Low first-trimester hemoglobin and low birth weight, preterm birth and small for gestational age newborns.

OBJECTIVE: To examine the relationship between first-trimester hemoglobin (Hb) concentration and risk of low birth weight (LBW), preterm birth and small for gestational age (SGA). METHODS: Data were obtained from a population-based prenatal care program in China. A total of 88,149 women who delivered during 1995-2000 and had their Hb measured in the first trimester were selected as study subjects. RESULTS: The prevalence of anemia (Hb<110 g/L) was 22.1% in the first trimester. The risk of LBW, preterm birth and SGA was increased steadily with the decrease of first-trimester Hb concentration. After controlling for confounding factors, women with Hb 80-99 g/L had significantly higher risk for LBW (OR=1.44, 95% CI 1.17-1.78), preterm birth (OR=1.34, 95% CI 1.16-1.55) and SGA (OR=1.13, 95% CI 0.98-1.31) than women with Hb 100-119 g/L. No elevated risk was noted for women with Hb> or =120 g/L. CONCLUSION: Low first-trimester Hb concentration increases the risk of LBW, preterm birth and SGA.     

Lack of association between genetic polymorphisms in three folate-related enzyme genes and male infertility in the Chinese population

PurposeThis study explored the possible association of four single nucleotide polymorphisms (SNPs) of the three folate-related enzyme genes: MTHFR C677T and A1298C, MTR A2756G and MTRR A66G, with male infertility in the Chinese population.MethodsThe polymorphic distributions of the four SNPs (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) were investigated by the method of SNaPshot in a Chinese cohort including 296 idiopathic infertile males with azoospermia or oligozoospermia and 204 fertile males.ResultsWe found no evidence for an association between any of these variants (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) and male infertility.ConclusionsThere is no evidence for an association between male infertility and polymorphism of the three folate-related enzyme genes in the Chinese population.     

SIRT1通过调控TET2促进小于胎龄儿下丘脑中星形胶质细胞分化

目的研究在小于胎龄儿下丘脑中,SIRT1是否通过调控TET2表达影响GFAP的DNA甲基化水平,最终促进星形胶质细胞分化。方法将12只SPF级SD孕大鼠,自孕第一天起随机分为对照组和SGA组,对照组繁殖饲料喂养,不限饮食直至自然分娩,SGA组8%低蛋白饲料喂养,自孕10天起50%限制饮食(以对照组前一天饮食平均量为标准),直至自然分娩。取两组出生第一天子鼠的下丘脑组织,双重免疫荧光染色观察GFAP、Tuj1的表达与分布,Western blot法和RT-PCR法检测新生鼠下丘脑组织中SIRT1、TET2、GFAP蛋白及mRNA表达,用焦磷酸测序测定GFAP启动子区域的DNA甲基化水平。体外培养SGA组和对照组子鼠的下丘脑神经前体细胞,分别用SIRT1激活剂和抑制剂对细胞进行处理,Western blot和RT-PCR法检测不同干预下SIRT1、TET2、GFAP蛋白及mRNA表达,用焦磷酸测序测定不同干预后GFAP启动子区域的DNA甲基化水平。结果与对照组相比,SGA组下丘脑中SIRT1、TET2、GFAP表达增加,GFAP启动子区域的甲基化水平降低,双重免疫荧光染色结果显示,SGA组的GFAP分布增多,Tuj1分布减少。体外神经细胞培养证实,抑制SIRT1的表达,降低了TET2、GFAP的活性,增加了GFAP启动子区域的甲基化水平;反之,SIRT1的激活会增加TET2、GFAP的表达,降低GFAP启动子区域的甲基化水平。结论在小于胎龄儿的下丘脑神经前体细胞中,SIRT1可能通过增强TET2的活性,继而改变GFAP启动子区域的甲基化水平,促进神经前体细胞向星形胶质细胞的分化。     

Association between low maternal low-density lipoprotein cholesterol levels in the second trimester and delivery of small for gestational age infants at term: a case-control study of the national center for child health and development birth cohort

