Raised maternal serum alpha-fetoprotein levels and low birth weight babies

In a retrospective study of low birth weight babies (less than 2.5 kg) born in one year it was found that statistically more maternal serum alpha-fetoprotein levels were above twice the median level than a control group of mothers producing larger babies (more than 3 kg). However, from the results the test cannot be accepted as being a prospective indicator or as a screening test of low birth weight in pregnant women.     

Can low birth weight after elevated maternal serum alpha-fetoprotein be explained by maternal weight?

Low birth weight infants are delivered with increased frequency in women who have elevated maternal serum alpha-fetoprotein values in the second trimester. Maternal serum alpha-fetoprotein elevations, however, are found more often in lighter-weight women, a group known to have lower-weight infants regardless of maternal serum alpha-fetoprotein levels. To clarify the association between elevated maternal serum alpha-fetoprotein levels and low birth weight independent of maternal weight, we applied a weight correction formula to maternal serum alpha-fetoprotein values from 9507 singleton viable pregnancies without major fetal malformations. Before adjusting for weight, 486 of the women (5.1%) had maternal serum alpha-fetoprotein values of 2.0 or more multiples of the median. The weight adjustment process removed 100 lighter-weight women from this category, added 58 heavier women, and led to an equivalent proportion of women in the various weight categories who were classified as having maternal serum alpha-fetoprotein values of 2.0 or more multiples of the median. Of the 388 low birth weight pregnancies (2500 g or less), 50 initially had maternal serum alpha-fetoprotein values of 2.0 or more multiples of the median; after weight adjustment, seven lighter-weight women were removed, four heavier women were added, the median birth weight fell from 2217 to 1956 g, and a threefold increase in risk was found for low birth weight outcome regardless of weight class. Maternal serum alpha-fetoprotein elevations predict increased risk for low birth weight outcome independent of maternal weight.     

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)     

Very low alpha-fetoprotein in Down syndrome maternal serum screening

OBJECTIVE: To establish the frequency of very low maternal serum AFP and to differentiate congenital AFP deficiency from those diseases known to be associated with low AFP. METHODS: AFP values below 2 microg/L and borderline values up to 3 microg/L were retrospectively analysed in 839 773 singleton pregnancies included in a programme for routine screening of trisomy 21 maternal serum markers. RESULTS: Serum AFP was undetectable (< or =2 microg/L) in 8 cases, giving a frequency of 1/105 000. The calculated risk of Down syndrome was > or =1/250 in 5 cases. Fetal karyotype was normal. Seven of these pregnancies went to term (39-41 weeks) uneventfully, and birth weight was normal (3050-4110 g). In the 8th case, fetal death occurred at 35 weeks due to severe maternal diabetes. AFP levels between 2.1 and 3.0 microg/L were noted in 7 other cases. The calculated risk of Down syndrome was > or =1/250 in 5 cases, and fetal karyotype was normal. Pregnancies went to term in 4 cases (33-41 weeks), and birth weight was normal (3000-3380 g). In 3 cases, low hCG (<0.6 MoM) was associated with low AFP, and fetal death occurred at 15 to 16 weeks. CONCLUSION: Once technical errors have been excluded (repeat assay in a second run, calcium assayed to exclude the interference of EDTA for fluorimetric methods, dilution to exclude interfering antibodies, running on an alternative analyser, checking a second sample), very low second-trimester maternal serum AFP should prompt ultrasound examination in order to check fetal viability. Congenital AFP deficiency, an extremely rare disorder (1/100 000), should be suspected. It has no consequences for fetal and infant development, and parents should be reassured.     

Pregnancy outcomes of women with elevated second-trimester maternal serum alpha-fetoprotein

ObjectiveThe aim of this study was to investigate the overall distribution of pregnancy outcomes in women with elevated second-trimester maternal serum alpha-fetoprotein (MS-AFP), and to determine the risk of adverse pregnancy outcomes (APOs) by MS-AFP level.Materials and methodsWe retrospectively analyzed the clinical data of 429 women with elevated MS-AFP (≥2.5 multiple of the median (MOM)) and 1555 women with normal MS-AFP (0.5–2.49MOM) from a total of 46,741 prenatally screened singleton pregnant women. The overall distribution of APOs of the two groups, the risk of APOs by MS-AFP level, and the predictive value of elevated MS-AFP to APOs were analyzed.ResultsThe incidence rate of APOs in elevated MS-AFP group was significantly higher than that in normal MS-AFP group (42.89 vs. 8.23%). In elevated MS-AFP group, the top three APOs, in term of incidence rate, were structural fetal abnormalities (7.93%), spontaneous abortion (7.46%) and preterm birth (7.23%); regarding to the risk, the top three APOs were stillbirth, spontaneous abortion and early-onset preeclampsia (odds ratio 35.98, 20.81 and 8.58 respectively). For structural fetal abnormalities, MS-AFP had predictive values for fetal open neural tube defects (ONTDs), gastroschisis and multiple malformations.ConclusionElevated MS-AFP is associated with increased risks of APOs. ONTDs complicate merely a small proportion of pregnancies with elevated MS-AFP, and the rest of them have high risks of obstetric complications. MS-AFP can help to identify these women at high risk of APOs in earlier second-trimester.     

