Scientists identify early signal of dangerous pregnancy complications

Good news! This could be a breakthrough!

"In a study published today [8/31/2026] ... scientists who analyzed blood samples from thousands of pregnant women found that low levels of a protein called ISM2 during the first trimester were associated with higher risk of both preeclampsia and fetal growth restriction later on.

Follow-up lab studies of placental cells showed ISM2 likely plays a causal role in the disorders, meaning the findings could help in the development of treatments, too. ...

The researchers measured blood levels of nearly 3000 proteins and found one in particular associated with both preeclampsia and fetal growth restriction: ISM2, a little-studied protein produced by the placenta. Specifically, lower blood levels of the protein at the 12-week blood test were linked to higher risks of preeclampsia, fetal growth restriction, or both. ...

What’s more, ISM2 levels were a better predictor of each condition than currently used proteins. ...

In lab experiments, the team found that blocking the production of ISM2 in stem cells that usually develop into normal, uterus-invading EVTs stopped that process from happening.

By contrast, artificially adding ISM2 into a cell line that usually lacks it induced recipient cells to migrate around lab dishes more like EVTs would. ..."

"... Both of these conditions are known to be linked to problems with the placenta not developing properly early in pregnancy, in particular a failure of specialised placental cells known as the extravillous trophoblast (EVT) to invade the mother’s womb and establish a healthy blood supply. ...

Of all mammals, humans have the deepest placental invasion, which reflects the massive demands of oxygen and nutrients required to manufacture the most complex machine ever known, the human brain. ..."

From the abstract:

"Preeclampsia and fetal growth restriction (FGR) are major causes of global morbidity and mortality. 

Both conditions are associated with impaired invasion of the uterus by extravillous trophoblast (EVT).

We performed proteomics in maternal serum obtained at ~12 weeks of gestational age in a prospective pregnancy cohort (Pregnancy Outcome Prediction Study). Here we show that low maternal serum isthmin-2 (ISM2) was the strongest protein signal (out of 2,904) in the first trimester of pregnancy for preeclampsia or FGR.

We validated the association in two independent cohorts (Pregnancy Outcome Prediction Study 2 and Improving Maternal Pregnancy And Child ouTcomes study).

ISM2 protein and mRNA are almost exclusively produced in the placenta, and, within the placenta, ISM2 mRNA is highly enriched in EVT. 

Knocking down ISM2 in cultured human trophoblast stem cells profoundly inhibited EVT invasion.

Conversely, expressing ISM2 in a cell line lacking endogenous ISM2 (HEK293 cells) promoted migration.

We conclude that ISM2 may be causally involved in the early pathophysiology of failed trophoblast invasion and that the protein and its associated pathways are potential targets for the prediction and prevention of preeclampsia and FGR."

Scientists identify early signal of dangerous pregnancy complications | Science | AAAS "Low levels of a placenta made protein predict preeclampsia and fetal growth restriction and could offer new target for prevention"

Pre-eclampsia discovery could lead to new test and treatments for at-risk pregnancies (original news release) "Cambridge scientists have identified a key protein that could act as a predictor for pre-eclampsia and fetal growth restriction, two of the major causes of stillbirth and of sickness among mothers and newborns."

Isthmin-2 is a first-trimester predictor of preeclampsia and fetal growth restriction (open access)

Fig. 2: The association between ISM2 and PE and FGR.

Fig. 3: ISM2 regulates EVT differentiation.

Teen Pregnancy Crisis in Philippines: Government Reports 138,697 Teen Mothers

Bad news!

(194) Teen Pregnancy Crisis in Philippines: Government Reports 138,697 Teen Mothers | WORLD DNA - YouTube

Pregnancy, breastfeeding associated with higher levels of cognitive function for postmenopausal women, new research shows

Amazing stuff!

"... Researchers used data from the Women’s Health Initiative Memory Study and the Women’s Health Initiative Study of Cognitive Aging, which annually assessed more than 7,000 women aged about 70 for up to 13 years.

Women are disproportionately affected by Alzheimer’s disease, something that has not been fully explained by the length of life span. Fox’s study aimed to address this question by examining the relationship between reproductive histories and cognitive function in a large group over a long period, something previous studies had not yet accomplished. ..."

"Key Takeaways

• Pregnancy and breastfeeding may improve long-term cognitive function in women. 
• The study found that an increase in cumulative time spent pregnant and time spent breastfeeding correlated with greater cognition, verbal memory and visual memory later in life. 
• The findings may open the door to potential advancements in preventative strategies targeting women at greater risk of Alzheimer’s disease.

..."

From the abstract:

"INTRODUCTION

The brains of female mammals evolved to undergo structural and functional changes during pregnancy and lactation, equipping them for motherhood. However, long-term cognitive health implications of these adaptations in women are poorly understood.

METHODS

In the Women's Health Initiative (WHI) Memory Study (WHIMS; n = 7427) and WHI Study of Cognitive Aging (WHISCA; n = 2304), postmenopausal women completed reproductive history interviews, annual global cognitive assessment from mean age 70 for up to 13 years, and multi-domain cognitive testing for up to 8 years.

RESULTS

Each additional month pregnant was associated with higher scores of global cognition.

Each additional month of breastfeeding corresponded to higher scores of global cognition, verbal memory, and visual memory. We observed equivalent results for binary formulations of gravidity and breastfeeding.

DISCUSSION

Low rates of fertility and breastfeeding may have implications for postmenopausal cognitive health at the population level. Next steps include examining mechanisms linking women's reproductive history with postmenopausal cognitive health.

Highlights

• Motherhood may leave an enduring mark on women's brains, shaping cognitive health.
• Over 7000 women were assessed annually from approximately age 70 for up to 13 years.
• Ever being pregnant and cumulative time pregnant were linked with better cognition.
• Ever having breastfed and more time breastfeeding were linked with better cognition.
• These results imply that declining fertility may affect cognitive aging in future generations.

