Medical Termination of Pregnancy (MToP) in the 1st trimester - the role of human chorionic gonadotropin and ultrasound in pregnancy diagnosis and MToP follow-up.

OBJECTIVE: In the Czech Republic, it is possible, to carry out Medical Termination of Pregnancy (MToP) in the 1st trimester up until the 49th day of secondary amenorrhea. The aim of the study is to analyse the significance of serum/urine human chorionic gonadotropin (hCG) assessment and ultrasound (US) examination in pregnancy diagnosis and MToP follow-up. METHODS: In 2017-2018, MToP was carried out in a total of 109 women by administering a combination of mifepristone (600 mg orally) and misoprostol (400 mcg orally). Serum/urine (LSUP - low sensitivity urine pregnancy test) hCG assessment and US examination were performed at pregnancy diagnosis and MToP follow-up. RESULTS: At pregnancy diagnosis, there was a positive and medium strong correlation between serum hCG and size of the gestational sac - GS (R = 0.711; P  1,000 IU/L and LSUP test was always positive). In 5.5% of women (6/109), a subsequent surgical intervention was carried out including those with ongoing pregnancy (N = 5); missed abortion (N = 1) was treated by additional misoprostol, where surgical intervention was not necessary. CONCLUSION: At pregnancy diagnosis, there is a positive and medium strong correlation between serum hCG and CRL. In MToP follow-up, a negative LSUP test enables reliable exclusion of ongoing pregnancy and missed abortion. In case of a positive LSUP test, US examination should be performed; however, surgical intervention should not be indicated solely on the basis of uterine cavity dilatation.

Performance of Fetal Medicine Foundation algorithm for first trimester preeclampsia screening in an indigenous south Asian population.

BACKGROUND: To evaluate the performance of the Fetal Medicine Foundation (FMF) preterm preeclampsia (PE) screening algorithm in an indigenous South Asian population. METHODS: This was a prospective observational cohort study conducted in a tertiary maternal fetal unit in Delhi, India over 2 years. The study population comprised of 1863 women carrying a singleton pregnancy and of South Asian ethnicity who were screened for preterm pre-eclampsia (PE) between 11 and 14 weeks of gestation using Mean Arterial Pressure (MAP), transvaginal Mean Uterine Artery Pulsatility Index (UtAPI) and biochemical markers - Pregnancy Associated Plasma Protein-A (PAPP-A) and Placental Growth Factor.. Absolutemeasurements of noted biomarkers were converted to multiples of the expected gestational median (MoMS) which were then used to estimate risk for preterm PE < 37 weeks using Astraia software. Women with preterm PE risk of ≥1:100 was classified as as high risk. Detection rates (DR) at 10% false positive rate were calculated after adjusting for prophylactic aspirin use (either 75 or 150 mg). RESULTS: The incidence of PE and preterm PE were 3.17% (59/1863) and 1.34% (25/1863) respectively. PAPP-A and PlGF MoM distribution medians were 0.86 and 0.87 MoM and significantly deviated from 1 MoM. 431 (23.1%) women had a risk of ≥1:100, 75 (17.8%) of who received aspirin. Unadjusted DR using ≥1:100 threshold was 76%.Estimated DRs for a fixed 10% FPR ranged from 52.5 to 80% depending on biomarker combination after recentering MoMs and adjusting for aspirin use. CONCLUSION: The FMF algorithm whilst performing satisfactorily could still be further improved to ensure that biophysical and biochemical markers are correctly adjusted for indigenous South Asian women.

Ultrasound assessment of maternal adipose tissue during 1st trimester screening for aneuploidies and risk of developing gestational diabetes.