Very low versus undetectable maternal serum alpha-fetoprotein values and fetal death

Very low maternal serum alpha-fetoprotein (MSAFP) levels (less than 10 ng/mL) are known to be associated with non-viable pregnancies, including conditions such as fetal death, molar pregnancies, and non-pregnancies. There has not been agreement, however, as to whether very low MSAFP levels indicate already existing fetal deaths or are actually predictive. We analysed 230 pregnancies with MSAFP levels less than 10 ng/mL from among 15,807 women (1.5 per cent) screened consecutively during a three-year period and identified 26 non-viable pregnancies, 22 of which were diagnosed sonographically as part of the screening process (17 missed abortions, 3 blighted ova, 2 non-pregnancies). Furthermore, 20 of these 22 pregnancies were associated with essentially undetectable MSAFP levels (less than 5 ng/mL). Our data indicate that pregnancies with MSAFP values less than 5 ng/mL are the group most strongly associated with fetal non-viability and that very low MSAFP values are not strongly predictive for fetal death.     

Maternal serum alpha-fetoprotein levels in low birth weight singleton pregnancies

Maternal serum alpha fetoprotein (MSAFP) measurement between 16 and 21 weeks gestation is used to define a group of women with an increased risk of fetal abnormality, particularly open neural tube defect. The test is strongly gestation dependent and women with high MSAFP levels require sonar scan examination to define gestation, exclude twins and examine the fetus for obvious malformation or death. It has been reported that women with no primary cause for raised MSAFP have an increased incidence of low birth weight babies. Conflicting reports have separately ascribed these to premature delivery and to intra-uterine growth retardation. We have studied the relationship between MSAFP and low birth weight infants with respect to both prematurity and retarded fetal growth. MSAFP values were expressed as multiples of the appropriate weekly median (MOM) values relating to normal pregnancies with normal outcomes at term. For our normal population an MSAFP value of 2 MOM is the 95% centile, i.e. 5% of normal outcome pregnancies of sure gestation will have MSAFP values in the second trimester which are at or above 2 MOM. Information was available on 389 women whose infants were liveborn singletons weighing 2.5 kg or less. 33 (8.5%) of these women had MSAFP greater than 2 MOM (p less than 0.005) and of the 145 women whose babies weighed less than 2 kg, 17 (11.7%) had MSAFP at this level (p less than 0.001) Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal serum alpha-fetoprotein and birth weight

Maternal serum alpha-fetoprotein (AFP) levels between 16 and 18 weeks of pregnancy were studied in relation to birth weight among 4198 singleton pregnancies resulting in a liveborn or stillborn infant without a neural tube defect. The highest mean birth weight (3365 g) was found among infants born to women with AFP values in the range 0.50 to 0.74 times the normal median for the relevant week of gestation. As the AFP decreased from this level to less than 0.25 times the median, the birth weight decreased by 193 g and the proportion of infants weighing 2500 g or less increased from 4 per cent to 11 per cent. As the AFP level increased from 0.50 to 0.74 times the median to 3.0 times the median or greater, the birth weight decreased by 371 g and the proportion of infants weighing 2500 g or less increased from 4 to 22 per cent. The negative association was the more important of the two since the magnitude was greater and it affected 92 per cent of pregnancies. The positive association among women with low ARP levels was substantially reduced when the analysis was restricted to women who had spontaneous labours. It seems that this minor positive association arises mainly because women in whom gestation is over-estimated tend to have both a low AFP and, later, an apparently prolonged pregnancy leading to the elective delivery of an infant who is, in fact, born early.     

Association of maternal serum progesterone in early pregnancy with low birth weight and other adverse pregnancy outcomes

Objective: To investigate the association of serum progesterone in first trimester with low birth weight (LBW, birth weight <2500?g) and other adverse pregnancy outcomes including hypertensive disorders of pregnancy, preterm delivery, premature rupture of membranes at term, and preterm premature rupture of membranes in a general population.

Methods: We conducted a cohort study of 263 women with low-risk singleton intrauterine pregnancies who had a spot serum progesterone measurement in the first trimester in a Singapore tertiary maternity hospital. Study outcomes were retrieved from clinical records. Follow-up data were available for 131 women. Univariate and multivariate logistic regression analyses were performed to assess the association of low serum progesterone (<35?nmol/L) with LBW and other adverse pregnancy outcomes.

