Association between Advanced Paternal Age and Low Birthweight in Thai Population

Objectives: To determine the association between advanced paternal age and low birthweightMaterials and Methods: This was a case-control study including primigravida women, age ≥ 18 years old, who delivered at Siriraj Hospital during January 2008 to December 2010. This study included 398 women who delivered the low birthweight infants. Matching total of 400 women with infant weight ≥ 2,500 g were served as the control group. Paternal age, parental characteristics and certain obstetric complications were compared between these two groups.Results: There was no statistically significant associations between paternal age older than 34 years old and low birthweight. Maternal age younger than 20 years had an increased risk of having a low birthweight infant comparing with the mothers aged 20-34 years (adjusted OR 2.31, 95%CI: 1.14-4.71). Severe preeclampsia, superimposed preeclampsia and eclampsia are significantly increased the risk of low birthweight (adjusted OR 3.59, 95%CI: 1.65-7.82). The association between preterm birth and low birthweight was remarkably significant (adjusted OR 16.06, 95%CI: 10.07-25.63).Conclusion: Advanced paternal age is not associated with low birthweight in Thai population. Teenage pregnancy, pregnancy associated hypertension at the level of severe preeclampsia or more, and preterm birth increased risk of low birthweight

Liquid-Diet with Alcohol Alters Maternal, Fetal and Placental Weights and the Expression of Molecules Involved in Integrin Signaling in the Fetal Cerebral Cortex

Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS). Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans) model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β1 and α3 integrin subunits and phospholipase-Cγ2 were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains

Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass

Aneuploidy has been well-documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening in a 24-h protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy and distinguishes certain meiotic from mitotic errors. In this study, our objective was to examine aneuploidy in human blastocysts and determine correspondence of karyotypes between trophectoderm (TE) and inner cell mass (ICM). We disaggregated 51 blastocysts from 17 couples into ICM and one or two TE fractions. The average maternal age was 31. Next, we ran 24-chromosome microarray molecular karyotyping on all of the samples, and then performed a retrospective analysis of the data. The average per-chromosome confidence was 99.95%. Approximately 80% of blastocysts were euploid. The majority of aneuploid embryos were simple aneuploid, i.e. one or two whole-chromosome imbalances. Structural chromosome aberrations, which are common in cleavage stage embryos, occurred in only three blastocysts (5.8%). All TE biopsies derived from the same embryos were concordant. Forty-nine of 51 (96.1%) ICM samples were concordant with TE biopsies derived from the same embryos. Discordance between TE and ICM occurred only in the two embryos with structural chromosome aberration. We conclude that TE karyotype is an excellent predictor of ICM karyotype. Discordance between TE and ICM occurred only in embryos with structural chromosome aberrations

Genetic analysis of embryonic and fetal tissues

In this thesis, genetic analysis has been performed on embryonic and fetal material. Firstly, it was used to demonstrate the presence of fetal cells in the cervical mucus of pregnant women in the first trimester. Several studies have shown that fetal cells are present in the cervical canal but some reports have not identified these cells. In the present study, fetal genetic material was demonstrated in the cervical mucus from 66 of 193 (34%) women who underwent termination of pregnancy and from 7 in 37 (19%) on-going pregnancies. The polymerase chain reaction (PCR) was more efficient in detecting fetal cells than fluorescent in situ hybridisation (FISH). Secondly, FISH was used to determine the level of the trisomic cell line in different tissues, including placenta, from first and second trimester trisomic fetuses obtained from termination of pregnancy. Several studies have suggested that there are correlations between the degree of mosaicism in a chromosomally abnormal fetus, the severity of the disease and the chance of survival to term. The level of abnormal cells obtained from this study appeared not to be correlated with the clinical manifestations and the survival potential. As a side-line of this work, the efficiency of FISH on metaphase and interphase nuclei from skin fibroblast cultures from a trisomic and a triploid fetuses was determined. Finally, FISH was used to determine the mosaicism in human embryos on day 5 post-insemination, both arrested and blastocyst stage embryos. Mosaicism was found in 80% of the arrested embryos and 90% of the blastocysts. This may have an implication for preimplantation genetic diagnosis using blastocyst biopsy. In conclusion, FISH and PCR were used to study fetal genetic material in cervical mucus; FISH was used to study percentages of abnormal cell lines in trisomic fetal tissues and blastomeres from day-5 embryos

Accuracy of Third Trimester Ultrasound for Predicting Large-for-Gestational Age Newborn in Women with Gestational Diabetes Mellitus

Objective: To determine the accuracy of ultrasonography for predicting a large-for-gestational-age (LGA) newborn in women with gestational diabetes mellitus (GDM). Materials and Methods: Singleton pregnancy, diagnosed with GDM were recruited. They underwent ultrasonography at 32-36 weeks’ gestation for fetal biometry. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Estimated fetal weight (EFW) was derived from these 4 parameters by Hadlock formula. Delivery of an LGA newborn in women with the ultrasound finding of LGA fetus was the primary outcome. Results: Of 345 studied women, 107 (31%) had an LGA newborn. EFW of ≥ 90 th percentile at third trimester ultrasonography was found in 13 women, all of whom had an LGA newborn. It had a positive predictive value (PPV), specificity, sensitivity and negative predictive value (NPV) of 100%, 100%, 12.1% and 71.7% respectively to predict LGA at birth. Considering each fetal parameter individually, AC > 90 th percentile and HC > 90 th percentile had odds ratios (OR) with 95% confidence intervals of the newborn being LGA of 6.5 (3.3-12.8) and 2.0 (1.0-4.0) respectively while EFW > 85 th percentile had the highest OR of 9.3 (1.1-77.9). Lowering cutoff values of EFW to 80 th and 70 th percentile increased the sensitivity and NPV for prediction of LGA at birth while reducing the PPV and specificity slightly. Conclusion: EFW derived from the third trimester ultrasonography in GDM had high PPV and specificity with low to moderate sensitivity and NPV to predict an LGA newborn in GDM

