TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

Killer Cell Immunoglobulin-like Receptor Genotypes and Reproductive Outcomes in a Group of Infertile Women: A Romanian Study.

A growing body of evidence suggests that endometrial immune disorders may be responsible for endometrial dysfunctions that can lead to gynecological and obstetrical pathology. The aim of this study was to explore the potential relationship between different killer cell immunoglobulin-like receptor (KIR) genotypes and reproductive outcomes. We conducted a prospective cohort study that included 104 infertile patients undergoing an in vitro fertilization procedure. All participants underwent clinical and ultrasound examination, genetic evaluation (KIR genotyping), endometrial washing fluid sampling for cytokine determination, endometrial tissue sampling for histologic assessment and hysteroscopic evaluation. Our analysis showed statistically significant lower levels of uterine cytokines TNF-α (p = 0.001) and IL-1beta (p = 0.000) in the KIR AA genotype group as compared to KIR AB and BB among study participants with chronic endometritis. The study results suggest that the KIR AA genotype population subgroups may be more susceptible to developing endometrial disorders such as chronic endometritis. The changes in the behavior of NK cells seem to be subtle and expressed as an altered regulatory pattern.

Spectrum of High-Risk Mutations among Breast Cancer Patients Referred for Multigene Panel Testing in a Romanian Population.

(1) Background: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing (NGS) is becoming a standard in medical care. There are insufficient genetic studies reported on breast cancer (BC) patients from Romania and most of them are focused only on BRCA 1/2 genes (Breast cancer 1/2). (2) Methods: NGS was performed in 255 consecutive cases of BC referred for management in our clinic between 2015-2019. (3) Results: From the 171 mutations identified, 85 were in the high-penetrance BC susceptibility genes category, 72 were pathogenic genes, and 13 genes were in the (variants of uncertain significance) VUS genes category. Almost half of the mutations were in the BRCA 1 gene. The most frequent BRCA1 variant was c.3607C>T (14 cases), followed by c.5266dupC (11 cases). Regarding BRCA-2 mutations we identified c.9371A>T (nine cases), followed by c.8755-1G>A in three cases, and we diagnosed VUS mutations in three cases. We also identified six pathogenic variants in the PALB2 gene and two pathogenic variants in (tumor protein P 53) TP53. (4) Conclusions: The majority of pathogenic mutations in the Romanian population with BC were in the BRCA 1/ 2 genes, followed by PALB2 (partner and localizer of BRCA2) and TP53, while in the CDH1 (cadherin 1) and STK11 (Serine/Threonine-Protein Kinase) genes we only identified VUS mutations.

Impact of Follicle Stimulating Hormone Receptor (FSHR) Polymorphism on the Efficiency of Co-Treatment with Growth Hormone in a Group of Infertile Women from Romania.

"Poor responders" (PR) are an important category of infertile women who experience a modest response to controlled ovarian stimulation. In this study, we evaluated response to growth hormone (GH) administration among PR patient subtypes stratified by follicle stimulation hormone receptor (FSHR) polymorphism (c.2039A > G p.Asn680Ser). We conducted a cohort study of 125 women with poor ovarian response, 58 of whom received GH in addition to the standard treatment, and 67 of whom received the standard treatment only. The Ala307Thr polymorphism genotypes were analyzed using a polymerase chain reaction-restriction fragment length polymorphism method, and the FSHR gene polymorphism was analyzed using a predesigned TaqMan SNP Genotyping Assay (rs6166). A comparative analysis detected statistically significant differences in mean mature follicles (p = 0.0002), metaphase-II oocytes (p = 0.0005), progesterone levels (p = 0.0036), and IGF levels (follicle IGF1, p = 0.0004) between GH-treated and non-GH-treated participants with the FSHR (Ser/Ser) polymorphism. However, the differences were modest among participants with the other two FSHR polymorphisms (Ser/Asn and Asn/Asn). The subcategory of patients with the FSHR Asn680Ser (Ser/Ser) polymorphism showed a stronger response when GH was added to the IVF protocol.

Correction: Self-reported and clinical periodontal conditions in a group of Eastern European postpartum women.

[This corrects the article DOI: 10.1371/journal.pone.0237510.].

Injectable platelet-rich fibrin influences the behavior of gingival mesenchymal stem cells.