Results: Low serum progesterone was associated with a significantly increased risk of LBW (adjusted odds ratio: 5.28 [1.02, 27.3]; p=0.047). Low serum progesterone was associated with a significantly increased risk of hypertensive disorders of pregnancy in univariate analysis (unadjusted odds ratio: 8.43 [1.31, 54.2]; p=0.025).

Conclusion: Low serum progesterone in the first trimester is a significant risk factor for LBW and possibly other placental dysfunction disorders such as hypertensive disorders of pregnancy. Further studies with larger sample sizes are needed to confirm the associations.     

Maternal serum alpha-fetoprotein and low birth weight in relation to gestational age

To determine when in the first and second trimester a raised serum alpha-fetoprotein (AFP) level best predicts low birth weight a case-control study was performed on 157 singleton low birth-weight (less than or equal to 2.5 kg) and 314 singleton control pregnancies (birth weight greater than 2.5 kg). The association between raised maternal serum AFP and low birth weight was confirmed, but there was no special time in pregnancy before 29 weeks gestation when a raised AFP level predicted low birth weight materially better than at any other time.     

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.     

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.     

Elevated maternal serum alpha-fetoprotein values. How low is high?

Most maternal serum alpha-fetoprotein (MSAFP) screening programs are set up with the goal of prenatal detection of fetal neural tube defects. It is also commonly accepted that MSAFP testing yields many false-positive results. Screening programs commonly utilize schemata that identify abnormal levels of MSAFP as greater than 2.5 multiples of the median (MOM) and also recommend two abnormal values before initiating ultrasound evaluation. Our pilot program evaluating obstetric outcomes found that 21 of the 29 women with elevated MSAFP values (greater than 2.0 MOM) eventually developed significant pregnancy management changes or complications of pregnancy. Thus, we believe that the use of MSAFP screening solely for the purpose of detecting fetal neural tube defects is inconsequential relative to its usefulness in detecting other pregnancy abnormalities. We also believe that ultrasound evaluation should be accomplished after the first abnormal value and that the cutoff of 2.5 MOM should be lowered to at least 2.0.     

Pregnancies associated with low maternal serum alpha-fetoprotein concentrations.

A program of routine screening for antenatal detection of neural tube defects by alpha fetoprotein (AFP) testing is described. It was decided to determine the outcome of all pregnancies in which the patients exhibited a low AFP level during the screening process. From May 1975 to September 1976, 3% (53 cases) of the 2100 women tested had low AFP levels. Since maternal serum AFP levels rise with increasing gestational age until 32 weeks, a large number of women with low AFP levels actually have gestational ages more advanced than originally thought. That was true in this test. Ultrasonic examination of the cases with low AFP levels halped in revision gestational ages for some of the women. Among the 49 women with low AFP levels at gestational ages from 12-16 weeks, 12% had a spontaneous abortion eventually, 2% (or 1 case) had a macerated stillborn infant, and 1 woman was not pregnant. All 4 of the women with low AFP levels at gestational ages above 16 weeks had their gestational ages revised downward following ultrasonic examination. The study show that most women with low AFP levels eventually deliver a normal infant; a low AFP level does appear to be associated with spontaneous abortion. A larger study might identify association with other abnormalities. The study data was graphed and tabulated.     

Elevated maternal second-trimester serum alpha-fetoprotein as a risk factor for placental abruption

OBJECTIVE: To analyze the association of second-trimester maternal serum alpha-fetoprotein (MSAFP) and free beta human chorionic gonadotrophin (MSbeta-hCG) levels to placental abruption. METHODS: Fifty-seven women with placental abruption and 108 control women without placental abruption were tested for second-trimester MSAFP and MSbeta-hCG levels as a part of a trisomy 21 screening program. Discriminatory cutoff levels for MSAFP were sought to predict placental abruption. RESULTS: The median of the MSAFP multiples of median (MoM) (1.21) was significantly higher in the abruption group than in the control group (1.07) (p = 0.004). In multivariate analysis, elevated MSAFP remained an independent risk factor for placental abruption when adjusting for other risk factors (parity >/= 3, smoking, previous placental abruption, preeclampsia, bleeding in II or III trimester, and placenta previa). MSAFP >/= 1.5 MoM had a sensitivity of 29% and a false-positive rate of 10%. The levels of the MSbeta-hCG MoM did not differ between the cases and the controls. CONCLUSION: Although second-trimester MSAFP levels are higher in women with subsequent placental abruption, the clinical usefulness of this test is limited due to low sensitivity and high false-positive rate.     

