Early rapid growth,early birth: Accelerated fetal growth and spontaneous late preterm birth

The past two decades in the United States have seen a 24% rise in spontaneous late preterm delivery (34–36 weeks) of unknown etiology. This study tested the hypothesis that fetal growth was identical prior to spontaneous preterm (n = 221, median gestational age at birth 35.6 weeks) and term (n = 3706) birth among pregnancies followed longitudinally in Santiago, Chile. The hypothesis was not supported: Preterm‐delivered fetuses were significantly larger than their term‐delivered peers by mid‐second trimester in estimated fetal weight, head, limb, and abdominal dimensions, and they followed different growth trajectories. Piecewise regression assessed time‐specific differences in growth rates at 4‐week intervals from 16 weeks. Estimated fetal weight and abdominal circumference growth rates slowed at 20 weeks among the preterm‐delivered, only to match and/or exceed their term‐delivered peers at 24–28 weeks. After an abrupt growth rate decline at 28 weeks, fetuses delivered preterm did so at greater population‐specific sex and age‐adjusted birth weight percentiles than their peers from uncomplicated pregnancies (P < 0.01). Growth rates predicted birth timing: one standard score of estimated fetal weight increased the odds ratio for late preterm birth from 2.8 prior to 23 weeks, to 3.6 (95% confidence interval, 1.82–7.11, P < 0.05) between 23 and 27 weeks. After 27 weeks, increasing size was protective (OR: 0.56, 95% confidence interval, 0.38–0.82, P = 0.003). These data document, for the first time, a distinctive fetal growth pattern across gestation preceding spontaneous late preterm birth, identify the importance of mid‐gestation for alterations in fetal growth, and add perspective on human fetal biological variability. Am. J. Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.     

Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth

The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16–22 weeks, 22–28 weeks, and 28–34 weeks in a multilevel mixed‐effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22–28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22–28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term‐delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre‐dating the preterm labor episode. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.     

Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in uterofetal hypoxic status

Background

Hypoxia in utero can lead to stillbirth and severe perinatal injury. While current prenatal tests can identify fetuses that are hypoxic, none can determine the severity of hypoxia/acidemia. We hypothesized a hypoxic/acidemic fetus would up-regulate and release hypoxia-induced mRNA from the fetoplacental unit into the maternal circulation, where they can be sampled and quantified. Furthermore, we hypothesized the abundance of hypoxia induced mRNA in the maternal circulation would correlate with severity of fetal hypoxia/acidemia in utero. We therefore examined whether abundance of hypoxia-induced mRNA in the maternal circulation correlates with the degree of fetal hypoxia in utero.

Methods

We performed a prospective study of two cohorts: 1) longitudinal study of pregnant women undergoing an induction of labor (labor induces acute fetal hypoxia) and 2) pregnancies complicated by severe preterm growth restriction (chronic fetal hypoxia). For each cohort, we correlated hypoxia induced mRNA in the maternal blood with degree of fetal hypoxia during its final moments in utero, evidenced by umbilical artery pH or lactate levels obtained at birth. Gestational tissues and maternal bloods were sampled and mRNAs quantified by microarray and RT-PCR.

Results

Hypoxia-induced mRNAs in maternal blood rose across labor, an event that induces acute fetal hypoxia. They exhibited a precipitous increase across the second stage of labor, a particularly hypoxic event. Importantly, a hypoxia gene score (sum of the relative expression of four hypoxia-induced genes) strongly correlated with fetal acidemia at birth. Hypoxia-induced mRNAs were also increased in the blood of women carrying severely growth restricted preterm fetuses, a condition of chronic fetal hypoxia. The hypoxia gene score correlated with the severity of ultrasound Doppler velocimetry abnormalities in fetal vessels. Importantly, the hypoxia gene score (derived from mRNA abundance in maternal blood) was significantly correlated with the degree of fetal acidemia at birth in this growth restriction cohort.

Conclusions

Abundance of mRNAs coding hypoxia-induced genes circulating in maternal blood strongly correlates with degree of fetal hypoxia/acidemia. Measuring hypoxia-induced mRNA in maternal blood may form the basis of a novel non-invasive test to clinically determine the degree of fetal hypoxia/acidemia while in utero.