Maternal malnutrition during pregnancy can lead to a small for gestational age (SGA) status among infants. In the present study, we compared the lipid levels during the second trimester in women who delivered SGA infants at term with those in women who delivered appropriate for gestational age infants at term, to examine whether abnormalities in maternal lipid levels could be a risk factor for the delivery of an SGA infant. We enrolled pregnant women who gave birth at the National Center for Child Health and Development (NCCHD), their infants, and who volunteered in a Birth cohort study at the NCCHD. We analyzed a total of 843 blood samples obtained from the women during the second trimester. Moreover, we used multi-regression analysis to assess the relationship between low-density lipoprotein cholesterol (LDL-C) levels during the second trimester and the risk of delivering an SGA infant. The adjusted odds ratio (OR) for LDL-C levels was 0.99 (95% CI, 0.98–0.99). These results indicate that a low LDL-C level during the second trimester was associated with an increased risk of delivering an SGA infant at term. The finding would not only help predict future SGA infant birth, but can also help prevent SGA infant birth.     

Hydramnios and small for gestational age are independent risk factors for neonatal mortality and maternal morbidity

Objective The objective was to evaluate the contribution of hydramnios and small for gestational age (SGA) as a combined pathology to maternal and neonatal morbidity and mortality.Methods The study population consisted of 192 SGA neonates with hydramnios, 5,515 SGA neonates with a normal amount of amniotic fluids, 3,714 appropriate for gestational age (AGA) neonates with polyhydramnios and 83,763 AGA neonates with a normal amount of amniotic fluid. A cross-sectional population based study was designed between the four study groups. Multiple logistic regression analysis was used to assess the contribution of these abnormalities and different risk factors to maternal and perinatal complications.Results The combination of hydramnios/SGA was found to be an independent risk factor for perinatal mortality (OR 20.55; CI 12.6–33.4). Congenital anomalies, prolapse of cord, hydramnios, SGA and grand multiparity were also independent risk factors for perinatal mortality. Independent risk factors for neonatal complications were prolapse of umbilical cord (OR 4.13; 95% CI 1.48–11.5), hydramnios/SGA (OR 2.72; 95% CI 1.81–4.07), chronic hypertension (OR 2.45; 95% CI 1.02–5.9), congenital malformations (OR 1.93; 95% CI 1.14–3.24) and SGA (OR 1.47; 95% CI 1.07–2). Significant independent risk factors for medical interventions during labor were fetal distress (OR 198.46; 95% CI 47.27–825.27), GDM Class B–R (OR 21.22; 95% CI 2.34–192.25), GDM class A (OR 4.64; 95% CI 2.62–8.21), severe pregnancy-induced hypertension (PIH; OR 7.74; 95% CI 2.35–25.42), hydramnios (OR 1.95; 95% CI 1.3–2.91), hydramnios/SGA (OR 1.84; 95% CI 1.12–3.02) and malpresentation (OR 1.56; 95% CI 1.32–1.84).Conclusion The combination of hydramnios and SGA is an independent risk factor for perinatal mortality and maternal complications. We suggest that the growth restriction of these fetuses is responsible for the neonatal complications, while the hydramnios contributes mainly to maternal complications.     

Cell-free fetal DNA and adverse outcome in low risk pregnancies

Objective

To analyze in a large prospective cohort study of low risk pregnancies whether cell-free fetal (cff) DNA in maternal plasma of the second trimester might be associated with the development of preeclampsia, preterm delivery, and small for gestational age.

Study design

A subset of a large prospective cohort study in serological RhD negative pregnant women with RHD positive fetuses was used. Cff DNA was determined through the detection of RHD specific sequences with real-time PCR.

Results

In 611 pregnancies, rates of 7.2% preeclampsia, 1.6% preterm birth ≤32, 2.9% ≤34, and 12.4% ≤37 weeks of gestation, 5.7% of small for gestational age <5th percentile, and 8.2% <10th percentile were observed. For none of these risk groups an association with cff DNA could be established.

