The effects of meperidine and epidural analgesia in labor on maternal heart rate variability.

BACKGROUND: Epidural and parenteral opioid analgesia are two common methods of pain relief in labor that may influence the autonomic nervous system. However, these effects on laboring women have not yet been adequately studied. The aim of our study was to assess the effects of these two methods of analgesia on autonomic nervous system modulation of maternal heart rate variability in laboring women. METHODS: A prospective observational study was conducted on 64 laboring women; 33 received epidural analgesia with bupivacaine and fentanyl and 31 intravenous meperidine and promethazine. Power spectral analysis and nonlinear methods were applied to digitized electrocardiograms performed before and after administration of analgesia, to assess maternal heart rate variability and autonomic equilibrium. RESULTS: Maternal heart rate significantly increased in women who received meperidine compared to those who had epidural analgesia. There was a significant increase in the low-frequency to high-frequency ratio (3.7+/-3.9 vs. 1.8+/-1.6, P<0.05), and a significant decrease of high-frequency spectral power in women who had meperidine compared to those who received epidural analgesia (163+/-91 vs. 98+/-100 ms(2)/Hz, P<0.05). CONCLUSIONS: Meperidine caused an autonomic nervous system shift towards sympathetic activation with abolition of respiratory sinus arrhythmia high-frequency spectral band. Conversely epidural analgesia had no significant effect on autonomic nervous system control of heart rate.

Sonographic nuchal markers for Down syndrome are more common but less ominous in gestations with a male fetus.

OBJECTIVE: A change in the normal male-to-female ratio has been reported in some autosomal trisomies (i.e., trisomy 21 or trisomy 18). The objective of the present study was to evaluate the male-to-female ratio in pregnancies with sonographic nuchal markers for Down syndrome. METHODS: The results of amniocenteses performed for isolated nuchal markers for Down syndrome were grouped by fetal sex and by maternal age. The male-to-female ratio in normal and trisomic gestations was compared. RESULTS: 584 fetal karyotypes were available for analysis. A significantly higher male-to-female ratio was observed. More affected gestations were observed in association with a female fetus. These differences were mainly attributed to the group of patients younger than 35 years that represents more than 80% of our study population. No difference was observed in pregnancies of patients older than 35 years of age. CONCLUSIONS: In patients younger than 35 years, sonographic nuchal markers for Down syndrome are more frequent (but apparently less ominous) in gestations with a male fetus. If the gender is known, counseling can be modified to include such differential risks.

Screening for neural tube defects.

Neural tube defects are separated into two main categories: (1) abnormalities of the skull and brain (anencephaly, acrania, and encephalocele) and (2) malformations of the spine (meningomyelocele or spina bifida). The cause of neural tube defects is not always clear, and include chromosomal abnormalities, single gene mutations, maternal disease, or maternal exposure to teratogens. Mostly the disorder emerges as a multifactorial trait. Routine screening for neural tube defects was introduced in the United Kingdom in the mid-1970s and the United States in the mid-1980s. The use of screening has resulted in a marked decline in the frequency of neural tube defects diagnosed at birth.

Sonographic findings of the umbilical cord: implications for the risk of fetal chromosomal anomalies.

In this review we summarize current knowledge on sonographic findings of the umbilical cord and the risk they impose for chromosomal abnormalities of the fetus. A Medline search of the literature was performed and the pertinent English-language literature was reviewed. Anatomical and Doppler abnormalities of the umbilical cord may be associated with an increased risk of chromosomal aberrations in the fetus. Therefore, level II prenatal sonography should also include a careful examination of the umbilical cord.

Ultrasound screening for fetal chromosome anomalies.

