Secular trends in congenital anomaly‐related fetal and infant mortality in Canada, 1985–1996

Prenatal diagnosis of major congenital anomalies and subsequent termination of affected pregnancies has been widely available as part of routine obstetric care in recent years. In this study, vital statistical data on stillbirths, live births, and infant deaths were used to examine secular trends in gestational age‐specific and category‐specific fetal and infant mortality due to congenital anomalies in Canada (excluding Ontario and Newfoundland) from 1985–1996. Comparisons of the rates between 1985–1987 and 1994–1996 were made using relative risks and 95% confidence intervals (CI). The overall fetal mortality rate due to congenital anomalies increased significantly, from 68.0 per 100,000 total births in 1985–1987 to 78.6 per 100,000 total births in 1994–1996, while the overall infant mortality rate due to congenital anomalies decreased significantly over the same period, from 2.47 to 1.79 per 1,000 live births. The fetal death rate due to congenital anomalies at 20–21 weeks of gestation increased approximately five‐fold (relative risk [RR] = 4.83, 95% CI = 3.28–7.11) from 4.5 to 21.5 per 100,000 fetuses at risk, while the rate at 37–41 weeks decreased by 30% (RR = 0.70, 95% CI = 0.50–0.97). Fetal death rates among pregnancies at 20–25 weeks of gestation increased in all categories of congenital anomaly except anencephaly and respiratory system anomalies. Congenital anomaly‐related fetal and infant deaths have increased at early gestation but declined at later gestation in Canada. These changes suggest an increase in prenatal diagnosis and selective termination of pregnancies with congenital anomalies in recent years. © 2001 Wiley‐Liss, Inc.     

Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome

PurposeSchizophrenia occurs in 20–25% of adults with 22q11.2 deletion syndrome (22q11.2DS). General population studies of schizophrenia report associations with perinatal complications, although effect sizes are generally low. We aimed to determine whether such factors are associated with expression of schizophrenia in individuals with 22q11.2DS.MethodsWe investigated the relationship of small for gestational age (SGA) birth weight (<3rd percentile for sex and gestational age) and prematurity (<37 weeks gestation) to expression of schizophrenia in a well-characterized cohort of 123 adults with 22q11.2DS. Outcome measures included adjusted odds ratios and positive and negative predictive values (PPV and NPV) for schizophrenia.ResultsSGA birth weight (OR = 3.52, 95% CI = 1.34–9.22) and prematurity (OR = 5.38, 95% CI = 1.63–17.75), but not maternal factors, were significant risk factors for schizophrenia in 22q11.2DS. Being born SGA or premature resulted in a PPV of 46% for schizophrenia; NPV in the absence of both features was 83%. Post hoc analyses suggested these perinatal complications were also associated with factors indicative of increased severity of schizophrenia.ConclusionIn 22q11.2DS, fetal growth and gestation may have a clinically significant impact on future risk for schizophrenia. These data advance our understanding of determinants of disease-specific expression in 22q11.2DS, with implications for other genomic disorders.     

Poor adherence to placebo or amiodarone therapy predicts mortality: results from the CAMIAT study. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial.

OBJECTIVE: This study examined the relationship between adherence, mortality, and psychosocial factors. METHODS: Subjects were 1141 patients participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. Poor adherence to study medication (amiodarone or placebo), measured by pill count over 2 years, was defined as the lower 20th percentile of the pill count distribution. Predictors of adherence were also studied and included demographic and cardiac variables and, in a subset of participants (N = 671), measures of depression, distress, hostility, and social support. RESULTS: In survival analysis controlling for cardiac and demographic variables, poor adherence in the placebo and amiodarone groups was associated with an increased risk of sudden cardiac death (relative risk (RR) = 2.11, 95% confidence interval (CI) = 1.03-4.56, p < .05; and RR = 3.15, 95% CI = 1.34-7.44, p < .01, respectively), total cardiac mortality (RR = 2.04, 95% CI = 1.12-3.72, p < .02; and RR = 2.49, 95% CI = 1.32-4.72, p < .01, respectively), and all-cause mortality (RR = 2.25, 95% CI = 1.27-3.97, p < .001; and RR = 2.34, 95% CI = 1.32-4.17, p < .004, respectively). Logistic regression analysis identified two predictors of poor adherence to placebo: age > 70 years (odds ratio = 2.18, 95% CI = 1.11-4.29, p < .03) and social activities in the month before the index heart attack (odds ratio = 1.02, 95% CI = 1.00-1.04, p < .05). CONCLUSIONS: Poor adherence is associated with a greater risk of mortality. The relationship between adherence and social activities suggests a higher motivation to adhere to treatment in individuals more engaged in enjoyable activities.     

