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Objective: To investigate whether antibiotic exposure during pregnancy was associated with childhood asthma and if this relationship was conditional on timing of exposure and mode of delivery., Design: A cohort study using multivariable logistic regression models adjusting for a priori defined confounders. Pregnant women were recruited from 1996 to 2002., Setting: The Danish National Birth Cohort., Patients: Of the 96 832 children in the cohort, 32 651 children were included in the study population., Main Outcome Measure: Parent-reported childhood asthma at 11 years., Results: A total of 5522 (17%) children were born to mothers exposed to antibiotics during pregnancy. In adjusted analyses, children born to exposed mothers had higher odds of asthma (OR 1.14, 95% CI 1.05 to 1.24). There was no association with antibiotic exposure in the first trimester (OR 1.02, 95% CI 0.83 to 1.26), but higher odds were observed for antibiotic exposure in the second to third trimester (OR 1.17, 95% CI 1.06 to 1.28), compared with unexposed children. The overall association between antibiotics during pregnancy and childhood asthma was only observed in vaginally born children (OR 1.17, 95% CI 1.07 to 1.28) but not in caesarean section born children (planned caesarean section: OR 0.95, 95% CI 0.66 to 1.37; caesarean emergency: OR 0.96, 95% CI 0.73 to 1.28). In exposed vaginally born children, the odds for childhood asthma requiring treatment during the preceding year were 34% higher (OR 1.34, 95% CI 1.21 to 1.49), compared with unexposed vaginally born children., Conclusions: Antibiotic exposure in mid-to-late pregnancy is associated with higher odds of childhood asthma in vaginally born children. Mode of delivery may modify the association., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Acute hyperglycemia affects the fetoplacental circulation. This study aims to investigate the possible effect of acute hyperglycemia induced by 50 g oral glucose tolerance test (OGTT) on fetoplacental circulation in women between 24 and 28 weeks of gestation., Materials and Methods: Between January 2019 and April 2019, a total of 29 women who were between 24 and 28 weeks of gestation with a singleton gestation and were in low-risk group were included in this prospective study. All patients underwent fetal biometric measurements using ultrasonography (USG) and were administered 50 g OGTT. Before and 1 h after the test, Doppler USG was used to measure uterine artery, umbilical artery (UA), middle cerebral artery (MCA), pulsatility index (PI), resistance index (RI), and systolic/diastolic (S/D) ratio. The cerebroplacental ratio (CPR) was calculated as the ratio of the MCA-PI/UA-PI., Results: There was a decline in the MCA-RI (p = 0.008) and UA-PI (p = 0.021) at 1 h after the administration of 50 g OGTT. Z-scores of the mean UA-PI, MCA-PI, and CPR were calculated and a statistically significant increase in the Z-scores of the mean UA-PI was observed (p = 0.028)., Conclusion: Our study results show that acute hyperglycemia induced by OGTT significantly increases the Z-scores of the UA-PI, affecting the fetoplacental circulation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The authors are solely responsible for the content and writing of the paper., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Current guidelines suggest that granisetron is an optional treatment for nausea and vomiting in pregnancy (NVP) despite lack of evidence to support fetal safety. We aimed to determine the association between early pregnancy exposure to granisetron and fetal/neonatal outcomes., Design: Medical records of patients treated for NVP during the first and second trimester between June 2013 to September 2015 were reviewed. Patients were asked to participate in the study by answering a detailed questionnaire regarding newborn's health and complementary data. Pregnancy outcomes of patients exposed to granisetron were compared with those of patients who were not exposed to granisetron., Results: 100 Granisetron exposed pregnancies were compared with 108 granisetron unexposed pregnancies. Exposure to granisetron occurred in the first trimester in 88 patients (94 fetuses). Maternal characteristics, history of anomalies in first degree relatives, co-exposure to other substances and extent of prenatal sonographic surveillance were comparable between both groups. Miscarriage rate was significantly lower among granisetron exposed patients compared to controls (0 vs 5.5 %, respectively, p = 0.03). Three major malformations were identified prenatally or postnatally in each of the groups (2.77 % Vs 2.83 %, p = 1). The rate of major malformations was similar between exposed and unexposed fetuses even after excluding second trimester exposure (3.2 % vs. 2.83 %, respectively p = 1). Mean gestational age at delivery, mean newborn weight and incidence of small for gestation age, were not significantly different between the groups., Conclusion: Granisetron exposure was not associated with increased risk for minor or major fetal anomalies. This study provides preliminary reassurance regarding the safety of in-utero exposure to granisetron., (Copyright © 2019. Published by Elsevier B.V.)

A mother presented with a fetus at 22±1 weeks of gestation with a sustained supraventricular tachycardia  (SVT) at initially 186 beat per minute (bpm). The fetal M-mode echocardiography showed a 1/1 atrio ventricular ratio (with short atrioventricular (AV) interval and a long ventriculo-atrial (VA) interval, suggesting a Persistent junctional reciprocating tachycardia (PJRT) . Upon  initial present no signs of heart failure or hydrops  were noted and treament was initiated with amiodarone and  digoxin . Fetus heart rate slowed  .Postnatal electrocardiogram  Confirmed  the diagnosis of PJRT New born was put on amiodarone and proparonal). Sinus rhythm was rapidly achieved 9 days later .The patient doing well at  10 months of age with maintain of sinus rhythm. Conclusion: our case report illustrates  a particular  form of  JRT   diagnosed  prenatal PJRT  , characterized  by  a good clinical tolerance, its absence of evolution towards cardiomyopathy  and its rapid and unusual response to antiarrhythmics.

Background: Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86)., Results: The top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels., Conclusions: These results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787.

