Deciphering the Impact of Early-Life Exposures to Highly Variable Environmental Factors on Foetal and Child Health: Design of SEPAGES Couple-Child Cohort
Abstract
:1. Introduction
1.1. Health Effects of Early-Life Environmental Exposures
1.2. Issues Related to Exposure Assessment
1.3. Issues Related to Assessment of Health and Biological Parameters
1.4. Study Aims
2. Design of SEPAGES Couple-Child Cohort
2.1. Study Population
2.1.1. Study Area
2.1.2. Recruitment
2.2. Pilot Study
2.3. Biological Samples
2.3.1. Urine Samples
2.3.2. Blood Samples
2.3.3. Biological Samples at Delivery
2.3.4. Fecal Samples
2.3.5. Other Biospecimens
2.4. Assessment of Exposure to Environmental Pollutants
2.4.1. Outdoor Exposome
Air Pollutants
Other Components of the Outdoor Exposome
2.4.2. Behaviors
Drug Use, Cosmetics, Cleaning Products
Nutrition and Diet
2.4.3. Internal Exposome
2.5. Biological Parameters and Health Outcomes Assessed
2.5.1. Respiratory Health
- -
- Functional residual capacity (FRC), a measure of lung volume and lung clearance index (LCI), which reflects inhomogeneity of the ventilation. These were assessed by multiple breath washout (MBW) technique using pure oxygen as tracing gas. These parameters reflect lung physiology and are considered early predictors of adverse respiratory health in childhood [70]. The mean of two to three valid measures conducted within an interval of 10-15 minutes was recorded [50].
- -
- Tidal breathing flow-volume loops (TBFVL) in quiet sleep. One hundred cycles were recorded per child. The main parameters assessed were respiratory frequency, mean respiratory flow and ratio of peak tidal expiratory flow to total expiratory time (tPTEF/tE), a proxy of bronchial obstruction.
2.5.2. Growth
2.5.3. Neurodevelopment
2.5.4. Methylome and Microbiome
2.5.5. Thyroid-Related Hormones
2.5.6. Immunological Parameters
2.5.7. Cardiovascular Health
2.6. Other Covariates
2.7. Overview of Data Collection, Storage and Management System
2.8. Secured Data Linkage
2.9. Ethical Agreements
3. Conclusions
3.1. A New Type of Cohort with Intense Exposure Assessment
3.2. Overview of First Findings and Analyses Currently Planned
3.3. Strengths and Weaknesses of the Cohort
3.4. Mode of Collaboration and Existing Collaborations
3.5. Epidemiology and Toxicology Joining Forces for DOHaD Research
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | Population of Pregnant Women | |||||||
---|---|---|---|---|---|---|---|---|
SEPAGES Women n = 484 | Approached but Not Included 1 n = 1841 | Whole Grenoble Area 2 n = 17,899 | Whole France 3 n = 12,950 | |||||
Age (years), mean ± SD | 32.7 ± 3.9 | 31.0 ± 4.7 | 31.1 ± 5.0 | 30.3 ± 5.2 | ||||
Age (categories) | (<0.001) 4 | (<0.001) 5 | (<0.001) 6 | |||||
<20 | 0 | (0.0) | 13 | (0.7) | 113 | (0.6) | 204 | (2.5) |
20–24 | 13 | (2.7) | 128 | (7.0) | 1483 | (8.3) | 1553 | (12.0) |
25–29 | 113 | (23.3) | 589 | (32.0) | 5116 | (28.6) | 4052 | (31.3) |
30–34 | 230 | (47.5) | 683 | (37.1) | 6656 | (37.2) | 4377 | (33.8) |
35–39 | 117 | (24.2) | 353 | (19.2) | 3626 | (20.3) | 2236 | (17.3) |
≥40 | 11 | (2.3) | 74 | (4.0) | 900 | (5.0) | 519 | (4.0) |