     

A new approach to predicting shoulder dystocia: fetal clavicle measurement

Background/aim This study aimed to evaluate the relationship between second- and third-trimester clavicle lengths and birth weight and shoulder dystocia.Materials and methods This prospective observational study included 181 patients who presented to the Private Etlik Lokman Hekim Hospital for routine pregnancy visits between March 2019 and March 2020. In addition to routine pregnancy examinations, the patients also underwent ultrasonography twice at weeks 20–23 and 33–36 to determine the length of the fetal clavicle. The patients were evaluated for shoulder dystocia in the second stage of labor. The birth weight of the neonates was recorded. The primary objective of this study was to establish the relationship between third-trimester clavicle length and shoulder dystocia.Results Fetal clavicle length increases in the second trimester with the advancing gestational week but does not significantly change in the third trimester. We did not observe any significant difference for second trimester clavicle length between the type of delivery, birth weight, or shoulder dystocia. Moreover, we did not observe any significant difference for third trimester clavicle length between types of delivery. However, we found a significant relationship between third trimester clavicle length and birth weight and shoulder dystocia. The median third-trimester clavicle length was 39.5 mm (range: 30.7–43.9) in neonates who did not develop shoulder dystocia and 42.5 mm (range: 41.4–43.1) in the 3 neonates who developed shoulder dystocia. The third-trimester clavicle length cut-off for shoulder dystocia was calculated as 41.35 mm (sensitivity: 100.00%, specificity: 83.82%, accuracy: 84.5%). The third-trimester clavicle length cut-off for macrosomia (defined as birth weight of ≥4100 g) was 40.75 mm (sensitivity: 87.50%, specificity: 77.56%, accuracy: 78.05%).Conclusion Third-trimester fetal clavicle length, an important component of biacromial diameter, as measured by ultrasonography, is a practical and significant method for predicting macrosomia and shoulder dystocia.     

Maternal early second trimester pregnancy weight in relation to birth outcome among Bengalee Hindus of Kolkata,India

Objective: The study examined to what degree maternal early second trimester pregnancy weight is useful and efficient in predicting birth outcome of Bengalee women.

Subjects and methods: The cross-sectional retrospective study was conducted in a government general hospital in South Kolkata, India. This hospital serves the needs of people belonging to lower and lower middle class socio-economic groups. Data were collected by one-to-one interview for confirmation of age, history of last menstrual period (LMP) including medical disorders. Mother's weight was recorded at 14–18 weeks of pregnancy from the history of LMP. Birth weight was measured within 24?h of delivery and gestational age was assessed by Ballard's method using newborn physical and neurological maturity scoring. Of the 331 Bengalees, 295 mother–baby pairs met the recruitment criteria and were included in this study.

Result: Mean?±?SD maternal early second trimester pregnancy weight and birth weight were 45.9?±?7.0?kg and 2612?±?371?g, respectively. The difference in mean weight (3.74?kg) between mothers who delivered low birth weight (LBW) and normal birth weight (NBW) babies was statistically significant (t?=?4.497, p?<?0.001). Overall, the prevalence of LBW was nearly 34%. A higher incidence of LBW and lower mean birth weight was observed in first quartile or low weight (≤40?kg) mothers. The rate of LBW decreased (χ²?=?14.47, p?<?0.01) and mean birth weight increased significantly with increasing maternal weight (F?=?9.218, p?<?0.001). Risk ratio (RR) for LBW, intrauterine growth retardation (IUGR) and preterm birth in low weight (first quartile or <40.0?kg) mothers were 2.72 (95% confidence interval (CI): 1.45–5.10), 3.54 (95% CI: 1.17–10.74) and 1.97 (95% CI: 0.56–6.90), respectively, compared with heavier (>50.0?kg) mothers. Finally, the present data showed that the maternal weight of <46.0?kg is the best cut-off for detecting LBW with 66% sensitivity and 75% negative predictive power.

Conclusion: The findings suggest a positive association between maternal early second trimester pregnancy weight and birth outcome. The present study provided an efficient cut-off point for detecting LBW. Antenatal caregivers in health institutions and community health workers in the field can use this cut-off value for screening pregnant women at early second trimester.     

