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March of Dimes Award-Winning Study Identifies New Approach to Personalize Prevention of Preterm Birth

New research findings may soon help doctors personalize preterm birth prevention treatments by identifying which women at higher risk for preterm birth will be helped by progesterone injections. Injections of one type of progesterone, a synthetic form of a hormone naturally produced during pregnancy, have been shown to reduce the risk of recurrent preterm births More »

Study Suggests Women 35 and Older are at Decreased Risk of Having Anatomically Abnormal Child

In a study to be presented on Feb. 6 at 3 p.m. CST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting™, in New Orleans, researchers will report that women ages 35 and older are at a decreased risk of having a child with a major congenital malformation, after excluding chromosomal abnormalities. Advanced More »

Study Finds Multifaceted Intervention Leads to Significant Reduction of Cesarean Deliveries and Neonatal Morbidity

In a study to be presented on Feb. 6 in an oral plenary session at 8 a.m. CST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting™, in New Orleans, researchers will report that Cesarean deliveries reviews and best practices implementation are effective to provide optimal care by an appropriate management of medical More »

Study Finds Remifentanil Patient Controlled Analgesia Not as Effective as Epidural Analgesia in Managing Pain Relief during Labor

In a study to be presented on Feb. 7 at 1:30 p.m. CST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting™, in New Orleans, researchers will report findings which suggest remifentanil patient controlled analgesia is not equivalent to epidural analgesia for pain, pain appreciation scores, and overall satisfaction in women who request More »

Study Finds Obesity during Pregnancy is Independent Risk Factor for Long-Term Cardiovascular Morbidity

In a study to be presented on Feb. 7 at 2:45 p.m. CST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in New Orleans, researchers will report that obesity during pregnancy is an independent risk factor for long-term cardiovascular morbidity, and these complications tend to occur at a younger age. Researchers More »

Leaders in Women’s Health Convene to Save Mothers’ Lives

WASHINGTON, March 5, 2014—The Society for Maternal-Fetal Medicine (SMFM), the American Congress of Obstetricians and Gynecologists, the Association of Women’s Health, Obstetric and Neonatal Nurses, the Centers for Disease Control and Prevention, and other groups have created the Council on Patient Safety in Women’s Health Care.

“The Council on Patient Safety in Women’s Health Care is a collaborative effort with the goal of continually improving patient safety in women’s health care through multidisciplinary collaboration that drives culture change,” said SMFM board member and council chair Alfred Abuhamad.

Despite medical advances, mothers in the U.S. are more at risk of dying from pregnancy related problems today than they were in 1990. Women in the United States are twice as likely to have a life-threatening problem during pregnancy or childbirth than women in western Europe.

This week, the council launched a web site, Safe Health Care for Every Woman. To improve care, the site provides standardized tools for Severe Maternal Morbidity review. Hospitals can use these tools to identify problems with care delivery and reduce the chance of future life-threatening events.

“As high risk pregnancy experts, maternal-fetal medicine physicians lead patient safety programs throughout the country,” said Peter Bernstein, a SMFM board member and council member. “The first step is to identify the systems issues that put families at risk, and these Severe Maternal Mortality review forms facilitate that process.”

Excessive bleeding after childbirth is a leading cause of severe morbidity and mortality for pregnant women. In April, the council will release an Obstetric Hemorrhage Patient Safety Bundle with step-by-step, evidence-based tools to manage risk, prevent adverse events, and respond and debrief.

Later in the spring, the council will share Maternal Early Warning Criteria to identify mothers who require urgent bedside evaluation. Additional planned safety bundles will provide guidance on treatment of severe hypertension and prevention of venous thromboembolism in pregnancy.

“The council has brought together nurses, midwives, physicians, patient safety specialists and industry partners to realize our vision of safe healthcare for every woman,” Abuhamad said. “Together, we improve care.”

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The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine.  The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed.  For more information visit www.smfm.org.