In this study, we examined the effects of injectable platelet-rich fibrin (iPRF) on proliferation and osteodifferentiation in mesenchymal stem cells (MSCs) isolated from human gingiva. Gingival MSCs (gMSCs) were grown in experimental culture media with different concentrations of iPRF [5%, 10%, and replacement of fetal calf serum (FCS) in the standard media with 10% iPRF-10% iPRF-FCS]. Immunophenotyping of gMSCs was performed after seven days by flow cytometry, and their proliferation was examined after three and seven days using the Cell Counting Kit-8 method. After 14 days in culture, spontaneous osteogenic differentiation of gMSCs was evaluated via real-time polymerase chain reaction. All gMSCs were positive for cluster of differentiation (CD) 105, CD73, CD90, and CD44, and negative for CD34∕45, CD14, CD79a, and human leukocyte antigen, DR isotype (HLA-DR). Reduced expression of some surface antigens was observed in the gMSCs grown in 10% iPRF-FCS medium compared to the other groups. After three days, gMSCs grown in 10% iPRF had proliferated significantly less than the other groups. After seven days, proliferation was significantly higher in the 5% iPRF cells compared to the control, while proliferation in the 10% iPRF and 10% iPRF-FCS groups was significantly lower. No spontaneous osteogenic differentiation was observed in the presence of iPRF, as observed by low runt-related transcription factor 2 (RUNX2) expression. Some expression of secreted protein acidic and cysteine rich (SPARC) and collagen 1 alpha (COL1A) was observed for all the gMSCs regardless of the culture medium composition. gMSCs grown in 10% iPRF had significantly lower SPARC expression. In conclusion, 5% iPRF stimulated gMSC proliferation, and an excessively high concentration of iPRF can impair osteogenic induction.

Self-reported and clinical periodontal conditions in a group of Eastern European postpartum women.

Periodontitis is a highly prevalent condition leading to a continuous destruction of tooth-supporting tissues. It increases the risk for various systemic diseases and adverse pregnancy outcomes. Therefore, screening for periodontitis is important. Screening measures can range from self-reported symptoms to clinical full-mouth periodontal examination. The hypothesis of our study was that self-reported parameters and clinical definition perform equally well in identifying periodontitis patients. The aim of this study was to develop, validate its internal consistency, and evaluate a self-reported instrument against periodontal clinical evaluation for diagnosis of periodontitis in a group of postpartum women, as well as to describe their periodontal status and the risk factors associated with periodontal disease. A cross-sectional study on postpartum women was conducted in a tertiary university hospital, from April 2018 to March 2019. Sociodemographic and behavioral data, periodontal clinical parameters, and self-reported periodontal perception were collected. A 16-item questionnaire was developed to obtain information about perceived periodontal alterations and oral hygiene habits. The utility of the questionnaire was tested against a periodontal diagnosis based on a full-mouth periodontal examination. The questionnaire was applied in 215 postpartum women aged 29.16±5.54 years (mean age (y) ± standard deviation) having the following periodontal status: 16 individuals without periodontal disease (7.44%), 32 individuals with gingivitis (14.88%), 19 individuals with mild periodontitis (8.84%), 132 individuals with moderate periodontitis (61.39%), and 16 individuals with severe periodontitis (7.44%). A significant association was observed between oral hygiene score, smoking status, and periodontal conditions (p<0.05). A significant association between the self-reported items related to "gum swelling", "halitosis", "previous periodontal diagnosis" and "previous periodontal treatment" with clinical periodontitis have been identified (p<0.05). Using self-reported questionnaires for detection of periodontal disease was ineffective in our studied population, since self-reported parameters and clinical definition do not appear to perform equally in identifying periodontitis cases. Clinical periodontal examination remains the gold standard for screening. Periodontitis was frequent in our group and the severity was significantly associated with the oral hygiene score and smoking. These results underline the necessity for periodontal clinical examination during pregnancy.

Association between maternal/newborn genetic variants, placental pathology and spontaneous preterm birth risk: a Romanian population-based study.

