Pregnancy outcome after gestational exposure to metronidazole: a prospective controlled cohort study

BACKGROUND: Metronidazole is an important antibacterial agent commonly used in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The objective was to examine the fetal safety of metronidazole. METHODS: The Israeli Teratogen Information Service prospectively collected and followed up 228 women exposed to metronidazole in pregnancy, 86.2% of whom with first-trimester exposure. Pregnancy outcome was compared with that of a control group, who were counseled during the same period for nonteratogenic exposure. RESULTS: There was no difference in the rate of major malformations between the groups (3/190; 1.6% [metronidazole] vs. 8/575; 1.4% [control], P = 0.739). The rate of major malformations did not differ between the groups even after including elective terminations of pregnancy due to prenatally diagnosed malformations (5/192; 2.6% [metronidazole] vs. 12/579; 2.1% [control], P = 0.777). A reduced neonatal birth weight was found in the metronidazole group compared with controls without significant differences in the rate of prematurity or in gestational age at delivery. The mean birth weight was lower in the metronidazole group when comparing the subgroup of term infants. CONCLUSIONS: This study confirms that metronidazole does not represent a major teratogenic risk in humans when used in the recommended doses.     

Influence of moving to the UK on maternal health behaviours: prospective cohort study

Objective To compare health behaviours during pregnancy (smoking and alcohol consumption) and after birth (initiation and duration of breast feeding) between British/Irish white mothers and mothers from ethnic minority groups; and, in mothers from ethnic minority groups, to examine whether indicators of acculturation (generational status, language spoken at home, length of residency in the United Kingdom) were associated with these health behaviours.Design Prospective nationally representative cohort study.Setting England.Participants 6478 British/Irish white mothers and 2110 mothers from ethnic minority groups.Main outcome measures Any smoking during pregnancy; any alcohol consumption during pregnancy; initiation of breast feeding; breast feeding for at least four months.Results Compared with British/Irish white mothers, mothers from ethnic minority groups were less likely to smoke (15% v 37%) or consume alcohol (14% v 37%) during pregnancy but more likely to initiate breast feeding (86% v 69%) and breast feed for at least four months (40% v 27%). Among mothers from ethnic minority groups, first and second generation mothers were more likely to smoke during pregnancy (odds ratio 3.85, 95% confidence interval 2.50 to 5.93, and 4.70, 2.49 to 8.90, respectively), less likely to initiate breast feeding (0.92, 0.88 to 0.97, and 0.86, 0.75 to 0.99), and less likely to breast feed for at least four months (0.72, 0.62 to 0.83, and 0.52, 0.30 to 0.89) than immigrants, after adjustment for sociodemographic characteristics. There were no consistent differences in alcohol consumption. Among immigrants, for every additional five years spent in the UK the likelihood of mothers smoking during pregnancy increased by 31% (4% to 66%) and they were 5% (0% to 10%) less likely to breast feed for at least four months.Conclusions After immigration, maternal health behaviours worsen with length of residency in the UK. Health professionals should not underestimate women’s likelihood of engaging in risky health behaviours because of their ethnicity.     

Influence of maternal nutrition on outcome of pregnancy: prospective cohort study

ObjectiveTo investigate the relations of maternal diet and smoking during pregnancy to placental and birth weights at term.DesignProspective cohort study.SettingDistrict general hospital in the south of England.Participants693 pregnant nulliparous white women with singleton pregnancies who were selected from antenatal booking clinics with stratified random sampling.ResultsPlacental and birth weights were unrelated to the intake of any macronutrient. Early in pregnancy, vitamin C was the only micronutrient independently associated with birth weight after adjustment for maternal height and smoking. Each ln mg increase in vitamin C was associated with a 50.8 g (95% confidence interval 4.6 g to 97.0 g) increase in birth weight. Vitamin C, vitamin E, and folate were each associated with placental weight after adjustment for maternal characteristics. In simultaneous regression, however, vitamin C was the only nutrient predictive of placental weight: each ln mg increase in vitamin C was associated with a 3.2% (0.4 to 6.1) rise in placental weight. No nutrient late in pregnancy was associated with either placental or birth weight.ConclusionsConcern over the impact of maternal nutrition on the health of the infant has been premature. Maternal nutrition, at least in industrialised populations, seems to have only a small effect on placental and birth weights. Other possible determinants of fetal and placental growth should be investigated.