"

Pregnancy, breastfeeding associated with higher levels of cognitive function for postmenopausal women, new research shows | UCLA

Pregnancy and breastfeeding are associated with less later-life cognitive decline in a longitudinal, prospective cohort

Fig. 3 Results from primary hypotheses.

Immune cells prepare for pregnancy

Amazing stuff!

"In mammals, networks of immune cells within the uterus help to ensure tolerance to embryos, allowing implantation and a successful pregnancy. Foyle et al. examined how seminal fluid from male mice influenced the composition of T cells within the uterus in female mice. CD4+ and CD8+ T cells accumulated in the endometrium after mating; however, γδ T cells, a distinctive type of T cell with characteristics of both innate and adaptive immune cells, increased in abundance the most.

Consistent with their bolstered numbers, these γδ T cells had indications of elevated activation and proliferation. Therefore, seminal plasma, rather than sperm, is critical for stimulating these changes to uterine γδ T cells."

From the abstract:

"Seminal fluid elicits an immune response in the uterine mucosa after mating that impacts embryo implantation and pregnancy, but the underlying molecular and cellular events are unclear.

In this study, we report RNA sequencing to analyze the uterine response to seminal fluid after mating. Females exposed to seminal fluid of intact males exhibited gene expression changes on D3.5 post-coitum (pc) just prior to embryo implantation, compared to females mated with males surgically rendered seminal plasma deficient.

Functional enrichment analysis revealed genes related to T cell activation amongst those with the largest fold-changes. Using flow cytometry we then showed profound changes in uterine T cell abundance and phenotype regulated by seminal fluid contact. While CD4+ and CD8+ T cells were elevated by seminal fluid, the most conspicuous change was in CD4-CD8- T cells expressing γδ T cell receptors (TCR).

Mating with intact males caused a 8.3-fold increase in γδ T cell abundance compared to estrous virgin females, and a 22.4-fold increase in the proportion of γδ T cells expressing proliferation marker Ki67. Vγ6+ cells were the most abundant subpopulation in the uterus, followed by Vγ4+ and Vγ1+ T cells, and all three were similarly expanded after mating.

Seminal plasma was critical for γδ T cell accumulation and activation in the endometrium, and similar changes occurred in uterine-draining lymph nodes but not spleen. These findings identify γδ T cells as prominent in the immune response to seminal fluid and imply key roles in uterine immune regulation and reproductive success."

In Other Journals | Science

Seminal fluid expands the uterine gamma/delta T cell pool during early pregnancy in mice (open access)

Fig. 1 Effect of prior seminal fluid contact on the uterine endometrial transcriptome at implantation.

Doctors placed a stent in the heart of a fetus still inside the womb diagnosed with a rare and severe heart defect

Amazing stuff!

"Lauren and Alex Klingsporn were shocked by the news that their unborn son, Brooks, would need a series of surgeries after he was born to fix a rare and severe heart defect.

Brooks’ situation became even more desperate when doctors learned of another problem that was causing lung damage, making it unlikely he’d be healthy enough for the surgeries after birth. Babies born with Brooks’ condition have almost no chance of survival.

So, Texas Children’s Hospital tried something that sounds like science fiction. Doctors placed a stent in Brooks’ heart while he was still in the womb, a complex, high-risk procedure the hospital has performed only about 30 times over the past decade. ..."

"... Fetal cardiac intervention is complex surgery that is performed in the hospital. The mother and fetus are sedated, and an incision is made in the mother’s abdomen, similar to that for a cesarean section. An incision is made in her uterus, exposing the fetus. Guided by ultrasound images, a specialized needle is inserted into the heart of the fetus. A tiny tube, or catheter, with a balloon attached to it is introduced into the heart. The balloon is inflated to expand the valve and allow blood to flow. After the procedure, the fetus is returned to the mother’s uterus. Amniotic fluid is replaced, and the uterus and abdomen are closed. ..."

Texas Children's novel, in-utero surgery saved baby with rare defect

Fetal Cardiac Intervention

Brazil's mass Teen Pregnancy challenge and turnaround

Good news!

"Brazil once had one of the highest teenage pregnancy rates in Latin America, with ~750,000 Brazilian girls ages 15–19 giving birth in 2000.  

 

But over 25 years, births among that age have plummeted 44%, falling below 400,000 in 2019, with ~281,000 projected for 2025. 

 

Contraception intervention: The primary driver for the reversal has been the rapid expansion of birth control access, with free birth control, condoms, and IUDs provided by the country’s national health system, Sistema Unica de Saude.  

 

Outreach: Community health program Saude da Familia sends educators door to door to share family planning options ..."

Global Health NOW: U.S., Canada Risk Measles-Free Status; WHO Warns of Tobacco Treaty Interference; and Brazil's Teen Pregnancy Turnaround

How Brazil reversed its teenage pregnancy epidemic "Prosperity, education and social media have all played a part in tackling one of the country’s largest and most stubborn health challenges"

Study finds link between gut microbiome and the placenta in pregnant women

Amazing stuff!

"New research in mice shows that a species of gut bacteria, Bifidobacterium breve, regulates the placental production of hormones which are critical for healthy pregnancy.

Pregnant mice without B. breve in their guts were also found to experience a higher rate of complications and increased early foetal loss.

B. breve occurs naturally in the human and mouse gut microbiome and increases in late pregnancy in both species. But stress or obesity in pregnant [mice or women] can alter its abundance. ..."

"Pregnant women with plenty of 'good' gut bacteria may have stronger, healthier pregnancies, according to new research.  

For the first time, scientists have shown that beneficial bacteria helps regulate placental hormones essential for supporting a developing baby. ..."

From the abstract:

"Background

Recent studies have shown that the maternal gut microbiota can regulate placental growth, particularly the transport region, in association with fetal growth. However, the specific role of certain microorganisms in modulating the hormonal production of the placenta, which is critical for supporting fetal development and maintaining a healthy pregnancy, remains largely unexplored. In this context, the objective of this study is to determine whether the maternal colonisation with the early life gut bacterium Bifidobacterium breve UCC2003 regulates placental endocrine function.