 

 

SMFM Physicians Recommend NIPT for High-Risk Patients

WASHINGTON, March 5, 2014—A paper published on Feb. 27, 2014 in the New England Journal of Medicine titled DNA Sequencing versus Standard Prenatal Aneuploidy Screening has garnered a great deal of media attention focused on the use of maternal serum cell-free DNA screening, or noninvasive prenatal testing (NIPT) for aneuploidy in average risk patients. The authors, supported by one of the commercial laboratories, compared NIPT with traditional screening for aneuploidy using serum analytes on a relatively small number of average risk patients. The study was too small to compare detection rates, but the authors report that the false positive rate of NIPT is lower and therefore the test “merits serious consideration as a primary screening method for fetal autosomal aneuploidy.

While this measured conclusion appears reasonable, the serious consideration that the authors propose requires further data, and the study by Bianchi et al has to be viewed in the context of its many limitations. Most importantly, the study is underpowered to compare the detection rates, and it is generally not valid to compare false-positive rates in isolation.

NIPT uses cell-free DNA from maternal serum to screen for common fetal aneuploidies with high sensitivity and specificity. It also uses next generation sequencing to directly measure fetal DNA in the maternal circulation, and clinical tests are now available using this technique. While there are differences in the methodologies employed by the commercial laboratories, overall the reported performance is similar, with detection rates for Down syndrome above 99 percent and false positive rates that are less than one percent. This makes this screening test an attractive alternative to traditional serum screening for aneuploidy for patients.

Currently, the Society for Maternal-Fetal Medicine (SMFM) recommends that NIPT is most appropriate for high-risk patients. The five high-risk criteria currently include maternal age 35 years or older at delivery, sonographic findings indicating an increased risk of aneuploidy, history of a prior pregnancy with a trisomy, positive screening results for aneuploidy, including first trimester, sequential, integrated, or quadruple screen, or parental balanced Robertsonian translocation with increased risk for trisomy 13 or 21.

This recommendation has been based primarily on the more limited evidence regarding the utility of NIPT in low- or average-risk pregnant women, and validation studies that have generally been limited to high-risk populations. Understandably, there is a keen interest in performing the same type of validation studies in a low-risk population.

The study compared only false positive rates for trisomies 18 and 21, although all commercially available products also include testing for trisomy 13 and the sex chromosomes, which have higher false positive rates. A high percentage of the samples for NIPT were collected in the third trimester – at gestational ages when clinical aneuploidy screening is not performed and is not clinically relevant, yet when fetal DNA amounts are far higher allowing better test performance. The authors compared NIPT with standard prenatal screening with a variety of first and second trimester tests that have a broad range of performance characteristics. Fewer than three percent of patients had integrated screening, which is the prenatal screening method with the best performance, including the lowest false positive rate. In addition, traditional screening can detect risk for a broad array of structural, chromosomal and perinatal abnormalities.

“The importance of these in a low-risk population may be far greater than the impact of trisomy 18 and 21, which are relatively rare in a younger maternal cohort.  It is important to note that this study included only five Down syndrome. Five cases of trisomy 21 in the population of 1909 patients represents a rate of 1 out of 381, which is substantially higher than the population risk of 1 out of 700 that would be expected in a truly “average” or “low-risk” cohort,” said Dr. Vincenzo Berghella, president of SMFM. “Finally and importantly, when considering population screening, some patients who choose NIPT will fail to obtain a result. While that number was just under 1 percent in this study, rates as high as 12 percent have been published, especially in overweight and obese women.”

SMFM has reviewed the evidence, including this recent paper, and feels that while NIPT is a promising new technology, and this new report is important and excellent news, it is not enough to change current ACOG and SMFM recommendations. Given that just eight aneuploidies were present in the entire cohort of patients, the true test performance is difficult to determine.

“Further evidence comparing costs, false positive rates for all included analyses, ability to obtain a result, and overall test performance for all detectable abnormalities in larger numbers of truly average risk patients are required to justify changing recommendations regarding population based prenatal screening from just high-risk pregnancies, to all pregnancies. We eagerly await the results of ongoing research studies which will address these issues,” said Berghella.