INTRODUCTION: The objective of the present study is to compare the sonographic measurement of subcutaneous adipose thickness and visceral adipose thickness during 1st trimester screening for aneuploidies between non-diabetic pregnant women and patients who develop 1st trimester or 2nd trimester gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Adipose thickness was measured by transabdominal ultrasound imaging in pregnant women attending our clinic for screening for fetal aneuploidies between 11 and 13 weeks of gestation. During the 1st trimester all patients were evaluated for fasting glycemia in accordance with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations. Patients with confirmed fasting glycemia (FPG) ≥92 mg/dL were diagnosed as 1st trimester GDM. Patients with FPG <92 mg/dL underwent a 75-g oral glucose tolerance test between 24 and 28 weeks. RESULTS: The study population included 238 non-diabetic women, 29 women with 1st trimester GDM and 28 women with 2nd trimester GDM. Mean subcutaneous adipose thickness and visceral adipose thickness values in non-diabetic women were 9.8 mm (standard deviation [SD = 4.9) and 7.2 mm (SD = 3.5), respectively. Values in women with 1st trimester GDM were 12.8 mm (SD = 6.5) and 9.9 mm (SD = 4.4). In the 2nd trimester GDM group, the mean subcutaneous adipose thickness was 11.1 mm (SD = 4.6) and the mean visceral adipose thickness 10.5 mm (SD = 5.3). Multiple logistic regression analysis showed that visceral adipose thickness, but not subcutaneous adipose thickness, was significantly and independently associated with both 1st trimester GDM (OR 1.15, 95% CI 1.02-1.29) and 2nd trimester GDM (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05-1.34). CONCLUSIONS: Sonographic thickness of maternal visceral adipose tissue was greater in women with GDM than in non-diabetic patients, independently of other known risk factors associated with GDM in the 1st and in the 2nd trimester of pregnancy. Thus, this measurement may be considered of clinical use in 1st trimester screening.

Expression of HLA-G and KIR2DL4 receptor in chorionic villous in missed abortion.

OBJECTIVE: Human leukocyte antigen-G (HLA-G) is a molecule that was first known to confer protection to the fetus from destruction by the immune system of its mother. HLA-G expression is mainly restricted to the fetal-maternal interface on the extravillous cytotrophoblast, placenta, amnion.Methods: The purpose of this study is to investigate the HLA-G and KIR2DL4 expression in chorionic villous among 2 groups with missed abortion: group 1 - 27cases with normal karyotype and group 2 - 22 with fetal polyploidy. Criteria of inclusion: abortive material from two groups of women with missed abortion; 6-12 weeks gestational age, singleton pregnancy, cytogenetic of chorionic villous was obligatory - normal fetal karyotype and polyploidy of fetus.Results: During IHC investigations the average relative area of HLA-G expression in trophoblast was counted (in 1st group 33.9 ± 3.5 and in 2nd group 38.6 ± 2.8). Expression of HLA-G the most verified in extravillous chorion stroma. The average relative area of KIR2DL4 receptor was not statistically different among two groups (31.6 ± 2.4 and 32.2 ± 1.7). CONCLUSIONS: These results suggest the role of HLA-G for the progression in early reproductive losses. Low expression of HLA-G is associated with pregnancy complications and can be one of the reasons for spontaneous abortion.

Expression of vitamin D and vitamin D receptor in chorionic villous in missed abortion.

The contemporary world despite its enough developed medicine and generally highly enlightened population faces a great problem of vitamin, micro-element and nutrient deficiency turning to become the XXI century pandemic. Along with that significant growth of interest can be seen towards vitamin D importance for reproductive physiology. The fact is that vitamin D receptors (VDR) have been detected in women's ovarium tissue, fallopian tubes, decidua and placenta. Some recent years studies have proven that vitamin D may act as immune regulator during implantation. During early pregnancy the trophoblast release vitamin D, which produces anti-inflammatory reaction and also induce decidual tissue growth for successive pregnancy. It was a comparison between the expression of Vitamin D and VDR in chorionic villous in cases of normal pregnancy and missed abortion groups. 64 samples of chorionic villous were taken: 32 from missed abortion and 32 from the induced abortion group. Abortive material was taken from two groups of women residing in North-West region of Russia: missed abortion and pregnancy terminated at woman's wish (induced abortion); 6-12 weeks of gestation, singleton pregnancy. Immune histochemical examination showed homogenous distribution of vitamin D and VDR expression in syncytiotrophoblasts, cytotrophoblasts and chorion villus stroma.Vitamin D expression relative area was 10,3% which is statistically different from the induced abortion group - 15,4% (p<0,01). VDR expression analysis showed its homogenous distribution in chorionic villus structures in both groups. High VDR expression was detected in chorion villus stromal components. In missed abortion group, the morphometry results showed distinctly lower relative area of vitamin D expression against the comparison group (35,9 ± 1,8; 56,1 ± 2,4 p < 0,01). Also in missed abortion group, positively significant correlation has been determined between the level of vitamin D in blood and VDR relative area expression (r = 0,412). In missed abortion group, definite vitamin D and VDR expression decrease was detected compared to the induced abortion group. The results witness vitamin D importance for pregnancy progress.

