The influence of gestational age and smoking habits on the risk of subsequent preterm deliveries.

BACKGROUND: Previous preterm delivery and maternal smoking are associated with increased risks of preterm delivery. It is not known whether gestational age at the time of a preterm delivery is correlated with gestational age in successive preterm deliveries and whether changes in smoking habits influence the subsequent risk of preterm delivery. METHODS: We studied the associations among smoking habits, previous very preterm or moderately preterm delivery (before 32 weeks and at 32 to 36 weeks, respectively), and the risk of a subsequent very preterm or moderately preterm delivery in a population-based cohort of 243,858 women in Sweden between 1983 and 1993. The results were adjusted for covariates known to be associated with preterm delivery. RESULTS: The odds ratios for very or moderately preterm delivery in a subsequent pregnancy among women with a previous very preterm delivery, as compared with women who had a previous term delivery, were 12.4 (95 percent confidence interval, 9.1 to 17.0) and 7.1 (95 percent confidence interval, 6.0 to 8.4), respectively. Among women with a previous moderately preterm delivery, the corresponding odds ratios were 2.3 (95 percent confidence interval, 1.9 to 3.0) and 5.9 (95 percent confidence interval, 5.5 to 6.3), respectively. The odds ratios for a very preterm second delivery among the women who smoked 1 to 9 cigarettes per day and those who smoked 10 or more cigarettes per day, as compared with nonsmokers, were 1.4 (95 percent confidence interval, 1.1 to 1.7) and 1.6 (95 percent confidence interval, 1.3 to 2.0), respectively. The corresponding odds ratios for moderate preterm delivery were 1.3 (95% confidence interval, 1.2 to 1.4) and 1.5 (95 percent confidence interval, 1.4 to 1.6). The women who quit smoking between pregnancies were not at increased risk for very or moderately preterm delivery, whereas the women who started to smoke in the second pregnancy had the same risk as those who continued to smoke. CONCLUSIONS: The risk of a very preterm delivery in successive pregnancies is increased primarily among women with a previous very preterm delivery. Changes in smoking habits influence the risk of preterm delivery as well.     

Second-trimester serum chorionic gonadotropin concentrations and complications and outcome of pregnancy

BACKGROUND: Maternal serum chorionic gonadotropin is measured to screen for fetal chromosomal abnormalities. Whether the results can also be used to predict the risk of complications or an adverse outcome of pregnancy is not known. METHODS: We reviewed the medical records of 28,743 girls and women in whom chorionic gonadotropin was measured during the second trimester of pregnancy (between July 1, 1995, and January 31, 1997), seeking information about the complications and outcome of their pregnancies. We excluded girls and women who had preexisting risk factors for complications or an adverse outcome of pregnancy. RESULTS: Higher serum chorionic gonadotropin concentrations were associated with higher rates of stillbirth (odds ratio for every increase in chorionic gonadotropin of 1 multiple of the median, 1.4; 95 percent confidence interval, 1.1 to 1.9). There was no relation between higher serum chorionic gonadotropin concentrations and the risk of gestational diabetes, premature rupture of membranes or intrauterine growth retardation or small size for gestational age (odds ratio, 1.1; 95 percent confidence interval, 0.9 to 1.2). Higher serum chorionic gonadotropin concentrations were associated with a risk of placental abnormalities (odds ratio, 1.5; 95 percent confidence interval, 1.3 to 1.7), pregnancy-induced hypertension (odds ratio, 1.4; 95 percent confidence interval, 1.3 to 1.5), and preterm delivery without pregnancy-induced hypertension (odds ratio, 1.1; 95 percent confidence interval, 1.0 to 1.2). Inclusion in certain racial or ethnic categories (black, Filipino or Pacific Islander, unknown race or ethnic group, and "other," which included those of Middle Eastern descent and Native Americans) was a better predictor of the risk of an adverse outcome than serum chorionic gonadotropin values. CONCLUSIONS: Measurements of serum chorionic gonadotropin are of little clinical value for predicting the risk of complications and the outcome of pregnancy.     

