Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health1. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.

BACKGROUND: Intrauterine growth retardation (IUGR) is a very serious prenatal condition with 3-5% incidence of all pregnancies. It results from numerous factors, including chronic placental insufficiency. IUGR is associated with an increased risk of mortality and morbidity and is considered a major cause of fetal mortality. Currently, treatment options are significantly limited and often result in preterm delivery. Postpartum, IUGR infants also have higher risks of disease and neurological abnormalities.
METHODS: The PubMed database was searched using the keywords \"IUGR\", \"fetal growth restriction\", \"treatment\", \"management\" and \"placental insufficiency\" for the period between 1975 and 2023. These terms were also combined together.
RESULTS: There were 4160 papers, reviews and articles dealing with the topic of IUGR. In total, only 15 papers directly dealt with a prepartum therapy of IUGR; 10 of these were based on an animal model. Overall, the main focus was on maternal intravenous therapy with amino acids or intraamniotic infusion. Treatment methods have been tested since the 1970s to supplement the fetuses with nutrients lacking due to chronic placental insufficiency in various ways. In some studies, pregnant women were implanted with a subcutaneous intravascular perinatal port system, thus infusing the fetuses with a continuous amino acid solution. Prolongation of pregnancy was achieved, as well as improvement in fetal growth. However, insufficient benefit was observed in infusion with commercial amino acid solution in fetuses below 28 weeks\' gestation. The authors attribute this primarily to the enormous variation in amino acid concentrations of the commercially available solutions compared with those observed in the plasma of preterm infants. These different concentrations are particularly important because differences in the fetal brain caused by metabolic changes have been demonstrated in the rabbit model. Several brain metabolites and amino acids were significantly decreased in IUGR brain tissue samples, resulting in abnormal neurodevelopment with decreased brain volume.
CONCLUSIONS: There are currently only a few studies and case reports with correspondingly low case numbers. Most of the studies refer to prenatal treatment by supplementation of amino acids and nutrients to prolong pregnancy and support fetal growth. However, there is no infusion solution that matches the amino acid concentrations found in fetal plasma. The commercially available solutions have mismatched amino acid concentrations and have not shown sufficient benefit in fetuses below 28 weeks\' gestation. More treatment avenues need to be explored and existing ones improved to better treat multifactorial IUGR fetuses.

OBJECTIVE: Fetal anemia secondary to incompatibility between maternal-fetal blood types can result in hydrops and demise. Intrauterine transfusions have improved survival in experience centers. Our objective was to determine the practice patterns amongst fetal centers.
METHODS: Thirteen fetal centers across the world were surveyed. Results from all participating centers were recorded, analyzed, and presented as ratios. Questions on the survey were related to experience of the physician, preferred methods of transfusion, fetal surveillance, and timing of delivery.
RESULTS: Differences amongst centers were as follows: 54% of the centers performed transfusions in operating room, the remaining did them in a clinic room or close to the operating room; 31% did not use maternal anesthesia, 31% used oral or intravenous sedation and 38% used a combination of local with oral or intravenous sedation. The similarities include: 84% performed intravenous transfusions, while 2 centers reported intraperitoneal and intracardiac transfusions were performed for very early cases; 85% of centers performed the last transfusion at 34-35 weeks and 77% electively delivered their patients at 37 weeks.
CONCLUSIONS: Method of transfusion and delivery timing was similar in most centers; however, differences were seen in location of procedure, anesthetic coverage, and surveillance. Further assessment is needed to determine if these differences in practice have any potential neonatal effects.

