From Medscape Medical News
Laurie Barclay, MD
August 25, 2010 — The Committee on Obstetric Practice of the American College of Obstetricians and Gynecologists recommends antimicrobial prophylaxis for all cesarean deliveries unless the patient is already receiving appropriate antibiotics (eg, for chorioamnionitis), according to a Committee Opinion report in the September issue of Obstetrics and Gynecology. This antibiotic prophylaxis should be given within 60 minutes of starting the cesarean delivery.
"Antimicrobial prophylaxis for cesarean delivery has been a general practice for cesarean deliveries because it significantly reduces postoperative maternal infectious morbidity," the committee writes. "These antibiotics have been administered intraoperatively after umbilical cord clamping for two theoretic concerns related to the fetus:
1) antibiotics in neonatal serum may mask newborn positive bacterial culture results; and
2) fetal antibiotic exposure could lead to an increase in newborn colonization or infection with antibiotic-resistant organisms.
Recently, several randomized clinical trials investigated the timing of antimicrobial prophylaxis for cesarean delivery."
Based on surgical research data, antimicrobial prophylaxis to prevent surgical site infection should ideally begin within 30 minutes, and definitely within 2 hours, of skin incision.
For longer surgery, the same dose of antibiotic may need to be given again at intervals of 1 or 2 times the half-life of the drug. The review authors write that "preoperative [antibiotic] administration significantly reduces endometritis and total maternal infectious morbidity compared with administration of antibiotics after umbilical cord clamping."
Antimicrobial prophylaxis for cesarean delivery typically employs narrow-spectrum antibiotics, such as a first-generation cephalosporin, effective against gram-positive bacteria, gram-negative bacteria, and some anaerobic bacteria. A single 1-g intravenous dose of cefazolin usually results in a therapeutic level for 3 to 4 hours, but obese women may need larger doses.
Clindamycin with gentamicin is a reasonable option for women with a significant allergy to β-lactam antibiotics, such as cephalosporins and penicillins.
Studies to date suggest that preoperative antimicrobial prophylaxis does not appear tohave any harmful effects on the mother or infant, nor is it associated with an increase in neonatal infectious morbidity or selection of antimicrobial-resistant bacteria causing neonatal sepsis. However, additional prospective evaluation is needed because these studies lacked sufficient power to assess those outcomes.
"The Committee on Obstetric Practice recommends antimicrobial prophylaxis for all cesarean deliveries unless the patient is already receiving appropriate antibiotics (eg, for chorioamnionitis) and that prophylaxis should be administered within 60 minutes of the start of the cesarean delivery," the committee concludes. "When this is not possible (eg, need for emergent delivery), prophylaxis should be administered as soon as possible."
Obstet Gynecol. 2010;116:791-792.
Tuesday, August 31, 2010
Vitamin C and E Supplementation May Not Prevent Spontaneous Preterm Birth
From Medscape Medical News
Laurie Barclay, MD
August 27, 2010 — Vitamins C and E supplementation beginning at 9 to 16 weeks of gestation in nulliparous women at low risk may not reduce spontaneous preterm births, according to the results of a randomized, double-masked, placebo-controlled trial reported in the September issue of Obstetrics & Gynecology.
"Preterm [premature rupture of membranes (PROM)] has been associated with many factors, including ascorbic acid deficiency (vitamin C)," write John C. Hauth, MD, from the University of Alabama at Birmingham, and colleagues from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
"These observations are of great importance because if vitamin C supplementation reduces the occurrence of preterm PROM, then a deficiency of vitamin C is a modifiable risk factor and supplementation would be a corrective interventional behavior.
Our intent was to assess further the hypothesis that daily maternal antioxidant supplementation with vitamins C and E from early pregnancy would reduce the incidence of spontaneous preterm birth attributable to either spontaneous labor or preterm PROM."
In the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network trial, nulliparous women at low risk were randomly assigned to daily vitamin C and E supplementation or matching placebo to determine the effect on adverse outcomes from pregnancy-associated hypertension.
Participants (n = 10,154) received 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery.
In this secondary analysis, the studied endpoints included preterm birth attributable to PROM and total spontaneous preterm births (attributable either to PROM or spontaneous labor).
Of 9968 participants with available outcome data, 4992 were in the vitamin group and 4976 in the placebo group. Of 1038 women (10.4%) who delivered preterm, 698 (7.0%) had spontaneous preterm birth, including 356 (7.1%) randomly assigned to daily vitamin C and E supplementation and 342 (6.9%) assigned to placebo. Delivery after preterm PROM occurred in 253 women (2.5%), and delivery after spontaneous preterm labor occurred in 445 (4.5%).
Compared with the placebo group, the supplementation group had similar births attributed to preterm PROM at less than 37 and 35 weeks of gestation, but fewer births before 32 weeks of gestation (0.3% vs 0.6%; adjusted odds ratio, 0.3 - 0.9). Preterm PROM occurring before 32 weeks of gestation was also less frequent in women in the vitamin group (0.36% vs 0.64%; P = .046).
Total spontaneous preterm births across gestation were similar in the placebo group and in the supplementation group.
"Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births," the study authors write.
Limitations of this study include possible type 1 (alpha) error, as well as the clinical imprecision of determining the spontaneous preterm birth subcategories of preterm PROM or spontaneous preterm labor.
"Our results, taken in context with similar trials regarding vitamin C and E supplementation, do not support either the clinical use for prevention of spontaneous preterm birth or its neonatal sequelae or further trials of this treatment in similar populations at low risk," the study authors conclude.
Obstet Gynecol. 2010;116:653-658. Abstract
Laurie Barclay, MD
August 27, 2010 — Vitamins C and E supplementation beginning at 9 to 16 weeks of gestation in nulliparous women at low risk may not reduce spontaneous preterm births, according to the results of a randomized, double-masked, placebo-controlled trial reported in the September issue of Obstetrics & Gynecology.
"Preterm [premature rupture of membranes (PROM)] has been associated with many factors, including ascorbic acid deficiency (vitamin C)," write John C. Hauth, MD, from the University of Alabama at Birmingham, and colleagues from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
"These observations are of great importance because if vitamin C supplementation reduces the occurrence of preterm PROM, then a deficiency of vitamin C is a modifiable risk factor and supplementation would be a corrective interventional behavior.
Our intent was to assess further the hypothesis that daily maternal antioxidant supplementation with vitamins C and E from early pregnancy would reduce the incidence of spontaneous preterm birth attributable to either spontaneous labor or preterm PROM."
In the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network trial, nulliparous women at low risk were randomly assigned to daily vitamin C and E supplementation or matching placebo to determine the effect on adverse outcomes from pregnancy-associated hypertension.
Participants (n = 10,154) received 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery.
In this secondary analysis, the studied endpoints included preterm birth attributable to PROM and total spontaneous preterm births (attributable either to PROM or spontaneous labor).
Of 9968 participants with available outcome data, 4992 were in the vitamin group and 4976 in the placebo group. Of 1038 women (10.4%) who delivered preterm, 698 (7.0%) had spontaneous preterm birth, including 356 (7.1%) randomly assigned to daily vitamin C and E supplementation and 342 (6.9%) assigned to placebo. Delivery after preterm PROM occurred in 253 women (2.5%), and delivery after spontaneous preterm labor occurred in 445 (4.5%).
Compared with the placebo group, the supplementation group had similar births attributed to preterm PROM at less than 37 and 35 weeks of gestation, but fewer births before 32 weeks of gestation (0.3% vs 0.6%; adjusted odds ratio, 0.3 - 0.9). Preterm PROM occurring before 32 weeks of gestation was also less frequent in women in the vitamin group (0.36% vs 0.64%; P = .046).
Total spontaneous preterm births across gestation were similar in the placebo group and in the supplementation group.
"Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births," the study authors write.
Limitations of this study include possible type 1 (alpha) error, as well as the clinical imprecision of determining the spontaneous preterm birth subcategories of preterm PROM or spontaneous preterm labor.
"Our results, taken in context with similar trials regarding vitamin C and E supplementation, do not support either the clinical use for prevention of spontaneous preterm birth or its neonatal sequelae or further trials of this treatment in similar populations at low risk," the study authors conclude.
Obstet Gynecol. 2010;116:653-658. Abstract
Saturday, August 28, 2010
Early Age at Menopause Linked to Angina Post MI
From Medscape Medical News
Emma Hitt, PhD
August 24, 2010 — Women who have an early menopause, at 40 years or younger, are at higher risk for angina after a myocardial infarction (MI) vs women who experience menopause at 50 years or older, new research suggests.
Susmita Parashar, MD, with Emory University, in Atlanta, Georgia, and colleagues reported their findings in the July 21 online issue of Menopause: The Journal of The North American Menopause Society.
According to the researchers, women who experience early menopause may be at risk for cardiovascular disease morbidity and mortality because of a deprivation of estrogen after menopause; however, "no descriptions of its prognostic importance among women with known coronary heart disease have been reported," which may help in the risk stratification and management of this patient group.
In addition, the study authors note that angina symptom-driven care for women accounts for most costs associated with care in women with coronary heart disease.
In the current study, 493 women were interviewed by telephone 1 year after discharge from the hospital for MI on aspects of behavioral, treatment, and health status measures. Mean age at menopause (AAM) was 45.2 ± 7.8 years.
Participants were classified by AAM: 40 years or younger, 41 to 49 years, and 50 years or older. The researchers then determined whether age predicted 1-year post-MI angina and severity of angina while taking into account pre-MI angina, demographics, comorbidities, MI severity, and quality of care.