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The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine.  The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed.  For more information visit www.smfm.org.

 

SMFM Physicians Urge Caution when Interpreting Recent Study on Tylenol and Childhood ADHD

WASHINGTON, March 3, 2014—In response to a recent study of Tylenol exposure during pregnancy and childhood ADHD, high-risk pregnancy experts are urging caution when interpreting results.

“These results are interesting, but it’s premature to change the advice we give to patients,” said Dr. Vincenzo Berghella, president of the Society for Maternal-Fetal Medicine.

In the recent study of acetaminophen and childhood development, the authors found higher rates of ADHD-like behavioral problems among children whose mothers had taken acetaminophen during pregnancy. In the US, acetaminophen is mostly found in Tylenol as well as other pain medications. More than half of the women included in the study had taken acetaminophen at some point during their pregnancy.

Using a standardized score for ADHD-like behavior, the authors found that 3.4 percent of children whose mothers had taken acetaminophen had an elevated score, compared with 2.5 percent of never-users. This 1.36-fold difference diminished to 1.13-fold when the authors accounted for factors such muscle or joint pain, mental health problems, and fever or illness during pregnancy that differed between mothers who did and did not take acetaminophen.

“The study has a number of limitations and its results need to be considered in context,” Berghella said. “The authors found a less-than-one-percent difference in risk.”

Berghella also noted that an association found in an observational study does not necessarily equate with causation. Unmeasured differences between mothers who did and did not take acetaminophen, such as differences in susceptibility to pain, might be behind the use of acetaminophen as well as explain their child’s risk of ADHD-like behavioral problems. In other words, the reason the acetaminophen was taken could have been the real culprit, and not the acetaminophen itself.

“In fact, as the authors state, maternal infections or immunologic factors have been linked to childhood ADHD. These are the conditions for which acetaminophen is often used, so this is what is called ‘confounding,’ a finding which seems due to a factor, but is in fact due to another issue (e.g. infection) linked to both the exposure (e.g. acetaminophen) and outcome (e.g. ADHD).”

It is also important to note that the association with ADHD was mostly seen with prolonged use, sometimes weeks or months, a practice that is not typical of how acetaminophen is prescribed in most pregnancies. Tylenol is one of the few medications we can use in pregnancy to treat pain and control the temperature during a fever.

“Publicity about the study results might actually lead to worse outcomes for mothers and infants,” Berghella said. “For example, high fever during pregnancy is associated with increased risk of complications. Women with febrile illnesses who don’t treat their fever in order to avoid Tylenol might increase the risk of serious complications.”

Other medications to control pain or fever, such as ibuprofen and other non-steroidal anti-inflammatory drugs, have well-described risks for the fetus, including damage to the developing kidneys and changes in blood flow to the fetal heart. Substituting these pain medications to Tylenol may lead to more harm.

Additional studies are needed in order to determine whether acetaminophen causes ADHD. “We need prospective studies of all drugs used in pregnancy and lactation, not just acetaminophen, so that pregnant women or women considering pregnancy can make informed decisions about treatment,” Berghella said. “These results underscore the need for well-designed studies of medication safety in pregnancy and lactation.”

“Most drug trials do not include pregnant women, leaving mothers and their providers with limited information to weigh the risks and benefits of treatment,” Berghella continued. “This gap in understanding has become increasingly problematic as more women delay childbearing and rates of chronic disease rise, because more mothers than ever before are requiring medications to manage conditions such as diabetes, hypertension, depression, and asthma.”

Women should not take any medications, even over the counter medications, without consulting their care provider. As mentioned above, acetaminophen containing medications are still safer than other medications to control pain or fever. If needed, it should be taken for a limited time. If the symptoms persist after few days on acetaminophen, then follow up with the care provider is needed in order to consider other treatments.

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The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine.  The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed.  For more information visit www.smfm.org.

March of Dimes Award-Winning Study Identifies New Approach to Personalize Prevention of Preterm Birth

New research findings may soon help doctors personalize preterm birth prevention treatments by identifying which women at higher risk for preterm birth will be helped by progesterone injections.