Ultrasound evidence for aneuploidy may be found in almost every organ of the fetus and can be used to modify the risk of aneuploidy. The diagnosis of these minor anomalies on second-trimester ultrasonography will increase the risk of an abnormal karyotype whereas the absence of these findings may reduce this danger. The most specific and most ominous isolated markers for fetal aneuploidy are nuchal findings (edema or cysts), indicating the need to obtain a fetal karyotype in all cases irrespective of maternal age or results of biochemical serum screening. Hyperechoic fetal bowel is apparently also a strong indicator of fetal aneuploidy. Other isolated sonographic markers may increase the risk of an abnormal karyotype three- to ninefold. Most sonographic markers for aneuploidy specify an increased risk for Down syndrome, but choroid plexus cysts are apparently more specific for trisomy 18. Along with other screening methods, ultrasound screening for fetal aneuploidy should be used routinely to identify additional pregnancies at need for evaluation of fetal karyotype.

Ontogeny of isolated ultrasound markers for fetal aneuploidy.

OBJECTIVE: To evaluate the natural history of isolated ultrasound markers for fetal aneuploidy observed at 14-16 weeks of affected gestations. STUDY DESIGN: 76 aneuploid gestations were diagnosed among a predominantly low-risk population undergoing targeted ultrasonography in the early second trimester. Indications for evaluation of fetal karyotype included fetal malformations or sonographic markers for aneuploidy, maternal age over 35 years and abnormal serum screening results. Markers were re-evaluated at the time of amniocentesis or at pregnancy termination for fetal anomalies. RESULTS: Sonographic markers for aneuploidy (SMA) were observed in 68 of 76 aneuploid gestations diagnosed in the study group. In 46 cases, SMA were associated with major fetal malformations and in 22 cases, markers were isolated. Only 2 of 22 isolated markers for aneuploidy were documented at the time of amniocentesis. CONCLUSION: Isolated ultrasound markers for aneuploidy are transient and may disappear later on in gestation. Transvaginal sonography at 14-16 weeks of gestation appears to provide the best time window for detection of markers for fetal abnormal karyotype.

Unequal pronuclear size--a powerful predictor of embryonic chromosome anomalies.

PURPOSE: Our purpose was to evaluate whether pronuclei of unequal size, observed in 13.7% of zygotes evaluated after in vitro fertilization (IVF), are predictive of chromosome anomalies in the developing embryo. METHODS: Five ploidy of 38 embryos grown from zygotes with unequal-sized pronuclei was assessed by fluorescent in situ hybridization (FISH). Twenty-six embryos developed after intracytoplasmic injection of sperm (ICSI) and 12 embryos were derived from conventional IVF. RESULTS: Chromosome anomalies were documented in the ICSI and IVF groups in 88.5 and 50% of cases, respectively. CONCLUSIONS: We suggest that FISH should be employed to examine the ploidy of zygotes with unequal pronuclei, prior to embryo transfer.

Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.

Assisted reproduction technologies and ovulation induction for treatment of infertility continue to cause high order multiple gestations. Increased perinatal morbidity and mortality, as well as maternal morbidity, may complicate these pregnancies. Selective fetal reduction, an acceptable therapeutic approach in these cases, is usually performed at or after the ninth week of gestation, with KCl injected in the vicinity of the fetal heart, and is associated with a total pregnancy loss rate of 11.7%. We report our experience with 90 women who underwent early (mean 7.5 weeks gestation, range 7. 0-8.0 weeks) transvaginal selective embryo aspiration. The mean number of viable embryos before and after reduction was 3.5 and 2.1 respectively. Six (6.7%) pregnancies were lost before 24 gestational weeks. One miscarriage occurred at the tenth gestational week. The other five pregnancies were aborted at 17.3-21.6 weeks gestation. Additional interventions were performed in three of these pregnancies: genetic amniocentesis in two cases and cervical suture in one case. In the subset of 39 patients with>/=4 embryos, only one (2.6%) pregnancy loss was recorded. This loss rate is significantly lower (P < 0.05) than the 15.3% loss rate in patients with >/=4 fetuses calculated from other work. Four (4.4%) other pregnancies were complicated by premature delivery (25-28 weeks gestation). Mean gestational age of delivered pregnancies in our series was 35.7 weeks. In conclusion, early transvaginal embryo aspiration is a simple and relatively safe method for multiple pregnancy reduction. The overall pregnancy loss rate associated with early embryo aspiration is similar to that of procedures performed at later gestational age, but is significantly lower when the initial number of embryos is four or greater.

