Table 3 Summary table of findings from included studies
First Author & Year | Results from paternal exposure | Quality score ± |
|---|---|---|
Body composition | ||
Bowatte et al. 2022 [25] | Both ever asthma risk in offspring and asthma before age 10 years old were associated with father’s high BMI trajectory (relative risk ratio [RRR] = 1.72 [95% CI: 1.00, 2.97] and RRR = 1.70 [95% CI: 0.98, 2.93], respectively). In the sex-stratified analysis, only the high BMI trajectory of fathers was associated with offspring ever allergic asthma (RRR = 2.04 [95% CI: 1.12, 3.72]; P = 0.02) | 5 |
Broadney et al. 2017 [35] | Paternal pre-pregnancy body mass index [BMI] categories overweight [25.0—29.9 kg/m2], obese class I [30.0—34.9 kg/m2], and obese class II/III [> 35 kg/m2] are associated with reduced neonatal IgM levels (β = -0.08, [95% CI: -0.13, -0.03], P = 0.001); (β = -0.07, [95% CI: -0.13, -0.01], P = 0.029]); (β = -0.11, [95% CI: -0.19, -0.04], P = 0.003). Paternal overweight or obesity (class I or II/III) is not associated with the neonatal inflammation score (β = 0.003, [95% CI: -0.10, 0.11]); (β = 0.05, [95% CI: -0.07, 0.17]); (β = 0.07, [95% CI: -0.09, 0.23]) or CRP level (β = 0.02, [95% CI: -0.04, 0.09]); (β = 0.01, [95% CI: -0.07, 0.09]); (β = 0.004, [95% CI: -0.10, 0.10]) | 6 |
Casas et al. 2017 [36] | Zero association identified between paternal pre-pregnancy underweight [< 18.5 kg/m2] or obese fathers [≥ 30 kg/m2] and cognitive and psychomotor scores; Global cognitive index (β = 2.78, [95% CI: -8.40, 13.97]), (β = 0.51, [95% CI: -1.68, 2.69]); Memory (β = 4.63, [95% CI: -7.04, 16.31]), (β = 1.67, [95% CI: -0.62, 3.95]); Motor (β = -5.42, [95% CI: -17.51, 6.67]), (β = -0.96, [95% CI: -3.35, 1.42]). There is also no association between behavioural outcomes at pre-school age and underweight or obese fathers; ADHD Inattention (IRR = 3.46, [95% CI: 0.77, 15.49]), (IRR = 2.12, (95% CI: 0.73, 6.17); Hyperactivity (IRR = 1.38, [95% CI: 0.39, 4.76]), (IRR = 1.38, [95% CI: 0.96, 1.99]); Childhood Asperger Syndrome Test [CAST] (IRR = 0.85, [95% CI: 0.50, 1.46]), (IRR = 1.01, [95% CI: 0.91, 1.13]) | 9 |
Chen et al. 2021 [37] | The birth defect rate was significantly higher when paternal prepregnancy BMI ≥ 25 kg/m2 in IVF cycles (aOR 1.82, 95% CI: 1.06,3.10). Couples with paternal prepregnancy BMI ≥ 25 kg/m2 had a four-fold increased risk of congenital malformations of the musculoskeletal system (aOR 4.38, 95% CI: 1.31,14.65) P = 0.017 compared to couples with paternal prepregnancy BMI < 25 kg/m2. This association still remained after adjustment for confounding factors (aOR 4.55, 95% CI 1.32–15.71). No association was seen between paternal prepregnancy BMI and risk of other subcategories of birth defects | 5 |
Fang et al. 2020 [38] | Pre-pregnancy BMI was roughly associated with TTP among men with BMI ≥ 24 (FOR 0.97 95%CI: 0.95,0.99); however, this association for men disappeared after adjusting for demographic characteristics (aFOR 1.01 95%CI: 0.98,1.02). Following logistic regression, no association was observed between male pre-pregnancy BMI ≥ 24 and subfecundity (aOR 0.97 95%CI: 0.92 – 1.03) | 5 |
Fleten et al. 2012 [39] | Using absolute BMI values, paternal pre-pregnancy BMI and offspring BMI at age 3 years are associated (β = 0.038, [95% CI: 0.033, 0.044], P = 0.018). Using BMI as z-score [standard deviation] (β = 0.125, [95% CI: 0.107, 0.143], P = 0.805), there is no longer an association | 6 |
Guo et al. 2022 [40] | Following multivariate adjustment, husbands who were underweight had significantly higher risk (OR = 1·17 [95% CI: (1·15, 1·19)] of SGA compared with the husband with normal BMI. In addition, a significant and increased risk of LGA was observed for overweight and obese men (OR = 1·08 [95% CI: 1·06,1·09]); (OR = 1·19 (95% CI: 1·17, 1·20)] respectively. Reduced paternal BMI was associated with an increased risk of SGA when paternal BMI was less than 22·64 (P non-linear < 0·001). Meanwhile, increasing paternal BMI were associated with an increased risk of LGA when paternal BMI was more than 22·92 (P non-linear < 0·001) | 6 |
