Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women.

Limited evidence revealed conflicting results on relationship between phthalate exposure and clinical pregnancy loss (gestational weeks >6). A prospective cohort study in Chinese pregnant women (n = 3220) was conducted to investigate the association between urinary phthalate metabolites and clinical pregnancy loss (gestational weeks 6 to 27; n = 109). Morning urine samples during gestational weeks 5 to 14 (mean 10.42) were collected to measure monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). The concentrations of low- and high-molecular weight phthalate metabolites (ΣLMWP <250 Da and ΣHMWP >250 Da) were calculated. Adjusted logistic regression models showed increased risks of clinical pregnancy loss in women with higher creatinine- normalized concentrations of MEP, MBP, MEOHP, MEHHP, ΣLMWP and ΣHMWP. Stratified analysis by gestational weeks (10 weeks) of miscarriage indicated positive associations of MEP, MEOHP, MEHHP and ΣHMWP with embryonic loss (during gestational weeks 6 to 10). The only association of foetal loss (during gestational weeks 11 to 27) was observed with MEHHP. Our findings suggested that Chinese women who were exposed to phthalates during early pregnancy had an increased risk of clinical pregnancy loss, especially embryonic loss.

Levels of Phthalate Metabolites in Urine of Pregnant Women and Risk of Clinical Pregnancy Loss.

Toxicological studies have shown that phthalate esters (PAEs), a class of widely used and environmentally prevalent chemicals, can increase the abortion rate in animals, but epidemiological evidence is scarce. This study aimed to explore the relationship between the urinary concentration of phthalate metabolites and the risk of clinical pregnancy loss. A total of 132 women who underwent clinical pregnancy loss (cases) and 172 healthy pregnant women (controls) were recruited from Beijing, China. Eight phthalate metabolites in urine were determined by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono(2-ethlyhexyl) phthalate (MEHP), were detected in at least 95% of the urine samples, with the highest median concentration of 51.0 µg/g of creatinine for MnBP of all participants. The differences in urinary concentrations of phthalate metabolites between cases and controls were evaluated using the Mann-Whitney U test. The concentrations of MEP (median of 18.7 µg/g of creatinine), MiBP (23.3 µg/g of creatinine), and MnBP (58.2 µg/g of creatinine) detected in the cases were significantly higher than those (15.7 µg/g of creatinine for MEP, 19.4 µg/g of creatinine for MiBP, and 43.9 µg/g of creatinine for MnBP) in the controls (p < 0.05). Increasing risks of clinical pregnancy loss were observed from the first to fourth quartiles of the MEP, MiBP, and MnBP concentrations (p < 0.05 for trend). We concluded that exposure to MEP, MiBP, and MnBP was associated with an increased risk of clinical pregnancy loss.

The acute phase protein ceruloplasmin as a non-invasive marker of pseudopregnancy, pregnancy, and pregnancy loss in the giant panda.

After ovulation, non-pregnant female giant pandas experience pseudopregnancy. During pseudopregnancy, non-pregnant females exhibit physiological and behavioral changes similar to pregnancy. Monitoring hormonal patterns that are usually different in pregnant mammals are not effective at determining pregnancy status in many animals that undergo pseudopregnancy, including the giant panda. Therefore, a physiological test to distinguish between pregnancy and pseudopregnancy in pandas has eluded scientists for decades. We examined other potential markers of pregnancy and found that activity of the acute phase protein ceruloplasmin increases in urine of giant pandas in response to pregnancy. Results indicate that in term pregnancies, levels of active urinary ceruloplasmin were elevated the first week of pregnancy and remain elevated until 20-24 days prior to parturition, while no increase was observed during the luteal phase in known pseudopregnancies. Active ceruloplasmin also increased during ultrasound-confirmed lost pregnancies; however, the pattern was different compared to term pregnancies, particularly during the late luteal phase. In four out of the five additional reproductive cycles included in the current study where females were bred but no birth occurred, active ceruloplasmin in urine increased during the luteal phase. Similar to the known lost pregnancies, the temporal pattern of change in urinary ceruloplasmin during the luteal phase deviated from the term pregnancies suggesting that these cycles may have also been lost pregnancies. Among giant pandas in captivity, it has been presumed that there is a high rate of pregnancy loss and our results are the first to provide evidence supporting this notion.

Evaluation of a urinary test as a diagnostic tool of a nonprogressive pregnancy.

OBJECTIVE: To evaluate the performance of a one-step test detecting intact hCG and free ß-hCG isoforms in the urine of pregnant women to diagnose an abnormal pregnancy. DESIGN: Prospective study. SETTING: Emergency gynecology departments in teaching hospitals. PATIENT(S): Five hundred twenty-six patients were enrolled, 272 who were not pregnant and 254 who were pregnant. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): Semiquantitative determination of intact urinary hCG of supposedly not pregnant and pregnant women with vaginal bleeding and/or vaginal pain between 5 and 8 weeks of amenorrhea. RESULT(S): The sensitivity and specificity of the urine test for diagnosing nonpregnancy were, respectively, 100% (252/252) and 100% (272/272). The sensitivity and specificity of the urine test for diagnosing ectopic pregnancy (EP) were, respectively, 97% (32/33) and 83% (142/171). The negative predictive value is 99.3% (142/143). The sensitivity and specificity or the urine test for diagnosing miscarriage were, respectively, 89.6% (43/48) and 83% (142/171). The negative predictive value is 96.6% (142/147). CONCLUSION(S): Abnormal pregnancy, such as an EP or a miscarriage, can be rapidly detected with the one-step test for intact hCG and free ß-hCG isoforms. If ultrasound cannot confirm the localization and/or evolution of a pregnancy, using this test reduces medical supervision and repeated quantification of hCG.