Conclusion

Cff DNA in maternal plasma of the second trimester was not found to be a marker for an adverse pregnancy outcome in low risk pregnancies.     

Update on the birth weight standard and its diagnostic value in small for gestational age (SGA) infants in China

Objectives: To identify the difference between the current newborn birth weight standard and the previous standard in China, and to evaluate the diagnostic value of newborn birth weight in small for gestational age (SGA) infants.

Methods: A retrospective analysis was conducted of 112?441 delivery cases in 2011, from 39 hospitals at different levels in 14 provinces and autonomous regions. Cases with incomplete data, gestational age?<24 weeks, or severe fetal malformations or fetal death were excluded. Data were recorded and entered on hard paper copies and into an online database. SPSS 18.0 and SAS 9.2 statistical software were used for data analysis.

Results: This study included 109?004 valid cases with an average birth weight of 3226.02?±?525.82?g. Birth weight changed significantly from 1988 for all gestational ages. In preterm infants with gestational age?<37 weeks, birth weight for each gestational week was lower than that in the birth weight standard from 15 cities in China in 1988 (p?+6 weeks showed significantly higher average birth weights compared with the previous birth weight standards (p?Conclusions: The current birth weight standard used in Chinese medical institutions was enacted in 1988. This is not suitable for today’s socioeconomic and clinical requirements, and needs to be updated. Diagnosis of preterm infants with SGA based upon the updated demographic birth weight standard manifested higher accuracy and avoided unnecessary medical interventions. However, the updated demographic birth weight standards were no better diagnostically than the previous standard for full-term infants. Customized birth weight standards from larger sample sizes and multi-center studies will be necessary to determine the appropriate birth weight standards in developing countries.     

Analysis of amino acids and acyl carnitine profiles in low birth weight,preterm, and small for gestational age neonates

Objective: To analyze the amino acids (AA) and acyl carnitine (AC) profiles in dry blood spot (DBS) specimens of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA), and to compare the concentration difference of AA and AC with those without above.

Methods: This is a retrospectively study. Eight thousand nine hundred and seventy-nine uncomplicated pregnant newborns were enrolled into the study. DBS were collected on the third day of life, and concentrations of 11 types of AA, free carnitine and 30 types of AC were detected by using high-performance liquid chromatography tandem mass spectrometry (HPLC–MS). Shapiro–Wilk test and Kruskal–Wallis rank test were applied in statistical analysis.

Results: Concentrations of most AA and AC in infants born in SGA were significantly higher than those in non-SGA group, while lower in LBW and PTB groups than those in non-LBW and non-PTB groups (p?Conclusions: The difference of concentration of AA and AC in the subgroups suggested there may be a dysutilization of AA and AC in SGA, but an inborn insufficient of AA and AC in LBW and PTB neonates.     

Evaluation of carnitine deficit in very low birth weight preterm newborns small for their gestational age

Objective: To verify whether small-for-gestational-age (SGA) preterm newborns represent a special risk group for carnitine deficiency. Secondary outcome includes assessment of longitudinal differences of total carnitine (TC), free carnitine (FC) and acylcarnitines between SGA and appropriate-for-gestational-age (AGA).

Methods: A retrospective study to evaluate carnitine and acylcarnitines profile on 144 very-low-birth weight newborns (VLBW), classified as AGA (n?=?73) and SGA (n?=?71), was performed by tandem mass spectrometry, during their first 5 weeks of life. Carnitine deficiency was defined as FC <40?µmol/L and FC/TC <0.7.

Results: Carnitine deficiency was observed in the two study groups throughout the monitoring period (maximum FC: 36.05?µmol/L in AGA and 32.24?µmol/L in SGA). FC/TC remains under 0.7 in both with progressive improvement. Unlike expected, a comparatively higher value of TC, FC and total acylcarnitines (tAC) was found in SGA during the first 2 weeks, with significant relevance on day 3–5, especially for tAC (p?<?0.001). The only acylcarnitine with persistently lower value in SGA is C5 (p?<?0.05 in first 2 weeks).

