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Identical FSH & LH values at baseline in two different trials

August 1, 2021

My first PubPeer comment

As anyone who’s tried to expose fraudulent research by writing a “letter to the editor” will know, it can be fustrating. Editors prevaricate, authors obfuscate, and time ticks by.

PubPeer (click here) is an alternative. Publish the facts, let the author reply, and readers, editors, regulators and employers can judge for themselves. If you enter the author’s email when you submit, PubPeer automatically notifies them that one of their papers has been commented on.

It has been a powerful way to expose fabricated laboratory research, where authors have manipulated images. It can also be used for fabricated clinical studies.

To protect whistleblowers, comments can be anonymous – they just need to stick to verifiable facts – but I’ll be signing mine. Here’s my first. To read it on PubPeer (click here).

It refers to this paper:

Rezk M, Shaheen AE, Saif El-Nasr I. Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial. Gynecol Endocrinol. 2018 Apr;34(4):298-300. doi: 10.1080/09513590.2017.1395838. Epub 2017 Oct 27. PMID: 29076376.

Table 1 has identical values for FSH and LH as Table 1 in a different paper in the same journal from 2016.

Rezk M, Sayyed T, Saleh S. Impact of unilateral versus bilateral laparoscopic ovarian drilling on ovarian reserve and pregnancy rate: a randomized clinical trial. Gynecol Endocrinol. 2016;32(5):399-402. doi: 10.3109/09513590.2015.1124262. Epub 2015 Dec 15. PMID: 26670076.

Present paper
file

Rezk et al 2016
file
The earlier paper reported a trial comparing two surgical treatments with 105 participants, and the present paper a trial of two medical treatments with 202 participants. The earlier paper recruited “from October 2014 to July 2015”. The present paper recruited “between the middle of October 2016 and the beginning of May 2017”. The later paper does not reference the earlier one.

Both have the same first author, and originate from Menoufia university, Egypt.

Jim Thornton

Why use ripe-tomato as a Covid in pregnancy source?

July 30, 2021

People often ask us “What’s different about ripe-tomato? Why not use WHO (click here), Cochrane (click here), or PubMed (click here) Covid-19 databases instead?”

Serious systematic reviewers, or guideline authors, should indeed use all those. But it will be a lot of work, searching, accessing, reading and deduplicating.

Ripe-tomato has done it for you, for primary sources in pregnancy. It isn’t perfect, but we’ve not missed much. Friends and colleagues soon tell us if we have!

But haven’t the WHO/Cochrane Living Systematic Review (LSR) team and Johns Hopkins each done the work too? Yes and no.

Shakila Thangiratinam and her WHO/Cochrane LSR team (click here) have a more complete, and better indexed, database. Dozens of people update it full time – and check ripe-tomato. But it’s not publicly accessible. The reference lists and appendices of their publications reveal the sources they used, but they keep the master database to themselves.

Johns Hopkins Center for Humanitarian Health has two related repositories. COVID-19, Maternal and Child Health, and Nutrition (click here) and COVID-19, Breastfeeding, Infant Feeding, and Breast Milk (click here). Both broader in topic than ripe-tomato and not limited to primary sources. Update 1 May 2021. The two John Hopkins repositories ceased updates from 30 April. They remain publicly available but are no longer updated.

Ripe-tomato’s unique features

Primary sources only. Anyone whose ever studied Covid-19 realises that secondary sources, reviews, editorials, comments and opinion pieces outnumber the primary sources many times. Not on ripe-tomato.org

Duplicate publications noted. Another major problem for all Covid evidence synthesisers. If you’re writing a review, creating a reference list for an article, or refereeing a paper on Covid-19 in pregnancy, ripe-tomato is your friend. We’ve caught and recorded most of the obvious duplicates. Use us.

Easy access. Some sources are behind paywalls, and some difficult to access. Don’t ask how we do it. But where possible, beside a link to the source website, we also provide a direct link to our own uploaded copy.

Newspaper reports (click here). A deduplicated list of primary newspaper stories about people with Covid-19 in pregnancy. From Italy’s “patient one”, the partner of Juventus footballer, Daniele Rugani, and the wife of the British Prime Minster, to a transgender man who caught Covid during his pregnancy. The list of nearly 700 heartbeaking and heartwarming stories is unique. It’s not complete – English language reports are over represented – but there’s nothing else like it in the world.

Click here for Ripe-tomato.org’s Covid-19 in pregnancy navigation page.

Jim Thornton

Bloody awful tripe?

July 10, 2021

This Be The Verse and The Trees

This Be The Verse is Philip Larkin’s most famous poem. In his latest book, Inside Story, (p 117) Martin Amis notes that it has a technically near identical sister, The Trees, which is more optimistic. Although Larkin apparently wrote “Bloody awful tripe” on the manuscript of the latter, he published it in High Windows, and it’s not.

This Be the Verse

They fuck you up, your mum and dad.
They may not mean to, but they do.
They fill you with the faults they had
And add some extra, just for you.

But they were fucked up in their turn
By fools in old-style hats and coats,
Who half the time were soppy-stern
And half at one another’s throats.

Man hands on misery to man.
It deepens like a coastal shelf.
Get out as early as you can,
And don’t have any kids yourself.

The Trees

The trees are coming into leaf
Like something almost being said;
The recent buds relax and spread,
Their greenness is a kind of grief.

Is it that they are born again
And we grow old? No, they die too.
Their yearly trick of looking new
Is written down in rings of grain.

Yet still the unresting castles thresh
In fullgrown thickness every May.
Last year is dead, they seem to say,
Begin afresh, afresh, afresh.

(Not) Giving Women Good Sex

April 5, 2021

Is this fraud?

My colleague, Susan Bewley, drew my attention to the Journal of Sex Research last week (click here or Spielmans 2020 Re Analyzing Phase III Bremelanotide Trials for Hypoactive Sexual Desire Disorder in Women). The author, Glen Spielmans, Professor of Psychology at Metropolitan State University in Minnesota, dissects two pivotal phase-3 trials (click here or Kingsberg Obstetrics & Gynecology November 2019), which had led the US Federal Drug Administration (FDA) to license bremelanotide, trade name Vyleesi, to treat women with hypoactive sexual desire disorder (HSDD).

One of the original co-primary outcomes in each trial was switched, many pre-specified outcomes went unreported and new ones appeared, scores were reported as dichotomous rather than as the prespecified means, cut-off values varied for no apparent reason, and other outcomes were claimed as supportive without data. Spielmans also noted that more women (18 or 19% bremelanotide v 3 or 9% placebo) dropped out of the active groups, and questioned whether the various shifts in subsets of sexual behaviour scores, even in the unlikely event they were real, were of clinical significance.

He is correct on all counts. But altered co-primary outcomes in two drug licensing trials? How did that get past the FDA?

Background

Bremelanotide is a polypeptide, related to melanocyte stimulating hormone (MSH). Ever since someone noticed in the 1960s that MSH caused rats to become sexually aroused, chemists have been fiddling with the pharmacology in the hope of creating a female Viagra. In 2016, Palatin Technologies, who own the rights, convinced themselves in a phase-2 dose-finding trial (PT-141-54 in the FDA report) (click here or clayton 2016) that the stuff worked at higher doses. The planned sample size was 100 per group. The pre-specified primary outcome was change in satisfying sexual events (SSE) per month.

PlaceboLow doseMediumHigh dose
No. randomised 99 100 9999 
Analysed (at least 1 dose & 1 follow-up visit)  91 87 7574 
Dropped out 8 1324 25 
Additional satisfying sexual events per month 0.2 0.6 0.7 0.8

The authors claimed a dose response relationship (bottom row) but were coy about the row above – I’ve extracted it for you. Without knowing what they were getting, three times as many women on the higher doses dropped out. In a double-blind trial this can only mean one thing, side effects. There were many more, mainly nausea, flushing and headache, in the active treatment groups

Such non-random differential drop out pretty much invalidates the results. If women who stayed the course were more stoical, or had a greater desire for their sexual problems to be sorted, it’s hardly surprising to see a small increase in SSEs.

But what do I know? These data were judged sufficiently promising to set up two pivotal efficacy trials for FDA approval. 

The trials

Both had the same title “Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder (HSSD)” on Clinicaltrials.gov.

They both studied the allegedly most effective, high dose of bremelanotide, 1.75mg, from the dose-finding study.

They were both reported in the same paper (click here or Kingsberg Obstetrics & Gynecology November 2019). For the FDA analysis (click here or FDA bremelanotide).

Study 1 (labelled BMT-301 in Kingsberg and FDA papers) had a planned sample size of 550 (actual 723) and ran from December 2014 to July 2016, (registry here). Study 2 (labelled BMT-302) had the same planned sample size of 550 (actual 714) and ran from January 2015 to August 2016, (registry here). I could find no explanation for the 30% sample size increases, in either the Kingsberg paper or the FDA report.

Despite their identical eligibility criteria, and almost identical recruitment periods, both trials appear to have been run in the same 91 centres.

The original co-primaries for both trials were:

1.       Change in Female Sexual Function Index–desire domain (FSFI-D). The desire domain is the sum of; “Over the past 4 weeks, how often did you feel sexual desire or interest?” – responses range from 1 “Almost never or never” to 5 “Almost always or always” – and; “Over the past 4 weeks, how would you rate your level (degree) of sexual desire or interest?” – responses range from 1 “Very low or none at all” to 5 “Very high”.

2.       Change in absolute number of sexually satisfying events (SSE) per month.

Of thirteen planned secondary outcomes, the twelfth was this question from the Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO); “are you bothered by low sexual desire?” Responses range from 0 “never” to 4 “always”.

Both trial results would have been negative had the co-primary outcomes remained unchanged. Although absolute numbers of SSEs are not reported in either the paper nor the FDA report, the latter states “neither treatment nor placebo arm showed any improvement” (p 126).

This looks suspicious. SSEs are more meaningful than “bothered by low sexual desire” which is little more than a different aspect of the other co-primary.

But on 27 October 2014 (click here) the FDA had held a workshop with patients about Female Sexual Dysfunction.

The company claimed that workshop participants had stated that SSEs were a poor efficacy outcome. Some quotations e.g. “Several [participants] stressed the importance of feeling desire regardless of whether it is accompanied by a satisfying sexual event” (p6), could be interpreted this way, although others e.g. “Participants largely appeared to believe that having satisfying sexual events was important to them” (p13) suggest the opposite. Even on its own terms this is hardly a convincing argument.

But the workshop had been captured by pharma. Here’s what independent experts, Leonore Tiefer, Ellen Laan and Rosemary Basson wrote about it at the time (click here or Tiefer),

Participants had their expenses paid by [a group funded by] pharmaceutical companies, […] had met the morning of the first day in their hotel to hear presentations and prepare their talking points.

They had each received a green shawl, identifying them with the ‘’even the score’’ campaign that accused the FDA of sexism in handling [female sexual disorder] drug applications [and] arrived at and departed together by chartered bus.

It looks like the FDA was pressured into agreeing the switch, to avoid accusations of sexism in the way they treated applications for female and male sexual treatments.

And the timing of the switch? The alteration was requested on 10 October 2016. Study BMT-301 had been completed on July 26 that year, and study BMT-302 on Aug 4th.