Of the women, 132 (26.8%) experienced early menopause at 40 years or younger. These women were more often smokers but otherwise had similar comorbidities and characteristics as women experiencing later menopause both before and after MI.
However, the rate of 1-year angina in women with an AAM of 40 years or younger (32.4%) was double that of women with an AAM of 50 years or older (12.2%) in a multivariable analysis (relative risk, 2.09; 95% confidence interval [CI], 1.38 - 3.17), as was the severity of angina (odds ratio, 2.65; 95% CI, 1.34 - 5.22 for a higher severity level).
"Early menopause is a significant predictor of angina at 1 year after MI, independent of comorbidities, MI severity, and quality of care," Dr. Parashar and colleagues conclude.
According to the researchers, deprivation of endogenous estrogen may increase the extent of vascular inflammation, endothelial and microvascular dysfunction, and coagulation abnormalities; and decrease arterial compliance, all of which could cause angina in the setting of coronary artery disease.
"A simple, inexpensive, and easily administered question regarding age at menopause may help identify high-risk women and guide efforts toward improving treatments and quality of life of post-MI women," they suggest.
Menopause. Published online July 21, 2010. Abstract
Emma Hitt, PhD
August 24, 2010 — Women who have an early menopause, at 40 years or younger, are at higher risk for angina after a myocardial infarction (MI) vs women who experience menopause at 50 years or older, new research suggests.
Susmita Parashar, MD, with Emory University, in Atlanta, Georgia, and colleagues reported their findings in the July 21 online issue of Menopause: The Journal of The North American Menopause Society.
According to the researchers, women who experience early menopause may be at risk for cardiovascular disease morbidity and mortality because of a deprivation of estrogen after menopause; however, "no descriptions of its prognostic importance among women with known coronary heart disease have been reported," which may help in the risk stratification and management of this patient group.
In addition, the study authors note that angina symptom-driven care for women accounts for most costs associated with care in women with coronary heart disease.
In the current study, 493 women were interviewed by telephone 1 year after discharge from the hospital for MI on aspects of behavioral, treatment, and health status measures. Mean age at menopause (AAM) was 45.2 ± 7.8 years.
Participants were classified by AAM: 40 years or younger, 41 to 49 years, and 50 years or older. The researchers then determined whether age predicted 1-year post-MI angina and severity of angina while taking into account pre-MI angina, demographics, comorbidities, MI severity, and quality of care.
Of the women, 132 (26.8%) experienced early menopause at 40 years or younger. These women were more often smokers but otherwise had similar comorbidities and characteristics as women experiencing later menopause both before and after MI.
However, the rate of 1-year angina in women with an AAM of 40 years or younger (32.4%) was double that of women with an AAM of 50 years or older (12.2%) in a multivariable analysis (relative risk, 2.09; 95% confidence interval [CI], 1.38 - 3.17), as was the severity of angina (odds ratio, 2.65; 95% CI, 1.34 - 5.22 for a higher severity level).
"Early menopause is a significant predictor of angina at 1 year after MI, independent of comorbidities, MI severity, and quality of care," Dr. Parashar and colleagues conclude.
According to the researchers, deprivation of endogenous estrogen may increase the extent of vascular inflammation, endothelial and microvascular dysfunction, and coagulation abnormalities; and decrease arterial compliance, all of which could cause angina in the setting of coronary artery disease.
"A simple, inexpensive, and easily administered question regarding age at menopause may help identify high-risk women and guide efforts toward improving treatments and quality of life of post-MI women," they suggest.
Menopause. Published online July 21, 2010. Abstract
Saturday, August 14, 2010
The Diagnosis of Gestational Diabetes
From Medscape Diabetes & Endocrinology
Change Is in the Air
Laura A. Stokowski, RN, MS
08/04/10
A Parallel Epidemic
The word "epidemic" is so overused that it has lost its undercurrent of urgency. We are experiencing epidemics of obesity, high cholesterol, cardiovascular disease, and diabetes. An epidemic has become the norm. Even the word "pandemic," thanks to swine flu, no longer conveys a sense of gravity. New words are needed to describe the overarching implications of a society in which type 2 diabetes afflicts at least 1 in 10 people and, quite possibly, many more.
The prevalence of gestational diabetes mellitus (GDM) will likely grow, as it has in the past, in direct proportion to that of type 2 diabetes.[1] Indications are that GDM already parallels the rapid increase in type 2 diabetes. In a US medical center where the screening method and diagnostic criteria for GDM have remained constant, the prevalence of this complication of pregnancy doubled in 8 years -- a 12% increase per year that cannot be explained by changes in age, ethnic distribution, or previous history of GDM among screened pregnancies.[2]
Arguably more disturbing than the number of people diagnosed with type 2 diabetes or GDM is the number of people who have prediabetes (ie, impaired fasting glucose and/or impaired glucose tolerance).
Currently, an estimated 19% of people over the age of 20 have prediabetes,[3] and this is the pool from which childbearing women are drawn.
Gestational Diabetes Mellitus
Gestational diabetes is glucose intolerance with onset or first recognition during pregnancy.
Pregnancy is already a diabetogenic state, with progressive deterioration of insulin resistance and glucose tolerance that become more significant in the third trimester.
Neonatal problems of offspring of frankly diabetic mothers (eg, congenital defects, spontaneous abortion, fetal macrosomia, birth injury, hypoglycemia, polycythemia, and hyperbilirubinemia) are well described. Exposure to diabetes during gestation also increases the risk for childhood and adult obesity, diabetes, and cardiovascular disease. However, risk for adverse outcomes associated with degrees of maternal hyperglycemia that are short of overt diabetes remains controversial.
In the United States, GDM is commonly diagnosed using either the World Health Organization's criteria (the same as those used to diagnose diabetes in nonpregnant women), or on the basis of a woman's risk of developing diabetes in the future. Neither of these methods links the key metabolic aberration of GDM (ie, maternal hyperglycemia) with the risk for adverse outcomes in the fetus and newborn. Most experts agree that new, more clinically relevant, risk-based criteria for the diagnosis of GDM are needed, especially considering the similarities between GDM and prediabetes. However, levels of maternal glucose intolerance that correlate with poor neonatal outcomes had not been sufficiently ascertained until the results of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study were reported.
The HAPO Study
The HAPO epidemiologic study was the first to conclusively establish a relationship between elevated maternal glucose concentrations and undesirable perinatal outcomes in women not previously diagnosed with diabetes.
The HAPO study clarified the association between multiple adverse outcomes of pregnancy and degrees of hyperglycemia less severe than those diagnostic of diabetes. Data for establishing internationally agreed-upon diagnostic criteria for GDM were also provided. This well-controlled study involved 25,000 women in 9 countries -- a multicultural, ethnically diverse cohort. All women underwent a 2-hour oral glucose tolerance test (OGTT) with a 75-g glucose load at 24-32 weeks' gestation, and random plasma glucose testing at 34-37 weeks. Results were blinded unless a woman's fasting, 2-hour, or random glucose values were elevated to a level that mandated immediate treatment.
Primary outcomes were macrosomia (ie, birth weight > 90th percentile), primary cesarean delivery, and clinical neonatal hypoglycemia and hyperinsulinemia (ie, cord serum C-peptide > 90th percentile). The analysis aimed to determine whether threshold levels of maternal glucose -- for any of the 1-hour, 2-hour, or fasting plasma glucose (FPG) levels -- could be identified for any of the negative outcomes. They found that each of the primary outcomes was associated not only with extremely high maternal glucose concentrations, but in a continuous and graded manner across the full range of observed glucose levels,[9] which precluded easy identification of threshold levels where risk for adverse outcomes rose. The relationship between maternal glucose levels and fetal growth and neonatal outcome seemed to be a basic biologic phenomenon, and not a clearly demarcated disease state, as had previously been thought.
Several secondary outcomes were also evaluated in the HAPO study, including preeclampsia, preterm delivery (ie, delivery at < 37 weeks' gestation), shoulder dystocia and/or birth injury, hyperbilirubinemia, and admission to neonatal intensive care. Shoulder dystocia or birth injury, preterm delivery, and preeclampsia were significantly associated with ≥ 1 elevated glucose values.[9] The blinding of maternal glucose (except when overt diabetes was suggested) is a strength of the HAPO study, because maternal glucose was not a factor in obstetric management. It is also promising that the study's findings did not vary by medical center or country. The results are therefore applicable globally and can be used to develop criteria for classifying gestational diabetes world-wide. Next Step: New Diagnostic Criteria The HAPO investigators did not attempt to translate their findings into new criteria for the diagnosis of gestational diabetes.[8] This task fell to a committee of experts, the International Association of Diabetes and Pregnancy Study Groups (IADPSG), who met to review the data, form a consensus, and make recommendations. A pivotal decision involved the threshold for diagnosing GDM using data from fasting glucose and 2-hour OGTT. This threshold would be somewhat arbitrary, because no inflection points were apparent in the linear relationships between maternal glucose concentrations and outcomes.[8] The IADPSG examined the strong linear associations between risk for neonatal outcomes and the 3 measures of maternal glucose (FPG, 1-hour OGTT, and 2-hour OGTT). The threshold was set at an odds ratio of 1.75, which identified 16.1% of the pregnant population as having GDM (Table 1). Table 1. Proposed and Current Thresholds for the Diagnosis of GDM Maternal glucose test Proposed diagnostic thresholda Above threshold (cumulative %) Current thresholda Fasting plasma glucose 92 mg/dl (5.1 mmol/L) 8.3 95 mg/dl (5.3 mmol/L) 1 hour plasma glucose 180 mg/dl (10 mmol/L) 14.0 180 mg/dl (10 mmol/L) 2 hour plasma glucose 153 mg/dl (8.5 mmol/L) 16.1 155 mg/dl (8.6 mmol/L) aWith 75 g OGTT Only 1 of these cut-offs (FPG, 1-hour OGTT, or 2-hour OGTT) must be met or exceeded to diagnose GDM, unlike current American Diabetes Association (ADA) criteria, which require 2 elevated glucose levels to diagnose GDM. The proposed thresholds are those for which the odds of having a baby with birth weight, cord C-peptide, or neonatal body fat in the > 90th percentiles are 1.75 times the estimated odds of these outcomes at mean glucose values. Setting the threshold higher would decrease the number of women diagnosed with GDM, but would also fail to identify many women whose glucose concentrations place them at the same risk for adverse pregnancy outcomes, and who might benefit from treatment. In this study, 1.7% of patients were unblinded because of elevated FPG or OGTT results. When these patients are included, the total incidence of gestational diabetes in pregnant women rises to 17.8%.