CD8+ T cells in fetal membranes display a unique phenotype,and their activation is involved in the pathophysiology of spontaneous preterm birth

Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal–fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T-cell immunophenotyping in the placentas, fetal membranes, umbilical cord blood, and maternal peripheral blood. Our data showed a differential enrichment of T cells during the third trimester of human pregnancy, with CD4⁺ T cells being more observable within the umbilical cord blood, whereas CD8⁺ T cells became relatively more abundant in fetal membranes. CD4⁺ and CD8⁺ T cells derived from fetal membranes were dominated by effector memory T cells and exhibited extensive expression of activation markers but decreased expression of homing receptor. In comparison with term births, fetal membrane CD8⁺ T cells, especially the central memory subset, were significantly increased in frequency and showed more profound activation in spontaneous preterm birth patients. Finally, using an allogeneic mouse model, we found that T-cell-activation-induced preterm birth could be alleviated by the depletion of CD8⁺ T but not CD4⁺ T cells in vivo. Collectively, we showed that CD8⁺ T cells in fetal membranes displayed a unique phenotype, and their activation was involved in the pathophysiology of spontaneous preterm birth, which provides novel insights into the immune mechanisms of preterm birth and potential targets for the prevention of this syndrome. © 2023 The Pathological Society of Great Britain and Ireland.     

Timing is everything: A reconsideration of fetal growth velocity patterns identifies the importance of individual and sex differences

Fetal growth has been posited to follow a “timing hypothesis” sequence in which the second trimester favors a single growth velocity peak in body length and the third trimester accommodates a single growth velocity peak in weight accrual. To our knowledge, this proposition has never been tested with high‐frequency longitudinal ultrasound data from normally growing human fetuses. The present study examined whether fetal growth in leg length had its peak velocity at or about 20–26 gestational weeks and declined subsequently and whether estimated fetal weight velocity was maximal at or about 33 weeks and declined subsequently; if the greatest acquisition of leg length occurred in the second trimester and weight in the third trimester; and if birth outcomes reflected these relationships. The data in this study included approximately weekly longitudinal ultrasound data collected from 44 maternal/fetal pairs in Brussels, Belgium. Diaphyseal lengths of the femur and tibia provided information on leg growth and estimated fetal weight was assessed from the biparietal and occipital‐frontal head diameters and transverse and anterior–posterior diameters of the abdomen. Growth patterns were investigated from individual growth curves derived from daily growth velocity z‐scores. Paired t‐tests compared individuals' trimestral increments in leg length and fetal weight. Least‐squares regression models employing the robust procedure for repeated measurements were used to test for relationships between trimester, size, growth rates, and birth outcome, controlling for day of measurement, sex, maternal smoking, and gestational age at birth. The normal fetuses in this study grew by pulsatile patterns of leg and estimated weight acquisition, not a single peak and decline process. Greater incremental growth in estimated fetal weight occurred during the second trimester and leg length in the third trimester. Individual and sex effects were significant in growth velocity patterns. Girls grew with greater synchrony between leg and weight growth and were accelerated by comparison with boys, with faster leg growth predicting lower ponderal index by the second trimester. Birth outcomes were sex‐specific in timing effects and predictive variables. These results support the importance of sex‐specific analyses, reemphasize the common notion that girls grow faster than boys, and direct attention to cross‐talk between energy resources and growth. Am. J. Hum. Biol. 15:667–680, 2003. © 2003 Wiley‐Liss, Inc.     

Maternal fat mass at mid-pregnancy and birth weight in Brazilian women

Abstract

Background: The relationship between maternal body composition and foetal development is unclear.

Aim: To determine the relationship between maternal body composition [fat mass (FM) and fat-free mass (FFM)] and foetal growth and birth weight, independent of potential confounding factors.

Subjects and methods: This study consisted of 92 women, normal and overweight/obese, recruited from the Instituto Fernandes Figueira in Rio de Janeiro, Brazil. Body composition (FM and FFM) was estimated using bioelectrical impedance. Foetal growth was assessed using serial ultrasound measurements at the second and third trimester and infant's weight and length were measured at birth. Multiple linear regression analyses were used to determine the association between maternal FM and FFM and birth weight adjusted for gestational age (BWt) and change in estimated foetal weight (ΔEFW), controlling for infant gender, maternal serum glucose, energy intake, parity, height and income.

Results: Maternal FM, but not FFM, was positively associated with BWt (p?=?0.02) and borderline with ΔEFW (p?=?0.05). FM expressed as a percentage of body weight (%FM) showed a significant positive association with BWt (p?<?0.001) and ΔEFW (p?<?0.01). Using backward linear regression analysis, FM was a significant predictor of BWt (p?<?0.001) and ΔEFW (p?=?0.03), but not change in femur length.

Conclusion: In this small sample of normal and overweight/obese women, maternal FM at mid-pregnancy is associated with neonatal BW and foetal growth.     

