Pregnancy in Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is accompanied by motor symptoms such as bradykinesia, rigidity and resting tremor.¹ It is often recognised as a disease of the elderly, with an average age of onset of 55 years.² As such, there is little experience with effects of pregnancy on PD, as few women with PD are of childbearing age. Also, younger women diagnosed with PD may elect not to become pregnant, or to electively abort a pregnancy, due to a variety of reasons. 

These issues range from the effects pregnancy may have on PD and also how PD impacts pregnancy, including treatment issues, conception and delivery issues, the outcome of the pregnancy and issues surrounding childcare. The data regarding pregnancy in PD is limited mainly to case reports and retrospective series, as well as some animal studies regarding PD medications. The aim of this review is to examine and assess the available information and highlight insufficiency in data, if there is any.

Effects of pregnancy on PD

It is believed that pregnancy has an effect on the symptoms and time course of PD. There have been different suggestions made regarding how this comes about.³ Some suggest that changes of pharmacokinetics of medications due to volume and metabolic changes of pregnancy are responsible for the effects of pregnancy on PD symptoms.⁴ Others have postulated that changes in hormone levels such as oestrogen cause the change in PD symptoms.⁵

Reports regarding dopaminergic and antidopaminergic effects of oestrogen in the past have been mixed. More recently oestrogen has been suggested to have a beneficial effect on PD, as it may have dopamine-sparing properties.⁶ This may explain any increase in medication required in the early postpartum period, when oestrogen levels decline rapidly.⁷

Some reports have shown no change, or even an improvement, in PD symptoms, but the majority of cases showed a worsening during pregnancy and/or postpartum, usually without a return to baseline afterwards. Exacerbation of PD is seen as an increase in symptoms, Unified Parkinson’s Disease Rating Scale (UPDRS) scores or medication requirements.³

An example of a case report where the symptoms of Parkinson’s worsened was reported by Shulman et al, 2000. A 33-year-old woman was evaluated prepartum, intrapartum and postpartum. Before pregnancy she experienced slowness in day-to-day activities but was capable of working full-time. It was found that her motor symptoms increased significantly, and that her UPDRS scores increased during the pregnancy and postpartum period, despite an increase in levodopa usage throughout the pregnancy and the first two months postpartum. Pramipexole was started after this, and levodopa was dropped and stabilised, but after 15 months postpartum she didn’t return to her pre-pregnancy level of function. She was unable to return to work, but was capable of looking after her child, who had developed normally.⁷

A literature review by Hagell et al, 1998, found that in case reports of 33 pregnancies in 24 women with PD, 46% of the pregnancies resulted in a worsening of PD symptoms. In some cases the progression was more marked than others.⁸ However, it cannot be said with any certainty that this progression of PD symptoms is anything other than the result of a natural disease progression.

Although the majority of case reports show a decline in the disease state, there have been cases with no changes in PD symptoms,⁸ and some with an improvement in symptoms.⁹

Treatment of PD during pregnancy

There is limited medical experience of managing PD in a pregnant patient and, apart from some animal studies, most of the data available regarding anti-Parkinson medication use in pregnant Parkinson’s patients is anecdotal. There is also some information available regarding anti-Parkinson medication used in pregnant women who didn’t suffer from PD,¹⁰ though it must be remembered that doses administered were probably not as high as in a Parkinson’ s patient.

The main concern with regards to medication of Parkinson’s disease is the risk of teratogenicity to the developing foetus. Bromocriptine and pergolide, both dopamine agonists, are both category B medications, conveying no significant risk to the foetus in animal studies, nor a risk to the foetus in humans throughout each trimester.¹¹ Data are only available regarding second and third trimester exposure in humans. Breastfeeding is not considered safe in dopamine agonists. All other drugs used in PD treatment have a category C rating, which means that animal studies suggest some risk, but that human studies are not available.¹¹

Animal studies with levodopa did not show teratogenicity, apart from one study which demonstrated circulatory system malformations and growth retardation.⁸ Despite this, in the majority of cases where levodopa was administered in pregnant women with or without Parkinson’s disease, pregnancies were completed without complications and the children were healthy.¹²

Shulman et al, 2000, reported a good foetal outcome from a PD patient treated with carbidopa/levodopa throughout her pregnancy, and reviewed 14 other reports where there was no teratogenicity reported with levodopa, either alone or in combination with carbidopa or benserazide, apart from one infant with osteomalacia associated with carbidopa/levodopa administration.⁷

Selegiline, a monoamine oxidase B inhibitor, has been theorised to slow the progression of PD, but is contraindicated (as indicated by the distributor) in pregnancy. There has been a case where a 39-year-old continued taking selegiline in addition to levodopa throughout her pregnancy against medical advice, and she experienced an improvement in her symptoms and drug response. She gave birth to a healthy child who developed normally. However, the safety of selegiline with regards to pregnancy, embryonic and foetal development, birth or postpartum development cannot be affirmed by this individual case. 