Glucose Testing Considerations
The finding that slight differences in maternal glucose levels are associated with marked differences in outcomes throws intoclear relief the importance of precision in glucose testing. Odds ratios and frequencies for outcomes increase substantially over relatively small changes in glucose. While the handling of blood samples in research is tightly controlled, the real world typically introduces extensive variability. Even a small error in test results caused by poor handling or analytic technique could result in the misclassification of a patient.
For reliable diagnosis and classification of hyperglycemia in pregnancy, venous plasma or serum glucose must be analyzed with a highly accurate enzymatic method. The collection, handling, and transport of blood samples to minimize pre-analytic glycolysis are extremely important. The IADPSG recommends that only venous samples be used for glucose determination, emphasizing that capillary and venous samples are not interchangeable. If the plasma is not separated promptly, the blood sample should be kept cold, because glycolysis will continue in the presence of red and white blood cells, falsely reducing the patient's blood glucose level by 5-15%. It is often mistakenly believed that as soon as the blood is placed in sodium fluoride (a glycolysis inhibitor), glycolysis will stop, but in fact, sodium fluoride has little effect on glycolysis in the first 1-2 hours after sample collection.Point-of-care glucose testing with handheld glucose meters is not appropriate for the diagnosis of GDM.
Significance of Proposed Guidelines
Lowering the diagnostic threshold will undoubtedly raise the frequency of hyperglycemic disorders seen in clinical practice. This would matter less if it could be shown that a benefit can be derived from improving even mild aberrations in glucose metabolism during pregnancy. The longstanding debate about the value of screening pregnant women for hyperglycemia has centered on uncertainties about the treatment benefit.
Benefit of treating GDM. In May 2008, the US Preventive Services Task Force concluded that there was inadequate evidence to recommend treatment of GDM, largely because of inadequate prospective studies.[14] A subsequent review concluded that treatment of GDM after 24 weeks of pregnancy improves some maternal and neonatal outcomes; however, evidence for screening before 24 weeks' gestation is more sparse.[15] The gestational time at which hyperglycemia screening should be initiated, and the level of hyperglycemia that warrants aggressive intervention remain controversial.[16]
In 2005, the results of ACHOIS (Australian Carbohydrate Intolerance Study in Pregnant Women), a 10-year multicenter randomized trial, were published.[17] ACHOIS assessed whether treating mild GDM would reduce perinatal morbidity and mortality. Treatment with dietary counseling, self glucose monitoring, and insulin when indicated, significantly reduced adverse primary outcomes (ie, perinatal death, shoulder dystocia, and birth trauma), neonatal adipoinsular macrosomia, maternal preeclampsia, and labor induction. Landon and colleagues conducted a randomized controlled trial sponsored by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD-MFMU) Network, compared untreated women with mild GDM with those receiving treatment (nutritional counseling, diet therapy, insulin if needed, etc.).[18] Significant reductions in macrosomia, neonatal fat mass, shoulder dystocia, preeclampsia, and cesarean section were seen in the treated cohort.
Both treatment trials revealed a positive effect of treatment in preventing large for gestational age (LGA) births, macrosomia, and shoulder dystocia.
Together, these 2 studies argue convincingly for a treatment benefit for mild GDM.While neither study found significant effects of treatment on neonatal morbidities such as hypoglycemia or hyperbilirubinemia, their findings of reduced neonatal fat mass, LGA, and macrosomia have important implications for long-term child and adult health. Excess neonatal fat and adipoinsular macrosomia are linked to childhood obesity and later development of diabetes. If these findings are real, then the successful treatment of maternal GDM, even mild GDM, could positively influence the health of the next generation.
Health system burden.
Although the new criteria are expected to double the number of women diagnosed with GDM, the rate will be consistent with the high prevalence of obesity and glucose intolerance in the general population. Donald R. Coustan, MD, Professor of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Division of Maternal-Fetal Medicine, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, explained the implications of classifying such a large slice of the pregnant population as having GDM and the potential burden on high-risk maternity care:
"Currently (as of 2007), the Centers for Disease Control and Prevention tells us that 10.7% of adult Americans have diabetes; furthermore, the American Diabetes Association states that 19% of adult Americans have prediabetes. So 17% is not such an extreme prevalence for GDM, which is quite similar to prediabetes in its severity. In the 2 randomized trials of identification and treatment of mild GDM (ACHOIS in Australia and NICHD-MFMU in the US), only 20% and 8%, respectively, of treated patients required insulin; the rest were managed successfully with diet. The burden will be in having adequate numbers of dietitians, and there will likely be creative approaches to educating newly diagnosed women, such as group counseling sessions. Self glucose monitoring could also increase the burden, but these milder forms may not require testing every day."
Others have raised concerns that the higher-risk GDM diagnostic label, irrespective of a woman's degree of glucose control, could stimulate an increase in perinatal interventions, earlier deliveries, caesarean section rates, babies admitted to special care nurseries, healthcare costs,[19] and psychological distress and anxiety related to the diagnosis of GDM.[15]
Implications for Clinical Practice
The IADPSG Consensus Panel recommendations are currently being considered for adoption by leading consumer and professional organizations such as the ADA and the American Congress of Obstetricians and Gynecologists. In a recent update of their position statement on diagnosis and classification of diabetes, the ADA said the following about the consensus panel's recommendations:
"At the time of publication of this update, ADA is planning to work with US obstetrical organizations to consider adoption of the IADPSG diagnostic criteria and to discuss the implications of this change. While this change will significantly increase the prevalence of GDM, there is mounting evidence that treating even mild GDM reduces morbidity for both mother and baby."[11]
If adopted, the new guidelines are expected to have immediate, widespread clinical implications.
Changes in screening for GDM. The detection strategy recommended by the IADPSG has 2 phases:
1.Testing for overt diabetes at the initial prenatal visit. Universal early testing in populations with a high prevalence of type 2 diabetes is recommended; others may choose to test only high-risk groups (Table 2)
2.A 75-g OGTT after an overnight fast at 24-28 weeks' gestation in all women not previously diagnosed with overt diabetes or GDM.
Table 2. Low and High Risk Factors for GDM[4,10]
Low risk for GDM
•Age < 25 years •Normal body weight •No family history (1st degree) of DM •No history of abnormal glucose metabolism •Not of ethnic/racial group with high prevalence of DM (African-Americans, Asian-Americans, Hispanic- Americans, Native Americans, Pacific Islanders) High risk for GDM •Maternal age > 35 years
•Marked obesity
•Personal history of GDM
•Previous infant > 4 kg
•Pre-diabetes
•Glycosuria
•Strong family history of DM
•Hypertension before pregnancy
or in early pregnancy
•Ethnic/racial group with high prevalence of DM (African-Americans, Asian-Americans, Hispanic-Americans, Native Americans, Pacific Islanders)
The proposed screening strategy and cut-offs for the diagnosis of GDM are summarized in Table 3.
Table 3. Proposed Screening for GDM
When Diagnosis Test Cut-off for diagnosis
1st prenatal visit Overt diabetes FPG 126 mg/dL (7.0 mmol/L)
HbA1C ≥ 6.5%
Randoma 200 mg/dL (11.1 mmol/L)
24-28 weeks Gestational diabetes FPG 92 mg/dL (5.1 mmol/L)
75g OGTT-1 hr 180 mg/dL (10.0 mmol/L)
75g OGTT-2 hr 153 mg/dL (8.5 mmol/L)
aConfirmation required.
Women who exceed the threshold for GDM on FPG (92 mg/dl or 5.1 mmol/L) at the first prenatal visit are diagnosed as having gestational diabetes. Women whose FPG at first prenatal visit is below 92 mg/dL (5.1 mmol/L) are tested with a 2-hour OGTT at 24-28 weeks to rule out GDM.
Dr. Coustan addressed the issue of how these guideline changes might affect primary maternity care: "In some ways, life will be easier for clinicians if the new recommendations are adopted:
1.We will go from a 2-step screening procedure (50-g challenge, then 100-g 3-hour OGTT if challenge test is positive) to a 1-step procedure;
2.The glucose load used for the OGTT decreases from 100 g to 75 g, which may improve patient acceptance;
3.The 75-g, 2-hour test is the same as that used in nonpregnant adults, although diagnostic thresholds will be different, so less likelihood of error with the lab doing the wrong test;
4.A single elevated value (out of the 3 blood samples -- FPG, 1-hour, and 2-hour) will be sufficient to diagnose GDM, rather than the current requirement for 2 elevated values (out of 4) . . . this will eliminate the 'borderline' state of one abnormal value and the quandary as to how to treat these patients.