Key messages

• Placental and infant birth weights were not associated with the intake of any macronutrient early or later in pregnancy
• After adjustment for the effects of maternal height and smoking, only vitamin C independently predicted birth weight. The expected mean difference in birth weight for infants with mothers in the upper and lower thirds of intake was about 70 g
• Vitamin C was the only nutrient that independently predicted placental weight, but again this relation was of doubtful clinical significance
• Among relatively well nourished women in industrialised countries, maternal nutrition seems to have only a marginal impact on infant and placental size. Other causes of variation in the size of clinically normal infants should now be investigated

     

Birth outcomes following cesarean delivery on maternal request: a population-based cohort study

BACKGROUND:Data on the effect of cesarean delivery on maternal request (CDMR) on maternal and neonatal outcomes are inconsistent and often limited by inadequate case definitions and other methodological issues. Our objective was to evaluate the trends, determinants and outcomes of CDMR using an intent-to-treat approach.METHODS:We designed a population-based retrospective cohort study using data on low-risk pregnancies in Ontario, Canada (April 2012–March 2018). We assessed temporal trends and determinants of CDMR. We estimated the relative risks for component and composite outcomes used in the Adverse Outcome Index (AOI) related to planned CDMR compared with planned vaginal delivery using generalized estimating equation models. We compared the Weighted Adverse Outcome Score (WAOS) and the Severity Index (SI) across planned modes of delivery using analysis of variance.RESULTS:Of 422 210 women, 0.4% (n = 1827) had a planned CDMR and 99.6% (n = 420 383) had a planned vaginal delivery. The prevalence of CDMR remained stable over time at 3.9% of all cesarean deliveries. Factors associated with CDMR included late maternal age, higher education, conception via in vitro fertilization, anxiety, nulliparity, being White, delivery at a hospital providing higher levels of maternal care and obstetrician-based antenatal care. Women who planned CDMR had a lower risk of adverse outcomes than women who planned vaginal delivery (adjusted relative risk 0.42, 95% confidence interval [CI] 0.33 to 0.53). The WAOS was lower for planned CDMR than planned vaginal delivery (mean difference −1.28, 95% CI −2.02 to −0.55). The SI was not statistically different between groups (mean difference 3.6, 95% CI −7.4 to 14.5).Interpretation:Rates of CDMR have not increased in Ontario. Planned CDMR is associated with a decreased risk of short-term adverse outcomes compared with planned vaginal delivery. Investigation into the long-term implications of CDMR is warranted.

Cesarean delivery is the most common inpatient surgical procedure in North America,^1,2 where rates often exceed World Health Organization recommendations (10%–15% of deliveries).³ Given the financial and resource implications of cesarean deliveries on health care systems, the contribution of cesarean deliveries on maternal request (CDMR) to rising cesarean section rates is of ongoing interest. Women may prefer CDMR for many reasons, including scheduling convenience, anxiety regarding labour pain, perceptions that the quality of obstetrical care is better for women who have cesarean deliveries, and concerns about possible urinary incontinence and sexual dysfunction after vaginal delivery.^4–7 Challenges in characterizing the epidemiology of CDMR include the lack of internationally accepted case definitions and inconsistencies in documentation that hinder meaningful comparisons across jurisdictions.^8–11 In Canada, the prevalence of CDMR has been estimated at 2% of cesarean deliveries,¹² but robust contemporary data are lacking.The benefits of vaginal delivery are well known and include a lower risk of transient tachypnea of the newborn, newborn exposure to the vaginal microbiome, shorter maternal hospital stays and lower risk of complications associated with abdominal surgeries. The findings of 1 Canadian study suggest that midpelvic operative vaginal delivery is associated with a greater risk of severe birth and obstetric trauma than cesarean delivery.¹³ Evidence on the risks and benefits of CDMR is sparse, and existing data are inconsistent.^14–19 Analyses are frequently limited by inadequate case definitions and unaddressed confounding from baseline maternal and neonatal factors.^4,11 Professional organizations in the United States, Canada and Europe do not recommend CDMR over vaginal delivery.^11,20–22 Patient counselling is suggested to inform patients of pain management options, and of potential benefits and harms related to cesarean deliveries. However, obstetrical care providers often accede to patient preferences, given the ethical imperative of patient autonomy. ^23–27 Contemporary, high-quality observational studies leveraging robust population-based data are required. Our objective was to evaluate the trends, determinants and outcomes of CDMR compared with planned vaginal delivery using an intent-to-treat approach.     

