Initially in hospital

At minimum, BP should be measured during the time of peak postpartum BP elevation (for all postnatal women), on days three to six after delivery so that the rise in BP, which may be to severe levels, does not go undetected. The onset of this BP rise usually coincides with mobilisation of extracellular fluid and expansion of intravascular volune. Unfortunately, small trials have not been able to prevent this rise in BP by administration of prophylactic furosemide.

If postnatal BP rises to severe levels (i.e., a systolic BP ≥ 160 mmHg or diastolic BP ≥ 110 mmHG) then there is consensus that antihypertensive therapy should be given. Oral or parenteral agents are available. Oral options include labetalol or nifedipine capsules whereas parental options include labetalol or hydralazine most commonly.

Women with pre-existing or gestational hypertension may have their antihypertensive therapy re-initiated postpartum if they were taking it prior to delivery. The potential advantages of this practice would be to decrease the risk ofnon-severe, and particularly severe, hypertension postpartum. However, postnatal antihypertensive therapy has not been shown to decrease the development of postnatal severe hypertension, shorten hospital stay, or result in any other beneficial or adverse effects in very small published, randomised controlled trials (3 trials, 313 women). A group of women who probably should be treated with antihypertensive therapy postpartum, even when they are not hypertensive at the time, are those with co-morbid conditions, such as renal disease. The more traditional BP goal of <130/80 mmHg can be re-initiated at that time.

If postnatal antihypertensive therapy is administered, it is unclear which antenatal antihypertensive agent may be best for this purpose. Agents that were also used antepartum are commonly used postpartum, with the choice driven by concerns about adverse maternal effects, and not concerns about breastfeeding which is discussed below. Many practitioners are uncomfortable using methyldopa because of its historical association with depression outside pregnancy, and concerns that this drug may increase the already high incidence of postpartum depression. Labetalol is used commonly but may be associated with postural hypotension and must be given three to four times a day. Dihydropyridine calcium channel blockers, like long-acting nifedipine, are associated with edema at high dosage.

Finally, non-steroidal anti-inflammatory drugs (NSAIDs) for analgesia should be used with caution postpartum in women with pre-eclampsia and not at all in those women with a rise in their serum creatinine and/or a delivery complicated by placental abruption. Case reports also suggest that NSAID therapy postpartum may contribute to postpartum hypertension and labile BP, something to consider if BP is difficult to control. These drugs are included in ‘self medication’ so they may not be listed in the patient’s medication administration record from pharmacy.

Breastfeeding on antihypertensive medication

All of the commonly used antihypertensives are considered to be acceptable for use during breastfeeding by the American Academy of Pediatrics. Acceptable medications incude central alpha-blockers (methyldopa), beta-blockers (labetalol, propranolol, metoprolol and atenolol), calcium channel blockers (nifedipine and verapamil), angiotensin-converting enzymes (captopril, enalapril, and quinapril), vasodilators (hydralazine), and thiazide diuretics (hydrochlorothiazide and chlorthalidone). The available studies have been small and evaluated maternal serum/plasma drug and/or active metabolite concentrations in breast milk, infant serum, plasma or urine. Few case reports or series have described any clinical adverse effects in infants. However, the calculated fetal dose of each has been estimated to be less than 10% of the recommended therapeutic dose, a threshold below which pharmacological effects are extremely unlikely to occur. However, any breastfed baby who is potentially exposed to drugs through breast milk should be observed and any behavioural (e.g., excessive crying) and/or physiological concerns (e.g., diarrhea) should be brought to the attention of the baby’s(ies’) care providers; in our practice, neonatal side effects from maternal antihypertensive therapy during breastfeeding are rare.

There is one caveat regarding breastfeeding and antihypertensive medications. Preterm and low birth weight infants may have immature drug clearance systems and as such, may need to be closely monitored for the neonatal effects of antihypertensive medications taken by the mother. There is particular concern about the angiotensin converting enzyme (ACE) inhibitors, at least initially until the premature baby is stabilised, but the concerns expressed by neonatogists are largely theoretical. Milk can be pumped and discarded pending the ability to breastfeed, and in the meantime, breast milk banks are available in many neonatal intensive care units (NICUs).

