Effect of Fetal Sex on Maternal and Obstetric Outcomes

Abstract

Fetal sex plays an important role in modifying the course and complications related to pregnancy and may also have an impact on maternal health and well-being both during and after pregnancy. The goal of this article is to review and summarize the findings from published research on physiologic and pathologic changes that may be affected by fetal sex and the effect of these changes on the maternal and obstetrical outcomes. This will help create awareness that fetal sex is not just a random chance event but an interactive process between the mother, the placenta, and the fetus. The reported effects of male sex on the course of pregnancy and delivery include higher incidence of preterm labor in singletons and twins, failure of progression in labor, true umbilical cord knots, cord prolapse, nuchal cord, higher cesarean section rate, higher heart rate variability with increased frequency, and duration of decelerations without acidemia and increased risk of gestational diabetes mellitus through the poor beta cells function. Similarly, female fetal sex has been reported to modify pregnancy and delivery outcomes including altered fetal cardiac hemodynamics, increased hypertensive diseases of pregnancy, higher vulnerability of developing type 2 DM after pregnancy possibly because of influences on increased maternal insulin resistance. Placental function is also influenced by fetal sex. Vitamin D metabolism in the placenta varies by fetal sex; and the placenta of a female fetus is more responsive to the relaxing action of magnesium sulfate. Male and female feto-placental units also vary in their responses to environmental toxin exposure. The association of fetal sex with stillbirths is controversial with many studies reporting higher risk of stillbirth in male fetuses; although some smaller and limited studies have reported more stillbirths with female fetus pregnancies. Maternal status such as BMI may in turn also affect the fetus and the placenta in a sex-specific manner. There is probably a sex-specific maternal–placental–fetal interaction that has significant biological implications of which the mechanisms may be genetic, epigenetic, or hormonal. Determination of fetal sex may therefore be an important consideration in management of pregnancy and childbirth.

Immune checkpoint molecules soluble program death ligand 1 and galectin‐9 are increased in pregnancy

“…HLA‐G G*0106 variant contributed by the father has been shown to increase the risk for preeclampsia in multigravida pregnancies irrespective of sex . Other factors, such as differences in endocrine and vascular physiology, likely have important roles in regulating fetal‐maternal interactions between male and female fetuses . Taken together with our current results, these data suggest that maternal immune responses are variable based on the sex of the fetus, requiring researchers to consider fetal sex in experimental design.…”

“…The sex of the fetus is another important variable which must be considered when studying fetal‐maternal interactions. Many pregnancy outcomes have been associated with the sex of fetus; for example, male fetuses have an increased incidence of preterm birth and gestational diabetes, whereas mothers carrying female fetuses more often present with hypertensive disorders . In the current study, blood levels of galectin‐9, but not sPD‐L1, were significantly higher in pregnancies with male fetuses compared to females.…”

“…Human reproduction is a delicate balance between immune tolerance and activation that, if disrupted, can result in negative pregnancy outcomes such as preterm birth and miscarriage . Additionally, gestational complications have been linked to the sex of the fetus . Thus, a clearer understanding of how this process is regulated could provide a wealth of knowledge useful for treating pregnancy complications.…”

The Association between Placental Location in the First Trimester and Fetal Sex

“…A study on 5376 pregnant women revealed that location of placenta in the first trimester of pregnancy could predict of 97.97% of female cases and 97.92% of male cases. They concluded that there is a more tendency toward right placement of placenta in male pregnancies while the tendency is toward left placement in female pregnancies [18]. In the current study, in most female cases, the placenta was located anteriorly, the placental position was located posteriorly in male pregnancies.…”

A maternal “mixed, high sugar” dietary pattern is associated with fetal growth

“…Potential sexual dimorphism in the effects of maternal dietary patterns on fetal growth has been largely overlooked in previous studies, with the majority using only pooled analyses. However, male sex is an established risk factor for adverse pregnancy outcomes, suggesting a greater sensitivity in males to the in utero environment when compared with females (Al-Qaraghouli & Fang, 2017;Peelen et al, 2016). There are also demonstrated differences in the patterns of fetal and infant growth for males and females as well as sex-specific differences in the influence of maternal nutritional status and inflammatory state on neonatal fat and lean mass (Broere-Brown et al, 2016;O'Tierney-Ginn, Presley, Minium, deMouzon, & Catalano, 2014).…”