A meta-analysis of case-control and cohort studies with interval-censored exposure data: application to chorionic villus sampling

Chorionic villus sampling (CVS) is a valued method of prenatal diagnosis that is often preferred over amniocentesis because it can be performed earlier, but which has also raised concern over a possible association with increased risk of terminal transverse limb deficiency (TTLD). We present and apply a meta-analytic method for estimating a combined dose-response effect from a series of case-control and cohort studies in which the exposure variable is interval-censored. Assuming coarsening at random for the interval-censoring, and calling upon the familiar result of Cornfield to pool case-control and cohort information on the association between a rare binary outcome and a multilevel exposure variable, we form a likelihood-based model to assess the effect of gestational age at the time of CVS on the presence or absence of a rare birth defect. Effect estimates are computed with a variant of the EM algorithm termed the method of weights, which enables the use of standard weighted regression software. Our findings suggest that CVS exposure at early gestational age leads to an increased risk of TTLD.     

The relationship between maternal and offspring birth weights after maternal prenatal famine exposure: the Dutch Famine Birth Cohort Study

We examined the impact of famine-induced changes in maternal birth weight (MBW) on the association between MBW and offspring birth weight (OBW). Women born before, during, and after the Dutch Famine of 1944-1945 were interviewed at ages 41 to 46 years. Women (n = 582) and their children (n = 1,111) were included in the analysis if both mother and child were singleton and the child was not delivered preterm. Mean birth weight (BW) of women with first-trimester exposure (n = 110) was 154 g higher (p = 0.008), and mean BW of women with third-trimester exposure (n = 138) was 251 g lower (p < 0.001) than mean BW of unexposed women (n = 302). First-born offspring of women with first-trimester exposure were 72 g heavier (95% confidence interval [CI], -57 to 201; p = 0.27), and offspring of women with third-trimester exposure were 43 g lighter (95% CI, -170 to 79; p = 0.47) than offspring of unexposed women. Among unexposed women, each 100 g increase in MBW was associated with 25 g (95% CI, 12 to 37) increase in OBW (adjusted for maternal age, smoking, weight, and height and offspring sex). This association was attenuated in famine-exposed women (first-trimester change in OBW = 20 g per 100 g MBW; 95% CI, -1 to 41; third-trimester change in OBW = 14 g per 100 g MBW; 95% CI, -9 to 37). When MBW and trimester of maternal famine exposure were considered in a joint model, there was no independent effect of trimester of maternal famine exposure on OBW. Associations were less consistent for later-born offspring. We conclude that maternal prenatal famine exposure does not affect the association between maternal and offspring BW. Trimester of exposure was not a determinant of OBW, other than through its effect on MBW. Nevertheless, acute famine may impact on second-generation BW distributions indirectly, through its effect on the distribution of MBW.     

Association between long-term exposure to ambient air pollution and COVID-19 severity: a prospective cohort study

Background:The tremendous global health burden related to COVID-19 means that identifying determinants of COVID-19 severity is important for prevention and intervention. We aimed to explore long-term exposure to ambient air pollution as a potential contributor to COVID-19 severity, given its known impact on the respiratory system.Methods:We used a cohort of all people with confirmed SARS-CoV-2 infection, aged 20 years and older and not residing in a long-term care facility in Ontario, Canada, during 2020. We evaluated the association between long-term exposure to fine particulate matter (PM_2.5), nitrogen dioxide (NO₂) and ground-level ozone (O₃), and risk of COVID-19-related hospital admission, intensive care unit (ICU) admission and death. We ascertained individuals’ long-term exposures to each air pollutant based on their residence from 2015 to 2019. We used logistic regression and adjusted for confounders and selection bias using various individual and contextual covariates obtained through data linkage.Results:Among the 151 105 people with confirmed SARS-CoV-2 infection in Ontario in 2020, we observed 8630 hospital admissions, 1912 ICU admissions and 2137 deaths related to COVID-19. For each interquartile range increase in exposure to PM_2.5 (1.70 μg/m³), we estimated odds ratios of 1.06 (95% confidence interval [CI] 1.01–1.12), 1.09 (95% CI 0.98–1.21) and 1.00 (95% CI 0.90–1.11) for hospital admission, ICU admission and death, respectively. Estimates were smaller for NO₂. We also estimated odds ratios of 1.15 (95% CI 1.06–1.23), 1.30 (95% CI 1.12–1.50) and 1.18 (95% CI 1.02–1.36) per interquartile range increase of 5.14 ppb in O₃ for hospital admission, ICU admission and death, respectively.Interpretation:Chronic exposure to air pollution may contribute to severe outcomes after SARS-CoV-2 infection, particularly exposure to O₃.

