Elevated second-trimester maternal serum hCG in patients undergoing haemodialysis.

Prenatal Down syndrome screening with maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotrophin (hCG) has become common. High levels of maternal serum hCG and low levels of AFP have been associated with an increased risk of fetal Down syndrome. In this paper, we report five pregnancies in patients undergoing long-term haemodialysis, all of whom had false-positive second-trimester Down syndrome screening results. All of our five patients had extremely high levels of maternal serum hCG, but normal AFP values for their gestational age, and all had serious complications during pregnancy.     

Elevated maternal serum alpha-fetoprotein levels and maternal risk factors. Their association with pregnancy complications.

Maternal serum alpha-fetoprotein (MS-AFP) screening programs identify a population of pregnant women with elevated MS-AFP values. When the levels are unassociated with a fetal anomaly, those women have a high incidence of pregnancy complications. Such patients were compared to a population with normal MS-AFP values to determine the incidence of historical risk factors and to ascertain if their presence affected the rate of pregnancy complications. A total of 358 patients were followed prospectively, 23 with elevated MS-AFP levels and 335 with normal levels (control group). Historical risk factors were more frequent in the patients with elevated MS-AFP levels. There was a fourfold increase in the rate of pregnancy complications when a patient had both risk factors and elevated MS-AFP levels as compared with elevated MS-AFP levels alone. In the control group, patients with known risk factors experienced twice the incidence of pregnancy complications as did patients with no risk factors. Using multiple logistic regression analysis, elevated MS-AFP levels were shown to be an independent variable in the risk assessment. The results of this study have wide application in the counseling and follow-up of patients identified by MS-AFP screening programs.     

Association between second-trimester isolated high maternal serum maternal serum human chorionic gonadotropin levels and obstetric complications in singleton and twin pregnancies

OBJECTIVE: The purpose of this study was to examine the clinical significance of high maternal serum human chorionic gonadotropin levels in the second trimester in singleton and twin pregnancies within the Ontario maternal serum screening program. STUDY DESIGN: The study group comprised 564 women with singleton pregnancies with total maternal serum human chorionic gonadotropin levels of > or =4.0 multiples of the median (MoM) and serum marker alpha-fetoprotein levels of <2.0 MoM. The cases were matched with 1692 control subjects who had both serum marker alpha-fetoprotein levels and maternal serum human chorionic gonadotropin levels of <2.0 MoM. The second part of the study comprised 93 twin pregnancies with maternal serum human chorionic gonadotropin levels of > or =5.0 MoM and serum marker alpha-fetoprotein levels of <4.0 MoM; the control group (n = 1496) had serum marker alpha-fetoprotein levels of <4.0 MoM and maternal serum human chorionic gonadotropin levels of <5.0 MoM. The final part of the study included 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM). RESULTS: Of the singleton pregnancies with maternal serum human chorionic gonadotropin levels of > or = 14;4.0 MoM, 22.5% had severe adverse obstetric outcomes, compared with only 10.9% of the matched control population (P =.001). Women with markedly elevated maternal serum human chorionic gonadotropin levels had significantly increased risks of having spontaneous miscarriage, small-for-gestational-age infants, pregnancy-associated hypertensive disorder, and preterm delivery. Of the women with twin pregnancies with high maternal serum human chorionic gonadotropin levels (> or =5.0 MoM), 71% had at least one complication (such as miscarriage and preterm delivery) compared with 55.3% in the control group. Finally, 23 of 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM) had serious adverse outcomes (such as fetal abnormalities, pregnancy-associated hypertensive disorder, premature separation of placenta, intrauterine growth restriction, neonatal respiratory distress syndrome, and neonatal jaundice). CONCLUSION: Pregnancies with an elevated maternal serum human chorionic gonadotropin level are associated with adverse obstetric outcomes. Increased maternal and fetal surveillance is warranted in these pregnancies.     

