Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale

AbstractOne of the most frequent causes of maternal and perinatal morbidity is represented by hypertensive disorders during pregnancy. Women at high risk must be subjected to a more intensive antenatal surveillance and prophylactic treatments. Many genetic risk factors, clinical features and biomarkers have been proposed but none of these seems able to prevent pre-eclampsia onset. English literature review of manuscripts focused on calcium intake and hypertensive disorders during pregnancy was performed. We performed a critical analysis of evidences about maternal calcium metabolism pattern in pregnancy analyzing all possible bias affecting studies. Calcium supplementation seems to give beneficial effects on women with low calcium intake. Some evidence reported that calcium supplementation may drastically reduce the percentage of pre-eclampsia onset consequently improving the neonatal outcome. Starting from this evidence, it is intuitive that investigations on maternal calcium metabolism pattern in first trimester of pregnancy could represent a low cost, large scale tool to screen pregnant women and to identify those at increased risk of pre-eclampsia onset. We propose a biochemical screening of maternal calcium metabolism pattern in first trimester of pregnancy to discriminate patients who potentially may benefit from calcium supplementation. In a second step we propose to randomly allocate the sub-cohort of patients with calcium metabolism disorders in a treatment group (calcium supplementation) or in a control group (placebo) to define if calcium supplementation may represent a dietary mean to reduce pre-eclampsia onset and to improve pregnancy outcome.

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Exposure to Propylthiouracil in the First Trimester of Pregnancy and Birth Defects: A Study at a Single Institution

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa204 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Ai Yoshihara ◽

Jaeduk Yoshimura Noh ◽

Natsuko Watanabe ◽

Miho Fukushita ◽

Masako Matsumoto ◽

...

Keyword(s):

Medical Treatment ◽

Birth Defects ◽

Antithyroid Drug ◽

First Trimester ◽

Control Group ◽

Graves Disease ◽

Increased Risk ◽

Group A ◽

First Trimester Of Pregnancy ◽

Maternal Thyroid

Abstract Context Medical treatment of Graves disease during the first trimester has been the subject of controversy ever since treatment with an antithyroid drug during the first trimester was reported to possibly be associated with an increased risk of birth defects in newborns. Objective We investigated whether the incidence of birth defects among newborns born to mothers with Graves disease (GD) treated with propylthiouracil (PTU) during the first trimester of pregnancy was higher than in a control group that was not exposed to any medication. Methods We reviewed the cases of 1913 women with GD who gave birth between January 1, 2015, and May 31, 2019. Detailed information concerning the outcome of pregnancy and the presence of birth defects was collected at the first visit after the delivery and again 1 year after delivery. We classified the mothers and infants into 3 groups according to the treatment the mother had received for GD in the first trimester of pregnancy: a group in which the mothers had been treated with PTU alone (PTU group), a group in which the mothers had not been treated with any medication (control group), and a group in which the mothers had received some other medical treatment, such as thiamazole, potassium iodide, or 2 or more drugs (other treatment group). Results The incidence of malformed infant births was 5.5% (30/541 infants) in the PTU group and 5.7% (27/ 475 infants) in the control group. There were no specific birth defects in the PTU group, and there were no significant differences between PTU dosages or maternal thyroid function according to whether mothers had delivered a child with a birth defect. Conclusion The results of our retrospective study showed that treatment with PTU during the first trimester of pregnancy did not increase the incidence of birth defects among newborns.

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Prospective, Controlled, Multicentre Study of Loperimide in Pregnancy

Canadian Journal of Gastroenterology ◽

10.1155/2000/957649 ◽

2000 ◽

Vol 14 (3) ◽

pp. 185-187 ◽

Cited By ~ 43

Author(s):

A Einarson ◽

P Mastroiacovo ◽

J Arnon ◽

A Ornoy ◽

A Addis ◽

...