Let’s summarise. More than two months after the studies had been completed, on the basis of a dodgy, pharma-captured workshop conducted two years earlier, the trial sponsors persuaded the FDA to allow the co-primary endpoints to be switched. They were changed from a meaningful predefined outcome justified by the pilot dose-finding study, the number of satisfying sexual events, to the twelfth of thirteen secondary outcomes. And guess what? Bremelanotide, which did not alter the number of satisfying sexual events, magically improved this suddenly important secondary outcome.

Spielmans doesn’t say it, but I do. This must be a data-driven outcome switch. If so, that’s fraud. 

Jim Thornton

Update 10 April 2021

Yesterday Dr Kingsberg and her colleagues replied to Dr Spielmans’ critique (click here or paper), and Dr Spielmans replied to her reply (click here or paper). Despite much bluster, in my opinion, she failed to deal with any of his substantive points. But judge for yourself.

With regard to whether the co-primary outcome switch was data driven, Kingsberg writes;

He also alludes to “data peeking” in his introduction and that the FDA allowed the “sponsor’s request for satisfying sexual events (SSEs) to move from the co-primary to the key secondary outcome …. a year after the trials had begun.” What Spielmans omitted is that the FDA published a guidance document (2016) for designing clinical trials in which SSEs were no longer required to be a primary endpoint for HSDD treatment trials. Instead, trials could now include measures reflecting the hallmark criteria of the condition: loss of (i.e., deficiency or absence of) sexual desire (i.e., FSFI-D) and distress about lack of desire (i.e., FSDS-DAO #13). The approval from the FDA to change the primary endpoint, after discussion with the FDA review division, came prior to the data lock [my emphasis] in these well-conducted, randomized, double-blind, multicenter placebo-controlled trials, with pre-established statistical analysis plans. 

Note the non-denial choice of words. No-one doubts that the outcome switch came “prior to the data lock”. The issue is whether the sponsor had seen the data prior to the outcome switch request.

Philosophy for children P4C2 – clarification

March 11, 2021

The power of randomisation

Mistake in my P4C-2 post yesterday (click here). The result is still negative, and the report still turgid, but when describing the distribution of the pooled reading and maths scores, I suggested that the authors had not shown them by group, and made the snide comment “Perish the thought that an educationalist would ever show you anything remotely near to the raw data!”

Forgive me. Further down appendix I of the main report (click here) are “intervention” (p 100) and, controls (p 102). But different pages? This is a randomised trial where half the pupils got philosophy teaching and half did not. Readers want to compare the two groups side by side. Come on EEF!

To help I’ve reordered the graphs here p4c2 result histograms p number. Intervention group left, control right. Page one, free school meal (FSM) pupils and page two all pupils. Reading scores before maths scores.

It’s rather revealing. For each outcome and for each subgroup not only are the means and ranges almost identical but also the shapes of the distributions. Not exactly identical – these are different populations – but remarkably similar. Go on, check. Click the link above and then scroll down comparing left to right. The shape of the control distribution of reading scores among FSM pupils is different from the shape of the control maths scores, but both are almost identical to the respective reading and maths scores for the intervention group.  Same for the whole sample.

Not only did the intervention, Philosophy for Children, have no effect on maths or reading but, since it had no effect, we can see how beautifully, when you have a large sample size, randomisation really does generate comparable groups.

Well I think it beautiful.

Jim Thornton

 

Philosophy for Children (P4C) – trial 2

March 9, 2021

Still doesn’t work. Really doesn’t. Not even a tiny benefit.

Five years ago a rather nice randomised trial, run by the Education Endowment Foundation (EEF) (click here), tested the effect on reading and writing, of teaching philosophy to primary school children. The result was negative, but unwisely the EEF entrusted evaluation to a group of educationalists who were determined to find a positive result. By ignoring their original analysis plan, doing a data-driven analysis of change scores, and picking a favourable subgroup, children entitled to free school meals, they managed to convince themselves that teaching little children to be kind to their teddy bears helped wth reading and maths (click here for my analysis of where they went wrong). The newspapers picked up the story and headlines flew round the world (click here).

Fortunately I wasn’t the only one to smell a rat (see here and here). Professor Gorard, the lead evaluator, sent me a patronising email and blocked me on social media, but the EEF did the right thing. They realised they’d boobed, decided not to published the misleading analysis in a peer-reviewed journal [but see footnote], and did the trial again. The results are just in (website here, main report here, or for those with access problems Philosophy_for_Children_report_-_final_-_pdf).

The second trial, P4C-2, was also a cluster design but larger, 75 intervention and 123 control schools, compared with the original trial’s 26 intervention and 22 control. The protocol (click here) and analysis plan (click here) were published and adhered to. The biggest risk with cluster trials is differential recruitment or measurement of outcomes related to knowing the cluster, but this was avoided by using the 2019 Key Stage 2 (KS2) reading scale score as the primary outcome. KS2 reading and maths are measured independently on all pupils in the country, whether or not they or their schools participated. Since Gorard’s data dredging had shown the most “benefit” among children receving free school meals, the primary analysis was planned for this group.  Analysis was by intention to treat.

The report is 125 pages long, and a turgid read, – education researchers love making simple things complicated – but the essence is easy to describe. There is a CONSORT flow diagram (Fig 1, p33 not shown here), few pupils were lost to follow-up (Table 12, p36 not shown here), and the randomisation achieved a balance of both schools and pupils at baseline (Table 13, p37 not shown here). The primary and main secondary outcomes are in Table 14, p38 (click on thumbnail to read).

The presentation is rather strange. For each group they report the mean score and the 95% confidence interval for the mean. The actual score distributions are relegated to appendix I, p98.

Don’t be mislead by the words intervention and control into reading these as distributions by group.  Perish the thought that an educationalist would ever show you anything remotely near to the raw data!  These are pooled results for reading and maths, each for the whole sample and the free school meals subgroup; four distributions in total. They tell us nothing about the effect of the intervention, but they allow the reader to see that scores are roughly normally distributed with mean values between 100 and 105, a range of 80-120 and a standard deviation of roughly 12.

Turning back to table 14 above we can see that the absolute mean differences between group are tiny fractions of a single score point, i.e trivial.  The Hedges g column expresses the difference as a fraction of the pooled standard deviation. Tiny by any standards. Even those educationalists who prefer the effect size to significance testing, ignore effect sizes of <0.2 and generally only consider one of >0.4 as “meaningful”. These are 0.01 to 0.05. For frequentists like me, despite the large sample size, the result is not remotely “statistically significant”.

The rest of the report discusses how well various schools implemented the intervention and searches for a signal related to how well P4C was implemented, but finds nothing.

In summary a well-designed and well-analysed negative trial. We can be confident of the result, and confident also that the trial has not missed a worthwhile small effect.

Some Twitter commenters have said, “But surely we don’t teach moral philosophy to help chidren with reading or maths. We do it to help them grow up to be better kinder people.” They make a good point. The trial says nothing about the effect of P4C on moral behaviour, and everyone supports primary school teachers continuing to teach their pupils to be kind and honest. But education planners should stop paying large sums to Sapere, the creator of P4C, and displacing lessons to teach it, in the hope of improving reading and maths.

It’s a ground-breaking trial

I wonder where it will get published. In my field a negative, large well-conducted cluster trial like this, – the AFFIRM trial of encouraging awareness of fetal movements in pregnancy for example – doesn’t languish in an obscure specialist journal but gets published as a full length paper in the most prestigious medical journal in the world, The Lancet (click here). This report will need a rewrite, but a major general science journal, Science or Nature, should publish it for its methodological importance.

The EEF has shown how to evaluate an educational intervention properly. Imagine if they used the same methods to compare phonics with whole language to teach reading, or to test whether drilling children in tables was helpful or harmful. Imagine that!

Jim Thornton

Footnote added 13 March. I’d missed it. The EEF did publish the misleading analysis in a peer reviewed journal, (click here or 1467-9752.12227), albeit with weaker conclusions. “… for […] attainment outcomes in the short term, an emphasis on developing reasoning is promising, especially for the poorest students, but perhaps not the most effective way forward.”

The singer, the painter & the randy politician

February 8, 2021

Ann Ford by Thomas Gainsborough

   

It’s 1760. Bath is booming. The agricultural revolution has increased the population, and created a new class of landed gentry, but the industrial revolution has hardly started. Coal is mined locally, the town is dirty and smoky, and there are no canals, let alone railways. Just stage coaches along the fast but dangerous new turnpikes, often past the bodies of hanged highwaymen. But Bath is fashionable. Wealthy gentry move their households to the first English spa town for the winter season. Gainsborough, facing stiff competition in London, decides to try his hand. This is his advertisement.

21-year-old Ann Ford had started singing privately at her father’s house in London, but has had to run away to Bath to sing in public. She is good, but the crowds titter at a woman behaving so outrageously. Philip Thicknesse, Gainsborough’s mentor, and later Ann’s husband, sets up a meeting, and soon the six foot painting stands in the front window of Gainsborough’s studio. The silvery dress attracts attention and the pose is exciting. No well brought up woman crosses her legs in public! As one future customer notes “a most extraordinary figure, handsome and bold; but I should be very sorry to have any one I loved set forth in that manner.” The viola da gamba, a man’s instrument, peeping out from behind the red curtain, refers to the latest scandal .

William Villiers, the 52-year-old Earl of Jersey, wants Ann, and offers her the extraordinary sum of £800 a year to be his mistress, with the promise of marriage when his ailing wife dies. Not only does she refuse, but when he tries to sabotage her first public concert in retaliation, she publishes a pamphlet, A Letter from Miss F—d to a Person of Distinction, defending her position.  Amazingly Villiers replies, and a juicy pamphlet war ensues – the Kim Kardashian of Bath scrapping with a publicity hungry politician. Fun for all, and great for Gainsborough. His career thrives.

The painting is now in the Cincinnati Art Museum (click here).

Jim Thornton

Above mostly from Gainsbrough; a portrait by James Hamilton. Weidenfield & Nicholson, London 2017.

Covid-19 vaccines, pregnancy & fertility

January 14, 2021

Primary sources

Primary scientific reports of clinical data on the safety and effectiveness of SARS-CoV-2 vaccines in pregnancy, and in women of childbearing age. In reverse order. Regularly updated. Click here for ripe-tomato.org’s Covid-19 navigation page. Thank you Susan Bewley and Keelin O’Donoghue for getting this started. Click here for “Vaccine in pregnancy news reports“.  We are not providing running totals by vaccine or control group but Viki Male @VikiLovesFACS is doing so here. .

Update 10 September – sources 59 and 60 added. Source 19 updated.