The days and weeks following hospital discharge

Following discharge from hospital, it is unclear what the role is of postpartum home blood pressure monitoring and self-adjustment of antihypertensive medication. It is well known that many automated machines have been demonstrated to be inaccurate in pregnancy and most inaccurate in women with pre-eclampsia, with an estimated underestimation of BP of approximately 5 mmHg. However, there is wide variation between patients. The monitors recommended for use are the Microlife 3BTO and the Watch BP. Any monitor should be checked against office BP measurement to ensure that the device is accurate.

On average, antihypertensive agents are needed for longer in women with pre-eclampsia (approximately two weeks) compared with those with gestational hypertension without proteinuria (approximately one week), although there is substantial variability between women and no reliable way to predict the course of individual women. Outpatient follow-up is the key.

Six weeks to six months postpartum

At the six week postpartum visit, hypertension may represent the continuation of an antenatal hypertensive disorder (in up to 50% of women) or an underlying essential or secondary form of hypertension. Although most of the pregnancy-related changes in physiology will have resolved by six weeks postpartum, small changes in many parameters, including BP, have been documented thereafter. Therefore, it is our practice to give women at least three months postpartum to have BP normalise before giving them a diagnosis of hypertension.

When women are still hypertensive or require antihypertensive therapy at three to six months postpartum, a reasonable conclusion is that hypertension will persist. Essential as well as secondary hypertension causes should be considered and evaluated according to existing guidelines. This is an important exercise as many investigations that are done for secondary causes of hypertension are either altered by pregnancy physiology (e.g., aldosterone to renin ratio) or involve ionising radiation to the abdomen and cannot be performed in pregnancy (e.g., CT scan of the abdoment for an adrenal mass). Also, pregnancy may alter the values of associated cardiovascular disease risk markers, such as cholesterol (up to a three-fold increase), triglycerides (up to a ten-fold increase), or serum glucose (decreased initially in the first trimester, followed by a rise).

Initial concerns following delivery

There are a number of pre-eclampsia mimickers which are worthy of discussion ( Table 1 ). Mild hypertension and sub-nephrotic range proteinuria can be manifestations of pre-existing hypertension and preexisting renal disease, as well as new onset of preeclampsia and gestational hypertension. The differential diagnosis of severe hypertension and HELLP syndrome is more broad. It includes such disorders as TTP/HUS, exacerbation of systemic lupus erythematosus and exacerbation of preexisting renal disease. These are defined and discussed below. Many of these are thrombotic microangiopathies. They are important to recognise because they require different therapeutic interventions. Key issues to consider are the urinary sediment (which must be collected by urinary catheter because of lochia), and the time course of the abnormalities relative to delivery, manifestations that may point to disease processes other than pre-eclampsia, such as a skin rash of lupus.

When pre-eclampsia worsens postpartum, the clinical picture may be confused in particular with the hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) syndrome. Pre-eclampsia and TTP/HUS can look remarkably similar and it may be very difficult to practice watchful waiting among women with severe disease prior to day five postpartum. Thrombocytopenia may be severe in both. Compared with HUS, substantial renal failure is less usual in pre-eclampsia which is not associated with an active urinary sediment. Unlike TTP, fever is not a feature of pre-eclampsia, although postpartum infection (e.g., endometritis) could co-exist and confuse the picture. Also unlike TTP, the neurological manifestations of pre-eclampsia do not typically include confusion or focal findings unless the patient is postictal from eclampsia, experiencing side effects from magnesium sulphate, or has experienced a stroke. The distinction between deteriorating pre-eclampsia or that which is failing to improve over the initial postpartum days is that unlike HUS/TTP, pre-eclampsia will not improve with plasma exchange/plasmapheresis and as such, this therapy should be reserved for women who continue to deteriorate beyond the fifth postpartum day.