Objective: The objective of this study was to determine the association between maternal/newborn single-nucleotide polymorphisms (SNPs) in three candidate genes, placental pathology and the risk of spontaneous preterm birth (SPTB) in a Romanian population.Methods: We performed a prospective case-control study in a tertiary maternity in Romania, including 79 mother-newborn pairs with SPTB and 81 mother-newborn pairs with term delivery. Using real-time Polymerase Chain Reaction (PCR), three SNPs rs8192282 A > G, rs2277698 C > T and rs34003 A > C located on interleukin 6 receptor (IL6R), tissue inhibitor of matrix metalloproteinase-2 (TIMP2) and fibroblast growth factor 1 (FGF1) genes were assessed. The minor allele and genotype frequencies were compared between groups. Multilocus genetic association analyses were performed. From pathology reports, the morphological and histopathological examination of the placentas were extracted.Results: The rs34003 C/C genotype frequency in newborns FGF1 gene was significantly higher in the spontaneous preterm birth (SPTB) group compared to the control group (p = .045). In single-locus analyses, C/C genotype was associated with an increased risk of spontaneous preterm birth (OR = 2.59, 95%CI: 1.02-6.58). Additionally, this homozygote genotype was correlated with the presence of placental pathology, especially with the inflammatory and vascular lesions (p < .01). The prediction model based on rs34003 C/C genotype - placental pathology joint influence had a statistically significant regression coefficient (p < .01, OR = 7.76, 95%CI: 4.03-14.93). Single nucleotide polymorphisms related to IL6R gene in maternal samples and FGF1 gene in newborns were associated with spontaneous preterm delivery in multilocus genetic association analyses (p = .028, OR of 2.375).Conclusions: Our results indicate that rs34003 C/C genotype in newborns FGF1gene is correlated with the occurrence of placental pathological lesions and with an increased SPTB risk. The association of two SNPs in maternal and fetal genes doubled the risk of spontaneous preterm birth in our population.

The role of imaging techniques in the diagnosis, staging and choice of therapeutic conduct in pregnancy associated breast cancer.

Breast cancer diagnosed during pregnancy is at increasing incidence due to the increased frequency of obesity, the postponement of the first pregnancy to later decades of life and the advances of diagnostic techniques. Clinical and imaging diagnosis is difficult during gestation due to adaptive changes of the maternal organism , the mammary glads in particular. Furthermore, the therapeutic approach is limited both by the possible side effects on the fetus and by the skepticism of the couple over these therapeutic regimens.The present paper aims to review the main diagnostic steps to confirm pregnancy associated breast cancer, as well as the therapeutic possibilities during this period, related to the potential adverse effects concerning pregnancy.

The influence of reproductive factors on breast cancer risk in women with pathogenic mutations.

PURPOSE: To assess the influence of reproductive factors in the occurrence of breast cancer in women, taking into account the presence/absence of genetic predisposing mutations. METHODS: 100 patients with breast cancer were included. The genetic testing was conducted through a multigene panel. Reproductive characteristics were noted for all patients: age of menarche, age of the patient at first full term pregnancy, number of pregnancies, number of full-term pregnancies, breastfeeding interval, number of abortions, and menopausal status at the time of diagnosis. The patients were divided into three groups according to their mutations: BRCA1, positive for mutations other than BRCA1 and negative. RESULTS: The risk of breast cancer was not influenced by the number of abortions, parity, age at first pregnancy, age at menarche and menopausal status, or by oral contraceptive use in carriers of pathogenic mutations group in the BRCA1 group. The present study has demonstrated the protective effect of breastfeeding only in patients without genetic risk (p=0.0344). In contrast, breastfeeding did not influence breast cancer occurrence in BRCA1 mutation carriers' group (p=0.2321). CONCLUSIONS: Breastfeeding represents a protective mechanism only in patients without genetic breast cancer predisposing mutations. Environmental and reproductive factors can impact the risk and the age of onset of breast cancer in patients carrying pathogenic mutations, but the mechanisms of action are not fully understood.

Renin-angiotensin system gene variants and risk of early- and late-onset preeclampsia: A single center case-control study.

