gestational diabetes

Answering the Unknowns of Taxanes for Breast Cancer During Pregnancy

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Taxane exposure during pregnancy appears to be safe for mothers and offspring, according to a new retrospective cohort analysis. The findings shed light on a relatively unstudied topic. “Our cohort with 103 patients represents the most extensive study to date, and our main goal was to have homogeneous reporting of adverse events,” Ana Ferrigno Guajardo, MD, said in an interview. She presented the results at the San Antonio Breast Cancer Symposium.

“Breast cancer during pregnancy is a very challenging clinical situation as the expected antineoplastic effects of treatment must be carefully balanced against potential detrimental consequences on the developing fetus,” said Dr. Guajardo. She is a resident physician at Yale University School of Medicine.

Anthracycline-based chemotherapy agents are generally used during pregnancy because there is more safety data available for them, but some studies have shown that taxanes may have better efficacy in some clinical situations. “Cohort studies that have been done in the past [show] that taxane use is mostly deferred to the postpartum period, and we are not really sure of the impact that can have on survival in patients postponing treatment,” said Dr. Guajardo.

There are potential safety concerns with taxanes because neonates lack the cytochrome enzymes to metabolize the drugs, which creates a theoretical risk of adverse effects due to prolonged activity. On the other hand, pregnant women metabolize taxanes faster, and there are placental barriers that can inhibit high molecular weight molecules like taxanes from reaching the fetus, according to Dr. Guajardo.

In addition to pregnancy outcomes, the researchers followed 28 infants, and found that 87% were found to be completely healthy, “so we were relatively reassured. But of course we think that there’s a need for prospective studies that validate our findings regarding the safety taxanes,” said Dr. Guajardo.

Although there is no direct comparison group, the findings correlate well with studies of the general population and other chemotherapy agents. “We have large cohorts with mostly anthracycline-based chemotherapy agents during pregnancy that we can compare our results to, and overall, we were reassured that the prevalence of complications that we found in our cohort was very similar or even lower to those reported in the literature with patients treated with anthracycline-based therapy,” said Dr. Guajardo.

Compared with the general population, the team found higher rates of preterm births, neonatal ICU admissions, and premature membrane rupture, and infants that are small for gestational age. However, with the exception of the latter, all of these risks have been seen in pregnant women treated with other types of chemotherapy. “Perhaps it would be interesting to see if the incidence of small for gestational age neonates might be a bit higher in this population when compared to anthracycline-based therapy agents, but that does require a study that has a comparator group,” said Dr. Guajardo.

The researchers recruited 103 women with an average age of 34 years from 10 centers in 6 countries: United States, France, Spain, Mexico, Italy, and Costa Rica. The great majority were also treated with anthracyclines during gestation, and nearly all (97%) were treated with paclitaxel. The live birth rate was 98%, and 43.4% were preterm, 24% were small for gestational age, 16% were admitted to the neonate ICU, and 12.5% had hyperbilirubinemia.

Obstetric complications included intrauterine growth restriction (9%), preterm premature rupture of membranes (5%), gestational diabetes mellitus (5%), hypertensive disorders (4%), and pregnancy loss (2%).

After the presentation, Virginia Borges, MD, professor of medical oncology at University of Colorado Anschutz Medical Center, served as a discussant.

“Highlights of this study [include] that it is an international cohort from over six countries with over 100 cases of women included specifically focusing on the use of paclitaxel. They demonstrated safe outcomes for the pregnancies and the mothers,” Dr. Borges said during her presentation.

She went on to highlight several key points that physicians should consider when treating pregnancy-related breast cancer. “We want to achieve prepartum treatment wherever feasible to tackle that cancer before delivery of the child to prevent a pregnancy-related breast cancer from potentially turning into a postpartum breast cancer,” she said.

