Dataset Information

Association of Maternal Inflammation During Pregnancy With Birth Outcomes and Infant Growth Among Women With or Without HIV in India.

ABSTRACT:

Importance

The association of elevated levels of specific inflammatory markers during pregnancy with adverse birth outcomes and infant growth could indicate pathways for potential interventions.

Objective

To evaluate whether higher levels of certain inflammatory markers during pregnancy are associated with preterm birth (PTB), low birth weight (LBW), and infant growth deficits.

Design, setting, and participants

In this cohort study of pregnant women with or without HIV, 218 mother-infant pairs were followed up from pregnancy through 12 months post partum from June 27, 2016, to December 9, 2019. Pregnant women aged 18 to 40 years and between 13 and 34 weeks of gestation who were receiving antenatal care were enrolled in a cohort stratified by HIV status; sampling was based on convenience sampling from women receiving antenatal care at Byramjee Jeejeebhoy Government Medical College.

Exposures

Levels of multiple circulating inflammation markers during the third trimester of pregnancy.

Main outcomes and measures

The primary study outcome was PTB (<37 weeks' gestation). Secondary outcomes were LBW (<2500 g) and repeated measures (delivery; 6 weeks post partum; and 3, 6, and 12 months post partum using multivariable generalized linear models) of infant growth outcomes (length-for-age, weight-for-age, and weight-for-length z scores).

Results

The median age of the 218 women at enrollment was 23 years (IQR, 21-27 years). In multivariable models, higher pregnancy levels of interleukin 17A were associated with increased odds of both PTB (adjusted odds ratio [aOR], 2.62; 95% CI, 1.11-6.17) and LBW (aOR, 1.81; 95% CI, 1.04-3.15). Higher levels of interleukin 1β were associated with increased PTB (aOR, 1.47; 95% CI, 1.15-1.89) and infant growth deficits (lower length-for-age z score: adjusted β = -0.10; 95% CI, -0.18 to -0.01; lower weight-for-age z score: adjusted β = -0.07; 95% CI, -0.14 to 0.001).

Conclusions and relevance

This study suggests that increased levels of certain systemic inflammatory markers, including interleukin 1β and interleukin 17A, during pregnancy were associated with adverse birth outcomes and infant growth deficits. Future studies should evaluate whether potential interventions to modulate specific inflammatory pathways during pregnancy could improve birth outcomes and infant growth.

SUBMITTER: Shafiq M

PROVIDER: S-EPMC8696571 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Maternal Inflammation During Pregnancy With Birth Outcomes and Infant Growth Among Women With or Without HIV in India.

Shafiq Mehr M Mathad Jyoti S JS Naik Shilpa S Alexander Mallika M Yadana Su S Araújo-Pereira Mariana M Kulkarni Vandana V Deshpande Prasad P Kumar Nathella Pavan NP Babu Subash S Andrade Bruno B BB Leu Cheng-Shiun CS Khwaja Saltanat S Bhosale Ramesh R Kinikar Aarti A Gupta Amita A Shivakoti Rupak R

JAMA network open 20211201 12

<h4>Importance</h4>The association of elevated levels of specific inflammatory markers during pregnancy with adverse birth outcomes and infant growth could indicate pathways for potential interventions.<h4>Objective</h4>To evaluate whether higher levels of certain inflammatory markers during pregnancy are associated with preterm birth (PTB), low birth weight (LBW), and infant growth deficits.<h4>Design, setting, and participants</h4>In this cohort study of pregnant women with or without HIV, 218 ...[more]

PMID: 34935918

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Project description:BackgroundAnemia during pregnancy may be associated with poor infant outcomes, although its consequences may vary based on etiology and timing.ObjectivesWe examined the associations between anemia and anemia-related biomarkers during pregnancy and infant outcomes [birthweight, gestational age at birth, birthweight-for-gestational age percentile, and infant hemoglobin (Hb) at 6 wk of age] in Nagpur, Eastern Maharashtra, India.MethodsWe conducted a prospective cohort study of 200 pregnant women. In the first trimester, venous blood was collected to assess Hb via cyanmethemoglobin analysis, micronutrient status (ferritin, vitamin B12, and folate), and inflammation (C-reactive protein). Hb was also assessed in capillary samples using a hemoglobinometer in the first and third trimesters for mothers and at 6 wk for infants. Associations were assessed using generalized linear models controlling for background characteristics.ResultsIn the first trimester, high (compared with normal) venous Hb was significantly associated with lower gestational age at birth [β: -1.0 wk, 95% confidence interval (CI): -1.9, -0.2] and higher birthweight-for-gestational age percentile (β: 20.1, 95% CI: 9.0, 31.2). Mild anemia, moderate anemia, and high (compared with normal) capillary Hb were significantly associated with lower birthweight (β: -147.7 g, 95% CI: -243.4, -51.7; β: -77.7 g, 95% CI: -123.9, -31.4; and β: -236.0 g, 95% CI: -478.0, -48.1) and birthweight-for-gestational age percentile (β: -7.3, 95% CI: -13.7, -0.9; β: -8.4, 95% CI: -14.1, -2.8; and β: -8.9, 95% CI: -15.9, -1.9). Higher serum ferritin was significantly associated with higher birthweight (β: 2.0 g, 95% CI: 0.1, 3.9) and gestational age at birth (β: 0.01 wk, 95% CI: 0.00, 0.01). In the third trimester, mild anemia was significantly associated with lower gestational age at birth (β: -0.5 wk, 95% CI: -0.7, -0.3).ConclusionsAssociations between maternal anemia during pregnancy and infant outcomes were mixed indicating further studies are needed to better understand these relationships.