Methods

Pregnant germ-free mice were colonized with or without Bifidobacterium breve UCC2003 (BIF) during pregnancy. The endocrine region of the placenta (junctional zone, Jz) was collected to assess its metabolic profile using metabolomics, the expression of key nutrient uptake genes, hormones and synthetic genes by qPCR, and proteome using LC-MS/MS.

Results

BIF colonised dams had increased lactate and taurine concentrations in the placental Jz. BIF presence was also associated with upregulated expression of nutrient carriers, particularly those involved in large neutral amino acid and monocarboxylate uptake (e.g., Slc7a8 and Slc16a4).

Additionally, key hormones, such as prolactins and pregnancy-specific glycoproteins, were upregulated. The Jz proteome was changed in BIF colonised dams, with over 400 proteins dysregulated. Pathway analysis revealed more than 150 biological processes were altered, including transcriptional activity, protein synthesis, cell cycle progression, and metabolic regulation. Proteins regulated by BIF in the placental Jz were correlated with fetal growth and nutrient levels (namely glucose). Notably, maternal-associated BIF reduced the number of fetal resorptions (early fetal loss).

Conclusions

In germ-free mice, maternal-associated gut Bifidobacterium breve UCC2003 regulates placental endocrine capacity, by altering its metabolic profile and ability to produce endocrine factors. This study provides the first clear evidence that the maternal gut microbiota not only influences placental transport function, but also regulates its endocrine outputs."

Study finds link between gut microbiome and the placenta

‘Good’ gut bacteria boosts placenta for healthier pregnancy (original news release) "Cambridge scientists discover how probiotics may help prevent miscarriages, gestational diabetes and preeclampsia"

Placental endocrine function is controlled by maternal gut Bifidobacterium in germ-free mice (open access)

Fig. 1 Maternal B. breve supplementation induces changes in specific metabolites and nutrient carriers in the endocrine zone of the mouse placenta.

A historic phase 3 trial evaluating the efficacy and safety of antimalarial drugs in the first trimester of pregnancy in Africa. Really!

One may cynically ask why is this trial started in Africa and not anywhere else? Are Africans used as guinea pigs? 

Certainly, Africans suffer severely from Malaria, but ???

Is it not enough to give antimalarial drugs to women before pregnancy?

"A historic phase 3 trial evaluating the efficacy and safety of antimalarial drugs in the first trimester of pregnancy—aimed at addressing a longstanding gap in malaria research—enrolled its first patient; the trial is being conducted in Mali, Burkina Faso, and Kenya. ..."

"

• Through the SAFIRE consortium, experts from Africa and Europe are closing a critical treatment gap for women in early pregnancy.
• Each year, over 12 million pregnant women are exposed to malaria in sub-Saharan Africa.
• Findings will inform global malaria treatment guidelines and help expand treatment options for pregnant women.

The Safety of Antimalarials in the FIRst trimEster (SAFIRE) consortium has enrolled its first patient in Mali, marking the official start of the first-ever Phase 3 adaptive platform trial evaluating the efficacy and safety of antimalarial drugs in the first trimester of pregnancy. ... "

"... An Africa-Europe partnership, SAFIRE is addressing long-standing gaps in malaria research and treatment for pregnant women, who have been systematically excluded from drug development programmes, depriving them of newer, better treatments. ..."

Global Health NOW: Tobacco Use Falls, Industry Pivots; Aid Cuts Hit Yemen Amid Measles Crisis; and Conversion Therapy Goes Before the Court

First patient enrolled in historic Phase 3 clinical trial to treat malaria in first-trimester pregnancy "Major milestone in Africa’s first-ever study assessing malaria treatments in early pregnancy"

First patient enrolled in historic Phase 3 clinical trial to treat malaria in first-trimester pregnancy (original news release) "Major milestone in Africa’s first-ever study assessing malaria treatments in early pregnancy"

Skin-to-skin contact associated with positive brain changes in preterm infants

Good news! Common sense would tell you that!

"“Kangaroo care,” or skin-to-skin contact, may be neuroprotective and is associated with neonatal development in areas of the brain involved in emotional regulation in preterm infants, according to a new preliminary study from Weill Cornell Medicine, Burke Neurological Institute and Stanford Medicine.

Even short sessions correlated with noticeable effects on brain imaging scans, which is important because more than half of preterm infants have risk for neurodevelopmental impairment.  ..."

"Highlights: 

• Skin-to-skin care in preterm infants born before 32 weeks was linked to measurable differences in brain development.

• Longer cuddle sessions were associated with signs of brain growth in regions tied to emotional and stress regulation as well as memory. 

• Both session length and amount per day mattered, with longer skin-to-skin sessions showing the strongest associations.

• Even after adjusting for medical and social factors—like gestational age, socioeconomic status and the frequency of family visits—brain differences remained.

• Researchers say the findings underscore how nurturing touch during a critical window may influence how a preemie’s brain develops.

..."

From the abstract:

"Background and Objectives

Preterm birth is associated with altered white matter development and long-term neurodevelopmental impairments. Skin-to-skin care has known benefits for physiologic regulation and bonding in preterm infants, but impacts on early brain structure remain unclear. The aim of this study was to describe the association between in-hospital skin-to-skin care and white matter microstructure in very preterm infants, focusing on frontolimbic tracts involved in stress regulation and socioemotional development.

Methods

The design was a single-center retrospective observational analysis of clinical data from the electronic medical records and diffusion MRI scans.

Participants were infants born at <32 weeks gestational age (GA) who received a routine predischarge MRI.

Skin-to-skin care was quantified as duration per instance and daily exposure rate (in minutes) before the MRI was obtained.

Diffusion MRI assessed mean diffusivity (MD) and fractional anisotropy (FA) in the cingulum, anterior thalamic radiations (ATRs), and uncinate fasciculus. Hierarchical regression models evaluated associations between skin-to-skin care and white matter metrics, adjusting for GA, medical acuity, postmenstrual age at scan, and MRI coil type.

