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Developmental Biology - Sex Determination

Fewer Baby Boys for Stressed Moms

Stress during pregnancy may affect baby's sex and even risk preterm birth...

It's becoming well established that maternal stress during pregnancy can affect fetal and child development as well as birth outcomes, and a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian now identifies the types of physical and psychological stress that may matter most.

The study was published online in the journal Proceedings of the National Academy of Sciences, or PNAS.

"The womb is an influential first home, as important as the one a child is raised in, if not more so," says study leader Catherine Monk, PhD, professor of medical psychology at Columbia University Vagelos College of Physicians and Surgeons and director of Women's Mental Health in the Department of Obstetrics & Gynecology at NewYork-Presbyterian/Columbia University Irving Medical Center.
Stress can manifest in a variety of ways, both as a subjective experience and in physical and lifestyle measurements. Monk and her colleagues examined 27 indicators of psychosocial, physical, and lifestyle stress collected from questionnaires, diaries, and daily physical assessments of 187 otherwise healthy pregnant women (ages 18 to 45).

About 17% (32) of the women were psychologically stressed, with clinically meaningful high levels of depression, anxiety, and perceived stress. Another 16% (30) were physically stressed, with relatively higher daily blood pressure and greater caloric intake compared with other healthy pregnant women. The majority (nearly 67%, or 125) were healthy.

Fewer Baby Boys with Mental Stress?

The study suggests pregnant women experiencing physical and psychological stress are less likely to have a boy.

On average, around 105 males are born for every 100 female births. But in this study, the sex ratio in the physically and psychologically stressed groups favored girls, with male-to-female ratios of 4:9 and 2:3, respectively.
"Other researchers have seen this pattern after social upheavals, such as the 9/11 terrorist attacks in New York City, after which the relative number of male births decreased. This stress in women is likely of a long-standing nature.

Studies have shown males are more vulnerable to adverse prenatal environments, suggesting highly stressed women may be less likely to give birth to a male due to the loss of prior male pregnancies, often without even knowing they were pregnant."

Catherine C. Monk PhD, Department of Obstetrics and Gynecology, Columbia University Medical Center; Division of Behavioral Medicine, New York State Psychiatric Institute; Department of Psychiatry, Columbia University, New York, New York, USA.

Other Impacts of Stress

Physically stressed mothers, with higher blood pressure and caloric intake, were more likely to give birth prematurely than unstressed mothers.

Among physically stressed mothers, fetuses had reduced heart rate-movement coupling — an indicator of slower central nervous system development — compared with unstressed mothers. Psychologically stressed mothers had more birth complications than physically stressed mothers.

Social Support Matters

What most differentiated the three groups was the amount of social support a mother received from friends and family, researchers found.

For example, the more social support a mother received, the greater likelihood of her having a male baby. When social support was statistically equalized across the groups, the stress effects on preterm birth disappeared. "Screening for depression and anxiety are gradually becoming a routine part of prenatal practice," says Monk. "But while our study was small, the results suggest enhancing social support is potentially an effective target for clinical intervention."

An estimated 30% of pregnant women report psychosocial stress from job strain or related to depression and anxiety, according to the researchers. Such stress has been associated with increased risk of premature birth, which is linked to higher rates of infant mortality and of physical and mental disorders, such as attention-deficit hyperactivity disorder and anxiety, among offspring.

How a mother's mental state might specifically affect a fetus was not examined. "We know from animal studies that exposure to high levels of stress can raise levels of stress hormones like cortisol in the uterus, which in turn can affect the fetus," says Monk. "Stress can also affect the mother's immune system, leading to changes that affect neurological and behavioral development in the fetus. What's clear from our study is that maternal mental health matters, not only for the mother but also for her future child."

Despite decades of prenatal programming research showing that “the womb may be more important than the home” with respect to offspring health outcomes, no studies of which we are aware have considered multiple indicators of maternal stress to identify the types of maternal stress that most influence developing offspring. This study’s key contributions include the use of a data-driven procedure to specify types of maternal stress—psychological and subclinical physical health indicators—that predict offspring outcomes including sex at birth, risk of preterm birth, and fetal neurodevelopment. Social support is a key factor differentiating the stress groups and a malleable intervention target to improve offspring outcomes.

