SEARCH

SEARCH BY CITATION

Keywords:

  • Birthweight;
  • maternal age;
  • placental weight;
  • ratio

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

Please cite this paper as: Haavaldsen C, Samuelsen S, Eskild A. The association of maternal age with placental weight: a population-based study of 536 954 pregnancies. BJOG 2011;118:1470–1476.

Objective  To study the association of maternal age with placental weight, birthweight and placental weight/birthweight ratio.

Design  Population-based study.

Setting  Medical Birth Registry of Norway.

Population  All singleton births in Norway in the period 1999–2008 (n = 536 954).

Methods  Z-scores of placental weight and birthweight were calculated and divided into deciles. The proportions with a small or a large placenta were calculated within each maternal age group. Also, the odds ratios of having a small (lowest decile) and a large (highest decile) placenta, according to maternal age, were estimated, with and without adjustment for birthweight in grams, parity, smoking, pre-eclampsia and diabetes.

Main outcome measures  Placental weight, birthweight and placental weight/birthweight ratio.

Results  The mean placental weight increased with maternal age: 647.1 g in women below the age of 20 years and 691.3 g in women aged 45 years or older. Among the oldest group of women (≥45 years) 15.8% of placentas were in the highest decile of placental weight z-score, whereas this was true for just 7.0% of women below the age of 20 years (Wald test, P < 0.001). Using women younger than 20 years of age as a reference, the odds ratio for having a placenta in the highest decile of placental weight z-score was 2.50 (95% CI 1.92–3.26) for women aged 45 years or older, after adjustment for offspring birthweight, parity, maternal smoking, pre-eclampsia and diabetes.

Conclusion  We found an association between increased placental weight and maternal age, and this finding may be important in understanding the causes of adverse events associated with high maternal age.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

It has become increasingly common to postpone childbirth. The trend of delaying pregnancy creates new challenges for obstetric care, as older mothers have an increased risk of complications such as fetal death,1 pre-eclampsia,2 and preterm delivery.2,3 The mechanisms behind age acting as a co-factor for pregnancy complications remain largely unknown. Age-related changes in maternal metabolism,4 deterioration of myometrial function,5 poorer placental perfusion,6 and thereby impaired transplacental flux of nutrients with increased maternal age,6 have been suggested as possible explanations.

The placenta is essential in supplying the fetus with oxygen and nutrition. A well-functioning placenta is necessary for a successful pregnancy. Placental function is difficult to assess; however, placental weight has been suggested to be an indicator of placental function, and placentas that are low in weight may be less functional.7,8 The known association of pregnancy complications with increased maternal age may be mediated by impaired placental function.

Previous studies suggest that older mothers have an increased risk of delivering an infant that is small for gestational age.9 As placental weight and birthweight are closely correlated, it is to be expected that older mothers also have smaller placentas.10 Whether maternal age is associated with placental weight is, however, to our knowledge unknown. Our hypothesis proposes that older mothers have smaller and thereby less functional placentas compared with younger mothers, even when differences in birthweight according to maternal age are taken into account.

We studied the association between maternal age and placental weight, birthweight and placental weight/birthweight ratio. The association of maternal age with placental weight was also estimated after adjustment for offspring birthweight, parity, maternal smoking, pre-eclampsia and diabetes. Our study sample included all singleton pregnancies in Norway during the period 1999–2008, which gave a total of 536 954 births.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

All births after 16 weeks of gestation have been registered in the Medical Birth Registry of Norway since 1967 (http://www.mfr.no).11 The notification is compulsory, and is made by the midwife or attending physician shortly after delivery. Placental weight has been registered in the Medical Birth Registry since 1999.

Our study population included all births in Norway in the period 1999–2008 (n = 588 710). Information on placental weight was missing for 25 501 births. Maternal age was not registered for 60 women, and information on gestational length and birthweight was not available for 3848 and 782 births, respectively. We excluded multiple pregnancies and pregnancies lasting less than 22 weeks. Pregnancies with the following outlying values were excluded: recorded gestational length greater than 45 weeks; placental weight less than 25 g or more than 2500 g; and offspring birthweight less than 250 g or more than 6500 g. We also excluded births in which the sex of the offspring was not recorded or was unknown. A total of 21 565 births were thus excluded, leaving 536 954 pregnancies for statistical analysis.

The placentas were weighed fresh, with membranes and umbilical cord attached, within 1 hour of delivery. Placental weight was measured in grams. As placental weight varies by length of gestation, and length of gestation may vary by maternal age, we made an adjustment for length of gestation by calculating z-scores of placental weight, using means and standard deviations of placental weight by gestational week in the study population.12 The z-scores were also adjusted for sex, as placental weight is associated with the sex of the offspring.13 Hence, by using z-scores of placental weight, adjustments are included for both length of gestation at delivery and sex of the offspring. The placental weight z-scores were divided into deciles, where the smallest 10% of placentas were coded as 1 and the largest 10% of placentas were coded as 10. Hence, placentas in the lowest decile of placental weight z-score may be interpreted as small for gestational age, and the placentas in the highest decile may be interpreted as large for gestational age. The expected proportion within each decile is 10%, and for each age group the sum of proportions is 100%. Also, z-scores of birthweight were calculated and divided into deciles, as they were for placental weight.

