Study population and sample recruitment
Eligible patients will be enrolled during the ultrasound scan of the
first trimester combined screening test for aneuploidies
(11-13+6 weeks), according to the following inclusion
criteria: singleton viable pregnancy undergoing prenatal screening,
gestational age between 11 and 13+6 weeks of
pregnancy, further confirmed by a crown-rump length (CRL) measurement of
45-84 mm, and signed written informed consent. Language barrier, any
known maternal disease or required chronic therapy, oocyte donation
pregnancy, as well as fetal congenital anomalies and aneuploidies
confirmed at birth, represent the exclusion criteria.
Figure 1 summarizes the study step points with maternal, fetal and
neonatal data collection.
At enrollment, all women will fill a general questionnaire covering
details on age, pregestational body mass index (BMI), ethnicity, mode of
conception, lifestyle habits, family and personal history. A modified
version of the nutritional checklist developed by the International
Federation of Gynecology and Obstetrics (FIGO) in 2015 will be used to
provide a 0 to 10 nutritional score measuring the adherence to a healthy
diet and lifestyle, as presented in Figure 2. Additional adaptations of
the checklist are based on the Italian guidelines on maternal nutrition
during pregnancy, including one additional question on the consumption
of iodized salt and the modified recommended intake of fruit and
vegetables to five portions per day. In detail, the FIGO Nutrition
Checklist consists of four sections covering 1. specific dietary
requirements (e.g. diet or allergy), 2. BMI calculation, 3. diet
quality, and 4. specific micronutrients deficiency queries (e.g. folic
acid), thus giving the healthcare providers the possibility to collect
baseline information on maternal nutritional status and to promote
conversations about nutrition during pregnancy. A one-point score is
calculated in case of affirmative answer for: consumption of meat 2–3
times per week, fruit and vegetables at least 5 times per day, fish 1–2
times per week, dairy products daily, whole cereals at least once per
day, sweet and snacks less than 5 times per weeks, first trimester
hemoglobin concentrations higher than 11 g/L, folic acid
supplementation, use of iodized salt, and sun exposure at least 10–15
min per day. The questionnaire provides a final calculation of a 0 to 10
score, as the sum of single question scores.
As required by the first trimester combined screening test, biochemical
parameters and fetal ultrasound parameters will be collected.
Biochemical parameters, including serum pregnancy-associated plasma
protein-A (PAPP-A) and free β-human chorionic gonadotropin (free β-HCG),
will be obtained from one venous blood sample collected at 10 weeks of
gestation, by using a solid-phase two-site sequential chemiluminescent
immunometric assay (BRAHMS Kryptor, Hennigsdorf, Germany). All
ultrasound measurements will be performed by a Fetal Medicine Foundation
certified sonographer according to the International Society of
Ultrasound in Obstetrics and Gynecology (ISUOG) guidelines. In addition
to parameters required for the combined screening test and including
crown-rump length (CRL), nuchal translucency (NT), and biparietal
diameter (BPD), transabdominal measurements of Doppler velocimetry of
uterine arteries (UA) and two-dimensional placental volume will be
performed. Transabdominal UA Doppler velocimetry is achieved identifying
the artery along the uterine body from a midsagittal section and moving
laterally to the paracervical vascular plexus (12). The two-dimensional
estimated placental volume (EPV) measurement will be performed according
to the formula proposed by Sonek J. et al, by acquiring assessment of
placental width (measuring the distance among placental edges,
perpendicular to surface of placenta), height (as distance from
uteroplacental interface to line used to measure width) and thickness
(as distance from uteroplacental interface to fetal surface of placenta)
(13).
As required by national guidelines of low risk pregnancy care, second
(20-22 weeks) and third (30-32 weeks) trimester ultrasound data of fetal
biometry (BPD, HC, AC, FL) and Doppler velocimetry (uterine arteries
doppler, fetal umbilical artery Doppler, fetal middle cerebral artery
Doppler) will be obtained from medical records. Data on delivery
outcomes, including gestational age, delivery mode, blood loss, neonatal
data and placental weight will be recorded from medical registry or
phone interview.
The recruitment process and follow up will last 30 months.