There have been no studies regarding selegiline treatment alone in pregnant animals. 

Given the limited experience of the effects of monoamine oxidase B inhibitors during pregnancy and the likelihood that selegiline or selegiline-derived metabolites may pass into the foetus, withdrawal of selegiline is still recommended.⁹

There have been indications that amantadine increases risks of complications during pregnancy and malformations, including miscarriage, particularly during the first trimester. However, data regarding amantadine are only available in four case reports.⁴ Increase in drug dosages should be considered due to increase in plasma volume and pharmacokinetic changes during pregnancy.¹³ Also, drug dosages may need to be increased if the pregnant patient experiences a deterioration of their PD during their pregnancy.⁷

To summarise the availability of data on treatment of PD in pregnancy, there have been examples of successful treatment of pregnant women with PD using levodopa, carbidopa, benserazide, pergolide, pramipexole, cabergoline, selegiline and trihexyphenidyl. There are few or no data regarding the use in pregnancy of entacapone, tolcapone, bromocriptine (in typical PD dosages), ropinirole, rasagiline or benzatropine. The evidence regarding amantadine suggests that this drug should be avoided over all others in the treatment of pregnancy in PD.³

Effect of PD on pregnancy

While there is concern for the effects of PD medication on pregnancy and its outcome, there has been little evidence of any effect of PD itself throughout the duration of pregnancy and the pregnancy outcome. In a study by Golbe et al, 1987, 18 women who had a total of 24 pregnancies since the onset of their Parkinson’s symptoms were interviewed. 

Out of the 24 pregnancies, there were three miscarriages, four elective abortions and 17 term pregnancies. The majority of case reports further showed that most pregnancies came to term^14,8 apart from cases where it was elected to abort the foetus,¹⁵ or pregnancies which ended in miscarriage, due to factors unrelated to PD.¹⁶ Apart from amantadine being associated with various obstetric complications, including miscarriage, overall it was found that there was no marked increase in obstetric complications or foetal defects than would be expected in a group of pregnant women without PD.⁴

There may be conception and delivery issues associated with PD. There is no evidence of PD directly affecting fertility and conception, though difficulties may arise due to self-image changes, resulting in difficulty with sexual intimacy and social withdrawal. Difficulty with self-care may lead to avoidance of sexual activity.¹¹ In fertility problems unrelated to PD, there has been a successful case report of an IVF pregnancy resulting in a healthy baby born to a woman without any worsening of her Parkinson’s symptoms.¹³

Regarding delivery, not much difficulty is reported and the majority are delivered at full term,⁴ though some patients may have to deliver by Caesarean section due to motor issues.¹⁴

Post-delivery, the mother may experience difficulties caring for her child, depending on how progressive their PD might be. The caring of a child by women with PD requires planning and development of a support system.¹¹ Another concern post-delivery is that of breastfeeding. There are few data regarding the risks of breastfeeding concerning anti-Parkinson drugs. Almost all drugs are excreted into breast milk and are bioavailable to an infant, and therefore the possible risks and the benefits of breastfeeding must be kept in mind. 

If a mother decides to breastfeed, any abnormal signs or symptoms the child shows should be considered with respect to drug effects.⁷ There is a lack of long-term outcome data in relation to children born to mothers with PD. One case followed the child over a period of 10 years and found somatic and mental development to be within normal percentiles⁹ but this is not sufficient data so as to be conclusive.

Conclusion

In conclusion, pregnancy in PD is a rare occurrence, and there are few data available in relation to it. As the majority of evidence is of an anecdotal nature, it does not provide concrete evidence regarding the effects of pregnancy on PD, nor does it provide sufficient recommendation regarding the management of PD during pregnancy and postpartum. 

However, it can be used as a guide for what to consider in reproductive planning. Any woman with PD who is considering becoming pregnant should be made aware of a possible link between pregnancy and a worsening of their disease, though this effect is controversial. It should also be made known to her that there are few data to support the safety of most PD medication, but that in the majority of cases where pregnant women received anti-Parkinsonian medication, treatment was successful. 

The information regarding medication can also provide a rough clinical guide for neurologists, though caution is encouraged where less clinical evidence is available. Careful management is of utmost importance in pregnancy with PD. It should be ensured that women with PD considering pregnancy understand the chronic progressiveness of their disease and its motor symptoms, and how they may affect the ability to care for a child later on. 

References

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