**7.3 Impact on fetal development and monitoring of fetal development during lupus pregnancy**

As mentioned above, fetal risks of lupus pregnancy include pregnancy loss, preterm birth, premature rupture of membranes and FGR. Preterm birth is more frequent than pregnancy loss, and even if its relation to pre-eclampsia and disease activity is established, a causative factor may not be identified [22]. Other fetal complications associated with SLE include infants small for gestational age and infants with low birth weight [33]. Neonatal intensive care unit admissions are also more prevalent in these newborns.

Zhan Z et al., in a retrospective study identified that the best method to monitor adverse pregnancy complications during third trimester of pregnancy is by doing an umbilical artery Doppler. Nevertheless, the umbilical artery Doppler can be initiated in the second trimester in monitoring for neonatal heart block for possible earlier intervetion [49]. The use of hydroxychloroquine (HCQ ) is associated with


*sFlt-1 – soluble fms-like tyrosine kinase; PIGF – placental growth factor.*

#### **Table 2.**

*Differentiation of preeclampsia from lupus nephritis flare in pregnancy.*

a lower incidence of FGR the risk of preterm delivery, whether spontaneous or induced, in lupus pregnancy [50, 51]. As prematurity decreases, there will also be a reduced risk of neonate complications, as respiratory distress syndrome, intraventicular hemorrhage, sepsis, hypoglycemia, jaundice requiring phototherapy, enterocolitis, among others [50]. Among the different studies done so far, it should be noted that children with in utero exposure to HCQ did not developed visual, auditory, developmental or growth abnormalities.

## **7.4 Delivery**

The objective in a pregnant lupus patient would be a vaginal spontaneous delivery at term, data reveals that these women have a high prevalence of cesarean section. This procedure should be restricted to obstetric indications, once it represents an additional risk factor for venous thromboembolism, hemorrhage, infection and repercussion in future pregnancies. During labor, women exposed to long-term oral steroids may need intravenous hydrocortisone to overcome the physiologic stress of labor and delivery. Prophylactic or therapeutic anticoagulation should be interrupted as spontaneous delivery starts or, if induced labor or cesarean section is scheduled, it should be discontinued 12 or 24 hours before. Epidural or spinal anesthesia can be safely administrated until 12 hours after the last dose of anticoagulant.

Postpartum care must focus on a possible lupus flare or coexisting pre-eclampsia [31]. Women who underwent anticoagulation should continue it for at least 6 weeks after delivery in a prophylactic dose. Safe contraception should be offered and progestogens can be an appropriate option.

## **8. Treatment & prevention of complications during pregnancy**

Therapeutic management in SLE patients is one of the most important aspects when planning a pregnancy. The main goal is to assure the most effective treatment to maintain disease remission, while keeping the ability to treat disease flares and guaranteeing maximum safety for the fetus. As mention on Section 3, disease activity should be under control (3 to 6 months) prior to pregnancy.

In order to decrease maternal and fetal complications, the the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) [20, 52] developed general recommendations describing which drugs are safe during pregnancy and which ones should be avoided. Also, the Unites States Food and Drug Administration (FDA) has changed the way of labelling medication safety during pregnancy and lactation. Previously, it was based on letters, which classified drugs from A to D, according to its increased risk for the fetus. Drugs classified as had not enough evidence or information available. Nowadays, this classification reflects more the quantity and quality of the data known for each drug. For practical proposes, the current drug options available to treat SLE pregnancy has been divided into 4 main categories:

#### **8.1 Drugs recommended during SLE pregnancy**

#### *8.1.1 Hydroxychloroquine*

Hydroxychloroquine (HCQ ) is an antimalarial agent used for its immunomodulatory effects. Although HCQ crosses the placenta, it does not seem to have toxic effects on the fetus [53]. On the contrary, this drug is recommended to all women with SLE, whether they are pregnant or not, as it decreases the

**95**

data [52, 58].

*8.2.2 Glucocorticoids*

*Systemic Lupus Erythematosus Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.99008*

*8.1.2 Low-dose acetylsalicylic acid*

cations, regardless the presence of aPLs [56].

*8.2.1 Non-steroidal anti-inflammatory drugs*

**8.2 Drugs with a safe profile during pregnancy**

tively, if needed, to control SLE manifestations during pregnancy.

absolute necessity, amniotic fluid monitoring is necessary [57].

ibuprofen appear to have much stronger ductal effects than LDA [57].

antibodies [55].

risk of flares, reduces the risk of pre-eclampsia and preterm birth [54]. Various studies have also shown positive effects of HCQ in pregnant women with APS (higher birth rates and fewer pregnancy complications) versus untreated patients, concluding that SLE pregnant women that have aPL, also known as "aPL carriers" also benefit from HCQ . Furthermore, some studies suggest that HCQ decreases the occurrence of CHB and cutaneous involvement in neonatal lupus, in fetuses whose mothers are carriers of anti-Ro/SSA and anti-La/SSB

Low dose acetylsalicylic acid, as known as, "low dose aspirin" (LDA) is recommended in all women with SLE during pregnancy, it should be started during pre-conception period in case of a planned pregnancy and no later than 16 weeks. LDA (75-150 mg/day) has proved to reduce the risk of pre-eclampsia and its compli-

