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Objective: To investigate the association of the maternal serum albumin (MAlb) level with fetal growth and fetal growth restriction (FGR) risk in term-born singletons., Design: Prospective cohort study., Setting: Four hospital maternity units of the Tongji Maternal and Child Health Cohort study initiated from September 2013 to April 2016 at Wuhan City, in central China., Patient(s): A total of 3,065 mother-offspring pairs., Intervention(s): None., Main Outcome Measure(s): Fetal growth was evaluated by birth weight (BW) and birth length. Fetal growth restriction was defined as BW below the 10th percentile., Result(s): All MAlb levels were within the upper limit of normal. After adjustment for liver function parameters, inflammatory indicators, and others, a reverse U-shaped relationship between MAlb and fetal growth was observed. Specifically, BW increased significantly with an increasing MAlb level when the MAlb level was <36.1 g/L (per g/L: β = 36.8; 95% CI, 0.8, 72.7) but decreased with increasing the MAlb level when the MAlb level was >36.1 g/L (per g/L: β = -15.1; 95% CI, -21.2, -8.9). There was a similar association between MAlb and birth length. Furthermore, the adjusted odd ratios of FGR across increasing tertiles of the MAlb levels were 1.0 (reference), 1.1 (0.7, 1.8), and 1.7 (1.0, 2.6)., Conclusion(s): There was a reverse U-shaped association between MAlb and fetal growth. A higher MAlb level was associated with an increased risk of FGR., Clinical Trial Registration Number: NCT03099837., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Fetal growth restriction (FGR) refers to impaired and insufficient intrauterine growth potential caused by a variety of adverse factors and is a serious perinatal complication that leads to fetal or neonatal mortality and morbidity. FGR has numerous causes, and its pathogenesis has not been fully understood. Recently, increasing numbers of researchers have begun to focus on the placenta, the only link between the fetus and the mother. The placenta is a vital organ that plays key roles in fetal development. PLAC1 is a trophoblast-specific gene located on the X chromosome and is important for placental development. However, the biological role of PLAC1 in fetal growth restriction is not well understood. In this study, we investigated the changes in the expression of placental-specific protein 1(PLAC1) in the placentas of pregnant women with FGR and in the placentas of normal pregnancies. We also explored the regulation of PLAC1 in the growth of trophoblast cells., Methods: Western blotting was used to detect the expression of PLAC1 in FGR and in normal placenta tissues. Cell counting kit 8 (CCK-8), wound healing, and transwell assays were used to detect the effects of PLAC1 knockdown on trophoblast cell proliferation, migration, and invasion. Western blotting was used to detect the expression of PLAC1 under hypoxic conditions, and the cell viability and apoptosis of trophoblast cells in a low oxygen concentration after overexpression of PLAC1 were detected by CCK-8 and flow cytometry assay., Results: Compared with the placentas in the control group of normal pregnancies, the expression of PLAC1 in the placentas of the FGR group was significantly down-regulated ( p <0.05). Knocking down PLAC1 by siRNA significantly inhibited the proliferation, migration, and invasion of trophoblast cells. After treatment with alow oxygen concentration, the expression of PLAC1 protein was significantly reduced ( p <0.05). The overexpression of PLAC1 can reverse the cell viability of trophoblast cells ( p <0.05) and inhibit apoptosis of trophoblast cells ( p <0.05) in low oxygen concentration., Conclusion: The expression of PLAC1 was reduced in fetal growth restriction and did not protect trophoblast cells from hypoxic damage, suggesting that PLAC1 may be an important regulator in the occurrence of fetal growth restriction., (© 2021 by the Association of Clinical Scientists, Inc.)