Hoek et al. 2022 [41] | Paternal periconceptional BMI is negatively associated with the fertilization rate (β = − 0.01, [SE = 0.004], P = 0.002]); for every increase in paternal BMI point the fertilization rate decreased 1%. Paternal BMI is not associated with the TMSC (β = − 2.48, [SE = 1.53], P = 0.11]), the KIDScore (β = − 0.01, [SE = 0.02], P = 0.62]), the embryo usage rate (β = − 0.001, [SE = 0.004], P = 0.84]), a positive pregnancy (β = 0.03, OR = 1.03, P = 0.49), fetal heartbeat (β = 0.03, OR = 1.03, P = 0.51) or live birth (β = 0.01, OR = 1.01, P = 0.82) | 8 |
Johannessen et al. 2020 [33] | Among offspring with ECRHS/RHINE fathers who had become overweight during puberty, there was an increased risk of adult offspring’s asthma without nasal allergies (RRR = 2.36 [95% CI: 1.27, 4.38]), compared with fathers who had never been overweight. Offspring’s overweight status at age 8 years was positively associated with adult offspring’s asthma without nasal allergies (RRR = 1.50 [95% CI: 1.05, 2.16]. The risk of offspring’s overweight status at age 8 years was greater if the father was overweight at the same period [OR = 2.23 [95% CI: 1.45, 3.42] compared with the offspring having fathers who had never been overweight | 6 |
Lonnebotn et al. 2022 [34] | Fathers’ overweight before puberty had a negative indirect effect, mediated through sons’ height, on sons’ forced expiratory volume in one second (FEV1) (beta (95% CI): − 144 (− 272, − 23) mL) and forced vital capacity (FVC) (beta (95% CI): − 210 (− 380, − 34) mL), and a negative direct effect on sons’ FVC (beta (95% CI): − 262 (− 501, − 9) mL); statistically significant effects on FEV1/FVC were not observed | 7 |
Moss et al. 2015a [42] | Paternal preconception overweight [25.0—29.9 kg/m2] and obesity [> 30 kg/m2] is not associated with gestational age (-0.19, [95% CI: -1.30, 0.91], P = 0.37); (-0.39, [95% CI: -1.71, 0.94], P = 0.28), or offspring birthweight (35.6, [95% CI: -1.40, 211.3], P = 0.34); (76.8, [95% CI: -74.6, 228.1], P = 0.16) | 7 |
Mutsaerts et al. 2014a [43] | No association identified between paternal pre-pregnancy BMI and spontaneous preterm birth (OR = 0.99, [95% CI: 0.93, 1.06]) or SGA (0.96, [95% CI: 0.91, 1.01]) | 3 |
Noor et al. 2019 [44] | Cord blood DNA methylation at 9 CpG sites is associated with paternal BMI independent of maternal BMI (P = < 0.05). Methylation at cg04763273, between TFAP2C and BMP7, decreased by 5% in cord blood with every 1-unit increase in paternal BMI (P = 3.13 × 10 -҆ꝰ), decreases persist at ages 3 (P = 0.002) and 7 (P = 0.004). Paternal BMI is associated with methylation at cg01029450 in the promoter region of the ARFGAP3 gene; methylation at this site is also associated with lower infant birthweight (β = − 0.0003; SD = 0.0001; P = 0.03) | 7 |
Pomeroy et al. 2015 [23] | Paternal pre-pregnancy BMI is positively associated with neonatal neck-rump length (β = 0.12, P = 0.008) and the distal limb segments [lower arm/lower leg length] (β = 0.09, P = 0.006);(β = 0.09, P = 0.003). Neonatal birthweight (β = 0.08, P = 0.003), proximal limb segments [upper arm/thigh length] (β = 0.10, P = 0.001);(β = 0.08, P = 0.008), relative upper limb length (β = 0.10, P = 0.002) and relative lower limb length (β = 0.09, P = 0.004) are associated with paternal height only. Neonatal head circumference and adiposity are only associated with maternal pre-pregnancy height and BMI | 6 |
Retnakaran et al. 2021 [45] | Offspring birthweight increases by 10.7 g per unit increase in paternal pregravid BMI ([95% CI: 0.5, 20.9], P = 0.04), yet paternal pregravid BMI is not an independent predictor for LGA (aOR = 1.15, [95% CI: 0.92, 1.44]) or SGA (aOR = 0.88, [95% CI: 0.67, 1.17]). When modelled separately, paternal pregravid weight (P = 0.04), not height (P = 0.43), is associated with offspring birthweight | 8 |
Robinson et al. 2020 [46] | No association identified between paternal BMI overweight [≥ 25 kg/m2- < 30 kg/m2], obese class I [≥ 30 kg/m2- < 35 kg/m2] and obese class II [≥ 35 kg/m2] and offspring behavioural issues or psychiatric symptoms at 7–8 years; P trend for behavioural outcomes range from 0.13 [Maternal reported ADHD diagnosis] to 0.79 [Prosocial behaviours] | 7 |
Sun et al. 2022 [47] | Compared with normal weight men, paternal pre-pregnancy overweight was associated with a significantly increased risk of preterm birth (aOR 1.34 95% CI: 1.25,1.45) and low birth weight (aOR 1.60 95% CI: 1.46–1.74) in offspring. There was also an increased risk of preterm birth (aOR 1.26 95% CI: 1.14,1.40) and low birth weight (aOR 1.40 95% CI: 1.25,1.58) in offspring of paternal pre-pregnancy obesity | 7 |
