Rio Birth Cohort Study on Environmental Exposure and Childhood Development – PIPA Project

Carmen Ildes R. Fróes Asmus; Arnaldo Prata Barbosa; Armando Meyer; Nataly Damasceno; Ana Cristina Simões Rosa; Roberto Medronho; Antônio Jose Ledo A. da Cunha; Josino Costa Moreira; Thatiana V. R. de B. Fernandes; Marlos Martins; Ronir Raggio Luiz; Volney de Magalhães Câmara

doi:10.5334/aogh.2709

Figures & Tables

Table I

Schedule for Data Collection.

	Prenatal	Birth	3m	6m	12m	24m	36m	48m
Clinical Exam
Anthropometric		×	×	×	×	×	×	×
Physical Exam		×	×	×	×	×	×	×
NCPDTests¹			×	×	×	×	×	×
Biological Samples
Umbilical Cord Blood		×
Meconium		×
Tissue samples²		×
Maternal milk			×	×
Urine (child)			×	×	×	×	×	×
Urine (mother)	×
Blood (mother)	×
Saliva (child)		×	×	×	×	×	×	×
Questionnaires
Gestation: 32^nd week	×
Birth		×
Follow up		×	×	×	×	×	×	×

[i] ¹ Neuromotor, cognitive and psychologic developmental tests; ²umbilical cord and placenta.

Table II

Environmental pollutants, types of sample and biological matrices.

Biologic Matrix	Environmental Pollutants	Types of sample
Prenatal: 27th to 32nd week.
Blood	Metals⁽¹⁾; Organochlorine pesticides; Bisphenol; Polychlorinated biphenyls (PCBs); Phthalates;	Parents
Urine	Metals⁽¹⁾ Pyrethroids; Bisphenol; Phthalates.	Parents
Birth
Umbilical Cord Blood	Metals⁽¹⁾ Organochlorine pesticides; Polychlorinated biphenyls (PCBs);	Newborn
Meconium	Metals⁽¹⁾	Newborn
Postnatal until 4 years old
Urine	Metals⁽¹⁾ Pyrethroids; Bisphenol; Phthalates.	Newborn/infant/toddler
Maternal Milk ⁽²⁾	Metals⁽¹⁾ Organochlorine pesticides; Polychlorinated biphenyls (PCBs).	Mother

[i] ⁽¹⁾ Metals: Lead, Arsenic. Cadmium and Mercury.

⁽²⁾ In the 3^rd and 6^th follow-up months.

Table III

Recruitment and participation in the PIPA Pilot Study.

Enrollment: October and November/2017 (2 months):
All pregnant women that attended the Prenatal Maternity School Program/UFRJ: 209 were invited to participate: 142 (67.9%): agreed.
Phase 1_PreNatal: 142 pregnant women, 139 (98%) collected blood, 142 (100%) urine and hair samples.
Phase 2_Birth: 135 (95, 1%) newborns: 126 (93%): collected umbilical cord blood samples; 54 (40%) collected urine samples; 117 (86.7%) collected meconium samples.
Phase 3_Follow-up: 130 eligible newborns: 77 (59%) returns (1^st, 3^rd or 6^th months).
A total of 177 newborns urine samples and 151 maternal milk samples were collected

Table IV

Comparison between the PIPA Pilot Study population data and Rio de Janeiro municipality population data.

Maternal Characteristics		PIPA Pilot Study		MRJ*
		%	(N)	%	(N)
Maternal age (139)⁽¹⁾	15 to 19 years old	8.6	(12)	13.9	(11194)
	20 to 39 years old	84.2	(117)	82.2	(66024)
	Up to 40 years old	7.2	(10)	3.9	(3154)
Years of Study (137)⁽¹⁾	Lower than 8 years of study	7.3	(10)	1.5	(13724)
	Higher than 8 years of study	92.7	(127)	82.5	(64494)
Ethnicity (135)⁽¹⁾	White	23.9	(34)	36.6	(29057)
	Non-White	71.1	(101)	63.4	(50230)
Newborn Characteristics		PIPA Pilot Study		MRJ*
		%	(N)	%	(N)
Gender	Male	57.3	(75)	51.1	(42,223)
	Female	43.7	(56)	48.9	(40,370)
BirthWeight ⁽¹⁾**	1.000–2500	9	(12)	8.6	(7,143)
	2500–3999	82.7	(110)	86.2	(71,224)
	> 4000	8.3	(11)	5.1	(4,234)
Birth Weight Adequacy for Gestational Age⁽¹⁾***	SGA	9.2	(11)	9.3	(165)****
	AGA	81.5	(97)	74.8	(1,324)****
	LGA	9.2	(11)	15.9	(282)****

[i] * MRJ: Rio de Janeiro Municipality. Source: MS Datasus/Sinasc–2016.

