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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

It was previously believed that sex differentiation took place when the undifferentiated gonads formed either testes or ovaries. Studies in recent years indicate that sex differentiation begins at conception. The SRY gene on the Y-chromosome is already transcribed at the 2-cell stage and triggers growth acceleration in the XY embryos. This accelerated growth is believed to be important for the male embryo as it allows complete testicular differentiation before the levels of oestrogenic hormones become too high as pregnancy progresses. It is well known that the death rate is higher for male than for female fetuses and that the increase is about 30% in chromosomally normal spontaneous abortions (i.e. significantly higher than at birth). National figures from Sweden show that boys are more likely to be delivered prematurely, accounting for 55–60% of all newborns between 23 and 32 gestational weeks. Neonatal deaths in these gestational weeks are also more common among boys. In 1993, the overall 1-year mortality rate (including all gestational weeks) in Sweden was 5.4% for boys and 4.1% for girls. The difference in infant mortality (within 1 year) is most pronounced at extremely early birth (23–24 gestational weeks) being 60% for boys compared with 38% for girls. The release of catecholamines during labour is an important defence mechanism by a hypoxic fetus. Preterm females have significantly higher catecholamine levels than males, which may explain the better outcome in females after a hypoxic event. Deaths occurring secondary to respiratory distress syndrome are greater for males and their cognitive recovery from perinatal intracranial haemorrhage is worse. Pulmonary hypoplasia after preterm rupture of the membranes is significantly more common among male newborns.Gender differences in mode of delivery, fetal heart rate in labour, acidaemia at birth, and age degenerative changes will also be discussed.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

In the perinatal field, gender differences for short- and long-term outcomes for the infant are often observed. It is generally believed that females have a better outcome after preterm birth. In this review some aspects of these differences from conception through birth are discussed.

Sex Ratio

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

It has been suggested that certain biological and environmental factors may have an impact on the sex of the baby. Numerous studies have reported associations with birth order, parental age, social class, paternal occupation, season of birth, and calendar period of delivery. However, in a large population study, Maconochie and Roman found no evidence that gender determination was anything other than a chance process1. The sex ratio male versus female was 1.06 in a population of 549,048 births. The sex ratio was unrelated to gender of preceding siblings, maternal age, maternal height, maternal social class, and year of delivery and season of birth.

The Y Chromosome

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

The Y chromosome contains the primary sex determination gene, SRY, which has been found in all mammals analysed, suggesting that the SRY gene is at least 130 million years old2. It might be as much as 300 million years old, although it has reduced its size by one third from its original size and lost about 97% of its genes. Most of the genes of the Y chromosome are involved in establishing a male gender. Over the course of time, the Y chromosome has degenerated and now contains only 50 genes compared to almost 3000 in the X chromosome. Therefore, the Y chromosome is highly repetitive and mostly non-functional (probably no surprise to half of the population without one). The reason for this is that 95% of the Y chromosome never exchanges DNA with the X chromosome. Some researchers speculate that the Y chromosome might, in another 100 million years, disappear completely and that in the future male characteristics may only be a special attribute found in women. (For further reading see Nature 2001; 409 (Feb 15).

Sex Differentiation and Metabolism

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

Sex differentiation begins at conception. It was previously believed that sex differentiation occurred when the undifferentiated gonads developed to an ovary or a testis. However, the Y chromosome with the testis-determining SRY gene may already have been transcribed at the two-cell stage3. Studies in murine and bovine embryos have demonstrated that the Y chromosome accelerates the growth of XY embryos4. This accelerated early growth and development is fuelled by a higher metabolic rate. In pre-implantation bovine embryos, Tiffen et al.5 showed that total glucose metabolism was twice as high in male embryos compared with female embryos. This provides the XY embryo with an advantage in development and thus male fetuses seem to be more advanced than female ones before the gonads have differentiated. Therefore, the XY embryos have a better chance in the race to develop testes before the accumulation of oestrogenic hormones becomes too high6.

Cord Artery Blood Glucose Levels

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

It has been suggested that the higher metabolic rate observed in individuals of male gender may be sustained throughout life6. If so, male newborns would have higher glucose levels at birth. With this hypothesis in mind, cord blood glucose levels were analysed in term deliveries7. Blood was taken from the artery immediately after birth and was analysed for blood glucose and acid base balance (including lactate). In samples from 3000 cases, the male newborn had a mean blood glucose level of 3.87 (SD 1.27) mmol/L compared with 3.71 (SD 1.22) mmol/L in female newborns. Furthermore, 58% of the male newborns had blood glucose levels above the 95th centile and only 43.3% with values below the 5th centile. No differences between genders were seen regarding cord artery blood glucose levels in cases with planned caesarean sections. Thus, one might speculate that the differences in cord artery blood glucose levels are due to gender differences in response to labour stress. There were significantly more male than female neonates with acidaemia (pH < 7.10) in the group with high glucose values and 7 of 9 cases with severe acidaemia in this group were boys; one of these had signs of neonatal encephalopathy and later developed cerebral palsy.