Sundaram et al. 2017 [48] | Male BMI [25—< 35 kg m2] and [≥ 35 kg m2] is not associated with TTP, when modelled individually; (aFOR = 0.92, [95% CI: 0.70, 1.22]), (aFOR = 0.83, [95% CI: 0.53,1.28]). Obese class II couples (BMI. > 35.0 kg/m2) associate with fecundability (aFOR = 0.41, [95% CI: 0.17, 0.98]) having a longer TTP in comparison to couples with normal BMI (< 25 kg/m2) (aFOR = 0.91, [95% CI: 0.25, 3.37]) | 8 |
Umul et al. 2015 [49] | Increasing paternal BMI is inversely associated with sperm concentration (P = 0.02), sperm motility (P = 0.04), the clinical pregnancy rate (P = 0.04), and the live birth rate (P = 0.03). Zero association identified between paternal BMI and the fertilization rate (P = 0.89) or the implantation rate (P = 0.62) | 2 |
Wei et al. 2022 [50] | Paternal pre-pregnancy overweight and obesity are associated with a higher risk of low birth weight (LBW) (overweight: OR = 1.637, 95% CI: 1.501,1.784); (obesity: OR = 1.454, 95% CI: 1.289, 1.641) and very low birth weight (VLBW) (overweight: OR = 1.310, 95% CI: 1.097,1.564); (obesity: OR = 1.320, 95% CI: 1.037, 1.681). Paternal pre-pregnancy underweight is associated with a lower risk of LBW (OR = 0.660, 95% CI: 0.519, 0.839). Parents who were both excessive-weights in pre-pregnancy BMI, as well as overweight mothers and normal-weight fathers before pre- pregnancy, were more likely to have offspring with LBW, VLBW, and extremely low birth weight (ELBW) | 6 |
Wei et al. 2021 [51] | Paternal pre-pregnancy BMI overweight (OW) did not present associations with newborn relative telomere length (TL) in cord blood, even following adjustments (percentage change 0.93 (95% CI: -5.59,8.14));P = 0.772 or stratification by newborn sex (percentage change 2.09 (95% CI: -7.53,12.72));P = 0.686. Analysis of the combined effects of parental weight status on newborn TL showed that TL was significantly shortened among newborns whose mothers were overweight and fathers were of healthy weight when compared with those whose mothers and fathers were both of normal weight (percentage change − 8.38 (95% CI: − 15.47, − 0.92)); P = 0.028 | 6 |
Xu et al. 2021 [52] | Each standard deviation (SD) increment of paternal BMI (approx 3.27 kg/m2) is associated with an additional 29.6 g increase of birth weight ([95% CI: 5.7, 53.5], P = 0.02). As a continuous variable, one-unit increase in paternal BMI (1.0 kg/m2) is associated with a 9.6 g increase of offspring birth weight ([95% CI: 2.3, 17.0], P = 0.01). The association between paternal preconception body weight and offspring’s birth weight is pronounced in male neonates and neonates with overweight mothers or mothers with excessive gestational weight gain [GWG] (P = < 0.05) | 7 |
Yang et al. 2015 [53] | Fathers overweight [BMI 24.0—27.9 kg/m2] or obese [BMI ≥ 28.0 kg/m2] before pregnancy have an elevated risk of giving birth to a macrosomic infant, compared with their normal weight counterparts (aOR = 1.33, [95% CI: 1.11, 1.59]);(aOR = 1.99 [95% CI: 1.49,2.65]). Paternal pre-pregnancy weight only [≥ 75.0 kgs], not height, is associated with increased risk of macrosomia (aOR = 1.49, [95% CI: 1.16, 1.92]) | 6 |
Zalbahar et al. 2017 [24] | Overweight or obese [OW/OB] fathers [> 25 kg/m2] and normal weight mothers [< 25 kg/m2] have an increased risk of offspring OW/OB at both the 5 to 14 year plus the 14 to 21 year follow-up (aOR = 2.34, [95% CI: 1.50, 3.65]);(aOR = 2.27, [95% CI: 1.60, 3.24]). This risk increases further when both parents are OW/OB (aOR = 9.95, [95% CI: 5.60, 17.69]); (aOR = 12.47, [95% CI: 7.40, 21.03]); for every unit increase in paternal and maternal BMI z-score, offspring BMI z-score increased, on average, by between 0.15% (kg m2) and 0.24% (kg m2) throughout the 5, 14 and 21 year follow-up | 5 |
Zhang et al. 2020 [54] | Underweight [< 18.5 kg/ m2] male partners prolong a couples' TTP (aFOR = 0.95, [95% CI: 0.94, 0.96]) compared to male partners with normal BMI [18.5—23.9 kg/m2]. A combination of normal BMI women and overweight men [24.0—28.9 kg/m2] have the greatest opportunity for pregnancy (aFOR = 1.03, [95% CI: 1.02, 1.03]), a combination of obese women and underweight men have the least opportunity for pregnancy (aFOR = 0.70, [95% CI: 0.65, 0.76]) | 9 |
Alcohol | ||