“If the tumor is ER+/HER2-, we now see we can safely give anthracyclines and taxanes from 12 to about 35 weeks of gestation. We don’t want to get too close to the delivery with chemotherapy. If a patient is HER2+, I prefer to give the anthracycline portion while the person is pregnant and then after delivery incorporate the taxane with the HER2 targeted therapies as there’s some older data showing concurrent therapy looks a bit better than sequential. In triple negative breast cancer, again I prefer to give the anthracycline and delay the taxane and carboplatin to overlap with immunotherapy so we are getting the necessary synergy there as well,” Dr. Borges added.

Gestational diabetes combined with overweight or obesity increases severe COVID-19 risk

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Pregnant women with gestational diabetes, combined with periconceptional overweight or obesity, had an increased risk for severe COVID-19, according to results of a prospective observational study.

This was especially prevalent among pregnant women who required insulin therapy, data from the COVID-19 Obstetric and Neonatal Outcome Study (CRONOS) showed.

Data derived from Kleinwechter HJ, et al. Am J Obstet Gynecol. 2022;doi:10.1016/j.ajog.2022.05.027.
Data derived from Kleinwechter HJ, et al. Am J Obstet Gynecol. 2022;doi:10.1016/j.ajog.2022.05.027.

“Most important for clinicians to know is that not only pre-existing diabetes, but also gestational diabetes is a risk factor for severe COVID-19, especially when it occurs in overweight individuals,” Ulrich Pecks, MD, a professor in the department of obstetrics and gynecology at the University Hospital Schleswig-Holstein in Kiel, Germany, told Healio. “Presumably, the severity of the diabetic metabolic condition also plays a role.”

While it is known that gestational diabetes mellitus (GDM) is a common pregnancy complication — global prevalence was 13.4% in 2021 — research on the association of GDM and maternal and neonatal pregnancy outcomes among pregnant women infected with SARS-CoV-2 are lacking.

Pecks and colleagues conducted an analysis of 1,490 women (mean age, 31 ± 5.2 years; 40.7% nulliparous) who had COVID-19 between April 3, 2020, and Aug. 24, 2021, none of whom were vaccinated, according to Pecks.

“A general recommendation for vaccination during pregnancy was not issued in Germany until September 2021 … unfortunately, vaccination rates among pregnant women are still low at about 40%,” he said.

Maternal outcomes

Overall, results showed that GDM was not associated with adverse maternal outcomes (OR = 1.5; 95% CI, 0.88-2.57). However, women with overweight or obesity and GDM were at an increased risk for adverse maternal outcomes (adjusted OR = 2.69; 95% CI, 1.43-5.07). Women with GDM who had overweight or obesity and required insulin therapy were at an even greater risk for a severe course of COVID-19 (aOR = 3.05; 95% CI, 1.38-6.73).

“According to our analyses, BMI and a diabetic metabolic condition play the largest roles, ahead of maternal age and other pre-existing conditions such as asthma or hypertension,” Pecks said. “The only factor more important is the gestational week of infection. Women in the third trimester have a significantly higher risk of a severe course than women in the first trimester.”

Pecks mentioned that the virus variant does play a role.

“With omicron, we see much less severe courses than with the previous variants, but they sometimes occur, and we observe a positive effect from vaccination here as well,” he said. “It cannot be emphasized often enough how valuable vaccination is against COVID-19. I have seen and cared for several women suffering from COVID-19, all of them unvaccinated. The great fear of affected women who came into the clinic because of breathing difficulties was terrible.”

Neonatal outcomes

The analyses also showed that maternal GDM and maternal pre-conceptional overweight or obesity increased the risk for adverse fetal and neonatal outcomes (aOR = 1.83; 95% CI, 1.05-3.18). Regardless of GDM status, having overweight or obesity were influential factors in maternal (aOR = 1.87; 95% CI, 1.26-2.75) and neonatal outcomes (aOR = 1.81; 95% CI, 1.32-2.48) compared with having underweight or normal weight.

A vast majority of newborns experienced little to no effect from their mothers’ COVID-19 disease, Pecks noted.

“Here, we can fortunately reassure the affected women. However, there are secondary phenomena that can affect the newborn, such as premature birth due to COVID-19,” Pecks said. “We also confirm with our study that gestational diabetes mellitus is a serious risk for the pregnancy and the fetus, but fortunately can be easily recognized and treated.”