5.With the recommendation from IADPSG about how to diagnose pre-existing diabetes when patients present early in pregnancy with high glucose values, clinicians will be able to remove the ambiguity about how to manage such patients."
Prompt treatment of newly diagnosed women with GDM is important. Most fetal weight accretion occurs in the third trimester, so treatment should begin as soon as the diagnosis is made. Treatment strategies for GDM include dietary modifications, regulated exercise, and pharmacologic agents. Most women can be managed with diet and exercise, and will not require insulin.[20]
Preconception care. As many as half of pregnancies in the US are unplanned.[21] Thus, women with chronic medical conditions such as diabetes might not have the opportunity to take steps to optimize management of their diabetes before becoming pregnant. Adverse outcomes are more likely to occur in women with GDM who do not receive preconception counseling.[22]
When providers are able to do preconception assessment and counseling, women who have prediabetes should be taught how to improve their metabolic control prior to conception, in order to reduce the likelihood of birth defects if they progress to diabetes. Lifestyle interventions have been shown to prevent the progression of prediabetes to diabetes in a randomized trial.[23] With help, women may be able to avoid the risks of a diabetic pregnancy. Every healthcare provider who takes care of a woman of reproductive age has something to contribute to preconception care, by diagnosing prediabetes and helping that individual avoid progression to diabetes and its attendant risks during pregnancy.
Conclusion
If the IADPSG's proposed criteria for GDM diagnosis are adopted, we will be able to identify gravidas who have increased risks for adverse outcomes, such as large, fat, or hyperinsulinemic babies and cesarean section delivery.[8] Along with new evidence for a treatment benefit for GDM, the time may be right for a new approach to the screening of pregnant women for potentially correctable alterations of glucose metabolism. Clinicians should stay tuned for further developments, such as official adoption of the IADPSG recommendations, and be prepared for the changes to clinical practice that will inevitably follow.
References
Change Is in the Air
Laura A. Stokowski, RN, MS
08/04/10
A Parallel Epidemic
The word "epidemic" is so overused that it has lost its undercurrent of urgency. We are experiencing epidemics of obesity, high cholesterol, cardiovascular disease, and diabetes. An epidemic has become the norm. Even the word "pandemic," thanks to swine flu, no longer conveys a sense of gravity. New words are needed to describe the overarching implications of a society in which type 2 diabetes afflicts at least 1 in 10 people and, quite possibly, many more.
The prevalence of gestational diabetes mellitus (GDM) will likely grow, as it has in the past, in direct proportion to that of type 2 diabetes.[1] Indications are that GDM already parallels the rapid increase in type 2 diabetes. In a US medical center where the screening method and diagnostic criteria for GDM have remained constant, the prevalence of this complication of pregnancy doubled in 8 years -- a 12% increase per year that cannot be explained by changes in age, ethnic distribution, or previous history of GDM among screened pregnancies.[2]
Arguably more disturbing than the number of people diagnosed with type 2 diabetes or GDM is the number of people who have prediabetes (ie, impaired fasting glucose and/or impaired glucose tolerance).
Currently, an estimated 19% of people over the age of 20 have prediabetes,[3] and this is the pool from which childbearing women are drawn.
Gestational Diabetes Mellitus
Gestational diabetes is glucose intolerance with onset or first recognition during pregnancy.
Pregnancy is already a diabetogenic state, with progressive deterioration of insulin resistance and glucose tolerance that become more significant in the third trimester.
Neonatal problems of offspring of frankly diabetic mothers (eg, congenital defects, spontaneous abortion, fetal macrosomia, birth injury, hypoglycemia, polycythemia, and hyperbilirubinemia) are well described. Exposure to diabetes during gestation also increases the risk for childhood and adult obesity, diabetes, and cardiovascular disease. However, risk for adverse outcomes associated with degrees of maternal hyperglycemia that are short of overt diabetes remains controversial.
In the United States, GDM is commonly diagnosed using either the World Health Organization's criteria (the same as those used to diagnose diabetes in nonpregnant women), or on the basis of a woman's risk of developing diabetes in the future. Neither of these methods links the key metabolic aberration of GDM (ie, maternal hyperglycemia) with the risk for adverse outcomes in the fetus and newborn. Most experts agree that new, more clinically relevant, risk-based criteria for the diagnosis of GDM are needed, especially considering the similarities between GDM and prediabetes. However, levels of maternal glucose intolerance that correlate with poor neonatal outcomes had not been sufficiently ascertained until the results of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study were reported.
The HAPO Study
The HAPO epidemiologic study was the first to conclusively establish a relationship between elevated maternal glucose concentrations and undesirable perinatal outcomes in women not previously diagnosed with diabetes.
The HAPO study clarified the association between multiple adverse outcomes of pregnancy and degrees of hyperglycemia less severe than those diagnostic of diabetes. Data for establishing internationally agreed-upon diagnostic criteria for GDM were also provided. This well-controlled study involved 25,000 women in 9 countries -- a multicultural, ethnically diverse cohort. All women underwent a 2-hour oral glucose tolerance test (OGTT) with a 75-g glucose load at 24-32 weeks' gestation, and random plasma glucose testing at 34-37 weeks. Results were blinded unless a woman's fasting, 2-hour, or random glucose values were elevated to a level that mandated immediate treatment.
Primary outcomes were macrosomia (ie, birth weight > 90th percentile), primary cesarean delivery, and clinical neonatal hypoglycemia and hyperinsulinemia (ie, cord serum C-peptide > 90th percentile). The analysis aimed to determine whether threshold levels of maternal glucose -- for any of the 1-hour, 2-hour, or fasting plasma glucose (FPG) levels -- could be identified for any of the negative outcomes. They found that each of the primary outcomes was associated not only with extremely high maternal glucose concentrations, but in a continuous and graded manner across the full range of observed glucose levels,[9] which precluded easy identification of threshold levels where risk for adverse outcomes rose. The relationship between maternal glucose levels and fetal growth and neonatal outcome seemed to be a basic biologic phenomenon, and not a clearly demarcated disease state, as had previously been thought.
Several secondary outcomes were also evaluated in the HAPO study, including preeclampsia, preterm delivery (ie, delivery at < 37 weeks' gestation), shoulder dystocia and/or birth injury, hyperbilirubinemia, and admission to neonatal intensive care. Shoulder dystocia or birth injury, preterm delivery, and preeclampsia were significantly associated with ≥ 1 elevated glucose values.[9] The blinding of maternal glucose (except when overt diabetes was suggested) is a strength of the HAPO study, because maternal glucose was not a factor in obstetric management. It is also promising that the study's findings did not vary by medical center or country. The results are therefore applicable globally and can be used to develop criteria for classifying gestational diabetes world-wide. Next Step: New Diagnostic Criteria The HAPO investigators did not attempt to translate their findings into new criteria for the diagnosis of gestational diabetes.[8] This task fell to a committee of experts, the International Association of Diabetes and Pregnancy Study Groups (IADPSG), who met to review the data, form a consensus, and make recommendations. A pivotal decision involved the threshold for diagnosing GDM using data from fasting glucose and 2-hour OGTT. This threshold would be somewhat arbitrary, because no inflection points were apparent in the linear relationships between maternal glucose concentrations and outcomes.[8] The IADPSG examined the strong linear associations between risk for neonatal outcomes and the 3 measures of maternal glucose (FPG, 1-hour OGTT, and 2-hour OGTT). The threshold was set at an odds ratio of 1.75, which identified 16.1% of the pregnant population as having GDM (Table 1). Table 1. Proposed and Current Thresholds for the Diagnosis of GDM Maternal glucose test Proposed diagnostic thresholda Above threshold (cumulative %) Current thresholda Fasting plasma glucose 92 mg/dl (5.1 mmol/L) 8.3 95 mg/dl (5.3 mmol/L) 1 hour plasma glucose 180 mg/dl (10 mmol/L) 14.0 180 mg/dl (10 mmol/L) 2 hour plasma glucose 153 mg/dl (8.5 mmol/L) 16.1 155 mg/dl (8.6 mmol/L) aWith 75 g OGTT Only 1 of these cut-offs (FPG, 1-hour OGTT, or 2-hour OGTT) must be met or exceeded to diagnose GDM, unlike current American Diabetes Association (ADA) criteria, which require 2 elevated glucose levels to diagnose GDM. The proposed thresholds are those for which the odds of having a baby with birth weight, cord C-peptide, or neonatal body fat in the > 90th percentiles are 1.75 times the estimated odds of these outcomes at mean glucose values. Setting the threshold higher would decrease the number of women diagnosed with GDM, but would also fail to identify many women whose glucose concentrations place them at the same risk for adverse pregnancy outcomes, and who might benefit from treatment. In this study, 1.7% of patients were unblinded because of elevated FPG or OGTT results. When these patients are included, the total incidence of gestational diabetes in pregnant women rises to 17.8%.
Glucose Testing Considerations
The finding that slight differences in maternal glucose levels are associated with marked differences in outcomes throws intoclear relief the importance of precision in glucose testing. Odds ratios and frequencies for outcomes increase substantially over relatively small changes in glucose. While the handling of blood samples in research is tightly controlled, the real world typically introduces extensive variability. Even a small error in test results caused by poor handling or analytic technique could result in the misclassification of a patient.