Relative perinatal safety of salmeterol vs formoterol and fluticasone vs budesonide use during pregnancy

BackgroundRecent asthma guidelines endorse the safety of long-acting β₂-agonists (LABAs) and of mild and moderate doses of inhaled corticosteroids (ICSs) when required to control asthma during pregnancy, yet do not state a preferred medication within each class.ObjectiveTo estimate the relative perinatal safety with the use of salmeterol and formoterol (LABAs) and that of fluticasone and budesonide (ICSs) during pregnancy.MethodsA subcohort of pregnancies from asthmatic women was selected from health care administrative databases of Quebec, Canada. Low birth weight (LBW) was defined as weight less than 2,500 g, preterm birth (PB) as delivery before 37 weeks of gestation, and small for gestational age (SGA) as a birth weight below the 10th percentile. The effect of treatment with salmeterol vs formoterol and fluticasone vs budesonide on the outcomes was determined with generalized estimating equation models.ResultsThe LABA and ICS subcohorts were composed of 547 (385 salmeterol and 162 formoterol users) and 3,798 (3,190 fluticasone and 608 budesonide users) pregnancies, respectively. No statistically significant differences were observed for LBW (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.44-1.88), PB (OR, 1.11; 95% CI, 0.56-2.23), and SGA (OR, 1.16; 95% CI, 0.67-2.02) newborns between women exposed to salmeterol vs formoterol or between women exposed to fluticasone vs budesonide (LBW: OR, 1.08; 95% CI, 0.76-1.52; PB: OR, 1.07; 95% CI, 0.78-1.49; and SGA, OR: 1.10; 95% CI, 0.85-1.44).ConclusionThis study does not provide evidence of greater perinatal safety for one LABA or one ICS over the other.     

Do steatosis and steatohepatitis impact on sustained virological response (SVR) rates in patients receiving pegylated interferon and ribavirin for chronic hepatitis C infection?

The impact of steatosis on treatment response in chronic hepatitis C infection is controversial. The aim of this study was to determine whether steatosis ± steatohepatitis on pre‐treatment liver biopsy influenced sustained virological response (HCV RNA negative 6 months after completing therapy) in patients with chronic hepatitis C infection treated with pegylated interferon‐α and ribavirin. One hundred and seventy‐nine patients, median age 46 years (interquartile range 40–52), treated between 2001 and 2005. Histological evidence of steatosis was present in 93 patients (52%) and steatohepatitis in 33 patients (18%), 31 patients (17.3%) were cirrhotic. There were 106 (59%) responders, who were similar to non‐responders in respect to gender, age, and pre‐treatment ALT. On univariate analysis, infection with genotype 2 or 3 was associated with sustained virological response (odds ratio 6.5 (95% CI, 3.3–12.5); P < 0.0001), whereas cirrhosis and patient weight were associated with a reduced response (odds ratios 0.23 (95% CI, 0.11–0.48); P < 0.0001, and 0.97 (95% CI, 0.95–0.99); P < 0.01, respectively); steatohepatitis but not steatosis impacted on the likelihood of achieving sustained virological response (odds ratio 0.37 (95% CI, 0.17–0.77); P = 0.009, and P = 0.18, respectively). Multivariate analysis revealed that infection with genotype 1 or 4 (odds ratio 0.09 (95% CI, 0.03–0.32); P < 0.001) and pre‐treatment weight (odds ratio 0.94 (95% CI, 0.90–0.98); P = 0.002) were the only variables associated independently with sustained virological response. In chronic hepatitis C infection, although steatosis was associated with steatohepatitis, neither was shown to affect sustained virological response, which was influenced by genotype, patient weight and the presence of cirrhosis. J. Med. Virol. 82:958–964, 2010. © 2010 Wiley‐Liss, Inc.     

