Male Fetuses Are Associated With Increased Risk for Cesarean Delivery in Malaysian Nulliparae

Abstract

The association between fetal sex and outcome of pregnancy and labor has been well documented in western populations. However, no studies in Malaysia or other developing countries have examined the effect of fetal sex on such outcomes.

The main objective of this study was to determine the influence of fetal sex on the outcome of labor at term in a cohort of Malaysian nulliparae.

A retrospective observational study was designed using data from 4644 Malaysian nulliparae who gave birth consecutively to singleton male babies at Hospital Sultanah Aminah, Johor Bahru, after normal full-term pregnancies.

The results of this study indicate that mothers giving birth to male infants have a greater risk of requiring cesarean delivery because male babies are heavier and have statistically significantly greater head circumference (P < .001). These findings concur with those obtained in western populations and suggest that the differences in outcome observed are biological, not dictated by race, ethnicity, or environmental conditions. Such information could help in the antenatal assessment of Malaysian patients and stimulate more comprehensive studies of the mechanisms involved in this sex-based difference in outcomes. Reasons for such differences are proposed.

Introduction

The association between fetal sex and various outcomes of pregnancy[1–3] and labor[4–6] have been well documented in western populations. For example, the higher incidence of pregnancy-induced hypertension in women carrying male fetuses has been documented[7,8] and ascribed to higher levels of testosterone in those pregnancies.[9] Women carrying male infants also have a higher incidence of preterm labor and preterm premature rupture of membranes. The precise mechanisms involved in these outcomes remain unclear; however, male sex is considered to increase vulnerability by the action of androgen precursors. These precursors are involved in the production of estrogens, which may facilitate labor. Androgen precursors, such as dihydrotestosterone and testosterone, are also associated with delaying pulmonary maturity, resulting in increased risk for respiratory difficulties in the male newborn.[3]

Male sex of the fetus is also associated with gestational diabetes mellitus, fetal macrosomia, failure to progress, and cesarean delivery. However, this information is not available for countries such as Malaysia. We set out to document these findings so that we could conduct more detailed studies to better understand the basic mechanisms of fetal life and how fetal sex influences these mechanisms. Such information could also be of help in the antenatal counseling of pregnant women.

Objective

The main objective of this study was to assess the extent to which fetal sex influences the outcome of labor at term in a cohort of Malaysian nulliparae at term who gave birth at Hospital Sultanah Aminah, Johor Bahru, Malaysia.

Study Methods

Relevant data were retrieved from the Delivery Suite Records of Hospital Sultanah Aminah for January 1, 2007, to December 31, 2007. Only data from primigravid mothers giving birth at term to singleton babies with vertex presentations after spontaneous labor at term were included for analysis. Mothers with fetal malpresentations and complications known to affect fetal size and well-being, such as hypertension, smoking, bleeding, and diabetes, were excluded from the study. Patients using epidural analgesia were also excluded from this analysis. These criteria were used to minimize effects of confounders on the outcome of labor so that our observations were restricted, as far as possible, to fetal sex.

Hospital Sultanah Aminah is the main hospital for the State of Johor and delivers babies for approximately 20,000 mothers annually. The main outcome measures studied were color of amniotic fluid, birth weight, head circumference, Apgar score, need for induction or augmentation, mode of delivery, destination of baby, and incidence of postpartum hemorrhage. Chi-square tests and t tests were used for statistical analysis. P values less than .01 were considered to represent statistically significant differences.

Results

During the study period, 2367 male infants and 2277 female infants fulfilled the inclusion criteria. The male infants and female infants did not significantly differ in terms of ethnic composition and maternal age (Table 1).

Table 1.

Demographic Details

Variable	Number (Percentage) of Mothers Delivering Male Babies (n = 2367)	Number (Percentage) of Mothers Delivering Female Babies (n = 2277)
Ethnicity
Malaysian	1450 (61.2)	1370 (60.2)
Chinese	496 (21)	499 (21.9)
Indians	186 (7.9)	185 (8.1)
Others	235 (10.2)	223 (9.8)
Age Groups
≤19 y	218 (9.2)	207 (9.1)
20–29 y	1850 (78.1)	1756 (77.1)
30–39 y	288 (12.2)	302 (13.3)
≥40 y	11 (0.5)	12 (0.5)

Babies of patients carrying male fetuses had significantly higher mean birth weight and head circumference: 3052 (standard deviation [SD], 0.432) g compared with 2964 (SD, 0.420) g (P < .001), cm and 33.14 (SD, 1.427) cm compared with 32.74 (SD, 1.384) cm (P < .001). Male infants had a higher incidence of cesarean delivery (28% vs 24%; odds ratio, 1.25 [95% confidence interval, 1.07–1.43]; P < .001). A higher percentage of male babies were admitted to the Special Care Nursery (14.2% vs 12.4%), although the difference was not statistically significant (P = .056).

There was no significant difference between the sexes in the incidence of meconium-stained amniotic fluid, low Apgar score, induction or augmentation, and postpartum hemorrhage (Table 2).

Table 2.