Elevated maternal serum alpha-fetoprotein, second-trimester oligohydramnios, and pregnancy outcome

Although the primary purpose of maternal serum alpha-fetoprotein (AFP) screening is to detect open neural tube defects, the technique is of value in the diagnosis of other fetal abnormalities. Six patients from the Alpha-Fetoprotein Screening Program, Perinatal Region IV, were found to have twice elevated maternal serum AFP levels associated with severe early second-trimester oligohydramnios. Five of the fetuses were found to have urinary tract abnormalities. The source of the elevated maternal serum AFP is not clear. Pregnancy prognosis appears poor. These cases should be thoroughly studied so that patients may be accurately informed of the recurrence risk.     

Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free beta-hCG and with second-trimester uterine artery Doppler

BACKGROUND: Previous studies have shown an association between low first trimester maternal serum free beta-hCG and PAPP-A and subsequent development of pregnancy complications. Similarly, uterine artery Doppler in the late second trimester has shown that high impedance to flow is associated with increased risk for preeclampsia and fetal growth restriction. The objective of this study is to determine whether there is an association between the maternal serum concentration of PAPP-A and free beta-hCG at 11-13(+6) weeks with the uterine artery pulsatility index (PI) at 22-24 weeks, and secondly, to compare the screening characteristics of the two methods in the prediction of adverse pregnancy outcome. METHODS: Maternal serum PAPP-A and free beta-hCG at 11-13(+6) weeks and uterine artery PI at 22-24 weeks were measured in 4390 women with singleton pregnancies. Pregnancies with chromosomal defects or fetal anomalies were excluded. The biochemical and Doppler measurements were compared between those with normal outcome and those resulting in spontaneous preterm delivery, pre-eclampsia and fetal growth restriction (FGR). Detection rates using a combination of the biochemical and Doppler measurements were investigated. RESULTS: In the pregnancies resulting in pre-eclampsia (n = 64) and FGR (n = 172), the median PAPP-A was lower (0.844 and 0.813 MoM), the median uterine artery mean PI was higher (1.56 and 1.18) but the median free betahCG was not significantly different (0.923 and 0.933 MoM) than in the normal outcome group. In the preterm delivery group (n = 159), the median free beta-hCG (0.944 MoM) and uterine artery mean PI (1.06) were not significantly different from normal but the median PAPP-A (0.928 MoM) was significantly lower than normal. In screening for pre-eclampsia, the detection rate, for a 5% false-positive rate, was 14.1% for PAPP-A, 54.7% for uterine artery mean PI and 62.1% for a combination of PAPP-A and uterine artery mean PI. CONCLUSION: Maternal serum PAPP-A at 11-13(+6) of gestation is significantly lower in adverse pregnancy outcomes. The combination of first trimester serum PAPP-A and uterine artery mean PI at 22-24 weeks improves the screening efficacy for the prediction of pre-eclampsia.     

Does unexplained second-trimester (15 to 20 weeks' gestation) maternal serum alpha-fetoprotein elevation presage adverse perinatal outcome? Pitfalls and preliminary studies with late second- and third-trimester maternal serum alpha-fetoprotein.

Several reports have suggested that persons with an unexplained maternal serum alpha-fetoprotein elevation at 15 to 20 weeks' gestation are at an increased risk for a variety of other pregnancy complications (e.g., preeclampsia) and adverse perinatal outcomes (e.g., fetal death, low-birth-weight infants). However, ascertainment biases could explain some of these reported findings, and predictive value of unexplained elevated maternal serum alpha-fetoprotein levels in the prediction of pregnancy complications seems limited. If elevated second-trimester levels were truly predictive of pregnancy complications, we reason that third-trimester levels could prove even more useful. We thus studied late second-trimester and early third-trimester (24 to 36 weeks' gestation) maternal serum alpha-fetoprotein levels with the same enzyme immunoassay we use to evaluate routine second-trimester (15 to 20 weeks' gestation) levels. Values rose up to 32 weeks and fell slightly thereafter. Variance was greater than at 15 to 20 weeks but not so great as to preclude clinical usefulness in the third trimester. Of 279 women with a normal (0.4 to 2.49 multiples of the median) maternal serum alpha-fetoprotein value at 15 to 20 weeks' gestation, 270 (96.8%) showed levels in the same range later in gestation; however, none of six singleton pregnancies with unexplained maternal serum alpha-fetoprotein levels greater than 2.50 multiples of the median at 15 to 20 weeks' gestation showed maternal serum alpha-fetoprotein levels in this range at 24 to 36 weeks' gestation. The relationship between second- and third-trimester maternal serum alpha-fetoprotein levels in abnormal pregnancies remains to be elucidated in a large sample. Thus we are conducting not only cohort but also cross-sectional studies. Preliminary findings suggest that women with preterm premature rupture of membranes or with premature labor show elevated late second-trimester and early third-trimester maternal serum alpha-fetoprotein levels; however, larger sample sizes are necessary.     