PERSPECTIVE

BACK TO TOP Mary Jane Minkin, MD)

Mary Jane Minkin, MD

The paper by Pecks and colleagues reporting on the results of CRONOS reaffirms many of the known risk factors for more severe cases of COVID-19 and shows that — in combination — these risk factors can lead to more serious outcomes. We have known that pregnancy, obesity and diabetes individually contribute to more severe outcomes in COVID-19 patients.

Indeed, one of the first severe complications for pregnant women with COVID-19 that was noted was a presentation of a severe preeclampsia pattern. We certainly see preeclampsia more frequently in women with overweight and obesity who have GDM.

So, what shall we take away from this study? There is still a significant resistance among women who are contemplating pregnancy or are pregnant to receive COVID-19 vaccinations. Data like these reaffirm the potential consequences of COVID-19 in pregnancy, and we can explain these data to our patients to encourage vaccination. We can also use these data to encourage our patients with overweight or obesity to lose weight prepregnancy to minimize their risks, which can be particularly helpful to our patients who are still trying to wait out the pandemic before becoming pregnant.

Mary Jane Minkin, MD

Clinical professor of obstetrics and gynecology, Yale School of Medicine

Healio Women’s Health & OB/GYN Peer Perspective Board Member

Lupus doubles risk for gestational diabetes during pregnancy

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Patients with systemic lupus erythematosus are at double the risk for gestational diabetes during pregnancy compared with those without SLE, according to data published in The Journal of Rheumatology.

“Globally, [gestational diabetes mellitus (GDM)] prevalence is increasing, partly due to older maternal age at pregnancy and higher prevalence of obesity and diabetes,” Sofie A.M. Gernaat, MSc, PhD, of the Karolinska Institute, in Stockholm, and colleagues wrote. “Insulin resistance is an important risk factor for GDM and is more common in women with systemic lupus erythematosus (SLE) than in women from the general population. Whether women with SLE have a higher risk of GDM than women from the general population remains unclear.”

RH0222Gernaat_Graphic_01
Patients with SLE are at double the risk for gestational diabetes during pregnancy compared with those without SLE, according to data. Source: Adobe Stock.

To examine the risk for gestational diabetes among pregnant patients with SLE, compared to those without SLE, Gernaat and colleagues analyzed data from the population-based Swedish Lupus Linkage (SLINK) cohort and the Swedish Medical Birth Register. The researchers identified a total of 695 singleton pregnancies among patients with SLE, with a registered delivery date between Nov. 1, 2006, and Dec. 31, 2016, and matched each case with five non-SLE comparators from the general population, randomly sampled from the Total Population Register. Matches were made based on age, sex, calendar time and county.

Gernaat and colleagues defined gestational diabetes as at least one ICD-coded visit in the National Patient Register or Medical Birth Register. In addition, the researchers identified glucocorticoid and hydroxychloroquine dispensations within 6 months before and during pregnancy using the Prescribed Drug Register. Lastly, they used modified Poisson regression models, stratified by parity and adjusted for maternal age at delivery, year of birth and obesity to estimate risk ratios and confidence intervals for gestational diabetes associated with SLE.

According to the researchers, 2.6% of pregnancies among patients with SLE demonstrated gestational diabetes, compared with 1.4% among the 4,644 non-SLE matched control pregnancies. Adjusted risk ratios for gestational diabetes in the SLE population were 1.11 (95% CI, 0.38-3.27) for first deliveries and 2.03 (95% CI, 1.21-3.4) for all deliveries.

Among pregnancies in patients with SLE, gestational diabetes developed in 2.3% of those with at least one glucocorticoid dispensation before and/or during pregnancy, in 2.8% of those without glucocorticoids, in 2.4% of those with at least one hydroxychloroquine dispensation before and/or during pregnancy, and in 2.7% of those with hydroxychloroquine.