Experimental studies indicate that perinatal light exposure has enduring effects on affective behaviors in rodents; however, insufficient research has explored this hypothesis in humans. We examined photoperiod (i.e., day length) metrics during maternal pregnancy in relation to lifetime depression in the longitudinal Nurses' Health Study (NHS) and NHS II. 160,723 participants reported birth date and birth state (used to derive daily photoperiod based on published mathematical equations), and clinician-diagnosed depression and antidepressant use throughout adulthood. Logistic regression was used to estimate odds ratios (OR) (and 95% confidence intervals [CI]) for depression (defined as clinician diagnosis and antidepressant use) across quintiles of two exposures during maternal pregnancy: 1) total photoperiod (total number of daylight hours) and 2) differences between minimum/maximum photoperiod; each trimester of pregnancy was examined separately. Total photoperiod during maternal pregnancy was not associated with depression overall or by trimester of pregnancy. However, larger differences between minimum/maximum photoperiod during maternal pregnancy were related to lower odds of depression (multivariable [MV]-adjusted OR: 0.86, 95% CI: 0.83, 0.90 comparing extreme quintiles of exposure; p-trend<0.0001); this association appeared specific to the second trimester of pregnancy (MV-adjusted p-trends = 0.03, <0.0001, and 0.3 across the three trimesters, respectively). In addition, birth at higher latitude (where larger differences in minimum/maximum photoperiod exist) was associated with a significant reduction in the lifetime risk of depression. These findings are consistent with an emerging hypothesis in which perinatal light exposure may influence risk of depression, and they might be understood through the conceptual framework of adaptive developmental plasticity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Estimates suggest that nearly 30% of patients diagnosed with chronic myeloid leukemia (CML) are aged <49 years, with approximately half being women. For many of these women, childbearing concerns are a major factor as they initiate treatment with tyrosine kinase inhibitors, which are known to be teratogenic. During her presentation at the NCCN 23rd Annual Conference, Dr. Berman identified the challenges in helping women undergoing treatment for CML who want to have children, and emphasized the importance of an individualized and multidisciplinary approach to management. In addition, she encouraged NCCN to create a pregnancy registry of this patient population to enable clinicians to collect firm data to guide clinical decision-making., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Objective: To investigate the role of adjuvant 17-α-hydroxy-progesterone caproate (17OHP-C) in reducing the risk of preterm delivery <34 weeks and adverse perinatal outcomes in women with ≥3 second trimester pregnancy losses attributed to cervical insufficiency undergoing prophylactic cerclage., Material and Methods: Retrospective cohort study of women with prophylactic cerclage placed between 2006 and 2014 divided into a cohort of (i) those receiving adjuvant 17OHP-C (n=43), and (ii) controls with cerclage alone (n=59)., Results: Demographic characteristics were comparable in both groups. There was no significant difference in gestational age at delivery between the cerclage-17OHP-C group (33.4±5.6 weeks) and the cerclage-alone group (34.4±4.6 weeks); P=0.33. We noted a non-significant increase for deliveries <34 weeks in the cerclage-17OHP-C group (44.2%) compared to controls (28.8%) which remained non-significant after adjusting for confounders; P=0.46. There was no statistically significant difference in the rate of delivery <37, 32, 28 and 24 weeks. Adverse neonatal outcomes were comparable in both groups (cerclage-17OHP-C 48.8% vs. cerclage-alone 39%); P=0.43., Conclusion: Intramuscular 17OHP-C in combination with prophylactic cerclage in women with cervical insufficiency and ≥3 second trimester pregnancy losses had no synergistic effect in reducing the rate of recurrent preterm birth or improving perinatal outcomes.

Background: Our previous research showed that 4 h of maternal anesthesia with isoflurane during early gestation in pregnant rats leads to a deficit in spatial memory of adult male offspring. Because spatial memory is predominantly a hippocampally-mediated task, we asked the question if early gestational exposure to isoflurane affects development of the hippocampus in the offspring., Findings: Previously behaviorally characterized adult male rats that were exposed to isoflurane during second trimester were sacrificed at 4 months of age (N = 10 and 13, control and isoflurane groups, respectively) for quantitative histology of hippocampal subregions. Sections were stained with cresyl violet and the total number of cells in the granular layer of the dentate gyrus and the pyramidal cell layer in the CA1 region were determined by a blinded observer using unbiased stereological principles and the optical fractionator method. Data were analyzed using Student's t test; P < 0.05 was accorded statistical significance. Stereological examination revealed 9% fewer cells in the granular layer of the dentate gyrus of isoflurane-exposed adult rats compared to controls (1,002,122 ± 84,870 vs. 1,091,829 ± 65,791, respectively; Mean ± S.D, *P = 0.01). In contrast, there were no changes in the cell number in the CA1 region, nor were there changes in the volumes of both regions., Conclusions: Our results show that maternal isoflurane anesthesia in rodents causes region-specific cell loss in the hippocampus of adult male offspring. These changes may, in part, account for the behavioral deficits reported in adult rats exposed to isoflurane in utero.

Ovarian cancer is one of the most common types of solid carcinoma diagnosed during pregnancy. Taxane plus a platinum derivative is a combination therapy that is predominantly used in the treatment of ovarian cancer in non-pregnant women. Pregnancy adds various complexities to a course of treatment. In pregnant patients diagnosed with cancer during the first trimester, the risks of fetal malformations and fetal loss increase following the administration of cytotoxic drugs, and this is higher with multi-agent vs. single-agent chemotherapy (~ 25 vs. 10%). Exposure during the second and third trimester has little influence on teratogenic effects but increases the risk of intrauterine growth retardation, prematurity, low birth weight, and bone marrow toxicity. The present study aimed to review the maternal and fetal safety of treatment with taxane plus platinum derivatives for ovarian cancer during pregnancy. Relevant literature was retrieved from the Embase and PubMed databases using the search terms "ovarian cancer", "pregnancy", "taxane", "paclitaxel", "docetaxel", "platinum", "cisplatin", and "carboplatin". All available data up until September 2016 was synthesized, with no language restrictions. A total of 11 articles (including 13 pregnancies and 14 newborns) were retrieved that reported on the use of standard-dose taxane and platinum chemotherapy, including 9 cases treated with paclitaxel and carboplatin, 3 cases treated with paclitaxel and cisplatin, and 1 case treated with docetaxel and cisplatin. In 13 of the 14 (92.9%) births included, a healthy neonate was born, with follow-up ranging from 2 to 160 months. The average weight of the neonates at the time of delivery was 2,442.1 g. In 7 of 9 the case reports that provided survival data, the mother was alive and disease-free at the end of follow-up (ranging from 2 to 40 months). In conclusion, combination therapy with taxanes and a platinum derivative may play a significant role in the management of pregnant patients with ovarian cancer during the second and third trimester. Exposure to this combination of agents during the second and third trimester does not appear to have a significant bearing on fetal mortality and abortion.
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Supplementation with folic acid (FA) was proven to prevent neural tube defects (NTDs) and was recommended worldwide before and during early pregnancy. However, much less is known regarding the role of FA after the 12th gestational week (GW). This study aimed to investigate the related effects of continued FA supplementation after the first trimester of pregnancy on fetal growth. The study subjects came from the Ma'anshan-Anhui Birth Cohort Study (MABC) that recruited 3474 pregnant women from the city of Ma'anshan in Anhui Province in China during the period of May 2013 to September 2014. The information on use of vitamin and mineral supplements was recorded in different periods (the first/second/third trimester of pregnancy). Small-for-gestational-age (SGA) births were live-born infants that were <10th percentile of birth weight, and large-for-gestational-age (LGA) births were live-born infants that were ≥90th percentile of birth weight according to nomograms based on gender and gestational age from the latest standards. We used multivariable logistic regression to evaluate the effects of FA supplement consumption in the second/third trimester of pregnancy on the risk of LGA and SGA. In addition, propensity score analysis was also performed to examine the effects. In this prospective birth cohort study conducted in Chinese women who had taken FA in the first trimester of pregnancy, we found that continued FA supplementation with 400 micrograms/day in the second and third trimesters of pregnancy significantly increased the risk of LGA (RR = 1.98 (1.29, 3.04)). This relation was strong or monotonic after adjusting for maternal age, newborn's gender, maternal pre-pregnancy BMI, maternal education level, smoking, alcohol consumption and calcium supplementation. We did not observe that continuing FA supplementation after the first trimester of pregnancy remarkably decreased the risk of SGA. The propensity score analysis showed similar results. To confirm these findings, additional investigations or trials with a large sample and the tracking of folate status throughout pregnancy are recommended.