The obstetric outcome of singleton pregnancies following in-vitro fertilization/gamete intra-Fallopian transfer

The present study compares 465 singleton live deliveries fromin-vitro fertilization/gamete intra-Fallopian transfer (IVF/GIFT)pregnancies with a large control population to evaluate theincidence of pre-term delivery and small for gestational age(SGA) or very small for gestation age (VSGA) babies resultingfrom IVF/GIFT pregnancies. Overall the incidence of SGA or VSGAfrom an IVF/GIFT pregnancy is higher than from the normal obstetricpopulation (SGA odds ratio 1.76, 95% confidence interval (CI):1.38–2.25 and VSGA odds ratio 1.61, 95% CI: 1.05–2.46)particularly among primiparous women (SGA odds ratio 1.99, 95%CI: 1.25–3.16 and VSGA odds ratio 1.97, 95% CI: 1.49–2.62).After stratifying by the cause of infertility, only women withunexplained infertility had a significantly higher proportionof SGA/VSGA babies. There was a significantly higher incidenceof pre-term deliveries among the young primiparae (odds ratio5.02, 95% CI: 3.09–8.13). Thus the excess risk of deliveringa SGA/VSGA baby and pre-term delivery from an IVF/GIFT pregnancyseems to be largely confined to women with unexplained infertilityand young primiparae.     

Glucose Plasma Levels and Pregnancy Outcomes in Women with HIV

Abstract

Background: There is limited information on the relation between glucose levels in pregnancy and adverse perinatal outcomes in HIV-infected pregnant women. Objective: To evaluate the potential impact of fasting glucose levels on pregnancy outcomes in a large sample of pregnant women with HIV from a national study, adjusting for potential confounders. Methods: Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. The main outcomes evaluated in univariate and multivariable analyses were birthweight for gestational age >90th percentile (large for gestational age [LGA]), nonelective cesarean delivery, and preterm delivery. Glucose measurements were considered both as continuous and as categorical variables, following the HAPO study definition. Results: Overall, 1,032 cases were eligible for the analysis. In multivariable analyses, a birthweight >90th percentile was associated with increasing fasting plasma glucose levels (adjusted odds ratio [AOR] per unitary (mg/dL) increase, 1.04; 95% CI, 1.01–1.06; P = .005), a higher body mass index, and parity of 1 or higher. A lower risk of LGA was associated with smoking and African ethnicity. A higher fasting plasma glucose category was significantly associated with LGA occurrence, and AORs for the glucose categories of 90–94 mg/ dL and 95–99 mg/dL were 3.34 (95% CI, 1.09–10.22) and 6.26 (95% CI, 1.82–21.58), respectively. Fasting plasma glucose showed no association with nonelective cesar-ean section [OR per unitary increase, 1.00; 95% CI, 0.98–1.02] or preterm delivery [OR per unitary increase, 1.00; 95% CI, 0.99–1.02]. Conclusions: In pregnant women with HIV, glucose values below the threshold usually defining hyperglycemia are associated with an increased risk of delivering LGA infants. Other conditions may independently contribute to adverse perinatal outcomes in women with HIV and should be considered to identify pregnancies at risk.     

The course of pregnancy and delivery and the use of maternal healthcare services after standard IVF in Northern Finland 1990-1995

BACKGROUND: The objective of this study was to evaluate the course of pregnancy and delivery and the use of maternal healthcare after IVF. METHODS: This population-based cohort study included all women who had undergone IVF treatment in Northern Finland leading to delivery in 1990-1995 (n = 225) and control pregnancies derived from the Finnish Medical Birth Register (n = 671) matched for sex of the child, year of birth, area, maternal age, parity, social class and fetal plurality. The analyses were stratified by plurality. Outcome measures were pregnancy complications, mode of delivery, gestational length and the level of use of antenatal care. RESULTS: The results showed an increased risk for vaginal bleeding throughout pregnancy [relative risk (RR) 4.1, 95% confidence interval (CI) 2.5-6.7 for singletons; RR 6.9, 95% CI 2.5-19.2 for twins], threatened preterm birth (RR 1.8, 95% CI 1.1-2.9, singletons) and intrahepatic cholestasis of pregnancy (RR 3.8, 95% CI 1.0-15.0, singletons) in IVF pregnancies, as well as an increase in the use of specialized antenatal care. CONCLUSIONS: IVF pregnancies following standard, fresh ova IVF treatments are at greater risk of obstetric problems than spontaneously conceived pregnancies, and hence IVF mothers use more specialized antenatal care than others. The pregnancy complications after IVF are likely to be due to maternal characteristics regarding infertility and to a high incidence of multiple pregnancies.     

Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies with embryo reduction versus expectant management: new data and systematic review

BACKGROUND: Triplet pregnancies are associated with a high risk of miscarriage and early preterm birth. It is uncertain if the outcome is improved by embryo reduction (ER). METHODS: We examined trichorionic triplet pregnancies with three live fetuses at 10-14 weeks of gestation that were managed expectantly or by ER. The two groups were compared for the rates of miscarriage, defined as pregnancy loss before 24 weeks, and preterm delivery prior to 32 weeks. In addition, systematic searches were performed to identify studies comparing outcomes in expectant management versus ER in triplet pregnancies. RESULTS: We combined data from 365 pregnancies managed in our centre with those of five previous studies. In total there were 893 pregnancies. In the ER group (n=482) compared to the expectantly managed group (n=411), the rate of miscarriage was higher [8.1 versus 4.4%; relative risk (RR)=1.83, 95% confidence interval (CI)=1.08-3.16, P=0.036] and the rate of early preterm delivery was lower (10.4 versus 26.7%, RR=0.37, 95% CI=0.27-0.51, P<0.0001). It was calculated that seven (95% CI=5-9) reductions needed to be performed to prevent one early preterm delivery, while the number of reductions that would cause one miscarriage was 26 (95% CI=14-193). CONCLUSIONS: In trichorionic triplets, ER to twins is associated with an increase in the risk of subsequent miscarriage and decrease in risk of early preterm birth.     

Occupational exposures to aluminum and iron and risk of lung epithelium atypia in sudan

This study investigated the risk of lung cytological atypical changes in regards to occupational exposure to aluminum and iron. Detailed job histories were elicited from 130 incident cases with confirmed exposure to aluminum (50) or iron (80) and 157 population controls (nonexposed). Cytological atypia in sputum (dysplasia) was identified in four cases and none of controls (RR =10.8550; 95% CI = 0.5898 to 199.7815, P = 0.1086), hence, metaplasia was observed among 15 (11.5%) of the cases and 10 (6%) of controls (RR = 1.8115; 95% CI = 0.8424–3.8956; P = 0.1283). Evidences of viral infection were observed in 18 (14%) of the cases and 8 (5%) of controls (RR = 2.7173; 95% CI = 1.2213–6.0460; P = 0.0143). Moniliasis was observed in 28 (22%) of the cases and 19 (12%) of controls (RR = 1.6632; 95% CI = 0.9728–2.8435; P = 0.06). Cross‐categorizations of aluminum exposure and iron use suggest greater risk associated with iron exposure than aluminum in these workers. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Effects of informed consent for individual genome sequencing on relevant knowledge

Kaphingst KA, Facio FM, Cheng M‐R, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG. Effects of informed consent for individual genome sequencing on relevant knowledge. Increasing availability of individual genomic information suggests that patients will need knowledge about genome sequencing to make informed decisions, but prior research is limited. In this study, we examined genome sequencing knowledge before and after informed consent among 311 participants enrolled in the ClinSeq? sequencing study. An exploratory factor analysis of knowledge items yielded two factors (sequencing limitations knowledge; sequencing benefits knowledge). In multivariable analysis, high pre‐consent sequencing limitations knowledge scores were significantly related to education [odds ratio (OR): 8.7, 95% confidence interval (CI): 2.45–31.10 for post‐graduate education, and OR: 3.9; 95% CI: 1.05, 14.61 for college degree compared with less than college degree] and race/ethnicity (OR: 2.4, 95% CI: 1.09, 5.38 for non‐Hispanic Whites compared with other racial/ethnic groups). Mean values increased significantly between pre‐ and post‐consent for the sequencing limitations knowledge subscale (6.9–7.7, p < 0.0001) and sequencing benefits knowledge subscale (7.0–7.5, p < 0.0001); increase in knowledge did not differ by sociodemographic characteristics. This study highlights gaps in genome sequencing knowledge and underscores the need to target educational efforts toward participants with less education or from minority racial/ethnic groups. The informed consent process improved genome sequencing knowledge. Future studies could examine how genome sequencing knowledge influences informed decision making.     

Safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density: a meta-analysis

Purpose: The aim of this meta-analysis was to assess the safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density (BMD). Methods: Safety of denosumab was compared with placebo or bisphosphonates. A systematic literature search without language restriction was conducted up to January, 2014. The RevMan 5.1 software was used for statistical analysis. Results: A total of 11 English literatures were eventually identified. The pooled data in the overall analysis revealed that there was no significant difference when compared denosumab with placebo or bisphosphonates in any adverse events (AAE) (RR=0.99, 95% CI=0.98-1.01, p=0.29), serious adverse event (SAE) (RR=1.05, 95% CI=0.98-1.13, p=0.18), neoplasm/cancer (RR=1.14, 95% CI=0.95-1.37, p=0.16) and deaths (RR=0.77, 95% CI=0.57-1.04, p=0.09). However, significant differences were found when compared denosumab with placebo or bisphosphonates in SAE related to infection (RR=1.23, 95% CI=1.00-1.52, p=0.05) and non-vertebral fracture (RR=0.86, 95% CI=0.74-1.00, p=0.05). Subgroup analysis was performed by the type of drugs which was used in the control group. The results of subgroup analysis did not demonstrate the differences between denosumab and bisphosphonates in SAE related to infection (RR=1.13, 95% CI=0.63-2.03) and non-vertebral fracture (RR=1.31, 95% CI=0.87-1.98). Conclusions: Compared to placebo, denosumab treatment significantly decreased the risk of non-vertebral fracture but increased the risk of SAE related to infection in the postmenopausal women with osteoporosis or low BMD. However, no difference between the safety of denosumab and bisphosphonates was found.     

Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue

OBJECTIVES: This study examined the impact of depressive symptoms and social support on 2-year sudden cardiac death (SCD) risk, controlling for fatigue symptoms. METHODS: Myocardial infarction (MI) patients (N = 671) participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial completed measures of depression, hostility, and social support. RESULTS: After controlling for significant biological predictors, psychosocial predictors of increased SCD risk in the survival analysis were greater social network contacts (RR = 1.04; 95% CI = 1.01-1.06; p < .007), lower social participation (RR = 0.98; 95% CI = 0.96-1.00; p < .05), and, in placebo-treated patients, elevated depressive symptoms (RR = 2.45; 95% CI = 1.14-5.35; p < .02). Fatigue was associated with SCD (RR = 1.31; 95% CI = 1.11-1.53; p < .001), and, when included in the model, diminished the influence of depression (RR = 1.73; 95% CI = 0.75-3.98; p = .20). When the cognitive-affective depressive symptoms were examined separately from somatic symptoms, there was a trend for an association between cognitive-affective symptoms and SCD in placebo-treated patients after controlling for fatigue (RR = 1.09; 95% CI = 0.99-1.19, p < .06). CONCLUSIONS: Symptoms of depression and fatigue overlap in patients with MI. The trend for the cognitive-affective symptoms of depression to be associated with SCD risk, even after controlling for dyspnea/fatigue, suggests that the association between depression and mortality after AMI cannot be entirely explained as a confound of cardiac-related fatigue. The independent contribution of social participation suggests a role of both depressive symptomatology and social factors in influencing mortality risk after MI.     

Prevalence and risk factors for Down syndrome: A hospital‐based single‐center study in Western Mexico

Although Hispanics of Mexican origin in the United States have been identified as a population with a particularly higher rate of Down syndrome (DS), there is a paucity of studies concerning this topic in Mexico. The aim of this study was to determine the prevalence and risk factors for DS in a population from Western Mexico. For prevalence, 230 liveborn infants with DS were included from a total of 89,332 births occurring during the period 2009–2017 at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Mexico). In order to evaluate potential DS risks, a case‐control study was conducted among 633 newborns, including those 211 DS patients with full trisomy 21 (cases) and 422 infants without birth defects (controls). Data were analyzed using multivariable logistic regression analysis. The overall prevalence for DS was 25.7 per 10,000 (95% confidence interval [95% CI]: 22.4–29.1). Patients with DS had a significantly higher risk for family history of DS in distant relatives (adjusted odds ratio [aOR] = 4.4, 95% CI: 2.5–7.7), relatives with thyroid disease (aOR = 2.3, 95% CI: 1.2–4.0), maternal age ≤ 19 years (aOR = 5.1, 95% CI: 2.7–9.6) or ≥ 35 years (aOR = 3.3, 95% CI: 1.5–6.9), paternal age ≤ 19 years (aOR = 3.5, 95% CI: 1.7–7.4), pre‐pregnancy BMI ≥ 25 kg/m² (aOR = 1.6, 95% CI: 1.0–2.4), and pre‐pregnancy alcohol consumption (aOR = 1.8, 95% CI: 1.1–2.9). The identified risks in family history, and previously mentioned nutritional disadvantages were associated with DS in our sample and probably also to its increased prevalence in our population.     

