Background
Methods
Literature sources and search strategy
Study selection and data extraction
Results
Study | Study type, population and location | Exposure assessment | Conclusions | Reason for ineligibility |
---|---|---|---|---|
Pogoda and Preston-Martin, 1997. [35] | Follow up to population-based case–control study of pediatric brain tumors in Los Angeles county, CA, US, from 1984 through June 1991. Cases, N = 224, Controls, N = 218. | Household pesticide use from pregnancy to diagnosis assessed by phone interviews. | Risk was elevated for flea-tick pesticides, OR = 1.7, 1.1-2.6. | Round up was listed among pesticides (herbicides) used in law-garden. However, only associations between broad classes of pesticides and the outcome (brain tumors) were tested. Exposure assessment encompassed both pre and postnatal development and did not discriminate between the two periods. |
Larsen et al., 1998. [36] | Retrospective study of time-to-pregnancy (fecundability) among Danish farmers (N = 1146). Telephone interviews on time-to-pregnancy (How many months did it take your wife to get pregnant?) and reproductive history | Exposure data obtained by phone interviews (use of pesticides the year before the youngest child was born). Exposed groups: traditional farmers, traditional farmers who did not spray pesticides themselves, organic farmers. | Fecundability ratio between “traditional farmers who applied pesticides” and “organic farmers”: 1.3, 0.75 – 1.40. | Although GLY is mentioned in the Introduction section, authors did not investigate whether ‘time-to-pregnancy” was altered specifically by this herbicide. The authors tested only classes of “pesticides”. |
Nevison 2014. [37] | Ecological-type study design. Temporal trends (1970–2005) in autism compared to temporal trends in US application of GLY. Autism counts were from the Individuals with Disabilities Education Act (IDEA) database for 50 US states plus District of Columbia. | GLY exposure data were aggregated at the group level. Data were from US department of agriculture. | Increasing trends in application of GLY positively correlated to a marked rise in autism prevalence in the US. | In this study of temporal trends, data on potential exposure were aggregated at the whole US population level and encompasses preconception, pre-natal and postnatal periods of development. Moreover, the ecological study design leaves the door wide open for non-causal explanations for the observed parallel rise in temporal trends in GLY use and autism prevalence. |
Study | Study type, population and location | Exposure assessment | Adverse pregnancy outcome | Association with GLY – Statistical Analysis OR (CI 95 %) |
---|---|---|---|---|
Garcia et al., 1998 [13] | Case–control study with 261 matched pairs in 8 hospitals of Comunidad Valenciana, Spain. | Paternal exposure. Fathers were interviewed for obtaining detailed information on direct involvement in handling of pesticides. | Congenial malformation (any) | 1.23 (0.59-2.56) crude |
0.94 (0.37-2.34) adjusted | ||||
Rull et al., 2006 [14] | Case–control study. Rural California US population (California Birth Defects Monitoring Program) -1987-1991 (pooled data of 2 case–control studies)b. Controls: unmatched randomly sampled from all live born in the same sampling time without congenital anomalies diagnosed before the 1st birthday. | Maternal residential proximity (<1,000 m) to pesticide sprayed crops during early pregnancy /questionnaire (residential addresses 2 weeks or more during the periconceptional period linked to geographic distribution of crops; pesticide use reports). | NTDa | Conventional logistic regression models |
1.5 (1.0-2.4)-Single pesticide | ||||
1.5 (0.8-2.9)-Multiple pesticides | ||||
Yang et al., 2014 [16] | Case–control study. CA Birth Defects Monitoring Program, 1997–2006. San Joaquin Valley CA US. Cases (n = 763): infants/fetuses with anencephaly or spina bifida and those with cleft palate (CP) or cleft lip (CL) with or without CP. Diagnoses confirmed by clinical geneticists. Cases suspected to having singe-gene conditions, chromosome abnormalities and an identified syndrome were not eligible. Controls (n = 974) non-malformed live-born infants selected at random from birth hospitals. | Maternal residential proximity to pesticide sprayed crops during periconceptional period (time window of exposure: 1 month before to 2 monthsnths after reported date of conception) (computer-based questionnaire administered primarily by telephone 6 weeks to 24 months after the date of infant delivery). Mothers with diabetes were excluded. | NTD, orofacial clefts | 0.9 (0.5-1.9) – anencephaly |