Objective: Antitumour necrosis factor (TNF) during pregnancy in patients with IBD is related to high fetal anti-TNF levels. We evaluated maternal and child safety on discontinuing anti-TNF in the second trimester of pregnancy., Design: Two groups of women with IBD were prospectively followed-up during pregnancy: women in sustained remission stopped anti-TNF before week 25 (stop group) and the remaining group continued anti-TNF beyond week 30 (continue group). Maternal, birth and 1-year child outcomes were compared with children of non-IBD women., Results: Overall, 106 patients with 83 completed pregnancies were included. Relapse rate after week 22 did not differ between the stop (n=51) and continue (n=32) groups (5 (9.8%) versus 5 (15.6%), p=0.14). There was no difference in allergic reactions (p=1.00) or loss of response (p=1.00) postpartum between the two groups. Birth outcomes were comparable. Infants from both groups had lower birth weight (p=0.001), shorter gestational term (p=0.0001), were more often delivered via caesarean section (p=0.0001) and were less often breastfed (p=0.0001) compared with infants from non-IBD controls. Growth, infection rate, allergies, eczema and adverse reactions to vaccines were comparable across the stop and the continue groups as well as the children of anti-TNF-exposed and non-IBD women at 1 year., Conclusions: To limit anti-TNF exposure in utero, anti-TNF can be stopped safely in the second trimester in women with IBD in sustained remission. In patients not in sustained remission, anti-TNF may be continued without clear additional risks to the fetus. We observed excellent 1-year child outcomes compared with children from non-IBD controls., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To study the efficacy of 100 μg intravenous shot of carbetocin compared to 20 IU oxytocin intravenous infusion to prevent placental retention in second trimester medical termination of pregnancy., Methods: A double-blinded randomized controlled trial was conducted at Ain Shams University Maternity Hospital from 1 April 2013 to 30 November 2013. A total of 132 women between 14 and 24 weeks gestation indicated for termination were randomized to receive either 20 IU oxytocin infusion (n = 66) or 100 μg carbetocin shot (n = 66) after fetal expulsion. Patients were observed for time elapsed between fetal and placental expulsion, presence of placental retention and blood loss., Results: Third stage was 33.4 ± 20.4 min in oxytocin group & 23.1 ± 16.8 min in carbetocin group (p = 0.002). Eight patients (12.1%) in oxytocin group had complete placental retention versus two patients (3.0%) in carbetocin group (p = 0.05). Eight patients (13.8%) received oxytocin had remnants of placenta compared to four patients (6.2%) received carbetocin (p = 0.04). Sixteen patients (24.2%) received oxytocin and six patients (9%) received carbetocin needed surgical curettage (p = 0.04). Third stage blood loss was 87.2 ± 33.7 ml in carbetocin and 206.9 ± 35.2 ml in oxytocin groups (p = 0.001)., Conclusion: Carbetocin is superior to oxytocin infusion for management of placental delivery in second trimester abortion.

Objectives: We sought to compare the effectiveness of at least 1 h of 400 mcg of buccal misoprostol to overnight osmotic dilators for early second-trimester surgical abortion cervical preparation., Design: We conducted a retrospective cohort study, reviewing 145 consecutive charts to compare procedure duration for women who received 400 mcg of buccal misoprostol at least 1 h preprocedure vs. overnight osmotic dilators before dilation and evacuation between 14 weeks, 0 days and 15 weeks, 6 days' gestation. Primary outcome was procedure duration and secondary outcomes included maximum mechanical dilator size, estimated blood loss and side effects., Results: Sixty-four women (44.1%) received buccal misoprostol (mean 1.6 h), and 81 women (55.9%) received overnight osmotic dilators. Groups did not differ regarding mean gestational age or gynecologic history. All procedures in both groups were completed. Procedure duration was not significantly different between the misoprostol and osmotic dilator groups (median 11.0 min vs. 10.0 min, p=.22), even after multivariable linear regression (p=.17). The mean total cervical preparation duration was 1.6 h for women in the misoprostol group compared to 20.3 h in the osmotic dilator group (p<.001). Secondary outcomes did not differ between groups., Conclusions: We found that at least 1 h of preprocedure misoprostol decreased the duration of cervical preparation for early second-trimester procedures performed by an experienced surgeon., Implications: In this small, retrospective review, at least 1 h of preprocedure buccal misoprostol decreased the duration from cervical preparation initiation to procedure completion in early second-trimester procedures performed by an experienced surgeon. These results should be considered as a pilot evaluation, and further prospective study is needed to further clarify whether this short interval could be applied in general practice., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess differences in outcomes of misoprostol with or without mifepristone for second-trimester abortion., Methods: A randomized, double-blind, placebo-controlled trial of buccal misoprostol following placebo or 200mg mifepristone was done in Tunisia among women presenting for abortions at 14-21 weeks of pregnancy between August 2009 and December 2011. Women with a live fetus, a closed cervical os, no cervical bleeding, and no contraindications to study drugs were eligible and underwent randomization (block size 10). Participants returned 24 hours later to receive 400 μg buccal misoprostol every 3 hours until complete fetal and placental expulsion (maximum 10 doses, five per 24-hour period). The primary outcomes were rates of complete uterine evacuation at 48 hours and time to expulsion., Results: A total of 120 women were evenly randomized to treatment. Complete uterine evacuation at 48 hours was recorded in 55 (91.7%) women in the combined group versus 43 (71.7%) in the misoprostol alone group (relative risk 1.28; 95% confidence interval 1.07-1.53). Mean time to complete abortion was 10.4±6.6 hours in the group who received mifepristone versus 20.6±9.7 hours in the misoprostol alone group (P<0.001). Side effects were similar in both groups., Conclusion: Adding mifepristone before misoprostol can improve the quality of second-trimester abortion care by making the process faster., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

While urine has been an easily accessible and feasible matrix for human biomonitoring, analytical measurements in internal tissues and organs can provide more accurate exposure assessments to understand disease etiology. This is especially important for the endocrine active compound, bisphenol A (BPA), where studies investigating internal doses at sensitive periods of human development are currently lacking. Herein, BPA concentrations, BPA-specific metabolizing enzyme gene expression, and global DNA methylation were characterized across three matched tissues from elective pregnancy terminations of 2nd trimester human fetuses: the placenta, liver, and kidney (N=12 each; N=36 total). Compared to liver (free: 0.54-50.5 ng g(-1)), BPA concentrations were lower in matched placenta (<0.05-25.4 ng g(-1)) and kidney (0.08-11.1 ng g(-1)) specimens. BPA-specific metabolism gene expression of GUSB, UGT2B15, STS, and SULT1A1 differed across each tissue type; however, conjugation and deconjugation expression patterns were similar across the fetus. Average LINE1 and CCGG global methylation were 58.3% and 59.2% in placenta, 79.5% and 66.4% in fetal liver, and 77.9% and 77.0% in fetal kidney, with significant tissue-specific DNA methylation differences in both LINE1 (p-value<0.001) and CCGG content (p-value<0.001). Total BPA concentrations were positively associated with global methylation for the placenta only using the LINE1 assay (p-value: 0.002), suggesting organ-specific biological effects after fetal exposure. Utilizing sensitive human clinical specimens, results are informative for BPA toxicokinetics and toxicodynamics assessment in the developing human fetus., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To evaluate if the 72 hours interval between mifepristone and gemeprost has a similar efficacy compared to the 48 hours interval for second trimester termination of pregnancy, Study Design: Two-hundred and fifteen consecutive pregnant women, admitted to our hospital, for second trimester TOP, were included in this retrospective analysis. Standard protocol was followed for all patients. On the first day of the procedure oral mifepristone 200 mg was administered. After 72 (group A, n = 78) or 48 hours (group B, n = 113) women were admitted for administration of gemeprost 1 mg pessary as per protocol. The induction to abortion time was defined as the interval between the insertion of the first gemeprost pessary and the expulsion of the fetus., Results: There are no significant differences in the number of pessaries in the two groups. The induction to abortion interval was longer in group A than in group B. Twenty-one women required surgical evacuation of the uterus for retained placenta or incomplete abortion without difference between groups., Conclusion: A 48-hours interval between mifepristone and gemeprost leads to better results than a 72-hours interval, with a shorter abortion length and represents the elective method for second trimester TOP.