Fetal heart examination at the time of 13 weeks scan: a 5 years' prospective study.

Objective To evaluate our ability in classifying the fetal heart as normal or abnormal during the 1st trimester scan through fetal cardiac examination and determining the best time for this examination. Methods This was a prospective study performed on 3240 pregnant women to examine the fetal heart. Four chambers view and ventricular outflow tracts were mainly examined during the scan. We used grayscale and color mapping in the diagnosis. Color Doppler was used if additional information was needed, and all patients were rescanned during the 2nd trimester to confirm or negate our diagnosis. Results The cardiac findings were normal at both scans in 3108 pregnancies. The same cardiac abnormality was detected at both scans in 79 cases. In 36 cases there was false-positive diagnosis at the early scan; in 20 of these cases, there were mildly abnormal functional findings early in pregnancy with no abnormality found later. In 17 fetuses, there was discordance between the early and later diagnosis due to missed or incorrect diagnoses. The best time to do fetal heart examination during 1st trimester is between 13 and 13 + 6 weeks. Conclusion A high degree of accuracy in the identification of congenital heart disease (CHD) can be achieved by a 1st trimester fetal echocardiography.

Reference Ranges for Transvaginal Examined Fossa Posterior Structures in Fetuses from 45 to 84 mm Crown-Rump Length.

OBJECTIVE: The study aimed to describe reference values for structures of the posterior fossa in fetuses with a crown-rump length (CRL) between 45 and 84 mm. MATERIALS AND METHODS: This was a prospective, cross-sectional study including 216 normal appearing fetuses. In transvaginal acquired 3-dimensional volume blocks, the longest diameter of the vermis (VE), posterior membranous area (PMA), medulla-oblongata-pons angle (MOPA), diameters of the medulla oblongata (MO) and pons (PO), and the area of Blake's pouch (BP) were measured. Polynomial or linear regression analysis were performed to calculate the mean, 5th and 95th centile according to CRL. In 20 fetuses, intra- and interobserver repeatability were calculated. RESULTS: There is a curvilinear correlation between CRL and PO (PO [mean] = 1.3893 + 0.004356 × CRL + 0.000002610 × CRL3; SD = 1.6818 - 0.03765 × CRL + 0.000003831 × CRL3; R2 = 0.489); CRL and MO (MO [mean] = 1.5959-0.001905 × CRL + 0.000003362*CRL3; SD = -0.1417 + 0.005404 × CRL + 0.0000004988 × CRL3; R2 = 0.525); CRL and VE (VE [mean] = -0.3640 + 0.04302 × CRL+ 0.000001486 × CRL3; SD = 0.5854 - 0.004812 × CRL + 0.0000005896 × CRL3; R2 = 0.643); CRL and PMA (PMA [mean] = 0.6901 + 0.04307 × CRL - 0.0000008459 × CRL3; SD = -0.4232 + 0.02026 × CRL - 0.000001320 × CRL3; R2 = 0.272); CRL and BP (mm2; BP [mean] -12.2067 + 0.3334 × CRL - 0.00001262 × CRL3; SD = -1.6431 + 0.06380 × CRL+ 0.0000003257 × CRL3; R2 = 0.289). The relation between CRL and MOPA (°) is best described by a linear regression (MOPA [mean] = 79.6332 + 0.6122 × CRL; SD = 4.8453 + 0.07333 × CRL; R2 = 0.318). CONCLUSION: We provide reference values for anatomical structures of the posterior fossa of fetuses between 45 and 84 mm CRL. The established reference values might ease the diagnosis of fetal malformations in early pregnancy.

