Not so long ago, different academic researchers began to publish the results of studies on the fetal sex role in the formation of obstetric pathology. However, the information that allows explaining the mechanisms of differences in the characteristic gestational restructuring of the female body when bearing fetuses of different sexes is extremely limited [1-3]. In the future, it is the prevalence of cases of macrosomia, gestational diabetes mellitus (GSD) and type 2 diabetes mellitus (DM2) in mothers of boys [4-7]. This process indicates the need to take into account the fetus sex while studying obstetric morbidity, and especially in pregnant women suffering from GSD.

There is evidence that fetal sexual dimorphism is significant in assessing perinatal mortality. It is also indicated that the stillbirth rate among male fetuses is significantly higher compared to female fetuses [1][3][8][9].

In addition, a number of studies have shown the dependence of a certain obstetric pathology on the sex of the fetus being carried. Thus, pregnancy with a boy fetus increases the risk of the mother developing the threat of premature birth of infectious genesis1 [10], and in the case of a girl fetus, premature birth as a complication of preeclampsia [11-13]. It is noted that the male sex of the fetus is a risk factor for placental disease, umbilical cord abnormalities [14-17], since it is the mothers of boys who more often develop pathological trophoblast invasion [18]. In the same variant of sexual dimorphism, a greater percentage of cesarean sections [1][9][19] and stillbirths as a result of placental abruption are recorded [8].

The male sex of the fetus is characterized by higher rates of overgrowth (ratio 3.2:1) in comparison with the female sex of the fetus [20]. This is associated with a deficiency of placental sulfatase (linked to the X chromosome) in mothers of boys, leading to a decrease in estrogen levels and, accordingly, to prolongation of gestation in them [21].

Therefore, according to the above-mentioned information, it was decided to study the structure of obstetric morbidity, taking into account sexual fetus dimorphism in pregnant women suffering from GSD.

The study aimed to study the nature of obstetric pathology and delivery outcomes in pregnant women with gestational diabetes mellitus, depending on the sex of the fetus being carried.

In order to obtain the required data, the authors of this study conducted a retrospective analysis of 2014 pregnancy and childbirth histories of women suffering from GSD who applied to the NIIAP clinic of the Federal State Budgetary Educational Institution “RostSMU” of the Ministry of Health of Russia in the period from 2018 to 2021. According to the “fetal sex” criteria, two groups were formed: Group I (1012 pregnant women — with male fetuses (PMF)) and Group II (1002 pregnant women) — with female fetuses (PFF).

The inclusion criteria were gestational diabetes mellitus (WHO-criteria, 2013), a singleton first pregnancy.

The exclusion criteria included repeated pregnancies and childbirth; fetal malformations; the use of assisted reproductive technologies; decompensated forms of extragenital pathology; type 1 and type 2 diabetes mellitus; pregnant women with malformations; a woman's refusal to participate in the study.

For statistical analysis, the proportions (%) were compared using Pearson’s χ2 (chi-square) test.

The systemic goal of any functional system “mother – placenta – fetus” (FSMPF) is the birth of a healthy child. It goes in connection with which the verification of the observations of pregnant women in clinical groups, taking into account the sex of the fetus, involves a mandatory analysis of the features of the course of pregnancy with an assessment of the structure of obstetric complications and childbirth.

Initially, cases of GSD manifestation in pregnant women were retrospectively analyzed, depending on the sex of the fetus being carried. It was found that significantly more often GSD manifested in the second trimester of pregnancy in PMF (67.3% vs. 36.7% in PFF, p = 0.0308). In GSD, first-time mothers were also significantly more likely to bear male fetuses (63.2% vs. 36.8% in PFF, p = 0.0497).

In the process of analyzing the structure of obstetric morbidity, it was found that pregnant women with GSD of the PMF group were significantly more likely to have placental presentation (62.4% compared to 37.6% in BPD, p = 0.0116) and preeclampsia (57.1% compared to 42.9% in PFF, p = 0.0206).

In the situation of PFF, isthmic-cervical insufficiency (ICI) (58.9% vs. 41.1% in PMF, p = 0.0452), anemia (59.3% vs. 40.7% in PMF, p = 0.0381) and fetal growth retardation (FGR) (61.4% vs. 38.9% in PMF) significantly prevailed in the structure of complications (Fig. 1).

Placental abruption was significantly more common in PMF with GSD (69.4% vs. 30.6% in BPD, p = 0.0201) and cases of placental increment (66.7% vs. 33.3% in PFF, p = 0.0435). PMF was characterized by absolute dominance in a number of such birth abnormalities as placenta previa (59.4% vs. 40.6% in PFF, p = 0.0101), premature rupture of fetal membranes (69.3% vs. 30.7% in PFF, p = 0.0298), posterior occipital placenta previa (87.5% vs. 12.5% in PFF, p = 0.0417).