Elevated second trimester maternal serum β-HCG concentrations and subsequent adverse pregnancy outcome

Previous studies have found an association between elevated second trimester maternal serum α-fetoprotein (MS-AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum β-HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester β-HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum β-HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS-AFP was found in only one of these 4 patients. Elevated midtrimester maternal serum β-HCG may be an independent risk factor for subsequent adverse pregnancy outcomes.     

Elevated Amniotic Fluid Interleukin-6 Levels During the Early Second Trimester Are Associated With Greater Risk of Subsequent Preterm Delivery

PROBLEM: Subclinical intra-amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin-6 (IL-6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm. METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL-6 at 14–20 weeks in a group of women subsequently delivering at ≤ 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL-6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one-way ANOVA after log-transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis. RESULTS: There was an inverse correlation between AF IL-6 levels at 15–20 weeks and gestational age at delivery (r = ?0.16, P = 0.03). Women delivering at ≤ 34 weeks had significantly higher median AF IL-6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at ≥ 37 weeks. Logistic regression analysis showed that IL-6 was independently associated with PTD at ≤ 34 weeks after controlling for race and birth weight centiles (P = 0.039). CONCLUSIONS: AF IL-6 at 15–20 weeks can identify patients at risk for PTD at ≤ 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester. CAPSULE: Midtrimester amniotic fluid IL-6 concentrations are significantly higher in women subsequently delivering preterm at ≤34 weeks compared with those delivering at term.     

Changes in nutritional status among displaced North Korean children living in South Korea

Background: As many nations experience the nutrition transition, changes in the nutritional status of children moving from food insecure to food affluent societies has become an important, but infrequently studied, public health issue.

Aim: To determine changes in the nutritional status of North Korean children after relocating to food-affluent South Korea (SK) from food-deficient North Korea (NK) and relationships of current nutritional status with food environment at birth and exposure to food affluent environments.

Subjects and methods: Socioeconomic status, relocation history and anthropometric information were obtained from 70 NK children (6–15 years) living in SK, through questionnaires, interviews and direct measurements.

Results: Following the first 2 years in SK, the height and weight of NK children significantly (p?=?0.000) improved, yet they were still shorter (p?=?0.000) than SK peers, while the prevalence of obesity was similar to those of SK children. The likelihood of remaining stunted was significantly associated with older age and shorter residency in SK (p?Conclusion: Even a short exposure to food affluent environments improved the nutritional status among children, but linear growth deficits are slow to recover as overall nutritional status remains poor compared to peers without exposures to food insecurity.     

Prenatal phthalate exposure,infant growth,and global DNA methylation of human placenta

Prenatal phthalate exposure has been shown to be associated with reduced fetal growth. Epigenetic changes such as DNA methylation might be a molecular mechanism through which phthalate exposure affects fetal growth. In this study, we examined associations between prenatal phthalate exposure, infant growth, and global DNA methylation in human placenta samples. We measured global DNA methylation of 119 subjects [55 fetal growth restriction (FGR) cases and 64 normal controls], as assessed by long interspersed nuclear element‐1 (LINE‐1) methylation, via quantitative polymerase chain reaction‐pyrosequencing. Prenatal phthalate exposure was assessed by measuring maternal urinary phthalate metabolites concentrations using high‐performance liquid chromatography‐tandem mass spectrometry. Concentrations of mono (2‐ethyl‐5‐hydroxyhexyl) phthalate (MEHHP), mono (2‐ethyl‐5‐oxohexyl) phthalate (MEOHP), and SumDEHP (molar sum of MEHP, MEHHP, and MEOHP) were significantly higher in FGR cases than those in normal controls (P = 0.002, 0.003, and 0.002, respectively). Placental LINE‐1 methylation were found to be positively associated with fetal birth weight standard deviation scores, and negatively associated with urinary phthalate metabolites concentrations (MEHHP and SumDEHP). Every natural‐log unit increase in urinary concentrations of MEHHP and SumDEHP was associated with 0.015 (β = ?0.015, P = 0.150) and 0.012 kg (β = ?0.012, P = 0.167) decrease in birth weight mediated through LINE‐1 methylation. These findings suggest that changes in placental LINE‐1 methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth. Environ. Mol. Mutagen. 56:286–292, 2015. © 2014 Wiley Periodicals, Inc.     