“Women with SLE are at an almost twofold higher risk of GDM compared to women from the general population when looking at all deliveries,” Gernaat and colleagues wrote. “Early and proper screening for GDM, including SLE as a risk factor for GDM, may be a way to manage women with SLE and reduce associated maternal and fetal complications. Future studies should investigate the risks of diseases later in life associated with GDM in women with SLE, such as the risk of type 2 DM and cardiovascular disease. Also, the long-term effects in the children born to mothers with GDM associated with SLE are unclear.”

Gestational Diabetes Risk Higher After Previous Miscarriage

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Risk increased with each prior spontaneous abortion

A photo of an unused baby nursery in a home.

Spontaneous abortion — commonly known as miscarriage — was linked to a higher risk for subsequent gestational diabetes, a retrospective cohort study found.

Among over 100,000 pregnant women, those who previously experienced a miscarriage had a 25% higher relative risk for developing gestational diabetes during a subsequent pregnancy (RR 1.25, 95% CI 1.18-1.31), reported Liping Jin, MD, of Tongji University in Shanghai, and colleagues in JAMA Network Open.

This association was number-dependent, the group noted, with women who experienced more miscarriages seeing successively higher relative risks for gestational diabetes:

  • One spontaneous abortion: RR 1.18 (95% CI 1.11-1.26)
  • Two spontaneous abortions: RR 1.41 (95% CI 1.27-1.57)
  • Three or more spontaneous abortions: RR 1.43 (95% CI 1.22-1.67)

That being said, Jin’s group did not find a significant link between intentionally induced abortions and risk of gestational diabetes.

“Spontaneous abortion is one of the most common adverse outcomes in early pregnancy,” they pointed out, noting that about 30% of all pregnancies worldwide end this way.

This isn’t the first study to identify this link, they added, as a previous analysis found an even higher risk for gestational diabetes tied to a history of miscarriage.

Although the exact reason behind this association hasn’t been determined yet, Jin’s group said the source could be oxidative stress and inflammation, which increases one’s risk for cardiovascular and metabolic disease — in this case, gestational diabetes.

Given the ballooning rate of diabetes worldwide, the researchers advised all pregnant women with a history of miscarriage — and in particular those with recurrent spontaneous abortion — to attend more antenatal visits in order to monitor blood glucose regularly. These women should also be mindful of healthy eating and engaging in regular exercise, the group recommended.

“Considering the short- and long-term adverse effects of gestational diabetes on both mothers and their offspring, our findings may also have potential public health implications,” Jin’s group noted.

A total of 102,259 women (mean age 30) who visited one of the largest prenatal healthcare tertiary care hospitals in Shanghai from 2014 to 2019 were included in the final analysis. Those with multiple pregnancies, a history of gestational diabetes, or chronic diseases like hypertension, diabetes, kidney disease, and thyroid dysfunction were excluded from the study.

About 14% of the cohort had experienced a spontaneous abortion, 17.5% had experienced an induced abortion, and 3.9% had experienced both.

All participants underwent a standard fasting oral glucose tolerance test at 24 to 28 weeks of gestation, and 11.9% of the cohort were diagnosed with gestational diabetes.

Among women without an abortion history, median fasting blood glucose levels were 77 mg/dL compared with 79 mg/dL for those with a history of any type of abortion.

One limitation to the study was that data on spontaneous abortion were self-reported; due to the sensitive nature of this topic, Jin and colleagues noted that this number could very well have been underestimated. There were also no data on the timing between experiencing a miscarriage and the subsequent diagnosis of gestational diabetes, which could be a topic for future study.

Long-term cardiovascular risks greater than expected in gestational diabetes

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A greater risk for long-term cardiovascular outcomes was associated with the development of gestational diabetes than previously thought, according to prospective data presented at The Pregnancy Meeting.

“Previous studies suggested that a history of [gestational diabetes mellitus (GDM)] can be a risk factor for subsequent diabetes, hypertension, dyslipidemia and atherosclerotic cardiovascular diseases (ASCVDs), such as myocardial infarction or ischemic stroke,” Seung Mi Lee, MD, PhD, clinical associate professor of obstetrics and gynecology at Seoul National University College of Medicine in Korea, told Healio.

