During intrauterine life, external stimuli including maternal nutrition, lifestyle, socioeconomic conditions, anxiety, stress, and air pollution can significantly impact fetal development. The human brain structures begin to form in the early weeks of gestation and continue to grow and mature throughout pregnancy. This review aims to assess, based on the latest research, the impact of environmental factors on fetal and neonatal brain development, showing that oxidative stress and inflammation are implied as a common factor for most of the stressors. Environmental insults can induce a maternal inflammatory state and modify nutrient supply to the fetus, possibly through epigenetic mechanisms, leading to significant consequences for brain morphogenesis and neurological outcomes. These risk factors are often synergic and mutually reinforcing. Fetal growth restriction and preterm birth represent paradigms of intrauterine reduced nutrient supply and inflammation, respectively. These mechanisms can lead to an increase in free radicals and, consequently, oxidative stress, with well-known adverse effects on the offspring’s neurodevelopment. Therefore, a healthy intrauterine environment is a critical factor in supporting normal fetal brain development. Hence, healthcare professionals and clinicians should implement effective interventions to prevent and reduce modifiable risk factors associated with an increased inflammatory state and decreased nutrient supply during pregnancy.

Alterations in intrauterine fetal growth increase the risk of adverse perinatal and neonatal outcomes. In this retrospective study, we analyzed data of 906 pregnancies collected in our maternal fetal medicine center, with different patterns of growth: 655 AGA (Appropriate for Gestational Age), 62 SGA (Small for Gestational Age: fetuses born with a weight less than 10° centile, not diagnosed before delivery), 189 FGR (Fetal Growth Restriction, classified in early and late according to gestational week at diagnosis). For each group, we compared maternal characteristics, gestational age at delivery, and perinatal and neonatal outcomes. Risk factors for fetal growth alterations were advanced age, being primiparous, and a lower pregestational BMI. FGR fetuses were born at earlier gestational ages (32 [IQR 29–38] early-FGR and 38 [IQR 36–39] late-FGR), with blood gas values comparable to the AGA group but worse neonatal outcomes related to prematurity. Unexpected SGA fetuses born by vaginal delivery, managed as AGA, were more hyperlactacidemic (4.4 [IQR 2.7–5.5]) and hypoxemic (−5.0 [IQR −7.1–2.8]) at birth than both AGA and FGR. However, neonatal outcomes (accesses and days of hospitalization in NICU) were better than FGR, likely due to gestational age and birthweight similar to AGA.

The global rise in obesity presents serious concerns, particularly due to its association with pregnancy complications such as gestational diabetes, preeclampsia, cesarean delivery, and fetal macrosomia. Maternal obesity also contributes to intergenerational health risks, increasing the likelihood of long-term issues in offspring. Preconception counseling is an essential preventive measure to reduce complications; however, many women miss this opportunity due to unplanned pregnancies. This study explores the impact of pregestational body mass index (BMI) and gestational weight gain (GWG) on pregnancy outcomes, underscoring the importance of routine monitoring of these parameters. Existing studies identify both BMI and GWG as independent risk factors for adverse maternal and neonatal outcomes, with elevated BMI combined with excessive GWG posing an even greater risk. Specifically, a BMI > 30 kg/m² doubles the risk of complications such as gestational diabetes, hypertension, and cesarean delivery. Additionally, a review of national and international guidelines highlights a lack of consensus on managing gestational weight gain in women with obesity, particularly regarding antepartum surveillance and timing of delivery. Similarly, no specific guidelines have been established for underweight pregnant women. Additionally, few studies have thoroughly assessed the maternal and fetal risks associated with underweight during pregnancy. Despite this, numerous studies have highlighted an increased risk of preterm birth (PTB) and small-for-gestational-age (SGA) infants. This narrative review emphasizes the need for further research to develop tailored guidelines for managing pregnant women based on pregestational BMI, ultimately improving maternal and neonatal health outcomes.

