It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, βeta-human chorionic gonadotropin (β-HCG), and glycosylated hemoglobin (HbA1c) was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with an increase in β-HCG and HbA1C, and a decrease in total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

Introduction. The mechanisms of haemoglobin (Hb) subtype switch remain largely unknown even though it has a therapeutic potential (Bauer et al., 2012). In fact, reactivation of fetal haemoglobin (HbF) production in adult erythrocytes (F-cells) is protective in many Hb disorders. Pregnancy may represent the only physiological condition where HbF production increases transiently (Ibrahim et al, 2009; Yamada et al., 2012). Moreover, flow cytometry (FC), by intracellular staining using anti-HbF antibodies, has improved the evaluation of maternal F-cells (Corcoran et al., 2014; Chen et al., 2000). In this study, the objectives are: 1) to document HbF expression prospectively peri- and post-partum and confirm its maternal origin; 2) to assess potential causes of HbF modulation throughout pregnancy (i.e. β-hCG, EPO) and; 3) to identify gene differences between HbF-positive and HbF-negative pregnant women.

Objective: To evaluate the impact of early vs. late amniotomy on delivery mode in women undergoing induction of labor. Study design: 143 women admitted for induction were randomized to early amniotomy (EA, concomitant with the beginning of oxytocin infusion; n = 71) or to late amniotomy (LA, four hours after the beginning of oxytocin; n = 72). Randomization was stratified by parity. The primary outcome was the rate of cesarean. Secondary outcomes were duration of labor and intrapartum fever. Results: The cesarean rate was similar between groups (18% vs. 17% among nulliparous; and 3% vs. 0% among parous women, in EA and LA group, respectively). However, EA was associated with shorter oxytocin-to-delivery interval (12 vs. 15 h) and a non-significant decrease in intrapartum fever (3% vs. 25%) than LA in nulliparous women (p = 0.05). Conclusion: For women undergoing oxytocin induction, early amniotomy is associated with shorter labor in nulliparous women with no effect on the risk of cesarean section in both nulliparous and multiparous women.

Knowledge of the consequences of maternal obesity in human placental fatty acids (FA) transport and metabolism is limited. Animal studies suggest that placental uptake of maternal FA is altered by maternal overnutrition. We hypothesized that high maternal body mass index (BMI) affects human placental FA transport by modifying expression of key transporters. Full-term placentas were obtained by vaginal delivery from normal weight (BMI, 18.5-24.9 kg/m(2)) and obese (BMI > 30 kg/m(2)) women. Blood samples were collected from the mother at each trimester and from cord blood at delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR and Western blotting. Lipoprotein lipase (LPL) activity was evaluated using enzyme fluorescence. In vitro linoleic acid transport was studied with isolated trophoblasts. Our results demonstrated that maternal obesity is associated with increased placental weight, decreased gestational age, decreased maternal high-density lipoprotein (HDL) levels during the first and third trimesters, increased maternal triglyceride levels during the second and third trimesters, and increased maternal T3 levels during all trimesters, and decreased maternal cholesterol (CHOL) and low-density lipoprotein (LDL) levels during the third trimester; and increased newborn CHOL, LDL, apolipoprotein B100, and T3 levels. Increases in placental CD36 mRNA and protein expression levels, decreased SLC27A4 and FABP1 mRNA and protein and FABP3 protein expression, and increased LPL activity and decreased villus cytotrophoblast linoleic acid transport were also observed. No changes were seen in expression of PPARA, PPARD, or PPARG mRNA and protein. Overall this study demonstrated that maternal obesity impacts placental FA uptake without affecting fetal growth. These changes, however, could modify the fetus metabolism and its predisposition to develop diseases later in life.

Objective: To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers.Options: This guideline reviews the use of screening tools, general approach to care, and recommendations for clinical management of problematic substance use in pregnancy.Outcomes: Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation.Evidence: Medline, PubMed, CINAHL, and The Cochrane Library were searched for articles published from 1950 using the following key words: substance-related disorders, mass screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis, methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines. Results were initially restricted to systematic reviews and randomized control trials/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Searches were updated on a regular basis and incorporated in the guideline up to December 2009. Grey (unpublished) literature was also identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on the Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1).Benefits, harms, and costs: This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to health care and assistance with appropriate addiction care leads to reduced health care costs and decreased maternal and neonatal morbidity and mortality.