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.     

Fluconazole prophylaxis against fungal colonization and infection in preterm infants.

BACKGROUND: Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants. METHODS: We conducted a prospective, randomized, double-blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients. RESULTS: The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented. CONCLUSIONS: Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.     

Perinatal and obstetric outcomes of donor insemination using cryopreserved semen in Victoria, Australia.

This study compared the perinatal and obstetric outcomes of 1552 donor insemination pregnancies in Victoria, Australia, with a control group of 7717 normally conceived pregnancies from the general population. Data on the outcomes of pregnancies of at least 20 weeks gestation, for both groups, were obtained from the same population-based birth registry. The study showed that there were no significant differences between the donor insemination and control groups in the incidence of preterm birth, low birthweight, multiple birth, perinatal death and birth defects, or in the sex ratio. Pregnancies conceived by donor insemination were significantly more likely than controls to have an induced labour (OR = 1.6, 95% CI 1. 4-1.8), a forceps delivery (OR = 1.5, 95% CI 1.3-1.8) and/or a Caesarean section (OR = 1.6, 95% CI 1.4-1.9) and to develop pre-eclampsia (OR = 1.4, 95% CI 1.2-1.8) after adjusting for maternal age, multiple birth, parity and presentation. Reasons for the higher rate of induced and operative deliveries are not clear. Overall, the study's findings are reassuring for couples considering infertility treatment with donor insemination. The study illustrates the importance of complete follow-up in studies of pregnancy outcomes after assisted conception and the use of appropriate population-based control groups with comparable ascertainment of outcomes.     

Clinical determinants of the racial disparity in very low birth weight.

BACKGROUND. Although the risk of very low birth weight (less than 1500 g) is more than twice as high among blacks as among whites in the United States, the clinical conditions associated with this disparity remain poorly explored. METHODS AND RESULTS. We reviewed the medical records of over 98 percent of all infants weighing 500 to 1499 g who were born in Boston during the period 1980 through 1985 (687 infants), in St. Louis in 1985 and 1986 (397 infants), and in two health districts in Mississippi in 1984 and 1985 (215 infants). The medical records of the infants' mothers were also reviewed. These data were linked to birth-certificate files. During the study periods, there were 49,196 live births in Boston, 16,232 in St. Louis, and 16,332 in the Mississippi districts. The relative risk of very low birth weight among black infants as compared with white infants ranged from 2.3 to 3.2 in the three areas. The higher proportion of black infants with very low birth weights was related to an elevated risk in their mothers of major conditions associated with very low birth weight, primarily chorioamnionitis or premature rupture of the amniotic membrane (associated with 38.0 percent of the excess proportion of black infants with very low birth weights [95 percent confidence interval, 31.3 to 45.4 percent]); idiopathic preterm labor (20.9 percent of the excess [95 percent confidence interval, 16.0 to 26.4 percent]); hypertensive disorders (12.3 percent [95 percent confidence interval, 8.6 to 16.6]); and hemorrhage (9.8 percent [95 percent confidence interval, 5.5 to 13.5]). CONCLUSIONS. The higher proportion of black infants with very low birth weights is associated with a greater frequency of all major maternal conditions precipitating delivery among black women. Reductions in the disparity in birth weight between blacks and whites are not likely to result from any single clinical intervention but, rather, from comprehensive preventive strategies.     

Lower risks of adverse outcome in twins conceived by artificial reproductive techniques compared with spontaneously conceived twins