A 3′ untranslated region polymorphism rs2304277 in the DNA repair pathway gene OGG1 is a novel risk modulator for urothelial bladder carcinoma

Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR)_GG = 3.55, 95% confidence interval (CI) = 1.79–7.06] and XPC rs2228001 (OR_AC = 2.38, 95% CI = 1.43–3.94) with UBC. In stratified analysis with respect to smoking status, OGG1 rs2304277 and XPC rs2228001 exhibited increased risk in smokers [(rs2304277 OR_GG = 4.96, 95% CI = 1.51–16.30) (rs2228001 OR_AC = 2.19, 95% CI = 1.02–4.72)] as well as nonsmokers [(rs2304277 OR_GG = 2.95, 95% CI = 1.26–6.90) (rs2228001 OR_AC = 2.57, 95% CI = 1.31–5.04)]. These polymorphisms were also associated with both low‐grade [(rs2304277 OR_GG = 3.73, 95% CI = 1.72–8.09) (rs2228001 OR_AC = 2.18, 95% CI = 1.21–3.92)] and high‐grade tumors [(rs2304277 OR_GG = 3.45, 95% CI = 1.52–7.80) (rs2228001 OR_AC = 2.81, 95% CI = 1.48–5.33)] as well as with non–muscle‐invasive bladder cancer [(rs2304277 OR_GG = 4.03, 95% CI = 1.87–8.67) (rs2228001 OR_AC = 2.14, 95% CI = 1.20–3.81)] and muscle‐invasive bladder cancer [(rs2304277 OR_GG = 3.06, 95%CI = 1.31–7.13) (rs2228001 OR_AC = 2.95, 95%CI = 1.51–5.75)]. This is the first study on DNA repair gene polymorphisms and UBC in the Pakistani population. It identifies OGG1 rs2304277 and replicates XPC rs2228001 as significant modulators of UBC susceptibility.     

Probiotics for prevention of atopic diseases in infants: systematic review and meta‐analysis

Growing evidence underlines the pivotal role of infant gut colonization in the development of the immune system. The possibility to modify gut colonization through probiotic supplementation in childhood might prevent atopic diseases. The aim of the present systematic review and meta‐analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing atopic diseases. PubMed, Embase and Cochrane Library were searched for randomized controlled trials evaluating the use of probiotics during pregnancy or early infancy for prevention of allergic diseases. Fixed‐effect models were used, and random‐effects models where significant heterogeneity was present. Results were expressed as risk ratio (RR) with 95% confidence interval (CI). Seventeen studies, reporting data from 4755 children (2381 in the probiotic group and 2374 in the control group), were included in the meta‐analysis. Infants treated with probiotics had a significantly lower RR for eczema compared to controls (RR 0.78 [95% CI: 0.69–0.89], P = 0.0003), especially those supplemented with a mixture of probiotics (RR 0.54 [95% CI: 0.43–0.68], P < 0.00001). No significant difference in terms of prevention of asthma (RR 0.99 [95% CI: 0.77–1.27], P = 0.95), wheezing (RR 1.02 [95% CI: 0.89–1.17], P = 0.76) or rhinoconjunctivitis (RR 0.91 [95% CI: 0.67–1.23], P = 0.53) was documented. The results of the present meta‐analysis show that probiotic supplementation prevents infantile eczema, thus suggesting a new potential indication for probiotic use in pregnancy and infancy.     

