This was an observational cohort study of primigravidae only women induced for various medical reasons at the Maternity Unit of the Shrewsbury and Telford Hospitals (SaTH) NHS Trust, between January 2011 and December 2012. Inclusion criteria were women with singleton cephalic presentation deliveries induced for post-date pregnancy (gestational age>41 weeks), reduced fetal movements, fetal growth restriction, preeclampsia/eclampsia, gestational diabetes, term (>37 weeks) pre-labour rupture of membranes for more than 24 hours and any other medical condition. Exclusion criteria involved women with breech vaginal deliveries, stillbirths, fetal congenital abnormalities, multiple pregnancies and elective CS. Data were collected from the obstetric electronic database of the hospital and maternal data, labour/delivery data and neonatal data were all recorded.

The data that were recorded and included maternal age, Body Mass Index (BMI), ethnicity (white European, non-white European) and smoking. Other data also identified were the gestational age at delivery, route of birth (vaginal/CS delivery), epidural analgesia and liquor appearance (normal, meconium stained). Neonatal variables including fetal gender (male, female), birth weight, head circumference, Apgar scores (at 1 and 5 minutes), cord gases taken at delivery (arterial, venous) and admission to the neonatal intensive care unit were also obtained.

A literature review was conducted by searching the MEDLINE and EBSCO databases for the years 2000-2016 with the use of the following text words: fetal gender, induced labour, caesarean section, pregnancy outcome. The references of the relevant articles were also searched so as to capture any other reports that were not already identified in the electronic search.

Quantitative variables were expressed as mean values and standard deviations. Qualitative variables were expressed as absolute and relative frequencies. Student’s t-test and Fisher’s exact test were used to compare mean values and proportions respectively. Multiple logistic regression analysis was used to identify whether or not the fetal gender was an independent risk factor for CS delivery after adjusting for confounding factors. All reported p-values were two-tailed. Statistical significance was set at p<0.05 and analyses were conducted using SPSS statistical software (version 19.0). This research study was approved by the local institutional review board.

A total of 936 primigravidae women met the inclusion criteria over the two-year study period. These women gave birth to 493(52.6%) male neonates and 443(47.4%) female neonates [Table/Fig-1]. Between the two subgroups of women there was no difference in their demographic data in terms of maternal age, ethnicity, body mass index and smoking. More than half of all women were induced for post-date pregnancies. During labour the occurrence of meconium stained liquor and the use of epidural analgesia was also similar between the two subgroups.

The CS delivery rate was higher in primigravidae women who gave birth to male neonates in comparison to those with female neonates (23.7% vs 17.8%;p=0.029) thus, providing an unadjusted Odds Ratio of OR=1.48 (95%CI:1.07-2.04;p=0.016). Male gender fetuses had greater mean values of birth weight and head circumference in comparison to female neonates (p<0.001), even though gestational age at delivery was similar. Multiple logistic regression analysis after adjusting for birthweight and head circumference showed that, this gender-related difference in CS delivery rates was no longer significant. This indicates that, the higher rate of CS delivery in males when compared to female neonates could be explained by the increased birth weight and head circumference of male fetuses.

Emergency admissions to the neonatal Intensive Care Unit (ICU) following delivery were similar between male and female neonates. The mean values of arterial/venous pH from the umbilical cord sampling immediately after birth were also similar between male and female neonates. However, male neonates had lower Apgar scores of <7 at 1 minute after birth (p=0.02) in comparison to females.

Since, Hall and Carr-Hill first described in 1982 a 17% increase in CS in the presence of a male fetus [1], there have been several studies reporting on this gender-related phenomenon. An extensive review [10] published in 2007 that summarised the available evidence from these studies concluded that, the male fetal gender should be considered an independent risk factor for an adverse pregnancy outcome. Large population-based studies [11-19] from different countries reporting on the delivery outcome in relation to fetal gender have further quantified that the risk of CS delivery for male fetuses is increased by 8-48% [Table/Fig-2]. Other smaller cohort-based studies investigating the same male gender-effect on CS delivery rates have found that, the risk is increased by 25-47% in women with spontaneous onset labour [20,21] and by 83%-251% in women with induced labour [6-8]. There are few studies however, that failed to show any such association between fetal gender and the increased risk of CS delivery [22,23]. The lack of association between male fetal sex and increased risk of CS delivery or the varying magnitude of the male-gender effect on CS rates that has been observed could be explained by the different parturient populations across the various study designs described in the literature [23].