Objective: To characterize the inferior adrenal artery (IAA) pulsatility index (PI) in intrauterine growth-restricted (IUGR) fetuses without brain sparing., Methods: Twenty-three IUGR fetuses with a normal Doppler cerebroplacental ratio (CPR) and 23 normal controls were included in this prospective cross-sectional study. The PI of the IAA was recorded using routine transabdominal Doppler ultrasound. The differences in Doppler characteristics, perinatal outcomes, and steroidogenesis in the umbilical vein at birth (adrenocorticotropic hormone [ACTH] and cortisol [F] levels) were compared between the 2 groups. The correlations between IAA-PI and steroidogenesis were assessed in the IUGR group., Results: IAA-PI was significantly lower in IUGR fetuses than in normal controls (0.85 vs 1.18 at first scan, 0.78 vs 0.92 at last scan; both P < 0.001). The plasma F and ACTH levels in IUGR cases were significantly higher than those of the normal controls (18.2 vs 12.4 µg/dL and 280.5 vs 125.6 pg/mL for F and ACTH, respectively; both P < 0.001). There were negative correlations between IAA-PI and plasma F values and between IAA-PI and ACTH values in the IUGR group (r = -0.774 and -0.82 at first scan, r = -0.525 and -0.45 at last scan, respectively; P < 0.001)., Conclusion: Increased adrenal gland blood flow with concomitant increases in ACTH and F levels were observed in IUGR fetuses. IAA-PI is useful to assess early blood redistribution and may be beneficial for evaluating the steroidogenic response in high-risk pregnancies., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Little is known about the clinical value of the Hadlock and INTERGROWTH-21 st EFW standards for predicting adverse perinatal outcomes (APOs) in the third trimester. The purpose of this study was to study the association between low estimated fetal weight percentile (EFWc) in the third trimester and the risk of APOs and compare predictions of APOs between Hadlock and INTERGROWTH-21 st EFW standards. A prospective cohort of 690 singleton pregnancies with ultrasonography performed in the third trimester between March 2015 and March 2016 in China was conducted. EFW and the corresponding EFWc were measured using the Hadlock and INTERGROWTH-21 st standards, respectively. Cox proportional hazard models were used to assess the relationship between low EFWc (i.e., <5 percentile, P5) and the risk of APOs. Compared with fetuses with ≥P5 of the EFWc, fetuses with st standard.

Background: Whole-exome sequencing (WES) over the last few years has been increasingly employed for clinical diagnosis. However, one caveat with its use is that it inevitably fails to detect disease-causative variants that occur within noncoding RNA genes. Our experience in identifying pathogenic variants in the noncoding RNU4ATAC gene, in a Chinese family where two successive foetuses had been affected by severe microcephaly, is a case in point. These foetuses exhibited remarkably similar phenotypes in terms of their microcephaly and brain abnormalities; however, the paucity of other characteristic phenotypic features had made a precise diagnosis impossible. Given that no external causative factors had been reported/identified during the pregnancies, we sought a genetic cause for the phenotype in the proband, the second affected foetus., Results: A search for chromosomal abnormalities and pathogenic copy number variants proved negative. WES was also negative. These initial failures prompted us to consider the potential role of RNU4ATAC, a noncoding gene implicated in microcephalic osteodysplastic primordial dwarfism type-1 (MOPD1), a severe autosomal recessive disease characterised by dwarfism, severe microcephaly and neurological abnormalities. Subsequent targeted sequencing of RNU4ATAC resulted in the identification of compound heterozygous variants, one being the most frequently reported MOPD1-causative mutation (51G>A), whereas the other was a novel 29T>A variant. Four distinct lines of evidence (allele frequency in normal populations, evolutionary conservation of the affected nucleotide, occurrence within a known mutational hotspot for MOPD1-causative variants and predicted effect on RNA secondary structure) allowed us to conclude that 29T>A is a new causative variant for MOPD1., Conclusions: Our findings highlight the limitations of WES in failing to detect variants within noncoding RNA genes and provide support for a role for whole-genome sequencing as a first-tier genetic test in paediatric medicine. Additionally, the identification of a novel RNU4ATAC variant within the mutational hotspot for MOPD1-causative variants further strengthens the critical role of the 5' stem-loop structure of U4atac in health and disease. Finally, this analysis enabled us to provide prenatal diagnosis and genetic counselling for the mother's third pregnancy, the first report of its kind in the context of inherited RNU4ATAC variants.

Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95% CI 3·37, 179·51) g and 107·63 (95% CI 21·98, 193·28) g (P<0·05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation.

Background: Trophoblast invasion into the maternal endometrium serves an important function in human pregnancy. Dysregulation of the finely controlled process of trophoblast invasion can result in a wide spectrum of pregnancy abnormalities., Aims: We aimed to elucidate the relationship between the expression of matrix metalloproteinases and pregnancy complication., Study Design: The study group consisted of placental bed biopsy tissues obtained from normal vaginal deliveries (N=15), normal cesarean deliveries (N=15), pre-eclampsia (N=24) and fetal growth restriction (FGR) (N=10). We evaluated the expressions of MMP-2, -8, -9, -11, -19, -15 (MT2-MMP), -16 (MT3-MMP), and -24 (MT5-MMP), as well as TIMP-1 and -3, by applying Western blot and immunohistochemistry methods., Subjects: Human placental tissues were used for this study., Outcome Measures: The expressions of MMP-2, -8, -9, -11, -19, -15 (MT2-MMP), -16 (MT3-MMP), and -24 (MT5-MMP), as well as TIMP-1 and -3 in human placenta tissues., Results: Compared with those in normal pregnancies, the expression of MMP-2, -8, -9 and -11 was downregulated in villous tissues of pre-eclampsia and FGR cases (p<0.05). TIMP-1 and -3 were increased in pre-eclampsia and FGR (p<0.05). No significant difference was found between normal vaginal deliveries and cesarean deliveries., Conclusions: We speculate that the change in invasion-associated proteinase expression will affect placental development and may thus contribute to the development of complicated pregnancies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The present study investigated the effects of medium-chain TAG (MCT) on hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). At weaning (mean 21 (SD 1·06) d of age), twenty-four IUGR piglets and twenty-four normal-birth weight (NBW) piglets were selected according to their birth weight (BW; IUGR: mean 0·95 (SD 0·04) kg; NBW: mean 1·58 (SD 0·04) kg) and weight at the time of weaning (IUGR: mean 5·26 (SD 0·15) kg; NBW: mean 6·98 (SD 0·19) kg) and fed either a soyabean oil (SO) diet (containing 5% SO) or a MCT diet (containing 1% SO and 4% MCT) for 28 d. IUGR piglets exhibited poor (P<0·05) growth performance, lower (P<0·05) metabolic efficiency of hepatic glutathione (GSH) redox cycle, and increased (P<0·05) levels of reactive oxygen species, apoptosis and necrosis in hepatocytes compared with NBW piglets. The MCT diet increased (P<0·05) the average daily gain and feed efficiency of piglets during the first 4 weeks after weaning. Furthermore, MCT diet-fed piglets had a higher (P<0·05) GSH:oxidised glutathione ratio and increased (P<0·05) activities of glucose-6-phosphate dehydrogenase (G6PD) and GSH reductase. The expression of G6PD was up-regulated (P<0·05) by the MCT diet irrespective of BW. Moreover, malondialdehyde concentrations in the liver and apoptosis and necrosis levels in hepatocytes were decreased (P<0·05) by the MCT diet irrespective of BW. These results indicate that MCT might have auxiliary therapeutic potential to attenuate hepatic oxidative damage in IUGR offspring during early life, thus leading to an improvement in the metabolic efficiency of the hepatic GSH redox cycle.

The ratio of mid-arm circumference to occipital frontal circumference (MAC/OFC), an index of late gestation growth retardation, was determined in 175 healthy newborn term Chinese babies. The ratio of 0.31 (S.D., 0.02) was significantly higher than in recent data published for Asian, White and Black neonates: whether this is due to differences in measuring techniques or better intra-uterine nutrition remains to be seen. As an initial test of its potential usefulness this ratio was determined in 12 term Chinese babies who showed clinical signs of undernutrition. All but one had a ratio 2S.D. or more below the mean. The MAC/OFC ratio, with its ease of measurement, simplicity and cheapness, is a useful addition to existing methods for assessing late gestation nutritional status.