Project description:BackgroundWomen living with HIV-1 (WLHIV) are at higher risk of having an adverse birth outcome, but the underlying mechanism(s) are unknown. We hypothesized that HIV-associated endothelial activation could adversely impact placental function and lead to impaired fetal growth or stillbirth.MethodsWe used stored samples from WLHIV and HIV-negative women who had enrolled during pregnancy in the observational Botswana Tshipidi cohort. Written informed consent was obtained from the participants. We measured plasma levels of markers of endothelial activation (soluble vascular adhesion molecule 1 [VCAM-1], intercellular adhesion molecule 1 [ICAM-1] and E-selectin) from samples taken during pregnancy. We compared log10 biomarker levels by maternal HIV status and by the timing of ART initiation (ART prior to conception vs. during pregnancy; ART prior to sample collection vs. no ART prior to sampling) using t-tests and the Kruskal-Wallis rank test. We evaluated the association between these biomarkers and adverse birth outcomes (composite of stillbirth or small for gestational age [SGA]) using univariate and multivariate log-binomial regression controlling for maternal age (continuous) and timing of ART start. We also used generalized linear models (GLM) to evaluate the association between continuous birthweight (in grams) and gestational age (in weeks) and markers of endothelial dysfunction, adjusting for maternal age (continuous) and timing of ART relative to sample collection.ResultsSpecimens collected before delivery were available for 414 women (372 WLHIV and 42 HIV-negative women), with a median age of 28 years and median gestational age at sample collection of 30 weeks (range 26, 35 weeks). WLHIV had significantly higher median VCAM1 (p = 0.002) than HIV-negative women, but HIV-negative women had higher median ICAM1 (p = 0.01); e-Selectin levels did not differ by maternal HIV status. Women starting ART during pregnancy had higher log10 VCAM1 levels than those on ART before conception, regardless of whether the sample was collected before (p = 0.02) or after (p = 0.03) ART initiation. However, ICAM1 and e-Selectin did not differ significantly by ART status or ART timing. Ninety-eight women (91 WLHIV and 7 HIV-negative), or 9 (2%) and 89 (22%) included in this study, had a stillborn or SGA baby respectively. Univariate and adjusted analyses did not show significant associations between levels of any of the biomarkers with these adverse birth outcomes. However, lower birthweight (p = 0.03) and lower gestational age at delivery were associated e-Selectin and ICAM (p = 0.008), respectively.ConclusionMaternal HIV infection and lack of ART (or recent ART initiation) were associated with one marker of greater endothelial activation (VCAM-1), but not with other markers (ICAM-1 nor E-selectin) in pregnancy. e-Selectin was associated with lower birthweight and every unit increase in log ICAM-1 at delivery was associated with lower gestation age at delivery.

Project description:BackgroundFew data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.Methods and findingsPregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens.ConclusionsOverall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children.Trial registrationwww.controlled-trials.com ISRCTN13968779