Efforts to rule out underlying disease that may have predisposed to the pre-eclampsia, particularly renal disease, are best undertaken after resolution of dipstick protineuria and not before three to six months postpartum when pregnancy-related changes have resolved. As such, this issue is discussed below under ‘Care beyond six months postpartum’.

Postnatal work-up to rule out underlying disease

Pregnancy represents a unique opportunity to interact with the health care system and it is not unusual to pick up chronic diseases, like kidney disease, that require specific medical management in the long-term, and may also affect future pregnancy.

Special mention of thrombophilia screening is warranted. The association between thrombophilia and pre-eclampsia has been evaluated in several small observational studies and systematic reviews. The results have been conflicting. Some studies, particularly those that have focused on early severe pre-eclampsia, have demonstrated an association between inherited and acquired thrombophilias and adverse pregnancy outcomes, including pre-eclampsia ; however, in other studies, no relationship has been seen. As a result, there has been a move away from routine screening of these women, a trend that has been supported by the absence of an intervention that can improve subsequent pregnancy outcome. Routine screening for thrombophilia in women with history of a hypertensive disorder of pregnancy, including pre-eclampsia, is not recommended by the American College of Obstetrics and Gynecology (ACOG) as well as by British Committee for Standards in Haematology.

Conditions of concern may influence the choice of contraception. For example the contraceptive pill, would not be appropriate in women with uncontrolled hypertension or suspected antiphospholipid antibody syndrome (APS), pending BP control or a definitive APS diagnosis, respectively.

Counselling regarding recurrence in the next pregnancy

The recurrence risk of a hypertensive disorder and/or another placental disease depends in part on the hypertensive disorder that developed in the previous pregnancy, characteristics of the woman, and characteristics of the next pregnancy (e.g. multiple pregnancy or results of maternal serum screening).

Recurrence is highest (up to 65%) for women with a history of early onset, severe pre-eclampsia. They are most likely to have recurrent disease that is pre-eclampsia, although, approximately 34% will have gestational hypertension. Even when the subsequent pregnancy is normotensive, these women are still at increased risk of adverse perinatal outcomes such as intrauterine fetal growth restriction (IUGR), stillbirth, and preterm birth.

Women with history of HELLP (Hemolysis, Elevated Liver enzyme, Low Platelet) syndrome are also at high risk for adverse outcomes in a subsequent pregnancy, particularly when disease in their index pregnancy was early and/or severe. Recurrent disease is most likely to be pre-eclampsia without HELLP (in 48-55%), but 6-27% of women will develop recurrent HELLP.

Women with previous gestational hypertension may develop pre-eclampsia, although their recurrent disease is most likely to be gestational hypertension in 2/3 of cases. Recurrent hypertensive disease is lowest when the pre-eclampsia risk marker in the index pregnancy is no longer present. For example, recurrent pre-eclampsia is low among women who had their pre-eclampsia complicate a twin pregnancy.

Risk stratification in a future pregnancy can be further refined based on biomarkers (e.g. PAPP-A (Pregnancy Associated Plasma Protein A)), ultrasonographic imaging (e.g. uterine artery Dopplers), and other features in predictive models. Clinics that stratify risk are not widely available and often driven by local research interests but practitioners are encouraged to seek these out where available.

It is also important to discuss therapies that are available in future pregnancy to decrease the risk of recurrent pre-eclampsia. Preventative therapies are discussed in detail in Chapter ##. There are a few points worthy of emphasis, however, in hypertensive women. First, aspirin administered at bedtime has been associated with blood pressure reduction in both pregnant women and hypertensive non-pregnant subjects. Second, if antiphospholipid antibody syndrome that is suspected or confirmed postpartum does not warrant long-term aspirin therapy outside pregnancy; a decrease in thromboembolic complications was not demonstrated in women with lupus and secondary APS.