Context: Metformin is used to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS), although it is not approved for this indication and solid evidence is lacking. Midpregnancy Doppler ultrasound is one of the best methods for prediction of adverse pregnancy outcome., Objective: The objectives of the study were to investigate the following: 1) whether metformin treatment influenced the midpregnancy pulsatility index (PI) of the uterine artery; 2) whether metabolic or endocrine factors affect the PI of the uterine artery of PCOS women; and 3) whether PI predicted adverse pregnancy outcome in PCOS woman., Design: This is a substudy of a randomized, placebo-controlled, double-blind, multicenter study conducted at 11 secondary care centers. We randomly assigned 273 pregnancies to receive metformin or placebo, from the first trimester of pregnancy to delivery. In the present substudy, 231 pregnancies are included, ie, those who completed the ultrasound examinations., Main Outcome Measures: Midpregnancy PI in the uterine artery related to metformin use, androgen levels, an oral glucose tolerance test, and insulin levels was measured. We found no difference in the PI between the metformin and placebo groups. In multivariate analyses, fasting serum glucose of the first and second trimester correlated positively to the midpregnancy PI. Only in univariate analyses a weak correlation between androstenedione and PI was seen., Conclusions: Metformin treatment did not affect uterine artery blood flow, measured by PI. High fasting blood glucose correlated inversely to uterine artery blood flow. The midpregnancy PI correlated positively to preeclampsia, hypertension, and gestational diabetes mellitus in PCOS pregnancies. Androgen levels correlated only to PI in univariate analyses.

Design and Purpose: The supplemental administration of myo-inositol, D-chiro-inositol, folic acid and manganese (MDFM) was tested in a prospective, randomized, double-blind, placebo controlled clinical trial, pilot study, to test the hypothesis that its supplemental administration in the second trimester of pregnancy would improve glucose and glycemic parameters and blood pressure., Subjects and Methods: Non-obese uniparous healthy pregnant women between 13th and 24th week of pregnancy were divided into two groups: group I, control group with placebo, and the group II, women in treatment with myo-inositol, D-chiro-inositol, folic acid and manganese. The main outcome measures were the comparative analysis of the parameters analyzed at time 0, after 30 days and 60 days; secondary outcome measure was the overall analysis of investigated parameters., Results: 24 women were allocated to receive MDFM and 24 the placebo. The two groups did not significantly differ for demographic, lipidic and glycemic parameter and blood pressure. After 30 days, significantly lower cholesterol (p = 0.0001), significantly lower LDL (p = 0.0013), lower TG (p < 0.0001) and lower glycemia (p = 0.0021) were observed all favoring group II. No significant difference was observed for HDL, diastolic and systolic blood pressure. After 60 days, significant difference was observed for cholesterol (p = 0.0001), LDL (p = 0.0001), HDL (p = 0.0001), TG (p = 0.0001), glycemia (p = 0.0064), all favoring the group treated with MDFM. No significant differences were observed for systolic (p = 0.12) and diastolic blood pressure (p = 0.42). When examining for overall differences between the two groups, a significant difference was observed for examined parameters at time 0 and at time 60; cholesterol (p = 0.0001), LDL (p = 0.0001), HDL (p = 0.047), TG (p = 0.0001) and glycemia (p = 0.019) were reduced in the MDFM group. A significant reduction was also observed in group II for systolic blood pressure after 60 days of intervention (p = 0.0092), but not for diastolic blood pressure (p = 0.29)., Conclusions: MDFM administration after 30 days in pregnancy improved glycemic and lipidic parameters, with significant gain after 60 days, without affecting diastolic blood pressure levels.

Background: Supplementation with folic acid (FA) is recommended worldwide before and during early pregnancy because of its proven effect in preventing neural tube defects, but the role of FA after the 12th gestational week (GW) is much less clear., Objective: We investigated maternal folate and homocysteine responses and related effects in the newborn that resulted from continued FA supplementation after the first trimester of pregnancy., Design: Pregnant women, aged 18-35 y, who were attending an antenatal clinic in Northern Ireland with singleton uncomplicated pregnancies and reported taking FA supplements in the first trimester, were randomly assigned at the start of trimester 2 to receive 400 μg FA/d or a placebo capsule., Results: A total of 119 women (60 women in the placebo group; 59 women in the treatment group) completed the trial. From GWs 14-36, mean (±SD) serum folate decreased (from 45.7 ± 21.3 to 19.5 ± 16.5 nmol/L; P < 0.001) in unsupplemented women, whereas plasma homocysteine increased (6.6 ± 2.3 to 7.6 ± 2.3 μmol/L; P < 0.001). However, FA supplementation prevented these changes and resulted in a significant increase in red blood cell folate concentrations from 1203 ± 639 to 1746 ± 683 nmol/L (P < 0.001; GWs 14-36). Cord blood folate was significantly higher in the FA group than in the placebo group (red blood cell concentrations of 1993 ± 862 and 1418 ± 557 nmol/L, respectively; P = 0.001)., Conclusions: Continued supplementation with 400 μg FA/d in trimesters 2 and 3 of pregnancy can increase maternal and cord blood folate status and prevent the increase in homocysteine concentration that otherwise occurs in late pregnancy. Whether these effects have benefits for pregnancy outcomes or early childhood requires additional study.

The use of prescription opioids is becoming an increasing problem among women of reproductive age. More than half of pregnancies are unintended; therefore, many first-trimester exposures to opioids occur before pregnancy confirmation. Studies are limited about the fetal risks to opioid exposure in early pregnancy. One large study demonstrated an increased risk of certain heart defects and spina bifida with first-trimester exposure to opioids. It is important to counsel women whose fetuses were exposed to opioids in early pregnancy about the potential risks, encourage them to cease using opioids or seek alternative treatments when appropriate, and use the lowest effective dose when opioid treatment is to be continued. It is also valuable to screen for anatomic abnormalities such as neural tube and cardiac defects with available maternal serum testing and ultrasound imaging in the early second trimester. Birth Defects Research (Part A) 94:620-625, 2012. © 2012 Wiley Periodicals, Inc., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: Termination of pregnancy (TOP) for medical reasons is regularly performed using misoprostol. Presence of placental remnants followed by curettage, frequently complicate the procedure. Aim of this analysis is to audit our current policy for medical termination in late first and second trimester, looking at the management of third stage., Methods: A retrospective analysis of patient data was performed. Included were patients that underwent medical TOP in late first or second trimester. Patients were reviewed 6 weeks postdelivery. Characteristics of procedure, patient and pregnancy were analysed to determine factors associated with an increased risk of retained placenta/placental remnants., Results: We included 175 patients. Eighty-five patients (48%) underwent curettage immediately after delivery because of retained placenta or because placental remnants were suspected. Nineteen patients (11%) underwent curettage at later stage. All tissue was examined microscopically for confirmation of placental tissue. Analysis of characteristics of procedure, patients and pregnancies did not identify factors associated with an increased risk of retained placenta or placental remnants., Conclusion: A large number of immediate and late curettages was seen after medical TOP. Misoprostol-dose might play a role and the role of ultrasonographic assessment of the uterine cavity immediately post-placenta-delivery needs to be studied.