Genes involved in the regulation of metabolism, adipose tissue deposition, inflammation, and the appetite-satiety axis may play an important role in fetal development, and possibly induce permanent metabolic changes and fat accumulation. In this study we investigated: (1) obesity-related gene expression in maternal and cord blood of overweight/obese and normal-weight pregnant women; (2) associations between obesity-related gene expression in maternal and cord blood; and (3) associations of gene expression in each of maternal and cord blood with newborn adiposity.
Twenty-five overweight/obese and 32 normal-weight pregnant women were selected from the Araraquara Cohort Study according to their pre-pregnancy BMI. Maternal and cord blood gene expression of LEPR, STAT3, PPARG, TLR4, IL-6, IL-10, FTO, MC4R, TNF-α, and NFκB were investigated by relative real-time PCR quantification. The body composition of the newborns was assessed by air displacement plethysmography. Associations between maternal and cord blood gene expression and markers of newborn adiposity (weight, BMI, and fat mass%) were explored by linear regression models controlling for maternal age, pre-pregnancy BMI, maternal gestational weight gain, gestational age, and newborn sex.
There was higher TLR4, NFκB, and TNF-a expression, and lower IL-6 expression, in overweight/obese pregnant women and their respective newborns compared with normal-weight women and their newborns (p < 0.001). Maternal PPARG gene expression was associated with both weight and fat mass % of the newborns, and cord blood IL-10 expression was associated with BMI and fat mass %, controlling for confounders.
To our knowledge, this is the first study to evaluate the relationship of maternal and cord blood gene expression with adiposity markers of the newborn. Our results provide evidence for the contribution of maternal and cord blood gene expression-particularly maternal PPARG and TLR4 expression, and cord blood IL-10 expression-to newborn weight, BMI, and fat mass %.

In general terms, fetal growth restriction (FGR) is considered the impossibility of achieving the genetically determined potential size. In the vast majority of cases, it is related to uteroplacental insufficiency. Although its origin remains unknown and causes are only known in 30% of cases, it is believed to be related to an interaction of environmental and genetic factors with either a fetal or maternal origin. One hypothesis is that alterations in the gastrointestinal microbiota composition, and thus alteration in the immune response, could play a role in FGR development. We performed an observational, prospective study in a subpopulation affected with FGR to elucidate the implications of this microbiota on the FGR condition.A total of 63 fetuses with FGR diagnosed in the third trimester as defined by the Delphi consensus, and 63 fetuses with fetal growth appropriate for gestational age will be recruited. Obstetric and nutritional information will be registered by means of specific questionnaires. We will collect maternal fecal samples between 30 to 36 weeks, intrapartum samples (maternal feces, maternal and cord blood) and postpartum samples (meconium and new-born feces at 6 weeks of life). Samples will be analyzed in the Department of Biochemistry and Molecular Biology II, Nutrition and Food Technology Institute of the University of Granada (UGR), for the determination of the gastrointestinal microbiota composition and its relationship with inflammatory biomarkers.This study will contribute to a better understanding of the influence of gastrointestinal microbiota and related inflammatory biomarkers in the development of FGR.Trial registration: NCT04047966. Registered August 7, 2019, during the recruitment stage. Retrospectively registered. Ongoing research.

Phlebotomy losses greatly contribute to anaemia following preterm birth. Therefore, the possibility of drawing initial tests from the placenta seems attractive. There is a lack of literature regarding the feasibility and accuracy of pathology tests taken from umbilical arterial and venous (UAB/UVB) compared to blood collected from the newborn.
UAB and UVB complete blood pictures were compared with the initial neonatal blood test. The relationship between UAB, UVB and neonatal complete blood picture values was determined by Spearman\'s Rho correlation with absolute values compared by Kruskal-Wallis. P < 0.05 was considered significant.
Neonatal haemoglobin, white cell count, immature/total ratio and platelets were significantly correlated to the corresponding values in the UAB and UVB (all P < 0.001). While UAB and UVB haemoglobin and white cell count were similar, both were significantly lower than the neonatal values (P < 0.001 and P = 0.014, respectively). No difference was seen for immature/total ratio and platelet concentrations. UVB blood culture (BC) was feasible (90%), even with delayed cord clamping, and the UVB BC volume was significantly higher (P < 0.001), with a low rate of BC contamination (1.5%).
Our findings support the feasibility and accuracy of umbilical blood in place of blood collected from the newborn. This reduces the phlebotomy losses and allows higher blood volume collection which may increase the sensitivity of BC collection.