Project description:Background and aimsInfant adverse birth outcomes have been suggested to contribute to neonatal morbidity and mortality and may cause long-term health consequences. Although evidence suggests maternal prepregnancy body mass index (BMI) categories associate with some birth outcomes, there is no consensus on these associations. We aimed to examine the associations of maternal prepregnancy BMI categories with a wide range of adverse birth outcomes.MethodsData were from a population-based retrospective cohort study of 9,282,486 eligible mother-infant pairs in the U.S. between 2016 and 2018. Maternal prepregnancy BMI was classified as: underweight (<18.5 kg/m2); normal weight (18.5-24.9 kg/m2); overweight (25.0-29.9 kg/m2); obesity grade 1 (30-34.9 kg/m2); obesity grade 2 (35.0-39.9 kg/m2); and obesity grade 3 (≥40 kg/m2). A total of six birth outcomes of the newborn included preterm birth, low birthweight, macrosomia, small for gestational age (SGA), large for gestational age (LGA), and low Apgar score (5-min score <7).ResultsMaternal prepregnancy overweight and obesity increased the likelihood of infant preterm birth, with odds ratios (ORs) (95% CIs) of 1.04 (1.04-1.05) for overweight, 1.18 (1.17-1.19) for obesity grade 1, 1.31 (1.29-1.32) for obesity grade 2, and 1.47 (1.45-1.48) for obesity grade 3, and also for prepregnancy underweight (OR = 1.32, 95% CI = 1.30-1.34) after adjusting for all potential covariates. Prepregnancy overweight and obesity were associated with higher odds of macrosomia, with ORs (95% CIs) of 1.53 (1.52-1.54) for overweight, 1.92 (1.90-1.93) for obesity grade 1, 2.33 (2.31-2.35) for obesity grade 2, and 2.87 (2.84-2.90) for obesity grade 3. Prepregnancy overweight and obesity was associated with higher odds of LGA, with ORs (95% CIs) of 1.58 (1.57-1.59) for overweight, 2.05 (2.03-2.06) for obesity grade 1, 2.54 (2.52-2.56) for obesity grade 2, and 3.17 (3.14-3.21) for obesity grade 3. Prepregnancy overweight and obesity were also associated with higher odds of low Apgar score, with ORs (95% CIs) of 1.12 (1.11-1.14) for overweight, 1.21 (1.19-1.23) for obesity grade 1, 1.34 (1.31-1.36) for obesity grade 2, and 1.55 (1.51-1.58) for obesity grade 3.ConclusionOur findings suggest maintaining or obtaining a healthy body weight for prepregnancy women could substantially reduce the likelihood of important infant adverse birth outcomes.

Project description:HIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in women living with HIV vs. HIV-uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother-child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ≈26 week's gestation (n = 77 HIV-infected mothers; n = 190 HIV-uninfected mothers), at 6-10 weeks (n = 63 HEU infants and n = 159 HU infants) and at 24-28 months (n = 77 HEU children and n = 190 HU children). Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24-28 months. After correcting for multiple comparisons, HIV infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26 weeks gestation (GM-CSF and MMP-9, p < 0.05) and HEU children at 6-10 weeks (IFN-γ and IL-1β, p < 0.01), and at 24-28 months (IFN-γ, IL-1β, IL-2 and IL-4, p < 0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6-10 weeks, inflammatory markers (GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1β, IL-2, IL-4, IL-6 and NGAL, all p < 0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research.

Project description:ImportanceMaternal emergency department (ED) use before or during pregnancy is associated with worse obstetrical outcomes, for reasons including preexisting medical conditions and challenges in accessing health care. It is not known whether maternal prepregnancy ED use is associated with higher use of the ED by their infant.ObjectiveTo study the association between maternal prepregnancy ED use and risk of infant ED use in the first year of life.Design, setting, and participantsThis population-based cohort study included all singleton livebirths in all of Ontario, Canada, from June 2003 to January 2020.ExposuresAny maternal ED encounter within 90 days preceding the start of the index pregnancy.Main outcomes and measuresAny infant ED visit up to 365 days after the index birth hospitalization discharge date. Relative risks (RR) and absolute risk differences (ARD) were adjusted for maternal age, income, rural residence, immigrant status, parity, having a primary care clinician, and number of prepregnancy comorbidities.ResultsThere were 2 088 111 singleton livebirths; the mean (SD) maternal age was 29.5 (5.4) years, 208 356 (10.0%) were rural dwelling, and 487 773 (23.4%) had 3 or more comorbidities. Among singleton livebirths, 206 539 mothers (9.9%) had an ED visit within 90 days before the index pregnancy. ED use in the first year of life was higher among infants whose mother had visited the ED before pregnancy (570 per 1000) vs those whose mother had not (388 per 1000) (RR, 1.19 [95% CI, 1.18-1.20]; ARD, 91.1 per 1000 [95% CI, 88.6-93.6 per 1000]). Compared with mothers without a prepregnancy ED visit, the RR of infant ED use in the first year was 1.19 (95% CI, 1.18-1.20) if its mother had 1 prepregnancy ED visit, 1.18 (95% CI, 1.17-1.20) following 2 visits, and 1.22 (95% CI, 1.20-1.23) after at least 3 maternal visits. A low-acuity maternal prepregnancy ED visit was associated with an adjusted odds ratio (aOR) of 5.52 (95% CI, 5.16-5.90) for a low-acuity infant ED visit, which was numerically higher than the pairing of a high-acuity ED use between mother and infant (aOR, 1.43, 95% CI, 1.38-1.49).Conclusions and relevanceIn this cohort study of singleton livebirths, prepregnancy maternal ED use was associated with a higher rate of ED use by the infant in the first year of life, especially for low-acuity ED use. This study's results may suggest a useful trigger for health system interventions aimed at reducing some ED use in infancy.

Dataset Information

Association of Maternal Inflammation During Pregnancy With Birth Outcomes and Infant Growth Among Women With or Without HIV in India.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Maternal Inflammation During Pregnancy With Birth Outcomes and Infant Growth Among Women With or Without HIV in India.

Similar Datasets

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