Injections of one type of progesterone, a synthetic form of a hormone naturally produced during pregnancy, have been shown to reduce the risk of recurrent preterm births by about a third.

Nearly half a million babies are born too soon each year in the United States. Preterm birth (birth before 37 weeks of pregnancy) is the leading cause of newborn death, and babies who survive an early birth often face an increased risk of a lifetime of health challenges, such as breathing problems, cerebral palsy, intellectual disabilities and others. Even babies born just a few weeks early have higher rates of hospitalization and illness than full-term infants.  It is a serious health problem that costs the United States more than $26 billion annually

Tracy Manuck, M.D., assistant professor of Maternal Fetal Medicine and co-director of the University of Utah Prematurity Prevention Clinic at University of Utah Health Care, has been working to understand why progesterone treatments prevent preterm birth for some women but not for others. She hopes to determine whether there is a way to personalize their treatment based on their genetic makeup. She presented her latest findings at the Society for Maternal-Fetal Medicine’s 34th annual meeting, The Pregnancy Meeting™.

“This is the first step in using pharmacogenomics to prevent preterm birth,” said Edward R.B. McCabe, MD, March of Dimes chief medical officer. “There is a group of women in whom progesterone will be effective and others for whom it will not be and who will need different treatments. Knowing which group a woman belongs to would fast track her to the proper treatment. The goal is to find personalized treatments that work for individuals to prevent preterm birth.”

Dr. Manuck and her colleagues looked at 50 women followed in a prematurity prevention clinic at Intermountain Healthcare in Utah who received progesterone treatment and separated them by whether they responded to the treatment. The team then sequenced all of the areas of the women’s genomes that code for proteins and looked for genetic differences between the two groups.  The team identified several genes and general biologic pathways that were more likely to be expressed in women who did not respond to progesterone.

“Preterm birth is a complex health problem and it’s unlikely that we will find a single genetic cause,” said Dr. Manuck. “We know that not all women with a prior preterm birth can be helped by progesterone treatments, and we’re trying to identify who those women are.”

Dr. McCabe will present Dr. Manuck with the March of Dimes award for Best Abstract in Prematurity at the SMFM’s Annual Meeting.  2014 marks the 11th year the March of Dimes award has been presented. Dr. Manuck is a two-time recipient of the honor. She was honored in 2009 for research that looked at progesterone receptors and progesterone response.

“Dr. Manuck has continued to focus her research on progesterone, but her methods have evolved. She has gone from the traditional hypothesis testing approach to a discovery science approach, scanning the landscape to find informative areas and inviting researchers from a variety of disciplines to collaborate with her,” said Dr. McCabe. “She’s doing important work because she’s encouraging people to come out of their comfort zones and cross the boundaries between disciplines.”

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A copy of the abstract is available at http://www.smfmnewsroom.org and below.  For interviews please contact Vicki Bendure at Vicki@bendurepr.com 202-374-9259 (cell), or Meghan Blackburn at Meghan@bendurepr.com, 540-687-5099 (office) or 859-492-6303 (cell).

The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine.  The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed. Visit www.smfm.org.  

The March of Dimes is the leading nonprofit organization for pregnancy and baby health.  For more than 75 years, moms and babies have benefited from March of Dimes research, education, vaccines, and breakthroughs.  Find out how you can help raise funds to prevent premature birth and birth defects by walking in March for Babies at marchforbabies.org.  Find us on Facebook and follow us on Twitter. The 2014 March for Babies is sponsored nationally by the March of Dimes number one corporate supporter Kmart, Macy’s, Famous Footwear, Cigna, Sanofi Pasteur, Mission Pharmacal, United Airlines and Actavis.