Spontaneous Abortions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

Chromosome analysis of spontaneous abortions may be marred by errors, due to the high rate of chromosome abnormalities and possible contamination with maternal tissues. However Hassold et al.8 estimated that the male : female sex ratio was 1.32 of chromosomally normal, spontaneous abortions i.e. a 30% increased risk for male fetuses.

Still Births and One-Year Mortality

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

Since 1973, data from all deliveries in Sweden have been registered in a national medical birth registry. Included were pregnancies with a gestational duration of at least 28 completed weeks or less if the infant was alive at birth. National figures have been analysed from 1999–2000, which consisted of 175,382 newborns, of which 672 were stillbirth. The stillbirth rate was similar among male fetuses (3.8 per 1000) compared with female ones (3.9 per 1000). However, there was a greater than 50% increase in the number of male infants dying neonatally or within one year. In total, the rate of mortality up to one year was 3.44 per 1000 for males compared with 2.18 per 1000 for females.

Gender Differences and Gestational Weeks

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

National figures from 1999–2000 also show that there are an increased number of males among preterm births (Fig. 1). The effect was roughly constant between 24 and 37 gestational weeks. In contrast, there was an excess of female newborns delivered between 38 and 40 gestational weeks. The greatest difference was observed in week 39, with 23.2% females compared with 21.4% males being born. During 41 and 42 weeks' gestation there was again an excess in males, most pronounced in week 42 with 7.5% males compared with 5.9% females.

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Figure 1. Number of births in gestational weeks 24–32 in Sweden 1999–2000.

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Cooperstock and Campbell9 studied gender differences and interactions with gestational age, race and multiple births in a register study from New England with more than 1.9 million births. They found a 7.2% excess of males among white singleton preterm births, roughly constant over 20–37 weeks of gestation. There was also a male excess for twins up to 33 weeks of gestation, but not further. An interesting finding was that the increased number of males among white singleton preterm newborns was significantly different from comparable blacks with a 7.2% excess of males compared with 2.8%, respectively (P < 0.001). The data indicated that mechanisms responsible for preterm birth rates in blacks were independent of fetal gender. It is generally believed that the fetuses are involved in the onset of normal labour and that male fetuses may promote the onset of preterm birth. Suggested mechanisms have included the action of androgen precursors, which are involved in the production of oestrogen, that may be increased in males10 and may facilitate preterm labour11. An alternative mechanism proposed suggests that the induction of labour may be promoted by interleukin-1 in males12 an effect that may be exacerbated by the lower levels of the interleukin-1 receptor antagonist found in the amniotic fluid of preterm males13.

In Sweden 1999–2000, 2277 infants were born alive between 24 and 32 gestational weeks. Of these, 55% were males and 45% were females. The difference in neonatal mortality was, however, greater in males (9.1%) compared with females (5.6%). The difference was even greater at extremely early gestational ages, between 23 and 24 weeks, with a one-year infant mortality rate for males of 55% compared with 32% in females.

Respiratory Distress Syndrome and Lung Maturation

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

The gender difference in neonatal mortality within the first week for infants born between 24 and 32 gestational weeks in Sweden (1999–2000) was also greater in males (6.25%) compared with females (3.68%). These data support previous studies showing that the male excess in neonatal mortality was most prominent during the first week of life and that mortality related to respiratory distress syndrome (RDS) showed the largest male excess with a relative risk of 1.5714. The authors suggested that slower lung maturation among male fetuses was a major contributing factor to gender differences in neonatal mortality. Other studies have shown an elevated risk for male infants to develop RDS15 and also a greater effect of betamethasone prophylaxis in female infants16. Others have found an appreciable female advantage in cognitive recovery from RDS and its complications17. Vergani et al. studied risk factors for pulmonary hypoplasia after premature rupture of the membranes before 29 weeks' gestation18. They found that two thirds of the infants developing pulmonary hypoplasia were male.

Sex Ratio and Mode of Delivery

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

Lieberman et al.19 found among 1246 nulliparous women a caesarean section rate of 13.2% if they carried male fetuses compared with 9.6% for a female fetus. There was a 30% increase in caesarean sections for slow progress with a male fetus, but the difference disappeared after adjustment for birth weight, gestational age, and head circumference. An adjusted odds ratio of 2.20 persisted for the indication of fetal distress, which occurred in 2.8% males and 1.7% females.