Source 60 – case control study of vaccination rates among miscarrying and ongoing pregnancies in USA

From eight Vaccine Safety Datalink Sites (Kaiser Permanente: Washington, Northwest, Northern California, Southern California, and Colorado; Denver Health; HealthPartners; and Marshfield Clinic, Wisconsin) over seven 4-week surveillance periods from December 15, 2020, through June 28, 2021 (click here or source). Citation: Kharbanda EO, Haapala J, DeSilva M, et al. Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. JAMA. Published online September 08, 2021. doi:10.1001/jama.2021.15494

Source 59 – 259 vaccinated pregnant women from Israel

This MedRxiv preprint reports vaccinated women admitted for delivery during February to April 2021 at Hadassah Medical Center, Jerusalem (click here or source). It may overlap with source 19. Citation: Amihai Rottenstreich, Gila Zarbiv, Esther Oiknine-Djian, Olesya Vorontsov, Roy Zigron, Geffen Kleinstern, Dana G. Wolf, Shay Porat. Early versus late third trimester maternal SARS-CoV-2 BNT162b2 mRNA immunization maximizes transplacental antibody transfer and neonatal neutralizing antibody levels. medRxiv 2021.08.30.21262875; doi: https://doi.org/10.1101/2021.08.30.21262875

Update 9 September – source 58 updated

Update 8 September – source 67 added

Source 67 – 10,861 vaccinated pregnant women, & controls, from Israel

Data from Clalit Health Services, Tel Aviv (click here or source). Vaccinated between 20 December 2020 and 3 June 2021. Likely overlap with sources 24 and 65. The authors cite source 24, but their ref 16, to “an updated analysis of the same data over a longer period” is a letter reporting subgroups of source 24. Presumably an error. Citation: Dagan, N., Barda, N., Biron-Shental, T. et al. Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy. Nat Med (2021). https://doi.org/10.1038/s41591-021-01490-8

Update 2 September – source 66 added

Source 66 – case report from USA

The patient received the first injection of the Moderna mRNA1273 vaccine at 7 weeks gestation, and 13 days later developed acute-onset bruising and petechiae, and immune thrombocytopaenia (click here or study). Following steroid therapy she recovered. Apart from the gestational age, no pregnancy information was reported. From author affiliations she was probably cared for at the Cleveland Clinic, Ohio. Citation: Bennett C, Chambers LM, Son J, Goje O. Newly diagnosed immune thrombocytopenia in a pregnant patient after coronavirus disease 2019 vaccination. J Obstet Gynaecol Res. 2021 Aug 22. doi: 10.1111/jog.14978. Epub ahead of print. PMID: 34420249.

Update 27 August – source 65 added

Source 65 – 6,082 vaccinated pregnant women from Israel

Cared for by Clalit Health and vaccinated with the BNT162b2 vaccine between December 20, 2020 and May 24, 2021 (click here or source). Likely overlap with patients reported in source 24. Citation: Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, Hernán MA, Lipsitch M, Kohane I, Netzer D, Reis BY, Balicer RD. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med. 2021 Aug 25. doi: 10.1056/NEJMoa2110475. Epub ahead of print. PMID: 34432976..

Update 22 August – source 64 added

Source 64 – 39,985 vaccinated pregnant women in Canada

Update of source 53 (click here or source). Citation: COVID-19 Vaccination During Pregnancy in Ontario, Report #2: Covering December 14, 2020 to June 30, 2021 https://www.bornontario.ca/en/whats-happening/resources/Documents/BORN-COVID-19-Vaccination-During-Pregnancy-in-Ontario-Report-2—FINAL.pdf Accessed 22 August.

Update 19 August – source 63 added

Source 63 – 424 vaccinated pregnant women from USA

They all received an mRNA vaccine at New York University Langone Health prior to April 22, 2021 (click here or source). This centre has not reported vaccination data before, but the cases likely overlap with sources 26, 58 and 62. Citation: Megan E. Trostle MD , Meghana A. Limaye MD , Ms. Valeryia Avtushka, Jennifer L. Lighter MD , Christina A. Penfield MD MPH , Ashley S. Roman MD MPH , COVID-19 vaccination in pregnancy: early experience from a single institution, American Journal of Obstetrics & Gynecology MFM (2021), doi: https://doi.org/10.1016/j.ajogmf.2021.100464

Update 18 August – source 62 added

Source 62 – 17,525 pregnant, lactating or planning pregnancy people vaccinated.

Recruited to the University of Washington COVID-19 Vaccine in Pregnancy and Lactation Registry using chain-referral and snowball sampling (click here or source). 10, 790 got Pfizer-BioNTech BNT162b2 and 6,592 Moderna mRNA-1273. The authors admit likely overlap with Source 26. Citation: Kachikis A, Englund JA, Singleton M, Covelli I, Drake AL, Eckert LO. Short-term Reactions Among Pregnant and Lactating Individuals in the First Wave of the COVID-19 Vaccine Rollout. JAMA Netw Open. 2021;4(8):e2121310. doi:10.1001/jamanetworkopen.2021.21310

Update 16 August – source 61 added

Source 61 – nine pregnancies in Pfizer-BioNTech’s April FDA vaccine extension application

Among 2,260 participants aged 12-15 years, in the ongoing Study C4591001 randomised trial, nine pregnancies (3 BNT162b2, 6 placebo) were reported in Pfizer’s FDA application to extend emergency authorisation to this age group (click here or source). See p32. Citation: Pfizer-BioNTech COVID-19 Vaccine EUA Amendment Review Memorandum. April 9, 2021. https://www.fda.gov/media/148542/download. Accessed 16 August 2021

Update 14 August – sources 59 and 60 added

Source 60 – Two vaccinated women in Italy

Two healthcare workers had BNT162b2 mRNA vaccination during pregnancy at Fondazione IRCCS Policlinico San Matteo, Pavia (click here or source). Listed also as Study 788 here. Citation: Cassaniti I, Percivalle E, Zelini P, Nanhorngue KN, Parolo A, Bernardi V, Jorizzo G, Santer P, Perotti F, Spinillo A, Lilleri D, Baldanti F. Both SARS-CoV-2 infection and vaccination in pregnancy elicited neutralizing antibodies in pregnant women and newborns. Clin Microbiol Infect. 2021 Aug 6:S1198-743X(21)00442-0. doi: 10.1016/j.cmi.2021.08.004. Epub ahead of print. PMID: 34371204; PMCID: PMC8349424.

Source 59 – 50 vaccinated lactating women from USA

This MedXRiv preprint reports of 50 vaccinated lactating women selected from the COVID-19 Vaccine in Pregnancy and Lactation (COVIPAL) cohort study from December 2020 to June 2021 (click here or source). Two already had Covid. of the rest 27 women had the BNT162b2 vaccine and 21 mRNA-1237. The cohort comprises volunteers planning to deliver at University of California San Francisco Medical Center. Citation: Golan Y, Prahl M, Cassidy AG, Gay C, Wu AHB, Jigmeddagva U, Lin CY, Gonzalez VJ, Basilio E, Warrier L, Buarpung S, Li L, Asiodu IV, Ahituv N, Flaherman VJ, Gaw SL. COVID-19 mRNA Vaccination in Lactation: Assessment of adverse effects and transfer of anti-SARS-CoV2 antibodies from mother to child. medRxiv [Preprint]. 2021 Aug 3:2021.03.09.21253241. doi: 10.1101/2021.03.09.21253241. PMID: 34373861; PMCID: PMC8351783.

Update 13 August – sources 57 & 58 (HT Viki Male) added

Source 58 – 2,456 vaccinated pregnant people from the US

This ResearchSquare preprint reports 2,456 pregnant persons who received an mRNA COVID-19 vaccine preconception or prior to 20 weeks’ gestation, and enrolled in the v-safe COVID-19 Vaccine Pregnancy Registry 2020-21 (click here or source). This is a follow-up of women enrolled in the v-safe registry, and previously reported in source 26. Citation: Lauren Head Zauche, Bailey Wallace, Ashley N. Smoots, Christine K. Olson, Titilope Oduyebo, Shin Y. Kim, Emily E. Peterson, Jun Ju, Jennifer Beauregard, Allen J. Wilcox, Charles E. Rose, Dana Meaney-Delman, Sascha R. Ellington. Receipt of mRNA COVID-19 vaccines preconception and during pregnancy and risk of self-reported spontaneous abortions, CDC v-safe COVID-19 Vaccine Pregnancy Registry 2020-21. ResearchSquare preprint. https://doi.org/10.21203/rs.3.rs-798175/v1 Update 9 Sept. Peer reviewed citation: Zauche LH et al. Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion (letter). New Engl J Med. September 8, 2021 DOI: 10.1056/NEJMc2113891

Source 57 – 141 women vaccinated in pregnancy in UK

Of 1,328 pregnant women who gave birth at St George’s University Hospital, London, between 1 March and 4 July 2021, 141 had received at least one dose of vaccine (click here or source). There were no adverse effects. Citation: Blakeway H, Prasad S, Kalafat E, Heath PT, Ladhani SN, Le Doare K, Magee LA, O’brien P, Rezvani A, Dadelszen Pv, Khalil A, COVID-19 Vaccination During Pregnancy: Coverage and Safety, American Journal of Obstetrics and Gynecology (2021), doi: https://doi.org/10.1016/j.ajog.2021.08.007.

Update 12 August – source 56 added

Source 56 – no pregnancies in the UK series of VITT

Among 230 (170 definite, 50 probable) cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the Astra Zeneca, ChAdOx1 nCoV-19 vaccine, 119 were female, but none were reported to be pregnant (click here or source). Citation: Sue Pavord, Marie Scully, Beverley J. Hunt, William Lester, Catherine Bagot, Brian Craven, Alex Rampotas, Gareth Ambler, Mike Makris. Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. New Engl J Med. August 11, 2021 DOI: 10.1056/NEJMoa2109908

Update 8 August – source 55 added

Source 55- Case report of Pfizer-BioNTech vaccine from US

A 33-year-old doctor had the BNT162b2 SARS-CoV-2 vaccine at 29 & 32 weeks’ gestation, and delivered a healthy male infant with antibodies (click here or source). From author affiliations cared for at Jefferson Obstetrics and Gynecology, Charlottesville, Virginia. Citation: Mehaffey JH, Arnold M, Huffstetler E, Mehaffey RL, Quillian H, Mehaffey JH. Successful vertical transmission of SARS-CoV-2 antibodies after maternal vaccination. Birth. 2021 Aug 6. doi: 10.1111/birt.12582. Epub ahead of print. PMID: 34355820.

Update 2 August – source 54 added

Source 54 – Case of Cononavac in pregnancy from Turkey

A pregnant woman was vaccinated with Coronavac (Sinovac Life Science Co, Ltd, Beijing, China) at 28 and 32 weeks, and gave birth normally (click here or source). She was cared for at Memorial Bahçelievler Hospital, İstanbul. The authors claim this is the first case of antibody detection in cord blood after this vaccine. Citation: Soysal A, Bilazer C, Gönüllü E, Barın E, Çivilibal M. Cord blood antibody following maternal SARS-CoV-2 inactive vaccine (CoronaVac) administration during the pregnancy. Hum Vaccin Immunother. 2021 Jul 30:1-3. doi: 10.1080/21645515.2021.1947099. Epub ahead of print. PMID: 34325615.

Update 15 July – source 53 added. HT @DanielaDrandic

Source 53 – 30,892 vaccinated pregnant women in Canada

From Ontario (click here or source). “Cumulative incidence rates of pregnancy and birth outcomes among vaccinated individuals do not suggest any pattern of increased risk in these preliminary data.” Citation: COVID-19 Vaccination During Pregnancy in Ontario, Report #1: December 14, 2020 to May 31, 2021. https://www.bornontario.ca/en/whats-happening/resources/Documents/COVID-19-Vaccination-During-Pregnancy-in-Ontario-Report-1—FINAL.pdf Accessed 15 July.