Results

A total of 88 preterm infants (mean GA 29 weeks; 49% female) were included. Skin-to-skin care duration per instance was positively associated with MD in the cingulum (B = 0.002, 95% CI 0.0004–0.003, ΔR2 = 0.080) and ATRs (B = 0.002, 95% CI 0.0003–0.003, ΔR2 = 0.057).

Skin-to-skin care daily exposure rate was also positively associated with ATR MD (B = 0.038, 95% CI 0.001–0.076, ΔR2 = 0.046). Both skin-to-skin metrics were negatively associated with ATR FA (duration: B = −0.0005, 95% CI −0.001 to −0.0001, ΔR2 = 0.046; rate: B = −0.016, 95% CI −0.028 to −0.004, ΔR2 = 0.075). No significant associations were found for the uncinate fasciculus.

Findings remained significant after adjusting for socioeconomic status and visitation frequency and after excluding infants with white matter injury.

Discussion

Skin-to-skin care was associated with neonatal white matter microstructure in specific frontolimbic tracts. Limitations include the retrospective design and single-center setting. Future studies should consider how early caregiving experiences, such as skin-to-skin care, may influence brain development in preterm infants."

Skin-to-skin contact associated with brain changes in preterm infants | Cornell Chronicle

The power of touch: Skin-to-skin contact linked to preemie brain growth (original news release)

Skin-to-Skin Holding in Relation to White Matter Microstructure in Infants Born Preterm (open access)

Figure 2 Associations Between Skin-to-Skin Care Duration and White Matter Microstructure in Preterm Infants

Here’s what morning sickness during pregnancy really means

Good news!

"Key takeaways

• A UCLA study has found that “morning sickness” symptoms, including nausea, vomiting and aversions to certain foods and smells, are linked to the body’s natural, but complex, immune response during pregnancy.
• In the early stages of pregnancy, a unique mix of inflammatory responses alongside behavioral mechanisms that researchers believe are adaptive, like nausea, achieves a delicate balance, allowing the mother to tolerate and nourish the half-foreign fetus while also avoiding potentially harmful foods.
• The study could have workplace implications for pregnant women, helping to widen recognition that these symptoms are healthy and normal, both reducing stigma and paving the way for common-sense workplace accommodations.

... According to the National Institutes of Health, up to 80% of early-stage pregnant mothers experience some nausea, vomiting and aversions to certain foods and smells. While uncomfortable, these symptoms are not typically a sign that anything is wrong with the health of the mother or the developing fetus, but rather an indication of a delicate balance unique to pregnant women.  ..."

From the abstract:

"Background

During pregnancy, the maternal body undergoes extensive physiological adaptations to support embryonic growth, including whole-body remodeling, that may induce odor and food aversions, as well as nausea and vomiting. The biological mechanisms behind odor and food aversions, as well as nausea and vomiting in early pregnancy, remain largely unexplored. Our study investigated associations between these changes and cytokine profiles during pregnancy.

Methodology

A cohort of pregnant Latina women in Southern California (n = 58) completed a structured questionnaire on pregnancy “morning sickness”-related symptoms and aversions. Maternal plasma cytokine levels were measured between 5 and 17 weeks’ gestation.

Results

About 64% of participants experienced odor or food aversions, primarily to tobacco smoke and meat; 67% reported nausea, and 66% experienced vomiting. Multivariable linear regression models revealed that odor aversions were associated with increased pro-inflammatory T-helper-cell type (Th) 1 composite cytokine levels.

Women who found tobacco smoke aversive exhibited a shift toward Th1 immune responses, indicated by a higher Th1:Th2 ratio.

Food aversions also showed a positive association with Th1 cytokine levels. A borderline positive association was noted between nausea and vomiting and the Th1:Th2 ratio.

Conclusions

These findings are consistent with the hypothesis that gestational changes in olfactory and gustatory experience, and nausea and vomiting, reflect adaptive upregulation of behavioral prophylaxis in ways that could protect the fetus. If this elevated Th1:Th2 ratio and pro-inflammatory phenotype are part of the maternal and embryonic response to embryogenesis, the behavioral and biological markers that we explore may provide an accessible index of fetal development during early pregnancy."

Here’s what morning sickness during pregnancy really means | UCLA "UCLA’s latest findings show how a woman’s healthy inflammatory response during pregnancy is linked with unpleasant early-stage symptoms"

Of scents and cytokines: How olfactory and food aversions relate to nausea and immunomodulation in early pregnancy (open access)

Fig. 1 A conceptual model of the behavioral and immunological changes during pregnancy. Note: The intensity/sensitivity levels depicted are not based on specific observational data but are provided to facilitate a structured understanding of the phenomena under investigation, grounded in empirical evidence

Inflammation during pregnancy may prime offspring for anxiety

Good news! It has been suspected for decades that events during a woman's pregnancy may cause serious disorders etc. affecting her child possibly for the rest of the child's life. 

"Increased risk for anxiety may begin before birth, shaped by infection or stressful events during pregnancy, according to a new preclinical study ...

While scientists have long known that maternal difficulty during pregnancy may raise a child’s risk for psychiatric illness, the biological pathways between these prenatal experiences and later mental health have been unclear. ..."

From the highlights and abstract:

"Highlights

• Adverse gestational environment is a risk factor for psychiatric disorders

• Gestational adversity has variable neuronal transcriptomic effects

• The most affected hippocampal neurons are activated in a stressful environment

• Higher neuronal activity during transition from safe to threatening environment

Summary

An adverse gestational environment is a risk factor for the development of psychiatric disorders. Although studies have implicated modifications in neuronal DNA and chromatin, how these changes come about and lead to abnormal behaviors is not known.

We sought to identify persistent DNA/chromatin and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to anxiety. 

A proinflammatory environment shifted DNA methylation of enhancers and promoters and altered synapse-related gene expression, resulting in transcriptional heterogeneity in the vDG.

In animals with prior adversity, exposure to a threatening environment recruited vDG neurons with the greatest transcriptional changes, notably in synapse-relevant genes that also tended to be differentially methylated.