Maternal obesity has been associated with short- and long-term risks of pregnancy-perinatal adverse events, possibly due to alterations of placental mitochondrial bioenergetics. However, several detrimental mechanisms occurring in the placentas of women with obesity still need to be clarified. Here, we analyzed placental mitochondrial features and oxidative environment of 46 pregnancies in relation to pre-pregnancy BMI. Seventeen Caucasian normal-weight (NW) and twenty-nine women who were obese (OB) were enrolled. The protein expression of mitochondrial CypD and electron transfer chain complexes (C) I–V were measured, as well as ATP production and oxygen consumption rates (OCRs). The protein levels of the pro/anti-oxidant enzymes TXNIP, SOD2, and PON2 were also analyzed. Despite no differences in CypD expression, OCRs were significantly lower in OB vs. NW women. Accordingly, ATP synthase (CV) levels and ATP content were decreased in OB women, positively correlating with placental efficiency, suggesting a link between ATP deficiency and placental dysfunction. SOD2 expression negatively correlated with maternal BMI, indicating a possible impairment of antioxidant defenses with increasing BMI. These changes were worsened in 10 OB women presenting with gestational diabetes mellitus. Overall, these results suggest alterations of placental bioenergetics in pregnancies of women with obesity, possibly leading to placental dysfunction and altered fetal development and programming.

Placental development, maternal adaptations to pregnancy, and birth outcomes appear to differ based on fetal sex. The aim of this prospective cohort study was to investigate first trimester markers of feto-placental development and birth outcomes in a large population of healthy women with autologous pregnancies according to fetal sex. Healthy women with singleton pregnancies were enrolled at 11-13⁺⁶ weeks. At enrollment, maternal blood sample was collected for placental marker (Pregnancy Associated Plasma Protein A, free β-Human Chorionic Gonadotropin (HCG)), and ultrasound assessed mean pulsatility index of uterine arteries (UtA PI), placental volume and crown-rump length (CRL). Multi-adjusted generalized linear models were used to evaluate the associations between fetal sex, first trimester feto-placental markers, and pregnancy outcomes. Among 1052 pregnancies (523 male, 529 female), female fetuses showed lower first trimester mean UtA PI (β = -0.10 (95 % CI -0.16; 0.03), p < 0.01) and CRL (β = -0.49 (95 % IC -0.96; 0-04), p < 0.05), and higher free-β-hCG (β = 19.8 (95 % IC 13.8-25.8), p < 0.001) in multi-adjusted models. Female sex was associated with a 69 % lower risk of preterm delivery. Male fetuses showed higher birth weight (p < 0.001). After excluding women undergoing a planned cesarean section, male fetuses showed lower arterial cord pH values regardless of the delivery mode (β = -0.21; 95 %IC: -0.40; -0-01, p < 0.05). The present study highlights crucial differences in prenatal development and placentation between male and female fetuses, leading to significant differences in pregnancy duration and response to labor stress.

Maternal nutritional status represents a pivotal predictor of pregnancy outcome. This prospective observational study investigates the associations between maternal characteristics and nutritional habits at term, hemodynamic parameters, and pregnancy outcomes. Healthy women with singleton uncomplicated pregnancies were enrolled at 36–41 gestational weeks. At enrollment, a nutritional score (0–10) was calculated in order to quantify maternal adherence to a healthy diet and lifestyle. Maternal hemodynamic parameters were assessed by using the Ultrasonic Cardiac Output Monitor (USCOM), including cardiac output (CO), systemic vascular resistance (SVR) and Smith–Madigan inotropy index (SMII). Pregnancy outcomes were recorded at delivery. Associations between maternal characteristics and nutritional score, hemodynamic parameters, and pregnancy outcomes were investigated by using multi-adjusted generalized linear models. In total, 143 pregnancies were enrolled. Pregestational body mass index (BMI) was positively associated with SVR, and negatively associated with CO and SMII. Additionally, a positive association was detected between the nutritional score and SMII. Finally, CO was positively associated with birth and placental weight, while RVS showed a negative association with birth and placental weight. This study shows that maternal derangements in nutritional status and habits are associated with a compromised hemodynamic profile at term, with additional impacts on intrauterine growth.