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足月宝宝的性别特异性产期和新生儿结局

European Journal of Obstetrics & Gynecology and Reproductive Biology, pages 19 - 22

Abstract

Objective

The purpose of this study is to document the gender specific intrapartum and neonatal outcomes in term, singleton, appropriately grown babies.

Study design

De-identified, routinely collected data of all women meeting inclusion criteria between 2001 and 2011 were examined (n = 9223). Inclusion criteria were public (non-insured), primiparous women who had delivered singleton, appropriately grown babies at term. In this retrospective cohort study, we estimated 95% confidence intervals. Outcomes measured were maternal demographics, mode of delivery, birthweight, APGAR score, cord blood acidemia, respiratory distress, any resuscitation requirement, nursery admission and stillbirth rates.

Results

The sex ratio of male babies was 1.05:1 (4718 males; 4505 females,p = 0.85). Male babies were more likely to be delivered by instrumental (p = 0.004) or caesarean (p < 0.001). Birthweight was found to be a significant influencing factor on mode of delivery. Even after adjusting for birthweight, male babies were more likely to be delivered by instrumental delivery (OR 1.24,p < 0.001), as well as by emergency caesarean for failure to progress (OR 1.24,p = 0.04) and fetal distress (OR 1.38,p < 0.001). Male babies, despite having greater birthweights than female babies (p < 0.001), were more likely to have lower APGAR scores at 5 min (p = 0.004), require neonatal resuscitation (p < 0.001), develop respiratory distress (p = 0.005) and require nursery admission (p < 0.001). No statistical difference between male and female babies was found for cord blood acidemia (p = 0.58) or stillbirth (p = 0.49).

Conclusion

This large cohort study demonstrates that term, appropriately grown male babies in primiparous pregnancies fare more poorly in the intrapartum and neonatal periods than female babies. Even when birthweight was accounted for, male babies still required higher rates of intervention in the intrapartum and neonatal periods. This suggests gender may play an independent role in influencing pregnancy outcomes, although the underlying contributing physiology is not definitively established. The gender of the baby perhaps should be considered when counselling parents in the antepartum period.

Keywords: Gender, Intrapartum outcome, Neonatal outcome, Term delivery.

Introduction

With the exception of socially skewed birth ratios seen in some countries, the sex ratio at birth is surprisingly constant across different populations with 105–107 male births for every 100 female births [1] . Numerous demographic and environmental factors are believed to influence the sex ratio at birth [1] . Although the sex ratio at birth favors more male babies, the population sex ratio (the number of males to 100 females in the population) is reduced to 97.9–100.3 [2] , which has been attributed to subsequent increased male mortality [3] and in Australia at least, greater overall female life expectancy [4] .

Although more male babies are born, their perinatal and obstetric outcomes are substantially worse than for female babies [5] . Male babies are more likely to be associated with placental pathology disorders such as pre-eclampsia and placental abruption[6] and [7], as well as preterm delivery and caesarean delivery [5] . The longer-term outcomes are also affected with preterm male babies having substantially worse neurological outcomes than female babies [8] , including moderate to severe cerebral palsy [9] . Furthermore, in dichorionic twin pregnancies, the presence of a male co-twin is independently associated with worse neonatal outcomes [10] .

However, there is a gap in the literature exploring the gender specific intrapartum and neonatal outcomes for term, singleton, appropriately grown babies. Many of the larger institutional or population based studies have not differentiated between preterm and term deliveries and it is not clear if the differences in adverse outcomes are confounded by the worse outcomes in the preterm cohorts. The aim of this study was to describe the differences in intrapartum and neonatal outcome variables between appropriately grown male and female babies at term, in primiparous women.

Materials and methods

This was an 11 year retrospective cohort study conducted at Mater Mothers’ Hospital (MMH). MMH is one of two large perinatal tertiary referral centers in South East Queensland, Australia. Prospectively entered, routinely collected, de-identified data from the MMH's electronic maternity database, MatriX (Meridian Health Informatics, Surry Hills, New South Wales, Australia) were used. Ethics approval was obtained from the Mater Medical Research Institute (MMRI) Human Research Ethics Committee (reference number: EC00332).

Data were collated for public (non-insured), primiparous women aged between 18 and 40 years who had delivered appropriately grown, singleton babies at term (37–42 weeks) from January 2001 to December 2011.