The association between young maternal age and pregnancy outcome

Abstract

Objective: We aimed to determine the association between young maternal age at delivery with adverse pregnancy outcome in a single, tertiary, university-affiliated medical center.

Methods: A retrospective, cohort, matched control study using the first percentile distribution of maternal age at delivery (21 years old, n?=?461) as the study group, and four control groups by maternal age matched by parity in a 2:1 ratio (22–25, 26–30, 31–35 and 36–40 years; n?=?922 each).

Results: Women aged ≤21 years were found to have lower rates of chronic hypertension [compared with women aged 36–40 years old (0.0% versus 1.3%, p?<?0.05)], lower rates of gestational diabetes mellitus (GDM) (1.3% versus 3.7%, p?=?0.007), higher rates of perineal lacerations [compared with women aged 31–35 and 36–40 years old, 41% versus 31.8% and 31.1%, respectively, p?<?0.01)], higher rates of postpartum hemorrhage (4.6% versus 1.5%, p?<?0.0001) and higher rates of low 5-min Apgar score (2.2% versus 0.8%, p?=?0.004). No significant differences were found in terms gestational age at delivery, birth weight, fetal sex, intrapartum or antepartum mortality.

Conclusion: Young maternal age at delivery is associated with increased risk of short-term complications after delivery.     

The links between maternal histamine levels and complications of human pregnancy

Previous literature published since 1910 on maternal blood histamine levels and complications of pregnancy have been reviewed, showing links between hyper-histaminemia occurring in specific gestational complications including preeclampsia, spontaneous abortion, preterm labour and hyperemesis gravidarum. These complications may present with symptoms similar to those of experimentally induced high blood histamine or hyper-histaminemia in non-pregnant humans. Maternal levels of histamine in normal pregnancy decrease below values found in healthy non-pregnant women. However, in some complications of pregnancy, maternal blood histamine levels rise above those associated with normal pregnancy and may exceed normal non-pregnant circulating levels. These links between circulating maternal histamine levels and specific complications of human pregnancy suggest that further investigations to evaluate the outcome of managing maternal blood histamine levels during such complications may be warranted.     

Extremely high maternal serum alpha-fetoprotein levels at second-trimester screening.

Maternal serum alpha-fetoprotein (MSAFP) screening is widely used for the detection of open neural tube defects (NTDs) and a variety of other anomalies and complications. We examined the outcomes of 44 pregnancies with MSAFP elevations of 8 or more multiples of the median (MoM) from among 40,676 screened pregnancies. At the initial evaluation by ultrasound, 82% of the patients had at least one finding that may have accounted for the elevation. Approximately 45% of the fetuses had a major fetal anomaly, 25% died, 16% had an identifiable placental abnormality, and 5% had an underestimation of gestational age; 18% of the elevations remained unexplained after ultrasound. In follow-up of the pregnancies, all of those with an unexplained elevation after initial ultrasound had at least one obstetric complication or placental abnormality. The overall positive predictive value of an MSAFP value of 8 or more MoM for NTDs was 22.7%. The proportion of infants born alive in the overall group was low, with only 16 live births among 46 fetuses. The majority of the nonviable outcomes were associated with a fetus with a major anomaly that was terminated or died before 20 weeks. Of the live-born infants, 31% had a major anomaly, 19% had intrauterine growth retardation (IUGR) and an anomaly, 12.5% had IUGR without an anomaly, and 25% were preterm. Eighty-eight percent of those pregnancies with a live-born infant had at least one obstetric complication. Among pregnancies with MSAFP of 8 or more MoM, the majority are associated with large structural fetal anomalies or fetal death before 20 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

The association between maternal height and pregnancy outcomes in twin gestations

Objective: We sought to assess the association between maternal height and the risk of preterm birth, fetal growth restriction and mode of delivery in twin gestations.