Fetal growth patterns in Beckwith–Wiedemann syndrome

We provide data on fetal growth pattern on the molecular subtypes of Beckwith–Wiedemann syndrome (BWS): IC1 gain of methylation (IC1‐GoM), IC2 loss of methylation (IC2‐LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age‐corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1‐GoM (n = 21), UPD (n = 87), IC2‐LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1‐GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1‐GoM patients, lowest in IC2‐LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2‐LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1‐GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2‐LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2‐LoM, but manifest a body mass disproportion rather similar to that seen in IC1‐GoM cases.     

Modelling foetal growth in a bi-ethnic sample: results from the Born in Bradford (BiB) birth cohort

Background: Attempts to explain the increased risk for metabolic disorders observed in South Asians have focused on the “South Asian” phenotype at birth and subsequent post-natal growth, with little research on pre-natal growth.

Aim: To identify whether divergent growth patterns exist for foetal weight, head (HC) and abdominal circumferences (AC) in a sample of Pakistani and White British foetuses.

Subjects and methods: Models were based on 5553 (weight), 5154 (HC) and 5099 (AC) foetuses from the Born in Bradford birth cohort. Fractional polynomials and mixed effects models were employed to determine growth patterns from ～15 weeks of gestation-birth.

Results: Pakistani foetuses were significantly smaller and lighter as early as 20 weeks. However, there was no ethnic difference in the growth patterns of weight and HC. For AC, Pakistani foetuses displayed a trend for reduced growth in the final trimester.

Conclusion: As the pattern of weight and HC growth was not significantly different during the period under investigation, the mechanism culminating in the reduced Pakistani size at birth may act earlier in gestation. Reduced AC growth in Pakistanis may represent reduced growth of the visceral organs, with consequences for post-natal liver metabolism and renal function.     

Maternal vitamin D status and infant anthropometry in a US multi-centre cohort study

Background: Maternal vitamin D status in pregnancy is linked to foetal growth and may impact infant growth.

Aim: This study examined the association between maternal vitamin D status and infant anthropometry.

Subjects and methods: Data came from n?=?2473 mother–child pairs from the 12-site US Collaborative Perinatal Project (1959–1965). Maternal serum 25-hydroxyvitamin D (25(OH)D) was measured at?≤?26 weeks gestation. Multivariate-adjusted linear mixed models were used to relate maternal vitamin D status to infant z-scores for length (LAZ), head circumference (HCZ), weight (WAZ) and BMI (BMIZ), measured at birth and 4, 8 and 12 months.

Results: Infants with maternal 25(OH)D ≥30?nmol/L vs <30?nmol/L had LAZ and HCZ measures 0.13 (95% CI?=?0.03–0.23) and 0.20 (95% CI?=?0.11–0.28) units higher, respectively, across the first year of life. Similar differences in WAZ and BMIZ at birth were resolved by 12 months of age due to interactions indicating steeper age slopes in infants with maternal 25(OH)D <30?nmol/L.

Conclusion: Low maternal vitamin D status was associated with deficits at birth in infant weight and BMI that were recouped across the first year of life; associations with reduced measures of linear and skeletal growth were sustained from birth to 12 months.     

Serum insulin‐like growth factor‐I concentrations in late middle age: no association with birthweight in three UK cohorts

Background: Small body size at birth and during infancy is associated with an increased risk of adult osteoporosis and cardiovascular disease. Fetal programming of the growth hormone–insulin‐like growth factor (GH‐IGF) axis may provide a mechanism for these epidemiological findings. Aims: To determine whether measurements of GH and IGF‐I in late middle age were related to size at birth and in infancy. Methods: Overnight urinary GH excretion and fasting serum IGF‐I were measured in 309 men and 193 women from Hertfordshire (born 1920–1930) for whom birthweight and weight at 1 year were recorded. Serum IGF‐I was measured in men and women from Preston (n = 254, born 1935–1943) and Sheffield (n = 215, born 1939–1940) whose birthweight and other birth measurements were recorded. Results: Urinary GH and serum IGF‐I were not related to birthweight, other measurements at birth, or weight at 1 year. Conclusion: In contrast to previous studies in children or young adults, these data do not support the hypothesis that IGF‐I concentrations are programmed by intra‐uterine events, as assessed by birthweight, in late middle age.     

