RESUMEN
BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were associated with SGA and LGA in GDM pregnancies and controls. METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fß-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fß-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fß-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA. CONCLUSION: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fß-hCG levels are associated with SGA only in non-GDM pregnancies.
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Gonadotropina Coriónica Humana de Subunidad beta , Diabetes Gestacional , Macrosomía Fetal , Recién Nacido Pequeño para la Edad Gestacional , Primer Trimestre del Embarazo , Proteína Plasmática A Asociada al Embarazo , Humanos , Femenino , Embarazo , Proteína Plasmática A Asociada al Embarazo/análisis , Proteína Plasmática A Asociada al Embarazo/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Primer Trimestre del Embarazo/sangre , Adulto , Estudios de Casos y Controles , Estudios Retrospectivos , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Recién Nacido , Macrosomía Fetal/sangre , Macrosomía Fetal/epidemiología , Finlandia/epidemiología , Factores de Riesgo , Peso al NacerRESUMEN
OBJECTIVES: To evaluate different cut-off values of first trimester pregnancy associated plasma protein-A (PAPP-A) in screening for adverse pregnancy outcomes in a retrospective cohort study. METHODS: During the study period of 1.1.2014-31.12.2018, total of 23,482 women with singleton pregnancies participated in first trimester combined screening for chromosomal abnormalities. Maternal serum PAPP-A multiple of medians (MoM) levels were measured, and study population was divided into three study groups of PAPP-A ≤0.40 (n=1,030), ≤0.35 (n=630) and ≤0.30 (n=363) MoM. RESULTS: Small for gestational age (SGA), preterm birth (PTB) and composite outcome (SGA, hypertensive disorder of pregnancy (HDP) and/or PTB) were more frequent in all three PAPP-A MoM study groups and pre-eclampsia in ≤0.40 and ≤0.35 study groups than in their control groups (p < 0.05). The odds ratio (OR) for SGA varied from 3.7 to 5.4 and sensitivity and specificity from 6.9 to 13.8% and from 95.9 to 98.6%, between study groups. Using PAPP-A ≤0.30 MoM as a screening cut-off instead of PAPP-A ≤0.40 MoM, resulted in approximately 50% reduction in screening detection of SGA and PTB. CONCLUSIONS: PAPP-A ≤0.40 MoM should be considered as a primary screening cut-off for adverse pregnancy outcomes as approximately 23% will develop either SGA, HDP or PTB. It seems to be the best cut-off to screen for SGA.
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Preeclampsia , Nacimiento Prematuro , Embarazo , Humanos , Recién Nacido , Femenino , Resultado del Embarazo , Primer Trimestre del Embarazo , Proteína Plasmática A Asociada al Embarazo , Estudios Retrospectivos , Nacimiento Prematuro/diagnóstico , Nacimiento Prematuro/epidemiología , Retardo del Crecimiento Fetal/diagnóstico , BiomarcadoresRESUMEN
INTRODUCTION: The aim of the study was to determine the association of body mass index (BMI), self-reported symptoms or diagnosis of polycystic ovary syndrome (PCOS), and hyperandrogenemia with the occurrence of gestational diabetes mellitus (GDM) through reproductive life. MATERIAL AND METHODS: A cohort of women born in 1966 were investigated at ages 14, 31 and 46. Women with self-reported PCOS symptoms (presence of both oligo-amenorrhea and hirsutism) at age 31 or with formally diagnosed polycystic ovaries (PCO)/PCOS by age 46 formed the group of self-reported PCOS (srPCOS, n = 222) and were compared with women without self-reported PCOS symptoms or diagnosis (n = 1357). We investigated also the association of hyperandrogenism (hirsutism or biochemical hyperandrogenism) at age 31 with the occurrence of GDM throughout reproductive life. RESULTS: Self-reported PCOS alone was not a risk factor for GDM, but combined with overweight at age 31 (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.22-4.86) or 46 (OR 3.04, 95% CI 1.58-5.83) srPCOS was associated with GDM when compared with normal weight controls. The association disappeared when comparing overweight srPCOS women with overweight controls. However, hyperandrogenemia at age 31, but not hirsutism, was associated with GDM even after adjustment for BMI. CONCLUSIONS: The increased risk of GDM in women with srPCOS was mostly attributed to overweight or obesity. Importantly, normal weight women with srPCOS did not seem to be at increased risk for developing GDM. However, hyperandrogenemia was associated with GDM even after adjustment for BMI. These findings strengthen the importance of weight management in reproductive-age women and suggest a noteworthy role of hyperandrogenemia in the pathophysiology of GDM.