By November 2021, COVID-19 had caused more than 5 million deaths globally¹ and more than 29 400 in Canada.² The clinical manifestations of SARS-CoV-2 infection range from being asymptomatic to multiple organ failure and death. Identifying risk factors for COVID-19 severity is important to better understand etiological mechanisms and identify populations to prioritize for screening, vaccination and medical treatment. Risk factors for severity of COVID-19 include male sex, older age, pre-existing medical conditions and being from racialized communities.^3–5 More recently, ambient air pollution has been implicated as a potential driver of COVID-19 severity.^6–10Long-term exposure to ambient air pollution, a major contributor to global disease burden,¹¹ could increase the risk of severe COVID-19 outcomes by several mechanisms. Air pollutants can reduce individuals’ pulmonary immune responses and antimicrobial activities, boosting viral loads.⁸ Air pollution can also induce chronic inflammation and overexpression of the alveolar angiotensin-converting enzyme 2 (ACE) receptor,⁷ the key receptor that facilitates SARS-CoV-2 entry into cells.^12,13 Exposure to air pollution contributes to chronic conditions, such as cardiovascular disease, that are associated with unfavourable COVID-19 prognosis, possibly owing to persistent immune activation and excessive amplification of cytokine development.¹⁰ Thus, greater exposure to long-term air pollution may lead to severe COVID-19 outcomes.Reports exist of positive associations between long-term exposure to particulate matter with diameters equal to or smaller than 2.5 or 10 μm (PM_2.5 and PM₁₀), ground-level ozone (O₃) and nitrogen dioxide (NO₂), and metrics of COVID-19 severity (e.g., mortality and case fatality rate).^8–10 However, most studies to date have used ecological and cross-sectional designs, owing to limited access to individual data, which leads to ambiguity in interpreting the results, thus hindering their influence on policy. ^6,14 Ecological designs do not allow for disentangling the relative impacts of air pollution on individual susceptibility to infection and disease severity.¹⁴ Residual confounding by factors such as population mobility and social interactions is also problematic. Therefore, a cohort study with data on individuals with SARS-CoV-2 is a more appropriate design.^6,14 Studies that have used individual data were conducted in specific subpopulations^15,16 or populations with few severe cases,¹⁷ or had limited data on individual exposure to air pollutants.¹⁸ In Canada, 1 ecological study found a positive association between long-term exposure to PM_2.5 and COVID-19 incidence,¹⁹ but no published study has explored the association between air pollution and COVID-19 severity.We aimed to examine the associations between long-term exposure to 3 common air pollutants (PM_2.5, NO₂ and O₃) and key indicators of COVID-19 severity, including hospital admission, intensive care unit (ICU) admission and death, using a large prospective cohort of people with confirmed SARS-CoV-2 infection in Ontario, Canada, in 2020. The air contaminants PM_2.5, NO₂ and O₃ are regularly monitored by the Canadian government, and are key pollutants that are considered when setting air-quality policies. They originate from varying sources (NO₂ is primarily emitted during combustion of fuel, O₃ is primarily formed in air by chemical reactions of nitrogen oxides and volatile organic compounds, and PM_2.5 can be emitted during combustion or formed by reactions of chemicals like sulphur dioxide and nitrogen oxides in air) and they may affect human health differently.^20,21,22     

Human oocyte morphometry before and after cryopreservation: A prospective cohort study

The cryopreservation of human oocytes is an important strategy to spare fertility in women submitted to gonadotoxic therapy, ovarian surgery, or even to allow gestation by assisted reproduction technology after natural ovarian senescence. Methods to predict oocyte resistance to cryopreservation are still based on qualitative morphological assessment. In this study we evaluated whether morphometric characteristics of mature oocytes before vitrification and after warming are related to successful fertilization by intracytoplasmic sperm injection (ICSI). This was a prospective cohort study including 28 infertile women and 71 oocytes. Morphometric assessments included oocyte diameter, perivitelline space (PS), zona pellucida (ZP) and first polar body (PB). Out of 49 warmed oocytes, 27 (55%) survived cryopreservation and their pre-vitrification measures were similar to those of the 22 oocytes that perished. However, the oocytes that eventually failed to be fertilized had undergone more enlargement of the total diameter (p = 0.029) and shrinking of the PS (p = 0.033) after cryopreservation, compared to oocytes that were successfully fertilized. These findings suggest that the morphometric characteristics of fresh oocytes do not predict their survival to vitrification, while fertilization failure is associated with oocyte enlargement and PS shrinking after cryopreservation.     