Luan et al. 2022 [55] | The risks of rating scores on anxious/depressed were increased by 33% (RR = 1.33 [95% CI: 1.09, 1.61]) and 37% (RR = 1.37 [95% CI: 1.02,1.84]) among girls in the exposed group at ages 4 and 6, respectively. Risks of somatic complaints were increased by 18% (RR = 1.18 [95% CI: 1.00, 1.40]) and 65% (RR 1.65,[ 95% CI: 1.14, 2.38]) among boys in the exposed group at ages 4 and 6. Also, there was the increased risks of sleep problems (RR = 1.25[95% C:I 1.00,1.55]) in girls at age 4, thought problems (RR = 1.32 [95% CI: 1.01, 1.73]) in girls at age 6, and rule-breaking behaviours (RR = 1.35 [95% CI: 1.09, 1.67]) in boys at age 6 | 7 |
Milne et al. 2013 [27] | For both ALL and CBT case/control, there was some evidence of a U-shaped relationship between the amount of alcohol fathers consumed in the 12 months before the pregnancy and risk of both cancers. The odds ratios (ORs) fell with increasing consumption, to a minimum at 14–21 standard drinks a week, ALL (OR = 0.51 [95% CI: 0.32, 0.81]);CBT (OR = 0.58 [95% CI: 0.35,0.96]), and rose to a maximum at 28 drinks a week; ALL (OR = 1.20 [95% CI: 0.79,1.83); CBT (OR = 1.53 [95% CI:0.95, 2.44]). The p values for the quadratic terms in the ALL and CBT models were 0.005 and 0.02, respectively | 6 |
Moss et al. 2015a [42] | Paternal preconception alcohol intake > once a month is not associated with offspring birthweight (− 85.9, [95% CI: -336.2, 164.3], P = 0.50) or offspring gestational age (− 0.10, [95% CI: -0.96, 0.77], P = 0.83) | 7 |
Mutsaerts et al. 2014a [43] | Paternal preconception alcohol intake > 7 units/week is not associated with spontaneous preterm birth (OR = 1.08, [95% CI: 0.64, 1.83]) or SGA (OR = 1.07, [95% CI: 0.73, 1.56]) | 3 |
Xia et al. 2018 [56] | In the paternal alcohol-exposed group [> 81 g/wk], male offspring have shorter mean AGDs; for AGD-AP at birth (β =—1.73, P = 0.04) and 12 months (β = -7.29, P = 0.05), and shorter mean AGD-AS at 6 months (β =—4.91, P = 0.02). Female offspring have shorter mean AGD-AF (β = -0.72, P = 0.02) at birth yet longer mean AGD AC (β = 2.81, P = 0.04) and AGD-AF (B = 1.91, P = 0.04) at 12 months | 8 |
Zuccolo et al. 2016 [57] | Increased odds of microcephaly at birth with alcohol dose per occasion at 5 + units/sitting; [1—2 units] (OR = 1.48, [95% CI: 0.77, 2.84], P = 0.238), [3–4 units] (OR = 1.64, [95% CI: 0.85, 3.16], P = 0.140), [5 + units] (OR = 1.93, [95% CI: 1.01, 3.70], P = 0.048). The average paternal preconception alcohol dose per occasion and general head circumference at birth is not associated [1—2 units] (β = -0.00, [95% CI: -0.05, 0.04], P = 0.831), [3–4 units] (β = -0.00, [95% CI: -0.05, 0.04], P = 0.915), [5 + units] (β = -0.02, [95% CI: -0.07, 0.02], P = 0.293) | 4 |
Cannabis | ||
Har-Gil et al. 2021 [58] | Sperm quality is associated with cannabis use (6 [1.4], P = 0.022), compared with non-use (6[2.2], P = 0.50). Sperm volume (2.69/2.5 [1.6]), IVF fertilization (53/53 [59]), the IR (P = 0.46) and OPR (P = 0.508) are not associated with male cannabis use | 2 |
Kasman et al. 2018 [59] | Zero association identified between male cannabis use and TTP, regardless of frequency; [< 1/month] (aTR = 0.9, [95% CI: 0.7, 1.2], P = 0.43), [Monthly] (aTR = 0.9, [95% CI: 0.5, 1.8], P = 0.73), [Weekly] (aTR = 1.0, [95% CI: 0.3, 2.9], P = 1.00), [Daily] (aTR = 1.1, [95% CI: 0.79, 1.5], P = 0.65) | 6 |
Moss et al. 2015a [42] | Paternal preconception cannabis use is not associated with gestational age (0.41, [95% CI: -0.43, 1.25], P = 0.34) or offspring birthweight (201.9, [95% CI: -97.6, 501.3], P = 0.19) | 7 |
Nassan et al. 2019 [60] | Compared to males who are past or never cannabis users, couples where the male partner is a cannabis user at enrolment (n = 23) have increased probability of implantation (77.9, [95% CI: 53.5, 91.5], P = < 0.05) and live birth (47.6, [95% CI: 32.4, 63.3], P = < 0.05), independent of women's cannabis use. Clinical pregnancy is not associated with male cannabis use; (60.1, [95% CI: 42.6, 75.4]) | 7 |
Wise et al. 2018 [61] | Male current cannabis users (n = 100) present no association between cannabis use and fecundability (aFR = 1.01, [95% CI: 0.81, 1.27]) even following stratification by intercourse frequency (aFR = 1.35, [95% CI: 0.72, 2.53]) and timing of sexual intercourse (aFR = 1.05, [95% CI: 0.76, 1.45]). Paternal cannabis use [< 1 time/week] has slightly decreased fecundability (FR = 0.87, [95% CI: 0.66, 1.15]), compared with non-current users | 6 |
Physical activity | ||