Objective: To compare the efficacy of 1-day and 2-day mifepristone and misoprostol intervals for second trimester termination of pregnancy between 13 and 16 weeks., Methods: A prospective randomized cohort study of 100 women who underwent voluntary termination between 13 and 16 weeks of gestation. Patients were randomly assigned to receive 200mg of oral mifepristone, followed 1 day (group 1) or 2 days (group 2) later by 600 μg of vaginal misoprostol. All patients received 400 μg of oral misoprostol every 6 hours for a maximum of 2 doses. Main outcome measure was successful abortion rate at 24 hours after the start of misoprostol treatment. Secondary outcome measures were induction-to-abortion interval and frequency of adverse events., Results: The 24-hour successful abortion rate was similar between groups 1 and 2 (47 [94%] vs 50 [100%]; P = 0.241). The mean misoprostol-to-abortion interval was also similar (7.0 ± 3.0 vs 6.8 ± 4.3 hours; P = 0.744). Among the 86 patients for whom histological examination of the products of conception was performed, retained chorionic villi rates were higher in the 1-day regimen group compared with the 2-day regimen group (46.2% [18/39] vs 29.8% [14/47]; P<0.001)., Conclusion: A 2-day mifepristone-misoprostol interval resulted in fewer incomplete abortions than a 1-day interval for second trimester termination of pregnancy between 13 and 16 weeks., (Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Little is known about the impact of in utero exposure to antidepressants on children's long-term mental health. This study analyzed the impact of exposure to antidepressants during pregnancy on the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring., Methods: Claims-based data from 38,074 families were used to identify deliveries, parental mental health diagnoses, maternal exposure to antidepressants, and diagnosis or treatment for ADHD in the children. Multiple logistic regressions were performed using the presence of ADHD in the child by the age of 5 years as the dependent variable., Results: A diagnosis of ADHD in the mother or the father was associated with higher rates of ADHD in the children (OR = 4.15, p <.001 and OR = 3.54, p <.001, respectively). A diagnosis of bipolar disorder (OR = 5.08, p <.001), psychotic disorders (OR = 4.05, p =.02), or depressive disorders (OR = 2.58, p <.001) in the mother, but not in the father, increased the risk of ADHD in their children. Exposure to bupropion during pregnancy (OR = 3.63, p =.02), especially during the second trimester (OR = 14.66, p <.001), was strongly associated with increased risk of ADHD, whereas exposure to selective serotonin reuptake inhibitors was not (OR = 0.91, p =.74)., Conclusion: Children of mothers treated with bupropion during pregnancy have an increased risk of being diagnosed with ADHD; a possible causal effect needs to be further studied. Assessing the mental health of caregivers should be considered as part of the evaluation and treatment of children with ADHD.

Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway during pregnancy contributes to several pathologic pregnancies, such as hypertension, preeclampsia, and intrauterine growth restriction, but its effects on the fetus have not been fully examined. To determine how inhibition of the VEGF signaling pathway affects the fetal vascular development of mid pregnancy, we treated pregnant mice daily with either the VEGF receptor-2 (VEGFR-2) tyrosine kinase inhibitor KRN633 (300 mg/kg, p.o.) or the vehicle from 13.5 to 15.5 day of pregnancy. On the 16.5 day of pregnancy, the vascular beds in the placenta and several organs of the fetus were visualized by fluorescent immunohistochemistry. All mice treated with KRN633 appeared healthy, and total numbers of fetuses per litter were unaffected. However, weights of the placenta and fetus from KRN633-treated mice were lower than those from the vehicle-treated ones. No external malformations and bleeding were observed in the placenta and fetus, whereas immunohistochemical analyses revealed that the vascular development in labyrinthine zone of placenta and fetal organs examined (skin, pancreas, kidney, and lung) were impaired by KRN633 treatment. These results suggest that inhibition of the VEGF signaling pathway during mid pregnancy suppresses vascular growth of both the placenta and fetus without obvious health impairments of mother mice and increases the risk of induction of intrauterine growth restriction.

Prostaglandin E(1) analogues, gemeprost and misoprostol, are the most widely used drugs for medical termination of pregnancy within the first two trimesters of pregnancy. Gemeprost has been reported to be associated with acute cardiovascular accidents in a few cases, but no adverse cardiovascular events have been reported with misoprostol. For this reason, misoprostol has been considered a potentially safer drug and is widely recommended as a first-choice drug in combination with mifepristone. We report a case of a 32-year-old woman with active smoking and obesity, who developed an episode of transient acute coronary artery vasospasm following the administration of intravaginal misoprostol. This report illustrates that misoprostol can also be associated with acute coronary events, although it remains to be evaluated whether the risk is similar or lower to gemeprost., (Copyright 2010 S. Karger AG, Basel.)

We sought to estimate the effect of indomethacin on duration of pregnancy in women with dilated cervix between 14 (0)/ (7) to 25 (6)/ (7) weeks. Demographics, risk factors, and outcomes were compared in women 14 (0)/ (7) to 25 (6)/ (7) weeks with a dilated cervix > or = 1 cm who received indomethacin versus no indomethacin therapy, stratified for cerclage. Primary outcome was interval from presentation until delivery. Of 222 singleton gestations, 68 (31%) received indomethacin. In unadjusted and adjusted analyses, no significant differences were observed in interval from presentation to delivery and preterm birth < 28, < 32, or < 35 weeks comparing the indomethacin and no indomethacin groups, even after stratification for cerclage. In multivariate logistic regression analysis limited to women receiving cerclage, preterm birth < 32 weeks (odds ratio 0.56, 95% confidence interval 0.26, 1.25) and < 35 weeks (odds ratio 0.52, 95% confidence interval 0.23, 1.14) suggested a possible but not significant benefit for indomethacin use. Indomethacin therapy in women with dilated cervix at 14 (0)/ (7) to 25 (6)/ (7) weeks, regardless of cerclage or not, had no effect on pregnancy outcomes.