Effects of maternal occupational exposure to organic solvents on offspring visual functioning: a prospective controlled study

BACKGROUND: Previous studies in adults and animals with high level exposure to organic solvents suggested impairments in visual functioning. The objective of this pilot study was to examine the effects of maternal occupational exposure to organic solvents during pregnancy on offspring color vision and visual acuity, the development of which may be especially vulnerable to organic solvent exposure. METHODS: We conducted a prospective cohort study of 32 offspring of women who were exposed occupationally to organic solvents during pregnancy compared with 27 nonexposed children. Monocular and binocular color vision and visual acuity were assessed using the Minimalist Test and the Cardiff Cards, respectively. Children with known hereditary color vision loss were excluded. RESULTS: Solvent-exposed children had significantly higher error scores on red-green and blue-yellow color discrimination, as well as poorer visual acuity compared with the control group. Exposure index (an estimated measure of exposure intensity) was not significantly related to color discrimination or visual acuity score. Despite excluding all children with a known family history of color vision loss, clinical red-green color vision loss was found among 3 of the 32 exposed children compared with none of the matched controls. CONCLUSIONS: These preliminary findings suggest that occupational exposure to organic solvents during pregnancy is associated with an increased risk of color vision and visual acuity impairment in offspring. The importance of routine visual function screening in risk assessment after prenatal exposure to chemicals warrants further attention.     

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and the risk of selected birth defects: a prospective cohort study

Background

Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs.

Methods and Findings

We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0–12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4–1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9–15.7).

Conclusions

Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded.     

Light exposure among adolescents with delayed sleep phase disorder: a prospective cohort study

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n=16, 15.3±1.8 yrs) and unaffected controls (n=22, 13.7±2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00 h and 05:00 to 14:00 h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p< .02, 22:00-02:00 h) and less morning (p .05, 08:00-09:00 h and 10:00-12:00 h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p< .03, 5-7 h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p< .001 and p= .02, respectively) and morning (p= .01 and p< .001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p< .001). Increased total sleep time also correlated with increased exposure during the 9 h before sleep onset (p= .01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p< .001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD.     

The role of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence and prognosis: a meta-analysis of prospective cohort studies

Background

The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.

Methods

We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.

Results

The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients.

Conclusion

The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.     

Stress and survival after cancer: a prospective study of a Finnish population-based cohort

Stress has been suggested to reduce survival after cancer, but the results of previous studies have been contradictory. We investigated the hypothesis in a national cohort of adults in Finland. Of those who completed the Stressful Life Events scale and the Stress of Daily Activities scale, 1470 and 1882, respectively, later had cancer and were included in the analysis, covering 23 years of follow-up between 1982 and 2004. In Cox regression analysis, the multivariate hazard ratio (HR) was 0.99 (95% confidence interval [CI], 0.96-1.01) for total number of life events and the HR for the life change score was 0.99 (95% CI, 0.95-1.03). Further, the HR was 0.92 (95% CI, 0.69-1.22) for severe daily stress. Overall, the results of the current study do not support the hypothesis that stress reduces cancer survival.     