Runge psychoses.

This article describes periodic monthly psychoses that develop during the early months of pregnancy. It is probable that these are a variety of menstrual psychosis.

Three-dimensional placental volume and mean grey value: Normal ranges in a Turkish population and correlation with maternal serum biochemistry and Doppler parameters.

The aim of this study is to evaluate the relationship between three-dimensional (3D) ultrasound measurements of placenta at 11-13(6) weeks' gestation and maternal serum levels of pregnancy associated plasma protein-A (PAPP-A), free beta human chorionic gonadotrophin (fßhCG), Doppler parameters in early pregnancy. This prospective study consisted of 334 singleton pregnancies at 11-13(6) weeks' gestation. Placental volume and placental volumetric mean grey values were evaluated. The placental volume (cm(3)) was analysed using the Virtual Organ Computer-aided AnaLysis (VOCAL) imaging program and 3D histogram was used to calculate the volumetric mean grey value (%). Mean maternal age was 28.35 ± 7.55. Mean gestational age was 12.29 ± 0.68 weeks. Placental volume was 77.04 ± 35.74 cm(3). Mean grey value of the placenta was 34.38 ± 8.02%. Correlation analysis revealed that placental volume was significantly correlated with the crown-rump length (r = 0.173, p = 0.002), gestational week (r = 0.116, p = 0.036), ductus venosus pulsatility index (r = -0.101, p = 0.04) and maternal weight (r = 0.099, p = 0.037). There was a significant relation between the mean grey value of the placenta and maternal age (r = 0.131, p = 0.02), nuchal translucency (r = -0.109, p = 0.048), PAPP-A (r = 0.108, p = 0.04) and fßhCG (r = 0.104, p = 0.042). Volumetry of the placenta can be carried out with a high percentage of 1st trimester pregnancies. Volumetry during the 1st trimester could be helpful because of the less advanced state of placentation. This examination is easy to perform and the measurements can be acquired correctly and quickly.

Extremely large nuchal translucency measurement predicts adverse pregnancy outcome.

A prospective study was conducted to determine the outcome of pregnancies with 1st trimester nuchal translucency measurement of ≥ 6.5 mm. The risk of fetal abnormalities increases with enlarging nuchal translucency, being around 45% with a measurement of ≥ 6.5 mm. A total of 27,144 women with singleton pregnancies participated in the combined Down syndrome screening within the public healthcare system in Northern Finland. The study period was 1 May 2002 to 31 May 2009. The nuchal translucency measurement was ≥ 6.5 mm in 16 cases (0.06%). Pregnancy outcome was normal in one case (6.3%). The risk of abnormality was higher in our study than reported in the literature. According to our study, immediate diagnostic tests should be offered after an nuchal translucency measurement of ≥ 6.5 mm. We should also consider analysis of fetal micro-deletions associated with certain syndromes.

A 1st-trimester combined screening test in pregnant women of advanced maternal age in a Chinese population.

The purpose of this study was to evaluate the performance of the 1st-trimester combined screening test for trisomy 21 in different maternal age groups in a Chinese population. In this retrospective study, data on the 1st-trimester combined screening test (maternal age, fetal nuchal translucency, free ß-human chorionic gonadotrophin, pregnancy-associated plasma protein-A) were analysed. The study population of 17,556 pregnant women was subdivided into three groups according to maternal age: 16,113 were < 35 years of age; 1,228 were 35-39 years of age; and 215 were ≥ 40 years of age. The detection and false-positive rates of the 1st-trimester screening test for trisomy 21 or trisomy 18 in the three groups of women were 89.5 and 1.7%; 90.9 and 6.8%; and 100 and 22.3%, respectively. With increasing maternal age, the odds of being affected given a positive result (OAPR) were increased. The balance between the detection rate and false-positive rate of the 1st-trimester combined screening test is more favourable in women < 36 years with comparable OAPR. Although the false-positive rate increases with increasing maternal age, the performance of the 1st-trimester combined screening test in women ≥ 35 years is more effective than screening based on maternal age alone.