Moss et al. 2015a [42] | Zero association identified between paternal preconception bouts of physical activity per week and gestational age (0.02, [95% CI: -0.04, 0.07], P = 0.53) or offspring birthweight (1.7, [95% CI: -13.0, 16.4], P = 0.82) | 7 |
Mutsaerts et al. 2014a [43] | Paternal preconception physical activity of moderate intensity < 1 time/week is not associated with spontaneous preterm birth (OR = 0.76, [95% CI: 0.45, 1.27]) or SGA (OR = 1.33, [95% CI: 0.95, 1.87]) | 3 |
Smoking | ||
Accordini et al. 2021 [32] | Fathers’ smoking initiation in prepuberty (generation G1) had a negative direct effect on their own FEV1/FVC (Δz-score − 0.36, 95% CI: − 0.68, -0.04) compared with fathers’ never smoking. This exposure had a negative direct effect on both offspring’s FEV1 (− 0.36, 95% CI: − 0.63, − 0.10) and FVC (− 0.50, 95% CI: − 0.80, − 0.20) (generation G2). Fathers’ smoking initiation at later ages also had a negative direct effect on their own FEV1 (− 0.27, 95% CI: − 0.51, − 0.02) and FEV1/FVC (− 0.20, 95% CI: − 0.37, − 0.04), but no effect found on offspring’s lung function | 8 |
Accordini et al. 2018 [31] | Fathers’ smoking before they were 15 years old were associated with asthma without nasal allergies in their offspring [relative risk ratio ((RRR) = 1.43 95% CI: 1.01, 2.01]. The risk of fathers’ asthma (generation F1) was higher if their parents (generation F0) had ever had asthma (grandmothers’ asthma: (OR = 3.08 [95% CI: 1.96,4.85]); grandfathers’ asthma: (OR = 2.38 [95% CI: 1.51, 3.75]). The risk of asthma with or without nasal allergies in offspring (generation F2) was higher if the offspring’s father had ever had asthma (RRR = 2.37 and 1.70), respectively | 7 |
Carslake et al. 2016 [62] | Paternal smoking during pre-adolescence (< age 11) is not reliably or strongly associated with BMI among sons, with an estimated association close to zero (mean difference in kg m-2 (95% CI) was -0.18 (-1.75, 1.39) for sons aged 12 ± 19 and 0.22 (-0.53, 0.97) for all ages). Among daughters, early-onset paternal smoking was imprecisely associated with an elevated BMI (mean difference was 1.50 (0.00, 3.00) for daughters aged 12 ± 19 and 0.97 (0.06, 1.87) for all ages) | 6 |
Deng et al. 2013 [63] | During the periconceptional period, light paternal smoking [1–9 cigarettes/day] increases the risk of isolated conotruncal heart defects (aOR = 2.23, [95% CI: 1.05, 4.73]). Medium paternal smoking [10–19 cigarettes/day] increases the risk of septal defects (aOR = 2.04, [95% CI: 1.05, 3.98]) and left ventricular outflow tract obstructions (aOR = 2.48, [95% CI: 1.04, 5.95]). Heavy paternal smoking (≥ 20 cigarettes/day) provides even greater risk of isolated conotruncal heart defects (aOR = 8.16, [95% CI: 1.13, 58.84]) and left ventricular outflow tract obstructions (aOR = 13.12, [95% CI: 2.55, 67.39]). No association identified between paternal smoking and right ventricular outflow tract obstructions; light smoking (AOR = 1.84, [95% CI 0.88, 3.85]); medium smoking (aOR = 2.04, [95% CI: 0.71, 5.89]); heavy smoking (aOR = 6.02, [95% CI: 0.98, 36.77]) | 8 |
Frederiksen et al. 2020 [64] | Nil associations identified between paternal smoking before conception and childhood ALL (OR = 1.00, 95% CI: 0.73, 1.38). Paternal smoking before conception was associated with an increased risk of childhood AML in both the crude (OR = 2.55, 95% CI: 1.25, 5.21) and adjusted models (OR = 2.51, 95% CI: 1.21, 5.17) | 7 |
Knudsen et al. 2020 [30] | In the unadjusted analysis, father’s preconception smoking, both starting before or from age 15 years, was associated with increased offspring BMI. Following adjustments, father’s smoking onset ≥ 15 years was significantly associated with increased BMI in their adult offspring (0.551, [95% CI: 0.174, 0.929]) P = 0.004. Father’s preconception smoking onset ≥ 15 years was also associated with increased offspring FMI (2.590 [95% CI: 0.544, 4.63]) P = 0.014. Further, sons of fathers’ who started to smoke ≥ 15 years of age (interaction p = 0.014) had significantly higher FMI compared to sons of never smoking fathers | 5 |
Milne et al. 2013 [27] | Paternal preconception smoking showed no association with childhood brain tumor (CBT) risk (OR = 0.99 (95% CI: 0.71, 1.38); P = 0.54. There was also no association evident when paternal smoking was stratified by child’s age | 5 |