The outcomes of twins conceived by 136 women after medical assistance (MA) such as ovulation induction with or without assisted reproductive techniques, and twins conceived spontaneously (SP) by 72 women were compared. All 208 women were monitored from < 20 weeks gestation; they all delivered at > or = 24 weeks gestation. The chorionicity of the placenta was diagnosed antenatally and confirmed after delivery. There were 10 perinatal deaths; the physical and neurological status of the remaining 406 infants was assessed at 1 year of corrected age. There were no differences in gestational age at birth, the birth weights of the larger and smaller twins, the birth weight discordance, or the incidence of life-threatening major malformations between groups. Adverse infant outcomes, such as death, cerebral palsy and mental retardation occurred in nine (3.3%) of 272 MA twins compared with 12 (8.3%) of 144 SP twins (P < 0.05). The placenta was monochorionic in only three (2.2%) of 136 MA twin pregnancies compared with 41 (57%) of 72 SP twin pregnancies (P < 0.001). Of the 21 infants with adverse outcomes, nine had monochorionic placentas. Thus, the risk of an adverse outcome was 2.8-fold higher (95% confidence interval (CI) 1.2- 6.4) in monochorionic twins than in dichorionic twins (10 versus 3.7%; P < 0.05). There was no difference in the incidence of adverse infant outcomes between SP (4.8%) and MA (3.4%) twins with dichorionic placentas. These findings suggest that ovulation induction in itself was not associated with an adverse outcome of twin pregnancies. The lower frequency of monochorionic placentas in MA twins may have been responsible for the lower risk of an adverse outcome in MA twins.      

Predictors of infant mortality among college-educated black and white women, Davidson County, Tennessee, 1990-1994.

Strategies to reduce US infant mortality rates often focus on the black-white disparity in rates. Linked Infant Birth and Death Files for Davidson County, Tennessee, from 1990 through 1994 were used to determine infant outcomes for infants born to college-educated white and black women. Risks for adverse outcomes were identified by comparing infant deaths to live births using logistic regression analyses. The following variables entered the logistic model process: maternal and paternal age; race and education; nativity status; maternal risk factors; interpregnancy interval; parity; infant gender; tobacco or alcohol use; number of prenatal visits; trimester in which prenatal care began; marital status; gestational age; and birthweight. After adjustment for the effects of the other variables, a gestational age < 28 completed weeks of gestation was the most significant independent predictor of infant death. Black race was not identified as a significant predictor of infant mortality. Regardless of race, a decrease in infant mortality rates among college-educated women in this country depends on the prevention of preterm births. Strategies to diagnose early preterm labor must proceed from a comprehensive maternal care program for all women. Open channels of communication between patient and provider will form the cornerstone for preterm prevention-intervention programs. Analysis of state and local infant mortality data may identify regional differences in infant mortality rates and differences in risk factors associated with adverse infant outcomes.     

The differential effect of prenatal care on the incidence of low birth weight among blacks and whites in a prepaid health care plan

Black infants are born with low birth weights (less than 2500 g) and very low birth weights (less than 1500 g) at twice the rate of white infants. We investigated the effect of prenatal care delivered in a health maintenance organization on the birth weights of black and white infants at normal risk for low birth weight. Using birth certificates for all children born in 1978 in the California Kaiser-Permanente hospitals, we studied data on more than 31,000 black and white newborns whose mothers' ages and levels of education were comparable. The data show that black mothers used prenatal care less extensively and had a higher incidence of infants with low birth weights (8.4 vs. 3.6 percent) and very low birth weights (2.0 vs. 0.7 percent) than white mothers. The difference in the use of prenatal care, however, accounted for less than 15 percent of the difference in the incidence of low birth weight. The rates of low birth weight, very low birth weight, and preterm birth (less than 260 days' gestation) decreased with increasing levels of prenatal care for both blacks and whites. However, increasing levels of care were associated with a greater reduction among black infants than among white infants in low birth weight, very low birth weight, and low birth weight at term (greater than or equal to 260 days' gestation). When we compared mothers who received adequate care with those who received inadequate care, the relative risk of giving birth to a very-low-birth-weight infant was reduced 3.6-fold (95 percent confidence interval, 2.0 to 6.6) for black mothers and 2.1-fold (confidence interval, 1.3 to 3.4) for white mothers; the relative risk of giving birth to a low-birth-weight infant at term was reduced 3.4-fold (95 percent confidence interval, 2.2 to 5.4) for black mothers and 1.6-fold (confidence interval, 1.1 to 2.3) for white mothers. We conclude that even in a population of women at low risk for giving birth to low-birth-weight infants, prenatal care is more beneficial for blacks than for whites.     