Initially in hospital

At minimum, BP should be measured during the time of peak postpartum BP elevation (for all postnatal women), on days three to six after delivery so that the rise in BP, which may be to severe levels, does not go undetected. The onset of this BP rise usually coincides with mobilisation of extracellular fluid and expansion of intravascular volune. Unfortunately, small trials have not been able to prevent this rise in BP by administration of prophylactic furosemide.

If postnatal BP rises to severe levels (i.e., a systolic BP ≥ 160 mmHg or diastolic BP ≥ 110 mmHG) then there is consensus that antihypertensive therapy should be given. Oral or parenteral agents are available. Oral options include labetalol or nifedipine capsules whereas parental options include labetalol or hydralazine most commonly.

Women with pre-existing or gestational hypertension may have their antihypertensive therapy re-initiated postpartum if they were taking it prior to delivery. The potential advantages of this practice would be to decrease the risk ofnon-severe, and particularly severe, hypertension postpartum. However, postnatal antihypertensive therapy has not been shown to decrease the development of postnatal severe hypertension, shorten hospital stay, or result in any other beneficial or adverse effects in very small published, randomised controlled trials (3 trials, 313 women). A group of women who probably should be treated with antihypertensive therapy postpartum, even when they are not hypertensive at the time, are those with co-morbid conditions, such as renal disease. The more traditional BP goal of <130/80 mmHg can be re-initiated at that time.

If postnatal antihypertensive therapy is administered, it is unclear which antenatal antihypertensive agent may be best for this purpose. Agents that were also used antepartum are commonly used postpartum, with the choice driven by concerns about adverse maternal effects, and not concerns about breastfeeding which is discussed below. Many practitioners are uncomfortable using methyldopa because of its historical association with depression outside pregnancy, and concerns that this drug may increase the already high incidence of postpartum depression. Labetalol is used commonly but may be associated with postural hypotension and must be given three to four times a day. Dihydropyridine calcium channel blockers, like long-acting nifedipine, are associated with edema at high dosage.

Finally, non-steroidal anti-inflammatory drugs (NSAIDs) for analgesia should be used with caution postpartum in women with pre-eclampsia and not at all in those women with a rise in their serum creatinine and/or a delivery complicated by placental abruption. Case reports also suggest that NSAID therapy postpartum may contribute to postpartum hypertension and labile BP, something to consider if BP is difficult to control. These drugs are included in ‘self medication’ so they may not be listed in the patient’s medication administration record from pharmacy.

Breastfeeding on antihypertensive medication

All of the commonly used antihypertensives are considered to be acceptable for use during breastfeeding by the American Academy of Pediatrics. Acceptable medications incude central alpha-blockers (methyldopa), beta-blockers (labetalol, propranolol, metoprolol and atenolol), calcium channel blockers (nifedipine and verapamil), angiotensin-converting enzymes (captopril, enalapril, and quinapril), vasodilators (hydralazine), and thiazide diuretics (hydrochlorothiazide and chlorthalidone). The available studies have been small and evaluated maternal serum/plasma drug and/or active metabolite concentrations in breast milk, infant serum, plasma or urine. Few case reports or series have described any clinical adverse effects in infants. However, the calculated fetal dose of each has been estimated to be less than 10% of the recommended therapeutic dose, a threshold below which pharmacological effects are extremely unlikely to occur. However, any breastfed baby who is potentially exposed to drugs through breast milk should be observed and any behavioural (e.g., excessive crying) and/or physiological concerns (e.g., diarrhea) should be brought to the attention of the baby’s(ies’) care providers; in our practice, neonatal side effects from maternal antihypertensive therapy during breastfeeding are rare.

There is one caveat regarding breastfeeding and antihypertensive medications. Preterm and low birth weight infants may have immature drug clearance systems and as such, may need to be closely monitored for the neonatal effects of antihypertensive medications taken by the mother. There is particular concern about the angiotensin converting enzyme (ACE) inhibitors, at least initially until the premature baby is stabilised, but the concerns expressed by neonatogists are largely theoretical. Milk can be pumped and discarded pending the ability to breastfeed, and in the meantime, breast milk banks are available in many neonatal intensive care units (NICUs).