Maternal Parity 7 | (0.002) 4 | (<0.001) 5 | (<0.001) 6 | |||||
0 | 222 | (45.9) | 816 | (44.6) | 6036 | (39.7) | 5464 | (42.2) |
1 child | 214 | (44.2) | 721 | (39.4) | 6098 | (40.1) | 4609 | (35.6) |
≥2 children | 48 | (9.9) | 294 | (16.1) | 3071 | (20.2) | 2872 | (22.2) |
Marital status | (0.005) 4 | (<0.001) 6 | ||||||
In a relationship 8 | 483 | (99.8) | 1808 | (98.2) | NA | 9593 | (81.9) | |
No relationship | 1 | (0.2) | 33 | (1.8) | 2123 | (18.1) | ||
Education level | (<0.001) 4 | (<0.001) 5 | (<0.001) 6 | |||||
Primary school | 0 | (0.0) | 4 | (0.2) | 106 | (1.4) | 187 | (1.6) |
Secondary Education | 6 | (1.2) | 226 | (12.3) | 677 | (9.2) | 2489 | (21.3) |
High School education (Bac) | 23 | (4.8) | 316 | (17.3) | 1404 | (19.2) | 2521 | (21.6) |
Undergraduate or graduate | 452 | (94.0) | 1285 | (70.2) | 5141 | (70.2) | 6464 | (55.4) |
Nationality | (<0.001) 6 | |||||||
French | 394 | (94.7) | NA | NA | 10,083 | (85.9) | ||
Other European country 9 | 18 | (4.3) | 416 | (3.5) | ||||
African country | 0 | (0.0) | 993 | (8.5) | ||||
Other nationality | 4 | (1.0) | 243 | (2.1) | ||||
Working status during pregnancy | (<0.001) 4 | (<0.001) 5 | (<0.001) 6 | |||||
Employed | 434 | (92.9) | 1532 | (85.0) | 6806 | (75.0) | 7830 | (68.1) |
Unemployed | 13 | (2.8) | 79 | (4.4) | 508 | (5.6) | 1928 | (16.8) |
Housewife/parental leave/in training | 20 | (4.3) | 191 | (10.6) | 1757 | (19.4) | 1630 | (14.2) |
Not working, other | 0 | (0.0) | 0 | (0.0) | NA | 108 | (0.9) | |
Infertility treatment | (0.02) 6 | |||||||
None | 426 | (90.1) | NA | NA | 10,896 | (93.1) | ||
ART 10, ovulation induction | 47 | (9.9) | 805 | (6.9) | ||||
Height | (0.80) 6 | |||||||
<160 cm | 87 | (18.1) | NA | NA | 2,206 | (18.9) | ||
160–169 cm | 281 | (58.5) | 6744 | (57.8) | ||||
170–179 cm | 105 | (21.9) | 2587 | (22.2) | ||||
≥180 cm | 7 | (1.5) | 121 | (1.0) | ||||
Weight before pregnancy | (<0.001) 6 | |||||||
<50 kg | 44 | (9.1) | NA | NA | 968 | (8.3) | ||
50–59 kg | 205 | (42.4) | 3791 | (32.5) | ||||
60–69 kg | 147 | (30.4) | 3424 | (29.4) | ||||
70–79 kg | 59 | (12.2) | 1816 | (15.6) | ||||
≥80 kg | 29 | (6.0) | 1661 | (14.2) | ||||
BMI before pregnancy | (<0.001) 6 | |||||||
<18.5 kg/m2 | 29 | (6.0) | NA | NA | 863 | (7.4) | ||
18.5–24.9 kg/m2 | 364 | (75.8) | 7045 | (60.8) | ||||
25–29.9 kg/m2 | 67 | (14.0) | 2312 | (20.0) | ||||
≥ 30 kg/m2 | 20 | (4.2) | 1368 | (11.8) | ||||
Smoking before pregnancy | (<0.001) 6 | |||||||
0 | 385 | (89.1) | NA | NA | 8217 | (69.5) | ||
1–9 cig./day | 37 | (8.6) | 1350 | (10.9) | ||||
≥ 10 cig./day | 10 | (2.3) | 2132 | (19.6) | ||||
Smoking during pregnancy 11 | (<0.001) 6 | |||||||
0 | 402 | (93.3) | NA | NA | 9798 | (83.4) | ||
1–10 cig./day | 29 | (6.7) | 1447 | (12.3) | ||||
>10 cig./day | 0 | (0.0) | 499 | (4.2) |
Characteristic | Children Population | |||||
---|---|---|---|---|---|---|
Included in SEPAGES (n = 471) | Grenoble 1 (n = 17,899) | Whole France 2 (n = 13,158) | ||||
Sex | (0.18) 3 | (0.02) 4 | ||||
Girl | 218 | (46.5) | 8878 | (49.7) | 6630 | (52.0) |
Boy | 251 | (53.5) | 8986 | (50.3) | 6118 | (48.0) |
