Labetalol (alpha-Beta blocker)  is safe in pregnancy and no as such linear correlation with IUGR documented unlike  with B-blocker like atenolol or no association with fetal abnormality as reported with alpha blocker like prazosin.

My answer is always infavour of alpha methyl dopa. It is time tested. Labetalol is worldwide accepted. Nifedipin capsule is better than both in acute crisis. Tablet or retard can be used in chronic cases. However, I searched many review articles based on evidence; each of them concluded the experience of the physician that is essential in managing the cases. 

Let me ask you two questions. How can you diagnose a drug responsible for IUGR in hypertension with pregnancy? What are the benefits of prescribing drugs in pregnancy with hypertension?

Dear Dr. Prabhat, did you mean diagnosis of IUGR or clinical diagnosis of a drug causing IUGR? Your questions are not clear or may be its unreadable from my end. Anyway, there are several parameters one can consider:

Since placebo controlled studies are lacking, safety data for antihypertensive agents and surveillance study offers aid in diagnosing drugs causing birth defects/IUGR. Following delivery, one can estimate Apgar score, low birth weight, etc., to correlate with drug history, while  during pregnancy (perinatal period),  USG, Doppler, fetal monitoring, and physical diagnosis may be helpful. Well, you know better!   

http://www.ncbi.nlm.nih.gov/books/NBK62654/

Regards, Sidharta 

My questions were incomplete to show. My question is simple; how one can be confident in concluding the drug causing IUGR in hypertension or the Hypertension itself causing IUGR. Until or unless you are clear in this field it is very difficult to conclude in any research.

  Today, every one is trying to get evidence without knowing the situation; in what condition it has been conducted. Most of the guidelines are misleading, as a result some are being accepted in one country and rejected in other country.

 Dear Prabhat,

I get what you are saying hence I mentioned in the post that

1: there is no linear corelation with Labetalol causing IUGR and as Sidharta said that its most likely indirect correaltion(with IUGR etc) post delivery  people refer to drug use.

2: There is established evidence with IUGR and  Beta like atenolol (no doubt should be there)

Hope it helps

Methyldopa is a centrally acting agent and remains the drug of first choice for treating

methyldopa does not alter maternal cardiac output or blood flow to the uterus or kidneys, and does not seem to have adverse effects on uteroplacental or fetal hemodynamicsor on fetal well being and for all these reasons is generally considered the agent of choice for chronic blood pressure control in pregnancy 

methyldopa and labetalol are appropriate first-line agents. For the treatment of preeclampsia,

and ß-adrenoceptor blocker labetalol is a peripheral vasodilator which has been shown to be effective in pre-eclamptic and non-proteinuric hypertension in pregnancy. Available data suggest that the antihypertensive effect is not associated with compromised renal or uterine blood flow. When used for short periods (

Good but puzzling to others. 

Lets make it simplified. Hypertension if chronic, Alpha Methyl Dopa is prescribed by most of the clinicians. If not controlled dose can be increased or Nifedipine can be added. Nifedipine in acute or rapidly decreasing BP capsule form is ideal. When remote from term, retard tablet is ideal. Rest is just follow the protocol; monitoring the onset of complications and timely delivery of the baby.

Hypertension that is acute and more than 160 systolic or 110 diastolic, oral Nifedipine, IV labetalol, IV hydralazine could be used along with delivery timely. Failure to managing by IV labetalol or Hydralazine, expert's opinion is Nifedipine, could be prescribed by obstetricians. Not controlled, Nitroprusside or GTN has to be used by senior anesthetist with close monitoring. Magnesium Sulphate is often prescribed to prevent eclampsia. It has synergistic effect in decreasing BP in severe hypertension but that should not be followed routinely. Termination must be followed when condition is stable.

This is a complexed topic. The most important interventions are the understanding the clinical situation and available basic knowledge. Acquiring these two, application of evidence can save both the mother and baby. That is why most of the academician recommended highly the experience of the obstetricians managing the mothers with hypertension.    

Management of chronic hypertension in pregnancy 

A detailed history, physical examination and appropriate laboratory and cardiac testing are essential in seeking a possible cause for hypertension and to ascertain end-organ damage if present.