Study design: Cohort study of patients with twin pregnancies delivered from 2005 to 2014. We compared pregnancy outcomes between patients of short stature?≤159?cm to those of normal stature?≥160?cm. Patients with monoamniotic twins and major fetal anomalies were excluded. Pearson’s correlation, Chi-square and Student’s t-test were used as appropriate.

Results: Six hundred and sixty-six patients were included, 159 (23.9%) of whom had short stature (mean height 155.8?±?2.5?cm) and 507 (76.1%) of whom had normal stature (mean height 167.2?±?5.5?cm). There were no differences in outcomes between the groups in regards to preterm birth, gestational age (GA) at delivery, birth weight of either twin, preeclampsia, gestational diabetes or cesarean section rate. Results were similar when the groups were stratified by parity. As a continuous variable, maternal height did not correlate with GA at delivery (p=?0.388), cesarean delivery (p?=?0.522) nor the birth weight of the larger (p?=?0.206) or smaller (p?=?0.307) twin.

Conclusion: In twin pregnancies, maternal short stature is not associated with preterm birth, fetal growth restriction or cesarean section rate. This suggests that although anthropometric measurements have long been used to counsel patients in regards to outcomes, patients of short stature should be reassured that their height does not appear to lead to adverse twin pregnancy outcomes.     

Origin of raised maternal serum alpha-fetoprotein levels in second-trimester oligohydramnios.

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.     

Isolated low second-trimester maternal serum beta-human chorionic gonadotropin is not associated with adverse pregnancy outcome

OBJECTIVE: We investigated whether low human chorionic gonadotropin from maternal serum screening is associated with adverse pregnancy outcome. STUDY DESIGN: Women between 15 and 20 completed weeks of gestation who had a maternal serum screen performed from June 1999 to November 2001 were studied. Cases included women with human chorionic gonadotropin values of 0.5 and <2.0 multiples of the median, and estriol values of >0.6 and <2.0 multiples of the median. Control subjects were selected randomly from the population of women with normal values for all three analytes. RESULTS: There were 146 case subjects and 292 control subjects. There was no increased risk in the study group compared with the control subjects for preterm delivery, intrauterine fetal death, low birth weight, abruptio placentae, preeclampsia, or preterm premature rupture of membranes. CONCLUSION: An isolated low human chorionic gonadotropin level from second-trimester maternal serum screening is not associated with adverse pregnancy outcome.     

Intrahepatic cholestasis of pregnancy has no effect on maternal serum second trimester alpha-fetoprotein and hCG

OBJECTIVE: To investigate the association between intrahepatic cholestasis and Down's syndrome screening analytes (alpha-fetoprotein [AFP] and hCG) during the second trimester. DESIGN: Measurements of maternal serum AFP and hCG concentrations were retrospectively analyzed in relation to intrahepatic cholestasis in a cohort of 33 consecutive singleton pregnancies affected by cholestasis from January 1995 through December 1997 at the University Hospital of Kuopio, and then compared with those in healthy singleton control pregnancies (n=5680) from the same clinic over the same period of time. RESULTS: Geometric means of maternal serum AFP and hCG concentrations in pregnancies affected by cholestasis were 1.12 and 0.98 multiples of the median [MoM], respectively. Mean maternal age was significantly higher in the subjects than in controls (30.6 years compared with 28.8 years). In relation to Down's syndrome risk assessment, the pattern of the two markers together with maternal age indicated high risk as often in the study subjects as in the controls. CONCLUSION: Median serum AFP and hCG concentrations in pregnancies complicated by intrahepatic cholestasis were not significantly different from those in unaffected pregnancies. There is no need to take the hepatic disorder into account in maternal serum screening.     