A randomized trial of psychosocial support during high-risk pregnancies. The Latin American Network for Perinatal and Reproductive Research.

BACKGROUND. It is often suggested that psychological and social support and health education for women at high risk for delivering a low-birth-weight infant can improve the outcomes of pregnancy, but the evidence is inconclusive. We undertook this prospective trial to evaluate a program of home visits designed to provide psychosocial support during pregnancy. METHODS. At four centers in Latin America, 2235 women at higher-than-average risk for delivering a low-birth-weight infant were recruited before the 20th week of pregnancy. The women were randomly assigned either to an intervention group (n = 1115) that received four to six home visits from a nurse or social worker in addition to routine prenatal care or to a control group (n = 1120) that received only routine prenatal care (with a mean of eight prenatal visits). The principal measures of outcome were low birth weight (< 2500 g), preterm delivery (< 37 weeks of gestation), and specified categories of maternal and neonatal morbidity. RESULTS. The women who received the home visits as well as routine prenatal care had outcomes that differed little from those of the women who received only routine care. The risks of low birth weight (odds ratio for the intervention group as compared with the control group, 0.93; 95 percent confidence interval, 0.68 to 1.28), preterm delivery (odds ratio, 0.88; 95 percent confidence interval, 0.67 to 1.16), and intrauterine growth retardation (odds ratio, 1.08; 95 percent confidence interval, 0.83 to 1.40) were similar in the two groups. There was no evidence that the intervention had any significant effect on the type of delivery, the length of hospital stay, perinatal mortality, or neonatal morbidity in the first 40 days. There was no protective effect of the psychosocial-support program even among the mothers at highest risk. CONCLUSIONS. Interventions designed to provide psychosocial support and health education during high-risk pregnancies are unlikely to improve maternal health or to reduce the incidence of low birth weight among infants.     

Delayed childbearing and the outcome of pregnancy

Whether women who delay childbearing are at increased risk for adverse outcomes of pregnancy is of concern because of the growing proportion of first births to older women. We assessed the effect of advancing maternal age on the outcome of pregnancy in first births in a hospital-based cohort study of 3917 private patients who were 20 years of age or older with a singleton gestation. There was a slight elevation in the risk of having a low-birth-weight infant among women who were 35 years of age or older (adjusted odds ratio, 1.3; 95 percent confidence interval, 0.9 to 1.9) as compared with the risk among women 20 to 29 years of age. However, there was no evidence that women between 30 and 34 or those 35 and older had an increased risk of having a preterm delivery or of having an infant who was small for gestational age, had a low Apgar score, or died in the perinatal period. In contrast, even after controlling for sociodemographic and medical risk factors, we found that women who were 35 or older were significantly more likely to have specific antepartum and intrapartum complications and those who were 30 or older were significantly more likely to have both cesarean sections and infants who were admitted to the newborn intensive care unit. This study suggests that although older primiparous women have higher rates of complications of pregnancy and delivery, their risk of a poor neonatal outcome is not appreciably increased.     

Absence of cardiac toxicity of zidovudine in infants. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study Group

