Maternal hypothyroidism and the risk of preeclampsia: a Danish national and regional study.

BACKGROUND: Maternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se. METHODS: We conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort (n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999-2015. The regional cohort (n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011-2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity. RESULTS: In the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2-1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3-2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH < 2.5 mIU/L (ref.) were diagnosed with preeclampsia. Among women with TSH ≥ 6 mIU/L, the prevalence was 6.2% (aOR 2.4 (95% CI: 1.1-5.3)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women positive for TPO-Ab (> 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6-1.2)). CONCLUSIONS: In two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia.

Correction to: Foetal sex determination at the second trimester anomaly scan in Denmark.

This corrects the article pii: A5580.

Placental mosaicism in the era of chromosomal microarrays.

OBJECTIVE: Placental mosaicism for a subset of a chromosome, a structural chromosomal aberration, is thought to be a very rare finding in chorionic villus samples. Here, we present clinical and laboratory data on five cases with such mosaicism for structural chromosomal aberrations. METHODS: During a period of 6 months, chromosomal microarray was carried out on DNA extracted from 100 uncultured chorion villous samples from high-risk pregnancies. RESULTS: In five of 100 consecutively collected samples (5/100), mosaicism for a structural chromosomal aberration was detected. The mosaic aberration was subsequently detected in fetal tissue in three of the five cases. CONCLUSION: Chromosomal microarray can detect placental mosaicism for structural chromosomal aberrations. This kind of mosaicism may be more frequent than previously anticipated, and the fetal involvement seems difficult to predict. These findings highlight the complexity of mosaicism for structural chromosomal aberrations in prenatal samples in the chromosomal microarray era.

Foetal sex determination at the second trimester anomaly scan in Denmark.

INTRODUCTION: For decades, ultrasound has enabled determination of foetal sex. Foetal sex is medically indicated in sex-linked diseases, syndromes and multiple pregnancy, but genital malformations are rare. However, guidelines on standard views seem sparse and foetal sex determination is not considered mandatory. The aim of this study was to provide an initial overview on the practice of foetal sex determination in Denmark and the accuracy of the examinations at the second trimester anomaly scan at a regional and a university hospital. METHODS: Phone interviews from all 23 Danish foetal medicine departments concerning information, examination, registration, quality criteria and assessment of accuracy. The accuracy of foetal sex determination was assessed in 5,786 singleton pregnancies with live births at two departments by comparison of data from the second trimester anomaly scan (week 18 + 0 - 21 + 6) with the national Danish birth register. RESULTS: Second trimester foetal sex determination was not mandatory but conducted without guideline. Various approaches to information and documentation were used. Foetal sex was assessed in 86.7% of cases and the accuracy was 99.2% with no significant difference between the regional and the university hospital of the study. Sex determination was more inaccurate in females (18/2,118) than in males (18/2,271), p < 0.0001. CONCLUSIONS: Foetal sex determination by ultrasound is common practice in Denmark. No guideline existed and incorrect sex was determined in 8/1,000 foetuses, most often females. Foetal sex determination should be standardised extensively to avoid false diagnoses. FUNDING: none. TRIAL REGISTRATION: This study was approved by the Danish Data Protection Agency (record number: 2012-41-0050).

Nutrient deficiency and obstetrical outcomes in pregnant women following Roux-en-Y gastric bypass: A retrospective Danish cohort study with a matched comparison group.