Association between maternal weight gain and birth weight

OBJECTIVE: To investigate the association between maternal weight gain and birth weight less than 3,000 g and greater than or equal to 4,000 g in underweight (body mass index [BMI] less than 19.8 kg/m(2)), normal weight (BMI 19.8-26.0 kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI greater than 29.0 kg/m(2)) women, with emphasis on the use of the American Institute of Medicine (IOM) recommendations in Denmark. METHODS: We analyzed data from 2,248 women with singleton, term pregnancies. The relationship between weight gain and risk of birth weight less than 3,000 g and greater than or equal to 4,000 g was examined in the four BMI groups, and use of IOM recommendations was tested by logistic regression analyses. RESULTS: We found an inverse relationship between maternal weight gain and the proportion of infants with a birth weight less than 3,000 g. Birth weight greater than or equal to 4,000 g increased with an increasing weight gain in underweight and normal-weight women, but the association was less apparent in overweight and obese women. Underweight women seemed to benefit from gaining more weight than recommended by the IOM, because the odds ratio (OR) of birth weight less than 3,000 g was 0.3 (95% confidence interval [CI] 0.1-0.9) and the OR was 1.7 for birthweight greater than or equal to 4,000 g (95% CI 0.8-3.6). The normal-weight women had an increased risk of birth weight less than 3,000 g (OR 2.4, 95% CI 1.5-3.7) if weight gain was below the recommended range, and the OR of birth weight greater than or equal to 4,000 g was 1.9 (95% CI 1.5-2.5) when the women gained more than recommended. CONCLUSION: The IOM recommendations may provide a basis for Danish recommendations to pregnant women, although the upper recommended limit for underweight women may have to be increased.     

Association of maternal serum alpha-fetoprotein with persistent placenta previa.

OBJECTIVE: To evaluate the relationship between maternal serum alpha-fetoprotein (MSAFP) and the risk of persistent placenta previa. METHODS: We conducted a retrospective cohort study of singleton pregnancies with sonographic evidence of placenta previa at 15-20 weeks' gestation, between October 1991 and August 2000. Only pregnancies with MSAFP determination at 15-20 weeks' gestation and non-anomalous live-born infants > or =24 weeks' gestation were included. Pregnancies in which Cesarean delivery was performed for placenta previa were considered persistent; this was the primary outcome. RESULTS: Of 275 women with previa at 15-20 weeks' gestation, 33 (12%) had previa at delivery. Trend analysis revealed a greater likelihood of persistent previa with increasing MSAFP values (p=0.01). Mid-trimester MSAFP <1 multiple of the median (MoM) was associated with a decreased incidence of persistence of 4%, significantly less than the risk at > or =1 MoM (16%; p=0.01). CONCLUSIONS: There is an association between increasing MSAFP values and greater likelihood of persistent placenta previa. An MSAFP value <1 MoM is associated with a reduction in the risk of persistence of previa to delivery.     

Association between maternal periodontal disease and preterm delivery and low birth weight

ObjectiveIt has been suggested that periodontal disease is an important risk factor for preterm low birth weight (PLBW). The purpose of this study was to determine the association of maternal periodontitis with low birth weight (LBW) and preterm birth (PB).Materials and MethodsPregnant women (n = 211) aged 22–40 years were enrolled while receiving prenatal care. Dental plaque, probing depth, bleeding on probing, and clinical attachment level were used as criteria to classify three groups: a healthy group (HG; n = 82), a gingivitis group (GG; n = 67), and a periodontitis group (PG; n = 62). At delivery, birth weight was recorded.ResultsMean infant weight at delivery was 3084.9 g. The total incidence of preterm birth and LBW infants was 10.4% and 8.1%, respectively. The incidence of LBW infants was 4.2% for term and 40.9% for preterm gestations. Maternal height was not correlated with infant birth weight (p = 0.245). Significant differences in mean infant birth weight were observed among the HG, GG, and PG groups (p = 0.030). No significant relationship was found between periodontal disease and PB, but the association between periodontal disease and LBW was significant.ConclusionAfter appropriately controlling for confounding variables, our results do not support the hypothesis of an association that was observed in previous studies of maternal periodontal disease and infant PB, but the association between periodontal disease and LBW is significant.     

Very low maternal plasma alpha-fetoprotein concentration. An indication for follow-up

In the course of a screening programme for the detection of fetal neural tube abnormalities by measurement of maternal plasma alpha-fetoprotein (AFP), 57 patients were identified who had plasma AFP levels of less than 7 units/ml at 15-20 weeks gestation. follow-up at the time of screening included requests to confirm that the patient was pregnant and also to repeat the AFP test. Tow patients were lost to follow-up and of the remaining 55, 17 patients (31 per cent) were subsequently shown not to have a live fetus and 31 patients (56 per cent) had incorrect estimates of gestation. No particular reason for the very low plasma AFP could be identified in the other seven patients.