Keyword(s):

Birth Defects ◽

Chronic Diarrhea ◽

First Trimester ◽

Control Group ◽

Premature Births ◽

End Points ◽

Increased Risk ◽

First Trimester Of Pregnancy ◽

Cardiovascular Anomalies ◽

In Pregnancy

BACKGROUND: Loperamide is a synthetic piperidine derivative used for the treatment of both acute and chronic diarrhea. Little is known about its safety and risk in pregnancy. Human data are limited to one surveillance study of Michigan Medicaid patients, with 108 women exposed in the first trimester. In this study there were six major birth defects, three of which were cardiovascular anomalies.OBJECTIVES: To determine whether loperamide use in pregnancy is associated with an increased risk of major malformations. The secondary end points were rates of minor malformations, spontaneous and therapeutic abortions, and premature births, and mean birth weights.PATIENTS AND METHODS: Women counselled by five teratogen information centres on the safety and risk of loperamide in pregnancy were followed after delivery and compared with a similar group of women matched for age, smoking, alcohol and other exposures.RESULTS: One hundred and five follow-ups were completed; 89 of the women were exposed to loperamide in the first trimester of pregnancy. There were no statistically significant differences between the study group and the control group in any of the end points that were analyzed. However, of women who took loperamide throughout their pregnancy, 21 of 105 had babies who were 200 g smaller than babies in the control group.CONCLUSIONS: The results of this study suggest that the use of loperamide during pregnancy is not associated with an increased risk of major malformations.

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FRACTIONAL DETERMINATIONS OF URINARY 17-KETOSTEROIDS IN HYPEREMESIS GRAVIDARUM

Acta Endocrinologica ◽

10.1530/acta.0.0410123 ◽

1962 ◽

Vol 41 (1) ◽

pp. 123-128 ◽

Cited By ~ 6

Author(s):

Pentti A. Järvinen ◽

Sykkö Pesonen ◽

Pirkko Väänänen

Keyword(s):

Hyperemesis Gravidarum ◽

First Trimester ◽

Control Group ◽

Before And After ◽

Daily Urine ◽

First Trimester Of Pregnancy ◽

The Difference

ABSTRACT The fractional determination of 17-ketosteroids in the daily urine was performed in nine cases of hyperemesis gravidarum and in four control cases, in the first trimester of pregnancy both before and after corticotrophin administration. The excretion of total 17-KS is similar in the two groups. Only in the hyperemesis group does the excretion of total 17-KS increase significantly after corticotrophin administration. The fractional determination reveals no difference between the two groups of patients with regard to the values of the fractions U (unidentified 17-KS), A (androsterone) and Rest (11-oxygenated 17-KS). The excretion of dehydroepiandrosterone is significantly higher in the hyperemesis group than in the control group. The excretion of androstanolone seems to be lower in the hyperemesis group than in the control group, but the difference is not statistically significant. The differences in the correlation between dehydroepiandrosterone and androstanolone in the two groups is significant. The high excretion of dehydroepiandrosterone and low excretion of androstanolone in cases of hyperemesis gravidarum is a sign of adrenal dysfunction.

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A risk model that combines MAP, PlGF, and PAPP-A in the first trimester of pregnancy to predict hypertensive disorders of pregnancy

Journal of Human Hypertension ◽

10.1038/s41371-021-00488-6 ◽

2021 ◽

Author(s):

Yiming Chen ◽

Xue Wang ◽

Wensheng Hu ◽

Yijie Chen ◽

Wenwen Ning ◽

...

Keyword(s):

Risk Model ◽

First Trimester ◽

Hypertensive Disorders Of Pregnancy ◽

Hypertensive Disorders ◽

First Trimester Of Pregnancy

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Stroke in Pregnancy and Puerperium: Validated Incidence Trends With Risk Factor Analysis in Finland 1987–2016

Neurology ◽

10.1212/wnl.0000000000011990 ◽

2021 ◽

pp. 10.1212/WNL.0000000000011990

Author(s):

Liisa Karjalainen ◽

Minna Tikkanen ◽

Kirsi Rantanen ◽

Karoliina Aarnio ◽

Aino Korhonen ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Postpartum Period ◽