0.9 (0.5-1.4) – spina bifida | ||||
0.9 (0.7-1.3) - CL w/wo CP | ||||
0.9 (0.5-1.5) – CP alone | ||||
Carmichael et al., 2013 [15] | Case–control study. Study population was all male infants born from 1991–2004 to mothers who were residents of 8 CA Central Valley counties. Cases (n = 690) were infants with hypospadias ascertained by the CA Birth Defects Monitoring Program (1991–2004); Controls (n = 2195) were live-born male infants with no major malformation selected randomly from the birth population (n = 2195). | Maternal residential proximity (within a 500 m radius) to pesticide sprayed crops during early pregnancy (1–98 days after reported date of conception; 1–14 weeks embryonic age) /questionnaire. Birth certificate accession numbers were used to request access to maternal residential addresses at delivery. Data on pesticide applications (Pesticide Use Reporting records) were from the CA department of pesticide regulation. | Hypospadias | 0.68 (0.34-1.37) – lowest (total amount applied <1.22 lb) |
0.44 (0.19-1.01) – intermediate (total-amount applied 1.22-6.92 lb). | ||||
0.88 (0.48-1.64) – highest (total amount applied ≥6.93 lb). | ||||
Shaw et al., 2014 [17] | Case–control study. Study population was from the San Joaquim Valley of California, US (1997–2006). Cases were 156 infants/fetuses were infants with gastroschisis confirmed by clinical geneticists and the controls (n = 785) were non-malformed live-born infants randomly selected from birth hospitals to represent the population from which the cases arose. Cases with recognized or suspected to have single-gene conditions or chromosomal abnormalities or with identifiable syndromes were ineligible. Cases and controls whose mothers had diabetes were excluded from analysis. | Residential proximity (within 500 m radius) to pesticide applications (to estimate pesticide applications data were obtained from Pesticide Reporting Records from the California Dept of Pesticide Regulation). Maternal interviews (by phone) using a standardized computer-based questionnaire took place between 6 weeks and 24 months after infant’s estimated date of delivery. Mothers reported residential history from 3 month before conception through delivery, including dates and residences occupied for >1 month. Time window of exposure analyzed went from 1 month before to 2 months after the mother reported date of conception. | Gastroschisis | 0.9 (0.6-1.4) – crude OR |
0.9 (0.6-1.5) – adjusted OR | ||||
Garry et al., 2002 [18] | Cross-sectional study. Certified pesticide appliers (licensed between 1991 and 1996) in Red River Valley, Minnesota US. Participants randomly selected were invited by phone interview and asked to return a detailed written questionnaire on reproductive health and pesticide use assessment. Informants were at least one member of 695 families (228 male spouse applicators, 90 female spouses, 377 couples). | Each certified pesticide applicator was interviewed by phone on current and past use of pesticides with attention to product name, years used and no. of days per year applied. Approximately 6 months later participants were interviewed again by a written questionnaire. Spouses were also interviewed by phone and again by written questionnaire. Frequencies of the outcome were compared between those who reported the use of GLY and those who did not report the use. (dichotomous pesticide exposure). | ADD/ADHD | 3.6 (1.3-9.6) |
Waselak et al. 2007 [19] | Cross-sectional study. Farm couples were from the Ontario Farm Family Health Study (OFFHS), a study designed to retrospectively assess the effects of pesticide exposures on reproductive health. Couples were eligible if they were married or living as married, living year-around on a farm operation, and the wife was at most 44 years of age. Questionnaire were mailed to each farm family to get information on health status, pesticide use and farm-activity exposures. Farm wives were asked to self-report if “the doctor has ever told them” if their child had had chronic bronchitis or cough, asthma, hayfever or allergies. | Information on agricultural chemicals used on the farm 6 largest crops sown or harvested in 1991 were obtained through a questionnaire addressed to the farm operator. Information on historical farm chemical used was obtained by questionnaire. Questionnaires addressed to husband and wife asked information pertaining to chemical activities on the farm and around the home. The year and month of chemical use was matched with months and years leading up to and of each pregnancy. Pesticide exposures during the pregnancy period (month of conception until the month of delivery) were considered in the analysis of child health outcomes. Unexposed pregnancies were those with no reported pesticide use during the same period. Analysis: ratios exposed cases to total exposed to GLY. | Persistent cough / bronchitis, asthma, allergies | Male and female offspring combined (OR adjusted): cough/ bronchitis 0.71 (021–2.35) asthma 0.82 (0.35-1.90) hayfever/ allergies 0.98 (0.46-2.10) |