 

Abstract 9: Genetic Variation in Key Biologic Processes May Influence Response to 17-alpha hydroxyprogesterone Caproate (17P) for Recurrent Preterm Birth (PTB) Prevention

Authors: Tracy Manuck1, Scott Watkins2, M. Sean Esplin1, Michael Varner1, G. Marc Jackson1, Barry Moore2, Mark Yandell2, Lynn Jorde2

1Intermountain Healthcare and The University of Utah, Obstetrics and Gynecology, Salt Lake City, UT, 2The University of Utah, Human Genetics, Salt Lake City, UT 

Objective: We hypothesized that genetic variation affects variable response to 17P for recurrent PTB prevention.

Study Design: Women with ≥1 spontaneous singleton PTB <34 wks who received 17P were recruited prospectively and classified as a 17P responder (RES) or non-responder (NRES) by the difference in delivery gest. age (GA) between 17P treated & untreated pregnancies. Illumina® HiSeq2000 whole exome sequencing technology genotyped each woman for ~180,000 protein-coding exons. Exomes were compared between RES and NRES women using the Variant Annotation, Analysis & Search Tool (VAAST), a probabilistic search tool for identifying disease-causing variants, & compared to a KEGG pathway candidate gene list. The top 2.5% of genes (n=470) with the highest VAAST scores were then selected for pathway analysis. Genes were classified by the online Protein ANalysis THrough Evolutionary Relationships (PANTHER) system into known gene ontology molecular functions & biologic processes. Gene distributions within these classifications were compared to an online referent population to search for areas of over- and under- representation. Bonferroni-corrected p-values are reported.

Results: 50 women (41 RES, 9 NRES, all European ancestry) were included. RES and NRES did not differ with regards to parity, CI hx, or PPROM hx. RES delivered, on avg, +9.2 wks longer with 17P vs. +1.3 wks for NRES (p<0.001). All samples met genotype quality filters, and the avg depth of exome coverage was 51 +/- 18. Our VAAST analysis allowed for recessive inheritance & locus heterogeneity. The NOS1 gene scored highest in VAAST among the KEGG-pathway identified candidate genes (Figure). PANTHER analysis revealed several over- represented biologic processes (Table).

Conclusion: Using a novel analytic approach, we have identified over-represented genes in key processes (incl. the biologically plausible NO signal pathway) among RES to 17P, the 1st step in applying pharmacogenomics to PTB prevention.

Figure. Shown are 3 representative samples corresponding to women who are heterozygotes for the NOS1 (nitric oxide synthase 1) gene on chr 12. The NOS1 gene was the top hit among KEGG candidate genes and was in the top 10 hits on the overall VAAST gene list.

Figure. Shown are 3 representative samples corresponding to women who are heterozygotes for the NOS1 (nitric oxide synthase 1) gene on chr 12. The NOS1 gene was the top hit among KEGG candidate genes and was in the top 10 hits on the overall VAAST gene list.

Table. PANTHER gene ontology pathway analysis results comparing the distribution of the leading genes identified by VAAST within known molecular functions and biologic processes to evaluate for over- and under- representation. All statistically significant pathways were over-represented in our gene list.  *After Bonferroni correction for multiple testing

Table. PANTHER gene ontology pathway analysis results comparing the distribution of the leading genes identified by VAAST within known molecular functions and biologic processes to evaluate for over- and under- representation. All statistically significant pathways were over-represented in our gene list.
*After Bonferroni correction for multiple testing

Study Suggests Women 35 and Older are at Decreased Risk of Having Anatomically Abnormal Child

In a study to be presented on Feb. 6 at 3 p.m. CST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting™, in New Orleans, researchers will report that women ages 35 and older are at a decreased risk of having a child with a major congenital malformation, after excluding chromosomal abnormalities.

Advanced maternal age, traditionally defined as 35 and older, is a well-established risk factor for having a child with a chromosomal abnormality, such as Down syndrome. However, little information is available regarding the association between advanced maternal age and the risk for having a child with a major congenital malformation—a physical defect present at birth that can involve different parts of the body, including but not limited to the heart, brain, kidney, bones or intestinal track.