A presenter at The Pregnancy shared findings on the long-term cardiovascular risks associated with gestational diabetes. Source: Adobe Stock.
A presenter at The Pregnancy shared findings on the long-term cardiovascular risks associated with gestational diabetes.

However, these studies left gaps in our understanding of the risk for cardiovascular outcomes in older women, the risk for non-ASCVD and the impact of chronic metabolic comorbidities on cardiovascular outcomes, Lee said.

The researchers analyzed follow-up data from 219,330 women aged 40 to 69 years enrolled in the U.K. Biobank cohort study between 2006 and 2010 who had at least one live birth during that time. They noted onset of cardiovascular outcomes following GDM development and conducted a causal mediation analysis to determine the impact of known risk factors for cardiovascular outcomes.

According to the study, 13,094 (6%) women developed new cardiovascular outcomes, although the incidence rate was higher among those with a history of GDM (7.8 vs. 5.81 new incidences per 1,000 women-years; P < .001).

“GDM increased the risk of diverse cardiovascular outcomes, including coronary artery disease, myocardial infarction, ischemic stroke, peripheral artery disease, heart failure, mitral regurgitation and atrial fibrillation/flutter in elderly women,” Lee told Healio.

She added: “Chronic metabolic comorbidities partly explained the onset of cardiovascular outcomes after GDM history,” with overt diabetes linked to 23% of outcomes, hypertension linked to 10% and dyslipidemia linked to 10%, according to the study.

“Further studies are needed to determine whether these pathophysiologic mechanisms might also be applicable to the relationship between GDM and diverse cardiovascular outcomes,” Lee told Healio. “In addition, the result of the current study evokes the next question, whether women with GDM history may benefit from cardiovascular preventive strategies, such as intensive lifestyle modification [or] pharmacologic treatment including statin or aspirin therapy.”

Carbohydrate counting combined with DASH diet provides benefits in gestational diabetes

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Carbohydrate counting combined with the Dietary Approaches to Stop Hypertension eating plan may help women with gestational diabetes to lower fasting blood glucose, according to a study published in Clinical Nutrition.

In a randomized controlled parallel-arm trial of pregnant women with gestational diabetes from Jordan, participants randomly assigned to carbohydrate counting with a Dietary Approaches to Stop Hypertension (DASH) eating pattern had significantly lower fasting blood glucose (FBG), insulin and 1-hour postprandial glucose levels than those in a control group.

Women with gestational diabetes had lower fasting blood glucose with carbohydrate counting
Women with gestational diabetes randomly assigned to carbohydrate counting alone or with a DASH diet had lower home-monitored fasting blood glucose than those on a control diet. Data were derived from Allehdan S, et al. Clin Nutr. 2021;doi:10.1016/j.clnu.2021.11.039.

“These findings suggest that carbohydrate counting combined with DASH dietary intervention is more effective for improving glycemic control in gestational diabetes women,” Reema Tayyem, PhD, professor of clinical nutrition in the College of Health Sciences at Qatar University, and colleagues wrote. “The explanation for these findings is that participants of carbohydrate counting group and carbohydrate counting combined with DASH group distributed their carbohydrate intake throughout the day in three small to moderate meals and three to four snacks.”

Researchers recruited 75 pregnant women with gestational diabetes prescribed metformin between the 24th and 30th week of gestation to participate in the trial. All participants were attending antenatal clinics at Al-Bashir Hospital and Jordan University Hospital. Participants were randomly assigned to carbohydrate counting, carbohydrate counting combined with a DASH diet or a control diet with no carbohydrate counting. The intervention lasted 8 to 12 weeks from enrollment until delivery. The control diet contained about 45% to 55% carbohydrates, 15% to 20% protein and 25% to 30% fat. Those in the carbohydrate counting groups received education on food portion size, package labels, managing hyperglycemia and hypoglycemia and more, with calorie, protein, carbohydrate and fat content similar to the control diet. Those in the DASH diet group ate more fruits, vegetables, cereals, low-fat dairy and nuts and less lean meat. FBG, insulin, HbA1c and fructosamine levels were measured at baseline and the end of the study. Participants were asked to perform blood glucose monitoring at least four times daily. Newborn and maternal outcomes were obtained from medical records.