The days and weeks following hospital discharge

Following discharge from hospital, it is unclear what the role is of postpartum home blood pressure monitoring and self-adjustment of antihypertensive medication. It is well known that many automated machines have been demonstrated to be inaccurate in pregnancy and most inaccurate in women with pre-eclampsia, with an estimated underestimation of BP of approximately 5 mmHg. However, there is wide variation between patients. The monitors recommended for use are the Microlife 3BTO and the Watch BP. Any monitor should be checked against office BP measurement to ensure that the device is accurate.

On average, antihypertensive agents are needed for longer in women with pre-eclampsia (approximately two weeks) compared with those with gestational hypertension without proteinuria (approximately one week), although there is substantial variability between women and no reliable way to predict the course of individual women. Outpatient follow-up is the key.

Six weeks to six months postpartum

At the six week postpartum visit, hypertension may represent the continuation of an antenatal hypertensive disorder (in up to 50% of women) or an underlying essential or secondary form of hypertension. Although most of the pregnancy-related changes in physiology will have resolved by six weeks postpartum, small changes in many parameters, including BP, have been documented thereafter. Therefore, it is our practice to give women at least three months postpartum to have BP normalise before giving them a diagnosis of hypertension.

When women are still hypertensive or require antihypertensive therapy at three to six months postpartum, a reasonable conclusion is that hypertension will persist. Essential as well as secondary hypertension causes should be considered and evaluated according to existing guidelines. This is an important exercise as many investigations that are done for secondary causes of hypertension are either altered by pregnancy physiology (e.g., aldosterone to renin ratio) or involve ionising radiation to the abdomen and cannot be performed in pregnancy (e.g., CT scan of the abdoment for an adrenal mass). Also, pregnancy may alter the values of associated cardiovascular disease risk markers, such as cholesterol (up to a three-fold increase), triglycerides (up to a ten-fold increase), or serum glucose (decreased initially in the first trimester, followed by a rise).

Initial concerns following delivery

There are a number of pre-eclampsia mimickers which are worthy of discussion ( Table 1 ). Mild hypertension and sub-nephrotic range proteinuria can be manifestations of pre-existing hypertension and preexisting renal disease, as well as new onset of preeclampsia and gestational hypertension. The differential diagnosis of severe hypertension and HELLP syndrome is more broad. It includes such disorders as TTP/HUS, exacerbation of systemic lupus erythematosus and exacerbation of preexisting renal disease. These are defined and discussed below. Many of these are thrombotic microangiopathies. They are important to recognise because they require different therapeutic interventions. Key issues to consider are the urinary sediment (which must be collected by urinary catheter because of lochia), and the time course of the abnormalities relative to delivery, manifestations that may point to disease processes other than pre-eclampsia, such as a skin rash of lupus.

When pre-eclampsia worsens postpartum, the clinical picture may be confused in particular with the hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) syndrome. Pre-eclampsia and TTP/HUS can look remarkably similar and it may be very difficult to practice watchful waiting among women with severe disease prior to day five postpartum. Thrombocytopenia may be severe in both. Compared with HUS, substantial renal failure is less usual in pre-eclampsia which is not associated with an active urinary sediment. Unlike TTP, fever is not a feature of pre-eclampsia, although postpartum infection (e.g., endometritis) could co-exist and confuse the picture. Also unlike TTP, the neurological manifestations of pre-eclampsia do not typically include confusion or focal findings unless the patient is postictal from eclampsia, experiencing side effects from magnesium sulphate, or has experienced a stroke. The distinction between deteriorating pre-eclampsia or that which is failing to improve over the initial postpartum days is that unlike HUS/TTP, pre-eclampsia will not improve with plasma exchange/plasmapheresis and as such, this therapy should be reserved for women who continue to deteriorate beyond the fifth postpartum day.