Exclusion criteria included maternal age <18 or >40 years, gestation <37 weeks or >42 weeks, multiparity, multiple pregnancy, neonatal congenital anomaly or syndrome, birth weight <10th centile (<2500 g; Roberts and Lancaster [11] ) and privately insured patients.

Maternal demographics analyzed were: age, body mass index (BMI), ethnicity and smoking status at booking. Intrapartum outcomes recorded included mode of delivery and indication for caesarean or instrumental delivery. Neonatal outcomes obtained from the obstetric database were sex, birthweight, APGAR scores at 5 min, cord arterial pH <7.20, any resuscitation requirement, respiratory distress (as diagnosed by the attending pediatrician), neonatal nursery admission and stillbirth.

Statistical analysis was performed using Prism and Stata statistical software. Continuous and categorical variables were compared between groups usingt-tests and Chi-squared tests, respectively. For continuous variables, non-parametric methods were used when appropriate. Logistic regression analyses were used to determine odds ratios (ORs) when controlling for possible confounders.

Results

Of the total 90,802 deliveries at MMH over the course of the study, 9223 women met the inclusion criteria for this study ( Table 1 ). The median maternal age was 26.6 years (range 18–40) and the median maternal BMI was 23.7 kg/m2(range 14.02–63.06). Of the women included in the study, 3411 (37%) smoked, similarly distributed between mothers of male and female babies (50.8% vs 49.2%,p = 0.7). Women of Caucasian ethnicity comprised 6273 (68%) of the sample and 201 (2.2%) identified as Aboriginal or Torres Strait Islander (ATSI). The female to male sex ratio at birth for ATSI women was significant (58.7% vs 41.3%,p = 0.005).

Table 1 Maternal demographics for male and female babies.

Characteristic Total Male babies Female babies p Value
Number of women 9223 (100) 4718 (51.2) 4505 (48.8) 0.85
Maternal age*, median (range) 26.6 (18–40) 26.7 (18–40) 26.5 (18–40) 0.19
Maternal BMI*, (range) 23.7 (14.02–63.06) 23.7 (14.02–63.06) 23.7 (14.33–58.46) 0.78
Maternal smoking 3412 (37) 1734 (50.8) 1678 (49.2) 0.7
Maternal ethnicity (100)      
Caucasian (%) 6273 (68) 3229 (51.5) 3044 (48.5) 0.61
Asian (%) 1238 (13.4) 641 (51.8) 597 (48.2) 0.64
ATSI (%) 201 (2.2) 83 (41.3) 118 (58.7) 0.005
Other (%) 1511 (16.4) 765 (50.6) 746 (49.4) 0.66

All values are numbers (%) except* = age (years), BMI (kg/m2); BMI—body mass index; ATSI—Aboriginal and Torres Strait Islander.

The overall male to female sex ratio at birth was not significant (1.05:1, 4718 males: 4505 females,p = 0.85) although significant gender differences existed for intrapartum outcomes ( Table 2 ). Female babies were more likely to be born by normal vaginal delivery (NVD) (52.3% vs 47.7%,p < 0.001). More male babies required instrumental delivery (54.4% vs 45.6%,p = 0.004), including vacuum (57.6% vs 42.4%,p = 0.007) and forceps (59.9% vs 40.1%,p = 0.04) deliveries for failure to progress in the second stage. Of total deliveries, there were 2145 (23.3%) caesarean deliveries, of which 89.8% were emergency. More male babies required caesarean delivery (56.7% vs 43.3%,p < 0.001), including emergency caesarean for suspected fetal distress (57% vs 43%,p = 0.002) and for failure to progress (58.5% vs 41.5%,p < 0.001). When adjusted for birthweight, logistic regression analysis demonstrated male babies were more likely than females to require an instrumental delivery (OR 1.25,p < 0.001) or an emergency caesarean for either failure to progress (OR 1.24,p = 0.004) or suspected fetal distress (OR 1.38,p < 0.001).

Table 2 Comparison of mode of delivery between male and female babies.

