Related Articles

Background

Infants born to women who receive intrapartum antibiotics may have higher rates of infectious morbidity and mortality than unexposed infants.

Objective

To determine the association of maternal intrapartum antibiotics and early neonatal morbidity and mortality.

Methods

Secondary analysis of data from a multi-site randomized placebo-controlled clinical trial of antibiotics to prevent chorioamnionitis-associated mother-to-child transmission of HIV-1 and preterm birth in sub-Saharan Africa. Early neonatal morbidity and mortality were analyzed. In an intent-to-treat (ITT) analysis, infants born to women randomized to antibiotics or placebo were compared. Additionally, non-ITT analysis was performed because some women received non-study antibiotics for various clinical indications.

Results

Overall, 2659 pregnant women were randomized. Of these, 2466 HIV-1-infected and -uninfected women delivered 2413 live born and 84 stillborn infants. In the ITT analysis, there were no significant associations between exposure to antibiotics and early neonatal outcomes. Non-ITT analyses showed more illness at birth (11.2% vs. 8.6%, p=0.03) and more admissions to the Special Care Baby Unit (12.6% vs. 9.8%, p = 0.04) among infants exposed to maternal intrapartum antibiotics than among unexposed infants. Further analyses revealed greater early neonatal morbidity and mortality among infants of mothers who received non-study antibiotics than of mothers who received study antibiotics.

Conclusion

There is no association between intrapartum exposure to antibiotics and early neonatal morbidity or mortality. The associations observed in non-ITT analyses are most likely the result of women with peripartum illnesses being more likely to receive non-study antibiotics.

Preterm birth is the major cause of perinatal morbidity and mortality in the developed world, and spontaneous preterm labor is the commonest cause of preterm birth. Interventions to treat women in spontaneous preterm labor have not reduced the incidence of preterm births but this may be due to increased risk factors, inclusion of births at the limits of viability, and an increase in the use of elective preterm birth. The role of antibiotics remains unproven. In the largest of the randomized controlled trials, evaluating the use of antibiotics for the prevention of preterm births in women in spontaneous preterm labor, antibiotics against anaerobes and bacterial vaginosis-related organisms were not included, and no objective evidence of abnormal genital tract flora was obtained. Atosiban and nifedipine are the main tocolytic agents used to treat women in spontaneous preterm labor, but atosiban is the tocolytic agent with the fewest maternal – fetal side effects. A well conducted randomized controlled trial comparing atosiban with nifedipine for their effectiveness and safety is needed.

Background

Preterm birth, the birth of an infant prior to 37 completed weeks of gestation, is the leading cause of perinatal morbidity and mortality. Preterm infants are at greater risk of respiratory, gastrointestinal and neurological diseases. Despite significant research in developed countries, little is known about the causes of preterm birth in many developing countries, especially China. This study investigates the association between sciodemographic data, obstetric risk factor, and preterm birth in five Maternal and Child Health hospitals in Beijing, China.

Methods and Findings

A case-control study was conducted on 1391 women with preterm birth (case group) and 1391 women with term delivery (control group), who were interviewed within 48 hours of delivery. Sixteen potential factors were investigated and statistical analysis was performed by univariate analysis and logistic regression analysis. Univariate analysis showed that 14 of the 16 factors were associated with preterm birth. Inter-pregnancy interval and inherited diseases were not risk factors. Logistic regression analysis showed that obesity (odds ratio (OR) = 3.030, 95% confidence interval (CI) 1.166–7.869), stressful life events (OR = 5.535, 95%CI 2.315–13.231), sexual activity (OR = 1.674, 95%CI 1.279–2.191), placenta previa (OR 13.577, 95%CI 2.563–71.912), gestational diabetes mellitus (OR = 3.441, 95%CI1.694–6.991), hypertensive disorder complicating pregnancy (OR = 6.034, 95%CI = 3.401–10.704), history of preterm birth (OR = 20.888, 95%CI 2.519–173.218) and reproductive abnormalities (OR = 3.049, 95%CI 1.010–9.206) were independent risk factors. Women who lived in towns and cities (OR = 0.603, 95%CI 0.430–0.846), had a balanced diet (OR = 0.533, 95%CI 0.421–0.675) and had a record of prenatal care (OR = 0.261, 95%CI 0.134–0.510) were less likely to have preterm birth.