Efforts to rule out underlying disease that may have predisposed to the pre-eclampsia, particularly renal disease, are best undertaken after resolution of dipstick protineuria and not before three to six months postpartum when pregnancy-related changes have resolved. As such, this issue is discussed below under ‘Care beyond six months postpartum’.

Postnatal work-up to rule out underlying disease

Pregnancy represents a unique opportunity to interact with the health care system and it is not unusual to pick up chronic diseases, like kidney disease, that require specific medical management in the long-term, and may also affect future pregnancy.

Special mention of thrombophilia screening is warranted. The association between thrombophilia and pre-eclampsia has been evaluated in several small observational studies and systematic reviews. The results have been conflicting. Some studies, particularly those that have focused on early severe pre-eclampsia, have demonstrated an association between inherited and acquired thrombophilias and adverse pregnancy outcomes, including pre-eclampsia ; however, in other studies, no relationship has been seen. As a result, there has been a move away from routine screening of these women, a trend that has been supported by the absence of an intervention that can improve subsequent pregnancy outcome. Routine screening for thrombophilia in women with history of a hypertensive disorder of pregnancy, including pre-eclampsia, is not recommended by the American College of Obstetrics and Gynecology (ACOG) as well as by British Committee for Standards in Haematology.

Conditions of concern may influence the choice of contraception. For example the contraceptive pill, would not be appropriate in women with uncontrolled hypertension or suspected antiphospholipid antibody syndrome (APS), pending BP control or a definitive APS diagnosis, respectively.

Counselling regarding recurrence in the next pregnancy

The recurrence risk of a hypertensive disorder and/or another placental disease depends in part on the hypertensive disorder that developed in the previous pregnancy, characteristics of the woman, and characteristics of the next pregnancy (e.g. multiple pregnancy or results of maternal serum screening).

Recurrence is highest (up to 65%) for women with a history of early onset, severe pre-eclampsia. They are most likely to have recurrent disease that is pre-eclampsia, although, approximately 34% will have gestational hypertension. Even when the subsequent pregnancy is normotensive, these women are still at increased risk of adverse perinatal outcomes such as intrauterine fetal growth restriction (IUGR), stillbirth, and preterm birth.

Women with history of HELLP (Hemolysis, Elevated Liver enzyme, Low Platelet) syndrome are also at high risk for adverse outcomes in a subsequent pregnancy, particularly when disease in their index pregnancy was early and/or severe. Recurrent disease is most likely to be pre-eclampsia without HELLP (in 48-55%), but 6-27% of women will develop recurrent HELLP.

Women with previous gestational hypertension may develop pre-eclampsia, although their recurrent disease is most likely to be gestational hypertension in 2/3 of cases. Recurrent hypertensive disease is lowest when the pre-eclampsia risk marker in the index pregnancy is no longer present. For example, recurrent pre-eclampsia is low among women who had their pre-eclampsia complicate a twin pregnancy.

Risk stratification in a future pregnancy can be further refined based on biomarkers (e.g. PAPP-A (Pregnancy Associated Plasma Protein A)), ultrasonographic imaging (e.g. uterine artery Dopplers), and other features in predictive models. Clinics that stratify risk are not widely available and often driven by local research interests but practitioners are encouraged to seek these out where available.

It is also important to discuss therapies that are available in future pregnancy to decrease the risk of recurrent pre-eclampsia. Preventative therapies are discussed in detail in Chapter ##. There are a few points worthy of emphasis, however, in hypertensive women. First, aspirin administered at bedtime has been associated with blood pressure reduction in both pregnant women and hypertensive non-pregnant subjects. Second, if antiphospholipid antibody syndrome that is suspected or confirmed postpartum does not warrant long-term aspirin therapy outside pregnancy; a decrease in thromboembolic complications was not demonstrated in women with lupus and secondary APS.