Mode of delivery Number Male babies Female babies p Value
Total 9223 (100) 4718 (51.2) 4505 (48.8) 0.89
NVD 5183 (56.2) 2472 (47.7) 2711 (52.3) <0.001
Instrumental delivery 1895 (20.5) 1030 (54.4) 865 (45.6) 0.004
Vacuum 1510 (16.4) 824 (54.6) 686 (45.4) <0.001
FTP 425 (4.6) 245 (57.6) 180 (42.4) 0.007
Forceps 385 (4.2) 206 (53.5) 179 (46.5) 0.35
FTP 137 (1.48) 82 (59.9) 55 (40.1) 0.04
Caesarean section 2145 (23.3) 1216 (56.7) 929 (43.3) <0.001
Elective 218 (10.2) 123 (56.4) 95 (43.6) 0.12
Emergency 1927 (20.1) 1093 (56.7) 834 (43.3) <0.001
Suspected fetal distress 700 (7.58) 399 (57) 301 (43) 0.002
FTP 961 (10.4) 562 (58.5) 399 (41.5) <0.001

All values are numbers (%); NVD—normal vaginal delivery; FTP—failure to progress.

Neonatal outcomes ( Table 3 ) show male babies had greater birthweights than females overall (3623 g vs 3488 g,p < 0.001) and for each mode of delivery group (NVD 3558 g vs 3437 g,p < 0.001; instrumental 3615 g vs 3509 g,p < 0.001; caesarean 3762 g vs 3610 g,p < 0.001). Significantly more male babies had 5 min APGAR scores <7 (64.3% vs 35.7%,p = 0.004), neonatal resuscitation (54% vs 46%,p = <0.001), respiratory distress (59.6% vs 40.4%,p = 0.005) and nursery admission (60.1% vs 39.9%,p = <0.001) compared to female babies. Male babies delivered by NVD were more likely to require nursery admission (59% vs 41%,p < 0.001). Similarly, male babies born by instrumental delivery were more likely to have lower APGAR scores at 5 min (78.9% vs 21.1%,p = 0.002) and develop respiratory distress (68.4% vs 36.6%,p = 0.002).

Table 3 Neonatal outcomes by mode of delivery.

Outcome All delivery modes NVD Instrumental Caesarean
Males Females p Value Males Females p Value Males Females p Value Males Females p Value
Birthweight (g) median (range) 3623 (2550–5580) 3488 (2506–5470) <0.001 3558 (2550–5494) 3437 (2506–5335) <0.001 3615 (2570–5125) 3509 (2628–5030) <0.001 3762 (2593–5580) 3610 (2519–5470) <0.001
APGAR score <7 at 5 min 74 (64.3) 41 (35.7) 0.004 28 (56) 22 (44) 0.23 30 (78.9) 8 (21.1) 0.002 16 (59.3) 11 (40.7) 0.75
Cord pH <7.2 243 (52.4) 221 (47.6) 0.58 61 (46.6) 70 (53.4) 0.79 114 (52.1) 105 (47.9) 0.49 66 (58.4) 47 (41.6) 0.71
Requires resuscitation 2360 (54) 2013 (46) <0.001 723 (49.4) 742 (50.6) 0.19 659 (54.9) 541 (45.1) 0.7 978 (57.3) 730 (42.7) 0.63
Respiratory distress 168 (59.6) 114 (40.4) 0.005 47 (53.4) 41 (46.6) 0.28 64 (68.4) 37 (36.6) 0.002 57 (61.3) 36 (38.7) 0.37
Nursery admission 435 (60.1) 289 (39.9) <0.001 138 (59) 96 (41) <0.001 140 (60.6) 91 (39.4) 0.06 157 (60.6) 102 (39.4) 0.2
Stillbirth 9 (60) 6 (40) 0.49 5 (50) 5 (50) 0.85 3 (100) 0 (0) 0.11 1 (50) 1 (50) 0.84

All values are numbers (%) except birthweight. NVDs—normal vaginal delivery.

Comment

This large study demonstrates that term, singleton, appropriately grown male babies have worse intrapartum and neonatal outcomes compared to female babies. Although these results are broadly consistent with other published data what is striking about our results is that in the absence of any significant predisposing maternal or fetal conditions, gender appears to influence outcomes to such a marked degree. The value of this study lies in the large number of cases analyzed, the outcomes measured and that all cases were from the same centre and thus managed according to the same clinical guidelines and protocols.

It is known that male babies tend to have greater birthweights than females, and that male babies are more likely to be born by instrumental [12] or caesarean delivery[7], [12], and [13]compared to female babies. Our findings are consistent with this. In our study, caesarean delivery for male babies, when compared to female babies, was significantly higher for both failure to progress and suspected fetal distress. Liebermann et al. [14] suggested that the gender difference in caesareans for failure to progress, but not for suspected fetal distress, was attributable to greater birthweight and head circumference of male babies. Melamed et al. [15] however demonstrated that in the setting of failure to progress, caesarean delivery rates remained greater for male babies even after adjustment for potential confounders, including birthweight. In our study the overall difference in median birth weights was 135 g, 88 g more than the difference described by Liebermann et al. [14] . Why such a relatively small difference in birthweight has such a profound influence on mode of delivery is unclear. Despite the relatively small difference in birthweight, and even when birthweight was accounted for, our analysis demonstrated a male dominant gender difference for caesarean deliveries performed for both failure to progress and suspected fetal distress. This suggests the difference in outcomes may be underpinned by far more complex, gender specific factors.

