CARATTERIZZAZIONE DI PARAMETRI BIOMETRICI PLACENTARI E FETALI IN GRAVIDANZE DI DONNE OBESE

Title: Placental and Fetal Biometry in Obese Pregnant Women. Introduction: Placental biometry at birth has been shown to predict chronic disease in later life. Maternal obesity is a risk factor for adverse pregnancy outcomes, possibly because it is characterized by intrauterine low-grade inflammation. Barker’s hypothesis underlined that the maternal endocrine and nutritional environment can affect fetal metabolism thus the intrauterine environment of an obese woman might establish a pathologic fetal status via placental inflammation, compromising placental function and altering fetal growth and development. Herein we investigated the placental characteristics in singleton pregnancies of overweight (OW), obese (OB) and normal weight (NW) women. Sex specific differences in fetal and neonatal morbidity and mortality are well documented. Differences in birthweight are also recognised, with males generally larger than females at birth and placental weight and F/P weight ratio higher in males compared to females. Sex specific adaptation of the placenta to an external insult may be crucial for the differences in fetal growth and survival. While the effect of fetal sex on placental development and growth has been studying in depth, sex differences in the context of overnutrition still need to be evaluated. Thus we studied placental biometry and function in male/female fetuses of OW, OB and NW women. Methods: A total of 699 women were enrolled at delivery: 536 were NW (18<BMI>25 kg/m2), 115 were OW (25BMI<30 kg/m2) and 48 were OB (BMI≥ 30 kg/m2). This study was performed at the Dept of Clinical Sciences, Unit of Obstetrics and Gynecology, L. Sacco Hospital, University of Milan, Italy. Only singleton pregnancies delivering both by cesarean section and vaginal delivery were enrolled. Exclusion criteria were maternal syndromes, placenta previa, obstetrical complications (preeclampsia, gestational hypertension, gestational diabetes, intrauterine growth retardation, placental abruption), adverse neonatal outcomes, glucose tolerant test positive. Pregnancies carrying fetuses with abnormal karyotype, malformations and infections were also excluded from the study. Gestational age, maternal data (age, height, BMI, weight gain, hemoglobin -Hb and glucose), fetal data (weight, length, ponderal index and gas analysis at birth) and placental data (weight, larger -D- and smaller -d- diameters) were collected. Placental area was calculated as D x d x π/4. Assuming a constant density, placental thickness was estimated as: weight/area. We expressed placental efficiency using the fetoplacental weight ratio (F/P), calculated as birth weight divided by the placental weight. Results: maternal, fetal and placental characteristics in NW vs OW and OB Fetal weights were significantly higher in the OW and OB groups (3435,00±392,11 gr and 3477,00 ±434,21 gr vs 3344,00±385,71 gr; p<0,05). In the OW group only, placental weights (461,69±93,48 gr vs 434,24±92,47 gr; p<0,01) were higher and the thickness (1,72±0,37 cm vs 1,64±0,36 cm; p<0,05) was significantly increased leading to lower placental efficiency (7,64±1,26 vs 7,96±1,41; p<0,05), represented by lower F/P. OB women presented lower weight gain during pregnancy (8,40±7,30 kg vs 13,50±4,40 kg; p <0,01), lower Hb (11,03±1,18 gr/dl vs 11,46±1,22 gr/dl; p <0,05) and Ht levels (33,16±3,13 % vs 34,27±3,34 %; p<0,05) compared to NW. As expected by the exclusion criteria, there were no differences in the maternal blood glucose concentration in the three groups. maternal, fetal and placental characteristics in NW vs OW and OB carrying female fetuses and NW vs OW and OB carrying males fetuses OW and OB with female fetuses presented significantly higher fetal weights (3396,00±341,01 gr and 3516,00±352,05 gr vs 3289,00±379 gr; p<0,05 e p<0,01 respectively), lengths (50,10±1,91 cm and 50,21±1,71 cm vs 49,40±1,77 cm; p<0,05) and head circumferences (34,21±1,27 cm and 34,30±1,21 cm vs 33,69±33,50 cm; p<0,05) compared to NW. Only OW with females fetuses, presented lower Hb leverls (11,01±1,20 gr/dl vs 11,43±1,25 gr/dl; p<0,05), higher placental weights (477,02±90,61 gr vs 424,03±92,00 gr; p<0,01), higher placental thickness (1,81±0,37 cm vs 1,64±0,39 cm; p<0,05) and lower F/P weights ratio (7,32±1,26 vs 8,01±1,43 p<0,01) compared to NW with female fetuses. OB with female fetuses only, presented lower weight gain during pregnancy (7,30±8,50 kg vs 13,80±4,70 kg; p<0,01) compared to NW. On the contrary, OW and OB with male fetuses did not present any of the above mentioned differences compared to NW with male offspring. maternal, fetal and placental characteristics in male vs female fetuses in the NW, OW and OB group respectively In the NW group, fetal weights (3391,00±385,01 gr vs 3289,00±379,02 gr; p<0,01), lengths (50,20±1,85 cm vs 49,40±1,77 cm; p<0,01), head circumferences (34,39±1,21 cm vs 33,69±2,50 cm; p<0,01) and placental weights (442,00±91,00 gr vs 424,18±92,30 gr; p<0,05) were higher in male compared to female fetuses. On the contrary, in the OW and OB groups, fetal weights and lengths were not significantly different between genders, while placental weights tended to be higher and thicker in female compared to male fetuses, leading to lower F/P ratio in female vs male fetuses. Moreover, in the OW group Hb levels were significantly lower in female vs male offspring (11,00±1,21 gr/dl vs 11,60±1,10 gr/dl; p<0,01). Conclusions: In our population of non-syndromic OB women, we found lower Hb levels in the maternal blood, possibly accounting for the typical malnutrition of obese women. Interestingly, OW women only, who presented weight gain over the standard recommendation, had thicker and less efficient placentas, probably representing the expression of a higher level of inflammation associated with a worse nutritional status. We found different placental adaptation in response to low grade inflammation of OB/OW depending on fetal gender, having altered Hb and feto-placental changes only women carrying female fetuses. These may be part of a strategy aiming to ensure survival in the presence of another adverse event. On the contrary, males approach (without any changes) allows them to continue to growth normally, although expose them to higher risks of fetal complications if another adverse event happens during pregnancy. Further studies are needed to assess possible correlations between altered placental morphology and placental gene and protein expression involved in the placental exchange in obese women and to provide possible future therapies (i.e. diet) customized according to fetal sex.