This study has shown that, male gender fetuses in comparison to females have a 48% higher risk of CS delivery in primigravidae women with induced labour (unadjusted OR=1.48;95% CI:1.07-2.04; p=0.016). However, when adjusting for birthweight and head circumference this male-gender effect on the CS delivery rates was no longer existant. There are studies in the literature in support of our finding that the increased CS rate in males no longer persists after adjusting for birthweight [20,24]. Nevertheless, all the large population-based studies [Table/Fig-2] have shown that the male gender effect on CS delivery still remains after adjusting for birthweight [11-19] thus, indicating the existence of other underlying biological mechanisms beyond fetal weight itself that could account for this gender-related phenomenon.

There have been many explanations provided in the literature as to why male neonates have a higher CS delivery rate when compared to their female counterparts with the indication for operative delivery being labour dystocia or fetal distress. First, male neonates are heavier than females as shown by higher birthweights and higher rates of macrosomia (>4kg) [10,11,17,18,25], which could explain the higher CS rates due to labour arrest [20,24]. Second, increased rates of CS delivery due to fetal distress have been reported in male-bearing pregnancies [16,19,24,25]. It has been contemplated that, this may be the result of intrinsic gender-related differences in the fetal response to hypoxia. When hypoxia occurs during labour the release of catecholamines from fetuses is considered to be an important defense mechanism [24]. It has been postulated that, this catecholamine surge improves the ability of the fetus to withstand the effects of hypoxia [26,27]. Nevertheless, it has been demonstrated that, males have lower levels of catecholamines after asphyxia which may explain the worse outcome for males after a hypoxic event [28].

A third explanation comes from more recent studies that have shown that, male and female fetuses are different in terms of growth and development in utero due to sex-biased gene expression leading to divergent growth patterns [29]. It has been demonstrated that male fetuses grow faster in utero and they have smaller placentas than females relative to their birthweight [30,31]. The consequence of this is that when male fetuses are subjected to the stress of labour they have less placental reserves to use when sub-optimal conditions appear [29]. This may explain the finding why male fetuses have a higher incidence of fetal distress as reflected in being more likely to have abnormal fetal blood sampling and lower Apgar scores [8,12,18,19,21,24]. In our study, male neonates also had increased rates of lower Apgar scores of <7 at 1 minute after birth in comparison to females.

On review of the literature, there are only a few studies reporting on the association between fetal gender and pregnancy outcome in women with induced labour [6-8]. [Table/Fig-3] shows that, women being induced in comparison to those with spontaneous onset labours have a relatively higher risk of CS delivery even after adjustment for birthweight (83%-251% vs 25-47%) [6,7,20-23,25]. The physiological explanation given in the literature for the male gender effect in induced labour, in addition to the three pathophysiological mechanisms described earlier, is that there are different steroidal pathways regarding the onset of induced labour between female and male fetuses [6] and different fetoplacental responses to the induction of labour process between the fetal genders which could explain the higher IOL failure rates in male fetuses [7].

The main strength of this study is that, it has the largest to date sample size of 936 primigravidae women investigating the gender effect on delivery outcome in cases of induced labour. Second, the confounding effect of parity [32] in the induction of labour process was eliminated by including primigravidae only women. Third, all cases that were analysed in this study were from a single center and therefore, were managed according to the same clinical guidelines and protocols.

The limitations of this study include its retrospective nature of data collection and the inability to retrieve data about the cervical status of women when being induced. It is well-established in literature that cervical scoring in terms of the Bishop score is a key factor to the success of IOL [1,33,34]. For this reason, this variable could not be incorporated in the data analysis and therefore, adjust for any confounding effect.

This study has shown that male gender fetuses have a higher CS delivery rate in primigravidae women undergoing induction of labour and may be more vulnerable to fetal compromise when in labour. It has confirmed the findings from the previous few studies that reported on women with induced labour even though the male gender effect on the CS delivery rate in this study was much less than previously estimated.