Heavy fetal alcohol exposure is associated with a spectrum of neurological abnormalities, although the mechanism of injury is largely unknown. We previously reported attenuated cerebral blood flow response to hypoxia in fetal and newborn sheep which were exposed to alcohol earlier in pregnancy. One possible mechanism for this effect of alcohol on the developing cerebral vasculature is a decrease in cerebral microvessel density, similar to its effect on developing neurons. Therefore, we tested the hypothesis that prenatal alcohol exposure decreases cerebral microvessel density. Pregnant ewes received intravenous infusions of ethanol or saline during days 60-84 of gestation (term=150 days) and at 125 days of gestation we obtained the fetal brains for study. We immunohistochemically labeled vessels of the left cerebral forebrain hemispheres with antibody to endothelial nitric oxide synthase and then obtained unbiased stereological estimates of cerebral microvessel density using a modified optical fractionator method. We studied 20 fetal brains of which 9 were alcohol-exposed, 11 were saline-controls, and all were products of a twin gestation. Although brain and body weights were not different between groups, the alcohol-exposed group had significantly lower brain weight as a percentage of body weight. Estimates of cerebral microvessel density were not significantly different between alcohol-exposed and saline-control groups: 12.7+/-8.7 and 9.1+/-2.8 microvessels per mm(3), respectively (mean+/-SD, p=0.32). Since there is no change in estimated cerebral microvessel density after prenatal alcohol exposure, we conclude that decreased cerebral microvessel density is not a likely explanation for attenuated cerebral blood flow in response to hypoxia.

(1) The list of adverse effects of selective serotonin reuptake inhibitor (SSRI) antidepressants in pregnant women and their newborns continues to grow; (2) It was already known that, when taken towards the end of pregnancy, SSRIs could cause spontaneously resolving neonatal disorders, particularly neurological problems; (3) A case-control study has shown an association between maternal exposure to SSRI antidepressants after the 20th week of pregnancy and neonatal persistent pulmonary hypertension, with a 6-fold increase in the risk. Another study has provided similar results; (4) Diagnosis of depression must be made with care during pregnancy, and it should be remembered that not all patients with depression require drug therapy.

This study evaluated a new method for mid-gestation termination in the bitch, which consisted of ultrasound-guided administration of a single dose of d-cloprostenol, a PGF(2alpha) analogue, into a single gestational sac. Effects on serum progesterone concentration (P(4)) were also investigated. The study was performed between days 28 and 35 of gestation on 15 privately owned crossbred bitches, randomly divided into two groups: group A comprised 10 bitches treated with 15 microg per head d-cloprostenol diluted in 0.8 ml sterile saline (final volume 1 ml); group B comprised 5 bitches treated with 1 ml of sterile saline solution (0.9% NaCl), administered in the same way. In all bitches of group A, fetal death was successfully induced within 5 days (mean: 3.1 days, S.D. 1.2) with no clinical or behavioural complications. Mild adverse effects were observed in two bitches, each weighing less than 10 kg, including salivation, defecation and hyperventilation, which disappeared within 15 min. None of the subjects in group B aborted within 10 days post-treatment. In group A, P(4) declined 2.8 days before pregnancy termination to a mean value below 30 nmol/l (S.D. 2.9 nmol/l). However, two bitches showed a higher concentration of P(4) throughout the sampling period. Our study demonstrates that intra-vesicle administration of a single low dose of D-cloprostenol is an effective and safe technique for induction of abortion, which offers an additional option for termination of unwanted pregnancy in the mid-gestation bitch.

Background: The study was conducted to assess the effectiveness in inducing fetal demise through digoxin injection given 1 day prior to second-trimester pregnancy termination and to evaluate related maternal safety., Study Design: A retrospective cohort analysis of 1795 pregnant women between 17 and 24 weeks' gestation who received varying doses of digoxin by transabdominal intrafetal or intra-amniotic injection at the time of laminaria placement was conducted. Fetal heart activity documented by M-mode Doppler sonography on the subsequent day was considered failure. Digoxin dosages started at 1.0 mg for intrafetal and 0.5 mg for intra-amniotic injections and were progressively decreased based on best clinical judgment., Results: The overall rate of failure to achieve fetal demise was 6.6% (95% CI, 5.5-7.9). Failure rates varied according to route of administration and dosage. There were no failures using a 1.0-mg intrafetal dose, but failures occurred with lower doses. Failure rates were higher with 0.5 mg for intra-amniotic (8.3%) than intrafetal administration (3.6%). There were no adverse maternal events at any of the doses in this study., Conclusion: Intrafetal digoxin injection at a dose of 1.0 mg is safe and effective for fetal demise prior to pregnancy termination in the second trimester. Significantly lower doses are effective in most cases. Additional doses merit further testing.

Background: Second-trimester terminations can be performed via surgical or medical methods. It is essential to have the ability to safely and effectively perform induction terminations to offer a full range of services. Many studies of induction abortions report routine operative removal of the placenta after a set time period resulting in high rates of operative procedures., Study Design: A retrospective chart review was performed for 233 women who underwent second-trimester induction abortions between November 2003 and November 2006. All women received intraamniotic injection of digoxin for feticide 1 day prior to induction. All inductions were performed using a schedule of 400 mcg of misoprostol initially followed by 200 mcg every 6 h for a maximum of 48 h. There were three methods of administering misoprostol: (1) vaginal administration for all doses, (2) vaginal and buccal used in combination and (3) buccal for all doses. Spontaneous expulsion of the placenta was expected. Operative intervention was performed for excessive bleeding or to expedite hospital discharge after a minimum of 4 h. No manual removal of placenta was done., Results: The rate of operative intervention for retained placentas was 6% (14/233). Most (11/14) of the patients who underwent operative extraction for retained placentas did so to expedite discharge from the hospital. Overall, expectant management to allow spontaneous expulsion of the placenta for at least 4 h was not associated with serious morbidity., Conclusions: Our regimen of digoxin and misoprostol with a policy of expectant management of placental passage is associated with a very low rate of instrumented removal of the placenta. In the absence of bleeding, patients may be afforded intervals to at least 4 h for spontaneous expulsion of the placenta after fetal expulsion.

Background: Use of Dartmouth combination chemotherapy in pregnancy is scarcely reported, with only 1 report of its use in the late second and third trimesters and no report of its use in the first trimester., Case: This is the first reported case in which the Dartmouth combination chemotherapy regimen was inadvertently used in a pregnant woman during the first and second trimesters for treatment of metastatic melanoma. The infant was found to have isolated microphthalmos and severe hypermetropia at 1 year of age., Conclusion: Although a causal relationship cannot be established from a single case, this report does provide useful information to discourage the use of this chemotherapy regimen in the first trimester, which is the critical period for organogenesis.

Objective: The objective was to investigate the importance of previous obstetric history for termination of pregnancy in the second-trimester with gemeprost alone., Study Design: A consecutive series of 423 mid-trimester inductions of abortion at our teaching hospital was reviewed. Termination of pregnancy was carried out with 1mg of vaginal gemeprost every 3h up to three doses over a 24-h period, repeated the following day if necessary. Failed induction was defined as women undelivered by 96 h. The study population was then stratified by gestational age, parity, gravidity and previous uterine scars. Main outcome parameters were failed induction and complication rates. Statistical analysis was performed using the chi(2) test or Fisher's exact test for categorical data, and the t-test and linear regression for continuous variables., Results: No significant differences were found in the primary outcome parameters with regard to the obstetric parameters considered. The failed induction rate was 1.2% with an overall incidence of complications of 7.4%. Parity was the main factor that affected clinical response (time to abortion interval and number of pessaries)., Conclusion: Patients' obstetric history does affect the clinical response to gemeprost, but its safety and effectiveness are preserved. These data provide clinicians with important information for correct counselling.