In order to address this question, this retrospective study used obstetric and ultrasound information collected from over 76,000 women at the time they presented for their routine second trimester ultrasound at Washington University in St. Louis (Mo.). Researchers compared the incidence of having one or more major congenital malformations diagnosed at the time of ultrasound in women who were younger than 35 versus those women 35 years and older.

Also examined was the incidence of major malformations of women categorized by organ system including heart, brain and kidney. Overall, we found that advanced maternal age was associated with a 40 percent decreased risk of having a child with one or more major congenital malformations, after controlling for other risk factors. Specifically, the incidence of brain, kidney, and abdominal wall defects were decreased in this group of women, while the incidence of heart defects was unchanged.

“As more women are choosing to delay childbearing, they are faced with many increased pregnancy risks,” said Katherine R. Goetzinger M.D., M.S.C.I., one of the study’s researchers. “Findings from this study may provide some reassurance for these women regarding the likelihood of having an anatomically normal child.”

Goetzinger, an assistant professor of maternal-fetal medicine at Washington University in St. Louis School of Medicine, also noted that it is possible that advanced maternal age conveys a “survival of the fittest” effect, in which anatomically normal fetuses are more likely to survive.

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A copy of the abstract is available at http://www.smfmnewsroom.org and below.  For interviews please contact Vicki Bendure at Vicki@bendurepr.com 202-374-9259 (cell), or Meghan Blackburn at Meghan@bendurepr.com, 540-687-5099 (office) or 859-492-6303 (cell).

The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine.  The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed.  For more information visit www.smfm.org.

 

Abstract 34: Advanced Maternal Age and the Risk of Major Congenital Anomalies: Survival of the Fittest?

Authors: Katherine Goetzinger1, Anthony Shanks1, Anthony Odibo1, George Macones1, Alison Cahill1

1Washington University in St. Louis, Obstetrics & Gynecology, St. Louis, MO

Objective: Advanced maternal age (AMA) is a well-established risk factor for fetal chromosomal abnormalities secondary to defects in cell division; however, the relationship between AMA and major congenital anomalies remains unknown. The objective of this study was to determine if AMA is an independent risk factor for major congenital anomalies diagnosed at the time of second trimester anatomic survey, in the absence of aneuploidy.

Study Design: This is a retrospective cohort study of all patients with a singleton gestation presenting for second trimester anatomic survey over an 18 year period. Cases of aneuploidy were excluded. Study groups were defined by maternal age <35 versus ≥35 years. The primary outcome was the presence of one or more major fetal anomalies diagnosed at second trimester ultrasound. Univariate and multivariate logistic regression analyses were used to estimate the risk of major fetal anomalies in women who were AMA. The distribution of fetal anomalies by organ system was also compared between the study groups.

Results: Of 76,156 euploid fetuses, 2.4% (n=1,804) were diagnosed with a major anomaly. There was a significant decrease in the incidence of major fetal anomalies with increasing maternal age until the threshold of age 35. (p<0.001) AMA was significantly associated with an overall decreased risk for major fetal anomalies (aOR 0.59, 95% CI 0.52-0.66) after controlling for potential confounders. Specifically, the incidence of central nervous system (CNS), renal, and abdominal wall anomalies were decreased in women ≥35 years. This was contrasted by the similar rate of cardiac anomalies between the study groups. (Table)

Conclusion: AMA is associated with an overall decreased risk for major fetal congenital anomalies, driven by a decrease in CNS, renal and abdominal wall defects. These surprising findings may suggest that the “all or nothing” phenomenon plays a more robust role in embryonic development with advancing oocyte age, with anatomically normal fetuses being more likely to survive.

 

 *Adjusted for alcohol use, gestational diabetes, pre-gestational diabetes, and African American race †Adjusted for gestational diabetes, pre-gestational diabetes, and African American race ¶Adjusted for tobacco use, parity, and African American race

*Adjusted for alcohol use, gestational diabetes, pre-gestational diabetes, and African American race †Adjusted for gestational diabetes, pre-gestational diabetes, and African American race ¶Adjusted for tobacco use, parity, and African American race

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