Effectiveness of a single dose of oral misoprostol 600 µg for treatment in early pregnancy failure.

The purpose of this study was to examine the effectiveness, side-effects and acceptability of a single dose of oral misoprostol 600 µg for treatment of 1st trimester pregnancy failure. A prospective descriptive study was conducted on pregnant women of < 13 weeks' gestation, diagnosed as 1st trimester pregnancy failure. Patients were assigned to receive a single dose of misoprostol 600 µg orally and then evaluated 48 h after drug administration for complete abortion. A total of 55 women were recruited to the study. The complete abortion rate was 65.5%. Pain and diarrhoea were the most common side-effects. Acceptability and satisfactory rates were 70.9% and 70.9%, respectively. In conclusion, a single dose of oral misoprostol 600 µg is a fair method for the management of 1st trimester pregnancy failure. Side-effects are tolerable and satisfaction is high. Thus, this method may be used as an alternative treatment.

Abortion in the First Trimester. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015-094, December 2022) - Part 2 with Recommendations for Surgical Termination of Pregnancy and Follow-up Care After Termination of Pregnancy.

Purpose The aim was to develop evidence-based recommendations where possible. The guideline presents the medical principles and scientific evidence for indications, counselling of affected persons, performing terminations, the choice of method, and the care and monitoring of a terminated pregnancy up until week 12 + 0 of gestation p. c. Methods In accordance with the requirements for an S2k-guideline, the contents of the guideline were drafted following a systematic search of the literature by a representative interdisciplinary group of experts. Guideline authors held several formal meetings under the auspices of the German Society for Gynaecology and Obstetrics (DGGG) during which the contents of the guideline were finalised and agreed upon. Recommendations The guideline provides recommendations on the surgical termination of pregnancy and follow-up care after termination of pregnancy.

Abortion in the First Trimester. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015-094, December 2022) - Part 1 with Recommendations on Care Structures, Information and Advice on Decision-Making, Measures Before Abortion and Medical Abortion.

Purpose The aim was to develop evidence-based recommendations where possible. The guideline presents the medical principles and scientific evidence for indications, the counselling of affected women, performing terminations, the choice of method, and the care and monitoring of a terminated pregnancy up until week 12 + 0 of gestation p. c. Methods In accordance with the requirements for S2k-guidelines, the contents of the guideline were drafted following a systematic search of the literature by a representative interdisciplinary group of experts. Guideline authors held several formal meetings under the auspices of the German Society for Gynaecology and Obstetrics (DGGG) during which the contents of the guideline were finalised and agreed upon. Recommendations A total of 61 recommendations are provided, covering care structures, provision of information and counselling to support decision-making, the measures to be taken before terminating the pregnancy, and medical termination of the pregnancy.

Untargeted metabolomics on first trimester serum implicates metabolic perturbations associated with BMI in development of hypertensive disorders: a discovery study.

Goal: Body mass index (BMI) in early pregnancy is a critical risk factor for hypertensive disorders of pregnancy (HDP). The pathobiology of the interplay between BMI and HDP is not fully understood and represents the focus of this investigation. Methods: BMI and 1st-trimester serum samples were obtained from the Global Alliance to Prevent Prematurity and Stillbirth repository for 154 women (105 without HDP and 49 with HDP). Metabotyping was conducted using ultra-high-performance liquid-chromatography high-resolution mass spectrometry (UHPLC HR-MS). Multivariable linear regression and logistic models were used to determine metabolites and pathway perturbations associated with BMI in women with and without HDP, and to determine metabolites and pathway perturbations associated with HDP for women in categories of obese, overweight, and normal weight based on the 1st trimester BMI. These outcome-associated signals were identified or annotated by matching against an in-house physical standards library and public database. Pathway analysis was conducted by the Mummichog algorithm in MetaboAnalyst. Result: Vitamin D3 and lysine metabolism were enriched to associate with BMI for women with and without HDP. Tryptophan metabolism enrichment was associated with HDP in all the BMI categories. Pregnant women who developed HDP showed more metabolic perturbations with BMI (continuous) than those without HDP in their 1st-trimester serum. The HDP-associated pathways for women with normal weight indicated inflammation and immune responses. In contrast, the HDP-associated pathways for women of overweight and obese BMI indicated metabolic syndromes with disorders in glucose, protein, and amino acid, lipid and bile acid metabolism, and oxidative and inflammatory stress. Conclusion: High first-trimester BMI indicates underlying metabolic syndromes, which play critical roles in HDP development. Vitamin D3 and tryptophan metabolism may be the targets to guide nutritional interventions to mitigate metabolic and inflammatory stress in pregnancy and reduce the onset of HDP.