For reliable diagnosis and classification of hyperglycemia in pregnancy, venous plasma or serum glucose must be analyzed with a highly accurate enzymatic method. The collection, handling, and transport of blood samples to minimize pre-analytic glycolysis are extremely important. The IADPSG recommends that only venous samples be used for glucose determination, emphasizing that capillary and venous samples are not interchangeable. If the plasma is not separated promptly, the blood sample should be kept cold, because glycolysis will continue in the presence of red and white blood cells, falsely reducing the patient's blood glucose level by 5-15%. It is often mistakenly believed that as soon as the blood is placed in sodium fluoride (a glycolysis inhibitor), glycolysis will stop, but in fact, sodium fluoride has little effect on glycolysis in the first 1-2 hours after sample collection.Point-of-care glucose testing with handheld glucose meters is not appropriate for the diagnosis of GDM.
Significance of Proposed Guidelines
Lowering the diagnostic threshold will undoubtedly raise the frequency of hyperglycemic disorders seen in clinical practice. This would matter less if it could be shown that a benefit can be derived from improving even mild aberrations in glucose metabolism during pregnancy. The longstanding debate about the value of screening pregnant women for hyperglycemia has centered on uncertainties about the treatment benefit.
Benefit of treating GDM. In May 2008, the US Preventive Services Task Force concluded that there was inadequate evidence to recommend treatment of GDM, largely because of inadequate prospective studies.[14] A subsequent review concluded that treatment of GDM after 24 weeks of pregnancy improves some maternal and neonatal outcomes; however, evidence for screening before 24 weeks' gestation is more sparse.[15] The gestational time at which hyperglycemia screening should be initiated, and the level of hyperglycemia that warrants aggressive intervention remain controversial.[16]
In 2005, the results of ACHOIS (Australian Carbohydrate Intolerance Study in Pregnant Women), a 10-year multicenter randomized trial, were published.[17] ACHOIS assessed whether treating mild GDM would reduce perinatal morbidity and mortality. Treatment with dietary counseling, self glucose monitoring, and insulin when indicated, significantly reduced adverse primary outcomes (ie, perinatal death, shoulder dystocia, and birth trauma), neonatal adipoinsular macrosomia, maternal preeclampsia, and labor induction. Landon and colleagues conducted a randomized controlled trial sponsored by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD-MFMU) Network, compared untreated women with mild GDM with those receiving treatment (nutritional counseling, diet therapy, insulin if needed, etc.).[18] Significant reductions in macrosomia, neonatal fat mass, shoulder dystocia, preeclampsia, and cesarean section were seen in the treated cohort.
Both treatment trials revealed a positive effect of treatment in preventing large for gestational age (LGA) births, macrosomia, and shoulder dystocia.
Together, these 2 studies argue convincingly for a treatment benefit for mild GDM.While neither study found significant effects of treatment on neonatal morbidities such as hypoglycemia or hyperbilirubinemia, their findings of reduced neonatal fat mass, LGA, and macrosomia have important implications for long-term child and adult health. Excess neonatal fat and adipoinsular macrosomia are linked to childhood obesity and later development of diabetes. If these findings are real, then the successful treatment of maternal GDM, even mild GDM, could positively influence the health of the next generation.
Health system burden.
Although the new criteria are expected to double the number of women diagnosed with GDM, the rate will be consistent with the high prevalence of obesity and glucose intolerance in the general population. Donald R. Coustan, MD, Professor of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Division of Maternal-Fetal Medicine, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, explained the implications of classifying such a large slice of the pregnant population as having GDM and the potential burden on high-risk maternity care:
"Currently (as of 2007), the Centers for Disease Control and Prevention tells us that 10.7% of adult Americans have diabetes; furthermore, the American Diabetes Association states that 19% of adult Americans have prediabetes. So 17% is not such an extreme prevalence for GDM, which is quite similar to prediabetes in its severity. In the 2 randomized trials of identification and treatment of mild GDM (ACHOIS in Australia and NICHD-MFMU in the US), only 20% and 8%, respectively, of treated patients required insulin; the rest were managed successfully with diet. The burden will be in having adequate numbers of dietitians, and there will likely be creative approaches to educating newly diagnosed women, such as group counseling sessions. Self glucose monitoring could also increase the burden, but these milder forms may not require testing every day."
Others have raised concerns that the higher-risk GDM diagnostic label, irrespective of a woman's degree of glucose control, could stimulate an increase in perinatal interventions, earlier deliveries, caesarean section rates, babies admitted to special care nurseries, healthcare costs,[19] and psychological distress and anxiety related to the diagnosis of GDM.[15]
Implications for Clinical Practice
The IADPSG Consensus Panel recommendations are currently being considered for adoption by leading consumer and professional organizations such as the ADA and the American Congress of Obstetricians and Gynecologists. In a recent update of their position statement on diagnosis and classification of diabetes, the ADA said the following about the consensus panel's recommendations:
"At the time of publication of this update, ADA is planning to work with US obstetrical organizations to consider adoption of the IADPSG diagnostic criteria and to discuss the implications of this change. While this change will significantly increase the prevalence of GDM, there is mounting evidence that treating even mild GDM reduces morbidity for both mother and baby."[11]
If adopted, the new guidelines are expected to have immediate, widespread clinical implications.
Changes in screening for GDM. The detection strategy recommended by the IADPSG has 2 phases:
1.Testing for overt diabetes at the initial prenatal visit. Universal early testing in populations with a high prevalence of type 2 diabetes is recommended; others may choose to test only high-risk groups (Table 2)
2.A 75-g OGTT after an overnight fast at 24-28 weeks' gestation in all women not previously diagnosed with overt diabetes or GDM.
Table 2. Low and High Risk Factors for GDM[4,10]
Low risk for GDM
•Age < 25 years •Normal body weight •No family history (1st degree) of DM •No history of abnormal glucose metabolism •Not of ethnic/racial group with high prevalence of DM (African-Americans, Asian-Americans, Hispanic- Americans, Native Americans, Pacific Islanders) High risk for GDM •Maternal age > 35 years
•Marked obesity
•Personal history of GDM
•Previous infant > 4 kg
•Pre-diabetes
•Glycosuria
•Strong family history of DM
•Hypertension before pregnancy
or in early pregnancy
•Ethnic/racial group with high prevalence of DM (African-Americans, Asian-Americans, Hispanic-Americans, Native Americans, Pacific Islanders)
The proposed screening strategy and cut-offs for the diagnosis of GDM are summarized in Table 3.
Table 3. Proposed Screening for GDM
When Diagnosis Test Cut-off for diagnosis
1st prenatal visit Overt diabetes FPG 126 mg/dL (7.0 mmol/L)
HbA1C ≥ 6.5%
Randoma 200 mg/dL (11.1 mmol/L)
24-28 weeks Gestational diabetes FPG 92 mg/dL (5.1 mmol/L)
75g OGTT-1 hr 180 mg/dL (10.0 mmol/L)
75g OGTT-2 hr 153 mg/dL (8.5 mmol/L)
aConfirmation required.
Women who exceed the threshold for GDM on FPG (92 mg/dl or 5.1 mmol/L) at the first prenatal visit are diagnosed as having gestational diabetes. Women whose FPG at first prenatal visit is below 92 mg/dL (5.1 mmol/L) are tested with a 2-hour OGTT at 24-28 weeks to rule out GDM.
Dr. Coustan addressed the issue of how these guideline changes might affect primary maternity care: "In some ways, life will be easier for clinicians if the new recommendations are adopted:
1.We will go from a 2-step screening procedure (50-g challenge, then 100-g 3-hour OGTT if challenge test is positive) to a 1-step procedure;
2.The glucose load used for the OGTT decreases from 100 g to 75 g, which may improve patient acceptance;
3.The 75-g, 2-hour test is the same as that used in nonpregnant adults, although diagnostic thresholds will be different, so less likelihood of error with the lab doing the wrong test;
4.A single elevated value (out of the 3 blood samples -- FPG, 1-hour, and 2-hour) will be sufficient to diagnose GDM, rather than the current requirement for 2 elevated values (out of 4) . . . this will eliminate the 'borderline' state of one abnormal value and the quandary as to how to treat these patients.
5.With the recommendation from IADPSG about how to diagnose pre-existing diabetes when patients present early in pregnancy with high glucose values, clinicians will be able to remove the ambiguity about how to manage such patients."
Prompt treatment of newly diagnosed women with GDM is important. Most fetal weight accretion occurs in the third trimester, so treatment should begin as soon as the diagnosis is made. Treatment strategies for GDM include dietary modifications, regulated exercise, and pharmacologic agents. Most women can be managed with diet and exercise, and will not require insulin.[20]
Preconception care. As many as half of pregnancies in the US are unplanned.[21] Thus, women with chronic medical conditions such as diabetes might not have the opportunity to take steps to optimize management of their diabetes before becoming pregnant. Adverse outcomes are more likely to occur in women with GDM who do not receive preconception counseling.[22]
When providers are able to do preconception assessment and counseling, women who have prediabetes should be taught how to improve their metabolic control prior to conception, in order to reduce the likelihood of birth defects if they progress to diabetes. Lifestyle interventions have been shown to prevent the progression of prediabetes to diabetes in a randomized trial.[23] With help, women may be able to avoid the risks of a diabetic pregnancy. Every healthcare provider who takes care of a woman of reproductive age has something to contribute to preconception care, by diagnosing prediabetes and helping that individual avoid progression to diabetes and its attendant risks during pregnancy.