By using placental weight and birthweight in grams as untransformed variables, we calculated placental weight/birthweight ratios. The placental weight/birthweight ratio was divided into deciles, and a high ratio indicates a large placenta relative to offspring birthweight.

Maternal age at the time of delivery was coded as follows: <20 (reference), 20–24, 25–29, 30–34, 35–39, 40–44 and 45 years of age or older.

We calculated mean placental weights and birthweights in grams for each maternal age group. In addition, we estimated the Pearson’s correlation coefficient between the placental weight and the birthweight for each age group. Thereafter, we estimated the distribution of placental weight and birthweight z-score deciles in each maternal age group. Also, the distribution of placental weight/birthweight ratios in grams within the maternal age groups was calculated.

Lastly, we estimated the odds ratios of having a small (lowest decile) or a large (highest decile) placenta according to maternal age, with and without adjustment for birthweight in grams, parity, smoking, pre-eclampsia and diabetes. Parity was defined as number of previous deliveries after 16 weeks of gestation, and was coded as 0 or ≥1. Information on smoking was obtained at the first antenatal care visit, and occasional or daily smokers were defined as being smokers. Pre-eclampsia was defined as blood pressure ≥140/90 mmHg and proteinuria with dipstick score of ≥1. Diabetes included type-I or type-II diabetes mellitus, gestational diabetes or use of anti-diabetic medication during pregnancy. The Statistical Package for Social Sciences spss 16.0 (Chicago, IL, USA) was used for all statistical analyses.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

The mean age at delivery was 29.4 years, and 16.4% of the population were 35 years or older. The mean placental weight was 673.1 g (SD 152.1 g), and increased with maternal age: in women below the age of 20 years it was 647.1 g (SD 144.8 g), and in women aged 45 years or older it was 691.3 g (SD 163.9). The association between birthweight and maternal age displayed an inverse U-shaped curve, and mean birthweight was highest in women aged 30–34 years. The estimated correlations between placental weight and birthweight were similar within all age groups (Table 1).

Table 1.   Placental weight, birthweight, and correlation between placental weight and birthweight, according to maternal age, in 536 954 pregnancies during 1999–2008 in Norway
Maternal age (years)nMean placental weight, g (SD)Mean birthweight, g (SD)Correlation placental weight/birth weight
<2012 768647.1 (144.8)3410.8 (595.6)0.645
20–2479 989661.5 (149.0)3496.6 (577.1)0.632
25–29177 351670.4 (150.3)3559.0 (577.2)0.633
30–34178 653678.8 (152.7)3594.3 (584.9)0.629
35–3975 562681.4 (156.0)3573.3 (618.8)0.641
40–4412 189681.0 (162.2)3526.1 (652.4)0.661
≥45442691.3 (163.9)3497.5 (605.2)0.643
Total536 954673.1 (152.1)3559.1 (589.3)0.635

Older women were over-represented in the highest decile, and under-represented in the lowest decile of placental weight z-score (Figure 1). Among women aged 40–44 years, 12.4% were in the highest decile and 9.6% were in the lowest decile of placental weight z-score. In the oldest age group, i.e. mothers aged 45 years or older, the placental size distribution displayed a U-shaped pattern: 15.8% were in the highest decile and 10.4% were in the lowest decile of placental weight z-score. In women less than 20 years old, a different pattern was seen: the highest proportion of women had the smallest placentas, and the lowest proportion of women had the largest placentas. In this age group, 11.4% were in the lowest decile and only 7.0% were in the highest decile of placental weight z-score.

image

Figure 1.  Z-scores of placental weight in deciles according to maternal age among all women giving birth in Norway in the period 1999–2008 (n = 536 954).

Download figure to PowerPoint

Also, for birthweight z-score, teenage mothers were over-represented in the lowest decile (14.1%) and under-represented in the highest decile (5.6%). The offspring of women aged 40–44 years were equally distributed across birthweight deciles, whereas offspring of women aged 45 years or older were over-represented in the lowest decile of birthweight z-score (14.5%; Figure 2).

image

Figure 2.  Z-scores of birthweight in deciles according to maternal age among all women giving birth in Norway in the period 1999–2008 (n = 536 954).