Investigation of hypertension presenting prior to 20 weeks gestation

All patients:

Urinalysis for protein, blood and glucose. If proteinuria is evident on dip-stick analysis, a spot urine protein:creatinine ratio

Microscopy of centrifuged urinary sediment for white and red blood cells (including red cell morphology) and for casts

Mid-stream urine culture

Measurement of serum electrolytes, creatinine, uric acid and blood glucose

Full blood examination

ECG

Selected patients:

Renal Ultrasound should be considered, particularly if the hypertension is severe

Fasting free plasma metanephrines or 24-hour urine collection for estimation of catecholamine excretion if there is concern regarding a possible phaeochromocytoma. At least two consecutive collections are advised.

Clinical and laboratory monitoring

Because women with chronic hypertension are at high risk of developing preeclampsia, close monitoring for its maternal and fetal manifestations is necessary.

In addition to standard antenatal care, the following additional monitoring is indicated:

o Monitoring for signs of superimposed preeclampsia after 20 weeks gestation

o Assessment for proteinuria at every visit

o Laboratory assessment (as above) if worsening hypertension or proteinuria

o Assessment of fetal growth and wellbeing .

Admission to hospital or to a day assessment unit is recommended for women with worsening hypertension or proteinuria at any stage of pregnancy. This enables assessment of maternal and fetal welfare and facilitates discussion amongst all involved in the woman’s care. When necessary, pharmacological treatment may be commenced under close supervision.

Antihypertensive therapy                                                                                                                

First line drugs include methyldopa, labetalol and oxprenolol Second line agents are hydralazine, nifedipine and prazosin. These same agents may be used for treating gestational or chronic hypertension

 Anaesthetic technique

 Vaginal delivery

For labour and delivery, epidural analgesia is a useful adjunct to antihypertensive therapy for blood pressure control and improves renal and uteroplacental blood flow. When relatively contraindicated (e.g. severe thrombocytopenia, coagulopathy or sepsis), fentanyl or remifentanil patient-controlled intravenous analgesia is preferred. Although ephedrine usually does not cause rebound hypertension.occasionally vasopressors and epidural adrenaline (epinephrine) cause worrisome blood pressure elevation. Other drugs that are best avoided in severe preeclampsia include ergometrine .ketamine (hypertension); and the non-steroidal anti-inflammatory drugs and COX-2 specific inhibitors (impaired renal function and hypertension). Oxytocin should be given slowly in small doses to minimise its significant hemodynamic effects (101

Caesareansection                                                                                                                    

    Regional anaesthesia is preferred to general anaesthesia (GA) for caesarean section         

Management of non-severe pre-eclampsia

Initial evaluation

 Place of Care

A component of care through hospital day units and general practice can be considered for women with non-severe pre-eclampsia and non-proteinuric gestational hypertension. Eligibility will depend on the distance from the hospital, patient compliance and lack of progression of pre-eclampsia.

Confirmation of sustained elevated blood pressures and quantification of urinary protein excretion is an essential part of the initial evaluation. Laboratory testing should be performed in women with a sustained blood pressure between 90-99 mmHg and should include:

 Renal function tests including uric acid test

 Serum electrolytes

 Liver function tests

 Full Blood count

It is not necessary to perform a clotting profile in cases of non-severe pre-eclampsia and gestational hypertension if the platelet count is normal.

Fetal assessment with sonography to evaluate fetal weight, progression of fetal growth, amniotic fluid index and umbilical artery Doppler velocimetry should be performed at diagnosis and once every 4 weeks thereafter with more frequent monitoring if any parameters are

                     abnormal.

