Prenatal nitrate exposure from diet and drinking water and timing of puberty in sons and daughters: A nationwide cohort study

Prenatal Exposure to Nitrate in Drinking Water and Adverse Health Outcomes in the Offspring: a Review of Current Epidemiological Research

“…The included studies are presented in Table 1 with a short description of study design, exposure characteristics, investigated outcomes, adjustment parameters, and main findings. The majority of studies focused on adverse birth outcomes ( n = 9) [ 18 – 26 ], whereas health effects showing later in life were investigated in few studies ( n = 4) [ 27 – 30 ]. Eight studies were conducted in Denmark, four studies were conducted in the USA, and one study was conducted in Italy, Spain, and Korea.…”

“…For childhood central nervous system cancers, an OR of 1.65 (95% CI, 0.97, 2.81) was observed in the group exposed to > 25 mg/L Zumel-Marne et al, 2021 [ 28 ] Italy, Spain and Korea 85 cases and 343 controls Case-control study Exposure levels in tap water in the municipality of living in the year of the child’s birth Median exposure 3.9 mg/L NO 3 - Neuroepithelial brain tumors (diagnosed between the ages of 10-24 years) Educational level of the parents. The models were further stratified on the child’s sex, age, and country Higher odds of neuroepithelial tumors in study participants exposed to nitrate levels belonging to the second (OR 1.62 95% CI, 0.74, 3.53) and third tertile (OR 1.76 95% CI, 0.91, 3.41) compared with the first tertile Reproductive health Clemmensen et al, 2022 [ 29 ] Denmark 985 Cohort study Household-level information on nitrate exposure from public water systems in the period of pregnancy Median exposure 2.0 mg/L NO 3 - Semen parameters, testes volume and reproductive hormones in adult sons The mother’s age, smoking and educational level together with variables strongly associated with each specific outcome, e.g., spillage and abstinence time No observed associations between maternal nitrate exposure and the measured outcomes Clemmensen et al, 2022 [ 30 ] Denmark 15,819 Cohort study Household-level information on nitrate exposure from public water systems in the period of pregnancy Median exposure 2.0 mg/L NO 3 - Timing of puberty in sons and daughters Cohabitation and educational level of parents, the mothers age, smoking and alcohol intake, body mass index, and age at menarche No strong associations. The sons exposed to nitrate levels > 25 mg/L from maternal drinking water tended to obtain puberty earlier than sons exposed ≤ 1 mg/L with an average age difference of -1.2 months (95% CI, − 3.0, 0.6) …”

“…Although all studies relied on utilizing drinking water data from pre-existing monitoring programs of water quality, there are differences in their spatial and temporal resolution. Four studies studied nitrate measures in drinking water aggregated at the county, municipality, or census tract level [ 20 , 23 , 26 , 28 ], while nine studies were able to pinpoint the nitrate level supplied to the geocoded maternal residential addresses [ 18 , 19 , 21 , 22 , 24 , 25 , 27 , 29 , 30 ]. Eight studies could distinguish whether an address was served by a public or private well [ 18 , 19 , 22 , 24 , 25 , 27 , 29 , 30 ].…”

“…Four studies studied nitrate measures in drinking water aggregated at the county, municipality, or census tract level [ 20 , 23 , 26 , 28 ], while nine studies were able to pinpoint the nitrate level supplied to the geocoded maternal residential addresses [ 18 , 19 , 21 , 22 , 24 , 25 , 27 , 29 , 30 ]. Eight studies could distinguish whether an address was served by a public or private well [ 18 , 19 , 22 , 24 , 25 , 27 , 29 , 30 ]. Whether the studies accounted for temporal changes in exposure, either due to nitrate concentrations changes at the residence or moving to a different residence during the exposure time window, is described in the below section.…”

“…We identified four studies investigating the association between prenatal exposure to nitrate and health effects later in life [ 27 – 30 ]. Two studies investigated the risk of childhood cancer, and two studies investigated the potential association with reproductive health including semen quality in adult men and timing of puberty.…”