Differential effect of advanced maternal age on prenatal diagnosis of trisomies 13, 18 and 21.

Nondisjunction associated with advanced maternal age, a well-established factor in the etiology of autosomal trisomy, should equally affect all chromosomes. In this study we evaluate the association of advanced maternal age with the occurrence of potentially viable autosomal trisomies (13, 18 and 21). 275 aneuploid pregnancies were ascertained prenatally and were grouped according to chromosome anomaly diagnosed. Mean maternal age was significantly younger (p = 0.009) in pregnancies affected by trisomy 13 than in pregnancies with trisomy 21. An intermediate mean maternal age was observed in pregnancies affected by trisomy 18. Our study shows a trend of the more severe, but potentially viable, autosomal trisomies to be diagnosed at younger maternal age. This may substantiate the 'relaxed selection hypothesis' proposed to explain the association of aneuploid conceptions with advanced maternal age.

A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is caused by a mutation in the genes encoding the components of the glycine cleavage multi-enzyme system. More than 80% of the patients have defects in the gene encoding P-protein, whereas the rest of the patients have defects in the gene encoding T-protein. We have found a large Israeli-Arab kindred with NKH. At least 14 children were affected, and all the patients had seizures and respiratory failure within 2 days after birth. Enzymatic analysis revealed that T-protein activity was deficient in the liver specimen from one propositus. We screened this family for a mutation in the protein-coding region and exon/intron boundaries of T-protein gene by direct sequencing analysis. A missense mutation was found in exon 2; this resulted in an amino acid substitution from histidine to arginine at position 42 (H42R). Histidine 42 is conserved in human, bovine, chicken, pea, and Escherichia coli, suggesting that it has an important role in catalytic functions. Genotype analyses of 26 family members confirmed that the homozygous H42R mutation was completely associated with the onset of NKH. The availability of DNA testing facilitates the prenatal diagnosis of NKH and the identification of carriers, which is necessary for genetic counseling in the affected families.

Ultrasound imaging of fetal neck anomalies: implications for the risk of aneuploidy and structural anomalies.

This study summarizes 24,000 transvaginal ultrasound examinations which were performed in a predominantly low-risk population at 14-16 weeks' gestation. 1254 (5.2 per cent) fetuses had a nuchal fold or a non-septated cystic hygroma. Of these fetuses, 140 (11.1 per cent) had additional structural anomalies. Cardiovascular anomalies were the most commonly detected structural malformations. Forty-three (3.4 per cent) fetuses were aneuploid. Trisomy 21 was the most common chromosomal anomaly (n = 27). Aneuploidy was significantly more common in fetuses who had a nuchal finding and an associated structural anomaly. The prevalence of nuchal fold and non-septated cystic hygroma, as well as the incidence of their associated structural anomalies, was similar. Based on these data, it is concluded that a complete ultrasonic survey of the fetus and karyotyping are advocated in fetuses with a nuchal abnormality, irrespective of maternal age or triple serum screening results.

The geriatric gravida: multifetal pregnancy reduction, donor eggs, and aggressive infertility treatments.

OBJECTIVE: Recent technologic advances and societal acceptance have dramatically increased the use of donor eggs for infertile couples who require assisted reproductive technologies. Now many "older" couples can access assisted reproductive technologies to achieve pregnancies. We sought to evaluate the changing pattern of patients referred for multifetal pregnancy reduction as a result of donor eggs and age factors in aggressive infertility treatment. STUDY DESIGN: Patients undergoing multifetal pregnancy reduction from 1986 to 1996 were included and categorized by year groupings, age, and the use of donor eggs. RESULTS: A total of 523 patients were referred for and underwent multifetal pregnancy reduction. Before 1994, only 4 of 226 (1.8%) had received donor eggs, whereas in 1994 to 1996, 29 of 297 (9.8%) had received donor eggs (chi 2 = 12.6, p < 0.001). Eight of 9 patients aged > or = 45 years undergoing multifetal pregnancy reduction received donor eggs. There were no patients aged > or = 45 years before 1994 but 9 in 1994 to 1996. Four of 9 patients aged > or = 45 years with multifetal pregnancies chose reduction to singleton gestation. The proportions of patients aged > or = 40 years have increased from 0% to 11% in the last 8 years. CONCLUSIONS: The availability of donor eggs has dramatically increased the use of assisted reproductive technologies and subsequent use of multifetal pregnancy reduction in older patients. Older patients are more inclined to want reduction to singleton gestation; they cite parental demands, financial issues, and their ability to parent in their 60s and 70s as reasons for reduction to singleton gestation.