It was found that (by analogy with obstetric complications) complications associated with abnormal cervical function prevailed in the PFF group, in particular, immature cervix (62.2% compared to 37.8% in BPM, p = 0.0359) and labor disorders by type of cervical dystocia (61.8% compared to 38.2% in PMF, p = 0.0438)

While analyzing the complications of the third period of labor and the early postpartum period, more frequent cases of hypotonic bleeding, defects and intimate attachment of the placenta in PMF were noted. They led to the dominance of obstetric surgical aids, such as manual control of the uterine cavity and removal of the uterus.

The analysis of cases of birth injuries showed that the mothers of girls (FM) significantly more often than the mothers of boys (MM) revealed a cervical rupture (69.3% vs. 30.7%, respectively), which is explained by the predominance in this group of violations of the processes of maturation of the cervix and anomalies of labor activity. At the same time the rupture of the posterior labial commissure was significantly more often recorded in MM (71.9% compared to 28.1% FM), which is apparently associated with a large percentage of cases of large fetuses and diabetic fetopathy with GSD in this group (69.3% vs. 30.7% in FM and 65.8% vs. 34.2% in FM).

The condition of newborns (according to the Apgar scale), taking into account their gender in the group with GSD, also indicated not in favor of male newborns, since they had a lower score on the Apgar scale at the 1st minute (6 points or lower) after birth (65.3%). At the same time, higher values (8-9 points) were observed in newborn girls (59.7%).

The study of the nature of functional processes in the maternal body, depending on the sex of the fetus being carried, indicates a greater likelihood of developing GSD and a certain pool of other obstetric complications, that is, lower resistance and adaptive capacity of the maternal body and greater demands on the functional system “mother” in the case of male fetuses. Such a variant of vulnerability of the maternal organism by the “boy fetus” system is determined, on the one hand, by the specifics of hormonal and biochemical fetal-maternal signaling2 [16][22], on the other hand, by the features of stereoisomerism of central-peripheral integration in the process of bearing male fetuses3 [22].

According to the literature data, since the beginning of gestation, FM has activation of hormonal subsystems that determine the formation of eustress, which leads to greater stability of maternal metabolism to gestational restructuring. Whereas in mothers of boys, such a reaction of stress-liberating subsystems is absent in the early stages and occurs only in the second trimester of pregnancy, which is accompanied by a greater likelihood of distress, disorders of carbohydrate and fat metabolism, the occurrence of GSD and other pregnancy complications related to it. The results of the analysis of the incidence of GSD obtained by us coincide with publications on the manifestation of gestational diabetes in the second trimester of pregnancy in the overwhelming majority of cases in MM4 5.

The second possible mechanism of GSD formation related to the sex of the fetus is a change in the nature of functional hemispheric asymmetries that occurs with ambilateral and left-sided placentation, which is significantly more often detected in MM due to afferent impulses from the left-oriented uteroplacental complex. With an ambilateral and left-sided placentation, the vector of afferent impulses from the uteroplacental complex is directed to the non-dominant right exchange-associated hemisphere of the brain. Its activation during pregnancy contributes to an increase in sympatho-adrenal influences leading to vasospastic effects, a shift in metabolic homeostasis with an increase in the anabolic variant of metabolism, and so on. With this variant of stereoisomerism, the symmetry of functional processes in the uterus is formed in the FSMPF, contributing to the emergence of generalized forms of uterine activity characteristic of threatening preterm labor, fetoplacental disorders and preeclampsia.

The revealed links between the nature of obstetric complications and the course of labor with the sex of the fetus in pregnant women with GSD determine the importance of developing a monitoring system that takes into account the sex-specificity of the functional system “fetus”.

1. Botasheva T.L., Radzinsky V.E., Palieva N.V., Khloponina A.V. Sexual dimorphism of the fetus and functional features of the maternal organism at various stages of ontogenesis. Rostov-on-Don: Publishing and Printing complex of RSEU (RINH); 2019. 2. Radzinsky V.E., Botasheva T.L., Papysheva O.V., Volkova N.I., Kotaysh G.A., Palieva N.V., etc. Obesity. Diabetes. Pregnancy. Versions and contraversions. Clinical practices. Perspectives. Moscow: GEOTAR-Media; 2020. 3. Botasheva T.L., Radzinsky V.E., Palieva N.V., Khloponina A.V. Sexual dimorphism of the fetus and functional features of the maternal organism at various stages of ontogenesis. Rostov-on-Don: Publishing and Printing complex of RSEU (RINH); 2019. 4. Botasheva T.L., Radzinsky V.E., Palieva N.V., Khloponina A.V. Sexual dimorphism of the fetus and functional features of the maternal organism at various stages of ontogenesis. Rostov-on-Don: Publishing and Printing complex of RSEU (RINH); 2019. 5. Radzinsky V.E., Botasheva T.L., Papysheva O.V., Volkova N.I., Kotaysh G.A., Palieva N.V., etc. Obesity. Diabetes. Pregnancy. Versions and contraversions. Clinical practices. Perspectives. Moscow: GEOTAR-Media; 2020.