Objective: To assess the efficacy of medical abortion performed according to a single protocol from 5 through 14 weeks., Study Design: Retrospective observational study of medical abortions through 14 weeks performed from January 2000 through August 2001. The protocol combined 400mg of mifepristone orally, followed 48 h later by 800 microg of misoprostol, administered vaginally, and repeated after 4 h if the patient did not begin to abort. Outcome measures were the abortion rate, the rates of immediate manual uterine revision and of secondary vacuum aspiration, the time to expulsion, the misoprostol dose, and analgesic use., Results: The study included 512 medical abortions. The abortion rate was 98.4% and the secondary vacuum aspiration rate 8.2%. The uterine exploration rate was 1.4%, but these occurred only at gestations above 13 weeks. The mean time to expulsion was 4.4+/-1.9 h (1-28), and the mean misoprostol dose 860+/-180 microg (0-2000). None of the characteristics studied differed significantly as a function of gestation. 1.6% of patients had complications., Conclusion: Medical abortion was consistently effective through 14 weeks and can be offered as an alternative to the surgical technique.

Introduction: This retrospective study reports of 85 women in the second trimester with one prior cesarean section undergoing medical abortion of a viable unwanted pregnancy using vaginal misoprostol. Two regimens that were selected in a nonrandomized manner were used., Materials and Methods: Eighty-five women treated with vaginal misoprostol in a 3-year period were retrospectively analyzed. All received 400 mug of misoprostol initially and 22 (25.8%) aborted. Then Group A (n=43) received subsequent administration of 200 microg every 6 h, whereas Group B (n=20) received 400 microg/6 h., Results: All patients aborted. The groups had no statistical difference in mean age, gravidity, parity, gestational age, and time from previous cesarean section, and there was no difference in occurrence of side effects and mean induction to abortion time interval. The lower dosage group received a median of 600 microg of vaginal misoprostol (min 600 microg to max 1000 microg). There were no uterine ruptures, need for hysterotomy, or excess bleeding in any patient., Conclusions: This is the largest series reported to date of second-trimester pregnancy termination in cases with one previous cesarean section using only vaginal misoprostol. The study shows that both used regimens are safe and equally effective. All 85 women aborted.

Objective: To analyze the efficacy of intravenous ketanserin in controlling blood pressure of severe early-onset pre-eclamptic patients., Study Design: Pre-eclamptic patients (n=47) with a gestational age (GA) between 21 and 32 weeks were treated with intravenous ketanserin in a maximum dosage of 14 mg/h, to obtain a diastolic blood pressure of 90 mmHg or below. The number of patients reaching and maintaining target blood pressure was retrospectively assessed. Patient characteristics associated with an adequate or inadequate response to ketanserin treatment were identified., Results: With a maximum intravenous dosage of ketanserin, target blood pressure was not achieved in 15 (32%) patients. A high systolic blood pressure at the start of treatment was significantly (p=0.02) associated with failure of ketanserin treatment. The median period of ketanserin treatment in the responding group was 3 days (range 1-10 days). In 26 (55%) of initially successfully treated patients, additional antihypertensive drugs had to be added to maintain adequate blood pressure control., Conclusion: Intravenous ketanserin lacks antihypertensive efficacy in a substantial proportion of severe pre-eclamptic patients, despite high dosages. In patients who initially respond well to ketanserin treatment, additional antihypertensive treatment is often necessary to maintain adequate blood pressure control.

Objectives: To evaluate the effect of prolonged administration of high-dose prednisolone on early onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome during expectant management., Study Design: A randomized, double-blind trial was performed in 31 pregnant women with HELLP syndrome with an onset before 30 weeks gestation. Patients received either 50mg prednisolone or placebo intravenously twice a day. Primary outcome measures were the entry-to-delivery interval and the number of recurrent HELLP exacerbations in the antepartum period., Results: Serious maternal morbidity was considerable, in particular in the placebo group where even on maternal occurred as a consequence of liver rupture. The mean entry-delivery interval did not differ between the prednisolone group (6.9 days) and the placebo group (8.0 days). However, patients in the prednisolone group had a significant lower risk of a recurrent HELLP exacerbation after the initial crisis had subsided, as compared to patients in the placebo group (HR 0.3, with 95% CI 0.3-0.9). Platelet count recovered faster in the prednisolone group as compared to the placebo group (mean 1.7 days versus 6.2 days, P<0.01)., Conclusions: HELLP syndrome remote from term causes high risk for serious maternal morbidity and mortality. When expectant management is pursued in selected patients with a HELLP syndrome remote from term, prolonged administration of prednisolone reduces the risk of recurrent HELLP syndrome exacerbations.

Objective: To assess if alcohol drinking is a risk factor for small for gestational age (SGA) birth., Methods: Case-control study. Cases were 555 women (mean age 31 years, range 16-43) who delivered SGA babies at the Clinica Luigi Mangiagalli and the Obstetric and Gynecology Clinic of the University of Verona. The controls were 1966 women (mean age 31 years, range 14-43) who gave birth at term (> or =37 weeks of gestation) to healthy infants of normal weight at the hospitals where cases had been identified., Results: No increase in the risk of SGA birth was observed in women drinking one or two drinks/day in pregnancy, but three or more per day increased the risk: odds ratios (OR) were 3.2 (1.7-6.2) for > or =3 drinks during the first trimester, 2.7 (1.4-5.3) during the second and 2.9 (1.5-5.7) during the third., Conclusions: The study shows an increased risk of SGA births in mothers who drink > or =3 units/day of alcohol in pregnancy., (Published online 22 February 2006.)

The purpose of the research was to evaluate clinical course and efficiency of the method of termination of pregnancy in the first end second trimesters by means of antiprogesterone. 384 women aged 15 to 45 in the first end second trimesters of pregnancy were investigated. 300 women had an early pregnancy (range=2-7 weeks) requesting abortion. All these women first took 600 mg antiprogesterone pencroftone ("Pencroft-Fharma", Russia) and 48 hours later - 400 mkg prostaglandin misoprostol. 84 patients with gestation period ranged from 14 to 22 weeks. Their contractility utterly was caused with 400 mg pencroftone and 48 hours later with 400 mkg prostaglandin misopristol. In the first trimester completed abortion was observed in 96,7%, incomplete abortion in 1,7%; missed abortion in 2,3% cases, continuing pregnancy in 1 case. In the second trimester in the case of therapy with pencroftone and prostaglandin E1 misoprostol the clinical effect was observed in 96,4% cases. Antiprogesterone pencroftone is an effective for medical abortion during I-II trimesters of pregnancy. It is characterized by minimal risk of complications in the course and the post abortion period.