Seventy women completed the trial, including 24 in the control group and 23 each in the carbohydrate counting and the carbohydrate counting combined with DASH diet groups. At the end of the intervention, all three groups had decreases in FBG compared with baseline, with the carbohydrate counting group having a significantly lower FBG level of 78.5 mg/dL compared with the DASH group (80.9 mg/dL) and the control group (86.7 mg/dL; P = .021). The DASH group had a lower insulin level of 48.7 pmol/L compared with the carbohydrate counting group (79.3 pmol/L) and the control group (86.6 pmol/L; P = .026).

“The carbohydrate counting diet and the carbohydrate combined with DASH diet could significantly reduce the number of women who are required to initiate insulin therapy,” the researchers wrote. “One explanation for this finding is that the carbohydrate counting diet and the carbohydrate combined with DASH diet were effective in achieving glycemic control.”

In an analysis of daily home-monitored blood glucose, FBG was lower in the DASH group and the carbohydrate counting group vs. controls (81.8 mg/dL vs. 81.3 mg/dL vs. 88.4 mg/dL; P = .002). The DASH group had lower 1-hour plasma glucose than both the carbohydrate counting and control groups, specifically after breakfast and dinner (P < .001).

There were no differences in any maternal or neonatal outcomes between the three diet groups except for insulin therapy. Ten participants in the control group needed insulin compared with three each in the carbohydrate counting and DASH groups (P = .026).

“The carbohydrate counting combined with DASH diet appears to be a safe alternative to the conventional pregnancy diet for women with gestational diabetes and enlarges the range of dietary strategies that can be recommended to gestational diabetes pregnant women,” the researchers wrote.

Greater T2D Risk Seen in Women with Gestational Diabetes

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Long-term cardiovascular health may be compromised for mothers with gestational diabetes mellitus (GDM), a new study reported.

A retrospective cohort study found women with gestational diabetes mellitus (GDM) were nearly 22 times more likely to develop type 2 diabetes, in an adjusted model (adjusted incidence rate ratio 21.96, 95% CI 18.31-26.34, P<0.001), according to Barbara Daly, PhD, RN, of the University of Auckland in New Zealand, and colleagues.

The risks for hypertension and ischemic heart disease were also significantly increased among women who previously experienced GDM (aIRR 1.85, 95% CI 1.59-2.16, P<0.001; aIRR 2.78, 1.37-5.66, P=0.005, respectively), they reported in PLOS Medicine.

However, during the 25-year study period, there was no increased risk seen for cerebrovascular disease, which included stroke and transient ischemic attack, among women with GDM (aIRR 0.95, 95% CI 0.51-1.77, P=0.87).

Drawing upon the Health Improvement Network database in the U.K., the analysis included 9,118 women with a history of GDM, who were then matched with 37,281 pregnant controls. Women with GDM were more likely to be non-white, and were overweight or obese at baseline.

Among women who developed ischemic heart disease during follow-up, only around 36% also developed type 2 diabetes. The authors pointed out this suggested “that the risk of cardiovascular disease is not always mediated through type 2 diabetes.”

In an ethnic subgroup analysis, white, South Asian, and Afro-Caribbean women with GDM were all more likely to develop type 2 diabetes post-partum:

  • White: IRR 35.2 (95% CI 20.0-58.5)
  • South Asian: IRR 22.15 (95% CI 6.42-76.4)
  • Afro-Caribbean: IRR 15.40 (95% CI 6.54-36.25)

“The current National Institute for Health and Care Excellence (NICE) guidelines recommend screening for type 2 diabetes (between 6 and 13 weeks postpartum and an annual glycated hemoglobin test) and lifestyle changes (weight control, diet, and exercise) for women diagnosed with GDM,” the authors highlighted.