 For women without underlying medical problems, antihypertensive drug therapy should be used to keep systolic blood pressure at 130-155 mmHg and diastolic blood pressure at 80-105 mmHg. For women with underlying medical problems, such as diabetes or renal disease, there is some evidence that tighter control is beneficial and therapy should be used to keep systolic blood pressure at 130-139 mmHg and diastolic blood pressure at 80-89mmHg

If the initial dose of any antihypertensive drug fails to adequately control blood pressure, the dose should be increased incrementally until the maximum dose is reached. If adequate control of blood pressure has still not been achieved, a second antihypertensive agent may be introduced. This drug should be prescribed in addition to and not instead of the first agent

Delivery

The ultimate treatment for pre-eclampsia is delivery of the baby. After 37 completed weeks gestation consideration should be given to induction of labour. A clinical assessment should include the woman‟s symptoms, the severity of the pre-eclampsia, the well-being of the fetus and the favourability of the cervix. If the cervix is unfavourable and the pre-eclampsia is mild, for example, induction of labour may be deferred especially in a woman with a single prior caesarean section. Particular caution is also required in the obese parturient. In some clinical circumstances it may be necessary to proceed to an elective caesarean section.

Management of Severe Pre-eclampsia

Entry criteria

The criteria for managing a woman with these guidelines are subjective to a certain degree. However, the following are indicators of severe disease and justify close assessment and monitoring. They would not necessarily lead to delivery but assuming a diagnosis of pre-eclampsia, it is likely that maternal parameters will not improve until after delivery.

1. Eclampsia

2. Severe hypertension e.g. a systolic blood pressure over 160mmHg† with at least + proteinuria

3. Moderate hypertension e.g. a systolic blood pressure over 140 mmHg and/or diastolic blood pressure over 90 mmHg with significant proteinuria†† and any of:

 severe headache with visual disturbance

 epigastric pain

 signs of clonus

 liver tenderness

 platelet count falling to below 100 x 10 9/l

 alanine amino transferase rising to above 50iu/l

 creatinine >100mmol/l

†verage of 3 readings over 15 minutes

††at least “++”proteinuria OR PCR ≥0mg/mmol or 0.3g in 24 hours

4.3.2 General Measures

The woman should be managed in a quiet, well lit room in a high dependency care type situation. Ideally there should be one to one midwifery care. After initial assessment, charts should be commenced to record all physiological monitoring and investigation results, preferably in a High Dependency Unit (HDU) booklet or using HDU charts. All treatments should be recorded.

The consultant obstetrician on duty should be informed, so that they can be involved at an early stage in management. This should be documented in the notes.

A large bore intravenous cannula for infusing drugs or fluid should be inserted, but not necessarily used until either an indication presents or a decision is made to deliver. If intravenous fluid is given, it should ideally be administered by controlled volumetric pump.

Basic Investigations

Blood should be sent for:

 Serum electrolytes

 Liver function tests

 Full Blood count

 Clotting

 Group and save serum

All tests should be checked daily or more frequently if abnormal

Monitoring

• Blood pressure and pulse should be measured every 15 minutes until stabilised and then half hourly.

• An indwelling catheter should be inserted and urine output measured hourly whenever intravenous fluids are given.

• Oxygen saturation should be measured continuously and charted with the blood pressure. If saturation falls below 95% then medical review is essential.

• Fluid balance should be monitored very carefully. Detailed input and output recordings should be charted.

• Respiratory rate should be measured hourly.

• Temperature should be measured four hourly.

• When present, Central Venous Pressure (CVP) and arterial lines should be measured continuously and charted with the blood pressure.

• Neurological assessment should be performed hourly using either AVPU or GCS (see Appendix for details regarding these scales)

• Fetal well-being should be assessed carefully. In the initial stages this will be with a cardiotocograph but consideration should be given to assessing the fetus with a growth scan, liquor assessment and umbilical artery doppler flow velocity waveforms.

• Blood tests should be repeated every 12 hours whilst on the protocol. In the event of haemorrhage more frequent blood tests should be taken. In the presence of abnormal or deteriorating haematological and/or biochemical parameters, more frequent testing may be required e.g. every 4-8 hours.

Antenatal Fluid Management

Careful fluid balance is aimed at avoiding fluid overload. Total input should be limited to 80ml/hour. If syntocinon is used it should be at high concentration (30IU in 500mls, as per NICE guidelines) and the volume of fluid included in the total input. Oliguria at this point should not precipitate any specific intervention except to encourage early delivery

Thromboprophylaxis

Prior to delivery:

• Women with pre-eclampsia are at increased risk of thrombo emobolic disease. All patients should have anti-embolic stockings and/or flowtrons and/or heparin whilst immobile.