Finally, vDG activity was increased during transition from a safe to a threatening environment in animals with prior adversity but not in controls, suggesting their enhanced perception of a potential threat.

Our data outline a proinflammatory gestational environment-induced neurobiological sequence that leads to anxiety."

Inflammation during pregnancy may prime offspring for anxiety | Cornell Chronicle

Adverse gestational environment configures a subpopulation of ventral dentate granule cells for recruitment to drive innate anxiety (open access)

Graphical abstract

Figure 2 An adverse gestational environment preferentially alters methylation at intermediately methylated CGs in vDGCs

President Trump Links Autism With Tylenol use by pregnant women

That a US President mentions a single, specific drug in public statements like this is already a little unusual!

President Trump forgot to mention the safer alternatives for Tylenol available to pregnant women!

Even the lefty Johns Hopkins Bloomberg School of Public Health admits "An Environmental Health article in August that analyzed 46 previous studies found 27 had significant links between prenatal acetaminophen use and neurodevelopmental disorders.". 

However, these lefties could not resist to qualify their admission by dubiously stating "However, study co-author Ann Bauer, a University of Massachusetts epidemiologist, told NPR the U.S. government “may be jumping the gun,” adding: “I think those of us in the research community would like to see stronger evidence [???].”" How much stronger evidence do people suffering from Trump Derangement Syndrome need for a warning of pregnant women?

From the abstract:

"Background

Acetaminophen is the most commonly used over-the-counter pain and fever medication taken during pregnancy, with > 50% of pregnant women using acetaminophen worldwide. Numerous well-designed studies have indicated that pregnant mothers exposed to acetaminophen have children diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), at higher rates than children of pregnant mothers who were not exposed to acetaminophen.

Methods

We applied the Navigation Guide methodology to the scientific literature to comprehensively and objectively examine the association between prenatal acetaminophen exposure and NDDs and related symptomology in offspring. We conducted a systematic PubMed search through February 25, 2025, using predefined inclusion criteria and rated studies based on risk of bias and strength of evidence. Due to substantial heterogeneity, we opted for a qualitative synthesis, consistent with the Navigation Guide’s focus on environmental health evidence.

Results

We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations. Overall, the majority of the studies reported positive associations of prenatal acetaminophen use with ADHD, ASD, or NDDs in offspring, with risk-of-bias and strength-of-evidence ratings informing the overall synthesis.

Conclusions

Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs. Appropriate and immediate steps should be taken to advise pregnant women to limit acetaminophen consumption to protect their offspring’s neurodevelopment."

Global Health NOW: Trump Links Autism With Tylenol; Russia’s Infected Troops; and ‘Nicotine-Free’ Vapes Not Free of Health Concerns

Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology (open access)

At the frontier between two lives—the evolutionary origins of pregnancy

Amazing stuff!

"... uncovered new insights into how specialized cell types and communication networks at the interface between mother and fetus evolved over millions of years. These discoveries shed light on one of nature's most remarkable innovations—the ability to sustain a successful pregnancy. ...

Pregnancy that lasts long enough to support full fetal development is a hallmark evolutionary breakthrough of placental mammals ... the site in the womb where a baby's placenta meets the mother's uterus, and where two genetically distinct organisms—mother and fetus—are in intimate contact and constant interaction.

This interface has to strike a delicate balance: intimate enough to exchange nutrients and signals, but protected enough to prevent the maternal immune system from rejecting the genetically "foreign" fetus.

To uncover the origins and mechanisms behind this intricate structure, the team analyzed single-cell transcriptomes—snapshots of active genes in individual cells—from six mammalian species representing key branches of the mammalian evolutionary tree. These included mice and guinea pigs (rodents), macaques and humans (primates), and two more unusual mammals: the tenrec (an early placental mammal) and the opossum (a marsupial that split off from placental mammals before they evolved complex placentas). ...

Their focus was on two main players: placenta cells, which originate from the fetus and invade maternal tissue, and uterine stromal cells, which are of maternal origin and respond to this invasion.

Using molecular biology tools, the team identified distinct genetic signatures—patterns of gene activity unique to specific cell types and their specialized functions. Notably, they discovered a genetic signature associated with the invasive behavior of fetal placenta cells that has been conserved in mammals for more than 100 million years. ...

To better understand how the fetal-maternal interface functions, the study tested two influential theories about the evolution of cellular communication between mother and fetus.

The first, the "Disambiguation Hypothesis," predicts that over evolutionary time, hormonal signals became clearly assigned to either the fetus or the mother—a possible safeguard to ensure clarity and prevent manipulation. The results confirmed this idea: certain signals, including WNT proteins, immune modulators, and steroid hormones, could be clearly traced back to one source tissue.

The second, the "Escalation Hypothesis" (or "genomic conflict"), suggests an evolutionary arms race between maternal and fetal genes—with, for example, the fetus boosting growth signals while the maternal side tries to dampen them. This pattern was observed in a small number of genes, notably IGF2, which regulates growth. On the whole, evidence pointed to fine-tuned cooperative signaling.

"These findings suggest that evolution may have favored more coordination between mother and fetus than previously assumed ..."

From the abstract:

"How fetal and maternal cell types have co-evolved to enable mammalian placentation poses a unique evolutionary puzzle.

Here we integrate and compare single-cell transcriptomes from six species bracketing therian mammal diversity: opossum (a marsupial), Malagasy common tenrec (an afrotherian), mouse and guinea pig (rodents), and macaque and human (primates).

We identify a conserved transcriptomic signature of invasive trophoblast across eutherians, probably representing a cell type family that radiated with the evolution of haemochorial placentation.

In the maternal stroma, comparative analysis reveals that the endocrine decidual cell evolved from an immunomodulatory predecidual cell type retained in Tenrec and resembling early human decidua.