Conclusions

Obesity, stressful life events, sexual activity, placenta previa, gestational diabetes mellitus, hypertensive disorder complicating pregnancy, history of preterm birth and reproductive abnormalities are independent risk factors to preterm birth. Identification of remedial factors may inform local health and education policy.

(See the editorial commentary by Kourtis, on pages 493–4.)

Background. Protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) use in pregnancy has been associated with preterm deliveries in some observational studies.

Methods. HIV-infected, HAART-naive pregnant women with CD4+ counts ≥200 cells/mm3 were randomized between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine (PI group) or abacavir/zidovudine/lamivudine (NRTI group) in a clinical trial to prevent mother-to-child HIV transmission. Risk factors for preterm delivery (<37 weeks) and differences by randomization arm were evaluated for live infants by logistic regression.

Results. Preterm delivery rates were higher among 267 women in the PI group than 263 women in the NRTI group (21.4% vs 11.8%, P = .003). PI-based HAART was the most significant risk factor for preterm delivery [odds ratio = 2.03, 95% confidence interval 1.26–3.27, P = .004]. Mean change in maternal body mass index (BMI) 1 month after HAART initiation was lower in the PI group (P < .001); however, this was not significantly associated with preterm delivery. Neither infant hospitalizations nor mortality through 6 months of life differed by maternal regimen.

Conclusions. PI-based HAART was associated with increased preterm delivery but not increased infant hospitalizations or mortality in a clinical trial setting. The association between PI use and lower increase in BMI in late pregnancy warrants further study.

Background

Preterm birth occurs in 5%–13% of pregnancies. It is a leading cause of perinatal mortality and morbidity and has adverse long-term consequences for the health of the child. Because of the role selenium plays in attenuating inflammation, and because low concentrations of selenium have been found in women with preeclampsia, we hypothesized that low maternal selenium status during early gestation would increase the risk of preterm birth.

Methods

White Dutch women with a singleton pregnancy (n = 1197) were followed prospectively from 12 weeks’ gestation. Women with thyroid disease or type 1 diabetes were excluded. At delivery, 1129 women had complete birth-outcome data. Serum concentrations of selenium were measured during the 12th week of pregnancy. Deliveries were classified as preterm or term, and preterm births were subcategorized as iatrogenic, spontaneous or the result of premature rupture of the membranes.

Results

Of the 60 women (5.3%) who had a preterm birth, 21 had premature rupture of the membranes and 13 had preeclampsia. The serum selenium concentration at 12 weeks’ gestation was significantly lower among women who had a preterm birth than among those who delivered at term (mean 0.96 [standard deviation (SD) 0.14] μmol/L v. 1.02 [SD 0.13] μmol/L; t = 2.9, p = 0.001). Women were grouped by quartile of serum selenium concentration at 12 weeks’ gestation. The number of women who had a preterm birth significantly differed by quartile (χ2 = 8.01, 3 degrees of freedom], p < 0.05). Women in the lowest quartile of serum selenium had twice the risk of preterm birth as women in the upper three quartiles, even after adjustment for the occurrence of preeclampsia (adjusted odds ratio 2.18, 95% confidence interval 1.25–3.77).

Interpretation

Having low serum selenium at the end of the first trimester was related to preterm birth and was independent of the mother having preeclampsia. Low maternal selenium status during early gestation may increase the risk of preterm premature rupture of the membranes, which is a major cause of preterm birth.

Background

It has been estimated that 430,000 children under 15 years of age were newly infected with HIV in 2008, and more than 71% are living in sub-Saharan Africa. In the absence of intervention to prevent mother-to-child transmission, 30-45% of infants born to HIV-positive mothers in developing countries become infected during pregnancy, delivery and breastfeeding. The aim of this study was to assess infant feeding practice and associated factors of HIV positive mothers attending prevention of mother to child transmission and antiretroviral therapy clinics of Northwest Ethiopia.