Incidence of large for gestational age and predictive values of third-trimester ultrasound among pregnant women with false-positive glucose challenge test

This cohort study aimed to determine the association between false-positive 50-g GCT and incidence of LGA and to evaluate predictive roles of third-trimester ultrasonographic examination. A total of 200 women with false-positive 50-g GCT and 188 women without GDM risks were enrolled. Third-trimester ultrasonographic examinations were offered. Rate of LGA during third trimester and at birth were compared between groups. Factors associated with LGA and diagnostic properties of third-trimester ultrasonography were evaluated. Incidence of LGA by third-trimester ultrasound and at birth were significantly higher in women with false-positive GCT (19.0% vs. 10.6%, p = .03 and 22% vs. 13.8%; p = .04). Factors associated with LGA included multiparity (adjusted OR 2.32, p = .01), excessive weight gain (adjusted OR 2.57, p = .01) and LGA by ultrasound (adjusted OR 9.79, p < .001). Third-trimester ultrasonography had 47.1% sensitivity, 92.1% specificity and LR + and LR- of 5.96 and 0.57 in identifying LGA infants. Impact statement What is already known on this subject? Women with abnormal GCT but normal OGTT (false positive GCT) might have some degree of glucose intolerance so that GDM-related outcomes could develop, including LGA, macrosomia, shoulder dystocia, and caesarean delivery. Roles of ultrasonography in the prediction of LGA and macrosomia has been reported with mixed results. What do the results of this study add? The results showed that the incidence of LGA, by third-trimester ultrasound and at birth, were significantly increased in women with false-positive GCT. Multiparity, excessive weight gain and LGA by third-trimester ultrasound significantly increased the risk of LGA. Third-trimester ultrasonography had 47.1% sensitivity, 92.1% specificity and LR + and LR- of 5.96 and 0.57 in identifying LGA infants. What are the implications of these findings for clinical practice and/or further research? More intensive behavioural and dietary interventions, together with weight gain control and monitoring, may be needed in women with false-positive GCT to minimise the risk of LGA. Third trimester ultrasonographic examination might be helpful to detect and predict LGA at birth and should be included into routine clinical practice. Further studies that are more widely generalisable are needed to elucidate the relationship between false-positive GCT and adverse pregnancy outcomes and to investigate the benefits of ultrasonographic examination in the prediction of LGA and macrosomia

Prenatal screening tests and prevalence of fetal aneuploidies in a tertiary hospital in Thailand.

This study evaluated prenatal screening test performance and the prevalence of common aneuploidies at Siriraj Hospital, Thailand. We collected data from screening tests which are first-trimester test, quadruple test, and noninvasive prenatal tests (NIPT) between January 2016 and December 2020. Thirty percent (7,860/25,736) of pregnancies received prenatal screening tests for aneuploidies disorders, and 17.8% underwent prenatal diagnosis tests without screening. The highest percentage of screening tests was first-trimester test (64.5%). The high-risk results were 4% for first-trimester test, 6.6% for quadruple test, and 1.3% for NIPT. The serum screening tests for trisomy 13 and 18 had no true positives; therefore, we could not calculate sensitivity. For the first-trimester test, the sensitivity for trisomy 21 was 71.4% (95% confidence intervals (CI) 30.3-94.9); specificity for trisomy 13 and 18 was 99.9% (95% CI 99.8-99.9); and for trisomy 21 was 96.1% (95% CI 95.6-96.7). For the quadruple test, the specificity for trisomy 18 was 99.6% (95% CI 98.9-99.8), while the sensitivity and specificity for trisomy 21 were 50% (95% CI 26.7-97.3) and 93.9% (95% CI 92.2-95.3), respectively. NIPT had 100% sensitivity and specificity for trisomy 13, 18 and 21, and there were neither false negatives nor false positives. For pregnant women < 35 years, the prevalence of trisomy 13, 18, and 21 per 1,000 births was 0.28 (95% CI 0.12-0.67), 0.28 (95% CI 0.12-0.67), and 0.89 (95% CI 0.54-1.45), respectively. For pregnant women ≥35 years, the prevalence of trisomy 13, 18, and 21 per 1,000 births was 0.26 (95% CI 0.06-1.03), 2.59 (95% CI 1.67-4.01), and 7.25 (95% CI 5.58-9.41), respectively. For all pregnancies, the prevalence of trisomy 13, 18, and 21 per 1,000 births was 0.27 (95% CI 0.13-0.57), 0.97 (95% CI 0.66-1.44), 2.80 (95% CI 2.22-3.52), respectively