Fetal and maternal cell signalling shows a pronounced tendency towards disambiguation—the exclusive expression of ligands by only one partner—although few ligand–receptor pairs follow an escalatory arms race dynamic. Finally, we reconstruct the uteroplacental cell–cell communication networks of extinct mammalian ancestors, identifying signalling innovations and widespread integration of fetal trophoblast and maternal decidual cells into signalling networks. Together, these results reveal a dynamic history of cell type innovation and co-evolution at the fetal–maternal interface."

At the frontier between two lives—the evolutionary origins of pregnancy

At the Frontier Between Two Lives – The Evolutionary Origins of Pregnancy (original press release)

Cell type and cell signalling innovations underlying mammalian pregnancy (open access)

Fig. 1: Single-cell transcriptomic atlases of six mammalian species spanning the diversification of viviparity.

A literal window into how the fallopian tube transports embryos via a leaky peristaltic pump

Amazing stuff! However, you could not repeat this with a pregnant woman!

If only the embryo knew what was going on! 😊

"... most of the oviduct’s [fallopian tube] functions haven’t been observed in their natural environment. ...

Wang and colleagues have used “optical coherence tomography” (OCT) to peer inside the abdomens of female mice.  ...

The team performed surgery on 12 female mice, implanting a small window made of glass and resin to allow them to bypass the skin and muscle and directly visualise the fallopian tubes. ...

Doing this over time allowed the researchers to capture both the oviduct dynamics and the embryo movement within the fallopian tube. ..."

From the abstract:

"The mammalian oviduct (also called the fallopian tube) is an essential organ for natural pregnancy. As one of its major functions, the oviduct transports preimplantation embryos to the uterus for implantation. This is a critical process, and abnormalities are responsible for a range of reproductive disorders, such as tubal ectopic pregnancy and infertility, whose etiologies are unclear.

For transporting embryos, the oviduct is fundamentally a tubular mechanical pump with motile cilia lining the luminal epithelium and smooth muscle surrounding the mucosa wall. Although bidirectional movement of embryos has been observed during the transport process, how the oviduct produces this type of embryo movement remains unknown.

Understanding this pumping mechanism is vital to identifying the functional causes of oviduct-related reproductive disorders, but answering this question requires dynamic imaging of the transport process in its native environment, which is difficult to achieve in mammalian models.

Here, we use optical coherence tomography and apply in vivo dynamic 3D imaging of the mouse oviduct to uncover the oviduct pumping mechanism in transporting preimplantation embryos toward pregnancy.

By inhibiting the oviduct smooth muscle contraction, we first show that the oviduct muscular activity drives the bidirectional embryo movement. We then present a quantitative assessment of the oviduct contraction wave. This analysis, together with the embryo movement information, indicates that the forward movement of embryos is produced by peristalsis, while the backward embryo movement is generated by a suction process driven by the oviduct relaxation at earlier contraction sites, showing a leaky peristaltic pump.

Finally, we reveal how the net displacement of embryos is created under this pumping mechanism, which effectively transports embryos toward the uterus.

This work elucidates, for the first time, the oviduct pumping mechanism in transporting preimplantation embryos, paving the way for understanding the biomechanics of the mammalian oviduct."

A window into how the fallopian tube transports embryos

Researchers use OCT imaging to uncover how the fallopian tube transports embryos "Mouse study lays groundwork for understanding reproductive challenges like infertility and ectopic pregnancy"

In vivo dynamic imaging reveals the oviduct as a leaky peristaltic pump in transporting a preimplantation embryo toward pregnancy (open access)

(A) In vivo imaging setup with a clamp stabilising the window implanted on the right dorsal side of the mouse.

(B) In vivo bright-field image of the oviduct as well as the ovary and a portion of the uterus through the window.

(C) In vivo 3D OCT image of the oviduct showing its 3D morphology and structure through the window. Scale bars are 500 µm.

Fig. 2. In vivo 3D OCT imaging of the preimplantation embryo movement and the oviduct contraction and relaxation. The embryo movement is bidirectional in all regions of the oviduct isthmus and coincides with the oviduct muscular activity shown as contraction and relaxation (Visualization 1). Triangles of the same color point at the same embryo at different time points. Scale bar is 300 µm.

Do not become pregnant while in weight loss treatment

Some dangers of weight loss medications! Less weight, more sex appeal or more fun?

"Women using weight-loss drugs like Ozempic, Wegovy, and Mounjaro are being urged to use “effective contraception” after 40 women have reported becoming pregnant while taking the medications, a U.K. regulatory agency warns."

"Women taking popular medicines for weight loss and diabetes, sometimes referred to as “skinny jabs”, are being reminded to use effective contraception while taking these medicines and, in some cases, for up to two months between stopping the medicine and trying to get pregnant.  

These medicines must not be taken during pregnancy, while trying to get pregnant, or during breastfeeding. ..."

Global Health NOW: Europe’s Surge of Synthetic Drugs; Scotlandʼs Mission to Banish Cervical Cancer; and This Sausage Roll Tastes Like Wax

Women on “skinny jabs” must use effective contraception, MHRA urges in latest guidance

Consuming cannabis while pregnant appears to increase the risk of preterm birth, low birth weight, and infant death

Bad news! But to be expected! Cannabis consumption is not harmless not even in states like Oregon, where cannabis use is largely legitimized!

Why the certainty of evidence for risks in previous studies was classified as "very-low-to-low" is a mystery to me and casts some doubt about this meta study! That should have been a red flag immediately that something is wrong with the study!

"... “Patients are coming to me in their prenatal visits saying, ‘I quit smoking and drinking, but is it safe to still use cannabis?’” said lead author Jamie Lo, M.D., M.C.R., associate professor of obstetrics and gynecology (maternal-fetal medicine) ...

In fact, cannabis remains one of the most common substances used in pregnancy that’s still illegal under federal law, and, unlike declines in prenatal use of alcohol or nicotine, cannabis use is continuing to increase. Lo said many of her patients are reluctant to give up cannabis during pregnancy because it helps to reduce common prenatal symptoms such as nausea, insomnia and pain. ...