Omphalocele, advanced maternal age, and fetal morbidity outcomes

In this study we wanted to determine if the risk for adverse neonatal outcome among omphalocele-affected fetuses is increased among older gravidas. This was a retrospective cohort study on live-born infants with omphalocele delivered in New York State from 1983 through 1999. We compared infants of older (>or=35 years) with those of younger (<35 years) mothers with respect to the following fetal morbidity indices: low birth weight and very low birth weight, preterm and very preterm, and small for gestational age. We used adjusted odds ratios to approximate relative risks. Data on a total of 1,010 infants with omphalocele were analyzed. Mean gestational age and birth weight were similar in both maternal age categories: mean+/-standard deviation (SD) for infants with omphalocele born to older mothers=37.4 weeks+/-3.9 versus 38.0 weeks+/-5.1 for those of younger mothers (P=0.2); mean birth weights+/-SD for infants with omphalocele born to older mothers=2,813+/-871.1 versus 2,958+/-809.9 for those of younger mothers (P=0.08). Also, the two maternal age sub-groups did not differ with respect to the fetal morbidity outcome: low birth weight (OR=0.95; 95% CI=0.60-1.51), very low birth weight (OR=0.78; 95% CI=0.36-1.69), preterm (OR=0.95; 95% CI=0.58-1.57), very preterm (OR=0.73; 95% CI=0.34-1.58), and SGA (OR=1.00; 95% CI=0.44-2.27). Thus, advanced maternal age does not appear to be a risk factor for fetal morbidity outcomes among omphalocele-affected fetuses. This information is potentially useful in counseling affected parents.     

The M2 haplotype in the ANXA5 gene is an independent risk factor for idiopathic small-for-gestational age newborns

Hereditary thrombophilias can impair vascular placental functions and predispose to the birth of small-for-gestational age (SGA) babies. The placental anticoagulant protein annexin A5 (ANXA5) may contribute to this process. A functional haplotype (M2) within the ANXA5 gene is associated with fetal loss and venous thrombosis. This study investigated the prevalence of the M2 haplotype in a group of women with idiopathic SGA newborn babies. Seventy-eight women with at least one previous unexplained SGA birth and 195 controls all from Southern Italy were investigated. Hereditary thrombophilia was found in 13 (16.5%) cases and 21 (11%) controls (P < 0.05.). The M2 haplotype was found in 29% of cases (n = 23) and 15% of controls [n = 30; P = 0.001; OR = 2.3, 95% CI (1.17-4.48)]. Within the case group, 82.5% of the M2 haplotype carriers gave birth to babies with a birthweight below the 3rd percentile [P = 0.01; OR = 2.4, 95% CI (1.26-4.73)]. A logistic regression, corrected for age, parity and gravity showed that the M2 haplotype was independently associated with the delivery of an SGA new born [P = 0.029; OR = 2.6, 95% CI (1.1-6.0)]. In conclusion, the M2 haplotype of the ANXA5 gene confers a risk of delivering SGA babies.     

Secular trends in congenital anomaly-related fetal and infant mortality in Canada, 1985-1996.

Prenatal diagnosis of major congenital anomalies and subsequent termination of affected pregnancies has been widely available as part of routine obstetric care in recent years. In this study, vital statistical data on stillbirths, live births, and infant deaths were used to examine secular trends in gestational age-specific and category-specific fetal and infant mortality due to congenital anomalies in Canada (excluding Ontario and Newfoundland) from 1985-1996. Comparisons of the rates between 1985-1987 and 1994-1996 were made using relative risks and 95% confidence intervals (CI). The overall fetal mortality rate due to congenital anomalies increased significantly, from 68.0 per 100,000 total births in 1985-1987 to 78.6 per 100,000 total births in 1994-1996, while the overall infant mortality rate due to congenital anomalies decreased significantly over the same period, from 2.47 to 1.79 per 1,000 live births. The fetal death rate due to congenital anomalies at 20-21 weeks of gestation increased approximately five-fold (relative risk [RR] = 4.83, 95% CI = 3.28-7.11) from 4.5 to 21.5 per 100,000 fetuses at risk, while the rate at 37-41 weeks decreased by 30% (RR = 0.70, 95% CI = 0.50-0.97). Fetal death rates among pregnancies at 20-25 weeks of gestation increased in all categories of congenital anomaly except anencephaly and respiratory system anomalies. Congenital anomaly-related fetal and infant deaths have increased at early gestation but declined at later gestation in Canada. These changes suggest an increase in prenatal diagnosis and selective termination of pregnancies with congenital anomalies in recent years.