First Trimester ◽

Class Iii ◽

Hypertensive Disorders Of Pregnancy ◽

Risk Factor Management ◽

Incidence Trends ◽

Hypertensive Disorders ◽

Increased Risk

Objective:To investigate whether previously reported increasing incidence of pregnancy-associated stroke (PAS) is observed in chart-validated register data in Finland. In an exploratory analysis, we studied risk factors for PAS.Methods:We performed a retrospective population-based cohort study and nested case-control study in Finland 1987-2016. The Medical Birth Register (MBR) was linked with the Hospital Discharge Register to identify women with incident stroke (ischemic stroke, cerebral venous thrombosis, intracerebral or subarachnoid hemorrhage) during pregnancy or puerperium. Cases were verified from patient records. Incidence of PAS over the study period, in 5-year age groups and pregnancy/postpartum period were calculated per number of deliveries. Three matched controls were selected for each case from MBR to compare risk factors.Results:After chart review, 29.6% (257/868) of cases were PAS. The incidence of PAS was 14.5 (95%CI: 12.8-16.3) per 100,000 deliveries. Incidence increased from 11.1 to 25.2 per 100,000 deliveries from 1987-1991 to 2012-2016 (p<0.0001). Incidence increased by age from 9.8 to 29.9 per 100,000 deliveries from ages 20-24 to ages >40 (p<0.0001). During early postpartum period, incidence was 5-fold greater compared to the first trimester. Maternal mortality was 6.6%. In the multivariable adjusted model, smoking beyond 12 gestational weeks (odds ratio [OR] 1.8, 95%CI: 1.2-2.7), migraine (OR 16.3, 95%CI: 5.3-49.8), and hypertensive disorders of pregnancy (OR 4.0, 95%CI: 2.5-6.3) were the most important risk factors for PAS.Conclusion:PAS incidence is increasing stressing the importance of careful pregnancy surveillance and risk factor management, particularly in older expectant mothers and extending to puerperium.Classification of Evidence:This study provides Class III evidence that smoking beyond 12 gestational weeks, migraine and hypertensive disorders of pregnancy are associated with an increased risk of PAS.

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Association between statin use and the risks of glaucoma in Australia: a 10-year cohort study

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-318789 ◽

2021 ◽

pp. bjophthalmol-2021-318789

Author(s):

Yixiong Yuan ◽

Wei Wang ◽

Xianwen Shang ◽

Ruilin Xiong ◽

Jason Ha ◽

...

Keyword(s):

Large Scale ◽

Conditional Logistic Regression ◽

Control Group ◽

Case Group ◽

Conditional Logistic Regression Model ◽

The People ◽

Increased Risk ◽

Nested Case Control ◽

Statin Use

SynopsisIn a cohort of middle-aged and elderly Australians, we found that long-term statin use was associated with a higher risk of glaucoma onset. As to subtypes of statins, the increased risk was only found in rosuvastatin users.PurposeTo investigate the relationship between statin use and glaucoma onset in a 10-year longitudinal study.MethodsThis nested case–control study was based on data from a large-scale cohort of Australians aged over 45 years old. Medication exposure was identified by claims records from the Pharmaceutical Benefits Scheme during the follow-up period (2009–2016). The onset of glaucoma was defined as the people with at least three claims of antiglaucoma medications. Controls matched by age, gender and cardiovascular diseases were selected from participants without prescription of antiglaucoma medications. A conditional logistic regression model was used to assess the association between statin use and glaucoma onset.ResultsThe proportion of statin users was higher in the case group (40.5%) than that in the control group (38.4%). After adjusting for baseline characteristics and longitudinal claims records, statin use was not associated with glaucoma onset (OR 1.04, 95% CI 0.97 to 1.11). However, an increased risk of glaucoma onset was observed in participants with a longer duration of statin use (>3 years vs <1 year: OR 1.12, 95% CI 1.04 to 1.21). With respect to specific types of statins, participants taking rosuvastatin were more likely to suffer from glaucoma (OR 1.11, 95%CI 1.01 to 1.22). The use of other statins was not significantly associated with glaucoma onset.ConclusionsLong-term statin use was found to be associated with a higher risk of glaucoma onset in this study. Regarding specific types of statins, the increased risk of glaucoma onset was only observed in users of rosuvastatin.

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High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy Outcomes

American Journal of Perinatology ◽

10.1055/s-0039-1694005 ◽

2019 ◽

Vol 37 (01) ◽

pp. 008-013 ◽

Cited By ~ 4

Author(s):

Lydia L. Shook ◽

Mark A. Clapp ◽

Penelope S. Roberts ◽

Sarah N. Bernstein ◽

Ilona T. Goldfarb

Keyword(s):

Preterm Birth ◽

Gestational Age ◽

Small For Gestational Age ◽

First Trimester ◽

Hypertensive Disorders Of Pregnancy ◽

Aneuploidy Screening ◽

Hypertensive Disorders ◽

Increased Risk ◽

Adverse Pregnancy ◽

Fetal Fraction

Abstract Objective To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. Study Design This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th–95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Results A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant <fifth percentile, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.1–4.8, p = 0.039). There was no significant association between high FF and either preterm birth or hypertensive disorders of pregnancy. Conclusion Women with a high FF in the first trimester are at increased risk of delivering a small for gestational age infant <fifth percentile. Further investigation into the clinical implications of a high FF is warranted.