Methods

Institution based cross sectional study was conducted from January to May 2011 among all HIV positive mothers with less than two years old child attending prevention of mother to child transmission and antiretroviral therapy clinics in Gondar Town health institutions. A structured pre-tested questionnaire using interview technique was used for data collection. The data was entered and analyzed using SPSS version 16 statistical package.

Results

A total of 209 HIV positive mothers were included in the study. Of these, 187 (89.5%) had followed the recommended way of infant feeding practice while significant percentage (10.5%) had practiced mixed breast feeding. In multivariate analysis, disclosure of HIV status with their spouse, insufficient breast milk and occupational status were found to be independently associated (p-value of < 0.05) with recommended infant feeding practice. Lack of resource, stigma of HIV/AIDS, and husband opposition were also obtained as factors that influenced choice of infant feeding options by respondents.

Conclusions

Higher proportion of respondents used the recommended way of infant feeding practice by WHO as well as by Ethiopian Ministry of Health. However, mixed feeding in the first 6 months of age, an undesirable practice in infant feeding, were reported in this study. Infant feeding education that is aligned to national policy should be strengthened in primary health care, particularly in situations where prevention of mother to child transmission of HIV is prioritized.

Preterm birth is the leading cause of neonatal mortality and morbidity and long-term disability of non-anomalous infants. Previous studies have identified a prior early spontaneous preterm birth as the risk factor with the highest predictive value for recurrence. Two recent double blind randomized placebo controlled trials reported lower preterm birth rate with the use of either intramuscular 17 alpha-hydroxyprogesterone caproate (IM 17OHP-C) or intravaginal micronized progesterone suppositories in women at risk for preterm delivery. However, it is still unclear which high-risk women would truly benefit from this treatment in a general clinical setting and whether socio-cultural, racial and genetic differences play a role in patient’s response to supplemental progesterone. In addition the patient’s acceptance of such recommendation is also in question. More research is still required on identification of at risk group, the optimal gestational age at initiation, mode of administration, dose of progesterone and long-term safety.

Background

15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies.

Methods/Design

We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16–20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length.

Discussion

This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies.

Trial registration

Current Controlled Trials ISRCTN40512715

Background.

Cotrimoxazole prophylaxis is recommended for subgroups of human immunodeficiency virus (HIV)-infected adults and children to reduce all-cause morbidity and mortality. We investigated whether antenatal cotrimoxazole prophylaxis begun during pregnancy for HIV-infected pregnant women with low CD4 cell counts would affect birth outcomes.

Methods.

Cotrimoxazole prophylaxis was introduced as a routine component of antenatal care for HIV-infected women with CD4 cell counts <200 cells/μL during the course of a trial of mother-to-child HIV transmission in Lusaka, Zambia. Rates of preterm delivery, low birth weight, and neonatal mortality were compared for women with low CD4 cell counts before and after its introduction.

Results.

Among 255 women with CD4 cell counts <200 cells/μL, the percentage of preterm births (≤34 weeks of gestation) was lower (odds ratio [OR], 0.49 [95% confidence interval {CI}, 0.24-0.98]) after cotrimoxazole prophylaxis was introduced than before; there was a significant decrease in neonatal mortality (9% to 0%; P = .01) and a trend toward increased birth weight (β = 114 g [95% CI, -42 to 271 g]). In contrast, there were no significant changes in these parameters over the same time interval among women with CD4 cell counts ≥200 cells/μL.

Conclusion.

Antenatal provision of cotrimoxazole for HIV-infected pregnant women with low CD4 cell counts may have indirect benefits for neonatal health.

BACKGROUND

 Human immunodeficiency virus (HIV) is prevalent in many countries where small-for-gestational age (SGA) and premature delivery are also common. However, the associations between maternal HIV, preterm delivery and SGA infants remain unclear. We estimate the prevalence of SGA and preterm (<37 weeks) births, their associations with antenatal maternal HIV infection and their contribution to infant mortality, in a high HIV prevalent, rural area in South Africa.

