Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India

the CLIP working group

doi:10.1186/s12884-022-04714-y

Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India

the CLIP working group

Women & Children's Health

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Background: Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied. Methods: The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding. Results: Of 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia. Conclusion: In Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

Original language	English
Article number	407
Journal	BMC Pregnancy and Childbirth
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s12884-022-04714-y
Publication status	Published - Dec 2022

Keywords

Anemia in pregnancy
Global health
Hypertension

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10.1186/s12884-022-04714-y

Cite this

@article{285edff905504dfd9b8172784234a596,

title = "Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India",

abstract = "Background: Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied. Methods: The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding. Results: Of 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia. Conclusion: In Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.",

keywords = "Anemia in pregnancy, Global health, Hypertension",

author = "{the CLIP working group} and Bone, {Jeffrey N.} and Mrutyunjaya Bellad and Shivaprasad Goudar and Ashalata Mallapur and Umesh Charantimath and Umesh Ramadurg and Geetanjali Katageri and Maria Lesperance and {Woo Kinshella}, {Mai Lei} and Raiya Suleman and Marianne Vidler and Sumedha Sharma and Richard Derman and Magee, {Laura A.} and {von Dadelszen}, Peter and Bannale, {Shashidhar G.} and Chougala, {Keval S.} and Dhamanekar, {Vaibhav B.} and Joshi, {Anjali M.} and Kamble, {Namdev A.} and Kengapur, {Gudadayya S.} and Kudachi, {Uday S.} and Mastiholi, {Sphoorthi S.} and {I Mungarwadi}, Geetanjali and Esperan{\c c}a Sevene and Kh{\'a}tia Munguambe and Charfudin Sacoor and Eus{\'e}bio Macete and Helena Boene and Felizarda Amose and Orvalho Augusto and Cassimo Bique and {Ilda Biz}, Ana and Rog{\'e}rio Chia{\'u} and Silvestre Cutana and Paulo Filimone and Em{\'i}lia Gon{\c c}{\'a}lves and Marta Macamo and Sal{\'e}sio Macuacua and S{\'o}nia Maculuve and Ernesto Mandlate and Analisa Matavele and Sibone Mocumbi and Dulce Mulungo and Zefanias Nhamirre and Ariel Nhancolo and Cl{\'a}udio Nkumbula and Vivalde Nobela and Rosa Pires and Corsino Tchavana",

note = "Funding Information: PRE-EMPT, a grant awarded to University of British Columbia by the Bill & Melinda Gates Foundation (# OPP1017337). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and final responsibility for the decision to submit for publication. Bill and Melinda Gates Foundation,OPP1017337,OPP1017337,OPP1017337,OPP1017337,OPP1017337 Funding Information: We thank the Government of India for their permission to integrate the CLIP trial into their health systems with in-kind support and the entire CLIP India trialw CLIP India working group First and middle names Last names Shashidhar G Bannale Keval S Chougala Vaibhav B Dhamanekar Anjali M Joshi Namdev A Kamble Gudadayya S Kengapur Uday S Kudachi Sphoorthi S Mastiholi Geetanjali I Mungarwadi Esperan{\c c}a Sevene Kh{\'a}tia Munguambe Charfudin Sacoor Eus{\'e}bio Macete Helena Boene Felizarda Amose Orvalho Augusto Cassimo Bique Ana Ilda Biz Rog{\'e}rio Chia{\'u} Silvestre Cutana Paulo Filimone Em{\'i}lia Gon{\c c}{\'a}lves Marta Macamo Sal{\'e}sio Macuacua S{\'o}nia Maculuve Ernesto Mandlate Analisa Matavele Sibone Mocumbi Dulce Mulungo Zefanias Nhamirre Ariel Nhancolo Cl{\'a}udio Nkumbula Vivalde Nobela Rosa Pires Corsino Tchavana Anifa Vala Faustino Vilanculo Rahat N Qureshi Sana Sheikh Zahra Hoodbhoy Imran Ahmed Amjad Hussain Javed Memon Farrukh Raza Olalekan O Adetoro John O Sotunsa Sharla K Drebit Chirag Kariya Mansun Lui Diane Sawchuck Ugochi V Ukah Mai-Lei Woo Kinshella Shafik Dharamsi Guy A Dumont Tabassum Firoz Ana Pilar Betr{\'a}n Susheela M Engelbrecht Veronique Filippi William A Grobman Marian Knight Ana Langer Simon A Lewin Gwyneth Lewis Craig Mitton Nadine Schuurman James G Thornton France Donnay Romano N Byaruhanga Brian Darlow Eileen Hutton Mario Merialdi Lehana Thabane Kelly Pickerill Avinash Kavi Chandrashekhar Karadiguddi Sangamesh Rakaraddi Amit Revankar The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and final responsibility for the decision to submit for publication Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s12884-022-04714-y",

language = "English",

volume = "22",

journal = "BMC Pregnancy and Childbirth",

issn = "1471-2393",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Anemia and adverse outcomes in pregnancy

T2 - subgroup analysis of the CLIP cluster-randomized trial in India

AU - the CLIP working group

AU - Bone, Jeffrey N.

