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Table 6 Assessment considerations in periconceptional supplementation trials

From: Perspectives on the design and methodology of periconceptional nutrient supplementation trials

Study activity

Non-pregnant

Pregnant

Placenta

Post-partum

Child (birth – 24 months)

Health history and assessment

Exclusion criteriaa Demographic and socio-economic status; Food security, dietary and drug history; Morbidity, obstetric and reproductive histories; BP; mental health; workload

Uterine artery pulsatility (UtAPI) and resistance indices (UtARI) at 28–32 w gestation;b BP; Ultrasound: 1st trimester: gestational and yolk sac development; 2nd/3rd: biparietal diameter, HC, AC, FL; LMP; drug use

History of pre-eclampsia

Mental health

Gestational assessment, infant feeding practices, neuro-behavioural assessments, fat-free mass oto-acoustic emissions; drug use

Anthropometry c

Wt, Ht, MUAC, Skin-fold thickness, BMI, ultrasound of abdominal visceral fat

Wt, Ht, MUAC

Wt, diameter

Wt, Ht, MUAC, BMI

Wt, recumbent Lt, crown-rump Lt; head, upper arm, abdominal circumference

Haematology

Baseline anaemia

Hb, MCHC, MCV, red cell distribution width

Cord Hb, ferritin, sTfR

Hb, cord clamping time

Hb at 3, 6 12 months

Biochemistry

Iron biomarkers,d sera and RBC folate, micronutrient profiling, metabolome

Iron biomarkers, sera and RBC folate; amino acids, lipids, fatty acids, renal function, gluconeogenesis, anti-oxidant profile,e metabolome

Ratio plasminogen-activator inhibitor (PAI)-1: PAI-2,f uterine-artery Doppler waveform at 18–22 weeks gestation,f cord blood metabolitesg

Iron biomarkers, micronutrients, amino acids, lipids, fatty acids, breast milk composition

Iron and folate biomarkers, amino acids, lipids, fatty acids, micronutrients, anti-oxidant profile,e metabolome

Endocrinology

Adipose tissue-secreted hormones (adipokines): leptin, visfatin, resistin, apelin, omentin, sex steroids, growth factors

Cortisol, progesterone, oestradiol, thyroid function, pregnancy associated plasma protein-A (PAPP-A); free β-human chorionic gonadotrophin (β-hCG)

Cord placental growth factor (PlGF); soluble FMS-like tyrosine kinase-1 (sFlt1)h

Adipokines

Hormonal growth factors, glucose homeostasis

Infection

Blood/stool samples, STIsi HIV, bacterial vaginosis, vaginal microbiome

Bacterial vaginosis, STIs

Chorioamnionitis, malaria histology

Bacterial vaginosis, vaginal microbiome

Gut helminths, malaria, respiratory, diarrhoea, HIV, health attendances, fecal microbiome, thymic size

Inflammation

CRP, AGP

CRP, AGP

Specific maternal-cord antibody titres

CRP, AGP

CRP, AGP

Genotype profile

Blood storage

-

Micro RNAsj

-

Blood storage, micro RNAs

  1. Abbreviations: Wt weight, Ht height, MUAC mid-upper arm circumference, BMI body mass index, HC head circumference, AC abdominal circumference, FL femur length, CRP serum C-reactive protein, AGP alpha-1-acid glycoprotein, Hb haemoglobin, BP blood pressure, STI sexually transmitted infections, LMP last menstrual period
  2. a Dependent on study design and location these would include: sickle cell disease and hemoglobinopathies; severe anaemia (Hb <7 g/dl); diabetes; current pregnancy; pre-menarcheal subjects; severe malnutrition or other severe illness (see study design section)
  3. b The uterine artery pulsatility index (UtAPI) and resistance index (UtARI) at 28–32 weeks gestation and record of diastolic notching. Quantify systolic and diastolic components of the flow velocity waveform in a specific blood vessel over a single cardiac cycle, with higher values indicating downstream vascular resistance
  4. c Duplicate measurements
  5. d Serum ferritin, transferrin receptor (sTfR), hepcidin, free erythrocyte protoporphyrin, transferrin saturation
  6. e Metabolomic profiling
  7. f A surrogate marker of placental perfusion which correlates with trophoblast invasion [15]
  8. g Blood metabolites including: insulin, glucose, liver enzymes, amino acids, fatty acids
  9. h Placental growth factor (PlGF) is a proangiogenic factor sharing high homology with vascular endothelial growth factor; soluble FMS-like tyrosine kinase-1 (sFlt1) is a potent antagonist of vascular endothelial growth factor and PlGF signalling
  10. i Screening for regionally specific infections; parasitic infections (e.g., malaria, enteric helminthiasis, schistosomiasis); genital tract infections (e.g., bacterial vaginosis, STI syndromes)
  11. j Placental micro RNA expression of small non-coding RNAs that are involved in post-transcriptional gene regulation