Update 14 July – source 52 added

Source 52 – 3,698 vaccinated pregnant women in Scotland

3,698 pregnant women had been vaccinated in Scotland up to 31 May 2021 (click here or source). No outcome data but the following statement appears (p 31). “To date (13 July 2021), Public Health Scotland has not been notified of any serious pregnancy related adverse events following COVID-19 vaccination in pregnancy.” Citation: Public Health Scotland. COVID-19 Statistical Report As at 12 July 2021. Publication date: 14 July 2021. https://publichealthscotland.scot/media/8433/21-07-14-covid19-publication_report.pdf Accessed 14 July 2021

Update 13 July – source 51 added

Source 51 – 15,060 vaccinated pregnant women in Israel

In this cohort study pregnant women who received the Pfizer-BioNTech BNT162b2 mRNA vaccine had an adjusted hazard ratio for incident SARS-CoV-2 infection of 0.22 (95% CI, 0.11-0.43) compared with matched unvaccinated controls (click here or source). There were no severe adverse vaccine reactions. Data from Maccabi Healthcare Services, one of four heath funds in Israel, so no overlap with source 24 from a different fund. Possible overlap with sources 19, 39 and 49. Citation: Goldshtein I, Nevo D, Steinberg DM, et al. Association Between BNT162b2 Vaccination and Incidence of SARS-CoV-2 Infection in Pregnant Women. JAMA. Published online July 12, 2021. doi:10.1001/jama.2021.11035 Important

Update 9 July – source 50 added

Source 50 – 3 pregnant women in Turkish CoronaVac trial

Two were in the intervention group and one in the control, in this phase 3 trial of the CoronaVac, inactivated whole-virion SARS-CoV-2 vaccine, (Sinovac Life Sciences, Beijing, China) (click here or source). Citation: Mine Durusu Tanriover, Hamdi Levent Doğanay, Murat Akova, et al., and the CoronaVac Study Group. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. July 8, 2021. https://doi.org/10.1016/S0140-6736(21)01429-X

Update 7 July – sources 48 and 49 added

Source 49 – 539 vaccinated pregnant women and controls from Israel

539 pregnant women who had 2-doses of BNT162b2 vaccine between January-February 2021, and an age-matched unvaccinated control group (click here or source). The vaccinated women were recruited via social media. Citation: Bookstein Peretz S, Regev N, Novick L, Nachshol M, Goffer E, Ben-David A, Asraf K, Doolman R, Sapir E, Regev Yochay G, Yinon Y. Short-term outcome of pregnant women vaccinated by BNT162b2 mRNA COVID-19 vaccine. Ultrasound Obstet Gynecol. 2021 Jul 1. doi: 10.1002/uog.23729. Epub ahead of print. PMID: 34198360.

Source 48 – 16 vaccinated pregnant women from Poland

150 women had been vaccinated in pregnancy with BNT162b2 mRNA vaccine, and clinical details and cord serology are reported on 16 of them (click here or source). The pregnant women were all also medical doctors, and they gave birth at the Provincial Specialist Hospital in Olsztyn. Citation: Zdanowski W, Waśniewski T. Evaluation of SARS-CoV-2 Spike Protein Antibody Titers in Cord Blood after COVID-19 Vaccination during Pregnancy in Polish Healthcare Workers: Preliminary Results. Vaccines (Basel). 2021 Jun 19;9(6):675. doi: 10.3390/vaccines9060675. PMID: 34205434; PMCID: PMC8234119.

Update 1 July – source 47 added

Source 47 – one pregnant woman in Novavax trial

She was in the placebo group (click here or source) Citation: Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, Chadwick DR, Clark R, Cosgrove C, Galloway J, Goodman AL, Heer A, Higham A, Iyengar S, Jamal A, Jeanes C, Kalra PA, Kyriakidou C, McAuley DF, Meyrick A, Minassian AM, Minton J, Moore P, Munsoor I, Nicholls H, Osanlou O, Packham J, Pretswell CH, San Francisco Ramos A, Saralaya D, Sheridan RP, Smith R, Soiza RL, Swift PA, Thomson EC, Turner J, Viljoen ME, Albert G, Cho I, Dubovsky F, Glenn G, Rivers J, Robertson A, Smith K, Toback S; 2019nCoV-302 Study Group. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N Engl J Med. 2021 Jun 30. doi: 10.1056/NEJMoa2107659. Epub ahead of print. PMID: 34192426.

Update 26 June – source 46 added

Source 46 – 22,197 women vaccinated in pregnancy in USA

They amount to 16.3% of 135,968 pregnant women identified via CDC’s Vaccine Safety Datalink between December 14, 2020 and May 8, 2021 (click here or source). No pregnancy outcome data reported. Citation: Razzaghi H, Meghani M, Pingali C, Crane B, Naleway A, Weintraub E, Kenigsberg TA, Lamias MJ, Irving SA, Kauffman TL, Vesco KK, Daley MF, DeSilva M, Donahue J, Getahun D, Glenn S, Hambidge SJ, Jackson L, Lipkind HS, Nelson J, Zerbo O, Oduyebo T, Singleton JA, Patel SA. COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy – Eight Integrated Health Care Organizations, United States, December 14, 2020-May 8, 2021. MMWR Morb Mortal Wkly Rep. 2021 Jun 18;70(24):895-899. doi: 10.15585/mmwr.mm7024e2. PMID: 34138834.

Update 25 June – source 45 added

Source 45 – Post vaccination thromboses in the small pelvic veins; case report

A 50-year-old woman with a pulmonary embolus, and presumed vaccine-induced immune thrombotic thrombocytopenia, had multiple thromboses in the smaller veins of the pelvis (click here or source plus more pictures in the appendices here). She was not pregnant, and recovered. Citation: Guetl K, Gary T, Raggam RB, Schmid J, Wölfler A, Brodmann M. SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia treated with immunoglobulin and argatroban. Lancet. 2021 Jun 11;397(10293):e19. doi: 10.1016/S0140-6736(21)01238-1. Epub ahead of print. PMID: 34126043; PMCID: PMC8195494.

Update 14 June – sources 43 and 44 added

Source 44 – 38 vaccinated pregnant health-care workers

Twenty got Pfizer-BioNTech, and 18 Moderna (click here or source). Pregnancy-related events (gestational hypertension (1), threatened labor (1), miscarriage (1), premature delivery (1) from the Pfizer-BioNTech group and none from the Moderna group. Self-reported via SurveyMonkey. Citation: Kalyan Kadali RA, Janagama R, Peruru SR, Racherla S, Tirumala R, Madathala RR, Gajula V, Adverse effects of COVID-19 mRNA vaccines among pregnant women: A cross-sectional study on healthcare workers with detailed self-reported symptoms, American Journal of Obstetrics and Gynecology (2021), doi: https://doi.org/10.1016/j.ajog.2021.06.007.

Source 43 – Case report from Italy

A 42-year-old pregnant healthcare worker received the Comirnaty (Pfizer/BioNTech) mRNA vaccination at 31 and 34 weeks (click here or source). Cord blood antibodies were present. The hospital is not named but the authors came from Firenze, Italy. Citation: Riviello C, Pontello V. Maternal and neonatal SARS-CoV-2 antibodies assessment after mRNA maternal vaccination in the third trimester of pregnancy. Int J Gynaecol Obstet. 2021 Jun 11. doi: 10.1002/ijgo.13783. Epub ahead of print. PMID: 34115887.

Update 8 June – sources 40 to 42 added

Source 42 – 14 lactating women from Portugal

All vaccinated with Pfizer BNT162b2 mRNA (click here or source). From Centro Hospitalar Universitário Lisboa Central. Citation: Juliana Gonçalves, A. Margarida Juliano, Nádia Charepe, Marta Alenquer, Diogo Athayde, Filipe Ferreira, Margarida Archer, Maria João Amorim, Fátima Serrano, Helena Soares. Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination. medRxiv 2021.05.03.21256416; doi: https://doi.org/10.1101/2021.05.03.21256416

Source 41 – 6 lactating women from USA

Five vaccinated with BNT162b2 (Pfizer) and one with mRNA-1273 (Moderna) (click here or source). From University of California, San Francisco. Citation: Yarden Golan, Mary Prahl, Arianna Cassidy, Christine Y. Lin, Nadav Ahituv, Valerie J. Flaherman, Stephanie L. Gaw. COVID-19 mRNA vaccine is not detected in human milk. medRxiv 2021.03.05.21252998; doi: https://doi.org/10.1101/2021.03.05.21252998

Source 40 – 122 vaccinated women from USA

Eighty five had Pfizer-BioNTech, & 37 Moderna (click here or source). From Weill Cornell Medicine, New York. Citation: Malavika Prabhu, Elisabeth A. Murphy, Ashley C. Sukhu, Jim Yee, Sunidhi Singh, Dorothy Eng, Zhen Zhao, Laura E. Riley, Yawei J. Yang. Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates. bioRxiv 2021.04.05.438524; doi: https://doi.org/10.1101/2021.04.05.438524

Update 7 June – source 39 added

Source 39 – 86 vaccinated pregnant women from Israel

From eight Israeli hospitals (click here or source). Compared with 65 pregnant women who had had Covid – see study 714. Citation: Beharier O, Plitman Mayo R, Raz T, Nahum Sacks K, Schreiber L, Suissa-Cohen Y, Chen R, Gomez-Tolub R, Hadar E, Gabbay-Benziv R, Jaffe Moshkovich Y, Biron-Shental T, Shechter-Maor G, Farladansky-Gershnabel S, Yitzhak Sela H, Benyamini-Raischer H, Sela ND, Goldman-Wohl D, Shulman Z, Many A, Barr H, Yagel S, Neeman M, Kovo M. Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine. J Clin Invest. 2021 May 20:150319. doi: 10.1172/JCI150319. Epub ahead of print. PMID: 34014840.

Update 6 June – source 38 added

Source 38 – 47 vaccinated women undergoing IVF in Israel

Forty seven women underwent IVF and ICSI, both before and after BNT162b2 COVID-19 vaccination (click here or source). There were no major differences between the pre- and post-vaccination cycles. They were cared for at the Hadassah Hebrew-University Medical Center in Jerusalem. Citation: Myriam Safrai, Amihai Rottenstreich, Shmuel Herzberg, Tal Imbar, Benjamin Reubinoff, Assaf Ben-Meir. Stopping the misinformation: BNT162b2 COVID-19 vaccine has no negative effect on women’s fertility. medRxiv 2021.05.30.21258079; doi: https://doi.org/10.1101/2021.05.30.21258079

Update 3 June – sources 36 and 37 added

Source 37 – four pregnant & four breast-feeding women vaccinated

These authors report a convenience sample (overweight on health workers) of women who responded to an online survey in January 2021 (click here or source). 87/656 (13%) of non-pregnant, 4/216 (1.9%) of pregnant, and 4/122 (3.3%) of breast-feeding respondents had been vaccinated. Citation: Desmond Sutton, Mary D’Alton, Yijia Zhang, Ka Kahe, Ana Cepin, Dena Goffman, Anna Staniczenko, Hope Yates, Anna Burgansky, Jaclyn Coletta, Zev Williams, Cynthia Gyamfi-Bannerman, COVID-19 Vaccine Acceptance Among Pregnant, Breastfeeding and Non-pregnant Reproductive Aged Women, American Journal of Obstetrics & Gynecology MFM (2021), doi: https://doi.org/10.1016/j.ajogmf.2021.100403

Source 36 – interim report of S African Ad26.COV2.S vaccine study

This interim report (click here or source) of adverse thromboembolic events in the ongoing Sisonke study of the Ad26.COV2.S (Janssen) vaccine (NCT04838795) includes a a 38-year-old woman who had given birth to twins nine months before vaccination and presented with features of transient ischemic attack 8 days post vaccination. Citation: Simbarashe Takuva,Azwidhwi Takalani, Nigel Garrett, Ameena Goga, Jonny Peter, Vernon Louw, Jessica Opie, Barry Jacobson, Ian Sanne, Linda Gail‑Bekker, Glenda Gray. Thromboembolic Events in the South African Ad26.COV2.S Vaccine Study. NEJM. June 2, 2021 DOI: 10.1056/NEJMc2107920