Anti-glomerular Basement Membrane Glomerulonephritis During the First Trimester of Pregnancy.

A 28-year-old woman was admitted during the eighth week of her pregnancy because her clinical course was consistent with rapid progressive glomerulonephritis (RPGN). Anti-glomerular basement membrane antibody (anti-GBM Ab) and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) were positive, and the anti-GBM Ab titer being extremely high. She was treated with hemodialysis, plasma exchange and prednisolone. She survived the illness; however, neither the fetus nor her kidney function could be rescued. She had human leukocyte antigen (HLA)-DRB1*1502:01, which differs from the DRB1*1501 associated with anti-GBM GN. When patients have particular symptoms, we should check the urine and serum creatinine to exclude RPGN, even in cases of pregnancy.

Does abnormal ductus venosus pulsatility index at the first-trimester effect on adverse pregnancy outcomes?

AIM: The ductus venosus pulsatility index for veins (DV PIV) has become a popular marker of the first-trimester scan. The aim of this study is to search for any difference between groups with normal and abnormal DV PIV values in terms of adverse pregnancy outcomes. METHODS: We retrospectively evaluated 556 women whose first-trimester scan was performed. The ductus venosus pulsatility indices were examined at singleton pregnancies between 11 and 14 weeks of gestation. Patients were categorized as Group-I with normal DV PIV (DV PIV ≥ 0.73, ≤1.22) and as Group-II with abnormal DV PIV. Group-II was subgrouped as Group-IIA which composed of patients with DV PIV < 0.73 and as Group-IIB with DV PIV > 1.22. RESULTS: There were 451 subjects in Group-I and 105 subjects in Group-II (Group-IIA = 32 and Group-IIB = 73). The comparisons between major groups revealed a statistically significant increase about miscarriage (p = 0.002), stillbirth (p < 0.001), small for gestational age (p = 0.033), low birth weight (p < 0.001), fetal growth restriction (p = 0.048), and major congenital heart defect (p=<0.001) in Group-II. This difference is mainly due to Group-IIB. There is no difference in preterm delivery, preeclampsia and gestational diabetes between Group I and II. CONCLUSION: Routinely monitoring DIV PIV as a first-trimester screening should provide valuable information regarding adverse pregnancy outcomes such as miscarriage, stillbirth, small for gestational age, low birth weight, fetal growth restriction and major congenital heart defect.

[Epidemioclinical and ultrasonographic profile of hydatidiform moles in Abidjan]. / Profil épidemio-clinique et échographique des moles hydatiformes à Abidjan.