Objective: To review the information on fetal and perinatal autopsies, the process of obtaining consent, and the alternative information-gathering options following a prenatal diagnosis of nonchromosomal malformations, and to assist clinicians in providing postnatal counselling regarding fetal diagnosis and recurrence risks.Outcomes: To provide better counselling about fetal and perinatal autopsies for women and families who are dealing with a prenatally diagnosed non-chromosomal fetal anomaly.Evidence: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 and 2010, using appropriate key words (fetal autopsy, postmortem, autopsy, perinatal postmortem examination, autopsy protocol, postmortem magnetic resonance imaging, autopsy consent, tissue retention, autopsy evaluation). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.Benefits, harms, and costs: This update educates readers about (1) the benefits of a fetal perinatal autopsy, (2) the consent process, and (3) the alternatives when the family declines autopsy. It also provides a standardized approach to fetal and perinatal autopsies, emphasizing pertinent additional sampling when indicated.Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).Recommendations1. Standard autopsy should ideally be an essential part of fully investigating fetal loss, stillbirths, and neonatal deaths associated with non-chromosomal fetal malformations. (II-3A)2. Clinicians and health care providers approaching parents for autopsy consent should discuss the options for a full, limited, or step-wise postmortem examination; the issue of retained fetal tissues; and the value of autopsy and the possibility that the information gained may not benefit them but may be of benefit to others. This information should be provided while respecting the personal and cultural values of the families. (III-A)3. If parents are unwilling to give consent for a full autopsy, alternatives to full autopsy that provide additional clinical information must be presented in a manner that includes disclosure of limitations. (III-A)4. External physical examination, medical photographs, and standard radiographic or computed tomography should be offered in all cases of fetal anomaly(ies) of non-chromosomal etiology. (II-2A)5. Well-designed, large prospective studies are needed to evaluate the accuracy of postmortem magnetic resonance imaging. It cannot function as a substitute for standard full autopsy. (III-A)6. The fetal and perinatal autopsies should be performed by trained perinatal or pediatric pathologists. (II-2A)7. The need for additional sampling is guided by the results of previous prenatal and/or genetic investigations, as well as the type of anomalies identified in the fetus. Fibroblast cultures may allow future laboratory studies, particularly in the absence of previous karyotyping or if a biochemical disorder is suspected, and DNA analysis. (II-3A)8. In cases requiring special evaluation, the most responsible health care provider should have direct communication with the fetopathologist to ensure that all necessary sampling is performed in a timely manner. (II-3A)9. The most responsible health care providers must see the families in follow-up to share autopsy findings, plan for the management of future pregnancies, obtain consent for additional testing, and offer genetic counselling to other family members when appropriate. (III-A)

Background: Apolipoprotein D (ApoD) is a lipocalin involved in several processes including lipid transport, but its modulation during human pregnancy was never examined.Methods: We investigated the changes in the levels of ApoD in the plasma of pregnant women at the two first trimesters of gestation and at delivery as well as in the placenta and in venous cord blood. These changes were studied in 151 women classified into 9 groups in relation to their prepregnancy body mass index (BMI) and gestational weight gain (GWG).Results: Plasma ApoD levels decrease significantly during normal uncomplicated pregnancy. ApoD is further decreased in women with excessive GWG and their newborns. In these women, the ApoD concentration was tightly associated with the lipid parameters. However, the similar ApoD levels in low cholesterol (LC) and high cholesterol (HC) women suggest that the plasma ApoD variation is not cholesterol dependant. A tight regulation of both placental ApoD transcription and protein content is most probably at the basis of the low circulating ApoD concentrations in women with excessive GWG. After delivery, the plasma ApoD concentrations depended on whether the mother was breast-feeding or not, lactation favoring a faster return to baseline values.Conclusion: It is speculated that the decrease in plasma ApoD concentration during pregnancy is an adaptive response aimed at maintaining fetal lipid homeostasis. The exact mechanism of this adaptation is not known.

Selective study participation can theoretically lead to selection bias. We explored this issue in the context of a multicentre cohort study of socio-economic disparities in preterm birth. Women with singleton pregnancies were recruited from four large Montreal maternity hospitals and invited to return for an interview, vaginal examination and venepuncture at 24-26 weeks of gestation. We compared the observed preterm birth rate (ultrasound confirmed) among the 5146 cohort women to that expected based on all 108 724 Montreal Census Metropolitan Area (CMA) singleton births for 1998-2000. The observed preterm birth rate in the study cohort was 5.1%, compared with 6.3% in the CMA (P < 0.001) (unadjusted morbidity ratio [95% CI] = 0.80 [0.71, 0.90]). Within each stratum of maternal education and neighbourhood income (the latter based on postal code matched links to the 2001 Canadian census), cohort women had substantially lower rates of preterm birth than women from the CMA. No significant association between socio-economic status (SES) and preterm birth was observed in the study cohort, except among 'indicated' (non-spontaneous) cases. The association between neighbourhood income and preterm birth was biased to the null in the study cohort, with adjusted odds ratios in the poorest vs. richest quintiles of 1.01 [0.63, 1.64] in the cohort vs. 1.28 [1.18, 1.39] in the CMA, although no such bias was observed for the association with maternal education assessed at the individual level. We speculate that the lower-than-expected preterm birth rate and attenuated association between neighbourhood income and preterm birth may be related to selective participation by women more psychologically invested in their pregnancies. Investigators should consider the potential for biased associations in pregnancy/birth cohort studies, especially associations based on SES or race/ethnicity, and carry out sensitivity analyses to gauge their effects.

Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes mellitus (GDM) are associated with disturbance of fetal development which may also modify key features of placental functions. In this study, we evaluated the impact of maternal hypercholesterolemia on placental cholesterol and lipid metabolism in 59 women classified in two groups according to the median concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and 7 non-GDM women. We showed that high maternal circulating cholesterol is associated with a significant increase in the LDL-cholesterol, ApoB-100 and triglyceride concentrations in the maternal blood. However the level of cholesterol in the venous cord blood and placenta remains unchanged in response to modification in maternal cholesterol profile. The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated with modification in the maternal lipid profile but it increases the concentration of inflammatory cytokines (IL-1 beta and TNF-alpha) in placenta which correlates with a dramatic induction of FAS expression without affecting the expression of mature SREBPs proteins. In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development.

Physicians are frequently asked to give written or oral expert evidence on matters relating to the regulation of the medical profession and other proceedings integral to the functioning of the health care system. This policy statement is intended to guide those who choose to assist in the administration of justice and in the affairs of the profession in this way.

Objective: To study the effect of sublingual nitroglycerine as a tocolytic on the success rate of external cephalic version (ECV) in nulliparous and parous women.

Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.