Update 29 May – source 35 added

Source 35 – two pregnant and five breast-feeding women

The authors for this MedRxiv preprint report 15 women (two pregnant, five breast feeding) who received at least one dose of the BNT162B2 vaccine (click here or source). None of them showed any cross reactivity to human syncytin-1. Nor was any mRNA detected in breast milk. Citation: Citra NZ Mattar, Winston Koh, Yiqi Seow, Shawn Hoon, Aparna Venkatesh, Pradip Dashraath, Li Min Lim, Judith Ong, Rachel Lee, Nuryanti Johana, Julie SL Yeo, David Chong, Lay-Kok Tan, Jerry Chan, Mahesh Choolani, Paul Anantharajah Tambyah. Addressing anti-syncytin antibody levels, and fertility and breastfeeding concerns, following BNT162B2 COVID-19 mRNA vaccination. medRxiv 2021.05.23.21257686; doi: https://doi.org/10.1101/2021.05.23.21257686

Update 27 May – source 34 added

Source 34 – Ten pregnant women in Chinese vaccine (WIV04 and HB02) trial

In this interim analysis of a randomised trial (40,382 participants), conducted in six centres in the Middle East, of two SARS-Cov-2 vaccines (WIV04 and HB02) 5 pregnant women received the first dose of the WIV04 vaccine, 2 the HBO2 vaccine, and 3 placebo (click here or source). No pregnancy outcomes are reported. The vaccines were developed by the Wuhan Institute of Biological Products Co, Ltd, and the Beijing Institute of Biological Products Co, Ltd, both of which belong to the China National Biotec Group Company Limited. The trial centres were Sheikh Khalifa Medical City in Abu Dhabi and the Al Qarain Health Center in Sharjah, both in the United Arab Emirates (UAE); the Salmanyia Medical Complex in Bahrain; Vacsera Medical Center and Katameya Medical Center in Egypt; and Prince Hamza Hospital in Jordan. Citation: Al Kaabi N, Zhang Y, Xia S, et al. Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial. JAMA. Published online May 26, 2021. doi:10.1001/jama.2021.8565

Update 26 May – source 33 added

Source 33 – no pregnancies among three cases of Astra Zeneca VITT

There were no pregnant women among three cases (two women of childbearing age) of ischemic stroke associated with vaccine-induced immune thrombotic thrombocytopaenia (VITT) after the Astra Zeneca ChAdOx1 nCoV-19 vaccine (click here or source). See also Source 27. These case are probably not included in Source 27. Citation: Al-Mayhani T, Saber S, Stubbs MJ, et alIschaemic stroke as a presenting feature of ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopaeniaJournal of Neurology, Neurosurgery & Psychiatry Published Online First: 25 May 2021. doi: 10.1136/jnnp-2021-326984

Update 24 May – source 32 added

Source 32 – Birth outcomes for 140 women vaccinated in pregnancy

MedRxiv preprint. Cases collected by the Mayo clinic (click here or source). Citation: Regan N. Theiler, Myra Wick, Ramila Mehta, Amy Weaver, Abinash Virk, Melanie Swift. Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy. medRxiv 2021.05.17.21257337; doi: https://doi.org/10.1101/2021.05.17.21257337

Update 15 May – sources 30 and 31 added

Source 31 – USA. 84 vaccinated pregnant women and controls

From author affiliations identified through Feinberg School of Medicine, and the Ann and Robert H. Lurie Children’s Hospital of Chicago, Illinois (click here or source). Citation: Shanes ED, Otero S, Mithal LB, Mupanomunda CA, Miller ES, Goldstein JA. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination in Pregnancy: Measures of Immunity and Placental Histopathology. Obstet Gynecol. 2021 May 11. doi: 10.1097/AOG.0000000000004457. Epub ahead of print. PMID: 33975329.

Source 30 – USA. 30 pregnant and 16 lactating vaccinated women

Identified through the Beth Israel Deaconess Medical Center, Boston, Massachusetts (click here or source). Citation: Collier AY, McMahan K, Yu J, Tostanoski LH, Aguayo R, Ansel J, Chandrashekar A, Patel S, Apraku Bondzie E, Sellers D, Barrett J, Sanborn O, Wan H, Chang A, Anioke T, Nkolola J, Bradshaw C, Jacob-Dolan C, Feldman J, Gebre M, Borducchi EN, Liu J, Schmidt AG, Suscovich T, Linde C, Alter G, Hacker MR, Barouch DH. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA. 2021 May 13. doi: 10.1001/jama.2021.7563. Epub ahead of print. PMID: 33983379.

Update 6 May – source 29 added

Source 29 – five pregnancies in Novavax vaccine trial in South Africa

Two women became pregnant after their first dose in the vaccine arm and three in the control, in this trial of the Novavax NVX-CoV2373 vaccine (click here or source). Citation: Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L, Lalloo U, Masilela MSL, Moodley D, Hanley S, Fouche L, Louw C, Tameris M, Singh N, Goga A, Dheda K, Grobbelaar C, Kruger G, Carrim-Ganey N, Baillie V, de Oliveira T, Lombard Koen A, Lombaard JJ, Mngqibisa R, Bhorat AE, Benadé G, Lalloo N, Pitsi A, Vollgraaff PL, Luabeya A, Esmail A, Petrick FG, Oommen-Jose A, Foulkes S, Ahmed K, Thombrayil A, Fries L, Cloney-Clark S, Zhu M, Bennett C, Albert G, Faust E, Plested JS, Robertson A, Neal S, Cho I, Glenn GM, Dubovsky F, Madhi SA; 2019nCoV-501 Study Group. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 May 5. doi: 10.1056/NEJMoa2103055. Epub ahead of print. PMID: 33951374.

Update 5 May – source 28 added

Source 28 – 10 vaccinated & lactating women from Singapore

This MedRxiv preprint reports ten women who had received the Biontech BNT162b2 vaccine while lactating (click here or source). Citation: Jia Ming Low, Yue Gu, Melissa Shu Feng Ng, Zubair Amin, Le Ye Lee, Yvonne Peng Mei Ng, Bhuvaneshwari D/O Shunmuganathan, Yuxi Niu, Rashi Gupta, Paul Anantharajah Tambyah, Paul A MacAry, Liang Wei Wang, Youjia Zhong BNT162b2 vaccination induces SARS-CoV-2 specific antibody secretion into human milk with minimal transfer of vaccine mRNA medRxiv 2021.04.27.21256151; doi: https://doi.org/10.1101/2021.04.27.21256151

Update 2 May – source 27 added

Source 27 – no pregnancies among 21 women with thrombotic thrombocytopenia after Oxford/AZ or Janssen/J&J vaccines

Of 11 cases (including nine women age 22-49) of thrombotic thrombocytopenia after the Oxford/Astra Zeneca ChAdOx1 nCov-19 vaccine, none were currently or recently pregnant (click here or source). Citation: Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med. 2021 Apr 9. doi: 10.1056/NEJMoa2104840. Epub ahead of print. PMID: 33835769. Of 12 cases (all women under age 60) following the Janssen/Johnson & Johnson Ad26.COV2.S vaccine, none were currently or recently pregnant (click here or source). Citation: See I, Su JR, Lale A, et al. US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021. JAMA. Published online April 30, 2021. doi:10.1001/jama.2021.7517

Update 22 April – source 26 added

Source 26 – 35,691 vaccinated pregnant people from USA

The first peer reviewed publication with pregnancy outcome data from the v-safe and VAERS vaccine surveillance systems (click here or source). Citation: Tom T. Shimabukuro, Shin Y. Kim, Tanya R. Myers, Pedro L. Moro, Titilope Oduyebo, Lakshmi Panagiotakopoulos, Paige L. Marquez, Christine K. Olson, Ruiling Liu, Karen T. Chang, Sascha R. Ellington, Veronica K. Burkel, Ashley N. Smoots, Caitlin J. Green, Charles Licata, Bicheng C. Zhang, Meghna limchandani, Adamma Mba-Jonas, Stacey W. Martin, Julianne M. Gee, Dana M. Meaney-Delman, for the CDC v-safe COVID-19 Pregnancy Registry Team. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. New Engl J Med April 21, 2021 DOI: 10.1056/NEJMoa2104983 Important

Update 18 April – source 25 added

Source 25 – 131 reproductive-age vaccine recipients from USA

Further immunological studies from the same 84 pregnant, 31 lactating, and 16 non-pregnant women who received either the Pfizer/BioNTech or Moderna mRNA vaccines reported in source 15 (click here or source). Citation: Atyeo C, DeRiso EA, Davis C, Bordt EA, DeGuzman RM, Shook LL, Yonker LM, Fasano A, Akinwunmi B, Lauffenburger DA, Elovitz MA, Gray KJ, Edlow AG, Alter G. COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women. bioRxiv [Preprint]. 2021 Apr 5:2021.04.04.438404. doi: 10.1101/2021.04.04.438404. PMID: 33851165; PMCID: PMC8043455.

Update 16 April – source 24 added

Source 24 – 1,508 vaccinated pregnant women from Israel

There were 1,508 vaccinated pregnant women in this real world study of 596,618 people who received the BNT162b2 mRNA vaccine between December 20, 2020, and to February 1, 2021, and an equal number of matched unvaccinated controls (click here or study). Data from Clalit Health Services, insurer of about half the Israeli population. Citation: Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, Hernán MA, Lipsitch M, Reis B, Balicer RD. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med. 2021 Apr 15;384(15):1412-1423. doi: 10.1056/NEJMoa2101765. Epub 2021 Feb 24. PMID: 33626250; PMCID: PMC7944975.

Update 15 April – sources 22 and 23 added

Source 23 – Follicular function in nine vaccinated women from Israel

The authors of this MedRxiv preprint report follicular function in nine women vaccinated with the BNT162b2 mRNA vaccine (click here or source). They were cared for at Hadassah-Hebrew University Medical Center, in Jerusalem. Citation: Yaakov Bentov, Ofer Beharier, Arbel Moav-Zafrir, Maor Kabessa, Miri Godin, Caryn S. Greenfield, Mali Ketzinel-Gilad, Efrat Esh Broder, Hananel E. G. Holzer, Dana Wolf, Esther Oiknine-Djian, Iyad Barghouti, Debra Goldman-Wohl, Simcha Yagel, Asnat Walfisch, Anat Hersko Klement Ovarian follicular function is not altered by SARS-Cov-2 infection or BNT162b2 mRNA Covid-19 vaccination. medRxiv 2021.04.09.21255195; doi: https://doi.org/10.1101/2021.04.09.21255195

Source 22 – Twenty two vaccinated & breast-feeding women from USA

The authors of this MedRxiv preprint report SARS-CoV-2 IgA and IgG levels in the milk of 22 lactating women who had received the SARS-CoV-2 mRNA vaccine (Pfizer/BioNtech or Moderna) (click here or source). They were cared for at Shands Hospital, in Florida. Citation: Vivian Valcarce, Lauren S. Stafford, Josef Neu, Nicole Cacho, Leslie Parker, Martina Mueller, David J Burchfield, Nan Li, Joseph Larkin III Detection of SARS-CoV-2 specific IgA in the human milk of COVID-19 vaccinated, lactating health care workers medRxiv 2021.04.02.21254642; doi: https://doi.org/10.1101/2021.04.02.21254642

Update 14 April – source 15 updated

Update 13 April – source 22 added

Source 22 – 84 vaccinated breast feeding women from Israel

Women who had received 2 doses of the Pfizer-BioNTech vaccine and were breastfeeding (click here or source). There were no serious adverse events, and antibodies were detected in breast milk. Citation: Perl SH, Uzan-Yulzari A, Klainer H, et al. SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women. JAMA. Published online April 12, 2021. doi:10.1001/jama.2021.5782

Update 7 April – source 7 update.