** Total PIPA number: 133 newborns; Total number RJ: 82.601 newborns.

*** Total PIPA number: 119 newborns.

**** Source: Kale et all, 2018 [25]; Total live births: 1,771; SGA: Small for the gestational age; AGA: adequate for the gestational age; LGA: large for the gestational age.

⁽¹⁾ Incomplete data on the specific covariates.

Table V

Metal levels in mother and umbilical cord blood – Pilot study.

Metals	Sample	Geometric Mean (95% IC)	Min	Max
Pb (µg/dL)	Mother blood	3.74 (3.40–4.12)	1.11	15.26
Umbilical Cord Blood	3.85 (3.53–4.19)	1.43	16.03
Hg (µg/L)	Mother blood	1.00 (0.85–1.18)	0.33	13.32
Umbilical Cord Blood	1.11 (0.97–1.27)	0.35	6.38
Cd (µg/L)	Mother blood	0.30 (0.29–0.53)	0.002	22.43
Umbilical Cord Blood	0.41 (0.32–0.52)	0.004	17.41
As (µg/L)	Mother blood	10.27 (9.37–11.18)	0.33	36.48
Umbilical Cord Blood	10.31 (9.75–10.93)	4.89	19.94

[i] Metal limits of detection: Pb 0.015 μg/L; Hg 0.007 μg/L; Cd 0.002 μg/L; As 0.003 μg/L.

Table VI

3BPA and 4FBA metabolite detection rates – Mother and child urine.

Samples	N analysed	3PBA ng mL-1 Detection		4FPBA Detection
Samples	N analysed	N	Rate	N	Rate
Mother Urine	140	67	47.9%	14	10%
Urine newborn	34	8	23.5%	0	0
Urine 1^st follow up	26	5	19.2%	0	0
Urine 2^nd follow up	50	14	28%	0	0
Urine 3^rd follow up	56	12	21.4%	0	0

[i] Metabolite limits of detection: 3BPA 0.06 ng mL–1; 4FPBA 0.05 ng mL–1.

Table VII

PIPA Project Risk Points and Responding Strategies.

Risk points	Responding strategies
Management structure
Underestimating of research costs	Permanent search for financial support Careful evaluation of the Pilot Study
Underestimating number of required staff High research assistant and interviewer turnover	Permanent hiring and training
Laboratory capacity underestimation Absence of laboratorial capacity regarding some specific technical analyses	Searches for other laboratories with similar qualifications Searches for international partnerships
Establishment of an infrastructure to attend and monitor the population during the cohort period	Accomplishment of alternative attendance schemes for using non-occupied periods
High local government decision makers turnover	Development and maintenance of ongoing collaboration and information nets between the researchers, the maternity and family health center teams
Participant recruitment
Living far from Maternity: monetary displacement costs	Monetary provision to help the participants with displacement costs to the Maternity School, during the follow-up period
No time to answer the questionnaire and to collect the biological samples	Review of the Enrollment questionnaire and Seminar dynamics to optimize data collection. Maximize participant convenience: data collection efficiency; data collector flexibility.
Participant retention	“Health, Environment and Child Development Educational Program”
Faults in the follow-up visits	Ongoing sensibilization and contact Establishment of a reliable liaison between the research team and project participants Use of digital tools: social nets, PIPA website, interactive communication Maintain communication: phone calls, messages. Obtain other contact detail information;
Data Collection	Daily tracking of participants approaching due dates Reminders through direct communication in each data collection time-point Rescheduling appointments Ongoing interviewer training Recruiting specialized teams to collect biological samples
Quality Assurance
Incompleteness of covariate data	Rigorous information system infrastructure Questionnaire information collected directly within the database system, using a single data entry with periodic response verification Periodic data tracking and quality checks
	Unanimous adaptation of pre-specified data collection and management protocols Collecting data relating to numerous potential confounding variables Careful control through statistical analyses