METHODS

Data were collected, in a non-randomized intervention cohort study, on all women attending antenatal clinics (2001–2004), before the availability of antiretroviral treatment. Newborns were weighed and gestational age was determined (based on last menstrual period plus midwife assessment antenatally). Poisson regression with robust variance assessed risk factors for preterm and SGA birth, while Cox regression assessed infant mortality and associated factors.

RESULTS

Of 2368 live born singletons, 16.6% were SGA and 21.4% were preterm. HIV-infected women (n= 1189) more commonly had SGA infants than uninfected women (18.1 versus 15.1%; P = 0.051), but percentages preterm were similar (21.8 versus 20.9%; P = 0.621). After adjustment for water source, delivery place, parity and maternal height, the SGA risk in HIV-infected women was higher [adjusted relative risk (aRR) 1.28, 95% confidence interval (CI): 1.06–1.53], but the association between maternal HIV infection and preterm delivery remained weak and not significant (aRR: 1.07, 95% CI: 0.91–1.26). In multivariable analyses, mortality under 1 year of age was significantly higher in SGA and severely SGA than in appropriate-for-gestational-age infants [adjusted hazard ratio (aHR): 2.12, 95% CI: 1.18–3.81 and 2.77, 95% CI: 1.56–4.91], but no difference in infant mortality was observed between the preterm and term infants (aHR: 1.18 95% CI: 0.79–1.79 for 34–36 weeks and 1.31, 95% CI: 0.58–2.94 for <34 weeks).

CONCLUSIONS

Maternal HIV infection increases the risk of SGA, but not preterm births, in this cohort.

Background:

Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions.

Methods:

Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling.

Results:

Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4 – 6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses.

Conclusions:

The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.

Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD  = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥26) were overrepresented and short repeats (≤19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

Recurrent preterm birth is frequently defined as two or more deliveries before 37 completed weeks of gestation. The recurrence rate varies as a function of the antecedent for preterm birth: spontaneous versus indicated. Spontaneous preterm birth is the result of either preterm labor with intact membranes or preterm prelabor rupture of the membranes. This article reviews the body of literature describing the risk of recurrence of spontaneous and indicated preterm birth. Also discussed are the factors which modify the risk for recurrent spontaneous preterm birth (a short sonographic cervical length and a positive cervicovaginal fetal fibronectin test). Patients with a history of an indicated preterm birth are at risk not only for recurrence of this subtype, but also for spontaneous preterm birth. Individuals of African-American origin have a higher rate of recurrent preterm birth. The potential roles of genetic and environmental factors in recurrent preterm birth are considered.

Background

Preterm birth is the leading cause of perinatal morbidity and mortality. Risk factors for preterm birth include a personal or familial history of preterm delivery, ethnicity and low socioeconomic status yet the ability to predict preterm delivery before the onset of preterm labour evades clinical practice. Evidence suggests that genetics may play a role in the multi-factorial pathophysiology of preterm birth. The All Our Babies Study is an on-going community based longitudinal cohort study that was designed to establish a cohort of women to investigate how a women's genetics and environment contribute to the pathophysiology of preterm birth. Specifically this study will examine the predictive potential of maternal leukocytes for predicting preterm birth in non-labouring women through the examination of gene expression profiles and gene-environment interactions.

Methods/Design

Collaborations have been established between clinical lab services, the provincial health service provider and researchers to create an interdisciplinary study design for the All Our Babies Study. A birth cohort of 2000 women has been established to address this research question. Women provide informed consent for blood sample collection, linkage to medical records and complete questionnaires related to prenatal health, service utilization, social support, emotional and physical health, demographics, and breast and infant feeding. Maternal blood samples are collected in PAXgene™ RNA tubes between 18-22 and 28-32 weeks gestation for transcriptomic analyses.

Discussion

The All Our Babies Study is an example of how investment in clinical-academic-community partnerships can improve research efficiency and accelerate the recruitment and data collection phases of a study. Establishing these partnerships during the study design phase and maintaining these relationships through the duration of the study provides the unique opportunity to investigate the multi-causal factors of preterm birth. The overall All Our Babies Study results can potentially lead to healthier pregnancies, mothers, infants and children.