Conclusions: A carnitine deficiency was demonstrated in all VLBW. Although birth weight restriction has been suggested as a risk factor for impaired carnitine status, in our study, SGA was not related with higher carnitine deficiency.     

The use of cervical length and change in cervical length for prediction of spontaneous preterm birth in asymptomatic twin pregnancies

Objective

To assess the association between cervical length (CL) and change of CL over two measurements and preterm birth (PTB) at <32 weeks in asymptomatic twin pregnancies.

Study design

This study was undertaken in the multiple pregnancy antenatal clinic at the Security Forces Hospital (SFH), a tertiary care hospital in Riyadh, Saudi Arabia, between November 2005 and October 2010. This study involved 420 women with asymptomatic twin gestations, but only 209 unselected patients completed the study and met the inclusion criteria. All patients had a CL measurement by transvaginal ultrasound at 20–23 weeks, and a second CL measurement was done within 3–5 weeks of the initial measurement. Patients were classified into two groups, group A with significant shortening of CL, and group B without significant shortening of CL. Comparisons between the groups were performed using a chi-square test or a Fisher exact test for categorical variables, whereas Student's t-test or Wilcoxon's rank-sum test was used for continuous variables. We employed ROC curves to compare the diagnostic accuracy of actual cervical length and percent change in cervical length in predicting preterm birth events. All analyses were performed using the SAS/STAT software.

Results

There were 35 (16.7%) patients whose CL shortened by ≥25% (group A), and 174 (83.3%) whose CLs either did not shorten or shortened by <25% (group B). Preterm birth at <28, <30, <32, and <34 weeks gestation was higher in group A than in group B even if the CL was >25 mm. The use of CL shortening was superior, but not statistically significantly, to the use of CL for the prediction of PTB at <32 (P = 0.0524) and <34 weeks (P = 0.281), but CL was preferred for the prediction of PTB at <28 (P = 0.037) and <30 weeks (P = 0.0457).

Conclusion

The test of two CL measurements, the first between 20 and 23 weeks gestation and another CL measurement 3–5 weeks later, with a difference of ≥25%, is a good predictor for preterm birth in asymptomatic twin pregnancies, even if the CL is >25 mm.     

Population-based study on antenatal corticosteroid treatment in preterm small for gestational age and non-small for gestational age twin infants

Objectives: To assess the associations between antenatal corticosteroid use (ACU), mortality and severe morbidities in preterm, twin neonates and compare these between small for gestational age (SGA) and non-SGA twins.

Materials and methods: Population-based study using data collected by the Israel National Very Low Birth Weight infant database from 1995 to 2012, comprising twin infants of 24–31 weeks' gestation, without major malformations. Univariate and multivariable logistic regression analyses were performed.

Results: Among the 6195 study twin infants, 784 were SGA. Among SGA neonates, ACU were associated with decreased mortality (23.9% vs. 39.2%, p?p?=?0.0015), similar to the effect in non-SGA neonates (mortality 13.0% vs. 24.5%, p?p?P_interaction?=?0.69. Composite adverse outcome risk was also reduced in SGA (OR?=?0.78, 95% CI 0.50–1.23) and non-SGA groups (OR?=?0.78, 95% CI 0.65–0.95), P_interaction?=?0.95.

Conclusions: ACU should be considered in all mothers with twin gestation, at risk for preterm delivery at 24–31 weeks, in order to improve perinatal outcome.     