Gestational duration | (0.05) 3 | (<0.001) 4 | ||||
≤37 weeks of amenorrhea | 50 | (10.6) | 1908 | (10.7) | 1938 | (14.7) |
38–39 weeks of amenorrhea | 181 | (38.4) | 7919 | (44.5) | 5593 | (42.5) |
40 weeks of amenorrhea | 146 | (31.0) | 4793 | (26.9) | 3348 | (25.4) |
≥ 41 weeks of amenorrhea | 94 | (20.0) | 3194 | (17.9) | 2277 | (17.3) |
Weight at birth | (0.41) 3 | (<0.001) 4 | ||||
<1500 g | 2 | (0.4) | 157 | (0.9) | 140 | (1.1) |
1500–2499 g 2500–2999 g | 14 80 | (3.0) (17.2) | 740 3346 | (4.1) (18.7) | 840 2716 | (6.4) (20.6) |
≥3000 g | 369 | (79.4) | 13,629 | (76.3) | 9462 | (71.9) |
Length at birth | (0.09) 3 | (<0.001) 4 | ||||
≤47 cm | 42 | (9.1) | 1935 | (11.4) | 2376 | (19.7) |
48–49 cm | 124 | (26.8) | 5101 | (30.1) | 3700 | (30.6) |
50–51 cm ≥52 cm | 191 106 | (41.3) (22.9) | 6384 3513 | (37.7) (20.7) | 4220 1785 | (34.9) (14.8) |
Breastfeeding at birth | (<0.001) 3 | (<0.001) 4 | ||||
Yes | 431 | (93.9) | 12,901 | (77.0) | 7884 | (66.7) |
No | 28 | (6.1) | 3358 | (23.0) | 3936 | (33.3) |
Before Delivery | After Delivery | |||||||
---|---|---|---|---|---|---|---|---|
Matrix | Mother | Father | Delivery (mother) | Birth (child) | 2 months (child) | 12 months (child) | 24 months (child) | 36 months (child) |
Whole blood | 1 EDTA tube (3 mL) | 1 EDTA tube (3 mL) | 1 EDTA tube (3 mL) | One drop | ||||
Serum | 5 (500 µL) aliquots | 5 (500 µL) aliquots | 5 (500 µL) aliquots | 4 (250 µL) aliquots | 4 (250 µL) aliquots | |||
Plasma (EDTA) | 3 (500 µL) aliquots | 3 (500 µL) aliquots | 3 (500 µL) aliquots | 4 (250 µL) aliquots | 4 (250 µL) aliquots | |||
Plasma Heparine | 3 (500 µL) aliquots | 3 (500 µL) aliquots | 3 (500 µL) aliquots | |||||
Buffy Coat | 1 aliquot | 1 aliquot | 1 aliquot | 1 aliquot | 1 aliquot | |||
Blood-RNA | 1 Tempus™ tube (3 mL) | 1 Tempus™ tube (3 mL) | 1 Tempus™ tube (3 mL) | 1 Tempus™ tube (3 mL) | 1 Tempus™ tube (3 mL) | |||
Placental-RNA | 3 aliquots | |||||||
Placenta (PFA) | 1 aliquot | |||||||
Placenta | 2 aliquots | |||||||
Hair | ~200 mg | ~200 mg | ~200 mg | One strand | One strand | One strand | One strand | |
Urine | 44 to 64 samples | 1 spot sample | 1 spot sample | 1 spot sample | 9 samples | 9 samples | 14 samples | |
Stool | 3 aliquots (meconium) | 3 aliquots | 3 aliquots | 3 aliquots | 3 aliquots | |||
Milk | 3 (1.5 mL) aliquots | |||||||
Buccal cells | 2 samples | 2 samples | ||||||
Nasal cells | 2 samples | |||||||
Nails | 10 pieces |
Exposure | Tools/Biological Matrix | Time Points (M: Mother C: Child) |
---|---|---|
Urban exposome—personal measures | ||
PM2.5 concentration and oxidative potential | MicroPem (RTI International) 1 | M: Around 18 and 34 gestational weeks 2 C: Around 2 and 36 months 3 |
Soot (weekly measurement) | MicroAeth (AethLabs) 1 | M: Around 18 gestational weeks 2 |
NO2 mass concentration | Passive Sampler (Passam A.G) | M: Around 18 and 34 gestational weeks 2 C: Around 2, 12 and 36 months 3 |
Benzene, toluene, ethylbenzene, xylenes | Passive Sampler (Passam A.G) | M: Around 18 and 34 gestational weeks C: Around 2 months |