Maternal prenatal stress influences offspring neurodevelopment and birth outcomes including the ratio of males to females born; however, there is limited understanding of what types of stress matter, and for whom. Using a data-driven approach with 27 variables from questionnaires, ambulatory diaries, and physical assessments collected early in the singleton pregnancies of 187 women, 3 latent profiles of maternal prenatal stress emerged that were differentially associated with sex at birth, birth outcomes, and fetal neurodevelopment. Most women (66.8%) were in the healthy group (HG); 17.1% were in the psychologically stressed group (PSYG), evidencing clinically meaningful elevations in perceived stress, depression, and anxiety; and 16% were in the physically stressed group (PHSG) with relatively higher ambulatory blood pressure and increased caloric intake. The population normative male:female secondary sex ratio (105:100) was lower in the PSYG (2:3) and PHSG (4:9), and higher in the HG (23:18), consistent with research showing diminished male births in maternal stress contexts. PHSG versus HG infants were born 1.5 wk earlier (P < 0.05) with 22% compared to 5% born preterm. PHSG versus HG fetuses had decreased fetal heart rate–movement coupling (P < 0.05), which may indicate slower central nervous system development, and PSYG versus PHSG fetuses had more birth complications, consistent with previous findings among offspring of women with psychiatric illness. Social support most strongly differentiated the HG, PSYG, and PHSG groups, and higher social support was associated with increased odds of male versus female births. Stress phenotypes in pregnant women are associated with male vulnerability and poor fetal outcomes.

Kate Walsh, Clare A. McCormack, Rachel Webster, Anita Pinto, Seonjoo Lee, Tianshu Feng, H. Sloan Krakovsky, Sinclaire M. O’Grady, Benjamin Tycko, Frances A. Champagne, Elizabeth A. Werner, Grace Liu, and Catherine Monk.

The authors report no financial or other conflicts of interest.

The research was funded by a grant from the National Institutes of Health (R01MH092580).

Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cuimc.columbia.edu or columbiadoctors.org.

NewYork-Presbyterian is one of the nation's most comprehensive, integrated academic healthcare systems, encompassing 10 hospital campuses across the Greater New York area, more than 200 primary and specialty care clinics and medical groups, and an array of telemedicine services.

A leader in medical education, NewYork-Presbyterian Hospital is the only academic medical center in the nation affiliated with two world-class medical schools, Weill Cornell Medicine and Columbia University Vagelos College of Physicians and Surgeons. This collaboration means patients have access to the country's leading physicians, the full range of medical specialties, latest innovations in care, and research that is developing cures and saving lives.

Ranked the #5 hospital in the nation and #1 in New York in U.S. News & World Report's "Best Hospitals" survey, NewYork-Presbyterian Hospital is also recognized as among the best in the nation in every pediatric specialty evaluated in the U.S. News "Best Children's Hospitals" survey. Founded nearly 250 years ago, NewYork-Presbyterian Hospital has a long legacy of medical breakthroughs and innovation, from the invention of the Pap test to the first successful pediatric heart transplant, to pioneering the groundbreaking heart valve replacement procedure called TAVR.

NewYork-Presbyterian's 47,000 employees and affiliated physicians are dedicated to providing the highest quality, most compassionate care to New Yorkers and patients from across the country and around the world. NewYork-Presbyterian hospitals are not for profit and provide more than $1 billion in benefits every year to the community, including medical care, school-based health clinics and support for more than 300 community programs and activities. For more information, visit http://www.nyp.org and find us on Facebook, Twitter, Instagram, and YouTube.

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Oct 16 2019   Fetal Timeline   Maternal Timeline   News  

Stress affects mother's immune system

Maternal prenatal stress not only influences offspring neurodevelopment, but birth outcomes including ratio of males to females born. But, there is limited knowledge of what types of stress matter and for whom. CREDIT Public Domain.

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