The Center for Twin Research, Graduate School of Medicine, Osaka University, Suita City, Japan
Received date: November 13, 2015; Accepted date: December 01, 2015; Published date: December 13, 2015
Citation: Imaizumi Y (2015) Infant Mortality of Zygotic Twins and Influencing Factors in Japan, 1995–2008. Gynecol Obstet (Sunnyvale) 5:341. doi:10.4172/2161-0932.1000341
Copyright: © 2015 Imaizumi Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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We aimed to determine the infant mortality rates (IMRs) for monozygotic (MZ) and dizygotic (DZ) twins along with risk factors associated with these IMRs. Study design: IMRs of zygotic twins were estimated using vital statistics from Japan between 1995 and 2008. Results: In 1995, IMRs were 21.7 for MZ twins and 15.6 for DZ twins per 1000 deliveries, and they significantly decreased to 9.8 and 5.8, respectively, in 2008. During the study period, IMRs were the lowest at maternal ages (MAs) of 35–39 years for MZ (14.4) twins and 30–34 years for DZ twins (8.2). The highest IMRs were for MZ (23.6) and DZ (24.9) twins at MAs of <20 years. At MAs of 20–24 and 35–39 years, IMRs were significantly higher for MZ than DZ twins. IMRs were also the lowest at gestational ages (GAs) of 37 weeks for MZ (3.0) twins and 39 weeks for DZ twins (1.9). At GAs of <29 weeks and 33–34 weeks, IMRs were significantly higher for MZ than DZ twins. Conclusion: IMR was significantly higher for MZ than DZ twins, although these rates significantly decreased each year. For both MZ and DZ twins, mortality risk factors were MAs of <20 years and GAs of up to 35 weeks.
Although stillbirth and perinatal mortality rates for twins have been reported by many authors, infant mortality data are scarce, particularly for zygotic twins. Infant mortality rates (IMRs) for twins have decreased in Japan since 1974 [1-3]. Recognized risk factors for twin mortality include the sex and birth order of twins [1-4], zygosity [1,4], maternal age (MA) [1,3,4], gestational age (GA), birth weight (BW) [1,3,4], race [5-7], mother’s health condition, and monthly household expenditure .
The present study estimated IMRs for monozygotic (MZ) and dizygotic (DZ) twins in Japan between 1995 and 2008 and identified risk factors associated with these IMRs.
Data on twin live births (LBs) between 1995 and 2008 were obtained from national statistical records. The Statistics and Information Department, Ministry of Health, Labour and Welfare (Tokyo, Japan) maintains records covering the entire Japanese population. LB certificates include details about the nationality, sex, birth date, address, GA, BW, parental birth dates and ages, single or multiple births, and birth order in multiple births. Infant death (D) certificates contain the same information as LB certificates (excluding paternal age) as well as the date and cause of death.
Describing twin data
Infant death data were obtained for twin pairs with both LBs (Ds), one LB (D), and one LB (D)–one fetal death (FD). We estimated the number of MZ and DZ twins using the Weinberg method . MA and GA were not always the same for twin pairs because each twin could be born on a different date; therefore, in some cases, the number of like- or unlike-sexed twin pairs included odd numbers of twins.
To calculate IMRs for MZ and DZ twins, denominators (total live twin pairs at birth: both LBs at birth and one LB–one FD) were obtained from (Tables 1-3) of the study by Imaizumi and Hayakawa . For the purpose of our study, LB twin pairs [both LBs plus (one LB–one FD)/2] were used as the denominator. The numerators used were twin pairs of both LBs–Ds plus [one LB (S)–one LB (D)]/2 plus [one LB (D)–one FD]/2. IMRs for MZ and DZ twins are presented as 1000 twin pairs of infant deaths divided by LB twin pairs.
|Year||Both LB (D)||One LB (S) , one LB (D)||One LB (D), One FD||Twin pairs
|Both LB||One LB, one FD||Twin pairs of LBs||IMR||Odds ratio [95% CI]
MZ vs. DZ twins
Linear regression coefficient (p-value) of IMR on the year; MZ twins -0.82(<0.001); DZ twins -0.49 (<0.001)
LB: Live birth; (D): Infant death; (S): Survived; FD: Fetal death (12 weeks of gestation and over);
IMR: Infant mortality rate per 1000 twin pairs of LBs; CI: Confidence interval
Table 1: Infant mortality rate in zygotic twins, 1995-2008.