Conclusion
If the IADPSG's proposed criteria for GDM diagnosis are adopted, we will be able to identify gravidas who have increased risks for adverse outcomes, such as large, fat, or hyperinsulinemic babies and cesarean section delivery.[8] Along with new evidence for a treatment benefit for GDM, the time may be right for a new approach to the screening of pregnant women for potentially correctable alterations of glucose metabolism. Clinicians should stay tuned for further developments, such as official adoption of the IADPSG recommendations, and be prepared for the changes to clinical practice that will inevitably follow.
References
Wednesday, August 11, 2010
Prenatal Cigarette Exposure Increases Risk for Psychiatric Illness Into Adulthood
Megan Brooks
August 3, 2010 — The risk for psychiatric illness is significantly higher in young adults exposed to cigarette smoke in the womb relative to those without prenatal cigarette smoke exposure, even after adjusting for maternal psychiatric illness and other confounding factors, according to a Finnish study reported in the August issue of the Archives of General Psychiatry.
"This association seemed to be robust because it could be found in a large group of diagnoses and the dose relationship was also strong," first study author Mikael Ekblad, BM, of University of Turku, Finland, and colleagues note in the article.
Prenatal smoking exposure impairs fetal growth and modulates brain development, which may alter mental development of the offspring, they point out.
The researchers used population-based, longitudinal registry data to evaluate the effects of prenatal smoking exposure on psychiatric morbidity among 175,869 Finnish young adults born from January 1, 1987, through December 31, 1989, with follow-up lasting 18 to 20 years. They had information on mothers' smoking habits (self-reported) during pregnancy and other relevant background factors, as well as psychiatric history of mothers and offspring.
Smoking during pregnancy was reported by 26,075 mothers (15.3%). Of these, 8866 (34.0%) smoked more than 10 cigarettes a day. In 5487 children (3.2%), maternal smoking history was unknown.
The prevalence of any psychiatric diagnosis was 15.0% after excluding the children with unknown maternal smoking history. The prevalence was 13.7% in unexposed children (the reference group), 21.0% in those exposed to fewer than 10 cigarettes a day (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.47 – 1.60), and 24.7% in those exposed to more than 10 cigarettes a day (aOR, 1.85; 95% CI, 1.74 – 1.96).
Prenatal smoke exposure significantly increased the risk for most of the psychiatric diagnoses, with the exception of schizophrenia and anorexia diagnoses, the study authors report. The strongest effects were seen for psychiatric disorders due to psychoactive substance use and behavioral and emotional disorders. The lack of a statistically significant finding for schizophrenia may be due to a fairly low number of cases in the study.
There were 870 total deaths in the study population (5.7 per 1000), of which 64 (7.4%) were suicides (excluding children with unknown maternal smoking data). After adjusting for confounding factors, young adults exposed to >10 cigarettes a day during gestation had a significantly increased risk for early death (OR, 1.69; 95% CI, 1.31 – 2.19) compared with unexposed young adults. The mortality rate per 1000 children was 4.7 for unexposed children vs 6.3 and 9.1 for exposure to <10 and >10 cigarettes per day, respectively.
Results Generally Mirror Prior Studies
Commenting on the study for Medscape Medical News, David M. Fergusson, PhD, of the Department of Psychological Medicine, Christchurch School of Medicine & Health Sciences in New Zealand, who was not involved in the study, said, "The results are generally consistent with previous research that has suggested that maternal smoking may be associated with increased risks of at least some mental disorders."
In their report, Dr. Ekblad's team points to several study strengths, including a large national study population; the ability to control the child's outcome for maternal mental illness, which has not been done previously in similar large epidemiologic studies; and adjustment for a wide range of background factors, such as 5-minute Apgar scores, the child's birth weight, maternal age, and the mother's psychiatric morbidity before the child's birth.
Limitations of the study include lack of information on alcohol and illicit drug use during pregnancy; self-reported maternal smoking history; potential concern about accuracy of diagnoses; and lack of socioeconomic data, such as parents' educational level and exposure to passive smoke in the home, which can affect risk for psychiatric problems.
"The study," Dr. Fergusson noted, "adds to previous research by being based on a large population (but) is limited by the use of official record data."
The control of confounding factors is "limited," he added, "raising the possibility that the findings may reflect the presence of other factors, which are associated with pregnancy smoking. A further limitation is that the mechanisms by which pregnancy smoking may lead to increased risks of a wide range of mental disorders are by no means clear."
Nonetheless, Dr. Fergusson said this new study further reinforces public health messages regarding the adverse effects of smoking during pregnancy. "It is well known that pregnancy smoking increases the risk of miscarriage, stillbirth, and low-birth-weight infants. The present findings raise the possibility that exposure to pregnancy smoking may have adverse effects on longer-term mental health of offspring," he noted.
Arch Gen Psychiatry. 2010;67:841-849.
August 3, 2010 — The risk for psychiatric illness is significantly higher in young adults exposed to cigarette smoke in the womb relative to those without prenatal cigarette smoke exposure, even after adjusting for maternal psychiatric illness and other confounding factors, according to a Finnish study reported in the August issue of the Archives of General Psychiatry.
"This association seemed to be robust because it could be found in a large group of diagnoses and the dose relationship was also strong," first study author Mikael Ekblad, BM, of University of Turku, Finland, and colleagues note in the article.
Prenatal smoking exposure impairs fetal growth and modulates brain development, which may alter mental development of the offspring, they point out.
The researchers used population-based, longitudinal registry data to evaluate the effects of prenatal smoking exposure on psychiatric morbidity among 175,869 Finnish young adults born from January 1, 1987, through December 31, 1989, with follow-up lasting 18 to 20 years. They had information on mothers' smoking habits (self-reported) during pregnancy and other relevant background factors, as well as psychiatric history of mothers and offspring.
Smoking during pregnancy was reported by 26,075 mothers (15.3%). Of these, 8866 (34.0%) smoked more than 10 cigarettes a day. In 5487 children (3.2%), maternal smoking history was unknown.
The prevalence of any psychiatric diagnosis was 15.0% after excluding the children with unknown maternal smoking history. The prevalence was 13.7% in unexposed children (the reference group), 21.0% in those exposed to fewer than 10 cigarettes a day (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.47 – 1.60), and 24.7% in those exposed to more than 10 cigarettes a day (aOR, 1.85; 95% CI, 1.74 – 1.96).
Prenatal smoke exposure significantly increased the risk for most of the psychiatric diagnoses, with the exception of schizophrenia and anorexia diagnoses, the study authors report. The strongest effects were seen for psychiatric disorders due to psychoactive substance use and behavioral and emotional disorders. The lack of a statistically significant finding for schizophrenia may be due to a fairly low number of cases in the study.
There were 870 total deaths in the study population (5.7 per 1000), of which 64 (7.4%) were suicides (excluding children with unknown maternal smoking data). After adjusting for confounding factors, young adults exposed to >10 cigarettes a day during gestation had a significantly increased risk for early death (OR, 1.69; 95% CI, 1.31 – 2.19) compared with unexposed young adults. The mortality rate per 1000 children was 4.7 for unexposed children vs 6.3 and 9.1 for exposure to <10 and >10 cigarettes per day, respectively.
Results Generally Mirror Prior Studies
Commenting on the study for Medscape Medical News, David M. Fergusson, PhD, of the Department of Psychological Medicine, Christchurch School of Medicine & Health Sciences in New Zealand, who was not involved in the study, said, "The results are generally consistent with previous research that has suggested that maternal smoking may be associated with increased risks of at least some mental disorders."
In their report, Dr. Ekblad's team points to several study strengths, including a large national study population; the ability to control the child's outcome for maternal mental illness, which has not been done previously in similar large epidemiologic studies; and adjustment for a wide range of background factors, such as 5-minute Apgar scores, the child's birth weight, maternal age, and the mother's psychiatric morbidity before the child's birth.
Limitations of the study include lack of information on alcohol and illicit drug use during pregnancy; self-reported maternal smoking history; potential concern about accuracy of diagnoses; and lack of socioeconomic data, such as parents' educational level and exposure to passive smoke in the home, which can affect risk for psychiatric problems.
"The study," Dr. Fergusson noted, "adds to previous research by being based on a large population (but) is limited by the use of official record data."
The control of confounding factors is "limited," he added, "raising the possibility that the findings may reflect the presence of other factors, which are associated with pregnancy smoking. A further limitation is that the mechanisms by which pregnancy smoking may lead to increased risks of a wide range of mental disorders are by no means clear."
Nonetheless, Dr. Fergusson said this new study further reinforces public health messages regarding the adverse effects of smoking during pregnancy. "It is well known that pregnancy smoking increases the risk of miscarriage, stillbirth, and low-birth-weight infants. The present findings raise the possibility that exposure to pregnancy smoking may have adverse effects on longer-term mental health of offspring," he noted.
Arch Gen Psychiatry. 2010;67:841-849.
Monday, August 9, 2010
Risks for Preterm Births May Be Higher Among Overweight and Obese Mothers
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
July 28, 2010 — Risks for preterm births may be higher among overweight and obese mothers, according to the results of a systematic review and meta-analyses reported in the July 20 issue of the BMJ.
