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. 2020 May 2;26(5):650–669. doi: 10.1093/humupd/dmaa010

Table I.

Characteristics of included studies.

Author, year, country Study period Study design Study setting Number of pregnancies or cases and controls Proportion of ART pregnancies Definition of miscarriage Miscarriage ascertainment Adjusted risk estimates Risk factors adjusted for Methods of adjustment for maternal age
De la Rochebrochard and Thonneau (2002) , France 1991–1993 Retrospective cohort Population-based (European Study of Infertility and Subfecundity: Denmark, Germany, Italy, Spain) 3174 pregnancies Part of study population had infertility problems, otherwise not stated Not defined Self-reports Paternal age Maternal age AOR (95% CI) Country, number of the pregnancy, time to pregnancy, maternal and paternal smoking, history of miscarriage, history of ectopic pregnancy, history of induced abortion Logistic regression
Definition of new variable
‘couple age’, consisting of classes of maternal and paternal age combinations
20–29 20–29 1.0 (reference)
30–34 20–29 1.06 (0.61–1.86)
35–39 20–29 1.31 (0.56–3.07)
40–64 20–29 1.80 (0.52–6.24)
20–29 30–34 1.72 (0.62–4.74)
30–34 30–34 1.62 (0.93–2.82)
35–39 30–34 1.06 (0.52–2.17)
40–64 30–34 2.90 (1.26–6.67)
20–29 35–44 9.18 (1.80–46.66)
30–34 34–44 3.87 (1.24–12.02)
35–39 35–44 3.38 (1.76–6.47)
40–64 35–44 6.73 (3.50–12.95)
20–29 1.0 (reference)
30-34 0.93 (0.60–1.4) a
35–39 0.68 (0.42–1.12) a
40–64 1.31 (0.75–2.28) a
Slama et al. (2003), France 1985–2000 Retrospective cohort Population-based 2414 pregnancies Not stated Unplanned termination of pregnancy between 5 and 20 weeks Self-reports Paternal age Maternal age ARR (p-value or 95% CI) Area of recruitment Discrete time survival model
Adjusted for maternal age as continuous variable; used age, age squared and age cubed as covariates in the model
<25 <20 0.8 (0.64)
25–29 <20 0.7 (0.71)
30–34 <20 2.6 (0.39)
<25 20–24 1.2 (0.52)
25–29 20–24 1.0 (reference)
30–34 20–24 0.5 (0.23)
35–39 20–24 5.3 (0.01)
<25 25–29 1.3 (0.61)
25–29 25–29 1.1 (0.81)
30–34 25–29 0.90 (0.70)
35–39 25–29 1.1 (0.91)
>40 25–29 0.70 (0.77)
25–29 30–34 1.5 (0.27)
30–34 30–34 1.2 (0.51)
35–39 30–34 1.5 (0.28)
>40 30–34 1.5 (0.62)
25–29 35–39 7.0 (0.03)
30–34 35–39 3.3. (0.01)
35–39 35–39 2.2 (0.03)
>40 35–39 1.1 (0.91)
35–39 >40 1.6 (0.68)
>40 >40 11.2 (0.00)
20 <35 1.36 (0.98–1.90) Area of recruitment, maternal smoking, maternal alcohol consumption in first trimester, previous history of urogenital disorder
25 <35 1.0 (reference)
25 ≥35 1.95 (0.97–3.92)
30 <35 1.12 (0.93–1.35)
30 ≥35 1.32 (0.84–2.07)
35 <35 2.31 (1.42–3.75)
35 ≥35 1.40 (0.89–2.20)
40 ≥35 2.76 (1.51–5.04)
42 ≥35 4.46 (1.90–10.49)
Slama et al. (2003), France 25–29 1.0 (reference) Area of recruitment, maternal age
30–34 0.92 (0.57–1.52) a
35–39 1.21 (0.66–2.22) a
>40 1.01 (0.35–2.92) a
Nybo Andersen et al. (2004), Denmark 1997–1999 Prospective cohort Population-based (Danish National Birth Cohort Recruitment) 23 821 pregnancies 6% of total study population Early fetal death <20 weeks Hospital diagnosis Paternal age AHR (95% CI) Maternal age, parity, number of previous abortions, maternal alcohol and coffee consumption during pregnancy, maternal and paternal smoking, maternal and paternal occupational status Cox regression model
Maternal age entered in model in three different ways; using age continuously with restricted cubic splines instead of 5-year or 1-year groups yielded similar estimates for paternal age effects
≤24 1.17 (0.84–1.63)
25–29 1 (reference)
30–34 0.86 (0.72–1.03)
35–39 0.99 (0.79–1.25)
40–44 0.77 (0.55–1.09)
45–49 0.97 (0.56–1.69)
≥50 1.38 (0.66–2.88)
Slama et al. (2005) , France 1990–1991 Prospective cohort Population-based (Pregnancy Outcome Study: California) 5121 pregnancies Not stated Spontaneous abortion between 6 and 20 weeks Hospital diagnosis Paternal age AHR (95% CI) Maternal age, maternal smoking, maternal alcohol consumption, maternal caffeine consumption, paternal smoking in first trimester Cox regression model
Adjusted for maternal age as continuous variable, using a fractional polynomial approach
<25 1 (reference)
25–29 1.47 (1.04–2.08)
30–34 1.25 (0.84–1.88)
35–39 1.74 (1.12–1.72)
40–44 1.45 (0.85–2.46)
≥45 1.87 (1.01–3.44)