AU - Bellad, Mrutyunjaya

AU - Goudar, Shivaprasad

AU - Mallapur, Ashalata

AU - Charantimath, Umesh

AU - Ramadurg, Umesh

AU - Katageri, Geetanjali

AU - Lesperance, Maria

AU - Woo Kinshella, Mai Lei

AU - Suleman, Raiya

AU - Vidler, Marianne

AU - Sharma, Sumedha

AU - Derman, Richard

AU - Magee, Laura A.

AU - von Dadelszen, Peter

AU - Bannale, Shashidhar G.

AU - Chougala, Keval S.

AU - Dhamanekar, Vaibhav B.

AU - Joshi, Anjali M.

AU - Kamble, Namdev A.

AU - Kengapur, Gudadayya S.

AU - Kudachi, Uday S.

AU - Mastiholi, Sphoorthi S.

AU - I Mungarwadi, Geetanjali

AU - Sevene, Esperança

AU - Munguambe, Khátia

AU - Sacoor, Charfudin

AU - Macete, Eusébio

AU - Boene, Helena

AU - Amose, Felizarda

AU - Augusto, Orvalho

AU - Bique, Cassimo

AU - Ilda Biz, Ana

AU - Chiaú, Rogério

AU - Cutana, Silvestre

AU - Filimone, Paulo

AU - Gonçálves, Emília

AU - Macamo, Marta

AU - Macuacua, Salésio

AU - Maculuve, Sónia

AU - Mandlate, Ernesto

AU - Matavele, Analisa

AU - Mocumbi, Sibone

AU - Mulungo, Dulce

AU - Nhamirre, Zefanias

AU - Nhancolo, Ariel

AU - Nkumbula, Cláudio

AU - Nobela, Vivalde

AU - Pires, Rosa

AU - Tchavana, Corsino

N1 - Funding Information: PRE-EMPT, a grant awarded to University of British Columbia by the Bill & Melinda Gates Foundation (# OPP1017337). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and final responsibility for the decision to submit for publication. Bill and Melinda Gates Foundation,OPP1017337,OPP1017337,OPP1017337,OPP1017337,OPP1017337 Funding Information: We thank the Government of India for their permission to integrate the CLIP trial into their health systems with in-kind support and the entire CLIP India trialw CLIP India working group First and middle names Last names Shashidhar G Bannale Keval S Chougala Vaibhav B Dhamanekar Anjali M Joshi Namdev A Kamble Gudadayya S Kengapur Uday S Kudachi Sphoorthi S Mastiholi Geetanjali I Mungarwadi Esperança Sevene Khátia Munguambe Charfudin Sacoor Eusébio Macete Helena Boene Felizarda Amose Orvalho Augusto Cassimo Bique Ana Ilda Biz Rogério Chiaú Silvestre Cutana Paulo Filimone Emília Gonçálves Marta Macamo Salésio Macuacua Sónia Maculuve Ernesto Mandlate Analisa Matavele Sibone Mocumbi Dulce Mulungo Zefanias Nhamirre Ariel Nhancolo Cláudio Nkumbula Vivalde Nobela Rosa Pires Corsino Tchavana Anifa Vala Faustino Vilanculo Rahat N Qureshi Sana Sheikh Zahra Hoodbhoy Imran Ahmed Amjad Hussain Javed Memon Farrukh Raza Olalekan O Adetoro John O Sotunsa Sharla K Drebit Chirag Kariya Mansun Lui Diane Sawchuck Ugochi V Ukah Mai-Lei Woo Kinshella Shafik Dharamsi Guy A Dumont Tabassum Firoz Ana Pilar Betrán Susheela M Engelbrecht Veronique Filippi William A Grobman Marian Knight Ana Langer Simon A Lewin Gwyneth Lewis Craig Mitton Nadine Schuurman James G Thornton France Donnay Romano N Byaruhanga Brian Darlow Eileen Hutton Mario Merialdi Lehana Thabane Kelly Pickerill Avinash Kavi Chandrashekhar Karadiguddi Sangamesh Rakaraddi Amit Revankar The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and final responsibility for the decision to submit for publication Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Background: Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied. Methods: The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding. Results: Of 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia. Conclusion: In Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

AB - Background: Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied. Methods: The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding. Results: Of 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia. Conclusion: In Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

KW - Anemia in pregnancy

KW - Global health

KW - Hypertension

UR - http://www.scopus.com/inward/record.url?scp=85130028220&partnerID=8YFLogxK

U2 - 10.1186/s12884-022-04714-y

DO - 10.1186/s12884-022-04714-y

M3 - Article

C2 - 35562720

AN - SCOPUS:85130028220

SN - 1471-2393

VL - 22

JO - BMC Pregnancy and Childbirth

JF - BMC Pregnancy and Childbirth

IS - 1

M1 - 407

ER -

Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India

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Keywords

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