To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT).
A retrospective study.
Reference fetal medicine unit.
Sixty-two fetuses infected <14 weeks of gestation.
We defined second-trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA.
For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow-up were reported.
The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false-positive findings at MRI were mostly the result of hypersignals of white matter.
Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy.
Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks.

To evaluate the effect of blood sampling from the placental end of the umbilical cord compared with initial blood sampling from neonates, on the need for first packed red blood cell transfusion in extremely preterm infants. We hypothesized that cord blood sampling could delay the time to first blood transfusion.
In this single-center, assessor blind, randomized controlled trial, we included extremely low birth weight neonates <28 weeks of gestational age at birth. Five milliliter of blood for initial laboratory investigations was collected either from the placental end of the umbilical cord (study group) or from the neonate upon neonatal intensive care unit admission (control group). Both groups received similar anemia prevention strategies. The primary outcome was the time (in days) to the first packed red blood cell transfusion, and was compared using survival analysis.
Eighty neonates were enrolled. The time to first transfusion was significantly delayed in the cord sampling group (30 vs 14 days, hazard ratio: 0.44, [95% CI 0.27-0.72], P < .001). Fewer neonates in the cord sampling group were transfused in the first 28 days of life (30% vs 75%, P < .001). Overall transfusion requirements and other clinical outcomes were similar in the groups.
Initial blood sampling from placental end of umbilical cord, when combined with anemia prevention strategies, significantly prolonged the time to first transfusion and reduced the need for early transfusions among extremely premature neonates.
Ctri.nic.in/ (CTRI/2017/04/008320).

The aim of this study was to assess the performance of cardio-biparietal ratio measured by real-time two-dimensional ultrasound in predicting hemoglobin (Hb) Bart disease among fetuses at risk.
This prospective diagnostic study recruited pregnancies at risk for Hb Bart disease at 17 to 22 weeks\' gestation. Cardio-biparietal ratio and cardiothoracic ratio were measured before cordocentesis for Hb typing. The performance of the cardio-biparietal ratio and cardiothoracic ratio for identifying affected fetuses was evaluated.
Among 72 fetuses at risk, 31 were diagnosed as affected by Hb Bart disease. By using a cutoff 0.45, cardio-biparietal ratio had a sensitivity of 83.9%, specificity of 92.7%, positive predictive value of 89.7%, and negative predictive value of 88.4%, whereas cardiothoracic ratio using cutoff 0.5 had a sensitivity of 94.3%, specificity of 65.1%, positive predictive value of 68.8%, and negative predictive value of 93.3%.
Cardio-biparietal ratio is a new sonomarker to predict Hb Bart disease among fetuses at risk. This sonomarker is relatively effective and may be useful in areas of high prevalence of alpha thalassemia disease, limited number of experts in prenatal ultrasound, and difficult access to prenatal diagnosis.

Purpose: The aim of this pilot study was to estimate physiological parathyroid hormone (PTH) levels and their relationship with bone metabolism parameters in otherwise healthy preterm newborns with birth weight 1000-1500 g. Methods: PTH, 25(OH)D, S-Ca, S-P, and ALP were analysed from blood samples obtained from 20 preterm infants once a week up to the 36th gestational week. Results: Of the total 134 examined serum samples for PTH levels, the estimated range was 1.6-9.3 pmol/l (15.1-87.7 pg/ml). No statistically significant correlation of PTH level with that of S-Ca, S-P, or ALP was observed, except for the 56th day of life (p = .03; Rho = 0.76; n = 8). From the second month of life, there was a statistically significant relationship only between PTH and 25(OH)D (Rho = -0.71, p ≤ .0001). In our cohort, vitamin D deficiency (20 ng/ml) occurred in 75% at birth and at 30% in the 36th gestational week. Conclusions: The physiological range indicated by the measurements was close to the reference limits for adults (1-7 pmol/l; 9.4-66 pg/ml). PTH level above this range can be considered as hyperparathyroidism in preterm neonates.