Modulation of amniotic fluid activin-a and inhibin-a in women with preterm premature rupture of the membranes and infection-induced preterm birth

Citation Rosenberg VA, Buhimschi IA, Dulay AT, Abdel‐Razeq SS, Oliver EA, Duzyj CM, Lipkind H, Pettker CM, Buhimschi CS. Modulation of amniotic fluid activin‐A and inhibin‐A in women with preterm premature rupture of the membranes and infection‐induced preterm birth. Am J Reprod Immunol 2012; 67: 122–131 Problem Activins and inhibins are important modulators of inflammatory processes. We explored activation of amniotic fluid (AF) activin‐A and inhibin‐A system in women with intra‐amniotic infection and preterm premature rupture of the membranes (PPROM). Method of study We analyzed 78 AF samples: ‘2nd trimester‐control’ (n = 12), ‘3rd trimester‐control’ (n = 14), preterm labor with intact membranes [positive‐AF‐cultures (n = 13), negative‐AF‐cultures (n = 13)], and PPROM [positive‐AF‐cultures (n = 13), negative‐AF‐cultures (n = 13)]. Activin‐A levels were evaluated ex‐vivo following incubation of amniochorion and placental villous explants with Gram‐negative lipopolysaccharide (LPS) or Gram‐positive (Pam3Cys) bacterial mimics. Ability of recombinant activin‐A and inhibin‐A to modulate inflammatory reactions in fetal membranes was explored through explants’ IL‐8 release. Results Activin‐A and inhibin‐A were present in human AF and were gestational age‐regulated. Activin‐A was significantly upregulated by infection. Lower inhibin‐A levels were seen in PPROM. LPS elicited release of activin‐A from amniochorion, but not from villous explants. Recombinant activin‐A stimulated IL‐8 release from amniochorion, an effect that was not reversed by inhibin‐A. Conclusion Human AF activin‐A and inhibin‐A are involved in biological processes linked to intra‐amniotic infection/inflammation‐induced preterm birth.     

胎儿生长受限的早期诊治

胎儿生长受限（FGR）不仅使胎儿宫内发育落后,而且会影响到胎儿出生后的发育及生活质量。但其病因及生理机制未明,孕早中期对FGR的诊断困难,常在孕晚期才能诊断。因此如何早期预测FGR并对其进行诊疗,以获得较好的母婴结局一直是国内外研究的热点。现将对FGR早期诊断的方法及治疗进展进行综述。     

Genetic and environmental influences on infant weight and weight change: the Fels Longitudinal Study.

Despite significant progress in understanding the mechanisms by which the prenatal/maternal environment can alter development and adult health, genetic influences on normal variation in growth are little understood. This work examines genetic and nongenetic contributions to body weight and weight change during infancy and the relationships between weight change and adult body composition. The dataset included 501 white infants in 164 nuclear and extended families in the Fels Longitudinal Study, each with 10 serial measures of weight from birth to age 3 years and 232 with body composition data in mid-adulthood. Heritability and covariate effects on weight and weight z-score change from birth to 2 years of age were estimated using a maximum likelihood variance decomposition method. Additive genetic effects explained a high proportion of the variance in infant weight status (h2=0.61-0.95), and change in weight z-score (h2=0.56-0.82). Covariate effects explained 27% of the phenotypic variance at 0-1 month of age and declined in effect to 6.9% of phenotypic variance by 36 months. Significant sex, gestational age, birth order, birth year, and maternal body mass index effects were also identified. For both sexes, a significant increase in weight z-score (>2 SD units) (upward centile crossing) was associated with greater adulthood stature, fat mass, and percent body fat than decrease or stability in weight z-score. Understanding genetic influences on growth rate in a well-nourished, nutritionally stable population may help us interpret the causes and consequences of centile crossing in nutritionally compromised contexts.     

The impact of depression and fluoxetine treatment on obstetrical outcome

Summary Introduction: This study prospectively followed women over the course of pregnancy to assess the impact of depression and/or antidepressant treatment on obstetrical outcome.Method: Sixty-four outpatient women with an Axis I diagnosis of major depressive disorder or no psychiatric history were followed in each trimester of pregnancy with administration of the CES-D. A subset of the women with depression received treatment with fluoxetine during pregnancy. Subjects with a CES-D score greater than 16 at any time point were further assessed for the presence of an active major or minor depressive episode. Primary outcome variables included infant gestational age, birth weight, Apgar score, and admission to the neonatal intensive care unit.Results: Analyzable data were available for 62 women. No significant differences were found in outcome variables between those women with exposure to medication and/or prenatal depressed mood and those women without a history of depression.Conclusions: In contrast to other studies, our study did not demonstrate an adverse effect of fluoxetine exposure per se on obstetrical outcome. In addition, we did not find a significant impact of depression during pregnancy on obstetrical outcome.