Download figure to PowerPoint

We also estimated the distribution of placental weight/birthweight ratio in grams by maternal age. Older mothers were over-represented in pregnancies with a high placental weight relative to the birthweight (Figure 3). Among mothers aged 45 years or older, 13.8% were in the highest decile, whereas 8.4% were in the lowest decile. The corresponding figures in teenagers were 10.5 and 9.2%, respectively.

image

Figure 3.  Placental weight/birthweight ratio in deciles according to maternal age among all women giving birth in Norway in the period 1999–2008 (n = 536 954).

Download figure to PowerPoint

When estimating the association of maternal age with being in the highest decile of placental weight z-score, we found an increasing prevalence with increasing maternal age (Wald test, < 0.001). The odds ratio for having a placenta in the highest decile of placental weight z-score was 2.50 (1.92–3.26) for women aged 45 years or older, as compared with mothers who were less than 20 years old. The increased odds ratio for high placental weight in these mothers remained essentially unchanged after adjustment for offspring birthweight, parity, maternal smoking, pre-eclampsia and diabetes (Table 2).

Table 2.   Odds ratio for being in the lowest and the highest decile of placental weight z-score among women giving birth in Norway during 1999–2008 (n = 536 954)
Maternal age (year)Total birthsnOR (95% CI)OR (95% CI)*OR (95% CI)**OR (95% CI)***
  1. *Adjusted for birthweight.

  2. **Adjusted for birthweight, parity and smoking.

  3. ***Adjusted for birthweight, parity, smoking, pre-eclampsia and diabetes.

Lowest decile placental weight z-score
<2012 76814561111
20–2479 98988760.97 (0.91–1.03)1.11 (1.04–1.18)1.11 (1.05–1.18)1.12 (1.05–1.19)
25–29177 35117 9690.88 (0.83–0.93)1.11 (1.05–1.18)1.13 (1.06–1.20)1.13 (1.06–1.20)
30–34178 65316 8770.81 (0.77–0.86)1.09 (1.03–1.16)1.12 (1.06–1.19)1.13 (1.06–1.20)
35–3975 56269450.79 (0.74–0.84)1.01 (0.95–1.08)1.05 (0.99–1.12)1.06 (1.00–1.13)
40–4412 18911750.83 (0.76–0.90)0.98 (0.90–1.06)1.02 (0.94–1.12)1.04 (0.95–1.13)
≥45442460.90 (0.66–1.23)0.99 (0.72–1.37)1.03 (0.75–1.43)1.05 (0.76–1.45)
Total536 95453 344    
Highest decile placental weight z-score
<2012 7688931111
20–2479 98968201.24 (1.15–1.33)1.08 (1.00–1.16)1.08 (1.00–1.17)1.07 (1.00–1.16)
25–29177 35116 6931.38 (1.29–1.48)1.06 (0.99–1.14)1.07 (0.99–1.15)1.06 (0.98–1.14)
30–34178 65319 0721.59 (1.48–1.70)1.14 (1.06–1.23)1.14 (1.06–1.23)1.13 (1.04–1.21)
35–3975 56286891.73 (1.61–1.86)1.25 (1.16–1.35)1.25 (1.16–1.35)1.22 (1.13–1.32)
40–4412 18915161.89 (1.73–2.06)1.47 (1.34–1.61)1.46 (1.32–1.60)1.40 (1.27–1.53)
≥45442702.50 (1.92–3.26)2.31 (1.73–3.09)2.29 (1.72–3.07)2.17 (1.62–2.91)
Total536 95453 753    

The association of maternal age with having a placenta in the lowest decile displayed a U-shaped pattern. Teenagers and mothers aged 45 years or older had the highest odds ratio for a small placenta. However, the association of high age with a small placenta was not significant after adjustment for the other study factors (Table 2). In the lowest decile, there was no significant trend by maternal age (Wald test, = 0.21).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

In this study of all singleton births in Norway in the period 1999–2008 (n = 536 954), mothers aged 40 years and older had significantly larger placentas than younger mothers, a difference that remained after adjusting for offspring birthweight, parity, smoking, pre-eclampsia and maternal diabetes. Older mothers also had a higher placental weight relative to birthweight as compared with younger mothers.

The mode of delivery may influence placental weighing procedures, and older mothers are more frequently delivered by caesarean section than younger mothers. In our study population, 32% of women aged 45 years or older delivered by caesarean section, compared with 10% of women below the age of 20 years (data not shown). In a caesarean delivery, the placenta is removed immediately. After a vaginal birth, the delay in placental delivery could result in a lower weight caused by the leakage of blood from the placenta. This could result in an overestimation of large placentas among the oldest women in the group. However, the mean placental weight in deliveries with (673.1 g) and without (671.9 g) caesarean section was essentially the same. Also, in a separate analysis we excluded all women delivered by caesarean section, and the association of placental weight with maternal age remained unchanged.

We presented the distributions of placental weight according to maternal age as proportions in each decile of placental weight z-score for each age group. Length of gestation is closely related to placental weight, and, in our data, also to maternal age. To adjust for differences in length of gestation between the different maternal age groups, we used z-scores of placental weight.