Race-ethnicity-specific variation in multiple-marker biochemical screening: alpha-fetoprotein, hCG, and estriol.

OBJECTIVE: To identify any race-ethnicity-specific differences in serum alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3) levels in women between 14 and 21 weeks' gestation. METHODS: Data from the 3-year period 1992-1994 were analyzed from 208,257 women who had AFP screening, of whom 155,142 also had hCG and 62,121 also had E3 screened, between 14 and 21 weeks' gestation. Subjects were categorized into four groups: white, black, Asian, and Hispanic. RESULTS: There was a consistent pattern of analyte differences across gestational ages. Levels for AFP were generally higher in Asian and black women than in Hispanic and white women (median AFP at 16 weeks-31.2, 30.9, 27.4, 27.3, respectively), and levels of hCG and E3 were highest in Asians (hCG at 16 weeks-34.7, 30.3, 28.2, 26.8, respectively). Weight correction for AFP, hCG, and E3 levels did not compensate for the ethnic differences. CONCLUSIONS: Because hCG and E3 demonstrate the same general pattern of differences as AFP among ethnic groups, averaging values for all ethnic groups tends inappropriately to lower calculated Down syndrome risks for black and Asian women. Additionally, the slopes of the curves are not parallel, such that separate data bases are preferable to multiplicative correction factors. Separate data bases should be used in laboratories with volume sufficient to permit the establishment of race-ethnicity-specific regressions. Use of separate data bases should result in more accurate screening.

Maternal thyroid function does not alter maternal serum alpha-fetoprotein interpretation.

OBJECTIVE: Endocrine alterations of metabolism such as diabetes and obesity are known to affect maternal serum alpha-fetoprotein interpretation. Thyroid function has been questioned, e.g., because of binding globulins, but not adequately studied as to its impact upon maternal serum alpha-fetoprotein. The purpose of this study was to assess the possible effects of T4 and thyroid-stimulating hormone (TSH) on alpha-fetoprotein production, and to determine if thyroid function (hypothyroidism) alters maternal serum alpha-fetoprotein. METHODS: We evaluated maternal serum alpha-fetoprotein, T4, and TSH records of 25,551 patients, between 14 and 20 weeks' gestation, on whom both studies had been ordered by the patient's primary obstetrician to rule out maternal thyroid disease in pregnancy. Statistical analyses were performed by chi 2 and regression analysis. RESULTS: Patients were stratified according to thyroid function tests into two groups: hypothyroidism (T4 < 6.5 micrograms/dL and/or TSH > 5.0 micrograms/mL), and normal or hyperthyroidism (T4 > or = 6.5 micrograms/dL and/or TSH > or = 5.0 microU/mL). Maternal serum alpha-fetoprotein values were compared among groups for each gestational age. No significant variation or correlation of maternal serum alpha-fetoprotein and thyroid function was observed. CONCLUSIONS: Although other endocrine abnormalities are known to impact maternal serum alpha-fetoprotein values either through decreased production, decreased placental permeability, or plasma volume distribution alterations, maternal thyroid status does not interfere with proper interpretation of maternal serum alpha-fetoprotein.

No effect of fetal sex on amniotic fluid alpha-fetoprotein.