BACKGROUND: Changes in the renin-angiotensin-aldosterone system's (RAAS) activity due to different genetic variations could represent risk factors for the onset of preeclampsia. OBJECTIVE: To test and quantify the relationships of 8 RAAS gene polymorphisms (angiotensinogen (AGT)-M235T, AGT-T174M, angiotensin converting enzyme (ACE)-I/D, ACE8-A2350G, angiotensin II type 1 receptor (AGTR1)-A1166C, angiotensin II type 2 receptor (AGTR2)-C3123A, renin (REN)-G83A, aldosterone synthase (CYP11B2)-T344C) with susceptibility to early- (EOPE) and late-onset preeclampsia (LOPE). STUDY DESIGN: We performed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis in 217 pregnant women, of whom 87 pregnant women with EOPE/LOPE and 130 normal pregnant women. The relationship between the studied RASS gene polymorphisms and EOPE/LOPE was tested by multiple logistic regressions. RESULTS: The multivariate logistic regression analysis showed that AGT-M235T (adjusted OR = 4.63), AGT-T174M (adjusted OR = 4.13), REN-G83A (adjusted OR = 3) and CYP11B2-C344T (adjusted OR = 3.13) gene polymorphisms remained independent risk factors for EOPE. Moreover, ACE-I/D (adjusted OR = 4.04), ACE-A2350G (adjusted OR = 3.5), AGTR1-A1166C (adjusted OR = 2.73), and REN-G83A (adjusted OR = 2.67) polymorphisms remained independent risk factors for LOPE. The frequency of overweight was significantly different (p = 0.001) in pregnant women with EOPE, LOPE and the control group (LOPE:16, 29.6% vs. EOPE:12, 36.4% vs. control group:16, 12.3%). Pregnant women with EOPE had babies with a significantly lower mean birth weight (2067.9 ±â€¯887.9) in comparison to women with LOPE (mean ±â€¯SD: 2860.1 ±â€¯771.1, p < 0.001) and women with normal pregnancies, respectively (mean ±â€¯SD: 3324.9 ±â€¯484.9, p < 0.001). CONCLUSION: We confirmed the influence of the renin-angiotensin-aldosterone system through these 8 genetic variations on the onset of preeclampsia.

Potential clinical benefits and limitations of fetal virtopsy using high-field MRI at 7 Tesla versus stereomicroscopic autopsy to assess first trimester fetuses.

OBJECTIVE: The aim of this study was to establish the diagnostic accuracy of high-field magnetic resonance imaging (MRI) at 7 Tesla (T) compared with that of stereomicroscopic autopsy for assessing first trimester fetuses. METHODS: Nine consecutive cases of first trimester fetuses resulting from spontaneous and therapeutic pregnancy termination were considered. The cases were divided into two groups according to gestational age: the Embryo Group with cases of nine to 10 gestational weeks (GWs) and the Fetus Group with cases of 13 GWs. The first group was scanned using three-dimensional fast imaging with steady state precession (3D FISP), and the second group was scanned using a two-dimensional (2D) turbo spin-echo high-resolution T2-weighted imaging (T2 WI) protocol. A radiologist and two embryologists interpreted the images. All cases were evaluated by invasive autopsy, with pathologist blinded to the imaging results. In total, the database included 270 items for evaluation (9 cases × 30 structures/case). RESULTS: The global agreement between fetal high-field virtopsy and microscopic or stereomicroscopic autopsy was evaluated using 225 evaluation items visible by both methods. Overall, using microscopic examination and stereomicroscopic autopsy as the gold standard, fetal high-field virtopsy had a sensitivity of 94.6% [95% CI, 87.2-98.3] and a specificity of 97.6% [95% CI, 95-98.8]. The positive predictive value (PPV) was 93% [95% CI, 85.7-96.6], and the negative predictive value (NPV) was 98.2% [95% CI, 95.7-99.4]. Cohen kappa coefficient of agreement was k = 0.92 [95% CI, 0.82-0.97], and the McNemar test showed p = 1.00. CONCLUSIONS: Virtual autopsy using high-field MRI at 7 T can be considered a safe alternative approach to stereomicroscopic autopsy for the assessment of fetal structural anomalies at the end of the first trimester of pregnancy.

Prevalence of deleterious mutations among patients with breast cancer referred for multigene panel testing in a Romanian population.

AIM: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing is becoming more common in medical care.We report our experience regarding deleterious mutations of high and moderate-risk breast cancer genes (BRCA1/2, TP53, STK11, CDH1, PTEN, PALB2, CHEK2, ATM), as well as more recently identified cancer genes, many of which have increased risk but less well-defined penetrance. METHODS: Genetic testing was performed in 130 consecutive cases with breast cancer referred to our clinic for surgical evaluation and who met the 2016 National Comprehensive Cancer Network (NCCN) criteria for genetic testing. RESULTS: 82 patients had pathogenic/likely pathogenic mutations and VUS mutations, and 48 were negative; 36 of the pathogenic mutations were in the high-risk genes and 16 were in the moderate risk genes and only 5 cases in the intermediary risk group.From the VUS mutation group 21 cases were in the intermediary risk group, 9 cases were in the moderate risk group and only 7 cases in high risk group.The most frequent BRCA1 variant was c.3607C>T (7 cases) followed by c.5266dupC and c.4035delA (each in 4 cases). Regarding BRCA-2 mutations we identified c.9371A>T and c.8755-1G>A in 6 cases and we diagnosed VUS mutations in 3 cases. CONCLUSION: Our study identified 2 mutations in the BRCA1 gene that are less common in the Romanian population, c.3607C>T and c.4035delA. Both variants had particular molecular phenotypes, c.3607C>T variant respecting the triple negative pattern of BRCA1 breast cancer while c.4035delA were Luminal B HER positive.

