A systematic review of clinical data and reporting quality in NMDAR-antibody encephalitis and pregnancy
Authors: Harris Scarlett L , Binks Sophie NM , Skelly Donal , Fourie Hanine , Cherrington-Walker Phoebe , Bajorek Tomasz , Irani Sarosh R , Leite M Isabel , Handel Adam E , Al-Diwani Adam 
Published: December 2024

Background

NMDAR antibody encephalitis (NMDAR-Ab-E) can have an onset during, after, or prior to a pregnancy. In animal models, transplacental NMDAR-IgG transfer can affect neurodevelopment. In contrast, clinical reports of mothers affected by NMDAR-Ab-E typically are reassuring. We systematically reviewed maternal, infant, and childhood clinical data pertaining to NMDAR-Ab-E with an onset before, during, or after pregnancy and compared this to our single autoimmune neurology centre experience.

Methods

After pre-registration on PROSPERO (CRD42023408447), we searched PubMed and Scopus for NMDAR-Ab-E case reports/series with an onset before, during, or after pregnancy (last search 19/10/2023). We extracted maternal, neonatal, and childhood outcomes using an idealised checklist to derive summary statistics.

Results

After quality control we identified 66 pregnancies in 61 women from 48 reports or series. 72% of women recovered with minimal or no neurological deficits, comparable to non-pregnancy associated NMDAR-Ab-E. Likewise, 80% of pregnancies resulted in livebirths with a single neonatal death reported. Data on neonatal outcome measures were frequently unreported and childhood follow-up in only 60%. Our centre’s experience is consistent: 3/4 mothers recovered with no functional deficits and 7/8 children without evidence of compromise at median of two years follow-up.

Conclusions

Current evidence does not overall suggest unfavourable maternal, fetal, or childhood outcomes after NMDAR-Ab-E. However, the available sample is small, predominantly single case reports with modest follow-up, lacks standardisation, and data are often incomplete. Future approaches should address these caveats; developing multi-centre collaboration towards an international registry.

Key messages

What is already known on this topic

Some animals models of NMDAR-IgG transplacental transfer show adverse effects on brain development. However, caveats include species differences and potentially non-physiological exposures. Moreover, although some case reports identify adverse maternal and fetal outcomes, previous systematic reviews and single centre summaries of clinical data have been more reassuring.

What this study adds

We update and expand upon previous systematic reviews by including cases of NMDAR-Ab-E in the postpartum period and cases of pregnancy after recovery, as well as reporting the experiences of our autoimmune neurology centre. Additionally, we also focus on childhood outcomes and have contacted authors of published case reports for further follow-up. These data show generally good outcomes for mothers and children but reporting is patchy and not standardised.

How this study might affect research, practice or policy

To overcome these shortcomings in reporting we recommend collaboration amongst the autoimmune neurology clinical-research community to consolidate experience. This could include establishing an international registry to foster reporting standardisation and improve understanding of interactions between the illness, pregnancy, and potential effects on neonatal and childhood outcomes.