP of > 30 mmHg or diastolic BP > 15 mmHg compared with pre-conception or first trimester value in two recording of at least 4 Hour apart. Pre eclampsia is hypertension unique to pregnancy, diagnosed after 20W of gestation and associated with new onset proteinuria; Eclampsia if seizure occurs. HELLP syndrome (Hemolysis, Elevated liver enzyme, low platelet) is a variant of PE with involvement of liver giving rise to tender epigastric pain, and finally DIC. If the mother already having pre existing Hypertension but after 20 week, she develops new onset proteinuria, sudden increase in BP, thrombocytopenia or elevated liver enzymes, then Pre eclampsia with superimposed on chronic hypertension must be suspected. Finally, for the definition of subfertility or infertility. It is being defined as the failure of a couple of reproductive age to conceive after at least 1 year of regular coitus without contraception. Primary infertility exists when a woman has never been pregnant. Secondary infertility occurs when a woman has a history of one or more previous pregnancies [The Johns Hopkins Manual of Gynecology 3rd ed]. In approaching this patient, a close attention need to be paid as this might be the last pregnancy for her. Patient took almost four years to conceive after the miscarriage in the first pregnancy. The fertility rate of woman reduce half after the age of 35 years old. Furthermore, this pregnancy also being complicated by hypertension. Advanced maternal age is associated with a significantly increased risk of obstetric complications and intervention. It is associated with miscarriage, ectopic pregnancy, chromosomal disorder in fetal, placenta abnormalities (Pre Eclampsia, Abruptio placenta, Placenta Previa), multiple pregnancy, medical condition like Hypertension, DM and anemia, aneuploidy and fetal anomalies, increase maternal mortality. [I. Ataullah & T. Freeman-Wang, 2005] In a study by Ilse Delbaere et al, hypertension during pregnancy together with advanced maternal age is significantly important risk factor for preterm birth and low birth weight. This might be due to the poor placenta function. T’sang-T’ang Hsieh et al also reported that adverse perinatal outcomes in older women in Asian population can be attributed to the increased frequency of coexisting pregnancy complication including hypertension. In this patient, the blood pressure is normalized throughout pregnancy. These could be attribute to the normal changes in pregnancy in which although cardiac output rises in pregnancy, however there is relative greater fall in peripheral resistance [Kumar& Clark 6th edition]. Therefore, the decision not to start anti hypertensive in the early pregnancy is justifiable as it will cause hypotension and ultimately resulting in poor placenta function.
  • 3. After the 20 week of pregnancy, the baby is growing in size and the big uterus may cause the aortocaval compression, leading to maternal hypotension. As a compensatory response, there will be increased in sympathetic tone causing vasoconstriction and tachycardia and diversion of blood flow from the lower limbs through the vertebral plexus and the azygos veins to reach the right heart. This may explain why this patient have high blood pressure again at term.[Berhard H. Heidemann] In managing hypertension in pregnancy ACE inhibitors and Angiotensin Receptor Blockers are contraindicated as it may cause renal dysgenesis of the fetus. beta blocker is also contra indicated as it can cause Intrauterine growth restriction. Methyldopa and labetolol is the drug of choice in managing hypertension in pregnancy although nifedipine may be used as well. in the presence of hypertensive crisis, IV hydrallazine or IV labetolol may be used. Magnesium sulphate infusion can be used in pre eclampsia patient as a prophylaxis for eclampsia or if eclampsia occurs Monitoring of both mother and fetal condition is important in determining the next management. Pregnancy is allowed until estimated date of delivery if both mother and fetus in good condition. If patient develop pre eclampsia or eclampsia, then delivery is recommended. In this patient, induction of labour is justifiable because of advanced maternal age and hypertension. Furthermore, patient is already at 39 weeks of pregnancy. If she wants to wait, therefore she need close monitoring by daily CTG and weekly ultrasound as well as blood pressure readings. If she agrees to induction of labour, PGE(2) induction of labor is successful in approximately 75% of patients with hypertensive disorders and unfavorable cervix, with apparently no serious maternal or fetal complications. [Ben-Haroush A et al, 2005] Other method like membrane sweep and scratch, pitocin induction may be appropriated.. Reference: 1. Ataullah & T. Freeman-Wang, "The older obstetric patient", Current Obstetrics & Gynaecology, Volume 15, Issue 1, Pages 46-53, Elsevier, 2005 2. Bernhard H Heidemann, "Changes in Maternal Physiology During Pregnancy", Update in Anaesthesia, 2005 3. Ben-Haroush A, Yogev Y, Glickman H et al, "Mode of delivery in pregnant women with hypertensive disorders and unfavorable cervix following induction of labor with vaginal application of prostaglandin E.", Acta Obstet Gynecol Scand. 2005
  • 4. 4. Clinical Practice Guidelines: Management of Hypertension 3rd edition, Ministry of Health Malaysia, 2008 5. Mehrnoosh Aref-Adib, Theresa Freeman-Wang & Ifat Ataullah, "The older obstetric patient", Onstetrics, Gynaecology and Reproductive Medicine 18:2, Elsevier, 2007 6. Parveen Kumar & Michael Clark, " Clinical Medicine 6th ed", Elsevier Saunders, 2005 7. T’sang-T’ang Hsieh, Jui-Der Liou, Jenn-Jeih Hsu et al, "Advanced maternal age and adverse perinatal outcomes in an Asian population", European Journal of Obstetrics & Gynecology and Reproductive Biology 148: 21–26, 2010