25–29 1 (reference)
30–34 0.85 (0.57–1.28) b
35–39 1.18 (0.76–1.85) b
40–44 0.99 (0.58–1.67) b
≥45 1.27 (0.69–2.34) b
Kleinhaus et al. (2006) , USA 1964–1976 Nested case-control Population-based (Jerusalem Perinatal Study) Cases: n = 1506
Controls: n = 12 359 (live births)		 Only fertile women, otherwise not stated Spontaneous abortion <20 weeks Self-reports Paternal age AOR (95% CI) Maternal age, maternal diabetes, maternal smoking, history of spontaneous abortions, parity, interval from interview to previous pregnancy, maternal and paternal education, history of induced abortions Unconditional logistic regression
Adjusted for maternal age as a continuous variable; used orthogonal coding of parental ages
<25 0.59 (0.45–0.76)
25–29 1 (reference)
30–34 1.4 (1.2–1.6)
35–39 1.9 (1.6–2.3)
≥40 1.6 (1.2–2.0)
Maconochie et al. (2007) , UK 2001 Nested case-control Population-based (National Women’s Health Study) Cases: n = 603
Controls: n = 6116 (ongoing pregnancy >12 weeks)		 Cases: 7%
Controls: 3%		 Early miscarriage <13 weeks Self-reports Paternal age AOR (95% CI) Maternal age, year of conception, pregnancy order, history of miscarriage, history of live births Logistic regression
Coding of maternal age not stated
<25 1.18 (0.80–1.73)
25 1 (reference)
30 1.05 (0.83–1.33)
35 1.22 (0.94–1.59)
40 1.04 (0.71–1.53)
≥45 1.63 (1.08–2.47)
Baba et al. (2011) , Japan 2001–2005 Matched case-control Hospital-based Cases: n = 430
Controls: n = 830 (term delivery)		 Cases: 13%
Controls: 12%		 Early miscarriage <12 weeks Hospital diagnosis Paternal age AOR (95% CI) Maternal agec, year of the event, history of spontaneous abortion, history of induced abortion, treatment of infertility, maternal BMI, maternal smoking, maternal alcohol consumption, maternal employment, paternal smoking Conditional logistic regression
Matched for maternal age ± 3 years
<29 1 (reference)
29–39 1.14 (0.75–1.74)
≥40 1.65 (0.94–2.88)
Jaleel and Khan (2013), Pakistan 2007–2010 Case-control Hospital-based Cases: n = 200
Controls: n = 400 (ongoing pregnancy >24 weeks)		 Not stated Early miscarriage (otherwise not defined) Hospital diagnosis Paternal age AOR (95% CI) Maternal age, paternal genital tract infection Logistic regression
Coding of maternal age not stated
≤35 1 (reference)
36–40 16.44 (6.612–40.896)
41–45 13.738 (4.376–43.127)
>45 7.042 (1.269–39.090)
Xu et al. (2014) , China 2009–2012 Matched case-control Hospital-based Cases: n = 620
Controls: n = 1240 (ongoing pregnancy >12 weeks)		 Not stated Early miscarriage <13 weeks Hospital diagnosis Paternal age AOR (95% CI) Maternal agec, history of early miscarriage, history of induced abortion, vitamin supplementation, maternal smoking and alcohol consumption, maternal night shift work, frequent staying up late, physical exercise Conditional logistic regression
Matched for maternal age ± 3 years
<25 1 (reference)
25–29 0.94 (0.81–1.28)
30–34 1.04 (0.85–1.32)
35–39 0.97 (0.79–1.37)
≥40 1.16 (0.86–1.42)
25–29 1 (reference)
30–34 1.11 (0.90–1.40)b
35–39 1.03 (0.84–1.46)b
≥40 1.23 (0.91–1.51)b
Nguyen et al. (2019) , USA 2011–2015 Case-control Population-based (National Survey of Family Growth) Cases: 2300 pregnancies
Controls: 10410 pregnancies (live birth ≥37 weeks)		 Only spontaneous pregnancies Loss of clinically recognized pregnancy ≤12 weeks and < 20 weeks Self-reports Paternal age AOR (95% CI) Maternal age, ethnicity, income, marital status, pregnancy intention Generalized estimating equations logistic regression
Maternal age entered in model in four age categories
<20 weeks
<25 1.03 (0.85–1.25)
25–29 1 (reference)
30–34 1.04 (0.83–1.29)
35–39 1.11 (0.81–1.52)
40–44 1.10 (0.70–1.74)
45–49 1.49 (0.71–3.13)
≥50 2.05 (1.06–3.93)
≤12 weeks
<25 1.07 (0.86–1.32)
25–29 1 (reference)
30–34 1.10 (0.86–1.39)
35–39 1.08 (0.76–1.52)
40–44 1.10 (0.67–1.82)
45–49 1.49 (0.65–3.40)
≥50 2.30 (1.17–4.52)

aRecalculated from the risk estimates reported for the combinations of paternal and maternal age, as described in Statistical analysis. bRescaled to reference category 25–29, as described in Statistical analysis. cMatched for maternal age (±3 years)

ART, artificial reproductive technology; AOR, adjusted odds ratio; AHR, adjusted hazard ratio; ARR, adjusted rate ratio; CI, confidence interval