The goal of the study was to examine the association of maternal overweight and obesity with preterm birth and low birth weight in singleton pregnancies in developed as well as in developing countries. Sarah D. McDonald, from McMaster University in Hamilton, Ontario, Canada, and colleagues searched MEDLINE and EMBASE from their beginnings, as well as bibliographies of retrieved articles. Inclusion criteria were studies of the effect of overweight and obesity vs a reference group of women with normal body mass index (BMI), on 2 main study endpoints of preterm birth (< 37 weeks) and low birth weight (< 2500 g).
Using a piloted data collection form, 2 investigators independently reviewed titles, abstracts, and full articles; extracted information; and evaluated the quality of the retrieved studies. The 84 studies included in the meta-analyses enrolled a total of 1,095,834 women. Of these studies, 64 were cohort studies and 20 were case-control studies.
Compared with women of normal weight, overweight and obese women had a similar risk for preterm birth overall but an increased risk for induced preterm birth (relative risk [RR], 1.30; 95% confidence interval [CI], 1.23 - 1.37) and a lower risk of having an infant of low birth weight (RR, 0.84; 95% CI, 0.75 - 0.95). The reduction in the risk of having an infant of low birth weight was greater in developing countries vs developed countries (RR, 0.58; 95% CI, 0.47 - 0.71 vs RR, 0.90; 95% CI, 0.79 - 1.01).
Analyses to account for publication bias showed that when imputed "missing" studies were added, the apparent protective effect of overweight and obesity on low birth weight disappeared, whereas the risk for preterm birth appeared significantly higher in overweight and obese women (RR, 1.24; 95% CI, 1.13 - 1.37).
Compared with normal-weight women, very obese women were at 70% greater risk for induced preterm birth before 37 weeks and at 82% greater risk for early preterm birth (before 32 or 33 weeks).
"Overweight and obese women have increased risks of preterm birth and induced preterm birth and, after accounting for publication bias, appeared to have increased risks of preterm birth overall," the study authors write. "The beneficial effects of maternal overweight and obesity on low birth weight were greater in developing countries and disappeared after accounting for publication bias."
Limitations of this review include potential residual confounding and inability to determine causal relationships or underlying mechanisms.
"Future research is needed to try to determine why overweight and obese women are at risk of preterm birth, and to determine effective methods of weight loss in women of childbearing age before pregnancy," the study authors conclude. " ...Clinicians need to be aware that overweight or obesity in women is not protective against having infants of low birth weight and should consider surveillance when indicated. Ideally, overweight or obese women should have prepregnancy counselling so that they are informed of their perinatal risks and can try to optimise their weight before pregnancy."
The Canadian Institute of Health Research supported this study and 2 of its authors. A third study author was supported by the China Scholarship Council.
BMJ. 2010;341:c3428.
Clinical Context
It has become clear that the goals for gestational weight gain should be individualized. In a study by Nohr and colleagues of more than 60,000 term pregnancies, which was published in the December 2008 issue of the American Journal of Clinical Nutrition, researchers found that gestational weight gain of 16 kg or more interacted with a higher prepartum BMI to create a higher risk for delivery via cesarean and a low Apgar score after delivery, as well as a higher risk for postpartum weight retention. However, higher levels of gestational weight gain also reduced the risks for intrauterine growth restriction and a low birth weight at delivery, particularly among women who were underweight before pregnancy.
Other studies suggest that obesity does not protect against deliveries of infants with low birth weight. The current systematic review and meta-analysis addresses the issue of the effect of overweight and obesity on the risks for low birth weight and preterm delivery.
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
July 28, 2010 — Risks for preterm births may be higher among overweight and obese mothers, according to the results of a systematic review and meta-analyses reported in the July 20 issue of the BMJ.
The goal of the study was to examine the association of maternal overweight and obesity with preterm birth and low birth weight in singleton pregnancies in developed as well as in developing countries. Sarah D. McDonald, from McMaster University in Hamilton, Ontario, Canada, and colleagues searched MEDLINE and EMBASE from their beginnings, as well as bibliographies of retrieved articles. Inclusion criteria were studies of the effect of overweight and obesity vs a reference group of women with normal body mass index (BMI), on 2 main study endpoints of preterm birth (< 37 weeks) and low birth weight (< 2500 g).
Using a piloted data collection form, 2 investigators independently reviewed titles, abstracts, and full articles; extracted information; and evaluated the quality of the retrieved studies. The 84 studies included in the meta-analyses enrolled a total of 1,095,834 women. Of these studies, 64 were cohort studies and 20 were case-control studies.
Compared with women of normal weight, overweight and obese women had a similar risk for preterm birth overall but an increased risk for induced preterm birth (relative risk [RR], 1.30; 95% confidence interval [CI], 1.23 - 1.37) and a lower risk of having an infant of low birth weight (RR, 0.84; 95% CI, 0.75 - 0.95). The reduction in the risk of having an infant of low birth weight was greater in developing countries vs developed countries (RR, 0.58; 95% CI, 0.47 - 0.71 vs RR, 0.90; 95% CI, 0.79 - 1.01).
Analyses to account for publication bias showed that when imputed "missing" studies were added, the apparent protective effect of overweight and obesity on low birth weight disappeared, whereas the risk for preterm birth appeared significantly higher in overweight and obese women (RR, 1.24; 95% CI, 1.13 - 1.37).
Compared with normal-weight women, very obese women were at 70% greater risk for induced preterm birth before 37 weeks and at 82% greater risk for early preterm birth (before 32 or 33 weeks).
"Overweight and obese women have increased risks of preterm birth and induced preterm birth and, after accounting for publication bias, appeared to have increased risks of preterm birth overall," the study authors write. "The beneficial effects of maternal overweight and obesity on low birth weight were greater in developing countries and disappeared after accounting for publication bias."
Limitations of this review include potential residual confounding and inability to determine causal relationships or underlying mechanisms.
"Future research is needed to try to determine why overweight and obese women are at risk of preterm birth, and to determine effective methods of weight loss in women of childbearing age before pregnancy," the study authors conclude. " ...Clinicians need to be aware that overweight or obesity in women is not protective against having infants of low birth weight and should consider surveillance when indicated. Ideally, overweight or obese women should have prepregnancy counselling so that they are informed of their perinatal risks and can try to optimise their weight before pregnancy."
The Canadian Institute of Health Research supported this study and 2 of its authors. A third study author was supported by the China Scholarship Council.
BMJ. 2010;341:c3428.
Clinical Context
It has become clear that the goals for gestational weight gain should be individualized. In a study by Nohr and colleagues of more than 60,000 term pregnancies, which was published in the December 2008 issue of the American Journal of Clinical Nutrition, researchers found that gestational weight gain of 16 kg or more interacted with a higher prepartum BMI to create a higher risk for delivery via cesarean and a low Apgar score after delivery, as well as a higher risk for postpartum weight retention. However, higher levels of gestational weight gain also reduced the risks for intrauterine growth restriction and a low birth weight at delivery, particularly among women who were underweight before pregnancy.
Other studies suggest that obesity does not protect against deliveries of infants with low birth weight. The current systematic review and meta-analysis addresses the issue of the effect of overweight and obesity on the risks for low birth weight and preterm delivery.
Large Study Assesses Recent Data on Respiratory Morbidity in Late Preterm Neonates
From MedscapeCME Clinical Briefs
News Author: Emma Hitt, PhD
CME Author: Laurie Barclay, MD
July 28, 2010 — Respiratory morbidity rate in infants born during the late preterm period is substantially increased vs infants born at term, according to the largest investigation to date on the issue.
Judith U. Hibbard, MD, with the Department of Obstetrics and Gynecology at the University of Illinois at Chicago, and colleagues from the Consortium on Safe Labor reported the findings in the July 28, 2010, issue of the Journal of the American Medical Association.
According to the researchers, late preterm births (spanning from 34 weeks and 0 days to nearly 37 weeks of gestation) account for 9.1% of all deliveries and approximately 75% of all preterm births in the United States. Preterm deliveries are known to be associated with increased respiratory morbidity rates, but recent data from a large, US-based study are lacking.
"Given advances in obstetric and neonatal care over the last 20 years, we hypothesized that many published rates of morbidity may overestimate the clinical burden attributable to late preterm birth," the study authors note.
The researchers assessed short-term respiratory morbidity in 19,334 late preterm births and compared it with that of 165,993 term births in a contemporary cohort of deliveries in the United States.
Of the late preterm infants, 36.5% were admitted to a neonatal intensive care unit (NICU), and approximately one third of those had respiratory tract symptoms. By contrast, only 7.2% of the term infants were admitted to a NICU, and less than 10% of those had respiratory tract symptoms.
The incidence of respiratory distress syndrome was 10.5% for infants born late preterm (34 weeks of gestation) vs 0.3% for those born at term (38 weeks). Likewise, in late preterm births vs term births, transient tachypnea of the newborn was present in 6.4% vs 0.4%, pneumonia in 1.5% vs 0.1%, and respiratory failure in 1.6% vs 0.2%. Standard and oscillatory ventilatory support was also more common in late preterm births vs term births.
The risk for respiratory distress syndrome was much higher at 34 weeks of gestation (adjusted odds ratio [OR], 40.1; 95% confidence interval [CI], 32.0 - 50.3) vs 38 weeks of gestation (adjusted OR, 1.1; 95% CI, 0.9 - 1.4). At 37 weeks, the adjusted OR for respiratory distress syndrome was higher at 3.1 (95% CI, 2.5 - 3.7) vs 39 and 40 weeks. For infants born at 38 weeks, the risk for any respiratory morbidity was approximately the same at it was for infants born at 39 or 40 weeks.