Effect of Fetal Sex on Labor Outcomes and Events

Outcome or Events	Mothers Delivering Male Babies*	Mothers Delivering Female Babies*	Odds Ratio (95% Confidence Interval)	P Value for Difference
Total (n)	2367	2277
Amniotic fluid
Clear	2306 (97.4)	2200 (96.6)	1.32 (0.94–1.86)	.1
Meconium stained	61 (2.6)	76 (3.3)	0.76 (0.94–1.86)	.12
Blood stained	0	1 (0.1)
None	0	0
Apgar score ≥ 6	9 (0.4)	10 (0.4)	0.86 (0.35–2.13)	.75
Induction	25 (1.1)	17 (0.7)	1.42 (0.76–2.6)	.26
Oxytocin augmentation	88 (3.7)	69 (3)	1.23 (0.89–1.70)	.19
Mode of delivery
Spontaneous vaginal delivery	1440 (60.8)	1498 (65.5)	1.24 (1.10–1.40)	<.001
Cesarean delivery	661(28)	538(24)	1.25 (1.07–1.43)	.001
Forceps	31 (1.3)	23 (1)	1.30 (0.75–2.23)	.34
Vacuum	235 (9.9)	218 (9.5)	1.04 (0.86–1.26)	.68
Destination
Special care nursery	336 (14)	280 (12)	1.17 (0.99–1.39)	.056
Postnatal ward	2031 (86)	1997 (88)	0.85 (0.71–1.00)	.056
Postpartum hemorrhage	74 (3.1)	72 (3.2)	0.91 (0.71–1.37)	.94
Mean (SD) birth weights (g)	3052 (0.432)	2964 (0.420)		<.001
Mean (SD) head circumference (cm)	33.14 (1.427)	32.74 (1.384)		<.001

SD = standard deviation.

^*Unless otherwise noted, values are the number (percentage).

Discussion

In many societies, adverse outcomes in pregnancy and labor have often been ascribed to male fetal sex. Such conclusions were previously based largely on observational data and experience rather than on results of rigorous scientific investigation. In recent years, however, several studies conducted in western populations have confirmed that male sex of the fetus carries greater risk for such outcomes as preterm birth, preeclampsia, and intrapartum and neonatal hypoxia. Male sex has also been shown to be associated with a greater risk for cesarean delivery.

Our study, done in a developing country, Malaysia, also demonstrates a greater risk for cesarean delivery when the fetus is male, suggesting that this outcome is not influenced by race, ethnicity, or environmental conditions. We believe that association between adverse fetal outcome and fetal sex is indeed biological, one wherein the basic mechanisms are still being elucidated.

Our study suggests that the higher birth weight and greater head circumference in male fetuses could explain the increased rate of operative deliveries in mothers carrying male fetuses. Although we have not investigated the indications for cesarean deliveries in this study, it is possible that the male fetus is also more vulnerable to hypoxia during labor. Male fetuses are known to have lower catecholamine levels than their female counterparts and so are less protected against intrapartum hypoxia and its sequelae.[10] In this study, however, the presence of meconium staining of amniotic fluid and birth Apgar scores did not significantly differ between male and female fetuses.

The risk for operative delivery among mothers carrying male fetuses was first documented by Hall and Carr-Hill more than quarter of a century ago.[4] Since then, several other studies have drawn similar conclusions and have identified fetal macrosomia as the cause.[1,2,5,6] These studies, however, may have been biased because they did not always correct for all the confounders that could affect size at birth. Our study shows that male infants have not only significantly higher birth weights but also significantly larger head circumferences compared with female infants. Furthermore, our inclusion and exclusion criteria were designed to minimize the effects of as many confounding factors as possible. Demographic details of mothers in both groups were also very similar. Unfortunately, stratification of data by ethnic group was not appropriate because of the small numbers of non-Malaysian mothers. This will be the subject of a future study.

Why should male sex adversely affect obstetric performance in labor? The answer is complex and, to a large extent, hypothetical. One of the earlier explanations was put forward by Ounsted and Ounsted in 1970.[11] They suggested that the presence of a Y chromosome induced an antigenic dissimilarity between mother and conceptus, resulting in trophoblastic proliferation and thus at least a greater growth velocity with regard to birth weight. The SRY gene on the Y chromosome has also been implicated as a cause for accelerated growth in the male fetus, possibly because of its effect on the modulation of insulin-like growth factor.[12,13] More recent research has not witnessed such growth acceleration in male fetuses with androgen insensitivity syndrome. It appears, therefore, that androgen activity is also necessary to achieve accelerated growth in the male fetus.[14]

Despite the higher birth weight, larger head circumference, and higher incidence of cesarean delivery in male infants, the incidence rates of postpartum hemorrhage and induction or augmentation were not higher.

Conclusions

Women in labor with male fetuses are at higher risk for cesarean delivery. This may be due to the higher birth weight and larger head circumference of the male infant, as has been previously documented.[5,15] The precise mechanisms for such observations remain hypothetical, but observation of such results in different populations confirms a real biological difference between male and female fetuses and pregnancy outcomes. The results also add new information for counseling Malaysian mothers regarding mode of delivery in certain circumstances. For example, the presence of a male fetus could be a negative factor to consider when vaginal birth after previous cesarean delivery is being recommended. To enhance the validity of such advice, further study is required in the various ethnic groups in Malaysia wherein size at birth may vary.