Update 6 April– source 21 added

Source 21 – 69,337 women in v-safe were pregnant. 3,953 in v-safe vaccine register

As of March 29th, 69,337 v-safe participants indicated they were pregnant at the time they received COVID-19 vaccination. 3,953 women have also been enrolled in the v-safe COVID-19 Vaccine Pregnancy Registry. Click here for details. The data up to February 16 (published 1 March) (click here or source) includes 30,494 pregnancies (16,039 Pfizer/Biontech and 14,455 Moderna). Adverse events include 29 miscarriages and one stillbirth.

Update 2 April source 20 added

Source 20 – 27 vaccinated women from USA

Twenty seven vaccinated women who delivered at Prentice Women’s Hospital in Chicago, (January-March 2021) (click here or source). 25/28 (one set of twins) infants had positive cord IgG. The exact vaccine is not reported but the authors note that at the time Pfizer/BioNTech and Moderna/NIH were available. Citation: MITHAL LB, OTERO S, SHANES ED, GOLDSTEIN JA, MILLER ES, Cord Blood Antibodies following Maternal COVID-19 Vaccination During Pregnancy, American Journal of Obstetrics and Gynecology (2021), doi: https://doi.org/10.1016/j.ajog.2021.03.035.

Update 17 March – source 19 added

Source 19 – 20 vaccinated women from Israel

This MedRxiv preprint reports 20 pregnant women who received two doses of the Pfizer/BioNTech vaccine in late pregnancy in February 2021 (click here or 2021.03.11.21253352v1.full). All women efficiently transferred antibodies to the fetus. They were cared for at Hadassah Medical Center in Jerusalem. Citation: Amihai Rottenstreich, Gila Zarbiv, Esther Oiknine-Djian, Roy Zigron, Dana G. Wolf, Shay Porat. Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination medRxiv 2021.03.11.21253352; doi: https://doi.org/10.1101/2021.03.11.21253352 Update 10 September. Peer reviewed citation: Rottenstreich A, Zarbiv G, Oiknine-Djian E, Zigron R, Wolf DG, Porat S. Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination. Clin Infect Dis. 2021 Apr 3:ciab266. doi: 10.1093/cid/ciab266. Epub ahead of print. PMID: 33822014; PMCID: PMC8083549.

Update 10 March – sources 15 to 18 added

Source 18 – 6 postnatal vaccinated women in USA

The MedRxiv preprint describes six lactating women who received both doses of the Pfizer-BioNTech or Moderna vaccine between December 2020 and January 2021 (click here or 2021.02.23.21252328v1.full). They all developed IgA and IgG antibodies in breast milk within seven says. They were cared for at Providence Portland Medical Center, Oregon. Citation: Jill K. Baird, Shawn M. Jensen, Walter J. Urba, Bernard A. Fox, Jason R. Baird SARS-CoV-2 antibodies detected in human breast milk post-vaccination. medRxiv 2021.02.23.21252328; doi: https://doi.org/10.1101/2021.02.23.21252328

Source 17 – case report of 3rd trimester vaccination from USA

A 34-year-old woman received the Pfizer-BioNTech, mRNA vaccine at 32 weeks (click here or 13224_2021_Article_1436). The birth was uncomplicated and the baby had cord blood antibodies. The hospital is unnamed, but the authors were from University of Minnesota, Minneapolis. This is the first peer reviewed report of vaccination in pregnancy. Citation: Gill L, Jones CW. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies in Neonatal Cord Blood After Vaccination in Pregnancy. Obstet Gynecol. 2021 Mar 8. doi: 10.1097/AOG.0000000000004367. Epub ahead of print. PMID: 33684922.

Source 16 – 10 nursing mothers vaccinated in Israel

This MedRxiv preprint describes ten nursing mothers who received the Pfizer-BioNTech mRNA vaccine (click here or 2021.03.06.21252603v1.full). Clinical details and exact vaccine timings in supplementary table 1 (click here or media-1) From author affiliations the women were probably cared for at Lis Maternity & Women’s Hospital, Tel Aviv. Citation: Michal Rosenberg Friedman, Aya Kigel, Yael Bahar, Yariv Yogev, Yael Dror, Ronit lubetzky, Ariel Many, Yariv Wine BNT162b2 COVID-19 mRNA vaccine elicits a rapid and synchronized antibody response in blood and milk of breastfeeding women medRxiv 2021.03.06.21252603; doi: https://doi.org/10.1101/2021.03.06.21252603

Source 15 – 131 reproductive-age vaccine recipients from USA

This MedRxiv preprint includes 84 pregnant, 31 lactating, and 16 non-pregnant women who received either the Pfizer/BioNTech or Moderna mRNA vaccines (click here or 2021.03.07.21253094v1.full). From author affiliations the hospitals were probably Massachusetts General Hospital, and Brigham and Women’s Hospital, both in Boston, Massachussetts. Citation: Kathryn J Gray, Evan A Bordt, Caroline Atyeo, Elizabeth Deriso, Babatunde Akinwunmi, Nicola Young, Aranxta Medina Baez, Lydia L Shook, Dana Cvrk, Kaitlyn James, Rose De Guzman, Sara Brigida, Khady Diouf, Ilona Goldfarb, Lisa M Bebell, Lael M Yonker, Alessio Fasano, Sayed A Rabi, Michal A Elovitz, Galit Alter, Andrea G Edlow COVID-19 vaccine response in pregnant and lactating women: a cohort study medRxiv 2021.03.07.21253094; doi: https://doi.org/10.1101/2021.03.07.21253094 Update 14 March. For peer reviewed publication (click here or source). Citation: Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, Medina Baez A, Shook LL, Cvrk D, James K, De Guzman R, Brigida S, Diouf K, Goldfarb I, Bebell LM, Yonker LM, Fasano A, Rabi SA, Elovitz MA, Alter G, Edlow AG, COVID-19 vaccine response in pregnant and lactating women: a cohort study, American Journal of Obstetrics and Gynecology (2021), doi: https://doi.org/10.1016/j.ajog.2021.03.023.

Update 6 March – sources 13 and 14 added. (We do not plan to update these unless the links change).

Source 14 – UK Yellow card reports for COVID-19 vaccine AstraZeneca

Available here. The latest (25 Feb) report (click here or COVID-19_AstraZeneca_Vaccine_Analysis_Print) included 1 vaccine exposure before pregnancy, 30 during pregnancy and 9 postnatal (p 23). The adverse events included 4 spontaneous abortions, 1 or 2 preterm births, and ten cases of morning sickness (p 41). This was out of 42,917 reports, of 157,637 reactions, of which 244 were fatal. Readers should note that “Conclusions on the safety and risks of the vaccines cannot be made on the data shown in the Print alone” and “The overall safety experience with both vaccines is so far as expected from the clinical trials.”  https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/966183/COVID-19_AstraZeneca_Vaccine_Analysis_Print.pdf Accessed 6 March (Not updated unless links change)

Source 13 – UK Yellow Card reports for COVID-19 mRNA Pfizer- BioNTech vaccine

Available here. The latest (4th March) report (click here or COVID-19_mRNA_Pfizer-_BioNTech_Vaccine_Analysis_Print__2_) included 1 vaccine exposure before pregnancy, 37 during pregnancy and 9 postnatal (p 24). The adverse events included 16 spontaneous abortions, 2 or 3 preterm births, and four cases of morning sickness (p 42). This was out of 29,715 reports, of 85,179 reactions, of which 212 were fatal. Readers should note that “Conclusions on the safety and risks of the vaccines cannot be made on the data shown in the Print alone” and “The overall safety experience with both vaccines is so far as expected from the clinical trials.” https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/966631/COVID-19_mRNA_Pfizer-_BioNTech_Vaccine_Analysis_Print__2_.pdf Accessed 6 March. (Not updated unless links change)

Update 28 Feb – sources 11 and 12 added

Source 12 – Janssen register trial of Ad26.COV2.S in pregnancy

Janssen have registered an RCT of the vaccine Ad26.COV2.S in pregnant women (click here). Planned sample size 824. Anticipated primary completion date January 16, 2023

Source 11 – Pfizer/BioNTech register trial of BNT162b2 in pregnancy

Pfizer/BioNTech have registered an RCT of the vaccine BNT162b2 in pregnant women (click here). Planned sample size 4,000. Estimated primary completion date January 8, 2023

Update 24 Feb – source 10 added

Source 10 – Janssen Ad26.COV2.S Vaccine FDA briefing document

See p 52 for pregnancy data (click here or VRBPAC-02.26.21-Meeting-Briefing-Document-FDA). “Eight pregnancies were reported through January 22, 2021 (4 vaccine, 4 placebo). In 7 participants (3 vaccine, 4 placebo) vaccination was within 30 days after LMP, and in 1 vaccine recipient vaccination was prior to LMP. Unsolicited AEs related to pregnancy include spontaneous abortion (1 vaccine, 0 placebo), incomplete abortion (0 vaccine, 1 placebo), elective abortion (0 vaccine, 2 placebo) and ectopic pregnancy (1 vaccine, 0 placebo). Among participants in the vaccine group, two pregnancies are ongoing with outcomes unknown at this time.” Note: Janssen is a subsidiary of Johnson & Johnson, and the Ad26.COV2.S vaccine is usually referred to in the press as the “Johnson & Johnson vaccine”. Citation: Vaccines and Related Biological Products Advisory Committee Meeting. February 26, 2021. FDA Briefing Document. Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. Accessed 24 Feb 2021 https://www.fda.gov/media/146217/download

Update 21 Feb – Source 9 added – special HT Keelin O’Donogue. One out of 31,000 vaccinations!

Source 9 – one pregnant woman tested positive following vaccination

This preprint reports 31,069 people who received at least one dose of a COVID-19 vaccine via the Mayo Clinic health system, in Arizona, Florida, Minnesota, or Wisconsin, between December 1st 2020 and February 8th 2021. Of the 263 who subsequently received a positive PCR test, one (0.4%) was pregnant (table 3) (click here or Pawlowski pre print). In a propensity matched cohort of 2,630 unvaccinated individuals who also tested positive, seven (0.3%) were pregnant. Citation: Colin Pawlowski, Patrick Lenehan, Arjun Puranik, Vineet Agarwal, AJ Venkatakrishnan, Michiel J.M. Niesen, John C. O’Horo, Andrew D. Badley, John Halamka, Venky Soundararajan. FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. medRxiv 2021.02.15.21251623; doi: https://doi.org/10.1101/2021.02.15.21251623&nbsp;

Update 20 Feb – Source 8 added

Source 8 – 15,131 post vaccine pregnancies reported to V-safe

Up to 20 January 8,633 pregnancies related to, or following, the Pfizer-BioNTech vaccine and 6,498 after the Moderna vaccine had been self-reported to the CDC using the V-safe vaccine tracker (click here or 06-COVID-Shimabukuro). Over the same period nearly 22m people had received at least one vaccine dose, and 2M had registered with the V-safe vaccine tracker.  As of January 22nd, 227 pregnancies had also been enrolled in the V-safe pregnancy registry. Citation: Advisory Committee on Immunization Practices (ACIP): COVID-19 vaccine Safety update—January 2021 (slide deck)

Update 6 Feb – source 7 added

Source 7 – IgG in cord blood post SARS-CoV-2 vaccine

This Medxiv preprint reports detection of anti-SARS-CoV-2 IgG in a baby whose mother had received the Moderna mRNA COVID-19 vaccine three weeks prior to birth (click here or 2021.02.03.21250579v1.full). The baby was healthy, with normal newborn nursery course and subsequent well-infant evaluation. The hospital is unnamed but the authors were affiliated with Charles E. Schmidt College of Medicine, Boca Raton, Florida. Citation: Paul D Gilbert, Chad A Rudnick. Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination. medRxiv 2021.02.03.21250579; doi: https://doi.org/10.1101/2021.02.03.21250579 Update 7 April. Peer reviewed paper published in BMC Pediatrics (click here or source). Citation: Paul G, Chad R. Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination – a case report. BMC Pediatr. 2021 Mar 22;21(1):138. doi: 10.1186/s12887-021-02618-y. PMID: 33752624; PMCID: PMC7982334.