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Diabetes Gestacional/epidemiología , Hiperandrogenismo/epidemiología , Obesidad Materna/epidemiología , Sobrepeso/epidemiología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Síndrome del Ovario Poliquístico/epidemiología , Embarazo , Factores de RiesgoRESUMEN
PURPOSE: To evaluate the performance of first trimester maternal serum glycosylated (Sambucus nigra lectin-reactive) fibronectin in prediction of gestational diabetes mellitus (GDM). METHODS: In this case-control study, first trimester maternal serum glycosylated fibronectin and fibronectin were measured in 19 women who consequently developed GDM and in 59 control women with normal pregnancy outcomes. Adiponectin was used as a reference protein to evaluate relation of glycoprotein to SNA-lectin-reactive assay format. Samples were taken during gestational weeks 9+6-11+6. Data concerning GDM was obtained from the National Institute for Health and Welfare, which records the pregnancy outcomes of all women in Finland. RESULTS: There was no difference in maternal serum glycosylated fibronectin concentrations between women with consequent GDM [447.5 µg/mL, interquartile range (IQR) 254.4-540.9 µg/mL] and control women (437.6 µg/mL, IQR 357.1-569.1 µg/mL). Maternal serum fibronectin levels were significantly lower in GDM group (224.2 µg/mL, IQR 156.8-270.6 µg/mL), compared to the control group (264.8 µg/mL, IQR 224.6-330.6 µg/mL, p < 0.01). There was no difference in assay formats for adiponectin. CONCLUSION: There was no association between first trimester maternal serum glycosylated (SNA-reactive) fibronectin and GDM.
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Diabetes Gestacional/sangre , Fibronectinas/sangre , Adiponectina/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Fibronectinas/metabolismo , Finlandia , Productos Finales de Glicación Avanzada , Humanos , Pruebas de Detección del Suero Materno , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo/sangre , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. STUDY DESIGN: Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. RESULTS: Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. CONCLUSION: There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.
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Retardo del Crecimiento Fetal/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Humanos , Embarazo , Adulto JovenRESUMEN
Ectopic pregnancy after hysterectomy is a rare but potentially life-threatening condition. If ovaries are present, ectopic pregnancy should be ruled out in women with acute abdominal pain and history of hysterectomy. Our patient had an ectopic pregnancy six months after supracervical hysterectomy.
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Histerectomía/efectos adversos , Embarazo Ectópico/diagnóstico , Embarazo Ectópico/etiología , Adulto , Diagnóstico Diferencial , Femenino , Humanos , EmbarazoRESUMEN
The purpose of this prospective, population-based cohort study was to evaluate the roles of polycystic ovary syndrome (PCOS), obesity, weight gain, and hyperandrogenemia in the development of hypertensive disorders of pregnancy (HDP) through fertile age both in PCOS and in non-PCOS women. The study population-NFBC1966 (Northern Finland Birth Cohort 1966)-allowed a long-term follow-up of women from age 14 until 46 years who developed HDP (n=408) or did not (n=3373). HDP diagnosis was confirmed by combining hospital discharge records, data from Finnish Medical Birth Registers, and the questionnaire data at age 46. Women with self-reported PCOS (srPCOS; n=279), defined by both oligo-amenorrhea and hirsutism at age 31 or with PCOS diagnosis by age 46, were compared with women without reported PCOS (n=1577). Women with srPCOS had an increased HDP risk (odds ratio, 1.56 [95% CI, 1.03-2.37]), but the association disappeared after adjustment for body mass index. In women with srPCOS and HDP, body mass index increased from age 14 to 46 significantly more than in srPCOS women without HDP (median [interquartile range], 9.82 [6.23-14.6] and 7.21 [4.16-10.5] kg/m2, respectively; P<0.001). Also, in non-PCOS women, the increase was higher in women with (7.54 [5.32-11.62] kg/m2; P<0.001) than without HDP (6.33 [3.90-9.33] kg/m2; P<0.001). Increase in waist circumference between ages 31 and 46 years was associated with HDP but not with PCOS. Hyperandrogenemia at 31 or 46 years did not associate with HDP (1.44 [0.98-2.11]). In conclusion, obesity, especially abdominal obesity, and weight gain from adolescence to age 46, but not srPCOS or hyperandrogenemia, were associated with an increased risk of HDP.