Introduction: Data on safety issues and therapeutic outcomes of endoscopy in pregnancy remains limited especially in the local context. The concerns are that of safety in sedation and radiation to the foetus, effects on the pregnancy, the need for special precautions on mother and foetus during the procedure and long-term foetal outcome. We report a case series on four pregnant women to address these concerns and outline their therapeutic approaches., Methods: We reviewed four patients who underwent oral gastroduodenoscopy (OGD) or endoscopic retrograde cholangiopancreatography (ERCP) during their pregnancies. Lead aprons were used to shield the foetuses in all patients that underwent ERCP. Sedation was given when necessary, and an anaesthetist was employed in one case for close patient monitoring. Fluoroscopy was minimised and radiographs were taken only when essential., Results: The mean patient age was 27.8 years (range 23-35 years). The mean gestation was 21.5 weeks (range 14-32 weeks), with two patients each being in their second and third trimesters. The indications for ERCP were cholangitis and pancreatitis (one), choledocholithiasis on ultrasonography (two), and that for OGD was persistent vomiting (one). Two patients underwent sphincterotomy and one had a biliary stent inserted. One patient was lost to follow-up. The other three had a full-term normal delivery and all babies were healthy at birth with good birth weight and normal Apgar scores., Conclusion: Our series showed that endoscopic procedures in pregnancy are safe for both mother and foetus. However, these procedures should be restricted to cases with definite. indications and radiation exposure should be minimised with additional safety precautions such as minimal radiation exposure and the use of lead shield when applicable.

Preexisting hypertension complicates 5% of all pregnancies. The objective of this study was to evaluate steady-state atenolol pharmacokinetics and pharmacodynamics (n = 17) during the second trimester (2nd T), third trimester (3rd T), and 3 months postpartum. Pregnancy as compared to 3 months postpartum (nonpregnant control) resulted in significant (P < .05) changes, including the following: 42% (2nd T) and 50% (3rd T) increase in creatinine clearance, 38% (2nd T) and 36% (3rd T) increase in atenolol renal clearance, 12% (2nd T) and 11% (3rd T) decrease in atenolol half-life, 20% (2nd T) and 28% (3rd T) increase in cardiac output, 15% (2nd T) and 23% (3rd T) increase in resting heart rate, and 22% (2nd T) and 21% (3rd T) decrease in total peripheral resistance in subjects on steady-state oral atenolol for treatment of hypertension in pregnancy. In conclusion, the renal clearance of atenolol along with creatinine clearance is increased during pregnancy. However, this does not translate into an increase in apparent oral clearance of atenolol, possibly related to the high variability in bioavailability. Atenolol administration did not appear to change the pattern of the increase in cardiac output and the decrease in total peripheral resistance, which normally occurs during pregnancy.

Plasma nelfinavir concentration ratios (CRs) were calculated for all pregnant (n=27) and nonpregnant (n=48) human immunodeficiency virus type 1-infected women receiving the drug who visited our outpatient clinic. In pregnant women, mean and median nelfinavir CRs were significantly lower (P=.02 and P=.04, respectively), and 51% of the CRs were below the clinically relevant threshold of 0.90, compared with 35% of the CRs in nonpregnant women. After we adjusted for confounders, we found that the mean nelfinavir CR was 34% lower in pregnant women (P=.02). With targeted interventions, subsequent CRs in pregnant women showed a significant increase (median increase, 0.31; P=.01).

Objective: To determine if use of ecstacy during pregnancy has any harmful effects on pregnancy and the (unborn) child., Design: Prospective, descriptive., Methods: After the Teratology Information Service of the National Institute of Public Health and the Environment. Bilthoven, the Netherlands, was approached by a physician or midwife for information, the pregnancies that involved the use of ecstacy were followed by a follow-up questionnaire one month after the estimated date of birth., Results: A total of 49 pregnancies were followed. For 43 women, exposed early in pregnancy, data on course of pregnancy and health of baby are known. There were 3 elective terminations of pregnancy and 2 spontaneous abortions. There were 40 live-born babies (including one set of triplets); one of them had a congenital cardiac malformation. Beside ecstacy the mothers frequently also used other substances potentially harmful to pregnancy and child. The pregnancies were often unplanned; previous pregnancies had frequently been terminated., Conclusion: The sample size was too small to draw conclusions. As yet spontaneous abortions and congenital malformations did not appear to occur more frequently in pregnancies with use of ecstacy. The lifestyle of the ecstacy users seemed to be potentially harmful for pregnancy and child.

The effectiveness of three methods for second trimester pregnancy termination [TOP) was compared. A retrospective analysis was made in 34 cases with TOP by intraamniotic saline instillation and 19 cases with extra-amniotic appreciation of y ballon-catheter, followed by stimulation of uterine contractions by intravenous oxytocin infusion. The results were compared with the ones in 13 prospectively studied cases in which the extra-amniotic appreciation of the ballon-catheter was preceded by treatment of the cervix with 0.5 mg prostin E2 intracervically. In nulliparous patients the treatment of the cervix with y single dose prostaglandins did not shorten the mean abortion time neither reduced the percentage of unsuccessful and prolonged abortions. In parous patients the abortion time was significantly reduced. No failed or prolonged abortions were registered.

Background: The aims of the present study were to determine whether maternal hyperoxygenation affects human fetal pulmonary circulation and whether there is a gestational age-related response in the fetal pulmonary circulation to maternal hyperoxygenation during the second half of gestation., Methods and Results: Twenty women between 20 and 26 weeks of gestation and 20 women between 31 and 36 weeks of gestation with normal singleton pregnancies were randomized to receive either 60% humidified oxygen or medical compressed air (room air) by a face mask. Fetal aortic and pulmonary valve; ductus arteriosus (DA); and right (RPA), left (LPA), and distal (DPA) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before, during, and after maternal administration of either 60% oxygen or room air. Left and right ventricular cardiac outputs, DA volume blood flow, and RPA and LPA volume blood flows (Qp) were calculated. Foramen ovale volume blood flow (left ventricular cardiac output-Qp) was estimated. Pulsatility index (PI) values of DA, RPA, LPA, and DPA were calculated. Maternal hyperoxygenation did not change any of the measured fetal parameters between 20 and 26 weeks, whereas between 31 and 36 weeks, the PI values of RPA, LPA, and DPA decreased (P<.0001) and the PI of DA increased (P<.0001). In addition, Qp increased (P<.001), and DA volume blood flow (P<.01) and foramen ovale volume blood flow (P<.03) decreased. Left and right ventricular cardiac outputs were unchanged. All changes returned to baseline after maternal hyperoxygenation was discontinued., Conclusions: Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases with advancing gestation; this suggests that fetal pulmonary circulation is under acquired vasoconstriction at least after 31 to 36 weeks of gestation.

Objectives: The aims of this prospective study were to explore the changes in platelet angiotensin II (A-II) binding in pregnancy amongst Chinese women at high risk of developing pregnancy-induced hypertension (PIH) and the effects of low-dose aspirin and calcium supplementation on A-II binding., Methods: Platelet A-II binding was assayed in 15 non-pregnant women and in 63 pregnant women determined to be at risk of PIH on the basis of 2nd-trimester mean arterial pressure (MAP). The pregnant patients were randomized into three groups: control, low-dose aspirin, and calcium supplementation. A-II binding was assayed again during the 3rd trimester in half the women and 8 weeks after delivery., Results: A-II binding was negatively correlated with MAP measured in the left lateral position (p < 0.05) but not with MAP measured in the supine position. There were no significant differences between A-II binding in non-pregnant and pregnant women. Neither low-dose aspirin nor calcium supplementation caused significant reductions in A-II binding., Conclusion: The measurement of platelet A-II binding is unlikely to provide significant information regarding the risk of PIH over and above that obtained from measurement of 2nd-trimester MAP.