Risk for other respiratory disorders, including transient tachypnea of the newborn, pneumonia, and respiratory failure also followed a similar pattern of decreasing with gestational age.
"The results of our study support the recommendation that every effort should be made to delay delivery of infants until at least 38 weeks' gestational age to decrease respiratory morbidity," Dr. Hibbard and colleagues conclude.
This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The study authors have disclosed no relevant financial relationships.
JAMA. 2010;304:419-425.
Clinical Context
Late preterm birth is defined as 34 0/7 to 36 6/7 weeks of gestation. In the United States, 9.1% of all deliveries and three quarters of all preterm births are late preterm births.
Short-term morbidity rate is increased in neonates with late preterm births, especially respiratory morbidity, resulting in specialized care and prolonged neonatal hospital and NICU admissions. However, most previous studies evaluating these outcomes were in study samples more than a decade old or were recruited from small populations.
News Author: Emma Hitt, PhD
CME Author: Laurie Barclay, MD
July 28, 2010 — Respiratory morbidity rate in infants born during the late preterm period is substantially increased vs infants born at term, according to the largest investigation to date on the issue.
Judith U. Hibbard, MD, with the Department of Obstetrics and Gynecology at the University of Illinois at Chicago, and colleagues from the Consortium on Safe Labor reported the findings in the July 28, 2010, issue of the Journal of the American Medical Association.
According to the researchers, late preterm births (spanning from 34 weeks and 0 days to nearly 37 weeks of gestation) account for 9.1% of all deliveries and approximately 75% of all preterm births in the United States. Preterm deliveries are known to be associated with increased respiratory morbidity rates, but recent data from a large, US-based study are lacking.
"Given advances in obstetric and neonatal care over the last 20 years, we hypothesized that many published rates of morbidity may overestimate the clinical burden attributable to late preterm birth," the study authors note.
The researchers assessed short-term respiratory morbidity in 19,334 late preterm births and compared it with that of 165,993 term births in a contemporary cohort of deliveries in the United States.
Of the late preterm infants, 36.5% were admitted to a neonatal intensive care unit (NICU), and approximately one third of those had respiratory tract symptoms. By contrast, only 7.2% of the term infants were admitted to a NICU, and less than 10% of those had respiratory tract symptoms.
The incidence of respiratory distress syndrome was 10.5% for infants born late preterm (34 weeks of gestation) vs 0.3% for those born at term (38 weeks). Likewise, in late preterm births vs term births, transient tachypnea of the newborn was present in 6.4% vs 0.4%, pneumonia in 1.5% vs 0.1%, and respiratory failure in 1.6% vs 0.2%. Standard and oscillatory ventilatory support was also more common in late preterm births vs term births.
The risk for respiratory distress syndrome was much higher at 34 weeks of gestation (adjusted odds ratio [OR], 40.1; 95% confidence interval [CI], 32.0 - 50.3) vs 38 weeks of gestation (adjusted OR, 1.1; 95% CI, 0.9 - 1.4). At 37 weeks, the adjusted OR for respiratory distress syndrome was higher at 3.1 (95% CI, 2.5 - 3.7) vs 39 and 40 weeks. For infants born at 38 weeks, the risk for any respiratory morbidity was approximately the same at it was for infants born at 39 or 40 weeks.
Risk for other respiratory disorders, including transient tachypnea of the newborn, pneumonia, and respiratory failure also followed a similar pattern of decreasing with gestational age.
"The results of our study support the recommendation that every effort should be made to delay delivery of infants until at least 38 weeks' gestational age to decrease respiratory morbidity," Dr. Hibbard and colleagues conclude.
This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The study authors have disclosed no relevant financial relationships.
JAMA. 2010;304:419-425.
Clinical Context
Late preterm birth is defined as 34 0/7 to 36 6/7 weeks of gestation. In the United States, 9.1% of all deliveries and three quarters of all preterm births are late preterm births.
Short-term morbidity rate is increased in neonates with late preterm births, especially respiratory morbidity, resulting in specialized care and prolonged neonatal hospital and NICU admissions. However, most previous studies evaluating these outcomes were in study samples more than a decade old or were recruited from small populations.
Prenatal Anxiety Linked to Infant Illnesses and Early Life Antibiotic Use
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
August 2, 2010 — Maternal prenatal anxiety and stress are associated with infant illnesses and antibiotic use early in life, according to the results of a study reported online July 19 in Pediatrics.
"Evidence from both animals and humans suggests that maternal prenatal anxiety and stress can have adverse consequences on the offspring's development," write Roseriet Beijers, MSc, from the Behavioural Science Institute in Nijmegen, the Netherlands, and colleagues. "Animal models also show that prenatal stress has programming effects on the physical health of the offspring, such as immune functioning. In human studies, however, physical health outcomes are often restricted to birth complications; studies on the effects of acquiring illnesses are scarce."
The goal of the study was to determine whether maternal prenatal anxiety and stress are related to more infant illnesses and antibiotic use during the first year of life. The study sample consisted of 174 mothers with normal pregnancies and term deliveries who completed third-trimester questionnaires on general and pregnancy-specific anxiety and stress and who were tested for circadian cortisol levels in saliva.
Of the offspring, 71 were firstborns and 91 were boys. Monthly interviews of the mother during the infant's first year of life allowed collection of data concerning infant illnesses and antibiotic use.
Even after adjustment for many relevant confounders, prenatal anxiety and stress predicted considerable variance in infant illnesses and antibiotic use (9.3% for respiratory tract disease, 10.7% for general disease, 8.9% for skin diseases, and 7.6% for antibiotic use), based on hierarchic multiple regressions. In contrast, prenatal anxiety and stress were not associated with digestive tract illnesses.
Limitations of this study include poor generalizability because nearly all mothers were highly educated, lived together with their partner, had healthy pregnancies, and reported relatively mild or moderate prenatal stress. In addition, this study examined prenatal anxiety and stress only during late gestation, and infant health data were based on maternal report.
"This study is 1 of the first to link maternal prenatal anxiety and stress to infant illnesses and antibiotic use early in life," the study authors write. "As such, it provides a starting point for future research in larger and clinical samples. Follow-up studies are necessary to determine whether the effects of prenatal anxiety and stress on infant susceptibility to illnesses are transient, persistent, or even progressive."
The Netherlands Organization for Scientific Research supported this study. The study authors have disclosed no relevant financial relationships.
Pediatrics. Published online July 19, 2010. Abstract
Clinical Context
Different animal models have reported that prenatal stress has programming effects on the physical health of the offspring such as growth and immune functioning. In the same way, maternal stress and anxiety during pregnancy can affect the development of the offspring. Maternal stress can be reflected in diurnal cortisol levels such as higher evening cortisol levels and flattened diurnal rhythms.
This is a prospective study of healthy pregnant women to determine the association between maternal stress and anxiety as measured by questionnaires and by salivary cortisol and infant health in the first year.
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
August 2, 2010 — Maternal prenatal anxiety and stress are associated with infant illnesses and antibiotic use early in life, according to the results of a study reported online July 19 in Pediatrics.
"Evidence from both animals and humans suggests that maternal prenatal anxiety and stress can have adverse consequences on the offspring's development," write Roseriet Beijers, MSc, from the Behavioural Science Institute in Nijmegen, the Netherlands, and colleagues. "Animal models also show that prenatal stress has programming effects on the physical health of the offspring, such as immune functioning. In human studies, however, physical health outcomes are often restricted to birth complications; studies on the effects of acquiring illnesses are scarce."
The goal of the study was to determine whether maternal prenatal anxiety and stress are related to more infant illnesses and antibiotic use during the first year of life. The study sample consisted of 174 mothers with normal pregnancies and term deliveries who completed third-trimester questionnaires on general and pregnancy-specific anxiety and stress and who were tested for circadian cortisol levels in saliva.
Of the offspring, 71 were firstborns and 91 were boys. Monthly interviews of the mother during the infant's first year of life allowed collection of data concerning infant illnesses and antibiotic use.
Even after adjustment for many relevant confounders, prenatal anxiety and stress predicted considerable variance in infant illnesses and antibiotic use (9.3% for respiratory tract disease, 10.7% for general disease, 8.9% for skin diseases, and 7.6% for antibiotic use), based on hierarchic multiple regressions. In contrast, prenatal anxiety and stress were not associated with digestive tract illnesses.
Limitations of this study include poor generalizability because nearly all mothers were highly educated, lived together with their partner, had healthy pregnancies, and reported relatively mild or moderate prenatal stress. In addition, this study examined prenatal anxiety and stress only during late gestation, and infant health data were based on maternal report.
"This study is 1 of the first to link maternal prenatal anxiety and stress to infant illnesses and antibiotic use early in life," the study authors write. "As such, it provides a starting point for future research in larger and clinical samples. Follow-up studies are necessary to determine whether the effects of prenatal anxiety and stress on infant susceptibility to illnesses are transient, persistent, or even progressive."
The Netherlands Organization for Scientific Research supported this study. The study authors have disclosed no relevant financial relationships.
Pediatrics. Published online July 19, 2010. Abstract
Clinical Context
Different animal models have reported that prenatal stress has programming effects on the physical health of the offspring such as growth and immune functioning. In the same way, maternal stress and anxiety during pregnancy can affect the development of the offspring. Maternal stress can be reflected in diurnal cortisol levels such as higher evening cortisol levels and flattened diurnal rhythms.
This is a prospective study of healthy pregnant women to determine the association between maternal stress and anxiety as measured by questionnaires and by salivary cortisol and infant health in the first year.
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