Abstract
This study examines the association of placental weight with the risk of prenatal death using data from the Medical Birth Registry of Norway.
The placenta is a determinant of fetal growth, and infants who are born small for gestational age have an increased risk of infant death.1,2 Such knowledge suggests that placental factors may be associated with infant death, particularly in deaths shortly after birth.
Previously, low placental weight has been associated with increased risk of fetal death3 and with cerebral palsy in infants.4 By contrast, in preterm-born children, high placental weight and high placental weight relative to birth weight increased the risks.3,4 These previous findings suggest that placental weight may be associated with neonatal death and that associations may differ by gestational age at birth.
Therefore, we studied the association of placental weight with the risk of neonatal death. We also studied whether placental weight relative to birth weight was associated with neonatal death.
Methods
We used data from the Medical Birth Registry of Norway during January 1999 to December 2015, including all singleton infants in Norway without congenital malformations (n = 868 617) and all singleton infants with congenital malformations (n = 38 229). The study was approved by the Norwegian Data Inspectorate. The use of data from the Medical Birth Registry of Norway is regulated by law and the study was recommended by its advisory committee.
We grouped the distribution of placental weight (in grams) into quartiles within 2-week intervals of gestational age at birth. The associations of low (first quartile) and high (fourth quartile) placental weight with neonatal death were estimated as crude and adjusted odds ratios (aOR) with 95% confidence intervals. The second and third quartiles combined were used as the reference category. We made separate analyses among children born preterm (gestational weeks 29–36) and children born at term (gestational weeks 37-42) and we repeated the analyses using quartiles of placental weight relative to birth weight (placental weight/birth weight, in grams) as the exposure. Adjustments were made for offspring sex, parity (0 or ≥1), pregnancy after in vitro fertilization (yes/no), maternal age (years), maternal smoking (yes/no), preeclampsia (yes/no), and maternal diabetes (yes/no).
Results
Infants Without Congenital Malformations
In total, 492 of 868 617 infants without congenital malformations (0.06%) died during the neonatal period. Among the preterm born infants, high (aOR, 2.31; 95% CI, 1.63-3.27) and low placental weight (aOR, 1.56; 95% CI, 1.05-2.32) increased the risk of neonatal death (Table 1). Also, high placental weight relative to birth weight increased the risk of neonatal death among preterm-born children (aOR, 1.94; 95% CI, 1.40-2.70). Among the infants born at term, placental weight was not associated with neonatal death.
Table 1. Odds Ratios of Neonatal Death Among 868 617 Infants Without Congenital Malformations According to Gestational Age–Specific Quartiles of Placental Weight, Birth Weight, and Placental to Birth Weight Ratioa.
| Quartile | Neonatal Death | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Placental Weight | Birth Weight | Placental to Birth Weight Ratio | ||||||||||
| No. | OR (95% CI) | No. | OR (95% CI) | No. | OR (95% CI) | |||||||
| Yes | No | Crude | Adjusted | Yes | No | Crude | Adjusted | Yes | No | Crude | Adjusted | |
| Gestational Age, 29-36 wk (n = 39 641) | ||||||||||||
| First | 41 | 9345 | 1.45 (0.98-2.16) | 1.56 (1.05-2.32) | 42 | 9668 | 1.14 (0.78-1.67) | 1.29 (0.87-1.90) | 29 | 9936 | 0.79 (0.51-1.21) | 0.78 (0.51-1.21) |
| Second to third | 62 | 20 535 | 1 [Reference] | 1 [Reference] | 76 | 20 020 | 1 [Reference] | 1 [Reference] | 74 | 19 934 | 1 [Reference] | 1 [Reference] |
| Fourth | 69 | 9589 | 2.38 (1.69-3.36) | 2.31 (1.63-3.27) | 54 | 9781 | 1.45 (1.03-2.06) | 1.38 (0.97-1.97) | 69 | 9599 | 1.94 (1.39-2.69) | 1.94 (1.40-2.70) |
| Gestational Age, 37-42 wk (n = 828 976) | ||||||||||||
| First | 89 | 204 898 | 1.18 (0.91-1.54) | 1.18 (0.90-1.53) | 116 | 206 442 | 1.95 (1.51-2.52) | 1.90 (1.47-2.45) | 80 | 207 495 | 1.07 (0.82-1.41) | 1.09 (0.83-1.43) |
| Second to third | 151 | 411 649 | 1 [Reference] | 1 [Reference] | 120 | 416 265 | 1 [Reference] | 1 [Reference] | 149 | 414 620 | 1 [Reference] | 1 [Reference] |
| Fourth | 80 | 212 109 | 1.03 (0.78-1.35) | 1.03 (0.78-1.35) | 84 | 205 949 | 1.42 (1.07-1.87) | 1.43 (1.08-1.90) | 91 | 206 541 | 1.23 (0.96-1.59) | 1.20 (0.93-1.56) |
Abbreviation: OR, odds ratio.
