This document summarizes key information from a presentation on managing multiple sclerosis during pregnancy. It discusses various drug treatments for MS symptoms like spasticity, pain, and mobility issues. It notes that clinical trials on drug safety during pregnancy are limited. Physiological changes in pregnancy can impact drug absorption and dosage requirements. Major birth defects may occur early in pregnancy before the pregnancy is recognized. The risks and benefits of continuing or adjusting treatments need to be considered. Gabapentin appears to have no contraindications, while drugs like duloxetine and carbamazepine require careful consideration during pregnancy. Non-drug options should also be explored. Close monitoring by an MS team is recommended for pregnant women with MS.

1. Pregnancy Workshop
Dr Peter Brex
Consultant Neurologist
King’s College Hospital NHS Foundation Trust
MS Trust Annual Conference
3-5th November 2019
Jurys Inn Hinckley Island Hotel

3. Bladder
Oxybutinin
Solifenacin
Mirabegron
Botox
Bowels
Movicol
Spasticity
Baclofen
Tizanidine
Dantrolene
Clonazepam
Sativex (limited NHS)
Neuropathic pain
Amitriptyline
Gabapentin
Pregabalin
Duloxetine
Carbamazepine
Depression / Anxiety
SSRI
SNRI
Pregabalin
Oscillopsia
Gabapentin
Memantine
Walking speed
Fampridine (not available NHS)
Sexual Dysfunction
Sildenafil
Fatigue
Amantadine
Tremor
Propranolol
Clonazepam
Topiramate
DBS
MDT – annual review
MS nurse
Physiotherapy
OT
Wheelchair services
Tissue viability nurse
Social services

4. https://pn.bmj.com Published on-line 5th January 2019 and in the April 2019 print edition of Practical Neurology

6. Consider the possibility of pregnancy
when prescribing any drug to a fertile
women
• Is drug treatment essential?
• Threshold for treating during
pregnancy will vary on indication, e.g.
CBZ for pain versus epilepsy
• Advise on contraception
• Non-pharmacological options?
WwMS often will have a view on whether
they wish to take medicine during
pregnancy

7. No clinical trials
No Pregnancy Registers
Few case reports & investigator studies

8. A population-based stud in Northern Italy (4 million inhabitants) over a 3-year period (2009–2011)
21 exposed to Gabapentin - among the 9 newborns exposed during the first trimester, two
had a major birth defect, an isolated ventricular septal defect (VSD) in both cases
30 exposed to Pregabalin - among the 13 newborns exposed during the first trimester, 1
had a major birth defect, namely a VSD,
“Our findings should raise concerns over the use of these drugs in
women of childbearing potential.”

10. Physiological change Clinical implication
↑ heart rate and cardiac output
↑ intravascular volume
↑ Renal plasma flow
Haemodilution
↑ GFR
↑ Creatinine clearance
Altered pharmacokinetics of drugs – dose and
frequency adjustments, e.g. LTG, LEV
↑ blood flow to organs including skin ↑ skin temperature Altered absorption of transdermal
medications
↑Gastric transit time
↓ Gastric motility
Altered hepatic biotransformation
↓ Bile excretion
Drug toxicity
Altered efficacy
↓ Protein binding
↑ Total body fat composition
↑ free drug concentration
Anatomical change
Increasing gravid uterus, lumbar lordosis Urinary symptoms
Impaired Balance
Hormonal changes
↑ Oestrogen, Progesterone
↓ Substance P
Alteration in pain receptors Altered or reduced pain perception
↓ Anaesthetic requirements
Adapted from
Gaiser R. Physiologic changes of pregnancy. In: Chestnut D (Ed.). Chestnut’s Obstetric Anesthesia, 4th ed. Philidelphia: Mosby Elsevier, 2009: 15-29

12. Major congenital abnormalities could occur before pregnancy recognised

15. Baclofen withdrawal is a fairly well documented and possibly life threatening
phenomenon in adults. However, because it is rarely prescribed for use in
pregnant women the safety of intrauterine baclofen exposure and the effects of
abrupt postnatal cessation on the neonate are largely unknown. To date there
have been only a handful of case reports documenting the clinical
manifestations of baclofen withdrawal in the newborn with reported symptoms
ranging from hypertonicity and irritability to intractable seizures responsive

17. 1. Hellwig et al. Mult Scler 2008; 14(5): 718, 2. Airas L et al. Obstet Med 2012; 5: 94–97, 3. De las Heras et al. Mult Scler 2007; 13(8): 981-984
4. Confavreux C et al. N Engl J Med 1998; 339(5): 285-291, 5. Langer-Gould A et al. Arch Neurol 2009; 66(8): 958-963

18. Thomas W. Hale is a Professor of Pediatrics at Texas
Tech University School of Medicine, the Executive
Director of the InfantRisk Center, Executive Director of
the Clinical Research Unit, and Assistant Dean of
Research.
www.infantrisk.com

20. 1.Sivojelezova A et al. Am J Obstet Gynecol 2005;193(6): 2004-2009, 2.NICE guidance antenatal and postnatal mental health, 3.Dalton CM et al. Mult Scler 2008; 14(4): 571-572, 4.Berle JO et al. Curr
Womens Health Rev 2011; 7(1): 28–34, 5.Tandon SS et al. Obstet Med 2010; 3(3): 119–120, 6.American Academy of Pediatrics Committee on Drugs. Pediatrics 2001; 108(3): 776-789
Gabapentin
 No contraindication
 No additional intervention
Slides courtesy of
Dr Surabhi Nanda

21. Duloxetine
• Limited data in first trimester to suggest increased teratogenic
risk
• Increased risk of spontaneous first trimester miscarriage (2
studies) - cf PPC
• No association with IUGR or preterm birth
• Transplacental transfer ratio - 0.12 (12%)
• Breast feeding - infant exposure < 10% of the maternal dose
– acceptable
• No dose adjustments are needed in pregnancy
Carbamazepine
• Avoid in first trimester
Andrade, 2014
Lassen et al., 2016
Slides courtesy of
Dr Surabhi Nanda