The researchers found eight new studies since their previous update, raising the certainty of evidence from “very-low-to-low” to “moderate” for increased odds of low birth weight, preterm birth and babies being small for their gestational age. ..."

From the key points and abstract:

"Key Points

Question  Is cannabis use in pregnancy associated with neonatal outcomes?

Findings  In this updated systematic review and meta-analysis of 51 studies, prenatal cannabis use was associated with increased odds of preterm birth, small for gestational age, low birth weight, and perinatal mortality.

Meaning  Using cannabis in pregnancy was associated with increased risk of adverse neonatal outcomes; health care professionals should include this in their patient counseling, and increased public health measures are needed to raise awareness on safety of use.

Abstract

Importance  Prenatal cannabis use continues to increase, and cannabis remains the most commonly used illegal substance in pregnancy. Accumulating evidence suggests potential adverse effects on fetal and neonatal outcomes following cannabis use in pregnancy.

Objective  To update a living systematic review and meta-analysis to provide a timely understanding regarding cannabis use in pregnancy and fetal and neonatal outcomes.

Data Sources  The previous review was updated by searching bibliographic databases MEDLINE, CINAHL, PsycInfo, Global Health, and Evidence-Based Medicine Reviews Cochrane Database of Systematic Reviews from November 1, 2021, through April 4, 2024.

Study Selection  Cohort or case-control studies comparing pregnancies with and without prenatal cannabis use on prespecified fetal or neonatal outcomes with adjustment for confounders, such as co-use of tobacco products, were included. Two independent reviewers screened studies, with disagreements resolved through discussion.

Data Extraction and Synthesis  Included studies were extracted by 1 reviewer and confirmed by a second. Risk of bias was assessed with the Newcastle-Ottawa Scale. Random-effects meta-analyses of unadjusted and adjusted odds ratios (ORs) were performed for all primary outcomes. Results were synthesized using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Main Outcomes and Measures  Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small for gestational age (SGA), low birth weight (LBW; <2500 g), and perinatal mortality.

Results  For this update, 8 new studies with 1 709 998 participants were added, for a total of 51 studies synthesized (N = 21 146 938). From meta-analyses of adjusted effect sizes, moderate-certainty evidence indicated that cannabis use in pregnancy was associated with increased odds of LBW (20 studies; OR, 1.75; 95% CI, 1.41-2.18), PTB (20 studies; OR, 1.52; 95% CI, 1.26-1.83), and SGA (12 studies; OR, 1.57; 95% CI, 1.36-1.81), and low-certainty evidence indicated that it was associated with greater odds of perinatal mortality (6 studies; OR, 1.29; 95% CI, 1.07-1.55). Previously, the evidence was rated as very low or low certainty.

Conclusions and Relevance  Cannabis use in pregnancy was associated with greater odds of PTB, SGA, and LBW even after adjusting for co-use of tobacco products, and confidence in these findings increased from low in the prior review to moderate in the current meta-analysis. The findings of this study may help inform patient counseling and future public health policies."

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Evidence review raises concern about cannabis use in pregnancy (original news release) "OHSU research team finds moderate risk for preterm birth, low birth weigh"

Prenatal Cannabis Use and Neonatal Outcomes / A Systematic Review and Meta-Analysis (no public access)

Researchers identify almost 300 genetic disorders that can be treated before birth

Good news!

Again it is disgusting and annoying how Harvard U avoided to say "woman" for most likely ideological reasons! Women are either "pregnancies" or "patients" or "families" or "individuals".

"A new study identifies nearly 300 genetic disorders that can be treated during pregnancy or in the first week of life, forming the basis for a “treatable fetal findings list” that could be offered to pregnant patients.

The findings could improve the diagnosis of genetic conditions in pregnancy and enhance the treatment options available for fetuses that have these conditions ...

Over the past decade, genomic sequencing has become a vital tool to help inform prenatal diagnoses. Genomic sequencing tests, combined with family history, can help identify genes responsible for ultrasound abnormalities. They can also uncover incidental findings that may predispose a fetus or newborn to serious but treatable conditions, such as a heart condition that can be treated with medications or a gastrointestinal disorder that can be managed with fluid and electrolyte therapies. ...

Through a literature review, the authors identified a total of 296 genetic conditions, ranging from disorders with emerging fetal therapies to those where immediate postnatal treatment can prevent irreversible harm. The authors emphasize that timely detection of these conditions could reduce morbidity and mortality, offering families unprecedented opportunities for early intervention. ..."

From the abstract:

"The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade.

Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype but may be relevant to fetal and newborn health. There are currently no guidelines for reporting incidental findings from fetal GS.

In the United States, GS for adults and children is recommended to include a list of “secondary findings” genes (ACMG SF v.3.2) that are associated with disorders for which surveillance or treatment can reduce morbidity and mortality. The genes on ACMG SF v.3.2 predominantly cause adult-onset disorders.

Importantly, many genetic disorders with fetal and infantile onset are treatable as well.

A proposed solution is to create a “treatable fetal findings list,” which can be offered to pregnant individuals undergoing fetal GS or, eventually, as a standalone cell-free fetal DNA screening test.

In this integrative review, we propose criteria for a treatable fetal findings list, then identify genetic disorders with clinically available or emerging fetal interventions and those for which clinical detection and intervention in the first week of life might lead to improved outcomes. Finally, we synthesize the potential benefits, limitations, and risks of a treatable fetal findings list."

Researchers ID genetic disorders that can be treated before birth — Harvard Gazette "Timely detection could reduce morbidity, offers opportunities for early intervention"

Advancing precision care in pregnancy through a treatable fetal findings list (no public access)

Advancing precision care in pregnancy through an actionable fetal findings list (preprint, open access)

How the mother and embryo’s first moments of life shape longevity

Amazing stuff! Maternal obesity during pregnancy has consequences.

"... They conducted a pre-clinical trial and found that cellular processes within the egg at the time of fertilisation determine the telomere length in the offspring. ...

