Vitamin D status and its determinants in healthy pregnant women living in Switzerland in the first trimester of pregnancy.

OBJECTIVES: Our study aimed at assessing the prevalence and determinants of vitamin D deficiency (25-hydroxy-vitamin D [25(OH)D] < 20 ng/mL) in pregnant women in the first trimester living in Switzerland. METHODS: From September 2014 through December 2015, 204 pregnant women were conveniently recruited during their first clinical appointment at the Clinic of Obstetrics of the University Hospital Zurich (between week 6 and 12 of pregnancy). Blood samples were collected and a questionnaire focusing on lifestyle and skin colour was completed face-to-face with the responsible physician. Logistic regression analyses were performed with vitamin D status as dependent variable. RESULTS: 63.2% of the participating women were vitamin D deficient, and the median vitamin D concentration in the overall sample was 17.1 ng/mL [Q1, Q3: 9.78, 22.3]. The highest proportions of vitamin D deficiency were detected in women originating from Africa and Middle East (91.4% deficient, median vitamin D concentration of 10.7 ng/mL [Q1, Q3: 6.55, 14.45]) and from South-East Asia/Pacific (88.5% deficient, median vitamin D concentration of 8.4 ng/mL [Q1, Q3: 6.10, 14.88]). Multivariable logistic regression showed that significant risk factors of vitamin D deficiency were country of origin (women born in Switzerland and Germany had a lower risk than women born in other countries), smoking status (lower risk for former smokers) and intake of vitamin D supplements. CONCLUSIONS: Our results confirm a high prevalence of vitamin D deficiency in this Swiss cohort, in particular in women coming from Asian and African countries, and underline the importance of appropriate counseling and vitamin D supplementation in early pregnancy.

Effect of Iodine Nutrition on Pregnancy Outcomes in an Iodine-Sufficient Area in China.

Many studies focused on the association between thyroid disease and pregnancy outcomes. The present study explored the effect of iodine nutrition during the first trimester on pregnancy outcomes. One thousand five hundred sixty-nine pregnant, euthyroid women at ≤12 weeks of gestation in an iodine-sufficient area in China were recruited. According to the World Health Organization (WHO) criteria for iodine nutrition during pregnancy, participants were divided into four groups: adequate iodine (median urinary iodine concentration (UIC), 150-249 µg/L), mild deficiency (UIC, 100-150 µg/L), moderate and severe deficiency (UIC, <100 µg/L), and more than adequate and excessive (UIC, ≥250 µg/L) groups. Pregnancy outcomes, including abortion, gestational hypertension, pre-eclampsia, gestational diabetes mellitus (GDM), placenta previa, placental abruption, preterm labor, low birth weight infants, macrosomia, breech presentation, and cord entanglement, were obtained during follow-up. The results showed that there was no significant difference in general characteristics, including age, body mass index, abdominal circumference, systolic blood pressure, diastolic blood pressure, heart rate, smoking rate, and drinking rate, among the four groups. In the more than adequate and excessive group, thyroid-stimulating hormone (TSH) was greater and free thyroxine (FT4) was lower than any other groups but still within normal range. The thyroglobulin (Tg) level was greater in the moderate and severe deficiency group. The incidence of GDM was significantly greater in women with mild iodine deficiency than in women with adequate iodine nutriture (18.38 vs. 13.70%, p < 0.05). Compared with the adequate group, incidence of macrosomia was significantly greater in the more than adequate and excessive group (12.42 vs. 9.79%, p < 0.05). Mild iodine deficiency was an independent risk factor for GDM (odds ratio = 1.566, 95% confidence interval = 1.060-2.313, p = 0.024); more than adequate and excessive iodine was an independent risk factor for macrosomia (OR = 1.917, CI = 1.128-3.256, p = 0.016). In summary, during 1st trimester, both mild iodine deficiency and excessive iodine intake had adverse impacts on pregnancy outcomes in an iodine-sufficient area.

Effect of ethnicity on first trimester biomarkers for combined trisomy 21 screening: results from a multicenter study in six Asian countries.

OBJECTIVE: To assess differences between first trimester trisomy 21 screening markers free beta chain of the human chorionic gonadotrophin (ßhCG) and pregnancy-associated plasma protein A (PAPP-A) in pregnant women of six different Asian countries (China, Indonesia, Korea, Taiwan, Thailand, and Vietnam) and compare serum levels with those in women of European countries. METHODS: Median and multiple of median (MoM) values of free ßhCG and PAPP-A were determined in more than 3000 pregnant women from the Asian countries during their first trimester of pregnancy. Differences in MoM values between a European reference group from a previous multicenter evaluation and the Asian population were evaluated. Two different types of population correction factors for T21 risk estimation were assessed. RESULTS: An at least 10% difference of median MoMs between European and Asian PAPP-A values was found to be statistically significant (p < 0.0001). The specificity of the screening did not show a big difference in individual countries, when using the country-specific correction factor compared with the overall Asian correction factor (<1.4%). CONCLUSIONS: The use of a correction factor is recommended based on the differences in European and Asian MoM values. Developing country-specific medians in larger study populations can help identify clinical relevant differences and give the opportunity to explore a more accurate risk calculation.