BACKGROUND: Perinatal exposure to zidovudine may cause cardiac abnormalities in infants. We prospectively studied left ventricular structure and function in infants born to mothers infected with the human immunodeficiency virus (HIV) in order to determine whether there was evidence of zidovudine cardiac toxicity after perinatal exposure. METHODS: We followed a group of infants born to HIV-infected women from birth to five years of age with echocardiographic studies every four to six months. Serial echocardiograms were obtained for 382 infants without HIV infection (36 with zidovudine exposure) and HIV-58 infected infants (12 with zidovudine exposure). Repeated-measures analysis was used to examine four measures of left ventricular structure and function during the first 14 months of life in relation to zidovudine exposure. RESULTS: Zidovudine exposure was not associated with significant abnormalities in mean left ventricular fractional shortening, end-diastolic dimension, contractility, or mass in either non-HIV-infected or HIV-infected infants. Among infants without HIV infection, the mean fractional shortening at 10 to 14 months was 38.1 percent for those never exposed to zidovudine and 39.0 percent for those exposed to zidovudine (mean difference, -0.9 percent; 95 percent confidence interval, -3.1 percent to 1.3 percent; P=0.43). Among HIV-infected infants, the mean fractional shortening at 10 to 14 months was similar in those never exposed to zidovudine (35.4 percent) and those exposed to the drug (35.3 percent) (mean difference, 0.1 percent; 95 percent confidence interval, -3.7 percent to 3.9 percent; P=0.95). Zidovudine exposure was not significantly related to depressed fractional shortening (shortening of 25 percent or loss) during the first 14 months of life. No child over the age of 10 months had depressed fractional shortening. CONCLUSIONS: Zidovudine was not associated with acute or chronic abnormalities in left ventricular structure or function in infants exposed to the drug in the perinatal period.     

A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity

To study the role of infection in prematurity, we studied the demographic and obstetrical characteristics, chorioamnionic cultures, and placental histologic features of women who delivered prematurely and compared these findings with those in women who delivered at term. Microorganisms were isolated from the area between the chorion and the amnion (chorioamnion) in 23 of 38 placentas (61 percent) from women with preterm labor who delivered before 37 weeks' gestation and in 12 (21 percent) of 56 placentas from women without preterm labor who delivered at term (odds ratio, 5.6; 95 percent confidence interval, 2.1 to 15.6). The most frequent isolates from the placentas of those whose infants were delivered prematurely were Ureaplasma urealyticum (47 percent) and Gardnerella vaginalis (26 percent). The recovery of any organism from the chorioamnion was strongly associated with histologic chorioamnionitis (odds ratio, 7.2; 95 percent confidence interval, 2.7 to 19.5) and with bacterial vaginosis (odds ratio, 3.2; 95 percent confidence interval, 1.1 to 6.6). When multiple logistic regression was used to control for demographic and obstetrical variables, premature delivery was still related to the recovery of organisms from the chorioamnion (odds ratio, 3.8; 95 percent confidence interval, 1.5 to 9.9) and with chorioamnionitis (odds ratio, 5.0; 95 percent confidence interval, 1.6 to 15.3). The proportion of placentas with evidence of infection was highest among those who delivered at the lowest gestational age. We conclude that infection of the chorioamnion is strongly related to histologic chorioamnionitis and may be a cause of premature birth.     

The relationship of asthma medication use to perinatal outcomes

BACKGROUND: Maternal asthma has been reported to increase the risk of preeclampsia, preterm deliveries, and lower-birth-weight infants, but the mechanisms of this effect are not defined. OBJECTIVE: We sought to evaluate the relationship between the use of contemporary asthma medications and adverse perinatal outcomes. METHODS: Asthmatic patients were recruited from the 16 centers of the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network from December 1994 through February 2000. Gestational medication use was determined on the basis of patient history at enrollment and at monthly visits during pregnancy. Perinatal data were obtained at postpartum chart reviews. Perinatal outcome variables included gestational hypertension, preterm births, low-birth-weight infants, small-for-gestational-age infants, and major malformations. RESULTS: The final cohort included 2123 asthmatic participants. No significant relationships were found between the use of inhaled beta-agonists (n=1828), inhaled corticosteroids (n=722), or theophylline (n=273) and adverse perinatal outcomes. After adjusting for demographic and asthma severity covariates, oral corticosteroid use was significantly associated with both preterm birth at less than 37 weeks' gestation (odds ratio, 1.54; 95% CI, 1.02-2.33) and low birth weight of less than 2500 g (odds ratio, 1.80; 95% CI, 1.13-2.88). CONCLUSIONS: Use of inhaled beta-agonists, inhaled steroids, and theophylline do not appear to increase perinatal risks in pregnant asthmatic women. The mechanism of the association between maternal oral corticosteroid use and prematurity remains to be determined.     