Objectives

Previous studies have investigated the consequences of late preterm birth between 34 – 36 weeks gestation, but less is known about the “indicated” reasons and potential differences in neonatal outcomes from various delivery indications. . In singletons, we characterized precursors for late preterm birth and incidences of neonatal morbidities and perinatal mortality by gestational age and precursor.

Methods

Using retrospective observational data, we compared 15,136 gestations born late preterm to 170,593 deliveries between 37 0/7 and 41 6/7 weeks. We defined the following categories of precursors for late preterm delivery: “spontaneous labor”, “premature rupture of the membranes (preterm PROM)”, “indicated” delivery and “unknown.” Incidences of neonatal morbidities were calculated according to category of precursor stratified by gestational age at delivery. Neonatal morbidities and mortality associated with potentially avoidable deliveries (e.g. “soft” precursors or elective) were compared between late preterm births and neonates born at 37 – 40 weeks.

Results

Late preterm birth comprised 7.8% of all births and 65.7% of preterm births. Percentages of precursors were 29.8% spontaneous labor, 32.3% preterm PROM, 31.8% indicated and 6.1% unknown. Different precursors for delivery were associated with varying incidences of neonatal morbidity. One in 15 neonates delivered late preterm for “soft” or elective precursors, and neonatal morbidity and mortality were increased compared to delivery ≥ 37 weeks for these same indications

Conclusion

A significant number of late preterm births were potentially avoidable Elective deliveries should be postponed until 39 weeks' gestation. More prospective data is needed to guide which indications can be managed expectantly.

Background

Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.

Methods/design

We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups.

Discussion

Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.

The number of pregnant women who have type 2 diabetes and the number found to have gestational diabetes are progressively increasing. In the future as many as 20% of pregnant women may have a diagnosis of diabetes. Although there is consensus regarding many issues in the treatment of pregnant women with diabetes, there are few evidenced-based studies upon which to base the timing of delivery. There must be a balance between increased neonatal morbidity of late preterm and early term delivery and fetal mortality. Potential adverse outcomes associated with late preterm and early term delivery include respiratory problems as well as other metabolic dysfunctions characteristic of the preterm infant of a mother with diabetes. Delivery at term increases the risk of fetal demise, fetal overgrowth, and birth injury. Even among diabetic women who are in good glycemic control, the risk of intrauterine fetal demise in third trimester appears greater than that of neonatal death. Additional prospective data are urgently needed to better understand the short and long-term risks and benefits of the timing of delivery in this very common obstetrical dilemma.

Background

Vitamin D is a strong immunomodulator and may protect against adverse pregnancy outcomes, mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV), and child mortality.

Methods

A total of 884 HIV-infected pregnant women who were participating in a vitamin supplementation trial in Tanzania were monitored to assess pregnancy outcomes and child mortality. The association of these outcomes with maternal vitamin D status at enrollment was examined in an observational analysis.

Results

No association was observed between maternal vitamin D status and adverse pregnancy outcomes, including low birth weight and preterm birth. In multivariate models, a low maternal vitamin D level (<32 ng/mL) was associated with a 50% higher risk (95% confidence interval [CI], 2%–120%) of MTCT of HIV at 6 weeks, a 2-fold higher risk of MTCT of HIV through breast-feeding among children who were HIV uninfected at 6 weeks (95% CI, 1.08–3.82), and a 46% higher overall risk of HIV infection (95% CI, 11%–91%). Children born to women with a low vitamin D level had a 61% higher risk of dying during follow-up (95% CI, 25%–107%).

Conclusions

If found to be efficacious in randomized trials, vitamin D supplementation could prove to be an inexpensive method of reducing the burden of HIV infection and death among children, particularly in resource-limited settings.

Background

Use of highly active antiretroviral therapy (HAART), a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development.

Methods

Our objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5 kg) and preterm birth rates (<37 weeks) were compared between those exposed and unexposed to HAART during pregnancy. Effects of different HAART regimen and duration were assessed.