Physical activity | ActiGraph accelerometer (ActigraphCorp) 1 | M: Around 18 and 34 gestational weeks C: Around 2, 12 and 36 months |
Noise | App NoiseTube (NoiseTube) 1 | M: Around 18 and 34 gestational weeks 2 C: Around 2 and 36 months 3 |
Time-space activity | Dispersion model (10 m grid) of PM2.5, PM10 and NO2 coupled with GPS and diaries data | M: Around 18 and 34 gestational weeks 2 C: Around 2 and 36 months 3 |
Temperature | Thermometer DL 101T (VoltCraft) | M: Around 18 and 34 gestational weeks 2 C: Around 2 and 36 months 3 |
Cleaning and cosmetic products | Camera on a smartphone and Cobanet 4 smartphone application (EpiConcept) | M: Around 18 and 34 gestational weeks 2 C: Around 2 and 36 months 3 |
Drugs | Photographs and questionnaires | M: From conception onwards |
Urban exposure—estimates at the home address | ||
PM2.5, PM10 and NO2 | Dispersion model (10 m grid) of PM2.5, PM10 and NO2 | Home addresses estimate available for whole follow-up |
Temperature, atmospheric pressure | Meteorological stations and models | |
Chemical exposome5 | ||
Phenols Bisphenols A, AF, B, S, F; triclosan; triclocarban; methyl, ethyl, butyl, propyl parabens; benzophenone 3. | Urine (mother child) | M: Around 18 and 34 gestational weeks 2 C: Around 2, 12 and 36 months 3 |
Phthalates MEP (DEP metabolite) MiBP (DiBP metabolite) MnBP (DBP metabolite) MBzP (BBP) MEHP (DEHP metabolite) MEHHP (DEHP metabolite) MEOHP (DEHP metabolite) MECPP (DEHP metabolite) MMCHP (DEHP metabolite) oh-MiNP (DINP metabolite) oxo-MiNP (DINP metabolite) cx-MiNP (DINP metabolite) | Urine (mother child) | M: Around 18 and 34 gestational weeks 2 C: Around 2, 12 and 36 months 3 |
DINCH metabolites | Urine (mother, child) | M: Around 18 and 34 gestational weeks 2 |
oh-MINCH oxo-MINCH oh-MPHP | C: Around 2, 12 and 36 months 3 | |
Organophosphate pesticides metabolites DMP, DMTP, DEP, DETP, ΣDAP 6 | Urine (mother) | Around 18 and 34 gestational weeks 2 |
Perfluorinated compounds 5 PFSAs (including PFOS, PFHxS), 11 PFCAs (including PFOA, PFNA), 3 FOSAs | Serum | M: Around 18 gestational weeks |
Health Outcome | Assessment | Whom | Time Point |
---|---|---|---|
Foetal Growth | Ultrasound records Measurements (birth) | Foetus Newborn | 12, 22, 32 gestational weeks Birth |
Postnatal growth | Clinical assessments (weight, height, skin folds) | Child | At birth, 2, 12 and 36 months |
Questionnaires | Child | Every 3 to 12 months | |
Respiratory health | Lung function test: spirometry, exhaled NO | Mother and father | 1 year after delivery (M); Inclusion (F) |
Lung function test: multiple breath washout test, tidal breathing flow-volume loops Lung function test: forced oscillation technique (FOT) | Child | 2 months 36 months | |
Questionnaires (respiratory symptoms and diseases) | Mother Father Child | First and third trimesters Inclusion Every 3 to 12 months | |
Allergy | Skin prick tests (12 allergens for mother and father; 5 allergens for the child) | Mother Father Child | 1 year after delivery Inclusion 36 months |
Neuro-Development/Neurological outcomes | ADBB scale WPPSI-IV Eye tracking N-Back WAIS | Child Mother | 12 months 36 months 5, 12 and 24 months 1 3 years after delivery |