The team conducted the trials using mouse models and found that when mitochondrial activity is disrupted, whether by high oxygen levels, or conditions such as maternal obesity and metabolic syndrome, the embryo fails to properly “reset” its telomere length. This leads to babies being born with shorter telomeres. ..."

"... “Some babies are born with shorter telomeres than others, increasing their lifetime risk of chronic diseases associated with ageing.

“As just one example, shorter telomeres are observed in children of women with obesity or metabolic syndrome. As adults, these individuals are at increased risk of premature mortality from cardiovascular events, like a heart attack or stroke, even when they are not obese themselves. ...

“There are specific types of cellular damage during the very first days of embryo development which cause the defect in the telomeres of the embryo, which causes them to be shorter at the time of birth,”...

“The process is highly responsive to signals from the mother’s body. Our findings show maternal health and environmental conditions at the time of conception can have long-term consequences and can even influence the offspring’s susceptibility versus resilience to ageing-associated diseases in later life. ..."

From the abstract:

"The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known.

We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis.

Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization.

Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length."

How embryo’s first moments of life shape longevity

Embryo development holds key to healthy lifestyles (original new release)

Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization (open access) "Researchers from the University of Adelaide have discovered that the earliest days of embryo development have a measurable impact on a person’s future health and ageing."

Fig. 1: Telomere elongation during pre-implantation embryogenesis is impaired by oxidative stress.

Substantial u-shaped remodeling of the brain in a pregnant woman

Amazing stuff!

"During pregnancy, the brain undergoes substantial remodeling. However, longitudinal characterization of these changes is lacking. Servin-Barthet et al. analyzed magnetic resonance imaging scans before, during, and after pregnancy in 127 women undergoing their first pregnancy.

Gray matter volume decreased rapidly during pregnancy and partially recovered (albeit slowly and only partially) postpartum. Volume changes were correlated with alterations in estrogens and were particularly evident in high-order cognitive networks. At the behavioral level, stronger gray matter volume recovery was associated with reduced hostility toward the newborn. Understanding brain adaptation during pregnancy could be leveraged to promote well-being during the postpartum period."

From the abstract:

"Growing evidence places the gestational period as a unique moment of heightened neuroplasticity in adult life.

In this longitudinal study spanning pre, during, and post pregnancy, we unveil a U-shaped trajectory in gray matter (GM) volume, which dips in late pregnancy and partially recovers during postpartum.

These changes are most prominent in brain regions associated with the Default Mode and Frontoparietal Network.

The U-shaped trajectory is predominantly linked to gestational factors, as it only presents in gestational mothers and correlates with fluctuations in estrogens over time.

Finally, the mother’s mental health status mediates the relationship between postpartum GM volume recovery and maternal attachment at 6 months postpartum. This research sheds light on the complex interplay between hormones, brain development, and behavior during the transition to motherhood. It addresses a significant knowledge gap in the neuroscience of human pregnancy and opens new possibilities for interventions aimed at enhancing maternal health and well-being."

In Other Journals | Science

Pregnancy entails a U-shaped trajectory in human brain structure linked to hormones and maternal attachment (open access)

Fig. 1: Longitudinal cortical gray matter volume trajectory across pregnancy and postpartum (N = 179).

What's behind preterm birth? Scientists discover a molecular timer

Good news!

"... Now, ... researchers have discovered a molecular timer in mice that plays a role in controlling when they give birth. Surprisingly, the timer is activated in the very first days of pregnancy and operates within the uterus. ...

were studying a protein called KDM6B which regulates gene activity. They suspected that during pregnancy, KDM6B could help regulate the genes involved in the transition to labor.

KDM6B works by removing methyl chemical groups from histones ... 

The team noticed that when they blocked KDM6B, pregnancies in the mice became longer, and their babies were born later than usual. ...

But when they carried out detailed analyses on different cell types, they found that KDM6B's effects on pregnancy length were tied to a different cell type called fibroblasts. These structural cells are not typically considered to play a role in the regulation of labor. Moreover, KDM6B regulated these fibroblasts during the first days of pregnancy. ...

Further experiments on mice revealed that shortly after conception, more methyl groups appear on histones near certain genes in uterine fibroblasts. In response, these genes remain inactive, which enables the uterus to support pregnancy.

Over the course of pregnancy, levels of methylation on these histones fade in a slow and steady way, eventually reaching low enough levels that the nearby genes—related to pregnancy events like labor—are activated. This erosion, which does not require KDM6B, functions as a timer. ..."

From the highlights and abstract:

"Highlights

• H3K27me3 levels are adjusted over the uterine fibroblast genome in early pregnancy

• KDM6B deficiency leads to over-accumulation of H3K27me3

• Elevated H3K27me3 is linked to prepartum gene misexpression and delayed labor

• H3K27me3 progressively erodes to induce genes post-midgestation

Summary

Current efforts investigating parturition timing mechanisms have focused on the proximal triggers of labor onset generated in late pregnancy.

By studying the delayed parturition phenotype of mice with uterine fibroblast deficiencies in the histone H3K27me3 demethylase KDM6B, we provide evidence that parturition timing is regulated by events that take place in early pregnancy.

Immediately after copulation, uterine fibroblasts engage in a locus-specific epigenetic program that abruptly adjusts H3K27me3 levels across their genome. In the absence of KDM6B, many of the adjusted loci over-accumulate H3K27me3.

This over-accumulation leads to nearby genes being misexpressed in mid-to-late gestation, a delayed effect partly attributable to a second locus-specific but KDM6B-independent process initiated within uterine fibroblasts soon after implantation.

This second process employs progressive H3K27me3 loss to temporally structure post-midgestational patterns of gene induction. Further dissection of the ways uterine programming controls parturition timing may have relevance to human pregnancy complications such as preterm labor."

What's behind preterm birth? Scientists discover a molecular timer

What’s Behind Preterm Birth? Scientists Just Found a Big Clue (original press release) "UCSF researchers discovered a molecular timer that gets activated in the first days of pregnancy and influences when mice give birth."

KDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice (no public access)

Uterine fibroblast cells, in the mouse uterus, shown in red

Graphical abstract