Update 25 Jan – source 6 added

Source 6 – Astra Zeneca/Oxford. Safety & Efficacy report, Lancet

The supplementary appendix of the interim safety and efficacy report of four trials of the Astra Zeneca/Oxford (ChAdOx1 nCoV-19) vaccine reports one spontaneous abortion in the intervention group and one in the control group. For main paper (click here or PIIS0140673620326611) appendix (here or mmc1). These cases are presumably included in Source 3. Citation: Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O’Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8. Erratum in: Lancet. 2021 Jan 9;397(10269):98. PMID: 33306989; PMCID: PMC7723445.

Update 18 Jan – source 5 added

Source 5 – BioNTech/Pfizer. Safety and Efficacy report, NEJM

The Safety and Efficacy report of the phase 2/3 placebo controlled trial of the BioNTech/Pfizer (BNT162b2 mRNA) Covid-19 Vaccine (click here or nejmoa2034577) includes four pregnancies in the vaccine group and five in controls. These will overlap with those in studies 1 and 4Citation; Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Türeci Ö, Nell H, Schaefer A, Ünal S, Tresnan DB, Mather S, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10. PMID: 33301246; PMCID: PMC7745181.

Update 15 Jan – source 4 added

Source 4 – Comirnarty. EMA asessment report

See p 109 for pregnancy data (click here or comirnaty-epar-public-assessment-report_en). Comirnarty is the EU name for the BioNTech/Pfizer vaccine. The data therefore likely overlap with Source 1. Citation: European Medicines Agency. 21 December 2020. EMA/707383/2020. Committee for Medicinal Products for Human Use (CHMP). Assessment report. Comirnaty. Common name: COVID-19 mRNA vaccine (nucleoside-modified) Procedure No. EMEA/H/C/005735/0000. Accessed 14 January 2021. https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf&nbsp;

Update 14 Jan – Sources 1-3 added

Source 3 – Astra Zeneca/Oxford. MHRA public assessment report

See p 48 onward for pregnancy data (click here or UKPAR_COVID_19_Vaccine_AstraZeneca_05.01.2021). Citation: Medicines and Healthcare products Regulatory Agency. Public Assessment Report. Authorisation for Temporary Supply. COVID-19 Vaccine AstraZeneca, solution for injection in multidose container COVID-19 Vaccine (ChAdOx1-S [recombinant]). Department of Health and Social Care (DHSC) AstraZeneca AB. Accessed January 14 2021. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/949772/UKPAR_COVID_19_Vaccine_AstraZeneca_05.01.2021.pdf&nbsp;

Source 2 – Moderna. FDA briefing document

See p 44 onward for pregnancy data (click here or VRBPAC-12.17.20-Meeting-Briefing-Document-FDA_0). Citation: U.S. Food and Drug Administration. Vaccines and Related
Biological Products Advisory Committee meeting—December 17, 2020—FDA briefing document—Moderna COVID-19 vaccine. Accessed January 14, 2021. https://www.fda.gov/media/144434/download

Source 1 – BioNTech/Pfizer. FDA briefing document

See p 42 onwards for pregnancy data (click here or VRBPAC-12.10.20-Meeting-Briefing-Document-FDA). Citation: U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee Meeting, December 10, 2020. FDA Briefing Document. Pfizer-BioNTech COVID-19 Vaccine. Accessed January 14 2021. https://www.fda.gov/media/144245/download&nbsp;

Jim Thornton

Cock and balls

December 27, 2020

Mr & Mrs Andrews, and Thomas Gainsborough’s sexual innuendo

Although they had commissioned it, the Andrews’s disliked this painting so much that they never let Gainsborough finish it, and hid it away for nearly 200 years. Now in the National Gallery, it is recognised as the unquestioned masterpiece of Thomas Gainsborough’s early years.  

Part of its fame comes from its mention in “Civilisation”, Kenneth Clark’s book and BBC series, and later in “Ways of Seeing”, John Berger’s critique of Clark (click here). Clark, and the general public, loved the romantic landscape. Berger argued that the painting was an arrogant statement of wealth and privilege. Both were correct.

Thomas Gainsborough was living hand to mouth when he painted it – his father, John Gainsborough, had gone bankrupt – and he found it hard to remain deferential. This couple from his home of Sudbury – Thomas had been to school with Robert Andrews – were inheritors of “new money”. The marriage linked the fortunes of Mr Andrews’ father, also Robert, with that of his neighbour William Carter. Carter and the older Mr Andrews owned equal shares in Auberies, the estate pictured in the painting. Frances, the future Mrs Andrews, was Carter’s daughter, and her mother, Carter’s wife, the daughter of John Gainsborough’s principle creditor. Thomas was commissioned to celebrate the marriage and inheritance. 

Gainsborough considered himself primarily a landscape painter, and although the composition, with the figures off-centre, revealing so much landscape, was unusual for this sort of dynastic art – one reason it is so popular today – it is unlikely that this caused the ruction. Robert was surely happy to show off his modern farming techniques. Gainsborough also catches Frances’ disdainful expression, perhaps the lowly painter was rather over familiar, but there was a bigger reason for the falling out. Look closely at Robert’s waist1

At Robert’s belt, a bag for his shot and powder hangs – the shot in the left section, the powder in the tube with the knot in it on the right. This is what Robert’s muzzle loading flintlock needs to fire. Now whatever does the bag look like? Yes, its shape unmistakeably echoes male genitalia, while its form and proximity to the gun demonstrates explosive purpose. It is placed decidedly beside the crotch, so we may be being led to understand that Robert is remarkably well hung. However, on the left, above the tower of what is possibly Long Melford Church, dark clouds are gathering, and in the enclosure below, more or less where a swimming pool is now, and set on the same horizontal line as Robert’s significant powder-and-shot bag, are a pair of trapped donkeys. Did Gainsborough see his patrons as trapped donkeys?

Or the unfinished space on Frances’s lap. Was it intended to add a baby, a pet dog, or what?

The empty space is more or less egg shaped […] in her right hand an apparently meaningless furry or feathery extension, nearly as long as her lower arm, emerges from the partially expressed object on her lap. The drily painted beginnings of a small oval, merely a swish or two of the brush, runs over thin grey under-drawing which extends down to a dangling knob-shape. It is unquestionably there, in plain sight. This is not a pet cat, or a lap-dog, or a baby, but a dead cock pheasant – or it was going to be. Had Gainsborough completed it, the pheasant’s head and neck would rhyme exactly, and rather too clearly, with the limp game bag at Robert’s waist and the flabby glove in his hand. As it is, as Gainsborough has left it, Frances Andrews has a drawing of a penis on her skirt.

We can only guess what Frances said when she saw the painting. But we know the result. 

Jim Thornton

  1. None of this was worked out by me. Most of the facts, and both quotations, are from Gainsborough, a Portrait by James Hamilton. Weidenfeld & Nicholson, London, 2017.

Birth carers lost to Covid-19

December 13, 2020

Looking after mothers and babies during childbirth never stops – nights, weekends, holidays, the lights in the labour and neonatal wards are always on – and it didn’t stop for Covid.  Midwives, obstetric and neonatal nurses, neonatologists, anaesthetists, sonographers, cleaners, porters, auxiliaries, doulas, obstetricians, and many others, carried on as usual. A few paid with their lives.

Some caught Covid-19 in the line of duty, some elsewhere; I’ve made no attempt to separate them. Listed by month of death. Email Jim Thornton for those missed. Thank you Shakila Thangaratinam and Tara Pauly for initial encouragement and for alerting me to some names. 

There seem to be more OBGYN’s than midwives, which is implausible. The explanation is probably that some countries don’t use the term midwife, and that the internet is biased towards recording deaths of doctors before other health professions. 

Some resources used – Venezuela (click here), Italy (click here), Russia (click here), UK/BMJ (click here), US physicians (click here), Iran (click here), Medscape (click here), New York State Nurses Association (click here), Lancet (click here).

I will update.

March 2021 – Jim Dornan added

March 2021 

Jim Dornan age 73, OBGYN, Belfast, Northern Ireland. Death announced on 15 March (click here).  

January 11 update – Jose Jimenez, Gregory Michael, Unnamed midwife from Whittingdon, Adaín Landeros, Tomás Hernández Quijano, Jaime Hernández Rodríguez, Georgi Hubchev, José Alfredo Jiménez Turrubiates, Duško Kljakić, Halil Yucel Kutun, Katia Kohler, Mark Laser, and Biljana Natic ​​Ljumovic added. Details below.

January 2021

An unnamed midwife “originally from Zimbabwe” is reported to have died from Covid-19 at the Whittingdon Hospital in London in early January (click here).

Gregory Michael, age 56, OBGYN, Miami Beach, Florida on 3 January (click here). Cause thrombocytopaenia, two weeks after receiving the BioNTech/Pfizer Covid vaccine. The relation between the two events is under investigation.

December

 

November

Joel Antonio Contreras Gámez, age 87, OBGYN, Táchira, Venezuela, on 24 November (click here).

Liliana Somogy, OBGYN, Carabobo, Venezuela, on 19 November (click here). 

Pierantonio Meroni, age 83, OBGYN from Como, Italy, on 17 November (click here or here).

Héctor Enrique Torrealba Rodríguez, age 68, OBGYN, Carabobo, Venezuela, on 12 November (click here).

Adaín Octavio Girón Landeros, age 42, OBGYN, Hospital General de Zacatecas, Zacatecas, Mexico, on 12 November (click here).

October

Carlos Fayanás, age 73, OBGYN, Juncal Sanatorium in Temperley, Lomas de Zamora, Argentina, on 22 October (click here). 

Georgi Hubchev, age 66, OBGYN, University Hospital “Virgin Mary” Burgas, Bulgaria, on 17 October (click here).

Jose Inés Alcántara Jimenez, age about 64, OBGYN, Hospital General Iguala, Iguala, Guerrero, Mexico on 12 Octobe (click here).

Rafael Colmenares, OBGYN, Trujillo, Venezuela, on 1st October (click here).

Nikolay Vasechko, age 59, a doctor in diagnostic ultrasound in Dobrinsky Regional Hospital, Lipetsk, Russia, in October (click here). 