A couples-focused intervention for smoking cessation during pregnancy: The study protocol of the Quit Together pilot randomized controlled trial.

Tobacco smoking remains the leading global cause of preventable disease and death. Preconception and pregnancy smoking are high in Central and Eastern Europe. Quit Together is a partnership between a US university and a Romanian university, obstetrics and gynecology clinics in Romania, and other community partners in Romania. The objective of the Quit Together pilot study is to adapt, enhance and test the implementation feasibility and initial efficacy of an evidence-based pregnancy and postnatal couple intervention for smoking cessation in Romania. Quit Together builds on the Motivation and Problem Solving (MAPS) approach, enhanced by targeting the couples' smoking behavior and focusing on dyadic efficacy for smoking cessation. The study is an ongoing randomized controlled trial of 120 Romanian pregnant smokers and their partners. Participants are randomized to: 1) an intervention arm consisting, typically, of up to 8 prenatal and postnatal telephone counseling calls for the women and 4 for their partners, combining motivational strategies and problem-solving/coping skills to encourage the woman to quit smoking and the partner to support her decision; and 2) a control arm (usual care). The primary outcome is maternal biochemically verified smoking abstinence at 3 months postpartum. Quit Together has the potential to identify effective strategies to increase maternal smoking cessation during pregnancy and smoking abstinence after birth. If effective, Quit Together is expected to have a sustainable positive impact on the health of the child, mother and partner, and potentially reduced health system costs.

Maternal/fetal eNOS-Glu298Asp genotypes and their influence on the severity, prognosis, and lipid profile of preeclampsia.

OBJECTIVES: To analyze the contribution of maternal eNOS-Glu298Asp genotypes and also the association with fetal genotypes to the development of preeclampsia, prognosis, and maternal dyslipidemia. METHODS: Sixty-nine pairs of preeclamptic mothers/newborns and 94 pairs of normotensive mothers/newborns were genotyped for eNOS-Glu298Asp using PCR-RFLP methods. RESULTS: Women carriers of at least one Asp298 allele had a 1.53-fold (p = NS), 1.88-fold (p = NS), and 2.08-fold (p = .05), respectively, increased risk to develop PIH, mild, or severe preeclampsia. If both the mother and the newborn were carriers of the Asp298 allele, the risk for preeclampsia was 5.09-fold higher (p < .001). Preeclamptic women with severe preeclampsia had significantly higher cholesterol (mg/dl, 287.23 ± 43.01 versus 235.36 ± 45.01, p = .02) and LDL (mg/dl, 194.9 ± 42.8 versus 144.98 ± 54.84, p = .04) levels and lower HDL levels (mg/dl, 32.12 ± 5.48 versus 57.84 ± 20.59, p = .02) compared to noncarriers. Also, higher LDL levels (mg/dl, 188.76 ± 46.61 versus 136.75 ± 41.85, p = .03) and lower HDL levels (mg/dl, 32.8 ± 5.64 versus 61.06 ± 22.45, p = .02) were found in preeclamptic women with severe preeclampsia whose newborns were carriers of the Asp298 allele. CONCLUSIONS: The eNOS-Glu298Asp variant (in mothers and newborns) in association with dyslipidemia could affect bioavailability of NO and could represent an increased risk for preeclampsia.

D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

AIM: To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. MATERIALS AND METHODS: We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. RESULTS: Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. CONCLUSION: The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

Imagistic and histopathological description of a cystic nephroma during early second trimester of gestation. Case report.

Cystic nephroma is a rare and benign renal tumour of unknown origin, usually diagnosed in the first years of childhood or during adult life. To our knowledge, there are no records in the literature of this particular tumour being descried prenatally. We present a case of a fetus diagnosed with cystic nephroma on 16 weeks of gestation. The renal tumour was evaluated by prenatal ultrasound, post mortem with 7T magnetic resonance imaging, and conventional autopsy.

Newborn APOE genotype influences maternal lipid profile and the severity of high-risk pregnancy - preeclampsia: Interaction with maternal genotypes as a modulating risk factor in preeclampsia.