Pregnancy outcomes after maternal exposure to simvastatin and lovastatin

BACKGROUND: Our objective was to determine the frequency of adverse outcomes after maternal exposure to simvastatin and/or lovastatin during pregnancy in postmarketing experience. METHODS: We reviewed the Merck & Co., Inc. (West Point, PA) pharmacovigilance database for reports of exposure to simvastatin or lovastatin during pregnancy. The reports were classified as prospective (reported prior to pregnancy outcome) or retrospective (reported after pregnancy outcome) and were evaluated for timing of exposure, outcome, congenital anomalies, and other events. Outcome rates were calculated for prospective pregnancies. RESULTS: We identified 477 reports (386 prospective and 91 retrospective) with 225 prospective outcomes reported: 154 live born infants, 49 elective abortions, 18 spontaneous abortions, and 4 fetal deaths. Six congenital anomalies were reported: chromosomal translocation, trisomy 18, hypospadias, duodenal atresia, cleft lip, and skin tag. The rate of congenital anomalies (congenital anomalies/live births plus fetal deaths) was 3.8%, which is similar to the background population rate (3.2%; relative ratio, 1.21; 95% 1-sided upper confidence interval [CI], 2.02). There were 13 retrospective reports describing a range of congenital anomalies. No specific pattern of anomalies was identified in either the prospective or retrospective reports. Rates for other outcomes were similar to background rates. CONCLUSIONS: Although the number of reports was relatively small, there was no evidence of a notable increase in congenital anomalies in women exposed to simvastatin or lovastatin versus the general population. Greater reporting of congenital abnormalities in the retrospective cohort is not unexpected and may reflect a reporting bias. Drugs should be used during pregnancy only if the benefits outweigh the risks. Simvastatin and lovastatin remain contraindicated during pregnancy.     

Predictors of poor perinatal outcome following maternal perception of reduced fetal movements--a prospective cohort study

Background

Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). RFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency.

Objective

To identify predictors of poor perinatal outcome after maternal perception of reduced fetal movements (RFM).

Design

Prospective cohort study.

Methods

305 women presenting with RFM after 28 weeks of gestation were recruited. Demographic factors and clinical history were recorded and ultrasound performed to assess fetal biometry, liquor volume and umbilical artery Doppler. A maternal serum sample was obtained for measurement of placentally-derived or modified proteins including: alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (hPL), ischaemia-modified albumin (IMA), pregnancy associated plasma protein A (PAPP-A) and progesterone. Factors related to poor perinatal outcome were determined by logistic regression.

Results

22.1% of pregnancies ended in a poor perinatal outcome after RFM. The most common complication was small-for-gestational age infants. Pregnancy outcome after maternal perception of RFM was related to amount of fetal activity while being monitored, abnormal fetal heart rate trace, diastolic blood pressure, estimated fetal weight, liquor volume, serum hCG and hPL. Following multiple logistic regression abnormal fetal heart rate trace (Odds ratio 7.08, 95% Confidence Interval 1.31–38.18), (OR) diastolic blood pressure (OR 1.04 (95% CI 1.01–1.09), estimated fetal weight centile (OR 0.95, 95% CI 0.94–0.97) and log maternal serum hPL (OR 0.13, 95% CI 0.02–0.99) were independently related to pregnancy outcome. hPL was related to placental mass.

Conclusion

Poor perinatal outcome after maternal perception of RFM is closely related to factors which are connected to placental dysfunction. Novel tests of placental function and associated fetal response may provide improved means to detect fetuses at greatest risk of poor perinatal outcome after RFM.     

Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study

Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants.Design Prospective cohort study with estimates of relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension.Setting Spanish university department.Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years.Main outcome measures Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up. Confirmed cases of type 2 diabetes.Results Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios adjusted for sex and age were 0.41 (95% confidence interval 0.19 to 0.87) for those with moderate adherence (score 3-6) and 0.17 (0.04 to 0.75) for those with the highest adherence (score 7-9) compared with those with low adherence (score <3). In the fully adjusted analyses the results were similar. A two point increase in the score was associated with a 35% relative reduction in the risk of diabetes (incidence rate ratio 0.65, 0.44 to 0.95), with a significant inverse linear trend (P=0.04) in the multivariate analysis.Conclusion Adherence to a Mediterranean diet is associated with a reduced risk of diabetes.     

Disability in young people and adults one year after head injury: prospective cohort study

ObjectiveTo determine the frequency of disability in young people and adults admitted to hospital with a head injury and to estimate the annual incidence in the community.DesignProspective, hospital based cohort study, with one year follow up of sample stratified by coma score.SettingFive acute hospitals in Glasgow.Subjects2962 patients (aged 14 years or more) with head injury; 549 (71%) of the 769 patients selected for follow up participated.ResultsSurvival with moderate or severe disability was common after mild head injury (47%, 95% confidence interval 42% to 52%) and similar to that after moderate (45%, 35% to 56%) or severe injury (48%, 36% to 60%). By extrapolation from the population identified (90% of whom had mild injuries), it was estimated that annually in Glasgow (population 909 498) 1400 young people and adults are still disabled one year after head injury.ConclusionThe incidence of disability in young people and adults admitted with a head injury is higher than expected. This reflects the high rate of sequelae previously unrecognised in the large number of patients admitted to hospital with an apparently mild head injury.