National figures from Sweden (1999–2000) demonstrated an increased number of emergency caesarean sections when the mother was carrying a male infant (8.3%) compared with a female infant (7.1%). Comparable figures for deliveries during gestational weeks 23 to 32 showed a 23% caesarean section rate when a male fetus was involved compared with 20.2% for females. The reason for this difference is unknown but may be associated with different responses to hypoxia. The release of catecholamines during labour is an important defence mechanism by the hypoxic fetus. Preterm females have significantly higher catecholamine levels after asphyxia than boys, which may explain the better outcome for them after a hypoxic event20.

Dawes et al. showed that during the last hour of labour, the female fetus was associated with significantly more tachycardia (150–200 beats per minute)21. In contrast, the male fetus had significantly more bradycardia (fetal heart rate 50–119 beats per minute). One may speculate that obstetricians are more alert for interventions when bradycardia appears, which may explain the higher rate of caesarean section for fetal distress in males.

Sex Ratio and Acidaemia at Birth

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

We analysed 15,840 acid–base balances in cord artery blood at term delivery with long-term follow-up of acidotic infants22. Pronounced acidaemia (pH < 7.0) was found in 61 infants of whom 39 (64%) were male newborns, which was significantly higher than female newborns (36%). The proportion of male and female newborns within the pH range 7.0–7.04 (47 boys and 46 girls) was similar to those without acidaemia. Ten infants had a complicated neonatal course; mild encephalopathy (n= 4); moderate encephalopathy (n= 3); intraventricular haemorrhage (grade II) (n= 1); and infant mortality (n= 2). In both cases of infant death, autopsy showed ischaemic cerebral lesions. Two of the eight infants with encephalopathy who survived had cerebral palsy at follow-up. Male gender was significantly associated with neonatal neurological complications (P= 0.04). The four newborns who died or developed cerebral palsy were all males. Developmental screening at four years of age showed that attention deficits occurred more often in male infants (10 of 13 cases), whereas speech problems occurred at similar rates in males and females (15 of 27 cases were male).

Placenta Praevia

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

Demissie et al. found in a cohort analysis that the male : female ratio at birth was significantly higher in women with placenta praevia (1.19) than those without placenta praevia (1.05, P < 0.001)23. The association of placenta praevia with male gender persisted when the analysis was either stratified or adjusted for the effects of maternal age, maternal parity, maternal smoking during the index pregnancy, race/ethnicity, gestational age and birth weight. A meta-analysis of seven published articles confirmed the findings in the cohort study with a 14% excess of placenta praevia for males.

Age Degenerative Changes

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

The higher metabolic rate in males compared with females remains throughout life and may result in a shorter life span for males6. The question is whether the higher metabolic rate also has an impact on age-related degenerative changes in the brain. From birth, men are associated with a larger brain volume than women, which is a natural consequence of a larger body volume. However, studies using magnetic resonance imaging show that during their lifetime males lose brain substances at a higher rate than females24,25. The loss is greatest in the frontal lobe, which is associated with abstract thinking, planning and psychological inhibition. The frontal lobe, which is significantly larger in males at the age of 18–40 years, is reduced in volume to the same size as women during the period 41–80 years. Also, in the temporal lobe, men lose brain cells more rapidly than women, but the reduction is comparatively smaller.

The reduction of brain substance in males can be correlated with cognitive changes, such as attention and verbal memory, without comparable effects in women. A possible explanation for the gender difference is that the cerebral blood flow is higher in elderly women than in men. Women seem to adapt to reductions in glucose metabolism in brain matter more efficiently26. Males try, without success, to compensate the loss by having a higher metabolic activity in the remaining brain tissue.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References

There is evidence that females have an advantage over males with a better outcome in the perinatal period, particularly after preterm birth. The gender difference seems to persist throughout life, particularly regarding age-related degenerative changes in the brain. Although there are gender differences originating from the period early after conception, the exact mechanisms responsible for the continued differences later in life remain to be determined.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sex Ratio
  5. The Y Chromosome
  6. Sex Differentiation and Metabolism
  7. Cord Artery Blood Glucose Levels
  8. Spontaneous Abortions
  9. Still Births and One-Year Mortality
  10. Gender Differences and Gestational Weeks
  11. Respiratory Distress Syndrome and Lung Maturation
  12. Sex Ratio and Mode of Delivery
  13. Sex Ratio and Acidaemia at Birth
  14. Placenta Praevia
  15. Age Degenerative Changes
  16. Conclusion
  17. References
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