WOMAN'S HEALTH
Active military service may heighten women’s risk of having low birthweight babies
Findings highlight need for more female-specific research in armed forces, say study authors
Active military service may heighten a woman’s risk of having a low birthweight baby, suggests a review of the available scientific evidence published online in the journal BMJ Military Health.
The findings highlight the need for more research specifically focused on women in the armed forces, and their reproductive health in particular, conclude the study authors.
Worldwide, increasing numbers of women are on active service in their country’s armed forces. The UK Armed Forces, for example, has set a target of 30% female representation by 2030. And more and more countries are deploying women in combat units, and in other challenging environments, such as submarines, note the study authors.
Mounting evidence suggests that stress experienced during pregnancy is associated with birth complications, such as preterm delivery and low birthweight. And a military career and lifestyle expose service personnel to a wide range of physical, mental, and environmental stressors that could potentially influence pregnancy outcomes.
The study authors therefore wanted to explore the potential impact of active military service on the risks of preterm labour and birth, low birthweight, and stillbirth.
They scoured research databases for relevant studies, and included 21 that met all the eligibility criteria in their analysis. The studies, which involved 650,628 women serving in the US military, were all published between 1979 and 2023.
Ten of the studies included a comparison group—usually the wives of active service personnel. By way of a proxy for those that didn’t include a comparator, the study authors drew on national data from the US National Vital Statistics for any given year.
Analysis of the study results indicated no heightened risk of preterm birth among pregnant active service women. But there were significant methodological differences; most studies had a moderate to high risk of bias; and several included only small sample sizes, caution the study authors.
There was no observed association between branch of military service and increased risk of preterm birth, although again this should be interpreted cautiously as 5 studies included mixed service samples and the study design varied considerably, say the study authors.
There was no clear evidence for an increased risk of stillbirth among women on active military service, either.
But nearly two thirds (62.5%) of the studies concluded that women on active service may be at heightened risk of having a low birthweight baby, including one study with the lowest risk of bias. And 4 of the 5 studies that included a comparison group also indicated an increased risk of low birthweight.
Seven of the 8 studies reporting on low birthweight were carried out in single-service settings. Both of those from the US Air Force suggested a higher prevalence of low birthweight babies born to active duty military personnel.
But some 53% and 38% of the studies reporting on preterm birth and low birthweight, respectively, didn’t have a matched comparison group and relied on a proxy drawn from national statistical data.
This introduces a risk of systematic error as the baseline characteristics of the two groups are inherently different, caution the study authors.
Women on active military service will also be medically screened before any tours of duty and will have fewer co existing conditions, while national data will include high risk and multiple pregnancies, they explain.
Only observational studies were included in the review, and the data collection methods and/or adjustment for influential factors varied, acknowledge the study authors. Only 8 studies reported on smoking status despite a high prevalence of smoking in the military and the fact that smoking is associated with several health issues before and during pregnancy.
The data also focused exclusively on the US military, which although unsurprising given that it is one of the largest in the world, this does limit the generalisability of the findings to armed forces personnel elsewhere, highlight the study authors.
Nevertheless, they conclude: This review highlights a need for more female-specific research in armed forces, beyond the US military setting, to inform military maternity pathways and policies in ways that safeguard mothers and their babies while enhancing military readiness.”
JOURNAL
BMJ Military Health
METHOD OF RESEARCH
Systematic review
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Effect of active-duty military service on neonatal birth outcomes: a systematic review
ARTICLE PUBLICATION DATE
22-Apr-2024
Excessive pregnancy weight gain and substantial postpartum weight retention common in military health care beneficiaries
THE OBESITY SOCIETY
ROCKVILLE, Md.— Compared to their civilian counterparts, excessive pregnancy weight gain is more frequent among military health care beneficiaries, in particular active duty personnel, and is associated with costly maternal/neonatal complications. Women in this sample with excessive pregnancy weight gain were also three times more likely to have substantial postpartum weight retention, according to a new study published in the journal Obesity, The Obesity Society’s (TOS) flagship journal.
Substantial weight retention at 12 months postpartum was also more common among military health care beneficiaries in this sample than previously documented in civilian samples. Postpartum weight retention is a key concern for the United States military because it impacts active duty women’s ability to pass their fitness tests and is also associated with long-term maternal overweight and obesity.
“These results emphasize the importance of weight management before, during and after pregnancy for military populations, given the high health care costs of weight-related health complications affecting the mother and baby as well as the importance of maintaining fitness in the active duty population,” said Rebecca Krukowski, PhD, professor, Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, Va. Krukowski is the corresponding author of the study.