However, only 58% of women with GDM in the analysis reported having a glycemic measurement in the first year post-partum, according to medical records. This eventually decreased to only 40% and 24% of such women undergoing a glycemic measurement in years 2 and 3 after delivery.

The authors also added, “there is no recommendation to screen, identify, and actively manage cardiovascular risk factors (including hypertension, dyslipidemia, and smoking) in women diagnosed with GDM in the postpartum period in the current 2015 NICE guidelines.”

“Guideline recommendations for screening and management of hypertension, lipids, and smoking cessation are lacking and need to be reviewed,” they suggested.

While around 80% of women with GDM reported a blood pressure measurement in the first year after delivery, only half of those women had a measurement in years 2 and 3 post-partum. During the first 3 years after delivery, only around 28% and 23% of women with GDM had serum cholesterol or triglycerides measured, respectively.

 Although the authors stated their findings were congruent with prior observational analyses, they noted their effects estimates were higher for type 2 diabetes and ischemic heart disease compared with prior studies, as well as lower effect estimates for hypertension.

“The findings report on a large population and identify an at-risk group of relatively young women ideally suited for targeting of risk factor management to improve long-term metabolic and cardiovascular outcomes,” they wrote, adding that “targeting these high-risk women may also provide better value for money for prevention programs, as they are already known to general practice.”

“While the value of preventing cardiovascular outcomes requires further studies, there is some evidence that targeting this subgroup of women may yield benefits in reducing conversion to type 2 diabetes,” the authors stated.

Metabolites in early pregnancy may indicate risk for gestational diabetes

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In early pregnancy, a combination of 17 metabolites appear to be linked to later risk for gestational diabetes, according to recent findings.

In a nested case control study, researchers evaluated 178 women with gestational diabetes and 180 control women who were enrolled in the Omega study, a prospective cohort study aimed at assessing maternal diet and lifestyle risk factors associated with pregnancy complications.

Blood samples from early pregnancy were assayed for non-targeted metabolite profiling using a gas chromatography-mass spectrometry platform. Receiver operating characteristic (ROC) curves were constructed to assess the predictive performance of different sets of indicators, consisting of known patient characteristics and the set of selected metabolites. The researchers calculated the area under the curve (AUC) corresponding to these ROC curves, and differences between AUCs were compared.

The researchers found that levels of the following 17 metabolites distinguished the gestational diabetes cases from control participants. These included fatty acids (linoleic acid, oleic acid, myristic acid); sugars and alcohols (d-galactose, d-sorbitol, o-phosphocolamine); amino acids (l-alanine, l-valine, 5-hydroxy-l-tryptophan, l-serine, sarcosine, l-pyroglutamic acid, l-mimosine); and organic acids (l-lactic acid, glycolic acid, fumaric acid and urea). The range of fold changes of comparative profusion of these metabolites was 1.47 for linoleic acid in participants with gestational diabetes compared with 1.57 in controls, and 0.78 for 5-hydroxy-l-tryptophan vs. 0.71 in controls. The AUC was significantly improved, from 0.71 to 0.87, by addition of these selected metabolites to a set of established gestational diabetes risk factors such as BMI, lifestyle habits and family medical history.

“While the observed statistically significant improvement in the AUC and relevance of functions of identified metabolites in [gestational diabetes] pathogenesis is encouraging, clinical implications of using these metabolites as predictors of [gestational diabetes] needs further investigation,” the researchers wrote. “Future similar investigations that evaluate joint abundance of metabolites, integrate clinical characteristics with metabolites, use multiple platforms, and analyses of multiple specimen types can advance our understanding of metabolite perturbations in [gestational diabetes].”

Gestational Diabetes May Be Tied to Autism in Children

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Women who develop gestational diabetes early in their pregnancy have a higher chance of having a child with autism than women who don’t develop the condition, a new study suggests.

Researchers found that mothers-to-be who developed gestational diabetes — high blood sugar during pregnancy in women who have never had diabetes — by their 26th week of pregnancy were 63 percent more likely to have a child diagnosed with an autism spectrum disorder (ASD) compared with women who did not have gestational diabetes at any point during their pregnancy (and who also did not have type 2 diabetes prior to pregnancy).