AlphaLISA for the determination of median levels of the free ß subunit of human chorionic gonadotropin in the serum of pregnant women.

Measurement of the free ß subunit of human chorionic gonadotropin (free ß-hCG) in serum is useful for prenatal screening. Concentrations of free ß-hCG vary in different races. Conventional assays used for such measurements have limitations. We applied the AlphaLISA to measure levels of free ß-hCG in maternal serum during 8-20 weeks of gestation in women from southern China. Two anti-free ß-hCG antibodies were used: one was coated on AlphaLISA acceptor beads and the one was biotinylated. The assay also contained donor beads coated with streptavidin. The AlphaLISA assay detection limit was 0.11 ng/mL, and the analytical range was 0.11-200 ng/mL. The intra- and interassay coefficients of variation were 1.32%-2.50% and 3.44%-5.45%, respectively. The correlation with commercial Eu(3+)-labeled free ß-HCG-TRFIA assay was good (y = 1.045x + 1.580, r(2) = 0.978). Median levels of free ß-hCG in maternal serum at 8-20 weeks gestation were higher in women from southern China compared with those reported in women from other countries. The AlphaLISA for free ß-HCG could become the assay of choice for applications in clinical diagnostics. The established median value of free ß-HCG is helpful in clinical diagnosis specific for southern Chinese women.

Correction of first trimester biochemical aneuploidy screening markers for smoking status: influence of gestational age, maternal ethnicity and cigarette dosage.

OBJECTIVE: To examine the gestational age, maternal ethnicity and cigarette dosage effects of the reduction of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free-ß human chorionic gonadotrophin (free hCGß) in smokers. METHODS: Maternal serum PAPP-A and free hCGß corrected for confounders, excluding smoking, in first trimester smokers and nonsmokers were compared by gestational age, maternal ethnicity and cigarette dosage. A small set of second trimester smokers and nonsmoker controls were analysed for PAPP-A along with free hCGß and assessed for gestational age effects of smoking. RESULTS: Pregnancy-associated plasma protein A reduction by smoking in the first trimester was not influenced by gestational age, however free hCGß levels were only significantly reduced in weeks 12 and 13 in smokers. Ethnicity and cigarette dosage were also found to influence the reduction of both makers in smokers in the first trimester. In second trimester smokers, PAPP-A was found to be reduced by less and free hCGß reduced by more than in the first trimester, although no second trimester gestational age effect on smoking was found. CONCLUSIONS: Current methods of correcting for smoking status may be an oversimplification of a more complex subject.

First-trimester prediction of preeclampsia in nulliparous women at low risk.

OBJECTIVE: To identify clinical characteristics and biochemical markers in first-trimester samples that would possibly predict the subsequent development of preeclampsia. METHODS: We conducted a multicenter observational study in 2,434 nulliparous women at low risk to identify biomarkers that possibly predict preeclampsia. Clinical history, complete blood count, and biochemical markers were assessed in the first trimester. The trophoblast and angiogenesis markers ADAM-12, pregnancy-associated plasma protein-A, placental protein 13, placental growth factor, soluble fms-like tyrosine kinase-1, and endoglin were measured in a case-control subset of 174 women with preeclampsia and 509 women in the control group. RESULTS: Univariable analysis revealed maternal age, race, marital status, years of education, source of medical payment, prenatal caregiver, body mass index (BMI, calculated as weight (kg)/[height (m)]), and systolic blood pressure at enrollment were significantly associated with preeclampsia. Mean platelet volume was greater at enrollment in women who later had development of preeclampsia (median 9.4 compared with 9.0 femtoliter (fl); P=.02). First-trimester concentrations (multiples of the median) of ADAM-12 (1.14 compared with 1.04; P=.003), pregnancy-associated plasma protein-A (0.94 compared with 0.98; P=.04), and placental growth factor (0.83 compared with 1.04; P<.001) were significantly different in women who had development of preeclampsia compared with women in the control group. The optimal multivariable model included African American race, systolic blood pressure, BMI, education level, ADAM-12, pregnancy-associated plasma protein-A, and placental growth factor, and yielded an area under the curve of 0.73 (95% confidence interval 0.69-0.77) and a sensitivity of 46.1% (95% confidence interval 38.3-54.0) for 80% specificity. CONCLUSION: A multivariable analysis of clinical data and biochemical markers in the first trimester did not identify a model that had clinical utility for predicting preeclampsia in a nulliparous population at low risk. LEVEL OF EVIDENCE: II.

Serum placental growth factor and fms-like tyrosine kinase 1 during first trimester in Chinese women with pre-eclampsia--a case-control study.