Data for military health care beneficiaries were obtained from the Military Health System Data Repository. More than 48,000 women who had given birth in 2018 and 2019 were included. Researchers examined relationships among overweight and obesity, pregnancy weight gain, maternal and neonatal complications and substantial postpartum weight retention.
Pregnancy weight gain was determined by the amount of weight gained between a measured pre-pregnancy weight to a delivery weight. The amount of pregnancy weight gain was then compared to the national guidelines for pregnancy weight gain from the National Academy of Medicine. For body mass index, women were classified into four categories: underweight, healthy, overweight, and obesity based on the pre-pregnancy weight and height. Substantial postpartum weight retention was defined as retention of at least 10 pounds at 12-months postpartum compared with pre-conception weight. Clinical outcomes potentially related to pregnancy weight gain and body mass index were abstracted from the maternal and neonatal health care records. For maternal clinical outcomes, cases of preeclampsia, pregnancy-induced hypertension, gestational diabetes and caesarean delivery were identified. For neonatal outcomes, researchers identified infants who experienced intrauterine growth restriction, were small or large for gestational age, had low birth weight and had a neonatal intensive care unit admission.
Results showed that 75% of TRICARE beneficiaries had excessive pregnancy weight gain. Military spouses and other family members were less likely than active duty women to have excessive pregnancy weight gain. Those with excessive pregnancy weight gain and/or overweight or obesity were more likely to have maternal complications such as pregnancy-induced hypertension and cesarean delivery. The findings also showed that 42% of the military beneficiaries had substantial postpartum weight retention. Additionally, women with excessive pregnancy weight gain were three times more likely to have substantial postpartum weight retention. Researchers add that pregnancy-related weight gain above the national guidelines and substantial postpartum weight retention may make it challenging to regain the required fitness levels for active duty women and for these women (who want to serve their country) to maintain their career in the military.
Other authors of the study include Wen You and Carol Copeland, Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, Va. Copeland is also with the 59th Medical Wing, Clinical Health Psychology, Joint Base San Antonio, Texas. Erin Solomon, Department of Psychology, University of Memphis, Memphis, Tenn.; Juan Lang, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Ky.; Emily Stone, Geneva Foundation, Bethesda, Md.; Rosemary Estevez Burns, 59th Medical Wing, Clinical Health Psychology, Joint Base San Antonio, Texas; Zoran Bursac, Department of Biostatistics, Florida International University, Miami, Fla.; Marion E. Hare, Department of Preventative Medicine, University of Tennessee Health Science Center, Memphis, Tenn.; and Teresa M. Waters, Augusta University, Institute for Public and Preventative Health, Augusta, Ga.
The authors declared no conflicts of interest.
The study, titled “Overweight/Obesity, Gestational Weight Gain, Postpartum Weight Retention and Maternal/Neonatal Complications in the Military” will be published in the May 2024 issue of Obesity.
# # #
The Obesity Society (TOS) is the leading organization of scientists and health professionals devoted to understanding and reversing the epidemic of obesity and its adverse health, economic and societal effects. Combining the perspective of researchers, clinicians, policymakers and patients, TOS promotes innovative research, education and evidence-based clinical care to improve the health and well-being of all people with obesity. For more information, visit www.obesity.org.
JOURNAL
Obesity
Women’s heart disease is underdiagnosed, but new machine learning models can help solve this problem
Using machine learning, scientists built more accurate models to predict heart disease risk and found that women are underdiagnosed compared to men, highlighting the need for sex-specific criteria
When it comes to matters of the heart, cardiovascular disease in women is underdiagnosed compared to men. A popular scoring system used to estimate how likely a person is to develop a cardiovascular disease within the next 10 years is the Framingham Risk Score. It is based on factors including age, sex, cholesterol levels, and blood pressure.
Researchers in the US and the Netherlands have now used a large dataset to build more accurate cardiovascular risk models than the Framingham Risk Score. They also quantified the underdiagnosis of women compared to men. The results were published in Frontiers in Physiology.
“We found that that sex-neutral criteria fail to diagnose women adequately. If sex-specific criteria were used, this underdiagnosis would be less severe,” said Skyler St. Pierre, a researcher at Stanford University's Living Matter Lab. “We also found the best exam to improve detection of cardiovascular disease in both men and women is the electrocardiogram (EKG).”
