Sickle Cell Burden In Pregnancy Exposes Gaps In Early Screening, Family Testing

Sickle cell disease (SCD) is emerging as a significant concern in pregnancy in parts of central India, with a new study showing that affected women face a substantially higher burden of complications—from preterm births and low birth weight to Caesarean deliveries and blood transfusions.

The findings, based on screening of 11,602 pregnant women in Chandrapur, Maharashtra, between 2017 and 2022, also pointed to another concern: screening often happens after the crucial first trimester, while partners and children of women found to have abnormal haemoglobin are not consistently tested.

Researchers from the ICMR-Centre for Research Management and Control of Haemoglobinopathies, Chandrapur, and other ICMR institutions found that 0.25% of the women screened had sickle cell disease (HbSS), while 0.38% had sickle beta-thalassaemia. Another 5.18% were found to carry the sickle-cell trait (HbAS), while 1.8% had the beta-thalassaemia trait.

The study, published in the Indian Journal of Medical Research (IJMR), comes at a time when India is pursuing an ambitious goal of eliminating sickle cell anaemia as a public health problem by 2047. It suggests that antenatal care could provide one of the most important entry points for identifying women and families at risk.

Pregnancy can be particularly challenging for women with SCD. The study found that women with HbSS disease had an average hospital stay of 13 days, and their babies had an average birth weight of 2.25 kg. About 33.3% had preterm births, 83.3% underwent Caesarean delivery and half required blood transfusions during delivery.

Experts said these findings reinforce the need to identify SCD early rather than waiting until complications develop.

“Pregnancy in women with sickle cell disease is considered high-risk because physiological changes during pregnancy can aggravate anaemia and increase the risk of vaso-occlusive crises, infections, hypertensive disorders and other complications,” said Dr Manisha Madkaikar, one of the senior researchers involved in the study.

“Early identification allows the woman to be monitored more closely and managed by a multidisciplinary team, which can make a substantial difference to maternal and foetal outcomes,” she said.

The study also found a gap in the timing of screening. Of 4,457 women for whom trimester-wise data were available, only 32.9% were screened during the first trimester. Screening was carried out in the second trimester for 37.2% and in the third trimester for 29.9%.

This delay can have consequences because identifying a woman early gives healthcare teams time to test her partner, provide genetic counselling and, where appropriate, offer prenatal diagnosis.

“First-trimester screening is particularly important because it provides sufficient time for cascade screening of the spouse and, when both partners are at risk, for prenatal diagnosis and counselling,” said Dr Malay B Mukherjee, associated with the ICMR haemoglobinopathy research programme.

The genetic nature of SCD makes partner screening especially important. A person with sickle-cell trait is generally healthy but can pass the affected gene to a child. If both parents carry the sickle-cell gene, each pregnancy carries a 25% chance of the child having sickle cell disease, a 50% chance of carrying the trait and a 25% chance of inheriting neither altered gene.

Yet the study found that family screening remains incomplete.

Among 334 women who could be contacted for retrospective follow-up, only 61.1% reported that their spouses had been screened. Screening among their children was even lower: just 42.5% of 532 children had been tested.

The researchers said children of affected women and carriers should be specifically targeted for screening so that those at risk can be identified early and linked to care.

“The fact that children's screening was lower than spousal screening is an important gap. Once a woman is identified as having a haemoglobinopathy, the family should not be considered screened until the relevant family members have also been tested,” said Dr Madkaikar.

The study also illustrates how antenatal screening can move beyond simply diagnosing the mother. During the study period, 66 high-risk couples were identified and counselled for prenatal diagnosis. Of these, 53 opted for prenatal testing through amniocentesis or chorionic villus sampling.

Among them, 11 foetuses were found to have the HbSS pattern. The couples were counselled about the findings and advised regarding pregnancy options. Five opted for medical termination, two continued the pregnancy, while the outcome was unavailable for four couples.

The researchers stressed that prenatal diagnosis and any decision following an affected result must remain centred on informed counselling and the couple's autonomy, taking into account medical, ethical, social and cultural considerations.

“Prenatal diagnosis is not merely a laboratory procedure. It has significant emotional, ethical and social implications for families. Couples need accurate information and non-directive counselling so that they can make informed reproductive decisions,” said Dr Aruna Anil Jawade, associated with the research team.

For India, the findings have particular relevance because the National Sickle Cell Anaemia Elimination Mission launched by Prime Minister Modi in Shahdol, Madhya Pradesh, in 2023, with the aim to eliminate sickle cell disease as a public health problem by 2047, is the centenary of India’s independence. It targets universal screening of seven crore people aged between 0 and 40 in high-burden tribal districts, spread across 278 districts in 17 states.

The challenge, however, is to ensure that screening does not remain a one-time exercise. Identification of a pregnant woman with SCD or sickle-cell trait should trigger a cascade of services — partner testing, family screening, genetic counselling, prenatal diagnosis where indicated and appropriate clinical follow-up — and caution the doctors.

“Detection alone is not sufficient,” agreed Lt Dr C.B.S. Dangi, Nodal Head of the Sickle Cell and Thalassaemia Elimination Programme, NCC Directorate (MP and Chhattisgarh), commenting over the study observation. He was not part of the study.

Having over two decades of research experience in haemoglobinopathies, Dr Dangi said greater emphasis was needed on genetic testing and counselling of carriers so they understand their status and reproductive choices.

“Unless we break the gene transfer, we will not be able to eliminate this genetic disorder. Otherwise, we will remain caught in a vicious cycle of the disease,” he said.

Dr Dangi stressed that prenatal and antenatal testing, particularly among identified carriers and at-risk couples, needs to become an integral part of India’s elimination strategy.

Also, “migration from regions with high SCD prevalence, such as Madhya Pradesh and Chhattisgarh, to metros like Delhi and Bengaluru and beyond is normal,” said Dr Dangi, adding that this has contributed to rising numbers of affected people in areas that were previously less familiar with the disease.

The study researchers too warned that a positive screening result should not automatically be equated with disease. “Sickle-cell trait and sickle-cell disease are different conditions, and confirmatory testing is required to establish the haemoglobin pattern and guide counselling.”

For women with confirmed SCD, pregnancy requires closer monitoring for anaemia, pain crises, infections and pregnancy-related complications. The baby's growth and wellbeing also need to be monitored carefully.

“Pregnancy should not be seen as a period when sickle cell disease is discovered for the first time. Ideally, women should know their haemoglobin status before conception,” said Dr Prabhakar Kedar, another member of the research team.

That points to a larger shift needed in India's approach: moving sickle-cell screening from pregnancy alone to the preconception and adolescent years.

In regions with a high burden of haemoglobinopathies, making first-trimester screening routine, ensuring partner and child testing, and embedding genetic counselling into maternal healthcare could therefore be among the most important steps towards translating India's sickle-cell elimination ambition into outcomes on the ground, said the study.