Although larger infants tend to have higher survival rates[16] and [17], male gender is associated with increased morbidity and perinatal mortality [18] . In a large study from Israel, Simchen et al. [19] demonstrated poorer outcomes in male babies, with the risk of adverse sequelae further exaggerated in male, small for gestational age babies. In our study, male babies had lower 5 min APGAR scores, higher rates of respiratory distress, greater need for resuscitation and more nursery admissions. Explanations for this male disadvantage remain elusive though there are some important postulations.

It is theorized that the greater subcutaneous fat in female babies, rather than the overall birthweight, contributes to their better neonatal outcomes [20] . Furthermore, preterm female infants have higher catecholamine levels after asphyxia than males, perhaps explaining the better outcomes for girls after a hypoxic event [21] . These findings are not restricted to humans. When replicated in animal studies, female animal fetuses demonstrated better neuroprotection after cooling compared to males [22] and animal models by Loidl et al. [23] and Meng and Drugan [24] both demonstrated greater female survival after perinatal asphyxia. In adults admitted to intensive care units, the mechanisms accounting for this dimorphism are, in part, related to differential cytokine responses to injury, with men expressing a more robust proinflammatory profile [25] . It is possible that male babies may mount a similar pro-inflammatory response influencing perinatal outcome.

A recent study from our group demonstrated gender specific differences in feto-placental perfusion [26] with appropriately grown, term male fetuses having increased cerebral blood flow and decreased umbilical venous flow relative to female counterparts. This is a pattern similar to that seen in growth-restricted fetuses with impaired placental function. This cerebral redistribution, altering the cerebroumbilical blood flow ratio, has also been shown to be predictive of intrapartum compromise [27] .

The causes for gender specific perfusional changes are unclear. Palumbo et al. [28] reported that in women with polycystic ovarian syndrome with hyperandrogenemia, decidual trophoblast invasion was impaired with an inverse correlation with endovascular invasion and testosterone levels. This raises the possibility that a similar mechanism may exist in women carrying male fetuses and that relative suboptimal placentation may be one factor responsible for some of the adverse outcomes documented in this and other studies [29] .

We acknowledge that our study does have some limitations. These include its retrospective design and some of the inherent problems in obtaining data from a large database, including incomplete data entry. Furthermore a large number of women who delivered at MMH were excluded, as they did not meet the lower-risk pregnancy inclusion criteria set out in this study. Despite these limitations, this large study supports previous works and further, demonstrates the male dominant gender difference in intrapartum and neonatal outcomes even in appropriately grown term babies.

The findings of this study may then have implications on how patients are counseled about intrapartum and neonatal events. Although there is insufficient evidence at the present time to alter intrapartum management on the basis of fetal gender, it is possible that in the future an individualized risk based profile taking into account the gender of the baby may be used in obstetric management.

Condensation

Gender appears to independently influence intrapartum and neonatal outcomes with male babies requiring more obstetric and neonatal interventions than female babies.

Conflict of interest statement

There are no conflicts of interest or financial or funding agreements to disclose.

Acknowledgements

The authors thank Prof David Tudehope (Mater Children's Hospital, South Brisbane, Queensland, Australia) and Ms Barbara Soong (Mater Mothers’ Hospital, South Brisbane, Queensland, Australia) for their contributions in the preparation of this manuscript. Study conducted in Brisbane, Queensland, Australia.

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Footnotes

a Mater Medical Research Institute—University of Queensland, Level 3, Aubigny Place, Raymond Terrace, South Brisbane 4101, QLD, Australia

b Institute for Reproductive and Developmental Biology, Imperial College London, London W12 0HS, UK

lowast Corresponding author at: Mater Research Institute/University of Queensland, Maternal & Fetal Medicine, Mater Mothers’ Hospital, Level 3, Aubigny Place, Raymond Terrace, South Brisbane 4010, QLD, Australia. Tel.: +61 7 31638844.