Ko et al. 2014 [65] | Paternal preconception smoking [11–20 cigarettes/day] has a negative effect on overall infant birthweight (β = -19.17 [7.74], P = 0.013) but is not associated with gestational age (β = -0.05 [0.028], P = 0.108). Paternal preconception smoking [> 20 cigarettes/day] is not associated with preterm delivery (1.07, [95% CI: 0.84, 1.35]), low birth weight (1.14, [95% CI: 0.87, 1.27]), or small for gestational age [SGA] (1.12, [95% CI: 0.90, 1.40]) | 5 |
Moss et al. 2015a [42] | Paternal preconception smoking at least one cigarette/day for one month is not associated with gestational age (− 0.31, [95% CI: − 1.20, 0.59], P = 0.50) or offspring birthweight (− 219.6, [95% CI: − 537.0, 97.8], P = 0.18) | 7 |
Mutsaerts et al. 2014a [43] | Paternal smoking [1–10 cigarettes/day] or [< 10 cigarettes/day] 6 months prior to conception, is associated with an increased risk of SGA (OR = 1.69; [95% CI: 1.10, 2.59]); (OR = 2.25, [95% CI: 1.51, 3.37]) but not spontaneous preterm birth (OR = 1.34, [95% CI: 0.74, 2.41]); (OR = 1.13, 95% CI: 0.59, 2.14) | 3 |
Northstone et al. 2014 [66] | In sons whose fathers started smoking < 11 years, mean differences in BMI, waist circumference, and fat mass all show increases in measures at ages 13, 15 and 17; at 13 years BMI (2.83, [95% CI: 1.20, 4.25]), waist circumference and fat mass (4.83, [95% CI: 0.98, 8.68], P = 0.014);(5.79, [95% CI: 2.67, 8.91] P = < 0.0001), and at 15 years BMI (2.03 [95% CI: 0.45, 3.6]), waist circumference and fat mass (4.84, [95% CI: 0.99, 8.66], P = 0.006); (5.50, [95% CI: 1.88, 9.30], P = 0.004). At 17 years there is an association with BMI (3.25 [95% CI: 1.15, 5.35]) and fat mass (10.6 [95% CI: 5.40, 15.9], P = < 0.0001); waist not recorded. Daughters' measurements vary with associations at ages 9 (all measurements), 11 (lean mass P = 0.023), 13 (waist circumference P = 0.004 & lean mass P = 0.028) and 17 (fat mass P = 0.012) | 7 |
Orsi et al. 2015 [67] | Pre-conception paternal smoking was significantly associated with ALL (OR = 1.2 [95% CI: 1.1,1.5)] and AML (OR = 1.5 [95% CI: 1.0–2.3]). For ALL, the ORs were higher for smoking\10 cigarettes daily than for the highest consumption; no significant trend was evidenced. For AML, significant trends were evidenced for both periods (p trend = 0.03 and 0.02, respectively), with ORs of close to 2.0 for smoking more than 15 cigarettes daily. No joint effect of paternal and maternal smoking was detected | 7 |
Sapra et al. 2016 [68] | Paternal cigarette smoking is associated with a longer TTP compared with never users (aFOR = 0.41, [95% CI: 0.24, 0.68]); attenuated slightly after adjusting for cadmium (aFOR = 0.44, 95% CI: 0.24, 0.79). When modelling partners together, paternal cigarette smoking remains associated with a longer TTP (aFOR = 0.46, [95% CI: 0.27, 0.79]), also attenuated after adjustment for cadmium (aFOR = 0.50, [95% CI 0.27—0.91]). Zero association identified between TTP and exposure to any other tobacco products including cigars (FOR = 0.70, [95% CI: 0.45, 1.08]) or snuff and chew tobacco (FOR = 1.17, [95% CI: 0.70, 1.95] | 7 |
Svanes et al. 2017 [69] | Non-allergic early-onset asthma (asthma without hay fever) was more common in the offspring with fathers who smoked before conception (OR = 1.68 [95% CI: 1.18,2.41]). The risk was highest if father started smoking before age 15 years (OR = 3.24 [95% CI: 1.67,6.27]), even if he stopped more than 5 years before conception (OR = 2.68 [95% CI: 1.17, 6.13]).Both a father’s early smoking debut (P = 0.001) and a father’s longer smoking duration (P = 0.01) before conception increased non-allergic early-onset asthma in offspring, even with mutual adjustment and adjusting for number of cigarettes and years since quitting smoking. A father’s smoking debut before age 11 years (102 fathers) showed the greatest increased risk (OR = 3.95, [95% CI: 1.07,14.60]), followed by smoking debut ages 11–14 (OR = 1.75, [95% CI: 1.07,1.86]) and smoking debut after age 15 (OR = 1.37, [95% CI: 1.00,1.86]). Longer duration of smoking was also associated with an increased risk, up to 1.8-fold for those smoking for more than 10 years (OR = 1.76, [95% CI: 0.96,3.25]) | 6 |
Wang et al. 2022 [70] | Hazard ratio (HR) of preterm birth (PTB) was 1.07 (95% CI, 1.06–1.09), compared with women without preconception paternal smoking. Compared with participants without preconception paternal smoking, the fully adjusted HRs of PTB were (1.04 [95% CI: 0.99,1.08]), (1.05 [95% CI: 1.01, 1.08]), (1.06 [95% CI: 1.03, 1.09]), (1.14 [95% CI: 1.07, 1.21]) and (1.15 [95% CI: 1.11, 1.19]) for participants whose husband smoked 1–4, 5–9, 10–14, 15–19, and ≥ 20 cigarettes/day respectively (P linear < 0.05) | 5 |