Results

Among HAART-unexposed infants, 27% (60/224) were low birth weight compared with 23% (90/388) of early HAART-exposed (exposed <28 weeks gestation) and 19% (76/407) of late HAART-exposed (exposed ≥28 weeks) infants (p = 0.05). In the early HAART group, a higher CD4 cell count was protective against low birth weight (AOR 0.57 per 50 cells/mm3 increase, 95% CI 0.45-0.71, p < 0.001) and preterm birth (AOR 0.68 per 50 cells/mm3 increase, 95% CI 0.55-0.85, p = 0.001). HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001), with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p < 0.001, and AOR 5.6, 95% CI 2.1-15.2, p = 0.001, respectively).

Conclusions

In this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.

Background

Maternal morbidity and mortality among HIV-infected women is a global concern. This study compared mortality and health outcomes of HIV-infected and HIV-uninfected mothers at 18–20 months postpartum within routine prevention of mother-to-child transmission of HIV (PMTCT) services in a rural district in Malawi.

Methods

A retrospective cohort study of mother-child dyads at 18–20 months postpartum in Zomba District. Data on socio-demographic characteristics, service uptake, maternal health outcomes and biometric parameters were collected.

Results

173 HIV-infected and 214 HIV-uninfected mothers were included. HIV-specific cohort mortality at 18–20 months postpartum was 42.4 deaths/1000 person-years; no deaths occurred among HIV-uninfected women. Median time to death was 11 months post-partum (range 3–19). Women ranked their health on a comparative qualitative scale; HIV-infected women perceived their health to be poorer than did HIV-uninfected women (RR 2.4; 95% CI 1.6–3.7). Perceived maternal health status was well correlated with an objective measure of functional status (Karnofsky scale; p<0.001). HIV-infected women were more likely to report minor (RR 3.8; 95% CI 2.3–6.4) and major (RR 6.2; 95% CI 2.2–17.7) signs or symptoms of disease. In multivariable analysis, HIV-infected women remained twice as likely to report poorer health [adjusted OR (aOR) 2.3; 95% CI 1.4–3.6], as did women with low BMI (aOR 2.1; 95% CI 1.1–4.0) and scoring lowest on the welfare scale (aOR 2.0; 95% CI 1.1–3.8).

Conclusions

HIV-infected women show increased mortality and morbidity at 18–20 months postpartum. In our rural Malawian operational setting, where there is documented under-application of ART and poor adherence to PMTCT services, these results support attention to optimizing maternal participation in PMTCT programs.

Background

Observational studies have suggested that low serum vitamin levels are associated with increased mother-to-child transmission (MTCT) of HIV and increased preterm delivery. We aimed to determine the efficacy of vitamins on the prevention of MTCT and preterm delivery by systematically reviewing the available randomized controlled trials [RCTs]. We conducted systematic searches of 7 electronic databases. We extracted data from the RCTs independently, in duplicate.

Results

We included 4 trials in our review. Of the three trials on Vitamin A, two suggested no difference in MTCT, while the third and largest trial (n = 1078) suggested an increased risk of MTCT (Relative Risk 1.35, 95% Confidence Interval [CI], 1.11–1.66, P = 0.009). Two of the vitamin A trials addressed the impact of supplementation on pre-term delivery; one suggested a benefit (RR 0.65, 95% CI, 0.44–0.94) and the other no difference. All three vitamin A trials found no significant effect on infant mortality at 1 year. Of the two trials that looked at multivitamin use, only one addressed the prevention of MTCT, and found a non-significant RR of 1.04 (95% CI, 0.82–1.32). Two of the multivitamin trials found no significant effects on pre-term delivery. The single multivitamin trial examining children's mortality at 1 year yielded a non-significant RR of 0.91 (95% CI, 0.17–1.17).

Conclusion

Randomized trials of vitamins to prevent MTCT have yielded conflicting results without strong evidence of benefit and have failed to exclude the possibility of harm.

Objective

We examined the risk of preterm birth in relation to prepregnancy BMI (kg/m2), waist circumference, adult weight gain, and gestational weight gain among African-American women.