Relationships between physical abuse during pregnancy and risk factors for preterm birth among women in Manitoba

OBJECTIVE: To describe the prevalence and correlates of physical abuse during the year of pregnancy and to explore the association between physical abuse and other risk factors for preterm birth. DESIGN: Secondary analysis of data from a case-control study of risk factors for preterm birth. SETTING: Two tertiary care hospitals in the Canadian province of Manitoba. PARTICIPANTS: Six hundred eighty postpartum women who delivered a live singleton newborn after spontaneous onset of labor. MAIN OUTCOME MEASURES: Instruments included the Abuse Assessment Screen, Prenatal Psychosocial Profile, Perceived Stress Scale, and a questionnaire to collect data on demographic characteristics, complications during pregnancy, and lifestyle behaviors. RESULTS: Sixty-four women (9.4%) reported being physically abused during the year of pregnancy. Abused women were significantly more likely to be younger, single, of lower income, and less educated than nonabused women. Significant correlates of abuse, after adjusting for other factors in a logistic regression, included the following: illicit drug use, low support from partner, moving two or more times in the past year, high life event stress, bladder infection during pregnancy, Aboriginal race/ethnicity, and single marital status. CONCLUSION: This study suggests that physical abuse during pregnancy is associated with other risk factors for preterm birth, particularly stress and behavioral risk factors such as substance abuse.     

The role of depressive symptoms in the pathway of demographic and psychosocial risks to preterm birth and small for gestational age

Objective

depressive symptoms during pregnancy are associated with preterm birth (PTB) and small for gestational age (SGA). Depressive symptoms and PTB and SGA, however, share similar demographic and psychosocial risk factors. Therefore, we investigated whether depressive symptomatology is an independent risk factor, or a mediator in the pathway of demographic and psychosocial risks to PTB and SGA.

Design

multicentre follow-up study.

Participants and setting

pregnant women (n=1013) from midwifery practices, secondary hospitals and a tertiary hospital in three urban areas in the Netherlands.

Measurements

initial risk factors and depressive symptoms were assessed with the Mind2Care instrument, including Edinburgh Depression Scale (EDS) during early pregnancy. Pregnancy outcomes were extracted from medical records. A formal mediation analysis was conducted to investigate the role of depressive symptoms in the pathway to PTB and SGA.

Findings

a univariate association between depressive symptoms and PTB (OR:1.04; 95% CI:1.00–1.08) was observed. After adjusting for the risk factors educational level and smoking in the mediation analysis, this association disappeared. One educational aspect remained associated: low education OR: 1.06; 95%–CI:1.02–1.10.

Key conclusions

depressive symptomatology appeared no mediator in the pathway of demographic and psychosocial risks to PTB or SGA. The presumed association between depressive symptoms and PTB seems spurious and may be explained by demographic and psychosocial risk factors.

Implications for practice

for the prevention of PTB and SGA, interventions directed at demographic and psychosocial risk factors are likely to be of primary concern for clinicians and public health initiatives. As depressive symptoms and PTB and SGA share similar risk factors, both will profit.     

Respiratory outcome in preterm small for gestational age fetuses with or without abnormal umbilical artery Doppler and/or maternal hypertension

Objective.?To study respiratory outcome in preterm small for gestational age (SGA) fetuses with or without signs of intrauterine growth restriction due to placental insufficiency, and with or without maternal hypertension.

Methods.?This was a retrospective study of 187 neonates with birth weight <10^th percentile and gestational age <34 weeks. Results from umbilical artery Doppler velocimetry were used to identify the abnormal Doppler subgroup.

Results.?No significant difference in respiratory outcome between SGA fetuses with normal (SGA-N) or abnormal (SGA-A) umbilical artery Doppler examination was found. Within the SGA-A group, the respiratory distress syndrome (RDS) incidence (OR 5.6, 95% CI 1.7–18.3), RDS grade (OR 6.7, 95% CI 1.2–38.5), and need for surfactant (OR 5.3, 95% CI 1.1–24.4) were higher in infants of women with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome as compared to those of normotensive mothers.

Conclusions.?Lung maturation is not accelerated with placental insufficiency. SGA-A fetuses of mothers with HELLP syndrome have a significantly poorer respiratory outcome than those with healthy mothers. Possibly, fetuses of mothers with HELLP syndrome are subjected to ‘oxidative stress’ causing lung damage rather than lung maturation.