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Dietary Approaches to the Prevention of Neural Tube Defects

Nutrition and Health ◽

10.1177/026010608300200408 ◽

1983 ◽

Vol 2 (3-4) ◽

pp. 181-189 ◽

Cited By ~ 1

Author(s):

K. M. Laurence

Keyword(s):

Neural Tube ◽

First Trimester ◽

Subsequent Pregnancy ◽

Vitamin Supplementation ◽

Control Group ◽

Dietary Counselling ◽

Increased Risk ◽

Diet Study ◽

Group 5 ◽

Dietary Education

Two dietary studies are reported on women resident in Glamorgan and Gwent who had had a child with a neural tube defect (NTD). In the first study the contemporaneous inter-pregnancy and pregnancy diets of 415 women were recorded. Blood samples were taken and analysed for folates and vitamin B12. The quality of the diets correlated with the serum and red cell folate concentrations. The diets during the subsequent pregnancy were worse than the inter-pregnancy diet. Half of the women, selected on a geographical basis were advised to improve their diet before and during the next pregnancy. Of these women 174 reported 186 pregnancies in time for a further diet study. Of the women counselled to improve their diet 75% had done so, compared to 10% of those not counselled. There were 8 recurrences of NTD in 186 pregnancies, all the 8 mothers receiving a poor diet during the first 3 months of pregnancy. In the second study the interpregnancy diets of 244 women who had had a child with a NTD were compared to the diets of their own sisters and a group of professional women. The diet of the index cases was worse than that of either control group. 5 mothers who had poor diets during the first 3 months of the pregnancy had a child with a NTD. It is concluded that women on a better diet during the first trimester have a lower risk of NTD recurrence. Dietary counselling can be effective in improving the diet in women at increased risk for NTD. Improvement in the diet of prospective mothers by dietary education at school should not be neglected. The relationship between improvements in diet, folic acid and vitamin supplementation, in the prevention of recurrence of NTD is discussed.

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Babies exposed to newer-generation antiepileptic drugs (compared with no antiepileptic drug exposure) in the first-trimester of pregnancy are not at increased risk of major birth defects

Evidence-Based Medicine ◽

10.1136/ebmed-2011-100096 ◽

2011 ◽

Vol 17 (2) ◽

pp. 66-67

Author(s):

Jose F Tellez-Zenteno

Keyword(s):

Antiepileptic Drug ◽

Antiepileptic Drugs ◽

Birth Defects ◽

Drug Exposure ◽

First Trimester ◽

Increased Risk ◽

First Trimester Of Pregnancy

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Effect of teriparatide in fracture healing of intertrochanteric fracture: a prospective study

International Journal of Research in Orthopaedics ◽

10.18203/issn.2455-4510.intjresorthop20184386 ◽

2018 ◽

Vol 4 (6) ◽

pp. 918

Author(s):

Sanjeev K. Singhal ◽

Naresh Aggarwal ◽

Ajay Sharma

Keyword(s):

Prospective Study ◽

Fracture Healing ◽

Large Scale ◽

Intertrochanteric Fracture ◽

Calcium Supplementation ◽

Geriatric Trauma ◽

Controlled Study ◽

Control Group ◽

Intertrochanteric Fractures ◽

Early Return

Background: Intertrochanteric fracture is a relatively common and serious medical issue in geriatric trauma result in serious health problems and decrease health related quality of life. Faster time-to-union is important for early return to daily activities and reduction of complications. Teriparatide has been shown to accelerate fracture-healing. The purpose of the present prospective, randomized, controlled study was to evaluate the effect of teriparatide on the course of intertrochanteric fracture-healing.Methods: Forty patients of intertrochanteric fractures who underwent surgical intervention between June 2016 and May 2017 were enrolled in this prospective study and followed for minimum of six months. Group A included patients who received only calcium supplementation; patients in Group B received teriparatide along with calcium supplementation postoperatively.Results: The mean time to fracture healing was between 8-12 weeks for the treatment group, compared with 12-16 weeks for the control group. There was also significant effectiveness with regards to Parker and Palmer mobility score at 6 months.Conclusions: Postoperative use of teriparatide for 6 months appears to be an effective adjunct therapy in the treatment of patients with intertrochanteric fractures. However, because of the limited power of the study a large-scale cohort study is still required for determining the efficacy of teriparatide.

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