Questionnaires VineLand MChat MacArthur SRS and BRIEF-P | Child | 12 and 24 months 24 months 12 and 24 months 36 months | |
Cardiovascular health | Electrocardiogram (ECG), blood pressure | Mother and Father | During pregnancy and 1 year after delivery (M) At inclusion (F) |
Blood pressure | Child | At 2, 12 and 36 months |
Cohort Generation and Period | Recruitment Period and Participants | Biospecimens | Personal Measurements | Typical Example | Limitations |
---|---|---|---|---|---|
First generation (1990s and before) “Birth cohorts” | Birth or later. Children only generally. | After delivery only: maternal and possibly child spot biospecimens | None (questionnaire or model-based assessment exposure) | ALSPAC [87], GINI cohorts | Limited ability to investigate the effect of pregnancy exposures (besides atmospheric pollutants) |
Second generation (2000-) | Pregnancy. Mother and child. | Pregnancy maternal spot (urine and blood) samples. Possibly DNA (mother, child, placenta) and child postnatal blood | Possibly use of a dosimeter during a single follow-up period | EDEN [88], INMA [89] cohorts | Limitations in terms of assessment of exposure to non-persistent compounds |
Third generation (From after 2015) | Early pregnancy or preconception. Mother, father, child. | Repeated pregnancy maternal and child (possibly pooled) urine samples. Blood (mother, father, chord, offspring), DNA, RNA, possibly live cells (mother, father, offspring), placental sample, microbiome… | Repeated use of personal monitors for air pollutants, radiation, noise, temperature…. Detailed time space activity information. | SEPAGES cohort | Possible challenges to implement for a large sample size (1000-100,000 families), unless very large funding available |
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Lyon-Caen, S.; Siroux, V.; Lepeule, J.; Lorimier, P.; Hainaut, P.; Mossuz, P.; Quentin, J.; Supernant, K.; Meary, D.; Chaperot, L.; et al. Deciphering the Impact of Early-Life Exposures to Highly Variable Environmental Factors on Foetal and Child Health: Design of SEPAGES Couple-Child Cohort. Int. J. Environ. Res. Public Health 2019, 16, 3888. https://doi.org/10.3390/ijerph16203888
Lyon-Caen S, Siroux V, Lepeule J, Lorimier P, Hainaut P, Mossuz P, Quentin J, Supernant K, Meary D, Chaperot L, et al. Deciphering the Impact of Early-Life Exposures to Highly Variable Environmental Factors on Foetal and Child Health: Design of SEPAGES Couple-Child Cohort. International Journal of Environmental Research and Public Health. 2019; 16(20):3888. https://doi.org/10.3390/ijerph16203888
Chicago/Turabian StyleLyon-Caen, Sarah, Valérie Siroux, Johanna Lepeule, Philippe Lorimier, Pierre Hainaut, Pascal Mossuz, Joane Quentin, Karine Supernant, David Meary, Laurence Chaperot, and et al. 2019. "Deciphering the Impact of Early-Life Exposures to Highly Variable Environmental Factors on Foetal and Child Health: Design of SEPAGES Couple-Child Cohort" International Journal of Environmental Research and Public Health 16, no. 20: 3888. https://doi.org/10.3390/ijerph16203888