Title: Pregnancy complications in last pregnancy and mothers’ long-term cardiovascular
mortality: does the relation differ from that of complications in first pregnancy? A population-
based study
Version: 2 Date: 20 Jan 2023
Reviewer's report:
Thank you for the opportunity to review this paper.  It is well written, nicely presented in the
tables and figures, and despite its limitations I believe it will make a contribution to the literature
after a careful revision.
Specifically, I believe a significant revision of the introduction, discussion of limitations and
recommendations for future research should address the existing evidence that pregnancy losses
(natural and induced) are significantly associated with higher rates of cardiovascular disease
and CVD related deaths. (See a list of references that should be included in the introduction and
discussion below.)
My initial impulse when I began to read the paper was that I should recommend rejecting
it until you had undertaken a reanalysis that at least controlled for the number of each
woman’s reproductive losses, including record linkage to the Norwegian Registry of Pregnancy
Termination.   But upon additional research, I discovered that unlike the Finland and Denmark
abortion registries, the Norwegian registry does not provide a means of record linkage to the
death registry.  That is a significant shortcoming since studies of the Finland and Denmark data
reveal elevated rates of death associated with both miscarriage and induced abortions.
In addition, both forms of pregnancy loss are also associated with higher rates of CVD and
abortion has been significantly associated with higher rates of death from cardiovascular diseases
in at least one large study of low income women from California.
In light of the above observations (and citations below), it is clear that your team’s analysis
of Norway’s data falls far short of “taking women´s complete reproduction into account,” as
declared in the abstract.
Therefore, I believe the paper would be improved by a substantial discussion of the facts that
(a) pregnancy loss is significantly associated with elevated rates of CVD and premature death,
but (b) Norway’s abortion registry lacks the information necessary to link to death certificates,
therefore (c) your analysis is significantly weakened by the absence of information on pregnancy
losses, yet (d) your findings underscore the importance of investigating CVD and mortality rates
in light of women’s complete reproductive histories, therefore (e) you recommend additional
research in countries and data bases that allow construction of complete pregnancy outcome
histories and even that Norway’s Registry of Pregnancy Termination should be revised to
facilitate record linkage for such research purposes in a manner that will still fully protect the
privacy rights of individuals.
All that said, it appears that you might be able to at least partially address the issue by
including a control variable related to treatment for miscarriage.  In the paper “Role of maternal
age and pregnancy history in risk of miscarriage: prospective register based study” https://
doi.org/10.1136/bmj.l869, Norwegian medical records have been used to identify at least a
substantial percentage of miscarriages.  However, I recognize that would require a complete
revision of your analyses and paper, which is why I would accept deferring that task to a future
paper, provided your discussion indicates the importance of such additional analyses.
Following are the references discussed above which should be included in your expanded
introduction and in the discussion of your study’s limitations and your recommendations for
future research.
Harry Kyriacou, Abdulrahman Al-Mohammad, Charlotte Muehlschlegel, Lowri Foster-Davies,
Maria Eduarda Ferreira Bruco, Chloe Legard, Grace Fisher, Fiona Simmons-Jones, Clare Oliver-
Williams, The risk of cardiovascular diseases after miscarriage, stillbirth, and induced abortion:
a systematic review and meta-analysis, European Heart Journal Open, Volume 2, Issue 5,
September 2022, oeac065, https://doi.org/10.1093/ehjopen/oeac065
Tsulukidze M, Reardon D, Craver C. Elevated cardiovascular disease risk in low-income
women with a history of pregnancy loss. Open Heart. 2022 Jun;9(1):e002035. doi: 10.1136/
openhrt-2022-002035. PMID: 35680171; PMCID: PMC9185659.
Reardon DC, Ney PG, Scheuren F, Cougle J, Coleman PK, Strahan TW. Deaths associated
with pregnancy outcome: a record linkage study of low income women. South Med J. 2002
Aug;95(8):834-41. PMID: 12190217.
Reardon DC, Thorp JM. Pregnancy associated death in record linkage studies relative to
delivery, termination of pregnancy, and natural losses: A systematic review with a narrative
synthesis and meta-analysis. SAGE Open Med. 2017 Nov 13;5:2050312117740490. doi:
10.1177/2050312117740490.