The finding does not mean that autism is common among children born to women who had gestational diabetes.

“Autism is still rare,” said study co-author Anny Xiang, a research scientist at Kaiser Permanente Southern California in Pasadena. The findings show that, although the risk of having a child with autism is still low among women who have gestational diabetes early in pregnancy (before 26 weeks), the study did find a relationship between these women and an increased risk that the child would have autism, Xiang said. [7 Ways Pregnant Women Affect Babies]

The study, published today (April 14) in the Journal of the American Medical Association, looked at more than 320,000 children born in Southern California between 1995 and 2009. About 8 percent of the kids were born to mothers who had pregnancy-related diabetes, and 2 percent had mothers with type 2 diabetes.

During an average follow-up period of 5.5 years, nearly 3,400 children in the study were diagnosed with an ASD, including such conditions as autistic disorder and Asperger syndrome that can cause social, communication and behavioral problems in children.

After the researchers considered other factors that can influence a child’s chances of developing autism — such as the mother’s age, education, income, ethnicity, prior pregnancies and the sex of the child (autism is five times more common in boys than in girls) — the impact of having gestational diabetes early in pregnancy was muted, but the link still held. Gestational diabetes by the 26th week of pregnancy was found to increase a child’s risk of autism by 42 percent compared with the risk of autism for children whose moms did not have gestational diabetes when these factors were considered.

Early exposure

The exact reason for the link is unclear. However, one underlying factor could be that the early months of pregnancy are a critical time period for brain development, Xiang told Live Science.

If a developing fetus is exposed to elevated blood sugar levels during this important period of brain development, this may have some connection to the behavioral changes seen in autism after birth, she said.

Moreover, the study’s other findings hint that elevated blood sugar during early pregnancy plays a role in the link. For example, the researchers found that children born to women who developed pregnancy-related diabetes after 26 weeks were not at greater risk of being diagnosed with autism than kids whose mothers never had type 2 or gestational diabetes.

In addition, the study found no increase in autism risk among the children born to women who knew they had type 2 diabetes before having a baby. This may be because these women are probably taking medication to control their blood sugar levels throughout pregnancy, Xiang said.

Because women who have no risk factors for diabetes may not be screened for the disease until the 24th to 28th weeks of pregnancy, gestational diabetes can go undetected during early pregnancy, she said.

Xiang cautioned that women who had gestational diabetes during pregnancy don’t need to panic or worry. The results suggest that for every 1,000 mothers who had pregnancy-related diabetes by 26 weeks, seven children may develop autism spectrum disorders, Xiang said.

 

HKDC1, BACE2 could predict gestational diabetes before pregnancy.

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Data collected from the Hyperglycemia and Adverse Pregnancy Outcomes Study have led researchers to identify variants in two novel genes which they said are associated with measures of glucose and insulin levels among pregnant women.

 “With additional study and verification of these and other risk genes, we could one day have genetic risk profiles to identify individuals at elevated risk for developinggestational diabetes,” M. Geoffrey Hayes, PhD, from the division of endocrinology, metabolism, and molecular medicine at Northwestern University Feinberg School of Medicine, said in a press release.

 

Hayes and colleagues conducted a discovery genome-wide association study in a large cohort of pregnant mothers from various ancestries from the Hyperglycemia and Adverse Pregnancy Outcomes Study (n=4,437). The women were administered an oral glucose tolerance test at approximately 28 weeks gestation to determine genetic loci linked to measures of maternal metabolism, researchers wrote.

The researchers identified two novel genome-wide significant associations in glucose metabolism and HKDC1 and insulin secretion and BACE2 within two genes. Researchers wrote that these data suggest the genes’ underlying roles could play a significant role in hypoglycemia during pregnancy compared with women who are not pregnant.

“Together with the results of earlier studies, our findings suggest that the roles of HKDC1 in glucose metabolism and BACE2 in insulin secretion are more important during pregnancy than in the nongravid state,” researchers wrote.

Source: Endocrine Today