AIM: To establish the role of the interaction between maternal and newborn apolipoprotein E (APOE) genotypes on the risk, lipid profile and prognosis of preeclampsia (PE). MATERIALS AND METHODS: Forty-seven preeclamptic women and 94 normotensive pregnant women and their newborns were genotyped for APOE using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Maternal APOE-ε4 allele was associated with an about eight times higher risk of PE (adjusted OR = 8.4, 95% CI: 2.51-28.17, p = 0.001). The multivariate logistic regression model showed that the newborn APOE-ε4 allele was associated with an about six times higher risk of PE (adjusted OR = 5.6, 95% CI: 2.09-15.21, p = 0.001) for the given gestational age levels. Pregnant women with severe PE whose newborns carried the APOE-ε4 allele delivered at earlier gestational ages neonates with a lower birth weight compared to pregnant women with newborns negative for this allele. Higher TG and LDL-C levels and lower HDL-C levels were found in pregnant women with severe PE whose newborns were carriers of the APOE-ε4 allele compared to preeclamptic women whose newborns were carriers of the ε3/ε3 genotype. If we checked the combined effect of the mother/newborn genotypes on the risk of PE, we found that the risk to develop PE was 15.4-fold (p < 0.001) increased if mothers or newborns were carriers of the APOE-ε4 allele. The risk increased to 20.02 (p < 0.001) if both the mother and newborn were carriers of the APOE-ε4 allele. CONCLUSIONS: Our study confirms the maternal/newborn APOE genotype interaction influences the risk for PE, as well as prognosis and lipid profile.

A couple-focused intervention to prevent postnatal smoking relapse: PRISM study design.

BACKGROUND: Maternal smoking is one of the most modifiable factors with clear adverse effects for the fetus and the entire family. Addressing the dearth of pregnancy smoking interventions with partner support, PRISM (Prevent Relapse In SMoking) is a partnership between a research institution and the two largest state-owned obstetrics and gynecology clinics in Cluj-Napoca, Romania. The study will assess the efficacy of a couple-focused telephone-counseling program to prevent smoking relapse among mothers who quit smoking closely before or during pregnancy. METHODS/DESIGN: The intervention is a program for couples based on motivational interviewing delivered over the phone after birth. The study is an ongoing randomized controlled trial of 250 Romanian women recruited soon after childbirth, who quit smoking in the six months before pregnancy or no later than the end of the first pregnancy trimester and remained abstinent (which was biochemically verified) until delivery. Participants were randomized to: (1) a control arm (usual care); and (2) an intervention arm consisting of up to 4 postnatal counseling calls for mothers and their partners using motivational interviewing to encourage the woman to remain smoke-free and the partner to support her decision. The primary outcome is maternal smoking abstinence at 6 months postpartum (biochemically verified). DISCUSSION: PRISM has the potential to identify strategies to reduce maternal postnatal relapse and increase partner quitting. If successful, the program may be an effective method to prevent and reduce smoking, which may lead to improved child, mother, and partner health both in the short and the long term.

Maternal smoking during pregnancy and birth outcomes in a sample of Romanian women.

Smoking during pregnancy is causally associated with reduced birth weight and is strongly related to preterm birth. Smoking cessation in early pregnancy seems to reduce these risks, although the research evidence is limited. In a sample of Romanian women, differences in birth outcomes were assessed between non-smokers and women who continued to smoke during pregnancy and non-smokers and women who stopped smok- ing when they found out about the pregnancy. Pregnant women were recruited in two urban clinics (N= 474). A baseline questionnaire collected information on their smoking status, depressive symptoms, stress, demographics, and other characteristics at recruitment. The women reported the newborn weight and birth term by phone in the first weeks following birth. Descriptive statistics and multivariate regressions were used to ana- lyze the relationship between smoking status during pregnancy and birth outcomes. Over 61% (N = 290) women were non-smokers, 15% (N= 72) smoked during pregnancy, and 24% (N= 112) quit smoking when they found out about the pregnancy. Compared to non-smokers, continuous smokers delivered babies 165 grams lighter (95% CI -313, -17). Women who stopped smoking when they ascertained the pregnancy had higher odds of delivering a newborn who was small for gestational age compared to non-smokers (OR= 2.16, 95% CI 1.05, 4.43). Elevated maternal stress was associated with reduced birth weight (-113 grams, 95% CI -213, -11), and higher odds of a preterm birth (OR=2.8, 95% CI 1.17, 6.76). In a predominantly urban sample of Romanian women, continuous maternal smoking during pregnancy was a risk factor for restricted foetal growth. Smoking cessation when the pregnancy was ascertained did not seem to reduce this risk. Smoking prevention efforts should therefore begin before pregnancy and should integrate psychological components, addressing maternal stress in particular.