Neurologic and developmental disability after extremely preterm birth. EPICure Study Group

BACKGROUND AND METHODS: Small studies show that many children born as extremely preterm infants have neurologic and developmental disabilities. We evaluated all children who were born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland from March through December 1995 at the time when they reached a median age of 30 months. Each child underwent a formal assessment by an independent examiner. Development was evaluated with use of the Bayley Scales of Infant Development, and neurologic function was assessed by a standardized examination. Disability and severe disability were defined by predetermined criteria. RESULTS: At a median age of 30 months, corrected for gestational age, 283 (92 percent) of the 308 surviving children were formally assessed. The mean (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes, referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively. Fifty-three children (19 percent) had severely delayed development (with scores more than 3 SD below the mean), and a further 32 children (11 percent) had scores from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3 percent) had hearing loss that was uncorrectable or required aids. Overall, 138 children had disability (49 percent; 95 percent confidence interval, 43 to 55 percent), including 64 who met the criteria for severe disability (23 percent; 95 percent confidence interval, 18 to 28 percent). When data from 17 assessments by local pediatricians were included, 155 of the 314 infants discharged (49 percent) had no disability. CONCLUSIONS: Severe disability is common among children born as extremely preterm infants.     

Folic acid antagonists during pregnancy and the risk of birth defects

BACKGROUND: Multivitamin supplementation in pregnant women may reduce the risks of cardiovascular defects, oral clefts, and urinary tract defects in their infants. We evaluated whether the folic acid component of multivitamins is responsible for the reduction in risk by examining the associations between maternal use of folic acid antagonists and these congenital malformations. METHODS: We compared data on exposure to folic acid antagonists that act as dihydrofolate reductase inhibitors and to certain antiepileptic drugs for 3870 infants with cardiovascular defects, 1962 infants with oral clefts, and 1100 infants with urinary tract defects with data for 8387 control infants with malformations the risk of which is not reduced after vitamin supplementation. Mothers were interviewed within six months after delivery about their medication use. RESULTS: The relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors during the second or third month after the last menstrual period, as compared with infants whose mothers had no such exposure, were 3.4 (95 percent confidence interval, 1.8 to 6.4) and 2.6 (95 percent confidence interval, 1.1 to 6.1), respectively. The relative risks of cardiovascular defects, oral clefts, and urinary tract defects after maternal exposure to antiepileptic drugs were 2.2 (95 percent confidence interval, 1.4 to 3.5), 2.5 (95 percent confidence interval, 1.5 to 4.2), and 2.5 (95 percent confidence interval, 1.2 to 5.0), respectively. Use of multivitamin supplements containing folic acid diminished the adverse effects of dihydrofolate reductase inhibitors, but not that of antiepileptic drugs. CONCLUSIONS: Folic acid antagonists, which include such common drugs as trimethoprim, triamterene, carbamazepine, phenytoin, phenobarbital, and primidone, may increase the risk not only of neural-tube defects, but also of cardiovascular defects, oral clefts, and urinary tract defects. The folic acid component of multivitamins may reduce the risks of these defects.     

The Effect of Single Embryo Transfer on Perinatal Outcomes in Japan

Objective: In 2007 and 2008, the Japan Society for Reproductive Medicine and the Japan Society of Obstetrics and Gynecology issued a recommendation for single embryo transfer (SET). Thereafter, SET was implemented in 73% of in vitro fertilization (IVF) cases in Japan. The purpose of this study was to evaluate the effects of compliance with the SET recommendation on perinatal outcomes.Methods: An electronic audit of the perinatal database of the Japanese Society of Obstetrics and Gynecology was conducted from 2001 through 2010. The database comprised data of 610,726 women. Totally, 20,923 women conceived through IVF. To compare perinatal outcomes, these women were categorized into two study groups depending on whether they conceived before (2004-2005, n = 3,865) or after (2009-2010, n = 6,842) the SET recommendation statement was issued.Results: The proportion of women who conceived through IVF increased from 1.3% in 2001 to 4.8% in 2010. Compliance with the SET recommendation led to a decrease in the incidence of twin pregnancies (33.9% versus 13%, p < 0.01), incidence of preterm delivery (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.50-0.59), low birth weight (OR: 0.42, 95% CI: 0.39-0.45), and neonatal intensive care unit admission (OR 0.70, 95% CI 0.65-0.76), but an increase in the incidence of monochorionic twins (1.6% versus 2.5%, p < 0.01).Conclusion: Compliance with the SET recommendation improved perinatal outcomes by reducing the incidence of twin pregnancies.     