Underdiagnosis due to heart differences
Anatomically, female and male hearts are different. For example, female hearts are smaller and have thinner walls. Yet, the diagnostic criteria for certain heart diseases are the same for women and men, meaning that women’s hearts must increase disproportionally more than men’s before the same risk criteria are met.
When the researchers quantified the underdiagnosis of women compared to men, they found that the use of sex-neutral criteria leads to severe underdiagnosis of female patients. “Women are underdiagnosed for first degree atrioventricular block (AV) block, a disorder affecting the heartbeat, and dilated cardiomyopathy, a heart muscle disease, twice and 1.4 times more than men, respectively,” St. Pierre said. Underdiagnosis of women was also found for other heart disorders.
Old vs new
To achieve more accurate predictions for both sexes, the scientists leveraged four additional metrics that are not considered in the Framingham Risk Score: cardiac magnetic resonance imaging, pulse wave analysis, EKGs, and carotid ultrasounds. They used data from more than 20,000 individuals in the UK Biobank – a biomedical database comprising information from approximately half a million UK individuals aged 40 and older – who had undergone these tests.
“While traditional clinical models are easy to use, we can now use machine learning to comb through thousands of other possible factors to find new, meaningful features that could significantly improve early detection of disease,” explained St. Pierre. Just 10 years ago, these methods were not available, which is why assessment scales like the Framingham Risk Score have been used for half a century.
Using machine learning, the researchers determined that of the tested metrics, EKGs were most effective at improving the detection of cardiovascular disease in both men and women. This, however, does not mean that traditional risk factors are not important tools for risk assessment, the researchers said. “We propose that clinicians first screen people using a simple survey with traditional risk factors, and then do a second stage screening using EKGs for higher risk patients.”
Paving the way for custom medicine
The present study provides a first step into rethinking risk factors for heart disease. Leveraging new technologies is a promising way to improve risk prediction. However, there are some limitations to the study which should be addressed in the future, the researchers said.
One such limitation is the fact that in the UK Biobank sex is treated as a binary variable. Sex, however, is inherently complex, relating to hormones, chromosomes, and physical characteristics, all of which may fall somewhere on a spectrum between ‘typically’ male and ‘typically’ female.
In addition, the study population was middle-aged and older people residing in the UK, so the results may not be transferable to people from other backgrounds and ages. “While sex-specific medicine is one step in the right direction, patient-specific medicine would provide the best outcomes for everyone,” St. Pierre concluded.
JOURNAL
Frontiers in Physiology
METHOD OF RESEARCH
Data/statistical analysis
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Sex-specific cardiovascular risk factors in the UK Biobank
ARTICLE PUBLICATION DATE
23-Apr-2024
COI STATEMENT
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The authors also declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Follow-up 50 years on finds landmark steroid study remains safe
A follow-up analysis 50 years later finds no adverse heart health risk from Professor Graham 'Mont' Liggins' landmark steroid study to reduce illness and death for pre-term babies
A new study has found there are no adverse long-term cardiovascular health consequences for the now-adult children of mothers who were given corticosteroids because they were at risk of early birth in a landmark trial conducted in Auckland, New Zealand, 50 years ago.
The Auckland Steroid Study by obstetrician Professor Graham ‘Mont’ Liggins and paediatrician colleague Dr Ross Howie from 1969 to 1974 in Green Lane Hospital, Auckland, found that two corticosteroid injections given to pregnant women at risk of early (preterm) birth halved the incidence of respiratory distress in the babies and significantly reduced neonatal deaths.
Co-author of the new study, Dr Anthony Walters, says: “It was clear there were short-term benefits, but steroids are potent medications, and some have serious side effects."
He and colleagues carried out an analysis of the health data of 424 of the 1218 infants born about half a century ago. Their research found no evidence of adverse consequences for cardiovascular health, pre-diabetes and diabetes - health issues that were a possible risk based on animal studies but unlikely to develop in humans until they reached middle age.
“We’ve proven we don’t need to worry,” Walters says. “We are confident that although preterm babies have a whole range of health problems as they grow up, these are not caused by the steroid.”
The Liggins Institute continues to look at how steroids might be used as a treatment to reduce complications at birth, says Professor Dame Jane Harding of the Liggins Institute’s LiFePATH research group. “There are ongoing trials about the use of steroids to prevent lung disease in newborn babies. This study provides reassurance that these trials should go ahead.”
The study is part of the ANCHOR research programme, following up on the original Auckland Steroid Study and the later ACTORDS study, a multi-centre study at 23 centres across New Zealand and Australia between 1998 and 2004 to see if repeated courses of corticosteroids reduced the risk of lung disease and other serious illness.