OBJECTIVE: To investigate the association between first trimester maternal placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels with subsequent development of pre-eclampsia (PE). METHODS: This is a matched case-control study using stored serum samples collected from non-smoking Chinese women with singleton pregnancies who underwent first trimester screening for aneuploidy. Each case that developed PE was matched with a control whose maternal age, weight, gestational age and date of blood collection were within ± 2 years, ± 5 kg, ± 1 day, and ± 2 weeks of the index case, respectively. Non-parametric paired test was used to compare the PlGF and sFlt-1 levels. PlGF and sFlt-1 were transformed to their equivalent multiple of the median (MoM) using the matched control as the expected median value. The 95% confidence interval (CI) of the estimated median PlGF and sFlt-1 MoM in those with PE was determined. RESULTS: The median PlGF level in the 27 study cases with PE was lower than that of the matched controls (42.9 pg/ml versus 59.8 pg/ml; p = 0.001). The median PIGF MoM was 0.71 (95% CI 0.63-0.92). There was no statistically significant difference in sFlt-1 levels between those with PE and their matched control (p = 0.648). The median sFlt-1 MoM was 1.01 (95% CI 0.65-1.3). CONCLUSIONS: Women who developed PE had lower serum PlGF levels but normal sFlt-1 levels in the first trimester.

The relationship between PTH and 25-hydroxy vitamin D early in pregnancy.

OBJECTIVE: Measure serum PTH and 25(OH)D in a cross-sectional sample of pregnant women at 11th through 13th weeks' gestation to examine vitamin D status and consider implications. DESIGN: Observational: we retrieved residual sera stored at -20 °C after routine first trimester Down's syndrome screening, distributed over 12 months. PATIENTS: 430 African American women and 586 Caucasian women. MEASUREMENTS: PTH and 25-hydroxy vitamin D [25(OH)D] immunoassays. RESULTS: PTH medians were: 1·33 pmol/l (African American women); 1·20 pmol/l (Caucasian women) (t = 0·43, P = 0·7). Concentrations were highest in winter and decreased significantly in spring, fall, and summer. There was a direct PTH/weight relationship in Caucasian (t = 3·12, P < 0·002), but not African American women (t = 1·34, P = 0·18). Median 25(OH)D concentrations were 47·5 nmol/l (African American women) and 65 nmol/l (Caucasian women) (t = 13·7, P < 0·001). Concentrations were lowest in winter and rose significantly in spring, fall, and summer. Reciprocal 25(OH)D/weight relationships existed for both racial groups (t =-4·31 P < 0·001; t = 4·54, P < 0·001, respectively). Among 68 Caucasian women who smoked, median PTH and 25(OH)D concentrations were somewhat lower (P = ns). In separate regression models with PTH and 25(OH)D [dependent variables] and season, weight and smoking [independent variables], the only qualifying interactive term was in the Caucasian PTH model (season*1/weight). A regression model applied to adjusted scatter plots of PTH vs 25(OH)D indicated a weak relationship. CONCLUSIONS: The PTH/25(OH)D relationship is weaker during early pregnancy than in non-pregnant adults, making it unreliable for estimating vitamin D sufficiency. A suitable reference point for sufficiency might be the maternal 25(OH)D level considered sufficient for adequate transfer to neonates.

Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use.

OBJECTIVE: To determine first-trimester thyroid function values and associations with thyroperoxidase antibody (TPO-Ab) status, smoking, emesis, and iodine-containing multivitamin use. METHODS: We collected information by interview, questionnaire, and blood draw at the initial obstetric visit in 668 pregnant women without known thyroid disease. We compared thyroid-stimulating hormone (TSH), total thyroxine (T4), and free T4 index (FT4I) values by TPO-Ab status. Multiple regression was used to identify characteristics associated with thyroid function values. RESULTS: The following median (range containing 95% of the data points) thyroid function test values were obtained in 585 TPO-Ab-negative women: TSH, 1.1 mIU/L (0.04-3.6); FT4I, 2.1 (1.5-2.9); and T4, 9.9 microg/dL (7.0-14.0). The following median (range containing 95% of the data points) thyroid function test values were obtained in 83 TPO-Ab-positive women: TSH, 1.8 mIU/L (0.3-6.4) (P<.001); FT4I, 2.0 (1.4-2.7) (P = .06); and T4, 9.3 microg/dL (6.8-13.0) (P = .03) (P values denote statistically significant differences between TPO-Ab-positive and negative participants). Among TPO-Ab-negative participants, TSH level was not associated with use of iodine-containing multivitamins, smoking, or race. TSH increased 0.03 mIU/L for every year of maternal age (P = .03) and decreased by 0.3 mIU/L for every increase in parity (P<.001). T4 decreased 0.04 microg/dL for every year of maternal age (P = .04). Mean FT4I was 2.05 in smokers and 2.20 in nonsmokers (P<.01). There were no relationships between T4 or FT4I and parity, race, or iodine-containing multivitamin use. CONCLUSION: TPO-Ab status of pregnant women should be considered when constructing trimester-specific reference ranges because elevated serum TPO-Ab levels are associated with higher TSH and lower T4 values.