Wang et al. 2018 [71] | Women with exposure to paternal preconception smoking have increased odds of SA (aOR = 1.11, [95% CI: 1.08, 1.14], P = < 0.01). This association is evident when smoking > 10 cigarettes/day, P = < 0.01; [10–14 cigarettes/day] (aOR = 1.11, [95% CI: 1.06, 1.16]), [15–19 cigarettes/day] (aOR = 1.21, [95% CI: 1.09, 1.33]) and ≥ 20 cigarettes/day (aOR = 1.23, [95% CI: 1.17, 1.30) | 6 |
Wesselink et al. 2019 [72] | Male current regular smoking, current occasional smoking, and former smoking is not associated with fecundability (FR = 0.96, [95% CI: 0.70, 1.34]), (FR = 0.83, [95% CI: 0.61, 1.13]), (FR = 1.14, [95% CI: 0.97, 1.35]) | 5 |
You et al. 2022 [73] | For those with only preconception exposure, compared with children without paternal smoking, the risk of childhood overweight and obesity was increased (OR = 1.41 [95% CI: 1.17, 1.85]). Following further adjustments, for lifestyle and dietary factors, this effect remained statistically significant (OR = 1.54 [95% CI: 1.14, 2.08]). When stratified by sex, the effects of only preconception exposure on childhood overweight and obesity was statistically significant for only boys (p < 0.05) | 7 |
Zhou et al. 2020 [74] | There is an increased risk of birth defects in the continued-smoking (OR = 1.87, [95% CI: 1.36, 2.56], P < 0.001) and decreased-smoking groups (OR = 1.41, [95% CI: 1.10, 1.82], P = 0.007). Continued paternal smoking is associated with an elevated risk of congenital heart diseases (OR = 2.51, [95% CI: 1.04, 6.05], P = 0.040), limb abnormalities (OR = 20.64, [95% CI: 6.26, 68.02], P < 0.001), digestive tract anomalies (OR = 3.67, [95% CI: 1.44, 9.37], P = 0.007) and neural tube defects (OR = 4.87, [95% CI: 1.66, 14.28], P = 0.004). There is no association between continued paternal smoking and clefts (OR 1.44, [95% CI: 0.34, 5.90], P = 0.625) or gastroschisis (OR = 2.63, [95% CI: 0.82, 8.40] P = 0.103) | 7 |
Zwink et al. 2016 [75] | Paternal periconceptional tobacco consumption is lower in the fathers of EA/TEF patients [Any smoking] n = 20 (20%) P = 0.003, compared with fathers of isolated ARM patients [Any smoking] n = 49 (40%) P = 0.003 | 4 |
Stress | ||
Bae et al. 2017 [76] | There is a 76% increase in risk of fathering a male infant (RR = 1.76, [95% CI: 1.17, 2.65]) in men diagnosed with anxiety disorders compared with those not diagnosed. This association is strengthened (RR = 2.03, [95% CI: 1.46, 2.84]) when modelled jointly for the couple | 6 |
Mutsaerts et al. 2014a [43] | Paternal paid working hours < 16 h/week is not associated with spontaneous preterm birth (OR = 2.21, [95% CI: 0.78, 6.26]) or SGA (OR = 0.76, [95% CI: 0.23, 2.45]) | 3 |
Wesselink et al. 2018 [77] | Men's baseline PSS scores are not associated with fecundability; [PSS score 10—14] (FR = 0.95 [95% CI: 0.79, 1.15]), [PSS Score 15–19] (FR = 1.07 [95% CI: 0.86, 1.33]), [PSS Score 20–24] (FR = 1.02 [0.76, 1.36]), [PSS Score ≥ 25] (FR = 1.03 [0.69, 1.54]) | 7 |
Nutrition | ||
Bailey et al. 2014 [29] | No significant associations identified with paternal dietary intake of folate or vitamin B6 or vitamin B12 and risk of ALL; (OR = 1.37 95% CI: 0.78, 2.40) | 5 |
Greenop et al. 2015 [28] | No significant associations identified between risk of childhood brain tumors (CBT) and energy adjusted dietary folate > 509.5 (mcg) (OR = 0.85 95% CI: 0.56,1.28) or energy adjusted B6 > 1.71 (mg) (OR = 0.98 95% CI: 0.66,1.47). A high B12 intake (> 5.91(mcg)) was not significantly associated with an increased risk of CBT (OR = 1.74 95% CI: 1.14, 2.66) | 5 |
Hatch et al. 2018 [78] | Male intake of sugar-sweetened beverages is associated with reduced fecundability (aFR = 0.78 95% CI: 0.63, 0.95) for ≥ 7 sugar-sweetened beverages per week compared with none. Fecundability was further reduced among those who drank ≥ 7 servings per week of sugar-sweetened sodas (aFR = 0.67 95% CI: 0.51, 0.89). The largest reduction in fecundability was seen in men who consumed seven or more energy drinks per week (FR = 0.42; 95% CI: 0.20, 0.90). Diet sodas did not have significant association with fecundability at ≥ 7 servings per week (aFR = 0.93 95% CI: 0.71, 1.2) | 6 |