Following delivery:

• Low molecular weight heparin (dose adjusted on early pregnancy weight) should be given daily until the patient is fully mobile (7 days if delivered by Caesarean section).

• Low molecular weight heparin should not be given until 4-6 hours after spinal anaesthesia.

• An epidural catheter should be left in place for at least 12 hours after low molecular weight heparin administration. Following removal of an epidural catheter low molecular weight heparin should not be given for 4-6 hours

The treatment of severe hypertension

Systolic blood pressure ≥160mm Hg requires prompt treatment

The aim of stabilisation of blood pressure is to reduce the blood pressure to

The Management of Eclampsia

Call appropriate personnel - including the resident Anesthetist.

 Remember ABC.

 Give the loading dose of Magnesium Sulphate 4g over 5-10 minutes intravenously and start an infusion of Magnesium Sulphate (see above).

 Diazepam may be administered if the fitting continues at the discretion of the Anesthetist 5-10 mg intravenously.

 Once stabilised the woman should be delivered.

 Oximetry should be instituted if not already in place.

Management of recurrent fits

Give a further bolus dose of Magnesium of 2g and increase the rate of infusion of Magnesium to 1.5g / hour. Continue observations and consider the need for ventilation. If two such boluses do not control seizures, then other methods should be instituted such as the administration of conventional anticonvulsants.

Send blood for magnesium levels aiming for a level of 1.97-3.28 mmol/l (4.8-8.4mg/dl). Hospitals use different units for measuring magnesium. Check which units your hospital uses.

It is essential to consider other causes of seizures. It may be appropriate to organise crani imaging scan when the woman is stabilised

The Timing and Mode of Delivery of Women

The mode of delivery should be discussed with the consultant obstetrician. If gestation is under 34 weeks, induction of labour is unlikely to be successful and consideration should be given to delivery by Caesarean section. After 34 weeks‟ gestation, vaginal delivery should be considered in a cephalic presentation. Vaginal prostaglandins will increase the chance of success. Anti hypertensive treatment should be continued throughout assessment and labour. In cases where delivery does not occur vaginally within 12-24 hours, the mode of delivery should be reconsidered by a senior obstetrician. In cases of severe pre-eclampsia even when the baby has died or is not viable, it may be appropriate to expedite delivery by caesarean section in the mother‟s interests if induction of labour is prolonged.

Immediate post natal care

Women who have received treatment for severe pre-eclampsiaand-Eclampsia should be monitored in hospital until at least the 3rd postnatal day and have 4 hourly blood pressure measurements.

It is important to predict and anticipate the need for antihypertensives in order to avoid delaying discharge and to prevent severe hypertension

Beta blockers (eg. Atenolol, labetalol), alpha-adrenergic blockers (eg. doxazocin), angiotensin converting enzyme (ACE) inhibitors (enalapril, captopril) and calcium antagonists (e.g. nifedipine, amlodopine) are all safe to use in a woman who is breast feeding. Diuretic treatment is safe but should be avoided in breastfeeding women.

After day 3-4 women may be discharged when asymptomatic, provided the haematology and biochemistry results are normal or improving and the blood pressure is < 150/100

 Those on treatment should have follow up arranged either for their GP or for a hospital clinic within 2 weeks.

 There should be direct communication with the GP via a phone call or discharge note. This should include:

 who will provide follow-up care, including medical review if needed (GP or secondary care)

 frequency of blood pressure monitoring

 thresholds for reducing or stopping treatment (e.g. BP130/80 reduce treatment,

Everything is given in any standard textbook. I could not understand its reason. I need clarification, not any protocol of the following headings

In case of chronic hypertension, blood pressure must be normalized before 20 weeks if mother attends early. If BP is well controlled, then what are the clinical sighs, detected for diagnosis of superimposed preeclampsia?

If BP is normal, laboratory investigations are no longer needed. WHY??

HOW is superimposed preeclampsia diagnosed?

There is no term of 'non-severe pre-eclampsia'. 

Would you please kindly read my blog(http://www.daiya-lc.jp/plap/index.html: dated, December 30,2012)?  I hope you might have reconsider about your question.