Population studies of placental function are scarce.14,15 Only a few studies have examined the association between maternal age with both placental weight and birthweight.16–19 The number of women included in these studies has generally been low, and the results have been inconsistent.

We believe that the risk of impaired placental function increases with age. We therefore hypothesized that older mothers have smaller placentas than younger mothers, but found the opposite to be true. Why older mothers have larger placentas is not easily explained. Diabetes and pre-eclampsia are associated with maternal age, and may also be associated with placental weight.14,20–23 However, adjustments for pre-eclampsia and diabetes did not alter the association of high maternal age with a large placenta. Hence, age-related factors other than pre-eclampsia and diabetes may explain the association of high maternal age with a large placenta. Hypertension is a risk factor for a small placenta.21 The prevalence of hypertension increases with age, and a lower placental weight in older mothers is therefore expected. We had limited information on non-pregnancy-induced hypertension, and adjustment could not be made. Nevertheless, hypertension at high maternal age is not likely to explain our findings.

Obese pregnant women may have larger placentas and a higher placental weight/birthweight ratio.21,24 Our results could therefore be biased if older women have the highest body mass indices. Population studies in Norway, however, suggest that young women have the highest body mass indices.25 Hence, it is unlikely that our results represent an overestimation of the association of maternal age with placental weight. Unfortunately, maternal weight and height are not reported to the Medical Birth Registry, and could therefore not be adjusted for.

Different stressors in pregnancy have been suggested to cause impaired placental blood flow,26,27 and factors associated with stress, such as a high level of physical activity,28,29 hyperemesis,30 and low socio-economic status,21,31 have been related to a large placenta. Hyperemesis, characterized by nausea and vomiting, and thus resulting in reduced energy uptake, is most often experienced in the first trimester of pregnancy, and seems to occur more often in younger rather than older women.32 Thus, hyperemesis cannot explain the higher prevalence of large placentas in older mothers. We have little information about the level of physical activity or socio-economic status according to maternal age in Norway.

High maternal age in itself may be considered a stress factor in pregnancy. Hence, similar mechanisms that cause large placentas in pregnancies with the conditions described above may play a role in the pregnancies of older mothers. It might be suggested that the enlargement of the placenta is a biological compensatory mechanism for placental dysfunction, and secures a threatened pregnancy. It is conceivable that the blood circulation in the myometrium differs by age. Impaired circulation and thus reduced oxygenation of the placental bed in older women may initiate placental growth through increased angiogenesis. Previous studies have shown an altered balance of angiogenic factors in threatened pregnancies, such as pregnancies with pre-eclampsia,33 and in pregnancies with growth restriction in the offspring.34 Whether there is an association of placental size with angiogenic factors is, to our knowledge, not known.

The enlarged placentas in older mothers may also be explained by differential selection by age of pregnancies that continue beyond the first trimester. Maybe only healthy pregnancies with well-functioning and large placentas are successful among the oldest women, whereas pregnancies with less functional and small placentas result in miscarriages in this age group. In younger women, a larger proportion of pregnancies with non-optimal placentation and placental dysfunction may still result in the delivery of an infant.

Both high and low placental weight/birthweight ratios have been associated with an increased risk of stillbirth and adverse neonatal outcome.35,36 A high placental weight/birthweight ratio has also been associated with an increased risk of cardiovascular disease in adulthood.37 A very small placenta is known to be dysfunctional. The association of high placental weight and function, however, remains unclear. A large placenta relative to birthweight may be a well-functioning placenta, but may also indicate dysfunction. The association of a high placental weight/birthweight ratio with pre-eclampsia, and also with increased risk of cardiovascular death later in life, suggests non-optimal placental function in pregnancies with a relatively large placenta. As older mothers have an increased risk of fetal death, our finding may be important in the search for causes of adverse pregnancy outcomes associated with high maternal age. Studies of adverse pregnancy outcomes associated with large placentas should therefore be encouraged.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

In our study of all births in Norway in the period 1999–2008, we found older mothers to have larger placentas than younger mothers. Older mothers were also over-represented in the highest decile of placental weight/birthweight ratio. Our finding encourages studies on the associations of a large placenta and disproportionate placental weight/birthweight ratio with adverse pregnancy outcomes.

Contribution to authorship

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

C.H. analysed the data and wrote the article. S.O.S. contributed to the data analysis, the interpretation of the results and writing the article. A.E. had the original idea for the study, and contributed to the analysis and writing of the article.

Details of ethics approval

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

The Norwegian Data Inspectorate and the Publication Committee of the Medical Birth Registry of Norway approved our study.

Acknowledgement

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References

We would like to thank the Medical Birth Registry of Norway for providing us with this unique data set.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interests
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgement
  13. References