The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. The HIV Infection in Newborns French Collaborative Study Group.

BACKGROUND. Early diagnosis of human immunodeficiency virus (HIV) infection in infants born to infected mothers is important for the infants' medical care, but the presence of maternal antibodies makes serologic tests uninformative. METHODS. In a cohort study of 181 infants born to HIV-infected mothers, we assessed the diagnostic value of HIV viral culture and testing for the presence of p24 antigen. The infants were tested at birth, again during the first 3 months, then followed and tested at the age of at least 18 months. RESULTS. Of the 181 infants, 3 died of HIV infection and 37 were seropositive after the age of 18 months. Viral cultures at birth were positive in 19 of the 40 infected infants and in none of the uninfected infants, yielding a sensitivity of 48 percent (95 percent confidence interval, 32 to 63 percent) and a specificity of 100 percent (95 percent confidence interval, 97 to 100 percent). By the age of three months, 30 of the 40 infants (75 percent) had positive cultures; again, there were no false positive results among the infants who were tested a second time, of the 141 who remained uninfected. The sensitivity of testing for p24 antigen at birth was only 18 percent, with a specificity of 100 percent. The presence of p24 antigen at birth was associated with the development of early and severe HIV-related disease (P less than 0.04). CONCLUSIONS. Viral culture at birth can correctly identify about half of newborns with HIV infection. The fact that this usually sensitive technique fails to identify about half the ultimately infected neonates suggests that vertical transmission of HIV may occur late in pregnancy or during delivery.     

Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants.

BACKGROUND: Antenatal glucocorticoid therapy decreases the incidence of several complications among very premature infants. However, its effect on the occurrence of cystic periventricular leukomalacia, a major cause of cerebral palsy, remains unknown. METHODS: We retrospectively analyzed a cohort of 883 live-born infants, with gestational ages ranging from 24 to 31 weeks, who were born between January 1993 and December 1996 at three perinatal centers in the Paris area. The mothers of 361 infants had received betamethasone before delivery, the mothers of 165 infants had received dexamethasone before delivery, and the mothers of 357 infants did not receive glucocorticoids. We compared the rates of cystic periventricular leukomalacia among the three groups of infants in bivariate and multivariate analyses after adjustment for confounding factors. RESULTS: The rate of cystic periventricular leukomalacia was 4.4 percent among the infants whose mothers had received betamethasone, 11.0 percent among the infants whose mothers had received dexamethasone, and 8.4 percent among the infants whose mothers had not received a glucocorticoid. After adjustment for gestational age, the mode of delivery, and the presence or absence of chorioamnionitis, prolonged interval between the rupture of membranes and delivery (>24 hours), preeclampsia, and the use of tocolytic drugs, antenatal exposure to betamethasone was associated with a lower risk of cystic periventricular leukomalacia than was either the absence of glucocorticoid therapy (adjusted odds ratio, 0.5; 95 percent confidence interval, 0.2 to 0.9) or exposure to dexamethasone (adjusted odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). The adjusted odds ratio for the group of infants whose mothers had received dexamethasone as compared with the group of infants whose mothers had not received a glucocorticoid was 1.5 (95 percent confidence interval, 0.8 to 2.9). CONCLUSIONS: Antenatal exposure to betamethasone but not dexamethasone is associated with a decreased risk of cystic periventricular leukomalacia among very premature infants.     

Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.