Adjustments were made for offspring sex, parity (0 or ≥1), pregnancy after in vitro fertilization (yes/no), maternal age (years), maternal smoking (yes/no), preeclampsia (yes/no), and maternal diabetes (yes/no).
Infants With Congenital Malformations
In total, 467 of the 38 229 infants with congenital malformations (1.22%) died during the neonatal period. Among the preterm-born infants, the associations of placental weight with neonatal death displayed similar patterns as for infants without congenital malformation (Table 2). However, in term-born infants with congenital malformations, low placental weight increased the risk of neonatal death (aOR, 1.96; 95% CI, 1.48-2.60). Although the placental weight was low among the infants who died, birth weight was relatively lower. Thus, high placental weight relative to birth weight increased the risk of neonatal death in term-born infants with congenital malformations (aOR ,1.82; 95% CI, 1.37-2.41).
Table 2. Odds Ratios of Neonatal Death in 38 229 Infants With Congenital Malformations According to Gestational Age–Specific Quartiles of Placental Weight, Birth Weight, and Placental to Birth Weight Ratioa.
| Quartile | Neonatal Death | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Placental Weight | Birth Weight | Placental to Birth Weight Ratio | ||||||||||
| No. | OR (95% CI) | No. | OR (95% CI) | No. | OR (95% CI) | |||||||
| Yes | No | Crude | Adjusted | Yes | No | Crude | Adjusted | Yes | No | Crude | Adjusted | |
| Gestational Age 29-36 wk (n = 4187) | ||||||||||||
| First | 79 | 1042 | 1.93 (1.39-2.68) | 2.02 (1.45-2.82) | 99 | 1132 | 2.22 (1.63-3.04) | 2.47 (1.80-3.39) | 45 | 946 | 1.05 (0.72-1.52) | 1.04 (0.72-1.52) |
| Second to third | 71 | 1808 | 1 [Reference] | 1 [Reference] | 72 | 1831 | 1 [Reference] | 1 [Reference] | 83 | 1826 | 1 [Reference] | 1 [Reference] |
| Fourth | 65 | 1122 | 1.48 (1.05-2.08) | 1.47 (1.04-2.08) | 44 | 1009 | 1.11 (0.76-1.63) | 1.10 (0.75-1.63) | 87 | 1200 | 1.60 (1.17-2.17) | 1.59 (1.17-2.17) |
| Gestational Age 37-42 wk (n = 34 042) | ||||||||||||
| First | 102 | 8606 | 1.93 (1.46-2.55) | 1.96 (1.48-2.60) | 138 | 9242 | 2.80 (2.13-3.66) | 2.93 (2.23-3.85) | 55 | 8123 | 1.14 (0.82-1.59) | 1.14 (0.82-1.59) |
| Second to third | 99 | 16 127 | 1 [Reference] | 1 [Reference] | 86 | 16 096 | 1 [Reference] | 1 [Reference] | 98 | 16 539 | 1 [Reference] | 1 [Reference] |
| Fourth | 51 | 9057 | 0.92 (0.65-1.29) | 0.89 (0.64-1.26) | 28 | 8452 | 0.62 (0.40-0.95) | 0.58 (0.38-0.90) | 99 | 9128 | 1.83 (1.38-2.42) | 1.82 (1.37-2.41) |
Abbreviation: OR, odds ratio.
Adjustments were made for offspring sex, parity (0 or ≥1), pregnancy after in vitro fertilization (yes/no), maternal age (years), maternal smoking (yes/no), preeclampsia (yes/no), and maternal diabetes (yes/no).
Discussion
We found that high placental weight increased the risk of neonatal death in preterm-born infants. This finding is novel and difficult to explain. It is possible that underlying adverse intrauterine conditions, such as fetoplacental hypoxemia, could induce biological responses that result in placental enlargement,5 and also increase the risk of preterm birth and neonatal death.
Conclusions
We found that preterm born infants with either high or low placental weight had an increased risk of neonatal death. In term-born infants, low placental weight was associated with an increase in the risk of neonatal death among infants with congenital malformations. These findings may help to identify infants at increased risk of neonatal death.
References
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