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Hiperandrogenismo/fisiopatología , Hipertensión Inducida en el Embarazo/fisiopatología , Obesidad/fisiopatología , Síndrome del Ovario Poliquístico/fisiopatología , Aumento de Peso/fisiología , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , Modelos Logísticos , Persona de Mediana Edad , Vigilancia de la Población , Embarazo , Estudios Prospectivos , Factores de Riesgo , Autoinforme , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the performance of first-trimester measurement of fetal nuchal translucency (NT) in the detection of severe congenital heart defects (CHDs). METHODS: During the study period of 1 January 2008 - 31 December 2011, NT was measured in 31,144 women as a part of voluntary first-trimester screening program for Down's syndrome in Northern Finland. NT was measured by personnel trained on the job by the experienced staff. No certification or annual audits are required in Finland. However, the recommendation is that the examiner should perform 200 scans on average per year. Severe CHD was classified as a defect requiring surgery in the first year of life or a defect that led to the termination of the pregnancy. All severe CHDs diagnosed during the study period in Northern Finland could not be included in this study since all women did not participate in the first-trimester screening and some cases were missing important data. RESULTS: Fourteen (17.7%) out of 79 severe CHDs were found with NT cutoff of 3.5 mm. Amongst the 79 severe CHD cases, there were 17 chromosomal abnormalities. With NT cutoffs of 2.0 and 1.5 mm the detection rates would have increased to 25.3% (n = 20) and 46.8% (n = 37). Using a randomly selected control group of 762 women with normal pregnancy outcomes, false positive rates (FPRs) were calculated. For NT cutoffs of 1.5, 2.0 and 3.5 mm, the FPRs were, 18.5, 3.3 and 0.4%, respectively. CONCLUSIONS: A greater than 3.5 mm NT measurement in the first-trimester ultrasound is an indication to suspect a fetal heart defect but its sensitivity to detect severe CHD is poor. In our study, only 17.7% of severe CHDs would have been detected with an NT cutoff of 3.5 mm.
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Cardiopatías Congénitas/diagnóstico por imagen , Medida de Translucencia Nucal , Adulto , Estudios de Casos y Controles , Femenino , Finlandia/epidemiología , Humanos , Tamizaje Masivo/estadística & datos numéricos , Embarazo , Resultado del Embarazo/epidemiología , Primer Trimestre del Embarazo , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fß-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Results: Both PAPP-A and fß-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fß-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fß-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fß-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.
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Biomarcadores/análisis , Cardiopatías Congénitas/diagnóstico , Pruebas de Detección del Suero Materno/métodos , Primer Trimestre del Embarazo/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Femenino , Finlandia , Cardiopatías Congénitas/sangre , Humanos , Valor Predictivo de las Pruebas , Embarazo , Proteína Plasmática A Asociada al Embarazo/análisis , Proteína Plasmática A Asociada al Embarazo/metabolismo , Diagnóstico Prenatal/métodos , Adulto JovenRESUMEN
OBJECTIVE: Maternal thrombophilia is a risk factor for adverse pregnancy outcomes. The aim of this study was to elucidate the controversial role of fetal and paternal thrombophilia in the development of severe placenta-mediated pregnancy complications. STUDY DESIGN: The study group comprised 126 mothers, 72 fetuses and 58 fathers. 111 mothers, 50 fetuses and 91 fathers acted as controls. 106 couples were selected to study the thrombophilias of paternal inheritance, 58 from the study group and 48 from the control group. The prevalence of factor V Leiden mutation, prothrombin G20210 A mutation and homozygous 10-methylenetetrahydrofolate reductase C677 T mutations were compared between the study and control groups to study whether maternal, fetal or paternal thrombophilias increase the risk of severe preeclampsia, intrauterine growth restriction, placental abruption and stillbirth. RESULTS: The total prevalence of fetal thrombophilic mutations was 8.3% in the study group and 14.0% in the control group. Paternal prevalence of thrombophilic mutations was 6.8% and 4.3%, respectively. There were no statistical differences between fetal or paternal thrombophilic mutations between the study and control groups. CONCLUSION: Fetal or paternal factor V Leiden mutation is not associated with severe placenta-mediated pregnancy complications.
