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Polycystic ovary syndrome (PCOS) is a complex and frequent disorder with a heterogeneous clinical presentation varying throughout life, from birth up to post-menopause. Although mostly known for its reproductive consequences, PCOS is associated with metabolic abnormalities related to insulin resistance and obesity. Children born from PCOS mothers are considered to be at risk for early insulin resistance, leading to development of PCOS and metabolic abnormalities in childhood and adolescence. Obesity and insulin resistance are considered as states of low- and pro-inflammation associated with endothelial dysfunction. In addition, it has been shown that endothelial dysfunction develops from the first decade of life in response to genetic and environmental risk factors. Therefore, offspring of women with PCOS may be at increased risk for vascular disease later in life. Moreover, some evidence suggests that early life respiratory disease also contributes to later life cardiovascular consequences. The number of studies on offspring of PCOS mothers is low and a systematic follow up of children born form PCOS mothers has not been performed yet. the investigators propose a systematic evaluation of cardiometabolic and pulmonary health characteristics of children (aged 2,5-8 years) born from mothers diagnosed with PCOS. A saliva sample will be performed to determine the biochemical androgenic status of the children. Mothers of these children have undergone standardized phenotyping prior to conception; the investigators will therefore be able to correlate the metabolic status of the mother around the time of conception and the cardiometabolic and pulmonary health of their offspring.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Children born from mothers who are diagnosed with PCOS | Children at the age of 2.5-4 years or at the age of 6-8 years born from mothers who are diagnosed with PCOS at the University Medical Centre in Utrecht (UMCU) in the period 2004-2012 (n=891) will be asked to participate. Children who were born before the diagnosed PCOS of their mothers at the UMCU will be asked to participate too. All mothers have been diagnosed with PCOS according to standardised extensive diagnostic work-up and have given informed consent to be approached for future research purposes. | ||
| Children who participated in the WHISTLER study | Children who participated in the WHISTLER 3 (11-163) and WHISTLER/Cardio study (10-194) in 2002-2012. The children were born from mothers with a regular cycle prior to conception who conceived naturally. The children were examined at the age of 2.5-4 years or at the age of 7-8 years. The data of the WHISTLER 3 and WHISTLER/Cardio study have already been collected. |
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| Measure | Description | Time Frame |
|---|---|---|
| Pulse wave velocity (age 2.5-4 years) | The pulse wave velocity will be measured twice using the Arteriograph at the right arm. This measurement will start by performing a blood pressure measurement at the first phase. In the second phase the pulse wave recording for pulse waveform analysis is performed. First the device will inflate back to the measured diastolic value and register the pulse waves and second, the device inflates further to the suprasystolic value (to the measured systolic value +35 mmHg), occluding the brachial artery completely in this way and registers the pulse waves. | 12 months |
| Echocardiography (age 2.5-4 years) | Echocardiography will be performed in a supine position. Three ECG electrodes will be attached on the skin. The child can watch a movie during the measurements. Using M-mode and Tissue Doppler Echocardiography several measurements of the systolic and diastolic function of the right and left ventricle will be performed. | 12 months |
| Anthropometry (both age categories) | Body height and weight will be measured to the nearest 0.1 cm and 0.1 kg respectively without wearing shoes. Distance between the jugular fossa and symphysis will be measured (needed for calculation of pulse wave velocity). Waist circumference will be measured twice at the bare skin using a non-elastic measuring tape, between the superior iliac anterior spine and the lowest rib in a horizontal line, at the end of a normal expiration. Hip circumference will be measured twice over light clothing at the most posterior point of the buttocks. Thoracic circumference will be measured at the end of the expiration and signs of respiratory disease will be noted. | 12 months |
| Carotid intima media thickness (age 6-8 years) | The carotid IMT will be determined by using ultrasound based on the gold standard Wall Track System (Art.lab System, Esaote and the Cardiovascular Research Institute Maastricht). | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Airway resistance (both age categories) | Measurements of the airway resistance will be measured with the MicroRint using the interrupter technique according to standardized criteria. The child breathes passively through a mouthpiece. A rapidly occluding valve automatically interrupts the airflow for a period so brief as to be imperceptible to the patient. The airway resistance will automatically be computed. |
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Inclusion Criteria:
Exclusion Criteria:
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Cases Children born from mothers who are diagnosed with PCOS at the UMCU will be asked to participate. Children who were born before the diagnosed PCOS of their mothers at the UMCU will be asked to participate too. All mothers have been diagnosed with PCOS according to standardised extensive diagnostic work-up and have given informed consent to be approached for future research purposes.
Controls Children who participated in the WHISTLER study (protocol number 10-194) in . The children were born from mothers with a regular cycle prior to conception and who conceived naturally. The children were examined at the age of 2.5-4 years or at the age of 6-8 years. The data of the WHISTLER 3 and WHISTLER/Cardio study have already been collected.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University medical Center Utrecht | Utrecht | Utrecht | 3584 CX | Netherlands |
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saliva, serum, plasma
| Fat mass determination (6-8 years) | The intra-abdominal fat will be assessed by ultrasound by determination of the distance between the posterior side of the linea alba and the anterior vertebrae. The subcutaneous fat will be determined by measuring the distance between the anterior side of the linea alba and the skin. Both fat compartments will be assessed longitudinally. | 12 months |
| Blood sample (6-8 years) | The venous puncture will be performed for the collection of the blood sample by using a butterfly needle, since this needle is smaller than the needles commonly used for venous puncture (vacutainer system) and will therefore reduce the pain of the venous puncture for the children. The venipuncture will be performed in a vein in the cubital fossa. Two different tubes of blood will be drawn, one sodium-heparin and one lithium-heparin tube, with in total a maximum of 19 cc blood. Prior to the venous puncture, a local anaesthetic, xylocaine spray, will be used at the location of the puncture. | 12 months |
| 12 months |
| Saliva sample (both age categories) | Saliva will be collected unstimulated by spittinh in a paper cup or with a Salimetrics children's swab. The saliva will be stored in a freezer (-80 degrees) | 12 months |
| Flow-volume measurements | Flow-volume measurements will be performed by using spirometry. | 12 months |
| Inflammatory markers in exhailed air | Nitric Oxide levels will be measured in exhaled air | 12 months |