The following drugs have an acceptable safety profile, but should be used selec-

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control

Discordant findings from large retrospective studies have shown an increased risk of miscarriage in the first trimester with the use of NSAIDs [52]. These drugs should be avoided after 32 weeks of gestation, because of the risk of premature closure of the *ductus arteriosus,* with the exception of aspirin. Indomethacin and

Some studies suggest that high doses of aspirin may increase the risk of fetal or neonatal bleeding or bruising in the 3rd trimester. However, these data is not robust enough to warrant conclusions. The use of selective cyclooxygenase (COX)-2 inhibitors is not recommended in pregnancy, due to the lack of safety

Glucocorticoids (GC) have a remarkable path in the treatment of autoimmune diseases, such as SLE. Yet, its chronic use is associated with multiple side-effects and organ damage [59]. Prednisone and prednisolone are glucocorticoids recommended during pregnancy due to its pharmacokinetics and its shorter duration of action, since they are metabolized by placental enzymes the fetus is basically unexposed. The recommended daily dose should be ≤7.5 mg of prednisone. Doses superior to 10 mg/day are associated with preterm delivery, premature rupture of membranes and FGR. Higher doses should be reserved for organ-threatening situations, when the benefits outweigh the risks [60]. For hypothalamic–pituitary–adrenal axis suppression, for example, we use doses superior to 5 mg/day for at least 3 weeks, after the first trimester, so that labor and delivery can be managed accordingly.

symptoms in patients with rheumatic diseases. However, these drugs should be prudently used during pre-conception period and during pregnancy, as they can provoke oligohydramnios, due to reduced fetal glomerular filtration rate. In case of

#### *Systemic Lupus Erythematosus Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.99008*

*Lupus - Need to Know*

**7.4 Delivery**

a lower incidence of FGR the risk of preterm delivery, whether spontaneous or induced, in lupus pregnancy [50, 51]. As prematurity decreases, there will also be a reduced risk of neonate complications, as respiratory distress syndrome, intraventicular hemorrhage, sepsis, hypoglycemia, jaundice requiring phototherapy, enterocolitis, among others [50]. Among the different studies done so far, it should be noted that children with in utero exposure to HCQ did not developed visual,

The objective in a pregnant lupus patient would be a vaginal spontaneous delivery at term, data reveals that these women have a high prevalence of cesarean section. This procedure should be restricted to obstetric indications, once it represents an additional risk factor for venous thromboembolism, hemorrhage, infection and repercussion in future pregnancies. During labor, women exposed to long-term oral steroids may need intravenous hydrocortisone to overcome the physiologic stress of labor and delivery. Prophylactic or therapeutic anticoagulation should be interrupted as spontaneous delivery starts or, if induced labor or cesarean section is scheduled, it should be discontinued 12 or 24 hours before. Epidural or spinal anesthesia can be safely administrated until 12 hours after the last dose of anticoagulant. Postpartum care must focus on a possible lupus flare or coexisting pre-eclampsia [31]. Women who underwent anticoagulation should continue it for at least 6 weeks after delivery in a prophylactic dose. Safe contraception should be offered and

**8. Treatment & prevention of complications during pregnancy**

ity should be under control (3 to 6 months) prior to pregnancy.

Therapeutic management in SLE patients is one of the most important aspects when planning a pregnancy. The main goal is to assure the most effective treatment to maintain disease remission, while keeping the ability to treat disease flares and guaranteeing maximum safety for the fetus. As mention on Section 3, disease activ-

In order to decrease maternal and fetal complications, the the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) [20, 52] developed general recommendations describing which drugs are safe during pregnancy and which ones should be avoided. Also, the Unites States Food and Drug Administration (FDA) has changed the way of labelling medication safety during pregnancy and lactation. Previously, it was based on letters, which classified drugs from A to D, according to its increased risk for the fetus. Drugs classified as had not enough evidence or information available. Nowadays, this classification reflects more the quantity and quality of the data known for each drug. For practical proposes, the current drug options available to treat SLE pregnancy has been

Hydroxychloroquine (HCQ ) is an antimalarial agent used for its immunomodulatory effects. Although HCQ crosses the placenta, it does not seem to have toxic effects on the fetus [53]. On the contrary, this drug is recommended to all women with SLE, whether they are pregnant or not, as it decreases the

auditory, developmental or growth abnormalities.

progestogens can be an appropriate option.

divided into 4 main categories:

*8.1.1 Hydroxychloroquine*

**8.1 Drugs recommended during SLE pregnancy**

**94**

risk of flares, reduces the risk of pre-eclampsia and preterm birth [54]. Various studies have also shown positive effects of HCQ in pregnant women with APS (higher birth rates and fewer pregnancy complications) versus untreated patients, concluding that SLE pregnant women that have aPL, also known as "aPL carriers" also benefit from HCQ . Furthermore, some studies suggest that HCQ decreases the occurrence of CHB and cutaneous involvement in neonatal lupus, in fetuses whose mothers are carriers of anti-Ro/SSA and anti-La/SSB antibodies [55].