Hoek et al. 2019 [79] | In spontaneously conceived pregnancies, there is a negative association between paternal RBC folate status and CRL trajectories, in Q2 [875–1,018 nmol/L;] (β = -0.14; [95% CI:—0.28, -0.006], P = 0.04) and Q4 [1,196–4,343 nmol/L] (β =—0.19, [95% CI:—0.33, -0.04], P = 0.012). A negative association also exists for EV trajectories in Q4 (β =—0.12, [95% CI: -0.20, -0.05], P = 0.001). No association identified between paternal RBC folate status and CRL or EV trajectories in IVF-ICSI pregnancies [Q4] (β = 0.03, [95% CI: -0.07, 0.13], P = 0.55), (β = 0.03, [95% CI: -0.03, 0.08], P = 0.32) | 7 |
Lippevelde et al. 2020 [80] | In Young-HUNT1, an extra serving of fruit per week in the paternal diet, during adolescence, is associated with a 2.35 g increase in offspring placenta weight [95% CI: 0.284, 4.42], P = 0.03. A slightly shorter birth length is associated with increased paternal vegetable intake during adolescence (β = -0.048, [95% CI: -0.080, -0.016], P = 0.003) and a lower ponderal index is associated with paternal whole grain bread consumption (β = -0.003, [95% CI: -0.005, -0.001], P = 0.01). Paternal lunching regularly in adolescence is associated with an increase in offspring head circumference (β = 0.160, [95% CI: 0.001, 0.320], P = 0.05). Birthweight is not associated with any paternal dietary exposures; [Fruit] (β = 5.84 [95% CI: -0.983, 12.7], P = 0.1). These associations are not observed in Young-HUNT3 | 8 |
Martin-Calvo et al. 2019 [81] | A 400 μg/day increase in preconception paternal folate intake is associated with a 2.6-day longer gestation [95% CI: 0.8, 4.3], P = 0.004. This association is strongest in multifetal pregnancies (β = 10.7, [95% CI: 4.6, 16.8]). Zero association identified between paternal folate intake and gestational age-specific birthweight (β = -11.4, [95% CI: -28.2, 5.4]) | 7 |
Mitsunami et al. 2021 [82] | Paternal adherence to either dietary patterns 1 or 2 is not associated with the fertilization rate during IVF or ICSI ([Pattern 1] P = 0.59, [Pattern 2] P = 0.06), ([Pattern 1] P = 0.72, [Pattern 2] P = 0.94). Zero association identified between male dietary patterns and probabilities of implantation, clinical pregnancy, or live birth; ([Pattern 1] P = 0.68, [Pattern 2] P = 0.43), ([Pattern 1] P = 0.35, [Pattern 2] P = 0.68), ([Pattern 1] P = 0.53, [Pattern 2] P = 0.10) | 7 |
Moss et al. 2015a [42] | Males eating fast food more frequently have infants born earlier than men who eat fast-food less frequently (-0.16, [95% CI: -0.32, 0.00], P = 0.04). There is no association between paternal fast-food consumption and birthweight (-36.0, [95% CI: -89.8, 17.8], P = 0.19) | 7 |
Oostingh et al. 2019 [83] | Zero association identified between paternal dietary patterns and CRL or EV in spontaneous pregnancies; [Whole wheat grains and vegetables] (β = -0.006 [95% CI: -0.069, 0.058]), (β = 0.001 [95% CI: -0.022, 0.021]), and in IVF/ICSI pregnancies, (β = -0.015 [95% CI: -0.061, 0.031]), (β = -0.006 [95% CI: -0.025, 0.013]), independent of maternal dietary patterns | 6 |
Twigt et al. 2012 [84] | Paternal Preconception Dietary Risk Score [PDR] did not affect the chance of pregnancy after IVF/ICSI treatment (OR = 0.95 [95% CI: 0.48,1.86]) P = 0.88 | 5 |
Wesselink et al. 2016 [85] | Total caffeine intake among males was associated with fecundability for ≥ 300 mg vs. < 100 mg/day (OR = 0.72, 95% CI: 0.54, 0.96) | 6 |
Xia et al. 2016 [86] | Men's total dairy intake is not associated with the fertilization rate [Conventional IVF] (0.75, [95% CI: 0.60, 0.86], P = 0.29), [ICSI] (0.72, [95% CI: 0.58, 0.82], P = 0.18], the implantation rate (0.58, [95% CI: 0.40, 0.74], P = 0.87), the clinical pregnancy rate (0.51, [95% CI: 0.34, 0.68], P = 0.54), or the live birth rate (0.46, [95% CI: 0.28, 0.65], P = 0.65) | 7 |
Xia et al. 2015 [87] | A positive association identified between paternal poultry intake and the fertilization rate, [Model 1] P = 0.05, [Model 2] P = 0.03, [Model 3] P = 0.03, [Model 4] P = 0.04, with a 13% higher fertilization rate among men in the highest quartile of poultry intake compared with those in the lowest quartile (78% vs. 65%) [Model 4]. Men's total meat intake is not associated with the implantation rate (0.52, [95% CI: 0.37, 0.67], P = 0.67), clinical pregnancy rate (0.45, [95% CI: 0.32, 0.59], P = 0.56), or live-birth rate (0.35, [95% CI: 0.22, 0.50], P = 0.82) | 7 |