Table 2 Studies of parental exposures to glyphosate and birth defects or functional disorders in the progeny

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).

NTD^a

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)