INTRODUCTION: The purpose of our study was to describe the epidemioclinical and ultrasonographic features of hydatidiform moles (HM) in Abidjan. METHODS: We conducted a cross-sectional study in the Department of Radiology, University Teaching Hospital of Yopougon over a 6-year period (January 2011-December 2016). In this study we describe the epidemioclinical and ultrasonographic profile of patients with HM. Ultrasonographic exams were performed using a mixed-methods approach (intravaginal and subpubic) based on B-mode and Color Doppler by senior radiologists. Anatomopathological examination of uterine content was performed. RESULTS: Out of 12190 obstetric ultrasound performed, twenty-five cases of HM were diagnosed reflecting a radiological referral rate of 0.2%. The average age of patients was 33.4 years, ranging from 22 to 50 years. There was no dominant age class. The main clinical signs associated with amenorrhea (100%) included abdominal mass 36% and vaginal bleeding 28%. Ultrasound showed hypertrophic uterus in 100% of cases, homogeneous uterus in 96% of cases and myomatous uterus in 4% of cases. MH had an average thickness of 42.7 mm with vesicular appearance in 68% of cases, "honeycomb" appearance in 16%, multicystic appearance in 12% and snowstorm appearance in 4%. MHs were classified as partial in 4% of cases, complete in 92% of cases and invasive in 4% of cases. Hypertrophic ovaries were found in 44% of cases with macrofollicles in 32% of cases and cysts in 8% of cases. Ultrasonographic diagnosis of HM was confirmed by anatomopathological examination in 100% of cases. CONCLUSION: HMs are rare in Abidjan and are dominated by the complete hydatidiform mole. Its occurrence at the extreme ages wasn't found.

Maternal progesterone levels are modulated by maternal BMI and predict birth weight sex-specifically in human pregnancies.

OBJECTIVE: Successful pregnancy outcome is the result of a tailored adaptation of the maternal endocrine and immune system throughout gestation. We aimed to investigate if maternal endocrine, anthropometric and life style factors assessed longitudinally throughout pregnancy allow prediction of birth weight. STUDY DESIGN: Data on maternal factors and obstetrical characteristics from 220 pregnancies from a German prospective pregnancy cohort were analyzed using univariate and multivariate regression models. The association between maternal progesterone levels at the end of the 1st (gw 12-14), the 2nd (gw 22-24) and the 3rd trimester (gw 34-36) and birth weight of children born at term was examined. Interaction terms were included to identify possible sex-specific associations. Furthermore, associations between maternal and obstetric characteristics and progesterone levels were tested. RESULTS: After controlling for possible confounders, progesterone in the 2nd trimester emerged as an independent predictor for birth weight in pregnancies with female (p=0.01), but not male fetuses (p=0.6). In female fetuses each increase of progesterone by 1ng/ml in the 2nd trimester was associated with an increase of birth weight by 6.8g (95%-CI=1.44-12.24). Maternal 1st trimester BMI showed a significant inverse correlation to progesterone levels throughout gestation (p<0.0001 in the 1st and 2nd, p=0.01 in the 3rd trimester). This inverse association between maternal BMI and progesterone levels was confined to overweight women. CONCLUSION: Our data support that maternal progesterone levels have the potential to serve as early biomarker for reduced birth weight and underpins the importance of normal weight when entering the reproductive phase.

Mono-(2-ethylhexyl) phthalate induces apoptosis through miR-16 in human first trimester placental cell line HTR-8/SVneo.

Phthalates have been linked to adverse pregnancy complications. Mono-(2-ethylhexyl) phthalate, an active metabolite of di-(2-ethylhexyl) phthalate and an endocrine disruptor, has been shown to induce apoptosis in various cell types including placental cells. However, the mechanism of action of MEHP induced apoptosis is still unknown. We hypothesized that apoptosis may be mediated in part through altered microRNA(s) in placenta under MEHP exposure. In the present study, we report that MEHP increases miR-16 expression in a time- and dose-dependent manner (p<0.05), while inducing apoptosis in HTR-8/SVneo. Cells treated with MEHP showed a dose-dependent increase in cytotoxicity and reactive oxygen species along with decreased cell viability. Consistent with significant increase in apoptosis analyzed by flow cytometry, we detected decreased anti-apoptotic BCL-2 at transcriptional and translational levels with MEHP (p<0.05). Knockdown of miR-16 did not decrease the BCL-2/BAX protein expression ratio in the presence of MEHP when compared to negative control demonstrating that MEHP induces apoptosis directly through miR-16. In conclusion, our study demonstrates for the first time that MEHP induces miR-16, which in turn, alters BCL-2/BAX ratio leading to increased apoptosis. This study provides a novel insight into MEHP induced epigenetic regulation in placental apoptosis which may lead to pregnancy complications.