OBJECTIVE: Roux-en-Y gastric bypass surgery and small-for-gestational-age births are known to be associated although the etiology is not fully understood. This study aimed to investigate pregnancy outcomes and maternal nutritional status among pregnant women with a history of Roux-en-Y gastric bypass using maternal anemia and gestational weight gain as indicators of micronutrient and macronutrient deficiency in pregnancy. STUDY DESIGN: The study was designed as a retrospective matched cohort study. All Roux-en-Y-gastric-bypass-operated pregnant women (n=151) who were followed in the outpatient obstetric clinic at Aalborg University Hospital in Denmark and gave birth between 1 January 2010 and 31 December 2013 were included. Each Roux-en-Y-gastric-bypass-operated woman was closely matched with a non-Roux-en-Y-gastric-bypass-operated woman. Primary outcomes were small-for-gestational-age birth, maternal anemia and gestational weight gain. The two groups (matched 1:1) were compared by paired tests on all measures, conditional logistic regression for paired binary data and the paired t-test or Wilcoxon signed-rank test for paired continuous data. RESULTS: The risk of small-for-gestational-age birth (odds ratio (OR)=2.67, 95% confidence interval (CI); 1.04-6.82) and maternal anemia (OR=3.0, 95% CI; 1.09-8.25) were significantly increased for the Roux-en-Y gastric bypass group compared to the non-Roux-en-Y gastric bypass group. No significant difference was found in gestational weight gain (p=0.169) between women with a history of Roux-en-Y gastric bypass (11.51kg±8.97 standard deviation (SD)) and non- Roux-en-Y-gastric-bypass-operated women (12.18kg±6.28 SD). CONCLUSION: A history of Roux-en-Y gastric bypass surgery increases the risk of small-for-gestational-age birth and anemia, while a finding of differences in gestational weight gain is uncorroborated. Our findings suggest a role of micronutrient deficiency rather than reduced gestational weight gain in the etiology of small-for-gestational-age birth among women with a history of Roux-en-Y gastric bypass surgery.

The rate of invasive testing for trisomy 21 is reduced after implementation of NIPT.

INTRODUCTION: The non-invasive prenatal test (NIPT) was introduced in the North Denmark Region in March 2013. NIPT is offered as an alternative to invasive tests if the combined first trimester risk of trisomy 21 (T21) is ≥ 1:300. The purpose of this study was to investigate the effect of NIPT implementation among high-risk pregnancies in a region with existing first-trimester combined screening for T21. The primary objective was to examine the effect on the invasive testing rate. METHODS: This was a retrospective observational study including high-risk singleton pregnancies in the North Denmark Region. The women were included in two periods, i.e. before and after the implementation of NIPT, respectively. Group 1 (before NIPT): n = 253 and Group 2 (after NIPT): n = 302. RESULTS: After NIPT implementation, the invasive testing rate fell from 70% to 48% (p < 0.01), and the number of high-risk women refusing further testing dropped from 26% to 3% (p < 0.01). NIPT successfully detected four cases of T21; however, two out of three sex-chromosomal abnormalities were false positives. No false negative NIPT results were revealed in this study. CONCLUSIONS: In the North Denmark Region, the implementation of NIPT in high-risk pregnancies significantly reduced the rate of invasive testing. However, the proportion of high-risk women who opted for prenatal tests increased as the majority of women who previously refused further testing now opted for the NIPT. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (No. 2015-104).

[Life-threatening Pneumocystis pneumonia in a previously healthy pregnant woman].

Pneumocystis pneumonia (PCP) is one of the most common infections in patients with HIV. Pneumocystis jirovecii rarely gives rise to symptoms in immunocompetent individuals. PCP has been reported in individuals with immunosuppression. We report a case of life-threatening PCP in an otherwise healthy pregnant woman. Pregnant patients should be considered to be relatively immunosuppressed, and more opportunistic infections should be included in differential diagnosis considerations.

[Seizures caused by subarachnoid haemorrhage in a pregnant woman].

This case report describes a pregnant woman of gestational week 37 + 2 days who was admitted to the hospital with first-time seizures. The patient was stabilized, and an acute caesarian section was performed due to the possible aetiology of eclampsia and the advanced gestational age. Because of the atypical clinical history and normal maternal blood samples a computed tomography of the cerebrum was performed demonstrating a subarachnoid haemorrhage. A computed tomography-angiography revealed an aneurism at the anterior communicating artery. The aneurism was coiled the following day to reduce the risk of rebleeding.