Annual changes in IMRs for zygotic twins
Table 1 and Figure 1 show the annual changes in IMRs for MZ and DZ twins between 1995 and 2008. IMRs for both MZ and DZ twins decreased year by year. The linear regression coefficients of IMRs for MZ and DZ twins on the year were –0.82 and –0.49, respectively. These values are significant at the 0.1% level. By 2008, IMRs had declined to approximately 1/2 of the 1995 value for MZ twins and 1/3 for DZ twins.
In every year except 2007, the IMR was higher in MZ than DZ twins, and was significant at the 5% level.
IMRs in zygotic twins by MA
Table 2 shows IMRs for zygotic twins by MA during the study period. IMRs were the lowest at MAs of 35–39 years for MZ twins and 30–34 years for DZ twins. IMRs for MZ twins at MAs of 35–39 years were significantly lower than those at MAs of <20 and 20–24 years. For DZ twins, IMR at MAs of 30–34 years was significantly lower than that of other MAs, with the exception at MAs of 20–24 and ≥40 years. IMRs were also significantly higher in MZ than DZ twins for MAs between 20–24 and 35–39 years.
|Maternal age||Both LB (D)||One LB (S), one LB (D)||One LB (D), one FD||Pairs of Ds||Both LB||One LB, one FD||Pairs of LBs||IMR||Odds ratio [95% CI]||Odds ratio [95% CI]:
MZ vs. DZ twins
|＜20||8||22||6||22.0||920.0||22.0||931.0||23.6||1.66* [1.05-2.63]||0.95 [0.43-2.08]|
|20-24||62||202||35||180.5||8276.0||219.5||8385.8||21.5||1.51* [1.19-1.90]||2.38* [1.73-3.28]|
|25-29||128||432||83||385.5||23161.0||633.5||23477.8||16.4||1.14 [0.93-1.41]||1.64* [1.40-1.92]|
|30-34||103||373||83||331.0||22590.5||591.5||22886.3||14.5||1.01 [0.81-1.24]||1.79* [1.53-2.08]|
|35-39||38||129||32||118.5||8129.5||206.5||8232.8||14.4||1.00: Reference||1.47* [1.16-1.85]|
|≥40||4||22||4||17.0||1058.0||37.0||1076.5||15.8||1.10 [0.66-1.83]||1.71 [0.88-3.30]|
LB: Live birth; (D): Infant death; (S): Survived; FD: Fetal death (12 weeks of gestation and over); IMR: Infant mortality rate per 1000 twins pairs of LBs; CI: Confidence interval
Table 2: lnfant mortality rate in zygotic twins by maternal age, 1995-2008.
IMRs for zygotic twins by GA
Table 3 shows IMRs for zygotic twins by GA during the study period. IMR for MZ twins was 696 at GA of <24 weeks and decreased as GA increased beyond 37 weeks (3.0). IMRs for MZ twins were similar at GA of ≥ 36 weeks (3.0–6.2). For DZ twins, IMR was 589 at GA of <24 weeks and continued to decrease as GA increased beyond 39 weeks (1.9) (except for at 38 weeks). At GAs of <29 weeks and 33–34 weeks, IMRs for MZ twins were significantly higher than those for DZ twins.
|Gestational age||Both LB (D)||One LB (S), one LB (D)||One LB(D), one FD||Twin pairs of Ds||Both LB||One LB,
|Twin pairs of LBs||IMR||Odds ratio [95% CI]||Odds ratio [95% CI]:
MZ vs. DZ twins
|<24||92.0||31||22||118.5||142.0||56.5||170.3||696.0||751.2* [493.4-1143.7]||1.58* [1.06-2.36]|
|24||56.0||62||27||100.5||179.0||64.5||211.3||475.7||297.7* [204.0-434.5]||1.82* [1.25-2.65]|
|25||46.5||106||28||114.0||274.0||57.0||302.5||376.9||198.4* [139.5-282.2]||2.58* [1.79-3.72]|
|26||38.0||111||26||106.5||369.0||73.0||405.5||262.6||116.9* [82.8-165.0]||2.35* [1.61-3.43]|
|27||34.5||86||34||94.5||507.0||82.5||548.3||171.5||68.3* [48.4-96.5]||2.26* [1.51-3.36]|
|28||23.0||112||31||94.5||658.0||105.5||710.8||131.6||49.7* [35.3-70.0]||3.45* [2.19-5.44]|
|29||7.5||64||14||46.5||684.5||107.0||738.0||63.0||22.1* [14.8-32.8]||1.48* [0.93-2.38]|
|30||6.0||50||10||36.0||845.5||106.0||898.5||40.1||13.7* [9.0-21.0]||1.26* [0.76-2.08]|
|31||6.0||54||7||36.5||1194.5||102.5||1245.8||29.3||9.9* [6.5-15.1]||1.30* [0.79-2.14]|
|32||5.5||61||7||39.5||1777.0||113.5||1833.8||21.5||7.2* [4.8-10.9]||1.65* [0.97-2.78]|