Jagadish Rai, age 70, OBGYN, Raju Clinic, BC Road, Bantwal, India, in October (click here). 

September 

Tatyana Babaytseva, age 53, ultrasound doctor, Uryupinsk District Hospital, Volgograd, Russia, in September (click here).

Pedro Sánchez, age 65, Distrito Capital, Venezuela, on 21 September (click here).

Freddy Lacroix, OBGYN, Carabobo, Venezuela, on 20 September (click here).

Adeline Fagan, age 28, trainee OBGYN, Houston, Texas, on 19 September (click here).

Ana Mercedes Flores, OBGYN, Maternidad del Sur, Carabobo, Venezuela, on 13 September (click here).

Elio José Margiotta Figueroa, age 60, OBGYN, Nueva Esparta, Venezuela, on 7 September (click here).

Manuela Fernández Lanz, age 60, OBGYN, Bolívar, Venezuela, on 3 September (click here).

August

Pedro Luis Cedeño, age 56, OBGYN, on 30 August (click here).

Andrés del Orbe, OBGYN, Táchira, Venezuela on 30 August (click here).

Julia Morales, OBGYN, Trujillo, Venezuela, on 28 August (click here).

Franklin Urdaneta, OBGYN, Zulia, Venzuela, on 24 August (click here). 

Junny Macabril, OBGYN, Bolivar, Venezuela, on 24 August (click here).

Kathlynne Abat-Senen, age 43, neonatologist from Manila, Philippines, On 23 August (click here). 

Dalia Gabriela Sosa Atondo, age 28, OBGYN, Culiacán, Mexico, on 21 August (click here or here). She was pregnant. Her baby survived. 

Jesús García, OB/GYN, Hospital Materno Infantil “Dr Pastor Oropeza,” Caracas, Venezuela on 20 August (click here). 

Carlos Alberto Amaya, neonatologist, Hospital de Niños Benjamín Bloom, San Salvador, El Salvador on 18 August (click here).

Ángel Ruben Alzurutt Riera, OBGYN, from Ciudad Guayana, Venezuela on 17 August (click here). 

Yamil Abou Assali, age 60, OBGYN, Barinas, Venezuela, on 8 August (click here).

Felipe De La Cruz Luna, OBGYN, Apartadó, Colombia on 5 August (click here). 

Halil Yucel Kutun, age 67, OBGYN, Ozel Bag Hospital, Diyarbakir, Turkey, on 4 August (click here).

Jesús Peña Peña, age 67, OBGYN, Hospital de Santa Bárbara, Mérida, Venezuela on 4 August (click here). 

July 

Alcira Perache, age 52, OBGYN, Hospital Dr Raúl Leoni, Ciudad Guayana, Bolívar, Venezuela, on 31 July (click here).  

Germán Mauricio Erazo Santos, OBGYN, Hospital Gabriela Alvarado, Danlí, Honduras on 29 July (click here). 

Óscar Urenda, age 72, OBGYN, Santa Cruz, La Paz, Bolivia, On July 23 (click here).

Ana Henríquez Salazar, age 52, OBGYN, Distrito Capital, Venezuela, on 22 July (click here).

María Consuelo González, OBGYN, Distrito Capital, Venezuela, on 13 July (click here).

Doreen Lugaliki, age 39, OBGYN in Kenya on 10 July (click here). 

Jesús Romero, age 54, OBGYN,  Rosario de Perijá, Zulia, Venezuela. on 10 July (click here).

Elias José Hani Jimeno, age 64, OBGYN, Clínica Misericordia, Ciénaga, Magdalena, Colombia in July (click here).

Matilde Ramírez García,  OB-GYN, Hospital Regional de Coatzacoalcos “Dr. Valentin Gomez Farias,” Coatzacoalcos, Veracruz, Mexico, on 3rd July (click here). 

José Alfredo Jiménez Turrubiates, OBGYN, Hospital General Matamoros “Dr. Alfredo Pumarejo,” Matamoros, Tamaluipas, Mexico, on 2 July (click here)

Nola Mae Moore, age 98, family practitioner, King County, Washington, USA, who had delivered almost 5,000 babies in partnership with her husband, in June (click here). 

June

Jorge Leal, age 56, OBGYN, Zulia, Venezuela, on 28 June (click here).

Manuel Romero, age 54, OBGYN, Maracaibo, Zulia, Venezuela, on 24 June (click here). 

Sergio de la Fuente Burton, age 73, OBGYN, American Hospital, Cancun, Mexico, on 2nd June (click here).

May 

Ramon César Aparicio Osorio, OBGYN, director of Hospital Materno Infantil Vicente Guerrero, Chimalhuacán, Mexico in May (click here).

Carla de Oliveira Obelar, age 42, neonatal nurse, Rio de Janeiro, Brazil, in May (click here).

Ahmed Al-Annie, OBGYN, from Banha Insurance Hospital, Banha, Egypt in May (click here).

Eder Aguilar Rojas, OBGYN from Iquitos, Peru in May (click here).

Nicolás Hernández Hernández, OBGYN from Iquitos, Peru in May (click here).

Margaret Njenga, midwife, Barts Health NHS Trust, London, UK, in May (click here). 

Safaa Alam, age 30, midwife, Birmingham, UK in May (click here or here).

Jaime Hernández Rodríguez, OBGYN, General Hospital of Zona 13 de Matamoros.Tamaluipas, Mexico  (click here).

Esperanza Bravo Ruíz, neonatologist, Puebla, Mexico, on May 13 (click here). 

Daniel Mojica, administrator, Hospital de Gineco Obstetricia No. 3 de La Raza, Mexico City, Mexico on 9 May (click here).

Duško Kljakić, age 52, OB-GYN,  General Hospital “Blažo Orlandic,” Bar, Montenegro, on 9 May (click here).

Veselago Larisa Mikhailovna, age 71, OBGYN, St. Petersburg, Russia on 8 May (click here).

Claudio Antonio Figueiredo Reis, age 63, OBGYN, Hospital Anita Gerosa, Ananindeua, Brazil on 6 May (click here).

Svetlana Vinokur, age 56, obstetric nurse, NYC Health+Hospitals/Coney Island, Brooklyn, New York, on 1 May (click here).

April 

Reinaldo Albernás, age 54, OBGYN, in Hospital San Rafael de Alajuela, Alajuela, Costa Rica, in April (click here).

Khanyafi Garifullin, age 61, OBGYN from Dzerzhinsk City hospital, Moscow, Russia, on 30 April (click here).

Avelar Feitosa Ribeiro, OBGYN, Hospital Divina Providência, Marituba, Pará, Brazil, on 27 April (click here). 

Azinet Pudpud, age 61, neonatal nurse, Lincoln Hospital, New York, on 27 April (click here). 

Elma Cavalida, a maternity assistant at Northwick Park Hospital, on April 26 (click here). 

Gerardo Zenteno Gutiérrez, OBGYN, Clínica de Especialidad Nuestra Señora de Los Ángeles, Puebla, Mexico, on April 25 (click here).

Shree Vishna Rasiah, age 49, neonatologist, Birmingham, UK, on 23 April 2020 (click here or here)

Arthur Tayengco, age 81, OBGYN, University of Nevada-Las Vegas School of Medicine, USA, on 22 April (click here or here).

Alicia Soto Guerrero, age 65, radiologist, Sinaloa, Mexico, previously intern in OBGYN, on 20 April (click here or here).

Tomás Hernández Quijano, OBGYN IMSS Hospital Vicente Guerrero, Acapulco, Mexico between 19 and 23 April (click here).

Joshua Yasuo Suzuki, age 78, OBGYN, Seattle, USA, on April 19 (click here or here).

Linda Clarke, age 66, midwife, Wigan, UK, on 16 April (click here). 

Alberto Guidetti, age 76, OBGYN, Arzignano and Valdagno Hospitals in Creazzo, Italy, on 15 April (click here).

Emeka Chugbo, age 60, OBGYN, Lagos, Nigeria, on 15 April (click here. See also here).

Emma Altagracia Barba Demorizi, Dominican Republic, on 14 April (click here).

Katia Kohler, OBGYN, Santana de Parnaiba, Brazil, on 13 April (click here).

Raimundo Ferreira Rodrigues, age 75, OBGYN, Manaus, Brazil, on 12 April (click here). 

Betty Cruz Yagual, age 61, OBGYN, Santiago de Guayaquil, and El Cisne, Health Centers, in Ecuador, on 10 April (click here). 

Edoardo Valli, age 63, OBGYN at Santa Famiglia obstetric clinic, Rome, on 9 April (click here).

Luis Caldera-Nieves, age 63, OBGYN, from Jackson South Community Hospital in Palmetto Bay, Miami, Florida on 8 April (click here). 

Susan Sisgundo, neonatal nurse, Bellevue Hospital, New York, on April 8 (click here).

Alice Kit Tak Ong, age 70, midwife from North London, UK, on 7 April (click here or here).

Aria Sigaroudi, midwife, Sari, Iran, on 7 April (click here). 

Mark Laser, age 63, OBGYN, Women’s Healthcare, Trumbull, Connecticut, on 7 April (click here).

Luis Caldera-Nieves, age 63, OBGYN, Miami, Florida, on 7 April (click here).

Jack Zoller, OBGYN, New Orleans, Louisiana on 2 April (click here). 

Lynsay Coventry, age 54, midwife, Princess Alexandra Hospital Trust, Harlow, Essex, UK, on 2 April (click here). 

Hamza Pacheeri, age 80, OBGYN, Birmingham, United Kingdom on April 1 (click here). 

March

Ricardo A. Alcivar Zambrano, age 67, Neonatologist, Guayaquil, Ecuador, in March (click here).

Gianfranco D’Ambrosio, OBGYN and GP, Italy, on 30 March (click here).

Irving Buterman, age 78, OBGYN, New York, on March 30 (click here).

Washington Germán Tutasi Jaramillo, age 68, OBGYN, Ambate, Ecuador, on March 28 (click here). 

Carlos Enrique Burbano Freire, age 50, Guayaquil, Ecuador, on 26 March (click here).

Biljana Natic ​​Ljumovic, age 59, OBGYN, Niš, Serbia, on 25 March (click here). 

Liliana Ortega Miranda, age 45, OBGYN, Hospital Nacional Sergio Bernales, Comas, Peru, on 23 March (click here). 

Jean-Marie Boegle, age 66, OBGYN, Mulhouse, France, on 22 March (click here or here).

Valter Tarantini, age 72, OBGYN, Forlì, Italy, on 19 March (click here or here).

Roberto Mileti, age 59, OBGYN, San Marco, Italy, on 30 March (click here).

Month unknown

Bugornikova Galina Valentinovna, age 59, OBGYN, Ust-Pristanskiy, Altai Territory, Russia (click here).

Anusheh Beikian, OBGYN, Rasht, Iran (click here).

Seyyedeh Azemat Mousavi, OBGYN, Sari, Iran (click here). 

Dr. Ali İhsan BULUT, OBGYN, Istanbul (click here)

Ibtihal Hammoud, OBGYN, Aden, Yemen (click here)

Walid Yahya Abdelhaleem, age 32, OBGYN, Almuneerah General Hospital, Cairo, Egypt (click here)

Jim Thornton

Note. For ease of searching, and because many countries use the generic term gynaecologist to include obstetrician, I’ve classified obstetricians, gynaecologists and doctors who practice both, all as OBGYNs. Similarly I’ve classified paediatricians who practice neonatology as neonatologists. 

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