Study | Study type, population and location | Exposure assessment | Reproductive outcome | Association with GLY – Statistical Analysis OR (CI 95 %) / CFRa |
---|---|---|---|---|
Savitz et al., 1997 [20] | Retrospective cohort study. Ontario Farm Family Health Study (OFFHS), farms likely to be full-time family-run operations were selected based on 1986 Canadian Census of Agriculture. Couples were considered as eligible (telephone interview) based on residence on or near the farm-year-round, and age of female partner (≤44 years old). Among 1898 farm couples with completed questionnaires (from farm operator, husband and wife), 3984 pregnancies were identified. | Paternal exposure assessed by questionnaire interview. Men were asked about their farm activities over the past 5 years. Five activities were presumed to involve direct pesticide exposure: mixing or applying crop herbicides, insecticides, and fungicides, yard herbicides, livestock chemicals and building pesticides. Male partners engaged in any activity associated with direct pesticide exposure for ≥1 month in the time window of 3 months before conception to the time of conception. | Abortion | 1.5 (0.8-2.7) – adjusted– abortion (crop) |
1.4 (0.7-2.8)–adjusted– abortion – (yard) | ||||
2.4 (0.8-7.9)–adjusted– pre-term delivery (crop) | ||||
0.8 (0.2-2.3)–adjusted- SGA- (crop) | ||||
Pre-term delivery | ||||
SGA births | ||||
Curtis et al., 1999 [21] | Retrospective cohort study. OFFHS – same as described above. Only planned pregnancies were selected for the analysis regardless of the pregnancy outcome. | Paternal exposure assessed by questionnaire interview. Pesticide used on the farm (monthly use) during the month trying to conceive or at any time during the prior 2 months to capture the time dependent exposure interval that may have affected spermatogenesis (64 days). | Fecundability | GLY exposure / CFRa : adjusted |
Woman activity regardless man activity - 0.61 (0.30-1.26) | ||||
Man activity / no woman activity 1.30 (1.07 – 1.56) (↑fecundability) Farm pesticide use/no couple activity | ||||
1.26(0.94-1.69) No pesticide use/engaged in activities 1.00 (0.91-1.09) | ||||
Arbuckle et al., 2001 [22] | Retrospective cohort study. OFFHS – same as described above | Paternal exposure assessed by questionnaire interview. Male farm activities in the period from 3 months prior to conception through the month of conception were assessed by questionnaire and evaluated in relation to miscarriages, pre-term delivery and SGA births. | Abortion | 1.7 (1.0-2.9)–pre-conceptional exposure and late abortion (12–19 weeks) 1.1 (0.7-1.9) – pre-conceptional exposure and early abortion (<12 weeks) 1.1 (0.7-1.7) – post-conceptional exposure and abortion at any gestational age. |
Sanin et al., 2009 [23] | Ecological-type study design. 2004–2005 Outcome was time to pregnancy evaluated by questionnaire interview (How many months have you having sexual intercourse before you became pregnant for the first time?) women were invited to participate if their first pregnancy during the last 5 years and did not take contraceptives the year before becoming pregnant. 2751 women were included in the analysis. 159 women who reported consultation with a physician for fertility problems were excluded from multiple regression and alternative models. | Exposure measurement: Five regions of Colombia with different agricultural practices and presence or not of aerial spray for eradication of illicit crops with GLY | Time-to-pregnancy | Aerial spraying of GLY was not consistently associated with a delayed time to pregnancy. |
Sathyanarayana et al. 2010 [24] | Multiple regression analysis of birth weight. Pesticide applicators and their spouses enrolled between 1993 and 1997, Iowa and North Caroline US. (2246 women). | Exposure assessed by interview and questionnaire | Birth weight | Mean birth weight ± SD: 3586 ± 546 g. |
GLY-associated change in birth weight: 4 g, −40 to + 48 g. (NS) |
Year (12 mo) | Malformed infants (hospital-based records, N)a | Births in the region (population-based registry) (N) | Birth defects rates (/ 10,000 births) |
---|---|---|---|
1997-8 | 46 | 24,030 | 19.1 |
2001-2 | 60 | 21,339 | 28.1 |
2008-9 | 186 | 21,808 | 85.3 |