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Resistencia a la Proteína C Activada/genética , Enfermedades Fetales/genética , Herencia Paterna/genética , Enfermedades Placentarias/genética , Complicaciones Hematológicas del Embarazo/genética , Desprendimiento Prematuro de la Placenta/epidemiología , Desprendimiento Prematuro de la Placenta/genética , Resistencia a la Proteína C Activada/epidemiología , Adulto , Estudios de Casos y Controles , Factor V/genética , Femenino , Enfermedades Fetales/epidemiología , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/genética , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Mutación , Enfermedades Placentarias/epidemiología , Preeclampsia/epidemiología , Preeclampsia/genética , Embarazo , Complicaciones Hematológicas del Embarazo/epidemiología , Resultado del Embarazo , Prevalencia , Protrombina/genética , Mortinato/epidemiología , Mortinato/genéticaRESUMEN
OBJECTIVE: To develop a predictive risk model for early-onset pre-eclampsia (EO-PE) using maternal characteristics, combined screening markers, previously reported biomarkers for PE and mean arterial pressure (MAP). METHODS: This retrospective study was conducted at Oulu University hospital between 2006 and 2010. Maternal serum from first trimester combined screening was further analyzed for alpha fetoprotein (AFP), placental growth factor (PlGF), soluble tumor necrosis factor receptor-1 (sTNFR1), retinol binding protein-4 (RBP4), a disintegrin and metalloprotease-12 (ADAM12), soluble P-selectin (sP-selectin), follistatin like-3 (FSTL3), adiponectin, angiopoietin-2 (Ang-2) and sex hormone binding globulin (SHBG). First, the training sample set with 29 cases of EO-PE and 652 controls was developed to study whether these biomarkers separately or in combination with prior risk (maternal characteristics, first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotrophin (fß-hCG)) could be used to predict the development of EO-PE. Second, the developed risk models were validated with a test sample set of 42 EO-PE and 141 control subjects. For the test set MAP data was also available. RESULTS: Single marker statistically significant (ANOVA p<0.05) changes between control and EO-PE pregnancies were observed with AFP, RBP4 and sTNFR1 with both training and test sample sets. Based on the test sample set performances, the best detection rate, 47% for a 10% false positive rate, was achieved with PlGF and sTNFR1 added with prior risk and MAP. CONCLUSION: Based on our results, the best first trimester biomarkers to predict the subsequent EO-PE were AFP, PlGF, RBP4 and sTNFR1. The risk models that performed best for the prediction of EO-PE included prior risk, MAP, sTNFR1 and AFP or PlGF or RBP4.
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Presión Arterial/fisiología , Preeclampsia/diagnóstico , Valor Predictivo de las Pruebas , Primer Trimestre del Embarazo/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Diagnóstico Precoz , Femenino , Humanos , Proteínas de la Membrana/sangre , Preeclampsia/sangre , Embarazo , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Proteínas Plasmáticas de Unión al Retinol/análisis , Estudios Retrospectivos , alfa-Fetoproteínas/análisisRESUMEN
BACKGROUND: Current screening methods for gestational diabetes mellitus (GDM) are insufficient in detecting the risk of GDM in the first trimester of the pregnancy. Recent metabolomic studies have detected altered amino acid and acylcarnitine concentrations in type 2 diabetes (T2D). Because of the similarities between T2D and GDM, the determination of these metabolites may be useful in early screening for GDM. AIM: To evaluate the association between GDM and first-trimester maternal serum concentrations of ten amino acids and 31 acylcarnitines. METHODS: This retrospective case-control study included data from pregnant women screened at Oulu University Hospital between 1.1.2008 and 31.12.2011. A total of 31,146 women participated voluntarily in a first-trimester combined screening (for chromosomal abnormalities). The study population included 69 women who developed GDM during pregnancy and 295 women without diabetes before or after pregnancy. The serum concentrations of ten amino acids and 31 acylcarnitines were analyzed from frozen serum samples taken in the first-trimester screening. Multiple of median (MoM) values were compared between the two groups. RESULTS: In the GDM group, serum levels of arginine were significantly higher (1.13 MoM vs. 0.97 MoM), and those of glycine (0.93 MoM vs. 1.03 MoM) and 3-hydroxy-isovalerylcarnitine (0.86 MoM vs. 1.03 MoM) significantly lower compared to the control group (all p < 0.01). In each case, arginine, glycine, and 3-hydroxy-isovaleryl-carnitine would have detected 46%, 32%, and 39% of GDM cases, with a false-positive rate of 20%. Combining these three metabolites with the first-trimester serum marker pregnancy-associated plasma protein A (PAPP-A) and prior risk (age, BMI, and smoking) achieved a detection rate of 72%. CONCLUSION: There are significant differences in the serum levels of arginine, glycine, and 3-hydroxy-isovalerylcarnitine between controls and women who subsequently develop GDM. These differences were already existent in the first trimester of the pregnancy. The use of metabolites in combination with prior risk and first-trimester PAPP-A represents a reliable method to identify women at risk of GDM.