|33||4.0||54||7||34.5||2379.5||97.5||2428.3||14.2||4.7* [3.1-7.3]||1.80* [1.04-3.13]|
|34||3.0||77||2||42.5||3886.5||96.0||3934.5||10.8||3.6* [2.4-5.4]||1.84* [1.13-2.98]|
|35||7.0||60||9||41.5||6806.5||143.0||6878.0||6.0||2.0* [1.3-3.0]||1.07 [0.71-1.62]|
|36||3.0||77||7||45.0||14193.5||171.0||14279.0||3.2||1.04 [0.7-1.5]||0.84 [0.58-1.21]|
|37||5.0||93||7||55.0||18014.0||167.5||18097.8||3.0||1.00 :Reference||1.16 [0.82-1.63]|
|38||3.0||45||5||28.0||7733.5||88.0||7777.5||3.6||1.2 [0.8-1.9]||1.23 [0.74-2.03]|
|39||0.0||25||1||13.0||3206.0||47.0||3229.5||4.0||1.3 [0.7-2.4]||2.17 [0.90-5.25]|
|≥40||1.0||14||0||8.0||1269.0||31.5||1284.8||6.2||2.1 [0.98-4.3]||1.29 [0.50-3.36]|
LB: Live birth; D: Infant death; FD: Fetal death (12 weeks of gestation and over); IMR: Infant mortality rate per 1000 twins pairs of LBs;CI: Confidence interval
Table 3: Infant mortality rate in zygotic twins by gestational age, 1995-2008.
To provide context for the present study, we used data from the study by Imaizumi et al (Table 2)  to recalculate IMRs for MZ and DZ twins in 1974, finding IMRs of 47.51 (116 × 1000/2441.5) for MZ twins and 45.23 (64 × 1000/1415) for DZ twins. These IMRs were similar for MZ and DZ twins [odds ratio (OR) 1.05, 95% confidence interval (CI): 0.77–1.44] and were significantly higher than those in 1995 (MZ twins: OR 2.22, 95% CI: 1.70–2.91; DZ twins: OR 3.00, 95% CI: 2.14–4.20). In the 21 years from 1974 to 1995, the corresponding IMRs for MZ and DZ twins dramatically decreased to 21.7 and 15.6, respectively. By 2008, these rates had again markedly decreased by 1/2 and 1/3 respectively. The improved medical care may explain the declining IMRs for MZ and DZ twins in the last 34 years. From (Figure 1), the ratio of IMRs for DZ twins and singletons was 4.2 in 1995 and decreased to 2.6 in 2008 where IMR was significantly higher in DZ twins than singletons in each year. Our results also indicated that risk factors such as MA and GA influence IMRs for MZ and DZ twins.
We found that IMRs were significantly higher for MZ than DZ twins in every year except 2007. During 1995–2008, the overall IMRs were 16.3 (1056 × 1000/64990) for MZ twins and 9.1 (840 × 1000/91857) for DZ twins (Table 1). The study by Imaizumi and Hayakawa  reported that there were 352 infant deaths due to twinto- twin transfusion syndrome (TTTS) during 1995–2008. However, overall, there were 1056 infant MZ twin pair deaths during the same period (Table 1). This indicates that 16.7% (176/1056) of IMRs for MZ twins was explained by TTTS.
There may be some errors in the estimated infant deaths for MZ and DZ twins resulting from the available data. For example, we found that the data contained cases where there were different addresses for twin pairs due to migration between birth and death. Twenty five twin pairs with one LB (D)–one FD (unknown sex) were eliminated due to unknown MZ and DZ twins. Data from Imaizumi (Table 3)  and Imaizumi and Hayakawa (Table 2)  indicate that the total number of infant deaths (males and females) was 1365 for 1995–1998 and 2670 for 1999–2008. However, we found that there were 3792 infant deaths for individual MZ and DZ twins (Table 1), giving an estimated proportion of 94.6% [3792/(4035-25)] infant deaths for zygotic twins. Another minor underestimation might be present for 2008 as some infants surviving in 2008 may have died in 2009. As far as vital statistics is used to estimate IMRs for zygotic twins, it seems not possible to avoid an error of about 5%.
We are grateful to the staff of Statistics and Information Department, Ministry of Health, Labour and Welfare in Japan.