OBJECTIVE: To evaluate the effect of fetal sex on the concentration of amniotic fluid alpha-fetoprotein (AF-AFP) in singletons and twins. MATERIAL AND METHODS: Amniocentesis was performed for advanced maternal age between 15 and 20 weeks of gestation. Only patients with normal karyotypes, uncomplicated gestations and normal ultrasound examination were included. AFP was measured in amniotic fluid by RIA and results, expressed as multiples of the median (MoM), were grouped according to fetal sex and were compared by t test. RESULTS: A total of 603 singleton pregnancies (294 females and 309 males) and 45 twin pregnancies discordant for sex met the inclusion criteria. The mean AF-AFP in singleton males was 1.06 vs. 1.04 MoM in singleton females. In twins, the mean AF-AFP was, respectively, 1.05 and 1.07 MoM (p > 0.05). CONCLUSION: Gender had no impact on AF-AFP in singleton or twin pregnancies, suggesting that the differential influence of sex hormones on the activity of the AFP gene is negligible.

Faint and positive amniotic fluid acetylcholinesterase with a normal sonogram.

OBJECTIVE: Both faint and positive amniotic fluid acetylcholinesterase determinations have been associated with fetal abnormalities. We evaluated the effect of a normal sonogram and positive or faint acetylcholinesterase level on the risk for anomalies. STUDY DESIGN: Between Jan. 1, 1989, and Feb. 1, 1995, 4859 amniocenteses were performed. Twenty-three cases of abnormal acetylcholinesterase determinations combined with normal sonograms were identified, and pregnancy outcomes were determined. RESULTS: One abnormal karyotype was identified (45,X/47,XXX mosaic). No neural tube defects were seen in infants with an abnormal acetylcholinesterase determination and normal sonogram. One fetus of a twin pregnancy had a ventral wall defect that was not detected on ultrasonography. Seventy-three percent of infants were normal at birth, but 27% of the pregnancies had abnormal outcomes. CONCLUSIONS: Advances in ultrasonography have led to improved detection of fetal abnormalities. With a normal karyotype, repeat invasive testing may not be necessary.

Abnormal biochemical serum screening versus 2nd-trimester ultrasound-detected minor anomalies as predictors of aneuploidy in low-risk patients.

OBJECTIVE: To compare the yield of multiple-marker biochemical screening with that of minor fetal anomalies observed on ultrasound for detection of aneuploidy in low-risk patients. METHODS: The results of 1,073 amniocenteses performed because of abnormal biochemical screening tests were compared against 197 amniocenteses performed for minor anomalies as detected on level II ultrasound at 15-22 weeks of gestation. RESULTS: False-positive results were observed in about 7% of serum screening patients and in 1.7% of the ultrasound cases. Chromosomally abnormal fetuses were detected in 2% of the amniocenteses performed because of abnormal serum screening and in 2.5% of the cases with ultrasound-defined minor anomalies. CONCLUSIONS: Both methods identify patients at risk for abnormal karyotypes. Although the evaluation of serum biochemical markers yielded more false-positive results, it is more suitable than ultrasound for mass population screening.

Second-trimester minor ultrasound anomalies: impact on the risk of aneuploidy associated with advanced maternal age.

OBJECTIVE: To determine the impact of the presence or absence of minor ultrasound anomalies for the risk of aneuploidy in patients already at high risk because of advanced maternal age. METHODS: Eleven hundred forty-four women having amniocentesis for advanced maternal age were divided into those with minor ultrasound anomalies (n = 62) and those without (n = 1082). Two hundred fifty-nine women younger than 35 years but with minor anomalies on ultrasound were also included. RESULTS: Fetal aneuploidy was found in six of 62 (9.7%) women of advanced maternal age with minor ultrasound anomalies, in five of 1082 (0.5%) women older than 35 years with normal ultrasound results, and in five of 259 (1.9%) women younger than 35 years with minor ultrasound anomalies. CONCLUSION: Minor ultrasound anomalies increase considerably the risk of aneuploidy in women older than 35 years, and their absence lowers that risk slightly. Minor ultrasound anomalies in the fetuses of women younger than 35 raises their risk to that of a 39-year-old women in her second trimester. Ultrasound can be used to modify genetic risks at counseling and may help patients in their decision to have invasive testing.