The effect of fetal gender on second-trimester maternal serum inhibin-A concentration

Second-trimester serum inhibin-A is increasingly used as a fourth marker in addition to the triple test to screen for Down syndrome. We investigated whether fetal gender had an effect on serum inhibin-A concentration. A retrospective analysis was done on 316 normal pregnancies and 48 Down syndrome pregnancies in which maternal serum inhibin-A assays were performed between 15 and 20 weeks of gestation and in which the fetal sex was known. The median inhibin-A MoM (95% CI) for normal pregnancies in the presence of a male fetus was 0.93 (range 0.88-1.03). This was significantly lower than that in the presence of a female fetus (median MoM=1.04). The gender difference was not observed in the Down syndrome pregnancies. The increased inhibin-A concentration would lead to a 2.3-fold higher false-positive rate in the presence of a female fetus (10.6% vs. 4.6%; p<0.05, Chi-square test). Because of the small number of cases studied, the results need to be substantiated by a larger series. If the gender effect is confirmed, adjustment for fetal sex may be necessary when inhibin-A is used as a screening marker.     

Association between maternal panic disorders and pregnancy complications and delivery outcomes

BACKGROUND: The objective of the study was to evaluate the possible association between panic disorders during pregnancy and pregnancy complications, as well as birth outcomes: gestational age and birth weight, as well as preterm birth/low birthweight in newborns. METHODOLOGY: Comparison of newborn infants (without any defects) born to mothers with or without panic disorder in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Main outcome measures were medically recorded pregnancy complications, as well as gestational age and birth weight, proportion of preterm birth and low birthweight. PRINCIPAL FINDINGS: Of 38,151 controls, 187 (0.5%) had mothers with panic disorders during pregnancy. Among pregnancy complications, anemia and polyhydramnion showed a higher prevalence in women with panic disorder. There was a higher proportion of males among newborn infants born to mothers with panic diseases compared to newborn infants of mothers without panic disorders. Pregnant women with panic disorders had a shorter (0.4 week) gestational age (adjusted t = 2.3; p = 0.02) and a larger proportion of preterm births (17.1% versus 9.1%) (adjusted POR with 95% CI = 1.9, 1.3-2.8). However, there was no significant difference in the mean birth weight and rate of low birthweight between the two study groups. CONCLUSION: Panic disorders during pregnancy were associated with anemia, a shorter gestational age and a larger proportion of preterm birth. Further studies are needed to confirm and explain or disprove the male excess among newborn infants born to mothers with panic disorders.     

The association between maternal pre-pregnancy body mass index and pregnancy outcomes of preeclampsia

ObjectiveTo evaluate the effects of pre-pregnancy maternal body mass index (BMI) to pregnancy outcomes in patients diagnosed as preeclampsia.Materials and methodsThis was a retrospectively study on women who had been diagnosed as preeclampsia and delivered at Seoul National University Bundang Hospital between June 2017 and March 2020. Multifetal gestation, major fetal anomaly, and fetal death in utero were excluded. A total of 150 singleton pregnancies were included and divided into four groups according to the pre-pregnancy BMI classification: underweight (<18.5 kg/m², n = 6), normal (18.5–22.9 kg/m², n = 66), overweight (23.0–24.9 kg/m², n = 26), and obese (≥25.0 kg/m², n = 52). Pregnancy outcomes including gestational age at delivery, birthweight, and delivery modes were reviewed.ResultsThe rates of preterm birth before 34 weeks of gestation were 67%, 49%, 35%, and 27% for underweight group, normal BMI group, overweight group, and obese group, respectively (p-trend = 0.006). The birthweight of newborn increased significantly as pre-pregnancy BMI increased (p-trend<0.001). The proportions of small for gestational age (SGA) were highest in underweight group and decreased as pre-pregnancy BMI increased (67%, 41%, 42%, and 10% for each group, respectively, p-trend<0.001).ConclusionThe rates of preterm birth before 34 weeks and SGA increased as pre-pregnancy BMI decreased in patients with preeclampsia.Implications for practiceWomen with underweight before pregnancy are at the highest risk for preterm birth and SGA, therefore they need to be monitored more intensively when diagnosed as preeclampsia.