Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India
Authors: Bone Jeffrey N. , Bellad Mrutyunjaya , Goudar Shivaprasad , Mallapur Ashalata , Charantimath Umesh , Ramadurg Umesh , Katageri Geetanjali , Lesperance Maria , Woo Kinshella Mai-Lei , Suleman Raiya , Vidler Marianne , Sharma Sumedha , Derman Richard , Magee Laura A. , von Dadelszen Peter ,   the CLIP working group, Bannale Shashidhar G. , Chougala Keval S. , Dhamanekar Vaibhav B. , Joshi Anjali M. , Kamble Namdev A. , Kengapur Gudadayya S. , Kudachi Uday S. , Mastiholi Sphoorthi S. , I Mungarwadi Geetanjali , Sevene Esperança , Munguambe Khátia , Sacoor Charfudin , Macete Eusébio , Boene Helena , Amose Felizarda , Augusto Orvalho , Bique Cassimo , Ilda Biz Ana , Chiaú Rogério , Cutana Silvestre , Filimone Paulo , Gonçálves Emília , Macamo Marta , Macuacua Salésio , Maculuve Sónia , Mandlate Ernesto , Matavele Analisa , Mocumbi Sibone , Mulungo Dulce , Nhamirre Zefanias , Nhancolo Ariel , Nkumbula Cláudio , Nobela Vivalde , Pires Rosa , Tchavana Corsino , Vala Anifa , Vilanculo Faustino , Qureshi Rahat N. , Sheikh Sana , Hoodbhoy Zahra , Ahmed Imran , Hussain Amjad , Memon Javed , Raza Farrukh , Adetoro Olalekan O. , Sotunsa John O. , Drebit Sharla K. , Kariya Chirag , Lui Mansun , Sawchuck Diane , Ukah Ugochi V. , Woo Kinshella Mai-Lei , Dharamsi Shafik , Dumont Guy A. , Firoz Tabassum , Betrán Ana Pilar , Engelbrecht Susheela M. , Filippi Veronique , Grobman William A. , Knight Marian , Langer Ana , Lewin Simon A. , Lewis Gwyneth , Mitton Craig , Schuurman Nadine , Thornton James G. , Donnay France , Byaruhanga Romano N. , Darlow Brian , Hutton Eileen , Merialdi Mario , Thabane Lehana , Pickerill Kelly , Kavi Avinash , Karadiguddi Chandrashekhar , Rakaraddi Sangamesh , Revankar Amit 
Published: May 2022

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.