JOURNAL
PLoS Medicine
METHOD OF RESEARCH
Data/statistical analysis
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Cardiovascular outcomes 50 years after antenatal exposure to betamethasone: Follow-up of a randomised double-blind, placebo-controlled trial
ARTICLE PUBLICATION DATE
21-Apr-2024
Analyzing the impact of ovulation-inducing agents on the quality of embryo
Settling a long-standing debate, researchers analyze the effects of artificial ovarian stimulation on fertility using a mouse model and live-cell imaging
Low birth rates have become a serious problem in many developed countries throughout the world, with Japan being a prime example. In Japan particularly, aging and stress have led to a massive rise in infertility, which now affects one in every 4.4 couples. To find a workaround this condition, many couples have now turned to assisted reproduction technologies (ARTs) and in vitro fertilization (IVF) for conception. However, even though ARTs and IVF methods are well-established and have been widely used for over four decades, birth rates post IVF in Japan are still critically low, peaking at a meager 10.2%.
One of the reasons behind the low success of IVF is closely related to the quality of the eggs or ‘oocytes’ collected from the ovaries. Today, there are two main approaches in clinical practice to obtain oocytes — the first being the stimulated cycle method and the other being the natural cycle method. In the stimulated cycle method, the patient is administered ovulation-inducing agents orally or through multiple injections. This enables doctors to extract multiple mature oocytes in one go. In contrast, the natural cycle method avoids or uses minimal administration of inducing agents, and typically only one or two oocytes can be collected per month as a part of the natural ovulation cycle. However, there is an ongoing debate regarding which method is better. This is important because not only does this impact couples differently, but also, there is no firm evidence on whether the ovulation inducing method affects the quality of the embryo.
Now, to address this knowledge gap, a research team from Japan conducted a study using an animal model to pry into the differences between oocytes collected using natural and stimulated approaches. This study was published online on 18 March 2024 in the Journal of Reproduction and Development and was conducted by Professor Kazuo Yamagata from the Faculty of Biology-Oriented Science and Technology (BOST), Kindai University, embryologist Mayuko Kurumizaka from Yokohama City University, Dr. Tatsuma Yao from Fuso Pharmaceutical Industries, Ltd., and Dr. Mikiko Tokoro from Asada Ladies Clinic.
Sharing the motivation behind their study, Prof. Yamagata explains, “Although the influence of ovarian stimulation on embryo quality has been described, this issue remains controversial. Here, we analyzed the influence of ovarian stimulation on developmental speed and chromosome segregation using live-cell imaging.”
The experimental protocol involved establishing two groups of female mice to collect oocytes from. The ‘stimulated group’ was treated with ovulation-inducing agents whereas the other ‘non-stimulated group’ was not given any drugs. Next, all the viable oocytes were fertilized using sperm obtained from a single male mouse, and the development of the embryos were monitored by live-cell imaging.
Initial experiments confirmed that the stimulated mice produced roughly 1.4 times more viable oocytes than the non-stimulated mice. Then, to assess developmental abnormalities in the fertilized oocytes, the researchers employed a novel live-cell imaging technique, which had been previously developed by the team to perform long-term observations of preimplantation embryos. By injecting the embryos with small amounts of RNA encoding a fluorescent protein, intracellular processes of some embryos could be observed. This approach enabled the visualization of embryonic development in a near-natural state.
Detailed observations of the developing embryos revealed no significant differences between both groups, suggesting that stimulation did not adversely affect the formation and distribution of chromosomes, or the process of cell multiplication. Interestingly, the researchers noted that initial cellular divisions were slightly faster in embryos produced from stimulated oocytes, leading to faster development. This is important since faster initial development can translate into higher chances of successful implantation.
Taken together, the results indicate that the stimulated cycle method is a viable technique to collect more number of oocytes than the natural cycle method and has no adverse effect on the quality of eggs. Although further research is needed in this domain, the research team expects their findings to have important implications in the future of fertility science. “Our study provides fertility clinics and patients with useful information that will help them decide whether to pursue ovarian stimulation or not,” concludes Prof. Yamagata.
We surely hope that this study paves the way for further research that may improve the process and success of ARTs.
Assessing the impact of ovulation-inducing drugs on the chromosome segregation of eggs
JOURNAL
Journal of Reproduction and Development
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Animals
ARTICLE TITLE
Effect of ovarian stimulation on developmental speed of preimplantation embryo in a mouse model
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