Methods

Using prospective data from the Black Women's Health Study, we assessed the association between maternal anthropometric factors and preterm birth among 7,841 singletons born to women ages 21–44 in 1995–2003. We compared mothers of infants born three or more weeks early (597 spontaneous preterm births (SPTB); 517 medically-indicated preterm births (MPTB)) with mothers of 6,727 term infants. We used generalized estimating equation models to derive odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders.

Results

Women with prepregnancy BMI <18 were at increased risk of SPTB and MPTB relative to normal weight women (BMI 20–24), and obese women (BMI ≥30) were at increased risk of MPTB. There were modest positive associations between waist circumference, a measure of central adiposity, and both preterm birth subtypes. Adult weight gain was also positively related to both preterm birth subtypes. Associations with SPTB were generally stronger for gestations of <32 weeks. Low gestational weight gain (<0.5 lbs/week) was associated with an increased risk of SPTB among normal weight and obese women. High gestational weight gain (≥1.5 lbs/week) was associated with increased risk of SPTB among overweight (BMI 25–29) and obese women.

Conclusion

Our data suggest that prepregnancy adiposity (overall and central), prepregnancy weight gain, and gestational weight gain influence risk of preterm birth among African-American women.

Preterm delivery (PTD), defined as birth before 37 completed weeks of gestation, is the leading cause of perinatal morbidity and mortality. Evaluation of the cervical morphology and biometry with transvaginal ultrasonography at 16–24 weeks of gestation is a useful tool to predict the risk of preterm birth in low- and high-risk singleton pregnancies. For instance, a sonographic cervical length (CL) > 30 mm and present cervical gland area have a 96-97% negative predictive value for preterm delivery at <37 weeks. Available evidence supports the use of progesterone to women with cervical length ≤25 mm, irrespective of other risk factors. In women with prior spontaneous PTD with asymptomatic cervical shortening (CL ≤ 25 mm), prophylactic cerclage procedure must be performed and weekly to every two weeks follow-up is essential. This article reviews the evidence in support of the clinical introduction of transvaginal sonography for both the prediction and management of spontaneous preterm labour.

Aims

To compare clinical status, mother-to-child transmission (MTCT) rates, use of prevention of (PMTCT) interventions and pregnancy outcomes between HIV-infected injecting drug users (IDUs) and non-IDUs.

Design and setting

Prospective cohort study conducted in seven human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Centres in Ukraine, 2000–10.

Participants

Pregnant HIV-infected women, identified before/during pregnancy or intrapartum, and their live-born infants (n = 6200); 1028 women followed post-partum.

Measurements

Maternal and delivery characteristics, PMTCT prophylaxis, MTCT rates, preterm delivery (PTD) and low birth weight (LBW).

Findings

Of 6200 women, 1111 (18%) reported current/previous IDU. The proportion of IDUs diagnosed with HIV before conception increased from 31% in 2000/01 to 60% in 2008/09 (P < 0.01). Among women with undiagnosed HIV at conception, 20% of IDUs were diagnosed intrapartum versus 4% of non-IDUs (P < 0.01). At enrolment, 14% of IDUs had severe/advanced HIV symptoms versus 6% of non-IDUs (P < 0.001). IDUs had higher rates of PTD and LBW infants than non-IDUs, respectively, 16% versus 7% and 22% versus 10% (P < 0.001). IDUs were more likely to receive no neonatal or intrapartum PMTCT prophylaxis compared with non-IDUs (OR 2.81, p < 0.001). MTCT rates were 10.8% in IDUs versus 5.9% in non-IDUs; IDUs had increased MTCT risk (adjusted odds ratio 1.32, P = 0.049). Fewer IDUs with treatment indications received HAART compared with non-IDUs (58% versus 68%, P = 0.03).

Conclusions

Pregnant human immunodeficiency virus-infected injecting drug users in Ukraine have worse clinical status, poorer access to prevention of mother-to-child transmission prophylaxis and highly active antiretroviral therapy, more adverse pregnancy outcomes and higher risk of mother-to-child transmission than non-injecting drug user women.

Background

Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates.

Methods/Design

Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%.

Discussion

This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications.

Trial Registration

The protocol is registered in the clinical trial register number ISRCTN08132825.